Dataset Viewer
text
stringlengths 0
128k
|
---|
Is there a java SDK
Is there a java SDK, how can I use the program call instead of the command to call the API?
Closing as duplicate of https://github.com/istio/istio/issues/9683
|
double.toStringAsFixed() sould have an option to truncate instead of round
toStringAsFixed will round the double to the nearest number, but sometimes this is not desirable. I would be helpful if we could choose if the String is generated using round, ceil, floor or truncate.
Since num is sealed, adding optional parameters to methods should be effectively non-breaking.
The biggest issue here is that we don't have the corresponding functionality in JavaScript, where we use the Number.prototype.toFixed function. That makes it very hard to add this extra functionality and compile it to efficient JavaScript.
Can we make a javascript only implementation of truncate and etc, and not have to rely on the language?
It's actually remarkably hard to implement a correct float-64 "toString" behavior, and I have no reason to believe it should be easier to do trunc/floor/ceil than round.
You have to convert the binary representation to a decimal representation, and know when to stop in order to be efficient. Both JS and Dart native uses a highly specialized piece of code (yep, same code, Mozilla uses a different one) to do that
That's the complexity of the code we'd need to implement in JavaScript. I don't think that's something we'd want to create - and maintain as part of the platform libraries.
I see... should I close this then?
(still waiting for the dartvm to make a come back to Chrome... a man can dream)
We can keep it open as a request, and if JS adds the functionality we need, or, say, we think WASM-compiling the C++ code becomes a viable approach, then we can revisit it at that point.
|
Is it possible to auto paste and click a button in the website by chrome extension?
I would like to make a two steps operation on a video URL by using chrome extension. First, paste the URL to another website's textbox.(For example, https://www.urlgot.com/). And then click the "search" button. Could I do it automatically by chrome extension? Is this operation allowed by chrome? I got a list of URLs of video and corresponding captions to download. So I want to do it automatically by calling related websites. I just wonder these could be done by chrome extension.
Thank you for any advice.
Your extension will need a content script to access the web page. Then it's a rather trivial DOM operation so yeah it's possible, but the question is too broad as it comprises the basics of DOM and the extension architecture. Break down the task into parts and look for examples for each one.
@wOxxOm Now I only want to do the paste and click steps. I will try to use content script as you said. But I am new in Chrome scripting. Could you give me some hints or sketch about script? It is a pitty that I could not accept your advice as an answer. Thank you!
|
A Remarkable Case of Elevated Carcinoembryonic Antigen after Surgical Treatment of Rectal Cancer: A Search for its Mysterious Cause
an ongoing elevation of serum CEA levels, for which she underwent four sequential PET-CT scans within one year without any sign of malignancy. Other causes of elevated CEA levels were investigated and excluded by additional blood tests and imaging studies. Available literature was extensively reviewed but revealed no further possible explanations for the high CEA serum level. Conclusion: The manifestation of an exponential rise of CEA levels following the treatment of colorectal cancer in the absence of abnormalities is a rare presentation and remains a mystery. The cause of the elevated CEA is yet to be elucidated.
Introduction
Serial measurements of carcinoembryonic antigen (CEA) serum levels can be indicative of recurrent disease after treatment of colorectal carcinoma and is therefore frequently used as a biomarker in follow-up [1]. However, it is also elevated to a significant degree in a number of other malignant and non-malignant conditions. This is due to its diverse functions in cell adhesion, in intracellular and intercellular signaling, and during complex biological processes such as cancer progression, inflammation, angiogenesis, and metastasis [2]. Common malignant causes for an elevated carcinoembryonic antigen include ovarian cancer, breast cancer, thyroid cancer and non-small cell lung cancer [3]. Benign causes contain cigarette smoking, mucinous cystadenoma of ovary/appendix, cholecystitis, liver cirrhosis, pancreatitis, inflammatory bowel disease and several medications [4]. In this case, we present a patient with ongoing elevating CEA levels without a clear cause.
Case Presentation
A 57-year-old female with a 32 pack per year smoking history and a past medical history of bilateral fibroadenoma and cataract and a family history of cardiovascular disease presented with a persistent change in bowel habits with rectal bleeding. Patient received no medication at the time and did not have any known allergies. During colonoscopy, a malignant looking tumour was found at 11cm from the anal verge. Pathological findings confirmed the diagnosis of adenocarcinoma of the rectum. The CEA level was elevated, 10.4ng/ml (normal level <5ng/ml), and CT and MRI imaging showed a cT3N2 rectal tumour without evidence of distant metastases. Additional findings on the 18F-FDG PET-CT scan were benign nodules in the lung, described as calcifications and a pancreas cyst with a homogenous aspect without solid components for which follow-up was advised. The patient received neoadjuvant chemoradiation therapy (25x2Gy + 1300mg capecitabine on treatment days). The capecitabine was discontinued after the first dose because of coronary spasms. Radiotherapy was continued and 6 weeks after final treatment, a re-staging MRI was performed. This showed a partial response (ycT2N1) and a laparoscopic low anterior resection with an end-to-end stapled anastomosis was performed.
Despite initial good clinical recovery, patient developed a leucocytosis on day 4 postoperatively and a CT-scan was executed which revealed anastomotic leakage. A re-laparoscopy with a deviating ileostomy was performed, together with placement of a pre-sacral drain and ceftriaxone/metronidazole intravenously. After this, recovery looked promising until patient developed a pre-sacral abscess for which she received an Endo-sponge® for drainage. At the same time, patient suffered from stoma dermatitis which was healed after surgical revision of the ileostomy. Further recovery was without further complications. Final pathology revealed γpT3N0 adenocarcinoma. Patient underwent regular follow-up according to the Dutch National Oncological Guidelines and the ileostomy was closed 3,5 months after the initial surgery [5].
