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The intense vasoconstriction that occurs in the renal vascular bed as a result of increased activity of the sympathetic nervous system can be caused by two mechanisms in the dog: 1) Activation of the renal sympathetic efferent nerves and 2) Adrenal catecholamines reaching the kidney via an adreno-renal vascular network. Both of these sympathetic mechanisms facilitate renal retention of sodium. Experimentally-induced cardiac arrhythmias have been used to elicit these sympathetic mechanisms in the pentobarbital anesthetized dog because with the onset of a tachyarrhythmia there is an abrupt decrease in mean arterial pressure and cardiac output which results in an immediate compensatory increase in sympathetic tone (activation of the renal sympathetic nerves). Upon cessation of an arrhythmia there is rapid return to control levels of flow in all vascular beds except the renal. The principal investigator found that this post-arrhythmic renal vasoconstriction is due to catecholamines which reach the kidney from the adrenal medulla without entering the systemic circulation via an adreno-renal vascular network. The next objective of this proposal is to determine the receptor which activates adrenal catecholamines to flow through the adreno-renal vascular network to produce post-arrhythmic renal vasoconstriction and to learn whether other cardiovascular responses not related to cardiac arrhythmias activate this receptor. Other objectives are to investigate the importance of these sympathetic mechanisms in the renal retention of sodium during the development of hypertension in the spontaneously hypertensive rat and congestive heart failure in the dog (animal models in which there is chronically increased activity of the sympathetic nervous system).
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Dwayne "The Rock" Johnson Sells His Hidden Hills Mansion For $4.9 Million
According to TMZ, Dwayne "The Rock" Johnson has sold his stunning Hidden Hills mansion, and he nearly got it for the $4.9 million asking price. Located 22 miles from Hollywood, the 9,120-square-foot home features six bedrooms, seven bathrooms, an infinity pool, and one hell of a home theater.
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Q:
HTML manipulation lets me break into private betas
I managed to (again) break into a private beta. I used a simple procedure, I copied the login form from another site and used the SE.com openID login. It didn't complain at all, and I wasn't committed to the site on Area51.
Does this need to be fixed? (I realize that it's no biggie if a few people break into private betas)
The older system used to check one's openid against a list of committers. The newer system only allows logging in via a (unique for each user) link, but the original checks in the openid system seem to have been removed since the OpenID login page no longer is there. It probably would be a simple fix to add these checks to /users/authenticate.
A:
We no longer check against a list of committers. The old system was quite robust -- so much so that nearly every private beta had people emailing us for help getting in. We finally decided that making these secure was just not that important, and made it so anyone with the link could get in.
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Cheeky Angel [Sub: Eng] Episode 18
Description
Megumi-chan is a girl with a secret past. She used to be a boy until she met a person she thought was a magic user. This person gave him/her a magical book from which a genie appears to grant one wish when blood is applied to it. Megumi made the wish to be a man in a man’s body but the genie has a twist: he grants wishes backwards so he turns Megum… more Megumi-chan is a girl with a secret past. She used to be a boy until she met a person she thought was a magic user. This person gave him/her a magical book from which a genie appears to grant one wish when blood is applied to it. Megumi made the wish to be a man in a man’s body but the genie has a twist: he grants wishes backwards so he turns Megumi-kun aged 9 to Megumi-chan. Years pass and Megumi enters High School where she immediately beats up the school bully who of course falls in love with her. She is looking for that book again to be able to reverse the spell placed upon her.
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GEN News Highlights
ProNAi to Couple DNAi Therapies with Marina’s Liposomal Delivery System
(Page
1
of
1)
Marina Biotech and ProNAi Therapeutics entered into an exclusive license agreement regarding DNAi-based therapeutics. Marina Biotech's Smarticles® liposomal delivery technology will be used, and ProNAi will have the option to select any number of gene targets. Marina could receive up to $14 million for each target in total up-front fees as well as clinical and commercialization milestone payments.
ProNAi will have full responsibility for the development and commercialization of any products arising under the agreement. Marina is entitled to royalties on sales. “DNAi are short single-strand unmodified oligonucleotides designed to silence genes by interfering with DNA,” explains Charles L. Bisgaier, Ph.D., president and CEO of ProNAi Therapeutics. “The DNAi silencing approach is differentiated from that of RNAi, antisense, or miRNA in that it targets genomic sequences within the noncoding region of DNA, disrupting transcription.
“The progress and delivery validation in the clinic this past year on the novel DNAi-Smarticles formulation gives us confidence to bring forward more first-in-class drug candidates alone or with partners,” Dr. Bisgaier continues. “ProNAi is now positioned to advance additional cancer therapies from its preclinical leads targeting other oncogenes such as c-myc and k-ras while also exploring other disease targets in areas such as inflammation and genetics diseases.”
Dr. Bisgaier notes that 22 patients have been dosed with lead candidate PNT2258 in a Phase I trial in advanced solid tumors. In this open-label, single-arm, dose-escalation trial, patients receive PNT2258 as an intravenous infusion once daily for five consecutive days of every 21-day cycle. ProNAi plans to report the results of this Phase I study later this year.
PNT2258 is targeted against the anti-apoptotic bcl-2 oncogene and encapsulated in Marina's Smarticles technology. “This novel delivery technology offers protection for the DNAi oligonucleotide during systemic administration with good circulation times and extrahepatic tumor exposure,” Dr. Bisgaier notes.
Marina Biotech’s Smarticles technology has also been licensed to Mirna Therapeutics for the delivery of miRNA mimics. Inked last December, the deal could earn Marina Biotech $63 million in total up-front fees as well as clinical and commercialization milestone payments over and above royalties on sales.
Marina Biotech’s own pipeline comprises a clinical program in familial adenomatous polyposis and two preclinical programs in bladder cancer and malignant ascites. The company also has an exclusive agreement with The Debiopharm Group covering the bladder cancer program. "Besides advancements within our own internal research programs, we have now been able to establish two license agreements broadening the application of the Smarticles technology to the systemic administration of both single- and double-stranded oligonucleotide therapeutics,” remarks J. Michael French, president and CEO of Marina Biotech.
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Find Cheap Flights
Cheap Flights to Kalgoorlie
Cheap Flights to Kalgoorlie
Planning a trip to Kalgoorlie? Compare and choose from cheap flights to Kalgoorlie using Webjet’s travel tools and advanced booking technology. Whether you’re travelling in a few months or in a few days, Webjet has a huge range of cheap flights with various departures to get you to Kalgoorlie-Boulder.
Make the journey to Kalgoorlie with a flight from one of the carriers that service Kalgoorlie-Boulder Airport several times daily, including Qantas and Virgin Australia.
Travelling to Kalgoorlie
Kalgoorlie is a unique outback city that become one of Australia’s most prominent mining centres. Featuring a charming regional character of its own, Kalgoorlie offers plenty to see and do both in the city centre and further afield.
If it’s your first time visiting, familiarise yourself with the city’s streets at your own pace and discover Kalgoorlie’s most popular sights with a self-guided walking tour around the city. Explore the history of the mining city with a visit to one of the area’s many museums. Whether you’re looking to learn about the city’s mining past, the history of the city’s racing club or the involvement of locals during wartime, there are plenty of exhibits which trace back Kalgoorlie’s past and explain its present.
Stop by Kalgoorlie’s KCGM Super Pit to see the largest open cut gold mine in Australia and understand the contribution that mining makes to the city’s community. With a visit to the sprawling Super Pit you’ll soon understand why Kalgoorlie’s goldfields are the largest gold producing region in Australia.
Kalgoorlie Airport is located 7 kilometres outside the town centre, so why not hire a car to make for an easy transfer and create your own self-drive itinerary of Kalgoorlie and its surrounding regions?
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The Campaign for Free Expression: It’s Time for the World to Stand Up
October 2, 2012
The Center for Inquiry is proud to announce the launch of the Campaign for Free Expression, an initiative designed to combat the rising tide of blasphemy and incitement laws—laws used to criminalize criticism of religion or apostasy—and reassert the primacy of perhaps the most fundamental human right: the right to freedom of expression.
Here’s the official press release heralding the start of the campaign. Keep reading to see how you can get involved.
To fight the efforts of governments to criminalize speech critical of religion, and to push back against calls for global restrictions on free speech, the Center for Inquiry launches the Campaign for Free Expression. Timed to commence with International Blasphemy Rights Day, the Campaign aims to increase public awareness of threats to free expression, and develop plans to fight back, both in the world’s halls of power and at the grassroots.
Over the next several months, the Campaign will highlight cases of those being persecuted for “blasphemy” – expressing doubts about or criticizing religion –beginning with the unveiling of a content-rich campaign website and a powerful video introducing viewers to the names and faces of those who sit in jail or fear for their lives as a result of exercising their freedom to speak.
“Governments are punishing their citizens for speaking their minds about religion, and opportunistic extremists are using religious sensitivities as an excuse to mete out violent mob justice, killing innocents and terrorizing entire communities,” said Ronald A. Lindsay, President and CEO of the Center for Inquiry. “The time has come for all of us as a global community to stand up and declare this blatant violation of human rights to be unacceptable.”
The world has been hotly debating several cases of men and women charged with blasphemy or other offenses against religion, such as Indonesia’s Alexander Aan, sentenced to prison for declaring his atheism on Facebook; Rimsha Masih of Pakistan, accused of desecrating a Quran; Saudi poet Hamza Kashgari, charged with defaming Muhammad on Twitter; the Russian band Pussy Riot, jailed for a defiant performance at a Moscow church; as well as many, many others.
“As President Obama recently told the UN, the way to combat bigoted and intolerant speech is not with violence, but with more speech,” said Michael De Dora, CFI’s director of public policy, “No one has the right not to be offended, and centuries-dead religious figures certainly need no protection from insult.”
De Dora added, “For those whose freedom or safety is in jeopardy because they had the courage to speak their mind, we will speak for them.”
The Campaign will be waged on many different fronts over the coming months. Apart from the content on the website and stirring video, you cantake actionby writing to world governments, the U.S. Congress and White House, and the United Nations, and you can learn a lot more about the state of free expression in a new CFI report, Dissent Denied: A Survey on Global Blasphemy and Incitement Laws.
You can also follow the official Campaign for Free Expression Twitter account at @CFICFE (and look for the hashtag #CFICFE), as well as the official Facebook page, to keep up to date with news and opportunities to get involved.
This campaign is at the heart of what CFI stands for, and we’re looking forward to the coming months as we work to awaken the world to what is a growing human rights crisis, and hopefully inspire the global community to stand up in defense of free speech.
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[Cite as State v. Huff, 2020-Ohio-1064.]
IN THE COURT OF APPEALS
TWELFTH APPELLATE DISTRICT OF OHIO
BUTLER COUNTY
STATE OF OHIO, :
Appellee, : CASE NO. CA2019-06-104
: OPINION
- vs - 3/23/2020
:
TODD S. HUFF, :
Appellant. :
CRIMINAL APPEAL FROM BUTLER COUNTY COURT OF COMMON PLEAS
Case No. CR2018-12-2100
Michael T. Gmoser, Butler County Prosecuting Attorney, John C. Heinkel, Government
Services Center, 315 High Street, 11th Floor, Hamilton, Ohio 45011, for appellee
Rodriguez & Porter, Ltd., Paul W. Shonk, 5103 Pleasant Avenue, Fairfield, Ohio 45014, for
appellant
S. POWELL, J.
{¶ 1} Appellant, Todd S. Huff, appeals the decision of the Butler County Court of
Common Pleas denying his motion to suppress. For the reasons outlined below, we affirm
the trial court's decision.
{¶ 2} Huff was charged with one count of aggravated possession of drugs in
violation of R.C. 2925.11(A), a fifth-degree felony. The charge arose after Huff admitted to
Butler CA2019-06-104
Butler County Sheriff Deputy Jeffrey Stevison that the methamphetamine found hidden in a
cigarette pack located on the nightstand next to his bed belonged to him. After denying
Huff's motion to suppress, the matter proceeded to a one-day jury trial. Following
deliberations, the jury returned a verdict finding Huff guilty as charged. The trial court
sentenced Huff to a 12-month prison term. Huff now appeals the trial court's decision
overruling his motion to suppress, raising the following single assignment of error for review.
{¶ 3} THE TRIAL COURT ERRED BY OVERRULING THE APPELLANT'S
MOTION TO SUPPRESS.
{¶ 4} In his single assignment of error, Huff argues the trial court erred by denying
his motion to suppress. In support, Huff argues the trial court erred by finding he was not
subject to a custodial interrogation when Deputy Stevison asked him whether the
methamphetamine found hidden in the cigarette pack belonged to him, thereby alleviating
the need for Huff to be advised of his Miranda rights.1 We disagree.
{¶ 5} Appellate review of a ruling on a motion to suppress presents a mixed
question of law and fact. State v. Gray, 12th Dist. Butler No. CA2011-09-176, 2012-Ohio-
4769, ¶ 15, citing State v. Burnside, 100 Ohio St.3d 152, 2003-Ohio-5372, ¶ 8. When
considering a motion to suppress, the trial court, as the trier of fact, is in the best position
to weigh the evidence in order to resolve factual questions and evaluate witness credibility.
State v. Vaughn, 12th Dist. Fayette No. CA2014-05-012, 2015-Ohio-828, ¶ 8. This court is
bound to accept the trial court's findings of fact if they are supported by competent, credible
evidence. State v. Durham, 12th Dist. Warren No. CA2013-03-023, 2013-Ohio-4764, ¶ 14.
"An appellate court, however, independently reviews the trial court's legal conclusions
1. We note that Huff cites extensively from the trial transcript rather than the transcript of the hearing on his
motion to suppress. However, when ruling on a motion to suppress this court is "limited to the evidence
presented at the suppression hearing in our review of the trial court's decision on the motion to suppress."
State v. Clarke, 12th Dist. Butler No. CA2000-11-234, 2001 Ohio App. LEXIS 4737, *3, fn.1 (Oct. 22, 2001).
-2-
Butler CA2019-06-104
based on those facts and determines, without deference to the trial court's decision, whether
as a matter of law, the facts satisfy the appropriate legal standard." State v. Cochran, 12th
Dist. Preble No. CA2006-10-023, 2007-Ohio-3353, ¶ 12.
{¶ 6} The issuance of Miranda warnings is only required when police subject a
person to custodial interrogation. State v. Byrne, 12th Dist. Butler Nos. CA2007-11-268
and CA2007-11-269, 2008-Ohio-4311, ¶ 10, citing State v. Biros, 78 Ohio St.3d 426, 440
(1997). "Miranda defines custodial interrogation as any 'questioning initiated by law
enforcement officers after a person has been taken into custody or otherwise deprived of
his freedom of any action in any significant way.'" (Emphasis omitted.) State v. Matthews,
12th Dist. Butler No. CA2012-09-175, 2013-Ohio-3482, ¶ 10, quoting Miranda v. Arizona,
384 U.S. 436, 444, 86 S.Ct. 1602 (1966). The determination of whether a custodial
interrogation has occurred "depends on the objective circumstances of the interrogation,
not on the subjective views harbored by either the interrogating officers or the person being
questioned." State v. Coleman, 12th Dist. Butler No. CA2001-10-241, 2002-Ohio-2068, ¶
24, citing Stansbury v. California, 511 U.S. 318, 323-324, 114 S.Ct. 1526 (1994). "In judging
whether an individual has been placed into custody the test is whether, under the totality of
the circumstances, a 'reasonable person would have believed that he was not free to
leave.'" State v. Gumm, 73 Ohio St.3d 413, 429 (1995), quoting United States v.
Mendenhall, 446 U.S. 544, 554, 100 S.Ct. 1870 (1980).
{¶ 7} Deputy Stevison was the lone witness to testify at the suppression hearing.
Deputy Stevison testified that he was dispatched to investigate a report that drugs had been
found within a single-family home located in Hamilton, Butler County, Ohio. Upon Deputy
Stevison's arrival at that home, a resident of the home, V.M., allowed Deputy Stevison to
come inside. Deputy Stevison testified that once he was inside, he immediately observed
Huff sitting on the couch in the living room next to a "younger gentleman." The record
-3-
Butler CA2019-06-104
indicates that this younger gentleman, who Deputy Stevison testified looked no older than
19 years old, was subsequently identified as V.M.'s son. The record also indicates that
V.M. and Huff were at that time engaged to be married.
{¶ 8} Seeing as "they were all right there" in the living room, Deputy Stevison asked
V.M., V.M.'s son, and Huff, "what's going on?" V.M. responded and told Deputy Stevison
that Huff had been living in the home with her and her son to "sober up" and "get clean."
V.M., however, told Deputy Stevison that she had found what she believed were "drugs in
the bedroom that [Huff] was staying in on the nightstand inside a cigarette pack." Upon
learning of the supposed drugs hidden in the cigarette pack, Deputy Stevison asked V.M.
and V.M.'s son where the cigarette pack was. To this, V.M.'s son stood up and removed
the cigarette pack from under the couch cushion where he had been sitting. V.M.'s son
then handed the cigarette pack to Deputy Stevison. Deputy Stevison testified that V.M. had
put the cigarette pack under the couch cushion to "temporarily hid[e] it, so that Mr. Huff
could not get to it because [Huff] was aware that they had called the police."
{¶ 9} Deputy Stevison testified that after being handed the cigarette pack by V.M.'s
son, he opened the cigarette pack and discovered "[i]nside the cigarette pack, inside
another plastic baggie was a crystal-like substance inside of it." Deputy Stevison testified
that he then asked Huff "whose cigarette pack it was" and "if it was his cigarette pack." Huff
admitted to Deputy Stevison that the cigarette pack belonged to him. Deputy Stevison then
asked Huff "whose crystal-like substance was inside the pack and in the baggie." Huff
admitted to Deputy Stevison that the substance hidden inside the cigarette pack also
belonged to him. Deputy Stevison then removed the substance from the cigarette pack and
asked Huff, "is this yours?" Deputy Stevison testified that Huff responded, "Yes. His
response was very slow." The crystal-like substance was later determined to be
methamphetamine.
-4-
Butler CA2019-06-104
{¶ 10} Huff argues the trial court erred by denying his motion to suppress since he
was in custody when Deputy Stevison asked him whether the methamphetamine found
hidden in the cigarette pack belonged to him. However, although there is no dispute that
Deputy Stevison did not advise Huff of his Miranda rights prior to asking him about the
methamphetamine, the record is clear that Huff was not in custody when he was questioned
by Deputy Stevison. This is because Huff was neither handcuffed nor was Huff detained,
threatened, physically intimidated, or patted down by Deputy Stevison prior to Deputy
Stevison asking Huff about the methamphetamine. This includes Deputy Stevison
refraining from using any type of physical force on Huff and Deputy Stevison keeping his
firearm holstered both before and after speaking with Huff.
{¶ 11} Huff was also not overpowered, tricked, or coerced in any way by Deputy
Stevison when Deputy Stevison asked Huff about the methamphetamine. See, e.g., State
v. Frost, 12th Dist. Fayette No. CA2018-11-023, 2019-Ohio-3540, ¶ 20 (appellant was not
subject to a custodial interrogation where appellant was not handcuffed, threatened,
overpowered, tricked, or coerced in any way when being questioned by two police officers
inside his home). In fact, Deputy Stevison never gave any commands to V.M., V.M.'s son,
or Huff upon entering the home prior to asking Huff about the methamphetamine. As
Deputy Stevison testified:
Q: Okay. When [you] came in the door, did you give any
demands to the three of them sitting there?
A: No.
Q: Did you tell them to keep their hands out where you could
see them or anything of that nature?
A: No. Nope.
{¶ 12} The record instead indicates that Deputy Stevison, being the only law
enforcement officer present at the scene, was calm when speaking with Huff and merely
-5-
Butler CA2019-06-104
trying to ascertain whether the methamphetamine found hidden in the cigarette pack
belonged to Huff given the allegations that the cigarette pack was located on the nightstand
next to his bed. This all occurred while Huff sat unrestrained on the couch in the living room
of the home where he was then residing with his fiancé, V.M., and V.M.'s son to "sober up"
and "get clean." That Huff may have known V.M. or V.M.'s son had called the police is
immaterial. An individual is not in custody simply because that person knows the police
have been called and dispatched to the scene. This is particularly true here when
considering Deputy Stevison specifically testified that Huff was free to leave upon his arrival.
See, e.g., State v. Robinson, 12th Dist. Butler No. CA2015-01-013, 2015-Ohio-4533, ¶ 14
(appellant was not subject to custodial interrogation where appellant was never threatened
and never told that he was under arrest or that he was not free to leave when being
questioned by a police officer outside appellant's home in an unmarked police cruiser).
{¶ 13} Just as the trial court found, Huff "was not detained, arrested, or in custody"
when asked by Deputy Stevison whether the methamphetamine found hidden within the
cigarette pack belonged to him. That is to say, contrary to Huff's claim, there was nothing
"faulty" with the trial court's analysis. Rather, given the facts established by Deputy
Stevison's testimony elicited at the suppression hearing, the trial court properly determined
that Huff was not subject to a custodial interrogation when Deputy Stevison asked him about
the methamphetamine. Considering this court's prior similar holdings, including this court's
holdings in Frost and Robinson cited above, such a decision does not invite "absurd results"
as Huff suggests. This holding instead fully complies with the law as to whether a custodial
interrogation has occurred. Therefore, because Huff was not subject to a custodial
interrogation when Deputy Stevison asked him whether the methamphetamine found
hidden within the cigarette pack belonged to him, the trial court did not err by denying Huff's
motion to suppress. Huff's single assignment of error lacks merit and is overruled.
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Butler CA2019-06-104
{¶ 14} Judgment affirmed.
M. POWELL, P.J., and PIPER, J., concur.
-7-
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Q:
Windows Update Error 80244019 after long time searching for updates
I have not updated my Windows system for over 5 months now (Windows 7, 64bit, SP1). This happened by mistake, not on purpose, because Windows update was set to install updates manually with prompting at 3:00 am.
Today I tried to install the updates. The following happened in sequence:
I started updating a set of files totalling to 400 Mb or so, but I had to cancle after 1 minute, because Windows had to restart for a different reason.
After restart, I started update manually again, but it hang on "preparing system for installation".
Subsequently I ran the Windows update fix tool: https://support.microsoft.com/en-gb/gp/windows-update-issues/en
This lead to a partial fix only. The tool ran unfortunately in German. It says "Windows update error" in the second row and the first two items say "not fixed"
I ran the update tool again. Now apparently it was reset, since the earlier runs were not visible anymore. I had to search for updates again, which took a long time (3 hours). Then it stopped with error 80244019. See image. It says in german unknown error 80244019.
I am now trying to run fix: https://support.microsoft.com/en-us/kb/3102810 right now, but this fix says "Searching for updates on this computer" and does not show progress so far.
After installation of this fix, Windows Update found and installed the updates successfully again.
However: it only find Windows updates and in fact it says "You receive updates: only for windows" on the start page. In fact I remember unchecking a box for "receiving updates for other Microsoft products" following an advice in this thread: Windows Update fails with code 80244019. I did this before installing the MSU in step 5. Now, however, I cannot find this check box back in the MSU setting. See image. How can I now configure MSU to find MS Office updates etc.?
Screenshot translation: There are only two check boxes: "Make available recommended updates in the same way as critical updates" and "Allow all users to install updates". An option to to switch on searching for other updates is missing.
Edit: I found a screenshot on MS Office Help which shows how MSU should look and in fact looked before I updated it in step 5. You can see that the checkbox for "other MS products" which is checked in the example disappeared. It is the box I unchecked before step 5. In fact there is another checkbox below the yellow marked area which also disappeared after the MSU update. Very strange.
Again I need your help; perhaps this is a new topic and would deserve a new thread, but because it occures following the fix of the 80244019 problem, I leave it here.
EDIT 2: I opened a new thread adressing the new issue described in step 7 only here: Microsoft update (MSU) does not find updates for other Microsoft products (e.g. Office) after MSU update
A:
To fix the update problem install https://support.microsoft.com/en-us/kb/3102810.
To fix the missing checkbox problem after the update follow instructions in Microsoft update (MSU) does not find updates for other Microsoft products (e.g. Office) after MSU update.
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Email a Friend:
If you are in the mood for a flat with a bite then grab this lovely skimmer from Poetic License. A gray snakeskin leather upper is detailed with a pointed toe and grommet design paired with a lovely bow atop the vamp.
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SEATTLE — The Yankees were informed by MLB that plate umpire Gabe Morales shouldn’t have granted the Dodgers time in the ninth inning of last Saturday’s 2-1 loss at Dodger Stadium.
That call likely cost the Yankees a run.
Manager Aaron Boone was told Morales should not have stopped the play with Gleyber Torres on his way home while Dodgers second baseman Max Muncy was laying on the ground with the ball after Brett Gardner cut his legs out on a slide.
“It shouldn’t have been called,’’ Boone said before the Yankees’ 7-0 win over the Mariners on Tuesday night.
Boone said he has moved on from the incident.
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1. Field of the Invention
The invention concerns a method for the manufacture of a superconductor with a layer of the A-15 phase of the system Nb--Al or Nb--Al--Ge, respectively, as well as apparatus for carrying out this method.
2. Description of the Prior Art
The A-15 phases of the systems Nb--Al and Nb--Al--Ge become superconducting at relatively high temperatures and lose this state only in very strong magnetic fields. In the system Nb--Al the A-15 phase has the composition Nb.sub.3 Al or a composition which deviates only slightly therefrom. For Nb.sub.3 Al, the maximum transition temperatures of T.sub.c = 18.8.degree. K as well as upper critical magnetic fields B.sub.c2 of approximately 30 Tesla at 4.2.degree. K have been given. For the A-15 phase of the system Nb--Al--Ge with a niobium content of about 75 atomic precent in the range of compositions of about Nb.sub.3 (Al.sub.1.sub.-x Ge.sub.x) with 0<x.ltoreq.0.25, maximum transition temperatures of T.sub.c =20.7.degree. K and upper critical magnetic fields B.sub.c2 of about 40 Tesla at 4.2.degree. K have been reported (see Zeitschrift fuer Naturforschung 25a (1970), pages 1659 to 1669). These properties of the A-15 phases of the systems Nb--Al and Nb--Al--Ge are not exceeded by any superconductor that has become known to date. The A-15 phases mentioned are therefore of great technical interest, for instance, for application in superconducting magnet coils.
However, the technical application of these materials has not been successful heretofore because of various obstacles. On the one hand, the critical current densities reached so far are relatively low. Thus, melted or powder-metallurgically prepared samples of the A-15 phases mentioned, for instance, have critical current densities j.sub.c of only about 10.sup.3 amps/cm.sup.2 in a magnetic field of 5 Tesla and at a temperature of 4.2.degree. K. Only by three methods has it been possible to date to produce superconducting layers with values of the critical current density, which are of technical interest, of 10.sup.4 amps/cm.sup.2 or more. This includes two methods for the manufacture of superconductors with layers of the A-15 phase of Nb--Al--Ge and a method for the manufacture of a superconductor with a layer of the A-15 phase of Nb--Al. In the two first-mentioned methods, an Nb--Al--Ge layer is in each case applied to a carrier by cathode sputtering or by condensation in a high vacuum (see J. Vac. Sci.Technol. 7 (1970), page 127 ff. and J. Appl. Phys. 43 (1972), page 2407 ff.). In the last-mentioned method (Metallurgical Transactions 3, (1972), pages 1177 to 1181), an aluminized niobium foil having an aluminum diffusion seam is annealed for 8 to 15 seconds at a temperature above 1870.degree. C, to prepare a superconductor with an Nb.sub.3 Al layer. The aluminum was applied here to the niobium foil by melting an aluminum wire over the foil or by vapor deposition or by electrolytic precipitation from a hot aluminum salt bath of about 300.degree. to 500.degree. C. To form the aluminum diffusion seam, the coated foil was heated to a temperature of between 800.degree. and 900.degree. C. Although the methods mentioned furnish A-15 layers with relatively high critical current densities, they do not yet appear to be suitable for the manufacture of technically usable superconductors with such layers. First, each of these methods requires considerable apparatus means, and in addition it is also most doubtful whether the methods, by which up to now only short wire samples have been prepared, can be modified for making long superconducting wires or ribbons, such as are required for winding superconducting coils.
A further difficulty, which so far has been in the way of a technical application of the A-15 phases mentioned, is that these phases are very brittle and can be deformed elastically only to a slight degree. In technically usable superconductors, therefore, the A-15 layers must be only a few .mu.m thick and should lie as close to the neutral fiber of the conductor as possible. With the prior art expensive methods, the manufacture of long conductors with such thin layers would seem to present considerable difficulties. Although methods are known for manufacturing superconductors with layers of A-15 phases of other systems, particularly with layers of Nb.sub.3 Sn and V.sub.3 Ga, which fulfill these requirements, such as the deposition of Nb.sub.3 Sn on a suitable carrier from the gaseous phase or the diffusion of tin or gallium into niobium or vanadium wires, respectively, from copper-tin or copper-gallium sheaths which surround these wires, it has not been possible so far, to apply either method in a satisfactory manner for the manufacture of superconductors with Nb.sub.3 Al or Nb.sub.3 (Al,Ge) layers.
It is an object of the invention to make possible the manufacture of superconductors with a layer of the A-15 phase of the system Nb--Al or Nb--Al--Ge as simply as possible, where at the same time the highest possible transition temperatures and critical current densities which are usable for technical applications are to be achieved. In particular, the continuous manufacture of long wires or ribbons with thin layers of the A-15 phases mentioned should also be possible.
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Q:
How to make a 'struct' Nullable by definition?
struct AccountInfo
{
String Username;
String Password;
}
now if I want to have a Nullable instance I should write:
Nullable<AccountInfo> myAccount = null;
But I want make the struct Nullable by nature and it can be used like this (without use of Nullable<T>):
AccountInfo myAccount = null;
A:
You can't. Struct are considered value types, and by definition can't be null. The easiest way to make it nullable is to make it a reference type.
The answer you need to ask yourself is "Why is this a struct?" and unless you can think of a really solid reason, don't, and make it a class. The argument about a struct being "faster", is really overblown, as structs aren't necessarily created on the stack (you shouldn't rely on this), and speed "gained" varies on a case by case basis.
See the post by Eric Lippert on the class vs. struct debate and speed.
A:
When you declare it, declare it with a "?" if you prefer
AccountInfo? myAccount = null;
A:
The short answer: Make it a class.
The long answer: This structure is mutable which structs should never be, doesn't represent a single value which structs always should, and has no sensible 'zero' value which structs also always should, so it probably shouldn't be a value type. Making it a class (reference type) means that it is always possible for it to be null.
Note: Use of words such as "never" and "always" should be taken with an implied "almost".
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Urgent need to reorganize heart failure management: from paradoxes to heart failure clinics.
Despite the decreasing incidence of ischaemic heart disease and despite major medical advances in heart failure, the prevalence and mortality of chronic heart failure in the population is rising and the prognosis remains grim. Chronic heart failure is a complex disease, which is characterized by its progressive nature. In this paper, we approach the complexity of heart failure from four paradoxes: epidemiology, diagnosis, therapy and economical impact respectively. Taking these paradoxes into account, we formulate a number of essential components of alternative heart failure management programmes. Combating chronic heart failure requires the organization of centres for continuous care--as opposed to the traditional crisis intervention centres--preferably with a multidisciplinary structure to provide a "holistic approach" adapted to each patient's unique set of medical, psychosocial, physical and financial conditions. Patients taken care of in these novel multidisciplinary heart failure clinics have shown improved clinical status, decreased hospitalization rates, increased quality of life, longer life and lower costs.
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Renal computed tomography with 3-dimensional angiography and simultaneous measurement of plasma contrast clearance reduce the invasiveness and cost of evaluating living renal donor candidates.
Renal computed tomography (CT), 3-dimensional CT angiography (3D-CTA), and simultaneous measurement of glomerular filtration rate (GFR) by x-ray fluorescence determination of plasma contrast clearance (PCC) are alternatives to intravenous urography (IVU), renal arteriography (RA), and 24-hr urine creatinine clearance (CrCl) for evaluation of renal structure and function in living renal donor (LRD) candidates. To determine if CT, 3D-CTA, and PCC provide data comparable to IVU, RA, and CrCl, both methods were used to evaluate 23 LRD candidates. Costs were also compared. Conventional RA identified 19 accessory arteries and one case of medial fibroplasia. Each of these anomalous vessels was recognized on 3D-CTA. Venous anatomy was more clearly delineated on 3D-CTA than the venous phase of conventional RA. CT demonstrated 3 benign cysts and a single, small intraparenchymal calcification in 3 renal units. GFRs measured by PCC and CrCl were 91 +/- 4 and 132 +/- 7 ml/min/1.73m2, respectively (r = 0.64, P < 0.05). Total cost for CT/3D-CTA/PCC was 46% less than that of IVU/RA/CrCl and 40% less than RA/CrCl. CT/3D-CTA/PCC provided reliable structural and functional data at substantially less cost, discomfort, and inconvenience to the living renal donor candidate. As such, CT/3D-CTA/PCC is superior to conventional methods for evaluation of the living renal donor candidate.
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The NHS has its limitations.
Virginia Bottomley's announcement about the closure of some London hospitals illustrates the effect of the internal market system in the NHS.
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Following his abysmal performance against the Nationals last night, Pedro Beato was sent back to Buffalo by the Mets. The team has recalled Manny Acosta to take Beato's place on the roster and in the bullpen.
Beato only threw a total of 4.1 innings since he was called up from the minors, but he posted a 10.38 ERA and 5.14 FIP over the short span. In 24.0 innings with Buffalo before he joined the Mets, Beato had a 1.13 ERA but a 4.03 FIP. He wasn't very good last year — he allowed too many walks and did not record enough strikeouts — and has not shown any improvement this year.
As for Acosta, he was incredibly bad with the Mets over the first two months of the season, but he deserves another shot in the big leagues now, which was evident a week ago. In short, Acosta has been dominant in his time with Buffalo since his demotion, and he was a very good relief pitcher for the Mets between 2010 and 2011. It is incredibly unlikely that we will replicate his horrendous early-season performance in this stint with the Mets.
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Genomic microstructure and differential expression of the genes encoding UDP-glucose:sinapate glucosyltransferase (UGT84A9) in oilseed rape (Brassica napus).
In oilseed rape (Brassica napus), the glucosyltransferase UGT84A9 catalyzes the formation of 1-O-sinapoyl-beta-glucose, which feeds as acyl donor into a broad range of accumulating sinapate esters, including the major antinutritive seed component sinapoylcholine (sinapine). Since down-regulation of UGT84A9 was highly efficient in decreasing the sinapate ester content, the genes encoding this enzyme were considered as potential targets for molecular breeding of low sinapine oilseed rape. B. napus harbors two distinguishable sequence types of the UGT84A9 gene designated as UGT84A9-1 and UGT84A9-2. UGT84A9-1 is the predominantly expressed variant, which is significantly up-regulated during the seed filling phase, when sinapate ester biosynthesis exhibits strongest activity. In the allotetraploid genome of B. napus, UGT84A9-1 is represented by two loci, one derived from the Brassica C-genome (UGT84A9a) and one from the Brassica A-genome (UGT84A9b). Likewise, for UGT84A9-2 two loci were identified in B. napus originating from both diploid ancestor genomes (UGT84A9c, Brassica C-genome; UGT84A9d, Brassica A-genome). The distinct UGT84A9 loci were genetically mapped to linkage groups N15 (UGT84A9a), N05 (UGT84A9b), N11 (UGT84A9c) and N01 (UGT84A9d). All four UGT84A9 genomic loci from B. napus display a remarkably low micro-collinearity with the homologous genomic region of Arabidopsis thaliana chromosome III, but exhibit a high density of transposon-derived sequence elements. Expression patterns indicate that the orthologous genes UGT84A9a and UGT84A9b should be considered for mutagenesis inactivation to introduce the low sinapine trait into oilseed rape.
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Q:
Sampling continuous function in Matlab
I'm new to matlab, and in this academic exercise they asked us to do a sampling from a continuous function.
My original functions are:
x = sin(pi * t);
y = cos(2 * pi * t / 3);
z = x + y - 2;
In the interval
t = -8:0.001:8;
Then they asked us to make a sampling, z(n), of z with a period of Ts=0.01 seconds.
My idea was to save in a new vector the values of z, jumping through z ten by ten positions:
n = numel(z);
Zd = z(0:10:z);
This idea came from the fact that 0.01 seconds is ten times less accurate then the first 'continuous' interval t. But matlab says that this is not possible and gives me the error:
??? Subscript indices must either be real positive integers or logicals.
Can somebody give me some hint on this?
A:
As 2 @Memming said, matlab indexes start at 1 and not 0, and that was my problem.
Thanks.
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It certainly didn’t take long for rookie first-round pick T.J. Hockenson to make his presence known in Detroit.
Selected eighth overall in the 2019 NFL Draft, Hockenson was one of the catalysts to Detroit’s offense in Week 1, catching six passes for 131 yards and a touchdown. He led the team in receiving yards and was tied with Kenny Golladay for the second-most targets on the team with nine (Danny Amendola had a whopping 13).
Hockenson certainly looks the part of a future TE1, but how soon will he get there? Is he there now? And just how good could he be?
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The Tools
The unique skill set of the 6’5” Hockenson was on full display in Week 1. Hockenson is a remarkable route runner for his size. He has great balance and light feet, allowing him to make quick cuts that cause instant havoc for any linebacker guarding him. Meanwhile, his height makes him extremely tough to cover for cornerbacks and quarterback Matthew Stafford took advantage of that on Hockenson’s touchdown, finding him in the back of the end zone and lofting a ball to where only Hockenson could get it.
Hockenson also has great hands and a solid catch radius to boot. He’s excellent at catching passes while on the go, giving the offense a lot of flexibility in how to use him. In Week 1, he looked more like a wide receiver than a tight end with some of the plays he was running. He even came out of the backfield like a running back for one of his routes that resulted in a catch and a solid gain.
Hockenson only played two years of college football at Iowa after redshirting his freshman year. During his final collegiate season in 2018, he caught 49 passes for 760 yards and six touchdowns. He also rushed for a touchdown. So he certainly has shown the ability to put up big numbers when he gets high usage, something we don’t always have evidence of for highly-touted tight ends coming into the league.
The System
The Lions have been abundantly clear in their approach to emulate the Patriots’ system in their own. They brought in Bob Quinn from the Patriots’ front office to serve as their general manager, then brought in Matt Patricia from the Patriots’ coaching staff to serve as their head coach. One thing that we certainly know from the past decade of Patriots football is that it breeds fantastic tight end usage and production, enabling Rob Gronkowski to set several all-time records for the position including 17 receiving touchdowns in 2011.
The Lions are in the midst of shifting from the pass-heavy offense featured under the Jim Caldwell reign to a run-heavy offense under Patricia. Instead of seeing Stafford launch deep balls to Marvin Jones every drive, we should be seeing more running plays and more medium-distance throws to Kenny Golladay and Hockenson. Just as the Patriots groomed Gronkowski into a #1 target on offense, the Lions could very much revolve their passing game around Hockenson sooner rather than later.
Dynasty Dream
As veteran fantasy players should know, the tight end position can be a royal headache. If you find yourself outside the Travis Kelce and Zach Ertz inner sanctum, you could easily end up throwing out a prayer week-in and week-out for any production whatsoever at the position.
Hockenson is in an extremely rare position for a tight end. He’s an extremely talented rookie in a tight end-friendly system without another tight end blocking his path toward targets. Plus, he’s already delivered a TE1 fantasy week one week into his career.
In a rookie class that lacks a Saquon Barkley or Christian McCaffrey-like talent, there’s certainly an argument that Hockenson could be the best dynasty asset in the group. Josh Jacobs is probably the only other rookie who has as good or better of an opportunity with little competition for touches at his position on his team. But David Montgomery and Miles Sanders, often the next two highest-ranked rookies in the class after Jacobs, look to have an uphill battle for consistent and significant touches on a weekly basis.
But back to Hockenson vs. Jacobs as the best dynasty asset in the class. Running backs come and go often, like the undrafted Phillip Lindsays and Austin Ekelers of the world. Plus, who’s to say for certain that the Raiders won’t bulk up their backfield next year with a No. 2 running back that threatens Jacobs more than Jalen Richard. Meanwhile, the Lions will be locked into Hockenson as their primary, high-usage tight end for many years to come. And finding a tight end in a situation like that as a rookie, who could be a legit top-3 mainstay at the position for several consecutive years is extremely rare. So if we were redrafting the rookie class in dynasty formats again right now, Hockenson would be my pick ahead of Jacobs.
Redraft Value
As far as Hockenson’s value this season goes, he should certainly be owned in every single league, first off. The path towards a TE1 season is certainly not an arduous one. Trey Burton finished as a fantasy TE1 last year and he only topped 40 receiving yards in three of his 16 games. So not only is a TE1 season in reach for Hockenson this year, it’s very likely.
Outside of the top five or six at the position, the race to fill up the TE1 tier is wide open and Hockenson is going to be one of the top competitors in snatching one of those open spots. So I’d still rank him behind Kelce, Ertz, George Kittle, Evan Engram and O.J. Howard for sure. Then I’d probably keep Hunter Henry in that sixth spot for now. But after that, Hockenson’s my guy, followed by Delanie Walker, Jared Cook and Darren Waller.
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Condylectomies for prolonged bilateral temporomandibular dislocation.
An unusual case of old unreduced bilateral temporomandibular joint (TM joint) dislocation is presented. Extensive reviews of English and Japanese literature described managing such cases by various methods including closed or open joint reduction. However, successful bilateral condylectomies carried out in seven months old dislocation, provided free range of painless movements and good stability. As there is no possibility of redislocation or painful degenerative arthritis following this procedure, it's role in African environment is described.
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Saturday, November 22, 2008
PORTLAND, Maine (AP) - Authorities in Maine say no charges are planned against the owner of a store where a sign invited customers to bet on a date when President-elect Barack Obama would be assassinated. Cumberland County Sheriff Mark Dion said Friday that Oak Hill General Store owner Steve Collins denied any knowledge of the "Osama Obama Shotgun Pool" sign.
Today, the Portland Press-Herald ran two articles that fleshed out the story of the sign and highlighted the strong response by residents of Portland members of the University of Southern Maine community to this and other recent displays of bigotry, ignorance, and intolerance within the state. Good for the members of the Portland community and the USM students and faculty.
It's something of a paradox of course -- in an open, enlightened, and educated culture, we must be tolerant of other beliefs and ideas but do we break that covenant when we are not tolerant of intolerance?
(Obviously, the attack upon a Portland man wearing makeup following a theatrical production because he "looked gay" has no bearing on tolerance or the First Amendment -- he was assaulted and all of the people of Portland should feel safer once the Neanderthals who did it stand trial for their crime...more on this in a minute.)
