text
stringlengths
2
1.05M
repo_name
stringlengths
5
101
path
stringlengths
4
991
language
stringclasses
3 values
license
stringclasses
5 values
size
int64
2
1.05M
Dionysius Sebwe Dionysius "Dion" Sebwe (born March 7, 1969 in Monrovia) is a retired Liberian football defender. He has served as the Deputy Minister for Operations in the Liberian Ministry of Defense. Sebwe attended Park College where he played soccer. In March 1995, the Kansas City Wiz selected Sebwe in the 1996 MLS College Draft. On April 17, 1996, the Wiz released Sebwe. Sebwe served in the U.S. Army and is a former member of the Liberia national football team. His brother is Kelvin Sebwe. References External links Dionysius Sebwe interview Category:1972 births Category:Living people Category:Liberian footballers Category:Liberian expatriate footballers Category:Association football defenders Category:Sportspeople from Monrovia Category:2002 African Cup of Nations players Category:FC Utrecht players Category:SC Heerenveen players Category:Orlando Sundogs players Category:Sporting Kansas City players Category:Minnesota Thunder players Category:Eredivisie players Category:Expatriate footballers in the Netherlands Category:Expatriate soccer players in the United States Category:USISL A-League players Category:USL A-League players Category:Sporting Kansas City draft picks
null
minipile
NaturalLanguage
mit
null
KweséESPN takes a look at the biggest winners and losers after the first four match days of Africa Cup of Nations 2019 qualifying. WINNERS First Qualifiers There can be no bigger winner than Madagascar, who became the first country to qualify for the 2019 Africa Cup of Nations. The homeland of the CAF president did so in record-breaking style -- first, with two full games to spare, and doing so for the first time in their history. Great news for the country, although television commentators... Mohamed Salah scored twice as Egypt booked their place at the African Nations Cup. Egypt and Senegal qualified for the African Nations Cup thanks to wins against Tanzania and Burundi. First-half goals from Premier League duo Sadio Mane and Mame Biram Diouf sealed a 2-0 win for Senegal at Burundi and ensured they will win Group K, having won five games from five, scoring 11 times and conceding just twice. The other game in that group saw Namibia run out 1-0 winners against Niger with Peter Shalulile's 15th-minute goal settling the game. Mohamed Saleh and Egypt have eliminated Stanley Amuzie and Nigeria from next year's African Nations Cup. Nigeria will not be competing at the 2017 African Nations Cup after losing 1-0 to Egypt on Tuesday. Ramadan Sobhy took advantage of a missed clearance to put Egypt atop qualifying Group G at Borg El-Arab Stadium, where a longstanding ban on fans attending games in large numbers in Egypt was temporarily lifted. Nigeria faced a must-win game after Chad withdrew from their group earlier this week. Under CAF's rules, all of Chad's previous results are thrown out, leaving Nigeria with just two points...
null
minipile
NaturalLanguage
mit
null
Former Sars commissioner Tom Moyane speaks during a press briefing held at Sars offices in Pretoria on 14 March 2018. Picture: Jacques Nelles The lobby group is now asking renewed questions about Jonas Makwakwa. With the National Prosecuting Authority (NPA) refocusing its attention on suspended South African Revenue Service (Sars) commissioner Tom Moyane, the next question has to be what is happening with Jonas Makwakwa and Kelly-Ann Elskie. They were alleged to be “involved in or facilitating corrupt activities” while at Sars. However, the NPA was yesterday unable to verify the status of any investigation or case into Makwakwa or Elskie. The NPA’s renewed interest in Moyane comes as a result of civil rights group Corruption Watch requesting a certificate confirming the authority had declined to prosecute Moyane. Corruption Watch wanted this in order to institute its own, private, prosecution. “We are pleased the NPA is reviewing its decision not to prosecute Moyane,” said David Lewis of Corruption Watch yesterday. “We’ve long held the evidence is pretty strong and he should be prosecuted.” The NPA has appeared to many to be less than enthusiastic about prosecuting Moyane, Makwakwa and Elskie, based on verifiable documentary evidence, compared to its attempts to take action against Ivan Pillay, Johann van Loggerenberg and Andries Janse van Rensburg on what appeared to be mostly word of mouth testimony. The storm around Makwakwa and Elskie broke in late 2016 after a Financial Intelligence Centre (FIC) report over their banking transactions was leaked. Makwakwa was then Sars’ chief officer of business, individual taxes and digital information systems while Elskie – also a Sars employee – appeared to have had a personal relationship with Makwakwa from which she benefited. According to the FIC, Makwakwa’s personal bank account was the primary account used to receive and disburse funds. “Credits into this account increased yearly from R1 358 817.01 in 2010 to R3 418 925.43 in 2015 (approximately 15%). Likewise, MJM’s [Makwakwa’s] payments have grown over this period, creating a dependency on suspicious cash deposits and payments to maintain his current standard of living. These payments are of concern as they originate from unknown sources,” the report stated. As far as Elskie was concerned, the FIC found three cash deposits, totalling R450 200, into her personal bank account. “The cash deposits were structured into two payments of R160 000 each and a payment of R130 200,” stated the FIC report. It added the deposits were made over three consecutive days into three different branches of the same bank, all within a 10km radius.
null
minipile
NaturalLanguage
mit
null
Now Commenting On: No setbacks for McCutchen in return to action Bucs star feels good after going 0-for-4 in first game back from rib fracture Email Print McCutchen receives ovation 0:25 8/19/14: Andrew McCutchen receives a standing ovation during his first at-bat since returning from the disabled list By Tom Singer / MLB.com | PITTSBURGH -- Andrew McCutchen returned to action Tuesday, hoping to help roust the Pirates from their nightmare. Instead, he became part of it. Even with McCutchen off the disabled list and back on the field, the Bucs took it on the chin from the Braves, the 11-3 defeat their worst since dropping a 12-2 game on May 31 in Los Angeles to the Dodgers. McCutchen was hitless in four at-bats as veteran Aaron Harang stymied the Pirates, striking out once and bouncing into a double play. In the big picture, however, what McCutchen did was not as important as how he felt. "Yeah, I felt pretty good. Just trying to get back in the swing of things. Hopefully, that happens sooner rather than later," said McCutchen, who was back at his familiar spots -- three-hole, center field -- upon being reinstated after having been sidelined with an avulsion fracture of his 11th rib. At that, McCutchen did have the Pirates' most puzzling at-bat of the night: In the sixth, he smoked a grounder at third baseman Chris Johnson, who threw to first for the out with McCutchen still in the batter's box. "Just a weird swing ... and I fell, kinda tripped over my other foot. That was about it," McCutchen said. "I felt good. No [discomfort], nothing at all." McCutchen did not play the entire game, leaving following his final at-bat in the eighth. There was no sense exposing him to unnecessary first-day stress given the lopsided score. "He aggravated nothing," manager Clint Hurdle confirmed after the game. "Just getting him out of the game. Got his at-bats in, moving on." McCutchen served the minimum time during the first DL stint of his career, gradually working himself back into game shape. "I'm ready to go. I'm good to go," McCutchen had said prior to batting practice. "Can't wait." To make room for McCutchen on the active roster, utility man Michael Martinez was optioned to Triple-A Indianapolis. "This is why I took 15 days, so I wouldn't have to [monitor myself when I returned], just go out there and play," McCutchen said. "I feel healed. I feel great. The legs feel great, the arm feels great, the ribs feel great, the body feels great." McCutchen injured himself on Aug. 3, but did not go on the DL until eight days later. The Bucs went 5-9 during his absence, yet actually responded well until the losing streak that reached seven with Tuesday's defeat. "It's been pretty frustrating to watch," McCutchen admitted. "Kinda like watching your best friend out there, on the track or something, and something happens and you want to go out there and help him, and you can't. "You got all your guys out there, grinding every single day, and you want to be out there to help them, and you can't. But I'm just part of the puzzle. I'm not going to put pressure on myself. I'm not going to try to carry the team, just do my job, help the club win with whatever it takes." At the time of his injury, the National League's reigning Most Valuable Player was among the league leaders in virtually every offensive category. Upon his return, McCutchen still led the league with an on-base percentage of .411 and was tied for fourth in batting at .311. Despite the lack of results -- for both himself and for the team -- McCutchen considered the game a key development as the Bucs anticipate the stretch drive for a postseason spot. "Yeah, definitely. That's something I'll try to do, just get back in the rhythm of things," McCutchen said. "That'll come. Getting the first out of the way was good." Tom Singer is a reporter for MLB.com and writes an MLBlog Change for a Nickel. He can also be found on Twitter @Tom_Singer. This story was not subject to the approval of Major League Baseball or its clubs.
null
minipile
NaturalLanguage
mit
null
Patient concerns about COVID-19 have colored almost every session I've conducted in my practice for the last week, no matter who the client was and no matter what problems had brought them into therapy to begin with. But one concern kept coming up for my single clients — as well as friends and colleagues who live alone — in particular: the isolation they expected to experience while working from home if (or more likely when) their offices closed for health reasons. As one friend who lives alone said to me: “Of course I can work from home. But can I stay sane while I’m doing it?” Studies seems to confirm that closing public settings is an effective means of protecting us physically from COVID-19 — but doing so will also create a different, if less potentially deadly, set of problems for some people. During a time of national stress, contact with others is one of the basic ways that people deal with anxiety, sadness, loneliness, depression, panic and other powerful and potentially difficult emotions, but not all of us live with other people. So social isolation through working from home may be good news in terms of containing the virus, but bad news in terms of easing our anxiety. For instance, a professional woman told me: “I’ve never wanted to work remotely. I can’t imagine what it would be like to be alone in my apartment all day, doing my work.” Get the think newsletter. This site is protected by recaptcha And a man who works in finance said: “I do my best work with people making lots of noise around me; I thrive on the high activity level. Being alone in my apartment is going to make me less productive — and it might just drive me nuts.” The problems inherent to working from home are not just poised to affect extroverts. Despite the plethora of Twitter and Facebook jokes about this imposed isolation being the stuff that introverts’ dreams are made of, many introverts also need contact with other people — just in different amounts and ways from their extroverted co-workers. Literature, sociology and psychology are filled with reminders that we all have some (albeit different levels of) need for time with others, whether we define ourselves as shy or outgoing, introverted or extroverted, or a group person or a loner. As Nancy McWilliams, one of the most popular synthesizers of contemporary psychotherapeutic practices, notes, most contemporary models of psychotherapy privilege the significance of relationships in psychological and emotional health. And research has shown that stress can exacerbate both physical and emotional difficulties, and that one of the ways that we ameliorate the stress is through social contact. Thus, the very activity that will hopefully contain the spread of the COVID-19 virus can be creating its own strain on our bodies and our psyches. So, though it may take a little ingenuity and extra work, finding healthy human contact while sequestered at home and following CDC guidelines is going to be extremely important during this crisis. In their book "Connected: The Surprising Power of Our Social Networks and How They Shape Our Lives," scientists Nicholas A. Christakis and James H. Fowler share research about the power of social connections to affect how we feel, think and act. When we’re forced to be away from the important — albeit perhaps unrecognized — social interactions at work, it’s crucial to find other ways to fill the need for connection. For example, though it's all but gone out of fashion, talking to other people, whether on the telephone or via video conferencing, can both fill in for normal social interactions and break the cycle of focusing on the bad news, while using the same technology that connects you to colleagues and work. Further, you can use the need for social distancing as an opportunity to reach out to people you have wanted to get to know better, either socially and/or for business. Many people are going to be in the same boat as you, looking for positive ways to connect to people while limiting physical contact; you can look into newly virtual classes, online movie- or television-watching parties or, like the Italians, try to organize or participate in a "Sound Flashmob" of music lovers. Similarly, research has shown that exercise is effective in lowering stress, in part because it both lowers stress hormones and raises the endorphins or “feel good” chemicals in your body. And, it has also long been a way of connecting. A client, for instance, told me that she was staying away from her yoga studio, but that she desperately missed the few minutes of social contact before and after class. She decided to solve the problem by doing online yoga with a buddy. “We’re at our own homes, but we open up the app and start the class at the same time; and then we talk for a few minutes when it’s over, just like we would do when we were at a class.” Still, there are people all around us who don’t have the luxury of self-isolating: first responders, health care workers and even people in service industry jobs (many of whom who don’t get paid time off), for example, are also frightened, anxious and stressed. A friendly smile and a question about how they’re doing when you do have to interact with them can go a long way toward ameliorating their discomfort — and, as a nice secondary gain, your own. As Harvard political scientist Robert D. Putnam describes in his book "Bowling Alone," working in isolation can be something of an oxymoron. Social interactions often optimize our strengths and keep us engaged in work. Connecting with someone who is not a colleague might not feel exactly like you're doing work, but it is a way of enhancing our own — and their — humanity, and keeping our sanity.
null
minipile
NaturalLanguage
mit
null
Surgical interventions for age-related cataract. Cataract is the major cause of global blindness, accounting for 40 to 80% of all blindness in developing countries. The number of people blind from cataract is expected to rise due to the changing age distribution and increasing life expectancy. There is currently no proven intervention to prevent cataract and surgery is the only form of treatment. The objective of this review is to compare the effects of different surgical interventions for age-related cataract. We searched the Cochrane Controlled Trials Register - CENTRAL/CCTR, which contains the Cochrane Eyes and Vision Group specialised register (Cochrane Library Issue 3 2001), MEDLINE (1966 to August 2001), EMBASE (1980 to September 2001), the reference lists of identified trials, and we contacted investigators and experts in the field for details of published and unpublished trials. We included randomised controlled trials evaluating surgical treatment for people with age-related cataract. Two reviewers independently extracted data and discrepancies were resolved by discussion. Where appropriate, relative risks, odds ratios and weighted mean differences were summarised after assessing heterogeneity between the studies. We used a fixed effect model due to the low number of trials in each comparison. We identified six trials that randomised a total of 7828 people. Phacoemulsification gave a better visual outcome than extracapsular surgery and gave a similar average cost per procedure in one trial conducted in the UK. Extracapsular surgery with posterior chamber lens implant and intracapsular surgery with or without an anterior chamber intraocular lens implant gave acceptable visual outcomes at 12 to 24 months after surgery. In three large trials in south Asia, best-corrected visual acuity of less than 6/60 ranged from 0.5 to 4%. Higher rates of poor outcome were observed in a multicentre study with 19 surgeons compared to a single-centre study with two surgeons. This review provides evidence from one randomised controlled trial that phacoemulsification gives a better visual outcome than extracapsular extraction with sutures. However, this trial was conducted in a developed country specialised hospital setting and extrapolation to other settings must be made with caution. This review also found evidence that extracapsular cataract extraction with a posterior chamber lens implant provides better visual outcome than intracapsular extraction with aphakic glasses. This finding is also based on the results of a single trial. The long term effects of posterior capsular opacification need to be assessed in larger populations. The data in the review suggest that intracapsular extraction with an anterior chamber lens implant is an effective alternative to intracapsular extraction with aphakic glasses, with similar safety. Further data from developing regions are needed to compare all aspects of intraocular lens surgery with the three main surgical procedures - intracapsular extraction with an anterior chamber lens, extracapsular surgery with a posterior chamber lens with or without sutures.
null
minipile
NaturalLanguage
mit
null
1. Introduction {#sec1-ijms-18-00155} =============== Wound healing is a complex multistep process comprised of three overlapping but distinct phases: inflammation, proliferation and remodelling. It begins with the inflammation phase, where neutrophils and macrophages are recruited to the wound site to remove cell debris and phagocytose infectious pathogens. This is followed by the proliferation stage, where re-epithelialization and the formation of granulation tissue begin to close the wound. Angiogenesis, the formation of new blood vessels, is important during both the inflammation and proliferation phases, forming angiogenic capillary sprouts that allow for recruitment of inflammatory cells to the wound for debris removal, invasion of the fibrin/fibronectin-rich wound clot, and reorganization of a microvascular network to maintain the new granulation tissue being formed \[[@B1-ijms-18-00155]\]. Finally, during the remodelling phase, fibroblasts reorganize the collagen matrix, forming a closed wound \[[@B2-ijms-18-00155]\]. All three phases must occur in the proper sequence and time frame in order for a wound to heal successfully. Excessive macrophage accumulation during the inflammation and proliferation stages may prolong the inflammatory response leading to delayed wound healing and scar formation at the injury site. Macrophage phenotype has also been reported to change throughout the wound healing process, alternating between inflammatory M1 and repair M2 phenotypes \[[@B3-ijms-18-00155]\]. The regulation of these phenotypes has been shown to affect wound functionality and the extent of scar tissue \[[@B4-ijms-18-00155]\]. Wounds that exhibit impaired healing frequently enter a state of pathological inflammation, with most chronic wounds developing into ulcers. The incidence of chronic wounds is associated with ischemia, diabetes mellitus, venous stasis disease or pressure \[[@B5-ijms-18-00155]\]. Chronic, non-healing wounds greatly impact a person's quality of life and, when left untreated, sometimes lead to amputation, resulting in an enormous health care burden \[[@B6-ijms-18-00155],[@B7-ijms-18-00155]\]. While current therapies provide some relief, there is a need for the continued development of novel therapies that address the debilitating effects of impaired wound healing. CC-chemokines are small inflammatory cytokines that have been shown to play a key role in the induction of inflammation and inflammation-mediated angiogenesis. In the wound healing process, macrophage infiltration is highly regulated by CC-chemokine gradients released by hyper-proliferating keratinocytes, fibroblasts and other macrophages \[[@B8-ijms-18-00155],[@B9-ijms-18-00155]\]. In human wounds, a host of CC-chemokines including CCL1, CCL2, CCL3, CCL4, CCL5 and CCL7 are expressed during the first week after injury and high levels of CCL2 have been found in human burns \[[@B10-ijms-18-00155],[@B11-ijms-18-00155]\]. Additionally, studies in excisional wounds have found localized expression of CCL2 and CCL3 in the epidermis, while CCL3 is expressed in follicular epithelium and sebaceous glands \[[@B12-ijms-18-00155]\]. CC-chemokines regulate key angiogenic processes such as the recruitment of inflammatory cells to the wound, to provide support for proliferating and migrating cells \[[@B13-ijms-18-00155]\], and the formation of granulation tissue \[[@B9-ijms-18-00155]\]. Furthermore, incubation with the recombinant CC-chemokines CCL2 and CCL5 stimulate angiogenic functions such as endothelial cell tubulogenesis and migration \[[@B14-ijms-18-00155],[@B15-ijms-18-00155],[@B16-ijms-18-00155],[@B17-ijms-18-00155],[@B18-ijms-18-00155]\]. Therefore, manipulation of the CC-chemokine family may modulate key wound healing processes to confer benefits. To date, studies have inhibited a single CC-chemokine and shown modest or no effect on wound healing. CCL2 knockout mice have delayed re-epithelialization and reduced angiogenesis in the early stages of wound repair, whilst the CCL3 knockout mice have normal wound healing \[[@B19-ijms-18-00155]\]. Similarly, CCR1 knockout models have no alteration in wound healing \[[@B20-ijms-18-00155]\]. Inhibition of a single CC-chemokine, however, may not be as effective in modulating wound healing due to redundancies in CC-chemokine signalling \[[@B21-ijms-18-00155],[@B22-ijms-18-00155]\]. A broad-spectrum CC-chemokine inhibition approach may therefore have increased efficacy. The broad-spectrum CC-chemokine inhibitor "35K" is a 35 kDa soluble protein produced by the Vaccinia virus that uniquely inhibits only the CC-chemokine class \[[@B23-ijms-18-00155]\]. It recognizes and binds to common structural features shared by most CC-chemokines, preventing binding to their cognate receptors \[[@B24-ijms-18-00155]\]. Broad-spectrum CC-chemokine inhibition using 35K inhibits a host of inflammatory diseases including atherosclerosis, acute peritonitis, hepatitis and liver fibrosis \[[@B25-ijms-18-00155],[@B26-ijms-18-00155],[@B27-ijms-18-00155],[@B28-ijms-18-00155]\]. Given the inhibitory effects of 35K on inflammatory-mediated diseases and the role of CC-chemokines in angiogenesis, we sought to elucidate the effect of broad-spectrum CC-chemokine inhibition on wound healing. We found that topical application of 35K enhanced wound closure, blood flow perfusion and neovascularisation at the early-mid stages of wound healing. Augmentation of wound angiogenesis by 35K was mediated via an increase in the pro-angiogenic and pro-repair cytokine TGF-β. In addition, 35K treatment inhibited wound levels of inflammatory transcription factor NF-κB and reduced collagen deposition at the late stages of wound healing in the 35K-treated wounds, suggesting a reduction in scar formation. Taken together, these findings show that broad-spectrum inhibition of CC-chemokines may be beneficial for the promotion of wound healing by suppressing inflammation and promoting wound closure and neovascularisation and reducing scar formation. 2. Results {#sec2-ijms-18-00155} ========== 2.1. Topical 35K Increases Wound Blood Perfusion and the Rate of Wound Closure in Early-Mid Stage Wound Repair {#sec2dot1-ijms-18-00155} -------------------------------------------------------------------------------------------------------------- Topical treatment of wounds with 35K protein caused significantly faster wound closure throughout the early to mid-stages of wound healing at Day 7 (42%, *p* \< 0.05) and Day 8 (33%, *p* \< 0.05) compared to PBS treated wounds ([Figure 1](#ijms-18-00155-f001){ref-type="fig"}a). Using Laser Doppler imaging, it was revealed that 35K protein augmented wound blood perfusion ([Figure 1](#ijms-18-00155-f001){ref-type="fig"}b). The Laser Doppler Index (LDI), used as a marker of wound angiogenesis and determined as the ratio of 35K:PBS wounds, was significantly elevated in the 35K treated wounds in the early stages following wounding (Day 3, 4), compared to PBS control wounds (values above 100% indicate increased wound blood perfusion with 35K treatment relative to PBS control). In the later stages of the wound healing process, at seven days post-wounding, blood perfusion started to decline in wounds treated with 35K, compared to the PBS treated control wounds. After Day 7, blood perfusion fluctuated along the baseline and very little blood perfusion was detected. There were no significant increases or decreases to the end point. 2.2. Inhibition of CC-Chemokines by 35K Increases Neovessel Formation in Early Stage Wounds but Decreases Neovessels in Late Stage Wounds {#sec2dot2-ijms-18-00155} ----------------------------------------------------------------------------------------------------------------------------------------- To investigate wound angiogenesis, neovessels and arterioles were assessed. In the early stages of wound healing (Day 4), there was an increase in the presence of wound neovessels in the 35K treated wounds as determined by CD31+ staining (182%, *p* \< 0.05, [Figure 2](#ijms-18-00155-f002){ref-type="fig"}a). However, at Day 10 post-wounding, there were significantly fewer wound neovessels (39% decrease, *p* \< 0.05) following 35K treatment. At Day 21, there were no differences in neovessels between 35K and PBS treated wounds. A similar biphasic pattern was also seen with the arterioles (α-actin+ staining), although, at Day 4, the trend for an increase in arterioles did not reach significance, but there was a significant 48% decrease in arterioles (*p* \< 0.05) in the 35K treated wounds at Day 10 post-wounding ([Figure 2](#ijms-18-00155-f002){ref-type="fig"}b). No CD31+ and α-actin+ staining is detected in IgG controls ([Figure S1](#app1-ijms-18-00155){ref-type="app"}). 2.3. Inhibition of CC-Chemokines by 35K Modulates Pro-Angiogenic Markers TGF-β and Vascular Endothelial Growth Factor (VEGF) in Early and Late Stage Wounds {#sec2dot3-ijms-18-00155} ----------------------------------------------------------------------------------------------------------------------------------------------------------- The expression of key angiogenic markers TGF-β and vascular endothelial growth factor (VEGF), known to be involved in wound healing, were measured next. Interestingly, TGF-β expression was significantly higher in 35K-treated wounds in the early stages of wound repair (Day 4 post-wounding, 88%, *p* \< 0.05, [Figure 3](#ijms-18-00155-f003){ref-type="fig"}a). However, in the later stages post-wounding (Day 10), the expression of TGF-β had normalised back to control levels. There were no differences in VEGF protein levels at Day 4 post-wounding between treatment groups. In the later stages, wounds from both treatment groups had significantly lower levels of VEGF protein, compared to wounds at Day 10 (*p* \< 0.01). The protein levels of fibroblast growth factor-2 (FGF-2), were also measured, but no differences were detected ([Figure S2a](#app1-ijms-18-00155){ref-type="app"}). Neither were there changes in wound protein levels of HIF-1α, a regulator of VEGF ([Figure S2b](#app1-ijms-18-00155){ref-type="app"}). 2.4. Inhibition of CC-Chemokines by 35K Reduces Inflammation but Has No Effect on Wound Macrophage Content {#sec2dot4-ijms-18-00155} ---------------------------------------------------------------------------------------------------------- Broad-spectrum CC-chemokine inhibition suppressed the mRNA levels of p65, the active subunit of NF-κB, with 34% and 62% decreases seen in Day 4 and 10 in 35K treated wounds respectively, compared to PBS treated wounds (all *p* \< 0.05, [Figure 4](#ijms-18-00155-f004){ref-type="fig"}a). A similar trend was observed for mRNA levels of the macrophage marker CD68, which were also lower in the 35K treated wounds but did not reach significance (Day 4: 39% ns; Day 10: 30% ns, [Figure 4](#ijms-18-00155-f004){ref-type="fig"}b). Despite this, histological analysis of macrophages in wound sections did not find a difference in CD68+ cells in 35K and PBS treated wounds at Day 4, 10, and 21 post-wounding ([Figure 4](#ijms-18-00155-f004){ref-type="fig"}c). Analysis of wound macrophage phenotype revealed that there were no significant changes in the mRNA levels of M2 macrophage marker CD206 in the 35K treated wounds ([Figure S3a](#app1-ijms-18-00155){ref-type="app"}). Interestingly, M1 macrophage markers CD80 and CD86 were unchanged at Day 4 but elevated in Day 10 35K treated wounds (278% and 342% respectively, *p* \< 0.01, [Figure S3b,c](#app1-ijms-18-00155){ref-type="app"}). No CD68+ staining is detected in IgG control ([Figure S1](#app1-ijms-18-00155){ref-type="app"}). 2.5. Inhibition of CC-Chemokines by 35K Decreases Collagen Formation in Late Stage Wounds {#sec2dot5-ijms-18-00155} ----------------------------------------------------------------------------------------- Milligan's trichrome staining was used to detect the collagen content in the wounds as a marker of tissue remodelling. While no differences in collagen deposition were observed at Day 4 and 21 between 35K and PBS wounds, a 25% decrease (*p* \< 0.05) in collagen content was seen in the 35K treated wounds at Day 10 ([Figure 5](#ijms-18-00155-f005){ref-type="fig"}a). The picrosirius red stain was imaged under polarized light to differentiate between type III and type I collagen. There was 10--100 times more type I collagen to type III collagen (across Day 4--21), but there were no significant differences between 35K and PBS treated wounds at each time point ([Figure 5](#ijms-18-00155-f005){ref-type="fig"}b). 2.6. Topical 35K Suppresses CC-Chemokine Expression in the Wounds {#sec2dot6-ijms-18-00155} ----------------------------------------------------------------- The effect of 35K on wound CC-chemokine protein and gene expression was measured. There was a significant decrease in CCL5 protein levels in 35K treated wounds at both the Day 4 (36%, *p* \< 0.05) and Day 10 (66%, *p* \< 0.05) time points ([Figure 6](#ijms-18-00155-f006){ref-type="fig"}a). There were also similar decreases in CCL5 mRNA levels in wounds treated with 35K (Day 4: 32%, ns and Day 10: 62%, *p* \< 0.05, [Figure 6](#ijms-18-00155-f006){ref-type="fig"}b). CCL2 protein levels were lower in wounds at the Day 4 time point (41%, *p* \< 0.05, [Figure 6](#ijms-18-00155-f006){ref-type="fig"}c), but the trend for a decline at the Day 10 time point did not reach significance following 35K treatment. This was consistent for wound CCL2 mRNA levels in which 35K treatment decreased CCL2 wound mRNA at the Day 4 time point (36%, *p* \< 0.05, [Figure 6](#ijms-18-00155-f006){ref-type="fig"}d), with no significant decrease in Day 10 wounds. 3. Discussion {#sec3-ijms-18-00155} ============= The stages of the wound healing process encompass the most complex biological processes that occur in human life. An imbalance can greatly affect the outcome of wound repair, with impaired wound healing often leading to severe unfavourable outcomes such as amputation. This highlights the need to develop novel agents that promote wound recovery. CC-chemokines have been shown to play a key role in the promotion of inflammation and inflammatory-induced angiogenesis, two important processes involved in wound healing. To date, only single CC-chemokine intervention studies have been done, with minimal to no benefit, suggesting that a broad-spectrum inhibition approach may have improved efficacy. In this study, we report that topical application of the broad-spectrum CC-chemokine inhibitor "35K" decreased wound CCL5 and CCL2 protein levels, leading to enhanced wound healing and wound neovascularisation during the early stages of wound healing. Histological analysis of wounds showed that 35K treatment significantly increased neovessels in the early stages of wound healing, when angiogenesis is most important. Mechanistically, we found that the classical VEGF-mediated angiogenic pathway was not responsible for the augmentation of angiogenesis by 35K, but, instead, 35K elevated the pro-angiogenic and pro-repair cytokine TGF-β. Furthermore, 35K treated wounds had significantly lower mRNA levels of p65, the active subunit of the inflammatory transcription factor NF-κB. In addition, 35K treated wounds at Day 10 had lower collagen content, suggesting a reduction in scar formation. Taken together, these findings suggest that broad-spectrum inhibition of CC-chemokines may be an alternate therapeutic approach to improve wound healing by simultaneously suppressing inflammation while augmenting neovascularisation at the critical early stages of wound repair. Macroscopic wound measurements revealed that wound closure was faster in 35K treated wounds compared to PBS treated control wounds. This was supported by the increased blood flow perfusion observed during the early stages post-wounding in 35K treated wounds. At this stage (\~Day 3), perfusion is critical to support the wound healing process to supply the wound with nutrients and growth factors, and accelerate debris removal \[[@B2-ijms-18-00155],[@B29-ijms-18-00155]\]. Increased blood flow perfusion also allows for increased oxygenation to help maintain the newly forming wound tissue \[[@B30-ijms-18-00155]\]. This early boost in perfusion may support the increased closure seen at Day 7 and 8. By Day 7, wound blood perfusion then started to decline in the 35K treated wounds. At this stage, remodelling is commencing, and, whilst neovessels are still present, the impetus for new wound neovessels has started to decline, supporting the decrease in wound blood perfusion at this stage. After Day 7 post-wounding, there is very little detectable blood perfusion using the Laser Doppler for both treatments. Consistent with our blood perfusion measurements, the current study also found that topical application of 35K increased the presence of wound neovessels at Day 4, and, at Day 10, neovessels and arterioles were reduced in the 35K treated wounds. At this late stage, the wound has nearly healed, re-epithelialization is complete, inflammation has ceased, a scar has formed and collagen remodelling from type III to type I collagen begins \[[@B31-ijms-18-00155]\]. Importantly, as the wound healing process is near-completion, angiogenesis may decline to allow for continued remodelling \[[@B9-ijms-18-00155],[@B32-ijms-18-00155]\]. The lower number of neovessels and arterioles seen at Day 10 suggest that these wounds have healed quicker and have now entered the remodelling phase. However, at Day 21, the wounds are further in the remodelling phase, bringing stability to neovessel content. The reduction in collagen content of the 35K treated wounds at Day 10 may further lead to reduced scar formation, as scars are mainly comprised of collagen \[[@B33-ijms-18-00155]\]. At Day 21, the collagen content returns to a stable level, when compared to PBS wounds. This suggests that whilst the wounds may have less scar the stability of the skin is not compromised. Interestingly, at Day 4 there is 10 times more type I collagen than type III, and, when the wound is completely healed and undergoing remodelling, there is an increase of 50 times in type I collagen in wounds. These findings are consistent with previous studies where reduced fibrosis was detected in the kidneys and lungs of mice following inhibition of the chemokine receptors CCR1 or CCR5 \[[@B34-ijms-18-00155],[@B35-ijms-18-00155],[@B36-ijms-18-00155]\]. Angiogenic mediators such as VEGF and FGF-2 are released by various cell types including endothelial cells, fibroblasts, keratinocytes and macrophages. VEGF is primarily produced by endothelial cells, whilst FGF-2 is produced by fibroblasts. Interestingly, 35K had no effect on these key angiogenic mediators involved in wound healing. Furthermore, we found no change in wound HIF-1α expression, which regulates VEGF and is triggered in response to tissue ischemia. This suggests that there was sufficient blood perfusion and oxygenation to the wounds. VEGF is involved in angiogenesis and synthesis of collagen in the wound \[[@B8-ijms-18-00155],[@B37-ijms-18-00155]\]. It is produced by wound fibroblasts, keratinocytes and macrophages \[[@B8-ijms-18-00155],[@B32-ijms-18-00155],[@B38-ijms-18-00155]\]. VEGF levels remained unchanged in 35K treated wounds, suggesting that VEGF is not involved in the augmentation of wound healing and wound angiogenesis by 35K. An alternative suggestion is that VEGF expression increased very early post-wounding with 35K, which was missed at the Day 4 time point. Studies have shown increases in VEGF just 24 h post-wounding \[[@B39-ijms-18-00155]\], which then return to baseline once angiogenesis is underway. There was, however, an increase in wound neovessels with 35K treatment at the Day 4 time point, despite no changes in VEGF or HIF-1α. Interestingly, both VEGF and HIF-1α are induced by NF-κB in inflammatory pathological angiogenesis. This study found that 35K significantly inhibited p65 (active NF-κB subunit) mRNA levels. This reduction in NF-κB may be part of the reason for the lack of change in VEGF and HIF-1α and suggests that 35K was preventing pathological excessive wound angiogenesis. Furthermore, the reduction in wound CC-chemokine levels by 35K would also contribute to the suppression of pathological angiogenesis that can compromise wound repair if it persists in the later stages of healing. The increase in angiogenesis seen during early wound healing, where it is critical, is likely to be the result of increased TGF-β expression in the Day 4 35K treated wounds. TGF-β increases key angiogenic functions including endothelial cell proliferation and migration \[[@B40-ijms-18-00155],[@B41-ijms-18-00155]\]. TGF-β also has a number of roles in the wound repair process including fibroblast proliferation, collagen formation and remodelling of the extracellular matrix \[[@B42-ijms-18-00155]\] and the initiation in the formation of granulation tissue \[[@B43-ijms-18-00155]\]. TGF-β stimulates contraction of fibroblasts \[[@B44-ijms-18-00155]\] and promotes the migration of keratinocytes in the wound \[[@B45-ijms-18-00155]\] which promotes wound closure. Taken together, our results demonstrate that 35K does not augment wound angiogenesis via the classical HIF-1α/VEGF angiogenic pathway but rather through the induction of TGF-β, and may in fact suppress excessive pathological angiogenesis in the mid-late stages of wound repair via inhibition of NF-κB and CC-chemokine levels. Despite the reduction in NF-κB by 35K, there were no changes in the number of wound macrophages as may have been expected. Macrophages can be roughly divided into pro- and anti-inflammatory phenotypes (M1 and M2) and both are involved in different stages of wound healing \[[@B46-ijms-18-00155]\]. Our results indicate an increase in the M2 macrophage phenotype during the early wound healing stage (TGF-β, CD206), which is known to be associated with improved wound repair, sufficient formation of granulation tissue and new vascular networks \[[@B46-ijms-18-00155]\]. Interestingly, there was a surprising increase in M1 macrophage markers at Day 10 (CD80, CD86), which is inconsistent with the reduction in NF-κB at this time point. However, previous studies have shown that the presence of M1 macrophages at this late-stage does not affect the wound healing process \[[@B4-ijms-18-00155]\]. There was a decrease in CCL5 and CCL2 protein in the tissues of wounds treated with the CC-chemokine inhibitor 35K. This would typically be associated with a decrease in macrophages; however, no significant reductions in macrophages were observed. A previous study reported that despite dominant expression of CCL2 in dermal mouse wounds, a relatively low CCL2 level correlated with optimal monocyte accumulation \[[@B12-ijms-18-00155]\], indicating that a reduction, but not complete ablation of CCL2, may not affect macrophage recruitment in the early stages of wound healing. However, at the later stage (i.e., Day 10), the wound is preparing to enter the remodelling phase in which macrophages undergo apoptosis and chemokines and angiogenesis are subsequently reduced. Additionally, chemokines from other classes and other cytokines that are not affected by 35K (for example CX~3~CL1, IL-1, IFN-γ) are released from the wound site and may have assisted in maintaining macrophage infiltration \[[@B47-ijms-18-00155]\], even with lower CCL2 and CCL5 levels. This may explain the consistent macrophage levels seen in our study despite the reduction in CC-chemokine levels. 4. Materials and Methods {#sec4-ijms-18-00155} ======================== 4.1. Generation and Isolation of 35K Protein {#sec4dot1-ijms-18-00155} -------------------------------------------- A recombinant adenovirus overexpressing 35K (Ad35K) was generated as described previously \[[@B48-ijms-18-00155]\]. To isolate 35K protein, 20 large flasks of Ad293 cells (293AD cell line, AD-100, Cell Biolabs Inc., San Diego, CA USA) were infected with 5 × 10^11^ Ad35K virus particles. After 24--48 h, cells were microscopically examined for evidence of complete cytopathic effect (CPE). 35K protein was isolated from Ad35K viral media using anti-HA tagged agarose-conjugated beads (A2095, Sigma-Aldrich, St. Louis, MO, USA). The media was run through a column packed with anti-HA agarose beads to bind 35K protein, which was then eluted from the column with 3 M sodium thiocyanate into 1 M Trizma Base (pH 8). Isolated 35K protein was dialyzed into sterile PBS and then filtered through 0.45 μm low protein binding syringe filter (Pall Corporation, Port Washington, NY, USA). The concentration of 35K protein was determined by measuring absorbance at 280 nm and aliquoted to 200 nM before freezing at −80 °C. 4.2. Murine Wound Healing Model {#sec4dot2-ijms-18-00155} ------------------------------- All experimental procedures and protocols were conducted with approval from the Sydney Local Health District Animal Welfare Committee (\#2013/027A), and conformed to the Guide for the Care and Use of Laboratory Animals (United States National Institute of Health, Bethesda, MD, USA). To explore the effect of broad-spectrum CC-chemokine inhibition on wound healing, a murine model that closely mimics the human wound healing process was used \[[@B49-ijms-18-00155]\]. Briefly, C57Bl6/J wildtype mice were anesthetized by inhalation of methoxyflurane. Then, a 6 mm biopsy punch was used to outline two circular full-thickness excisions, 5 mm in diameter, that include the panniculus carnosus created on the dorsum, one on each side of the midline of the mouse. A 0.5 mm thick silicone splint (Life Technologies, Carlsbad, CA, USA) was then placed around the wound and secured with interrupted sutures. For each mouse, one wound received purified 35K protein (200 nM in 50 μL PBS) and the other endotoxin-free PBS (50 μL, vehicle control), topically applied daily beginning on the day of wounding (Day 0). A transparent occlusive dressing (Opsite™ Flexifix™, Smith & Nephew, London, UK) was then applied. Mice were given carprofen (5 mg/kg) daily 3 days post-surgery to alleviate any pain. Digital images were taken and micro-callipers were used to measure wound area daily along the *x*-, *y*- and *z*-axes. Blood perfusion in wound areas was determined using Laser Doppler Perfusion Imaging (moorLDI2-IR, Moor Instruments, Devon, UK). For this study, two cohorts were taken at 4 (*n* = 12), 10 (*n* = 12), or 21 (*n* = 7) days after wounding. Both PBS and 35K treated wounds were collected for histological, protein and gene analysis. 4.3. Immunohistochemistry {#sec4dot3-ijms-18-00155} ------------------------- Wound tissues were fixed in 4% (*v*/*v*) paraformaldehyde overnight, and then embedded in paraffin. Furthermore, 5 µm wound sections were taken from the midpoint. Wounds were assessed for neovessels by detection with rabbit polyclonal anti-CD31 antibody (1:100, ab28364, Abcam, Cambridge, UK), arterioles by detection with mouse monoclonal smooth muscle α-actin antibody (1:100, A5691, Sigma-Aldrich) and for macrophages by detection with mouse monoclonal anti-CD68 antibody (1:100, ab31630, Abcam) staining. Secondary antibodies were pre-diluted horseradish peroxidase (HRP) secondary antibody α-rabbit (K4011, Dako) or pre-diluted HRP secondary antibody α-mouse (K4007, Dako, Glostrup, Denmark) for CD31 and CD68, respectively. The staining was visualized using 3,3′-Diaminobenzidine (DAB) (Dako) for CD31 and CD68 or Vector Red alkaline phosphatase substrate (SK-5100, Vector Laboratories, Burlingame, CA, USA) for smooth muscle α-actin. Appropriate IgG controls were used for all antibodies. Collagen was measured following Milligan's trichrome staining. Picrosirius red staining, imaged under polarized light, was used to differentiate type I and type III collagen. For all histological quantification, three sections were imaged at 10× magnification, the images were tiled and "stitched" to obtain the entire wound cross section for each treatment group per mouse (*n* = 7--12) and assessed using Image-Pro^®^ Premier 9.0 software (Media Cybernetics, Rockville, MD, USA). 4.4. Protein Expression {#sec4dot4-ijms-18-00155} ----------------------- Wound tissues were homogenized in lysis buffer (80 mM Tris HCl, 10 mM NaCl, 50 mM NaF, 5 mM Na~4~P~2~O~7~, 15 mM Triton-X 100). Wound tissue lysates (50 μg) were subjected to Western immunoblotting and probed for HIF-1α (1:1000, NB100-105, Novus Biologicals, Littleton, CO, USA) α Tubulin (1:5000, AB40742, Abcam) was used to confirm even protein loading. Commercially available ELISA kits (Quantikine, RnD Systems, Minneapolis, MN, USA) were used to determine protein levels of VEGF, CCL2 (MCP-1) and CCL5 (RANTES) in 100 μg of wound tissue lysates, while FGF-2 protein levels were measured in 50 μg of wound tissue lysates. 4.5. Gene Expression {#sec4dot5-ijms-18-00155} -------------------- Total RNA was isolated from wound samples using TRI reagent (Sigma-Aldrich). Furthermore, 300 ng total RNA was reverse transcribed using the iScript cDNA synthesis kit (Bio-Rad, Hercules, CA, USA) before amplification using the iQ SYBR Supermix (Bio-Rad) in a Bio-Rad Cfx384 thermocycler. The following mouse primers were used to probe for HIF-1α (F 5′-TCCCTTGCTCTTTGTGGTTGGGT-3′, R 5′-AACGTAAGCGCTGACCCAGG-3′), VEGF (F 5′-GAGTACCCCGACGAGATAGAGT-3′, R 5′-GGTGAGGTTTGATCCGCATGA-3′), p65 (F 5′-AGTATCCATAGCTTCCAGAACC-3′, R 5′-ACTGCATTCAAGTCATAGTCC-3′), CD68 (F 5′-GGGGCTCTTGGGAACTACAC-3′, R 5′-GTACCGTCACAACCTCCCTG-3′), TGF-β (F 5′-GGATACCAACTATTGCTTCAGCTCC-3′, R 5′-AGGCTCCAAATATAGGGGCAGGGTC-3′), CD206 (F 5′-CAGGTGTGGGCTCAGGTAGT-3′, R 5′-TGTGGTGAGCTGAAAGGTGA-3′), CD80 (F 5′-ACCCCCAACATAACTGAGTCT-3′, R 5′-TTCCAACCAAGAGAAGCGAGG-3′), CD86 (F 5′-CAGCTCACTCAGGCTTATGTTT-3′, R 5′-TGTTTCCGTGGAGACGCAAG-3′), CCL2 (F 5′-GCTGGAGCATCCACGTGTT-3′, R 5′-ATCTTGCTGGTGAATGAGTAGCA-3′), CCL5 (F 5′-GCAAGTGCTCCAATCTTGCA-3′, R 5′-CTTCTCTGGGTTGGCACACA-3′) and 36B4 (F 5′-CAACGCAGCATTTATAACCC-3′, R 5′-CCCATTGATGATGGAGTGTGG-3′). Relative changes in gene expression were normalized using the ΔΔ*C*~t~ method to 36B4 as the housekeeping gene. 4.6. Statistics {#sec4dot6-ijms-18-00155} --------------- All results are expressed as mean ± SEM. All data were compared using an unpaired two-tailed *t*-test. Significance was set at a value of *p* \< 0.05. 5. Conclusions {#sec5-ijms-18-00155} ============== In conclusion, our findings show that broad-spectrum CC-chemokine inhibition via topical application of 35K enhanced wound closure through the early promotion of neovascularisation. Furthermore, inhibiting the CC-chemokine class resulted in a reduced inflammatory state as indicated by reduced NF-κB. Mechanistically, 35K augmented wound angiogenesis via the induction of the pro-angiogenic cytokine TGF-β, rather than the HIF-1α/VEGF angiogenic pathway. Taken together, our findings (summarized in [Figure 7](#ijms-18-00155-f007){ref-type="fig"}) demonstrate that broad-spectrum CC-chemokine inhibition may improve wound healing by suppressing the inflammatory state of the wound while augmenting wound angiogenesis and suppressing scar formation. This work was supported by the Heart Research Institute (PhD scholarship to Anisyah Ridiandries) and the Heart Foundation of Australia (Career Development Fellowship \#CR07S3331 to Christina A. Bursill). The authors acknowledge the facilities as well as the scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility (ammrf.org.au) node at the University of Sydney: Sydney Microscopy & Microanalysis. Supplementary materials can be found at [www.mdpi.com/1422-0067/18/1/155/s1](www.mdpi.com/1422-0067/18/1/155/s1). ###### Click here for additional data file. Joanne Tan and Christina Bursill developed the study and designed the experiments. Anisyah Ridiandries and Joanne Tan performed the experiments. Anisyah Ridiandries, Joanne Tan and Christina Bursill interpreted the data and wrote the manuscript. Anisyah Ridiandries, Joanne Tan and Christina Bursill reviewed and edited the manuscript. The authors declare no conflict of interest. ![Topical 35K increases the rate of wound closure and wound blood perfusion in early-mid stage wound repair. Two full thickness wounds were created on C57Bl/6J mice (*n* = 7--12). Mice received daily topical application of 35K protein (200 nM) or PBS (vehicle). (**a**) representative images of the wounds and wound blood perfusion using Laser Doppler imaging (high (red) to low (blue) blood flow); (**b**) wound area was calculated from the average of three daily diameter measurements along the *x*-, *y*- and *z*-axes. Wound closure is expressed as a percentage of initial wound area at Day 0. Black circles are PBS treated wounds; grey triangles are 35K treated wounds; and (**c**) the 35K:PBS wound blood flow perfusion ratio was determined using Laser Doppler imaging (LDI). Data is represented as mean ± SEM. Points above the dotted line represent an improvement with 35K treatment. Statistical analysis was performed by an unpaired two-tailed *t*-test. \* *p* \< 0.05 compared to PBS treated wounds.](ijms-18-00155-g001){#ijms-18-00155-f001} ![Inhibition of CC-chemokines by 35K increases neovessel formation in the early stages of wound repair but decreases neovessels in later stages. Immunocytochemistry was used to detect the presence of neovessels and arterioles. Photomicrographs represent wounds stained for (**a**) CD31+ neovessels (stained brown, noted by black arrows) and (**b**) α-SMC+ arterioles (stained pink, noted by black arrows). Three tiled images were taken per wound (*n* = 7--12/treatment). Scale bars represent 50 μm. Data is represented as mean ± SEM. Statistical analysis was performed by an unpaired two-tailed *t*-test. \* *p* \< 0.05 compared to PBS treated wounds.](ijms-18-00155-g002){#ijms-18-00155-f002} ![Modulation of pro-angiogenic markers following inhibition of CC-chemokines by 35K in early and late stage wounds. RNA and protein were isolated from PBS and 35K treated wounds at both the early (Day 4) and late (Day 10) time points (*n* = 12/time point); (**a**) real-time PCR was used to measure mRNA levels of TGF-β; (**b**) vascular endothelial growth factor (VEGF) protein levels were detected by ELISA. Data is represented as mean ± SEM. Statistical analysis was performed by an unpaired two-tailed *t*-test. \#\# *p* \< 0.01, \#\#\# *p* \< 0.001 compared to respective treatment group wounds at Day 4. \* *p* \< 0.05 compared to PBS treated wounds.](ijms-18-00155-g003){#ijms-18-00155-f003} ![Inhibition of CC-chemokines by 35K reduces inflammation but has no effect on wound macrophage content. Total RNA was isolated from PBS and 35K treated wounds at both the early (Day 4) and late (Day 10) time points (*n* = 12/time point). Real-time PCR was used to measure mRNA levels of (**a**) p65, the active subunit of the key inflammatory transcription factor NF-κB and (**b**) macrophage marker CD68; (**c**) immuno-histochemistry was used to detect the presence of wound macrophages. Photomicrographs represent wound sections stained for CD68+ macrophages (stained brown, noted by black arrows). Three tiled images were taken per wound (*n* = 7--12/treatment). Scale bars represent 50 μm. Data is represented as mean ± SEM. Statistical analysis was performed by an unpaired two-tailed *t*-test. \* *p* \< 0.05 compared to PBS treated wounds.](ijms-18-00155-g004){#ijms-18-00155-f004} ![Inhibition of CC-chemokines by 35K decreases collagen formation in Day 10 wounds. Masson's trichrome staining was used to detect the collagen content in the wounds. (**a**) green staining in wound sections is collagen, purple staining are nuclei; (**b**) to differentiate collagen type, wound sections were stained red with picrosirius and imaged under polarized light. Green represents Type III collagen, yellow to red represents Type I collagen. Three tiled images were taken per wound (*n* = 12 or 7/treatment). Scale bars represent 50 μm. Data is represented as mean ± SEM. Statistical analysis was performed by an unpaired two-tailed *t*-test. \* *p* \< 0.05 compared to PBS treated wounds.](ijms-18-00155-g005){#ijms-18-00155-f005} ![Topical 35K suppresses CC-chemokines in wound tissues. Protein and RNA were isolated from PBS and 35K treated wounds at both the early (Day 4) and late (Day 10) time points (*n* = 12/time point). ELISAs and real-time PCR was used to measure protein and mRNA levels of (**a**,**b**) CCL5 and (**c**,**d**) CCL2. Data is represented as mean ± SEM. Statistical analysis was performed by an unpaired two-tailed t-test. \* *p* \< 0.05, \*\* *p* \< 0.01 compared to PBS treated wounds.](ijms-18-00155-g006){#ijms-18-00155-f006} ![Summary of proposed 35K action in wound healing. Broad-spectrum CC-chemokine inhibition by 35K has a significant impact on key mechanisms involved in wound healing. In addition, 35K enhances wound closure through the early promotion of neovascularisation via the induction of TGF-β, rather than the HIF-1α/VEGF angiogenic pathway. 35K treatment reduces inflammation via inhibition of NF-κB, which may help to stave off pathological angiogenesis in the later stages of wound repair, along with the reductions in CCL5 and CCL2 but with no change in macrophages. Finally, 35K suppresses collagen deposition at the late stage of wound healing, but not early, indicative of reduced scar formation.](ijms-18-00155-g007){#ijms-18-00155-f007} [^1]: These authors contributed equally to this work.