I Follow-up -the Rise of CEA
The first postoperative CEA level was 2.8, followed by 4.4 three months later. Patient was asymptomatic and during this early follow-up, she underwent ileostomy closure surgery without complications. Because of the rise of CEA, 18F-FDG PET-CT scan was performed without any signs of recurrent disease. Three months later, patient was seen again, this time complaining about changing bowel movements resulting in frequent defecation up to 8 times a day. On rectal examination, the anastomosis was palpated and was considered unremarkable and no palpable rectal mass was found. CEA further increased to 10.0 and therefore another 18F-FDG PET-CT scan was executed, again no abnormalities were found. Three months later, patient had similar complaints and experienced mild weight loss and this time CEA had risen to 25.6. Again, a 18F-FDG PET-CT scan was performed showing no signs of recurrent disease. Three months later, patient was seen again, this time with a CEA level of 57.2.
As three sequential 18F-FDG PET-CT scans had previously not shown any sign of recurrent disease, patient was referred to a tertiary oncological centre for additional advice. A fourth 18F-FDG PET-CT scan within one year was performed, this time together with a MRI scan of the rectum, both without any abnormalities. On all scans, the calcifications in the lung and the pancreas cyst did not differ from previous findings. Colonoscopy was performed and was negative for recurrent disease. After the second opinionwithout new insightspatient underwent follow-up and at her following visit, CEA levels continued to rise, up to 163.6. Again, a 18F-FDG PET-CT scan was made without abnormalities. At this visit patient complained of headaches, abdominal pain and further weight loss (3kg in 3 months). She was referred to the neurologist for further consultation. An MRI of the brain showed no sign of metastatic disease or other abnormalities.
After one year of follow-upwithout any signs of recurrence, despite an extremely elevated CEAdiagnostic laparoscopy was performed as a last resort. The entire abdomen was evaluated but no signs of recurrent disease were found.
II Other Examination for Causes of CEA Elevated Levels
During follow-up, several additional blood tests and imaging were performed to rule out other causes of elevated CEA. Since CEA is often elevated in other malignant diseases, additional tumour markers such as carbohydrate antigen 19.9 were tested but were within normal values (CA 19.9 11.7u/ml (<37u/ml)). Thyroid hormones were tested, both to rule out thyroid cancer as well as endocrinological disorders, since hypothyroidism is a common endocrinological disorder in which CEA levels can rise [6]. Neither thyroid (stimulating) hormones, nor parathyroid hormones were abnormal. Patient had a pack year history of 32 years but had stopped smoking for over 9 years at the time of diagnosis and did not restart during illness or follow-up. Other types of cancer (breast, NSCLC) and inflammatory disease (cholecystitis, pancreatitis, IBD) that are potential causes of elevated CEA were all ruled out by the sequential 18F-FDG PET-CT scans.
Discussion
CEA levels have been shown to be associated with tumour burden in patients with colorectal cancer and can therefore be used as marker in follow up [1]. It can however also be elevated in a number of benign conditions and other malignancies. In the present case the more commonly known conditions that cause an elevated CEA were excluded: ovarian cancer, pancreatic cancer, gastric cancer and thyroid cancer [3]. In addition, a literature search revealed several case reports presenting rare entities that cause elevated CEA levels, such as head and neck cancer, mucinous adenocarcinoma of the lip, hypothyroidism, a apocrine hidrocystoma and lithium use, but none of these were helpful for our patient [7][8][9][10][11][12]. With elevated CEA levels as high as in our patient, distant or local recurrence of the rectal cancer was on the top of our differential diagnosis list, followed by a second primary tumour. The patient underwent four sequential 18F-FDG PET-CT scans that did however not reveal a recurrence or a second primary tumour, and more specifically no change in the pancreatic cyst or the benign looking lung nodules. A recent study shows that 18F-FDG PET-CT is sensitive, specific, and accurate in investigating patient with elevated CEA and without known primary malignancy [13]. When CEA serum levels rise above 14.31ng/L, the diagnostic value of 18F-FDG PET-CT for malignant tumours becomes even more reliable [14]. Peritoneal metastases are known to elude standard imaging, and because our patient had some abdominal complaints and weight loss eventually a diagnostic laparoscopy was performed [15].
For the patient the most difficult part in the follow up has been how to cope with the distress of the uncertainty. The second opinion in a dedicated oncology referral centre, while not providing any definitive answers, mainly served to alleviate some of this distress. Both the patient and the doctor know there is an increasing likelihood of recurrent disease with at present no signs or clues where this would be located, and if there would still be a chance for cure. It could turn out to be a solitary metastasis that can be surgically removed, it could be diffuse bone marrow invasion with a dire prognosis, or it could be something entirely different. The only option we currently have is to wait and repeat the imaging, mindful of Sir William Osler's quote: "medicine is a science of uncertainty and an art of probability".
|
Make it official?
Thank you for creating this ❤️ 🎈
Are you interested in placing this under @floating-ui/solid?
@lxsmnsyc it's okay that it doesn't support interactions, just the positioning is fine. If created, that would be a separate package like @floating-ui/solid-interactions, but yeah, the interactions package is vastly more complex and is still in v0, so it wouldn't make sense to translate it especially as it's in flux still.
I see, that makes sense. I do feel the urge to work on it given that I'm also working on solid-headless.
Regarding the API, is it possible to match @floating-ui/react-dom like this if it makes sense, or better to use external signals? In React you can access the elements via position.refs.reference.current:
I did consider it initially however given that Solid doesn't have refs, reference and floating is going to be a setter function ((ref: T) => void) but the thing is, users won't be able to access the underlying ref value, hence why the current API design is to delegate the ref assignment to the user and the user must pass the value to the useFloating function instead.
I am open to discuss this further.
I see, that makes sense 👍
It should be relatively straightforward to duplicate the react-dom folder as solid in Floating UI's repo and replace files with the index.ts file you've created — the build setup should work with it. Would you be willing to make a PR?