But back to the topic of the sign in the window and the black figures hung in effigy...they highlight again a thorny question -- where does free speech end and the abridgment of others' rights to a safe life begin? The courts have grappled with this for years, attempting to find a balance between the critically important First Amendment and the civil rights granted to all members of the community to keep them safe from defamation, intimidation, discrimination, or victimization. Sadly, no clear bright line yet exists, with lower and higher courts batting limits and reversals back and forth like a grim ping-pong ball. As a result, communities come to rely upon other laws to punish violators and protect the innocent from what might otherwise be considered "hate speech.
Consider the case of Robert A. Vincent vs St. Paul in which a teen was arrested after burning a cross on the front yard of an African-American family. Rather than charge him under more established ordinances that addressed topics such as terrorist threats, arson, or criminal damage to property, he was instead charged with the violation of a statute that criminalized activities such as burning crosses or Nazi swastikas. The U.S. Supreme Court eventually tossed the conviction noting that, while "burning a cross in someone's front yard is reprehensible. St. Paul has sufficient means at its disposal to prevent such behavior without adding the First Amendment to the fire."
In the end, the Court's decision rested on the belief that St. Paul's statute unconstitutionally made speech and forms of expression (a burning cross) aimed at racial or religious minorities illegal but not other types of speech that might have targeted "unprotected" groups. The same standard and question of fairness is often applied to the concept of "hate crimes" -- should the punishment be more severe if someone is convicted of assaulting a black man or a lesbian because he is black or she is gay vs. assaulting a Caucasian man or a straight woman?
I'm not a lawyer and can't speak to the constitutionality of hate crimes legislation either at the state or federal level. I do recognize that hate-filled members of our society clearly target those they believe are different or a threat. I also believe that when these fearful bullies (because that's what drives them -- fear -- and they then seek to prey on the weak either in packs or from the shadows due to their cowardice) perpetrate an assault, whether physical, emotional, or otherwise, they should be prosecuted and made to pay for their crimes. Strapping them to the side of a mountain where eagles can feast on their entrails might be a good start...you've got to love those ancient Greeks. They knew how to punish someone. Honestly though, speaking as heterosexual white male, I do want to know that if I get my ass kicked by some ignorant cave dweller who sought me out because I held a different political belief, said cave dweller would be punished just as severely.
I'm an ardent defender of the right to free speech as well as the right of a minority to be safe from repression by the majority. I also am proud that the right to free speech extends to the freedom for members of a community to tell the scared, ignorant fools perpetrating bigoted, racist, homophobic, xenophoic acts that the community categorically rejects those messages of hate and intolerance. The examples set by the Portland community and by protestors nationwide speaking out against the discrimination now written into law by California Proposition 8 are ones that we should remember and support. While there's no law against people saying things that are stupid and ignorant, the law also allows us to stand up and announce that discrimination and intolerance have no place in our society.
--------------------------
By the way, there is at least one notable exception in the case of spoken, written, or implied threats actually resulting in a violation of law: legitimate threats against the President, Vice President, and the POTUS-elect and VPOTUS-elect...though the sign in the store window certainly doesn't meet that threshold. A slightly drier presentation of this statute may be found here though it seems to be more restrictive that the first explanation. How does it account for spoken threats or e-mail? Is e-mail considered the same as snail mail in this case because it is interstate communications/commerce?
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Our Lives in the Marsh
“A marsh is one of the most receptive environments on earth. It is always open to the sky and all the winds and weather that flow in and recede like the tides in endlessly recurring motion. In its own, self-generating body it accommodates innumerable forms of life all responding to that common sea.
Tags
Other Blogs from My Deep Dark Past
Before kicking off "Walks in the Marsh," my first experience with writing blogs actually came as a result of my job. Rather than a single company blog, I experimented with event-specific blogs to provide a near-real time look at what was going on when I went out on the road:
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During infection of Escherichia coli, bacteriophage T4 usurps the host transcriptional machinery, redirecting it to the expression of early, middle, and late phage genes. This machinery is driven by E. coli RNA polymerase, which, like all bacterial polymerases, is composed of a core of subunits (beta, beta', alpha1, alpha2, and omega) that has RNA synthesizing activity and a specificity factor (sigma). The sigma protein identifies the start of transcription by recognizing and binding to sequence elements within promoter DNA. During exponential growth, the primary sigma of E. coli is sigma70, which, like all primary sigmas, is composed of four regions. Sigma70 recognizes DNA elements around positions -10 and -35 of host promoter DNA, using residues in its central portion (regions 2 and 3) and C-terminal portion (region 4), respectively. In addition, residues within region 4 must also interact with a structure within core polymerase, called the beta-flap, to position sigma70 region 4 so it can contact the -35 DNA. T4 takes over E. coli RNA polymerase through the action of phage-encoded factors that interact with polymerase and change its specificity for promoter DNA. Early T4 promoters, which have -10 and -35 elements that are similar to those of the host, are recognized by sigma70 regions 2 and 4, respectively. However, although T4 middle promoters have an excellent match to the sigma70 -10 element, they have a phage element (a MotA box) centered at -30 rather than the sigma70 -35 element. Two T4-encoded proteins, a DNA-binding activator (MotA) and a T4-encoded co-activator (AsiA), are required to activate the middle promoters. AsiA alone inhibits transcription from a large class of E. coli promoters by binding to and structurally remodeling sigma70 region 4, preventing its interaction with the -35 element and with the beta-flap. In addition to its inhibitory activity, the AsiA-induced remodeling allows the N-terminal domain of MotA (MotA NTD) to bind to the C-terminus of sigma70 and the C-terminal domain of MotA (MotA CTD) to bind to the MotA box. This process is called sigma appropriation. Despite dozens of activator crystallographic structures and recent RNA polymerase structures, there is only one complete structure of an activator/RNA polymerase/DNA complex. However, the type of activation performed by this crystallized complex is fundamentally different from that of sigma appropriation. We combined biochemical analyses, available structures, and modeling to develop a structural model of sigma appropriation. Our work has depicted how AsiA/MotA redirects sigma, and therefore RNA polymerase activity, to a T4 middle promoter DNA and how the flexibility of sigma region 4 is likely crucial for this process. Our work suggested that MotA interacts with its DNA binding motif using a previously unidentified interaction mechanism in which the double wing helix structure of the CTD contacts the major groove of the DNA and the linker contacts the minor groove. In collaboration with the laboratory of Dr. Steve White (St Judes), we have now solved the crystal structure of the MotA linker-CTD with the DNA. Our results confirm that MotA CTD binds the DNA across the major groove via multiple interactions with the flanking sugar-phosphate backbones. It uses just two amino acids to read the MotA box motif, and the flexible N-terminal linker region interacts both specifically and non-specifically with the minor groove. In wild type T4 DNA, position 5 of cytosines are modified via hydroxymethylation/glucosylation. Out structure indicates that MotA CTD provides a cavity within the complex that is ideally positioned to accommodate this moiety and thereby increase the strength and specificity of the interaction. Using EMSAs and surface plasmon resonance, we have demonstrated that DNA containing the beta modification significantly enhances MotA binding affinity, primarily by decreasing the off-rate. Our results indicate that the double-wing domain of MotA represents an entirely new way in which a small protein module can recognize and bind DNA.
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Putin Warns Kadyrov In Connection With Reprisals Against Militants’ Families
December 18, 2014 20:01 GMT
Chechen leader Ramzan Kadyrov (left) and Igor Kalyapin, head of the Committee to Prevent Torture (KPP)
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Putin Warns Kadyrov In Connection With Reprisals Against Militants’ Families
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In the course of his annual press conference on December 18, Russian President Vladimir Putin made clear his disapproval of the reprisals undertaken against the families of the fighters who attacked Grozny on December 4. Putin described as “understandable” what he termed Chechen Republic head Ramzan Kadyrov’s subsequent “emotional” demand that the family homes of the fighters responsible be burned to the ground and their relatives expelled from Chechnya.
At the same time, Putin said that even if the families in question were aware of the militants’ intentions, “that does not give anyone, including the leaders of the Chechen Republic, the right to engage in extra-judicial reprisals.”
“In Russia everyone must abide by the laws in force in our country. No one is considered guilty until he has been sentenced by a court,” Putin stressed.
Human rights activists calculate that eight dwellings in Gudermes, Yandy, Engelyurt, Alpatovo, and Katyr-Yurt were torched last week; not all belonged to the families of men killed during the December 4 attack. Kadyrov and other Chechen officials have also threatened and vilified Committee to Prevent Torture (KPP) head Igor Kalyapin, who called on Russian Prosecutor-General Yury Chaika and Investigative Committee head Aleksandr Bastrykin to rule on whether Kadyrov had exceeded his authority by issuing the order to burn militants’ families’ homes.
Putin also divulged that the law-enforcement agencies are conducting a “preliminary investigation” in order to establish the connection between Kadyrov’s outburst and the subsequent burning of the homes, and the identity of the masked men responsible.
Putin’s implicit criticism of Kadyrov is in stark contrast to his initial praise of the Chechen authorities’ response to the December 4 attack, during which, as Putin recalled at his press conference, 14 Chechen police officers were killed. Meeting with Kadyrov late on December 4, Putin assured him that “you have nothing to blush for.”
Putin’s remarks at the press conference will also inevitably reignite speculation as to whether Kadyrov’s days in power are numbered -- all the more so since during an interview with NTV earlier this week, Kadyrov himself twice mentioned that he might quit his current post. In the course of a diatribe against the Chechen insurgents who attacked Grozny, Kadyrov said he is “ready to write a letter of resignation and leave the post of republic head in order to do battle with these devils.”
Asked to comment on the stated intention of three Ukrainian parliamentarians to bring criminal charges against him for having threatened them, Kadyrov laughed off that possibility, adding that he “intends to ask the president to release me from post of republic head” in order to travel to Ukraine’s breakaway Donbas region to “defend the interest of the citizens who are waging war there, and to capture and destroy those devils, who have neither conscience or honor.”
It is not clear whether by that latter category Kadyrov meant only the Ukrainian lawmakers in question or also the Djokhar Dudayev peacekeeping battalion headed by former Chechen field commander Isa Munayev which is fighting alongside the Ukrainian armed forces.
It is conceivable that Kadyrov had been warned that he has incurred Putin’s displeasure, and rather than risk public disgrace by being formally dismissed offered to resign as a face-saving solution for both of them. Putin’s spokesman Dmitry Peskov was quoted on December 17, however, as having told Interfax that Putin has not received a formal request from Kadyrov to be relieved from his post. That suggests Putin was intent on publicly upbraiding Kadyrov and reining him in, but is not (yet) thinking in terms of replacing him.
An article published three days ago in the Russian weekly “Versiya,” which on occasion floats trial balloons on behalf of government agencies, nonetheless suggests that Putin has an additional good reason to be angry with Kadyrov. The author, Ruslan Gorevoy, recalled that Kadyrov’s plenipotentiary in Kyiv, Ramzan Tsitsulayev, fled to Ukraine following a botched attempt by police last month to apprehend him in a sting operation on suspicion of involvement in an illegal cash withdrawals racket. Tsitsulayev, according to Gorevoy, subsequently mobilized a group of Chechens in Vynnytsya in early December a bid to gain control of financial assets belonging to Ukrainian President Petro Poroshenko.
Poroshenko and members of his immediate entourage reportedly have considerable financial interests in the Russian Federation which the Russian authorities have until now refrained from expropriating. Gorevoy predicted that Tsitsulayev’s gambit in Vynnytsya could trigger reprisals by Kyiv in the form of the confiscation of Russian-owned businesses on Ukrainian territory. If Putin is, as some analysts suggest, already concerned at the prospect of forfeiting the support of Russian oligarchs who are suffering under the brunt of international sanctions, the last thing he wants is to put them at risk of incurring the loss of assets in Ukraine.
-- Liz Fuller
About This Blog
This blog presents analyst Liz Fuller's personal take on events in the region, following on from her work in the "RFE/RL Caucasus Report."It also aims, to borrow a metaphor from Tom de Waal, to act as a smoke detector, focusing attention on potential conflict situations and crises throughout the region. The views are the author's own and do not represent those of RFE/RL.
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Embattled TBS late-night host Samantha Bee took the stage to accept a Television Academy Honors award Thursday night and defended calling White House advisor Ivanka Trump a “cunt,” lashed out at the Trump administration “treating people legally seeking asylum as criminals,” and thanked her bosses at Turner Broadcasting for having her back.
“You know, the thing is our show is steeped in passion. Every week I strive to show the world as I see it, unfiltered. Sometimes I should probably have a filter. I accept that. I take it seriously when I get it right and I do take responsibility when I get it wrong,” Bee said, according to Indiewire, to a star-studded audience at the event, held at Neuehouse in Hollywood.
“Our piece attracted controversy of the worst kind,” Bee said of the segment about the Trump administration’s immigration and border policies that ended with her calling Ivanka Trump a “feckless cunt” who needed to “do something about [her] dad’s immigration practices.”
“We spent the day wrestling with the repercussions of one bad word, when we all should have spent the day incensed that as a nation we are wrenching children from their parents and treating people legally seeking asylum as criminals,” Bee added. “If we are OK with that then really, who are we?”
The Full Frontal host’s pre-taped trash talk against Ivanka Trump was met with swift rebuke from social media to the White House. Two of the weekly show’s advertisers, Autotrader and State Farm, suspended their sponsorship of the show. First Lady Melania Trump excoriated Bee for her remarks and the media for resistance to reprimand those kinds of attacks.
Bee apologized for her remarks late Thursday. TBS applauded Bee’s apology but did little else.
“Samantha Bee has taken the right action in apologizing for the vile and inappropriate language she used about Ivanka Trump last night,” TBS said in a statement. “Those words should not have been aired. It was our mistake too, and we regret it.”
On Thursday night, the 48-year-old comedian was unrepentant.
“I can tell you, as long as we have breath in our bodies and 21 minutes of airtime once a week, repeats on Saturdays, that we as a show will never stop shouting [about] the inhumanities of this world from the rooftops and striving to make it a better place” said Bee. “But in a comedy way.”
Flanked by her writers and producers, Bee praised her staff who had been honor by the Television Academy for covering the Time’s Up and #MeToo movements.
“Our staff poured everything we have into these #MeToo pieces,” Bee said. “They wrote jokes through tears and panic attacks, they pushed each other to be honest and more fearless. I can only imagine what it takes to say these powerful famous, admired men abused me and I won’t be silent. No matter the consequences, Me Too.”
“Leaders of the #MeToo movement are changing the world. And we are honored to stand with you and support you as best we can,” Bee added. “There is power in saying what you feel without apology… OK, and sometimes you also have to apologize.”
Bee concluded her remarks by heaping praise on her Turner Broadcast bosses, saying, “you always have our back and we appreciate that so deeply.”
It is still unclear if Time Warner CEO Jeff Bewkes will follow the lead of Disney CEO Bob Iger, who called Valerie Jarrett to apologize for a tweet from Roseanne Barr just one day before Bee attacked Ivanka Trump.
Follow Jerome Hudson on Twitter: @JeromeEHudson
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Fire test report: DCLG BS 8414 test no.4
The report of the result of the fourth large scale test which shows how Aluminium Composite Material (ACM) cladding with a fire retardant polyethylene filler with stone wool insulation behave in a fire.
Documents
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Details
Update: the report dated 9 August version 1.0 contained a typographical error. The report above has been corrected.
This report is the fourth of a series, commissioned by the Department for Communities and Local Government (DCLG) intended to establish how different types of Aluminium Composite Material (ACM) panels in combination with 2 different types of insulation behave in a fire.
On 6 July the Independent Expert Advisory Panel recommended a series of large scale, BS 8414 tests be carried out in order to help building owners make decisions on any further measures that may need to be put in place.
This series of tests initially included 6 combinations of cladding systems. The detailed design of each test specimen has been reviewed by the Expert Panel and other industry bodies to ensure that it is representative of the systems that are in common use including the way it is fixed. These 6 tests incorporate each of the 3 common types of ACM panel, with core filler materials of unmodified polyethylene (PE), fire retardant polyethylene, and limited combustibility mineral. The 2 insulation materials used in the testing are rigid polyisocyanurate foam or non-combustible stone wool.
To further build the evidence available for experts and building owners so they can make informed safety decisions, on 8 August government commissioned a seventh large scale test – testing ACM with fire retardant polyethylene filler (category 2 in screening tests) with phenolic foam insulation.
Test no.4 relates to a cladding system formed using ACM panels with a fire retardant polyethylene core and a stone wool foam insulation.
The test result shows that this combination of materials can meet the criteria set out in building regulations guidance BR 135.
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“Five-term incumbent Mayor Chris Louras of Rutland, Vermont was defeated this Town Meeting Day. He lost to Alderman Dave Allaire by a margin of 52 percent to 34 percent. Allaire swept all four wards,” WCAX reported Tuesday night.
“Louras had beaten Allaire in two previous mayoral elections,” Seven Days Vermont reported.
It was not even close on Tuesday, as Louras (pictured) was crushed in a humiliating defeat that was as much a rejection of his personal character as it was of his pro-refugee policies.
Louras made headlines last year when it was reported that, beginning in 2015, he secretively attempted to resettle 100 Syrian refugees in the small Vermont city he has served as mayor since 2007.
“Mayor Christopher Louras has unveiled a plan, developed in near-secrecy, to resettle 100 Syrian refugees who fled the onslaught of the Islamic State and are exiled in sprawling Jordanian camps,” the Boston Globe reported in May.
“If approved by the State Department and others, the resettlement would begin in October and gradually send Rutland more Syrian refugees than are currently living anywhere else in New England. . . The influx would be a jolt of instant cultural diversity for Rutland, where there are no mosques and no other Syrian immigrants,” the Globe noted.
“Prior to announcing the resettlement of Syrian refugees, Rutland Mayor Louras held secret meetings with representatives of the Vermont Refugee Resettlement Program, the State Department, the U.S. Department of Homeland Security, U.S. Committee for Refugees and Immigrants and Gov. Peter Shumlin,” Bruce Parker reported at Vermont Watchdog in July 2016, two months after Louras sprang the announcement on an unsuspecting community.
The U.S. Committee for Refugees and Immigrants (USCRI) is one of the largest and most powerful voluntary agencies (VOLAGs) who, as a group, have been paid more than $1 billion annually by the federal government to resettle refugees in the United States.
“The mayor pitched the plan, without consulting the Board of Aldermen, as a humanitarian imperative and economic development initiative,” Seven Days Vermont reported, adding:
After months of conflict, Louras in September appeared to have scored a legacy-defining victory when the U.S. State Department announced that Rutland had been approved as a resettlement site and would begin accepting refugees. But President Donald Trump’s executive orders cracking down on immigration from Syria and other Muslim countries scuttled the plan. Only two Syrian families made it to Rutland.
The defeat of Louras was a stinging rebuke to the pro-refugee movement in a state where Hillary Clinton defeated Donald Trump by a 61 percent to 32 percent margin.
Louras blamed his loss on his support of refugees, and blamed the “emotions” of voters who rejected him rather than his own actions.
“Though I wanted to think this was not a referendum on refugee resettlement, I continue to believe, as I’ve articulated, Rutland is a microcosm of the national conversation on immigration and refugees, and ultimately it was not an election on the issues but an election based on emotions,” Louras told the Associated Press.
The victorious Allaire focused immediately on the need to rebuild confidence in the local government.
“One of the first things I want to do is restore the trust in City Hall . . .That’s what I’m going to do,” the Associated Press reported he said at an election night victory party.
The problems that ended Louras’s ten year administration as mayor were largely self-inflicted.
While Vermont is generally a refugee-welcoming state, the idea of dumping 100 Syrian refugees into this small city in Vermont that is already struggling economically seemed to defy common sense and logic, even to an area that preferred Hillary Clinton to Donald Trump.
Even more damaging to Louras, however, was the secretive and authoritarian manner in which he went about pursuing his objective of bringing 100 Syrian refugees to Rutland.
The liberal Vermont of 2017 is nothing like the rock-ribbed conservative Vermont of the 1950s, but the majority of Vermonters living in Rutland still know the abuse of governmental authority when they see it.
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Real Madrid midfielder James Rodriguez offered to Man Utd
Manchester United have been offered the chance to buy Real Madrid attacking midfielder James Rodriguez, according to Sky sources.Rodriguez is expected to leave Real this summer after becoming frustrated at the lack of playing time under Zinedine Zidane.
Real signed the 25-year-old from Monaco for £71m after he helped Colombia reach the quarter finals of the 2014 World Cup in Brazil.The current European champions want to recoup most of the transfer fee they paid three years ago, but a source close to the player believes they will accept an offer in the region of £50m.
Rodriguez has the same agent as United manager Jose Mourinho - Jorge Mendes - and is currently contracted at the Bernabeu until the summer of 2020.Rodriguez has scored 36 goals in 109 appearances for Real and was part of the squad that won the Champions League last season.
In April, Mourinho spoke of his confidence that United will have conducted some "interesting" transfer business by the end of the summer transfer window.Sky Sports News HQ understands United are also interested in signing Atletico Madrid forward Antoine Griezmann, should he become available in the summer."I'm sure, at the end of the summer, probably we won't have exactly my first options, because it's difficult to succeed in every attempt," Mourinho said."But I'm sure we're going to do something interesting and something to improve our team for next season."I'm not a silly manager to say I give the names and you have to give me the players - not at all."I give the names, I give the options, I give the second options in case the first options are not possible, but I give all the information based on my analysis, my experience and projections for the future."
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Salem, Ore. – A proposed 10-year, $8.2 billion transportation infrastructure bill for Oregon has been unveiled.
The measure introduced Wednesday would impose higher gas taxes, increased vehicle title and registration fees, tolls on portions of Interstate 5, and a payroll tax to fund public transit.
The Statesman Journal reported large cities would have to salt at least 25 percent of their roads if more than 2 inches of snow falls over a 12-hour period. And a proposed tax on new car sales also would apply to used cars.
The public will have a chance to weigh in on the bill at hearings on Monday, Tuesday and Wednesday.
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San Ysidro School District employees to undergo training on attendance reporting
The San Ysidro School District will pay as much as $9,750 for training and manuals on student attendance reporting in an effort to not repeat a past error.
The mistake occurred when the district over reported attendance for the 2015-16 school year by 262 students. As a result of the miscalculation, the state, which doles out funds to schools based on attendance, overpaid the San Ysidro district about $5.2 million.
In February, the school board agreed to repay the state.
Now the board has approved a contract with a firm that will help the district ensure employees, from teachers to administrators, property record and report attendance.
“This is a step forward,” said Chief Business Official Marilyn Adrianzen, who was hired in July. “It’s a big step forward.”
In the coming months, the firm, Wenger & Associates, will review the adequacy of the online system that the district uses to log attendance and generate data to report to the state. A key task will be to ensure the codes the district uses — such as the code for an unexcused absence — are in line with the state’s guidelines on attendance reporting.
Wenger & Associates will also develop customized manuals for teachers, school attendance clerks and other district employees.
Training, which will take place once the materials are finalized, will include two workshops and web conferences.
The manuals will be used by Wenger & Associates to help the district become certified by the state in attendance reporting.
The contract with the firm, approved unanimously by trustees on Oct. 11, runs through June. Under the agreement, the costs for the firm’s services will not exceed $9,750.
“We needed to bring in Wenger & Associates so that everyone is on the same page and trained in all of the areas of (student attendance) accounting,” Adrianzen said.
She noted the district of about 5,000 students, which has faced leadership and financial troubles in recent years, is working to improve in many areas with a new superintendent, Gina Potter, at the helm. Potter was hired in May.
“We’re trying to put the district back together,” Adrianzen said.
The district’s error in 2016 occurred under the leadership of former Superintendent Julio Fonseca, who resigned in September. An audit completed in June found he and former Assistant Superintendent Arturo-Sanchez-Macias were each overpaid more than $160,000, mostly in insurance and vacation payouts, during their two-year tenure with the district.
The incorrect student attendance figure for the 2015-16 school year was used to calculate the district’s funding for two consecutive years. The state uses the larger number between the current and previous year, and the attendance inaccurately reported for 2015-16 year was greater than the attendance for the 2016-17 year.
When the error was discovered as part of a routine audit in 2016, the district decided to put the funds aside and dispute the findings. In November, interim Chief Business Official Peter Wong determined the audit was accurate and recommended the board approve an agreement to repay the state.
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Sergei Bubka wants 2012 stadium promise honoured
London's Olympics organisers must be faithful to their promise and retain the 2012 stadium's running track after the Games, according to Sergei Bubka.
West Ham and Tottenham Hotspur are the preferred bidders for the Stratford venue, but Spurs have made it clear they intend to rip out the track.
"We shook hands and had a deal," said IOC member Bubka in Monaco.
"In 2005, it was guaranteed to us the track would stay - this is a matter of dignity," added the pole vault great.
While Tottenham plan to make the east-London stadium an 80,000-seat venue, West Ham want to create a 60,000-capacity arena for football, athletics, concerts and community use in a collaboration with Newham Council.
Bubka insisted he had received more guarantees the track would be kept during a three-day inspection visit in September before London withdrew its bid to host the 2015 athletics World Championships.
"I was the chairman of the evaluation commission for London and Beijing 2015 and they told us the track would remain, I saw it written in documents," said Bubka, who is an International Association of the Athletics Federation (IAAF) senior vice president.
"The United Kingdom has an unbelievable story of athletics (feats) and I can't believe we are talking about such a thing," added the world pole vault record holder, who was speaking at an IAAF council meeting.
Bubka also plans to talk to Sebastian Coe, head of the London 2012 organising committee, who is also in Monaco.
Meanwhile, Tottenham chairman Daniel Levy has criticised the lack of public money that has been made available for the club's proposed new stadium.
Spurs are hoping to move from White Hart Lane to either a new purpose-built ground close to the current site or the Olympic Stadium.
"This development has not attracted a penny of public money," said Levy, in regards to the new site in Tottenham. "Arsenal and Wembley were both awarded public sector assistance."
"Our development has the potential to kickstart regeneration in one of the most deprived boroughs in London, where land values are poor and yet no regeneration monies are available to it," added Levy.
Earlier in the week, Tottenham's proposal to take over London's Olympic Stadium with AEG after the Games in 2012 was branded as "completely unacceptable" by UK Athletics (UKA).
"Anything they might propose for an athletics legacy has to be a compromise to the stadium continuing to operate at a world-class level. To my mind that is completely unacceptable," added UKA chairman Ed Warner.
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Q:
Calculating time taken for a set percentage of a reaction to occur based on half-life
The half-life of a first order homogenous gaseous reaction: $\ce{SO2Cl2 -> SO2 + Cl2}$ is 8.0 minutes. How long will it take for the concentration of $\ce{SO2Cl2}$ to be reduced to 1% of the initial value?
I solved it this way:
Let initial mass be 100, so that the final mass is 1.
$$100 \cdot (\frac{1}{2})^n=1$$
I solve this for n, and multiply it by 8.0 to get the time taken.
Answer is spot on, and the method is identical to the one used in half life questions in Physics. Yet my Prof insists that I solve for the rate constant first, and then find half-life from that, and that my answer is wrong because n, the value for number of half-life periods, cannot be a decimal value.
The questions I found online all explicitly ask for the rate constant, which the question I got doesn't ask for.
Is my method right/wrong? Can you guys provide proof?
A:
Ryan showed that the rate constant is given by $k=\frac{ln(2)}{t_{1/2}}$. So the concentration at time t is given by
$$C=C_0\exp(-kt)=C_0e^{-ln(2)\frac{t}{t_{1/2}}}$$But,
$e^{-ln(2)}=\frac{1}{2}$. Therefore, $$C=C_0\left(\frac{1}{2}\right)^{\frac{t}{t_{1/2}}}$$Substituting $n=\frac{t}{t_{1/2}}$ gives
$$C=C_0\left(\frac{1}{2}\right)^n$$
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Forty names, games, teams and minutiae making news in college football (#TeamFreeSpeech T-shirts sold separately in Columbus):
HOW LONG IS TOO LONG?
LSU’s three-game losing streak has brought down a surprising amount of heat upon the second-winningest coach in school history. As Yahoo Sports reported Monday, the school is “prepared” to pass the hat and buy out The Hat in Baton Rouge.
Which just goes to show the cannibalistic nature of the Southeastern Conference, the pressure to win big, and the high price of not beating your biggest rival for a while. It’s also illustrative of the two-edged sword of continuity – coaches crave it, but longevity can work against them sometimes. With that in mind, The Dash looks at coaches who have won big but lost some mojo, and are in danger of overstaying their welcome:
Les Miles (1), LSU. His record is 110-32 in 11 seasons in Baton Rouge. Repeat: 110-32. The Tigers are thinking seriously about paying a gazillion dollars in buyout money to get rid of a coach who has averaged 10 wins per year for more than a decade, plus whatever the cost would be to bring in a new rock star (Jimbo Fisher, Line One). This in a state where higher education funding has been under siege, and where massive cuts were fended off last spring. It’s shameful. But the lesson for Les is this: beat Nick Saban or find your job on the line. Miles has lost five straight to the former LSU coach, starting with the 2012 BCS championship game shutout, and that has become intolerable for LSU diehards. Miles also has failed to put a modernized offense on the field, perpetually squandering elite wide receiver talent. But still: 110-32. And may get fired.
Mark Richt (2), Georgia. The Dash doesn’t expect Richt’s 15th season as coach of the Bulldogs to be his last – but losing for the second straight year to rival Georgia Tech could definitely change that. Especially this Georgia Tech team, which is 3-8 and the biggest bust of 2015. Like Miles, Richt’s overall record is excellent: 144-51, an average of 9.6 wins per year. But sitting on a gold mine of local talent hasn’t translated into a ton of SEC championships – just two of those, and none since 2005. And in a stretch where the SEC won seven straight national titles and had nine teams play in eight straight BCS championship games, none of them was Georgia. Staff acrimony and awful quarterback play have been the issues with this team, which was crushed by Alabama and Florida and blew a big lead against Tennessee. But still: 144-51. And may get fired.
If there is an ally out there for Richt and Miles as the storms rage, it may be the Phil Fulmer (3) cautionary tale at Tennessee. He was the most recent case of an SEC coach with a great résumé – 152-52 in 17 seasons, with the 1998 national title trophy – to be pushed out in 2008 amid declining returns. Since then Tennessee has gone 42-44 and is on its third coach.
Or, at LSU, there is the Charley McClendon (4) cautionary tale. He coached the Tigers from 1962-79 and remains the school’s winningest coach with 137 victories. His career tailed off in his final six seasons, going 40-27-2 over that span, and he was forced out. What followed was basically a two-decade stay in Mediocreville, with 10 losing seasons between 1981-99. That’s why Saban’s arrival in 2000 was a godsend, and why the fan base still is fixated by him today. He transformed LSU, left LSU and now specializes in beating LSU. And the fans can’t stand it.
Story continues
The general feeling outside of the states of Louisiana and Georgia is that they’d better be careful what they wish for. In a league like the SEC, it’s not difficult to go from 9-3 and unhappy to 5-7 and utterly miserable. But the amount of in-state talent for both LSU and Georgia to have first run at is enough to believe things could be better. That’s why Les Miles and Mark Richt are on the clock.
Two guys who have effectively killed the same out-with-the-old talk this season:
Kirk Ferentz (5), Iowa. He began his 17th season in Iowa City with an approval rating that was probably at its lowest point since starting his tenure with consecutive seasons of 1-10 and 3-9. He’s ending his 17th season in what could be a Coach For Life comfort zone. The Hawkeyes are 11-0 for the first time in school history, have clinched the Big Ten West and remain in the CFP hunt (we’ll find out exactly where they stand Tuesday night when the new rankings are released). A schedule that features six conference opponents with losing records certainly has helped, but this team has clearly exceeded expectations and upgraded a program that had gone just 26-25 the previous four seasons. Ferentz almost certainly will be the Big Ten Coach of the Year.
Bob Stoops (6), Oklahoma. It might be best to say that Stoops has silenced the Change Is Needed talk instead of killing it. Because if the Sooners lose in Stillwater on Saturday with a Big 12 title and potential College Football Playoff berth on the line, that chatter will make a comeback. A 10-2 season is a fine thing, but when the losses are to your two biggest rivals as a solid favorite in both games? That leaves a coach open to criticism. Still, Stoops’ staff shakeup in the offseason has paid immediate and substantial dividends, making last year’s 8-5 record more of a radar blip than an indicator of a program in decline. Athletic director Joe Castiglione has been resolutely supportive of Stoops, and with good reason. He’s too good to let go.
A SPIN AROUND THE COACHING CAROUSEL
View photos Will Houston's Tom Herman make the jump to a Power 5 program? (Getty) More
A busy hire-and-fire year is reaching crunch time, as seasons end and job searches intensify. Establishing a Herman Watch (7) to stalk the movements and parse the words of Houston coach Tom Herman might be a good idea. And maybe a Chip Watch (8), although there are no reliable reports that Chip Kelly is itching to get back to college football. But for now, a broad-strokes look at the job market will have to do:
Virginia Tech (9) – Leaving: Frank Beamer. Arriving: The Dash is betting the mortgage on Memphis coach Justin Fuente, and betting that it happens quickly next week. Word is that athletic director Whit Babcock has his man, and has for a while now, and Fuente is that man. He’s done a remarkable job at previously moribund Memphis, going 18-6 over the past two seasons. It’s possible that tumbling dominoes at LSU and points elsewhere (namely Florida State) unspring this, but unlikely. A Fuente hiring would also keep Rich Rodriguez in place at Arizona.
South Carolina (10). Left: Steve Spurrier. Arriving: Could this finally be the job that makes Kirby Smart leave Nick Saban’s side at Alabama? It’s believed that South Carolina was pretty far down the road with Tom Herman, but that’s changed. Mark Dantonio is an alum, but that doesn’t feel like the right job for him. He already has the right job for him.
Syracuse (11). Left: Scott Shafer. Arriving: Is this the re-entry point for Greg Schiano? Has had success in the northeast, and his name hasn’t generated as much interest at some other locales as might have been expected. (There was some chatter about Schiano and Miami, but it may not be front-burner chatter.) Remains to be seen if athletic director Mark Coyle would reciprocate any Schiano interest, but he seemingly would be a very good hire at a school that has been down on its football luck for most of the last decade.
Miami (12). Left: Al Golden. Arriving: Unknown. The Charlie Strong rumors wouldn’t die, but the Texas coach gave a definitive statement Monday that he’s “not going anywhere” and told his players as much. If Strong is out, Alabama assistant coach, former Hurricane player and former Florida International head coach Mario Cristobal has a ton of backing and could well be the guy. There also is booster sentiment for former Miami coach Butch Davis, which is swell if you want to overlook the huge academic/agent scandal on Davis’ watch in the North Carolina program plus Miami’s recent death march through the NCAA judicial process. (Seriously, does this stuff even matter to some people?) Schiano, Mississippi State’s Dan Mullen or an outside-the-box candidate could appear if the Cristobal train doesn’t make it to the station.
View photos Has Clay Helton done enough as interim coach at USC to be named the next full-time hire? More
USC (13). Left: Steve Sarkisian. Staying: Clay Helton? The interim coach has done a nice job, and there may be some sentiment for hiring him full-time – but that would be impossible if he finishes the regular season with losses to Oregon and UCLA. Add in a loss to Notre Dame and you pretty much have the trinity of teams USC fans hate losing to most. Where this search is going beyond the iffy Helton candidacy is one of the great mysteries of 2015. Herman would seem like a good choice here, but nobody is connecting those dots with any degree of certainty at this point. Kyle Whittingham’s name came up quickly after Sarkisian was fired, in part due to Utah’s hot start and in part due to his clashes with school administration. He’s a very good coach, but can USC hire a guy who is 19-25 in Pac-12 games? Even Sark was better than that (24-21) at Washington. Spitball the idea of Mullen here, though it would not seem to be a natural fit.
Missouri (14). Left: Gary Pinkel. Arriving: Unknown. Athletic director Mack Rhoades skillfully navigated through an arduous situation with the campus unrest and short-lived but very public player boycott – then he lost the best coach in school history to health issues. Expect Mizzou to approach a short list of candidates this week – but the logical and popular choice of Herman may not be on it. Rhoades hired him at Houston, but getting him to follow his old boss to Columbia may be difficult. Herman could be eyeballing other jobs, or might seriously consider staying for a second year at Houston now that the school has upped his salary to $3 million and could have a killer team coming back in 2016. One potential advantage to that strategy: if Texas opens and Herman has another great season, it’s a short drive from Houston to Austin. Fuente would have been a logical name, but he’s expected to be off the market. So who else would be a candidate? Former Mizzou player and current defensive coordinator Barry Odom, who would maintain continuity – but would have to find someone to rejuvenate a dreadful offense. If the school would like to retrace Pinkel’s MAC-to-Mizzou footsteps, there are good coaches at Toledo (Matt Campbell), Bowling Green (Dino Babers) and Western Michigan (P.J. Fleck). Jeff Brohm of Western Kentucky could be an attractive name. Don’t expect Miles to be on the Mizzou short list if he gets forced out at LSU. A complicating factor at Missouri: there is no full-time chancellor after the Concerned Student 1950 protest led to a leadership purge.
Virginia (15). Leaving: Mike London. Arriving: ????. The school has said nothing publicly, but it has been widely taken as fact that London will be dismissed after the Cavaliers’ game against Virginia Tech on Saturday. This could be a job that appeals to Brohm, whose high-octane offense seemingly would play well for a fan base anesthetized by six years of LondonBall. Whether Brohm (17-7 in two seasons at WKU) would appeal to Virginia remains to be seen.
Tulane (16). Potentially leaving: Curtis Johnson. Arriving: ????. The move from Conference USA to the American Athletic Conference hasn’t been a good one for the Green Wave or for Johnson’s job security, apparently. There has been considerable speculation that Johnson will be out sometime after Tulane (3-8) plays Tulsa on Friday. He was 9-16 in two seasons in C-USA, including a 7-6 year, but is just 6-17 since Tulane joined the American. Tulane recently built a cozy, on-campus stadium and undoubtedly would like to capitalize on that investment with an upgraded on-field product. Problem is, the school has to name an athletic director first. A search committee and search firm is believed to be closing in on a hire in that department.
Rutgers (17). Potentially leaving: Kyle Flood. Arriving: The Piscataway Fire Department, to put out the dumpster fire that is Scarlet Knights football. There are no reports that Flood will be fired, but neither has anyone in the school administration publicly stated support for the embattled coach. His popularity with fans has reached this level: a public service announcement featuring Flood that appeared on the stadium big screen Saturday during Rutgers’ home loss to Nebraska prompted a chorus of boos from the fans. After a season that has been miserable for many reasons beyond the 4-7 record, it’s very hard to envision a scenario in which Flood returns. Maybe Schiano comes to the wood-chopping rescue of his former school and replaces his former assistant, but it might be better for Rutgers to have a fresh start.
WHEN A POWER 5 JOB HAS NO POWER
A source told The Dash that it would not be a shock to see “a Power 5 coach taking a better mid-major” job this offseason. Which raised the question: which football programs are operating far enough beneath their membership privilege to make a group-of-five job an actual step up? The list:
View photos Could Kansas coach David Beaty bolt for a group-of-five gig? (AP) More
Kansas (18). Jayhawks are one loss away from the first winless season by a Power 5 team since 2008. Average home attendance this season in 50,071-seat Memorial Stadium: 27,020. The program has been atrocious for a while now (seven-year record: 12-59) and it will take a long time to dig out of the toxic dump that was the Charlie Weis Era. David Beaty is in his first year as a head coach and first at Kansas – but would you blame him for leaving?
Colorado (19). This is the Buffaloes’ 10th straight losing season, spanning three different coaches. If they can win at Utah on Saturday (unlikely), they will reach five wins for the first time since 2010. Attendance isn’t quite Kansas-level bad, but Colorado still is playing in front of an average of 11,000 empty seats in 50,475-seat Folsom Field every home game. Mike McIntyre had success at San Jose State before coming to Boulder; wouldn’t be inconceivable of him to want to go back to that level.
Indiana (20). The Hoosiers have to beat Purdue on Saturday to become bowl-eligible for the first time since 2007 and just the second time since 1993. Beating Purdue is not hard, but beating Purdue for the third straight season is – last time Indiana did it was 1945-47. It would also be a second straight Big Ten road win, something the Hoosiers last performed in ’93. Fans lobbied for ESPN “GameDay” to come to Bloomington when Indiana was 4-0; Hoosiers then lost their last four home games of the year. Kevin Wilson probably won’t get fired, but he will have completed five years on the job without a bowl bid if Indiana loses to the Boilermakers.
Honorable mention to California, which has a coach who is annually rumored ready to leave for a non-Power 5 job in Sonny Dykes. The third-year coach has the Golden Bears (6-5) bowl-bound for the first time since 2011, and contract extension talks are ongoing. But would a Texan have an eye on Houston if Tom Herman leaves?
Mid-major jobs that could be considered better than the worst Power 5 jobs: Houston, Central Florida, South Florida, Cincinnati, Boise State, San Diego State, Memphis if it’s sustainable after Fuente.
THE SPOILERS
There are nine teams with a fighting chance at a playoff spot right now: Clemson, Alabama, Oklahoma, Baylor, Notre Dame, Iowa, Michigan State, Florida and North Carolina. (Ohio State and Oklahoma State also have a shot, but it's unlikely.) All nine true contenders face a season-ruining risk this weekend. The Dash appraises the teams that have the opportunity to upset everything:
Auburn (21). The opponent: Alabama. The location: Auburn. The line: Alabama by 13. Last time they played at Jordan-Hare Stadium, the Tigers triumphed as a 10-point underdog – you might remember how that particular game ended. This time around the 6-5 Tigers might require something even more improbable to win. But Auburn got a little motivation from Alabama center Ryan Kelly on Monday, when he was asked about Tigers defensive end Carl Lawson: "I honestly don't know who that is," Kelly said, and did not appear to be joking. Lawson has missed most of the last two seasons with injuries, but he was a freshman All-American in 2013, played in the Iron Bowl that season, and one presumes he will try to introduce himself to Kelly at some point Saturday. Dash pick: Alabama 20, Auburn 10.
Oklahoma State (22). The opponent: Oklahoma. The location: Stillwater. The line: Oklahoma by 6 ½. Oklahoma State still could harbor playoff chances of its own if it wins this game, and Baylor and Notre Dame both lose. But the 10-1 Cowboys are playing from the outside after they were brought back to Earth by Baylor last week, losing 45-35 in a game that was not as close as the score. (The Bears were minus-three turnovers or it would have really gotten ugly.) If Sooners quarterback Baker Mayfield cannot play, give the Pokes a decent chance. But early signs are that Mayfield will be cleared after sitting out part of Oklahoma’s one-point win over TCU Saturday. Dash pick: Oklahoma 35, Oklahoma State 28.