null
minipile
NaturalLanguage
mit
null
Many will remember 2011 for its economic troubles, the beginning of the 2012 presidential election campaign, and unprecedented political demonstrations around the world and closer to home. But the Organic Trade Association, headquartered in Brattleboro, VT, wants people to also remember the six myths that research busted about organic agriculture and consumer acceptance of organics during the year. On Dec. 19 the OTA issued its Six Myths Busted by Organic in 2011 report, which highlights news that defied the old stereotypes. Myth No. 1 is that “organic is a niche market.” The OTA reported that new research shows that 78 percent of U.S. families said that they purchase organic products. Organic fruits and vegetables captured more than 11 percent of the total fruits and vegetables market in 2010. Organic buyers are more likely to be Asian, African American, or Hispanic than non-buyers. They are more likely to report household incomes of $35,000 and higher and are more likely to be under 25. Myth No. 2 is that “U.S. consumers are ambivalent about genetically modified organisms.” The OTA reported that nine in 10 parents say it is important to label genetically engineered foods, and 78 percent of parents are concerned that genetically engineered foods could lead to unintended side effects in the environment or in animals. The third myth is that “organic foods are too expensive for the average family.” The OTA reported that 78 percent of U.S. families now buy organic food at least some of the time and that smart shoppers can and do make organic choices on a budget. The OTA offers strategies for consumers looking to enjoy the benefits of organic products for less, the report said. The fourth myth is that “organic farming cannot feed the world.” The OTA stated that recent research from Iowa State University’s long-term trials found that conventional and organic produced similar yields, while organic produced better profit and resulted in better soil quality. The Oct. 20, 2011 issue of Nature outlined solutions for a cultivated planet to meet growing food needs. It stated that to meet the world’s future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture’s environmental footprint must shrink dramatically. Myth No. 5 addresses the “concern about agrichemicals being yesterday’s news.” Last spring, three independent, government-funded studies published in Environmental Health Perspectives found that children whose mothers were exposed to common agricultural pesticides are more likely to experience impaired or delayed cognitive development. Organic, the OTA stated, is the only agricultural system that verifies — using certification and inspection — that toxic and synthetic pesticides and fertilizers are not used at any point in the production process. Lastly, myth No. 6 regards the “jobless recovery” as it applies to organics. An OTA study revealed that the organic industry grew by nearly 8 percent in 2010, and added jobs at four times the national average. With four in 10 families buying more organic products than they did one year ago, organic is growing — and hiring. Forty percent of companies in the organic sector hired full-time employees in 2010 and 46 percent of organic businesses anticipated hiring full-time employees in 2011. Information for the OTA report came from various studies, including the OTA’s 2011 Organic Industry Survey and its U.S. Families’ Organic Attitudes & Beliefs 2011 Tracking Study.
null
minipile
NaturalLanguage
mit
null
BLOOMINGTON – No one had to say a thing. IU senior forward Juwan Morgan had just limped off the court, putting barely any weight on his right leg as redshirt sophomore guard Vijay Blackmon and director of athletic performance Clif Marshall guided him to the bench. The Hoosiers trailed Northwestern by three points with 3:30 left in the game. The player IU seemed to need most, its offensive catalyst and veteran leader, winced in pain and looked unlikely to return. Buzzer breakdown:Romeo Langford leads IU to 68-66 win over Northwestern Subscribe: Get award-winning reporting for this special introductory price Yet IU didn’t panic. No one, on a team that appeared overwhelmed even with Morgan on the court against Duke, looked around curious about who might step up. Coach Archie Miller didn’t have to pull anyone aside and challenge them to deliver the program the season’s Big Ten opener. Romeo Langford knew his place. The freshman guard, the IndyStar Mr. Basketball and McDonald’s All American, hit IU’s next shot to bring the Hoosiers within one. Langford then blocked a shot by Northwestern’s Vic Law on the Wildcats’ next possession, and IU would soon take a one-point lead on free throws from junior guard Devonte Green. Later, with 39 seconds left and the score tied at 63, he hit a floater to give the Hoosiers the lead for good. A lead he helped protect on Northwestern’s next possession as he deflected a pass off Law and out of bounds. “Kind of looked at the group that we had and said this is kind of how we’re going to do it,” Miller said. “We stuck with those guys and did a good job defensively. And guys made a couple of really good plays. Romeo obviously had a couple big finishes for us in the last couple minutes.” It’s unclear at this time what the extent of Morgan’s injury is. Miller told reporters after the game he didn’t know what happened and hadn’t had a chance to see Morgan or speak with the doctors or trainers about him. The team treated the last few minutes like it would if Morgan, who finished with 17 points and 12 rebounds, had fouled out. What is clear, is Indiana (6-2, 1-0 in Big Ten) has rebounded from its blowout loss against Duke. The Hoosiers defeated a Wildcats (6-2, 0-1) squad that wasn’t fazed by Assembly Hall in a game neither team led at any point by more than five points. And IU’s star freshman showed he could take over a back-and-forth game that had 28 ties and 12 lead changes. “We just knew that it was crunch time and we still gotta do what it takes to win,” said Langford, who led IU with 20 points. Insider:What kind of player IU is getting in Trayce Jackson-Davis IU must improve from the free-throw line. TheHoosiers hit just 11 of 19 attempts, a 57.9 percent clip, but helped offset that with 16 points off 11 turnovers by the Wildcats. Just three made 3s on 11 shots didn't help either. But IU’s offense still put up a 55.1 percent mark from the field. The Hoosiers, who at times this season have been without four or five players at a given practice, persevered through the struggles that came with lineups that lacked chemistry on offense and defense. They didn’t fold when the Wildcats responded to each run the Hoosiers tried to make. Or when Northwestern looked like it might pull away. “It’s hard, man, you play a conference game like that this early in the season with that much at stake,” Miller said. “It’s an intensity level in there that’s not like any other nonconference game.” Sophomore forward Justin Smith, who Miller said will be more confident on the floor once he’s able to take care of the ball better, echoed that sentiment when he said IU’s Big Ten schedule is “going to be a dogfight every night.” And until Morgan’s status is clear, the concern that came from the time he spent off the floor will likely linger. But in those final moments IU showed it could, at least for a stretch, remain poised without him. That’s confidence the team will need if more close games are coming. “It's definitely a reality check,” Green said. “If we're going to be coming down the wire almost every night maybe.” Sign up: Get the latest IU hoops news delivered to your inbox Follow IndyStar sports reporter Jordan Guskey on Twitter at @JordanGuskey or email him at [email protected]. INDIANA 68, NORTHWESTERN 66 NORTHWESTERN (6-2) — Turner 3-5 2-2 9, Law 6-14 2-3 16, Kopp 2-8 1-2 6, Pardon 11-15 2-3 24, R.Taylor 4-11 0-0 9, Nance 0-3 0-0 0, Benson 0-0 0-0 0, Gaines 1-5 0-0 2, Ash 0-0 0-0 0. Totals 27-61 7-10 66. INDIANA (6-2) — Morgan 8-13 1-3 17, Smith 2-5 4-6 8, Durham 3-4 0-0 7, Langford 8-13 3-3 20, Phinisee 1-2 1-4 3, Fitzner 1-4 0-0 3, Davis 2-3 0-0 4, McRoberts 0-0 0-0 0, Green 2-5 2-3 6. Totals 27-49 11-19 68. Halftime—Indiana 37-33. 3-Point Goals—Northwestern 5-17 (Law 2-4, Kopp 1-2, Turner 1-3, R.Taylor 1-5, Gaines 0-1, Nance 0-2), Indiana 3-11 (Durham 1-1, Langford 1-3, Fitzner 1-4, Green 0-1, Morgan 0-2). Fouled Out—Turner. Rebounds—Northwestern 29 (Pardon 10), Indiana 25 (Morgan 12). Assists—Northwestern 9 (Turner 3), Indiana 9 (Morgan 3). Total Fouls—Northwestern 20, Indiana 16.
null
minipile
NaturalLanguage
mit
null
Coinspaid is a rising star of the crypto gateway market Coinspaid is a rising star of the crypto gateway market Coinspaid is ending the year positively. In the recent article Best Bitcoin Casino has predicted a perspective for Coinspaid to become World’s No.1 crypto payment gateway in 2019. Best Bitcoin Casino is a leading space to explore the online gambling world. In the catalog, they list the online casinos and the providers of casino software. The thing that we like the most is the rating system, so you can pick a trusted vendor. Plus, Best Bitcoin Casino provides a complete guide on the gambling events in the world, plus the platform is a good news aggregator. At the beginning of 2018, Coinspaid started taking over the leadership of the market. It was a sequence of harvesting the big clients, leaders of e-gaming, online betting, and online casino industries. Combined altogether the platforms made publicity for Coinspaid that obviously was a fortune for the project. Apart from that, the Coinspaid team helped to navigate the road to success. Being a big complimentary piece, the team provided high-quality services and customer support just on time. The work on the platform makes a very smooth experience and doesn’t get complicated as the platform getting bigger. That’s why our clients like us. Next year is seen as a very promising one for the platform to look forward. We expect to reach major players of American and Asian markets, that will bring a big challenge and new acquisitions for us. The process itself is very smooth and won’t get complicated after the platform acquired the support of new crypto pairs.
null
minipile
NaturalLanguage
mit
null
Conventionally, it has been known that electric wires included in wire harnesses to be arranged underneath the floor of a vehicle and the like are inserted into electric wire sheathing members having a tubular shape so as to be protected. For example, in the wire harness disclosed in JP 2015-106466A mentioned below, a metal pipe is used as the electric wire sheathing member so as to also hold the wiring path of electric wires. The metal pipe is bent into a predetermined shape using a pipe bender. There has been demand to use a resin pipe instead of the above-mentioned metal pipe in order to reduce the weight of a vehicle. However, there has been a problem in that even when a resin pipe is bent using a pipe bender, a phenomenon (springback) in which a bent portion slightly returns to the original state is likely to occur when the resin pipe is removed from the pipe bender. The present design was made based on the foregoing circumstances, and it is an object thereof to provide an electric wire sheathing member including a resin pipe with which springback can be suppressed, and a wire harness.
null
minipile
NaturalLanguage
mit
null
The present invention relates to toners for use in developing electrostatic images by dry development electrophotography, electrostatic printing and the like. Dry development electrophotography utilizes finely divided dry toners or developers. Dry toners typically contain natural or synthetic resins having a coloring agent, such as carbon black, dispersed therein. Dry developers typically are two component systems which contain dry toners combined with magnetic carrier particles. Dry development processes include, for example, cascade, hair brushing, magnetic brushing, impression and powder cloud processes. All of these processes involve developing a formed electrostatic latent image using the toner. After the image is developed by the toner, the image is "fixed." Fixation can be effected by melting the resin particles in the toner thereby fusing them together. Melt fixing can be accomplished by applying heat and/or a solvent to the toner image generally after the image has been transferred to sheet of paper. In the heat fixing method, heat is applied to the sheet of paper by means of heated fuser rollers. The heated fuser rollers apply both heat and pressure to the sheet, thereby permanently fixing the toner image onto the sheet. The surfaces of the fuser rollers are typically made from, or coated with, a non-stick material to prevent the toner from preferentially sticking to the surface of the rollers. Residue on the fuser rollers can be deposited on sheets which subsequently pass through the rollers, which results in poor image quality. One method which has been used to prevent or minimize this problem is to coat the surface of the fuser roller with a non-stick material, such as a fluorocarbon resin and/or to apply a silicone oil to the roller so that a thin coating of the oil is maintained on the roller. This method suffers from several drawbacks: for example, the heat from the fuser rollers can cause odors to emanate from the liquid and/or the roller coating, and the use of an the silicone liquid requires a complex apparatus for metering the liquid to the rollers. Another method which has been used to reduce sticking is adding a wax, such as paraffin or polyolefin wax, to the toner itself. In theory, the wax component should be sufficiently incompatible with the toner resin so that it does not mix with the tone resin. This is to ensure that when the paper imprinted with the toner image passes through the hot fuser rollers, the wax can rise to the surface of the toner thereby forming a waxy coating which prevents the toner from sticking to the rollers. However, paraffin waxes and polyolefin waxes (e.g., polyethylene or polypropylene) may adhere to the roller and/or paper surface, thereby reducing the quality of the image. In some toner compositions, the polyolefin wax is sufficiently compatible with the toner resin that it associates with the resin and does not tend to rise to the surface of the toner particles to prevent the toner from sticking to the fuser rollers. The result is the occurrence of offset and the resulting poor quality images. It is an object of the present invention to provide a dry toner which is free of polyethylene, polypropylene or paraffin wax, and which does not require the use of oils or other liquids for use in developing electrostatic images.
null
minipile
NaturalLanguage
mit
null
11 Food Photos We Liked in 2011 December 22, 2011 Photo Credit: Jenna Weber | Eat, Live, Run Chocolate Cherry Chunk Cookies (Fresh Tastes) They are ooey, they are gooey, and they make you want to put your face through your computer screen. These chocolate cherry chunk cookies from our Fresh Tastes food blog were created by Jenna Weber of Eat, Live, Run, and the picture alone tells you just how delicious this recipe must be. I have heard this version as well -- That musicians finishing at 3-4am went to all night diners as menus were changing and wanted something hearty and dinner like such as Fried Chicken and Something light and sweet - i.e. waffles and syrup and such the marriage was made --- Now me -- I like chicken and waffles with sausage gravy! This is a fantastic bake - thank you Beca! We have done roughly 10 bakes from recipes from this show and this was the best. We followed everything almost exactly to recipe and it tastes great. A few notes- don't boil the syrup too long - we did so the first time through, then found that it sets really quickly in the pan and will even set before being ab One of the greatest salads of all time. I prefer the classic buttery croutons on top rather than a croissant on the bottom. But THEE most decadent version was served to me years ago at the Claremont Hotel in Oakland, CA. The waiter grated fresh, black truffles generously over the top just before bringing it to the table. Oh, the aroma wafting from that plate It is the same thing as Jello. In England it comes in a thick jelly bar that you melt in hot water. In the US it is powder but its the same thing. Just use 1/3 the water because you need it to be really firm. The quantities are too small in this recipe. I doubled the sponge recipe and got only 16 jaffa cakes using one tablespoon of batter for each one. You can use a muffin tin. Just put one tablespoon of the batter in a buttered muffin tin. Each Jaffa cake is tiny to the American eye but that is what they are supposed to be like. Also Americans can use regular Or
null
minipile
NaturalLanguage
mit
null
Stock Remaining Stock Remaining Digestive Aid As we age, hydrochloric acid and digestive enzyme secretion both decline; there is a natural need to replenish the body's digestive enzymes. Add to that the many additional factors—poor eating habits, inadequate chewing, “eating on the run,” and over-consumption of alcohol—that contribute to digestive problems. Essential Enzymes™ is highly effective because it is a Bio-Aligned Formula™ that contains a wide array of enzymes that break down proteins, fats, milk sugars, fiber, and carbohydrates in a wide pH range. It aids the body's natural digestive process, maximizing the body's utilization of the nutrients in the diet while decreasing digestive discomforts. 1 capsule with water at the beginning of each meal (or open capsule and sprinkle over food). If the meal is very large or unusually high in fat or protein, a second capsule can be taken. Do not sprinkle on hot food. If you are pregnant, may become pregnant, or breastfeeding, consult your health care professional before using this product. Keep out of the reach of children. Suitable for vegetarians. Supports the digestive system. Helps support the stomach break down foods. Aid in digesting proteins, fats, fibre, dairy and carbohydrates.
null
minipile
NaturalLanguage
mit
null
Client Review Brian is a wonderful, understanding attorney. - Leslie Loveland Uriah Personal Injury Attorneys Are you a victim of an accident due to someone else’s negligence? If so, you need the legal expertise and experience of the personal injury lawyers at Alabama Personal Injury Lawyers. We are passionate about providing the best legal representation and assistance to personal injury victims in Uriah Alabama. We will work hard to aggressively protect your rights and seek the justice that you truly deserve. Your recovery begins in getting the right compensation that you need for medical bills, pain and suffering, loss of wages, permanent impairment, and limited employment opportunities. Our goal is to see you get the maximum payout for your personal injury claims. We are focused on achieving the best results whether we are negotiating settlements on your behalf or fighting for your interests in the courtroom. Being a dedicated Uriah personal injury law firm, Alabama Personal Injury Lawyers takes pride in the success of our clients. We only provide the best legal representation and sound legal advice. We don’t collect legal fees until we secure a settlement for you. Automobile accidents can be traumatic. Serious physical injuries are just the beginning of the challenges that you will be facing. You will also have to deal with long term financial and psychological issues. Moreover, the legal complexities that you have to go through when filing your claim can significantly affect your ability to recover. Our years of experience and expertise can certainly help you lessen the stress. Let Alabama Personal Injury Lawyers handle the difficult legal battle so you can focus on your road to healing. Alabama Personal Injury Lawyers can help his clients find affordable medical care for their injuries if needed. You are not alone in this battle. We at Alabama Personal Injury Lawyers want to fight it with you. Complete Personal Injury Law Firm If you are suffering with personal injuries due to the actions, negligence, or failure to act of someone other than yourself, you have the legal rights to demand fair compensation for your losses which can range from medical expenses to long term employment issues. We at Alabama Personal Injury Lawyers provides expert legal support, representation, insight, and advice specializing in personal injury law. Our passion stems from helping the victims, and their families, receive justice and compensation that they need during their road to recovery. Our practice areas are: Car Accident Injuries – In 2017 alone, there were over 156,000 car crashes with almost 50,000 injuries and nearly 1,000 fatalities. Recklessness, driving under the influence, distracted driving, faulty vehicles, and dangerous road conditions are just some of the reasons for these accidents. This is why you should work closely with an excellent car accident injury lawyer that puts your interests forward. Here at Alabama Personal Injury Lawyers, our car accident injury lawyers are committed to providing you with aggressive, strategic, and experienced legal representation. Automobile Accident Injuries – Injuries from automobile accidents can range from minor pain to major medical issues. Recovery alone is stressful and challenging for anyone. Dealing with insurance companies for fair settlement requires experience. Our Uriah AL automobile injury lawyers are ready to fight for your rights by providing the most comprehensive legal counsel on all automobile injury matters. Alabama Personal Injury Lawyers will aggressively seek justice and will hold any individual or business entity liable for your suffering. Motorcycle Accident Injuries – Serious injuries sustained during a motorcycle accident can lead to long term medical issues. Because you are more exposed to risks and dangers when riding a motorcycle, you are more likely to suffer from severe and long-lasting injuries. The sooner you can start your recovery, the sooner you can get your life back. The motorcycle accident attorneys at Alabama Personal Injury Lawyers represent your interests against individuals, corporations, or other entities. We aggressively fight for fair and equitable compensation for your injury or loss. Truck Accident Injuries – Truck accidents, especially those involving passenger vehicles, have a higher chance of resulting in fatal injuries. Broken bones, head injuries, and even death are more likely when trucks are involved in accidents. Legal claims are more complicated due to the involvement of trucking companies and insurance agencies. Alabama Personal Injury Lawyers will make sure that you have access to the best personal injury attorneys and legal resources to protect you during legal battles. Alabama Personal Injury Lawyers will make sure that you have access to the best personal injury attorneys and legal resources to defend you during legal disputes. We are fearless in seeking justice and fair compensation that you truly deserve whether you are going against individuals, private corporations, insurance companies, or other entities. What To Do When You Are Injured Getting injured in a serious vehicular accident is distressful and traumatic. Nobody is prepared for the results of such events. When you find yourself dealing with such a situation, what do you do? As a trusted Uriah, AL personal injury law firm, Alabama Personal Injury Lawyers has a proven process to claims for various personal injury cases. You can start protecting yourself the moment the accident happens by: Seek Medical Treatment – Prioritize your medical needs during accidents. Identify and describe each pain, ache, or symptoms whether you consider them irrelevant or minor. Provide as much detail as possible not only for your treatment but for your medical records as well. Hire an Attorney – Handling legal matters alone are stressful enough. Doing this while recovering from a serious injury is near impossible. Seek the expertise of Alabama Personal Injury Lawyers and participate in our Free Consultations and Free Case Reviews. Our personal injury attorneys will aggressively seek all means to protect your interests. Through our sound legal advice, expert insight, and detailed guidance, we will get you the justice and compensation that you need to begin your healing process. Build the Case – Alabama Personal Injury Lawyers will ensure that you have a strong case against the at-fault party. We will determine the best compensation that you need through detailed investigations, gathering police and medical reports, and analyzing relevant information related to the accident. Communication – Because you are our top priority, we will make sure that we are in contact through each step of the process. You will know precisely where we are in the case and its current status. Our legal experts will ensure that you understand each aspect of the case and what we can do to increase your chances of a successful outcome. Our monthly reviews will keep you updated and knowledgeable. Settlement – We will prepare the settlement demand by compiling all pertinent details and documents such as medical records, billing information, lost wages, and more. Our attorneys will discuss the demand with you and ensure that all losses are accounted for. Once agreed, we will present this demand to the defense lawyer or claims adjuster. We will handle the negotiations until we can present a final offer to you where you will decide to accept or reject it. Injury Lawsuit – Ideally, your claims should be settled outside the court to minimize the stress. However, in cases that we need to fight in the courtroom, our experienced lawyers at Alabama Personal Injury Lawyers will aggressively defend you and your interests to maximize the compensation package and minimize the court time. Post-Settlement – Once the lawsuit is in your favor or a settlement is reached, your funds will be settled according to the agreement. It will be deposited into a trust account before disbursement. Once all the bills have been paid at negotiated and reduced rates, you will receive the final settlement check. Suffering an injury due to negligence is very frustrating, and even more so when you have to face challenges in claiming the compensation you are entitled to. We at Alabama Personal Injury Lawyers are dedicated to making your recovery easier for you by making sure that your interests are protected during the entire legal process. Serving all of Alabama, an experienced personal injury attorney at Alabama Personal Injury Lawyers is ready to support you. Let’s Talk Now- Free Consultation The support of a competent Uriah automobile accident injury attorney can make all the difference. Our experienced legal experts are here to help you get your life back by fighting aggressively for your interests. We will help you focus on your recovery by supporting the legal battle that will get you the fair compensation that you deserve. Alabama Personal Injury Lawyers is the Uriah automobile accident injury law firm that will finally put your mind at ease. We are ready to fight any individuals, corporations, companies, and even government bodies to get the compensation that you deserve. You cannot afford to wait. No representation is made that the quality of legal services to be performed is greater than the quality of the legal services performed by other lawyers. The information on this website is for general information purposes only. Nothing on this site should be taken as legal advice for any individual case or situation. This information is not intended to create, and receipt or viewing does not constitute, an attorney-client relationship.
null
minipile
NaturalLanguage
mit
null
Saint Helena plover The Saint Helena plover (Charadrius sanctaehelenae), locally known as the wirebird due to its thin legs, is a small wader endemic to the island of Saint Helena in the mid-Atlantic. The bird is similar in appearance to the Kittlitz's plover of sub-Saharan Africa, but is rather larger. It is the national bird of St Helena and has been depicted on the country's coins. Populations in general have been declining. Threats include predation by cats, the introduction of the common myna, deforestation, off-road vehicle use, the Saint Helena Airport and a projected windfarm. In 2016, the population had recovered to about 560 mature individuals, from a previous minimum of less than 200 in 2006; consequently, the species was downlisted to Vulnerable from its previous assessment of Critically Endangered. Description Kittlitz's plover is the Saint Helena bird's closest relative. The Saint Helena plover is generally larger but not as well-marked as the Kittlitz's plover, which is native to sub-Saharan Africa. Its size is around 15 cm (6 in). The bird was first mentioned in 1638, and is the national bird of Saint Helena, featured on the island's coat of arms and flag. Some older local 5 pence coins (those issued prior to 1998) have the wirebird on the reverse. This plover is resident all year on the open areas of Saint Helena, and it is thought that the widespread deforestation on the island, while generally harmful for the island's ecosystem, has in fact benefitted this particular species, since it lives in open clearings in the forest. Status and conservation Saint Helena plover numbers have been fluctuating, but in general the trend has been downward since at least the 1970s. Feral cats and accidentally introduced rats are believed to have played a significant role in the decline, as, to a lesser extent has the introduced common myna. A census in 1988–89 recorded roughly 450 birds, although that number declined sharply over the following decade, due to causes not fully understood. By the late 1990s and early 2000s, censuses suggested that the bird's numbers had stabilised at about 350 adults. However, surveys done in 2005–6 recorded another sharp decline, with only some 200–220 adult birds remaining. Due to its dropping numbers and uncertain prospects, the Saint Helena plover was uplisted to Critically Endangered in the 2007 version of the IUCN Red List. A reassessment in 2016 suggested that the population had recovered somewhat from this minimum and may be slowly increasing; as a consequence, the species was downlisted to Vulnerable. The reasons for the previous decline and ongoing inhibition of population growth decline remain elusive. Habitat loss—due to changes in agricultural practices, increases in invasive plant populations, and development—has almost certainly had an impact. The increasing use of off-road vehicles threatens nests and eggs. Feral cat populations are increasing, as trapping levels have declined and fewer people neuter their pet cats. Construction activity has apparently dispersed some of the smaller subpopulations. The newly-built Saint Helena Airport at Prosperous Bay Plain has altered one of the major patches of remaining habitat, especially as other grassland is now slated for reforestation to aid recovery of the island's ecosystem, and a major wind turbine project has been proposed for the species' most important breeding area. There are currently projects underway led by the RSPB to monitor the birds and try to stop their decline. References External links St Helena National Trust – St Helena Wirebird or Plover Website with information on the bird Category:Charadrius Category:Birds of Saint Helena Island Category:Birds described in 1873
null
minipile
NaturalLanguage
mit
null
Reforms at TVETs will boost growth aspirations. Kenya’s higher education, science and technology sector is set for major reforms aimed at promoting a knowledge-based economy to improve national prosperity and global competitiveness. This would involve interaction of institutions and processes to enable the generation and conversion of knowledge into goods, processes and services. The move by the government to ensure trainers at Technical and Vocational Education and Training (TVET) institutions join the public service is aimed at boosting their performance and make the sector attractive. The scheme, which is undergoing the final review by the Public Service Commission, will see the technical training tutors leave the Teachers Service Commission. In the new system, TVET trainers will have their own terms of service unlike in the past when they were lumped together with primary and secondary school colleagues. Technical education training would also not be assessed in the same way as formal education, with teaching skewed towards competence rather than on theory. The latest developments come in the wake of the government’s recent move to establish TVET Authority to manage technical training institutions as part of the efforts to reposition technical and vocational education. The renewed focus on vocational and technical education is one of the strategies aimed at addressing youth unemployment. Building quality institutions that would develop the required manpower to enhance the capacity of Kenyan youths to contribute to the expansion of the economy is a move in the right direction. This goal of equipping the youth with relevant skills is being pursued through a two-pronged approach, the first being the requirement that all secondary schools must have skills acquisition content introduced in their curricula. The second approach is what used to be called village polytechnics will be renamed vocational training centres whose personnel must have been trained at the Technical Training Centre in Nairobi. There is no doubt that this level of commitment and investment in the technical education has never been witnessed in Kenya before. The current shortage of artisans, plumbers and technologists is due to failure by previous governments to prioritise the development of technical education. But with more emphasis on technical education, youths are going to get the right type of training that would empower them to become job creators and active players in the economy. What the government is doing is to redefine education and give the youths the knowledge and skills to effectively compete and face the challenges in the job market. Currently, many youths complain of lack of employment opportunities, even though majority of them lack the relevant skills. Meanwhile, the proposal that students joining technical training institutions will have an option of taking subjects related to their careers is also a step in the right direction. This is aimed at ensuring that students exploit their talents and attain specialisation in their areas. Once this is fully effected, students wishing to join technical training institutes would have a curriculum that is flexible and learner-friendly. It would be tailored to offer functional subjects and will be simplified to meet learners’ needs. This basically aims at offering skills that are important for day-to-day life and work as opposed to expansive and complex content that may not add value to learners’ lives. The system has proved successful in both developed and developing countries where students specialise as early as possible to prepare for careers of choice. In some countries, students start specialisation in secondary school. By the time they join university or technical institutes, the students emphasise on research work and less on class work because they are already equipped with the knowledge about their respective careers. The renewed focus on vocational and technical education by the government is one of the best strategies in making the sector attractive to Kenyans besides meeting the needs of the youth in the job market.
null
minipile
NaturalLanguage
mit
null
1. Field of the Invention The present invention relates to an electric bell, and more particularly to an electric bell having a mechanism for supporting an electromagnetic unit. 2. Description of the Prior Art Typical electrical bells comprise an electromagnetic unit disposed between two spring leaves and having a stem that may be driven to strike the spring leaves. However, the typical electric bell has no supporting mechanism designed for supporting the electromagnetic unit such that a number of fasteners and a number of supporting ribs or walls are required to be secured to the electric bell for supporting the electromagnetic unit, and such that the electromagnetic unit may not be easily secured in place. A number of additional tools are required for assembling or attaching the electromagnetic unit to the electric bell. The present invention has arisen to mitigate and/or obviate the afore-described disadvantages of the conventional electric bells.
null
minipile
NaturalLanguage
mit
null
We depend upon the generosity of people like you to help us improve pediatric health and enhance the patient care experience. Because at Children’s, we don’t just care for children, we care for the most amazing people on earth. Cleft Lip and Palate Posts navigation Choosing where to bring your child for care is a major decision. We understand you want all the information you can get. And you want it in a clear, straightforward form that helps you make the right choice for your family. The ear, nose and throat (ENT) and facial plastic surgery program at Children's Minnesota offers a full range of services focused on the medical and surgical treatment of conditions that affect the head and neck. Children's Minnesota's Ear, Nose and Throat (ENT) and facial plastic surgery program diagnoses and treats routine and complex conditions in babies, children and teens. In fact, Children's has the only pediatric ENT program in the state dedicated exclusively to kids with disorders of the head and neck. The cleft and craniofacial center at Children's Minnesota offers a full range of services for babies, children and teens with simple to complex cleft and craniofacial issues. But one thing is always the same: our commitment to excellence. The cleft and craniofacial clinic at Children's Minnesota is one of the premier programs in the region dedicated exclusively to diagnosing and treating cleft and craniofacial disorders in babies, children, adolescents and young adults.
null
minipile
NaturalLanguage
mit
null
Summary:The Kurzweil integral technique is applied to a class of rate independent processes with convex energy and discontinuous inputs. We prove existence, uniqueness, and continuous data dependence of solutions in $BV$ spaces. It is shown that in the context of elastoplasticity, the Kurzweil solutions coincide with natural limits of viscous regularizations when the viscosity coefficient tends to zero. The discontinuities produce an additional positive dissipation term, which is not homogeneous of degree one.
null
minipile
NaturalLanguage
mit
null
Day: June 19, 2010 [Lozzless] has a steady hand and plenty of confidence in his hacking skills. The video above is worth watching for the full eight minutes. In it you’ll see him convert a lens into what he calls a SuperMacro lens with a working aperture. The process involves fashioning a connector ring from a lens cap, modifying an Electro-focus lens mount, and assembling the parts to do his bidding. We don’t have the photography background to fully understand what he’s doing here, but we can appreciate the process, and the results are shown at the end of the clip. This little art piece might be just the thing to add that mad scientist look to your room. It’s called the Coachella lamp and it makes use of several throwback display devices. At the top an Argon discharge lamp puts out ultraviolet light. Protruding from each of the four sides you can see a set of decatrons. There’s also four Nixie tube bar graphs standing tall from each corner of the base. The final touch is the colored glow in the center which is provided by LEDs. We’ve embedded some video of the device after the break. The lamp is powered by a wall outlet and controlled with an Arduino. We’ve seen deactrons used as timing devices and would love to see some clock functionality added to the lamp. Trying to decipher the time from the different Nixie displays would put this up there with some of those other hard to read timepieces. This Arc Reactor is a great re-creation of the fictional source of Iron Man’s power. It’s really just a holder for a bunch of LED’s, but it exhibits some fine craftsmanship which we enjoy in any project. This rendition is much more true to the movie than the last look-a-like we saw. These might end up being for sale (the webpage narrative is kind of weird) but you really shouldn’t be wearing this kind of thing around unless you made it yourself, or if you can add it to some kind of Iron Man simulator.
null
minipile
NaturalLanguage
mit
null
Cloning, expression, and characterization of single-chain variable fragment antibody against mycotoxin deoxynivalenol in recombinant Escherichia coli. Deoxynivalenol (DON), a mycotoxin produced by several Fusarium species, is a worldwide contaminant of food and feedstuffs. The DON-specific single-chain variable fragment (scFv) antibody was produced in recombinant Escherichia coli. The variable regions of the heavy chain (V(H)) and light chain (V(L)) cloned from the hybridoma 3G7 were connected with a flexible linker using an overlap extension polymerase chain reaction. Nucleotide sequence analysis revealed that the anti-DON V(H) was a member of the V(H) III gene family IA subgroup and the V(L) gene belonged to the Vlambda gene family II subgroup. Extensive efforts to express the functional scFv antibody in E. coli have been made by using gene fusion and chaperone coexpression. Coexpression of the molecular chaperones (DnaK-DnaJ-GrpE) allowed soluble expression of the scFv. The scFv antibody fused with hexahistidine residues at the C-terminus was purified by immobilized metal affinity chromatography (IMAC). Soluble scFv antibody produced in this manner was characterized for its antigen-binding characteristics. Its biological affinity as antibody was measured by surface plasmon resonance (SPR) analysis and proved to be significant but weaker than that of the whole anti-DON mAb.
null
minipile
NaturalLanguage
mit
null
Hell or High Water A crash into terminal F ruptures a water main, causing rising floodwaters to threaten airport operations. Meanwhile, US Immigration and Customs Enforcement prepares a secure aircraft to deport detainees who are in the country illegally. From This Episode Miami-Dade Fire Rescue Miami-Dade Fire Rescue Miami-Dade Fire Rescue workers receive instructions for how to control a water leak on the airfield.9601280 Miami-Dade Fire Rescue workers receive instructions for how to control a water leak on the airfield. Miami-Dade Fire Rescue Captain Miami-Dade Fire Rescue Captain Miami-Dade Fire Rescue Captain, Nick Marian, is alerted to an accident on the airfield.9601280 Miami-Dade Fire Rescue Captain, Nick Marian, is alerted to an accident on the airfield. Khristine Perez Khristine Perez Khristine Perez watches as the plane carrying the University of Alabama football team arrives for the BCS Championship Game.9601280 Khristine Perez watches as the plane carrying the University of Alabama football team arrives for the BCS Championship Game. Albert Cordeschi Albert Cordeschi Albert Cordeschi describes how airplanes do not have a reverse gear, so “tugs” are used to push back the planes so they can taxi the runway.9601280 Albert Cordeschi describes how airplanes do not have a reverse gear, so “tugs” are used to push back the planes so they can taxi the runway. Lauren Stover Lauren Stover Lauren Stover describes how security is her first priority. 9601280 Lauren Stover describes how security is her first priority. Police K-9s Police K-9s Police K-9s are an important asset to the airport’s overall security.9601280 Police K-9s are an important asset to the airport’s overall security. Albert Cordeschi Albert Cordeschi Albert describes the different types of tugs that work on the airfield.9601280 Albert describes the different types of tugs that work on the airfield. Senior Terminal Operations Agent Tony Cooper Senior Terminal Operations Agent Tony Cooper Senior Terminal Operations Agent Tony Cooper describes how high security flights are orchestrated by US Immigration and Customs Enforcement. 9601280 Senior Terminal Operations Agent Tony Cooper describes how high security flights are orchestrated by US Immigration and Customs Enforcement. The Miami-Dade Fire Rescue firefighters The Miami-Dade Fire Rescue firefighters The Miami-Dade Fire Rescue firefighters trace the pipe leading to the water leak in order to shut off the source of the flooding. 9601280 The Miami-Dade Fire Rescue firefighters trace the pipe leading to the water leak in order to shut off the source of the flooding. MIA’s crew and the Orange Bowl organizers MIA’s crew and the Orange Bowl organizers MIA’s crew and the Orange Bowl organizers take their places to greet the University of Alabama football team when they arrive.9601280 MIA’s crew and the Orange Bowl organizers take their places to greet the University of Alabama football team when they arrive. Officer "Stretch" Rutledge Officer "Stretch" Rutledge Officer "Stretch" Rutledge rounds up the Miami-Dade Police Motorcycle officers to safely escort the University of Alabama football team off the airfield.9601280 Officer "Stretch" Rutledge rounds up the Miami-Dade Police Motorcycle officers to safely escort the University of Alabama football team off the airfield. Dickie Davis, Ken Pyatt and Lauren Stover Dickie Davis, Ken Pyatt and Lauren Stover Dickie Davis, Ken Pyatt and Lauren Stover get ready to welcome the crowds expected to arrive for the BCS National Championship football game.9601280 Dickie Davis, Ken Pyatt and Lauren Stover get ready to welcome the crowds expected to arrive for the BCS National Championship football game.
null
minipile
NaturalLanguage
mit
null
996 F.2d 1126 37 ERC 1105, 62 USLW 2131, 23 Envtl.L. Rep. 21,437 UNITED STATES of America, Plaintiff-Appellant, Cross-Appellee,Alabama Department of Environmental Protection and State ofAlabama, Intervenors-Plaintiffs-Appellants, Cross-Appellees,v.ILCO, INCORPORATED, a/k/a Interstate Lead Company, Inc. andDiego Maffei, Defendants-Appellees, Cross-Appellants,Leeds Excavating & Paving Company, Inc., et al., Defendants. No. 91-1004. United States Court of Appeals,Eleventh Circuit. Aug. 4, 1993. Alton B. Parker, Spain, Gillon, Grooms, Blan & Nettles, Birmingham, AL, for State of Alabama. Katherine Adams, U.S. Dept. of Justice, Washington, DC, for U.S. Charles de Saillan, U.S. E.P.A., Washington, DC, for appellees. Charles R. Driggars, Sirote & Permutt, Birmingham, AL, for ILCO, Inc. John A. Bryson, M. Alice Thurston, U.S. Dept. of Justice, Appellate Section, Washington, DC, for appellants. Appeals from the United States District Court for the Northern District of Alabama. Before FAY and DUBINA, Circuit Judges, and FLOYD R. GIBSON*, Senior Circuit Judge. FAY, Circuit Judge: 1 This case is an enforcement action filed by the United States Environmental Protection Agency and the State of Alabama against a secondary lead smelter for violations of federal and state environmental law. The district court held the defendant liable and awarded civil penalties and cleanup costs to the government, and ordered compliance with the law. Although the government received a favorable decision, it has appealed the district court's conclusion that the lead components reclaimed from spent batteries are raw materials. The district court reasoned that because the smelter recycles the components into lead ingots, the components must be raw materials, and not hazardous waste subject to the provisions of the Resource Conservation and Recovery Act. The defendant has cross-appealed the district court's order awarding penalties and cleanup costs to the government. Because we find the district court's order well founded in fact and law, we affirm it in all but one respect. We reverse the court's conclusion regarding the lead components reclaimed from spent batteries because EPA, in accordance with its authority granted by Congress, has defined "discarded material" to include "recycled material." BACKGROUND 1. Industry Overview1 2 Over the years in the United States there has been a steady increase in the number of vehicle batteries which become useless and subject to disposal. In 1986 the number stood at approximately 70,000,000. Each spent battery is a potential pollutant of the environment and can have serious deleterious effects on people and animals living in the area where the battery may be discarded. Even a small number of batteries thrown into the woods, discarded along roadways or in government designated garbage areas represent a significant threat to the water we drink, the food we eat and under limited circumstances, the air we breathe. The source of this trouble in a battery is lead.... [Because lead is an expensive element, an industry has developed over the years] to reclaim the lead from spent batteries.... [In the mid-Seventies] there were approximately 50 secondary lead smelters in the United States reclaiming the lead from about 90% of all spent batteries. The smelters were themselves a major source of pollution; surface water run-off and process water discharged by the smelters created very real health-threatening problems; on-site and off-site storage or disposition of waste became an increasing risk to the quality of life; and even the air was dangerously polluted by emissions from the smelters. [In response to these problems] all levels of government began to amend existing laws and to enact new laws and regulations placing much greater controls over ownership and operation of such smelters. Compliance with these new environmental laws and regulations ... placed such a financial burden on the operation of secondary lead smelters that about 60% of the smelters operating in 1976 were out of business by 1986, and the approximately 20 smelters remaining were reclaiming only about 70% ... [of all discarded batteries.] Thus in 1986 only 55,000,000 of the available 70,000,000 batteries were reclaimed, leaving the 15,000,000 unreclaimed spent batteries to endanger the health of all persons near the site of their repose. The 55,000,000 reclaimed batteries produced about 60% of all lead used in the United States.... [This brief overview demonstrates the secondary lead smelting industry] is a most vital industry not only to our economy but also to [our] environment.... Without the industry, over 70,000,000 contaminated batteries would be scattered throughout our country annually. [Nevertheless, the heart of this industry centers around the handling of hazardous materials. Exempting the industry from regulation cannot be justified on the theory that its contribution to resolving our environmental problems outweighs the environmental harm caused by its operations.] 2. Factual and Procedural Background 3 Against this industry backdrop the present case unfolds, spanning nearly a decade of interaction between the Environmental Protection Agency ("EPA"), the Alabama Department of Environmental Management ("ADEM") and Interstate Lead Company, Inc. ("ILCO"). The voluminous facts are very briefly set forth. 4 ILCO owned and operated a secondary lead smelting facility in Leeds, Alabama, from the 1960's until operations ceased in 1992. As such, it was one of the 20 smelters remaining in the country which reclaimed spent batteries. In 1986 ILCO reclaimed over 2,500,000 batteries, or about 5% of those reclaimed in the United States. Diego Maffei is the president and majority shareholder of ILCO. 5 ILCO purchased batteries from various suppliers and placed them in a reclamation process. Incoming batteries were cracked open and drained of sulfuric acid. The rubber or black plastic battery boxes were chipped and washed to remove lead particles. The lead battery components known as "plates and groups" were then removed from the broken batteries and run through ILCO's smelting process to produce lead ingots for sale. The operation produced several waste products which were the subject of litigation in the district court: waste acid, wastewater treatment sludge, broken battery casings or "chips," and emission control dust and blast slag from the smelting process. EPA asserted, and continues to argue on appeal, that the reclaimed lead plates and groups were also waste products. The defendants viewed the plates and groups as raw materials essential to the lead recovery industry. 6 EPA and ADEM initiated this case as an enforcement action against ILCO and its president, Diego Maffei, seeking an injunction to curtail ongoing violations of environmental laws and regulations at ILCO's plant in Leeds and seeking penalties for past violations.2 The amended complaint contained six claims, but two settled during trial. Of the four remaining claims, EPA first alleged ILCO violated the Clean Water Act ("CWA"), 33 U.S.C. §§ 1251-1387, by improperly discharging waste water at or near the plant site in violation of its NPDES permit,3 and subsequent to March 1984 without any permit.4 The second and third claims concerned the treatment, storage and disposal of hazardous wastes since 1980 in violation of the Resource Conservation and Recovery Act ("RCRA"), as amended by the Hazardous and Solid Waste Amendments of 1984, 42 U.S.C. §§ 6901-92k. In the second claim EPA charged ILCO with maintaining storage areas, an incinerator and a treatment tank, all containing hazardous waste, in violation of regulations applicable to their status as an interim facility and maintaining other storage facilities and a landfill without the requisite permit.5 The third claim encompassed the same RCRA violation, alleging that the facility permitted releases of hazardous waste into the environment. The fourth claim focused upon alleged violations of the Comprehensive Environmental Response, Compensation, and Liability Act ("CERCLA"), 42 U.S.C. §§ 9601-75, at a place known as "the Church of God site," located about six miles north of the plant. ILCO was charged with dumping hazardous waste in a ravine behind the Church of God, which released or threatened to release hazardous substances into the environment. Consequently, EPA sought recovery for the excavation costs incurred in removing the waste. 7 This appeal arises from a finding of liability against ILCO and Maffei under the CWA and the RCRA, and a judgment awarded to EPA for cleanup costs. The district court ordered the defendants (1) to pay a $3.5 million penalty for violations of RCRA, the CWA and state laws,6 (2) to attain compliance with the laws, and (3) to reimburse the United States $845,033 for prejudgment interest and response costs incurred by EPA in performing a cleanup at the Church of God. The court found the lead plates and groups to be solid waste as defined in 40 C.F.R. § 261.2 because they exhibit the characteristic of "Extraction Procedure toxicity" for lead and cadmium as defined in that regulation. However, the court also held the plates and groups at the ILCO facility were not "hazardous waste," accepting ILCO's argument that it did not "discard," but rather purchased the plates and groups as raw materials for the purpose of recovering lead values. EPA and ADEM appeal this ruling.7 DISCUSSION 8 The sole question of law raised by EPA on appeal is whether lead parts, which have been reclaimed from spent car and truck batteries for recycling purposes, are exempt from regulation under RCRA. The standard of review is de novo. Novak v. Irwin Yacht and Marine Corp., 986 F.2d 468, 470 (11th Cir.1993). Reviewing the interpretive decisions of an administrative agency is a two-step process: If Congress has clearly and directly spoken to the precise question at issue, effect must be given to the expressed intent of Congress. If the court finds the statute silent or ambiguous with respect to the specific issue, it must ask whether the agency's regulation is based on a "permissible" or "reasonable" construction of the statute. Chevron USA, Inc. v. National Resources Defense Council, 467 U.S. 837, 842-45, 104 S.Ct. 2778, 2781-83, 81 L.Ed.2d 694 (1984). Considerable weight and deference are afforded an agency's interpretation of a statute entrusted to its administration. Id. at 844, 104 S.Ct. at 2782. 9 Because Congress has not spoken to the precise question at issue, we must decide whether EPA has reasonably construed the RCRA to permit regulation of the recycling of hazardous materials. There is no question that the materials at issue are hazardous; the district court specifically found the plates and groups were "Extraction Procedure toxic" for lead and cadmium. If it is permissible for EPA to determine that "solid waste," as defined by Congress, includes materials that are recycled, then the lead plates and groups were "hazardous waste" and must be managed accordingly. We conclude that EPA's regulations are a reasonable exercise of its authority granted by Congress. For this reason and those to follow, we find the lead plates and groups that ILCO reclaims from spent batteries fall squarely within the law and regulations governing the storage, disposal and treatment of hazardous waste. 10 The RCRA, as amended, 42 U.S.C. §§ 6901-92k (1988), is a comprehensive environmental statute, which grants EPA authority to regulate solid and hazardous wastes from "cradle-to-grave." American Petroleum Institute v. EPA, 906 F.2d 729, 732 (D.C.Cir.1990). "Congress' 'overriding concern' in enacting RCRA was to establish the framework for a national system to insure the safe management of hazardous waste." American Mining Congress v. EPA, 824 F.2d 1177, 1179 (D.C.Cir.1987) (AMC I). RCRA directs EPA to promulgate regulations establishing a comprehensive management system for hazardous wastes. 42 U.S.C. §§ 6921-39b (1988). 11 Before a material can be designated and regulated as a "hazardous waste," it must first be determined to be a "solid waste." See 42 U.S.C. § 6903(5) (1988). Solid waste includes: 12 any garbage, refuse, sludge from a waste treatment plant, water supply treatment plant, or air pollution control facility and other discarded material, including solid, liquid, semisolid, or contained gaseous material resulting from industrial, commercial, mining, and agricultural operations, and from community activities.... 13 42 U.S.C. § 6903(27) (1988) (emphasis added). 42 U.S.C. § 6921 directs the Administrator of the EPA to identify those solid wastes which are "hazardous" and whose management should therefore be governed by RCRA.8 In particular, § 6921 requires the Administrator both to "promulgate criteria for identifying the characteristics of hazardous waste" and, using these criteria, to list "specific hazardous wastes."9 See American Petroleum, 906 F.2d at 733. 14 Pursuant to its authority, EPA has promulgated regulations which specifically address discarded lead-acid batteries. Without clarifying the meaning of "discarded," Congress defined solid waste as "any discarded material" not otherwise exempted from regulation.10 EPA has filled the statutory gap by defining "discarded material" as any material which is abandoned, recycled, or inherently wastelike. 40 C.F.R. § 261.2(a)(2) (1992). "Recycled material" refers to, inter alia, spent material which has been reclaimed. 40 C.F.R. § 261.2(c)(3) (1992). A material is " 'reclaimed' if it is processed to recover a usable product, or if it is regenerated. Examples are recovery of lead values from spent batteries...." 40 C.F.R. § 261.1(c)(4) (1992). "Reclaimed material" clearly includes lead values derived from the plates and groups at issue here. Furthermore, these battery components fall within the § 261.1(c)(4) definition of recycled material because ILCO runs the plates and groups through a smelting process to recover a usable product, lead, which is then cast into ingots and sold. Thus, having met the definition of "recycled," the lead components are discarded material as defined in 40 C.F.R. § 261.2(a)(2). 15 The regulations also specify those recycled materials which are solid wastes. They include "spent materials" that are recycled by "reclamation," or are "accumulated, stored, or treated before recycling" by reclamation. 40 C.F.R. § 261.2(c) (1992). A "spent material" is "any material that has been used and as a result of contamination can no longer serve the purpose for which it was produced without processing." 40 C.F.R. § 261.1(c)(1) (1992). Thus, the applicable regulations are unambiguous with respect to spent lead components used in a recycling process: spent materials "are solid wastes when reclaimed." 40 C.F.R. § 261.2(c)(3) and Table 1 (1992). 16 ILCO argues that it has never "discarded" the plates and groups and, therefore, the material it recycles is not "solid waste" as defined in RCRA § 6903(27). The lead plates and groups are, no doubt, valuable feedstock for a smelting process. Nevertheless, EPA, with congressional authority, promulgated regulations that classify these materials as "discarded solid waste." Somebody has discarded the battery in which these components are found. This fact does not change just because a reclaimer has purchased or finds value in the components. 17 The regulations reflect EPA's policy decision11 that spent batteries, including their lead components, became "part of the waste disposal problem," AMC I, 824 F.2d at 1186, when the original consumer discarded the battery. It is unnecessary to read into the word "discarded" a congressional intent that the waste in question must finally and forever be discarded, as ILCO seems to argue. It is perfectly reasonable for EPA to assume Congress meant "discarded once." Were we to rule otherwise, waste such as these batteries would arguably be exempt from regulation under RCRA merely because they are potentially recyclable. Previously discarded solid waste, although it may at some point be recycled, nonetheless remains solid waste. See American Petroleum, 906 F.2d at 741 (holding that "discarded" material sent by steel mills to a metal recovery facility remained a solid waste in the hands of the metal recoverer); and American Mining Congress v. EPA, 907 F.2d 1179, 1186-87 (D.C.Cir.1990) (AMC II) (materials awaiting recycling may be classified as "discarded," whether the materials were discarded by one user and sent to another for recycling, or stored before recycling by the person who initially discarded them in land disposal units). Compare AMC I, 824 F.2d at 1187, n. 14 (used oil collected and recycled by a reclaimer is "discarded" and subject to regulation) with 824 F.2d at 1184, 1190 ("materials retained [by the generating industry] for immediate reuse" or "passing in a continuous stream or flow from one production process to another" are not "discarded" within the meaning of RCRA). Therefore, we find these batteries and their contents are "discarded" within the everyday sense of the word. Their secondary character as recyclable material is irrelevant to that determination. See AMC I, 824 F.2d at 1192-93 and AMC II, 907 F.2d at 1186-87. 18 We have found nothing in the language of the statute, and ILCO has brought forth nothing from the legislative history to show that EPA's policy choice is not one Congress would have sanctioned. See AMC II, 907 F.2d at 1186. On the contrary, application of these regulations to spent batteries and parts generated by consumers comports with Congress' intent in RCRA to address the problems posed by hazardous waste. The House Committee explained: 19 It is not only the waste by-products of the nation's manufacturing processes with which the committee is concerned: but also the products themselves once they have served their intended purposes and are no longer wanted by the consumer. For these reasons the term discarded materials is used to identify collectively those substances often referred to as industrial, municipal or post-consumer waste; refuse, trash, garbage and sludge. 20 H.R.REP. No. 1491, 94th Cong., 2d Sess. 2 (1976), reprinted in 1976 U.S.C.C.A.N. 6238, 6240 (emphasis added). We, therefore, will not disturb an agency's policy choice that is reasonably consistent with the purpose of the statute. Chevron, 467 U.S. at 845, 104 S.Ct. at 2783. CONCLUSION 21 For the foregoing reasons, we REVERSE the district court's determination that the lead plates and groups are "raw materials" and hold they are "hazardous waste" subject to regulation under RCRA, but AFFIRM its decision in every other respect. The case is REMANDED for proceedings consistent with this opinion. * Honorable Floyd R. Gibson, Senior U.S. Circuit Judge for the Eighth Circuit, sitting by designation 1 This concise description is quoted, in large part, from the district court's unreported opinion. See United States v. ILCO, 32 Env't Rep.Cas. (BNA) 1977, 1990 WL 300298 (N.D.Ala.1990) 2 The original complaint was filed by EPA in March 1985. ADEM subsequently intervened, asserting similar claims under comparable state law. EPA and ADEM assert the same issue on appeal. In the interest of simplicity, therefore, we refer only to EPA and violations of federal law, which will include all claims made by ADEM for state law violations 3 The Clean Water Act establishes a National Pollutant Discharge Elimination System ("NPDES") requiring a permit for discharge of any pollutant into waters of the United States. 33 U.S.C. § 1342 (1988) 4 ILCO's permit expired on January 27, 1982. The company did not submit a complete application for renewal until March 5, 1984, and withdrew that application on March 23, 1984. ILCO thereafter continued to discharge pollutants into state waters 5 RCRA requires that facilities storing hazardous wastes apply for and obtain an operating permit which ensures adequate compliance with regulatory storage and handling procedures. See generally 42 U.S.C. §§ 6922-25 (1988). This permit requirement can be met by obtaining a permit issued by EPA or a state agency to which such authority has been delegated, see 42 U.S.C. § 6925(c)(1) and § 6926 (1988), or it can be satisfied by meeting the statutory criteria established by Congress for "interim status," which is the functional equivalent of a permit. 42 U.S.C. §§ 6925(a) and (e) (1988) 6 The court awarded $2 million to the United States and $1.5 million to the State of Alabama 7 ILCO has cross-appealed, claiming the district court erred in awarding EPA costs for the removal action at the Church of God site and in assessing penalties for violations of RCRA and CWA. We have reviewed these arguments and the decision of the district court. The factual findings fully support the action ordered by the district court and the record, in turn, provides ample support for these findings; they warrant no further discussion 8 We are not unmindful of the potential circularity generated by these interdependent definitions, that is, to be "hazardous waste" a material must first be defined as "solid waste," but the EPA has the authority to define materials destined for recycling as a subset of "solid waste." See AMC I, 824 F.2d at 1187 ("EPA's various arguments based on the statute itself are, upon analysis, circular, relying upon the term "solid waste" or "hazardous waste" to extend the reach of those very terms.") 9 Accordingly, the regulations define two categories of hazardous waste: "listed" waste and "characteristic" waste. Listed wastes are produced by a particular type of industrial process and are given a unique identifying code number. 40 C.F.R. § 261.30 (1992). Characteristic wastes are those wastes which exhibit certain characteristics of ignitability, corrosivity, reactivity or Extraction Procedure toxicity. 40 C.F.R. § 261.21-24 (1992) 10 Defendants do not claim to fall within any exception 11 The EPA has interpreted plates and groups as solid waste under these regulations for five years. See 57 Fed.Reg. 960-61 (Jan. 9, 1992) ("With regard to lead plates and groups, the materials are solid wastes under the federal regulations because they are spent materials being reclaimed") and at n. 2 (citing prior agency actions and interpretive statements indicating that lead plates and groups are solid waste under the federal regulations.). The agency's application of its own regulation in this instance is entitled to substantial deference. See, e.g., Borden v. Meese, 803 F.2d 1530, 1535 (11th Cir.1986) ("Courts accord great deference to the interpretation of statutes and regulations by the agency charged with administering that regulatory scheme.")