After that, we can create a documentation page on the website (which will likely be similar to your current README)
Yes, that's sounds great. I'll do it in my free time, thanks!
|
what is the name of the designer of the incline whose upper end was located in the neighborhood that has the zip code of 15210 ?
john h. mcroberts
|
# [Dice Roller](http://alexa.amazon.com/#skills/amzn1.ask.skill.cf49c20b-96c9-4229-9ac1-723362eb6693)
 0
To use the Dice Roller skill, try saying...
* *Alexa open dice roller*
* *Alexa start dice roller*
* *Alexa launch dice roller*
Dice Roller is an application to allow you to ask Alexa to roll a dice for you ! Useful if you do not have a dice and you want to play games.
***
### Skill Details
* **Invocation Name:** dice roller
* **Category:** null
* **ID:** amzn1.ask.skill.cf49c20b-96c9-4229-9ac1-723362eb6693
* **ASIN:** B01LYKA12Q
* **Author:** SupHerman
* **Release Date:** September 22, 2016 @ 05:12:04
* **In-App Purchasing:** No
|
using DesignTE.View.NoteEditing;
using System;
using System.Collections.Generic;
using System.Linq;
using System.Text;
using System.Windows.Forms;
namespace DesignTE.View
{
public sealed class SideTabControl : TabControl
{
private const string NoteTabTitle = "笔记编辑器";
private const string TaskListTabTitle = "任务";
public SideTabControl()
{
Dock = DockStyle.Fill;
//SideBarTabs.Alignment = TabAlignment.Bottom;
ImageList imageList = new ImageList();
imageList.Images.Add(DesignTE.Properties.Resources.sticky_note_pin);
ImageList = imageList;
NoteTab = new TabPage(NoteTabTitle) { ImageIndex = 0 };
NoteEditor = new NoteEditor { Dock = DockStyle.Fill };
NoteTab.Controls.Add(NoteEditor);
TabPages.Add(NoteTab);
}
public NoteEditor NoteEditor { get; set; }
public TabPage NoteTab { get; private set; }
//TODO: Should be handled the way 'View Calendar' ribbon command is done.
public TabPage TaskListTab
{
get
{
return TabPages.Cast<TabPage>().FirstOrDefault(p => p.Text == TaskListTabTitle);
}
}
}
}
|
The type 'string' is not compatible with the type 'seq<'a>'
I have no idea why the following code doesn't compile with F# 4.0 on VS2015 RC:
That's quite strange since there's no error if I run the same code in F# Interactive. Is it a compiler bug or am I missing something?
module Number
let digitNames = ["zero"; "one"; "two"; "three"; "four"
"five"; "six"; "seven"; "eight"; "nine"]
let toWord (number:seq<char>) =
number
|> Seq.map (fun n -> digitNames.[int n - 48])
|> String.concat " "
let toWord' (number:string) =
number
|> Seq.map (fun n -> digitNames.[int n - 48]) // Error: The type 'string' is not compatible with the type 'seq<'a>'
|> String.concat " "
let toWord'' (number:string) =
(number :> seq<char>) // Error: The type 'string' is not compatible with the type 'seq<'a>'
|> Seq.map (fun n -> digitNames.[int n - 48])
|> String.concat " "
You must be developing a portable library I think. For strange reason, the profile 7/78/259 System.Runtime.dll binary doesn't record System.String as implementing IEnumerable<char>. I checked this by looking at:
ildasm "C:\Program Files (x86)\Reference Assemblies\Microsoft\Framework\.
NETCore\v4.5\System.Runtime.dll"
Likewise the Profile7 facade DLL doesn't implement this:
ildasm "C:\Program Files (x86)\Reference Assemblies\Microsoft\Framework\.
NETPortable\v4.5\Profile\Profile7\System.Runtime.dll"
Later "4.6" profiles do implement this. AFAIK it's not possible to the get the Visual F# Tools to target the 4.6 portable profiles (Profile31, 32, 44, 84, 151, 157)
You can workaround this by using seq { for c in "F#" -> c } which uses the F# rule that strings have a "GetEnumerator()" method.
Closing this as it's not strictly speaking a bug - the portable profiles are what they are.
|
U.S. DEPARTMENT OF JUSTICE, IMMIGRATION and NATURALIZATION SERVICE, Petitioner/Cross-Respondent, v. FEDERAL LABOR RELATIONS AUTHORITY, Respondent/Cross-Petitioner.
No. 92-4652.
United States Court of Appeals, Fifth Circuit.
June 25, 1993.
Douglas Ross,' Dept, of Justice, Washington, DC, for petitioner-cross-respondent.
Richard Zorn, Wm. R. Tobey, William E. Persina, Sol., Arthur A. Horowitz, David M. Smith, Federal Labor Relations Authority, Washington, DC, for respondent-cross-petitioner.
Alexia Fay McCaskill, American Federation of Gov’t. Emp., William Kanter, Deputy Staff Director, U.S. Dept, of Justice, Mark D. Roth, American Federation of Gov’t. Emp., Washington, DC, for intervenor.
Before POLITZ, Chief Judge, REAVLEY and BARKSDALE, Circuit Judges.
POLITZ, Chief Judge:
The United States Immigration and Naturalization Service seeks review of the determination by the Federal Labor Relations Authority that it committed an unfair labor practice. The FLRA seeks enforcement of its order. For the reasons assigned, we grant the petition for review, in part and order enforcement in part.
Background
This dispute has its genesis in revisions by the INS in its policy on the use of firearms by employees. Negotiations between the agency and the employees’ collective bargaining representatives, the National Border Patrol Council and the National Immigration and Naturalization Service Council of the American Federation of Government Employees AFL-CIO, concluded with several unresolved disputes. The INS contended that six proposals advanced by the unions were nonnegotiable because they addressed matters reserved to management’s discretion. After mediation was deemed likely to be ineffective, the unions asked the Federal Service Impasses Panel to review the matter. Before the Impasses Panel acted, however, the INS implemented its revisions, both those agreed upon and those in dispute. The Impasses Panel thereafter determined that it did not have jurisdiction because negotiability was controverted. At the unions’ request, the FLRA reviewed the negotiability of the six proposals and determined that only Proposal 5 and portions of Proposals 1 and 2 were negotiable. The INS sought our review of the negotiability of Proposal 5. In a decision rendered on October 20, 1992, we ruled that Proposal 5 was not negotiable.