Florida State (23). The opponent: Florida. The location: Gainesville. The line: Seminoles by 2. Unless Fisher spends all week talking to agent Jimmy Sexton about getting him to Baton Rouge, this is a good situation for Florida State. The offensively challenged Gators are staggering down the stretch of an overachieving season, with shaky wins over Florida Atlantic and Vanderbilt this month. And the 'Noles have played well since their playoff hopes were extinguished by Clemson on Nov. 7. Dash pick: Florida State 17, Florida 16.
View photos Will Mark Dantonio's Spartans make the playoff? (AP) More
Penn State (24). The opponent: Michigan State. The location: East Lansing. The line: No line, due to Michigan State injury uncertainty at quarterback. The Nittany Lions’ only road win of the season was by a point over a 2-9 Maryland team that outgained Penn State by 103 yards on the day. In other words, not much reason to believe James Franklin’s team is walking into Spartan Stadium and robbing Michigan State of a playoff bid. Still, it’s entirely reasonable to expect a Sparty hangover from the triumph in Columbus, and if Connor Cook cannot play it will again turn Michigan State one-dimensional. So could it be close? Sure, it could be close. Dash pick: Michigan State 21, Penn State 14.
Nebraska (25). The opponent: Iowa. The location: Lincoln. The line: Iowa by 2. The miniscule point spread against a 5-6 opponent shows that The Dash isn’t the only one underwhelmed by the Hawkeyes. During their bye week, the Cornhuskers were dealing with a rape allegation and investigation involving three players, including starting quarterback Tommy Armstrong. The investigation is ongoing and no charges have been filed, and first-year Nebraska coach Mike Riley said there will be no player suspensions for this game. It’s been a largely lousy season for the 5-6 Huskers, but they are the only team to have beaten Michigan State and would love to say the same about Iowa by Friday night. Dash pick: Nebraska 26, Iowa 24.
Stanford (26). The opponent: Notre Dame. The location: Palo Alto. The line: Stanford by 3 ½. The Cardinal were eliminated from playoff contention Nov. 14 by Oregon, in part because they fumbled two center-quarterback exchanges. That’s a bad way to have your season marred. But Stanford gets its own shot at ruining someone’s season, and gets a crippled Notre Dame team in its backyard. The Fighting Irish have impressively overcome injuries all season, but last week star cornerback KeiVarae Russell broke a leg and star running back C.J. Prosise sprained an ankle, and that may finally be the tipping point on the season. Dash pick: Stanford 31, Notre Dame 28.
TCU (27). The opponent: Baylor. The location: Fort Worth. The line: Baylor by 1 ½. Injured Horned Frogs quarterback Trevone Boykin may be back for this one, after missing the loss at Oklahoma and much of the close escape over Kansas. If so, TCU has a chance to exact revenge after three-point losses to the Bears each of the past two seasons. But Baylor looked like it figured some things out about Life Without Seth Russell against Oklahoma State, pounding a solid defense for 304 rushing yards and 700 yards total. Dash pick: Baylor 47, TCU 41.
North Carolina State (28). The opponent: North Carolina. The location: Raleigh. The line: North Carolina by 6 ½. The Wolfpack has beaten all the bad teams on the schedule: Troy, Eastern Kentucky, Old Dominion, South Alabama, Wake Forest, Boston College, Syracuse. It has lost to all the decent-to-good teams on the schedule: Louisville, Virginia Tech, Clemson, Florida State. North Carolina is a good team, with a much tougher defense than the one the Wolfpack mauled in a rout last season. Dash pick: North Carolina 31, North Carolina State 20.
South Carolina. The opponent: Clemson. The location: Columbia. The line: Clemson by 17 ½. The Dash suspects the Head Ball Coach saw this trainwreck coming in early October and wanted no part of a season-ending beatdown at the hands of the arch-rival, so it was time to resign/retire. After losing to The Citadel last week, the Gamecocks may be too demoralized to put up any resistance against a team hell-bent on playing for a national title. Dash pick: Clemson 41, South Carolina 14.
OTHER RIVALRY GAMES OF IMPORT
It’s that wonderful weekend when the hate reaches a boiling point at locales around the country. The big rivalry games that impact the playoff race are mentioned above. Some others worth watching here:
View photos Who will win the first clash between Urban Meyer and Jim Harbaugh? (Getty) More
Ohio State-Michigan (29). The Spartans dealt a one-two punch so destructive to their two biggest rivals that this is the result: a matchup everyone has been talking about since January is now relegated to second-tier status. Beating the Wolverines on the last play was one thing; beating the Buckeyes on the last play means Meyer-Harbaugh I is only vital to the Big Ten East race if Michigan State were to lose to Penn State. Nevertheless, it’s Meyer-Harbaugh I. And Michigan is better than expected. And Ohio State is worse than expected. And Ezekiel Elliott will start and undoubtedly get the ball 25 times after nuking the coaching staff Saturday night for not giving him enough carries. So, yeah, there are reasons to watch. Dash pick: Michigan 20, Ohio State 16.
UCLA-USC (30). Even though both teams have the unmistakable aroma of disappointment about them, the crosstown rivalry will decide the Pac-12 South title. And it is one of the great uniform matchups of the year, every year. Hard to believe, but it’s been seven seasons since USC last won the conference title. UCLA last won it in 1998. If Josh Rosen continues his long streak of passes without an interception and the Bruins don’t fumble, they should win. Dash pick: UCLA 28, USC 22.
Mississippi-Mississippi Sate (31). The Egg Bowl has been significant, compelling and unpredictable in recent years. The underdog has won at home each of the past two meetings, and State fits that profile this time around in Dak Prescott’s final game at Davis Wade Stadium. “I came back for this reason,” Prescott said Monday, referencing the Bulldogs’ upset loss in Oxford in 2014. His late-blooming Heisman Trophy candidacy could get a boost here as well. Dash pick: Mississippi State 29, Mississippi 27.
Virginia Tech-Virginia (32). The Hokies are playing for a bowl bid, and to send Frank Beamer out of this rivalry on a winning note. The Cavaliers are playing to send London out with a win. And befitting a rivalry, there is some ethical contortion going on to make sure the best players are on the field. Tech is only suspending defensive end Dadi Nicolas for a half after deciding that this was unintentional contact with an official. Urban Meyer himself would think that’s soft. The ACC should have stepped in and suspended Nicolas for the full game as a statement that it is protecting its referees. Dash pick: Virginia Tech 22, Virginia 19.
Washington State-Washington (33). The Apple Cup pits a Cougars team trying to finish its best season since 2003 against a Huskies team trying to get bowl eligible for the sixth straight season. Mike Leach is the Pac-12 Coach of the Year, while Chris Petersen has a young team that could be dangerous in 2016. It could come down to the status of Cougars QB Luke Falk, who is iffy after suffering an apparent head injury in his team's win over Colorado last Saturday. Dash pick: Washington 32, Washington State 31.
Big Ten trophy games (34) Indiana, Minnesota and Illinois all are 5-6 and all playing in rivalry games for bowl eligibility. The Hoosiers take on Purdue for the Old Oaken Bucket. The Gophers are playing Wisconsin for Paul Bunyan’s Ax. And the Illini face Northwestern for the Land of Lincoln Trophy – the more acceptable replacement for the Sweet Sioux Tomahawk that was first awarded in 1945. Those are some stakes. Dash picks: Purdue 41, Indiana 40; Wisconsin 24, Minnesota 14; Northwestern 25, Illinois 21.
ALSO IMPORTANT
Two big games outside the power five conferences:
Navy-Houston (35). Battle for the AAC West and a possible swanky bowl bid between one-loss teams having great seasons. Keenan Reynolds’ dark-horse Heisman charge also a storyline. And Herman Watch, of course. Dash pick: Navy 35, Houston 31. A result Notre Dame would certainly cheer.
Western Kentucky-Marshall (36). Last year the Hilltoppers won 67-66 on a gutsy two-point conversion call by Brohm. This year, with the C-USA West title in the balance and both teams 9-2, expect plenty more points. Dash pick: WKU 59, Marshall 56.
Dashette Adriana Fonseca (37) matters greatly as well.
COACH WHO EARNED HIS COMP CAR THIS WEEK
Mark Dantonio (38), Michigan State. May have done the best one-week coaching job of anyone in America in 2015 to get the Spartans ready to beat Ohio State without star quarterback Connor Cook. Michigan State revels in the no-respect role, even if it has to manufacture it sometimes. This time there was no manufacturing needed, and the Spartans stunned the world. Between Dantonio and Tom Izzo, nobody has a better one-two coaching tandem than athletic director Mark Hollis.
COACH WHO SHOULD TAKE THE BUS TO WORK
View photos Urban Meyer and Ohio State are on the outside of the playoff picture with little hope left. (AP) More
Urban Meyer (39), Ohio State. If Dantonio coached the Game of the Year on Saturday, Meyer may have done the equal and opposite job. Whether it was a badly flawed gameplan or an in-game play-calling choke or simply a failure to ever get the Buckeyes firing like they did at the end of last season, the loss in the Horseshoe fully exposed a team that has seriously underachieved. And when key players were publicly turning pro within minutes after the loss, you wonder whether the buy-in to team over individual was ever there this season.
POINT AFTER
When hungry in Knoxville, The Dash recommends a visit to the reliably awesome Calhoun’s On The River (40). The place is mobbed on gameday, so plan accordingly. Try the brisket, try the ribs, try any meat you like. And try an Appalachian Pale Ale from Smoky Mountain Brewery with all that meat. Thank The Dash later.
Popular college football video on Yahoo Sports:
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Republican West Virginia Delegate Brian Kurcaba
Republican West Virginia Delegate Brian Kurcaba
“Obviously rape is awful,” Kurcaba said. “What is beautiful is the child that could come from this.”
West Virginia Del. Brian Kurcaba (R) made the comments — which were first reported by Charleston Gazette staffer David Gutman — during a public hearing on Thursday. A health committee in the legislature was debating a proposed 20-week abortion ban. Kurcaba was explaining why he opposed a Democratic-sponsored amendment to add an exception for rape victims.
Aaaaaand another enlightened Republican has weighed in on rape.That was rising GOP star, West Virginia Delegate Brian Kurcaba. Tara Culp-Ressler has the details:On behalf of sane women everywhere who would like to have a say in their health decisions following a traumatic incident like rape: Thanks for your concern, Mr. Kurcaba. Now kindly retire to your cave.
The Charleston Gazette's Gutman reports that the 20-week abortion ban bill the House of Delegates committee was debating, is "one of 11 introduced so far this legislative session that seek to restrict women’s access to abortion." The push by Democrats to include "an exception for cases of rape or incest failed, largely along party lines."
Apparently Republican West Virginia lawmakers have nothing better to do than perpetuate their attack on the rights of women to make their own healthcare decisions. Perhaps next they can take up our right to vote.
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Russia has agreed to reopen a major Cold War listening post on Cuba that was used to spy on America, it was reported today.
Moscow-based daily Kommersant claimed Russia and Cuba have struck a deal 'in principle' after President Vladimir Putin visited the island last week.
Citing several sources within Russian authorities, the respected daily wrote: 'The agreements were finalised while President Vladimir Putin visited Havana last Friday.
The former Russian listening station at Lourdes some 20 miles south of Havana is seen in this December 2000. It was mothballed a year later but could reopen, it is reported
Moscow dismantled its radar stations in Lourdes in 2001 as part of cutting back military installations abroad. The stations were built in 1964 after the 1962 Cuban missile crisis
Satellite dishes for the Lourdes radar station, which was Russia's biggest covert military outpost abroad. Around 1,500 Russian engineers, technicians and soldiers observed submarine activity from the base built in 1964
The signals intelligence facility near Havana at Torrens, also known as Lourdes, was the largest Russian SIGINT site abroad, but has been mothballed since 2001.
It covered a 28 square-mile area with 1,000-1,500 Russian engineers, technicians, and military personnel working at the base.
Russia had closed the Lourdes spy base south of Havana on Putin's orders to save money and due to a warming of relations with the U.S. after the September 11 attacks.
But Moscow has since shown a new interest in Latin America and its Cold War ally Cuba and relations with the West have deteriorated amid the Ukraine crisis.
The base was set up in 1964 after the Cuban missile crisis to spy on the United States.
Just 155 miles from the U.S. coast, it was the Soviet Union's largest covert military outpost abroad with up to 3,000 staff.
Russia's President Vladimir Putin (left) hugs Cuba's President Raul Castro after a meeting at the Revolution Palace in Havana last week
Raul Castro welcomed Vladimir Putin, where they met to discuss bilateral agreements. Before that, both presidents participated together to a flower offering to the Sovietic International Soldier Mausoleum
It was used to listen in to radio signals including those from submarines and ships and satellite communications.
'All I can say is - finally!' one Russian source told Kommersant of the reported reopening.
The defence ministry and military high command declined to comment on the report to Kommersant.
Ahead of Putin's visit to Cuba last week as part of a Latin American tour, Russia agreed to write off 90 per cent of Cuba's debt dating back to the Soviet era, totalling around $32 billion.
Russia paid Cuba rent of $200 million per year to use the base in the last few years it was open.
A former head of Russia's foreign intelligence service, Vyacheslav Trubnikov, told the newspaper the base would strengthen Russia's international position.
'Lourdes gave the Soviet Union eyes in the whole of the western hemisphere,' he said.
'For Russia, which is fighting for its lawful rights and place in the international community, it would be no less valuable than for the USSR.'
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fnatic Academy have pulled out of the ESEA Premier playoffs, HLTV.org has learned.
The Swedish team had been due to clash with Kinguin in the quarter-finals but have decided to forfeit the match due to the tournament's roster lock.
The news is bound to heighten speculation about the future of fnatic's main team, who have been heavily linked with roster changes since PGL Major Krakow.
Maikil "Golden" Selim's squad recently attended the Europe Minor as Ballistix after PGL ruled that academy teams should have a different "nametag and logo" to differentiate themselves from their organisations' main rosters.
Golden & co withdraw from ESEA Premier playoffs
After taking down Envy in their opening match, fnatic Academy were sent to the group's Lower Bracket by BIG, with a 2-0 defeat against Vincent "Happy" Schopenhauer's men eventually sealing their fate in the tournament.
Kinguin will advance straight to the ESEA Premier semi-finals, in which they will face the winner of the match between Epsilon and FlipSid3.
Below you can find the match-ups for remaining quarter-final encounters, scheduled for August 15:
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Callum Jones
Officers investigating the murder of Northamptonshire man Jon Casey have released details of the man they are seeking in connection with the offence.
The 35-year-old father of two from Ecton Brook was stabbed in Barrack Road, Northampton, close to the Lazeez restaurant, shortly before 5.30pm on Friday January 16, 2015.
Picture of flowers at scene of murder in Barrack Road, near Lazeez restaurant
Officers investigating his death want to locate 21-year-old Waijs Dahir, who lived in Semilong Road Northampton at the time of the murder.
Detective Inspector Louise Hemingway said: “For the past year, Mr Casey’s family have had to live with the knowledge that the person who killed Jon has not yet been brought to justice.
“That is why we have issued the details of Waijs Dahir today in the hope that he, or anyone who knows where he is, will contact us so we can speak to him about what happened in Northampton town centre a year ago.”
Waijs Dahir, who was a student at the University of Northampton at the time, originates from Coventry. He returned there shortly after the murder occurred and then left the country on Saturday January 17, 2015
Jon was a much loved son, brother, partner and dad and his family desperately want his killer to be brought to justice for his murder.
Speaking a year after the death, his family said: “The sadness of losing our Jon Boy is what our family wakes up to every day. Knowing that we will never see him, hear him or hug him again is what we must learn to live with.
“There are no words for our sadness and there will never be enough tears.
“Nothing can change the horror of what happened one year ago when our Jon, a partner, a son, a brother and a daddy to two little girls was taken from us so cruelly.
“Our Jon is gone and this world for us will always be a sadder place.
“As a family we ask that if you have any information that can bring the person who ended our Jon’s life to justice to please contact Northamptonshire police.”
Anyone with information about Mr Dahir’s whereabouts, or any other information about the death of Jon Casey, can call Northamptonshire Police on 101, quoting Operation Nanny. An email address is available should this be preferred at [email protected]
Alternatively, people can call the independent charity Crimestoppers anonymously on 0800 555 111 or use the anonymous online form at www.crimestoppers-uk.org.
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Rosalie van der Hoek
Rosalie van der Hoek (born 16 December 1994) is a Dutch tennis player.
She has career-high WTA rankings of 760 in singles, achieved on 31 December 2018, and 146 in doubles, set on 11 November 2019.
Van der Hoek made her WTA Tour debut at the 2017 Citi Open in the doubles main draw, partnering Chayenne Ewijk.
ITF Finals
Doubles: 47 (29 titles, 18 runner–ups)
ITF Junior finals
Singles (0–1)
Doubles (5–6)
External links
Category:1994 births
Category:Living people
Category:Dutch female tennis players
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A data warehouse system, also referred to as an “enterprise data warehouse,” is a system used for reporting and data analysis. Data warehouses are central repositories of integrated data from one or more disparate sources. Data warehouses store both current and historical data and are used for creating analytical reports for knowledge workers throughout the enterprise. Examples of reports could range from annual and quarterly comparisons and trends to detailed daily sales analyses.
In such a system, various types of data may be loaded. Furthermore, the number of users and the types of reports that are generated may vary. Additionally, various types of hardware may be utilized and complex configurations may be introduced to the data warehouse system by the user. As a result, various problems may occur in the data warehouse system, such as hardware problems, software problems and configuration problems.
The processing of queries submitted to the data warehouse system may be delayed, fail, etc. because of any of these problems. Due to the large number of queries executed on the data warehouse system, the high complexity of the query operations executed on the data warehouse system and the inter-dependencies between the system components (both physical and logical), there has not been a means for effectively diagnosing the problems causing the delay or failure of the processing of the queries. As a result, it may be difficult to determine which query-level problems require attention and which do not.
Currently, monitoring systems attempting to detect and determine which hardware, software and configuration problems in the data warehouse system caused the delay or failure of the processing of the queries focus on predictive monitoring of the hardware, checking the data/system catalog for consistency as well as monitoring the performance of the queries over time. Such systems are deficient in only focusing on particular aspects of the data warehouse system thereby not providing early diagnosis of the hardware, software and configuration problems in the data warehouse system that can cause delay and failure of the processing of queries to the data warehouse system.
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Mobile computer systems, such as laptop or notebook computers, usually include a CD-ROM drive which can be used for music enjoyment. Typically, a user listens to an audio CD through a standard set of headphones while typing or using the computer. Further, audio may be enjoyed by the user from other sources, such as DVD drives and other storage devices, and network connections as well as part of games and other applications which provide an audio component.
Since a notebook computer is mobile, the user is able to operate the computer in a variety of locations while still listening to audio via the headphones. However, many of these locations present a noisy environment to the user. The quality of the audio heard by the user is reduced when mixed with background noise from the local environment. For instance, when a user listens to music while operating the notebook computer on an airplane flight, engine noise is mixed in with the audio provided from the CD, even when using headphones. Office locations also present noisy environments to the user.
Consumer electronic manufacturers have introduced standalone headphones that have a noise reduction system incorporated directly into the headphone. Since a standard headphone set does not contain any processing capability, manufacturers of the noise reduction headphones add a microcontroller or digital signal processor (DSP) to provide a noise canceling signal. Noise reduction systems detect ambient sound surrounding the user and generate a sound wave which is opposite the sensed ambient sound. The opposite sound wave is combined with the ambient sound, resulting in cancellation of the ambient sound.
Because these standalone headphones have noise cancellation capability, they are more costly than a standard headphone set. The addition of a microcontroller or a DSP, and a built-in microphone to collect the ambient noise contribute directly to the increased cost, which in general may be as much as five times more than the standard headphone set.
Therefore, what is needed is a cost effective way to reduce or cancel environmental background noise normally heard by a user through a standard set of headphones while listening to audio while using a mobile computer system. For the reasons stated above, and for other reasons stated below which will become apparent to those skilled in the art upon reading and understanding the present specification, there is a need in the art to provide a noise reduction scheme for a mobile computer system without incorporating additional circuitry directly into a standard headphone set.
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Q:
Is it possible to post a status to your facebook wall through a url query?
In twitter it's possible by doing:
https://twitter.com/intent/tweet?text=THIS IS MY MESSAGE IT NEEDS ENCODING
Then it will bring up twitter with that message, and let you choose whether or not you want to tweet it.
I was wondering if there's a similar way with facebook posting a message through a link?
Thanks!
-Tim
A:
Yes - and you don't need an app registered to do so! The only down side, is that you have to include a URL.
The query is simply:
https://www.facebook.com/sharer/sharer.php?u=<URL>&t=<text>
For example - https://www.facebook.com/sharer/sharer.php?u=http%3A%2F%2Fshkspr.mobi%2Fblog%2F&t=Check%20out%20this%20cool%20blog
Both the URL and the text will have to be URL encoded. As I said, it won't work without a URL.
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Introduction and background
===========================
This is an account of a phenomenological study examining nursing students' perception of nursing professional identity during severe acute respiratory syndrome (SARS) outbreak. The study was a qualitative one involving interviews with a convenience sample of 10 nursing students.
Hong Kong was put on world stage due to SARS outbreak in Spring, 2003. In connection with this event, nurses were portrayed by the media as heroic, self-sacrificing and having a strong sense of morality ([@bib17]; ([@bib15]. During the SARS crisis, 386 health care workers contracted the diseases out of a total of 1755 victims. Of these 240 were nurses and one nurse subsequently died ([@bib8].
Nursing students in Hong Kong during this critical period were removed from all clinical placements in different training hospitals. The main reason was safety and the other reasons were that they were neither covered by health insurance for this kind of epidemic disease nor seen as competent enough to help. Even senior students were restricted from placement in hospitals. In this regard, they might have experienced feeling of own inadequacy as well as unachieved professionalism. Since nursing jobs certainly held elements of risk when caring for SARS patients, especially undetected cases, nursing students at this moment were likely to be motivated to clarify their devotion to and reaffirm the meaning of nursing to them.
Through this unique crisis experience, we were interested in finding out how the impact of this SARS event might have affected these learners in identifying with the profession. From an educational point of view, we wanted to see how this study could help enrich and strengthen the development of professional identity.
Importance of professional identity
===================================
On one hand, building up a positive professional identity is crucial in attracting and retaining quality nurses; on the other it helps students confirm their career choice early in their program ([@bib3]). After all, it highlights the ethical nature of the professional culture that ultimately leads to quality future practice. [@bib10] showed that perceptions of nursing significantly affect career choice of Hong Kong high school students. [@bib20] interviews with British nursing students indicated that holding a positive nursing image helps sustain motivation and retention in the nursing program. [@bib16] affirmed that professional identity is foundational to the assumption of various nursing roles. [@bib6] assured that professional identity with inherent ethical virtue contribute much to quality nursing practice. Given the current increasing public demand of high quality care in Hong Kong, professional and motivated nurses are in great need. Therefore, it is of deep concern for nursing schools to recruit and retain students who are capable and contented with their nursing identity.
Review of the literature
------------------------
Professional identity in this study was defined as self-identification with a profession. A sense of identity is defined as an organized understanding of how our personality trait, values, and beliefs fit together in defining who we are ([@bib19]). "Professional identity refers to the nurse's conception of what it means to be and act as a nurse; that is, it represents nursing students' philosophy of nursing. As such it serves as a basic frame of reference in nurses' deliberation and enactment in nursing...." ([@bib5]) "Professional identity is defined as the values and beliefs held by a nurse that guide nursing students' thinking, action and interaction with patients". Hence, values are inherent in establishing professional identity.
With a model of personal and professional development, [@bib6] posited that the existence of professional identity is contingent on personal identity. She argued that an individual develops a sense of personal identity by appropriating beliefs, emotions and motivation that are socially appreciated. [@bib5] stated that "professional identity emerges through a process of self-formation in which social interaction and self-reflection are the basic processes". She opined that working as a nurse involves a realization of self, at the same time, nurses are being perceived by society as responsible for patients' well-being, they are required to be other-oriented in thoughts and actions. Based on these interlink relationships, personal as well as professional identity, with appropriation of social appreciated values, is established through a reciprocal process of social interaction. In between, self-reflection of own thoughts and actions are the key to the processing of both personal and professional identification.
[@bib2] suggested that reflective activities such as self talk and narrative recounts on life stories enhance self formation. This self formation is subject to periodic transitions which are often triggered by emotionally powerful life events ([@bib12]). The process of periodic and incidental recounts of "who am I?" helps to revise and extend a self-organizing systems in form of emotional and cognitive processing ([@bib11]). In other words, it is through this integration of cognitive and emotional components during a reflective process that leads to organizing of personal and professional self.
Aims of the study
-----------------
The aim of this study was to address the question: *'How would nursing students perceive professional identity during the SARS outbreak ?'* Subjects were asked: '*What do you think about nursing and being nurses during the SARS outbreak?'*
Sample and data collection
--------------------------
This study used a convenience sample. There were a total of 10 subjects; all are undergraduate nursing students. The students were fully informed of the purpose and the procedure of the study. They were invited for interview on a volunteer basis. They were free to decline to participate any time and clear explanation was given beforehand to assure that anonymity and confidentiality were protected. The students were interviewed in groups of three to four. Some of the senior student participants attended community volunteer works such as dispatching health pamphlets; SARS information hotline; health exhibition; counseling of relatives of SARS victims etc. during the SARS outbreak. They provided more data related to their contact with the public. Data was obtained by interview.
Research approach and data analysis
-----------------------------------
This is a phenomenological study which attempts to uncover the perceptions that nursing students attached to what is nursing identity in the context of the SARS outbreak. The research approach is to reveal the *essence* of what it means to subjects pertaining to their lived experiences. [@bib4] stated that phenomenology seeks to render lived experience intelligible. Phenomenology is about addressing, identifying, describing, understanding and interpreting the experiences people have in their day to day lives.
The perceived world of students in this study was investigated through experiential descriptions in terms of feelings, meanings, perceptions and reactions to the events. Essential themes pertaining to various domains of interpretation were derived from these descriptions in an attempt to capture and characterize the unique experiences.
Participants were encouraged to articulate what new understanding can be found related to their experiences as nursing students facing SARS crisis. Open-ended thematic interviews were conducted by three researchers. The interviews were tape-recorded and transcribed verbatim for analysis. Approximately 10 h of audiotape resulted in over 40 pages of transcripts. A collaborative approach to analysis was employed. Intensive discussions on the phenomenological themes of the lived experiences were made among the research team, insights and understandings were derived from the data. The themes were examined, analyzed, re-interpreted and reformulated as appropriate during the process as suggested by [@bib14]. A range of themes were sorted and these are reported as below.
Findings
========
Three main themes were generated from the data. They were: (1) Appreciation and sharing of nursing identity. (2) A sense of moral duty. (3) A change of worldviews and feeling of self growth.
Appreciation and sharing nursing identity
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A number of subjects emphasized the impact of SARS. They found that they became aware of the importance of nursing roles and they valued health.
One reported:"To review all those three years of nursing education, SARS is the most impressing experience. The event made it clear to me what is nursing. Though every one knows that health is important, at this moment, I can see how important it is. All of a sudden, a lot of negative emotions are coming up. I understand more about the importance of nursing and I ascertain I will continue my career in nursing."
Another noted that there is a call for quality and certain requirements for nurses. She suggested:"Nurses should widen their scope of services. In this critical condition, I see there will be a lot of unknown epidemic diseases coming up. What is most important to nurses is non-stop learning. They should always keep their knowledge updated ... I think the most important quality of nurses is willingness to accept changes and to renew ..."
One of the respondents appreciated staff nurses who took risk of life for others and understood that the nursing job would involve altruistic elements. She accounted:"Nurses are not able to stay at home. They need to work for over 10 h. This is touching because they could only talk to their relatives through telephone"
A number of participants were warned by their parents not to take any SARS related volunteer work. They needed to rethink and make options whether they took on the identity of nursing or ordinary people. They needed to strike a balance between their obligation to family and society.
One student, who had shown hesitation before whether to continue nursing training accounted:"I know some other nursing students are thinking of withdrawal from nursing, they are at cross roads and rethinking the job nature of Nursing. Half of our group did not continue with clinical placement because of lacking Personal Protection Equipment, N95 in clinical areas. They perceived high risk inward .... I thought of withdrawal from Nursing, because infectious disease might come one after the other. Apart from SARS, we have to take risk of contracting MRSA; Hepatitis B. My family advised me to think about that as well. At this point, I have to critically think about this. As times go by, I become more and more determined to stay in the profession."
Several students repeated the same themes that they were having a sense of pride being nurses and accounted:"They (Nurses) are being great,They are being heroicHK nurses have already illustrated Nurses' spiritBeing proud of our nurses"
Several, who joined volunteer works during SARS outbreak, felt the respect given by the public and shared the nursing identity."One of the subject accounted: Public welcomed us when we told them we are poly-U Nursing students. They smiled to me, stopped and listened to me. They showed respects to us. I feel that expectation from public is very high. I feel I have great responsibility .... I was asked a lot of questions by public, I was treated as a nurse consultant."
A sense of moral duty
=====================
Some students seemed to have a strong sense of morality. They considered that they were obliged to help as there was an imminent need for help from society. In addition, they resented being labeled as "passive" university students. They expressed their discontent with self-centered people.
One of them, who attended volunteer work accounted:"I did not want to worry my parents, so I did not turn up for voluntary work that day. And then, I felt regret. I am a higher diploma year III student, I will be a registered nurse next year. This SARS looks so close to me. .... I am annoyed by the rigorous comment from internet that university students nowadays no longer take up the social responsibility ... Finally, I joined the voluntary work. At that moment, I felt the solidarity and a sense of belonging as a Poly-U nursing student. ...... It is of imminent need from society, and I have knowledge and skills, if I am not going to help (joining volunteer work), who is going to?"
Embraced with a strong sense of morality, one of students reported:"I am especially resentful to those peers who always think of own benefits, only worry about delayed placement or registration as Registered Nurse. They should think of their obligation. As a member of society, they should be clear of what the most critical thing to do at this moment ... Majority of HK people are self-centered, demanding, they always draw benefit from the government, but never think of own obligation. I feel shamed that University students are always accused of being passive"
Change of worldview and feeling of self-growth
==============================================
Having a sense of uncertainty experiencing the SARS crisis, and a feeling that government and community sectors were not dealing with the crisis well, most of the students reported that they felt they understand more about the things and the people around them and they felt suddenly being grown up:"Under this critical situation, the most important thing I can see is that everything is changing. Life is uncertain ... Every level of the society should go for a reflection: Hospital Authority, schools, community and every single person ... All HK people should take care of their health. We should put emphasis on health promotion and education. Although there are a lot of people died, I am upset. I am sure all HK people will take note of health promotion and education. Actually, HK is inadequate in health promotion. People focus on their work, not their health ... This time, they will shift their focus to maintenance of health, to keep fit and to maintain personal and environmental hygiene"
One accounted her feeling of self growth:"I feel suddenly being grown up, I understand much more. I am thinking of family and career, future prospect and social obligation. I feel I have wider perspectives, not merely thinking of myself, but thinking of the future ... I should value life and time"
Another showed positive attitudes when facing uncertainty and they accounted:"Problems are of multiple components and perspectives. We should allow a wide variety of ideas expressed among people ... The public take SARS much more fearful than we do. I understand why they are so fearful, because they are in fear of unknown ... I can show my positive perspectives through message board and sharing, showing people how I can eliminate risk by taking universal precautions."
Discussion and implications for nursing education
=================================================
Referring to the themes identified from above, a sense of closeness and pride in being nurses were developed among respondents; a professional identity was affirmed through appreciation of nursing jobs; and a sense of morality was held by nursing students. They recognized the value of nursing. The essence of the values reflected in these interviews was commitment to the profession and moral responsiveness to society. The SARS experience affected their view through alerting them the unknown risk of life and the value of health. They acknowledged the vulnerability of life with deep thought and further appreciated health related work. They were getting to recognize the value of nursing as a profession that concerns other's life and being altruistic in nature.
The findings also suggested a reorientation of interviewees' worldviews. Here, the worldview refers to "assumptions about the world in which we operate have come to constrain the way we see ourselves and our relationships" ([@bib1]). Students reported a sudden awareness of self being grown up and made a review of their own career; life and family. Moreover, participants commented on the inadequacy of the government, individuals and community sectors in handling SARS. This suggests nursing students' searching of their own positions and their relations to society. The SARS crisis challenged a person's views of the values of life and their relations to others. The event triggered a re-evaluation of the values and roles of self and society. All these findings confirmed with what [@bib5] mentioned "professional identity emerges through a process of self-formation in which social interaction and self-reflection are the basic processes.".
The findings related to the theme: "a sense of morality" are highly loaded with emotional terms such as "I felt upset"; "I am especially resentful..."; "I feel the solidarity..."; "I feel shamed..."; "I felt regret." etc. while the students in this study also reported their cognitive understanding about the social facts that "problems (mismanagement of SARS) are of multiple components" and "public is in fear of unknown". Data showed a mix of emotional and cognition components that according to [@bib11] help to revise the self-organizing systems of self system. Data also showed that interviewees initiated constructive actions of self to bring a better change of world through "I can show my positive perspectives through..."; "I can show people how I can eliminate risks by taking universal precautions" These findings seem to reveal a transition of subjects' nursing conception to actions.
After all, the study confirmed that there was a great impact of the SARS crisis which profoundly enhanced the professional identity of these nursing students. This involves a reorientation of own relations to society; a review of health and life, and a reconstitution of professional identity by nursing students.
From this study, we found respondents getting a stronger sense of nursing identity through evaluation upon the SARS related issues. In addition, the SARS experience had provided a good opportunity for experiential learning. The event exposed students to reflective observations that involve looking back at experience and considering its significance. The findings suggest experiential reflective thinking ([@bib9]) around social events such as SARS outbreak could possibly promotes a professional identification.
Incorporating SARS experience into nursing curriculum
=====================================================
In [@bib7]'s study, participants gained positive influences in professional identification from basic nursing education. [@bib21], affirmed that education plays a major part in restructuring nursing students' orientations to nursing. According to [@bib18], the most important aspects of professional education are acquisition of worldviews of that discipline. This involves a change of perspectives of own relationship to that particular discipline. [@bib13] used the term 'perspective transformation' to describe the process of becoming aware of our assumptions about oneself and others. He suggests two paths to perspective transformation: one is a sudden insight; the other is through series of transitions which permits one to revise his/her assumptions about oneself and others.
The SARS outbreak was unique in promoting a sense of belonging and bonding that made nursing students feel a part of the nursing profession. More importantly, the event provoked an instant positive change of perspectives regarding nursing identity. However, tremendous way of change is too much for us; rather, we would like to turn this critical experience into a learning opportunity. We suggest a steady instillation of nursing identity into the minds of nursing students. By incorporating SARS experiences into nursing education curriculum, a sharing session is proposed to be integrated with nursing subjects such as ethics or professional development. This session will introduce students to a rich array of materials related to SARS events, including featured story and reports, thematic video. As life stories provide a great deal of information to students as to how they should view their professional worlds, this session will have nursing professionals' sharing their vivid life experiences with SARS.
Discussion in the session will be focused on in-depth reflection upon SARS issues. For instances, how nurses struggle with and reflect upon their individual or collective experiences in various social and ethical dimensions; how the media at the time portray nursing image; how the paradoxes of nurses being victimized heroes could have happened. We hope that a recapturing and re-evaluating upon the experiences helps learners to articulate what they have learned and gain an understanding of the meaning of being a nurse.
Further, discussion could be focused on the similarities and differences between the Chinese nurses and their cultures in the Chinese mainland, Taiwan, Hong Kong, and Singapore. From the perspectives of ethnicity, culture, and the adoption of certain moral and altruistic attitudes to life, the complexity of nursing identities could be grasped and internalized.
The proposed session aims not only at the mere sharing of experiences, but training for critical thinking which involves clarification of own values and levels of commitment to the profession and society; and an appreciation of the value of life and health related jobs. Through these simulated experiencing exercises, the link between the learning experience and the reflective activity is hoped to be strengthened, assumptions about the relations of oneself to others revised and a nursing professional worldview frame identified.
Conclusion
==========
SARS outbreak is not merely a time of crisis, but a time for a reconstruction of personal view and worldview for the nursing profession. Through this event, nursing identity was affirmed among nursing students. Making sense of this event and incorporating that into educational activities would promote a process of self-growth and professional identification for nursing students.
[^1]: Tel.: +852 2766 6419 (Office); fax: +852 2364 9663 (Office).
[^2]: Tel.: +852 2766 6385 (Office); fax: +852 2364 9663 (Office).
[^3]: Tel.: +852 2766 7932 (Office); fax: +852 2364 9663 (Office).
[^4]: Tel.: +852 2766 4417 (Office); fax: +852 2364 9663 (Office).
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Workplace hostility: defining and measuring the occurrence of hostility in the workforce.
The purpose of this study was to define a comprehensive construct, workplace hostility, encompassing sub-areas of harmful workplace behaviors. Key characteristics include: perception of the target, persistence, intentionality, nonphysical nature, and organizational affiliation. Pilot study participants (N=42, students and N=35, workers) were small convenience samples. Main study participants (N=393, 70% female) were working individuals and almost 50% reported 1 to 5 years in their current jobs. The two pilot studies collected were surveys face-to-face. The main study used on-line surveys. Based on the pilot studies, items from the Workplace Hostility Inventory (WHI) were judged as a reasonable set. Results from the main study suggested three subscales related to perceptions of being subjected to hostility: interference with work, denigration, and exclusion. Supervisors produced greater distress on all factors, but only exclusion predicted a desire to leave the organization. Distress was greater when the perpetrator was a woman or a group. After controlling for feelings toward coworkers and supervisors, WHI was not related to job satisfaction. The WHI was found to be an inclusive construct, representing numerous concepts. The WHI is comprehensive and global, encompassing the previous overlap in existing research.
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Q:
Set HTML using JQuery
I try to change HTML using JQuery
jQuery("#message").html() = "Done";
but the console complains "Uncaught ReferenceError: Invalid left-hand side in assignment" How can I make it valid?
A:
Close, you want
jQuery("#message").html("Done");
A:
It is
$('#message').html('Done');
A:
jQuery("#message").html("Done");
Please read documentation you will feel better, at least your code...
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For many Singaporeans, the Wuhan respiratory virus seemed like a distant concern as they headed back to work and school in early January. News of the outbreak in central China likely crossed their Facebook news feed through the subsequent weeks, but few bothered to share or further interact with those posts.
That changed dramatically on January 23 because of two major developments. The first was the early morning announcement by the Chinese authorities that Wuhan, the epicenter of the outbreak, would be locked down with all public transport suspended.
The second breaking news development came around 9pm that same day, this time with the Singapore authorities announcing the city-state’s first confirmed case of the Wuhan coronavirus.
These two developments, together with news of the worsening outbreak in China and elsewhere around the world, sparked a spectacular surge in social media interaction — which has become a flawed but useful barometer of public attitudes in Singapore given the paucity of opinion polls.
For instance, CNA’s FB post on the first confirmed case was shared more than 25,700 times - a clear indication of the heightened concern among Singaporeans.
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No other consideration – and certainly no other commodity – has as much influence on American foreign policy as oil. In the second decade of the 21st century, the United States is completely dependent on a vast and steady supply of petroleum products in order for it to function in any familiar way.
On the political front, voices from all sides lament the nation’s lack of alternatives to “foreign oil.” Breaking free of our dependency on a finite substance that comes largely from a volatile part of the world is a goal most Americans profess to share. But the political reality is that there are huge obstacles to changing the way we live and do business. People want cheap, plentiful gas to fuel their cars. There’s clear resistance to a carbon tax. Oil companies are massively huge players in American politics. Our relationships with oil-producing countries are tentative at best. And none of this is new.
Arabian Oil, published by the University of North Carolina Press in 1949, provides a look back at a problem which has changed surprisingly little during the 60-plus years since the book’s publication. The authors’ main focus is on economics and business: they tell us what’s involved in the extraction and marketing of oil from Middle Eastern nations. But they also voice a concern that’s echoed by political observers in the present day: American dollars spent on petroleum products may prop up governments, or perpetuate dynasties, of questionable merit.
American companies pay millions of dollars directly to the rulers of oil-rich countries for the right to run their oil operations. A portion of that income, Mikesell and Chenery tell us, is then distributed to tribes or factions within the country’s population.
Since there is little distinction between the revenues of the monarch and those of the state which he governs, the payments appear as the largess of a benevolent tribal leader to his less opulent followers.
Perhaps the most fascinating single aspect of the volume appears at its end. Chapter 8 is entitled “Prospects and Conclusions,” and was clearly intended to close the book. But there’s an appended Chapter 9 – “Some Recent Developments” – that begins:
Since February 1948 when the foregoing chapters were completed, political and economic events affecting the future of Arabian oil have moved rapidly. The serious political disturbances in the Middle East have interfered with both current operations and planning for the future.
The political situation in the Middle East had been volatile since before World War I, but by 1949 it was becoming explosive. It’s doubtful that this book’s authors could have guessed that issues that were just then beginning to emerge would still be reverberating across the globe more than sixty years later. This scholarly text focuses largely on the economics of oil, but also urges the United States to devise a sane and workable “foreign petroleum policy.” In the book’s tacked-on final chapter, the authors register dismay at the rapidity with which seemingly unbreakable, long-term international agreements could be dissolved, and various economies thrown into turmoil. It’s an alarm that continues to echo in today’s headlines.
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Amyotrophic lateral sclerosis, commonly referred to as Lou Gehrig's disease, is characterized by selective, premature degeneration and death of motor neurons in the motor cortex, brain stem and spinal cord. The loss of motor neurons causes progressive muscle paralysis ultimately leading to death from respiratory failure. Approximately 90% of all amyotrophic lateral sclerosis cases are sporadic amyotrophic lateral sclerosis, without a family history of the disease, and the other approximately 10 percent of cases are cases of familial amyotrophic lateral sclerosis. Despite significant efforts to identify risk factors and potential susceptibility genes, the etiology of sporadic amyotrophic lateral sclerosis remains largely unknown.
Various rodent models carrying dominant mutations of the human superoxide dismutase (SOD1) that is causative in about 20 percent of familial amyotrophic lateral sclerosis cases, have been instrumental to model motor neuron toxicity in amyotrophic lateral sclerosis. These models have demonstrated that not only motor neurons, but also non-neuronal cell types including microglia and astrocytes play a significant role in disease onset and progression. Studies have identified microglia as mediators of motor neuron death in amyotrophic lateral sclerosis by a yet undetermined inflammatory mechanism. Insight into the mechanisms underlying motor neuron death in amyotrophic lateral sclerosis as a result of neuroinflammatory effects is pertinent for the development of successful therapies for amyotrophic lateral sclerosis.