null
minipile
NaturalLanguage
mit
null
Teleflora's Shades Of Brilliance Bouquet Item # TEV32-3A It's impossible not to light up at the sight of this brilliant box of blooms. Radiant as a rainbow, this lush, luxurious gift blends modern style with the timeless beauty of lilies, roses and alstroemeria. Substitution Policy Due to seasonal availability, if the exact flowers or container you have selected are not available, our expert florist will create a beautiful bouquet with the freshest available flowers. We will only substitute items of equal or higher value.
null
minipile
NaturalLanguage
mit
null
Terms & Conditions $15.00 service fee/per room will be applied per stay and it will be included with the NC tax amount on your receipt. Cancellations made 14 days prior to your arrival will receive 100% refund. Please be aware that if you cancelled a reservation paid with credit card, we will be charging a 3.5% banks fees for the total amount for your authorized deposit.
null
minipile
NaturalLanguage
mit
null
Matt D’Souza CEO of Blockware Solutions joins me to talk about his team’s recent research piece on Bitcoin Halving and analysis from a mining perspective. In this conversation, we chat: Market participant profiles Miner electricity distribution Shut off and breakeven cost Mining Rigs Scenario Analysis Why some miners operate at a loss Difficulty adjustment dynamics Why Efficient miners welcome the halving Matt D’Souza links: Sponsor links: Stephan Livera links: Podcast Transcript: Stephan Livera: Matt, welcome to the show. Matt D’Souza: Hey, thank you for having me. Stephan Livera: So, Matt, I know you’ve done some pretty cool work here with this recent Bitcoin Halving and mining analysis research report just recently released and that is from 17th of March, 2020. So but let’s start with a little bit about you and what is Blockware solutions and how did you get into Bitcoin mining? Matt D’Souza: Yeah, that’s a great question. It was, you know, I really started investing in this space in 2015 and 2016. I launched a digital currency hedge fund hedge fund called blockchain opportunity fund in 2017 and it was far more Ethereum focused, far more web 3.0 focused. And then probably around quarter three of 2017, a friend of mine had brought up these arbitrages in the mining space and kind of showed how there’s, there’s a lot of friction between the U.S. And China. And that’s really how we launched blocker solutions as hardware brokers. So what’s critical is that allowed me to see how much infrastructure was getting spent around the world for Bitcoin mining rigs. You know, people discuss how there’s ICOs and other things getting the spending on web applications for Ethereum and web 3.0. The amount of spending in the Bitcoin network, the network effects that’s created dwarfs web 3.0 and, everything else in blockchain, you have billions of dollars worth of infrastructure, electricity spending, facilities spending to secure the Bitcoin network. Matt D’Souza: That’s a network effect. That’s, power. And that allowed me to start to deeply research Bitcoin and understand it more. And the fund actually did a significant pivot in 2018 and, and we’ve had more of a investment thesis in Bitcoin. We still believe in web 3.0, but there’s been a pivot due to that. I don’t understand it. And now Blockware solutions, we’ve grown significantly. You know, got, we were healthy through 2018 we had a great year in 2019 quarter 1 in 2020 is our best quarter. So over the past 12 months, we’ve probably sold about 30,000, 86 to the U.S. market, placed about 25 megawatts worth of miners in hosting facilities. And in quarter four of 2019, I launched another fund. It’s a Bitcoin mining fund with my partner Mike Stelzner. It’s called Blockware mining or mining in Kentucky. We’re running about 180 Petahash and it’s a three prong strategy. Matt D’Souza: We self mine, we resell our mining rigs, we allow miners to mine in our facility. And what we’re doing is we’re looking to bring as much hash to the US as possible and we’re making it really easy for us miners to mine in the U.S. And do it economic. We’re getting miners all in costs about 5.8 cents. They don’t have to wait two months or two and a half months for lead times on mining rigs. And they have an exceptional group of technologists that are managing these units. This group, they, were some of the first miners on Zcash, Sia coin. And, dash they controlled over 10% of the network there. They’re called Naveah exceptional technologists. Some of them had been mining since 2011, 2011. So that’s what we’re marrying together to really give US miners a competitive advantage in this space. Cause mine is just all about survivability and that’s what we’re bringing. So miners don’t pay for cap ex and they only have their electricity rate. They get to maximize their hash. And that’s what’s gonna make them successful. Stephan Livera: Yeah. And so the interesting thing there is that it may seem at first glance that US mining is not as competitive as other countries around the world. Why, do people have that view? And then in your view, why is that not necessarily right? Matt D’Souza: Yeah, it’s actually very inaccurate. I mean it’s, what we’re very good at is strategy and models. When you have other minds in the world, they may be paying a hundred, 150,000 per megawatt to pay for their transformers electrical infrastructure. They’re building and then they’re getting maybe 3.2 cents. So when you model all of that out and you put in the cap ex, amortize it 5.8 cents without having to pay for a facility and all that infrastructure and just buying mining rigs in and just deploying cash to Terahash, that’s like the equivalent of of 3.6 cents electricity and paying 150,000 per megawatt in build out. So it’s two different models. You can elect to deploy to just mining rigs and get a rate of about 5.8 and that’s, and we believe that’s significantly better. You’re maximizing your hash or you especially cause you’re getting in the most efficient technology. That’s really what’s critical. The fact that these S17 pluses are so efficient, they’re so efficient where the impact of electricity is decreased. If you’re in our report, we show that one a table. How a miner with the recent electricity run in the old generation, S9 has a higher break even price than a miner running 7.5 cents electricity running the next generation S17. Stephan Livera: Yeah. That’s a really interesting analysis. And let’s break into that. I think let’s start though with the market participants though. So as you spell out in your report, you spell out that the three that you assess, there are investment funds, the HODLers and then the miners. So can you just break some of those down? How are you viewing them from a mining and a Bitcoin price impact point of view? Matt D’Souza: If you’re, anyone who’s involved in Bitcoin for the most part is pretty bullish. I mean, all these investment funds and HODLers, they’re just about all alone only, and they have high conviction, but the thing is they could buy their Bitcoin and in two weeks they could, they could lose conviction and sell and they’re done. The miners are truly the most bullish. They have the highest conviction. They’re buying mining rigs with 3-4 year life cycle. They’re buying a hosting fee. They’re buying a warehouse and repurposing it into a mining facility, ripping up the walls, putting in these industrial grade fans. And those have five year life cycles. That’s what they’re getting married to three to five years. And they’re putting, they’re injecting all their capital in there and they may not earn back for 18 months and they can’t just turn around in two weeks and sell that stuff. Matt D’Souza: Right? It’s, illiquid. It’s not as repurposable these ASICs right? They’re mining rigs ASICs, only for Bitcoin. So they can’t change their opinions. They’re the ones with the highest conviction. But the thing is they’re getting their Bitcoin every day and they have to sell the Bitcoin to cover their electricity expenses. And that’s what’s going on in the space, which creates sell pressure on the Bitcoin network every day. You know, I think it’s 1800 Bitcoins a day, 54,000 Bitcoin a month. That is issued you know, pre Halving and that’s how much Bitcoin is released to miners. You know, when you think about how do prices get affected, it’s not, the trading volume on exchanges is really churn. It creates volatility and it affects price more short term. Right? BitMex had that liquidation. Bitcoin was at 7,800. It fell all the way to 3,800 but look, we’re right back at 66 right? Matt D’Souza: That’s, churn and volatility from speculators. That’s not what affects the intermediate and long term price. What affects the intermediate and long term price is net cash in net cash out and miners, unfortunately are net cash out because they have to fund their electricity expenses. It’s not because they don’t have conviction, it’s they have a bill every month and they have to fund it, so we’re getting net cash out from the miners. They have to sell their electricity are their Bitcoin to fund electricity. Sometimes they’re buying more mining rigs and we need positive sentiment. We need positive sentiment from funds and HODLer’s to be buying bitcoin as well to counterbalance the mining sell pressure. Stephan Livera: Yeah. That’s a really interesting way of putting it because you’re saying basically that investment funds might, although generally are bullish, they have the ability to exit at any moment and walk away if they get tested. And then similarly now I think longer term HODLer’s , they have pretty strong conviction as well. But they can theoretically exit their position at any time. But I think the point you’re making here is that miners, because of their big upfront investment, they can’t just walk away at the drop of a hat. And so they’re in some way, there is a commitment there and that’s a pretty interesting fact that you could almost say a Bitcoin miners are more bullish than you are, than the typical HODLer. Matt D’Souza: Exactly. And when you put things into numbers, 54,000 Bitcoin released every month is a quarter billion dollars. That’s $540 million of potential sell pressure going to miners to sell for their electricity. Now they don’t sell it all, but that’s the potential. Now, how do you counterbalance that? Are funds and HODLer’s raising a half a billion a month, no chance. And of course miners aren’t selling all that, so it’s not as pessimistic as I initially proposed it, but that’s the potential. And realistically, and that’s what we show in the paper. We only model out how much electricity needs to get spent and that accumulates to about 40 to 50% of that, you know, half a billion. That’s what needs to get spent unless a mine, you know we’re getting some interesting minds out there and are raising a ton of capital. You know, it’s fun. It’s there. VC funds, hedge funds, they’re raising a ton of capital, they’re getting excellent balance sheets and they’re just accumulate in the Bitcoin. So those miners are high conviction. They’re paying electricity with cash rather than their Bitcoin and they’re holding all their Bitcoin. Those guys are the best for the network because they’re truly removing supply off the network. They’re getting all the new Bitcoin and they’re holding it. That is excellent for the price of Bitcoin. Stephan Livera: Yeah, it’s interesting to put it that way. And so yeah, you spell out some of the potential sell pressure but as you say. Some of them are more bullish than that and they’re trying to hold it back as much as they can. And so I think this also comes into the different levels of price or layers, as you say in the report that there are some miners who are above 7 cents per kilowatt hour. And then there are some that are below, you know 3 cents a kilowatt hour and so on. So could you just spell out for us a little bit around some of those different levels and how you figure out how many people are at these different levels and layers? Matt D’Souza: That’s a great question. So, Blockware solutions. We’ve, a majority of our business, we sell a majority of that North America, a lot of the U S market. But you know, I’ve been asked to speak around around the world at different conferences. You know, I was in Chengdu, the miner update team through a great conference in Chengdu in October. I’ve visited these large mines in Sichuan province. We visited the mines in the Pacific Northwest, Washington state. One of my partners has visited upstate New York mines. So we’ve, they’re all in our network miners in Kazakhstan, Iran, Venezuela. We just shipped several seventeens to Venezuela last week. So all over the U.S. Canada. So we, you know, we talked to these clients, what are you’re running, what’s your electricity rate, what’s your megawatt capacity? And we communicate directly with the pools. I mean we’re talking with Poolin. Matt D’Souza: We talk F2pool almost every two or three days. We talk to BitMain everyday, and Canaan. So we’ve gotten excellent peer review on our piece and understanding what electricity rates are at different geographical locations and what most importantly, what mining rigs are they running. And we also have our own pool. We have the Blockware pool. So we have, we have miners on there and we can see what workers they’re running a worker that’s 13.5 Terahash or is it 73 Terahash. And that’s how we know it’s an old Gen verse a next gen. So that’s how we’ve modeled out the network. And this is what’s really interesting. The miners with three cents or lower. They’re all still running S9s and the Canaan 10 Terahash or eBang is the 13 Terahash. I know a colleague who is mining and Kazakhstan, he, you know, really, really intelligent individual. Matt D’Souza: He raised some family office money and they launched like in November of 2019 you’d think? All right halvings coming up they’re buying next gen’s no, they have sub two cent power and they went and bought a bunch of the ebangs because their earn back is two or three months. So markets are efficient. I think cryptocurrency markets are the least efficient market of markets, but it’s still a market. And when you pour water at the top of the mountain, you have gravity and the water is going to go to the lowest point. It’s going to trickle down to the lowest point. And that’s what’s going to happen in the mining rig space. The S9’s, if someone has 6 cent electricity or 5 cent electricity, they have to sell it. You won’t be able to mine it at a hosting facility and it’s going to the cheapest power in the world. Matt D’Souza: It’ll, it might take three times. They might sell it to someone with three cents and then, and then it’s going to become unprofitable for the individual three cents and he’s going to sell it to someone with subsidized power and it’s all going to flow and trickle down to the cheapest power in the world. And these S9s are flowing to Kazakhstan, they’re flowing to Venezuela, they’re flowing to subsidized power in Iran. We have a client in Arizona who’s got solar power and he’s got zero cost and they’re flowing over there. So markets are fairly efficient. These S9s many of them are going to shut off and become obsolete. Many miners are just not going to want to deal with doing the shipping and stuff and they’ll junk them, but other ones are going to flow to the cheapest power in the world. Someone may have a negotiated deal with the utility where the power is basically free or they’re just paying variable costs, you know, the cost to deliver the electricity. So that’s how it’s going to work. These will disperse a cost across the globe and get to the cheapest power. Stephan Livera: Yeah, I love that insight. I think that’s a very underappreciated point and that really comes through very strongly from your report. Could you please just outline a little bit around what the different rigs are? So you’ve got the old generation Bitmain S9 and the next generation S17. Can you just spell out a little bit for the listeners around, you know, what’s that dynamic there and what are the different generations? Matt D’Souza: That’s a great question cause this really influences the market. I think we focus on 2, units, the S9, which is 13.5 Terahash and consumes 1400 Watts. Now the S17 plus, which is what we’re running at Blockware mining and that is 3 Terahash and consuming 3000 Watts. So it’s about, it’s about 2.1 times the amount of energy consumption, but it’s about 5.5 I think it 5 or 6 maybe. Yes, 6 times the Terahash output. So 2.1 more watt consumption, but six about six times the Terahash output, right? So, you’re consuming 2 times the Watts, but getting 6 times the output. That is radical efficiency, significant efficiency. So what does that, what does that do? You know, before I needed to run 70 machines, 70 S9’s to get one Petahash now I’m running 14 machines to get one Petahash 70 S9 to get one Petahash, 14 S17+ to get one Petahash and the watt consumption, you’re running the math, you’re I think it’s so 14 x 3000 Watts = 4.2 Right? Matt D’Souza: And the S9, 1400 Watts times, 70. Here I got my calculator eight times 1400 that’s 98,000 Watts. So it’s significantly more efficient. And what that does is it reduces the impact of electricity because you’re consuming less Watts to get more hash. And that’s why it keeps, and that’s why it keeps these high electricity miners in the game. So people with 5 cents, 6 cents that are at hosting facilities, they can mine very profitably if they’re in the NextGen. But if they have S9’s, they’ve blown out, you’ve gotta be two and a half cents or lower because of, you know, difficulty in the price of Bitcoin. So it’s a complete game changer. Stephan Livera: Yep. And so, I guess that’s, so you’re outlining there, why if you have a high electricity cost, not like crazy high, but like reasonable in the high, in the higher ranges, you can still make it work with next generation hardware. And then you’re saying also that if you have in the lower range of electricity costs, right, you’re in the better and the you can make a work even with the old hardware. Now the other question I guess is it just that because of the capital expenditure required to get the new hardware, that’s why sometimes people will stay using the old hardware if they have a good elctricity cost. Matt D’Souza: You hit it on the head. There’s an opportunity cost, the opportunity cost of depleting your Bitcoin treasury to upgrade to NextGen. If you’re at two and a half cents or lower, it doesn’t make sense. You’re better off holding the Bitcoin. You’re not really doing much for your, for your shutoff price. You’re not really lowering your breakeven price that much and it just doesn’t make sense to take on spending, you know, 2000 or 2,500 for NextGen depleting your Bitcoin and it’s a game of marginal returns. Matt D’Souza: You’re hitting marginal returns cause your electricity expense is lower. But if you’re at 6 cents, you have no choice. You got to get the NextGen. And that’s what’s really cool about this and how we’ve modeled it all out. You know, Blockware mining. We’re at 5.5 cents and we’re able to, we’re better off not depleting our capital towards infrastructure. You know, building out a facility transformers, because we’re in the newest technology, the most efficient technology. So we’re actually far better off having the 5.5 cent rate, not deploying 150 or $300,000 per megawatt for transformers, switch gears, electrical infrastructure, paying for management, paying for a facility, rent, all that stuff. We’re better off deploying all that capital just into machines maximizing our hash. And it’s because the 5.5 cents isn’t as impactful to us because we’re in such efficient machines. Stephan Livera: Yeah. Right. And just for some context for the listeners just reading from the chart here at 5.5 cents electricity rate per kilowatt hour. The break even costs if you are on S9 is $7,762 Bitcoin price. But the break even cost at S17 is $2,700. So it’s a big difference there because you’re using the next generation hardware. So I think this is a much more accurate way to think of this idea of shutting off. And so Matt, could you just explain a little bit around this idea of miner capitulation and then why is that so commonly misunderstood or what’s wrong about people who say “Oh miners are going to capitulate and it’s all over for Bitcoin”? Matt D’Souza: It’s I call it a healthy cleanse. It’s look at what happens. It’s an efficiency. We’re creating efficiencies in the market. You know, I think one of the biggest, I don’t want to get too deep into what’s going on with the economy and all that stuff. It’s going to be a big tangent, but when you do bailouts and all that stuff, you’re keeping inefficient companies in the game. There’s things that you need to bill out and kind of intervene a bit, but there’s no reason everyone should get a bailout. If you’re an inefficient company you go through bankruptcy, an efficient company comes, takes your assets and takes pieces of your departments that are healthy and profitable and the stuff that’s unprofitable gets wiped out and that’s healthy for an economy. Mining is one of the best examples of this. Matt D’Souza: You get a miner who overspent on their facility, have S9s running, running at 7 cent a watt electricity, they should get wiped out. They, they are going to get blown out. And what happens is there’s 12 and a half Bitcoin that’s released that’s going that every, you know, every block that’s going to go to whoever is mining. So once miners, when the price of Bitcoin goes down and those miners shut off, when the price of Bitcoin goes down, it creates margin pressure for everyone on the network. Now when the inefficient miner shuts off the Bitcoin he was earning, it gets distributed to everyone else. And that improves the margins of the miners that survive. And that’s what’s critical. It’s a self correcting mechanism. Miner capitulation is about difficulty and then also inefficient miners blowing out the inefficient miners blow out difficulty adjusts right? Right now in a couple hours, difficulty is going to adjust 60 or 70%. Matt D’Souza: It’s going to be one of the largest ever. The price of Bitcoin went down. Everyone’s experiencing margin compression. All these miners running S9’s probably have shut down and we watched the pools. All the Asian pools were really shutting down. So I think it’s a lot, in Russia and China that are actually shutting down the S9 there. They’re no longer gonna earn Bitcoin and that Bitcoin is going to go to the guys who are running S17s and who are running efficiently and their margins are going to get better. It’s going to, right now, Bitcoin’s at 6,600 in, in a couple of hours as difficulty adjusts 16%. It’s going to be like Bitcoin being at 7,800. That’s how it works because the margin, because of difficulty, profit goes up 16% and that’s what’s critical. Capitulation is a very good thing. It’s removing the inefficient miners. Matt D’Souza: They no longer get their rewards, their rewards get allocated to the efficient miners. The guys that have deployed correctly that have low electricity and those are the strong hands. We want Bitcoin in their hands because they don’t have to sell as much Bitcoin. Their margins are good. They don’t have to sell as much Bitcoin. There’s less sell pressure on the network and Bitcoin price could increase. I almost think of it like the equity markets. Think about like Fidelity Contra or Vanguard account. These are the large funds who know what they’re doing and, and when the market drops a bit, they don’t just, they don’t sell. They’re coming in and they’re supporting the market and they’re buying and these equities, they go into strong hands and they have a time horizon of one year, one, one to four years. So coin is getting, when you get miner capitulation, Bitcoin starts getting allocated to the efficient miners with strong balance sheets, low electricity rates, the proper mining infrastructure. And it’s, it’s getting accumulated with guys who’ve been doing this for years who have seen this show before and they’re going to be holding that Bitcoin and now you’re taking Bitcoin off Bitcoin supply off the market and you’re reducing sell pressure on the network. And that’s what positions us to move up to the next leg in the price of Bitcoin. Stephan Livera: Yeah, that’s really fascinating. So I guess just to summarize for listeners, it’s something like as the Bitcoin price tanks, some miners have to shut off, right? The inefficient miners have to shut off and it becomes more profitable for the better miners. And also we get the downwards difficulty adjustment, meaning it becomes slightly less difficult to mine that Bitcoin. And that is what in turn rewards the best miners because they can now make more for the same amount of work that they were doing. And then as you were saying, they’re the strong holders they want to hold. And so that in some way diminishes or decreases the downwards sell pressure that exists just permanently or just continuously on the network. Matt D’Souza: You’re writing our second report. You got it. Stephan Livera: No, I think it was a, it was a great explanation from you and from reading the report. I think that was really interesting. And so let’s now that, what we spoke through, there was like the example where the price goes down, right? We have a crash. What, can you just talk through what it looks like when the price is on the bull run? Like when the price is rising, what does it look like? Does that invite more people into the market and then some of those people are inefficient and then they just get wiped out in the next crash? Matt D’Souza: Yeah, it’s totally cycles and just, you know, you explained it really well. I think we really need to give a tip of the hat to Satoshi. I mean, one of the most ingenious pieces of the Bitcoin network is difficulty. It’s just a self correcting mechanism that maintains the margins of the efficient miner. When too many miners come online and Bitcoin corrects, you know, too many miners come online, margins get compressed, Bitcoin corrects and miners have to shut off. Then difficulty kicks in, improves the margins for the efficient miners. And now what you just discussed, it’s going to be the opposite. Difficulty is going to, it’s going to Bitcoin, when Bitcoin starts to rise, everyone starts buying mining rigs. You know, it’s human psychology. It’s truly a market. People don’t buy low and sell high. Most people buy high and sell low, right? Matt D’Souza: They, it’s fear and greed. So when Bitcoin starts to rise, all these miners start deploying to mining rigs again and, and there’s that finite amount of Bitcoin that’s released. So it’s getting distributed amongst several miners and that’s what makes difficulty go up and difficulty. Like I said, it’s a self correcting mechanism. Difficulty is going to punish all these miners that have chased price and deployed mining rigs. If you’re going to get difficulty’s going to go up. Mining margins are going to compress. And once Bitcoin corrects in price those inefficient miners get wiped out again, and the cycle continues, then difficulty will be a positive where it’s gonna adjust lower and restore margins. So it, it keeps things in a band. Difficulty keeps margins in a band. And when price gets too high and too many miners come online, you get margin compression. And when you get miner capitulation on the downside, bitcoin price corrects miners shut off, difficulty adjust favorably and margins get. So it’s why I say difficulty is this ingenious self-correcting mechanism. It’s kind of a gravity. And what it’s doing is it brings margins back for those efficient miners over the intermediate and longterm. Stephan Livera: Very cool. And so if we, so we’ve spoken through if Bitcoin’s price goes down or up just on its own. Now, if we talk about actually the halving impact, right? So the amount of block reward or block subsidy to be precise, halves, can you talk us through some of the ways to think through that? Matt D’Souza: So it’s, it’s going to be extremely healthy. We, believe that the miners at about 6.5 and there’s differences. You know, you actually brought this up, I kind of missed it explaining it. But if you’re paying 6.5 cents, that’s not horrible. If you’re not paying anything towards capex. If you’re just paying for machines and you’re getting 6.5 that’s pretty good. If you’re getting three sons, you’re paying for infrastructure and all that stuff, then that’s how that balances out. So that’s critical. I don’t recommend miners who are paying 6.5, 7 cents, eight cents, and they’re running it at their house, paying for their own infrastructure, transformers build out, they’re going to get wiped out. That’s horrible. So that’s number one. When you see those layers of people at 5.5, 6 and a half, 7, they’re in hosting facilities, but that’s also their break even price at the end of the day. Matt D’Souza: So I just wanted to clarify that. Now when you’re discussing the halving and what’s happening, we encourage the Halving. We don’t fear it. We welcome it because we understand what it’s going to do and what it’s going to do for our profit margins over the next six months. Being at our layer, 5.5 for blockware mining is extremely healthy. What’s going to happen is it’s going to be, it’s going to be like an onion. There’s going to be layers that peel off this onion, those S9s are gonna blow out. If Bitcoin is still around 10,000 after the Halving. S9 are going to blow out, that’s all the old generation. So S9 from 7 cents to probably two and a half, three, two and a half cents, they’re going to blow out. They’re going to shut off. Now you have that other tier, of those T2T30’s InnoSilicon, they’re like mid generation. Matt D’Souza: Those are all going to blow out too, up to probably five cents. They are going to blow out. And if Bitcoin happens to be at five, six thousand after the halving even six and a half, 7,000 miners with 7 cents running S17s are going to have to shut off. So people at six and a half and lower running next gen, they’re going to have an amazing difficulty adjustment, right? When all those miners shut off, difficulty is going to adjust significantly. 30-40% and their margins are going to come back. There’s going to be friction. It’s not like a light switch. You know, it takes time for these miners to shut off because a lot of these miners who are in hosting contracts, they don’t, if they don’t pay their hosting contract, they lose their equipment. So they’re not going to just let their equipment go. Matt D’Souza: They’re going to wait to deplete their balance sheets and all that. So it might take two to four months of friction for all of that to wipe out. And there’s other large miners who have negotiated rates with utility companies that they have to consume a specific amount or their 4 cent electricity turns into five and a half. There’s all types of deals out there that are going to make some miners operate at a loss, which creates more sell pressure ’cause all the Bitcoin they’re mining is going to get sold and then they have to tap into their treasury and that has to get sold to. So that’s more sell pressure. So we need all that to blow up. I think, I don’t like price targets, but if Bitcoin is in these suppressed levels through the Halving, it may take another two or three months of extreme miner capitulation for all those miners to blow out. And then difficulty is going to adjust and profit margins are actually going to be better for these efficient miners running the S17 pluses and in that six cent band or lower their profit margins are going to be better after the halving than before. Stephan Livera: Right. And so it’s an interesting insight there as well that the typical thing you hear people say is, Oh, but if the price drops, then these miners can instantly shut off. But it’s an interesting point you make there, that that’s not reality for many miners. They’ve got negotiated deals in place. They have a certain contract in place where they can’t just immediately turn off or not all of them can at least. And then some of them are playing the speculation game as well, where they may temporarily just wear the loss because they’re kind of hoping for a longterm bullish aspect. Matt D’Souza: And that’s the worst part. I mean, I think that’s what really drove the two downturns. The one, after we peaked out in June, 2019, you know, because I run the hedge fund as well and I trade OTC with one of the largest groups in Chicago. We’d discuss analyses and they were telling me how their miner mining clients, they pumped the brakes. So when Bitcoin was going from 8,000 to 13,000, they stopped selling their Bitcoin. They were looking at 20,000. They’re not, they weren’t interested in the moon. They were interested in Mars. So that’s where they thought we were going. They stopped selling their Bitcoin and then Bitcoin rolled over at 13,000. It went till, you know, 12,000, 11,000, 10,000 and these guys started feeling the pressure and they started puking and, and that’s what drove it. You know, that’s what drives it down. Matt D’Souza: It’s miners that don’t make, create a plan and they don’t trade the plan. You got to have a plan. You gotta have a strategy and you stick with it. It’s a game of discipline. Mining is all about survivability, deploying at the right times and being, having an excellent treasury management. And some of these guys elect to turn into speculators and that hurts them significantly. And you know, in January, I was so concerned, I heard the same thing from the OTC desk. They’re like, yeah, these guys, they’re not selling. And I knew once we get get to about 7,800, they’re all going to start puking again. And that’s, you know, you had that sell pressure. And then of course the BitMex liquidations, people being on margin coupled with the U.S. Equities really driving all assets lower. It was just a perfect storm for the sell off. So Stephan Livera: Yeah, that’s an interesting one. And when it comes to electricity deals, right, so as you say, it’s a very important factor. What is your electricity right now? I’ve heard that it can be difficult to negotiate a good rate or you might have trouble staying in a certain area that you might, you know, there might be a political risk of having the miner in that jurisdiction or you kind of get shunted out. What are some of the strategies and ways to try and negotiate in a good electricity rate and keep that rate? Matt D’Souza: So in the, U.S. There’s actually far more stability. Like ,I just couldn’t, there’s so much volatility in Bitcoin mining. I don’t know how people do it and some of these other countries, cause you can just get shut down over night. There’s like that there’s enough volatility and problems in Bitcoin mining. I don’t know how people do it with the, with you know, that you, you don’t get excellent uptimes with the power. And you know, if your Internet’s down 15- 20% of the time, what good is that your revenue is down 20%. Right? A lot of these countries have blackouts and 20% of the day power is shut off and people are running mining rigs there. So to us it’s, you know, from a risk management perspective, I don’t get involved in an asset or I could just lose, there’s a, there’s a 15 or 20% chance where I just lose because it’s not in my control. Matt D’Souza: That doesn’t make sense to me. And that’s why it’s so critical to be deployed in like the U.S. Or Canada where there’s stability and, and the municipalities are working with you and they appreciate you because they have, you know, a lot of mining operations. We’re not running them in New York City or Chicago or LA. You’re going into rural areas where they have excess electricity, cheap land. Right? Markets are efficient. You’d go where the power’s cheap, the utilities have excess, and you’re, you’re, it’s a communal relationship. Now I think when utilities a lot, there’s not a lot of negotiation power, but you have to go to places, you know, you want to try and get this cocktail of cheap power, cheap land and a good climate. It’s, difficult, but it’s out there. You gotta do, you gotta do the work and if you can get a place that has a lot of excess power, then, then you have a communal relationship, right? Matt D’Souza: But you’re not really going to be able to push utilities around. You still are somewhat at their mercy. But the goal is to have three to five year contracts locked in with utilities, if they’ll do that. I mean,I’ve got a really savvy group in the state of Washington. They’ve been around the block for a few years and, and they’ve done a great job with, with negotiating their contracts. I know there’s sub three cents and they’ve put in a lot of work. They did the due diligence and they got it done. So it can be done. Stephan Livera: Yeah. And is there, do you face, I suppose in the U.S. and Canada mining operations will face a little bit more scrutiny around things like auditing and so on, but at the same time that might also help you from an outside investor point of view. Has that been your experience? Matt D’Souza: Yeah, I mean we are a U.S. Entity. We get our audits, everything, you know, by the book, it’s good for us and it’s good for our investors, right? Our LPs want it. It makes it a more attractive product that allows us to get debt financing as well. So, absolutely. I mean, we pay our taxes, everything. This is, like I said, this is a game. Mining is a game of not screwing it up. From, what you’re buying to how you’re operating to the treasury management, to the, to the regulation, to the taxation. Mining is, it’s a very lucrative operation. You know, with our mining fund, Bitcoin is down. I don’t know what it’s down on the year. Maybe 30%. We’re up, we’re up significantly. We make money in a sideways and downward market. If you’re holding Bitcoin, you’re losing money. Matt D’Souza: If you’re mining and you have a diversified product like ours where you self mine, you resell rigs, you take on hosting contracts, you have three revenue streams, right? And that’s allowed us to significantly outperform the price of Bitcoin. So from our perspective, we’re trying to do the, all the small things, right? We’re trying to be very diligent, be very disciplined with our treasury management. And it’s a game of survivability. Miners are survivors and, we’re going to be in the game. It’s about staying in the game. A lot of other miners blow out, make poor decisions, overspend. And they blow out. And, and a lot of times with, whether it’s invested in equities or assets, you make a majority of your money in a month or two or the whole year, you know? And when Bitcoin went from 5,000 to 10,000, margins were insane. Matt D’Souza: I mean, earn backs were so short. So you gotta be in the game. If you take yourself out of the game, it’s game over. Right? So if, if, if Bitcoin, if difficulty is going down as it is and lead times are two and a half months and out of nowhere, Bitcoin sprints up to 10,000 and we have our mining rigs running, we’re going to make, we’re going to make eight months worth of money in two months. So you gotta be diligent, you gotta be doing the right things, just stay in the game and you’re going to have segments of the year, one or two month segments of the year where you’re going to make 80% of your money. So you gotta be positioned. Stephan Livera: Yeah. That’s also a really fascinating insight and it makes a lot of sense when you think about it because it’s like you’ve set up your whole operation to try and be efficient, have a certain cost, but then all of a sudden the thing you’re making or the thing you are producing has just shot up in value because Bitcoin just does Bitcoin things and goes volatile. And then it just, during that period, you’re just minting it. Right. So that’s a really interesting and it’s kind of aligns as well with even if you look at people like Thomas Lee who talks about Bitcoin from an investment point of view, he says, if you weren’t holding Bitcoin, there were certain days in the year where if you just weren’t holding Bitcoin on that day, you missed out on a massive return. And it’s a similar kind of aspect with mining because if you weren’t mining in a good operational cost then you missed out on the massive gain that was available during that day. Matt D’Souza: Exactly, exactly. And unfortunately, and that’s, how we’re set up. We have our mining rigs we’re accumulating, but unfortunately most miners, they see those days where Bitcoin spikes and then they’re ordering their mind and rigs and then they’re not getting plugged in for two and a half months. And right our self-correcting friend, difficulty has already punished them and brought margins back to normal and then they get their mind and rigs two and a half months later in margins have compressed again and normalized. Right. So that’s why as you said, you gotta be in the game and position when the opportunity, if the opportunity’s there and you’re not ready, you miss the opportunity. So you have to, you have to be positioned before the opportunity comes. Stephan Livera: Yeah. It’s like that luck is when preparation meets opportunity kind of thing. So I guess projecting out, right? Like, so we’re all bullish on Bitcoin. We think this thing is going way, way higher. What does it look like when the block reward component, sorry, the block subsidy component of the block reward comes down and well, hopefully most of that, a lot more of that reward is coming out of fees. Do you think that changes the dynamic, therefore mining how you think about mining, and I know this is kind of maybe 15 years out. Do you have any thoughts around what that looks like? Matt D’Souza: Yeah, It doesn’t concern me at all. This is what’s interesting. I think Bitcoin is digital gold. I don’t think fees are ever gonna drive the network. And we need to put things into perspective. Right now, if I have 100,000 in cash and I park it in a bank, I’m paying a fee in Germany, you’re paying negative interest in Japan, you’ve been paying negative interest rates in Germany, now you’re paying negative interest rates. So we can go to I believe if this matures out five, 10 years, Bitcoin’s going to be at a significantly higher price. There’s going to be miners, there’s going to be holders with a hundred million dollars worth of Bitcoin, $10 million worth of Bitcoin. If I buy gold right now and I buy $1 million worth of gold, I pay insurance, I pay, the storage costs. So I’m paying essentially a negative interest rate right now if I have Gold, a significant amount, right? Matt D’Souza: It’s in a vault. You don’t keep it in your house if you’ve got, a significant amount. So when you look at the parallel systems or comparable assets, people are already paying a fee for to store these, these store values and now currencies, they’re doing it. If you put your money in a bank account, you’re paying a negative interest rate. So that’s the world we already live in. Now with Bitcoin, forget mining rewards getting halved and transaction fees, we can go to zero rewards and if we have a robust system in 10-20 years where, this stuff is valuable and it’s like digital gold, while people are going to be willing to pay a quarter percent and you don’t have to, right? You don’t have to put it in a vault because you have your private keys. So that cost isn’t there. Matt D’Souza: But I’m willing to pay a quarter percent to the miners to subsidize them because the comparable world like gold or, currencies with negative interest rates are already there and they’re probably more expensive. And, if I want to move my gold, it’s not portable, like digital currency, jump on a plane, go, wherever you got your digital currency. Just on a ledger. So that doesn’t scare me at all. I mean it, because, because there’s a dynamic for us to get to that state, that means Bitcoin succeeded. And if Bitcoin succeeded, it’s at a significantly higher price. It’s significantly more valuable. And if it’s more valuable, we have the incentive to, pay that quarter percent or half a percent to miners to secure the network. And right. Like that’s, what we’re doing in the real world with gold insurance, storage costs all that stuff. So, so it’s, when you think about what the real world looks like, that’s normal. Matt D’Souza: That’s normal to not pay is abnormal. So, so yeah, that doesn’t concern me at all. And also, I don’t know what’s going to happen with Bitcoin is lightning network and to take off is going to be a payment processor. I don’t really think so. I think it’s going to be digital gold. And if that’s the case, you don’t have a ton of transactions. And so therefore you don’t have a lot of transaction fees. People should be,\ holding their Bitcoin as a hedge or whatever. You know, when you get, you get these multi, these mega net worths especially in like China or other countries, it makes a lot of sense to diversify your assets. They put, they put their money in fine art, $20 million paintings, diamonds, property all around the world. And Bitcoin is just going to be another one. Matt D’Souza: It’s going to be another asset to the cocktail of store of value. And think about how attractive that is to the mega net worths. I’m talking about the billionaires to, have this on a ledger and be able to go wherever you want and no one can confiscate it. Right? And now, now I’m seeing sophisticated people with the Brain wallet, right? They’re memorizing their 24 words. So you know, on a ledger you have your 24 seed words. They’re not even they’re, I have a, I have a colleague who’s been mining since 2011 he has a brain wallet, so he’s memorized all 24 words about every two weeks. He tests to assure that he’s got all 24 words memorized and he can just not have a ledger or anything. He can go fly to Switzerland, buy a ledger, upload his seed character on that ledger and he’s got all this and then he can just throw out that ledger, go fly to Australia. Matt D’Souza: He’s got his 24 characters memorized in his head and he can get access to his coins there. Like, talk about immutability and portability, portability. You can’t beat it. That’s it’s going to be, and you, you factor in generational trends. The fact that millennials have just taken over baby boomers and the generation under us are more digital. China, 80% of payments in China are digital often mobile. It just resonates with, with the, with the upcoming generation, digital gold is going to make a lot of sense. We just need this technology to mature. Presently a technology in its infancy. There’s a lot of volatility, so it’s not truly a great store of value, but as technologies and commodities mature, the volatility gets sucked out. You know, gold, soybeans, oil, they’ve been around for hundreds of years, right? And they’re less volatile because the supply is better controlled if, if you’re an oil company drilling oil, you have a trade desk, you’re hedging out your futures and forward contracts, 12 months, you’re locking in margin and that reduces volatility. Matt D’Souza: And when the volatility is reduced, it’s more usable for the end user. And that’s how those commodities become usable and stick around. Bitcoin right now we have miners in China or wherever who just puke their supply. They’re the ones who are the suppliers, right? Bitcoin is probably going to be digital gold of commodity. And right now the people that are controlling the new supply, they just sell at will they market order when they get their coin from the pool. And that creates volatility and then it’s not as good as a store of value. And then it’s not as usable for the populace, but early adopters are getting into it. So once we get more commoditization and more maturity on the supply side, the miners, which we’re seeing and we get better financial products, which we’re seeing, this is all happening right in front of our face. CME futures, Bakkt, options, that’s going to reduce volatility. When that reduces volatility, this becomes a more effective store of value and therefore it becomes more usable and therefore it’s more of a digital gold. People can use it. So right now Bitcoin is a commodity in its infancy as that matures, it improves the narrative radically. Stephan Livera: Yup. And so looking out to the coming halving, right, so we are in late March now the Halving predicted for, call it 9th or 10th of May, so just a little over a month away. And so what we spoke about earlier is kind of getting at that idea that there might be a couple of months of, you know, shake out before the breakout. And I guess over time just those investment funds and the HODler’s and the people who are just stacking will basically keep purchasing new Bitcoins and there’ll just be less selling pressure continually coming from the miners. Because of the Halving. So is that basically your outlook on the Halving and the next few months following? Matt D’Souza: So um like funds and stuff. Buying Bitcoin because of the Halving? Stephan Livera: Yeah. And also just what happens to Bitcoin as an overall ecosystem over the next few months. I think historically we’ve seen the Halving happens and then it’s kind of the price starts to rise a few months later. Is that essentially what your view is on what’s coming? Matt D’Souza: So what we expect there’s, I think there’s three dynamics. It’s kind of like this perfect storm for Bitcoin. Number one, the supply supply side economics improve, right? The one thing that has effect is that the amount of supply of Bitcoin is going to get halved right? So if you have 50% less Bitcoin to sell, that’s great for the network, right? That sell pressure, 50% potential is removed. So that’s exceptional on the supply side. Economics for the price of Bitcoin. Now what does that do? Everyone knows that having is typically bullish, people understand that this supply side economics is going to improve. So that improved sentiment into the system you want, you know, it’s improved sentiment on the demand side, investment funds HODLer they naturally are going to try and lean bullish. They want to be bullish because they’re going all to Halving all less, less sell pressure, less supply. Matt D’Souza: This is good. And once prices start to improve, they’ll chase the momentum because sentiment improves on the demand side. Supply side economics improve cause there’s 50% less sell pressure that’s going to flow into the investment funds and the HODLers and that’s going to give them positive sentiment. And it’s, you know, markets are driven by sentiment, right? So, if they naturally right now I think everyone’s just very scared because of the US equities and what happened in Bitcoin. But overall all these participants want Bitcoin to go up and, and, and so it creates positive sentiment. If we get priced to start ticking up, I think people are going to chase the momentum because of that positive sentiment. So, so what that does is it carries over, an improvement on the demand side as well. And then there’s a third factor in there, which is all the debt financing, collateralization of Bitcoin. Matt D’Souza: That could be a whole another lover. You know, it wiped, it created a bunch of margin calls on the downside because people were over levered and got wiped out because there was such a nasty sell off. But a lot of miners, they’re starting to collateralize their Bitcoin and that reduces sell pressure on the network, right? So they get their Bitcoin and rather than selling it, they can collateralize it with a lender and they get, you know, USDT or Dai or whatever, and that now they’re able to get cash and pay their electricity. So the electricity bill is getting paid without having to sell Bitcoin. And, and it’s essentially removing supply off the network. You know, we’re kind of going through a reset because everyone got wiped out on the margin calls, but people are going to start collateralizing their Bitcoin again, they won’t have to sell their Bitcoin. They’ll be able to fund their electricity expenses. And what that will do is remove sell pressure and it’s another lever of basically improving the supply side. When you couple all these three together, that’s how you position for the next leg up in Bitcoin. Stephan Livera: Fantastic. Yeah, that’s a really great explanation and it’s a great report. I recommend listeners go and have a look at it and if listeners want to follow you online or keep up with Blockware solutions is doing where can they find you guys? Matt D’Souza: So you can find me on Twitter. We release a lot of information off my Twitter @mjdsouza2. You can also follow our Blockware solutions team. It’s @blockwareteam. And then of course check out our website. We have a miner resource center, you know, calculators, projections of difficulty, all of our hardware deals. That’s blockwaresolutions.com. And that’s also where we print our research. Join our newsletter, we’ll send out our research reports as well. Stephan Livera: Fantastic. Well, I’ve really enjoyed chatting with you. Thanks for joining me. Matt D’Souza: Likewise. Thank you so much.