Shortly after seeking FLRA review of the negotiability issue, the unions brought unfair labor practice charge's against the INS for implementing the revisions before the Impasses Panel had ruled. On April 30, 1992, prior to our decision on the petition for review of the negotiability order, the FLRA decided that the INS had violated section 7116(a)(1), (5), and (6) of the Federal Service Labor-Management Relations Statute. The INS timely petitioned for review and the FLRA cross-applied for enforcement of its order.
Analysis
The issue before us is whether an agency commits an unfair labor practice by implementing a change in a condition of employment when a union challenge is pending before the Impasses Panel and it is subsequently determined that the change is a nonnegotiable management prerogative. We conclude that neither the agency’s refusal to submit to the jurisdiction of the Impasses Panel nor its unilateral implementation of the change is an unfair labor practice.
The Federal Service Labor-Management Relations Statute, part of the Civil Service Reform Act of 1978, was enactéd in an effort to make the government function more efficiently and effectively. The legislation codifies the right of federal employees to organize and the duty of management to bargain, but tailors these rights and responsibilities “to meet the special requirements and needs of the Government.” In section 7101(b) Congress directed that the statute “be interpreted in a manner consistent with the requirement of an effective and efficient Government.”
If the parties bargain to impasse and mediation does not resolve their differences, the statute authorizes either side to invoke the services of the Federal Service Impasses Panel. The Impasses Panel is empowered to impose specific contract terms on the parties “unless [they] agree otherwise.” While a matter is pending before the Impasses Panel, under' FLRA rule the parties must maintain the status quo to the extent consistent with the necessary functioning of the agency. Failure to do so constitutes an unfair labor practice.
Certain matters, however, statutorily are exempted from the scope of mandatory bargaining, including, as pertinent herein, an agency’s internal security practices and the assignment of work. If management contends that a change falls within an exempted area, the Impasses Panel lacks authority to proceed unless and until the negotiability issues are resolved, subject to a limited exception defined by the FLRA. We agree with the reasoning of the FLRA as expressed in Commander Carswell Air Force Base, Texas and AFGE that the purposes of the statute are best furthered by allowing the Impasses Panel to resolve those disputes involving negotiability that are controlled by existing FLRA precedents. To that we would add “and existing controlling judicial precedents.”
In the case at bar, claiming nonnegotiability the INS implemented its policy revisions before the Impasses Panel declined jurisdiction. Ultimately it was determined that all of the changes, except for portions of two of the union’s proposals, were nonnegotiable. The INS concedes that it committed an unfair labor practice with respect to implementation of those measures found negotiable, but otherwise it denies wrongdoing. The FLRA insists that it was an unfair labor practice to implement any of the changes, negotiable or not.
Our 1984 decision in U.S. Dept. of Justice, INS v. FLRA persuades that the position taken herein by the FLRA is untenable. In the cited case, the INS implemented changes in employment conditions while a representation election was pending. Determining that the changes involved areas reserved to management’s discretion, we held that the INS had not committed an unfair labor practice because the FLRA was not authorized to suspend management rights. We therein stated:
Congress provided specifically in 5 U.S.C. § 7106 that “nothing in this chapter shall affect the authority of any management official of any agency” to exercise the rights reserved to management by that section.... By using the word “nothing” ..., Congress clearly expressed its intent with regard to management’s exercise of the rights which had been reserved to it. The use of such words makes it obvious that Congress did not intend to let the Authority decide whether, in its judgment, it was “necessary” for the INS to [make the desired changes] during the pendency of the election.... Construing the statute to allow the Authority to promulgate a rule which would bar management from exercising its reserved rights during the pen-dency of a representation question would hardly lead to an INS which was as effective and efficient as possible.
Similarly here, the position urged by the FLRA would suspend management rights pending Impasses Panel action. Neither the language nor spirit of the statute would so permit. Whereas unilateral implementation during Impasses Panel proceedings of a change that is determined to be negotiable might be an unfair labor practice, we hold that unilateral implementation of a change determined to be nonnegotiable is not.
The petition for review is GRANTED with respect to Proposal 5. Conversely, the cross-application for enforcement is DENIED with respect to Proposal 5 but is GRANTED with respect to the negotiable parts of Proposals 1 and 2.
. Dept. of Justice, INS v. FLRA, 975 F.2d 218 (5th Cir. 1992).
. 5 U.S.C. §§ 7101 et seq.
. S.Rep. No. 95-969, 95th Cong., 2d Sess. 4, reprinted in 1978 U.S.C.C.A.N. 2723, 2726.
. 5 U.S.C. § 7101(b).
. See also Dept. of Justice, INS v. FLRA, 991 F.2d 285 (5th Cir. 1993).
. 5 U.S.C. § 7119(b)(1).
. 5 U.S.C. § 7119(c)(5)(C); see also American Federation of Government Employees, AFL-CIO v. FLRA, 778 F.2d 850 (D.C.Cir.1985).
. Dept. of the Treasury, BATF and National Treasury Employees Union, 18 F.L.R.A. (No. 61) 466 (1985); see also National Ass'n of Government Employees v. FLRA, 893 F.2d 380 (D.C.Cir.1990).
. 5 U.S.C. § 7106(a)(1), (2)(B).
. American Federation of Gov't Employees, supra.
. 31 F.L.R.A. (No. 37) 620 (1988).
. 727 F.2d 481 (5th Cir.1984).
. 727 F.2d at 488.
. We therefore do not accord the deference normally owed to the interpretation of the agency charged with implementing the statute. See U.S. Dept. of Justice, INS, 975 F.2d at 225.