Accordingly, the present inventors have discovered that the mechanism underlying motor neuron death as a result of neuroinflammation is activation of NF-κB in microglia, and have used this knowledge to develop therapies for amyotrophic lateral sclerosis. The pharmaceutical compositions, methods and uses, and kits described herein can be used to treat sporadic or familial amyotrophic lateral sclerosis.
Several embodiments of the invention are described by the following enumerated clauses:
1. A method for treating a patient with amyotrophic lateral sclerosis by decreasing the expression of NF-κB in the patient, the method comprising the steps of administering to the patient a composition comprising an effective amount of a compound that decreases the expression of NF-κB in microglia or macrophages of the patient; and inhibiting motor neuron death in the patient.
2. The method of clause 1 wherein the expression of NF-κB is decreased in microglia.
3. The method of clause 1 wherein the expression of NF-κB is decreased in macrophages.
4. The method of any one of clauses 1 to 3 wherein the decrease in expression of NF-κB in microglia is effective for reducing the symptoms of amyotrophic lateral sclerosis.
5. The method of any one of clauses 1 to 4 wherein a decrease in the level of expression of NF-κB in astrocytes is not effective for reducing the symptoms of amyotrophic lateral sclerosis.
6. The method of any one of clauses 1 to 5 wherein the composition comprises an aqueous solution.
7. The method of any one of clauses 1 to 6 wherein the compound is selected from the group consisting of a drug, a peptide, and a nucleic acid.
8. The method of clause 7 wherein the compound is a nucleic acid.
9. The method of clause 8 wherein the nucleic acid functions by RNA interference or is an antisense RNA molecule.
10. The method of clause 8 wherein the nucleic acid is selected from the group consisting of an siRNA, an miRNA, and an shRNA.
11. The method of clause 10 wherein the nucleic acid is an shRNA.
12. The method of any one of clauses 8 to 11 wherein the nucleic acid is delivered to the patient in a bacterial vector or in a viral vector.
13. The method of any one of clauses 8 to 11 wherein the nucleic acid has the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.
14. The method of any one of clauses 12 to 13 wherein the vector is a viral vector.
15. The method of any one of clauses 1 to 14 wherein the amyotrophic lateral sclerosis is sporadic amyotrophic lateral sclerosis.
16. The method of any one of clauses 1 to 14 wherein the amyotrophic lateral sclerosis is familial amyotrophic lateral sclerosis.
17. The method of any one of clauses 1 to 16 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 1 mg/kg of patient body weight.
18. The method of any one of clauses 1 to 17 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 500 ng/kg of patient body weight.
19. The method of any one of clauses 1 to 18 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 100 ng/kg of patient body weight.
20. The method of any one of clauses 1 to 19 wherein the composition further comprises a carrier, an excipient, or a diluent, or a combination thereof.
21. The method of clause 20 wherein the composition comprises a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is a liquid carrier.
22. The method of clause 21 wherein the liquid carrier is selected from the group consisting of saline, glucose, alcohols, glycols, esters, amides, and a combination thereof.
23. The method of any one of clauses 1 to 22 wherein the composition is administered in a single-dose or a multiple-dose regimen.
24. A method for treating amyotrophic lateral sclerosis by inhibiting the activity of NF-κB in microglia or macrophages of a patient, the method comprising the step of administering to the patient a composition comprising an effective amount of a compound that inhibits the activity of NF-κB in microglia or macrophages of the patient; and inhibiting motor neuron death in the patient.
25. The method of clause 24 wherein the activity of NF-κB is decreased in microglia.
26. The method of clause 24 wherein the activity of NF-κB is decreased in macrophages.
27. The method of any one of clauses 24 to 26 wherein the decrease in activity of NF-κB in microglia is effective for reducing the symptoms of amyotrophic lateral sclerosis.
28. The method of any one of clauses 24 to 27 wherein a decrease in the level of activity of NF-κB in astrocytes is not effective for reducing the symptoms of amyotrophic lateral sclerosis.
29. The method of any one of clauses 24 to 28 wherein the composition comprises an aqueous solution.
30. The method of any one of clauses 24 to 29 wherein the compound is selected from the group consisting of a drug, a peptide, and a nucleic acid.
31. The method of clause 30 wherein the compound is a nucleic acid.
32. The method of clause 31 wherein the nucleic acid is delivered to the patient in a bacterial vector or in a viral vector.
33. The method of clause 32 wherein the vector is a viral vector.
34. The method of clause 33 wherein the vector is selected from the group consisting of a lentiviral vector, an adeno-associated virus vector, and an adenovirus vector.
35. The method of any one of clauses 31 to 34 wherein the nucleic acid has the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.
36. The method of any one of clauses 24 to 35 wherein the amyotrophic lateral sclerosis is sporadic amyotrophic lateral sclerosis.
37. The method of any one of clauses 24 to 35 wherein the amyotrophic lateral sclerosis is familial amyotrophic lateral sclerosis.
38. The method of any one of clauses 24 to 37 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 1 mg/kg of patient body weight.
39. The method of any one of clauses 24 to 38 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 500 ng/kg of patient body weight.
40. The method of any one of clauses 24 to 39 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 100 ng/kg of patient body weight.
41. The method of any one of clauses 24 to 40 wherein the composition further comprises a carrier, an excipient, or a diluent, or a combination thereof.
42. The method of clause 41 wherein the composition comprises a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is a liquid carrier.
43. The method of clause 42 wherein the liquid carrier is selected from the group consisting of saline, glucose, alcohols, glycols, esters, amides, and a combination thereof.
44. The method of any one of clauses 24 to 43 wherein the composition is administered in a single-dose or a multiple-dose regimen.
45. A pharmaceutical composition comprising a dosage form of a compound effective to decrease the expression of NF-κB in the microglia or macrophages of a patient with amyotrophic lateral sclerosis.
46. The composition of claim 45 wherein the expression of NF-κB in microglia is decreased.
47. The composition of claim 45 wherein the expression of NF-κB in macrophages is decreased.
48. The composition of any one of clauses 45 to 47 wherein the compound is selected from the group consisting of a drug, a peptide, and a nucleic acid.
49. The composition of clause 48 wherein the compound is a nucleic acid.
50. The composition of clause 49 wherein the nucleic acid is selected from the group consisting of siRNA, an miRNA, and an shRNA.
51. The composition of clause 50 wherein the compound is an antisense RNA molecule.
52. The composition of clause 50 wherein the nucleic acid is an shRNA.
53. The composition of any one of clauses 49 to 52 wherein the nucleic acid has the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.
54. The composition of any one of clauses 45 to 53, wherein the composition further comprises one or more carriers, diluents, or excipients, or a combination thereof.
55. The composition of clause 54 wherein the composition comprises a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is a liquid carrier.
56. The composition of clause 55 wherein the liquid carrier is selected from the group consisting of saline, glucose, alcohols, glycols, esters, amides, and a combination thereof.
57. The composition of any one of clauses 45 to 56 wherein the purity of the compound is at least 98 percent based on weight percent.
58. The composition of any one of clauses 45 to 57 wherein the composition is in an ampoule or a sealed vial.
59. The composition of any one of clauses 45 to 54 or 57 to 58 in the form of a reconstitutable lyophilizate.
60. A pharmaceutical composition comprising a dosage form of a compound effective to decrease the activity of NF-κB in the microglia or macrophages of a patient with amyotrophic lateral sclerosis.
61. The composition of claim 60 wherein the expression of NF-κB in microglia is decreased.
62. The composition of claim 60 wherein the expression of NF-κB in macrophages is decreased.
63. The composition of any one of clauses 60 to 62 wherein the compound is selected from the group consisting of a drug, a peptide, and a nucleic acid.
64. The composition of clause 63 wherein the compound is a nucleic acid.
65. The composition of clause 64 wherein the nucleic acid is selected from the group consisting of siRNA, an miRNA, and an shRNA.
66. The composition of any one of clauses 63 to 65 wherein the compound is an antisense RNA molecule.
67. The composition of clause 65 wherein the nucleic acid is an shRNA.
68. The composition of clause 67 wherein the nucleic acid has the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.
69. The composition of any one of clauses 60 to 68, wherein the composition further comprises one or more carriers, diluents, or excipients, or a combination thereof.
70. The composition of clause 69 wherein the composition comprises a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is a liquid carrier.
71. The composition of clause 70 wherein the liquid carrier is selected from the group consisting of saline, glucose, alcohols, glycols, esters, amides, and a combination thereof.
72. The composition of any one of clauses 60 to 71 wherein the purity of the compound is at least 98 percent based on weight percent.
73. The composition of any one of clauses 60 to 72 wherein the composition is in an ampoule or a sealed vial.
74. The composition of any one of clauses 60 to 69 or 72 to 73 in the form of a reconstitutable lyophilizate.
75. The method or pharmaceutical composition of any one of clauses 1 to 74 wherein the composition is in a dosage form selected from the group consisting of an inhalation dosage form, an oral dosage form, and a parenteral dosage form.
76. The method or pharmaceutical composition of clause 75 wherein the composition is in a parenteral dosage form and the parenteral dosage form is selected from the group consisting of an intradermal dosage form, a subcutaneous dosage form, an intramuscular dosage form, an intraperitoneal dosage form, an intravenous dosage form, and an intrathecal dosage form.
77. The composition of clause 59 or 74 in the form of a lyophilizate.
78. The composition of any one of clauses 45 to 54, 57 to 69, or 72 to 77 in the form of a solid.
79. A kit comprising a sterile vial, the composition of any one of clauses 45 to 78, and instructions for use describing use of the composition for treating a patient with amyotrophic lateral sclerosis.
80. The kit of clause 79 wherein the compound or composition is in the form of a reconstitutable lyophilizate.
81. The kit of clause 79 or 80 wherein the dose of the compound is in the range of 1 to 5 μg/kg of patient body weight.
82. The kit of any one of clauses 79 to 81 wherein the purity of the compound is at least 99 percent based on weight percent.
83. The kit of any one of clauses 79 to 82 wherein the compound or the composition is in a parenteral dosage form.
84. The kit of clause 83 wherein the parenteral dosage form is selected from the group consisting of an intradermal dosage form, a subcutaneous dosage form, an intramuscular dosage form, an intraperitoneal dosage form, an intravenous dosage form, and an intrathecal dosage form.
85. The kit of any one of clauses 79 to 84 wherein the composition further comprises a pharmaceutically acceptable carrier.
86. The kit of clause 85 wherein the pharmaceutically acceptable carrier is a liquid carrier selected from the group consisting of saline, glucose, alcohols, glycols, esters, amides, and a combination thereof.
87. Use of the composition of any one of clauses 45 to 78 for the manufacture of a medicament for treating amyotrophic lateral sclerosis.
88. The pharmaceutical composition of any one of clauses 45 to 78 for use in treating amyotrophic lateral sclerosis.
89. The method of any one of clauses 12, 33, or 34 wherein the nucleic acid is delivered to the patient in a viral vector and the viral vector is a lentiviral vector.
90. The method or composition of any one of clauses 1 to 89 wherein administration of the composition increases the survival of the patient by 90 days or greater.
91. The method or composition of any one of clauses 1 to 90 wherein the patient has a mutation in the SOD1 gene.
92. The method or composition of any one of clauses 1 to 91 wherein the purity of the compound is at least 90 percent based on weight percent.
93. The method of any one of clauses 1 to 44 wherein the expression of a proinflammatory marker is decreased.
94. The method of clause 93 wherein the proinflammatory marker is selected from the group consisting of CD68, CD86, and NOS.
95. A method for inhibiting the expression or the activity of NF-κB in microglia or macrophages to inhibit motor neuron death, the method comprising the steps of contacting the microglia or macrophages with a composition comprising an effective amount of an exogenous compound that decreases the expression or the activity of NF-κB in the microglia or the macrophages; and inhibiting motor neuron death.
96. The method of clause 95 wherein the expression of NF-κB is decreased in microglia.
97. The method of clause 95 wherein the expression of NF-κB is decreased in macrophages.
98. The method of any one of clauses 95 to 97 wherein the composition comprises an aqueous solution.
99. The method of any one of clauses 95 to 98 wherein the compound is selected from the group consisting of a drug, a peptide, and a nucleic acid.
100. The method of clause 99 wherein the compound is a nucleic acid.
101. The method of clause 100 wherein the nucleic acid functions by RNA interference or is an antisense RNA molecule.
102. The method of clause 100 wherein the nucleic acid is selected from the group consisting of an siRNA, an miRNA, and an shRNA.
103. The method of clause 100 wherein the nucleic acid is an shRNA.
104. The method of any one clauses 100 to 103 wherein the nucleic acid is delivered in a bacterial vector or in a viral vector.
105. The method of any one of clauses 100 to 104 wherein the nucleic acid has the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.
106. A method for treating a patient with amyotrophic lateral sclerosis, the method comprising the steps of administering to the patient a first composition comprising an effective amount of a first compound that decreases the expression or the activity of NF-κB in microglia or macrophages of the patient; administering to the patient a second composition comprising an effective amount of a second compound that decreases the expression of SOD-1 in astrocytes, motor neurons, neurons, and/or oligodendrocytes of the patient; and inhibiting motor neuron death in the patient.
107. A method for inhibiting the expression or activity of NF-κB in microglia or macrophages of a patient with amyotrophic lateral sclerosis and for inhibiting the expression of SOD-1 in the patient, the method comprising the steps of contacting the microglia or macrophages in the patient with a first composition comprising an effective amount of a first compound that decreases the expression or the activity of NF-κB in the microglia or the macrophages in the patient; contacting the astrocytes in the patient with a second composition comprising an effective amount of a second compound that decreases the expression of SOD-1 in astrocytes, motor neurons, neurons, and/or oligodendrocytes of the patient; and inhibiting motor neuron death.
108. The method of clause 106 or 107 wherein the expression of NF-κB is decreased in microglia.
109. The method of clause 106 or 107 wherein the expression of NF-κB is decreased in macrophages.
110. The method of any one of clauses 106 to 109 wherein the decrease in expression of NF-κB in microglia is effective for reducing the symptoms of amyotrophic lateral sclerosis.
111. The method of any one of clauses 106 to 110 wherein a decrease in the level of expression of NF-κB in astrocytes is not effective for reducing the symptoms of amyotrophic lateral sclerosis.
112. The method of any one of clauses 106 to 111 wherein the composition comprises an aqueous solution.
113. The method of any one of clauses 106 to 112 wherein the first compound is selected from the group consisting of a drug, a peptide, and a nucleic acid.
114. The method of any one of clauses 106 to 113 wherein the second compound is selected from the group consisting of a drug, a peptide, and a nucleic acid.
115. The method of clause 113 or 114 wherein the compound is a nucleic acid.
116. The method of clause 115 wherein the nucleic acid functions by RNA interference or is an antisense RNA molecule.
117. The method of clause 116 wherein the nucleic acid is selected from the group consisting of an siRNA, an miRNA, and an shRNA.
118. The method of clause 117 wherein the nucleic acid is an shRNA.
119. The method of clause 118 wherein the nucleic acid is delivered to the patient in a bacterial vector or in a viral vector.
120. The method of clause 119 wherein the nucleic acid has the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.
121. The method of clause 119 wherein the vector is a viral vector.
122. The method of any one of clauses 106 to 121 wherein the amyotrophic lateral sclerosis is sporadic amyotrophic lateral sclerosis.
123. The method of any one of clauses 106 to 121 wherein the amyotrophic lateral sclerosis is familial amyotrophic lateral sclerosis.
124. The method of any one of clauses 106 to 123 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 1 mg/kg of patient body weight.
125. The method of any one of clauses 106 to 124 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 500 ng/kg of patient body weight.
126. The method of any one of clauses 106 to 125 wherein the amount of the compound is in the range of about 1 ng/kg of patient body weight to about 100 ng/kg of patient body weight.
127. The method of any one of clauses 106 to 126 wherein the composition further comprises a carrier, an excipient, or a diluent, or a combination thereof.
128. The method of clause 127 wherein the composition comprises a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier is a liquid carrier.
129. The method of clause 128 wherein the liquid carrier is selected from the group consisting of saline, glucose, alcohols, glycols, esters, amides, and a combination thereof.
130. The method of any one of clauses 106 to 129 wherein the composition is administered in a single-dose or a multiple-dose regimen.
131. The method of any one of clauses 106 to 130 wherein the composition is in a dosage form selected from the group consisting of an inhalation dosage form, an oral dosage form, and a parenteral dosage form.
132. The method of clause 131 wherein the composition is in a parenteral dosage form and the parenteral dosage form is selected from the group consisting of an intradermal dosage form, a subcutaneous dosage form, an intramuscular dosage form, an intraperitoneal dosage form, an intravenous dosage form, and an intrathecal dosage form.
133. The method of any one of clauses 106 to 132 wherein administration of the first or the second composition increases the survival of the patient by 90 days or greater.
134. The method of any one of clauses 106 to 133 wherein the patient has a mutation in the SOD1 gene.
135. The method of any one of clauses 106 to 134 wherein the purity of the first or the second compound is selected from the group consisting of at least 90 percent, at least 95 percent, at least 96 percent, at least 97 percent, at least 98 percent, at least 99 percent, and at least 99.5 percent.
136. The method of any one of clauses 1 to 44, 75, 76, or 90 to 105 wherein the purity of the compound is selected from the group consisting of at least 90 percent, at least 95 percent, at least 96 percent, at least 97 percent, at least 98 percent, at least 99 percent, and at least 99.5 percent.
137. The method of any one of clauses 106 to 135 wherein the first composition and/or the second composition comprises an aqueous solution.
138. The method of any one of clauses 1 to 44, 75, 76, or 90 to 137 wherein the compound comprises an adeno-associated virus vector.
139. The method of any one of clauses 1 to 44, 75, 76, or 89 to 105 wherein the administration of the compound increases the survival of the patient for a number of days selected from the group consisting of at least 20 days, at least 30 days, at least 35 days, at least 40 days, at least 45 days, at least 50 days, at least 55 days, at least 60 days, at least 65 days, at least 70 days, at least 75 days, at least 80 days, at least 85 days, at least 90 days, at least 95 days, at least 100 days, at least 150 days, at least 200 days, at least 250 days, and at least 300 days compared to a patient who is not treated with the compound.
140. The method of any one of clauses 106 to 132, 134 to 135, or 137 wherein the administration of the first compound or the second compound increases the survival of the patient for a number of days selected from the group consisting of at least 20 days, at least 30 days, at least 35 days, at least 40 days, at least 45 days, at least 50 days, at least 55 days, at least 60 days, at least 65 days, at least 70 days, at least 75 days, at least 80 days, at least 85 days, at least 90 days, at least 95 days, at least 100 days, at least 150 days, at least 200 days, at least 250 days, and at least 300 days compared to a patient who is not treated with the first or the second compound.
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FILE - In this July 29, 2010, file photo, Maricopa County Sheriff Joe Arpaio speaks at a news conference in Phoenix. President Donald Trump plans to revitalize a long-standing program to deputize local police officers to enforce federal immigration law. The program was used in the past by Arpaio, then sheriff of metro Phoenix, to conduct immigration patrols that were later discredited in court. (AP Photo/Matt York, File)
FILE - In this July 29, 2010, file photo, Maricopa County Sheriff Joe Arpaio speaks at a news conference in Phoenix. President Donald Trump plans to revitalize a long-standing program to deputize local police officers to enforce federal immigration law. The program was used in the past by Arpaio, then sheriff of metro Phoenix, to conduct immigration patrols that were later discredited in court. (AP Photo/Matt York, File)
PHOENIX (AP) — To build his highly touted deportation force, President Donald Trump is reviving a long-standing program that deputizes local officers to enforce federal immigration law.
The program received scant attention during a week in which Trump announced plans to build a border wall, hire thousands more federal agents and impose restrictions on refugees from Middle Eastern countries.
But the program could end up having a significant impact on immigration enforcement around the country, despite falling out of favor in recent years amid complaints that it promotes racial profiling.
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More than 60 police and sheriff’s agencies had the special authority as of 2009, applying for it as the nation’s immigration debate was heating up. Since then, the number has been halved and the effort scaled back as federal agents ramped up other enforcement programs and amid complaints officers weren’t focusing on the goal of catching violent offenders and instead arrested immigrants for minor violations, like driving with broken tail lights.
Sheriff Joe Arpaio used the program most aggressively in metro Phoenix, and he became arguably the nation’s best-known immigration enforcer at the local level in large part because of the special authority. In a strange twist, he was thrown out of office in the same election that vaulted Trump to the presidency, mostly because of mounting frustration over legal issues and costs stemming from the patrols.
In his executive order this week, Trump said he wants to empower local law enforcement to act as immigration officers and help with the “investigation, apprehension, or detention” of immigrants in the country illegally.
The move comes at a time when the country is sharply divided over the treatment of immigrants. Cities such as Chicago and San Francisco have opposed police involvement in immigration while some counties in Massachusetts and Texas are now seeking to jump in.
Proponents say police departments can help bolster immigration enforcement and prevent criminals from being released back into their neighborhoods, while critics argue that deputizing local officers will lead to racial profiling and erode community trust in police.
Cecillia Wang, an American Civil Liberties Union attorney, said police bosses who want to get into immigration enforcement should consider what happened when 100 of Arpaio’s deputies were given the federal arrest power.
The longtime sheriff used the authority to carry out traffic patrols that targeted immigrants. The patrols were later discredited in a lawsuit in which a federal judge concluded Arpaio’s officers had racially profiled Latinos. The lawsuit so far cost county taxpayers $50 million.
“There are people like Joe Arpaio who have a certain political agenda who want to jump on the Trump bandwagon,” Wang said, adding later that the Arizona sheriff was “most vocal and shameless offender” in the program.
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When asked to comment on Trump’s effort to revitalize the program, a Department of Homeland Security spokeswoman said the executive orders would speak for themselves.
Traditionally, police stayed out of immigration enforcement and left those duties to federal authorities. But a 1996 federal law opened up the possibility for local agencies to participate in immigration enforcement on the streets and do citizenship checks of people in local jails.
Immigration and Customs Enforcement trained and certified roughly 1,600 officers to carry out these checks from 2006 to 2015.
The Obama administration phased out all the arrest power agreements in 2013, but still let agencies check whether people jailed in their jurisdiction were citizens. If they find that an inmate is in the country illegally, they typically notify federal authorities or hand them over to immigration officers. Today, more than 30 local agencies participate in the jail program.
Alonzo Pena, a retired deputy director of U.S. Immigration and Customs Enforcement who once oversaw such agreements with police agencies, said some officers were using the authority in ways that didn’t match the agency’s enforcement priorities.
He said federal officials need to closely monitor participants to ensure their actions don’t veer away from the goal of catching violent offenders and confronting national security threats. “It’s hard to regulate to make sure it’s followed,” Pena said.
In California, three counties nixed the program after state legislation and a federal court ruling in nearby Oregon limited police collaboration with immigration enforcement. Orange County still makes the immigration checks inside its jail and flags inmates for deportation officers, but won’t hold anyone on behalf of federal authorities out of legal concerns.
“The window has narrowed to a large extent,” said Orange County sheriff’s Lt. Mike McHenry.
With Trump in office, the program has new life.
Even before the change in administration, two Republican county sheriffs in Massachusetts said they were starting programs. In Texas, Jackson County sheriff A. J. “Andy” Louderback said two officers will get trained to run immigration jail checks this spring and nearby counties want to follow suit.
Louderback said teaming up with federal agents will cost his agency roughly $3,000 — a small price to pay to cover for officers while they’re on a four-week training course, especially in an area struggling with human smuggling. Once the program is underway, he said immigration agents will send a daily van to pick up anyone flagged for deportation from jail.
“It just seems like good law enforcement to partner with federal law enforcement in this area,” he said. “It takes all of us to do this job.”
Experts said Trump’s outreach to local law enforcement will create an even bigger split between sanctuary cities that keep police out of immigration enforcement and those eager to help the new president bolster deportations.
“There is no question that in order to do the type of mass deportation that he promised, it will require him conscripting local law enforcement agencies,” said Chris Newman, legal director of the National Day Laborer Organizing Network. “It is going to balkanize things ... and we’re going to see more of the extremes.”
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Taxin reported from Santa Ana, California.
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Follow Jacques Billeaud on Twitter at www.twitter.com/jacquesbilleaud and Amy Taxin at www.twitter.com/ataxin
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Carisoprodol (Soma(R)) is a centrally-acting skeletal muscle relaxant frequently prescribed for the treatment of acute musculoskeletal conditions. In recent years, there has been increasing concern regarding carisoprodol's potential as a drug of abuse. In 1991, carisoprodol was ranked 54th among 234 drugs with abuse potential. Only eight years later, the Drug Abuse Warning Network identified carisoprodol as the 14th most abused drug, ranking higher than oxycodone, methadone, and LSD. In support of this, recent reports have substantiated the dangers involved in carisoprodol abuse, including severe withdrawal leading to seizures and death. However, its mechanism of action remains unclear. Until recently, it was widely accepted that the sedative effects of carisoprodol were predominantly due to its metabolite, meprobamate. However, preliminary in vivo and in vitro studies conducted in our laboratory demonstrate that carisoprodol itself is active, and its actions appear to be mediated via novel modulation of the GABAA receptor (GABAAR), the predominant inhibitory neurotransmitter receptor in mammalian brain. This may underlie the capacity of carisoprodol to enhance the sedative effects of CNS depressants, contributing to its potential for abuse. Indeed, concerns about the rise in abuse of carisoprodol have led the Drug Enforcement Agency to contact the National Institute on Drug Abuse for assistance in determining the abuse liability of carisoprodol. Based on our preliminary findings, we hypothesize that carisoprodol itself causes depressive CNS effects, and that these actions are mediated via a novel interaction with the GABAA receptor. The overall goal of the proposed study is to identify the mechanisms that mediate carisoprodol abuse, at both the behavioral and molecular level. We will utilize both in vivo (drug discrimination and observation of intoxication, tolerance and withdrawal, and pharmacokinetic analysis) and in vitro (assessment of carisoprodol on specific configurations of recombinant GABAA receptors) approaches to address the following specific aims: 1) To characterize the discriminative stimulus effects of carisoprodol;2) To investigate whether carisoprodol produces effects on its own in vivo or requires being metabolized to meprobamate;3) To assess the extent of carisoprodol dependence and severity of withdrawal;4) To identify GABAA receptor subunits critical for allosteric modulatory and direct gating effects of carisoprodol;and 5) To identify GABAA receptor subunit domains that confer carisoprodol sensitivity. Given the present and potential dangers posed by carisoprodol abuse, it is of crucial importance to determine the mechanism of action of this drug. Our proposed studies will substantially increase our understanding of the mechanism of action of carisoprodol as a therapeutic agent and as a drug of abuse. This knowledge may provide insight into treating carisoprodol dependence, and withdrawal. PUBLIC HEALTH RELEVANCE: The muscle relaxant Carisoprodol (Soma(R)) is being abused increasingly at an alarming rate;withdrawal from overuse of this drug can cause seizures and even death. There is an urgent need to develop new drugs that can treat these symptoms, as well as new drugs that are less likely to be abused. The proposed studies will provide the fundamental information needed to address both of these current unmet medical needs.
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You Know You’re a Geography Student When…
1. Your bedroom wall is covered in maps
2. You own an item of clothing that has a map on it
3. …okay, you own more than one item of clothing with a map on it
4. In fact, you tend to buy everything possible that is decorated with maps
5. Your love is more than skin deep
6. You have a subscription to National Geographic
7. …and to work for them is your dream job
8. You know the Animaniacs Nations of the World song off by heart
9. You also have a tendency to be attracted to songs and artists with geographic names
10. You have a love/hate relationship with G.I.S
11. This shirt makes you shamelessly chuckle
12. …as does this picture
13. You have reflected upon your favourite projection
14. You have strong opinions regarding the name ‘North West’
15. You have or at least consider calling your pets/children geography related names (Gai, Atlas, India, etc.)
16. You become frustrated when people interchange England and Britain, Ireland and Northern Ireland, and commit other such rookie mistakes
17. You know who this man is, and you love him
18. You have a geography related blog
19. At some point in your academic career, you have coloured in a map
20. This painting fills you with pride
21. You likelove live to travel
22. ….but feel guilty about how it impacts the environment
23. You have been asked by your peers about what you want to do with your degree
24. …which has led you to question future prospects (or lack thereof)
25. …but then you stop, smile and remember that geography makes the world go round
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Item details
The Particles White Background features an elegant animation of white particles shining over a grey background. This animation is perfect as a background for minimalistic projects, festivities, invitations, anniversaries, fantasy videos, games and much more!
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[Morphological changes in chickens receiving cadmium with the feed].
An experiment was carried out with a total of 100 broiler chickens of the Plymouth Rock breed. From hatching up to the 56th day of age they were offered a maize-soybean ration that was balanced in terms of nutrients and exogenically supplemented with cadmium at various rates in the form of cadmium chloride. The birds were divided into five experimental groups. The first group was given the basic ration with 2.5 mg Cd per kg of feed. The second group was given the same ration with 5 mg Cd; the third group--the same feed with 10 mg Cd; and the fourth group--the same ration with 20 mg Cd. The morphologic studies revealed that the presence of Cd in the feed led to severe dystrophic and necrotic changes accompanied with hemorrhages in the kidneys, heart muscle, and liver. Besides, the birds of the second and third group showed thinning and prolongation of villi intestinales, and those of the fourth group--shortening and thickening of the villi in the small intestine. These changes were indicative of chronic toxic lesions.
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Justin B. Terry-Smith has been involved in Gay and HIV Activism since 1999. He is a Air Force 9/11 Disabled Vet. Raised in Silver Spring, MD, he now lives in Severn, MD with his husband Phil. He writes an HIV/STI Advice Column for A&U Magazine and is a Contributing writer for thebody.com. He earned an AA in Communications, a BA in Political Science, Masters and Doctorate in Public Health with a concentration in Infectious Disease.
Justin's HIV Journal
Thursday, March 26, 2009
Justin's HIV Journal: HIV in DC, Thank you Ongina
Hello Everyone,
Let me just start out by saying that I’m sorry for not writing you guys in a while, things have change a little bit.I recently just got a job with the IRS and so now my hours are 9-5 M-F.So as of now I’m a Federal Government Employee. It’s paramount that people with a disease like HIV have very good health insurance and the government does well in that category, when it comes to its employees.Well I hope you enjoy this entry.
Look at the video below !!!
According to the Washington Post, WashingtonDC leads the country in HIV/AIDS infections in major cities.Mayor Adrian M. Fenty released the report at a news conference.He called it a wake-up call for the District and one of the "most serious problems" facing the city. The report confirmed that at least 15,120 residents, about 3,000 per every 100,000 over the age of 12, have HIV or AIDS.
More than three-quarters -- 76 percent -- of the HIV infected are black, 70 percent are men and 70 percent are age 40 and older.
This is crazy; it hurts to see these numbers, they are so high.Several of my friends that are in this area are HIV Activist and are trying their best to stop the virus from spreading all over the city.A lot of them are not surprised but I can say that it also hurts me because this city, WashingtonDC, is my home.I feel responsible in some way.I also feel a responsibility to stop it or to help slow it down considerably.
Justin B Smith’s Video
Mayor Fenty also went on the say that only one baby was born with HIV in 2007, compared with 10 in 2005. Also, 70,000 residents were tested for HIV as part of an aggressive campaign, compared with 40,000 four years ago. The Centers for Disease Control and Prevention reported that the District is one of the top three jurisdictions in the country in conducting the most HIV tests and identifying the greatest number of HIV-infected residents.What should we do as a community?What should I do as an activist?I’m asking you right now YES YOU, TELL ME Leave a comment.
This spunky girl was just what the doctor ordered.I know I’m late in doing this but I needed to thank you Ongina from RuPaul’s Drag Race.RuPaul’s Drag Race is a show on the LGBT themed, Logo Station.The show is hosted by truest of all true Drag Queen’s RuPaul herself.The show is a competition in which a half full of Drag Queens compete to become America’s next drag super star.All of the contestants were great but one stuck out with her beautiful personality and courage.
There was a challenge that the girls had to promote MAC cosmetics.MAC AIDS Funds gives a lot of money towards the fight on HIV/AIDS.In this challenge the girls were suppose to make there own commercial for the MAC Cosmetics.Well Ongina shined through and won the competition.When she found out that she won she broke down and cried.The teary eyed Ongina crouched down and stood back up and announced that she was infected with the HIV virus.When I saw this I cried myself.
I would like to personally thank Ongina for doing this selfless, inspirational, and courageous act on national television.Thank you so much you are and will help others through your own strength.Thank you so much for helping to erasing the stigma of HIV/AIDS in our community. In the famous words of Ongina “You have to Celebrate Life”.
NEXT TRIP
Well I have a vacation coming up and Justin’s HIV Journal is going to San Francisco.I’m going with my partner Dr. Philip Terry of Prevention Works, which is a HIV/AIDS prevention organization.We’re going there because the NBJC (National Black Justice Coalition) is having a conference there and it should be great.I can’t wait.So you in the Bay Area
4 comments:
Justin. What do you mean my dear brother, when you say you 'feel responsible in some way' when you see the AIDS stats rising?
'That you feel a responsibility to stop it or help slow it down considerably'?
NO, NO, NO!!!!! Where are you even going to start? Please tell me!
The major reason (not the only reason, I know)that many people are continuing to contract the virus, yes, despite so much media attention, and other people doing their best to highlight this disease, is our refusal to change our sexual behaviour. It is our refusal to be responsible to ourselves.
Justin B Terry-Smith
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About Justin B Terry-Smith
My name is Justin B Terry-Smith, I'm a Black Gay man living in Laurel, Maryland and I am HIV+. I've decided to share my story because I feel it's important that people who have unprotected sex know what they might be getting themselves into. People have asked me why I am doing this, why have I put my personal business out like this. I tell them it is to help educate people, to make them aware and to make them think twice about having unprotected sex. This is my personal journey that needs to be told to help the community.
HIV is neither glamorous or a rite of passage. Watch the Journal and think twice.
In the words of Pedro Zamora, "I'm not dying. I'm living with it"
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Angiogenesis in metabolic-vascular disease.
Angiogenesis, literally formation of new blood vessels, is the main process through which the vascular system expands during embryonic and postnatal development. Endothelial cells, which constitute the inner lining of all blood vessels, are typically in a quiescent state in the healthy adult organism. However, in vascular and metabolic diseases, the endothelium becomes unstable and dysfunctional. The resulting tissue hypoxia may thereby induce pathological angiogenesis, which is a hallmark of disease conditions like cancer or diabetic retinopathy. However, recent evidence suggests that angiogenesis is also a major player in the context of further metabolic diseases, especially in obesity. In particular, deregulated angiogenesis is linked with adipose tissue dysfunction and insulin resistance. On the other hand, signalling pathways, such as the PI3K pathway, may regulate metabolic activities in the endothelium. Endothelial cell metabolism emerges as an important regulator of angiogenesis. This review summarises the role of angiogenesis in metabolic-vascular disease, with specific focus on the role of angiogenesis in obesity-related metabolic dysfunction and on signaling pathways, especially PI3K, linking cell metabolism to endothelial function.
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Rok Vodišek
Rok Vodišek (born 5 December 1998) is a Slovenian professional footballer who plays for Serie A side Genoa as a goalkeeper.
Career
Vodišek made his senior debut whilst on loan at Slovenian Second League club Šenčur on 13 March 2016 in a 4–1 loss to Triglav.
The following season, Vodišek returned to his parent club and made his debut for Olimija on 11 September 2016 in a 1–0 win over Gorica.
Genoa
On 2 July 2018, Vodišek signed with Italian Serie A club Genoa.
International career
Vodišek has represented Slovenia at under-17, under-19, and under-21 levels.
Career statistics
Notes
References
External links
Rok Vodišek profile at NZS
Category:1998 births
Category:Living people
Category:Association football goalkeepers
Category:Slovenian footballers
Category:Slovenian expatriate footballers
Category:Slovenian PrvaLiga players
Category:Serie A players
Category:NK Olimpija Ljubljana (2005) players
Category:Genoa C.F.C. players
Category:Slovenian expatriate sportspeople in Italy
Category:Expatriate footballers in Italy
Category:Slovenia youth international footballers
Category:Slovenia under-21 international footballers
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Project i2i: Bringing Philippine’s Unbanked into the Financial System
The Philippines have recently announced a potential test run of a real-time retail payments system developed by Consensys, which is based off of the Ethereum blockchain. The mission behind introducing this system is to get unbanked consumers into the country’s financial system.
The five banks that have been chosen, come from Mindanao, the second largest island in the country, which includes Cantilan Bank, PR Savings Bank, City Savings Bank, FairBank and Progressive Bank.
According to the Union Bank, which is the main Bank of the Philippines, the entirety of this project has been named the ‘Project i2i’, where i2i takes on several meanings including “island-to-island, institution-to-institution and individual-to-individual.” Additionally, they’ve stated that this action has been implemented to bring together rural banks with the Philippines’ main banking system in place.
Philippines financial network works differently, as some of its banks, mainly those situated in rural regions are not authorized to do as much as the main financial system. More specifically, these institutions neither belong to Bancnet nor do they belong to the Philippines Clearing House. This means that such rural banks do not have the authority to issue checks, but rather run basic financial services, mostly dealing with cash and money orders, for its people.
According to a statement made by the country’s central bank, over half of the cities in the Philippines remain unbanked. To resolve this disparity, the blockchain platform has been applied, as Said Union Bank’s operations chief, Henry Aguda:
“they don’t have to spend anything. They just have to load the application i2i in their computers, tablets, or smartphones then they can transact bank-to-bank”
As for the blockchain aspects of this $3 million project, Consensys’ Kaleido platform will be used, which is a service platform that was launched by the partnership between Amazon Web Services (AWS) and Consensys. The platform is known for its several features including consensus mechanisms, integrated analytics and multiple protocols.
The EVP at Cantilan Bank, Tanya Hotchkiss, sees a lot of hope in this project, as she believes this test run:
Furthermore, the executives involved are anticipating more for the reduced transaction fees than anything – possibly impacting the rates of the Philippine peso to go from PHP50 to PHP150. Will the Philippines succeed in their goal of getting in 100 rural banks into their main financial system by year-end?
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Case: 13-30261 Document: 00512449158 Page: 1 Date Filed: 11/21/2013
IN THE UNITED STATES COURT OF APPEALS
FOR THE FIFTH CIRCUIT
United States Court of Appeals
Fifth Circuit
No. 13-30261
FILED
November 21, 2013
Summary Calendar
Lyle W. Cayce
Clerk
AMY KIRKLAND,
Plaintiff-Appellant,
v.
BIG LOTS STORE, INC.,
Defendant-Appellee.
Appeal from the United States District Court
for the Western District of Texas
U.S.D.C. No. 3:12-CV-7
Before STEWART, Chief Judge, and SMITH and DENNIS, Circuit Judges.
PER CURIAM:*
Plaintiff-Appellant Amy Kirkland (“Kirkland”) appeals the district
court’s dismissal of her employment discrimination law suit against
Defendant-Appellee Big Lots Store, Inc. (“Big Lots”). We AFFIRM.
I. FACTUAL AND PROCEDURAL BACKGROUND
Kirkland worked as a cashier/stocker for Big Lots in West Monroe,
Louisiana from September 2008 until June 2009. Kirkland alleges that during
* Pursuant to 5TH CIR. R. 47.5, the court has determined that this opinion should not
be published and is not precedent except under the limited circumstances set forth in 5TH
CIR. R. 47.5.4.
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No. 13-30261
the latter stages of her employment, she experienced constant harassment by
fellow employees and, despite her complaints, Big Lots management never
made efforts to remedy the situation. Kirkland claims that the work
environment was unbearable because a fellow employee spread rumors that
Kirkland engaged in an extra-marital sexual relationship with one of Big Lots’
managers. Kirkland also claims that this employee told other employees that
Kirkland and her husband were “swingers” and that Kirkland’s husband had
“diseases.” Kirkland alleges that the stress and anxiety she experienced as a
result of these purportedly false allegations culminated in her resignation from
Big Lots on June 11, 2009.
In an effort to seek relief for what she considers a constructive discharge,
Kirkland initiated contact with the Louisiana Commission on Human Rights
(“LCHR”) 1 by submitting an intake questionnaire detailing allegations of sex
discrimination on the part of Big Lots. Kirkland claims that she mailed the
intake questionnaire on March 2, 2010, but the LCHR’s records indicate that
it received the intake questionnaire on May 6, 2010. On June 2, 2010, the
LCHR sent a letter to Kirkland acknowledging receipt of the intake
questionnaire. On September 15, 2011, the LCHR sent Kirkland a “Dismissal
and Notice of Rights” stating that “[b]ased upon its investigation, the LCHR
[was] unable to conclude that the information obtained establishe[d] violations
of the statutes.” The EEOC also reviewed Kirkland’s claims of discrimination
and issued its own “Dismissal and Notice of Rights” on October 4, 2011, making
the same findings as the LCHR.
1The LCHR is a state agency that has authority to remedy employment discrimination
pursuant to a work sharing agreement with the Equal Employment Opportunity Commission
(“EEOC”). Conner v. La. Dep’t. of Health & Hosp., 247 F. App’x 480, 481 (5th Cir. 2007) (per
curiam) (unpublished); La. Rev. Stat. Ann. §§ 51:2231─51:2265. Because the LCHR exists,
Louisiana is considered a “deferral state.” Conner, 247 F. App’x at 481.
2
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No. 13-30261
On January 4, 2012, Kirkland filed suit in the district court alleging
federal and state claims of employment discrimination on the basis of sex
pursuant to 42 U.S.C. §§ 2000e─2000e1 (“Title VII”) and La. Rev. Stat. Ann
§ 23:301. Big Lots moved to dismiss Kirkland’s suit arguing that it was time
barred and failed to state a claim upon which relief could be granted. The
district court granted Big Lots’ motion to dismiss on the grounds that
Kirkland’s claims to the LCHR were not timely filed. 2 Kirkland appeals the
dismissal herein.
II. DISCUSSION
A. Standard of Review
We review the district court’s dismissal under Federal Rule of Civil
Procedure 12(b)(6) de novo. Elsensohn v. St. Tammany Parish Sheriff’s Office,
530 F.3d 368, 371 (5th Cir. 2008). “A statute of limitations may support
dismissal under Rule 12(b)(6) where it is evident from the plaintiff’s pleadings
that the action is barred and the pleadings fail to raise some basis for tolling
or the like.” Jones v. Alcoa, Inc., 339 F.3d 359, 366 (5th Cir. 2003) (citations
omitted).