null
minipile
NaturalLanguage
mit
null
Protein analyses and reagents: microscale assay of calcium-binding activity of proteins and peptides using a nitrocellulose membrane. A simple and reliable method for the measurement of calcium binding to proteins and peptides was developed. It is composed of two procedures--filtration through a nitrocellulose membrane filter and estimation of 45Ca retained on the membrane. The routine assay was completed within a few minutes, and only microgram amounts of samples were necessary. This method permitted the quantitative determination of the calcium-binding activity of proteins and peptides including one with a molecular weight of as low as 4000. This method also permitted the detection of low-affinity interactions (Kd congruent to 10(-3) M), possibly because the nitrocellulose membrane did not show nonspecific binding of calcium and because a washing step was not employed in the routine assay. Ultrafiltration membranes when used in the apparatus gave no useful data.
null
minipile
NaturalLanguage
mit
null
Ever since Superman was first brought to the screen in 1941, superhero fans have always faced new adaptations of their favorite characters with both hope and trepidation. It’s part and parcel of being a fan of something whose canon is simply too big and sprawling to be directly adapted. What’s going to be included? What’s the tone? Will this new creative team do the character justice? Questions like these have generated good, clean nerd rage ever since Michael Keaton was cast as Batman. But for fans of Batman villainess/antiheroine Harley Quinn, there’s one more question to be asked when a new incarnation of the character looms—will this new project feature the Harley Quinn we know and love or will she only get to be the Joker’s “hot and crazy” girlfriend? I’ve been a fan of Harley Quinn since her debut in Batman: The Animated Series in 1992. I found her Bugs Bunny meets Lucille Ball chaotic neutral daffiness fascinating, laughed at her penchant for broad comedy, and loved her “friendship” with Poison Ivy. (I was a very confused and closeted kid, cut me a break.) Harley (as Dr. Quinzel) was the first comic book character I ever cosplayed as. I devoured her 2001 to 2003 self-titled series. I even bought every issue of Gotham City Sirens, Paul Dini’s perfectly serviceable book about Harley, Poison Ivy, and Catwoman often ruined by artist’s Guillem March’s inability to draw more than one kind of face on women. But ever since the New 52 came into our lives screaming “THIS AIN’T YOUR DADDY’S DC UNIVERSE!” at top volume in 2011, experience has worn me down when it comes to my beloved Harleen. I’d been excited to see what new adventures Harley would embark on after Gotham City Sirens. Seeing her pin the skinned face of her abusive ex-boyfriend to a coworker’s face and kissing it wasn’t exactly the sort of thing I’d been hoping for. And when Suicide Squad was announced, even though I thought Margot Robbie would make a fantastic Harley (just see her dry-as-a-bone parody of American Psycho for Vogue and her daffily cute interviews to promote Focus), my hackles were immediately raised at the idea of the brain trust behind the DC Extended Universe handling her. And, it turns out, said hackles were right on the money. This, of course, is not to say that there’s not quality Harley Quinn content out there. I still recommend her self-titled early aughts series to anyone remotely interested in her, even though it goes off the rails a bit after she gets back from Hell. (Long story.) Amanda Conner and Jimmy Palmiotti’s ongoing Harley Quinn series sees Harley, now based in Coney Island, go on a variety of wacky adventures. It’s been successful enough to warrant spin-offs like Harley Quinn and Power Girl and Harley Quinn’s Little Black Book. And she’s an integral part of DC Super Hero Girls, the high school AU turned best-seller. But in the wake of one poorly received Harley Quinn-centric film in Batman and Harley Quinn and ahead of potentially another poorly received Harley Quinn-centric film in the upcoming Joker and Harley Quinn movie described as “a criminal love story,” I’m left scratching my head and wondering—why is it apparently so hard to write Harley Quinn? I love Harley Quinn because she’s evolved past her origins as an aesthetically pleasing extra in Batman: The Animated Series into an engaging and complex character all her own. She’s a mentally ill queer Jewish antiheroine whose origin story is surviving the abuse she suffered at the Joker’s hands. She’s funny, fiercely loyal to her friends, and comfortable with her unique moral code and personal contradictions. Focusing only on her relationship with the Joker is the equivalent of taking the first sentence off of the “Early Life” section of someone’s Wikipedia page and pretending that’s the most interesting and important thing about them. “In 1832, at age 23, Lincoln and a partner bought a small generation store on credit in New Salem, Illinois” is a true and maybe even an influential part of Abraham Lincoln’s life, but you can see how it misses the highlights. But a surprising amount of creatives, especially those involved in the DC Extended Universe, overlook the Harley Quinn of the current comics, fully realized survivor and antiheroine, to focus on the woman she was when she was trapped in her abusive relationship with the Joker. It can be tempting to see this as nostalgia for Batman: The Animated Series. But it’s not. The real culprit is one of the more insidious elements of the male gaze—an inability to see a woman as a whole human being outside of her relationship with a man. That’s always a problem for female characters, but for Harley, this means that she’s literally defined by her abuser. Characterizing her as just the Joker’s main squeeze and centering the narratives with the biggest reach—such as her first onscreen debut—around him at best ignores and at worst romanticizes the toxicity of their relationship. It also ignores the wonderful character development she’s undergone ever since she debuted in “Joker’s Favor”. This myopic focus on her relationship with the Joker and, therefore, on her sexual desirability to straight men, becomes a case of missing the forest for the trees. Like downplaying the astonishing physical training Margot Robbie did to prepare for her role in Suicide Squad by putting her in stilettos. Like undermining Harley complaining that she gets treated like a whore by animating her with two butt cracks. Like overvaluing stories where Harley is hot, crazy, and just yearning for her puddin’ to take her away into domestic bliss over stories where she overcomes that abusive relationship to become an antiheroine all her own. Ultimately, writing Harley Quinn as a whole human being isn’t actually hard. Karl Kesel, Amanda Conner, and Marguerite Bennett, among many others, have proven time and again that you can. All you have to do is be cognizant and move past the male gaze that subtly implies that women aren’t whole human beings if they’re not being defined by a man, no matter how toxic that definition. There’s hope for Harley in the DC Extended Universe—despite rumors that the upcoming Joker and Harley movie will be replacing the upcoming Gotham City Sirens movie, Warner Brothers has confirmed that the latter remains in production. And maybe the upcoming Joker and Harley film will end with her kicking him to the curb. But you won't catch me holding my breath. To me, it’s very telling that Harley Quinn’s first two feature films have and will romanticize her relationship with the Joker before she even gets a chance to strike out on her own. So I’ll approach both the upcoming Joker and Harley movie and Gotham City Sirens the same way I do any Harley Quinn news—as the living embodiment of the yikes emoji.
null
minipile
NaturalLanguage
mit
null
Clinical Characteristics and Low Susceptibility to Daptomycin in Enterococcus faecium Bacteremia. Enterococcus faecium has high levels of resistance to multiple antibiotics, and the mortality due to E. faecium bacteremia is high. Accordingly, E. faecium strains with low susceptibility to daptomycin are a concern in clinical practice. This study assessed the predictive factors and prognosis of patients with bacteremia due to E. faecium as well as the antimicrobial susceptibility, particularly to daptomycin, among E. faecium isolates. The medical records of patients admitted to Osaka City University Hospital with E. faecalis (n = 60) and E. faecium (n = 48) bacteremia between January 2011 and March 2016 were retrospectively reviewed. The E. faecalis group (mean age: 62.0 years) included 22 women, and the E. faecium group (mean age: 59.1 years) included 19 women. Predictive factors for infection, prognosis, and isolate antimicrobial susceptibilities were evaluated. The mean Sequential Organ Failure Assessment score and mortality rate did not differ between the two groups. The independent predictors of E. faecium bacteremia in multivariate analysis included quinolone use (p = 0.025), malignancy (p = 0.021), and prolonged hospitalization (p = 0.016). Cardiovascular disease was associated with a reduced risk of E. faecium bacteremia (p = 0.015). Notably, the percentage of E. faecium isolates with low daptomycin susceptibility was higher than that of E. faecalis (8.5% vs. 0%, p = 0.036). Thus, E. faecium should be considered when administering antibiotic therapy to patients with a history of these predictors. Furthermore, the use of daptomycin should be avoided in case of E. faecium with low susceptibility to daptomycin.
null
minipile
NaturalLanguage
mit
null
Field of the Invention This invention belongs to the field of daily necessities. Specifically, it is a type of folding sofa with a wrap-around skirt. It can be folded into a flat shape and its elastic cloth fabric can wrap-around the support legs of the sofa. Technical Background Existing Chinese Application No. 201410405852.9 is a type of folding sofa which consists of leg frames on both sides and the main sofa body, where the leg frames include front legs and rear legs that are movably hinged together. The front legs are longer than the back legs. The longer sections of the front legs form the back-support section of the sofa. The main sofa body is made from soft fabric and consists of a one-piece integrated seat, arm rest, and back rest fabric. The rear of the back-rest fabric is equipped with a back rest wrapping fabric that fixes the back-rest fabric to the back-support sections of the front legs. The outward-facing side of the arm rest fabric is equipped with arm rest wrapping fabric that fixes the arm rest fabric to the upper sections of the rear legs. There is a reinforced cord between the uppermost section of the rear legs and a point on the upper section of the front legs such that the cord is horizontal to the ground when the sofa is opened. This stretched reinforced cord provides support for the arm rest fabric. The seat section of the main sofa body which is directly supported by the front and rear legs is formed when the back-rest fabric and the arm rest fabric are stretched open by opening the sofa. It is very comfortable to sit in. The back rest wrapping fabric and the arm rest wrapping fabric give the invention the feeling of width and size associated with a sofa. Since the main sofa body is supported only by the front and rear legs, the main sofa body fabric can easily lose its shape, especially when a user leaves the seat, thereby affecting the appearance of the sofa. Another shortcoming of this sofa is that its support legs are exposed, giving it an unsightly top-heavy impression, as is shown in FIGS. 6 and 7. Improving the deficiencies of the existing folding sofa, simulating the shape of a hard support sofa, and creating a comfortable folding sofa are the research objects of this invention.
null
minipile
NaturalLanguage
mit
null
Given a method name, it returns a List of methods that are available with this name. classA{methodx($a) {}}; classBisA{methodx() {}}; sayB.^can('x').elems; # OUTPUT: «2␤» forB.^can('x') { say.arity; # OUTPUT: «1, 2␤» } In this example, class B has two possible methods available with name x (though a normal method call would only invoke the one installed in B directly). The one in B has arity 1 (i.e. it expects one argument, the invocant (self)), and the one in A expects 2 arguments (self and $a).
null
minipile
NaturalLanguage
mit
null
Last weekend — Friday, Saturday and Sunday — not a single person was reported shot in all of New York City. The Big Apple is home to 8.6 million people and not a single reported shooting in the entire city. Compare that to the last full weekend of August in Memphis, Tennessee, a population of about 650,000. Seven people were shot and killed. All seven of the victims were men. Six of the dead were between the ages 23 and 49. The carnage is Memphis pales in comparison to Chicago’s deadly first weekend of August. At least 72 people were shot, including 12 fatally. Chicago, with a population of 2.7 million — about a third of New York City — hasn’t seen things improve. During the third weekend of August, 61 people were shot with eight dead. Do you think guns in Chicago are a problem? Police Superintendent Eddie Johnson told the USA Today that officers shut down 68 illegal block parties during the most recent deadly weekend seizing 83 guns, and arresting 29 people on gun charges. Deadly weekends are not exclusive to Chicago and Memphis. At least seven people were shot and killed during the last weekend in September in Baltimore. Police told CBS WJZ two people were gunned downed Saturday evening, with three more fatal shootings overnight Saturday, and another one Sunday morning and the seventh Sunday evening. Baltimore has a population of about 618,000 people. How has America’s largest city found the answer to gun violence? “NYPD has the best strategy, the best training ... because this department never rests on its laurels,” New York Mayor Bill de Blasio told the New York Post. “This department always seeks to get better.” The story is bleak in Chicago. "There is a shortage of values about what is right, what is wrong," Mayor Rahm Emanuel told CBS News. "We as a city, in every corner, have an accountability and responsibility. If you know who did this, be a neighbor. Speak up." Bill Gibbons of the Memphis Shelby Crime Commission told WREG.com, “I think what we’re facing is a situation where, unfortunately, people are trying to resolve conflict through violence, and we need to address that." If New York City has found the solution to gun violence why isn’t it being replicated? “We know far less about gun violence as a cause of injury and death than we do about almost every medical problem,” Dr. Elinore Kaufman, chief resident in surgery at Presbyterian/Weill Cornell Medical Center told Time. In 1996, Congressman Jay Dickey, a self-proclaimed “point-man” for the National Rifle Association, proposed a legislative amendment that removed millions of dollars from the Center for Disease Control’s budget earmarked for firearms-related research. Twenty-one years later, things haven’t changed. According to a 2017 study published in the Journal of the American Medical Association, gun violence research received what amounts to 5.3 percent of the federal funds dedicated to studying motor-vehicle accidents — even though guns and cars kill at about the same rate. According to the Washington Post, there are no national studies of who owns guns, how gun owners acquired their weapons, the theft of guns, the number of households with guns, the attributes of high-quality gun training or the risk factors associated with gun violence. As Congress hides from the NRA, states have been left to pick up the slack, and most states have been reluctant. The NRA is equally influential in state capitals across the country. However, California has stepped up. The state recently opened the nation’s first state-funded firearms-violence research center, on the Sacramento campus of the University of California-Davis. Garen Wintemute, the director of the center, told the Post, “California essentially said that the federal government wasn’t fulfilling its responsibility, so we’re going to step into the breach.” — Matthew T. Mangino is of counsel with Luxenberg, Garbett, Kelly & George P.C. His book The Executioner’s Toll, 2010 was released by McFarland Publishing. You can reach him at www.mattmangino.com and follow him on Twitter @MatthewTMangino. Never miss a story Choose the plan that's right for you. Digital access or digital and print delivery. Original content available for non-commercial use under a Creative Commons license, except where noted. Waynesboro Record Herald - Waynesboro, PA ~ 30 Walnut St. Waynesboro, PA 17268 ~ Privacy Policy ~ Terms Of Service
null
minipile
NaturalLanguage
mit
null
Prospective associations between peer victimization and aggression. The current study involved a short-term longitudinal study of young children (M = 44.56 months, SD = 11.88, N = 103) to test the prospective associations between peer victimization and aggression subtypes. Path analyses documented that teacher-reported physical victimization was uniquely associated with increases in observed physical aggression over time. The path model also revealed that teacher-reported relational victimization was uniquely associated with statistically significant increases in observed relational aggression over time. Ways in which these findings extend the extant developmental literature are discussed.
null
minipile
NaturalLanguage
mit
null
Radios Resources Police Radios Press Release RCC Selected by St. Johns County, Florida to Assist in Procuring a New P25 Countywide Radio System Woodbridge, NJ – RCC Consultants, Inc. has been selected by St. Johns County, Florida to assist the County in procuring a new, standards-based P25 interoperable 800 MHz voice radio system. The new system will serve all public safety and public service agencies in the County, the City of St. Augustine and the City of St. Augustine Beach. Public safety agencies within St. Johns County utilize VHF (150 MHz) and UHF (450 MHz) conventional radio systems that are not interoperable with other County or City agencies. The radio systems also suffer from poor coverage and a lack of available radio channels. Additionally, the County must bring its radio communications into compliance with Federal requirements for narrowbanding. Most large public safety agencies within Florida and around the nation have moved or are planning to move their radio system technology to a standards-based, P25 system to improve interoperability on a local and national level. Interoperable communications capability is especially important in coastal areas such as St. Johns County, where the realistic threat of hurricanes is an annual event. RCC has been working with the County to develop the radio system requirements for hurricane-hardened sites and in-building coverage Countywide. The proposed P25 trunked radio system will include fifteen 800 MHz channels and 11 hardened tower sites at key locations around the County. RCC is assisting in developing the Request for Proposal (RFP) that will be used for a competitive procurement of the voice radio system. Additionally, RCC will assist the County with proposal evaluations, provide FCC licensing support, and design a microwave system and a fire station alerting system. About RCC Consultants, Inc. RCC Consultants, Inc. is a global telecommunications consulting, engineering and integration firm. A leader in the public safety industry since 1983, RCC specializes in the design and implementation of radio communications systems, microwave and fiber optic systems, broadband, intelligent transportation systems and emergency telephone systems, as well as the design of communications centers, tower sites and monitoring facilities.
null
minipile
NaturalLanguage
mit
null
In their interesting study on the concomitant reduction in inflammatory and oxidative stress and mean amplitude of glycemic excursions (MAGE) following treatment with dipeptidyl peptidase-IV (DPP-4) inhibitors, sitagliptin and vildagliptin, in patients with type 2 diabetes, Rizzo et al. ([@B1]) propose that the reduction in MAGE leads to the reduction in indices of oxidative and inflammatory stress. However, the recent demonstration that sitagliptin exerts a rapid and potent anti-inflammatory effect commencing within 2 h of the intake of the first dose of 100 mg suggests that the anti-inflammatory effect is a direct one and not secondary to a reduction in MAGE, which would take longer ([@B2]). It is noteworthy that within 2 h of the intake of sitagliptin, there is a \>90% inhibition of the DPP-4 enzyme, a reduction in nuclear factor-κB binding, and the expression of several inflammatory mediators, including inhibitory κB kinase β, chemokine receptor 2, and Toll-like receptor 2 ([@B2]). In addition, there was a reduction in the expression of CD26 in mononuclear cells. CD26 is essentially DPP-4 bound to cell membranes. Thus, sitagliptin not only inhibits DPP-4 activity in plasma, it also suppresses the expression of cellular CD26. It is also noteworthy that the concentration of glucagon-like peptide 1 (GLP-1) increases significantly within 2 h of the intake of sitagliptin and that exenatide, a GLP-1 agonist, also exerts a rapid anti-inflammatory effect ([@B3]). Thus, GLP-1 may also contribute to the anti-inflammatory effect by DPP-4 inhibitors in the long term. These anti-inflammatory effects of DPP-4 inhibitors and GLP-1 agonists are important since they could contribute to potential antiatherogenic effects in the long term and thus reduce cardiovascular events. Indeed, in the retrospective analyses of various trials carried out with DPP-4 inhibitors, there is a strong signal showing a reduction in cardiovascular events ([@B4]). No potential conflicts of interest relevant to this article were reported.
null
minipile
NaturalLanguage
mit
null
If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. Shutdown Windows when pwd-protected screensaver is active... Hi. I have an API question. I'm using ExitWindowsEx function to shutdown Windows (usually Win2K). It is working fine, it shutsdown, restarts, etc. If a screensaver is active and password protected though, it does not work at all. Is there a way to "persuade" Win2K to shutdown even if a password-protected screensaver is active? I dont have a definate answer for ya unfortunately, but I wonder if it is possible to somehow find the threadID of the screensaver and kill it. I can remember a few years ago fooling around with a program called Sub7 (by mobman) which could do this remotely but that was very very naughty!!! It is indeed a naughty solution but i don't believe it will solve my problem. I'm using Win2K and it is most probable that the screensaver "tells" the system to lock itself so killing the ss will not unlock the system. This might work on a Win98 system. Originally posted by Illuvatan you're trying to shutdown windows while the workstation is locked isn't it ? windows 2000 has no password protected screensavers, windows locks the workstation and then starts the screensaver. Yes, that's what i'm trying to do... I know about all the things you mention here. And I don't know any way to unlock a workstation without entering a password. Maybe you could try using the shutdown.exe windows has. Windows has no such exe AFAIK. Perhaps you are talking about a third-party utility. In any case, do you know of any utility which will shutdown the system, even if it has been locked? * The Perfect Platform for Game Developers: Android Developing rich, high performance Android games from the ground up is a daunting task. Intel has provided Android developers with a number of tools that can be leveraged by Android game developers. * The Best Reasons to Target Windows 8 Learn some of the best reasons why you should seriously consider bringing your Android mobile development expertise to bear on the Windows 8 platform.
null
minipile
NaturalLanguage
mit
null
Low Blood Pressure (Hypotension) treatment Description Hypotension, also known as low blood pressure, is a condition in which the blood pressure during and after each heart beat is too low. Blood pressure measures the force of blood pumping inside arterial walls, and normal blood pressure falls between 90/60 mmHg and 120/80 mmHg. The top number is the systolic pressure (when blood vessels contract) and the bottom number is diastole pressure (resting heartbeat). When arteries dilate and there is not enough blood flow, it results in a decrease of pressure. The 3 different types of hypotension are: (1) Orthostatic hypotension - which occurs right after standing up from a sitting or lying down position (2) Neurally Mediated Hypotension (NMH) - resulting from a miscommunication between the brain and heart (3) Shock - severe drop in blood pressure brought on by a sudden drop in blood flow. Shock is an emergency condition where blood pressure cannot return to normal on its own. View more... Causes Two common causes of orthostatic hypotension are dehydration and old age. Other causes include anemia, severe infections, disorders of the central nervous system, pulmonary embolism, and certain medicines used to treat high blood pressure (hypertension), such as diuretics. Neurally mediated hypotension occurs after standing for a long period of time. Blood begins to pool in the legs, so the brain tells the heart that blood pressure is too high, and in turn blood pressure is decreased even more. Septic shock results from severe infections entering the bloodstream; hypovolemic shock occurs as a result of a major loss in body fluids, and cardiogenic shock is caused by a drastic decrease in the body's ability to pump blood (i.e. heart attack, pulmonary embolism, arrhythmia). View more... Prevention Avoiding alcohol, avoiding standing for a long time (if you have NMH), drinking plenty of fluids, getting up slowly after sitting or lying down, or using compression stockings to increase blood pressure in the legs. Common Symptoms If someone suffers from hypotension, their heart, lungs, brain, and other organs are not receiving an adequate amount of blood flow and oxygen. Common symptoms include dizziness, feeling light headed, blurry vision, confusion, weakness, nausea, and chest pain. A person with severe hypotension as a result of shock brought upon by heart failure or major blood loss will exhibit cold, clammy skin that is often blue or pale in color, weak and rapid pulses, and rapid, shallow breathing. Vasovagal syncope is brought upon by a severe drop in blood pressure and is the most common cause of fainting. View more... Rare Symptoms Less common symptoms are described as "an electric shock running through the body," or even "burning in one extremity." Other rare symptoms include constipation, diarrhea, myofascial pain, noise and light sensitivity, and weight loss and gain. Since blood flows to every minute part of the body, hypotension can affect literally any part of the body. Thus, the symptoms are innumerable and it is difficult to pinpoint exactly what rare symptoms of hypotension a person may exhibit. View more... Traditional Treatment Treatment for hypotension is determined by the cause of the low blood pressure. Low blood pressure without signs or symptoms is usually not unhealthy, and the body can usually correct itself. Treatment for those suffering from orthostatic hypotension is to increase fluid and electrolyte intake with IVs or to take medications that increase blood pressure. Your doctor can adjust your prescriptions if you are taking medications that cause NMH. Ibuprofen or indomethacin are helpful in treating postprandial hypotension (a drop in blood pressure after eating a meal). Vasovagal syncope can be treated with beta blockers, selective serotonin reuptake inhibitors, or fludrocortisone to prevent dehydration. View more... Alternative Treatment Herbs such as bayberry, ginger, hawthorn berry, ginseng, capsicum, mate, and vervain; Other alternative treatments include yoga therapy, acupressure, and healing through reflexology. Choose a condition to compare treatments based on user feedback. You can sort by Effectiveness, Holistic Benefits or Side Effects RateADrug user scores, or the number of Ratings. Scores gain significance with the number of ratings, so please share your experiences - rate your drug! A catheter based procedure that disrupts nerves around the kidneys to dramatically reduce high blood pressure is being tested in Australia. Additionally, herbal therapies are being studied including Rauwolfia, Stephania, Crataegus, and Panax.
null
minipile
NaturalLanguage
mit
null
Pennsylvania Railroad 6755 Pennsylvania Railroad 6755 is a 4-8-2 "Mountain" type steam locomotive built in 1930 for the Pennsylvania Railroad by the railroad's own Altoona Works as a member of the M1b locomotive class for mainline freight service. Retired from commercial service in 1957, the locomotive was preserved by the Pennsylvania Railroad and was placed on display at the Railroad Museum of Pennsylvania in Strasburg, Pennsylvania. The 6755 is the only M1 class locomotive to have survived into preservation. History The 6755 was built by the Altoona Works in 1930. The 6755 was a class M1a and was used predominantly in freight service, though it would occasionally be used for passenger trains. In 1953, the locomotive went back to the Altoona Works and was rebuilt into a class M1b. The locomotive continued to be used for freight service until January 1957 when it was retired from the roster. Today Today, the 6755 is on static display at the Railroad Museum of Pennsylvania in Strasburg, Pennsylvania. The 6755 has since been deteriorating at a rapid pace, with its boiler jackets removed in the early 2000s prolonged exposure to the elements has wreaked havock on major parts of the locomotive causing structural rust. The 6755 is one of the locomotives the museum plans to place inside the roundhouse currently under construction as of March 2014. See also NYC 3001- This is the New York Central Railroad's version of the M1 that survives. Just like the 6755, the 3001 was a dual service locomotive. References Category:Railway locomotives on the National Register of Historic Places in Pennsylvania Category:Transportation in Lancaster County, Pennsylvania Category:4-8-2 locomotives 6755 Category:Collection of the Railroad Museum of Pennsylvania Category:Standard gauge locomotives of the United States Category:Preserved steam locomotives of the United States Category:National Register of Historic Places in Lancaster County, Pennsylvania
null
minipile
NaturalLanguage
mit
null
APP Information Download Version 2.1.0 (468) Apk Size 33.12 MB App Developer BANDAI NAMCO Entertainment Inc. Malware Check TRUSTED Install on Android 4.1.x and up App Package com.bandainamcoent.saomdas.apk MD5 355a42205cc647bb1134c4bc1c032b07 Rate 4.36 Website https://bandainamcoent.co.jp/ Download SWORD ART ONLINE;Memory Defrag 2.1.0 APK App Description SWORD ART ONLINE;Memory Defrag is bandainamcoent,saomdas,action, content rating is Very Low Maturity (PEGI-7). This app is rated 4.36 by 110 users who are using this app. To know more about the company/developer, visit BANDAI NAMCO Entertainment Inc. website who developed it. com.bandainamcoent.saomdas.apk apps can be downloaded and installed on Android 4.1.x and higher Android devices. The Latest Version of 2.1.0 Available for download. Download the app using your favorite browser and click Install to install the application. Please note that we provide both basic and pure APK files and faster download speeds than APK Mirror. This app APK has been downloaded 41952+ times on store. You can also download com.bandainamcoent.saomdas APK and run it with the popular Android Emulators. Brave the virtual world with the heroes of Sword Art Online in one of Japan’s most popular anime role playing games, the brand-new action RPG, SWORD ART ONLINE;Memory Defrag! In SWORD ART ONLINE;Memory Defrag, players will join Kirito, Asuna, Leafa, and other fan favorite characters from the original manga and hit anime series from Japan. Take on the role of legendary heroes in this unique action role playing game as you unleash a flurry of skills to vanquish a formidable army of enemies on the dangerous virtual frontier! Master a variety of play styles, weapons, and skills such as Dual-wielding, one-handed swords, guns, bows, or magic to take on every kind of monster imaginable! Features: - Experience the original Japanese anime story and an all-new original storyline just for the game! - Play with all your favorite characters like Kirito, Asuna, Leafa, and more from the manga and anime series! - Join parties with friends and other players to take down massive boss monsters in multiplayer mode! - Free to play and fun for everyone! SUPPORT: https://bnfaq.channel.or.jp/contact/faq_list/1803 BANDAI NAMCO Entertainment Inc. Website: https://bandainamcoent.co.jp/english/ By downloading or installing this app, you agree to the BANDAI NAMCO Entertainment Terms of Service. Terms of Service: https://legal.bandainamcoent.co.jp/terms/ Privacy Policy: https://legal.bandainamcoent.co.jp/privacy/ Note: This game contains some items available for in-app purchase that can enhance gameplay and speed up your progress. In-app purchases can be disabled in your device settings, see https://support.google.com/googleplay/answer/1626831?hl=en for more details. This application is distributed under the official rights from the license holder. ©2017 REKI KAWAHARA/KADOKAWA CORPORATION AMW/SAO-A Project ©BANDAI NAMCO Entertainment Inc. Developed by WFS App ChangeLog A few bugs fixed. App Screens Permissions requires following permissions on your android device. android.permission.ACCESS_NETWORK_STATE android.permission.INTERNET android.permission.KILL_BACKGROUND_PROCESSES android.permission.VIBRATE android.permission.WAKE_LOCK com.anddoes.launcher.permission.UPDATE_COUNT com.android.vending.BILLING com.bandainamcoent.saomdas.permission.C2D_MESSAGE com.google.android.c2dm.permission.RECEIVE com.google.android.finsky.permission.BIND_GET_INSTALL_REFERRER_SERVICE com.htc.launcher.permission.READ_SETTINGS com.htc.launcher.permission.UPDATE_SHORTCUT com.majeur.launcher.permission.UPDATE_BADGE com.sec.android.provider.badge.permission.READ com.sec.android.provider.badge.permission.WRITE com.sonyericsson.home.permission.BROADCAST_BADGE android.hardware.faketouch android.hardware.screen.portrait Allows the app to view information about network connections such as which networks exist and are connected.Allows the app to create network sockets and use custom network protocols. The browser and other applications provide means to send data to the internet, so this permission is not required to send data to the internet.Allows the app to end background processes of other apps. This may cause other apps to stop running.Allows the app to control the vibrator.Allows the app to prevent the phone from going to sleep.In-app Billing on Google Play provides a straightforward, simple interface for sending In-app Billing requests and managing In-app Billing transactions using Google Play.Allows apps to accept cloud to device messages sent by the app's service. Using this service will incur data usage. Malicious apps could cause excess data usage.
null
minipile
NaturalLanguage
mit
null
Q: Show a subspace formed by a Klein bottle is homotopy-equivalent to $S^1 \vee S^1 \vee S^2$ I am trying to solve Hatcher, chapter 0, 20: Show that the subspace $X \subset \mathbb{R}^3$ formed by a Klein bottle intersecting itself in a circle, as shown in the figure, is homotopy equivalent to $S^1 \vee S^1 \vee S^2 = Y$.                                             I do not understand how $X$ can be homotopic to $Y$ since I do not think that they are even homologic. Intuitively, $H_2(Y)=\mathbb{Z}$ since a subspace $S^2$ disconnects $\mathbb{R}^3$ into two pieces. But $X$ 'disconnects' $\mathbb{R}^3$ only into one piece so $H_2(X)=0$. A: I'm not sure why you think $X$ disconnects $\mathbb{R}^3$ into "one piece" (I'm not sure what that would even mean); there's an inside and an outside to $X$, just like there is for the sphere. Here is a (pictoral) proof of the homotopy - of course, you should provide some justification for why each step is a homotopy equivalence: The order of the pictures is $\begin{smallmatrix} 1 & 2\\ 3 & 4\\ 5 & 6\end{smallmatrix}$.
null
minipile
NaturalLanguage
mit
null
Thus far the surprise has been pleasant as the precipitation from this late season Nor’easter remains more rain than snow falling from a darkened sky. I just got back from breakfast at Peg’s Place and am on hold waiting for a customer service representative to confirm rewards mileage on my account that I have earmarked for round-trip airfare to Dallas in August where a business conference will be conducted. I have been rather idle in the energy deregulation business for a few months and in attending Ambition I anticipate a much-needed revival in accelerating leadership development for business growth in all my endeavors. Tomorrow I have an appointment to review the opportunity with a friend at a local cafe and if she joins my business it will serve to ignite momentum. If not, it’s still an opportunity to forge a new connection, which is always a plus. Last night I enjoyed a hearty meal with family as my sister and brother-in-law served up generous portions of beer can chicken, sautéed veggies, tater tots and ginger bread along with cherry pie for desert. The laughter was equally generous as we indulged in our own twisted sense of humor queuing up Epic Rap Battles on You Tube before dinner and continuing with the very adult humor through the meal. There was talk of anal leakage from the Wow Doritos that my mother had stocked in the cabinet years ago due its olestra as a fat substitute, followed by joking about an alternative prescription for my brother in dealing with the symptoms of Rheumatoid Arthritis, taking Cialis as an 8 hour erection is sure to distract you from the pain of aching joints. During dessert I grabbed the Redi-Whip can and pretended to read from the label “Warning: Use only as directed. Caution for those with arthritis and hemorrhoids.” My sister immediately snatched the can out of my hands to verify the content on the label and chuckled once she realized I was teasing. We even rationalized my father’s consumption of booze suggesting he skip the wine and instead drink vodka straight up to reduce his sugar intake, which exacerbates diabetic symptoms. It was good medicine to make light of health challenges. Although doing so fully aware that auto-immune disorders are not to be taken lightly, laughter is very healing. Seems to be a growing consensus of unrest if not disgust among the citizenry of the United States of America. Where there is a lack of consensus is on how to address the widening gap between those in positions of political power, and those who are supposedly represented by these elected officials. The line between public and private sector has become increasingly blurred as campaigns are funded and votes influenced by cash-flush lobbyist groups working on behalf of the global multinational corporations. With the recent advent of the Occupy Wall Street movement we have a sizeable contingent claiming to represent the 99% against the imbalanced interests of the upper 1% in terms of representation and influence upon lawmakers. Political factions organize and mobilize only to be placated by cutting deals with those they are mislead to trust in gaining support. While I am certainly under no illusions that our current form of government is to be entrusted with the will of the people, I have my reservations about fighting the establishment. Historically, there may have been battles won and yet here we are centuries after the founding of this fine nation with an order of rule quite akin to the oppression the colonists had fled from Great Britain. It only goes to show that what we resist persists and the only true power of change must be in the hearts and minds of individuals gathering in solidarity. So long as we are divided and stratified by class, race or ideology we the people will invariably find ourselves under the thumb of fascism. We must take full responsibility for our thoughts, feelings and actions in awakening to our true nature as divine creations. To give up all hope for change, or to rise up in any form of resistance to what is, only makes us a victim. It is only in embracing with loving acceptance all parts of ourselves and this world we so abhor that transformation may occur. And in so doing the generations to come will truly inherit the wealth of the meek. In common wealth, SjK Advertisements Share this: Like this: Related Glad to hear of your light mood. Laughter is a wonderful healer. Prayers that all of your dreams come to fruition. Agree with the political words. I love what this country was founded upon, yet we are so far from there and I fear the anger will win. Blessings.
null
minipile
NaturalLanguage
mit
null
My Cup Runneth Over Just getting back from a Colorado vacation, if you don’t see God there you haven’t got your eyes open. Everywhere you look there is abundance, Mountains, wildlife… Picture with me walking down to a sparkling clear mountain lake, from a distance you can see the trout rising all over the surface, when you get close you see the fish easily in the clear mountain water, big beautiful rainbows and browns, cutthroats and brookies, as you stand there fishing a huge Mule Deer doe comes down next to you to feed on the brush not seeming to mind at all your intrusion. It’s a consecrated moment, yes looks closely into the word consecrated and you’ll find David’s cup overflowing. The Hebrew root of the words fill and consecrate are the same word, male’.So when God blessed the animals in Genesis 1:22 he told them “And God blessed them, saying, Be fruitful, and multiply, and fill H4390 the waters in the seas, and let fowl multiply in the earth”. Later when God told Moses to consecrate Aaron He used the same word in Exodus 28:41: And thou shalt put them upon Aaron thy brother, and his sons with him; and shalt anoint them, and consecrate H4390 them, and sanctify them, that they may minister unto me in the priest’s office. Go back with me to the lake and you know it deep inside all these fish and wildlife, this place is consecrated, my cup overflows, but don’t forget why: “The Lord is my Shepherd, I shall not want.” So how about your car is it consecrated, or is it in want? Want of gas, oil, air in the tires, a new timing belt. How is it that, this lake in Colorado is teaming with fish? Answer: there are fish and wildlife people in abundance with a 40 million dollar plus budget to make sure that this place is filled with wildlife. A full tank, a dip stick that reads full, tires with proper inflation, that life and life abundantly, consecrated. God’s economy is not one of lack but abundance. Work is involved but that too is good and really part of the joy of having God at your side knowing He is providing it all.