. See also American Federation of Gov’t Employees, 778 F.2d at 857 ("although the Labor-Management Act makes it an unfair labor practice to 'fail or refuse to cooperate in impasse procedures and impasse decisions ...,’ § 7116(b)(6), an agency is not guilty of an unfair labor practice if the FLRA or a reviewing court later determines that the issue was nonnegotiable”); Dept. of Treasury, BATF, supra (agency did not commit an unfair labor practice in implementing an Order while Impasses Panel proceedings were pending because the Order was not subject to the duty to bargain).
|
Edited by C. R. Matthews
In order to fully understand the folding mechanism of a protein, it is necessary to characterize every species populated along the folding pathway from the initial denatured state to the final native conformation. For several small proteins that fold with a two-state transition, direct characterization of folding is limited to the folded and unfolded states. An increasing number of small single-domain proteins, however, have been shown to fold with multi-state kinetics[@bib1 bib2 bib3 bib4 bib5 bib6 bib7 bib8 bib9] indicative of the population of partially folded intermediates along the pathway. These proteins provide an opportunity to dissect the structures populated en route to the native state, and both the structural and the dynamical characterization of these species have provided key insights into the organization of structure during protein folding trajectories.[@bib10 bib11 bib12] Studies of the folding mechanisms of the bacterial DNase-specific immunity proteins, Im7 and Im9, are particularly powerful as, despite their similarity in sequence,[@bib13] Im9 folds with an apparent two-state transition, while Im7 folds with a three-state transition via an on-pathway populated intermediate ([Fig. 1](#fig1){ref-type="fig"}).[@bib5 bib10 bib14 bib15 bib16 bib17] φ value analysis and native-state hydrogen exchange experiments have shown that the Im7 intermediate contains three of the four native helices (helices 1, 2, and 4) packed around a specific hydrophobic core that lacks helix 3.[@bib16 bib18] Selective destabilization of the native state by mutation (L53A I54A) to such an extent that the intermediate becomes the most stable species at equilibrium[@bib19] has allowed structural analysis of this partially folded state by NMR.[@bib20] The intermediate was found to contain native-like secondary structure in helices 1 and 4, partial formation of helix 2, the absence of helix 3, and a fluid, rather than a uniquely structured core.[@bib20] By using chemical shift analysis, hydrogen exchange, and φ values as restraints for molecular dynamics (MD) simulations, models of the kinetic intermediate have been proposed,[@bib10 bib14 bib20] in which helices 1, 2, and 4 are aligned in a native-like topology but their docking is reorganized to allow nonnative interactions to form between helices 2 and 4, while residues that ultimately form helix 3 remain highly disordered.[@bib10 bib14]
The extent of conformational heterogeneity within the Im7 folding intermediate is difficult to verify using ensemble techniques since such measurements typically yield parameters that are averaged over the entire ensemble of conformations within each population. By contrast, single-molecule experiments are ideal for the detection and characterization of rarely populated conformations in heterogeneous ensembles.[@bib21 bib22 bib23 bib24 bib25 bib26 bib27 bib28 bib29] Diffusion single-molecule fluorescence energy transfer (smFRET), in particular, is a powerful technique for studying the structural and dynamic properties of unfolded and folded protein subpopulations at equilibrium.[@bib21 bib22 bib27] Importantly, this technique can be used to quantify and characterize each species within an ensemble, even when populated to just a few percent. We have previously used smFRET to measure the effects of denaturant on the conformational properties of the native and unfolded states of Im9 and demonstrated that the unfolded ensemble becomes significantly compacted at lower denaturant concentrations while the native state shows only minor effects as chaotrope is titrated.[@bib30]
Here, we describe new experiments using diffusion smFRET, designed to directly probe the structural properties of Im7 in its native and trapped intermediate ensembles. We achieve this by measuring the FRET efficiency between dye donor--acceptor pairs introduced at defined points in the protein sequence, chosen to allow us to monitor the relative conformational arrangement and dynamics of each of the four helices at different points in the folding landscape. As well as examining the folded and intermediate states, the low stability of the double-dye-labeled trapped intermediate provides a means of directly monitoring the structural properties of the unfolded state under physiological conditions. Upon addition of kosmotrope under these conditions, the unfolded ensemble is highly compact and displays an increase in the peak width of *P* values, possibly reflecting a reduction in the rate of conformational exchange among iso-energetic unfolded but compact conformations, suggesting that the search process for folding is highly constrained from the onset.
Experimental design and characterization of cysteine variants of Im7
In order to investigate the structural properties of the unfolded, intermediate, and folded states of Im7 using smFRET, we identified solvent-exposed residues close to the center of each helix (Q17, V36, Y56, and K70 in helices 1, 2, 3, and 4, respectively), and cysteine residues were then introduced (see [Methods](#sec1){ref-type="sec"}) at pairs of these sites in both wild-type Im7 and the trapped intermediate (Im7 L53A I54A, referred to as I^eqm^).[@bib19] The variants are named according to the helices to which the dyes are attached; for example, Im7 Q17C K70C is referred to as Im7 H1H4. In total, three pairs of variants were studied for Im7 and Im7 I^eqm^ with dye-attachment sites in H1H4, H2H4, and H1H3. To amplify the sensitivity of smFRET to conformational changes in Im7 H1H3, we inserted 15 glycine residues into the loop connecting helix 1 and helix 2, in both Im7 and Im7 I^eqm^. The H1H3 variants are therefore named Im7 GlyH1H3 and Im7 I^eqm^ GlyH1H3. The expansion of this loop has previously been shown to have no effect on the folding mechanism of native Im7 or its folding intermediate (G. Spence and S.E.R., unpublished data).