B. Timeliness of Kirkland’s Filing with the LCHR
Kirkland argues that the district court erred in finding that her
complaint to the LCHR was untimely. Kirkland acknowledges that the
deadline for a timely filing in her case was April 7, 2010, 300 days from the day
she resigned from Big Lots. She claims that she mailed an intake
2Kirkland’s arguments on appeal focus on her Title VII claim and do not allege error
in the district court’s dismissal of the state law claim. For that reason, we consider any
argument with respect to the state law claim waived. See Cutrera v. Bd. of Sup’rs of La. State
Univ., 429 F.3d 108, 114 (5th Cir. 2005).
3
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No. 13-30261
questionnaire 3 to the LCHR on March 2, 2010 and offers her attorney’s “log” 4
as proof of this fact. Big Lots, conversely argues that Kirkland’s complaint was
not filed until May 6, 2010. As evidence, the LCHR offers the cover letter that
accompanied Kirkland’s intake questionnaire which is stamped as received by
the LCHR on May 6, 2010.
When an employment discrimination claim is brought in a deferral state,
an aggrieved employee must file a claim with the designated state agency or
the EEOC within 300 days of the alleged unlawful employment action. See
Nat’l R.R. Passenger Corp. v. Morgan, 536 U.S. 101, 109 (2002). “A claim is
time barred if it is not filed within these limits.” Id. Mailing is not filing for
the purposes of Title VII. See Taylor v. Gen. Tel. Co. of Sw. 759 F.2d 437, 440
(5th Cir. 1985). A claim is considered filed when it is received by the EEOC or
the state agency responsible for the administration of complaints of
employment discrimination. Id.; 29 C.F.R. § 1601.13(a)(4)(2)(a)(A) (2010).
Accordingly, Kirkland’s claim was not filed until it was received by the LCHR
on May 6, 2010. Again, the deadline for a timely filing in Kirkland’s case was
April 7, 2010. Because Kirkland’s intake questionnaire was not filed within
the 300-day period required by Title VII, her claims are time barred. See Zipes
v. Trans World Airlines, Inc., 455 U.S. 385, 393 (1982) (holding that in this
context, the filing deadline is tantamount to a statute of limitations).
3The submission of an intake questionnaire is “sufficient to set[] the administrative
machinery in motion” and may constitute a filing for the purposes of Title VII. See Conner,
247 F.App’x at 481 (citation and internal quotation marks omitted); Fed. Exp. Corp. v.
Holowecki, 552 U.S. 389, 404 (2008).
4In opposition to Big Lots’ motion to dismiss, Kirkland offered her attorney’s log of
activities related to this matter as evidence that the intake questionnaire was mailed to the
LCHR on March 2, 2010.
4
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No. 13-30261
Generally, when an employment discrimination charge is untimely filed
with the EEOC or designated state agency, a suit based upon the untimely
charge should be dismissed. Barrow v. New Orleans S.S. Ass’n, 932 F.2d 473,
476─77 (5th Cir. 1991). In limited circumstances, the filing deadline is subject
to equitable doctrines such as tolling or estoppel. Zipes, 455 U.S. at 393. The
plaintiff has the burden of providing a sufficient factual basis for tolling the
filing deadline. Conway v. Control Data Corp., 955 F.2d 358, 362 (5th Cir.
1992). We have recognized at least three circumstances where failure to timely
file may be excused under the equitable tolling doctrine: (1) a suit is pending
between the parties in the incorrect forum; (2) the claimant is unaware of facts
supporting her claim because the defendant intentionally concealed them; and
(3) the claimant is misled by the EEOC or designated state agency about her
rights. See Manning v. Chevron Chemical Co. 332 F.3d 874, 880 (5th Cir.
2003). 5
Kirkland argues that the equitable tolling doctrine should apply in this
case for reasons we find unavailing. Kirkland does not provide arguments
under the Manning factors or cite any case law that would otherwise support
equitable tolling in this case. Instead, she relies on the fact that despite her
untimely filing, the EEOC “nevertheless investigated [her] claim as if it had
been filed in a timely manner.” With respect to the EEOC’s investigation, the
record does not indicate that the EEOC made a finding as to the timeliness of
5This is not to say that the factors listed in Manning constitute an exhaustive list of
circumstances that justify equitable tolling. Situations other than those listed in Manning
could justify tolling. For example, we have stated that equitable tolling may be appropriate
“in rare and exceptional circumstances when a plaintiff is actively misled by the defendant
about the cause of action or is prevented in some extraordinary way from asserting his
rights.” Lovett v. Barbour Intern., Inc., 211 F. App’x 281, 284 (5th Cir. 2006) (per curiam)
(unpublished) (citation and internal quotation marks omitted).
5
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No. 13-30261
Kirkland’s claim. It simply provided a “Dismissal and Notice of Rights”
indicating that based on its review, Kirkland’s claims lacked merit. Morever,
the EEOC’s investigation of an untimely filed claim does not safeguard that
claim from dismissal pursuant to 12(b)(6). The EEOC’s decision to investigate
an untimely filed claim is its own prerogative, and, contrary to Kirkland’s
assertion, federal courts are expected to make “an independent determination”
as to a claimant’s “compliance with Title VII’s filing requirements.” Burrell v.
Brown, 228 F.3d 410, *4 (5th Cir. 2000) (per curiam) (unpublished) (citing
Chappell v. Emco Mach. Works Co., 601 F.2d 1295, 1304 (5th Cir. 1979)).
Accordingly, we hold that equitable tolling of the 300-day filing deadline is not
appropriate in this case.
Because Kirkland’s charges of discrimination were not timely filed, we
do not reach the merits of those charges to determine whether they state a
claim upon which relief can be granted.
III. CONCLUSION
For the foregoing reasons, we AFFIRM the district court’s dismissal of
Kirkland’s claims.
6
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It isn’t getting smaller, the amount of aluminium being poured into general engineering applications. Customers keep finding new ways to use the metal.
Engineering, in general
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Friday, April 11, 2014
CAT FRIDAY: Keep cats away from lilies this Easter
Easter weekend is now a week away, which could be bad for your cat(s) because of one major thing: Easter Lilies.
The trumpeted blooming flowers often given as gifts in the weeks leading up to Easter’s observance are certainly lovely icons of spring, but if you have cats — beware. Out of all types of plants that, when ingested, can cause minor to severe symptoms in cats, lilies are one of most dangerous and deadly of all cultivated plants. And that’s lilies of any kind — not just the traditional Easter Lily.
click to enlarge
Thankfully these lilies look fake, because this kitty is getting a little too close to the toxic plant.
Though obligate carnivores — meaning their diets must be animal protein-based — many domestic cats are naturally attracted to greenery both in and outside their homes because plants serve as a small source of fiber. Cats can’t efficiently digest plant matter, though, so if you see your cat nibble on something green only to puke it up later, that’s not unusual, either. Cats may intentionally eat plants to induce vomiting to pass a hairball.
That said, even if your cat has never shown interest in nibbling plants, it’s still a good idea to avoid the risks entirely by not bringing any lilies into your home.
It’s not known what specific toxin in lilies is so deadly to cats, but even one bite of a leaf or taste of pollen can bring on symptoms. If you suspect your cat has eaten part of any houseplant, seek immediate veterinary care. It’s also a good idea to take a picture of the suspected plant(s) if you’re not sure so the vet can give an accurate diagnosis and treatment.
Another thing to avoid at Easter if you have cats, especially kittens — fake Easter basket grass, at least of the non-paper variety. If accidentally ingested by a cat, the foreign object could potentially require surgery to remove.
The ASPCA has a 24-hour poison emergency hotline (888-426-4435; note there is a cost involved) for pet owners who are concerned their cat or dog is showing signs of ingesting a harmful substance, plant or not.
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FreeMarketDuck.com
Idaho's Weekly Journal of Local & National Commentary Week
2815
Washington, DC – With the Federal Reserve’s
wide-ranging efforts to address the ongoing Credit Crisis through
unprecedented money-creation activities, we are now likely witnessing the
final phases of the U.S. Dollar’s 64-year reign as the primary global
reserve currency. Few Americans understand the implications of this
dramatically unfolding global sea-change.
The U.S. Dollar was installed as
the lynchpin of the international monetary system in July 1944 by and among
the 44 Allied nations, and just as the end of WWII was in sight. At that
time, the U.S. owned or controlled well over half of the world’s wealth, and
the Bretton Woods Agreement (named after the small town in New Hampshire
where over 700 representatives of the leading industrialized nations met
that summer) created the financial architecture whereby the U.S. Dollar, as
backed by and exchangeable into gold at the rate of $35/oz, would function
as principal 'reserve currency' in the post-war global monetary system. The
dollar debuted in its newly-expanded role via the Marshall Plan and the
reconstruction of post-war Europe, when the U.S. paid dollars into the
accounts of foreign banks, both to maintain our overseas military bases as
well as to rebuild war-ravaged economies. Very importantly, all crude oil
transactions throughout the world were also designated to be priced in
dollars, regardless of which nations participated in the oil trades. In many
ways, the Bretton Woods Agreement can be seen as one of the great 'spoils of
war' for the U.S., and the dollar’s acceptance and dominance was subtly
reinforced throughout the subsequent Cold War and afterwards by America’s
enduring global military supremacy – the so-called 'Pax Americana.'
Bretton Woods thus represented
an enormous post-War economic advantage for America ever since, yet in
mirror fashion it emerged as a major problem for the other countries,
primarily because it created the possibility that the dominant U.S. could
simply print money, and do so essentially at the expense of diluting the
other nations' savings. Gold convertibility was to provide the discipline
whereby the U.S., as keeper of the 'reserve currency,' would keep its budget
in balance and the dollar as a sound reserve currency. That is, if other
nations were uncomfortable with the U.S. spending policies which might
dilute the value of their reserve savings, they could convert their dollar
savings into gold. But Bretton Woods allowed the U.S. some convenient
'wiggle room.' Over time, the U.S. chose a predictable political path in
ignoring key parts of the Agreement, often reminding the less-powerful
Europeans who had saved them from the Nazis, who had won WWII, and who was
now protecting them from the rising Soviet menace. In due course of the
post-World War II era, the U.S. began to spend far beyond its means both for
defense and foreign aid purposes, as well as for expanding domestic social
programs.
By the 1950’s the U.S. undertook
the expensive Korean War, and then in the 1960s the U.S. began to spend in
earnest for both the Vietnam War as well as for President Lyndon Johnson's
'Great Society' welfare and entitlement programs. These activities were
essentially financed by creating new debt and/or new inflated dollars, and
these efforts served to plant the seeds for significant dilution and
debasement of the other countries’ U.S. Dollar reserve accounts.
The era of ballooning U.S.
deficit spending and rising inflation was well underway by the late 1960s.
Over time, the Bretton Woods participants became increasingly frustrated
about the debasement of their dollar reserve savings, and French President
Charles de Gaulle even announced his intention to send a ship to the U.S. to
exchange France’s accumulated U.S. Dollars for gold at the official rate of
$35/oz. By 1971, the other European nations were also increasingly
uncomfortable, yet the dominant U.S. first downplayed and then later
summarily dismissed their concerns through President Richard M. Nixon, when
the U.S. officially and unilaterally suspended the gold-convertibility
'promise' of Bretton Woods. In officially closing the so-called 'Gold
Window’ on August 15, 1971, Nixon's Treasury Secretary John B. Connally
rebuffed the Europeans with his now-famous quote: "The dollar is our
currency, but it is your problem." So foreign central banks took it badly on
both ends – they were unable to keep Congress and the U.S. from spending
programs which were diluting their 'dollar reserve currency' savings, and
they were also unable to redeem their dollars for gold as promised.
With Nixon’s official
abandonment of the Bretton Woods gold-convertibility system, the global
economy moved thereafter to a 'floating' exchange-rate system where currency
rates were no longer fixed against each other and/or backed by gold. The
currency world entered a new and more speculative ‘Relativistic Age’ where
currency exchange rates instead varied constantly, depending on changing
perceptions of the strength of one another’s economies, and especially
reflecting their comparative internal structures of interest rates. With the
emerging need to 're-cycle' petrodollars following the Arab Oil Embargo of
1973, and with dollar fundamentals further weakened by continuing frequent
U.S. trade and budget deficits since the Vietnam era, the global economy
became increasingly awash in dollars by the late 1970s. With oil price
shocks and deficit-spending combining to produce double-digit inflation by
1979, a 'dollar rescue' of sorts developed in 1980, when U.S. Fed Chairman
Paul Volcker dramatically raised Fed Funds rates, eventually pushing the
Prime Rate to 21 1/2% by late 1981. Volcker’s Fed tenure represented a
painful adjustment period for the U.S. economy, but it won the U.S. great
praise around the world for bringing inflation under control. Unfortunately
for dollar-holders, the Volcker Era did not last.
With escalating social and
military spending through the Cold War, plus the dramatic increase in the
'Star Wars' military budgets during the Reagan Administration, the reasons
occasionally varied but America’s core political focus remained on greater
deficit spending, more borrowing, and a resulting deterioration of the
dollar’s fundamentals.
The U.S., admired widely for
decades as the ‘Wealthiest Nation on Earth,' quietly transitioned from being
a 'net lender' nation to a ‘net borrower’ nation in 1983. By 1985, U.S.
Treasury Secretary James A. Baker III initiated the ‘Plaza Accords’ among
the so-called ‘G-5’ countries, whereby foreign central banks coordinated to
reduce dramatically the floating exchange rate of the dollar. Spending for
defense and major declared wars through the 1980’s transitioned after the
collapse of the Soviet Union to spending for lesser undeclared wars against
terrorism and various other perceived regional threats in Panama, Granada,
Libya, and Somalia, and later in Afghanistan and Iraq. During the late
1980’s and early 1990’s, the U.S. Republican-led conservative movement
produced another noteworthy rescue round of ‘sound money’ initiatives which
had been championed by U.S. Speaker of the House Newt Gingrich, but these
'Balanced Budget' efforts were eventually abandoned under the relentless
political pressures of spending to attract votes for defense and for
continuing social programs.
The U.S. now ranks as the #1
borrower in the world, and our cumulative National Debt now stands at nearly
$9.4 Trillion at this writing. The annual net deficits have risen ever
faster since the World Trade Center Disaster in 2001, which produced the
reactionary ‘anti-terror’ wars in Afghanistan and Iraq starting in 2001 and
2003. Since 2006, America’s major trading partners and foreign lenders have
been asked to finance these expanding deficits by investing in new U.S. debt
at rates now approaching $1 Trillion per year. More recently the global
Credit Crisis has produced an even faster rate of deficit money-creation by
the Fed. With America’s history of deficit spending, plus a weakening U.S.
economy which no longer drives the global ‘growth engine,’ and now adding
the final coup de grace of the exported sub-prime syndication
contagion, foreign central banks have moved aggressively to diversify out of
exclusively dollar-denominated savings. The dollar has clearly lost its core
attraction as the reserve currency of choice of the world. With the
successful 2001 debut of the Euro and its growing acceptance by major
industrialized nations as an alternative currency, the tipping point of
other countries’ willingness to accept the dollar as the primary global
reserve currency may be approaching.
America has now grown accustomed
to borrowing from abroad to support its wars, its domestic programs, its
comfortable lifestyle, and its dependence on foreign crude oil. Global
investors have so far remained willing to lend to us based on our global
economic dominance and the perception of the U.S. as a perennial safe haven
for investments. But the cumulative borrowing over the past decades has now
escalated to dangerous levels, especially compared to our dramatically
weakening growth rates in comparison to other emerging economies such as
China and India. International investors have grown less willing to finance
America’s spendthrift habits and reckless foreign policy. With current
‘real’ U.S. inflation rates of 9% or so easily exceeding the sub-4% interest
rates earned on U.S. Treasuries, global investors clearly have more
attractive other investment options to consider.
The Credit Crisis has added a
greater sense of urgency to the dialogue of the continuing role of the
dollar. Since August 2007, the Fed has battled the sub-prime and derivative
credit crises with a wide array of new ‘fiat’ money-creation weapons - now
aggressively expanded to include new ‘liquidity injections,’ swaps, bond
auctions, the Exchange Stabilization Fund, the Plunge Protection Team, the
Bear Stearns direct lending rescue, ‘Term Securities Lending Facilities,’
collateralized purchases of credit card, auto loan & student loan
portfolios, plus even hints of the Fed engaging in outright corporate
recapitalization activities. These emergency Fed actions, often in concert
with the European Central Bank and the Bank of England, have temporarily
stabilized a chaotic scene, but at the expense of adding even further to the
escalating weaknesses in the dollar.
The Fed’s recent spectacular
levels of ‘instantaneous’ money-creation should produce additional major
dollar-dilution and forward inflation - and these deepening problems arrive
after the dollar has already
lost 50% of its value against the Euro since 2002 alone. The world economy
appears to be witnessing something akin to a developing ‘death-spiral’ of
the dollar, as OPEC nations now seek to raise their dollar-based oil prices
to keep ahead of increasing U.S. inflation rates, while these reactionary
price increases only escalate a still-further up-cycling of inflation. Since
2002, the dollar prices of other worldwide commodities including metals and
key raw industrial materials, as well as critical wheat, corn and rice food
staples, have likewise risen 3 to 7-fold in concert with oil. While
monetary inflation lies at the core of any price inflation, rising global
standards of living, tightening supplies, power & water shortages and the
occasional influences of Mother Nature in many of these markets may all
serve to exacerbate these developing inflationary trends.
With the added emergence of the
sub-prime crisis and the exporting of these infected mortgage portfolios and
their derivative problems around the globe, the rest of the world is even
more wary of dollars and dollar-denominated assets. But if not the dollar as
the global reserve currency, what else? Commodities in general plus the
precious metals group of gold, silver and platinum in particular have
witnessed major run-ups, as investors look to buy ‘things’ rather than ‘U.S.
Federal Reserve Obligations’ as more attractive alternatives to the steadily
weakening dollar. Over the past few years, world markets have also seen the
emergence of ‘Sovereign Wealth Funds,’ whereby individual nations have
dedicated their trade and payments surpluses to funds investing in
Euro-denominated assets, public companies and various commodities as
alternatives to weakening dollar-denominated assets and other paper
currencies. China, for example, has moved aggressively in Africa, South
America and elsewhere to secure major raw materials contracts, as well to
buy the companies which produce them. Other Middle Eastern, OPEC countries
and emerging nations have similarly created sovereign wealth funds in their
national interests, and many have used them as away to diversify out of
dollars.
The activities of the U.S. Fed since August
2007 promise a continuation of the inflationary trends noted below, and
there appears to be another major upswing in inflation just ahead as the
Fed’s massive money-creating actions since August 2007 work their way from
Wall Street and into the global financial system.
Representative Commodities Price
Comparisons 2003 vs 2008
2003
2008
$2.25
Corn
$6.10
$3.20
Wheat
$8.50 (U.S. stockpiles now
lowest since WWII)
$3.00
Rice
$21.00 (Primary food source
for 1/3 of the world’s population)
$27.00
Crude Oil
$125.00
$4.60
Silver
$17.00
$340.00
Gold
$885.00
$1.05
Euro
$1.55
The Arab world has occasionally expressed its
concerns about the falling dollar, and a few specific Arab states have
attempted in recent years to ‘de-couple’ crude oil from being priced in
depreciating dollars. Aspiring powers take note, invariably the U.S. has
responded subtly (and indirectly) by sending Vice President Dick Cheney and
yet another carrier to the Persian Gulf. But China and our other major
trading partners are also unhappy with being ‘forced’ to accept trade
dollars and convert them into steadily-depreciating U.S. Treasuries. Our
major trading partners and the OPEC nations currently invest nearly $1
Trillion in new financing each year to support our ever-growing trade and
spending deficits, and the severe troubles on Wall Street have deepened
their concerns about investing in depreciating dollar assets. With the Bush
Administration still enforcing an out-of-balance game of geopolitical
hardball, something has to give, and possibly soon.
A new stable global ‘reserve currency’ is
needed to correct these global trade, exchange and financing imbalances, and
to replace the faltering U.S. Dollar. What is needed is a new ‘reserve
currency’ which also provides a more stable medium of exchange, and this
concept is apparently in the works. The globally-accepted Euro now
constitutes a qualified new ‘reserve currency’ candidate, but it also can be
undermined by political spending flaws. In April 2008, global billionaire
financier and currency speculator George Soros commented at the European
Policy Studies think tank, “I don’t think that the Euro can replace the
dollar, and a system with two major reserve currencies is not a stable
system….The Euro, while it is obviously an alternative, is not a truly
attractive alternative, and therefore there’s a general flight from
currencies.” Soros continued on National Public Radio in May: “We
are in the midst of the worst financial crisis since the 1930s…In
some ways, [this crisis] resembles other crises that have occurred in the
last 25 years, but there is a profound difference: The current crisis marks
the end of an era of credit expansion based on the dollar as the
international reserve currency…A new paradigm is needed.” Gold and precious
metals may help to shape that new paradigm of replacing and/or backing
faltering paper currencies.
Gold has been prized as money by virtually
every major civilization in world history, and it has utilized as a stable
reserve currency many times before in European, British and American
history. As a rare and virtually indestructible metal, gold has served
repeatedly over the centuries virtually a class by itself as an effective
medium of exchange, yet it has also been periodically abandoned, ignored or
shunted aside by politicians who resent its fiscal discipline when they want
to spend more money to attract votes, or to pay for perceived military,
terrorist or financial threats. The last 37 years since the demise of
Bretton Woods has constituted just one of those periods where gold was
rejected or ignored, but as usual it keeps resurfacing as an unmistakable
store of value which cannot be printed out of thin air by governments. With
the Fed’s pursuit of spectacular money-creation policies which will
unmistakably lead to the further undermining of the dollar, gold again lies
waiting in the wings to return to its time-tested role as a stable medium of
exchange and reserve currency.
Nothwithstanding the official ‘disdain’
toward gold in recent decades, neither the U.S. nor the Europeans have ever
truly abandoned it. Enormous gold reserves have remained quietly and
unobtrusively on the balance sheets of the Federal Reserve Bank, the Bank of
England, the European Central Bank, the International Monetary Fund, and the
Bank for International Settlements, and a reactivation and revaluation of
gold, such as occurred during the Great Depression in March, 1933 under
President Franklin D. Roosevelt, may offer a true solution to the unfolding
global Credit Crisis. In March 2008, shortly after the Bear Stearns bailout,
former Dallas Fed Governor Robert McTeer commented notably on CNBC, "Gold is
the ultimate store of value in any financial system." It may now take one
more inflationary wave or another financial crisis of unknown dimensions to
finish the job and to usher in a new global era, perhaps restoring gold
convertibility to the global reserve currency equation.
What lies ahead? The world economy and
balance of trade among major trading partners with China and the OPEC
countries are seriously out of alignment, and a financial crisis and
resulting re-alignment seems inevitable. The foreign central banks have now
joined the Fed in spectacular money creation to inflate past the sub-prime
problems, and a stronger prospect remains for a global inflationary
upheaval, a major re-alignment of global currencies, and probably a period
of harder times for America. The U.S. will likely need to shift from being a
‘consuming nation’ back to an era of Americans as thrifty savers.(Retailers
take note.) Just imagine what will happen to the U.S. economy when we are no
longer able to ‘induce’ foreigners to provide us $1 Trillion per year in
deficit financing as we are doing today, and when that incremental $1
Trillion is not here to turn over a few times each year inside our
economy.(Retailers and everyone take note.) There will very likely be a
period of painful adjustment for the U.S. as we are forced to tighten our
belts and to modify the era of ‘U.S. as Net Consumer to the World.’
Notwithstanding the recent more hopeful
attitude on Wall Street, the August 2007 Credit Crisis which began with
overvalued mortgage portfolios will likely continue throughout 2008 and
beyond. The multi-trillion dollar ‘housing bubble’ was built on steadily
increasing housing values, yet real estate markets will clearly see
declining home values for some time ahead. There is a significant
likelihood, reinforced by the Fed’s recent expanded actions to buy up
distressed auto, credit card, and student loan portfolios, that the
sub-prime contagion is spreading to other sectors. The pressure may be off
in the short term, but the fundamental problems of downward-spiralling asset
portfolios and ‘mark-to-market’ accounting valuations still loom. As housing
values erode and defaults & foreclosures increase, more massive loan
portfolio write-downs, along with potentially even greater losses in the
financial derivatives arena, lie just ahead in the shadows.
With the Bear Stearns rescue precedent, the
imminent threat facing Wall Street financial institutions appears to have
been abated, at least for the moment. The emerging reality is that the Fed
has transformed a short-term crisis threatening a group of large financial
institutions into a longer-term and eventually more destructive inflationary
spiral to be borne by the average taxpayer, and where the average American’s
meager savings may be all but wiped out in the end. A weakening economy with
declining home prices and credit availability, coupled with strongly
increasing prices for food, gasoline and the necessities of life promise
trouble ahead. Our European friends may know just what these things mean
from their hyperinflationary experiences in the 1930’s, and they know just
how severe those consequences may be for all of us.
If the Fed consistently creates new liquidity
and money to wallpaper over our problems, the dollar cannot help but be
debased even further. Notwithstanding any occasional confusions as to the
true causes of inflation, massive money creation on Wall Street inevitably
will produce price inflation in the heartland. Dollar holders should clearly
beware, as the Fed has clearly opened wide the floodgates of the inflation
dam upstream, and a flood of money may soon engulf the financial landscape.
Purchasing power will slip underwater first, and unwary fixed dollar savers
may likely drown in this unfolding scenario.
The Fed may have telegraphed that massive
money-inflation was coming in March 2006, when it abruptly discontinued its
weekly release of the widely-followed Money Supply data. As John Lee’s chart
indicates below, M3, the widest measure of the U.S. money supply data, had
increased over 1500% from 1970-2006. With the Fed’s Credit Crisis responses
since last August, these numbers have likely accelerated even further, and
by some estimates the money supply growth is now running as high as 10 times
even the prior 2006 rates. The U.S. Labor Department’s Bureau of Labor
Statistics ‘official’ March 2008 CPI-U inflation rate of 3.98% (which
somehow carefully omits the 69% increase in food prices over the past year
as well as soaring energy costs) almost surely understates real ‘on the
street’ inflation by a very wide margin. Even more troubling to the
statistical purists who follow official inflation indicators, the U.S.
Commerce.
Department and BLS recently announced key
staff cutbacks in their critical data production areas. Although the core
statistics may now be more difficult to find, the average American can see
and feel the new reality of inflation, and there promises to be plenty more
ahead where that came from. The Fed’s recent massive money-creation on Wall
Street will produce even greater price inflation on Main Street in due
course, and perhaps surprisingly soon.
A picture is worth a thousand words and the
chart above is no different. There is 1,500% more paper money today than
there was in 1970. (Chart and comment courtesy John Lee, CFA/www.goldmau.com)
Competitive economic infrastructures have now
been built in Japan, China, India and elsewhere, and the U.S. no longer
controls global resources as it once did. But the U.S. still has options and
opportunities, and no country has broader or deeper resources, or does a
better job of implementing new ideas and concepts and technologies than we
do. It is very possible that an entirely new and more stable global economic
system may soon re-emerge, featuring a new U.S. energy policy as well as
pioneering U.S. nanotechnology and biotechnology developments as commercial
centerpieces. Given the inherent weakness of floating paper currencies which
can be created virtually at will by pandering, ambitious or reactionary
politicians and their allied central banks, the solution to budget deficits,
global trade imbalances and overall economic stability could very well
include some form of renewed official currency convertibility into gold.
Gold has represented sound money for thousands of years, and its rightful
place may be re-emerging as a beacon of stability in a world which grows
more wary and sea-sick of the floating U. S. Dollar with each new crisis.
Uncle Sam has captained the global reserve currency ship alone for 64 years,
and the sea-change replacement of the U.S. Dollar may lie just ahead.
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Q:
Constant Shared array in vb.net
Is there a way to create a constant shared array? The ovbious way :
Shared Const GX() As String = {"GS", "GP"}
Is not working, it says you can't use shared and const together.
If you use only const it says you can't declare a contant array in a class.
Thanks in advance
A:
I don't think it's possible. An alternative would be to use ReadOnly
Public Shared ReadOnly GX() As String = {"GS", "GP"}
A:
Sadly, you are not able to use Arrays in constants...
See here for details...
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Guardistallo massacre
The Guardistallo massacre was a Nazi German act of reprisal that took place close to Guardistallo, in Tuscany. On 29 June 1944, 57 people were killed and buried in a mass grave. A 23 old died from wounds suffered in the same occasion a few days afterward.
The cause of the massacre was suspected at the time to be a belief by German forces that Italian partisans had been hiding an American pilot who had been shot down in the area. A photoreconnaissance pilot from the 3rd Photorecon Group, 12th Air Force had, in fact, been downed by antiaircraft fire in the proceeding days and hidden by a resistance cell. He was successfully returned to Allied forces and survived the war.
References
Category:Massacres in Italy
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Signal transducing properties of the N-formyl peptide receptor expressed in undifferentiated HL60 cells.
Differentiated HL60 cells respond to challenge with ligand by mobilizing intracellular second messengers, resulting in superoxide production, degranulation, and actin polymerization with subsequent chemotaxis and phagocytosis. The functional capabilities of undifferentiated HL60 cells have not been similarly characterized due to the absence of the cell surface receptors required to initiate these processes. To investigate these properties, undifferentiated HL60 cells were transfected with one of the better characterized neutrophil chemotactic receptors, the N-formyl peptide receptor (FPR). Expression of the recombinant FPR gene product in FPR-transfected HL60 cells and the absence of the endogenous FPR in vector-transfected HL60 cells was demonstrated by Northern blot and flow cytometric analyses. FPR-transfected HL60 cells retained their ability to undergo granulocytic differentiation with dibutyryl cAMP, as determined by FMLP- and PMA-stimulated superoxide production. Furthermore, incubation of FPR-transfected HL60 cells for 5 days in the presence of FMLP resulted in limited differentiation as evidenced by the expression of functional C5a receptors. Binding studies of FPR-transfected HL60 cells demonstrated the presence of two binding affinities with dissociation constants of 0.6 and 33 nM, similar to dibutyryl cAMP differentiated HL60 cells and human neutrophils but contrasting the single high affinity state of the FPR expressed in mouse L cell fibroblasts. FPR-transfected HL60 cells displayed FMLP-dependent calcium mobilization with an EC50 of 3 nM and actin polymerization with an EC50 of approximately 10 nM. Actin polymerization was not observed in FPR-transfected L cell fibroblasts or undifferentiated vector-transfected HL60 cells. Both calcium mobilization and actin polymerization were sensitive to treatment with pertussis toxin, indicating the requirement for a Gi-like protein. Stimulation of either undifferentiated or differentiated HL60 cells with ATP resulted in pertussis toxin-insensitive calcium mobilization but was ineffective in producing actin polymerization. The results described herein show for the first time that undifferentiated HL60 cells can respond to chemoattractant receptor stimulation with many of the properties of the mature neutrophil. Transfected HL60 cells will provide an excellent system to study the characteristics of chemotactic receptors as well as the functional properties of myeloid cells.
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Human prothrombin fragment 1 and 2 inhibit bFGF-induced BCE cell growth.
Previously, we reported that the rabbit prothrombin fragment 2 (kringle 2 domain) has an anti-endothelial cell proliferative effect (Lee et al., J. Biol. Chem., in press). In this report, we show that not only rabbit prothrombin fragment 2 but also human prothrombin fragment 1 and 2 have an inhibitory effect on bFGF-stimulated BCE cell growth. Human prothrombin fragment 1 and 2 obtained as proteolytic fragments of human prothrombin display potent inhibitory effects on bovine capillary endothelial cells with a half-maximal concentration (ED50) of approximately 100 nM and 120 nM, respectively. As rabbit prothrombin fragment 2, the human prothrombin fragment 1 and 2 also inhibit angiogenesis in the chorioallantoic membrane (CAM) of chick embryos.
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MTA, LIRR unions: Informal contract talks to go through night
On Wednesday, July 16, 2014, MTA and Long Island Rail Road unions, heeding a call from Gov. Andrew M. Cuomo, returned to the bargaining table and committed to talk informally through the night and resume bargaining Thursday to avert a 12:01 a.m. Sunday strike. (Credit: Newsday / Chris Ware)
On Wednesday, July 16, 2014, MTA and Long Island Rail Road unions, heeding a call from Gov. Andrew M. Cuomo, returned to the bargaining table and committed to talk informally through the night and resume bargaining Thursday to avert a 12:01 a.m. Sunday strike. (Credit: Newsday / Chris Ware)
MTA and Long Island Rail Road unions, heeding a call from Gov. Andrew M. Cuomo, returned to the bargaining table and committed to talk informally through the night and resume negotiating Thursday to avert a 12:01 a.m. Sunday strike.
In a marked change of tone from earlier this week, when both sides sent dueling messages making their cases, LIRR union leaders and reps for the Metropolitan Transportation...
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MTA and Long Island Rail Road unions, heeding a call from Gov. Andrew M. Cuomo, returned to the bargaining table and committed to talk informally through the night and resume negotiating Thursday to avert a 12:01 a.m. Sunday strike.
In a marked change of tone from earlier this week, when both sides sent dueling messages making their cases, LIRR union leaders and reps for the Metropolitan Transportation Authority held a lengthy negotiation session Wednesday. Both sides indicated the five-hour talks were a positive sign.
In an earlier statement, Cuomo called for the two sides to return to the table. "We must do everything we can to prevent Long Islanders from being held hostage by a strike that would damage the regional economy and be highly disruptive for commuters," he said.
The developments came as the White House weighed in on the labor dispute affecting the nation's largest commuter railroad. Nearing the end of the federal process designed to avoid work stoppages, White House spokesman Keith Maley said President Barack Obama's administration hopes "both sides will be able to resolve this issue quickly in a way that is fair for workers, fair for the State of New York, and fair for residents in and around Long Island."
After calls from Long Island's congressional delegation Tuesday and from Cuomo Wednesday, the two sides met in the Times Square law office of Proskauer Rose. Shortly before 7 p.m., they broke off, promising to continue talking through the night over the phone and, if necessary, through video conferencing, before resuming in-person talks at 10 Thursday morning.
"I think being in a room is progress . . . We're having communication, and that brings us closer," lead union negotiator Anthony Simon said. "The message to the riding public is what we've said all along: We are not going to leave the table until we can do everything in our power to prevent a work stoppage."
Asked after the talks about the likelihood of a stoppage Sunday, Simon said the unions "don't want to alarm the public" and want to get the "rhetoric" between the sides out of the way.
While not disclosing whether either side put new offers on the table Wednesday, Simon said union leaders, who planned to stay in Manhattan Wednesday night, intended to spend their evening "crunching numbers . . . We need to go over a lot of things."
MTA chairman Thomas Prendergast attended the talks, but he left after a few hours.
The agency's current proposal calls for 17 percent raises for current workers over seven years and asks health care contributions of 2 percent of weekly wages. To help fund the raises, the MTA wants future workers to pay twice as much in health care costs, take twice as long to achieve top pay and contribute to pensions permanently, instead of for 10 years, as most now do.
The unions, following the recommendations of two federal mediation boards, want the 17 percent raises over six years, and, according to the MTA, have proposed much smaller concessions for future workers that amount to 0.15 percent savings from their previous offer.
MTA spokesman Adam Lisberg declined to characterize what went on at the bargaining table Wednesday, but he said the fact that negotiations were happening after a breakdown Monday was "a good sign."
"We remain committed to reaching a fair and reasonable solution at the bargaining table," Lisberg said at the end of Wednesday's talks. "And we're committed to doing whatever it takes to negotiate and make that happen . . . "
The productive meeting was a sudden shift in the dispute. Earlier, the LIRR's largest labor organization, the Sheet Metal, Air, Rail and Transportation Union, released an "open letter to riders" in which it predicted that the MTA's "irresponsible actions will cause a strike beginning this weekend."
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The Bihar model of prohibition seems to have taken off with a bang, with around 44,000 people put behind bars and over 10 lakh litres of liquor seized, during its one-year of enforcement since April 1, 2016.
It was in July 2015 that Bihar Chief Minister Nitish Kumar had made a pre-election promise to ban liquor in the state if he returned to power. Less than a week after assuming the chair, he announced on November 26, 2015, that sale and manufacture of countrymade and spiced liquor would be prohibited in Bihar from April 1, 2016.
Five days later, Nitish enforced total prohibition, and Bihar hasn't looked back since then with the entire state machinery put into execution of the law. It was even alleged by the Opposition that several other issues suffered due to focus on prohibition.
The scale of operations can be gauged from the fact that more than 2.13 lakh raids have been carried out by the police, excise and rail sleuths and almost 40,000 cases have been lodged in connection with them, besides the arrest of 43,978 persons, of which 43,941 were forwarded to jail, between April 1, 2016 and March 26, 2017.
At the time of prohibition, there were an estimated 44 lakh alcoholics in Bihar. "The previous year has been phenomenal with the impact of prohibition reaching far and wide. Independent research has shown how people have diverted their spends on milk, dairy products and other consumer goods," state excise commissioner Aditya Kumar Das told DNA.
The research Das is referring to has been conducted by Asian Development Research Institute (ADRI) and Jagjivan Ram Institute of Parliamentary Studies and Political Research (JRIPSPR), and have often found mention in Nitish's speech too.
The JRIPSPR has studied 600 families residing in slum areas of Patna, where one or more members were habitual drinkers. The study found that while domestic fights saw a dip of around 87 per cent, public brawls reduced by 93 per cent.
Assessing the impact on economy, the ADRI report claimed increase in sale of milk by 11 per cent, milk products by 17.5 per cent, stationery by 30 per cent, electrical goods by 51 per cent and automobiles by over 30 per cent.
The diversion of spending in other sectors, is what Nitish claims has helped Bihar ebb the Rs 5,000 crore revenue loss due to prohibition. The Bihar CM, in fact, has been touring the length and breadth of the country championing the prohibition agenda, purportedly with an eye on the 2019 general election.
The other side of prohibition includes rampant bootlegging with liquor bottles being sold for twice or thrice the MRP. Intelligence inputs with security agencies suggest that smuggling of psychotropic substances increased about 20-25 per cent after enforcement of total prohibition in Bihar.
With the government not renewing the license of breweries and distilleries in Bihar from April 1, 2017, thousands are fearing for their employment.
"There are slim chances that our companies will accommodate us anywhere else. After working for almost two decades in this sector, I cannot expect a job elsewhere," says Irshad Akhtar, one of the workers at a liquor manufacturing unit in Bihar.
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String Theory: The First Physical Model
The basic physical interpretation of string theory was as vibrating strings. As the strings, each representing a particle, collided with each other, the S-matrix described the result.
Consider this very informal way of looking at string theory, shown in this figure. Each particle is composed of a vibrating string. In the case of a proton, there are three quark strings. When these three strings come in contact, they bond together to form a proton.
So the proton is created by the interaction of the three quark strings touching each other. The proton is kind of a knot within the strings. Most people think of particles as solid spheres. In string theory, scientists view them as vibrating strings instead.
What are these strings like? The strings described were almost like rubber bands. There is a certain springiness to them. A phrase that describes them well is filaments of energy (as string theorist Brian Greene and others have called them).
Though most people think of particles as balls of matter, physicists have long thought of them as little bundles of waves (called wave packets), which is in line with describing them as strings.
In some other situations, physicists can treat particles as having no size whatsoever, but this is a simplification to make the math and theory more manageable. The way physicists treat particles depends a lot on the situation they’re working with.
This interpretation was put forth independently by Yoichiro Nambu, Holger Nielsen, and Leonard Susskind in 1970, earning all three men positions as founders of string theory.
According to Einstein’s work, mass was a form of energy, an insight demonstrated dramatically by the creation of the atomic bomb. Quantum theory showed physicists that matter was represented by the mathematics of wave mechanics, so even a particle had a wavelength associated with it.
In string theory, matter again takes on a new form. Particles of different types are different vibrational modes of these fundamental entities: energetic rubber bands, or strings. In essence, the more the string vibrates, the more energy (and therefore mass) it possesses.
Through all the transformations that string theory has undergone in the years since its discovery, this central concept remains (fairly) constant, although in recent years new objects in addition to strings have been introduced.
The basic physical model couldn’t have been simpler: The particles and forces in nature are really interactions between vibrating strings of energy.
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Fred is a male Tau'ri.
Biography Edit
1999 Edit
This section requires expansion
Fred is homeless, and he was the only one to talk to Ma'chello. Though he did not really understand who Ma'chello was and the importance of what he did, he understood that he was talking to a hero. (SG1: "Holiday")
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The most important challenge in wireless systems have always been faster and reliable wireless links. Recently, the need for higher data rates has grown exponentially over time leading to a problem called capacity crunch. Multi input multi output (MIMO) systems are one of the most important technologies to address this problem. Increasing the number of transmit and receive antennas to achieve higher wireless capacity has been the main trend in the wireless industry in recent years. High order MIMO and massive MIMO systems are typical examples of current MIMO technologies.
For MIMO systems to work successfully, accurate channel estimation is needed for each distinct link between receive and transmit antennas. To achieve this, a dedicated pilot signal is transmitted for each transmit antenna. As the number of transmit antennas increase, the number of pilot signals has to increase as well. This means more pilots occupy the transmit resources of the transmitter and significantly limit the transmit data rate. It is shown that the number of pilots required is a limiting factor of wireless capacity in high order or massive MIMO systems. Therefore, the problem is multiplexing as many pilots as possible into as few transmit resources as possible without creating interference between received pilot sequences. This requires design and selection of pilot sequences and their multiplexing scheme. The efficiency of such a scheme can be measured by the maximum number of pilots that can be transmitted per transmit symbol without any noticeable distortion in receiver channel estimation algorithms.
Ideally, the maximum number of pilots per transmit symbol is equal to the useful transmit symbol duration divided by the maximum channel delay spread. Note that the maximum number should be achieved without any compromise in channel estimation accuracy. In telecommunications, the delay spread is a measure of the multipath richness of a communications channel. In general, it can be interpreted as the difference between the time of arrival of the earliest significant multipath component (typically the line-of-sight component) and the time of arrival of the latest multipath components. In practice, achievable maximum number of pilots per symbol depends not only on the channel delay spread but also on the pilot sequences chosen and their multiplexing scheme.
Common sequences used as pilots for channel training include but not limited to pseudo noise like (PN), Walsh-Hadamard and perfect polyphase sequences (PPS). Another candidate is the cyclically shifted unit impulse sequence family. However, unit impulse sequence is difficult to use due to power amplifier ramp up problems and possible smoothing of the impulse function through transmitter front end processing among other problems. With the exception of the impulse sequence that is localized in time, all of the pilot sequences mentioned above are spread both in time and frequency without any localization.