null
minipile
NaturalLanguage
mit
null
INTRODUCTION ============ G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors, with approximately 800 genes identified in humans ([@b19-bt-26-101]). GPCRs transmit extracellular signals into the intracellular region resulting in interaction with various signaling proteins ([@b5-bt-26-101]; [@b34-bt-26-101]; [@b35-bt-26-101]). These GPCR signaling regulate vital signaling pathways, which are involved in critical physiological and pathological functions in various organs in the sensory, metabolic, endocrine, neuromuscular, and central nervous systems ([@b19-bt-26-101]; [@b26-bt-26-101]). Owing to their importance in physiology and pathology, approximately 30--40% of currently marketed drugs target GPCRs. GPCRs are composed of seven transmembrane α-helical domains with an extracellular N-terminus and an intracellular C-terminus ([Fig. 1A](#f1-bt-26-101){ref-type="fig"}). Although GPCRs share a common overall structure, the sequence similarity is relatively limited, and the sequences and lengths of the N-termini, cytoplasmic loops, and C-termini vary among GPCRs ([@b27-bt-26-101]). In 2003, human GPCRs were grouped into five families (Rhodopsin, Secretin, Adhesion, Glutamate, and Frizzled families) based on phylogenetic analysis ([@b8-bt-26-101]) ([Fig. 1](#f1-bt-26-101){ref-type="fig"}). Currently, a GPCR database, GPCRdb (<http://gpcrbd.org/>) ([@b18-bt-26-101]), classified human GPCRs into 286 Rhodopsin (excluding olfactory receptors), 15 Secretin, 33 Adhesion, 22 Glutamate (including three taste 1 receptors), and 11 Frizzled families ([@b16-bt-26-101]; [@b18-bt-26-101]). Twenty-five taste 2 receptors and six orphan receptors are not included in any of these families. Completion of the Human Genome Project revealed that many proteins have genetic variants such as nucleotide insertions, deletions, or exchanges. Although majority of the genetic variants are hypothesized to be functionally neutral ([@b14-bt-26-101]), some natural variants affect the function of the gene, usually involving non-synonymous or missense variants that change the amino acid sequence ([@b9-bt-26-101]). Genetic variants identified in GPCRs can influence receptor expression, proper folding, targeting within cell organelles, activation, function, desensitization, and ligand binding ([@b27-bt-26-101]; [@b10-bt-26-101]). Therefore, the genetic alterations in GPCRs are involved in the occurrence of genetic diseases and different drug responses ([@b28-bt-26-101], [@b29-bt-26-101]). It has been reported that there are extensive inter-patient variations in therapeutic responses to the GPCR-targeting drugs, that are caused by the genetic variations in GPCRs between patients ([@b7-bt-26-101]). Therefore, if we thoroughly understand the link between natural variants of GPCRs and the effects of these natural variants on disease development and drug responses, it would be possible to develop a rational scheme to selectively treat patients with genetically altered GPCRs. There have been efforts to analyze the genetic variations in GPCR families with respect to their functional consequences and/or in relation to their distribution in the structural context. For example, GPCRdb or GPCR NaVa (<http://nava.liacs.nl/>) is devoted to provide graphically accessible information on GPCR mutations and their known functional consequences ([@b30-bt-26-101]; [@b13-bt-26-101]). With these database resources, one can easily access the natural variant information of individual GPCRs, but understanding the bigger picture of the domain distribution of all known GPCR natural variants is not yet achieved. Comprehending the overall trend of domain distribution of GPCR natural variants would provide valuable information to prioritize the investigation of genotype-phenotype relationship and to predict yet-to-be-discovered natural variants. Currently, however, there are only few studies that analyzed the distribution of genetic variations of only a subset of GPCRs ([@b17-bt-26-101]; [@b24-bt-26-101]; [@b30-bt-26-101]). The present study analyzed the non-synonymous natural variants that occur in all human non-olfactory GPCRs from the five GPCR families (a total of 367 GPCRs) using UniProt (<http://www.uniprot.org/>) ([@b3-bt-26-101]) and GPCRdb databases. The positions of the natural variants were mapped onto the structural domains, and the occurrence patterns were analyzed. MATERIALS AND METHODS ===================== Database analysis ----------------- The list of human non-olfactory GPCRs was retrieved from GPCRdb (<http://gpcrdb.org/>). The classification of these GPCRs into five families and assignment of structural domains for all listed GPCRs were also based on GPCRdb. The non-synonymous natural variants of the listed human non-olfactory GPCRs were obtained from the UniProt database (<http://uniprot.org/>), and the positions of these variants were mapped on the structural domains based on the generic numbering system provided by GPCRdb. Dopamine receptor type 1 mutant construct generation and cell lines ------------------------------------------------------------------- Dopamine receptor type 1 (D1R) cDNA was described in previous studies ([@b6-bt-26-101]; [@b4-bt-26-101]). The DRY, WxP, NPxxY motifs were mutated to DHY, WxS, and NSxxY respectively via site-directed mutagenesis using PCR. Gαs-stably transfected HEK293 cell line was generated by selecting survived colonies after transfecting Gαs cDNA using Lipofectamine 2000 Reagent (ThermoFisher Scientific, Waltham, MA, USA) and G418 (Duchefa Biochemie, Haarlem, The Netherlands) antibiotic treatment. cAMP assay ---------- Gαs-stably transfected HEK293 cells were cultured in 12-well plate until the confluency reached 80%, and the cells were transfected with D1R wild type and mutant constructs. After 20--24 hrs later, about 3000 cells were seeded onto 96-well plate and were incubated for another 20--24 hrs in 5% CO~2~ at 37°C. The cells were pre-treated with 250 µM 3-isobutyl-1-methylxanthine (IBMX) (Sigma-Aldrich, St. Louis, MO, USA) and 200 µM Ro 20-1724 (Sigma-Aldrich) to prevent cAMP hydrolysis, and the D1R receptors were activated by 5 min incubation with 500 nM dopamine (Sigma-Aldrich) or buffer vehicle. cAMP levels were measured using cAMP-Glo^TM^ Assay kit (Promega, Fitchburg, WI, USA) according to the manufacturer's manual. The luminescence levels were detected by Synergy HTX (BioTek Instruments, Winooski, VT, USA). Immunofluorescence ------------------ D1R-expressing cells were washed with ice-cold PBS and fixed with 4% formaldehyde in PBS for 15 min. After washing out formaldehyde with PBS, cells were permeabilized with 0.25% Triton-X 100 in PBS for 5 min. After washing with PBS, cells were blocked with 10% BSA in PBS for 1 hr and incubated with FLAG M2 primary antibody (Sigma-Aldrich) for 2 hrs followed by Rhodamine Red-X secondary antibody (Invitrogen) for 1.5 hr. The immunofluorescence images were taken by Zeiss LSM 700 confocal microscope (Zeiss, Oberkochen, Germany). RESULTS ======= Distribution of GPCR non-synonymous natural variants within GPCR families ------------------------------------------------------------------------- Human GPCRs are categorized into five families based on phylogenetic analysis ([@b8-bt-26-101]). Each family shares seven transmembrane (TM) domains with varying N-termini and ligand-binding sites ([Fig. 1B--1F](#f1-bt-26-101){ref-type="fig"}) ([@b16-bt-26-101]). Several previous studies have analyzed the natural variants that occur in GPCRs ([@b21-bt-26-101]; [@b23-bt-26-101]; [@b17-bt-26-101]; [@b24-bt-26-101]; [@b30-bt-26-101]). However, these studies analyzed only a subset of GPCRs such as monoamine or peptide-binding GPCRs ([@b21-bt-26-101]; [@b17-bt-26-101]). In the present study, non-synonymous natural variants of all human non-olfactory GPCRs (except twenty five taste 2 and six un-categorized orphan receptors) were obtained from the UniProt database; UniProt annotates non-synonymous natural variants, including polymorphisms; variations between strains, isolates, or cultivars; disease-associated mutations; and RNA editing events, whereas mutations that induce major changes such as frame-shifts or premature stops are not annotated. Non-synonymous natural variants were found in approximately 72% (207 out of 286) of the Rhodopsin family, 80% (12 out of 15) of the Secretin family, 79% (26 out of 33) of the Adhesion family, 82% (18 out of 22) of the Glutamate family, and 55% (6 out of 11) of the Frizzled family GPCRs showing that natural variants occur in majority of the GPCRs in all GPCR families. Distribution of GPCR non-synonymous natural variants within structural domains ------------------------------------------------------------------------------ The positions of natural variants were mapped and assigned to 16 structural domains (i.e., one N-terminus, one C-terminal tail, seven TM domains, three intracellular loop regions, three extracellular loop regions, and 1 helix 8) for all 367 GPCRs ([Table 1](#t1-bt-26-101){ref-type="table"}, [Fig. 2](#f2-bt-26-101){ref-type="fig"}). In all GPCR families, relatively more GPCRs have non-synonymous natural variants in the N-terminus, C-terminal tail, and TM domains than in the extracellular or intracellular loops ([Table 1](#t1-bt-26-101){ref-type="table"}, [Fig. 2A](#f2-bt-26-101){ref-type="fig"}). Especially, the N-terminus contained the highest average number of non-synonymous natural variants in all GPCR families ([Fig. 2B](#f2-bt-26-101){ref-type="fig"}). The percentage of GPCRs with non-synonymous natural variants at the N-terminus or the average number of non-synonymous natural variants at the N-terminus were relatively smaller in the Rhodopsin family than in the other GPCR families ([Fig. 2A, 2B](#f2-bt-26-101){ref-type="fig"}). This is probably due to the shorter average N-terminal length of the Rhodopsin family compared to that of other GPCR families ([Table 1](#t1-bt-26-101){ref-type="table"}). It has been proven that the average number of non-synonymous natural variants at the N-terminus becomes similar to that at the other domains for all GPCR families when it was normalized by the average residue numbers of the N-terminal region ([Fig. 2C](#f2-bt-26-101){ref-type="fig"}). Higher average number of non-synonymous natural variants was observed within the TM domains (TMs 1--7) than in the intracellular or extracellular loops (ICLs 1--3 and ECLs 1--3); moreover, no non-synonymous natural variant was observed in ICL1, ICL3, and ECL3 of the Secretin family; ECL1 and ECL3 of the Adhesion family; ECL1 of the Glutamate family; and ICL1, ECL1, and ECL3 of the Fizzled family ([Table 1](#t1-bt-26-101){ref-type="table"}, [Fig. 2A, 2B](#f2-bt-26-101){ref-type="fig"}). When normalized by the average residue numbers, the occurrence of non-synonymous natural variants became similar throughout the TM, ICL, and ECL domains in all GPCR families except ICL2 of the Secretin family. The normalized average number of natural variants in ICL2 of the Secretin family was two to four times higher than that of the other TM, ICL, and ECL domains of the same family ([Fig. 2C](#f2-bt-26-101){ref-type="fig"}), which suggests that ICL2 of the Secretin family has higher frequency of non-synonymous natural variations than ICL2 of other GPCR families. In the present study, we divided the C-terminus into two domains, helix 8 (H8) and C-terminal tail ([Fig. 1A](#f1-bt-26-101){ref-type="fig"}). The H8 domain is an α-helical domain (approximately 12--26 residues) located parallel to the plasma membrane ([Fig. 1A](#f1-bt-26-101){ref-type="fig"}). The percentage of GPCRs with non-synonymous natural variants at the H8 domain and the average number of non-synonymous natural variants at the H8 domain are smaller than the TM α-helical domains ([Fig. 2A, 2B](#f2-bt-26-101){ref-type="fig"}). The C-terminal tail contains a relatively larger number of non-synonymous natural variants than the other intracellular domains ([Fig. 2A, 2B](#f2-bt-26-101){ref-type="fig"}), although this number also becomes relatively similar to that of the other intracellular domains after normalization by average residue number ([Fig. 2C](#f2-bt-26-101){ref-type="fig"}). Distribution of GPCR non-synonymous natural variants within helical domains and functional consequences ------------------------------------------------------------------------------------------------------- Non-synonymous natural variants of GPCRs can severely affect their functions such as membrane expression, activation, and drug interaction. As we describe in the present study, a high degree of genetic variation has been observed in the human GPCRs. However, the functional effects of the natural variants have been studied in only 218 (from 41 GPCRs) out of 1,440 non-synonymous natural variants (from 269 GPCRs) ([Table 2](#t2-bt-26-101){ref-type="table"}). Although the TM domains share certain degree of structural similarity, the sequences vary significantly between different GPCRs, with only a few conserved residues. Ballesteros and Weinstein developed a sequence-based generic GPCR numbering system for the Rhodopsin family GPCRs ([@b2-bt-26-101]). Subsequently, similar systems have been developed for other GPCR families ([@b20-bt-26-101]; [@b32-bt-26-101]; [@b31-bt-26-101]). In these systems, the residue numbers are assigned relative to the most conserved position in each TM, which is number 50. For example, in the Rhodopsin family, residue number 3.50 indicates the conserved arginine residue in TM3, and residue number 3.49 indicates one residue before the conserved arginine in TM3. Recently, a modified system was developed based on the GPCR crystal structures ([@b11-bt-26-101]), and GPCRdb assigned residue numbers for all GPCRs (except the olfactory receptors) using this new numbering system. It has been reported that disease-causing non-synonymous polymorphisms of GPCRs occur more frequently within the TMs than non-disease-causing non-synonymous polymorphisms ([@b17-bt-26-101]). Hence, to analyze the distribution pattern of the non-synonymous natural variants in these regions, we mapped all the non-synonymous natural variations in the TM and H8 domains based on the generic numbering system provided by GPCRdb ([Fig. 3](#f3-bt-26-101){ref-type="fig"}). In general, the non-synonymous natural variants are distributed throughout TM domains and H8 ([Fig. 3](#f3-bt-26-101){ref-type="fig"}). Overall, the occurrence of non-synonymous natural variants are not restricted to specific TM domains or residues. Nonetheless, we detected a few exceptional positions such as 3.50, 6.50, and 6.44, where more than nine non-synonymous natural variants were detected ([Fig. 3](#f3-bt-26-101){ref-type="fig"}). It is interesting to note that two of these exceptional residues are conserved residues with a residue number of x.50. More importantly, these conserved residues were found to have critical roles in the ligand-induced activation of GPCRs. In the Rhodopsin family, residue 3.50 is arginine ([Fig. 4A](#f4-bt-26-101){ref-type="fig"}, red stick), which is part of the D\[E\]R^3.50^Y motif; in X-ray crystal structures of the rhodopsin and a few other GPCRs, R^3.50^ in D\[E\]R^3.50^Y interacts with E^6.30^ forming an ionic lock in the inactive state, which is broken upon activation indicating that the ionic lock is an important factor for GPCR activation ([@b33-bt-26-101]). Among the 11 non-synonymous natural variations reported for residue R^3.50^, the conserved arginine was substituted with histidine in five cases, cysteine and leucine in two cases each, and glycine and tryptophan in one case each. Residue 6.50 is another conserved residue in the CWxP^6.50^ motif in the Rhodopsin family ([Fig. 4A](#f4-bt-26-101){ref-type="fig"}, orange stick) and has a critical function in GPCR activation; W^6.48^ is known to be a rotamer toggle switch that undergoes a conformational change upon agonist binding to induce movement of TM6 ([@b33-bt-26-101]). Among the nine non-synonymous natural variants reported in P^6.50^, four were substitutions with serine, two with arginine and leucine each, and one with alanine. Although less frequent than residues 3.50 and 6.50, residue 7.50 (proline in the Rhodopsin family) ([Fig. 4A](#f4-bt-26-101){ref-type="fig"}, green stick) also showed six non-synonymous natural variations: three were substituted with serine, and the other three were substituted with leucine, histidine, or arginine. P^7.50^ is also a part of a conserved motif (NP^7.50^xxY) with functional significance ([@b33-bt-26-101]). It is interesting to note that there is a bias (approximately 45%) of substituted amino acids in these conserved regions; 5 out of 11 R^3.50^ variations involved a substitution with histidine, 4 out of 9 P^6.50^ variations involved a substitution with serine, and 3 out of 6 P^7.50^ variations involved a substitution with serine. We have tested the functional consequences of the non-synonymous natural variants in these conserved residues by using dopamine receptor type 1 (D1R) as a model GPCR. D1R is a Rhodopsin family GPCR and has conserved D\[E\] R^3.50^Y, CWxP^6.50^, and NP^7.50^xxY motifs. Here, we mutated the conserved residues within D1R into the most frequently found non-synonymous natural variants: R^3.50^ into histidine, P^6.50^ and P^7.50^ into serine. All mutations in the conserved residues resulted in impairment of G protein activation ([Fig. 4B](#f4-bt-26-101){ref-type="fig"}). When the cellular expression was analyzed, the mutated D1R variants were localized not in the plasma membrane but inside of the cells ([Fig. 4C](#f4-bt-26-101){ref-type="fig"}), which suggests that the mutations in these conserved residues lead to mis-localization of the receptor and thus impaired signaling. It has been shown that the H8 domain has a critical role in the expression/localization and activation of GPCRs ([@b1-bt-26-101]; [@b15-bt-26-101]; [@b12-bt-26-101]; [@b25-bt-26-101]; [@b36-bt-26-101]). The H8 domain is located beneath the plasma membrane, with one side of the H8 domain in contact with the plasma membrane and the other sides exposed to the cytosol ([Fig. 1A](#f1-bt-26-101){ref-type="fig"}). The residues that interact with the plasma membrane (residues 8.50, 8.54, and 8.57/8.58) are hydrophobic, with residue 8.50 being a conserved phenylalanine or leucine. Interestingly, residues that contact the plasma membrane show no or less frequent non-synonymous natural variant occurrence than the residues that are exposed to the cytosol ([Fig. 3](#f3-bt-26-101){ref-type="fig"}, [4A](#f4-bt-26-101){ref-type="fig"}). DISCUSSION ========== Approximately 30--40% of marketed drugs target GPCRs, and 6 out of the top 15 selling small-molecule drugs target GPCRs according to the 2015 annual report by Pharma-Compass. With the high-resolution X-ray crystal structures of various GPCRs being published since 2007, the structural understanding of GPCR activation mechanism has greatly improved, and the structure-based drug design for GPCR-targeting drugs is of great interest in the pharmaceutical industry ([@b22-bt-26-101]). Given the pharmacological and pathological importance of GPCRs, it will be critical to understand their genotype-phenotype relationships, but only a few (approximately 15%) have been studied ([Table 2](#t2-bt-26-101){ref-type="table"}). Moreover, it has been suggested that the variability of the GPCR superfamily is not well defined, as its false positive rate is high (68%) ([@b23-bt-26-101]). Therefore, it is necessary to validate the natural variants in the databases and investigate the physiological and/or pathological consequences of the variants. The current study, for the first time, analyzed the distribution of all known non-synonymous natural variations from all 367 non-olfactory GPCRs (except twenty five taste 2 and six un-categorized orphan receptors) in the structural context. Majority of GPCRs showed non-synonymous natural variations mainly in the N-terminus and TM regions throughout five GPCR families ([Fig. 2](#f2-bt-26-101){ref-type="fig"}). Analysis of the positions of non-natural variations within the TM domains revealed their presence throughout the TM regions, and a few were more frequently detected in the conserved and functionally critical residues (x.50) ([Fig. 3](#f3-bt-26-101){ref-type="fig"}). Most of the non-synonymous natural variations in the conserved residues ([Fig. 4A](#f4-bt-26-101){ref-type="fig"}) have been detected in disease states such as Hirschsprung disease-2, X-linked nephrogenic diabetes insipidus, hyperthyroidism, hypogonadotropic hypogonadism, glucocorticoid deficiency 1, and retinitis pigmentosa according to the Uniprot database. The functional consequences and underlying mechanisms of these substitutions have not been fully understood, and only a few have been studied. For example, substitution of R^3.50^ with histidine in the gonadotropin-releasing hormone receptor or vasopressin V2 receptor has been reported to reduce receptor activity, whereas substitution with cysteine or leucine in the vasopressin V2 receptor increases receptor activity according to the UniProt database. Substitution of P^7.50^ with serine in the neuromedin-K receptor has been reported to impair receptor signaling. Here, we analyzed the functional consequences and underlying mechanisms of the most common non-synonymous natural variants in the conserved residues by using D1R as a model GPCR. We found that all the tested variants showed impaired cellular localization, which lead to impaired signaling ([Fig. 4B](#f4-bt-26-101){ref-type="fig"}, [4C](#f4-bt-26-101){ref-type="fig"}). We suspect that other Rhodopsin family receptors would show similar functional consequences when the conserved residues are substituted with the same amino acids (i.e R^3.50^ into histidine, P^6.50^ and P^7.50^ into serine). The comprehensive analysis of non-synonymous natural variants in the current study would provide valuable insight for future research in GPCR non-synonymous natural variants. Firstly, for example, the current study suggests that ICL2 of the Secretin family has more frequency of non-synonymous natural variants than ICL2 of other GPCR families. Therefore, researchers can expect that non-synonymous natural variants would occur in ICL2 of the Secretin family although it is rare in other GPCR families. Secondly, although we have tested functional consequences of non-synonymous natural variants in a few conserved residues, we did not analyze comprehensive outlook of the genotype-phenotype relationship of GPCRs. This was mainly because of relatively poor database in the genotype-phenotype relationship of GPCRs. The current study provided the distribution of non-synonymous natural variants of GPCRs in the structural context. With aid of the extensive structural studies of GPCRs recent 10 years ([@b33-bt-26-101]), this data would provide information for prioritization of the GPCR genotype-phenotype relationship investigation. This work was supported by the National Research Foundation of Korea funded by the Korean government (NFR-2015R1A1A1A05027473). ![Description of the general GPCR structure and five GPCR families. (A) The structural domains of GPCRs. (B--F) Representations of the conserved and distinct features of the Rhodopsin (B), Secretin (C), Adhesion (D), Glutamate (E), and Frizzled (F) families.](bt-26-101f1){#f1-bt-26-101} ![Occurrence of non-synonymous natural variations in GPCR families. (A) Percentage of GPCRs with non-synonymous natural variants in the specified structural domains among all GPCRs of each family. (B) The reported average numbers of non-synonymous natural variations within the specified structural domains, which are normalized by the total number of GPCRs in each family. (C) The reported average numbers of non-synonymous natural variations within the specified structural domains, which are normalized by the total number of GPCRs in each family and average residue number of each structural domain.](bt-26-101f2){#f2-bt-26-101} ![Distribution of non-synonymous natural variants within the TM and H8 domains. (A) The positions of non-synonymous natural variants within the TM and H8 domains were assigned based on the generic numbering system provided by GPCRdb (left column), and the numbers of detected non-synonymous natural variants in these positions are indicated (right column). The conserved residues in each domain (x.50) are colored in red, and conserved motifs with functional significance (i.e., DR^3.50^Y, CP^3.50^xW, and NP^3.50^xxY) are indicated at their structural positions. (B) The frequencies of non-synonymous natural variations are highlighted using color-coding and mapped onto the crystal structure of a model GPCR (PDB 3SN6).](bt-26-101f3){#f3-bt-26-101} ![Positions of the conserved motifs and functional consequences of non-synonymous natural variations in the conserved motifs. (A) Positions of x.50 conserved residues within the DR^3.50^Y (red), CP^6.50^xW (orange), and NP^7.50^xxY (green) motifs are shown with sticks, and H8 domain is highlighted with sticks and color-coded based on [Fig. 3](#f3-bt-26-101){ref-type="fig"}. The figure is based on the crystal structure of a model GPCR (PDB 3SN6). (B) D1R variants-mediated G protein activation is analyzed by measuring agonist-induced cAMP generation. T-test was used for the statistical analysis, and ^\*^indicates *p*\<0.05 from six experiments. (C) Cellular localization of D1R variants is analyzed by immunofluorescence assay.](bt-26-101f4){#f4-bt-26-101} ###### Summary of non-synonymous natural variants Family N-term TM1 ICL1 TM2 ECL1 TM3 ICL2 TM4 ECL2 TM5 ICL3 TM6 ECL3 TM7 H8 C-term ------------------------------- --------------- ---------- ---------- ----------- ----------- ---------- ---------- ---------- ----------- ----------- ----------- ---------- ----------- ---------- ---------- ------------- Rhodopsin (286)   Average residue \# 47 ± 73.4 32 ± 2.6 4 ± 8.5 31 ± 10.7 6 ± 9.6 37 ± 9.6 10 ± 7.0 25 ± 6.0 22 ± 13.2 39 ± 12.4 20 ± 35.9 36 ± 2.7 4 ± 18.3 29 ± 6.7 13 ± 2.5 47 ± 43.6   Natural variants 132 96 18 76 15 91 18 66 58 98 50 120 8 69 32 112   GPCRs with natural variants 65 53 14 38 13 40 13 39 36 63 35 56 8 39 27 74 Secretin (15)   Average residue \# 127 ± 19.3 42 ± 0.0 6 ± 4.0 28 ± 1.0 16 ± 5.2 36 ± 2.5 7 ± 0.3 29 ± 0.0 10 ± 1.6 34 ± 1.5 8 ± 1.0 27 ± 1.8 7 ± 0.3 28 ± 1.8 26 ± 0.0 50 ± 27.3   Natural variants 17 4 0 2 1 2 2 2 1 3 0 5 0 1 1 6   GPCRs with natural variants 8 3 0 2 1 1 2 2 1 2 0 4 0 1 1 5 Adhesion (33)   Average residue \# 983 ± 1,098.1 38 ± 0.0 6 ± 1.5 27 ± 1.2 7 ± 4.0 34 ± 0.9 9 ± 2.9 29 ± 0.0 13 ± 11.4 34 ± 0.0 19 ± 16.2 25 ± 0.7 5 ± 3.8 27 ± 3.8 16 ± 2.9 148 ± 149.0   Natural variants 98 2 1 1 0 7 1 4 2 5 2 2 0 1 1 8   GPCRs with natural variants 22 2 1 1 0 4 1 4 2 5 2 2 0 1 1 3 Glutamate (22)   Average residue \# 436 ± 222.8 27 ± 0.0 10 ± 0.8 24 ± 1.6 11 ± 22.2 33 ± 0.0 8 ± 21.4 26 ± 0.0 27 ± 6.6 25 ± 0.0 8 ± 7.7 25 ± 0.0 15 ± 22.6 29 ± 0.0 12 ± 0.0 210 ± 361.7   Natural variants 86 7 1 4 0 6 1 4 4 6 1 4 2 3 0 22   GPCRs with natural variants 15 5 1 2 0 3 1 2 4 3 1 3 2 2 0 9 Frizzled (11)   Average residue \# 233 ± 33.8 32 ± 0.0 6 ± 0.0 24 ± 0.3 30 ± 10.5 36 ± 0.0 4 ± 0.3 26 ± 0.0 19 ± 0.0 37 ± 0.0 8 ± 0.8 53 ± 3.4 12 ± 4.6 23 ± 0.0 16 ± 0.0 76 ± 76.1   Natural variants 21 2 0 1 0 1 0 2 1 3 0 4 0 3 2 8   GPCRs with natural variants 4 2 0 1 0 1 0 2 1 3 0 3 0 2 2 4 ###### Non-synonymous natural variants with known functional consequences Family Total \# of natural variants \# of natural variants with known functional consequences \% of natural variants with known functional consequences Total \# of GPCRs with natural variants \# of GPCRs with natural variants with known functional consequences \% of GPCRs with natural variants with known functional consequences ----------- ------------------------------ ----------------------------------------------------------- ----------------------------------------------------------- ----------------------------------------- ---------------------------------------------------------------------- ---------------------------------------------------------------------- Rhodopsin 1,059 155 14.6 207 31 15.0 Secretin 47 4 8.5 12 2 16.7 Adhesion 135 17 12.6 26 3 11.5 Glutamate 151 34 22.5 18 2 11.1 Frizzled 48 8 16.7 6 3 50.0 Total 1,440 218 15.1 269 41 15.2
null
minipile
NaturalLanguage
mit
null
16--Award_Ceremony/16_Award_Ceremony_Awards_Ceremony_16_317.jpg 3 214.313 102.867 43.2102 54.6392 0.987436 843.054 117.577 31.9633 41.9304 0.956604 600.055 135.75 30.5795 44.6133 0.868223
null
minipile
NaturalLanguage
mit
null
Brent Barrett to Play Hannibal Lecter in Parody Tuner Silence! The Musical About the Show Brent Barrett with play the Chianti-loving Hannibal Lecter in 'Silence! The Musical.' He has played Billy Flynn and the Phantom of the Opera, and now Broadway vet Brent Barrett will take on the role of serial killer Hannibal Lecter in Silence! The Musical, described as “unauthorized parody” of The Silence of the Lambs. Jenn Harris will co-star as FBI agent Clarice Starling in an off-Broadway mounting of the show, which is set to run June 24-August 13 at 80 St. Marks Place, directed and choreographed by Christopher Gattelli. Silence! The Musical features a book by Tony nominee Hunter Bell ([title of show]) and music and lyrics by Jon and Al Kaplan. The show began as a collection of songs that became popular on the internet, then a screenplay by the Kaplans that was adapted for the stage by Bell. Silence! was named Best Musical at the 2005 Fringe Festival and was successfully produced in London last season. In the Academy Award-winning film The Silence of the Lambs, rookie FBI agent Clarice Starling matches wits with the brilliant but insane cannibal, Dr. Hannibal Lecter, to catch the serial killer known only as Buffalo Bill. Clarice must face her own demons and race the clock to unlock Lecter’s clues before another innocent girl is killed and skinned by Bill. In the musical version, the action is narrated by a singing chorus of floppy-eared lambs and Buffalo Bill dances a hoedown while kidnapping hapless Catherine Martin. Barrett is currently playing Billy Flynn in Chicago and has appeared on Broadway in Annie Get Your Gun, Grand Hotel, West Side Story and Candide. He received an Olivier Award nomination for his performance in the London company of Kiss Me, Kate and played a two-year stint in the title role of Phantom – The Las Vegas Spectacular. Harris received a Lucille Lortel Award for her performance in Modern Orthodox. Her other off-Broadway credits include New Jerusalem and The Understudy, and she is a frequent guest star at Joe’s Pub: Our Hit Parade. Silence! will feature musical direction by Mark Hartman, with arrangements and orchestrations by Brian J. Nash. The show is being produced Off-Broadway by Victoria Lang, Rich Affannato and Donna Trinkoff.
null
minipile
NaturalLanguage
mit
null
Sex with minor wife: Delhi HC rejects plea against acquittal of man The Delhi High Court has dismissed the appeal of the state against a trial court order acquitting a 22-year-old man accused of eloping with a minor girl and raping her after tying the knot at Kolkata last year. New Delhi: The Delhi High Court has dismissed the appeal of the state against a trial court order acquitting a 22-year-old man accused of eloping with a minor girl and raping her after tying the knot at Kolkata last year. A bench of justices Pradeep Nandrajog and Mukta Gupta upheld the lower court verdict saying that the girl, who was 15 years and four months old at the time of the alleged offence, had willingly accompanied him and had consensual sex with him after the marriage. The bench also noted that the girl's mother was also of the view that her daughter will be happy with the accused. Delhi Police, in its appeal against the acquittal, alleged the consent of the girl was "immaterial" as she was a minor and hence her husband has wrongly been absolved by the lower court of the offence of kidnapping and the penetrative sexual?assault under the Protection of Children from Sexual offences (POCSO) Act. During the hearing, advocate Sumeet Verma, appearing for accused Suman Dass, referred to the penal provisions on rape and sexual assault and said the sexual intercourse by a man with his wife, who is not below the fifteen years of the age, is not rape. "The legislature did not omit Exception 2 of section 375 (rape) of the IPC (that says that sexual intercourse by a man with his wife who is not below 15 years of age is not rape) while revisiting the entire penal laws on rape and sexual assault recently," Verma argued. The court considered the plea and rejected the appeal of the state against the acquittal of Dass. A charge sheet against the accused under the IPC and the POCSO?Act was filed alleging he lured away a minor and raped her several times after marrying her. "In my opinion, it would neither serve the object of the present enactment nor the purpose of criminal laws to hold the accused guilty on the ground that he had sexual intercourse with the girl child below 18 years of age. "As the prosecution has not disputed the factum of marriage, it would not be conducive to mental, psychological, physical health of the prosecutrix that her lawfully married husband be sent to the jail. If they are happy about it, why put obstacles on their path"? the trial judge had said.
null
minipile
NaturalLanguage
mit
null
If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. Personally I don't see much difference between a serial killer and a habitual criminal who has killed multiple people. As if there is some moral superiority to killing someone in the course of a robbery rather than killing someone because she happened to be at 10050 Cielo Drive on a given evening. Then you probably agree with most Conservatives that Hate crimes legislation is stupid??? Why is it worse to murder somebody because you "hate" him versus murder in coincidence with another crime? Education without values, as useful as it is, seems rather to make man a more clever devil.C. S. LewisDo not ever say that the desire to "do good" by force is a good motive. Neither power-lust nor stupidity are good motives. (Are you listening Barry)?:mad:Ayn Rand Personally I don't see much difference between a serial killer and a habitual criminal who has killed multiple people. As if there is some moral superiority to killing someone in the course of a robbery rather than killing someone because she happened to be at 10050 Cielo Drive on a given evening. A habitual criminal kills as a means to an end. A serial killer derives pleasure from the act. That's not to say that the habitual criminal isn't a sadist, or the serial killer doesn't commit other crimes in the course of killing, just that the motives differ. The end result is the same. Originally Posted by NJCardFan Question: Does the very fact that Obama is half white and was raised primarily by his white grandparents make no never mind to anyone? That said, it goes to show that with Democrats and liberals, ideology covers up a big swath of an issue like that. This is why they vilify "real" black men like Cain and West. They vilify Cain and West because Cain. West, Clarence Thomas, Thomas Sowell, Walter Williams, DeRoy Murdock and a host of other black conservatives are the intellectual underground railroad. They threaten to lead people out of bondage to the welfare state, which feeds and houses them in return for votes, but denies them the tools to advance. Today's plantation doesn't use whips and chains, it fosters dependency through a culture of failure. This is also why they oppose vouchers for private schools, because the public schools provide the indoctrination in that culture. It's where kids are taught not to work, but to expect rewards. Originally Posted by djones520 Not true! Law and Order had a white serial killer who killed people of darker skin tone. :D I am suggesting the possibility that GotNews.com might be a hoax or troll site making @#$% up. I based that comment on the PJMedia article I linked, whose description and quotes from the killer's FB...
null
minipile
NaturalLanguage
mit
null
Facial Cleansing Cloths Remove Make Up Without Water Dear Dr. Dave and Dr. Dee, I am going camping where there is no running water, only an outhouse. The problem is that I want to wear makeup, but I do not want to sleep in makeup, so what should I do? Is sleeping in makeup over the weekend okay? Signed, Need fresh face Dear Need fresh face, It is important to clean your face and remove make up before going to bed. Make up, dirt, and oil that accumulates during the day can clog pores and cause pimples. Pre-moistened facial cleansing cloths would take off your make up and clean your face without water. These cloths are very popular not only for camping, but also for daily use. One cloth replaces soap, water, and eye make up remover, and leaves skin feeling fresh, clean, and smooth. Many cleansing cloths are soap free, alcohol free and contain vitamin E, moisturizers, and natural botanical extracts such as aloe or green tea. Facial cleansing cloths given overall high positive ratings by consumers at DrugStore.com are listed below. Prices vary from about $5 to $7 for a pack of 30 cloths. In addition, Costco sells Kirkland Signature Daily Facial Cleansing Towelettes that work very well and good bargain costing about $10 for 135 towelettes.
null
minipile
NaturalLanguage
mit
null
The Mini Maglite LED AAA with Pocketclip and batteries. An incredibly well balanced flashlight featuring 84 Lumens, 116 meters beam-distance and 5:45 hours run time provides flexibility in any situation. A Lifetime Tough flashlight that can fit in your pocket. Perfect for home or professional use. Red.
null
minipile
NaturalLanguage
mit
null
Remote Ischemic Conditioning for Preventing Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions/Coronary Angiography: A Meta-Analysis of Randomized Controlled Trials. It is uncertain whether remote ischemic conditioning (RIC) has a protective effect on contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI)/coronary artery angiography (CAG). We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of RIC on CI-AKI in such patients. PubMed, MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases were searched for RCTs that assessed the effect of RIC on CI-AKI in patients undergoing PCI/CAG. Ten RCTs with 1389 patients (RIC group, 757 and control, 632) were included. The RIC group significantly exerted a lower risk of CI-AKI compared to the controls (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.34-0.77, P = .001), and they had the similar effect on major adverse cardiovascular events within 1 year (OR = 0.36, 95% CI = 0.20-0.66, P < .001). The RIC reduced the rates of death within 30 days, but this was not significant (OR = 0.16, 95% CI = 0.02-1.34, P = .091). The RIC was associated with a significantly lower incidence of CI-AKI in patients following elective PCI/CAG (OR = 0.54, 95% CI = 0.33-0.87, P = .011). The RIC before not after the intervention was effective in reducing the occurrence of CI-AKI (OR: 0.37 vs 1.05, P = .022). The RIC of the upper arm has statistically significant effect on protecting CI-AKI but not that of the lower limb (OR: 0.41 vs 1.41, P = .004). The effect of RIC on CI-AKI was similar between patients with a mean estimated glomerular filtration rate <60 mL/min/1.73 m(2) and those with mean rates ≥60 (OR: 0.23 vs 0.41, P = .333). The RIC reduced the incidence of CI-AKI in those receiving PCI/CAG. And RIC of the upper arm significantly reduced the risk of CI-AKI but not RIC of the lower limb in patients undergoing PCI/CAG.
null
minipile
NaturalLanguage
mit
null
Role of central NO-cGMP pathway in vasopressin and oxytocin gene expression during sepsis. Sepsis induces massive production of inflammatory mediators, such as nitric oxide (NO), and causes neuroendocrine and cardiovascular alterations. This study investigates the involvement of the central NO-cGMP pathway in arginine vasopressin (AVP) and oxytocin (OXY) gene expression during sepsis induced by cecal ligation and puncture (CLP). Male Wistar rats received an i.c.v. injection of ODQ (0.25 μg/μL), a selective inhibitor of the heme site of soluble guanylate cyclase, or of 1% dymethilsulfoxide (DMSO), as vehicle. Thirty minutes after the injections, sepsis was induced by cecal ligation and puncture or the animals were sham operated. The ODQ pre-treatment did not alter the progressive NO increase observed after CLP. In the supraoptic nucleus (SON), this pretreatment increased the relative gene expression ratio of AVP and OXY in the initial phase of sepsis, but in the late phase, the gene expression of both hormones was reduced. In the paraventricular nucleus (PVN), soluble guanylate cyclase inhibition caused an even larger decrease in the relative gene expression ratio of AVP and OXY during sepsis. These results are indicative of a role of the NO-cGMP pathway in hormonal synthesis in the SON and PVN of the hypothalamus during polymicrobial sepsis.
null
minipile
NaturalLanguage
mit
null
ELLIPTIVE CURVE CRPTGRAPHY (ECC) Currently, security is necessary for us to protect our personal information from a vicious attacker. Recently, Elliptic Curve Cryptography(ECC) is attracting attention as a stronger security than before. The security of ECC is based on the computational difficulty of the Elliptic Curve Discrete Logarithm Problem(ECDLP). It depends on the computer’s performance and the number of computers that can be parallelized. As an example, 112-bit ECDLP was actually solved by a cluster of more than 200 PlayStation 3 game consoles for half a year and it is the largest size of ECDLP ever solved. The threat of parallel attacks has increased because advanced information and communication technologies facilitate parallel computing through the internet. It is crucially important to verify the practical security against parallel attacks. Therefore, We aim to evaluate the security of ECDLP by attacking to it actually. Now, we attack to the 114-bit ECDLP by about 200 computers (starBED) which provided from NICT. IoT (INTERNET OF THINGS) SECURITY IoT (Internet of things) / IoE (Internet of Everything) era has come. Everything will be connected to the Internet and various types of information are transmitted between not only computers but also small devices. Of course, it includes very sensitive and private information such as ID, birthday, credit card number, and so on. PC can efficiently and securely carry out encryption and decryption for the secure transmission; however, it is very heavy for small devices such as IC card and microcontrollers, namely IoT devices. PAIRING Pairings on elliptic curves is a relatively new and active area of research in cryptography which is often known as Pairing-based Crypto (PBC). By using some certain mathematics, pairing maps a pair of points on an elliptic curve into the multiplicative group of a finite field. Such technique yields several new cryptographic protocols that had not previously been feasible. One of the widely known protocols realized by PBC is identity-based encryption (IBE), which overcomes the need of knowing the receivers public key in prior of sending the secure message.Another innovative application of PBC is functional encryption which allows anyone who possesses a particular set of attributes defined during encryption stage, can decrypt the message. It is also known as attribute-based encryption (ABE). More and more novel ideas are in the pipeline from the academia and industry who are involved in research of PBC. Therefore we can say, pairing-based cryptography is now in the frontline of next generation of security. SECURE DATABASE The Secure Database targets big data that is one of the Information technology attracting the most attention now, because more information will have been rapidly uploaded on the Internet. It reduce the risk of leakage the data such as personal information, posts on SNS or even a log of the air temperature in a room, regardless the type of data. We use a unique block cipher as SSE (Symmetric Searchable Encryption) and process the data just as it is encrypted. It means that it doesn’t need to be decrypted each time we operate the database, so we can manage the data in better security. LATTICE BASED CRYTOGRAPHY The time for replacing the conventional computational system with the quantum computer is coming in the near future. It is known that the Shor’s algorithm with quantum computer enables us to solve the mathematical hardness such as prime factorization and Discrete Logarithm Problem. In other words, the conventional public key cryptographies, for example, RSA and Elliptic Curve Cryptography, will be broken by the quantum computer in polynomial time. In this context, a lattice-based cryptography called NTRU has been paid much attentions as post-quantum cryptography. It is constructed on the shortest vector problems and is able to encrypt data much faster than RSA. In addition, it can use for making a searchable cryptosystem which allows us to find the data without decryption. Such kinds of mathematical background and applications are investigated in our lab. ELLIPTIC CURVE DISCRETE LOGARITHM PROBLEM(ECDLP) Currently, security is necessary for us to protect our personal information from a vicious attacker. Recently, Elliptic Curve Cryptography(ECC) is attracting attention as a stronger security than before. The security of ECC is based on the computational difficulty of the Elliptic Curve Discrete Logarithm Problem(ECDLP). It depends on the computer’s performance and the number of computers that can be parallelized. As an example, 112-bit ECDLP was actually solved by a cluster of more than 200 PlayStation 3 game consoles for half a year and it is the largest size of ECDLP ever solved. The threat of parallel attacks has increased because advanced information and communication technologies facilitate parallel computing through the internet. It is crucially important to verify the practical security against parallel attacks. Therefore, We aim to evaluate the security of ECDLP by attacking to it actually. Now, we attack to the 114-bit ECDLP by about 200 computers (starBED) which provided from NICT. ACTIVITIES 2017 Associate Editor International Journal of Network and Computing Associate Editor, 2016-2017 IEICE Trans. Special Issue of SITA Associate Editor, 2016-2017 IEICE Trans. Special issue of SCIS Session Chair ICCE-TW2017 Organized Program Committee Member, 2015-2017 International conference DSD, AHSA WICS Co-Chair, 2015-2017 International conference CANDAR Co-Secretary International symposium ISITA2018 2016 Technical Program Committee International Symposium ISITA2016. Invited Lecture "Cryptographic Techniques in IoT Era" IEICE Society symposium Core Member Meeting A member of SMA and NICT:StarBED Advisor Domestic symposium SITA2017 A member of Chugoku IoT Research Meeting technical program committee, organizer and chair of special session "Advanced cryptography and its applications" International conference ICCE-TW Invited Lecturer "Cryptographic Techniques in IoT Era" IEICE Society symposium. A member of core member meeting SMA and NICT:StarBED Special lecture at 91岡山県技術・市場交流プラザ Special lecture@新技術協会 "Cryptographic Techniques in IoT Era" A member of Chugoku IoT Research Meeting Technical Program Committee, Organizer and Chair of Special Session "Advanced cryptography and its applications International conference ICCE-TW Committee Member IEICE Technical group of Hardware Security Associate editor IEICE Trans. special issue of IWSDA. Advisor Domestic symposium SITA2017 NEWS & EVENTS Advances in cybersecurity technology are important to meet the challenges of ensuring the safety and social acceptably of the proliferation of technology based cloud computing and internet of things (IoT). Information security technology is necessary for the Cloud and IoT era. Particularly, public key cryptography such as RSA cryptography and elliptic curve cryptography plays an important role since it enables digital authentications for users and devices. Information security technology based on cryptography is indispensable in the current information society centered on the Internet. While there are mathematical difficulties that many computing machines can not solve, we introduce that simple mathematics such as integer arithmetic and prime numbers are active. AWARDS Best Paper Award International conference IWCI2016. Design Award LSI・IP, May 2004. SCIS Paper Award Domestic conference SCIS2011. Excellent Paper Award The 2014 International Symposium on Communications and Information Technologies, 2014. Best Paper Award The 6th International Conference on Information Security Practice and Experience, 2010. Science and Technology Prize, Okayama Fundation for Science and Technology Basis Efficient for Fast Arithmetic Operations in Extension Field with Public Key Cryptography, 2007
null
minipile
NaturalLanguage
mit
null
NO. 07-09-00295-CR   IN THE COURT OF APPEALS   FOR THE SEVENTH DISTRICT OF TEXAS   AT AMARILLO   PANEL D   AUGUST 15, 2011     HERBERT FRANKLIN GARZA, APPELLANT   v.   THE STATE OF TEXAS, APPELLEE      FROM THE 100TH DISTRICT COURT OF CHILDRESS COUNTY;   NO. 5192; HONORABLE STUART MESSER, JUDGE     Before QUINN, C.J., and CAMPBELL and PIRTLE, JJ.     MEMORANDUM OPINION             Presenting ten points of error, appellant Herbert Franklin Garza appeals from his conviction by jury of the offense of delivery of a controlled substance to a child and the resulting sentence of sixty-five years of imprisonment in the Institutional Division of the Texas Department of Criminal Justice.  We affirm.       Background             Appellant was indicted for delivery of a controlled substance, methamphetamine, to Q.M., a minor.[1] The indictment included two enhancement paragraphs setting forth appellant’s two previous felony convictions.[2]               Evidence showed that Q.M., then fifteen years old, helped appellant with some work at an address in Childress, Texas.  Q.M., who is related to appellant, testified he expected to be paid in cash for his work, but appellant instead paid him with methamphetamine.  Q.M. told the jury he had used methamphetamine in the past so he knew what appellant gave him.  He said he smoked the drug with appellant and another individual. A few hours later, Q.M. went to the home of Dustin Dann.             Q.M.’s mother called police after she found Q.M. coming out of Dann’s house.  She saw Q.M.’s eyes were very “low,” he was sweating profusely, and his chin was moving back and forth erratically. She knew Q.M. was “real” high, so she called an ambulance and police.  Q.M. told his mother he was high because he had been smoking “ice.”  Over objection, the mother further testified appellant later told her he gave the methamphetamine to Q.M.             The officer who responded to the call testified Q.M.’s mother was “frantic, appeared to be scared, and concerned about her son.”[3]  Asked to describe Q.M.’s behavior, he said Q.M. “was sitting on a couch with his head hung, having a hard time keeping his eyes open.  His jaw was moving back and forth erratically.  He was very incoherent.  Almost on the verge of passing out.”  Concluding Q.M. showed signs of a possible overdose, the officer called emergency medical services.  Over appellant’s objections, the officer testified Q.M.’s mother told him Q.M. was “overdosing” on methamphetamine, and testified Q.M. told him he had smoked a “30 bag” of methamphetamine.[4]             Q.M. was transported to the hospital.  A physician testified without objection Q.M.’s mother told him Q.M. was there because he had smoked methamphetamine.  Q.M.’s medical files were admitted into evidence.  The hospital lab results indicated Q.M.’s urine tested positive for “cannabinoids and opiates.”  The doctor testified that was a mistake and should have read “cannabinoids and amphetamines.” Because of the positive drug finding, a sample of the urine also was sent to a Dallas commercial laboratory. That report confirmed Q.M.’s urine was positive for methamphetamine and marijuana.                                                                                Analysis Sufficiency of the Evidence             In appellant’s first, second, third and fourth points of error, he contends the only evidence that showed the substance was methamphetamine was the testimony of Q.M.  According to appellant, the testimony is contradictory in nature and provides conflicting times and events.  Appellant asserts Q.M.’s testimony is legally and factually insufficient to prove appellant delivered methamphetamine to Q.M.  As an initial consideration, we observe that appellant's appeal contends that the evidence is both legally and factually insufficient. Appellant's brief was prepared and filed before the Texas Court of Criminal Appeals issued its opinion in Brooks v. State, 323 S.W.3d 893 (Tex.Crim.App. 2010), wherein the court held that there is no distinction between a claim of legal, as opposed to factual, insufficiency of the evidence. Further, the court expressly overruled Clewis v. State, 922 S.W.2d 126 (Tex.Crim.App. 1996), and its purported application to factual sufficiency questions. Id. We will review appellant's claims of evidentiary sufficiency under the standard of review set forth in Jackson v. Virginia.[5] 443 U.S. 307, 319, 99 S.Ct. 2781, 61 L.Ed.2d 560 (1979). In assessing the sufficiency of the evidence, we review all the evidence, both proper and improper, in the light most favorable to the verdict to determine whether any rational trier of fact could have found the essential elements of the offense beyond a reasonable doubt. Jackson, 443 U.S. at 319; Ross v. State, 133 S.W.3d 618, 620 (Tex.Crim.App. 2004). When reviewing all of the evidence under the Jackson standard of review, the ultimate question is whether the jury's finding of guilt was a rational finding. See Brooks, 323 S.W.3d at 906-07 (discussing Judge Cochran's dissent in Watson v. State, 204 S.W.3d 404, 448-50 (Tex.Crim.App. 2006), as outlining the proper application of a single evidentiary standard of review). Under the Jackson standard, it is the jury’s role to reconcile conflicts, contradictions, and inconsistencies in the evidence, and to judge the credibility of witnesses.  Brooks, 323 S.W.3d at 900. A person commits an offense if the person knowingly delivers a controlled substance . . . to a . . . child." Tex. Health & Safety Code Ann. § 481.122 (West 2003). Not disputing that Q.M. was a child at the time of the offense, appellant argues there is no evidence to show he delivered methamphetamine to Q.M. We disagree.  Although Q.M.’s testimony may not have been free from inconsistencies, it was the role of the jury to reconcile any inconsistencies, conflicts or contradictions. Brooks, 323 S.W.3d at 900. Q.M. testified appellant gave him methamphetamine and smoked it with him.  He told his mother and the officer he had used methamphetamine.  Appellant’s mother testified appellant told her he gave the methamphetamine to Q.M.  Lab tests confirmed appellant had ingested methamphetamine. Viewed in the proper light, we conclude the evidence allowed a rational trier of fact to find, beyond a reasonable doubt, appellant knowingly delivered methamphetamine to Q.M.  The evidence is sufficient to support the verdict. We overrule appellant’s first, second, third and fourth issues. Admission of Hearsay Statements             In appellant’s fifth and sixth points of error, he challenges the admission of hearsay statements.  He first complains of the testimony by the officer of statements made to him by Q.M.’s mother when he responded to the call concerning Q.M.  She told the officer she thought her son had overdosed on methamphetamine. We review a trial judge's decision to admit or exclude evidence under an abuse of discretion standard. Oprean v. State, 201 S.W.3d 724, 726 (Tex.Crim.App. 2006);  Janecka v. State, 937 S.W.2d 456, 468 (Tex.Crim.App. 1996).   Only if the trial judge's decision to admit evidence was outside the zone of reasonable disagreement will we overrule the trial court's ruling. Montgomery v. State, 810 S.W.3d 372, 378 (Tex.Crim.App. 1991) (op on reh’g). The State argues the mother’s statement was admissible as an excited utterance under Rule of Evidence 803(2), and we agree.  Tex. R. Evid. 803(2).  An excited utterance is "[a] statement relating to a startling event or condition made while the declarant was under the stress of excitement caused by the event or condition." Tex. R. Evid. 803(2). To determine whether a statement is an excited utterance, trial courts should determine "whether the declarant was still dominated by the emotions, excitement, fear, or pain of the event or condition" when the statement is made. Factors that the trial court may consider include the length of time between the occurrence and the statement, the nature of the declarant, whether the statement is made in response to a question, and whether the statement is self-serving. Apolinar v. State, 155 S.W.3d 184, 190 (Tex.Crim.App. 2005). The court heard the officer describe Q.M.’s mother as “frantic,” “very distraught,” “scared,” and “concerned about her son” at the time she made the challenged statement.  The trial court reasonably could have considered the mother’s statements related to her son’s startling symptoms of drug overdose, and were made while she was under the stress of excitement caused by her observation of his symptoms.  They were statements made by a mother relating to her son’s condition, were not self-serving on her part and do not appear to have been made in response to questions from the officer. Appellant contends only that these statements did not qualify as excited utterances because of the “significant” amount of time that passed from Q.M.’s mother’s observation of her son to the statements.  However, the passage of time, standing alone, is not determinative.  See Sadler v. State, No. 10-07-00323-CR, 2009 Tex.App. LEXIS 2962, at * 11-12 (Tex.App.—Waco April 29, 2009, no pet.) (mem. op., not designated for publication) (statement made ten or eleven hours after assault admissible as excited utterance); Mayfield v. State, No. 04-02-00635-CR, 2003 Tex.App. LEXIS 7660, at *5-6 (Tex.App.--San Antonio Sept. 3, 2003, pet. ref'd) (mem. op., not designated for publication) (statement made after ten hours was admissible).  See also Snellen v. State, 923 S.W.2d 238, 242-43 (Tex.App.--Texarkana 1996, pet. ref'd) (statement made after 12-13 hours admissible).  While the exact timeline is not clear here, we see no abuse of discretion in the trial court’s admitting the statements of Q.M.’s mother concerning his use of methamphetamine, even if the statements were made several hours after Q.M. smoked the substance.  From the officer’s testimony, it seems clear Q.M. still was displaying symptoms of his ingestion of methamphetamine at the time of the mother’s statements. Appellant makes similar arguments with regard to Q.M.’s statement to the officer that he smoked a “30 bag” of methamphetamine.  Q.M. testified that after smoking methamphetamine and marijuana,[6] he “felt weird in [his] arms and I left. I started walking to my house and my mother picked me up.” He described the “weird” feeling in his arms as “freezing up, going up.”  Although he said he had smoked methamphetamine before, he had never before experienced such feelings.  The trial court reasonably could have determined the symptoms of overdose were startling to him, and that the challenged statement was made under the stress of his condition.  There was nothing self-serving about the statement in that context and was not in response to an interrogation.  The admission of Q.M.’s statement was within the range of reasonable disagreement, and so not an abuse of discretion.  Montgomery, 810 S.W.2d at 389. Alternatively, Q.M.’s statement was admissible under Rule 803(24), as a statement against interest. Under that provision, such a statement is one which was “at the time of its making…so far tended to subject the declarant to civil or criminal liability…that a reasonable person in declarant’s position would not have made the statement unless believing it to be true.”[7] Q.M. admitted to using .5 grams of methamphetamine, therefore admitting to a criminal offense. See Tex. Health & Safety Code Ann. § 481.115(b)) (West 2010) (providing possession of a controlled substance in an amount less than one gram is a state jail felony). We overrule appellant’s fifth and sixth points of error. Objection to Witness and Motion for Continuance             Appellant contends in his seventh point of error that the trial court erred when it overruled his objection and denied his motion for continuance in connection with the presentation of Mark McCain, an employee of the Dallas commercial laboratory, as a witness by the State.  Appellant asserts the State failed to properly disclose McCain as a witness, and by failing to do so, operated to surprise appellant and prevented him from seeking his own expert to assist him in cross-examination.  McCain’s testimony was used to establish Q.M. had methamphetamine in his urine. In criminal prosecutions, "[n]otice of the State's witnesses shall be given upon request." Martinez v. State, 867 S.W.2d 30, 39 (Tex.Crim.App. 1993). If the trial court allows a witness who does not appear on the State's witness list to testify, then we must determine whether the prosecutor's actions constituted bad faith and whether the defense could have reasonably anticipated the witness' testimony. Id. In considering whether the State acted in bad faith, reviewing courts have considered the following three areas of inquiry: (1) whether the defense shows that the State intended to deceive; (2) whether the State's notice left the defense adequate time to prepare; and (3) whether the State freely provided the defense with information (e.g., by promptly notifying the defense of new witnesses, by providing updated witness lists, or by maintaining an open file policy). Martinez v. State, 131 S.W.3d 22, 29 (Tex. App.--San Antonio 2003, no pet.). We review the granting or denial of a motion for continuance under an abuse of discretion standard. Heiselbetz v. State, 906 S.W.2d 500, 511 (Tex.Crim.App. 1995). To show the trial court abused its discretion in refusing to grant a motion for continuance, the defendant must show he was prejudiced by his counsel's inadequate preparation time. Id.; Duhamel v. State, 717 S.W.2d 80, 83 (Tex.Crim.App. 1986).             Here, more than a month before trial, the State provided notice it intended to rely on documents from the Dallas lab, LabCorp.  Nineteen days before trial, the State supplemented its witness list to include an unnamed LabCorp technician.  Four days before trial, the State provided to appellant the name of the technician, Mark McCain.  At trial, the court found no undue surprise because appellant was timely notified a LabCorp technician would testify, and offered appellant the opportunity to take time to interview McCain. Prior to McCain’s testimony, appellant informed the court he had visited with McCain. Appellant also conducted a complete cross-examination of McCain.             There was no showing or allegation the prosecutor acted in bad faith.  As the trial court found, appellant could have reasonably anticipated the testimony of McCain.  The trial court offered appellant the opportunity to take time to interview McCain before cross examining him and appellant did so. We see no abuse of discretion in the trial court’s denial of appellant’s motion for continuance or its permitting McCain to testify.  We overrule appellant’s seventh point of error. Rule of Evidence 403 objections              In his last three points of error, appellant argues the trial court erred in permitting the hearsay testimony of the responding officer and Q.M.’s mother over his objection that the testimony violated Rule 403 of the Rules of Evidence. Two of the challenged statements are the same as were addressed in appellant’s fifth and sixth points of error:  the responding officer’s testimony Q.M.’s mother told him “she thought her son had overdosed on methamphetamine”; and the officer’s testimony Q.M. told him “he had smoked a 30 bag of methamphetamine.”  The trial court overruled both Rule 403 objections, based on the Rule 403 balancing test.             Whether evidence is admissible under Evidence Rule 403 is a decision within the sound discretion of the trial court.  Montgomery, 810 S.W.2d at 386, 389.  Rule 403 allows for the exclusion of otherwise relevant evidence when its probative value "is substantially outweighed by the danger of unfair prejudice, confusion of the issues, or misleading the jury, or by considerations of undue delay, or needless presentation of cumulative evidence." Tex. R. Evid. 403.  Rule 403 favors the admission of relevant evidence and carries a presumption that relevant evidence will be more probative than prejudicial. Montgomery, 810 S.W.2d at 389. A trial court must balance (1) the inherent probative force of the proffered item of evidence along with (2) the proponent's need for that evidence against (3) any tendency of the evidence to suggest decision on an improper basis, (4) any tendency of the evidence to confuse or distract the jury from the main issues, (5) any tendency of the evidence to be given undue weight by a jury that has not been equipped to evaluate the probative force of the evidence, and (6) the likelihood that presentation of the evidence will consume an inordinate amount of time or repeat evidence already admitted. Casey v. State, 215 S.W.3d 870, 879-880 (Tex.Crim.App. 2007).             Here, the probative value of the evidence was not substantially outweighed by the danger of unfair prejudice.  Tex. R. Evid. 403.  “Unfair prejudice does not, of course, mean that the evidence injures the opponent's case -- the central point of offering evidence. Rather it refers to an undue tendency to suggest decision on an improper basis, commonly, though not necessarily, an emotional one.” Cohn v. State, 849 S.W.2d 817, 820 (Tex.Crim.App. 1993) (quoting GOODE, ET. AL., TEXAS PRACTICE: TEXAS RULES OF EVIDENCE: CIVIL AND CRIMINAL, § 403.2 (1988)).  The challenged testimony was evidence the victim identified the substance he received as methamphetamine.  The evidence was strongly probative of elements of the State’s case, and we see little risk it would suggest a decision on an improper basis.  The court did not abuse its discretion in its rulings on the Rule 403 objections.              Appellant raises the same contention with regard to the mother’s testimony that appellant told her he did not sell methamphetamine to Q.M. but he did smoke methamphetamine with the boy. This statement was apparently made the Sunday before trial at Q.M.’s grandmother’s house.  The statement, an admission by appellant,[8] also had strong probative value, both as to appellant’s conduct and his culpable mental state.  Unquestionably it prejudiced appellant’s defense, but the trial court was correct to find its prejudice was not unfair.             We overrule appellant’s eighth, ninth and tenth points of error.             Having overruled each of appellant’s contentions, we affirm the judgment of the trial court.                                                                                                   James T. Campbell                                                                                                             Justice   Do not publish.     [1] See Tex. Health & Safety Code Ann. § 481.122 (West 2003).   [2] Appellant plead “not true” to each of the two enhancement paragraphs. After hearing punishment stage evidence, the jury found the allegations in each to be true.  Those findings are not challenged on appeal. [3] During an earlier hearing outside the jury’s presence, the officer described Q.M.’s mother’s demeanor as “very distraught,” “seemed . . . really worried about her son,” “shaking, trembling, just scared.”   [4] The officer testified a “30 bag” was approximately .5 grams of methamphetamine.  [5] The previously-applied factual sufficiency standard considers whether the evidence supporting guilt, though legally sufficient, is so weak that the jury’s verdict seems clearly wrong and manifestly unjust, or evidence contrary to the verdict is such that the jury’s verdict is against the great weight and preponderance of the evidence.  Grotti v. State, 273 S.W.3d 273, 283 (Tex.Crim.App. 2008); Watson v. State, 204 S.W.3d 404, 414-15 (Tex.Crim.App. 2006).  Under that standard, the ultimate question is whether, considering all the evidence in a neutral light, the jury was rationally justified in finding guilt beyond a reasonable doubt.  Grotti, 273 S.W.3d at 283.  Even had we applied such a standard of review of the evidence, we could not sustain appellant’s sufficiency contentions.  From our review of the entire record, the finding of appellant’s guilt was neither clearly wrong and manifestly unjust nor against the great weight and preponderance of the evidence. [6] He testified he smoked the methamphetamine and then went to Dann’s house and smoked marijuana for about ten minutes. [7] Additionally, in criminal cases, a statement tending to expose the declarant to criminal liability is not admissible unless corroborating circumstances clearly indicate the trustworthiness of the statement.  Tex. R. Evid. 803(24). The medical evidence provided corroboration indicating the trustworthiness of Q.M.’s statement to the officer. [8] See Tex. R. Evid. 801(e)(2) (admission by party opponent).