Before labeling with fluorescent dyes, each Im7 variant was characterized using tryptophan fluorescence emission, equilibrium denaturation ([Fig. 2](#fig2){ref-type="fig"}; [Table 1](#tbl1){ref-type="table"}), and 1D ^1^H NMR (data not shown) to ensure that the mutations introduced had not perturbed the structural properties of the native and intermediate ensembles. The incorporation of cysteine was found not to substantially alter the structure or stability of native or partially unfolded Im7 variants. Thus, the native and intermediate states of all variants were destabilized by ≤ 4.5 kJ mol^− 1^ compared with their wild-type counterparts ([Table 1](#tbl1){ref-type="table"}) and all native variants gave rise to tryptophan fluorescence emission spectra that are highly quenched ([Fig. 2](#fig2){ref-type="fig"}, broken lines), indicative of the native-like stacking of the sequentially distant His47 and Trp75 pair.[@bib5 bib15] By contrast, the fluorescence emission spectrum of all of the trapped intermediate variants were more intense than those of either the unfolded or native states, consistent with formation of the previously identified hyper-fluorescent intermediate state.[@bib5 bib15] Finally, 1D ^1^H NMR spectra were similar to those observed previously for each state, confirming that introduction of two cysteine residues did not significantly alter the structure of the intermediate or native states.
Donor and acceptor fluorophores (Alexa 488 and Alexa 594) for FRET were then introduced into each variant by a two-step procedure (see [Methods](#sec1){ref-type="sec"}) that yielded proteins labeled with a single donor--acceptor pair. Steady-state anisotropy measurements exciting each fluorophore gave anisotropy values for all variants (both in folded and unfolded states) from 0.10 to 0.19 ([Table 1](#tbl1){ref-type="table"}), suggesting that both dyes have a high degree of flexibility in all conditions and, hence, are useful as FRET probes.[@bib27 bib31]
Conformational ensembles of the native and intermediate states of Im7
We first investigated the distribution of inter-dye distances for the three pairs of Im7 wild-type and I^eqm^ variants containing donor and acceptor dyes in different helical pairs using single-molecule diffusion experiments under conditions most commonly used for Im7 folding studies (0.4 M Na~2~SO~4~ at pH 7.0 and 10 °C). The FRET efficiency, herein referred as the proximity ratio or value (*P*, see [Methods](#sec1){ref-type="sec"}),[@bib21 bib32] was determined for each sample by measuring the number of detected donor and acceptor photons Id and Ia, respectively, from a single diffusing protein molecule in an integration time of 0.5 ms (see [Methods](#sec1){ref-type="sec"}). Histograms were then constructed of the *P* value, typically from 5000 such single molecules ([Fig. 3](#fig3){ref-type="fig"}). A peak centered on *P* = 0 of varying intensity is observed in all histograms and originates from proteins with a fluorescent donor but photobleached acceptor.[@bib21] This peak was ignored in subsequent analyses. Examination of the proximity ratio histograms for the native variants (bottom panels, [Fig. 3](#fig3){ref-type="fig"}a--c) shows a distribution at a high proximity ratio that fits well to a single Gaussian distribution, consistent with a single species being populated under these conditions. By contrast, the proximity ratio histograms for all the Im7 I^eqm^ variants show more complex behavior (top panels, [Fig. 3](#fig3){ref-type="fig"}a--c) and a second Gaussian is required to fit the data adequately. The peak at a higher proximity ratio in each case (*P* ≈ 0.90) likely reflects a folded conformation with short inter-helical separation populated by the intermediate. The peak at lower proximity ratio (*P* ≈ 0.75) reveals the presence of an ensemble of structures with a larger mean inter-dye separation reflecting the population of a more unfolded species.
Comparisons of the peak positions between the three helix pairs reveal further insights. For helices 1 and 4 ([Fig. 3](#fig3){ref-type="fig"}a), a highly populated species with *P* ≈ 0.93 for both Im7 H1H4 and Im7 I^eqm^ H1H4 is observed, indicative of efficient FRET and suggesting that these helices are closely packed in the trapped intermediate, consistent with previous MD simulations of this state.[@bib10 bib14] The mean proximity ratio of the most compact species for Im7 I^eqm^ H2H4 and for Im7 H2H4 ([Fig. 3](#fig3){ref-type="fig"}c) is also similar (*P* ≈ 0.90), implying that the distance between helices 2 and 4 in the intermediate ensemble, on average, is also native-like. For each of these helix pairs, the weight-averaged mean inter-helix distance for the intermediate ensemble derived from MD simulations[@bib10 bib14] ([Fig. 1](#fig1){ref-type="fig"}) is identical with the inter-helix distance in the native state (15.2 and 15.1 Å and 17.6 and 17.7 Å for Im7 H1H4 and Im7H2H4 variants, respectively, measured by the distance between the center of mass of each helix pair across the ensemble).[@bib14] By contrast, the positions of the folded peaks for Im7 GlyH1H3 and Im7 I^eqm^ GlyH1H3 ([Fig. 3](#fig3){ref-type="fig"}b) differ slightly, with mean proximity ratios *P* ≈ 0.82 and *P* ≈ 0.90, respectively. This suggests that helices 1 and 3 are, on average, in closer proximity in the intermediate state than in the native state and therefore in a nonnative relative orientation in at least the majority of molecules studied here. This is in contrast to the simulations that predict the weight-averaged separation to be greater in I^eqm^ and hence a smaller *P* value relative to the natively folded protein (18.0 and 14.7 Å, respectively).
In addition to revealing inter-dye distributions, analysis of proximity ratio histograms can provide insights into conformational dynamics.[@bib21 bib27 bib32 bib33 bib34] While the width of the proximity ratio distribution for a homogeneous and static species, such as the native state, is dominated by instrumental shot noise, additional broadening can indicate static conformational heterogeneity or inter-conversion between two or more distinct species on a time scale slower than, or similar to, the integration time used. The mean proximity ratios and width of the distributions of the trapped intermediate variants for the H1H4 and H2H4 pairs are indistinguishable from those of their wild-type analogues. This suggests little heterogeneity within the intermediate ensemble relative to its folded analogue.