In 3GPP UMTS and LTE systems, PN sequences are used for channel training in downlink such as Gold sequences. LTE uses PPS for the uplink. LTE uplink uses one transmit antenna; therefore, the maximum number of pilots per symbol is only one. In LTE downlink, there are only three pilots per OFDM symbol in average. Note that LTE pilots are staggered in time and frequency. Therefore, when calculating the maximum number of pilots per transmit symbol for LTE, the average number of distinct pilots per transmit symbol should be calculated from OFDM symbols that carry pilots within channel coherence time. For a normal cyclic prefix (CP), the channel with maximum delay spread is 5 μsec according to 3GPP standards. For a useful symbol length of 66.7 μsec this corresponds to 66.7/5˜13 pilots that can be transmitted within a symbol simultaneously. Taking into account the unused subcarriers and edge effects between transmit symbol boundaries, it realistic to assume 12 pilots per transmit symbol as a maximum goal. However, the pilots that are transmitted per OFDM symbol is only three for LTE downlink. The difference is very significant. This is due to the fact that long channel delay spreads cause highly frequency selective channels that requires more samples in the frequency domain, thereby limiting the maximum number of pilots that can be transmitted. More efficient channel training solutions are needed for future wireless systems that demand much higher number of pilots.
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Genetic mapping of bovine mitochondrial DNA from a single animal.
Using a physical map of bovine mitochondrial DNA derived from the liver of a single Holstein cow, we have determined the location of the genes specifying the large and small ribosomal RNAs by hybridization analysis and electron microscopic observations of R-loop forms. Also, the position of the origin of DNA replication (D-loop) has been located by electron microscopy. Additionally, the direction of D-loop expansion and the polarity of the large and small ribosomal RNA genes were determined.
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VR to hear information on results of audit of former government’s activity on Friday – Lytvyn
Verkhovna Rada of Ukraine...
The Verkhovna Rada of Ukraine will hear information of the Cabinet of Ministers of Ukraine concerning results of international audit of the former government’s activity on Friday, December 17 during an Hour of Questions to the Government.
According to an UNIAN correspondent, Speaker of the Verkhovna Rada of Ukraine Volodymyr Lytvyn said this at the news conference.
V. Lytvyn noted that it will be possible to hear information of the government on pension reform the next plenary week.
If you see a spelling error on our site, select it and press Ctrl+Enter
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Public sees plans for possible I-35 toll road
1of 4Buck Benson looks at plans during a public meeting held by the Texas Department of Transportation about the I-35 Northeast San Antonio Expansion Project on Thursday, February 26, 2015 at Morgan's Wonderland in San Antonio, TX. "I am a lawyer representing developers, so this is a big deal to me," he said.Photo: San Antonio Express-News
2of 4Sal Hernandez, a consultant, right, talks about the I-35 Expansion Project plans during a public meeting held by the Texas Department of Transportation about the I-35 Northeast San Antonio Expansion Project on Thursday, February 26, 2015 at Morgan's Wonderland in San Antonio, TX.Photo: San Antonio Express-News
3of 4Sal Hernandez, a consultant, right, talks about the I-35 Expansion Project plans during a public meeting held by the Texas Department of Transportation about the I-35 Northeast San Antonio Expansion Project on Thursday, February 26, 2015 at Morgan's Wonderland in San Antonio, TX.Photo: San Antonio Express-News
4of 4Mike Wikman speaks during a public meeting held by the Texas Department of Transportation about the I-35 Northeast San Antonio Expansion Project on Thursday, February 26, 2015 at Morgan's Wonderland in San Antonio, TX.Photo: San Antonio Express-News
A presentation Thursday about possible new managed lanes on Interstate 35 was met by the larger debate over toll lanes, with the project’s supporters saying tolls were needed to pay for vital new road capacity and critics calling them double taxation.
The $1.3-billion proposal would add four managed lanes — two in each direction — along I-35 from the Loop 410 South interchange near San Antonio Military Medical Center to FM 1103 in Schertz, according to Texas Department of Transportation plans.
The proposal would expand an already crowded section of Interstate 35 where traffic is only expected to worsen in the coming years, said Jonathan Bean, TxDOT San Antonio’s director of transportation, planning and development. From 1995 to 2012, Bean said, traffic along the corridor increased by 60 percent, and is forecasted to increase by an additional 47 percent by 2035.
“I hope that you’ll support this needed route for our community,” said Rob Killen, the chairman of the board of the North San Antonio Chamber of Commerce.
Killen, who said expanding I-35 was essential for the local economy, was one of about 20 people who spoke at the hearing. More than 200 people attended.
The new lanes would be elevated and situated between the main lanes and access road in each direction for most of the 15-mile stretch, and the existing highway and access lanes would remain free. New connecting ramps would be built to link the managed lanes with 410 South, 410 West and Loop 1604.
On the managed lanes, the cost of the toll would vary depending on the time of day or level of congestion. Some vehicles, like public transit or registered carpoolers, could generally use the lanes for free.
Bean said TxDOT did not have the money to build new lanes on I-35 without tolls. The toll would range from 17 cents per mile to 50 cents per mile, he said.
But Paul Henson, who lives off of O’Connor Road near I-35, said that everyone was already paying taxes for road construction and maintenance, and the toll amounted to a second tax.
Other critics of the proposal argued the toll road would only benefit people who could afford the extra money needed to access the lanes.
“That’s $7.50 one way, or 15 bucks a day in new toll costs,” toll-road opponent Terri Hall said about someone who would drive the entire stretch at peak pricing.
Hall, founder of Texans Uniting for Reform and Freedom, said Gov. Greg Abbott has promised new funding for roads, but others said the region could not wait to see if the state took action.
“We’ve got to move forward and solve this problem,” said Don Durden, chair of the San Antonio Mobility Coalition and president of the firm Civil Engineering Consultants.
While many of the proposal’s supporters said it was needed from an economic standpoint, Michael Garza noted that decreased congestion could make the stretch safer. Garza said his wife drives the section every day with their young son, and he gets worried about all the traffic.
The managed lanes, Garza said, would provide a choice.
“We have the opportunity now to have an alternate route,” he said.
Before anything can be built, the I-35 project still needs final environmental approval, which TxDOT officials say is expected to come this summer. At this point, there is no anticipated groundbreaking date, TxDOT said.
People can make additional comments about the proposal until March 9 at TxDOT’s website.
Drew Joseph joined the Express-News in 2013 . Before coming to San Antonio, he covered health for the San Franciso Chronicle, lobbying and campaign finance for National Journal and breaking news for the Oregonian. He is a San Francisco Bay Area native and went to Dartmouth College.
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Scientists Finally Figured Out How to Travel Faster Than the Speed of Light
One of the most cherished science fiction scenarios is using a black hole as a portal to another dimension or time or universe. That fantasy may be closer to reality than previously imagined.
Black holes are perhaps the most mysterious objects in the universe. They are the consequence of gravity crushing a dying star without limit, leading to the formation of a true singularity — which happens when an entire star gets compressed down to a single point yielding an object with infinite density. This dense and hot singularity punches a hole in the fabric of spacetime itself, possibly opening up an opportunity for hyperspace travel. That is, a short cut through spacetime allowing for travel over cosmic scale distances in a short period.
Researchers previously thought that any spacecraft attempting to use a black hole as a portal of this type would have to reckon with nature at its worst. The hot and dense singularity would cause the spacecraft to endure a sequence of increasingly uncomfortable tidal stretching and squeezing before being completely vaporized.
Flying Through a Black Hole
My team at the University of Massachusetts Dartmouth and a colleague at Georgia Gwinnett College have shown that all black holes are not created equal. If the black hole like Sagittarius A*, located at the center of our own galaxy, is large and rotating, then the outlook for a spacecraft changes dramatically. That’s because the singularity that a spacecraft would have to contend with is very gentle and could allow for a very peaceful passage.
The reason this is possible is that the relevant singularity inside a rotating black hole is technically “weak,” and thus does not damage objects that interact with it. At first, this fact may seem counterintuitive. But one can think of it as analogous to the common experience of quickly passing one’s finger through a candle’s near 2,000-degree flame without getting burned.
My colleague Lior Burko and I have been investigating the physics of black holes for over two decades. In 2016, my Ph.D. student, Caroline Mallary, inspired by Christopher Nolan’s blockbuster film Interstellar, set out to test if Cooper (Matthew McConaughey’s character) could survive his fall deep into Gargantua — a fictional, supermassive, rapidly rotating black hole some 100 million times the mass of our sun. Interstellar was based on a book written by Nobel Prize-winning astrophysicist Kip Thorne and Gargantua’s physical properties are central to the plot of this Hollywood movie.
Building on work done by physicist Amos Ori two decades prior, and armed with her strong computational skills, Mallary built a computer model that would capture most of the essential physical effects on a spacecraft, or any large object, falling into a large, rotating black hole like Sagittarius A*.
The fictional Miller’s planet orbiting the black hole Gargantua, in the movie ‘Interstellar.’
Not Even a Bumpy Ride?
What she discovered is that under all conditions an object falling into a rotating black hole would not experience infinitely large effects upon passage through the hole’s so-called inner horizon singularity. This is the singularity that an object entering a rotating black hole cannot maneuver around or avoid. Not only that, under the right circumstances, these effects may be negligibly small, allowing for a rather comfortable passage through the singularity. In fact, there may be no noticeable effects on the falling object at all. This increases the feasibility of using large, rotating black holes as portals for hyperspace travel.
Mallary also discovered a feature that was not fully appreciated before: the fact that the effects of the singularity in the context of a rotating black hole would result in rapidly increasing cycles of stretching and squeezing on the spacecraft. But for very large black holes like Gargantua, the strength of this effect would be very small. So, the spacecraft and any individuals on board would not detect it.
The crucial point is that these effects do not increase without bound; in fact, they stay finite, even though the stresses on the spacecraft tend to grow indefinitely as it approaches the black hole.
There are a few important simplifying assumptions and resulting caveats in the context of Mallary’s model. The main assumption is that the black hole under consideration is completely isolated and thus not subject to constant disturbances by a source such as another star in its vicinity or even any falling radiation. While this assumption allows important simplifications, it is worth noting that most black holes are surrounded by cosmic material — dust, gas, radiation.
Therefore, a natural extension of Mallary’s work would be to perform a similar study in the context of a more realistic astrophysical black hole.
Mallary’s approach of using a computer simulation to examine the effects of a black hole on an object is very common in the field of black hole physics. Needless to say, we do not have the capability of performing real experiments in or near black holes yet, so scientists resort to theory and simulations to develop an understanding, by making predictions and new discoveries.
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Bunker fuel metering system on barges or on shore
Our solution creates maximum transparency
Ship owners and port authorities have been increasingly installing special bunker fuel metering systems, containing Coriolis flowmeters. These systems replace traditional quantity measurement via sounding or reading off using the naked eye, which can be associated with uncertainties. Our new sophisticated and reliable bunker fuel metering system ensures transparent and highly accurate bunkering. Aggravating and time-consuming processes for resolving bunker disputes can thus be avoided.
Guaranteed profitability - Our system pays off
Our bunkering system, developed and patented by application specialists, ensures that air pockets are included correctly in the measurement when emptying tanks. Testing confirmed that our Promass Coriolis flowmeters capture even high-viscosity bunker fuels with excellent accuracy.
High transparency - Creating trust with metering profiles
With our certified bunker fuel measuring system, your risk of “flying blind” is now over. During the fueling process, multiple process parameters can be simultaneously monitored and even graphically displayed as “metering profiles” via a control panel. This means increased transparency and safety for both parties – the buyer as well as the supplier – before, during and after fueling. This saves you both time and money.
Unlimited security - Our measuring system is tamperproof
Both the individual devices and the entire measuring system are sealed after installation and thereby protected from unintentional tampering. And all of our devices are certified on accredited calibration facilities (ISO/IEC 17025), fulfilling the important requirement for seamless traceability according to national standards. Our measuring system guarantees that everything is running OK during bunkering as is ensured by a wide variety of interrogation and monitoring functions.
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Radicular artery
The posterior and anterior radicular arteries run along the posterior and anterior roots of the spinal nerves and supply them with blood.
Relationship to segmental medullary arteries
Radicular arteries can sometimes be replaced functionally by segmental medullary arteries. However, unlike those arteries, radicular arteries do not form anastamoses with the anterior or posterior spinal arteries. Radicular arteries are also generally smaller.
The Artery of Adamkiewicz is sometimes called "great radicular artery of Adamkiewicz", however it is in fact a segmental medullary artery.
References
Category:Arteries
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Central Michigan Chippewas
The Central Michigan Chippewas are the intercollegiate athletic teams that represent Central Michigan University (CMU), located in Mount Pleasant, Michigan. The school fields sixteen men's and women's intercollegiate teams that compete at the National Collegiate Athletic Association (NCAA) Division I level.
CMU was a member of the Illinois Intercollegiate Athletic Conference from 1950 to 1970. The school's athletics programs are affiliated with the NCAA and compete in the Mid-American Conference (MAC) with the exception of women's lacrosse, which competes in the Southern Conference. The school colors are maroon and gold, and the school, and its students and alumni are referred to as Chippewas which is sometimes shortened to Chips.
The nickname is used with consent of the nearby Saginaw Chippewa Indian Tribe. The university was placed on the NCAA's list of schools with "hostile or abusive" nicknames in August 2005, but appealed the decision, with the support of the Saginaw Chippewa Tribal Nation. On September 2, 2005 the university announced that their appeal of the decision had been upheld.
History
The school athletics logo has changed over time, once featuring an Indian spear, but is now a stylized block letter "C". Within the university this logo is often referred to as the "Flying C". The current version of the athletic trademark was first used in 1997.
Nickname
The Chippewas nickname was put forth by assistant football coach Lawrence "Doc" Sweeney in 1942 to replace the then-current Bearcats. He argued that Bearcats not only had nothing to do with the school and the area, but was also a nearly extinct beast that none of the students had ever seen or heard of. He further argued that not only was Chippewa the name of the school's yearbook, but the Chippewa River flows through Mount Pleasant, and the "American Indian image" would provide "... unlimited opportunities for pageantry and showmanship for the band as well as athletic teams." The new name was passed by a vote of the student body.
When negative reaction to racial stereotypes grew in the 1970s and '80's, it was recommended by the Michigan Civil Rights Commission that the Chippewas name be dropped. Instead, in 1989 the University instituted several measures to enhance the name, including special educational programs developed in conjunction with the Saginaw Chippewa Tribal Council, headquartered on the local Isabella Indian Reservation; orientation programs were set up to familiarize CMU students and staff with traditional Native American culture; the school's American Indian logos were eliminated along with tom-tom drumbeats by the pep bands and other activities that would reflect racial stereotypes.
Varsity sports
A member of the West Division of the Mid-American Conference (MAC), Central Michigan sponsors teams in seven men's and eleven women's NCAA sanctioned sports.
Baseball
Central's baseball team was NCAA Division II runner-up in 1971, having lost to Florida Southern College 4 to 0 in the championship game.
Men's basketball
Coach Davis was introduced by Central Michigan University as the Chippewas' 20th head men's basketball coach on April 3, 2012. In his inaugural season, he led a team of 8 new student-athletes to 11 wins. The seven non-conference victories match the 2002–2003 team's mark, and the most wins in the last 25 years. Four freshmen started for Coach Davis during the final 10 games of the season.
Under Coach Davis, Chris Fowler set the program record for a freshman with 167 assists, which ranks fourth all-time in single season history, securing him a spot on the All-MAC Freshman team. Fellow guard Kyle Randall led the MAC in scoring in 2013, averaging 18.7 points per game against conference opponents, en route to earning Second Team All-MAC and NABC All-District recognition.
Women's basketball
Football
The football team won the second NCAA Division II national championship in 1974 by defeating the University of Delaware 54 to 14. The team was voted national champion in the Associated Press College Division poll. The Chips have also been national runner-up twice.
In 2006, they won the MAC Championship in against Ohio and then defeated Middle Tennessee State in the Motor City Bowl. In 2007, the team defended their MAC Championship title in the game against Miami University, but lost to Purdue in the Motor City Bowl. The team was also beaten by Florida Atlantic in the 2008 Motor City Bowl.
Softball
The Chippewa softball team has appeared in two Women's College World Series in 1982 and 1987.
Men's swimming and diving
In 1958 the men's swimming and diving team was runner-up to North Central College at the second annual NAIA national meet, which was held in Muncie, Ind.
Wrestling
Chippewa Matmen have been at CMU dating back to 1955. Central Michigan Chippewa wrestling team is led by head coach Tom Borrelli are among the best in the nation each year competing in the NCAA Division I. Currently in his 22nd season with CMU wrestling, Borrelli has accomplished: 13 Mid-American Conference titles, seven top-15 national finishes in the last nine years, led the first program in MAC history to qualify all 10 wrestlers for the NCAA Championships, and named 2008 National Coach of the Year by two publications. Chippewa Wrestling has produced 2 Academic All-Americans in Mark DiSalvo (2006) & Wynn Michalak (2008), 53 NCAA All-Americans, and 2 individual NCAA Champions: Casey Cunningham (157) 1999, and John Rollins (137) 1959 & 1961 with 11 top-20 team finishes at the NCAA Wrestling Championships.
The wrestling practice facility, located at the CMU Events Center, opened during the 2010–11 season. The practice room includes three full-size mats, as well as an area adjacent to the mats for fitness equipment. The facility is located just steps from the competition floor at McGuirk Arena, providing an ideal warm-up area for the Chippewas during home dual meets.
Former Chippewa Wrestlers Phil Baroni and three-time All-American Jarod Trice are current Mixed Martial Artists. Baroni has competed in the UFC, Pride Fighting Championship, Bellator fighter. Trice is a currently an undefeated Bellator fighter.
Club sports
CMU currently supports the following club sports teams,
Women's lacrosse had been a club sport through the 2015 season, but became a full varsity sport in the 2016 season, playing in the Atlantic Sun Conference. The team moved to the Southern Conference when that league added women's lacrosse for the 2018 season.
Roller hockey
The roller hockey team was national runner-up in 2009 in the National Collegiate Roller Hockey Association (NCRHA) Division II tournament.
Men's rugby
The Central Michigan Rugby was initially established in November 1975. Founded as a Central Michigan University entity, a funding disagreement between the Club and University administration resulted in the club membership voting to become independent of the university, responsible for attaining their own autonomous funding sources, and become the Mount Pleasant Rugby Football Club on April 17, 1976. The team took on the name "EXILES" because of their new-found status even though three quarters of the roster was Central Michigan undergrad- and graduate students. The team played both city and university teams across Michigan and southern Ontario as well as "representing Central" as participants in the MAC tournaments at Bowling Green and Athens, Ohio in 1977 and 1978 as well as the Stroh's Great Lakes, Windsor Borderer's, and Traverse Cherry Pit tournaments.
The Club returned to a "club status sport" at the University in 1980 after sponsorship and funding rules were relaxed by the University. From Fall 1977 to the late 90's, the Exiles were a division 1 team in the MAC. Early 2000, were then moved to DIV 2 and played instate schools such as Grand Valley, Ferris State, and Western Michigan as a Club sport again for the university. The Rugby Club did make 2 Midwest Div 2 playoff appearances in 2008, and in 2011. In 2011 they made it to the Elite 8 round for the first time in team history by Defeating Xavier Rugby, but then falling to Northern Illinois. In that same year, In the Spring of 2011, The MAC Rugby Conference was reformed and Central announced they were to join the Conference along with school and state rivals Western Michigan, and are currently still in the Conference today.
References
External links
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Dramatically illuminated at night Harlem Park will
strike a prominent profile on the northern Manhattan
skyline.
Harlem Park is envisioned as the first high-profile landmark to
mark the rebirth of Harlem in the 21st Century. The building, a
layered silhouette of glass and masonry, will mark the gateway to
Harlem at 125th Street and Park Avenue.
The design strategy was to create a memorable and timeless image
that will remain a prominent landmark in Harlem as the neighborhood
continues to grow and change.
Image courtesy TEN
ArquitectosImage courtesy TEN
Arquitectos
The composition of the above-grade construction will appear as
an assemblage of distinct volumes corresponding to the multiple
functions within the complex.
At street level, retail spaces will wrap around the entire site to
activate the street level and encourage pedestrians to turn the
corner onto Park Avenue. Signage will be integrated into the
pedestrian level storefronts and facades to attract activity and
further activate the pedestrian experience.
The roof area of the mid-rise office block will contain
restaurants, spas, and other amenities. The Marriott Courtyard
Hotel will occupy the lower portion of the tower with luxury
residential units above.
Image courtesy TEN
ArquitectosImage courtesy TEN
Arquitectos
Norten would like the tower building to reflect the particular
colors of Harlem, reds, yellows, and greens, by applying a mosaic
of colored louvers behind the curved glass windows.
Tower detail courtesy TEN
Arquitectos
Harlem Park will act as the connecting node between east and west
Harlem, and establish and reinforce the standards of the 125th
Street corridor as it evolves as the Main Street of the
neighborhood in the years ahead. The Metro North Railroad across
the street, one direct stop from Grand Central Station, connects to
commuter suburbs in New York and Connecticut.
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1934–35 Tranmere Rovers F.C. season
Tranmere Rovers F.C. played the 1934–35 season in the Football League Third Division North. It was their 14th season of league football, and they finished 12th of 22. They reached the First Round of the FA Cup.
The first man to hold a position at Tranmere equivalent to what is today referred to as a manager was Bert Cooke, who was appointed manager in 1912, though the directors continued to choose the team for each game. Cooke stayed in charge for 23 years, the longest spell of any manager at the club. He oversaw the club's victory in the Lancashire Combination in 1914, promotion to the Central League in 1919 and, as founder members of Division Three North, their first Football League match on 27 August 1921. He also developed a string of talented local youngsters, including Dixie Dean and Pongo Waring. However, in 1935, Cooke's career ended in discredit; following illegal payments to directors and players, he was sacked and replaced by Jack Carr.
Football League
References
Category:Tranmere Rovers F.C. seasons
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Welcome to Texas justice: You might beat the rap, but you won't beat the ride.
Thursday, January 12, 2017
Community service in Austin muni court no sweet deal
Payment counter at Austin municipal court
Grits was at the Austin municipal court today with someone who'd allowed a warrant to be issued for a traffic ticket when she couldn't pay. I'd convinced her that, as she was in fact demonstrably indigent, she could get the warrant withdrawn by agreeing to perform community service. That turned out to be true.
Working from a preset formula with no inquiry as to her individual circumstances, the judge demanded 37.5 hours community service for a $460 fine - nearly a full work week for a single traffic ticket. That's about $12.26 of the fine waived per hour worked. Given that the estimated value of volunteer time for nonprofits is nearly double that (vis a vis how much they can estimate its value as an in-kind contribution), plus the fact that indigent people tend to have transportation issues and family obligations that might make a full week of community service onerous, that ratio seemed low to me. I bet the low rate contributes to people not completing community service and having their warrants reissued.
15 comments:
Anonymous
said...
By law, a municipal court defendant who is assigned community service in lieu of fines and costs is "considered to have discharged not less than $50 of fines or costs for each eight hours of community service performed." CCP 45.049(e).
Your friend discharged $460/(37.5/8) = $98.13 for each eight hours of community service. So the judge let her discharge at nearly twice the minimum rate.
"Working from a preset formula with no inquiry as to her individual circumstances".....this statement identifies one of the faulty cornerstones of our legal system that focuses on "one size fits all" punishment. This flies in the face of more nuanced responses to law breaking that highlight individual differences and needs, as noted in the House Corrections Committee interim report. While originally intended to deter crime, such broad brush policy has, instead, filled our jails and prisons with many who do not need to be there.....at great cost to everyone, except those who benefit financially from outmoded responses to "criminal" behavior.
I'd be curious as to what sort of service your friend did to get what amounts to double credit. Most community service work is not typically highly skilled, high paying work but things like picking up trash, janitorial work or other work that pays minimum wage to start so it sounds like she did get a bigger break than she could have.
@8:42/7:16, the minimum in state law is just that, a floor. She didn't get double credit, and was done no particular "good deed." She got what every other indigent defendant in Austin muni court gets. The fact that the value of the labor to the nonprofits receiving it is greater than the credit received by the laborer remains true regardless of the excuse for it. And observing that disparity doesn't "punish" muni court judges, that's flat out Orwellian. It's defendants being punished here, and by these lights they're being overpunished.
Thinking more on it, this is similar in many ways to the property theft thresholds, which were increased in 2015 for the first time in two decades. Inflation had caused the old amounts to become outdated but weren't changed in the law for years, when really they should be more or less indexed to inflation.
In this case, an antiquated provision sets a dollar-amount floor, but localities have already adjusted it upward because it's obsolete in the 21st century economy. In the meantime, a formal valuation exists that's updated every year that could be used. I now realize the Lege needs to update CCP 45.049(e) to account for that.
Has there ever been an offender, from your perspective, who was "justly" punished for their offense?
Of course it was a rhetorical question. When I first came to work for a healthcare provider in the CJ system I eagerly read your blog and benefited from the reasoned perspective you often exhibited and the thoughtful responses from avid readers. That was 2009. I have since found myself coming here much less often as I've observed your decent into an almost fanatical champion of diminishing consequences for those who choose to operate outside societies norms.
I only take the time to express my observations or impressions because you once were quite good at articulating your position and encouraging others to consider your persuasions. I fear your well placed compassion has descended into the arena where screeching liberals dwell and you're giving up your previous credibility as a persuasive debater.
Just my impression as a dentist in the system who also holds a current peace officer license.
@11:29, if observing real-world mathematical disparities in how the same person's labor is valued is descending "into the arena where screeching liberals dwell," I guess I'll plead guilty. To me, math is math, regardless of whether you think it's liberal or conservative, and $12.26 < $23.50.
If this blog has ever persuaded anyone of anything, it's been by insisting on reviewing facts and respecting math instead of taking a reflexively ideological position, and I've not taken one here. I didn't say people shouldn't be punished or do community service, I questioned whether an anachronistic law should be updated to reflect modern economic realities.
Grits...did I miss something in all of this? First, you claim your friend is indigent, based on what formula do you so quickly come to this conclusion? To hear you tell it, most of the time folks caught in the criminal justice system are indigent and they all need a little free government help (aka where the screeching liberals dwell). Second, why did your friend not go to the court like other responsible citizens and address the violation before it became a warrant? Third, is your "indigent" friend a skilled laborer of some kind that they would get paid more than $12.26 per hour at a job that was not community service? Or maybe your saying that they deserve more community service credit per hour to pay off a traffic ticket that they failed to take care of, at a rate per hour higher than the person working for a living at McDonalds?
If the state allows $50 for 8 hours worth of work and they are getting almost $100, it sounds like double credit to me too. Maybe "new" math has a different answer but frankly, they aren't doing the work for the city so who knows how credible the time is spent in the first place or if it benefits anyone beside the defendant. Just because other places credit more doesn't mean they are better, more fair, or more logical either.
Anon 2:50, I'm willing to bet the offense was not mentioned on purpose. Despite claims about reflexively ideological position's, when the facts don't suit the argument, Mr. Henson leaves them out or minimizes their importance. He's not alone in that so don't beat him up over it, just recognize that his pieces are best read in conjunction with other points of view for a more balanced understanding of the topics at hand.
Well stated, 6:23. I've been reading GFB for several years now and it is, in fact, a good source of information regarding the criminal justice system. But you definitely have to refine Mr. Henson's obvious liberal, anti-law enforcement biases from the posts to get to the useful information. He selectively uses statistics and data to support arguments which are not always justified…. you know, there are lies, damned lies and statistics. Unfortunately, his liberal and libertarian friends at the Legislature do the same thing. It brings to mind Ronald Reagan's quote, "the trouble with our liberal friends is not that they're ignorant, but that they know so much that isn't so."
To the above questions: the offense was a speeding ticket. I knew she was indigent because she's eligible for government benefits. The defendant did not go to court to take care of it because she had no money and couldn't pay. Also she has no car (why I took her). Like most people, she knows very little about courts or the justice system.
RE: what credit people should get for volunteer time. At root: I don't think a traffic ticket warrants a full work week of labor. But the larger point is that I'm not the one making the valuation. Nonprofits claim volunteer time is valued at a rate nearly double what the court values it. The court gives the defendant a long list of nonprofits. When volunteers work for those nonprofits, the amount the groups can credit as in-kind contribution is double the amount of credit the laborer receives with the state. Should nonprofits credit the labor value lower? That's beyond my ken to know and is a function of IRS rules, etc.. What I do know is that the labor is being valued differently for different government purposes, and there's an intellectual disconnect that disfavors defendants.
@Semperfine - you'd have to ask the Commission on Judicial Conduct about that, they're the ones who most prominently took her to task over that. And the issue wasn't the time so much as her usurping the role of the duty judge who should have been making the decision, if memory serves.
BTW, y'all realize, don't you, that this is a personal blog, not a news site? Everything you read here is an opinion piece. This blog exists to publish my arguments, not every argument, and not necessarily yours (though you're welcome to leave them in the comments). If anyone is just now figuring out that this site is "best read in conjunction with other points of view," then I'm afraid you've been a bit slow on the uptake. I'm supplementing MSM coverage on these topics with viewpoints not represented there; Grits isn't intended to be a primary news source.
"I always tell people interested in these issues that your blog is the most important news source, and have had high-ranking corrections officials tell me they read it regularly."
- Scott Medlock, Texas Civil Rights Project
"a helluva blog"
- Solomon Moore, NY Times criminal justice correspondent
"Congrats on building one of the most read and important blogs on a specific policy area that I've ever seen"
- Donald Lee, Texas Conference of Urban Counties
GFB "is a fact-packed, trustworthy reporter of the weirdness that makes up corrections and criminal law in the Lone Star State" and has "shown more naked emperors than Hans Christian Andersen ever did."
-Attorney Bob Mabry, Conroe
"Grits really shows the potential of a single-state focused criminal law blog"
- Corey Yung, Sex Crimes Blog
"I regard Grits for Breakfast as one of the most welcome and helpful vehicles we elected officials have for understanding the problems and their solutions."
Tommy Adkisson,Bexar County Commissioner
"dude really has a pragmatic approach to crime fighting, almost like he’s some kind of statistics superhero"
- Rob Patterson, The Austin Post"Scott Henson's 'Grits for Breakfast' is one of the most insightful blogs on criminal justice issues in Texas."
- Texas Public Policy Foundation
"Nobody does it better or works harder getting it right"
David Jennings, aka "Big Jolly"
"I appreciate the fact that you obviously try to see both sides of an issue, regardless of which side you end up supporting."
Kim Vickers,Texas Commission on Law Enforcement Officer Standards and EducationGrits for Breakfast "has probably broken more criminal justice stories than any TX reporter, but stays under the radar. Fascinating guy."
Maurice Chammah,The Marshall Project"unrestrained and uneducated"
John Bradley,Former Williamson County District Attorney, now former Attorney General of Palau
"our favorite blog"
- Texas District and County Attorneys Association Twitter feed"Scott Henson ... writes his terrific blog Grits for Breakfast from an outhouse in Texas."
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Identification of new candidate genes for retinopathy in type 2 diabetics. Valencia Study on Diabetic Retinopathy (VSDR). Report number 3.
To identify genes involved in the pathogenic mechanisms of non-proliferative diabetic retinopathy (NPDR), among which include oxidative stress, extracellular matrix changes, and/or apoptosis, in order to evaluate the risk of developing this retinal disease in a type2 diabetic (DM2) population. A case-control study was carried out on 81 participants from the Valencia Study on Diabetic Retinopathy (VSDR) of both genders, with ages 25-85years. They were classified into: (i)DM2 group (n=49), with DR (+DR; n=14) and without DR (-DR; n=35), and (ii)control group (GC; n=32). The protocols included a personal interview, standardised ophthalmological examination, and blood collection (to analyse the DNA for determining the gene expression (TP53, MMP9, and SLC23A2) in the study groups. Statistical analyses were performed using the SPSS v22.0 program. The TP53 and MMP9 genes showed a higher expression in the DM2 group compared to the GC, although the difference was only significant for the MMP9 gene (TP53: 10.40±1.20 vs. 8.23±1.36, P=.084; MMP9: 1.45±0.16 vs. 0.95±0.16, P=.036), and the SLC23A2 gene showed a significant lower expression in the DM2 vs CG (5.58±0.64 vs. 11.66±1.90, P=.026). When sub-dividing the DM2 group according to the presence of retinopathy, the expression of the TP53, MMP9 and SLC23A2 genes showed significant differences between the DM2-RD, DM2+RD and GC groups (TP53: 9.95±1.47 vs. 11.52±2.05 vs. 8.23±1.36, P=.038; MMP9: 1.47±0.20 vs. 1.41±0.27 vs. 0.95±0.16, P=.021; SLC23A2: 5.61±0.77 vs. 5.51±1.21 vs. 11.66±1.90, P=.018). Genes involved in extracellular matrix integrity (MMP9) and/or apoptosis (TP53), could be considered potential markers of susceptibility to the development/progression of NPDR. Interestingly, the SLC232A2 gene (ascorbic acid transporter) can be considered a protector of the risk of the development/progression of the retinopathy.
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Subcutaneous dirofilariasis of the eyelid and ocular adnexa. Report of six cases.
Six cases of subcutaneous dirofilariasis are reported, three located in the eyelid, two in the periorbital region, and one in the subconjunctival tissues. Three patients lived in Florida, two in North Carolina, and one in Mississippi. All patients were adults, ranging from 27 to 69 years of age (median age was 58 years). Most patients experienced an inflamed painful nodule that contained portions of a nematode. The morphologic features for identification of the worm as belonging to the genus Dirofilaria are outlined.
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In this Research & Commentary, Matthew Glans examines a a new study from the National Taxpayers Union Foundation that compares the predicted revenues from new state internet sales taxes to what has been generated by the new tax.
In this Research & Commentary, Matthew Glans examines a a new study from the National Taxpayers Union Foundation that compares the predicted revenues from new state internet sales taxes to what has been generated by the new tax.
Michigan Gov. Gretchen Whitmer's proposal to ban sales of flavored e-cigarettes is unlikely to reduce youth use e-cigarette use and her fearmongering campaign against THR products will likely lead to an increase in combustible use.
At least two of the five vaping-related deaths have been linked to products containing THC. Policymakers should refrain from enacting legislation and policies that could further restrict adult access to regulated tobacco harm reduction products.
In this Research & Commentary, Matthew Glans examines a new executive order from the Trump administration that would allow patients to use tax-advantaged health savings account funds to pay for direct primary care services.
In this Research & Commentary, Matthew Glans examines a proposed rule from the USDA that would close the categorical eligibility loophole that allows states to make applicants in certain programs automatically eligible to participate in SNAP.
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[Problem-solving in immunohematology: interpretation of ABO typing and its difficulties].
Practice in immunohematology is replete with complex problems that require practitioners' problem-solving performance. In immunohematology, the acquisition of the reasoning process and necessary skills for making clinical decisions is based on teaching problem-solving strategies which potentially reduce errors and improve patient outcome. We discuss the recognition and resolution of the common causes of discrepancies in ABO typing results using problem-solving strategies.
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Toronto Raptors Cannot Afford To Lose Game 5
If the Toronto Raptors hope to make it to the second round for just the second time in franchise history, the team cannot afford to lose Game 5 on their home court against the Brooklyn Nets.
With the series tied at 2-2 the Raptors must do everything in their power to avoid potentially reliving what happened the last time these two teams faced each other in the playoffs. In 2007 with LeBron James’ Cleveland Cavaliers waiting after sweeping the Washington Wizards in the first round, the Atlantic Division champion and third seeded Raptors lost to the sixth seeded Nets on the road in Game 6. Unable to force a Game 7 in Toronto in 2007, the last thing the 2014 Raptors want to do is have their life on the line on the road in another Game 6 against the Nets.
With James’ Miami Heat waiting for the winner of the series after sweeping the Charlotte Bobcats, the veteran Nets know they can’t allow a Game 7 to happen if they were to win Game 5. Brooklyn knows they’d be in for a war if they were to face the Heat in the next round and if they were to win Game 5 in Toronto they’d make it nearly impossible for the Raptors to escape Brooklyn with a Game 6 victory. Kevin Garnett and Paul Pierce understand the importance of closing out a series when given the opportunity with home court advantage; it’d be hard to imagine with them knowing the Heat are sitting and waiting they wouldn’t do everything in their power to avoid returning to Toronto for a seventh game.
With the impressive fan support the Raptors have received it’d also be hard to imagine the success-starved Air Canada Centre crowd would allow their team to lose a potential Game 7 in the event they won Game 5 but failed to close out the series in Game 6. The energy provided by those not only in attendance but also outside the arena would likely give the Raptors a significant boost in the potential deciding game. That’s not to say a crowd would defeat the Nets on their own — there’s no question the Raptors would have to deliver an incredible performance to advance. However, if Toronto was told before the series ever started they could just skip to Game 7 in Toronto, they’d take it in a heartbeat.
The Raptors have proven they aren’t afraid of Brooklyn and although the veteran Nets have experience on their side, Toronto has proven to be just as determined and focused as their opponents. With a seven game series likely favoring home court advantage, and veterans unlikely to let an opportunity at advancing slip away, there’s little doubt the winner of Game 5 will be the winner of this series.
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The housing and storing of equestrian paraphernalia presents certain problems with respect to supporting and storing the same when not in use. This pertains to such items as saddles, stirrups and straps, saddle pads, boots, leather dressing, and various other accouterments normally used in regard to equestrian activity. Frequently, a saddle is simply thrown over the upper edge of a stall divider, or in some circumstances, even a fence rail. Especially in regard to modern expensive saddles and the like, however, and particularly where saddles and related elements are not housed in a stable or the like, it is desirable to provide certain types of racks or boxes to support the same and contain them when not in use. Various developments have been made heretofore for purposes of supporting or storing saddles and the like under certain circumstances. For example, prior U.S. Pat. No. 2,809,755 to Martorello, dated Oct. 15, 1957, discloses a closet arrangement formed in the forward end of a horse trailer for purposes of containing a saddle. Also, especially for use in stables, suitable racks have been developed heretofore such as those disclosed in prior U.S. Pat. No. 3,688,912, to Wilmoth, dated Sept. 5, 1972 and U.S. Pat. No. 3,780,971 to De Filipps, dated Dec. 25, 1973, in which metal racks are illustrated of the type that are adapted to be secured to a vertical wall in a barn or stable and extend horizontally therefrom to receive a saddle with the stirrups draped from opposite sides.
The present invention has been devised for ready portable use and comprises a box-like structure having supporting rails described in greater detail hereinafter. In some respects, the preferred embodiment of the invention somewhat resembles a carpenter's or mechanic's toolbox, one example of which is shown in U.S. Pat. No. 4,122,944 to De Napoli, dated Oct. 31, 1978, which is simply a rectangular box having a single elongated handle rail extending above a closed top. Also, it is old to provide combination sawhorses and tool chests in which it might be considered that the top rail of the sawhorse might be a suitable support for a saddle. Combination sawhorses and tool chests are illustrated in certain prior U.S. patents, such as U.S. Pat. No. 1,404,266 to Brouner, dated Jan. 24, 1922, and U.S. Pat. No. 2,727,543 to Polselli, dated Dec. 20, 1955.
Still another holder and kit of interest is found in U.S. Pat. No. 2,592,212 to Turner, dated Apr. 8, 1952, and comprising a nursing bottle holder in which a central rail extends between end members of a box-like arrangement for purposes of supporting a nursing bottle.
While the art referred to above is representative of a number of different types of box-like supports and containers for a number of different items, the present invention has been designed particularly to support equestrian equipment, such as saddles, bridles, boots, and similar leather accouterments, as well as leather dressing materials and otherwise, and includes features not found in the prior art in the same relationship and for certain novel purposes, details of which are set forth below.
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Doggy Dan Pack Leader - An Overview
Doggy Dan Pack Leader - An Overview
And just when you think that it’s above, Saturday night will come all-around and lets just claim that Triga have still left the most important cock ‘til final… Preserve your spunk to the tip ‘cos you received’t be let down.
When the grown up Marjane is certainly (even) a lot more advanced and realistic, it's her childhood self we fell in love with, all large ideals and crazy schemes. Stroke of genius
Excitement Lightyear's title was motivated by astronaut Excitement Aldrin. Aldrin acknowledged the tribute when he pulled a Excitement Lightyear doll out through a speech at NASA, to rapturous cheers. He did not, having said that, obtain any endorsement expenses for the usage of his very first title. twelve. Lilo
Should you are going to instruct your pup the command “occur”, you need to be selected that every member with the house takes advantage of the identical term or phrase as part of a command. Normally, the Pet dog will turn out baffled.
Whether you may have just adopted a youthful pup or an Grownup Canine, you've got a lot of things to show your new companion. You would like your Canine to generally be beloved, trained and energetic, although not spoiled, a robotic or uncontrollable. Pet dogs could be naturals at Mastering manners and instructions, especially when you comprehend a vital element of their mother nature.
2. Canines should eat once the pack leader - The key reason why is usually that puppies want to be aware of (as wolves do) that the pack leader often eats 1st then They are really permitted to.
The rules are basically built to cause you to the pack leader from the eyes of your Pet dog. After This is often recognized then all else falls into put.
Also, his uncomfortable marriage with his father is significantly better than the typical orphan story, with bonus factors for the joke about his mother's breastplate. Stroke of genius
Their pleasant final exchange leaves the Film with a superior Observe, and is particularly the Main explanation why we're on the lookout ahead into the incoming sequel. Stroke of genius
In this article, we’ve compiled a summary of points you need to know when training your Doggy. Keep the following tips in mind for enjoyable, favourable and prosperous dog coaching.
Well known undercover journalist Emanuelle teams along with her Buddy Cora Norman to uncover a white slave ring that traffics in women kidnapped from various locales world wide. Her ... See comprehensive summary »
Most uneducated and somewhat disengaged (from their Canine) common public dog owners just don't need To place time in. They do not comprehend the things they are risking or carrying out to their dog while in the midst of that brief take care of.
Kanako fulfills a BDSM artist, who teaches Women of all ages an Extraordinary form of erotic submission - how to act like female dogs. It is really ruff and he even provides an actual Pet for her, but she more info goes with it. This increases her and her geeky husband's marriage. Director:
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One reason for the increased success of multi-user computing systems arises from the fact that their designs include substantial provisions for coping with power failures. Such systems have facilities that afford the user the luxury of experiencing a loss of primary power, and enable the system to resume processing as if no loss of supply voltage had been experienced. In general, such systems require battery back-up or some other power supply replacement that is activated in the event of a failure of the A/C main supply.