null
minipile
NaturalLanguage
mit
null
“This was the week of Kim Davis,” Real Time host Bill Maher declared Friday, three days after the Kentucky clerk who refused to issue marriage licenses to same-sex couples walked out of jail to a cheering crowd of Bible-thumpers who praised her for refusing to follow the law or do her damn job.She’s Republicans’ new hero, the “Rosa Parks of homophobia,” as Maher dubbed her Friday, matched in bigotry only by her hand-holding partner in hatred, Mike Huckabee, “the white Al Sharpton.”“They all got out there and said, ‘God’s law supersedes the courts, which actually is a very strong legal argument—in Saudi Arabia, but not here in America,” Maher said. “I don’t want to say that the super religious types are always hypocrites but here she is. Standing up for traditional marriage and then we find out she’s had multiple affairs, conceived twins out of wedlock, and has been married four times! That’s why she can’t give marriage licenses to the gays—she used them all for herself!”Daily Beast columnist Michael Moynihan, who was one of three panelists along with author Salman Rushdie and Center for Equal Opportunity Chairwoman Linda Chavez, had a sunnier outlook on Davis’s intentions. “I think that her intention here is to sort of slowly bring people around to the idea of gay marriage. She comes out of jail, every Republican is waiting to take their photo with her… everyone’s holding up crosses and Survivor’s ‘Eye of the Tiger’ is playing,” he said, describing the nightmarish scene. Maher also offered Davis’s husband, who wore an unironic pair of overalls and a straw hat to the ‘Welcome Back from Jail’ rally, some advice: “When people already think you’re brainless, it doesn’t help to dress like the Scarecrow.”Rushdie chalked up Davis’s delusional martyr complex to a “classic trope of the religious bigot.”“While they are denying people their rights, they claim their rights are being denied. While they are persecuting people, they claim to be persecuted. While they’re behaving colossally offensively, they claim to be the offended party,” he said.“Especially Christians,” Maher added. “I mean, the whole thing is based on a persecution complex. So when they say things like they’re criminalizing Christianity—really? You’re 70 percent of the population.”“But everybody does this,” Rushdie countered. “In India right now, [which has] a 85 percent Hindu majority, leaders are saying Hinduism is being threatened. In the Islamic world, the paranoia is routine: ‘The world is anti-Muslim.’ And so this is just a trope that they're stealing from other bigots.”Hateful, hypocritical, and unoriginal? Pick a fatal flaw, Davis.
null
minipile
NaturalLanguage
mit
null
Retinal neurones specific for centrifugal modulation of vision. The avian retina receives centrifugal projections from a midbrain nucleus, the isthmo-optic nucleus. We labelled target cells for the isthmo-optic fibres by intracellular injections of Lucifer Yellow in fixed retinal slices. The isthmo-optic recipient (IOR) cells had no major dendrites extending into the inner plexiform layer, but had a thin axon-like process running horizontally in the junction between the inner nuclear layer and the inner plexiform layer. The IOR cells were morphologically similar to the association amacrine cells of Cajal. Immunohistochemical localization of aspartate and glutamate in the IOR cells suggested that they may use these excitatory amino acids as neurotransmitters.
null
minipile
NaturalLanguage
mit
null
Q: What is the name of the 'resultset' argument in an ADODB.Command calling an Oracle stored procedure in Classic.ASP? I have the pleasure of maintaining a legacy application using Classic.ASP for the frontend and an Oracle database for the backend. We have an ongoing issues where we need to routinely update queries like the following to have an ever increasing value for the 'resultset' parameter Set cmdStoredProc = Server.CreateObject("ADODB.Command") cmdStoredProc.CommandText = "{call package_name.Procedure_Name(?,{resultset 1500, v_out_one, v_out_two})}" It started at 500, then a bug fix made it 1000, then 1500, and now it has became an issue again on my watch. Rather than follow in my predecessor's footsteps and arbitrarily increase it I'd like to know as much as possible about this feature but am struggling to find any documentation on it. Is there a specific name given to this feature / argument / parameter? Knowing this should be enough to allow me to find out more about it but a brief explanation of it or link to documentation on it would be advantageous. From the comments / answers it has become apparent that having the definition of the procedure that is being called could be useful: PROCEDURE Procedure_Name (n_site_id_in IN TABLENAME.site_org_id%TYPE, v_out_one OUT t_c_out_one, v_out_two OUT t_c_out_two) IS --Select the CC and account code and descriptions into a cursor CURSOR c1 IS SELECT a.out_one, a.out_two FROM TABLENAME a WHERE a.site_org_id = n_site_id_in ORDER BY a.out_one, a.out_two; i INTEGER DEFAULT 1; BEGIN FOR get_c1 IN c1 LOOP v_out_one(i) := get_c1.out_one; v_out_two(i) := get_c1.out_two; i := i + 1; END LOOP; EXCEPTION WHEN NO_DATA_FOUND THEN DBMS_OUTPUT.PUT_LINE('no data found'); WHEN OTHERS THEN DBMS_OUTPUT.PUT_LINE('sqlerrm '||SQLERRM); RAISE; END Procedure_Name; From this we can see the procedure has 3 parameters defined, 1 IN and 2 OUT, yet the call to the procedure seems to convert the 2 OUT parameters to a collection based on resultset. The driver in use is 'Microsoft ODBC for Oracle' (MSORCL32.DLL) A: The 'resultset' argument does not have any special name, it is just known as the resultset parameter. There are multiple ways it can be used: Return all the columns in a single result set (as it currently is): Set cmdStoredProc = Server.CreateObject("ADODB.Command") cmdStoredProc.CommandText = "{call package_name.Procedure_Name(?,{resultset 1500, v_out_one, v_out_two})}" Return each column as a single result set (to return 2 separate result sets): Set cmdStoredProc = Server.CreateObject("ADODB.Command") cmdStoredProc.CommandText = "{call package_name.Procedure_Name(?,{resultset 1500, v_out_one}, {resultset 1500, v_out_two})}" Read more about it here: https://docs.microsoft.com/en-us/sql/odbc/microsoft/returning-array-parameters-from-stored-procedures As assumed, it is used to set the limit on the amount of records that can be returned from the procedure call. The definition of the procedure shows that it is returning 2 arrays as output so an error will be thrown if either of them exceeds the limit set in the resultset parameter.
null
minipile
NaturalLanguage
mit
null
The2017CanSatCompetitionFinals,Ploiesti,19–23April on 19 April 2017 Starting from 19 April and until 23 April, seven student teams participate at the finals of the 2017 National CanSat Competition. The event is organised by ESERO Romania and it will take place at the Elie Radu Technical College and the George Valentin Bibescu Aerodrome in Ploiesti. The 2017 CanSat Competition is organised by ESERO Romania, a project of the European Space Agency (ESA), in collaboration with the Romanian Space Agency (ROSA). The 2017 edition is organised with the support of the Prahova County School Inspectorate and the Superior School of Civil Aviation. The teams selected for the final stage by ESERO Romania, in collaboration with ESA’s Education Office, are: The teams will present their projects in the order presented above, with the mention that the Microsat team withdrew from the competition. CanSats represent a simulation of a satellite integrated in the volume and shape of a standard beverages can. The challenge for the participant students resides in including all the major subsystems of a satellite – such as electricity power and communication – in a can with a volume of 330 milliters. The CanSats will be launched from an altitude of one kilometre, they should accomplish a mission and land in safe conditions. The projects selected for the 2017 edition will be launched with the assistance of a helicopter. The launching campaign will take place on the George Valentin Bibescu Aerodrome, in Ploiesti. Prior to the CanSat launch, the satellite designed by each team will need to pass a technical test, which will determine if it respects the competition restrictions in terms of size, weight, radio communication and parachute. The winning team of the national competition will qualify in the finals of the 2017 European CanSat Competition, organised by ESA.
null
minipile
NaturalLanguage
mit
null
Effect of reticulocytosis on lactate dehydrogenase isoenzyme distribution in serum: in vivo and in vitro studies. We investigated the effect of reticulocytosis on the lactate dehydrogenase (LD; EC 1.1.1.27) isoenzyme LD1/LD2 ratio in patients with and without evidence of hemolytic disease. Analysis of sera from patients with reticulocytosis and in vivo hemolysis showed a mean LD1/LD2 ratio of 0.92 compared with a ratio of 0.69 in patients with in vivo hemolysis and normal reticulocyte counts. Determination of LD isoenzymes in erythrocyte lysate revealed significantly increased LD1/LD2 ratios for patients with marked reticulocytosis compared with those for patients with normal-to-minimal increases in reticulocytes. Finally, separation of mature erythrocytes and reticulocytes by flow cytometry revealed marked differences in the LD1/LD2 isoenzyme distribution between these two cell types. The ability of hemolysis to cause a "flipped" LD1/LD2 ratio is dependent on the proportion of the hemolyzed cells that are reticulocytes.
null
minipile
NaturalLanguage
mit
null
Staunton, May 26 – The “most significant result” of the Ukrainian presidential elections was not the selection of Petro Poroshenko, his victory in the first round, or the defeat of Yuliya Tymoshenko but rather “the formal-legal death of the Putin myth about the so-called ‘split’ of Ukraine into a West-Central and South-Eastern part,” Andrey Illarionov say. As such, the Russian commentator says, the vote effectively represents “the funeral of Putin’s plan for the division of Ukraine, the final completion of the 20-year period of ‘Ukrainianization, [and] an important stage on the path to the Westernization and Europeanization of Ukraine.” In this Ukrainian election, in contrast to earlier presidential votes there, the winner was not someone who won the most votes in the west but lost the east or who won the east but lost the west. “For the first time, the president of Ukraine was chosen by the votes of all Ukraine, by the votes of the residents of all major Ukrainian macro-regions.” Even more, Illarionov says, the three trailing candidates received approximately the same level of support in the two regions, something that represents “the absolute victory of the national choice by Ukrainian citizens” of the entire country “of the western variant of development of a united Ukraine.” “In other words,” he continues, the Ukrainian election has led to the “total collapse of Putin’s plans” for that country. Ukraine “did not become Banderite or anti-Russian Federation or anti-Russian,” but that country, and indeed “practically” all of it, however, “has become anti-Putin” and seeks “integration in the western, that is, the contemporary world.”
null
minipile
NaturalLanguage
mit
null
Rob Goldman, Facebook's vice president of advertising, addresses that concern head on in a "Hard Questions" blog post Monday as he answers the question: "If I'm not paying for Facebook, am I the product?" "No. Our product is social media -- the ability to connect with the people that matter to you, wherever they are in the world," Goldman said in the post. He compared Facebook's free use and business model with advertising for websites, newspapers and search engines. "The core product is reading the news or finding information -- and the ads exist to fund that experience," he added. Facebook's argument dives into the semantics of what a "product" is, Daniel Ives, an analyst at GBH Insights, said. The company is actively "defending their advertising fortress," he said, going to great lengths to protect its model. He says Facebook is right when it says the company's product is the social network, but that product isn't what turned Facebook into a multibillion dollar company. "Their product is social media, but their ability to monetize comes from their advertising," Ives said. So yes, Facebook amassed billions of users through it's "product," but it was the company's data as a product for advertisers that lead to the company's fortune, he added. The blog post also touched on how much data the social network has on its 2 billion users. Goldman said Facebook doesn't sell information to advertisers but does collect data on people in bulk to help advertisers target specific groups. He gave an example of a bike shop that wanted to specifically reach female cyclists in Atlanta. If your Facebook profile suggests you fit the mold, the social network targets ads to you. "We provide advertisers with reports about the kinds of people seeing their ads and how their ads are performing, but we don't share information that personally identifies you," Goldman said. First published at 7:13 a.m. PT.Update at 11:25 a.m. PT: Adds comments from an analyst.
null
minipile
NaturalLanguage
mit
null
Fragrant Candles Unfortgettably Fragrant Candles In 5 Warm Holiday Scents Infused with fragrant oils rather than dipped in perfumes, our candles evoke the scents of the season. Apple and autumn spice candles bring to mind the beauty of fall; bayberry candles derive their woodsy aroma from the bayberry bush; pine candles have the heady fragrance of a New England forest; and hollyberry candles capture the rich essence of the Christmas season. You May Also Like... Beautifully Fragrant, Clean Burning Candles I purchased the Bayberry candle and I love it! The candle burns very clean and has a beautiful scent. The color is also very nice. January 10, 2015 Fragrant Memories I have been getting the bayberry pilar candles for quite some time. They remind me of my grandparent's home in Illinois and my grandmother's home in Kansas and my parent's home in Delaware. Every time they are lit, I am transported back to the wonderful times spent with my family; Christmas carols on the turntable, baking cookies, gaily wrapped presents and quiet nights in front of the fireplace with just the light of the Christmas tree reflecting on heirloom ornaments. The candles are very much a part of my Christmas. December 7, 2014 Virtually Scentless We were happy to see a Bayberry candle offered at the Vermont Country Store. They're really hard to find. Unfortunately, the candle had no discernible scent when burned. It barely had a scent even unlit and up close. I don't know if it had been sitting around for too long at the store or if it was just a poorly scented candle. We won't be ordering candles from the VCS again. November 15, 2014 family tradition My grandmother used to give bayberry candles for Christmas every year. After she passed away I continued the tradition. We make sure we burn them during the holiday season, "to the socket to bring good luck & money to our pocket" to the new year. October 13, 2014 The Only Candle in the House I only ever buy the VCS Bayberry candle. A six-inch pillar lasts for a year. The scent is spicy, warm, not overpowering and makes the house smell fabulous. January 9, 2014 9 inch pillar is a good size and burns evenly,trim wick for constant flame height I got the Holly and Bayberry 9 inch pillars. The aroma on the Holly is pleasant, I haven't started the Bayberry yet. The candle burns in the center evenly with small side walls that can be turned in. Not to many sites offering large candles this year. I also ordered the Pine scent but it was sold out. I've been ordering from the Vermont Country Store for 20 years and the quality is very good. Most items made in USA. December 21, 2013 Smell of Autumn Recently I have had trouble finding a fragrant candle. I have brought plenty of candles but they just burn and could not smell them hardly at all. Vermont Country Store was a last resort. To my surprise I could smell the candle without being on top of it or just a little when I blew it out. Thanks so much for now I can bring smell of fall into my living room. I recommend it to everybody who is looking for good fragrant candles. October 29, 2013 Your Bayberry candles are the best! These candles are truly the best bayberry candles I've ever burned. They have the true essence of bayberry without the heavy artificial scent that can be overpowering. they burn slow and last a long time! I love them and they make a great gift! Keep selling them! It's hard to find high quality candles like yours! October 15, 2013 What Our Customers Are Saying about Our Fragrant Candles … "These are the only scented candles that don't give me a headache, and they last for a really long time. The fragrances are lovely (my favorite is the bayberry) and they are a good value." - Jan, Littleton, CO "My sister sent a bayberry candle from VCS last Christmas after searching and searching for a true bayberry candle. Mom always burned one during the holiday season as legend has it that it will bring you good luck. Mom has not been able to find a bayberry candle for years until now. The candle smelled wonderful, even when it was not burning. It brought back happy memories of my childhood when Mom always burned the candles. The candle burned beautifully and evenly. It was true to the green of the candles from years ago. Worth every penny!"- Pam, Davis, IL
null
minipile
NaturalLanguage
mit
null
Lung capillary albumin leak in oxygen toxicity. A quantitative immunocytochemical study. The study is based on the hypothesis that lung endothelial cell permeability increases in 100% oxygen and predates the appearance of microscopically visible interstitial edema. Rats were exposed to either 100% oxygen or air in a chamber. Endogenous albumin was used as an index of permeability and measured by electron microscopic colloidal gold linked immunocytochemistry, quantified by systematic random methods. Albumin staining was expressed as relative albumin concentration (RAC), the ratio of gold particles (x 100) per point counted (gp.10(2)/pt) relating to each component. The RAC in lung perivascular/peribronchial interstitial ground substance after 24 h of hyperoxia was five times more than that of rats exposed to air for the same interval. The median value (interquartile ranges) for the oxygen-exposed group was 92.4 (39.5, 149.6) gp. 10(2)/pt compared with 14.7 (6.6, 25.9) gp. 10(2)/pt for the air-exposed group. After 60 h of 100% oxygen, the RAC was 103.4 (65.5, 148.9) gp. 10(2)/pt (60-h air exposed RAC was 11.6 (8.7, 60.4) gp. 10(2)/pt), no different from 24-h exposures. These results suggest that there was a significant leak of albumin to the perivascular/peribronchial interstitium by 24 h of exposure to 100% oxygen, which would indicate endothelial cell permeability to albumin increases earlier than has previously been reported.
null
minipile
NaturalLanguage
mit
null
A Macintosh enthusiast has apparently managed to load Windows XP on an Intel Mac, nabbing a nearly $14,000 prize. For some days, there has been discussion that the person who goes by the handle "narf" had managed the technically challenging feat. Photos were posted on Flickr, and much debate ensued. However, narf's method had to prove replicable before the contest was officially ended. On Thursday, though, the contest ended, and a winner was declared. "Contest has been won--updates to follow shortly," reads a short message on the contest's Web site. The contest, which has been running since just after Apple Computer announced the first Intel-based Macs, collected donations from individuals and companies to raise the prize money. Listen up Although both Macs and Windows PCs now use Intel chips, the task of loading Windows on the Intel Macs has proved more complicated, in part because both use different means of booting up. There had been hope that the next version of Windows would make things easier, but an Apple executive last week said booting Vista on Macs may not prove that easy, either. The win comes just ahead of an end-of-month deadline that would have seen the money go instead to the Electronic Frontier Foundation. The effort was launched by Colin Nederkoorn, who put up $100 of his own money, hoping his new Intel Mac would be able to replace his Windows PC. According to the rules, his Web site now has the rights to publish the solution. The solution appears to be available for download, though traffic to the site was heavy Thursday. An Apple representative was not immediately available for comment. Wil Shipley, who heads Mac software firm Delicious Monster Software, said he was "thrilled to bits" that the goal had been reached. Delicious Monster kicked in $1,000 of the prize fund. "Although Apple doesn't talk about it, the market share for Intel Macs is going to increase dramatically when they can run legacy Windows apps, especially games," Shipley said in an e-mail interview. "It's truly the best of both worlds." Shipley said he is pleased with the feat for both personal and business reasons. "As a gamer, I really appreciate not having to have a separate, crappy machine to feed my addiction," he said. "And as a Mac software author, every 0.01 percent market share that Apple gains for the Mac directly nets me thousands of dollars a year."
null
minipile
NaturalLanguage
mit
null
Kodiak seine fleet tests viability of new pollock fishery The Kodiak seine fleet is embarking on a new fishery to test the viability of catching pollock with that gear type, a species that is generally caught with trawl gear. The fishery will take place in state waters, within three miles of shore, under a special “commissioner’s permit” issued by the Alaska Board of Fisheries in January. It is likely that a close-shore pollock seine fishery might be successful in terms of catch; halibut charter boats in Homer frequently stop at the end of the Homer Spit and jig up pollock for bait, indicating large schools. While the fishery was originally also proposed for Kachemak Bay, it is only being carried out in Kodiak, because seine gear is not a legal gear type for groundfish in Kachemak Bay, which is a critical habitat area. It’s also an experimental gear type for groundfish, according to area management biologist Janet Rumble with the Homer office of the Alaska Department of Fish and Game. “We’re not even sure that seine is going to work,” Rumble said. One of the drivers behind the proposal is the perception that high groundfish populations, most notably pollock and cod, are driving down the shellfish populations, something Rumble acknowledged. “(Groundfish) are more plentiful now than they were before,” she said. “Tanner crab are not as plentiful, Dungeness are gone, shrimp is gone, we have these other two (species) that seem to be prevalent, so let’s fish for them. “I think people are interested in seeing how it would affect things if we had a little less pollock.” Boats using jig gear for cod are also now allowed to keep pollock, without a limit as a bycatch species. There are some questions about harvest timing in terms of market and product quality, and the timing of the first pollock test fishery, April 11 through June 8, reflects the desire to avoid conflict between the pollock and salmon seine fisheries. Another big question is potential bycatch, Rumble said. “If king salmon start coming up in the seines, these are things we’re all interested and worried about.” There are a myriad of other issues involved, including pollock stock assessments, the upcoming federal pollock catch shares program, observer coverage, and more. There are plans for a BOF work group to meet and attempt to hammer out those issues April 16.
null
minipile
NaturalLanguage
mit
null
Juho Reinvall Juho Reinvall (born 24 August 1988) is a Finnish judoka. He competed at the 2016 Summer Olympics in the men's 60 kg event, in which he was eliminated in the second round by Tsogtbaatar Tsend-Ochir. References Category:1988 births Category:Living people Category:Finnish male judoka Category:Olympic judoka of Finland Category:Judoka at the 2016 Summer Olympics Category:European Games competitors for Finland Category:Judoka at the 2015 European Games
null
minipile
NaturalLanguage
mit
null
Introduction {#Sec1} ============ Understanding patterns, determinants and consequences of inter-individual variation within populations is a central theme in current ecological research (Bolnick et al. [@CR16]; Dall et al. [@CR35]; Sih et al. [@CR110]; Wolf and Weissing [@CR119]). Individuals of natural populations often occupy only part of the species' ecological niche (Bolnick et al. [@CR15]; Stamps and Groothuis [@CR114]; Hart et al. [@CR57]) and that has given way to the idea of individual niche specialization (Bolnick et al. [@CR15]; Araújo et al. [@CR5]). Individual niche specialization challenges classical niche theory (e.g., summarized in Chase and Leibold [@CR29]), which has traditionally treated all individuals of a species as uniform regarding their ecological requirements and behavior (e.g., Chesson [@CR30]; Adler, et al. [@CR2]; Levine and HilleRisLambers [@CR77]; Letten et al. [@CR76]). Particularly, consistent inter-individual differences, e.g., animal personality (Gosling [@CR50]), were suggested to affect important ecological processes and to generate spatio-temporal variability that influences individuals' interactions with biotic and abiotic factors (Webster et al. [@CR115]; Bolnick et al. [@CR16]; Brodersen et al. [@CR20]; Wolf and Weissing [@CR119]; Pearish et al. [@CR98]; Best et al. [@CR13]; Holtmann et al. [@CR61]). Since interactions are essential in forming the ecological niche of an individual, the acknowledgement of consistent differences among individuals, and therefore the occupation of individual niches that together form the whole species niche should be imperative (Bolnick et al. [@CR15]). Such segregation into individual niches should decrease intraspecific competition and support the maintenance of variation in natural populations (Bolnick et al. [@CR15], [@CR16]; Wolf and Weissing [@CR119]). Many ecological interactions, both within- and between species, are mediated by spatio-temporal variation of habitat use (e.g., Chappell [@CR28]; Werner et al. [@CR116]; Boon et al. [@CR18]; Fischer and Schröder [@CR45]; Owen-Smith [@CR97]). Consequently, individual differences in movement and space use are key components of an individual's ecological niche. However, so far, ecological research has mainly focussed on individual specialization in diet (Bolnick et al. [@CR15]). Little is still known on how differential movement and space use might facilitate individual niche segregation. Therefore, the main aim of this study was to test whether consistent inter-individual differences in behavior predict space use and movement patterns in natural habitats thereby contributing to individual niche specialization. Many classical movement studies treat conspecific individuals as ecologically and behaviorally equivalent, even though evidence for individual differences is apparent in many of them (Liro and Szacki [@CR79]; Austin et al. [@CR8]; Nathan et al. [@CR93]; Hawkes [@CR58]; Beest et al. [@CR12]). Theoretical concepts, on the other hand, have taken individual variability in states into account and highlighted its importance for explaining intraspecific variation in movement patterns as well as the discrepancy between observed and expected behavior based on optimality approaches (Nathan et al. [@CR93]; Jeltsch et al. [@CR65]; Nilsson et al. [@CR94]; Spiegel et al. [@CR113]). Empirical studies testing predictions of these theoretical frameworks are recently emerging, suggesting that personality-dependent movement and space use should be incorporated into movement ecology studies (Chapman et al. [@CR27]; Harrison et al. [@CR55]; Spiegel et al. [@CR112]). As pointed out by Spiegel et al. ([@CR112]), the majority of those studies incur a problem of non-independency because they base their personality quantification directly on the movement data. Moreover, most studies only observed resulting space use patterns of different behavioral types, but the underlying movement pattern might be an equally important factor shaping the spatial dynamics of natural populations. Here, we, therefore, independently quantified consistent individual differences in behavior, using standardized experimental procedures, and movement and space use patterns, using automated radio-tracking under natural conditions. Movement in general can be separated into three distinctive types, foraging, dispersal and migration, depending on their spatio-temporal scale (Nathan et al. [@CR93]; Clobert [@CR31]; Jeltsch et al. [@CR65]). Up till now, most research regarding the influence of individual differences on movement has focused on dispersal, i.e., large-scale movement. In general, more aggressive, bolder or more explorative individuals tend to disperse and cover larger dispersal distances compared to less aggressive, shy or less explorative individuals (Cote et al. [@CR33]). For example, in western bluebirds (*Sialia mexicana*), the aggression of individuals positively affected their probability to colonize new areas, which supported a rapid range expansion of that species at the edges of its distribution (Duckworth and Badyaev [@CR39]; Duckworth and Price [@CR40]). Similarly, dispersing delicate skinks (*Lampropholis delicate*) had consistently higher levels of aggression compared to their resident conspecifics (Michelangeli et al. [@CR88]), fast-exploring individuals of wild great tits (*Parus major*) dispersed further than their slow-exploring conspecifics (Dingemanse et al. [@CR38]), and bolder individuals of the Trinidad killifish (*Rivulus hartii*) had larger dispersal distances than shy conspecifics (Fraser et al. [@CR46]). Besides extensive research on personality-dependent dispersal, only few studies focused on local movement types, even though those small-scale movements are of key importance regarding ecological interactions and the forming of individual niches (Kobler et al. [@CR68]; Pearish et al. [@CR98]; Best et al. [@CR13]; Farine et al. [@CR43]; Spiegel et al. [@CR112]). These studies indicate that movement within a habitat is also influenced by individual differences. In sleepy lizards (*Tiliqua rugosa*), for example, boldness predicted home range size and aggression influenced the intensity of use of habitat areas (Spiegel et al. [@CR112]). Furthermore, individual differences in behavior affected spatial distribution of individuals across microhabitats leading to a non-random distribution of behavioral types. For example, in pikes (*Esox lucius*) individuals consistently preferred different densities of vegetation cover in a lake and thereby occupied different areas which enabled the identification of different behavioral types (Kobler et al. [@CR68]). This behavioral type--environment correlation, where certain behavioral types are more frequently found in specific environments, could also be shown for a natural population of sticklebacks: individuals that emerged from a refuge faster were more likely to be in shoals with other sticklebacks (Pearish et al. [@CR98]). Behavioral type--environmental correlations, therefore, can refer to the social environment as well (Best et al. [@CR13]; Farine et al. [@CR43]). Resulting from this behavioral type--environment correlation, both in terms of abiotic, biotic or social environment, the spatial distribution of individuals is non-random. A non-random distribution of behavioral types within a population's habitat in turn influences the spatial overlap of these types. Consequently, the probability of individuals of similar behavioral type interacting, directly or indirectly, is much higher due to their spatial proximity and the use of similar resources. Individual differences, therefore, also result in non-random interactions between individuals (Pruitt and Ferrari [@CR100]; Wolf and Weissing [@CR119]; Pruitt and Modlmeier [@CR101]). Quantifying and considering individual differences of neighboring individuals in natural populations is, thus, crucial to understand how these individuals interact in space and time. Furthermore, both restricted interactions and the experience of different environmental conditions should be two key aspects of individual niche specialization and the shaping of ecological communities (Bolnick et al. [@CR15], [@CR16]). Empirical research testing these potential relationships is scarce, mainly due to challenges of quantifying behavioral variation of a set of neighboring individuals, while simultaneously tracking their movements through space. Small mammals play a key role in ecosystems, being foragers/consumers themselves, as well as being highly susceptible to ground and avian predation. Many small rodents, such as mice and voles, are highly dependent on the characteristics of their habitat to minimize predation, preferring heterogeneous habitats consisting of woody vegetation combined with grassy areas, like woodlands, shrubs, hedges and meadows (Hansson [@CR53]; Adler [@CR1]; Hansson [@CR54]; Fischer and Schröder [@CR45]) that offer cover from predation. They are sensitive to even small changes in habitat structure (e.g., cover) and this sensitivity can drive population dynamics and density fluctuations as well as foraging movements of individuals (Jędrzejewski et al. [@CR64]; Cook et al. [@CR32]; Alain et al. [@CR3]; Lee and Rhim [@CR75]). Small mammals, therefore, provide a suitable study system because individuals spatially interact, they are trackable in sufficient numbers, show quantifiable consistent differences in behavior, and inhabit vegetation structures which can be quantified as proxy of predation risk and habitat quality (Eccard et al. [@CR41]). Here, we used bank voles (*Myodes glareolus*) since personality traits like risk-taking, activity and exploration can be easily quantified under laboratory conditions (Korpela et al. [@CR69]; Šíchová et al. [@CR108]). Further, bank voles are sensitive to temporal changes in risk and adjust their behavior accordingly (Liesenjohann et al. [@CR78]; Hoffmann et al. [@CR60]). In detail, we investigated the following hypotheses: (1) free-ranging bank voles show measurable consistent inter-individual differences in movement-related behaviors. We predicted individuals to quantitatively differ in boldness and exploration, i.e., these behaviors to be repeatable. (2) Inter-individual differences in movement-related behaviors predict inter-individual differences in space use and movement. Since behavioral traits, such as boldness and exploration, have been shown to be related to home range size, movement within a habitat, and interspecific interactions (e.g., Pruitt and Ferrari [@CR100]; Wolf and Weissing [@CR119]; Spiegel et al. [@CR112]), they should also be key traits influencing the spatial patterns of a highly predated species such as bank voles. We predicted bolder and more explorative individuals to have larger home ranges, to have larger core areas, to move longer distances, and to spatially overlap more with conspecifics than less bold and explorative individuals. (3) Inter-individual differences in behavior are associated with differences in microhabitat use. Since boldness predicts risk-taking during foraging (e.g., Dammhahn and Almeling [@CR37]) and bank voles adjust their risk-taking to perceived predation risk under varying levels of cover (Eccard et al. [@CR41]), we expected home ranges and core areas of shy individuals to be characterized by higher maximum vegetation height and ground cover than those of bold individuals. Methods {#Sec2} ======= Study animals {#Sec3} ------------- Bank voles (Cricetidae, *M. glareolus*) are widely distributed throughout Eurasia and occupy heterogeneous habitats consisting of woody vegetation combined with grassy areas, like woodlands, shrubs, hedges and meadows (Mazurkiewicz and Rajska-Jurgiel [@CR84]; Hansson [@CR54]). The diet includes leaves, roots, seeds, fruits, and grass complemented with insects and other animal-based food (Gębczyńska [@CR47]; Ostfeld [@CR96]). The activity rhythm of bank voles is polyphasic with obvious activity peaks during twilight hours but additional activity bouts throughout the whole day occur (Baumler [@CR11]; Wójcik and Wolk [@CR117]). Populations fluctuate, with a cycle length of 3--5 years, with high densities in peak years, of up to 150 individuals per ha, followed by population crashes in the subsequent year (Ylönen et al. [@CR122]; Korpela et al. [@CR69]). The social organization is characterized by female territoriality, which is especially pronounced during the breeding season (April--October) when females reduce their home ranges and increase their exclusivity (Koskela et al. [@CR72], [@CR73]; Ylönen and Horne [@CR121]). Males are not territorial and usually spatially overlap several female territories (Mazurkiewicz and Mazurkiewicz [@CR83]; Andrzejewski and Mazurkiewicz [@CR4]; Ostfeld [@CR96]). Study sites {#Sec4} ----------- The study was conducted on five study sites in the *AgroScapeLabs*, a joint research platform of the Berlin-Brandenburg Institute for Biodiversity Research (<https://www.bbib.org/home.html>), in North-West Brandenburg, Germany (53°21′56.2″N, 13°48′17.3″E). This area is characterized by intensively used large agricultural fields which are pierced by small unused areas that serve as refuges for the local biodiversity, like hedges and fallow lands. We selected areas of fallow lands as study sites because they are expected to host a variety of rodent species and are confined areas due to their restriction by agricultural fields. The vegetation of these sites was always heterogeneous consisting of grassy areas, streaked with nettles and bushes and a few trees. The most common plants were nettles (*Urtica* spp.) and horehound (*Ballota* spp.). Capture--mark--recapture {#Sec5} ------------------------ We captured animals with Ugglan live traps (Grahnab Sweden, Special no. 2) between August and November 2016. At each study site, 55 traps were set up in a trapping grid with approximately 10-m distance between traps, (covering 0.31--0.49 ha). Trapping grids remained in place until the whole experimental run, including trapping, individual difference tests, VHF tracking and recapture of collared individuals (see below), on the respective site was over. Traps were baited with rolled oats and apples. Before trapping commenced for the first time on a study site, the traps were pre-baited for 24 h, after which the traps were activated and the initial trapping session started. Upon initial capture, each individual was marked with an individual fur cut, weighed, sexed, and determined to species. Trapping continued until \> 95% of the captured animals were marked. At the five study sites, we captured between 75 and 103 rodents, representing a density of 151--260 rodents ha^−1^, of which between 20 and 75 were bank voles (40--162 ha^−1^). Other species included striped field mouse (*Apodemus agrarius*), common vole (*Microtus arvalis*), field vole (*M*. *agrestis*), yellow-necked mouse (*Apodemus flavicollis*) and wood mouse (*A*. *sylvaticus,* species are presented with declining abundances). Individuals that entered the individual difference test (see below) were marked permanently with a passive integrated transponder (PIT, Euro I.D., trovan^®^ ID100) after their first individual difference test for identification in the second test when fur marks had partly grown back. Individual difference test {#Sec6} -------------------------- We tested for consistent between-individual differences on all five trapping grids using a standardized behavioral test in the field. Upon first recapture, each individual entered this test, excluding juveniles (\< 17 g body mass). The test setup consisted of an opaque plastic pipe (10.5 × 32 cm) with a swing door at each end, attached to a round arena (diameter 1.30 m, 30 cm height; Appendix Fig. A1). Captured individuals were placed in their respective trap in front of the test setup and left to enter it on their own accord. The setup excludes the need to handle individuals before testing, precluding possible influences of handling stress on behavioral expression during the test. The latency to leave the trap was noted, as a possible emergence test, but later discarded due to lack of repeatability (see below). Tests were conducted directly upon capture of individuals within their natural habitat at one location on each study site, without translocating them. During the test individuals were exposed to natural environmental conditions. We chose comparable test locations at each study site and restricted testing to days with favorable weather conditions (low wind speed, no rain). The setup is a combination of two established laboratory tests for individual differences in behavior of rodents (Archer [@CR6]; Herde and Eccard [@CR59]), the dark--light test and the open-field test (Appendix Fig. A1). The dark--light test measures willingness of individuals to enter an unknown and potentially risky area. The dark and ceiled compartment (pipe) is assumed to represent cover and safety, while the open and light arena represents an unknown, potentially risky area. By direct observation, we quantified the latencies to enter the arena with the head and with the full body (excluding tail) in seconds. If an individual did not enter the arena within 300 s, the latency was set to 300 s and the individual was gently forced out of the pipe into the arena by hand. Besides being the light compartment in the first test part of the test, the open arena also represents the classic open field setup where the individual behavior in a novel environment is quantified by assuming different levels of perceived risk in different arena parts. The border area, where the wall resembles cover, is assumed to be safe while the exposed middle part of the arena represents a high-risk area. Middle and border parts were divided in a way that they covered the same surface area. Furthermore, the arena was virtually divided into 16 sections to enable quantification of the exploration effort of each individual. We quantified the following variables via direct observation over the test period of 300 s: (1) the latency to enter the middle area for the first time (full body excluding tail), (2) the number of different sections entered, (3) the number of crossings into the middle area, (4) the number of jumps, and (5) the proportion of time spent active, which was assessed instantaneously every 10 s. Individuals were defined as active when they were either running, jumping, grooming or sitting and moving their head scanning the surroundings. This test part started immediately after individuals exited the dark compartment of the previous test part and a re-entering was made impossible by closing the swing door. Tests were repeated upon recapture of the individual (1--7 days later) at least twice for 62 individuals. Automated radio telemetry {#Sec7} ------------------------- On three of the five trapping grids with the highest densities (151, 198 and 222 rodents ha^−1^), we assessed space use and movement distances. At these sites, we equipped a total of 21 individuals (6--8 per site) with VHF radio transmitters (1.1 g, BD-2C, Holohil Systems Ltd., Canada) applied on a collar and tracked them via automated radio telemetry for a total of 4 days. We selected only individuals that were residential (i.e., recaptured \> 2 times) and had a body mass that allowed the carrying of a transmitter without exceeding a ratio of transmitter to body mass of 0.05. Females that were in the last stages of gestation, based on visual inspection, and expected to give birth within the tracking period were excluded, which resulted in 9 females being tracked and 12 males. Substantial effort was made to recapture animals to remove collars after data collection, including increasing the number of traps, using different types of live traps and bait and intensive trapping over several weeks. The tracking system contained a grid of eight omnidirectional antennas (GP 150 Winkler-Spezialantennen, Annaberg, Germany), surrounding the trapping grid at ground level, and two automated multi-channel receiving units (ARU, JDMC Corp, Illinois, US), each one connected to four of the antennas (Appendix Fig. A2). The ARUs recorded noise and signal strengths of the respective transmitter frequency at each connected antenna seven times in a row for 24 s every 20 min, i.e., ca. 96 times per day. We used the median signal strength of seven repeats per antenna for further calculations (see below) to reduce errors from atmospheric disturbances or sudden movements of the animal which can strengthen or weaken single signal pulses. Signal strength was summed up over each side of the arbitrary telemetry grid (3 antennas per side). The proportion of signal strength among the sides was used to calculate an isoline through the grid in both *x* and *y* direction, yielding *x--y* coordinates for each telemetry fix. Immediately before the tracking of animals commenced, we calibrated isolines based on known location points using rotating test transmitters. Accuracy of location calculation was ca. 10 m for each location point. Obvious outliers (distances of \> 50 m to other location points due to strong wind events) in location data were removed from the data set. Spatial analyses {#Sec8} ---------------- Home range size and overlap were based on kernel density analyses of 95% (defined as whole home range) and 50% (defined as core area) of location points. Home ranges, overlaps and movement distances were based on individual locations points of all 4 days of tracking. Spatial analyses were done with the R packages adehabitat (version 1.8.18), *adehabitatHR* (version 0.4.14) and *adehabitatLT* (version 0.3.21; Calenge [@CR22]). We were only able to track the movement and space use of a subset of individuals present at a site, which might impair the analysis of spatial overlap. Therefore, we additionally calculated the mean trapping point of each individual as a proxy of its home range center from capture--mark--recapture data for all trapped bank voles. Subsequently, we quantified the number of mean trapping points located within the home ranges and core areas of tracked individuals. This analysis allowed us to assess spatial interactions between tracked individuals and all residential individuals present at each site. Mean trapping points of individuals were based on 4.33 ± 3.56 (mean ± SD) captures/individual. The number of mean trapping points per tracked home range and core area was extracted with the program QGIS (version 2.18.14). Microhabitat structure {#Sec9} ---------------------- Habitat characteristics were determined by measuring the maximum vegetation height (in cm) in a square meter around each trap location of each trapping grid. This maximum vegetation height correlates well with average vegetation height (M. Dammhahn, unpublished data). We choose maximum vegetation height as a habitat characteristic because at our study sites, microhabitats mainly varied between areas of grass and herbal vegetation of ca. 94.6 ± 76.4 cm height and small trees and bushes of ca. 151.9 ± 105.6 cm height (Fig. A3). We assumed that bank voles moving in microhabitats dominated by grass (low maximal vegetation height, high cover) are less susceptible to ground predation (impaired movement of larger predators through dense vegetation) but more susceptible to avian predation (better visibility for aerial predators). Bank voles moving under trees and bushes are assumed to be better protected from aerial predation but more susceptible to ground predators. Percentage of ground cover (10 cm from the ground) was calculated afterwards on the basis of photographs taken of the square meter around the trap locations. Based on the trapping grid, we interpolated local maximum vegetation height and local percentage of ground cover with an inverse weighing of the distance between points using QGIS (version 2.18.14). We visually verified these interpolations by the use of satellite images. We then extracted the interpolated value for the respective habitat characteristic for each telemetry fix of individuals. These values were used to calculate means of maximum vegetation height and average ground cover for the home range and core area of individuals. Although distribution and availability of food resources also affect movement and space use of small mammals (e.g., Morris [@CR90]; Liesenjohann et al. [@CR78]), we focussed here only on vegetation cover (i.e., a proxy of predation risk) due to logistic challenges of quantifying distribution and availability of all major components of the omnivorous diet of bank voles at the home range scale. Statistical analyses {#Sec10} -------------------- ### Individual differences {#Sec11} Recorded variables were checked for consistency across test rounds by calculating repeatability according to Nakagawa and Schielzeth ([@CR91]) with the R package *rptR* (Version 0.6.405; Appendix Table A2). Latencies to emerge and investigate the arena were inverted for easier interpretation afterwards. Repeatable variables were then entered into a principal component analysis (PCA) with *oblimin* rotation to reduce the number of variables into meaningful components. All variables from the individual difference test were checked for suitability for a PCA by examination of the determinant of the correlation matrix, the Bartlett test, and the Kaiser--Mayer--Olkin (KMO) criterion (Field et al. [@CR44]). We retained components with an Eigenvalue \> 1 (Wold et al. [@CR118]). We tested repeatability of PC components as described above. Individual scores from the PCA were then entered into a Bayesian mixed-effects model with the experimental day (centered for the individual) as a fixed effect and individual as a random effect. This approach enabled us to account for differences in the time periods between consecutive tests (varying from 1 to 7 days, due to the unpredictability of recapturing individuals in a free-ranging population) and to control for the potential resulting variation of behavioral responses in the test setup (Hadfield et al. [@CR51]; Cowles [@CR34]; Marin and Robert [@CR80]). We extracted linear unbiased predictions based on the Bayesian mixed-effects model because this approach results in less biased estimates (Hadfield et al. [@CR51]) and used these estimates as quantitative measures for individual differences in further analyses. Furthermore, we calculated a Spearman rank correlation to test for an association between the two quantitative behavioral measures at the phenotypic level. ### Individual differences and space use {#Sec12} To test our predictions, we ran linear mixed-effects models (LMMs) and generalized linear mixed-effects models (GLMMs) according to the underlying structure of the data. If feasible, data were transformed before the statistical modeling to achieve normality and a LMM was calculated. If a normal distribution could not be achieved for the respective response variable, GLMMs were conducted modeling the appropriate error structure of the data via the underlying distribution family and corresponding link function. All models were run with either the function *lmer* or *glmer* from the R package *lme4* (Version 1.1-12; Bates [@CR10]). Since individuals originated from different study sites (with varying population densities, vegetation differences, and differences in surrounding matrices), we included study site as a random factor, specified as random intercept, in each model. In general, home range sizes can vary with population density (e.g., Erlinge et al. [@CR42]; Bond and Wolff [@CR17]), but population density did not explain variation in home range size in our data set (Table A5). Therefore, we decided to control for slight differences in population density among sites within the random structure of our models. Individual difference scores and sex of individuals were included as fixed effects in each model. Due to the small sample size, we could not include both behavioral scores in one model but run separate models with only one behavioral score instead. The proportion of explained variance by the fixed factors alone (marginal *R*^2^) and the fixed and random factors together (conditional *R*^2^) was estimated for each model according to Nakagawa and Schielzeth ([@CR92]). These values represent goodness-of-fit measures of GLMMs similar to the *R*^2^ value of generalized linear models (Johnson [@CR66]; Nakagawa and Schielzeth [@CR92]). The level of significance was set to *α* \< 0.05. All calculations were done with the program R (Version 3.3.0, R Core Team [@CR102]). Results {#Sec13} ======= Individual differences {#Sec14} ---------------------- All but two variables quantified in the individual difference test were repeatable over time (Appendix Table A2). Data reduction of repeatable variables via PCA rendered two meaningful components (Appendix Fig. A4a, Table A3) that cumulatively explained 78% of the variance in the data. On the first component, the latency to enter the middle area for the first time, the number of sections entered, the number of crossings into the middle area, and the proportion of time spent active had the highest loadings. The latency to investigate an unknown, open area and the latency to emerge with the full body into an unknown, open area had the highest loadings on the second component. Based on these loadings, the first component (explained variance: 52%) was interpreted as a measure of exploration and the second component (explained variance: 26%) as a measure of boldness (Appendix Fig. A4b). Higher values on the first component represent individuals with a higher number of crossings, sections explored, activity counts and shorter latencies to cross the central part of the arena, i.e., more explorative individuals. Higher values of PC2 correspond to shorter latencies to investigate and emerge into an unknown area, i.e., bolder individuals. Individual differences in both components were repeatable over time (PC1: *R* = 0.217, SE 0.122, 95% CI \[0.003, 0.450\], *p * = 0.023; PC2: *R* = 0.453, SE 0.125, 95% CI \[0.191, 0.672\], *p * = 0.001). The behavioral types of individuals selected for radio-tracking represent much of the populations' variation in exploration and intermediate boldness types (Appendix Fig. A5). Exploration and boldness were not correlated at the phenotypic level (*S* = 4823, rho = − 0.16, *p* value = 0.22). Individual differences and space use {#Sec15} ------------------------------------ ### Home range size and distance moved {#Sec16} Bolder bank vole individuals had larger home ranges, larger core areas and moved longer distances than shy individuals (Fig. [1](#Fig1){ref-type="fig"}a, b, e; Table [1](#Tab1){ref-type="table"}). Males and females did not differ in either home range or core area size or total distance moved. Exploration scores did not explain variation in home range and core area size but more explorative animals moved shorter distances compared to their less explorative conspecifics (Fig. A6; Table [1](#Tab1){ref-type="table"}). The random factor controlling for differences between study sites explained 9% of the variance in home range size and 0% in core area size (Table [1](#Tab1){ref-type="table"}). In total, the mixed models explained 47% (home range size), 44% (core area size) and 67% (total distance moved) of the variance in the data (Table [1](#Tab1){ref-type="table"}).Fig. 1Effects of boldness on home range and core area size (**a**, **b**), spatial interactions (**c**, **d**), and movement distance (**e**) of 21 radio-tracked bank voles, *Myodes glareolus*. Represented are effects obtained from LMMs or GLMMs (line and shaded 95%-confidence intervals) and raw data of individuals (dots). Model effects were back transformed to the original data scale for visual representation if neededTable 1Details and results of (G)LMMs on the effects of exploration and boldness on space use and movement patterns in bank voles, *Myodes glareolus* (*n* = 21)ResponsePersonality scoreEstimateSE*z/t-*value*χ* ^2^*dfp* value*R* ~m~*R* ~c~Home rangeBoldness155.6739.903.9015.05**1\< 0.001**0.380.47Exploration− 16.0812.661. 271.55**1**0.2140.320.30Core areaBoldness1.380.353.9215.35**1\< 0.001**0.440.44Exploration− 88.47134.410.660.43**1**0.5100.030.15Total distance movedBoldness161.3748.853.3010.91**10.001**0.270.69Exploration− 38.8116.352.375.64**10.018**0.070.33Intraspecific home range overlapBoldness− 0.020.013.129.71**10.002**0.370.49Exploration0.000.001.913.65**1**0.0560.100.38Intraspecific core area overlapBoldeness− 0.040.022.134.55**10.033**0.130.13Exploration0.010.011.151.32**1**0.2810.060.06No. of mean trapping points in home rangeBoldeness− 0.050.022.395.72**10.017**0.130.53Exploration0.000.020.030.00**1**0.9790.020.54No. of mean trapping points in core areaBoldeness− 0.080.032.466.07**10.012**0.130.64Exploration0.030.030.790.62**1**0.4320.040.68Max. vegetation height in home rangeBoldness− 0.740.342.164.66**10.031**0.140.55Exploration0.010.011.081.16**1**0.3150.020.46Max. vegetation height in core areaBoldness− 0.517.650.500.25**1**0.6150.210.70Exploration0.030.350.310.01**1**0.9270.060.09Ground cover in home rangeBoldness0.610.302.014.05**10.044**0.190.23Exploration0.050.110.470.22**1**0.6380.030.26Ground cover in core areaBoldness0.060.610.090.01**1**0.9280.010.01Exploration0.080.210.400.16**1**0.6920.090.09The fixed factor sex never showed a significant influence and was therefore excluded from the representation. Home ranges refer to Kernel 95% and core areas to Kernel 50%Statistically significant results are highlighted with bold font for *p* values*SE* the standard error of the estimates, *z/t-value* the *z* and the *t* statistic, *df* degrees of freedom, family describes the distribution of the error structure of the model, link the associated link function, *R*~*m*~ marginal *R*^²^ value based on fixed factors, *R*~*c*~ conditional *R*^²^ value including the study site as a random factor ### Intraspecific spatial overlap {#Sec17} Based on radio-tracking data, home ranges and core areas of bolder individuals overlapped less with conspecifics than home ranges and core areas of shyer individuals (Fig. [1](#Fig1){ref-type="fig"}c, d; Table [1](#Tab1){ref-type="table"}). The exploration score had no effect on the spatial overlap patterns of home ranges or core areas in bank voles (Fig. A6; Table [1](#Tab1){ref-type="table"}). Males and females did not differ in their overlap patterns of either home ranges or core areas. For the overlap of core areas, the mixed model explained 13% of the variance in the data and 49% for the overlap of home ranges; the random structure accounted for 0% in the core area models and 13% of the variance in the home range models (Table [1](#Tab1){ref-type="table"}). Including spatial information on all residential individuals, these patterns were confirmed. Bolder individuals had less mean trapping points of conspecifics within their home ranges and core areas (Fig. A7a, b; Table [1](#Tab1){ref-type="table"}). Sex or exploration did not affect the number of mean trapping points of conspecifics in home ranges and core areas. For core areas, the mixed model explained 64% of the variance in the data, 51% of that were added by the random effect; and for home ranges, 53% of the variance was explained with the random factor accounting for 40% (Table [1](#Tab1){ref-type="table"}). ### Vegetation height and ground cover {#Sec18} The maximum vegetation height of home ranges was on average between 80 cm and 111 cm and average ground cover was of 50%. The home ranges of bolder bank voles had a lower maximum vegetation height than those of their shyer conspecifics (Fig. [2](#Fig2){ref-type="fig"} a; Table [1](#Tab1){ref-type="table"}). In contrast, average percentage of ground cover was higher in home ranges of bolder as compared to shyer individuals (Fig. [2](#Fig2){ref-type="fig"}b; Table [1](#Tab1){ref-type="table"}). For core areas, no difference in maximum vegetation height and percentage of ground cover could be detected between bold and shy bank voles (Fig. [2](#Fig2){ref-type="fig"}c, d; Table [1](#Tab1){ref-type="table"}). Similarly, we did not detect a relationship between exploration score or sex and microhabitat characteristics of either home ranges or core areas. For the core areas the mixed model of the maximum vegetation height explained 70% of the variance in the data and 1% for amount of ground cover, random factors explained 49% and 0%, respectively. For the home ranges, the model regarding the maximum vegetation height explained 55% of the variance in the data and for the amount of ground cover 23%, random effects accounted for 41% and 4% of the explained variance (Table [1](#Tab1){ref-type="table"}).Fig. 2Effects of boldness on mean maximum vegetation and average ground cover of home ranges (**a**, **b**) and core areas (**c**, **d**) of 21 radio-tracked bank voles, *Myodes glareolus*. Represented are effects obtained from GLMMs (line and shaded area 95%-confidence interval) and raw data of individuals (dots). Model effects were back transformed to the original data scale for visual representation if needed Discussion {#Sec19} ========== Combining intensive capture--mark--recapture and simultaneous automated radio-tracking of individuals with known behavioral phenotypes with small-scale assessment of microhabitat quality, we showed that consistent individual differences in boldness predicted intraspecific variation in home range and core area sizes, movement patterns and microhabitat use of free-ranging bank voles. Bolder animals occupied larger home ranges, spatially overlapped less with conspecifics, and used areas with higher ground cover and lower maximum vegetation height compared to shyer conspecifics. These results indicate a covariance of spatial niche components and consistent individual differences in behavior suggesting segregation of behavioral types into individual ecological niches. Consistent inter-individual differences in movement-related behaviors {#Sec20} --------------------------------------------------------------------- Repeated behavioral tests of free-ranging bank voles revealed consistent inter-individual differences in boldness and exploration. Differences in both traits have been found to affect movement parameters in birds (Dingemanse et al. [@CR38]), lizards (Spiegel et al. [@CR112]) and fish (Fraser et al. [@CR46]). In bank voles, however, boldness was a better predictor of space use than exploration. Contrary to findings of some other studies (e.g., Herde and Eccard [@CR59] in common voles; Bajer et al. [@CR9] in European green lizards) exploration and boldness did not correlate at the phenotypic level in bank voles. We tested individuals directly in the field after capture, which is a rare approach (see also Martin and Réale [@CR81]; Dammhahn [@CR36]; Best et al. [@CR13]; Mella et al. [@CR86]), and allowed the individual to enter the test apparatus voluntarily, which might facilitate disentangling of boldness-related and exploration-related behaviors (Carter et al. [@CR26]; Perals et al. [@CR99]). Personality-dependent space use and movement {#Sec21} -------------------------------------------- We found a strong influence of boldness on home range size, core area size, and distances moved in bank voles. As predicted, bolder individuals occupied larger areas and moved longer distances compared to shy individuals, which is in accordance with previous studies on other species (Boon et al. [@CR18]; Minderman et al. [@CR89]; Spiegel et al. [@CR112]). In American red squirrels (*Tamiasciurus hudsonicus*) inter-individual differences in activity and aggression affected the maximum trapping distance and the number of trap locations (Boon et al. [@CR18]). In starlings (*Sturnus vulgaris*), areas explored in a novel environment test scaled positively with the size of individual home ranges obtained by radio-tracking (Minderman et al. [@CR89]). In sleepy lizards (*T. rugosa*), both boldness and aggression influenced space use behavior (Spiegel et al. [@CR112]) with boldness positively affecting the home range size, while aggression negatively impacted the intensity of use of areas close to the home range center. A strong relationship between boldness, a predictor of risk-taking (e.g., Dammhahn and Almeling [@CR37]), and spatial patterns in bank voles could be related to the general ecology of the species. In the following, we discuss several non-mutually exclusive explanations for this relationship. First, the main source of mortality for voles, and most small mammals, is predation by ground and avian predators, rendering them a key species in natural food chains (Halle [@CR52]; Jędrzejewski et al. [@CR64]; Korpimäki [@CR70]; Korpimaki et al. [@CR71]; Gliwicz and Dabrowski [@CR49]). Since boldness is a trait that is directly linked to mortality risk (Smith and Blumstein [@CR111]), it should have a strong impact on space use patterns which influence the exposure to predators (see also discussion on microhabitat use below). As expected, shy individuals range over shorter distances and over smaller, potentially more familiar areas, which should reduce their predation risk. Second, ranging further might enhance the chances of exploiting spatially dispersed and/or better-quality resources which might trade-off elevated mortality risk associated with this behavior, ultimately enabling the coexistence of individuals with different behavioral phenotypes in a population (Wolf and Weissing [@CR119]). Larger home ranges and longer movement paths might, thus, increase access to spatially dispersed resources for bolder individuals. Third, space use and movement of bold and shy individuals might reflect differential exploration styles between these behavioral types. Mettke-Hofmann et al. ([@CR87]) could show in parrots that differential exploration styles of resident (thorough explorers) and nomadic (superficial explorers) species influenced their choice of food; large proportion of the diet of thoroughly exploring parrots contained fruits and leaves; therefore, long-term available resources, while nomadic parrots preferred short-term available resources. Additionally, superficially exploring individuals are assumed to not deplete resources completely but rather shorten their average stay in, for example, a food patch and move on quickly to a new spot (Wolf et al. [@CR120]). Therefore, these individuals might need to cover larger distances and consequently range over larger areas to acquire sufficient resources (Mazza et al. [@CR85]). In contrast, shyer individuals cover less distance in the same amount of time, suggesting a more thorough exploration style. In that case, smaller distances and resulting smaller ranging areas might be sufficient in providing the necessary resources, because individuals know the area in which they move in great detail, enabling them to exploit all existing resources more optimally (Arvidsson and Matthysen [@CR7]). Thorough exploration of an open-field arena was indeed negatively related to moved distances in the field in our data set. Whether this link between behavioral variation and space use does indeed reflect different exploration styles requires further testing. Fourth, bold individuals might range further to fuel their elevated metabolism. In many species, boldness scales positively with metabolic rate and it has been shown that individuals with faster metabolic rates need more resources to satisfy their energetic requirements compared to shy individuals (Biro and Stamps [@CR14]; Careau et al. [@CR23], [@CR24]; Réale et al. [@CR103]; Mathot and Dingemanse [@CR82]). Since basal metabolic rate in bank voles is repeatable (Labocha et al. [@CR74]), has a heritable component and is related to other performance traits (Sadowska et al. [@CR104]), this hypothesis warrants further testing. Bolder individuals also occupied larger and more exclusive core areas as evident from the spatial overlap patterns and the number of mean trapping points of residential individuals within core areas and home ranges, which might indicate stronger territoriality. The social system of the bank vole is solitary and characterized by strong female territoriality, while males have larger, overlapping ranges (Bujalska [@CR21]; Gipps [@CR48]). Females generally keep core areas exclusive and meet intruders with high levels of aggression (Koskela et al. [@CR72], [@CR73]; Ylönen and Horne [@CR121]). However, under high population density---such as at our study sites with 99 ± 61 individuals ha^−1^---female territoriality could break down (Ylönen et al. [@CR122]). Interestingly, the relationship between boldness, core area size and exclusivity was not sex specific in our data. This pattern could mean monopolization of resources and decreased intraspecific competition might result from an increased competitive ability of bolder individuals in both sexes. With the data at hand, we cannot test whether bold individuals displace shy conspecifics or whether shy individuals avoid areas of bolder ones, but findings from other species often report behavioral syndromes between boldness and aggressiveness (Huntingford [@CR62]; Sih et al. [@CR109]) and bolder bank vole males are also dominant over shy individuals in encounters (Eccard, unpublished data). Shyer individuals overlapped spatially with more conspecifics, both for the tracked home ranges as well as with mean trapping points of residential individuals, which might indicate that they are not able to keep their roaming areas exclusive and might be confronted with higher levels of intraspecific resource competition but on the other hand might have more and easier access to mating partners which could positively affect their reproductive success. Furthermore, under natural conditions, bank voles are in competition not only with themselves but also with other rodent species; therefore, even if shy individuals are confronted with higher levels of intraspecific competition, they might have an advantage over bold individuals in interspecific interactions, leading to the maintenance of both personality types in the population. We could show that personality-dependent spatial overlap patterns lead to non-random intraspecific spatial interactions in bank voles. Whether this is a result of indirect exploitation competition, or of direct, aggressive intraspecific interactions, or a combination of both, cannot be answered with this study but might be an important avenue for future research. Personality-dependent occupation of microhabitats {#Sec22} ------------------------------------------------- At the core-area scale, there was no relationship between personality traits and microhabitat characteristics. Core areas represent the most frequently visited and used area of an individual, indicating home site, refuges or important food sources (Samuel et al. [@CR105]; Seaman and Powell [@CR106]). In the case of the bank vole, a species that occupies underground cavities where it builds its nest, stores food, and females raise their young (Braun and Dieterlen [@CR19]), it is most likely that the core area represents the site where such cavities can generally be found. Bank voles are active during day and night with an activity bout every three--four hours (Ylönen et al. [@CR122]; Braun and Dieterlen [@CR19]) in between which they retreat into the nest. These aspects make the core areas highly valuable (i.e., fitness relevant) for bank voles and it might be equally important for both bold and shy individuals that the nest is located in the safest area of each individual's home range. Indeed, core areas had both higher vegetation height and higher percentage of ground cover (Appendix Fig. A8) as compared to home ranges and, thus, represent areas that are greatly sheltered from both ground and avian predation. The highest level of risk for a prey species, such as the bank vole, is encountered during the active phases when they are roaming above ground in search for food and mating partners (Braun and Dieterlen [@CR19]). Therefore, it is not surprising that differences in the preferred vegetation cover can be found between bold and shy individuals at the home range level. Against our prediction and in contrast to other studies (Carrete and Tella [@CR25]; Holtmann et al. [@CR61]), bolder individuals more frequently used areas with high levels of ground cover and shy individuals were more frequently found in areas that potentially pose a higher predation risk. In our mixed habitat of grassland and shrub/tree islands, this means that bolder animals were using more grassy areas than shy animals (Fig. A3). This might further support a difference in competitive ability between the behavioral types leading to either the active displacement of shy individuals or competition avoidance, forcing shy individuals to settle in high-risk areas. In turn, shyer individuals might occupy smaller home ranges and move less to minimize their exposure in the risky roaming area leading to the observed space use patterns. Alternatively, it is also possible that individuals born in the areas of different levels of vegetation cover adjust their personality accordingly and that the environment shapes the personality rather than personality predicting the environment (Holtmann et al. [@CR61]). Based on our data, we can not disentangle which of these two mechanisms drives the observed patterns. However, given similar preferences of behavioral types for core area microhabitats, juveniles of either bold or shy females appear to initially experience similar microhabitat conditions. Personality-dependent preferred vegetation cover could also indicate susceptibility of behavioral types to different predators. Areas with low ground cover are usually paired with high maximum vegetation cover like trees and dense bushes on our study sites. Those vegetation characteristics limit the access of avian predators like, for example, common buzzards (*Buteo buteo*), which prefer hunting above open areas and are one of the most common predators of voles in Europe (Jędrzejewski and Jędrzejewska [@CR63]; Norrdahl and Korpimäki [@CR95]; Selas et al. [@CR107]). For such predators, areas of low maximum vegetation height and more ground cover might be more accessible putting bolder individuals at higher risk compared to shyer individuals. Ground predators like foxes (*Vulpes vulpes*) and least weasel (*Mustela nivalis*), which are also common predators of bank voles (Jędrzejewski and Jędrzejewska [@CR63]; Jędrzejewski et al. [@CR64]; Kjellander and Nordström [@CR67]), might, on the other hand, have an advantage in areas of low ground cover due to the higher exposure of prey individuals. Hence, shy individuals are likely more susceptible to ground predation based on their home range characteristics than bold individuals. Ultimately, the difference in home range vegetation cover might, therefore, indicate non-random predator--prey interactions for the behavioral types which could result in additional behavioral differences regarding predator avoidance and specialization of behavioral types to their microhabitat. Conclusion: personality and individual niche differentiation {#Sec23} ============================================================ Bank voles differ in their space use, movement and habitat choice according to their personality, resulting in non-random distributions of behavioral types within the habitat as well as non-random intraspecific spatial interactions. Depending on their behavioral type, individuals experience different levels of intraspecific competition over resources and occupy microhabitats of varying predation risk; hence, they occupy individual ecological niches. Within-species variation in ecological niches could reduce intraspecific competition because individual behavioral types are less similar in their resources use and experience different main predators and, thus, face reduced exploitation competition for food- and predator-free area. Our results indicate that, in addition to individual dietary niche separation (Bolnick et al. [@CR15]; Araújo et al. [@CR5]; Harrison et al. [@CR56]), spatial components of ecological niches can also vary among individuals. Whether and how these ecological consequences of inter-individual behavioral variation ultimately affect species coexistence (Chesson [@CR30]) and maintain variation in behavioral and ecological traits and their potential covariation in natural populations will be fascinating areas of future research. Electronic supplementary material ================================= {#Sec24} Below is the link to the electronic supplementary material. Supplementary material 1 (PDF 1620 kb) Experiments were conducted under the permission of the Landesamt für Umwelt, Verbraucherschutz und Gesundheit, Brandenburg (LUGV_7RO-4610/34 + 5\#86908/2011; V3-2347-44-2011). All applicable institutional and national guidelines for the care and use of animals were followed. Funding was provided by the German Science Foundation (DFG) within the BioMove research training group (DFG-GRK 2118/1). We thank Julia Hoffmann, Lisa Teckentrup, Maureen Schuster and Lina Mey for indispensable help during field work, Michael Ristow for support with the vegetation analysis, Florian Jeltsch for comments on a previous draft, and the Animal Ecology group at Potsdam University and the BioMove team for fruitful discussions. AS and MD designed the study, JAE developed the tracking methodology, AS collected the data, AH and MD contributed. AH analyzed the habitat characteristics data. AS did the statistical analyses and wrote the first draft of the manuscript. All co-authors revised the first draft of the manuscript. [^1]: Communicated by Peter Banks.