Trapped intermediates populate an unfolded ensemble in the absence of denaturant
Examination of the proximity ratio histograms for each of the I^eqm^ variants shows that an ensemble with a lower *P* value is co-populated with the folded state of each species (top panels, [Fig. 3](#fig3){ref-type="fig"}a--c), suggesting that an expanded or partially unfolded state is populated for these variants under native conditions. To elucidate the nature of this species, and to further study the folded members of the intermediate ensemble, we varied the solvent conditions from those known to favor a less-compact, more unfolded state (high-pH, low-sodium sulfate concentration) to those that have previously been shown to preferentially stabilize the intermediate state over the unfolded state (low-pH, high-sodium sulfate concentration).[@bib35 bib36] The proximity ratio histograms for the three Im7 I^eqm^ variants under these conditions are shown in [Fig. 4](#fig4){ref-type="fig"}. In all three cases, the relative population of the more highly unfolded species (lower *P* value) decreases with increasingly acidic conditions and/or in the presence of 0.4 M Na~2~SO~4~ while the more compact intermediate species concomitantly increases in a two-state transition. It may be expected that the ratio of the peak areas for the folded and unfolded species should reflect the relative stabilities of these variants, which are different as a consequence of the insertion of pairs of cysteine residues in different regions of the protein ([Table 1](#tbl1){ref-type="table"}). For example, in [Fig. 4](#fig4){ref-type="fig"}, at pH 6, the relative population of the unfolded to folded state is high for I^eqm^H1H4 while it is lower for both I^eqm^H2H4 and I^eqm^H1H3, which have similar stabilities. However, it should be noted that in our experiments, it is not molecules that are quantified but events in bins above a threshold. While these differences are actually accounted for in shot noise width analysis (see later), such effects complicate quantitative analysis of relative peak areas.
These data therefore support the assignment of the less-populated, lower-proximity-ratio species observed for the trapped intermediates to the unfolded state. It is noteworthy that the mean proximity ratio of the unfolded states of all the trapped intermediate variants shows a significant pH dependence, with apparent expansion as the pH is increased while the mean proximity ratios of the folded states of the trapped intermediate variants remain constant across the pH titration, obviating the pH dependence of the dyes as the origin of this effect. Note that both the donor and acceptor dye quantum yields have no significant pH dependence in the range 4--9.[@bib37 bib38] The isoelectric point of wild-type Im7 is ≈ pH 5. Therefore, as the pH is increased, it is plausible that the expansion in the unfolded state may be caused by electrostatic repulsion due to an increased negative charge. Importantly, at pH 7 and in the absence of Na~2~SO~4~, the unfolded state ensemble is highly populated for all I^eqm^ variants ([Fig. 4](#fig4){ref-type="fig"}, second row from the top). This provides the opportunity to study the unfolded ensemble of Im7 in weakly denaturing conditions, the initial starting species for the Im7 folding reaction.
The unfolded Im7 ensemble becomes increasingly compact under mild denaturing conditions
In order to explore the nature of the folded and unfolded species further, we performed a denaturant titration with the three Im7 and Im7 I^eqm^ helix pairs in the absence of kosmotrope. Shown in [Fig. 5](#fig5){ref-type="fig"} are the mean proximity ratios and mean peak widths obtained from such titrations, using urea as the denaturant. The positions of the folded peaks (corrected for refractive index, see [Methods](#sec1){ref-type="sec"}) for all Im7 I^eqm^ and Im7 folded species ([Fig. 5](#fig5){ref-type="fig"}a, top panel, squares) change by less than *P* ≈ 0.06 as a function of urea concentration over the detectable range, suggesting little difference in compaction consistent with these ensembles representing stably structured states with a well-defined fold (note that given the large error, the data for Im7 I^eqm^ GlyH1H3 are not included in this analysis). Similar minor compaction with decreasing urea concentration has been previously observed for the homologous protein Im9 when labeled with dye at positions 23 and 81 (helix 1 and close to the C-terminus, respectively)[@bib30] as well as for the native states of other proteins.[@bib39 bib40] It is unlikely that these effects arise from restricted dye motion as anisotropy measurements suggest that each fluorophore has a high degree of conformational freedom. There is always a possibility that for a given set of labeling positions, the presence of urea changes the local environment of the dye in a way that causes some quenching due to the specific local sequence. In this regard, it has recently been shown that Im7 is a frustrated protein with a highly malleable core and this may lead to slight changes in conformation.[@bib41]
In contrast with the behavior of the native and folded intermediate species, a substantial decrease in the inter-helical distance of the denatured state ensemble is observed as the denaturant concentration is decreased for all of the Im7 variants ([Fig. 5](#fig5){ref-type="fig"}a--c, top panels, triangles). In all cases, the effect is more pronounced than the changes observed for the folded ensembles, such that the *P* value changes by \> 0.12 for all proteins between 0 and 6 M urea. Compaction of the unfolded state has been observed previously for other proteins at low concentrations of denaturant.[@bib23 bib25 bib27 bib40 bib42 bib43 bib44 bib45 bib46 bib47 bib48 bib49] Similar compaction of the denatured state at low denaturant concentration is observed with FRET donor--acceptor fluorophore pairs attached to the N- and C-termini of Im7 (data not shown), suggesting that compaction in the denatured state is isotropic with all regions of the protein showing similar behavior, rather than being confined to specific regions of the polypeptide chain as was observed with CspTm.[@bib45]
As discussed above, the width of peaks in proximity ratio distributions contain information about dynamic conformational heterogeneity.[@bib21 bib27 bib32 bib33 bib34] The width of the distributions representing the native state or folded members of the intermediate ensemble ([Fig. 5](#fig5){ref-type="fig"}a--c, center and bottom panels, squares) is generally in excellent agreement with the expected shot noise limited width calculated as a function of denaturant concentration ([Fig. 5](#fig5){ref-type="fig"}a--c, center and bottom panels, broken lines, see [Methods](#sec1){ref-type="sec"} and Ref. [@bib30]). The peak width of the unfolded species for all variants ([Fig. 5](#fig5){ref-type="fig"}a--c, center and bottom panels, triangles) is independent of urea concentration under strongly denaturing conditions (\[urea\] \> 3 M) but slightly broader than that predicted by shot noise ([Fig. 5](#fig5){ref-type="fig"}a--c, center and bottom panels, broken lines, see [Methods](#sec1){ref-type="sec"}). This broadness offset has also been observed for protein L,[@bib34] CspTm,[@bib27] and Im9.[@bib30] The unfolded state for all variants shows significant additional broadening in the transition region, where both the folded state and unfolded state are populated ([Fig. 5](#fig5){ref-type="fig"}a--c, center and bottom panels, triangles). These findings suggest that the unfolded state ensembles of all six variants become not only more heterogeneous but also, on average, more compact, in weakly denaturing conditions, consistent with slowed fluctuations relative to the 0.5-ms measurement time between isotropically collapsed ensembles of conformationally heterogeneous states that occur under conditions favoring folding.