With the increasing complexity of multi-user computing systems,and a resulting geometric increase in the amount of available solid state memory in such systems, power fail protection requires substantially increased amounts of standby power. More specifically, the backup power supply must enable the data in the volatile memory bank to be stored prior to a total loss of supply voltage. The volatile memory must then be returned to the same state after power is restored. At typical speeds, using a disk to store data dumped from the volatile memory, substantial time may be required to accomplish such storage actions. For instance, if a multi-user system includes a 1-gigabyte quantity of data, such transfer would consume over 3 minutes of disk operating time. Future systems are expected to grow upwards of 4-gigabytes and thus, it would theoretically take over 10 minutes to save the data and another 10 minutes to reload.
Recent advances in the disk drives have led to the introduction of extremely small disk drives that are both inexpensive and high capacity. For instance, one such disk drive employs 1.3 inch disks, is smaller than a normal cigarette package, stores 40 megabytes and is available at a cost of less than $400. Such disk drives enable the storage of substantial amounts of data in a small package at very low cost.
Accordingly, it is an object of this invention to provide a data processing system with a volatile memory module whose contents are protected in the event of a power failure.
It is another object of this invention to provide a data processing system with power protected random access memory wherein nonvolatile memory modules are provided for the sole purpose of memory protection.
It is yet another object of this invention to provide a memory protection system that enables a computer, after a power-off and a subsequent power-on, to immediately reconstitute a memory state that existed at the power-off stage.
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In early 2018, activists in Massachusetts successfully fended off proposed legislation that targeted the Boycott, Divestment and Sanction (BDS) movement. However, the same bill has now been resurrected and it will have to be fought all over again.
Bill H.1685 (or the Act Prohibiting Discrimination in State Contracts) was filed in 2017 by State Representatives Steve Howitt (R) and Paul McMurtry (D), but it was drafted by the pro-Israel Jewish Community Relations Council (JCRC). It would have prohibited state agencies from entering into contracts of over $10,000 with companies if the company boycotted any organization based on its origin. Although the legislation didn’t specifically mention the BDS movement, its intentions were not concealed.
“This is a proud moment where the legislature can stand together in support of Israel” declared Howitt at the time. “This bill clarifies to businesses that either support BDS or who boycott Israeli-owned businesses and products that the Commonwealth of Massachusetts will not engage in commerce with them. I look forward to its quick passage.”
Over 100 Massachusetts faith and civil rights organizations formed a coalition called Freedom to Boycott to oppose the bill. Members from these groups, as well as constitutional lawyers and the ACLU of Massachusetts, testified against the legislation at its hearing in summer 2017. The bill was ultimately referred to “study” by an oversight committee, effectively killing its chances of passing during that session.
However, Howitt has now reintroduced the same exact bill, with the same exact constitutional concerns. It’s now Bill H. 2719 and this time he’s filing with Democratic State Rep. Paul Brodeur. “It’s one of these things where someone just clicks a button and refiles,” Jewish Voice for Peace (JVP) Boston’s Jill Charney told Mondoweiss. Charney said that this version of the bill doesn’t seem to have the same level of backing from local pro-Israel groups like the JCRC, but that JVP and other activists are taking it quite seriously nonetheless.
The hearing for this version of the bill will take place on November 19 and local activists will once again testify over the potential dangers of such legislation.
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15 N.Y.3d 867 (2010)
In the Matter of the Claim of PEGGY MAGIDSON, Appellant,
v.
STRATEGIC TELEMARKETING, INC., et al., Respondents.
WORKERS' COMPENSATION BOARD, Respondent.
Motion No: 2010-910.
Court of Appeals of New York.
Submitted August 9, 2010.
Decided October 19, 2010.
Motion for leave to appeal dismissed upon the ground that the order sought to be appealed from does not finally determine the proceeding within the meaning of the Constitution.
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You know the lady who spilled McDonald's coffee on herself and sued?
As they say in the video, it's practically become an urban legend — a lady spills hot coffee on her lap while driving, sues McDonald's and wins millions. People tell it as a tale of the legal system gone awry.
But that's not really what happened at all. This short documentary by The New York Time's Retro Report lays out the real story.
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Q:
sed bash substitution only if variable has a value
I'm trying to find a way using variables and sed to do a specific text substitution using a changing input file, but only if there is a value given to replace the existing string with. No value= do nothing (rather than remove the existing string).
Example
Substitute.csv contains 5 lines=
this-has-text
this-has-text
this-has-text
this-has-text
and file.text has one sentence=
"When trying this I want to be sure that text-this-has is left alone."
If I run the following command in a shell script
Text='text-this-has'
Change=`sed -n '3p' substitute.csv`
grep -rl $Text /home/username/file.txt | xargs sed -i "s|$Text|$Change|"
I end up with
"When trying this I want to be sure that is left alone."
But I'd like it to remain as
"When trying this I want to be sure that text-this-has is left alone."
Any way to tell sed "If I give you nothing new, do nothing"?
I apologize for the overthinking, bad habit. Essentially what I'd like to accomplish is if line 3 of the csv file has a value - replace $Text with $Change inline. If the line is empty, leave $Text as $Text.
A:
Text='text-this-has'
Change=$(sed -n '3p' substitute.csv)
if [[ -n $Change ]]; then
grep -rl $Text /home/username/file.txt | xargs sed -i "s|$Text|$Change|"
fi
A:
Just keep it simple and use awk:
awk -v t="$Text" -v c="$Change" 'c!=""{sub(t,c)} {print}' file
If you need inplace editing just use GNU awk with -i inplace.
Given your clarified requirement, this is probably what you actually want:
awk -v t="$Text" 'NR==FNR{if (NR==3) c=$0; next} c!=""{sub(t,c)} {print}' Substitute.csv file.txt
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Q:
Java Nested If condition
I need to have nested if condition but i see my code has the same logic for the else portion as well.
Syntax
if(outer_condition){
if(inner_condition){
}
else{
employee.setCompany("ABC");
employee.setAddress("DEF");
}
}
else{
employee.setCompany("ABC");
employee.setAddress("DEF");
}
Both Else portion has to execute the same logic, is there a way to avoid this and make single Else condition ?
Thanks
A:
You can combine both conditions with && operator.
if (condition1 && condition2) {
// If both conditions code
} else {
employee.setCompany("ABC");
employee.setAddress("DEF");
}
Note If the code of the if statement is absent as it seams from your code is better to replace it with
if (!condition1 || !condition2) {
employee.setCompany("ABC");
employee.setAddress("DEF");
}
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Background {#Sec1}
==========
Obesity has reached epidemic proportions in many countries around the world \[[@CR1]\]. Obesity is also known to lead to the development of insulin resistance \[[@CR2], [@CR3]\] and is associated with learning impairment and memory decline \[[@CR4]\]. Growing evidence from our group have clearly demonstrated that obesity in rats, induced by long-term high-fat diet (HFD) consumption, not only caused peripheral insulin resistance, but also brain insulin resistance, dyslipidemia, and increased oxidative stress \[[@CR3]\]. Furthermore, chronic HFD-fed rats have been shown to have the hippocampal synaptic dysfunction as indicated by the impairment of long-term potentiation (LTP) and dendritic spine loss, leading to cognitive decline \[[@CR4]--[@CR6]\]. In addition, mitochondrial dysfunction has been associated with a cognitive decline in rats fed chronically with HFD \[[@CR5], [@CR7]--[@CR14]\].
Recently, the role of gut microbiota, a group of beneficial microbes living inside the gastrointestinal tract, has been revealed in several human diseases including obesity \[[@CR15]\]. Human and rodents shared the similarity of gut microbiota in the phylum level which composed of the five major phyla including *Firmicutes*, *Bacteroidetes*, *Actinobacteria*, *Proteobacteria*, and *Verrucomicrobia* \[[@CR16], [@CR17]\]. Prolonged consumption of HFD resulted in an imbalance of gut microbiota termed "gut dysbiosis" by increasing the ratio of *Firmicutes* to *Bacteroidetes* (F/B ratio) and promoting the growth of *Proteobacteria* \[[@CR18], [@CR19]\]. Cumulative evidence showed that the modulation of gut microbiota by prebiotics and probiotics could be effective therapeutic strategies to improve obesity and insulin resistance \[[@CR20]\]. Prebiotics, non-digestible food ingredients which were digested by gut microbiota \[[@CR21]\], and probiotics, live micro-organisms which, when administered in adequate amount, confer health benefits on the host \[[@CR22]\], showed favorable effects by altering the composition and metabolism of gut microbiota and improved metabolic function in various animal models of metabolic syndrome \[[@CR23]\]. Previous study also demonstrated that consumption of probiotics had beneficial effects to the brain through gut-brain axis \[[@CR24]\]. Although probiotics had been shown to improve cognition and anxiety in hyperammonemia rats and also attenuated depression in humans \[[@CR25]\], inconsistent reports exist in which probiotics failed to modulate stress or cognitive performance in healthy male subjects \[[@CR26]\]. Furthermore, recent studies demonstrated that consumption of 10% of probiotic xylooligosaccharide (XOS) reduced the body weight, blood glucose, and cholesterol in streptozotozin-induced diabetic rats \[[@CR27]\]. In addition, a previous study demonstrated that 10^8^ colony-forming unit (cfu) of the *Lactobacillus paracasei* HII01 could survive in the acidic environment of the gastrointestinal tract and in the presence of gastric enzymes, bile salts, and considered as a safe dose \[[@CR28]\].
Microglia, the brain resident macrophage, has been proposed to play a crucial role in neurodegenerative disorders. It has been shown that microglia excessively pruned synapses and increased pro-inflammatory cytokines in models of Alzheimer's disease \[[@CR29], [@CR30]\]. Microglia are also associated with cognitive function \[[@CR31]\]. Chronic HFD consumption has been shown to trigger microglial activation, leading to cognitive impairment \[[@CR31]--[@CR33]\]. Recent studies also illustrated the communication linking between microglial function and host microbiota \[[@CR34], [@CR35]\]. Moreover, it has been shown that gut microbiota could modulate key transcriptional co-activators, transcription factors, and enzymes involved in mitochondrial biogenesis \[[@CR36]\]. Since mitochondria are the major producer of reactive oxygen species (ROS) \[[@CR37]\], which could cause microglia activation \[[@CR38], [@CR39]\], these ROS and pro-inflammatory cytokines released from activated microglia inhibited LTP, resulting in cognitive impairment \[[@CR40], [@CR41]\]. In addition, pro-inflammatory cytokines could also activate intrinsic apoptotic pathway \[[@CR42]\], which was attenuated by prebiotic and probiotics therapy \[[@CR43]\].
Despite these previous findings, the effects of prebiotic XOS, probiotic *L. paracasei* HII01, or its combination, an equal amount of XOS and *L. paracasei* HII01 as a synbiotics, on the modulation of microglia and cognitive functions by altering gut microbiota composition in an obese-insulin resistant model have not been investigated. We tested the hypothesis that prebiotic, probiotic, or synbiotics in obese-insulin resistant rats induced by chronic HFD consumption reduces gut dysbiosis and improves cognitive function by attenuating gut inflammation, peripheral insulin resistance, restoring hippocampal synaptic plasticity, decreasing brain mitochondrial dysfunction and hippocampal oxidative stress and apoptosis, and preserving microglial morphology.
Methods {#Sec2}
=======
Animals and diet {#Sec3}
----------------
All animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of the Faculty of Medicine, Chiang Mai University (Permit number: 13/2558 on May 12, 2015) and conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH guide, 8th edition, 2011). Male Wistar rats (180--200 g) were purchased from the National Laboratory Animal Center, Salaya campus, Mahidol University, Bangkok, Thailand. All rats were housed individually in a temperature-controlled environment (25 ± 0.5 °C) with a 12:12 h light-dark cycle. After 1 week of acclimatization, animals were fed with either a normal diet (ND; 19.77% energy from fat) or a high-fat diet (HFD; 59.28% energy from fat) for 12 weeks. All rats received reverse osmosis drinking water ad libitum. Food intake was recorded daily and body weight was recorded weekly. After 12 weeks, blood collection and behavioral assessment were measured in all animals. At week 13, the rats in each dietary group were randomly divided into four subgroups including ND- and HFD-fed rats oral feeding with phosphate buffer saline (PBS) as the vehicle group (NDV and HFV); ND- and HFD-fed rats oral feeding with prebiotics (10% XOS in PBS, 1 ml/day; NDPE and HFPE); ND- and HFD-fed rats oral feeding with probiotics (1 × 10^8^ cfu of *L. paracasei* HII01, 1 ml/day; NDPO and HFPO), and ND- and HFD-fed rats oral feeding with 2 ml of synbiotics (a 1:1 mixture of 10% XOS and 10^8^ cfu *L. paracasei* HII01; NDC and HFC). For prebiotics, 10% of XOS has been shown to reduce the body weight, blood glucose, and cholesterol in streptozotozin-induced diabetic rats \[[@CR27]\]. For probiotics, a previous study demonstrated that 10^8^ CFU of the *L. paracasei* HII01, which is a live microorganism, could survive in the acidic environment of the gastrointestinal tract and in the presence of gastric enzymes, bile salts, and considered as a safety dose \[[@CR28]\]. The prebiotic XOS was purchased from Shandong Longlive Biotechnology CO., LTD., Shandong, China, and probiotic *L. paracasei* HII01 was kindly provided by the Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Thailand. Rats received their assigned intervention for an additional 12 weeks.
At the end of the experimental protocol, the cognitive functioning of each rat was investigated and the oral glucose tolerance test (OGTT) was performed. Then, rats (*n* = 6/subgroup) were deeply anesthetized with isoflurane and killed by decapitation. The brain of each rat was quickly removed and carefully sliced in preparation for investigation, including extracellular recording (electrical-induced LTP) for hippocampal plasticity, brain mitochondrial function, hippocampal ROS production, and hippocampal apoptosis. Another group of rats (*n* = 6/subgroup) was also deeply anesthetized with isoflurane and subsequently perfused with 4% paraformaldehyde for determining microglial morphology. The experimental protocol is summarized in Fig. [1](#Fig1){ref-type="fig"}.Fig. 1The experimental protocol of the present study
Metabolic parameters determination {#Sec4}
----------------------------------
Plasma glucose and cholesterol levels were determined via colorimetric assay (Biotech, Bangkok, Thailand). The commercial colorimetric assay kit (Biovision, CA, USA) was used for determining plasma total LDL levels. Plasma insulin levels were also determined using the Sandwich ELISA kit (LINCO Research, MO, USA). Homeostasis Model Assessment (HOMA) was used for assessing the peripheral insulin resistance as described in previous studies \[[@CR44], [@CR45]\]. OGTT was performed as described by Pintana et al. \[[@CR5]\]. Briefly, rats were fasted overnight before the test and received 2 g/kg of glucose solution via oral gavage feeding. Blood samples were collected from the tail vein at 0, 15, 30, 60, 90, and 120 min after glucose administration. Areas under the curve (AUC) were calculated to evaluate glucose tolerance. To examine the brain oxidative stress, hippocampal malondialdehyde (MDA) level was determined by high-performance liquid chromatography (HPLC), as described in the previous studies \[[@CR46]\]. Serum lipopolysaccharide (LPS) levels were measured by colorimetric method using the Pierce® LAL Chromogenic Endotoxin Quantitation Kit (Thermo Fisher Scientific, USA). Serum was diluted (1:10) with sterile endotoxin-free water and inactivated at 70 °C for 15 min. Then, the heat-inactivated serum was incubated with limulus amoebocyte lysate (LAL) at 37° for 10 min as described previously \[[@CR19]\]. Next, substrate solution was added; the development of magenta-colored derivative was detected using the absorbance at 410 nm. The concentrations of serum LPS in the samples were then calculated using the standard curve and reported in EU/mL.
Tissue and brain slice preparation {#Sec5}
----------------------------------
Brain tissue in each rat was removed and immersed in ice-cold artificial cerebrospinal fluid (aCSF) containing high sucrose for 30 min. Brain slices (400 μm) were cut on a vibratome (Vibratome Company, MO, USA). The slices were transferred to a room temperature (22--24 °C) CSF solution for an additional 30 min and subsequently transferred to a recording chamber containing standard aCSF for extracellular recording. Other brain tissue or hippocampi were homogenated in solution buffer containing protease inhibiter for brain mitochondrial function, hippocampal ROS production, and immunoblotting.
Quantitative real-time PCR analysis {#Sec6}
-----------------------------------
Transcription levels of pro-inflammatory cytokine genes, IL-1β (5*′*-CACCTCTCAAGCAGAGCACAG-3*′* and 5*′*-GGGTTCCATGGTGAAGTCAAC-3′), IL-6 (5*′*-TCCTACCCCAACTTCCAATGCTC-3′ and 5*′*-TTGGATGGTCTTGGTCCTTAGCC-3′), and immunosuppressive cytokine IL-10 (5*′*-AGTCAGCCAGACCCACAT-3′ and 5*′*-GGCAACCCAAGTAACCCT-3′) were determined as previously described \[[@CR47]\]. In brief, the frozen colon and brain tissues in RNA preservative solution were homogenized by using 1 mm sterile zirconia/silica bead (Biospec Products, Bartlesville, US) and Minibeadbeater (Biospec Products, Bartlesville, US). Next, homogenized tissues were extracted from RNA using TRI reagent (TRIzol® Reagent, Ambion, Life Technologies, CA, US) according to the recommendations of the manufacturer. Then, a DNase treatment was performed by adding the DNA removal and inactivation kit (Ambion, Life Technologies, CA, US). The extracted tissue RNA was converted to complementary DNA (cDNA) using reverse transcription reagents (Tetro cDNA synthesis kit, Bioline, US). SYBR-Green (SensiFAST SYBR Lo-ROX kit, Bioline, US)-based real-time quantitative PCR was conducted using the primers and further analyzed by comparative Ct method. The mRNA expression levels of target genes were normalized with Gapdh (5′-GTATTGGGCGCCTGGTCACC-3′ and 5′*-*CGCTCCTGGAAGATGGTGATGG-3′) mRNA levels.
Extracellular recordings of hippocampal slices long-term potentiation {#Sec7}
---------------------------------------------------------------------
To determine hippocampal plasticity, the field excitatory postsynaptic potentials (fEPSP) slope of LTP was measured from CA1 area of hippocampal slices. LTP is a marker of hippocampal synaptic plasticity. \[[@CR3]\]. Briefly, brain slices were transferred to a submersion recording chamber and continuously perfused at 3--4 ml/min with standard aCSF warmed to 28--29 °C. Field excitatory postsynaptic potentials (fEPSPs) were evoked by stimulating the Schaffer collateral-commissural pathway with a bipolar tungsten electrode, while the fEPSPs recordings were taken from the stratum radiatum of the hippocampal CA1 region with micropipettes (3 MW) filled with 2M NaCl. LTP was induced by delivering high-frequency tetani \[high-frequency stimulation (HFS); four trains at 100 Hz; 0.5 s duration; 20 s interval\] at 1.5 times the baseline stimulation intensity. Experiments were performed for at least 40 min after HFS. The amount of potentiation was calculated at 40 min after tetanus. Data were filtered at 3 kHz, digitized at 10 kHz, and stored in a computer using pClamp9.2 software (Axon Instruments, CA, USA). The initial slope of the fEPSPs was measured and plotted against time \[[@CR3], [@CR8], [@CR9], [@CR11]--[@CR14], [@CR48]\].
Brain mitochondrial function {#Sec8}
----------------------------
Brain mitochondria were isolated as described in Pipatpiboon et al. \[[@CR11]\]. Mitochondrial protein was determined by the BCA assay as described previously \[[@CR5]\], and brain mitochondrial function including brain mitochondrial ROS, mitochondrial membrane potential change (ΔΨm), and mitochondrial swelling was determined \[[@CR13], [@CR14], [@CR48]\]. Brain mitochondrial ROS were measured using dichloro-hydrofluoresceindiacetate (DCFHDA) fluorescent dye. The change in mitochondrial membrane potential (ΔΨm) was measured using the fluorescent dye 5, 5¢, 6, 6¢-tetrachloro-1, 1¢, 3, 3¢-tetraethyl benzimidazolcarbocyanine iodide (JC-1), and brain mitochondrial swelling was determined by measuring the change in the absorbance of brain mitochondrial suspension at 540 nm. All were determined by following the methods described previously \[[@CR13], [@CR14], [@CR48]\].
Immunoblotting of hippocampal apoptotic and anti-apoptotic proteins {#Sec9}
-------------------------------------------------------------------
To investigate the hippocampal apoptosis, homogenate hippocampi were used, as described in the references \[[@CR13], [@CR14], [@CR48]\]. Examination of the level of apoptotic and anti-apoptotic protein expression was conducted with homogenates prepared from hippocampus tissue. These proteins were separated and identified by an immunoblot assay conducted with rabbit anti-bax (1:200; Santa Cruz Biotechnology, CA, USA), bcl-2 (1:1000; Cell Signaling Technology, MA, USA). For a loading control, immunoblotting for each membrane was incubated with anti-β-actin (1:4000; \#4967; Cell Signaling Technology, MA, USA). All membranes were incubated with a secondary goat anti-rabbit antibody conjugated with horseradish peroxidase (1:2000; \#7074; Cell Signaling Technology, MA, USA). The protein bands were visualized on ChemiDocÔ touch imaging system (Bio-Rad, CA, USA) using Amersham ECL Western blot detection reagents (GE Healthcare, Buckinghamshire, UK). The band intensity was measured by Scion Image, and the results were represented as average signal intensity (arbitrary) units.
### Immunofluorescent labeling for hippocampal plasticity, microglial morphology, and image analysis {#Sec10}
Animals were transcardially perfused with 4% paraformaldehyde, postfix for an additional 24 h, cryoprotected in 30% sucrose in PBS at 4 °C, and then frozen in isopentane and dry ice, and stored at − 80 °C. Then, the brains were cut using cryosection (Leica CM1950, Leica Biosystem Nussloch GmbH, Nussloch, Germany) at 20 μm. Sections were subjected to label immunofluorescence. The sections were quenched with 3% peroxide, blocked with 5% BSA, and incubated overnight at 4 °C with primary antibodies for Iba-1 (ab5076, Abcam, Cambridge, MA) for microglia morphology \[[@CR32]\]. After being washed three times in TBS, sections were incubated with AlexaFluor conjugated secondary antibodies; Iba1- AlexaFluor 488 anti-goat, for 1 h at 25 °C then rinsed in TBS. Sections were treated with copper sulfate in ammonium acetate buffer to quench endogenous autofluorescence of the brain tissue. To determine the microglial morphology, the series of z-stacks of microglia images were taken from confocal microscopy (Olympus flouview FV3000) and microglial morphology was measured by Imaris software 7.0 (Bitplane, Oxford instrument company, AG, Zurich, Switzerland). Three microglial cells per brain slice, three brain slices per animal and six animals per group were measured from the CA1 region of the hippocampus. All microglial morphology parameters including soma area, processes length and the number of primary branch projection (ramification) were measured from a 3D constructuring using Imaris. The number of Iba-1 positive cells and the mean fluorescent intensity were also measured. For visualization of dendritic spines, slices were labeled with the carbocyanine dye 1,1′-dioctadecyl-3,3,3′,3'-Tetramethylindocarbocyanine Perchlorate (DiI; Invitrogen), as described previously \[[@CR32], [@CR33]\]. Slices were incubated with appropriately placed DiI crystals for 48--72 h before being mounted on slides and coverslipped in 0.1 M Tris buffer. Sections were mounted on slides and coverslipped by the anti-fading mounting medium Fluoromount (Sigma-Aldrich Chemie, Steinheim, Germany). To assess the dendritic spine density, a series of 10 optical sections were taken every 0.25 mm in the *z*-plane, stacked into z-stacks of 2.5 mm, and shown as a z-projection of the total z-stack. For spine analysis, the three tertiary segments, 100--200 μm apart from the soma and 20--30 μm in dendritic length, were used to randomly measure dendritic spine density. Three neuronal cells per brain slice and three brain slices per animal were chosen for spine quantitative analysis. The number of spines was counted by double-blind hand counter \[[@CR48]\].
Cognitive function test {#Sec11}
-----------------------
The Morris water maze test was performed to determine cognitive function with two assessments, including five consecutive days of the acquisition test, and the probe test on day sixth. Time to find the platform was recorded in the acquisition test, and the time spent in the target quadrant was also recorded in the probe test \[[@CR46], [@CR49]\]. Data analysis of the MWM test was done manually from videotape recordings by the investigators, who were blinded to experimental groups. To determine locomotor activity, all animals were tested by open-field test \[[@CR50], [@CR51]\]. In this method, the apparatus consists of a rectangular-based box open from above (70 cm long and wide, and 90 cm in height). Each animal was placed into the box and allowed for 5-min exploration. After 10 mins of exploration time, the animals were taken out. The distance was counted using SMART 3.0 software (Panlab®, Harvard Apparatus, Barcelona, Spain).
### Gut microbiota analysis {#Sec12}
Feces of each animal were collected at the end of experimental protocol. Bacterial genomic DNA was extracted from rat fecal pellet using a commercial genomic DNA isolation kit (QIAGEN, Germany). Briefly, the fecal sample (0.25 g) was homogenized in QIAGEN ASL lysis buffer by a Minibeadbeater (BioSpec products, Bartlesville, USA). The extraction of bacterial genomic DNA was done following the manufacturer's instruction. The fractions of bacterial microbiota population (*Firmicutes/Bacteroidetes* ratio) were quantified using real-time quantitative reverse transcription PCR (qRT-PCR) as described previously \[[@CR52]\].
### Statistical analysis {#Sec13}
Data from each experiment were expressed as mean ± S.E.M. For all multiple comparisons, data were analyzed using a two-way ANOVA, followed by post-hoc Tukey's analysis. Correlations and regression analysis were also conducted to look at relationships between metabolic parameters and behavioral test. For behavioral test, the significance of the difference of acquisition test was calculated using repeated two-way ANOVA, followed by post-hoc Tukey's analysis. The significance of the difference of probe test at week 12 was calculated using an independent *t* test. A *p* \< 0.05 was considered as statistically significant.
Results {#Sec14}
=======
Long-term HFD consumption induced gut dysbiosis and systemic inflammation, which was attenuated by prebiotic XOS, probiotic *L. paracasei* HIIO1, or synbiotics {#Sec15}
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Pro-inflammatory cytokine interleukin (IL)-1 and IL-6 mRNA expression levels were significantly increased in the colon of rats fed with a HFD compared to rats fed with a ND, whereas the immunosuppressive cytokine IL-10 mRNA level was not altered (Fig. [2](#Fig2){ref-type="fig"}a--c). Diet-induced obese rats also developed the metabolic endotoxemia, the increased LPS in their sera (Fig. [2d](#Fig2){ref-type="fig"}), which was ameliorated by consumption of prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics (Fig. [2](#Fig2){ref-type="fig"}e). Collectively, chronic HFD consumption resulted in both local (colon) and systemic (metabolic endotoxemia) inflammation, and consumption of prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics could significantly reduce these low-grade inflammations. In this study, the pro-inflammatory mRNA levels of IL-1β and IL-6 from the whole brain tissues were not different among groups (Table [2](#Tab2){ref-type="table"}). However, the two hippocampi in each animal were sufficient only for protocol of dendritic spine, hippocampal ROS production, and Western blot analysis; therefore, we did not have enough hippocampal tissues for cytokine analysis.Fig. 2Effects of prebiotics, probiotics, or synbiotics on gut inflammation and endotoxemia induced by long-term HFD consumption. **a**--**c** The pro-inflammatory cytokine including IL-1β expression, IL-6 and IL-10, anti-inflammatory cytokine, expression respectively. **d** Serum LPS level of ND- and HFD-fed rats at 12th week. **e** Serum LPS level of ND- and HFD-fed rats after receiving prebiotics, probiotics, or synbiotics. ND: 12-week-normal diet-fed rats; HFD: 12-week high fat-fed rats; V: rats receiving PBS as vehicle; PE: rats receiving prebiotics; PO: rats receiving probiotics; C: rats receiving combination of prebiotics and probiotics as synbiotics (*N* = 6 of each group) \**p* \< 0.05 in comparison with the ND-fed rats; †*p* \< 0.05 in comparison with the HFD-fed rats receiving vehicle
Our findings demonstrated that HFD-induced gut dysbiosis, as indicated by an increased F/B ratio in HFD-fed rats treated with vehicle (0.479 ± 0.174), compared to that of ND-fed rats treated with vehicle (0.159 ± 0.235, *p* \< 0.05). The F/B ratio of HFD-fed rats treated with prebiotic XOS (0.089 ± 0.312), probiotic *L. paracasei HII01* (0.167 ± 0.522), or synbiotics (0.160 ± 0.188) was equally reduced when compared with the F/B ratio of HFD-fed rats treated with vehicle (0.479 ± 0.174, *p* \< 0.05). These findings indicated that long-term HFD consumption caused gut dysbiosis, and the supplement with prebiotics, probiotics, and synbiotics could attenuate gut dysbiosis, as indicated by decreased F/B ratio.
Long-term HFD consumption caused peripheral insulin resistance and dyslipidemia, and treatments attenuated these metabolic disturbances {#Sec16}
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After 12 weeks of HFD consumption, the body weight, plasma insulin level, and HOMA index of HFD-fed rats increased significantly when compared to ND-fed rats without alteration of the plasma glucose level (Table [1](#Tab1){ref-type="table"}). Moreover, rats fed with a HFD had significantly increased plasma total cholesterol and LDL cholesterol when compared to the ND-fed rats (Table [1](#Tab1){ref-type="table"}). Interestingly, 12 weeks of prebiotic XOS, probiotic *L. paracasei* HIIO1 or the synbiotics supplements had significantly decreased plasma insulin level, HOMA index, area under the curve of the oral glucose tolerance test (AUCg), plasma total cholesterol level, and LDL cholesterol level when compared to the HFD-fed rats receiving the vehicle (Table [2](#Tab2){ref-type="table"}). These findings suggested that long-term HFD consumption caused peripheral insulin resistance as indicated by hyperinsulinemia with euglycemia and increased HOMA index as well as dyslipidemia, which were improved by all treatments.Table 1The metabolic parameters at baseline and after 12 weeks of either ND or HFD consumptionMetabolic parametersBaselineNDHFDBody weight (g)225 ± 2459 ± 6\*540 ± 9\*†Food intake (g/day)21 ± 0.521 ± 0.224 ± 0.2\*†Plasma glucose (mg/dl)132.6 ± 6137.7 ± 4142.2 ± 5Plasma insulin (ng/ml)2.3 ± 0.34.6 ± 0.4\*6.0 ± 0.5\*†HOMA index22.4 ± 541.7 ± 4\*63.4 ± 7\*†Plasma total cholesterol (mg/dl)74.7 ± 272.5 ± 389.4 ± 3\*†Plasma total triglyceride (mg/dl)61.1 ± 565.2 ± 366.1 ± 5LDL cholesterol (mg/dl)21.5 ± 321.9 ± 334.1 ± 3\*†\**P* \< 0.05 in comparison with baseline group†*P* \< 0.05 in comparison with ND groupTable 2The metabolic parameters after 12 weeks of vehicle, prebiotic, probiotic, or synbiotics administration in ND-fed rats and HFD-fed ratsMetabolic parametersNDHFDNDVNDPENDPONDCHFVHFPEHFPOHFCBody weight (g)501 ± 9495 ± 11517 ± 14510 ± 13680 ± 24\*605 ± 30\*†689 ± 33\*600 ± 34\*†Food intake (g/day)20 ± 0.519 ± 0.721 ± 0.921 ± 0.425 ± 0.4\*23 ± 0.7\*25 ± 0.5\*24 ± 0.5\*Visceral fat (g)25 ± 227 ± 329 ± 333 ± 263 ± 3\*43 ± 5\*†65 ± 3\*48 ± 5\*†Plasma glucose (mg/d)132.3 ± 7140.5 ± 8137.5 ± 8141.6 ± 12139.2 ± 9142.1 ± 6137.8 ± 4132.1 ± 14Plasma insulin (ng/ml)4.8 ± 0.85.5 ± 15.4 ± 0.84.0 ± 17.8 ± 0.5\*5.5 ± 0.5†5.2 ± 1†5.0 ± 1†HOMA index40.3 ± 1050.0 ± 1455.8 ± 1150.9 ± 1294.6 ± 12\*55.6 ± 6†60.5 ± 8†39.8 ± 5†Plasma glucose AUC (AUCg) (mg/dl × min × 10^4^)2.1 ± 0.12.0 ± 0.12.2 ± 12.3 ± 0.12.9 ± 0.1\*2.1 ± 0.1†2.4 ± 0.1†2.2 ± 0.1†Plasma total cholesterol (mg/dl)74.4 ± 468.7 ± 465.9 ± 558.6 ± 5111.1 ± 8\*73.9 ± 3†78.8 ± 4†75.2 ± 6†Plasma total triglyceride (mg/dl)78.3 ± 1371.5 ± 668.7 ± 877.7 ± 784.9 ± 1073.3 ± 678.3 ± 474.5 ± 4Plasma LDL cholesterol (mg/dl)24.2 ± 522.3 ± 223.5 ± 622.7 ± 665.7 ± 10\*33.1 ± 4†35.3 ± 5†27.1 ± 5†Serum MDA (μmol/dl)3.72 ± 0.23.92 ± 0.13.91 ± 0.13.64 ± 0.25.76 ± 0.5\*3.31 ± 0.2†3.23 ± 0.3†3.16 ± 0.2†Brain MDA (μmol/mg protein)7.59 ± 1.88.10 ± 1.96.58 ± 1.62.01 ± 1.0\*15.0 ± 2.1\*8.23 ± 1.9†5.59 ± 1.1†1.84 ± 0.7\*†Brain IL-1β (fold change/gapdh)1.39 ± 0.50.45 ± 0.12.03 ± 0.11.82 ± 0.40.35 ± 0.10.71 ± 0.31.08 ± 0.60.51 ± 0.2Brain IL-6 (fold change/gapdh)1.27 ± 0.51.30 ± 0.810.68 ± 5.47.54 ± 1.21.10 ± 0.41.29 ± 0.13.57 ± 2.70.80 ± 0.2\**P* \< 0.05 in comparison with the NDV group†*P* \< 0.05 in comparison with the HFV group
Before treatment, we found a negative correlation between time in target quadrant of probe test with the metabolic parameters including body weight (*r* = − 0.689, *p* \< 0.01), insulin (*r* = − 0.658, *p* \< 0.01), HOMA index (*r* = − 0.756, *p* \< 0.01), plasma total cholesterol (*r* = − 0.724, *p* \< 0.01), and serum LPS level (*r* = − 0.877, *p* \< 0.01). After treatment with prebiotic, probiotic, or synbiotics, we found the negative correlations between time in target quadrant of probe test with the metabolic parameters and inflammatory markers including body weight (*r* = − 0.387, *p* \< 0.01), plasma total cholesterol (*r* = − 0.388, *p* \< 0.01), LDL cholesterol (*r* = − 0.492, *p* \< 0.01), colon IL-6 mRNA expression (*r* = − 0.355, *p* \< 0.01), fat mass (*r* = − 0.333, *p* \< 0.01), serum LPS level (*r* = − 0.312, *p* \< 0.05), and brain LPS level (*r* = − 0.466, *p* \< 0.01). Taken together, these findings added the potential mechanism regarding the protective effects of prebiotic, probiotic, or synbiotics on cognitive dysfunction in obese-insulin resistant rat that could occur possibly through the modulation of LDL cholesterol level, fat mass, and serum and brain LPS level as well as the level of colon IL-6 mRNA expression.
Prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics restored hippocampal plasticity impaired by long-term HFD consumption {#Sec17}
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To determine hippocampal plasticity, the fEPSP slope of LTP was measured from CA1 area of hippocampal slices. LTP is a marker of hippocampal synaptic plasticity. HFD-fed rats treated with the vehicle showed impaired hippocampal plasticity indicated by a significantly decreased mean fEPSP slopes compared to ND-fed rats, whereas all treatments effectively normalized the fEPSP slopes (*n* = 2--3 independent slices/animal, *n* = 6 animals/group; (Fig. [3](#Fig3){ref-type="fig"}a--b)) in these HFD rats. In addition, dendritic spine density was also significantly decreased in HFD rats, which was restored in HFD-fed rats treated with prebiotic XOS, probiotic *L. paracasei* HIIO1, or synbiotics (Fig. [3](#Fig3){ref-type="fig"}c--d). Taken together, long-term HFD consumption demonstrated hippocampal dysplasticity as indicated by impaired LTP and decreased dendritic spine density, and all treatments reversed these impairments.Fig. 3Effects of prebiotics, probiotics, or synbiotics on hippocampal plasticity. **a** Percentage normalized fEPSP slope of electrical-induced LTP by extracellular recording. **b** Mean fEPSP slope from 50 to 60 mins of electrical-induced LTP. **c** Representative images of Dil immunofluorescent under confocal microscopy (bar = 5 μm). **d** Mean dendritic spine density. ND: 24-week-normal diet-fed rats; HFD: 24-week high fat-fed rats; V: rats receiving PBS as vehicle; PE: rats receiving prebiotics; PO: rats receiving probiotics; C: rats receiving combination of prebiotics and probiotics as synbiotics (*N* = 6 of each group) \**p* \< 0.05 in comparison with the ND-fed rats; †*p* \< 0.05 in comparison with the HFD-fed rats receiving vehicle
Prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics improved brain mitochondrial dysfunction, hippocampal oxidative stress, and hippocampal apoptosis {#Sec18}
------------------------------------------------------------------------------------------------------------------------------------------------------------------
To determine brain mitochondrial function, the whole brain and hippocampus ROS production, brain mitochondrial depolarization, and brain mitochondrial swelling were measured. HFD-fed rats treated with the vehicle had increased brain and hippocampus ROS production (Fig. [4](#Fig4){ref-type="fig"}a--b), brain mitochondrial depolarization (Fig. [4](#Fig4){ref-type="fig"}c) as well as decreased brain mitochondrial absorbance indicating brain mitochondrial swelling (Fig. [4](#Fig4){ref-type="fig"}d). These impairments were attenuated by all treatments. In addition, to determine hippocampal apoptosis, the expression of apoptotic and anti-apoptotic proteins including bax and bcl-2 was determined. The increase of bax expression and decrease of bcl-2 expression found in HFD-fed rats treated with the vehicle was improved in HFD-fed rats receiving prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics (Fig. [4](#Fig4){ref-type="fig"}e--f). These findings demonstrated that all treatments ameliorated brain mitochondrial dysfunction, decreased hippocampal oxidative stress levels, and exerted anti-apoptotic effects.Fig. 4Effects of prebiotics, probiotics, or synbiotics on brain mitochondrial function, hippocampal oxidative stress, and hippocampal apoptosis. **a** Whole brain isolated mitochondrial ROS production. **b** Hippocampal ROS production. **c** Percent change of whole brain isolated mitochondrial depolarization when incubated with hydrogen peroxide. **d** Upper panel: representative images of brain mitochondrial morphology. Lower panel: whole brain isolated mitochondrial absorbance value. **e** Upper panel: representative immunoblotting images of Bax relative to actin expression. Lower panel: the expression of hippocampal Bax protein relative to actin. **f** Upper panel: representative immunoblotting images of Bcl-2 relative to actin expression. Lower panel: the expression of hippocampal Bcl-2 protein relative to actin. ND: 24-week-normal diet-fed rats; HFD: 24-week high fat-fed rats; V: rats receiving PBS as vehicle; PE: rats receiving prebiotics; PO: rats receiving probiotics; C: rats receiving combination of prebiotics and probiotics as synbiotics (*N* = 6 of each group) \**p* \< 0.05 in comparison with the ND-fed rats; †*p* \< 0.05 in comparison with the HFD-fed rats receiving vehicle
Microglial activation was attenuated by prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics in obese-insulin resistant rats {#Sec19}
----------------------------------------------------------------------------------------------------------------------------------------
To determine microglia morphology phenotype, soma size, and processes length, ramification number Iba-1 positive cell and mean fluorescent intensity were measured. Three microglial cells per brain slice, three brain slices per animal, and six animals per group were measured from the CA1 region of the hippocampus. The microglial morphology of Iba-1 immunofluorescent under confocal microscopy at CA1 of the hippocampus were demonstrated (Fig. [5](#Fig5){ref-type="fig"}a--h). There were no significant differences in all microglial morphology parameters among the ND-fed groups (Fig. [5](#Fig5){ref-type="fig"}a--d). Microglia from HFD-fed rats had amoeboid phenotype (Fig. [5](#Fig5){ref-type="fig"}e) as indicated by the significantly increased soma size (Fig. [5](#Fig5){ref-type="fig"}i), decreased process length (Fig. [5](#Fig5){ref-type="fig"}j), increased major projection and increased Iba-1 positive cell when compared to ND-fed rats (Fig. [5](#Fig5){ref-type="fig"}k--m). Prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics preserved all microglial morphology parameters (Fig. [5](#Fig5){ref-type="fig"}i--m). Collectively, HFD consumption led to microglial morphology changes which were attenuated in all treatments.Fig. 5Effects of prebiotics, probiotics, or synbiotics on brain microglia morphology. **a**-**h** Representative images of Iba-1 immunofluorescent under confocal microscopy at CA1 of the hippocampus (bar = 50 μm). **i** Soma area of Iba-1 positive cell. **j** Processes length of Iba-1 positive cell. **k** The ramification of Iba-1 positive cell. **l** Number Iba-1 positive cell. **m** Mean fluorescent intensity of Iba-1 positive cell. ND: 24-week-normal diet-fed rats; HFD: 24-week high fat-fed rats; V: rats receiving PBS as vehicle; PE: rats receiving prebiotics; PO: rats receiving probiotics; C: rats receiving combination of prebiotics and probiotics as synbiotics (3 microglial calls/slice, 3 slices/animal and 6 animals/ group) \**p* \< 0.05 in comparison with the ND-fed rats; †*p* \< 0.05 in comparison with the HFD-fed rats receiving vehicle
Cognitive dysfunction induced by long-term HFD consumption was ameliorated in prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics consumption {#Sec20}
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Cognitive function was determined by Morris water maze test. Twelve weeks of HFD consumption caused memory impairment as indicated by the increased time taken to reach the platform (Fig. [6](#Fig6){ref-type="fig"}a) and decreased time spent in the target quadrant in these rats, compared to 12-week ND-fed rats (Fig. [6](#Fig6){ref-type="fig"}b). After 12 weeks of receiving prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics in HFD-fed rats, the time to reach the platform was significantly decreased when compared to the vehicle group during the acquisition test (Fig. [6](#Fig6){ref-type="fig"}c). In addition, the time spent in the target quadrant during the probe test in HFD-fed rats with prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics was also significantly higher than that of the vehicle group (Fig. [6](#Fig6){ref-type="fig"}d). All of these findings suggested that all treatments effectively attenuate the impairment of learning and memory behaviors caused by long-term HFD consumption. The locomotor activity was determined by the open-field test. We found that long-term HFD consumption did not alter locomotor activity, indicating by distance (cm/10 min), when compared to ND-fed rats (2406 ± 560 cm vs. 2423 ± 690 cm for ND-fed rats and HFD-fed rats, respectively). Moreover, the locomotor activity of ND-fed rats and HFD-fed rats treated with prebiotic XOS, probiotics *L. HII01*, or synbiotics also was not significantly different when compared to ND-fed rats treated with vehicle (NDV 2368 ± 152 cm; NDPE 2658 ± 611 cm; NDPO 3038 ± 340 cm; NDC 2219 ± 444 cm; HFV 2498 ± 707 cm; HFPE 2542 ±646 cm; HFPO 2808 ± 686 cm; and HFC 3135 ± 1389 cm). These findings also indicated that the cognitive impairment during the Morris water maze test did not involve the motor function.Fig. 6Effects of prebiotics, probiotics, or synbiotics on cognitive function. **a** Time to reach the platform in acquisition test of Morris Water maze test of ND- and HFD-fed rats at 12th week. **b** Mean time spent in target quadrant of ND- and HFD-fed rats at 12th week. **c** Time to reach the platform in acquisition test of Morris Water maze test after receiving prebiotics, probiotics, or synbiotics. **d** Mean time spent in target quadrant after receiving prebiotics, probiotics, or synbiotics. ND: 24-week-normal diet-fed rats; HFD: 24-week high fat-fed rats; V: rats receiving PBS as vehicle; PE: rats receiving prebiotics; PO: rats receiving probiotics; C: rats receiving combination of prebiotics and probiotics as synbiotics (*N* = 6 of each group) \**p* \< 0.05 in comparison with the ND-fed rats; †*p* \< 0.05 in comparison with the HFD-fed rats receiving vehicle
Discussion {#Sec21}
==========
The major findings of the present study are as follows. The obesity caused by long-term HFD consumption had (1) low-grade inflammation found in both local (gut) and systemic (serum) sites, leading to low-grade systemic inflammation and the development of peripheral insulin resistance; (2) hippocampal dysplasticity; (3) brain mitochondrial dysfunction; and (4) cognitive decline. These impairments are possibly mediated through the induction of gut inflammation, brain and hippocampal oxidative stress, brain inflammation, hippocampal apoptosis, the reduction of dendritic spine density, and microglial dysfunction. Daily consumption of prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics for 12 weeks improved the brain function in these obese rats by attenuating gut and systemic inflammations, decreasing brain and hippocampal oxidative stress, increasing dendritic spine density, ameliorating microglial activation, and improving hippocampal dysplasticity and brain mitochondrial dysfunction, leading to restored cognitive function.