null
minipile
NaturalLanguage
mit
null
People are allowed to make mistakes and seek redemption, even in politics. But Stone never apologized and never seemed to grasp that he was a cog in a fog machine that denied voters the real information they deserved to make their constitutional choice. Stone’s continued presence on the political scene reinforced the idea that “the coverup is worse than the crime” instead of, “above all, don’t commit the crime.” It shouldn’t have taken this long for us to reject that amoral approach to power and leadership. AD AD The Nixon Foundation may have tried to distance the former president from his disgraced admirer on Friday, but Stone was not part of any rogue operation in the Nixon orbit. As a member of President Richard M. Nixon’s Committee to Re-Elect the President, better known as CREEP, Stone helped recruit a young operative to spy on a group of Quakers who had set up a peace vigil in front of the Nixon White House. Stone also admitted to Congress that he faked a contribution from the Young Socialist Alliance to Pete McCloskey, a liberal Republican who in 1972 was mounting a challenge to Nixon in the New Hampshire primary. After delivering the $135 in cash and receiving a receipt, Stone then drafted an anonymous letter to the conservative Manchester Union Leader with a photocopy of the receipt to discredit McCloskey. Stone did not merely engage in dirty tricks; in 1972, the then-19-year-old Stone was assigned by CREEP official Herbert “Bart” Porter to recruit a spy to penetrate the campaigns of Democratic presidential hopefuls. The secret Nixon agent, Michael W. McMinoway, introduced himself successively into the campaigns of Edmund Muskie, Hubert Humphrey and George McGovern. Stone became his case officer, receiving intelligence from McMinoway via a post office box in Washington. AD AD We are all innocent until proved otherwise, but Stone long ago gleefully admitted his guilt as an avid saboteur of our democracy. In this, he reflected an attitude that came from the top. Despite the touch of humanity he showed in one interview with David Frost, Nixon never really apologized for his political sins. He never admitted the full scale of the abuses and criminality of his administration and reelection campaign, choosing to reduce Watergate to a single break-in. In his recent book, “Nixon’s Secrets,” Stone presented himself as Nixon’s “closest political confidant” in Nixon’s “final campaign” for rehabilitation. According to Stone, he negotiated the “He’s Back” cover of Newsweek for Nixon in 1986. The goal was effectively to normalize criminal behavior by presidents one likes. Unlike Nixon, however, Stone never sought rehabilitation. He was a welcome player in both the 1980 and 1984 Reagan-Bush election campaigns. In 1982, at the request of lawyer Roy Cohn, President Ronald Reagan sent Stone a telegram to wish him a happy “’first anniversary’ of your ‘29th'” birthday. That summer, the Reagan White House noted in its files that “Roger Stone, who was President of the Young Republicans at age 20, was actively involved in the campaign for the President and is a great supporter of his.” And after Reagan’s reelection in 1984, office seekers wrote to Stone at his consulting firm looking for jobs with the administration. Eventually, Donald Trump came to enjoy the company, and political assistance, of Stone. In 2000, when Trump first dipped his toe into presidential waters, Stone seemed to be his sole campaign staffer. On Friday, White House press secretary Sarah Sanders sought to downplay the Trump-Stone relationship, insisting, “Stone is somebody who has been a consultant for dozens of Republican presidents and candidates and members of Congress.” Rather than exculpating Trump, that argument condemns the establishment that failed to cast Stone out.
null
minipile
NaturalLanguage
mit
null
Does religiosity help Muslims adjust to death?: a research note. Death is the end of life. But Muslims believe death is an event between two lives, not an absolute cessation of life. Thus religiosity may influence Muslims differently about death. To explore the impact of religious perception, thus religiosity, a cross-sectional, descriptive, analytic and correlational study was conducted on 150 Muslims. Self-declared healthy Muslims equally from both sexes (N = 150, Age range--20 to 50 years, Minimum education--Bachelor) were selected by stratified sampling and randomly under each stratum. Subjects, divided in five levels of religiosity, were assessed and scored for the presence of maladjustment symptoms and stage of adjustment with death. ANOVA and correlation coefficient was applied on the sets of data collected. All statistical tests were done at the level of 95% confidence (P < 0.05). Final results were higher than the table values used for ANOVA and correlation coefficient yielded P values of < 0.05, < 0.01, and < 0.001. Religiosity as a criterion of Muslims influenced the quality of adjustment with death positively. So we hypothesized that religiosity may help Muslims adjust to death.
null
minipile
NaturalLanguage
mit
null
Solvation Solvation describes the interaction of solvent with dissolved molecules. Both ionized and uncharged molecules interact strongly with solvent, and the strength and nature of this interaction influence many properties of the solute, including solubility, reactivity, and color, as well as influencing the properties of the solvent such as the viscosity and density. In the process of solvation, ions are surrounded by a concentric shell of solvent. Solvation is the process of reorganizing solvent and solute molecules into solvation complexes. Solvation involves bond formation, hydrogen bonding, and van der Waals forces. Solvation of a solute by water is called hydration. Solubility of solid compounds depends on a competition between lattice energy and solvation, including entropy effects related to changes in the solvent structure. Distinction from solubility By an IUPAC definition, solvation is an interaction of a solute with the solvent, which leads to stabilization of the solute species in the solution. In the solvated state, an ion in a solution is surrounded or complexed by solvent molecules. Solvated species can often be described by coordination number, and the complex stability constants. The concept of the solvation interaction can also be applied to an insoluble material, for example, solvation of functional groups on a surface of ion-exchange resin. Solvation is, in concept, distinct from solubility. Solvation or dissolution is a kinetic process and is quantified by its rate. Solubility quantifies the dynamic equilibrium state achieved when the rate of dissolution equals the rate of precipitation. The consideration of the units makes the distinction clearer. The typical unit for dissolution rate is mol/s. The units for solubility express a concentration: mass per volume (mg/mL), molarity (mol/L), etc. Solvents and intermolecular interactions Solvation involves different types of intermolecular interactions: hydrogen bonding, ion-dipole interactions, and van der Waals forces (which consist of dipole-dipole, dipole-induced dipole, and induced dipole-induced dipole interactions). Which of these forces are at play depends on the molecular structure and properties of the solvent and solute. The similarity or complementary character of these properties between solvent and solute determines how well a solute can be solvated by a particular solvent. Solvent polarity is the most important factor in determining how well it solvates a particular solute. Polar solvents have molecular dipoles, meaning that part of the solvent molecule has more electron density than another part of the molecule. The part with more electron density will experience a partial negative charge while the part with less electron density will experience a partial positive charge. Polar solvent molecules can solvate polar solutes and ions because they can orient the appropriate partially charged portion of the molecule towards the solute through electrostatic attraction. This stabilizes the system and creates a solvation shell (or hydration shell in the case of water) around each particle of solute. The solvent molecules in the immediate vicinity of a solute particle often have a much different ordering than the rest of the solvent, and this area of differently ordered solvent molecules is called the cybotactic region. Water is the most common and well-studied polar solvent, but others exist, such as ethanol, methanol, acetone, acetonitrile, and dimethyl sulfoxide. Polar solvents are often found to have a high dielectric constant, although other solvent scales are also used to classify solvent polarity. Polar solvents can be used to dissolve inorganic or ionic compounds such as salts. The conductivity of a solution depends on the solvation of its ions. Nonpolar solvents cannot solvate ions, and ions will be found as ion pairs. Hydrogen bonding among solvent and solute molecules depends on the ability of each to accept H-bonds, donate H-bonds, or both. Solvents that can donate H-bonds are referred to as protic, while solvents that do not contain a polarized bond to a hydrogen atom and cannot donate a hydrogen bond are called aprotic. H-bond donor ability is classified on a scale (α). Protic solvents can solvate solutes that can accept hydrogen bonds. Similarly, solvents that can accept a hydrogen bond can solvate H-bond-donating solutes. The hydrogen bond acceptor ability of a solvent is classified on a scale (β). Solvents such as water can both donate and accept hydrogen bonds, making them excellent at solvating solutes that can donate or accept (or both) H-bonds. Some chemical compounds experience solvatochromism, which is a change in color due to solvent polarity. This phenomenon illustrates how different solvents interact differently with the same solute. Other solvent effects include conformational or isomeric preferences and changes in the acidity of a solute. Solvation energy and thermodynamic considerations The solvation process will be thermodynamically favored only if the overall Gibbs energy of the solution is decreased, compared to the Gibbs energy of the separated solvent and solid (or gas or liquid). This means that the change in enthalpy minus the change in entropy (multiplied by the absolute temperature) is a negative value, or that the Gibbs energy of the system decreases. It is important to remember, however, that a negative Gibbs energy indicates a spontaneous process but does not provide information about the rate of dissolution. Solvation involves multiple steps with different energy consequences. First, a cavity must form in the solvent to make space for a solute. This is both entropically and enthalpically unfavorable, as solvent ordering increases and solvent-solvent interactions decrease. Stronger interactions among solvent molecules leads to a greater enthalpic penalty for cavity formation. Next, a particle of solute must separate from the bulk. This is enthalpically unfavorable since solute-solute interactions decrease, but when the solute particle enters the cavity, the resulting solvent-solute interactions are enthalpically favorable. Finally, as solute mixes into solvent, there is an entropy gain. The enthalpy of solution is the solution enthalpy minus the enthalpy of the separate systems, whereas the entropy is the corresponding difference in entropy. Most gases have a negative enthalpy of solution. A negative enthalpy of solution means that the solute is less soluble at high temperatures. The sum of the enthalpy and entropy changes throughout these steps is called the solvation energy. Enthalpy of solvation can help explain why solvation occurs with some ionic lattices but not with others. The difference in energy between that which is necessary to release an ion from its lattice and the energy given off when it combines with a solvent molecule is called the enthalpy change of solution. A negative value for the enthalpy change of solution corresponds to an ion that is likely to dissolve, whereas a high positive value means that solvation will not occur. It is possible that an ion will dissolve even if it has a positive enthalpy value. The extra energy required comes from the increase in entropy that results when the ion dissolves. The introduction of entropy makes it harder to determine by calculation alone whether a substance will dissolve or not. A quantitative measure for solvation power of solvents is given by donor numbers. Although early thinking was that a higher ratio of a cation's ion charge to ionic radius, or the charge density, resulted in more solvation, this does not stand up to scrutiny for ions like iron(III) or lanthanides and actinides, which are readily hydrolyzed to form insoluble (hydrous) oxides. As these are solids, it is apparent that they are not solvated. Strong solvent-solute interactions make the process of solvation more favorable. One way to compare how favorable the dissolution of a solute is in different solvents is to consider the free energy of transfer. The free energy of transfer quantifies the free energy difference between dilute solutions of a solute in two different solvents. This value essentially allows for comparison of solvation energies without including solute-solute interactions. In general, thermodynamic analysis of solutions is done by modeling them as reactions. For example, if you add sodium chloride to water, the salt will dissociate into the ions sodium(+aq) and chloride(-aq). The equilibrium constant for this dissociation can be predicted by the change in Gibbs energy of this reaction. The Born equation is used to estimate Gibbs free energy of solvation of a gaseous ion. Recent simulation studies have shown that the variation in solvation energy between the ions and the surrounding water molecules underlies the mechanism of the Hofmeister series. Macromolecules and assemblies Solvation (specifically, hydration) is important for many biological structures and processes. For instance, solvation of ions and/or of charged macromolecules, like DNA and proteins, in aqueous solutions influences the formation of heterogeneous assemblies, which may be responsible for biological function. Another example, protein folding occurs spontaneously, in part because of a favorable change in the interactions between the protein and the surrounding water molecules. Folded proteins are stabilized by 5-10 kcal/mol relative to the unfolded state due to a combination of solvation and the stronger intramolecular interactions in the folded protein structure, including hydrogen bonding. Minimizing the number of hydrophobic side-chains exposed to water by burying them in the center of a folded protein is a driving force related to solvation. Solvation also affects host–guest complexation. Many host molecules have a hydrophobic pore that readily encapsulates a hydrophobic guest. These interactions can be used in applications such as drug delivery, such that a hydrophobic drug molecule can be delivered in a biological system without needing to covalently modify the drug in order to solubilize it. Binding constants for host–guest complexes depend on the polarity of the solvent. Hydration affects electronic and vibrational properties of biomolecules. See also Saturated solution Solubility equilibrium Solvent models Born equation Supersaturation Water model References Further reading (part A), (part B), (Chemistry) Jiang D., Urakawa A., Yulikov M., Mallat T., Jeschke G. & Baiker A., 2009, "Size selectivity of a copper metal-organic framework and origin of catalytic activity in epoxide alcoholysis," Chemistry 15(45):12255-62, DOI 10.1002/chem.200901510. [One example of a solvated MOF, where partial dissolution is described.] External links Serafin, J.M. Transfer Free Energy and the Hydrophobic Effect. J. Chem. Educ. 2003, 80, 1194-1196. http://pubs.acs.org/doi/pdf/10.1021/ed080p1194 Category:Solutions Category:Chemical processes
null
minipile
NaturalLanguage
mit
null
Regular readers will doubtless appreciate The Leisure Review’s commitment to publishing well-informed and balanced articles for people who work in and care about the heritage part of our sector. But for one edition only we have allowed Mick Owen, buoyed by a week in heritage-rich Cornwall, to discuss the issues as he sees them. Evidence of a nautical heritage It may come as a surprise to those readers whose working life is bound by Jennie Price’s sport system that there is such a thing as a ‘heritage sector’, especially as most sports developers were drawn to their business by a ‘passion for sport', rather than the more appropriate ‘passion for endless meetings and box-ticking’. And sporty people can tend to be a tad blinkered. But according to the people who distribute lottery funding, ‘heritage’ runs “from museums, parks and historic places to archaeology, natural environment and cultural traditions”. Tesco has a much narrower definition and suggests that buying someone membership of English Heritage opens up a world “from storybook castles to breathtaking stately homes”, while Historic Scotland defines the heritage for which it is responsible as including monuments, shipwreck sites and battlefields but, curiously enough, neither shortbread nor tartan. Just what constitutes ‘heritage’ might be an ‘angels on the head of a pin’ debate, were it not for the fact that funding and support follows the definition. When UNESCO designated Saltaire a world heritage site it was not because the West Yorkshire industrial village had greatly influenced the garden city movement; it was so that agencies and individuals will continue to cough up for its preservation and protection. However, a recent trip to Cornwall has shown that ‘heritage’ takes many more forms than are dreamt of in the philosophies of most funding bodies. What, for example, is pilot gig racing, who funds it and should they? This form of rowing is clearly held to be a sport by Sport England, who bought at least four of the esoteric, six-person, clinker-built, Cornish elm craft required by gig clubs last year. And 44 gig-racing students from Cornish schools competed at the National Junior Indoor Rowing championships on 17 March last and acquitted themselves well. But the Cornish Pilot Gig Association – the world governing body – see themselves as “curators”, holding things in trust “for future generations” as much as a regulatory body; and the words ‘sport’ and ‘development’ are not paired anywhere on their website. The closest thing they employ to a buzzword is ‘community’ and, with men’s, women’s, under-16, under-14 and veterans’ classes at their events, it is clear that the gigs and their crews are woven into the fabric of Cornish coastal towns and villages. A week spent watching the Fowey estuary from various vantage points convinced me of the popularity of the pastime as the local club’s various crews fitted in training runs as and when the rowers were available and the boats were spare. If gig racing is a sport then it’s one founded in a deeper, more useful tradition. Which is an argument that might also be used for sailing around the south-west peninsula. Apparently, the deep water off the south coast of Cornwall is better for the weekend admirals and, with Fowey (did I tell you its pronounced ‘Foy’?) the most protected of natural harbours, it was no surprise as Easter approached to see the river filling with prettily-bobbing evidence that despite the credit crisis the ‘haves’ still have. But given they are following in a tradition that includes a man called Rashleigh who sailed with Drake and, confusingly, Raleigh, perhaps we have to allow them to follow their star – or their state-of-the-art navigation aids – unmocked. Evidence of the historic importance of the harbour include a fort flying an English Heritage flag, two 14th century blockhouses and some very old pubs, one of which belonged to the aforementioned Rashleigh in olden times. Which is where my research unearthed two more gems of Cornish heritage. Tribute is brewed by the 150-year-old, family-owned St Austell brewery and when purveyed in a genuine local pub by a friendly landlady it passes muster. No one would expect my up-country palate to adjust quickly enough in a week, despite great efforts to acclimatise it, but Tribute is hailed by no less a drinker than Roger Protz so it had to be worth the effort. And it was while I was working on this particular cultural project that the northern lass next to me remarked on a family of uniformly rotund, short people to-ing and fro-ing through the bar who were clearly not speaking English. “It’s either Cornish,” she said, “or they’re elves.” Too much Tolkien for her and a chance to rub shoulders with real native Kernewek speakers for me; unless they were Polish, of course. The re-growth of Kernewek in Kernow since the seventies is either an example of middle-class foolishness or the regeneration of something fundamentally valuable. Nothing instils a sense of place like its language (if you doubt me try telling someone from Sunderland you like her Geordie accent and see if you get lucky) so to experience local, country people using a language that goes back to pre-Roman times was, in my book, a turn-up. A bit like meeting Lenny Henry in the woods when out walking the dogs perhaps? Or smiling at Dawn French as she squeezed past you in her Daimler when you’re jogging along the esplanade? And yes, these did both happen to members of our party. Not so unlikely when you consider that last year they bought the big house on the cliff between our humble, rented, fisherfolk’s cottage and town, but nevertheless exciting in a ‘Hello’ sort of way. Not quite as exciting as finding out that Daphne du Maurier had lived in the house at the back of us for a bit, of course, but mildly titillating. In Fowey, you must understand, finding a house that the author of Rebecca and Jamaica Inn inhabited is a bit like finding an American tourist on the du Maurier trail: it’s not hard. In fact it’s a bit difficult to avoid the American, Spanish and German tourists as you pootle around the very few, very narrow Fowey streets. It’s a bit of a honey pot, you see, especially for cruise ships. It’s far from unusual to see a three- or four-storey monster squatting like an over-fed, maritime cuckoo in Fowey roads [‘Roads’: nautical term meaning a stretch of sheltered water near land. Ed] and with them come tourists seeking Daphne; and with them comes commercial opportunity. The town has more than its fair share of fudge shops, a proliferation of boutique hotels unusual in Cornish fishing ports and a ten-day Daphne Du Maurier Festival that boasts everything from an exhibition of census records in nearby Polruan and the Tywardreath Players offering The King’s General to Colin Dexter, Susan Penhaligon and Tony Benn chatting on. Say what you like about Ms Du Maurier – and I would like to say she writes structureless romances with unlikely plots and sketchy characterisation – but she has an enduring appeal and is as a magnet to all manner of people who just seem to love her. Which brings me back to Dawn. Because Dawn is a national treasure. She should fly an English Heritage flag. Like Morecambe and Wise she should be listed by the government and always free to terrestrial viewers. She epitomises something English, she is valued and we will miss her when she finally retires to her seaside retreat. And that is what defines whether something belongs in the heritage pile when we sort the funding washing. Forts are important, even if they are falling down, stuck on top of a dangerously steep hill and covered in seagull dung. Proper beer matters. Pilot gig racing is worth developing as it links communities internally and externally; and looks like a load of fun. And someone should fund them all. Mick Owen is the managing editor of The Leisure Review, managing director of TLR Communications Ltd and a connoisseur of romantic fiction. “A week spent watching the Fowey estuary from various vantage points convinced me of the popularity of the pastime as the local club’s various crews fitted in training runs as and when the rowers were available and the boats were spare. If gig racing is a sport then it’s one founded in a deeper, more useful tradition.” Natural harbours make natural homes for sailors A natural home for du Maurier A tough gig: Cornwall's esoteric take on what others might call 'rowing'
null
minipile
NaturalLanguage
mit
null
Q: Importing Contracts: What to do with contract number? I have a customer who is already using Contracts that wants to import a bunch of their old Contracts. One caveat is that the Salesforce auto-number for Contracts is prefixed with the current year, so all the old contracts have numbers that make them look like they were created this year. Anyone know if there is a way to 'fix' the numbers so that they agree with the year they were imported? Or even if we could make them '0000-####' so we know that they were imported? A: I faced the same issue with Order Number From salesforce help link Modifying Standard Auto-Number Fields The unique identifiers for solutions, cases, and contracts are standard auto-number fields. Each record is assigned a unique number with a specified format upon creation. You can modify the format and numbering for these auto-number fields. From Setup, click Customize, select the appropriate tab link, and then click the Fields link. Click Edit next to the name of the field in the Standard Fields list. Enter a Display Format to control such formatting details as the minimum number of leading zeros as well as any prefix or suffix for the number. See Custom Field Attributes. Format changes do not affect existing records; they are applied only to new records. Enter the number to be assigned to the next record that is created after you save your changes. Click Save.
null
minipile
NaturalLanguage
mit
null
After a busy weekend, here is one that’s very low-key with no big releases, so let’s see what might be worth seeing in a multiplex near you. Destroyer Directed by: Karyn KusamaWith: Nicole Kidman, Toby Kebbell, Tatiana Maslany, and Sebastian StanWhat is it about? A police detective reconnects with people from an undercover assignment in her distant past in order to make peace.Heads Up?Karyn Kusama’s (Girlfight, Jennifer’s Body, The Invitation) latest film was supposed to be Nicole Kidman‘s Training Day/Monster as she plays an anti-hero and “uglified” herself at the same time. Even though the Oscar hopes did not materialize, this film has mostly favorable reviews, with emphasis on how great Ms. Kidman is in the film. One of these favorable reviews came from our resident critic Faizan Rashid. In his ★★★★☆ stars review he wrote: “If the whole purpose of a truly transformative performance, the kind where the person playing it is largely altered, is to separate the movie star from the thespian, Kidman completely succeeds“. I think this is a film that mature audience might appreciate, so go for it. A Dog’s Way Home Directed by: Charles Martin SmithWith: Ashley Judd, Jonah Hauer-King, Edward James Olmos, and Bryce Dallas HowardWhat is it about? A female dog travels four hundred miles in search of her owner throughout a Colorado wilderness.Heads Up? This family film is designed in a lab to tug on your heart’s strings. If you have seen the trailer (or even think about the film title for a sec) then you know what’s gonna happen. Still, if you are looking for a harmless film to watch with the family, then you can do worse than this. Replicas Directed by: Jeffrey NachmanoffWith: Keanu Reeves, Alice Eve, Emily Alyn Lind, Thomas MiddleditchWhat is it about? A scientist becomes obsessed with bringing back his family members who died in a traffic accident.Heads Up? I don’t know about you, but I am always rooting for Keanu Reeves, presumably one of the nicest and most beloved men in Hollywood. But man this film is a failure on all levels, as it has been savaged by critics and shunned by audience upon its release in the US. I’m glad he has a John Wick sequel coming out later this year, but needless to say you should avoid this one. The Gandhi Murder Directed by: Karim Traïdia, Pankaj SehgalWith: Stephen Lang, Luke Pasqualino, Vinnie Jones, and Om PuriWhat is it about? A conspiracy theory period movie based on true events, that led to the eventual assassination of Mahatma Gandhi. .Heads Up? a JFK style historic thriller about a supposed conspiracy behind the assassination of Mahatma Gandhi. Does this sound intriguing to you? I myself am a bit curious, but not fully onboard. Thackeray Directed by: Abhijit PanseWith: Nawazuddin Siddiqui, Laxman Singh Rajput, Radha Sagar, and Amrita RaoWhat is it about? Biographical account of Shiv Sena Supremo, Balasaheb Thackeray.Heads Up? A biography of a controversial political figure who had a big presence on the Indian political and cultural scene since the 60s. While Thackerey himself was a hardliner whose policies you may agree with or not, his life makes for a fascinating story. And when portrayed by one of the best actors of our generation, this movie should make it to your watch-list. But the director has no track record, and it is easy to pander when making the movie in the subject’s stronghold city. Another movie to take the wait-and-watch approach with, or perhaps just watch it on streaming. About Abdullah Y Abdullah Y is based in Jeddah, Saudi Arabia. He is an avid consumer of everything Pop Culture; movies, TV, music, photography, podcasts, and social media. He loves to travel and to share his experiences.
null
minipile
NaturalLanguage
mit
null
<?xml version="1.0" encoding="utf-8"?> <!DOCTYPE book PUBLIC "-//OASIS//DTD DocBook XML V4.4//EN" "http://www.oasis-open.org/docbook/xml/4.4/docbookx.dtd"> <book> <bookinfo> <title>Unit Test: productionset.005</title> <releaseinfo role="CVS">$Id: productionset.005.xml 4105 2004-12-15 23:00:31Z xmldoc $</releaseinfo> <author><firstname>Norman</firstname><surname>Walsh</surname> <affiliation><address><email>[email protected]</email></address></affiliation> </author> </bookinfo> <preface><title>Preface</title> <para>This book tests EBNF constraint links that cross chunk boundaries.</para> </preface> <chapter><title>EBNF</title> <productionset> <production id="NT-SDDecl"> <lhs>SDDecl</lhs> <rhs><nonterminal def="#NT-S">S</nonterminal> 'standalone' <nonterminal def="#NT-Eq">Eq</nonterminal> <!-- The above line break in the source file has nothing to do with the line breaks in the output. --> (("'" ('yes' | 'no') "'") | ('"' ('yes' | 'no') '"')) </rhs> <constraint linkend="check-rmd"/> </production> <production id="NT-element"> <lhs>element</lhs> <rhs> <nonterminal def="#NT-EmptyElemTag">EmptyElemTag</nonterminal> <sbr/><!-- There will be a line break in the output because of the sbr. --> | <nonterminal def="#NT-STag">STag</nonterminal> <nonterminal def="#NT-content">content</nonterminal> <!-- The above line break has nothing to do with the output. --> <nonterminal def="#NT-SDDecl"/> </rhs> <constraint linkend="GIMatch"/> <constraint linkend="elementvalid"/> </production> <productionrecap linkend="NT-SDDecl"/> </productionset> </chapter> <chapter><title>Constraints</title> <constraintdef id="GIMatch" role="WFC"> <title>Element Type Match</title> <para>Some description...</para> </constraintdef> <constraintdef id="elementvalid" role="VC"> <title>Element Valid</title> <para>Some description...</para> </constraintdef> <constraintdef id="check-rmd" role="VC"> <title>Standalone Document Declaration</title> <para>Some description...</para> </constraintdef> <constraintdef id="NT-S"> <title>NT-S</title> <para>Just for link integrity...</para> </constraintdef> <constraintdef id="NT-Eq"> <title>NT-Eq</title> <para>Just for link integrity...</para> </constraintdef> <constraintdef id="NT-EmptyElemTag"> <title>NT-EmptyElemTag</title> <para>Just for link integrity...</para> </constraintdef> <constraintdef id="NT-STag"> <title>NT-STag</title> <para>Just for link integrity...</para> </constraintdef> <constraintdef id="NT-content"> <title>NT-content</title> <para>Just for link integrity...</para> </constraintdef> </chapter> </book>
null
minipile
NaturalLanguage
mit
null
Three-dimensional reconstruction of cells from serial sections and whole-cell mounts using multilevel contouring of stereo micrographs. A comprehensive computer-graphics-based system (STERECON) is described for tracing and digitizing contours from individual or stereopair electron micrographs. The contours are drawn in parallel planes within the micrographs. Provision is also made for tracing and digitizing in full three-dimensional (3-D) coordinates in any direction along linear structures such as cytoskeletal elements. The stereopair micrographs are viewed in combination with the contours being traced on a graphics terminal monitor. This is done either by projecting original electron micrograph (EM) negatives onto a screen and optically combining these images with contour lines being drawn on the monitor, or by first digitizing the images and displaying them directly on the monitor along with the contour lines. Prior image digitization allows computer enhancement of the structures to be contoured. Correction and alignment routines are included to deal with variable section thickness, section distortion and mass loss, variations in photography in the electron microscope, and terminal screen curvature when combining projected images with contour lines on the monitor. The STERECON system organizes and displays the digitized data from successive sections as a 3-D reconstruction. Reconstructions can be viewed in any orientation as contour stacks with hidden lines removed; as wire-frame models; or as shaded, solid models with variable lighting, transparency, and reflectivity. Volumes and surface areas of the reconstructed objects can be determined. Particular attention was paid to making the system convenient for the biological user. Users are given a choice of three different stereo-viewing methods.
null
minipile
NaturalLanguage
mit
null
Why Bar Hopping Beats Medication For Social Anxiety Symptoms OK, might be I proceeded to go a little too a lot to be able concept, but provide just a next to go into detail and you will probably fully grasp. A psychologist who is skilled in intellectual conduct remedy as soon as gave a spiel through which she detailed the most powerful methods for beating societal panic. Particularly she identified are nevertheless among the declare-of-the-skill strategies for struggling sociable anxiousness symptoms. She learned particularly though examining together with some specialists on social anxiousness in Great Britain. Just about the most efficient methods that was utilised necessitates the re-direction of emotional focus from oneself to people around you. Right here what previously worked around in the uk. The panic experts would lightly coach their socially anxious homework players before sending them to a pub. The study inquired the analysis subjects to speak to a few people in the pub while recognizing certain qualities of the people they talked to. So, one example is, anyone might be informed that they may need to remember that the color of eyes of the individual we were holding conversing with along with the amount of strengthOrexhaustion the person revealed of their deal with and the entire body language. We can also need to give you a thorough outline of your other half is hair do about causing the club and coverage to they. Why performed this work? How much does it do? Plainly gone to the technological info on the emotional factors concerned, this post would grow to be relatively boring before you got towards conclude. Therefore I minimize on to the chase preferably. You didn look for this Internet content to acquire learn more of internal ideas and neurological composition associated with sociable panic. You’ve always wondered where to start and how to practice it. And so the basic reply about why this operates is usually that the exploration themes minds were chaotic focusing on and examining anyone these were speaking to inside the tavern, which foliage a lesser amount of thought living space for self analysis and associated do-it-yourself-consciousness that raises panic. In other words, your brain can only hold its center on so many issues at the same time, considering crowd out your emotional functions that underlie the usual fast escalation of public stress and anxiety worries throughout a discussion that has a unknown person, the stress is a much smaller opposing forces you must handle. Plus the finest point about this style of moving remedy is it may get the eyes off the floor and on the peer of the other, which increases an optimistic interconnection and reduces the stress and anxiety you come to feel so when they get connected to somebody (with the exposure result). The reason stop-stress medicinal drugs can’t contest with the effectiveness of this kind of technique is the fact that anti-anxiety medication affects mental performance over a world wide level as opposed to a trouble-particular levels. We are able to numb your brain stress and anxiety reaction by disturbing the fight or flight effect using a try out-blocker medication. Or, we are able to numb serotonin levels by having a lot more GABA natural chemical through the use of among the list of minor tranquilizers. These methods get some worth, even so the result resembles employing a sledgehammer to penetrate your doorway as a substitute of your dwelling critical. The strategy I explained in this article is among several that was disclosed through the thorough subconscious analysis on the amount works and what doesn help increasing sociable nervousness warning signs. So, in case you are some of the most people that has been the unlucky sorry victim with the societal nervousness pitfall, remember to put on quit with hoping a medication or two. Deal with the stress and anxiety with everything else you got. Continue reading, understanding, and implementing new practices and you’ll get over cultural nervousness and too much shyness.
null
minipile
NaturalLanguage
mit
null
Service providers typically provide numerous voice and data services to end users (also referred to as subscribers). Examples of voice services are voice calls, call forwarding, call waiting, etc. Examples of data services are streaming audio, streaming video, Voice over Internet Protocol (VoIP), online gaming, and IP-TV. The data services are managed by a packet-switched (PS) core network, which interfaces the end user with external Packet Data Networks (PDN), such as the Internet. Some examples of PS-core networks are a General Packet Radio Service (GPRS) core network, an Evolved Packet Core (EPC) of a Long Term Evolution (LTE) network, etc. Mobile devices, such as cell phones, personal data assistants, smart phones, notebook computers, etc., may access the data services provided by the networks over an air interface with one or more base stations. The service providers use offline and online charging functions to keep track of the resource usage incurred by each device for using the various services. The 3GPP/3GPP2 standards groups have defined a set of specifications that may be used to implement online charging systems and offline charging systems in the various network domains (e.g., a circuit-switched domain, a packet-switched domain, and/or a wireless domain), IP multimedia subsystems (IMS), and emerging 3G/OMA application services. According to the 3GPP TS 32.240 specification, offline charging is a process where charging information for network resource usage is collected concurrently with the resource usage. The charging information is passed through a chain of charging functions, which results in the generation of Charging Data Record (CDR) files that are transferred to the network operator's billing domain for subscriber billing and/or inter-operator accounting. To implement offline charging, a Charging Trigger Function (CTF) is implemented in a network element that provides a service. The CTF collects information pertaining to chargeable events, assembles this information into matching charging events, and sends the charging events to a Charging Data Function (CDF), which may be implemented in the network element or in the Offline Charging System (OFCS). The CDF receives the charging events from one or more CTFs, and uses the information included in the charging events to construct CDRs. A CDR is a formatted collection of information about a chargeable event (e.g., time of call set-up, duration of the call, amount of data transferred, etc.) for use in billing and accounting. The CDF then sends the CDRs to a Charging Gateway Function (CGF) of the OFCS. The CGF acts as a gateway between the network and the billing domain. Therefore, the CGF collects CDRs from the CDF (and other CDFs), optionally correlates the CDRs and writes the CDRs into a CDR file, and makes the CDR file available to the billing domain. The 3GPP TS 32.240 specification provides for the support of Fully Qualified Partial CDRs (FQPCs) and Reduced Partial CDRs (RPCs) between a CDF and a CGF. A FQPC is a partial CDR that contains a complete set of the fields specified for the CDR type. This includes all the mandatory and conditional fields as well as those fields that the network operator has provisioned to be included in the CDR. A RPC is a partial CDR that only provides mandatory fields and information regarding changes in the session parameters relative to the previous partial CDR. As an example, the first partial CDR sent from a CDF to a CGF is a FQPC that includes all necessary fields. This FQPC acts as the basis for providing the missing information in RPCs subsequently received by the CGF for the same session. If information for the session has not changed, then the CGF may receive a RPC from the CDF. Upon receiving the RPC, the CGF is able to construct another FQPC from the RPC based on the prior FQPC it received for the same session.
null
minipile
NaturalLanguage
mit
null
A Difficult Site Shapes the House The undeveloped lot in a neighborhood usually has its shortcomings. This one slopes steeply down from the road, and the surrounding area drains into it. Wetland and property-line setbacks left only a small wedge-shaped buildable area. The site plan for the septic tank and leaching field with a 100-ft. separation from the well further constrained the siting of the house. As Michael Maines considered the orientation of the house, he wanted the front door to be clearly visible—a beacon guiding visitors to the entry—and for the long axis to be oriented for a south-facing solar array. Instead of squaring the house to the road, Maines turned the house at an angle. This moved the porch a comfortable distance from the retaining wall, and it brings the door into view earlier on the approach. The orientation is within 15° of south, important for passive-solar heating and PV. The sloping site made a walkout basement a natural choice. Some thought was given to placing the garage under the house, but an attached garage at grade preserves the aging-in-place flexibility of the floor plan, which allows for converting the first-floor flex room into a master bedroom. When taking a design from sketch to finished product, it helps to look at it from every possible angle. That’s why we’re pleased to be sharing the FHB House site plan, elevations, and floor plans, courtesy of SoftPlan architectural design software.
null
minipile
NaturalLanguage
mit
null
--- ID: "a5d0b0ad-ce4e-4e06-b821-f30416b7dec9" Parent: "2a513d39-d7c7-4c12-bc60-88e737a965b0" Template: "455a3e98-a627-4b40-8035-e683a0331ac7" Path: /sitecore/templates/Feature/Accounts/_UserProfile/Data/Interest DB: core SharedFields: - ID: "ab162cc0-dc80-4abf-8871-998ee5d7ba32" Hint: Type Value: "Single-Line Text" - ID: "ba3f86a2-4a1c-4d78-b63d-91c2779c1b5e" Hint: __Sortorder Value: 400 Languages: - Language: en Versions: - Version: 1 Fields: - ID: "25bed78c-4957-4165-998a-ca1b52f67497" Hint: __Created Value: 20151112T093916Z - ID: "5dd74568-4d4b-44c1-b513-0af5f4cda34f" Hint: __Created by Value: | sitecore\admin
null
minipile
NaturalLanguage
mit
null
1. Technical Field of the Invention The invention relates generally to communication systems; and, more particularly, it relates to session recovery after a restart of at least one communication device within single user, multiple user, multiple access, and/or MIMO wireless communications. 2. Description of Related Art Communication systems are known to support wireless and wire lined communications between wireless and/or wire lined communication devices. Such communication systems range from national and/or international cellular telephone systems to the Internet to point-to-point in-home wireless networks. Each type of communication system is constructed, and hence operates, in accordance with one or more communication standards. For instance, wireless communication systems may operate in accordance with one or more standards including, but not limited to, IEEE 802.11x, Bluetooth, advanced mobile phone services (AMPS), digital AMPS, global system for mobile communications (GSM), code division multiple access (CDMA), local multi-point distribution systems (LMDS), multi-channel-multi-point distribution systems (MMDS), and/or variations thereof. With various types of wireless communications (e.g., single-output-single-input (SISO), multiple-input-single-output (MISO), single-input-multiple-output (SIMO), and multiple-input-multiple-output (MIMO)), it would be desirable to use one or more types of wireless communications to enhance data throughput within a WLAN. For example, high data rates can be achieved with MIMO communications in comparison to SISO communications. However, most WLAN include legacy wireless communication devices (i.e., devices that are compliant with an older version of a wireless communication standard). As such, a transmitter capable of MIMO wireless communications should also be backward compatible with legacy devices to function in a majority of existing WLANs. Therefore, a need exists for a WLAN device that is capable of high data throughput and is backward compatible with legacy devices.
null
minipile
NaturalLanguage
mit
null
Mortality among employees of an Ontario factory manufacturing insulation materials from amosite asbestos. The mortality of workers from an Ontario factory manufacturing amosite asbestos insulation materials under poorly controlled environmental conditions is reported here. Seven (58%) of 12 deaths among exposed workers 10 or more years after first exposure were due to malignancies; four (25%) were from lung cancer, and there were two deaths from peritoneal mesothelioma. Those dying from mesothelioma were 47 and 49 years of age. Three (25%) of 12 deaths were from respiratory disease, two were attributed to asbestosis (in men 42 and 53 years of ages), and one to pneumonia in a 54-year-old male.
null
minipile
NaturalLanguage
mit
null
What Can I Do For You? More Details Stm mining equipment pty ltd celebrated nine years of service starting in the portable compressor industry and later moving on to earthmoving industry our office has been based in boksburg for the past six years and we strive to give our clients the best service we can provide the best priced machinery and good used parts Support air compressors an air compressor is a piece of mechanical equipment used in process plants or mills and shops to deliver a higher pressure of air cfm is the short for cubic feet per minute and it is how compressors are rated and the relates to the amount of air volume moved by the air compressor Robust energyefficient safe compressors and blowers for all mining applications perform in the harshest conditions rely on decades of mining experience compressed air for the mining industry we have been manufacturing equipment for the mining industry for over a century we help you maximize your operational efficiency and If you are looking for preowned compressors click on the image below of the compressors in order to find the seller details or more info mascus south africa construction mining compressor equipment compressors used equipment search close advanced search keyword used compressors for sale Mining applications where compressed air is especially useful include pneumatic tools compressed air is an excellent source of energy for power tools such as drills wrenches hack saws and other vital mining equipment that needs to be used in the deep underground stretches of the mines Homemining plant mining compressors for sale in uk top searches compressors for sale in zimbabwe mining compressors for sale mining 2008 certified organization and offer an array of air compressors and mining equipment such as two stage compressor multi stage compressor Offers 33727 mining equipment compressor products about 55 of these are general industrial equipment 12 are refrigeration heat exchange parts and 1 are other refrigeration heat exchange equipment a wide variety of mining equipment compressor options are available to you such as free samples paid samples If you are looking for preowned compressors click on the image below of the compressors in order to find the seller details or more info mascus south africa construction mining compressor equipment compressors used equipment search close advanced search keyword used compressors for sale Epiroc provides the innovative solutions you need to reach and surpass your goals across the globe our well tested equipment and services contribute to safer and more productive operations in surface and underground mining infrastructure projects civil works well drilling and geotechnical applications Mining is not only one of the greatest global industries it is also one of the most dangerous to work in unearthing precious resources takes quite a bit of precision using durable and reliable equipment at ingersoll rand we pride ourselves on being able to offer our customers the gamut of tools and equipment needed to work in the mining industry including everything from air compressors to Air compressor and mining services specializes in the construction and mining equipment in polokwane we are also a leader in our field air compressor and mining services specializes in the construction and mining equipment in polokwane we are also a leader in our field We are offering mining air compressor sandblasting equipment airless spray paint equipment gunite hopper a wide range of pneumatic breakers are available to work efficiently in hostile conditions manufacturing vt4 vt5 vt6 type air compressor we are also manufacturing electric screw air compressors from 20 to 70 hp Our durable hoist and winches are designed to thrive in the harsh environments found in mines around the globe most often used in underground mines they are typically used to transport equipment and to move raw materials smaller mines usually require 12 winches or hoists in capacities ranging from 1 to 6 tons while larger and deeper mines can require capacities up to 20 tons to move
null
minipile
NaturalLanguage
mit
null
Bangabandhu sattelite Bangabandhu Satellite 1, installed at a cost of Tk 2,702 crore, is yet to earn a penny in seven months of its launch with 15-year lifespan while technical complexity and lack of preparation have surfaced. Although the government earlier said that the satellite would realise its cost within seven years of its launch, unsold state of its capacity raised suspicion if the project would be a commercially success or remain as a ‘national pride’. Immediate-past posts, telecommunications and ICT minister Mostafa Jabbar earlier stated that the satellite was not just for technical or commercial purpose, but it was also a pride of the country. Bangladesh Television along with three of its wings — BTV World, Sangsad Bangladesh Television and BTV Chattogram — and four other private television channels are running trial broadcast using the satellite, installed with 14 C-band and 26 Ku-band Transponders each having capacity of 36 Megahertz bandwidth, said top officials at Bangladesh Communication Satellite Company Limited, a government-owned company formed to run the satellite. Besides, three government agencies — fisheries department, shipping ministry and cabinet division — have signed agreement for using the service, but none of them are paid subscriber of the satellite, launched on May 11, 2018 from NASA’s Kennedy Space Centre in Florida in the United States. RealVU, first direct-to-home satellite service provider in Bangladesh that has been running service using the Bangabandhu Satellite on trial, is expected to sign contract with the company. The company is yet to sign any commercial agreement to lease out capacity of the Bangabandhu Satellite 1 while commercial satellite companies usually lease out a major portion of their capacity before the launch, said officials at the Bangladesh Telecommunication Regulatory Commission, associated with operation of the satellite company. About technical complexity, company chairman Md Shahjahan Mahmood said that installation of separate equipment and high power amplifier was needed required at the receiver-end of television channels’ signals. Incompatibility between the existing technology and the technology used in Bangabandhu Satellite is the main reason behind the complexity, said Shahjahan, adding that the equipment was not available in Bangladesh market prompting the company to import 60 high power amplifiers from the United States for trial run of television broadcasting using the satellite. He said that the company would take measures to make the equipments available in Bangladesh market. Asked if the TV channels would feel comfortable with the use of Bangabandhu Satellite for broadcasting until the equipment was installed at the cable TV operators’ end, he said, ‘They might not but I hope that cable TV operators would install the technology as it would be available within next 15 days.’ The company was also facing problem as the television channels cannot broadcast signals directly from the stations using their own equipments incompatible with the technology of used in the satellite along with its location in the orbital slot. ‘To solve the problem, TV channels would send signals to BS 1 landing station located in Gazipur using fibre and the signals would be transmitted to BS 1 from there,’ Shahjahan said. He expressed hope that all local televisions would be able to operate commercial broadcasting using the satellite by January 2019. At a discussion in April 2018, Association of Television Channel Owners vice-president Mozammel Babu said that television channels needed to maintain 45 degree angle to connect the satellite placed in 119.1 degree orbital slot for which a six-storey building might cause problem. ‘We have already tested with a satellite placed in 121 degree orbital slot to understand how effectively we could be connected to a satellite at such an angle,’ he said. Speaking about the performance of 26 Ku-band transponders, Mozammel, also Ekattor TV managing director, said that the transmission under the Ku-band was interrupted even by a single drop of rain. Besides taking initiative to solve the technical problem in using the satellite by the Bangladeshi TV channels that would consume 10 per cent of total capacity of the 40 transponders, the company initiated a move to lease out service to South Asian countries alongside Indonesia, the Philippines, Myanmar, Tajikistan, Kyrgyzstan, Uzbekistan, Turkestan and a part of Kazakhstan. As part of the move, Thailand’s satellite company Thaicom has been appointed for two years under a revenue sharing model with the company. A company official said that the company had so far received a couple of proposals from foreign companies to take service from it.
null
minipile
NaturalLanguage
mit
null
Fiery, fierce and ferocious are all summed up in this BCBGeneration bootie. Secret B showcases a leather upper covered in a leopard print fur. A lace up closure, hidden 1/2 inch platform and a unique 4 1/2 inch faux wood heel perfects this style to fit right into your shoe closet. Leather Upper/Man Made Sole. multi-color. The MTNG 74259 finds a way to jazz up the everyday ankle boot. An eye catching man made leather upper delivers a lace up vamp for an easy fit. A 5 inch thick heel and 2 inch platform finish up this stunning style. Leather Upper/Man Made Sole. silver. Is there anything more fabulous than the Fulginiti? This ALDO bootie features an open concept with exposing cut outs and peep toe. Black leather drapes everything from the 1 1/2 inch platform to the 5 1/2 inch stiletto heel. Leather Upper/Man Made Sole. black.
null
minipile
NaturalLanguage
mit
null
Roger on Running: Diary from Iten An insider's look at life on the ground in Kenya Moses Mosop ran 45K today and went through 26.2 miles in 2 hours 16 minutes. At altitude! He plans to run Chicago but not try for the world record because he has some distraction due to his divorce. Mary Keitany has been away at the Lisbon half, and will be doing New York. I’d better not say how she plans to run it. But she intends to win and won’t be waiting around. It looks likely she will be wearing my watch in NYC. I had dinner with Jeroen the physio and Mary’s coach, Gabriele Nicola, who is really helpful to me and incredibly knowledgeable, an absolute fanatic when it comes to knowing times and splits. He analyzed every split from Mary’s Lisbon race to see where she can improve. He really cares about all his athletes. And Jeroen has become such a good friend I’m giving him my Aberdeen F.C. top. (The way they are playing this season, it might not count as a gift.) One really good friend is Enoch. I helped him set up an email and Facebook. He’d love to go to university but there’s no way his mother can afford it. Lornah and her husband, Pieter, have a great program that sends outstanding Kenyans to American colleges. The bad news is my running has stopped again, as the shin is far too sore. Did 100K on the gym bike yesterday, inspired by when Dad requested a treadmill in his chemo isolation room in 2007. [For Myles’ dad and his response to cancer, see “Roger on Running: Running Old and New.”] I hit the wall at 92K, but still did my 2-minute Ks target. No point in being down. I have a great physio who is far cheaper than home, and all the time in the world to work out and get mega fit. Bad things happen to everyone, it’s how you deal with them that sets you apart. Today I was sitting in the sun when Linet Masai shouted for my help. I ran over and in her living room a socket and extension cable was sparking. I made sure she was well away from it and got her to turn off the power. The plug had melted in the socket and snapped when I tried to pull it out. So I got a friend who was going to Eldoret to buy a new plug and socket, and dropped it off tonight after my stretching class with Jeroen, to Linet’s very shy sister Maggie. Five minutes later Linet came over, smiling but shy, asking how much she owed me, but I said nothing, it’s for a neighbor. When do you get opportunity to do a favor for a world-class athlete? Her smile went from ear to ear. It’s amazing to get to know her as an ordinary person at home, after reading about her, things like your magic description of her running, "Roger on Running: The New York Mini 10K." I showed Linet her fan site on Facebook, which she had never seen. Some days I watch soccer with her and all her sisters. Linet supports Chelsea, but no one is perfect. Berlin and Chicago — wow! All Kenya is very happy. According to Canova, Mosop was only in 85 percent shape. Before the race, he said Moses would run “around 2:05:40,” not a bad prediction. [Mosop won Chicago in 2:05:37 on Oct. 9.] In the gym on the way to the shower I got chatting with a guy who after about five minutes casually mentioned that he was one of Patrick Makau’s pacers in his Berlin world record. I also talked to Wilson Kipsang. He told me, “As athletes we have expectations and aims. As we accomplish these, they change. Now my expectation is the world marathon record, and my aim is to do that in Frankfurt on Oct. 30.” Gilbert Kirwa will be at Frankfurt, too, and Agnes Kiprop should win the women’s. Then comes New York, with Mary Keitany. It goes on and on. This is an incredible place! Three nights ago I picked up severe food poisoning and lost so much weight in 12 hours I was taken to hospital. Now I weigh the same as a Kenyan. Iten District Hospital was great, the staff were impressive and friendly. I was home in time to leave at 7 a.m. (see, I said I could do it!) for a local cross country race. Great trip, as Maggie was running, and others from the Masai family came along. They are incredibly friendly and helpful people, and they laugh, laugh and laugh some more all day long. The race was like no event I have ever seen — kids everywhere, big fields, incredibly fast. My training partner Dan ran 40:29 for 12.8K /7.95 miles, and only came 94th! He was first mzungo, and the kids had never seen a white man. I lost count of the number who asked me to sponsor them. Today I walked one hour, increasing the pace, and ran in the pool, which tests the breathing — and NO PAIN. Will try running again soon. My plan now is to get injury-free when I’m home, get a job to save some more money, and then come back here in March. I’ve made amazing new friends here, like Enoch, Jeroen and Linet. It’s opened up so many things I would like to do with my life, like coaching, and freelance journalism, and helping people find good therapists. I’ll do some of it here. This is a special country. Roger Robinson has done many things in a lifetime in running, including racing for England and New Zealand, setting masters records at Boston and New York, and working as stadium announcer and TV and radio commentator. Most of his jobs involve finding words to describe or analyze running. The first of his successful books, “Heroes and Sparrows: a Celebration of Running” was reissued this year. Senior writer for Running Times he has won three U.S. running journalism awards. “Roger on Running” appears monthly on runningtimes.com. Read all of Roger's articles here.
null
minipile
NaturalLanguage
mit
null
Q: How to prove irreducible and aperiodic Markov chain is regular If $\{X_n\}$ is a finite-state Markov chain, which is aperiodic and irreducible, how can I show it is regular? My attempt: For all $i,j$ states there exists $n\in\mathbb{N}$ such that $P^n_{ij}>0$. I was trying to proof using the aperiodicity that for some $M\in\mathbb{N}$, $P^n_{ij}>0$ for all $n\geq M$ and taking the maximums would give power of $P$ with only positive entries. Any suggestions? A: We know that if a (finite state space) Markov Chain is aperiodic, then there is some $n_0$ s.t. for all $n\ge n_0$ and all states $i$, $p_{ii}^n>0$. Let $i\ne j$ be states of the Markov Chain. Let $m_{ij}$ be the shortest time to go from $i$ to $j$, ie, the mínimum of all $m$ s.t. $p_{ij}^m>0$. (which is finite because the chain is irreducible), and let $M:=\max_{i,j}m_{ij}$. Now, let $n = M + n_0$ and $i\ne j$. We can write $p_{ij}^{n}=p_{ij}^{(n-m_{ij})+m_{ij}}$. By Chapman-Kolmogorov, we know $p_{ij}^{(n-m_{ij})+m_{ij}}=\sum_{k}p_{ik}^{n-m_{ij}}p_{kj}^{m_{ij}}$. Hence, $$ p_{ij}^{n}=p_{ij}^{(n-m_{ij})+m_{ij}}=\sum_{k}p_{ik}^{n-m_{ij}}p_{kj}^{m_{ij}}\ge p_{ii}^{n-m_{ij}}p_{ij}^{m_{ij}}>0 $$ as $n-m_{ij} = (M - m_{ij})+n_0\ge n_0$. Hence, $P^{M + n_0}>0$, ie, the chain is regular.
null
minipile
NaturalLanguage
mit
null
Tag Archives: polka There is quite a stash of fruit in the freezer, waiting to be used up. For the most part, I plan to jam or jelly. However, over the last few weeks I have been harvesting raspberries every other day and stowing them away. The plan had been to be jam them. However, when it was announced that work would be hosting a Macmillan coffee morning, and that colleagues were invited to bake, I thought about what I might do to support the event. I was racking my brain for a while. It is not usual for me to experiment, make a bake and inflict in on my colleagues. There have been crumbles and cakes made using allotment produce that have shared in the work kitchen. Depending on what it is, the bake doesn’t last long. The quickest to go and recently was a bakewell containing some home made jam. I remember putting it down, and coming back one hour later. A handful of crumbs was all that was left behind. I have never seen a pudding move so fast, and stood there a little perplexed as to how and why. I quite enjoy baking, I find it quite therapeutic; in most cases, I make a bake for home, and a second is taken to work. That doesn’t mean I’m a proper baker, I enjoy making mistakes and things, rather than showstoppers. So with Macmillan Coffee morning 2017, it seemed quite straight forward to volunteer something. I just couldn’t think of what I might make. Only, for youngest sister to look at me, and say cheesecake. “Make that cheesecake,” she said, “The baked one, you’ve not made on in a while. That was nice.” If in doubt, ask your sister. I haven’t made the baked cheesecake in a while, no, and it was nice. I think I have made a couple previously; one was with blueberries, another with strawberries, all the fruit was from the shop. Now I have my own fruit; blueberries have come and gone, strawberries are not my thing, those raspberries have now got an opportunity to actualise their potential. They are going into Ms.Farmah’s baked raspberry cheesecake. I just need to find some white chocolate to go with it. There is another reason why I wanted to support the event. Regular readers will be aware that two years ago, as a family we experienced the loss of my Maternal grandfather. Without the support of palliative care staff, his final days may have been even more difficult. Plus. he rather liked my allotment, and one of my fondest memories is Nana visiting. He would then ask what I had growing and what I planned to do with it all. So when I said my last goodbyes to him, I may have sent him off with a packet of sunflower and cabbage seeds. it seemed the right thing to do at the time. So this year’s raspberries are not just raspberries. I have just harvested what might be the last batch to freeze. There are a number of different raspberry varieties that are on the plot. We have: tulameen glen cova malling jewel autumn bliss polka fall gold Most are part of the all season collection that were planted last year. However, the autumn bliss, polka and fall gold are the varieties that specifically fruit as the autumn draws in. The all season collection was sunk last year, with the autumn bliss and polka varieties sunk last summer. The autumn bliss were the surprise quick croppers in autumn, having been rescued from a garden centre, and the polka were actually kindly donated by a friend and colleague. The autumn bliss canes were cut down as suggested, so we shall see how these develop. Pottering around today, I was looking to see if there was any sign of life in the large number of raspberry canes. Lo and Behold, the fall gold are showing green buds. This is somewhat surprising as the canes were only sunk recently. In comparison, the earlier planted canes of the all season collection are somewhat behind. They have rooted, there is resistance if you try and tug at the canes. However, the buds are only just forming at the knobbly bits of the canes.
null
minipile
NaturalLanguage
mit
null
Q: How much acceleration g-force can prevent pilot from moving their arms? Assuming that the craft’s engine is capable of any amount of acceleration, how much g-force would prevent the pilot from being able to move their limbs in order to control the space craft? There is an article about John Stapp surviving stopping at 46g, but that does not appear to document his ability to move during the test. Also I am assuming that the craft is not fully computerized and needs some pilot input of some kind. If there are better more technically correct words to describe what I am asking, please feel free to let me know and I can learn and edit the question. A: According to the book Human Engineering guide for Equipment Designers, authored by Wesley E. Woodson and Donald W. Conover and published by the University of California Press, suggests the following effects at various levels of g-force for Transverse, positive and negative g-forces. Effects of prolonged G ------------------------------------------------------------------------------------------- Transverse G forces ------------------------------------------------------------------------------------------- 2 g - visual acuity is reduced 4 g - gross body movement is difficult 8 g - respiration becomes difficult 10 g - difficult to hold head up, can't move limbs 12 g - breathing difficult without mechanical help 14 g - vision begins to fail ------------------------------------------------------------------------------------------- Positive G forces ------------------------------------------------------------------------------------------- 2 g - visual acuity is reduced 4 g - peripheral blindness, limb movement difficult 5 g - temporary blindness and loss of body control 6 g - unconsciousness ------------------------------------------------------------------------------------------- Negative G forces ------------------------------------------------------------------------------------------- 2 g - diminished vision and head pains 3 g - conjunctival haemorrhage, red-out, and mental confusion 4 g - probably haemorrhage and retinal bleeding With transverse g-forces being in the forwards directions from the chest (forcing a person into the back of their seat, positive being an upwards direction (driving the person into the floor) and negative being in a downwards direction (lifting a person off their seat). A: how much g-force would prevent the pilot from being able to move their limbs in order to control the space craft? How many times do they have to lift their arms? How much control of the limb do they need? Your arm weighs about 5% of your total body weight -- ~4kg for an 80kg male. The weight is evenly distributed across the musculature of the arm, so it's probably easier to lift an extra-heavy arm than to lift a dumbbell of equivalent mass. At 4g you're lifting an extra 12kg (~26 lbs) of arm -- doable for anyone in good physical condition, but your hand is going to be shaky and you will tire of it quickly. Much more than that and you won't reliably be able to hit a small switch, particularly as your perception is suffering from the g-force at the same time. At 10g you're looking at 36kg of extra weight across your arm, which I would guess most people can't hold up if they aren't dedicated weight trainers. (Do not give me a hard time about using mass vs weight/force units here.)
null
minipile
NaturalLanguage
mit
null
We are excited to welcome Principal Ben Renner to Hughes Middle School! Parents and students who would like to meet him are invited to join us from 5:30 p.m. to 6:00 p.m. on Tuesday, July 28 in the BISD Boardroom. The Burleson ISD Trustees have named Ben Renner principal of Hughes Middle School at the July 27 School Board Meeting. Renner comes to Burleson ISD from Mansfield ISD where he has served as assistant principal at both the middle school and high school levels since 2010. Prior to that, he worked in Joshua ISD as [...] It's that time again! Online Annual Registration for returning students will be completed via Family Access and will be available beginning August 1st. As part of this process, parents will have the opportunity to request transportation, and complete their proof of residency (POR) online if they meet all the following criteria: They still reside at the [...] Centennial High School has selected a dynamic staff of band directors for the 2015-2016 school year. Head Director Shawn Murphy brings his assistants, Kim Murphy and Richard Kearns, to CHS from Azle High School where they previously worked together as a team. Director Shawn Murphy graduated from from the University of North Texas in [...]
null
minipile
NaturalLanguage
mit
null
Data Snap: Understanding CrossFitters Outside of the Box On August 3rd, 640 extraordinarily fit men and women will converge on the Alliant Energy Center in Madison, Wisconsin in hopes of distinguishing themselves as among “the Fittest on Earth”. To achieve this distinction, they will compete in the 11th annual CrossFit Games. The Games are the cornerstone competitive event of CrossFit––the high-intensity, data-driven fitness regimen featuring grueling exercises and whiteboard scorecards filled with workout metrics. CrossFit has amassed a large and passionate following, and inspired curiosity among outsiders. Like CrossFitters, Factualites rely on data for inspiration and direction. So we turned to location data to understand the CrossFit enthusiast: Who are they? What do they do outside of the gym? And do they really abstain from alcohol, sugar, and pizza––i.e., the delights that make life worth living? By analyzing their real-world behavior using Factual’s proprietary Global Places and Observation Graph data, we uncovered a number of surprising insights. What does the real world behavior of CrossFitters tell us about who they are? CrossFit enthusiasts’ shopping behavior reveals that they tend to be upper-middle-class urbanites. They enjoy luxury goods, and their purchases veer toward specialty and quality –– whether they’re buying shoes or cheese. They eschew the convenience of supermarkets in favor of farmers markets and specialty food retailers. CrossFitters’ dining behavior confirms that they live relatively healthy (and fast-food-free) lives. Yet, they are unafraid to indulge on occasion. Wine bars, Korean restaurants, and even the occasional dessert shops are fair game (because if you’re going to break your diet, you’d better make sure it’s worth it.) Though they are less likely to visit “gyms and fitness centers” or other branded fitness chains (like SoulCycle), they do crosstrain. CrossFitters are twice as likely as the average person to cycle, swim, and hike and they are 41% more likely to visit yoga studios. While CrossFit enthusiasts have embraced western fitness, the data implies that they do not restrict themselves to western medicine. They are not much more likely to visit “sports medicine” offices, but they are almost twice as likely to visit holistic, alternative and naturopathic medicine locations and 54% more likely to visit acupuncture locations. Finally, the data also suggests that, when they party, they go all out. CrossFitters are over two times as likely to visit costumes retailers. Methodology The places people visit in the physical world are among the best indicators of who they are –– including their needs, interests, shopping preferences, and brand affinities. Using Factual’s proprietary Global Places and Observation Graph data, we analyzed the real world behavior of mobile device users who visited CrossFit locations in the United States multiple times in a given month. More specifically, we built a custom audience of visitors to CrossFit locations –– rather than relying on data about “gyms” or “fitness centers.” In order to analyze niche audiences, like CrossFit enthusiasts, you need a granular and customized audience definition. Factual’s Global Places data includes ~100 million businesses and points of interest worldwide––including niche categories like CrossFit boxes––and is updated in real-time to provide fresh and accurate coverage of the world’s brick-and-mortar businesses as well as local, regional, and national landmarks.
null
minipile
NaturalLanguage
mit
null
Galatians Bible Study – Week 1 – Part 2 – Chapters 1-2 Note: If you are looking for any posts you have missed, or a FREE copy of the study guide, you can find the table of contents by clicking here. Below are my thoughts for each of the chapters we studied this week along with the answers to the questions I posted in the study guide. Also, make sure that you get a copy of the coloring page I have pasted below. Have a great weekend! Galatians 1 Questions and Answers… When did Paul establish the church at Galatia? During Paul’s first missionary journey, we see that he sailed to Antioch, which is one of the cities in Galatia: “From Attalia they sailed back to Antioch, where they had been committed to the grace of God for the work they had now completed. On arriving there, they gathered the church together and reported all that God had done through them and how he had opened a door of faith to the Gentiles. And they stayed there a long time with the disciples.” – Acts 14:26-28 According to Biblestudy.org this was late Spring 44 A.D. to Fall 46 A.D. What is the main theme of this epistle? Paul was writing to the Galatians to set the record straight regarding the works of the law, and justification through faith in Jesus Christ. “Knowing that a man is not justified by the works of the law, but by the faith of Jesus Christ, even we have believed in Jesus Christ, that we might be justified by the faith of Christ, and not by the works of the law: for by the works of the law shall no flesh be justified.” – Galatians 2:16 Describe the two main reasons Paul wrote this letter. Some Jewish believers were questioning Paul’s authority while preaching a false doctrine that Gentiles should be keeping the law. Paul writes to both establish his authority and get the church back on track regarding justification by faith. “Paul, an apostle, (not of men, neither by man, but by Jesus Christ, and God the Father, who raised him from the dead;)” – Galatians 1:1 Who were these individuals trying to pervert the gospel and sway the Galatians? What were they saying about him? Look up Martin Luther’s Commentary on the epistle of Galatians for background on this question. In Martin Luther’s commentary on the Epistle of the Galatians, he writes, “These Jewish-Christian fanatics who pushed themselves into the Galatian churches after Paul’s departure, boasted that they were the descendants of Abraham, true ministers of Christ, having been trained by the apostles themselves, that they were able to perform miracles. In every way they sought to undermine the authority of St. Paul. They said to the Galatians: “You have no right to think highly of Paul. He was the last to turn to Christ. But we have seen Christ. We heard Him preach. Paul came later and is beneath us. It is possible for us to be in error–we who have received the Holy Ghost? Paul stands alone. He has not seen Christ, nor has he had much contact with the other apostles. Indeed, he persecuted the Church of Christ for a long time.” Why was Paul so upset that they were believing these lies? Paul had a passion to preach the gospel of Christ, and nothing but the truth of that gospel. He was invested in the lives of his converts as a father is to his children. In fact in Galatians 4:19, he refers to them as dear children, “My dear children, for whom I am again in the pains of childbirth until Christ is formed in you.” Anathema is to be banned or excommunicated. It can also mean a person or a thing that is doomed to destruction. What Paul is saying here is that when someone is perverting the gospel of Christ, we shouldn’t be entertaining that person as a brother in Christ. It’s important to note however that believers will have differing opinions when it comes to understanding the gospel. We have believers that are Baptist, others that are Pentecostal, and some that are Mennonite, etc. You can put them in a room with a chapter of the Bible and get three different opinions, and yet if they are God fearing men and women, you will find unity in the Spirit and a bond of peace. The important thing is that they are agreeing on the fundamental truths found in the Bible, some of them being that there is one God, who is infinitely perfect, existing eternally in three persons: Father, Son and Holy Spirit, that salvation comes by grace through faith in Jesus Christ, that He died on the cross and rose again on the third day, and that the Bible is the inspired Word of God. These men that Paul mentions were clearly trying to sew discord. They were bad mouthing God’s anointed apostle and perverting the gospel of grace through faith in Christ. What do we learn about Paul’s past from both this chapter and Acts 9:1-2? Paul (Saul) was a Pharisee of the tribe of Benjamin. He excelled above his peers, exceedingly zealous of Jewish tradition. He opposed the birth of the church and the gospel of Christ. Seeking to destroy the work of God, it was his mission to seize and punish the disciples. In fact, Saul was present at the stoning of Stephen as we see in Acts 7:58. Describe Paul’s conversion. (See Act 9:3-30) Paul was on the road to Damascus, in fact, he was on his way to the synagogues there. His mission was to arrest any followers of Christ and bring them back to Jerusalem. Before he got there, Jesus appeared to Paul in a bright light saying, “Saul, Saul, why persecutest thou me?” He was then instructed to go to the city where he would further be instructed. Paul was trembling–his companions were speechless. Paul was brought to the city of Damascus where he waited. He was blind, and didn’t eat or drink for three days. There was a disciple in that city named Ananias who was well aware of Paul’s reputation, and God told Ananias to go speak to Paul. Of course Ananias was afraid, but obedient to the command of God. “Ananias went his way, and entered into the house; and putting his hands on him said, Brother Saul, the Lord, even Jesus, that appeared unto thee in the way as thou camest, hath sent me, that thou mightest receive thy sight, and be filled with the Holy Ghost.” – Acts 9:17 Immediately Paul’s sight returned. He started eating again, and was strengthened. Paul didn’t waste anytime. The Bible tells us that he spent time with the disciples and then immediately began to preach the gospel of Christ in the synagogues. Explain why Paul felt the need to share his conversion. Paul needed to establish his authority and help the Galatians understand that he was not called by man, but called by the revelation of Jesus Christ. Not only that, but we also see in chapter 2 that Paul’s apostleship was confirmed by the other apostles. They understood that the gospel of uncircumcision was committed to Paul and that the gospel of circumcision was committed to Peter. These naysayers who spoke against Paul had no authority to do so. Paul on the other hand was given this authority by Jesus Christ. Galatians 2 Questions and Answers… How long had it been since Paul got saved according to verse 1? The timing of the events in Galatians 2 would seem to take place 14 years after Paul was converted. However, if you add the three years found in chapter 1:18 then you have a total of 17 years. What did Paul approach the church leaders about in private? He wanted to present them with the message that he was preaching to the Gentiles, and that God had revealed this mission to him. How did Paul’s ministry differ from that of Peter’s? Paul was called to preach the gospel to the Gentiles and Peter was ministering to the Jews. What does Paul mean in verse 4 when he says, “that they might bring us into bondage?” What were these spies trying to achieve? They were trying to hold the disciples accountable to the Mosaic law, when they had already been freed from that law of ceremonial cleansings, and sacrifices, and all of it’s traditions. Jesus is the fulfillment of the law to all who believe. You can’t serve two masters. Either you believe that you are justified by the works of the law, or you are justified by faith in Christ. One leads to death, while the other leads to life. “Now therefore why tempt ye God, to put a yoke upon the neck of the disciples, which neither our fathers nor we were able to bear?” – Acts 15:10 What made Peter revert back to the legalistic attitude/actions he once forsook? In Acts chapter 10, God gave Peter a vision through which He taught Peter that the Gentiles were not unpure or unclean. Immediately Peter understood that Jews were not forbidden to associate with Gentiles. In fact, Peter said, “I now realize how true it is that God does not show favoritism but accepts from every nation the one who fears him and does what is right.” (Acts 10:34) Peter understood that the Gentiles were called to salvation, in fact he was instrumental in ushering the first Gentile converts into Christianity. (Acts 11) The reason that Peter reverted back to his old ways when the Jews came to visit the church is because it was easier to avoid conflict than to deal with it. What was the result of this? He separated himself from the Gentiles, joined in the hypocrisy of his fellow Jews, and in the process he led Barnabas astray. Why did Paul confront Peter? Because they weren’t acting in line with the truth of the gospel. What is the ONLY thing that saves? The only thing that saves us is faith in Jesus Christ. Explain “justification.” “The act of God whereby humankind is made or accounted just, or free from guilt or penalty of sin.” (www.dictionary.com) Don’t Miss a Post – Subscribe Today! Your email address will not be published. Required fields are marked * Comment Name * Email * Website About the Author I'm an Evangelical Christian whose number one priority is to serve Jesus Christ in every area of my life. My husband Michael and I live in Manitoba Canada. Married 25 years, we have four children (three still at home), a bird and two pugs who are everyone's babies, especially mine! Our lives are basically surrounded with three things: our faith, music and everything books. I’m an award winning and New York Times best-selling author who is nothing without the grace of God. Read my testimony where I share my heart for this ministry... Email Newsletter Bible Studies & Links Search This Site Kind Words "I'm absolutely in awe of your writing, the way you pulled biblical principles and weaved them into life application. I'm amazed at how you were able to expand upon simple words like action, self discipline, motivation, intention, etc.--and write thought provoking information to actually help one change their mind-set and pursue their goals. The way you weaved my stories into all these principles leaves me speechless."
null
minipile
NaturalLanguage
mit
null
Follow Us 2016 Gift Guide For The Trendsetter Everyone has a trendsetter in their lives. She’s the woman who can effortlessly make knee-high boots look classy, or a sequin dress look even more dazzling. She has a style all her own, pairing pieces that no one else would—and making them all fit together for a unique look. What do you get her for the holidays? We found over a dozen things every trendsetter will adore this December. Read on for more! Slake Deluxe Wrap Bracelet There are wrap bracelets—and then there are I-Can’t-Stop-Looking-At-That wrap bracelets. Swarovski’s Slake Deluxe Wrap Bracelet falls into the latter category. The beautiful mix of crystals set on black Alcantara® will sparkle on her arm. Pair it with a holiday dress, or use it to dress up a more casual outfit. Find it at: Swarovski kate spade Flirty Back Mini Dress She’ll “wow” everyone when she walks into the room wearing the kate spade Flirty Back Mini Dress. The bateau neckline and deep-v back make it the perfect “classy on the front, sexy on the back” look. Pair this stunning mini dress with dark tights and heels for a perfect cocktail party look. Find it at: kate spade Bailey Bow UGG® Boots We can’t help but love these Bailey Bow UGG® Boots. The three satin bows are an eye-catching update to the iconic UGG® style. With a plush insole and flexible, lightweight outsole, these provide—true to expectation—both comfort and warmth. She will be wearing them every day this winter! Find it at: Journeys Viva La Juicy Women’s Fragrance Gift Set The woman with a full makeup vanity will love this three-piece Viva La Juicy Women’s Fragrance Gift Set. It includes a .17 oz Parfum, 1 oz Eau de Parfum Spray, and 1.7 oz Body Lotion. With hints of wild berries, jasmine, and vanilla, this sweet floral scent is perfect for the life of the party. Bonus: The parfum is small enough to carry around wherever she goes. Find it at: Fragrance Outlet Versace Medusa Visor Sunglasses Add a touch of glamour to her sunglasses with these Versace Medusa Visor frames. This particular style fuses visor and pilot shapes together, giving a modern spin to a classic look. The intricate gold detailing is sure to make her stand out in a crowd. This is the perfect gift for the woman who loves a hint of subtle luxury. Find it at: Sunglass Hut Leather Moto Jacket & Ruched Sweater Dress We’re in love with this look from Express. The (Faux) Leather Moto Jacket is both sophisticated and edgy, with quilted shoulder detailing and exposed metal zippers. It pairs perfectly with the Ruched Sweater Dress in Amazon Green. The dress is comfortable and stretchy, with front and back ruching, making it easy to dress up with heels or down with riding boots. Find it at: Express “Gorgeous” Over-the-Knee Boots For the woman who loves a great pair of shoes, she’ll be head over heels for these Steve Madden “Gorgeous” Over-the-Knee Boots. They cut right above the knee, making them a great boot to wear over skinny jeans or with a mini sweater dress (like the one above). The heels are just shy of 4″, giving you a bit of extra height for a dinner date or a night out with the ladies. Find it at: Steve Madden The Perfect NYE Outfits Help her ring in 2017 with a fun NYE outfit! For the woman who likes a little bit of shimmer, get her the Metallic Asymmetrical Hem Sheath Dress; it pairs well with a Glitter Wristlet and Steve Madden “Feelya” Heels in black. For the one who likes a lot of sparkle, she’ll go crazy for the Deep V-Neck Sequin Mini Dress in copper. Pair it with Steve Madden “Scene” Rose Gold Heels and a kate spade Champagne Bottle Wristlet. Cheers, darling!
null
minipile
NaturalLanguage
mit
null
Gino's Offer Online Ordering! Whether you are ordering just one Burrito, or alot of food for alot of people Gino's Online Ordering is a fun and easy way of creating your own order. We have drinks and more available too, or you can pick them out when you get here! If you would like to place an Online Order to Gino's click the red box above that says within "Order Online." It will take you to our Pre-ordering page with more information. If you have any questions you can call us at 541-884-6474 or email us at [email protected]
null
minipile
NaturalLanguage
mit
null
A Golgi study of the human Purkinje cell soma and dendrites. The Purkinje cells in apparently normal human cerebellum were investigated with the Golgi-Cox method. Most Purkinje cells have the long axis of the soma directed vertically to the pial surface. Even the small number of disoriented somata have the dendritic system adjusted to a normal vertical pattern by a bend in the primary or secondary dendrites. The primary dendrites of a single Purkinje cell ranged from one to four, the majority being one or two. There were occasional expansions of the dendrites.
null
minipile
NaturalLanguage
mit
null
Health Tips Depression can be one of the hardest times of someone’s life. Sufferers often feel misunderstood, tired and deeply unhappy. If these kinds of feelings sound familiar, you’re not alone. Millions of people suffer from depression every day. Here are a few tips about dealing with depression that might be able to help. Eating a balanced diet and making sure you take in the right amount of vitamins and nutrients is also essential to living a well balanced and healthy life. Fruits and vegetables are an essential part of one’s diet, and what you eat has been proven to have much to do with your mood. Get your personal life in order. When you suffer from depression, even ordinary tasks can get overwhelming. Get organized using small, easy to complete goals and you can keep from getting bogged down in the everyday duties that can keep you from working on your depression and can even make your symptoms worse. For those suffering from depression, try to practice relaxation techniques. If you use these techniques everyday, you may find your depression symptoms reduced and in general, you will feel more relaxed. You could practice yoga, meditation, deep breathing, or progressive muscle relaxation. Have a friend do these things with you. If you are suffering from depression, you should endeavor to keep active in social activities, even when it is the last thing you would want to do. When suffering from depression, it usually feels more comfortable to withdraw from the world and crawl into your protective shell. Closing yourself off from others will not help you beat depression though. You will find that being around others will help you feel less depressed. One of the common things that makes people depressed is their diet. Overeating, binge drinking, and starving are all ways that people use to suppress their feelings. Instead of doing this, let those feelings out. The poor diet always leads to other problems, so if it is recognized and dealt with, it can be handled properly and not lead to other problems in the future. To help you conquer your depression it is vital that you learn to develop a positive attitude and change the way you think. Research has shown that negative thinking plays a huge role in depression. Depressed people minimize their successes and accomplishments and, instead, focus on their failures and sorrows. The key to happiness is loving life in the face of suffering. No, you’re not crazy. Depression is a serious condition and should be treated with respect. When you are depressed, it is a sign of problems such as unresolved emotions or an actual, physical chemical imbalance. Depression is the body telling you it’s overwhelmed and needs assistance. Use these tips as the first steps on your journey to recovery. Depression can be a terrible feeling, but as time passes you will find that you are starting to feel a little better. Take your time and don’t force yourself to act happy if you aren’t. Everything is unfolding in perfect time, including you.
null
minipile
NaturalLanguage
mit
null
Move object on a path?? is it possible in Isadora (Actor, Actor-combination) to move an object (Picture) along a path (like in After Effects for Example??). I have to produce stuff where a simple shape is moving on a predefined path. I made this rough path recorder with 26 points not using DataArray but writing direct into Envelope++. Press r to reset, then on active scene window make path by clicking desired points(26) and press a to run object on the path. It works from the end to the beginning - so needs some more work, but I have no more time. If the path is really pre-defined why not render it in After effects??? Otherwise the DataArray actor is the go- you can feed the data with Duration (this will really help as it lets you create smooth curves and tween between values)- you can use it to record edit and create the data, then record the data into the data array for play back - meaning you dont have to use it live just for producing the path.
null
minipile
NaturalLanguage
mit
null
“Vice, virtue. It’s best not to be too moral. You cheat yourself out of too much life. Aim above morality. If you apply that to life, then you’re bound to live fully.” –Maude, “Harold and Maude” I used to think the best movie about how to live your life was “Auntie Mame.” That was before I saw “Harold and Maude.” “Auntie Mame” is still one of my favorites, but “Harold and Maude” is just one of those delightful, quirky, delicious, lovely movies that everyone should see at least once. Maude: A lot of people enjoy being dead. But they are not dead, really. They’re just backing away from life. *Reach* out. Take a *chance*. Get *hurt* even. But play as well as you can. Go team, go! Give me an L. Give me an I. Give me a V. Give me an E. L-I-V-E. LIVE! Otherwise, you got nothing to talk about in the locker room. Harold: You sure have a way with people. Maude:Well, they’re my species!
null
minipile
NaturalLanguage
mit
null
The statements in this section merely provide background information related to the present disclosure and may not constitute prior art. There are many known forms of backwashing devices in the art. For example, one commonly utilized device includes a hardened back scrubber wherein a central member houses a plurality of bristles that are designed to scrape and exfoliate the skin on a user's back. Another commonly utilized device includes specially made towels having an elongated construction so as to allow a user to run the towel body across their back. To this end, utilization of the soft elongated towels is much more soothing than the hardened back scrubber; however, the soft nature of these towels often causes them to fold and/or lose their shape when making contact with the users back. As such, the user must make several awkward movements and/or contortions of their body to ensure the towel cleans their entire back. In light of the above, it would be beneficial to provide a back and body washing device that combines the soft and comfortable nature of a traditional towel with the ability to maintain a specific shape during use.
null
minipile
NaturalLanguage
mit
null
Why Do Silver Trimers Intercalated in DNA Exhibit Unique Nonlinear Properties That Are Promising for Applications? Our investigation of one-photon absorption (OPA) and nonlinear optical (NLO) properties such as two-photon absorption (TPA) of silver trimer intercalated in DNA based on TDDFT approach allowed us to propose a mechanism responsible for large TPA cross sections of such NLO-phores. We present a concept that illustrates the key role of quantum cluster as well as of nucleotide bases from the immediate neighborhood. For this purpose, different surroundings consisting of guanine-cytosine and adenine-thymine such as (GCGC) and (ATAT) have been investigated that are exhibiting substantially different values of TPA cross sections. This has been confirmed by extending the immediate surroundings as well as using the two-layer quantum mechanics/molecular mechanics (QM/MM) approach. We focus on the cationic closed-shell system and illustrate that the neutral open-shell system shifts OPA spectra into the NIR regime, which is suitable for applications. Thus, in this contribution, we propose novel NLO-phores inducing large TPA cross sections, opening the route for multiphoton imaging.
null
minipile
NaturalLanguage
mit
null
There's something about the very best video games which inspires obsession over the smallest details. Whether it involves (over)analysing a blurry texture, trying to decipher a muffled audio clip or simply experimenting in the world for the fun of it, some games lend themselves to being endlessly broken down and forensically examined. It's the kind of thing that keeps the Stop 'n' Swop legend from Banjo-Kazooie alive in the minds of fans long after the mundane reality of the abandoned feature was revealed. There's something delicious in the mystery of it all! Super Mario 64 is one of those classics which still holds riches to discover even over two decades since release. Arguably its most tantalising mystery is the blurry text found in the Castle courtyard beneath a statue of a Power Star (pictured above). This statue, sometimes referred to as the 'Eternal Star', has been the subject of much speculation and heated debate over the years and still inspires curious minds to this day. Daniel Nodd, also known as No64DD, has been examining the evidence and believes he has found the truth behind the myth. Legend (or was it an April Fool's Day joke?) has it that the blurry text on the plaque reads either 'Eternal Star' or 'L Is Real 2401', the latter apparently referring to Luigi being a playable character in the game. Despite multiple supposed methods to unlock the lankier Mario brother circulating back in the day, he was never found in the game even with N64.com offering $100 to anyone who could prove Luigi was playable (and remember, $100 in 1996 money could buy you a race horse or small semi-detached residence). The mystery was compounded when the plaque also appeared in Dodongo's Cavern in The Legend of Zelda: Ocarina of Time. In the intervening years the question of the blurry text on the courtyard statue would bubble up every now and then, but a letter which appeared on reddit from a Nintendo Game Play Counselor in reply to a query back in 1998 arguably put a lid on the issue - it was simply a joke from the developers. The letter still didn't clear up exactly what the joke was, though... Daniel wasn't satisfied that the mystery had been solved and set about his own analysis of the plaques in both Super Mario 64 and Ocarina of Time using a couple of N64s and some image techniques to enhance the text. Let's have a look at his work... Note: Minor spoilers for Super Mario Odyssey follow, if you care about that sort of thing. You have been warned! With the use of multiple television screens and smartphone cameras, I was able to capture, categorize, and display the best possible examples of the image(s). To begin, I basically turned down all color and adjusted brightness and contrast on the CRT units, as well as turning up sharpness. The Nintendo 64s are running on AV and RF. Out of all the experimenting, taking photos in an inverted negative mode worked best. These are unmodded N64 consoles. The device on the blue console is simply a universal adapter to play Japanese games. The inscription uses the same in-game font from Super Mario 64. I applied it to each shot for better visual comparison. It reads: A Secret star lie here ~ I attempted to adjust the images even further through a few image apps you find on smartphones. Things like sharpness, shadows, white balance, etc. Finely tuning them worked to a point before affecting overall quality, but I also isolated and focused each section for a side-by-side comparison. You can start to recognize the curvature, and how much anti-aliasing begins distorting the graphic. This was taken in Ocarina of Time. Here, the inscription appears slightly bolder than SM64, but can clearly see the capital "S". This area begins to become affected by the grain smear of the marble-like texture, but you can make out the silhouette of the lowercase "e". Here, I wanted to point out the curvature of the lowercase "c", because this letter is also affected by smearing. This normal Elgato screen grab illustrates a primary line of distortion running diagonally, and areas of text that are affected by this in the path. Notice both lowercase "t"s in Secret star have the same slant at the bottom. The "Eternal star" theorists did get this one correct. Lowercase star is clearly visible. For the second line, the text gets smaller and more difficult to decipher. The lowercase "l" is heavily affected by the darkest streak on the memorial plaque, but the contours are still visible. here is almost italic in appearance, but the angle of the lowercase "h" starts to become visible. This image also displays the lowercase "e" in lie much better. And lastly, the final piece, which is actually a tilde. SM64 seems to have the best example. This was taken in black and white in 2015, back when I really started analyzing 'L is Real 2401'. These tildes "~" are commonly used as memorial scribes on tombstones, which is what is represented in both games. The dead Dodongo that resides in its cavern in OoT, and a castle Secret star that metaphorically resides in the courtyard of SM64. That was until Super Mario Odyssey. Daniel's reference to Super Mario Odyssey is a secret star found by donning the Mario 64 cap and suit and transforming the portly plumber into his 64-bit self. This enables you to enter the courtyard in that game (in all its polygonal retro glory) and finally find the fabled 'secret star' by spinning Cappy on the statue, putting a cap on a 21-year mystery. Or has it? In this day and age, why let facts and evidence get in the way of things - especially a good mystery - eh?! Our thanks to Daniel for sharing his findings and the forum where his research started. What do you think? Case closed? Putting aside the lack of verb conjugation, this certainly seems more plausible than all surviving Super Mario 64 carts suddenly unlocking Luigi in the year 2401. Feel free to share your thoughts and own theories below.
null
minipile
NaturalLanguage
mit
null