Previous studies demonstrated that long-term HFD consumption is known to lead to gut dysbiosis by enhancing the growth of *Proteobacteria*, which is mainly composed of Gram-negative LPS containing bacteria, in the gut in the gut content \[[@CR18], [@CR19]\] and impaired the gut barrier integrity by inhibition of tight junction proteins \[[@CR53]\]. This "leaky gut" found in the obese mice allows the luminal LPS and LPS-containing bacteria translocated from gut lumen to activate the innate immune cells in gut lamina propria, thus triggering the inflammatory response \[[@CR18], [@CR54]\]. Consistent with those reports, long-term HFD consumption in this study caused gut inflammation and increased the LPS level, in which it is possible that that amount of *Proteobacteria* should be increased in our HFD-fed rats. These findings suggested that obesity induced by HFD consumption caused gut inflammation, leading to low-grade systemic inflammation and the development of a peripheral insulin resistance. These undesirable effects were attenuated by consumption of prebiotics, probiotics, or synbiotics. In this study, the pro-inflammatory mRNA levels of IL-1β and IL-6 in the brain were not different among groups. Since this was done in the whole brain tissues, future studies are needed to investigate whether the pro-inflammatory cytokines in the hippocampal tissues would be different between the treatment groups and the control groups.
Although we found that only prebiotic XOS and synbiotics, not probiotic *L. paracasei* HIIO1, attenuated adiposity, which was the major source of pro-inflammatory cytokines, by decreasing the body weight and visceral fat, insulin resistance and dyslipidemia were still improved in all treatments. Currently, the beneficial role of probiotics on metabolic syndrome is still debated, at least one part was due to the strain-specific effect. For example, oral supplement of *Lactobacillus acidophilus*, *Lactobacillus ingluviei*, and *Lactobacillus fermentum* can cause weight gain \[[@CR55]\], whereas *Lactobacillus gasseri* and *Lactobacillus rhamnosus* promoted weight loss \[[@CR56]\]. Collectively, prebiotic XOS and synbiotics had beneficial effects to metabolic disturbance through systemic inflammation stemming from gut dysbiosis and adiposity, whereas probiotic *L. paracasei* HIIO1 had beneficial effects through systemic inflammation stemming only from gut dysbiosis. Our findings on probiotic supplement support this hypothesis.
In addition, blood-brain barrier (BBB) permeability was increased in a model of obesity-induced by HFD \[[@CR57]\] and also aggravated cognitive deficit by increasing the exposure of the brain to various cytokines, including LPS, IL-1β, IL-6, and tumor necrosis factor alpha (TNFα) \[[@CR58]\]. These undesirable effects were diminished in rats receiving prebiotic XOS, probiotic *L. paracasei* HIIO1, or synbiotics and restored cognitive function, possibly modulated through anti-oxidative and anti-inflammatory effects. Growing evidence demonstrates that the supplementary XOS decreased oxidative status in white sea bream juvenile \[[@CR59]\] and suppressed pro-inflammatory cytokines including IFNγ and IL-1β \[[@CR60]\]. Probiotics are also known to exert an anti-inflammatory effect since it has been shown previously that *Lactobacillus helveticus* decreased inflammatory markers including nitric oxide synthase (NOS), prostaglandin E2 (PGE2), and IL-1β in the brain \[[@CR25]\]. In addition, synbiotics, the combination of XOS and *Lactobacillus plantarum*, had greater antioxidant activity than single therapy, indicating that prebiotics, probiotics, or synbiotics could effectively decrease oxidative stress and inflammation not only in the gut and circulation, but also in the brain \[[@CR61]\]. Taken together, prebiotic XOS, probiotic *L. paracasei* HII01, or synbiotics (the combination of XOS and *L. paracasei* HII01) exerted an anti-oxidative effect and anti-inflammatory effect, leading to restored cognitive function impaired by HFD. Previous studies also demonstrated that obesity-induced cell apoptosis by increased Bax level, decreased Bcl-2 level, and impaired brain mitochondrial function, which were also seen in the present study \[[@CR48], [@CR62]\]. Interestingly, we found that prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics attenuated brain mitochondrial dysfunction, hippocampal ROS production, and hippocampal apoptosis.
Growing evidence has demonstrated the crucial roles of microglia on cognitive dysfunction in neurodegenerative disorders including excessive synaptic pruning of the brain with Alzheimer's disease \[[@CR29], [@CR30]\] and robust brain inflammation in obesity \[[@CR31]--[@CR33]\]. Previous studies demonstrated that HFD consumption increased activated microglia, leading to hippocampal dysplasticity including impairment of LTP, decreased dendritic spine density, as well as decreased synaptic protein such as postsynaptic density protein 95 (PSD-95), synaptophysin, and spinophilin, resulting in cognitive dysfunction \[[@CR31], [@CR33]\].
Although microglia played a crucial role in cognitive function and prebiotics, probiotics or synbiotics have been shown to exert protective effects on cognition \[[@CR26], [@CR30]\]; the link between gut microbiota modulating cognitive function through microglia has never been tested. In the present study, we demonstrated for the first time that long-term consumption of prebiotic XOS, probiotic *L. paracasei* HIIO1, or the synbiotics ameliorated microglial activation and restored cognitive function in diet-induced obese rats. There are three possible mechanistic explanations for the beneficial effects of the interventions we used in this study with prebiotics, probiotics, and synbiotics on brain cognitive function. First, prebiotics, probiotics, and synbiotics can mediate their effects through vagus nerve activation. It has been shown that consumption of *Bifidobacterium longum* exerted a vagal pathway-dependent anxiolytic effect in a chemically induced colitis mouse model \[[@CR63]\]. Second, prebiotics, probiotics, and synbiotics can attenuate microglial activation which occurs in response to metabolite profiles in diet-induced obesity \[[@CR18], [@CR19]\]. Third, the gut microbiota can increase the production of short-chain fatty acids (SCFAs) such as acetate, butyrate, and proprionate, which has been shown to be beneficial in metabolic syndrome \[[@CR64], [@CR65]\]. However, the beneficial effects of prebiotics, probiotics, or synbiotics are strain-specific. Further research is needed into the mechanisms behind the role of microglia in cognition and the signaling pathways involved in neuroglia communication.
Surprisingly, the synbiotics did not have the synergistic effect of the attenuation of inflammation, hippocampal oxidative stress, hippocampal apoptosis, mitochondrial dysfunction as well as microglial dysfunction in rats with an obese-insulin resistant condition. These findings suggest that the prebiotic XOS might not effectively promote the probiotic functions of *L. paracasei HII01* in vivo. Moreover, these observations suggest that inconsistent reports regarding the probiotic effect in the treatment of metabolic syndrome could be due to a strain-specific effect of this probiotic in a combination with a specific prebiotic fiber. This possibility has been supported by previous studies which demonstrated that XOS could not facilitate the growth of *Lactobacillus paracasei* \[[@CR66], [@CR67]\].
Conclusion {#Sec22}
==========
The present study showed that obese-insulin resistant condition, induced by prolonged HFD consumption, causes gut and systemic inflammation, peripheral insulin resistance, hippocampal dysplasticity, hippocampal oxidative stress, brain mitochondrial dysfunction, hippocampal apoptosis, and microglial morphological changes, resulting in cognitive decline. Moreover, this is the first report to show the possible link between gut microbiota modification by prebiotics, probiotics, or synbiotics supplement and the improvement of cognitive function in obese-insulin resistant rats. These neuroprotective effects may possibly be mediated through the attenuation of inflammation, hippocampal oxidative stress, hippocampal apoptosis, mitochondrial dysfunction as well as microglial dysfunction.
aCSF
: Artificial cerebrospinal fluid
AUG
: Areas under the curve
cDNA
: Complementary DNA
cfu
: Colony forming unit
fEPSP
: Field excitatory postsynaptic potentials
HFD
: High-fat diet
HFS
: High-frequency stimulation
HOMA
: Homeostasis Model Assessment
HPLC
: High-performance liquid chromatography
IL-1
: Interleukin 1
IL-6
: Interleukin 6
LAL
: Limulus amoebocyte lysate
LPS
: Lipopolysaccharide
LTP
: Long-term potentiation
MDA
: Malondialdehyde
ND
: Normal diet
OGTT
: Oral glucose tolerance test
ROS
: Reactive oxygen species
XOS
: Xylooligosaccharide
This work was supported by Thailand Research Fund TRF-RTA6080003(SCC), the Royal Golden Jubilee PhD program (PHD/0146/2558 TC&SC), TRG-5980198 (WP), TRG-5880041 (PT), The National Research Council of Thailand (SC), a NSTDA Research Chair Grant from the National Science and Technology Development Agency Thailand (NC) and Chiang Mai University Excellent Center Award (NC). The authors would like to thank Ms. Cicely Proctor, Ms. Thidarat Jaiwongkum, and Ms. Sasiwan Kerdpoo for their technical assistance in this project. A thank also goes to Ms. Maria Love for her editorial assistance of this manuscript.
Funding {#FPar1}
=======
All sources of funding for the research reported did not have any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Availability of data and materials {#FPar2}
==================================
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Please contact author for data requests.
TC performed the majority of data acquisition, data analysis, writing of the original draft, and revising of the manuscript. WT contributed to the data acquisition and data analysis. SY contributed to the data acquisition and data analysis for gut and systemic inflammation. KW contributed in the data acquisition. SE contributed to the data acquisition and data analysis. GM contributed to the data acquisition and data analysis. AL contributed to the data acquisition. AP contributed to the data acquisition. SS contributed to the preparation for probiotics and synbiotics. CC contributed to the preparation for probiotics and synbiotics. WP contributed to the data acquisition, data analysis, and drafting of the manuscript. PT contributed to the data acquisition for gut and systemic inflammation, data analysis, and drafting of the manuscript. NC contributed to the conception and design and the drafting or revising of the article. SCC contributed to the initial conception and design, data analysis and interpretation, and revision and finalization the manuscript. All authors read and approved the final manuscript.
Ethics approval {#FPar3}
===============
All animal studies were approved by the Institutional Animal Care and Use Committee (IACUC) of the Faculty of Medicine, Chiang Mai University (Permit number: 13/2558 on May 12, 2015) and conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH guide, 8th edition, 2011).
Consent for publication {#FPar4}
=======================
Not applicable.
Competing interests {#FPar5}
===================
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Publisher's Note {#FPar6}
================
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Liver Cancer
Liver cancer appropriately referred to as primary liver cancer is cancer resulting from cancerous cells in the liver. The liver serves to filter blood, create bile, to store and releasing sugars among other functions. Cancer from other organs can spread to the liver via blood circulation resulting in metastatic cancer. The liver is composed of many cells, which gives rise to different types of tumors, where some are noncancerous, and others are cancerous. The most common form of cancer from the liver is the hepatocellular carcinoma.
Signs and symptoms
Swelling or pain in the abdomen
Loss of appetite
Vomiting
Yellowing of the eye whites’ and the skin a condition known as jaundice
Liver cancer if detected early is treatable, hence the need to visit a doctor regularly for diagnosis. The procedure adopted depends on the stage of the liver cancer.
Surgery
This involves the treatment of the liver cancer through surgical means. Unfortunately, many people do not qualify for surgery due to the existence of other liver conditions. In other cases, cancer from the liver easily spreads through the body due to the purification process of blood. Therefore, treating the liver through surgical means could lead to eliminating the problem partially to reoccur later. However, in the present times, surgical methods have improved, and survival rates have improved tremendously.
A surgical process will use a general anesthesia and follow-up medications.
Anesthesia : A surgical process will use general anesthesia
Risks : Excessive bleeding, infection of the lung after surgery, Liver failure, Rejection of the liver by your body, the liver failing to work immediately necessitating another transplant, Loss of kidney function, Damage to the liver, Nausea, Fever, Fatigue, Pain, Loss of appetite, Mouth sores
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What happened, Novak?
Novak, the crowd-pleaser, never fires anyone. He cares too much about being the good guy, the benevolent patron — that’s a persona that matters to him. When he wants to be rid of an employee, what happens is that they “part ways,” by “mutual agreement,” and the employee releases a glowing statement about what a privilege it was to work with Djokovic.
In May he parted ways, by mutual agreement, with his entire coaching staff.
What‘s wrong, Novak?
What was most bizarre, throughout this phase of decline, was how little anyone seemed able to explain it. Novak himself was tongue-tied. “It was nothing physical,” he said in August, in the clearest explanation he ever offered for his wipeout. “It was some other things that I was going through privately.”
Oh, of course: some private … things. The tennis media is almost ritually circumspect. Tabloids have speculated furiously about the state of Djokovic’s marriage. Message-board posters have built elaborate theories on Jelena Djokovic’s air of wounded dignity in the player’s box. John McEnroe caused a minor dust up last week when he compared Djokovic’s downfall to that of Tiger Woods. But for the most part, the closer you get to the game itself, the more pundits have framed Djokovic’s nose-dive in terms that are careful and vague and respectful.
The vagueness may be appropriate. Djokovic’s marriage, if that was really the issue, is none of my business. (Which doesn’t mean I don’t find it fascinating.) It was disorienting, though, to see a great player’s decline take place inside this void of abashed euphemism.
Djokovic’s collapse helped both Federer and Nadal win majors. It made Murray the No. 1 player in the world. Yet when we try to explain it, it’s a weird blur, an afterimage of gossip. It’s left Djokovic’s identity even less clear — the rare instance when adversity seems to leave us knowing less, not more, about a player.
I learned a lot, along the way, about the steps Djokovic was taking to reverse course. At one point he hired a guru specializing in long hugs; a kind of New Age questiness is another one of his personas. I didn’t learn much at all about what was wrong, or how it felt.
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Introduction {#s1}
============
Endometrial cancer is the most common gynecologic malignancy in the United States, with an estimated 43,400 new cases diagnosed and 8000 deaths annually [@pone.0021912-Jemal1]. Most patients (71%) have disease confined to the uterus (FIGO stage I) [@pone.0021912-Jemal1] [@pone.0021912-Mikuta1]. In 1988 the International Federation of Gynecology and Obstetrics (FIGO) replaced clinical staging with surgical staging system for endometrial cancer [@pone.0021912-Mikuta1]. It is supported by several studies which indicate that as many as 25% and 50% of patients with clinical stage I, or II disease respectively had disease outside the uterus at the time of comprehensive surgical staging [@pone.0021912-Creasman1].
Whereas there is general agreement about the necessity of complete surgical staging for high risk endometrial cancer as the risk of nodal metastasis is high [@pone.0021912-Creasman2]; the need for pelvic and paraaortic lymphnode dissection with complete surgical staging for the low risk endometrial cancer has been debated passionately. [@pone.0021912-Kitchener1] [@pone.0021912-BenedettiPanici1] [@pone.0021912-Seracchioli1], [@pone.0021912-Uccella1]. The pendulum swings with some advocating only hysterectomy and bilateral salpingooophorectomy without node dissection for low risk endometrial cancer [@pone.0021912-Mourits1] while others advocating comprehensive surgical staging for all patients with low risk disease [@pone.0021912-Walker1]. Still others take an intermediate path and believe that only a small fraction of patients with low risk endometrial cancer may benefit from routine and comprehensive surgical staging including a lymphadenectomy and the rest may be adequately managed by routine hysterectomy with bilateral salpingooophorectomy [@pone.0021912-Mariani1]. The key question however, is how best to identify these patients who have seemingly low risk endometrial cancer but may need complete surgical staging instead. One widely used approach to address this critical question is the use of intraoperative frozen section (FS) in the decision making process. Here, the surgeon completes a hysterectomy and if the FS shows high risk features, such as high grade, deep myometrial invasion, lymphovascular space invasion, adnexal or cervical involvement; then a comprehensive surgical staging is undertaken and vice versa. This approach is not without its pitfalls. The intra-operative assessment of grade and myometrial invasion is based on a limited sample and may not be in agreement with the final pathology. In addition, obscuring frozen artifact and interobserver variability of gross tumor evaluation would also confound the intraoperative microscopic assessment. It is therefore important to find the agreement rate of the FS with respect to its prediction of the final pathology in the paradigm of the complete surgical staging of the low risk endometrial cancer. The literature on this issue so far is controversial with some suggesting FS to be reliable [@pone.0021912-Quinlivan1] [@pone.0021912-Shim1] whereas others refuting the same [@pone.0021912-Frumovitz1]. This controversy was highlighted by a recent study by Soliman et. al. where half of the physicians indicated that they do not use FS and the rest indicated that they use FS in their practice to decide when to perform lymphadenectomy in endometrial cancer [@pone.0021912-Soliman1]. Therefore further data is urgently needed to resolve the controversy in defining the role of FS in surgical staging of low risk endometrial cancer.
The primary aim of this study is to assess the agreement rate between FS and paraffin section (PS) in determining the grade, depth of myometrial invasion, cervical involvement and lymphovascular space involvement. The secondary aim is to assess the impact of disagreement between the FS and PS on the FIGO stage designation of patients with presumed stage I low-grade endometrial cancer by FS.
Materials and Methods {#s2}
=====================
Ethics statement {#s2a}
----------------
This study was approved by the institutional review board (IRB) of the Wayne State University. No patient consent was required because the data were analyzed anonymously in a deidentified fashion and it was a retrospective study. The institutional review board (IRB) of the Wayne State University specifically waived the need for consent.
This is a retrospective review of endometrial cancer patients treated at Wayne State University from 1995 to 2004. All the patients had pre-operative diagnosis of low-grade endometrial cancer by endometrial biopsy or curettage. Here, low grade refers to FIGO grade I and II. FIGO staging used in the paper refers to the FIGO 1988 system of surgical staging.
Primary treatment was exploratory laparotomy with total abdominal hysterectomy and bilateral salpingooophorectomy. The FS was then done on the specimen. If high-risk features were present on the FS, decision was taken to perform lymphnode dissection. Lymphadenectomy was also done on some low risk cases, based on the treating physician\'s discretion. The inclusion criteria were: endometrial cancer limited to uterus by clinical assessment & imaging studies, low grade histology by preoperative endometrial biopsy or dilation and curettage, and low grade (grade I & grade II) endometrial cancer by intra operative FS with none or \<50% myometrial invasion. Exclusion criteria were: intra-operative FS findings of grade III, lymphovascular space invasion (LVSI), poor prognosis histologic type like carcinosarcoma, serous papillary or clear cell cancer, patients with intra-operative FS that showed more than 50% depth of myometrial invasion and cases where extra uterine disease was identified during the surgery. Also patients with synchronous primary ovarian tumors were excluded.
Intraoperative FS assessment: the specimen was sectioned serially at 2--3 mm intervals, grossly examined and areas of maximum macroscopic depth of invasion were obtained for intra-operative assessment. Two sections were taken for FS analysis. For assessment of cervical involvement, two sections were obtained from the lower uterine segment and endocervical junction for FS assessment. A median of 4 sections were examined for each patient. The sections were reviewed by the on-call pathologist and reported to the surgeon. The maximum time from receiving the specimen to having the report was 20 minutes. All final pathology reports were determined by a gynecologic pathologist. For the study, the FS slides were also reviewed by a gynecologic pathologist together with the lymph node specimens without knowing the results of final pathology results. The agreement between the PS and FS was assessed using the agreement statistic, (kappa). Comparison between the categorical variables was assessed using the chi square test. A 'p' value of ≤0.05 was considered statistically significant. SPSS was the statistical software used for the analysis (SPSS Inc, Chicago, Ill).
Results {#s3}
=======
A total of 457 cases of endometrial carcinoma were treated by hysterectomy during this study period at our institution of which 177 cases were evaluated for tumor grade and depth of myometrial invasion by intra-operative FS. At the time of FS analysis, 18% (31/177) patients were found to have a high grade (FIGO grade III) tumor or a poor prognosis histology type and were hence excluded; leaving 146 patients for the final analysis. The median age of the study cohort was 60 (range 24--88) years.
Of the entire study cohort (n = 146), 73 (50%) were grade I, 45 (31%) were grade II and 28 (19%) remained ungraded on initial FS. These ungraded cases are not included in [table 1](#pone-0021912-t001){ref-type="table"} and are represented by (UG) in [figure 1](#pone-0021912-g001){ref-type="fig"}. Of the 73 cases with grade I disease, the FS and PS were in agreement in 41 (56.2%) patients but the final pathology grade was advanced to grade II in 32 (43.8%, [table 1](#pone-0021912-t001){ref-type="table"}, [figure 1](#pone-0021912-g001){ref-type="fig"}). For grade II by FS, 36 (80%) were correlated in the final pathology report, whereas 6 cases (13.3%) were upgraded to grade III & three (6.7%) cases were downgraded to grade I ([table 1](#pone-0021912-t001){ref-type="table"}, [figure 1](#pone-0021912-g001){ref-type="fig"}). Concordance between frozen and permanent section for assessment of grade was 65.3% (kappa 0.58, 95%CI 0.51--0.68).
{#pone-0021912-g001}
10.1371/journal.pone.0021912.t001
###### Comparison of histologic grade in frozen and permanent sections.
{#pone-0021912-t001-1}
Frozen section Permanent section diagnosis
---------------- ----------------------------- ------------------ ----------------
Grade 173 Grade 141(56.2%) Grade 232(43.8%) Grade 30
Grade 245 Grade 13(6.7%) Grade 236(80%) Grade 36(13.3)
Myometrial invasion was assessed in 146 patients. By FS, 47 were found to have no MI (FS stage 1A as no extrauterine disease identified at FS or preoperatively). Of these 47, 32(68%) were in agreement on PS ([table 2](#pone-0021912-t002){ref-type="table"}) whereas the remaining 15(32%) had varying degree of MI. On the other hand, 99 patients were reported to have \<50% MI on FS (IFS stage 1B as no extrauterine disease identified at FS or preoperatively). Of these, 73(74%) were in agreement (64 with final stage 1B whereas 9 with final stage II --[table 2](#pone-0021912-t002){ref-type="table"}). Of the remaining 26(26%), 12 had no MI whereas 14 were found to have ≥50% MI. Concordance between frozen and permanent section for assessment of myometrial invasion was (105/126) 72% (kappa 0.61, 95%CI 0.53--0.69).
10.1371/journal.pone.0021912.t002
###### Comparison of stage in frozen and permanent sections.
{#pone-0021912-t002-2}
Frozen section stage Permanent section stage
---------------------- ------------------------- ------------- --------- ------------ ---------- ----------- -------------
I A47 IA32(68%) IB11(23.4%) IC0 IIA1(2.1%) IIB0 IIIA0 IIIC3(6.3%)
IB99 IA12(12%) IB64(64.6%) IC7(7%) IIA7(7%) IIB2(2%) IIIA3(3%) IIIC4(4%)
Regarding the stage of the disease, 47 cases evaluated by FS were found to have stage IA disease of which 32 (68%) were in agreement, 11(23.4%) were upstaged to IB, 1 (2.1%) upstaged to IIA and 3(6.4%) upstaged to IIIC. On the other hand, 99 patients were thought to have stage IB disease by FS of which 64(64.6%) were in agreement, 12 (12.1%) down staged to IA, 7 (7%) upstaged to IC, 9 (9%) upstaged to II A & B (7% & 2% respectively), 3 (3%) upstaged to IIIA, and 4 (4%) upstaged to stage IIIC ([table 2](#pone-0021912-t002){ref-type="table"}, [figure 2](#pone-0021912-g002){ref-type="fig"}). The FS displayed no cervical involvement for 122 patients in the study cohort of which 16 (13%) were determined to be false negative by the permanent histology by virtue of identification of tumor involving the cervix. Concordance between frozen and permanent section for assessment of cervical invasion was 86.9% (kappa 0.78, 95%CI 0.65--0.91) The FS stage in these 16 patients was FIGO IA in 3 and FIGO IB in 13. By definition of the inclusion criteria, all patients were negative for LVSI by FS. However, on final pathology report, 34 (31.7%) patients had LVSI, 73 did not have LVSI and in the rest 39, it was not assessed. It is noteworthy that 4 (14.2%) of patients with stage IA, and 30 (37.9%) of stage IB by FS, had positive LVSI. Concordance between frozen and permanent section for assessment of LVSI was 68.3% (kappa 0.60, 95%CI 0.52--0.69).
{#pone-0021912-g002}
A total of 83 of 146 (56.8%) patients underwent lymph node dissection. Of these patients, 97.6% underwent pelvic while 42.1% underwent paraaortic lymph node dissection. The median number of pelvic nodes obtained was 7 (range 1--35) and that of paraaortic lymph nodes was 4 (range 1--14). In all, 7 (8.4%) had lymph node metastasis. Pelvic lymph node metastasis was found in 5 patients (6%), whereas aortic lymph node metastasis was found in 1 (1.2%). One patient had involvement of both, pelvic and paraaortic nodes (1.2%). Of the 47 patients who had FS stage IA disease, lymphadenectomy was done in 23 (48.9%) while 24 patients did not have complete surgical staging. Of those who underwent lymphadenectomy, 3 (13%) cases had positive lymph nodes and were upstaged from IA to IIIC. All of these 3 cases had a change in myometrial invasion from none to a median of 22% (18%, 22% and 32% individually). In addition, they also had a change of FS grade 2 to PS grade 3. Of the 99 patients with FS stage IB disease, 60(60.6%) patients had lymphadenectomy and 39 cases did not. A total of 6.7%(n = 4/60) patients in this subgroup had positive nodes and were upstaged to FIGO Stage IIIC ([figure 3](#pone-0021912-g003){ref-type="fig"}). The median myometrial invasion for these 4 patients was 58%. The overall rate of agreement between the FS and that of the PS for variables in question (grade, myometrial invasion, lymphovascular space invasion and cervical invasion) is presented in [table 3](#pone-0021912-t003){ref-type="table"} along with the agreement statistic; kappa.
{#pone-0021912-g003}
10.1371/journal.pone.0021912.t003
###### (%) Agreement between frozen section and paraffin section with the corresponding agreement statistic (Kappa) for different variables in endometrial cancer.
{#pone-0021912-t003-3}
Variable (%) Agreement Kappa (95% Confidence Interval for Kappa) p
------------------------------- --------------- ------- ------------------------------------- ----------
Myometrial invasion 72 0.61 0.53--0.69 \<0.0001
Cervical invasion 86.9 0.78 0.65--0.91 0.002
Lymphovascular space invasion 68.3 0.60 0.52--0.69 0.01
Grade 65.3 0.58 0.51--0.68 0.003
Discussion {#s4}
==========
The management of low risk endometrial cancer has been a subject of great controversy in our times. Central to the controversy remain the independent yet intertwined issues of lymphadenectomy and postoperative radiation therapy. Unfortunately, rather than forging ahead with a unified theory of treatment of this disease, there has been an emerging dichotomy between the European and the North American way of management of low risk endometrial cancer. The European approach depicts treatment of low risk endometrial cancer by performing a total abdominal hysterectomy and bilateral salpingooophorectomy without dissection of lymphnodes routinely. This approach had been demonstrated by several prominent treatment centers participating in some of the largest prospective randomized control trial programs in endometrial cancer [@pone.0021912-Mourits1], [@pone.0021912-Creutzberg1]. The advocates of this approach cite a perceived lack of benefit from routine lymphadenectomy in low risk endometrial cancer [@pone.0021912-Kitchener1] [@pone.0021912-BenedettiPanici1] along with achieving a potential benefit by sterilizing the nodal harbors of residual neoplastic clones in the lymphatic basins by aggressive use of adjuvant radiation [@pone.0021912-Creutzberg1]. In contrast is the North American approach advocating a routine lymph node assessment in endometrial cancer demonstrated by large cooperative group trial programs [@pone.0021912-Walker1] and suggested by the American College of Obstetrics and Gynecology [@pone.0021912-Hernandez1]. Supporters of this approach believe that surgical removal of lymphatic basins reduces tumor burden and minimizes the blanket use of unnecessary radiation, which will be given more frequently if surgical removal of lymphatic basins was not undertaken in this patient population. The gnawing limitations emanating from inadequate lymph node dissection and a lack of standard postoperative adjuvant treatment has introduced serious flaws in the prospective randomized lymphadenectomy trials [@pone.0021912-BenedettiPanici1] [@pone.0021912-Kitchener1] and has further fuelled the controversy surrounding the role of lymphadenectomy in low risk endometrial cancer [@pone.0021912-Dowdy1]. It has therefore become essential to examine an approach suggested by many as a reasonable compromise between the two polar opposite management strategies, namely; selective lymphnode dissection in low risk endometrial cancer based on high risk histology features discovered during intraoperative FS. This approach is based on the prerogative of maximizing pre-test probability of finding lymphnode metastasis if formal lymphadenectomy was undertaken and at least in theory, has the promise of avoiding the expense & morbidity of lymphadenectomy in patients who are at extremely low risk of lymphnode metastasis. On the other hand, it can also reduce the prescription of unnecessary blanket postoperative radiation. However, this intermediate approach of FS based selective lymphadenectomy in low risk endometrial cancer relies on two critical factors: the (%) agreement between FS and PS (because the historic risk factors for lymphnode assessment are based on final pathology rather than FS [@pone.0021912-Creasman2]) and the accuracy of these variables in predicting the actual lymphatic metastasis. In the present study, we evaluated the former of these two critical factors.
The first objective of this study was to correlate the grade and depth of myometrial invasion by FS with that of permanent pathology. Our results correlate with that of Frumovitz et al [@pone.0021912-Frumovitz1] who showed that FS analysis of tumor grade and depth of myometrial invasion are not always concordant with that of permanent sections. In the present study, for the intra-operative grade I, 44% were upgraded while in grade II, 13% were upgraded and 6.6% were downgraded. Hence in our series, there was 34.8% disagreement in assessing the grade of the tumor in comparison with PS. The clinical significance of upgrading in endometrial cancer was well depicted by Creasman et al. [@pone.0021912-Creasman2] in a seminal GOG study showing that a change of grade from I to II doubled the probability of middle third as well as outer third myometrial invasion; both of which signify a higher recurrence rate, poorer prognosis and generally call of additional adjuvant radiation [@pone.0021912-Creutzberg1] [@pone.0021912-Nout1]. Along the same lines, we observed that in assessment of depth of myometrial invasion, disagreement was found in 28% of the cases in comparison with the PS with the overall agreement rate of 72%. More importantly, 7% of the cases were upstaged from FIGO stage IB to IC; a subgroup of endometrial cancer patients with extremely poor prognosis [@pone.0021912-Creutzberg2]. In this study, lymph node dissection was done in 56.8% of the lesions evaluated by FS and positive lymphnodes were found in 8.4% of them overall. Our data display that 13% and 6.6% patients in FS stage IA and IB respectively had lymphnode metastasis. The seemingly paradoxical finding of a higher rate of nodal metastasis in FS stage 1A in comparison to FS stage 1B can be explained by the fact that the three patients who had the nodal metastasis in FS stage 1A were all upgraded from grade 2 to grade 3 along with an amended extent of myometrial invasion from none (on FS) to a median of 22% (on PS). These data display that if FS was used in isolation for risk stratification; 7% to 13% patients would have received suboptimal treatment by forgoing lymphadenectomy as they would have had positive nodes on lymphadenectomy. Although the statistical measure of agreement (kappa-[table 3](#pone-0021912-t003){ref-type="table"}) was generally in good/excellent range between the FS and PS; a 7%--13% prevalence of missed nodal metastasis seems clinically unacceptable for low risk endometrial cancer patients. Therefore, the interpretation of kappa in this specific scenario needs to be in context of the clinical implications rather than independent of the later. The risk of pelvic lymphnode involvement increases fivefold and that of paraaortic lymphnode involvement increases six fold as the depth of myometiral invasion changes from superficial to deep [@pone.0021912-Creasman2]. It is not unreasonable to expect that in routine clinical practice, disagreement of FS in prediction of grade, myometrial invasion and their cumulative impact on reducing the prevalence of surgical assessment of lymphnodes will be mutually multiplicative and has the potential of leading to the suboptimal treatment in a substantial number of patients. Similar to our study, others have reported a 5%--7% [@pone.0021912-Quinlivan1] [@pone.0021912-Shim1] risk of suboptimal surgical treatment of endometrial cancer patients when FS analysis is considered as the basis of surgical management. The overall agreement on LVSI between FS and PS was 68.3%. The probability of finding LVSI on PS was higher for FS stage 1B as compared to 1A (p = 0.02, Chi square). This observation will be consistent with the known risk stratification value of LVSI where a presence of the same signifies a higher risk category of endometrial cancer.
Selection of a section of endomyometrium for assessment of the maximum depth of invasion is based on gross evaluation of the tumor. This might prove to be difficult as often the findings could be subtle especially when associated with a grade I tumor. Furthermore, determination of the exact extent of myometrial involvement in the setting of FS is challenging as the invasion line can be extremely heterogeneous with presence of skip metastasis as pointed out by others [@pone.0021912-Quinlivan1]. FS has poor sensitivity to detect microscopic foci of the disease in the cervix, which could be found only in permanent sections [@pone.0021912-AttardMontalto1]. This was displayed in the present study where the FS was 13′% inaccurate on assessing the cervical involvement by the tumor in comparison to the permanent sections. The factors responsible for disagreement of FS grade include inadequate sampling to assess the amount of solid growth [@pone.0021912-Luzio1] and/or technical artifact associated with the surgery or FS process which might hamper the assessment of nuclear atypia. Evaluating additional sections would increase the agreement rate between the FS and PS however it will delay the time to diagnosis negating the advantage of this procedure [@pone.0021912-Quinlivan1]. Although we do not have data in support, but it seems likely that the errors in FS may be higher in absence of specialized gynecologic pathologists in many community hospitals. This would indirectly imply that where possible, referral to a gynecologic oncologist might be considered at the initial diagnosis of endometrial cancer because these physicians are specifically trained to perform accurate surgical staging of endometrial cancer.
Although the therapeutic value of lymphadenectomy is debatable in low risk endometrial cancer, the prognostic and treatment planning implications are clear [@pone.0021912-Klopp1]. Therefore, the consequences of errors that lead to incomplete surgical staging can be substantial. Patients who are incompletely staged at the time of the surgery and found to have high risk disease on final pathology, may need extended field radiotherapy or further staging procedures [@pone.0021912-BenShachar1] [@pone.0021912-Quinlivan1]. The combination of surgery and radiotherapy is associated with significant morbidity in up to 12% of the patients [@pone.0021912-BenShachar1]. Finally, the adverse financial impact of suboptimal surgical staging has been shown by many as well [@pone.0021912-BenShachar1], [@pone.0021912-Barnes1], [@pone.0021912-Fanning1].
The Limitation of this study is its retrospective nature combined with limited number of patients. However the data was collected from a single cancer center and the FS slides were reviewed and compared with the permanent sections by a gynecologic pathologist who was blinded to the final outcome at the time of assessment of the FS. Therefore, the bias in assessment of FS histology was minimized. It is to be noted that the application of the new FIGO 2009 staging criteria of the endometrial cancer to our data may decrease the disagreement rate of the myometiral invasion between FS and PS in terms of the upstaging. This is because the new FIGO 2009 staging clubs together the older (1988) stage IA and 1B. However, a large study of prospectively maintained data at the Memorial Sloan Kettering Cancer Center, New York [@pone.0021912-AbuRustum1], has highlighted the limitation of the new staging schema as it eliminates the group of patients with the best prognosis (i.e. old stage 1A = no myometrial invasion). It is also correctly noted that the predictive value of the prognosis for the new stage 1 system represents no improvements in comparison to the older system. Therefore, our data is presented according to the FIGO 1988 staging scheme.
In summary, our data displays that FS is poor indicator of tumor grade and depth of myometrial invasion compared with that of final permanent section report. Significant number of patients with low-grade endometrial cancer based on intraoperative FS will have a higher grade, a higher stage and presence of lymphovascular space invasion on final pathology. Because a substantial number of patients in our study underwent a lymphnode dissection and were not identified to be at risk of lymphnode metastasis by FS, we learned that the wisdom of basing a decision of lymphadenectomy in endometrial cancer on the FS may lead to suboptimal treatment of these patients. Hence, as recommended by the American College of Obstetricians and Gynecologists (ACOG) [@pone.0021912-Hernandez1] we support the notion of complete surgical staging along with lymphnode retrieval for patients with low grade early stage endometrial cancer unless medical contraindications exist.
**Competing Interests:**The authors have declared that no competing interests exist.
**Funding:**The authors have no support or funding to report.
[^1]: Conceived and designed the experiments: SK JPS RM AM RAF. Performed the experiments: SK SB JPS HM RAF. Analyzed the data: SK JPS HM RAF. Contributed reagents/materials/analysis tools: AM RM RAF. Wrote the paper: SK JPS AS RAF.
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Q:
php grouped table sorting 1 off
I am trying to achieve a sorted list with a section separator from a mysql table via php, but am having a bit of trouble. Instead of putting my soup in the soup header like I want, I am putting it in the following header(like I don't want)!
Here is the visual output:
2-Soup
3-Salad
2 Soup Demo: Tom KaKai
4-Entree
3 Salad Demo: Spinach Salad
4 Entree Demo: Pork Chop
4 Entree Demo: Spicy Topped Shrimp
here is my code:
$cat = null;
while($row = mysql_fetch_array($result))
{
if( $row['catnum'] != $cat )
{
echo '<h1>' . $row['catnum'] . '-' . $row['ctgry'] . '</h1>';
$cat = $row['catnum'];
}
echo "<table><tr><td>" . $row['catnum'] . " </td><td>" . $row['ctgry'] . "</td><td> " . $row['Shrt_Desc'] . "</td></tr>";
}
A:
You're not closing your <table> tag and are starting a new table for every DB row retrieved, so structurally your HTML page is a total mess.
You'd want something like this:
$first = true;
while ($row = mysql_fetch_array($result)) {
if ($row['catnum'] != $cat) {
if (!$first) {
echo '</table>'; // close the table if we're NOT the first row being output.
}
$first = false; // no longer the first table, so disable this check.
echo '<h1> etc...';
echo '<table>'; // start new table
$cat = $row['catnum'];
}
echo '<tr><td>' etc.... // output a table row
}
This code will only output the <table> and <h1> stuff when you change categories.
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Physical mapping of the genomic DNA of the Oryctes rhinoceros baculovirus, KI.
A non-occluded baculovirus, OBV-KI has been isolated from the insect pest, Oryctes rhinoceros. The viral genome is estimated to be 123 kb, with a G + C content of 43 mol% and no detectible methylated bases. A restriction map of the OBV-KI genome for BamHI, EcoRI, HindIII, PstI, SalI and XbaI has been constructed.
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Twitter goes crazy as Manchester United beat Swansea 4-0!
3 goals in 5 minutes towards the end of the game killed off any hope Swansea had of managing a point. Eric Bailly opened the scoring in te first half and it was only in the 81st minute that United doubled their lead through Romelu Lukaku.
However, things just escalated from there. Paul Pogba chipped Fabianski to make it 3-0 in the 83rd minute and then Anthony Marital scored off the bench once again to make it 4-0 in the 85th minute.
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Black Park dog walk, Buckinghamshire
Description
530 acres of attractive woodland, grassland and heathland with a lake in the middle.
You might recognise parts of the park - it's just down the road from Pinewood Studios and has been used as a location for parts of the 1960's Carry On ... films, as well as Harry Potter and the Philosopher's Stone, and the Chamber of Secrets.
Details
Mobility scooters are available free but must be booked in advance on 01753 511060. Training is provided. Tarmac path around the lake with seating every 100m
Lakeside cafe and toilets
Children's woodland play area
Walk
Several trails around the park, although with 530 acres it's just as nice to wander where the fancy takes you. The paths are quite stony, which is a bonus in wet weather.
There's a useful map that gives the terrain and steepness of the trail routes.
Member Reviews
Be the first to add a review
Edited: 21st February 2019. The details of this listing may have changed, and though the Driving with Dogs team do our best to confirm the accuracy of every listing, we cannot guarantee that the details are fully up to date and accurate.
If you know that any aspect of this listing is incorrect, please suggest an edit to let us know.
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