The properties of the native, intermediate, and unfolded ensembles in the presence of sodium sulfate
Further studies of the properties of the folded and unfolded states of Im7 H1H4 and Im7 GlyH1H3 and their analogous trapped intermediate constructs were performed in the presence of a kosmotrope (0.4 M Na~2~SO~4~, sample raw data are shown in [Fig. 6](#fig6){ref-type="fig"} and summarized in [Fig. 7](#fig7){ref-type="fig"}). Studies on Im7 I^eqm^ H2H4 and Im7 H2H4 were not included, as the presence of 0.4 M Na~2~SO~4~ results in poor separation of the distributions corresponding to the folded and unfolded species in the transition region, ruling out their quantitative analysis (data not shown). The stabilizing effect of the kosmotrope results in the folded intermediate species of Im7 I^eqm^ H1H4 and Im7 I^eqm^ GlyH1H3 being populated up to 3 M urea and the native states of Im7 H1H4 and Im7 GlyH1H3 up to 5.5 M urea ([Fig. 7](#fig7){ref-type="fig"}a, squares). This allows the effect of denaturant on the inter-helical distance (*P* value) and distribution width of these species to be quantified over a wider range of urea concentration than was possible hitherto. Similar to the denaturant titration in the absence of kosmotrope, no significant compaction is observed for the folded Im7 H1H4 and the folded Im7 I^eqm^ H1H4 conformations as denaturant concentration is decreased ([Fig. 7](#fig7){ref-type="fig"}a, top panel, squares). For the Im7 GlyH1H3 variants, contrasting behavior is seen: compaction occurs towards low denaturant concentrations, which was unclear in the absence of kosmotrope ([Fig. 5](#fig5){ref-type="fig"}b, top panel, squares, and [Fig. 7](#fig7){ref-type="fig"}b, top panels, squares) with a change in *P* value by up to 0.13 from 0 to 3.5 M urea. The cause of this apparent compaction is unclear and may be a consequence of the inserted glycine sequence and will require structural data with higher resolution to resolve. While differences are observed in inter-helical distance, the widths of both the H1H4 and GlyH1H3 native and intermediate folded ensembles remains shot noise limited across the entire denaturant range studied ([Fig. 7](#fig7){ref-type="fig"}a and b, middle and bottom panels, squares). This suggests that despite the significant compaction seen in the GlyH1H3 native and folded intermediate, the ensemble of interactions between helices 1 and 3 and 1 and 4 have native-like dynamics and homogeneity, irrespective of the concentration of denaturant.
The unfolded state ensembles of the proteins Im7 H1H4 and Im7 Gly H1H3 and their trapped intermediate analogues in the presence of 0.4 M Na~2~SO~4~ show a dramatic dependence of their inter-helical separation with denaturant concentration ([Fig. 7](#fig7){ref-type="fig"}a and b, top panels, triangles). Strikingly, in 0 M urea, the unfolded state ensemble becomes so compact~,~ (*P* ≈ 0.8) that its *P* ratio is close to that of the native ensemble. Correlated with this, a dramatic and highly significant change in the width of the unfolded state of the trapped intermediate is observed in mildly denaturing conditions ([Fig. 7](#fig7){ref-type="fig"}a and b, center panels, triangles), which is not observed for the folded state observed in the same experiment, obviating instrumental or processing artifacts as the cause.[@bib34] For both Im7 I^eqm^H1H4 and Im7 I^eqm^GlyH1H3 at denaturant concentrations between 1 and 3 M, the distribution width increases as the inter-dye separation decreases. The distribution width of the unfolded peak then decreases again as the concentration of urea is decreased below 1 M, possibly reflecting a decreased rate of conformational exchange among unfolded but compact conformations.
The results of this single-molecule study uncover new insights into the properties of the different species populated during the folding of Im7. The peak positions and distribution widths for the natively folded Im7 H1H4, Im7 H1H3, and Im7 H2H4 variants are narrow and at high *P* values as expected based on the known structure of Im7.[@bib13] Comparison of these data with those for their trapped intermediate analogues allows differences in the structure and dynamics of each state to be identified. Analysis of the proximity ratios between helix pairs suggests that the separations between helices 1--4 and 2--4 are indistinguishable between the native and folded intermediate states, at least for the positions measured. Interestingly, the proximity ratio of folded Im7 I^eqm^ GlyH1H3 is slightly higher than that of Im7 GlyH1H3 (*P* ≈ 0.90 and 0.82, respectively, [Figs. 3b and 7b](#fig3 fig7){ref-type="fig"}, top panel), indicating a shorter inter-residue distance, on average, for residues 17 and 56 in the intermediate ensemble, possibly consistent with this region being unstructured and occupying a highly nonnative location within the intermediate ensemble.[@bib10 bib15] φ value analysis for the intermediate state of Im7 revealed nonnative interactions between side chains in helices 2 and 4, specifically involving residues towards the C-terminal end of helix 2, including residues F41 and V42.[@bib16] Presumably then, the changes in side-chain packing needed to reach the native state involve subtle reorganization rather than large-scale inter-helix movements that would have been detected in the smFRET studies described here. These data accord with the analysis of the trapped intermediate by NMR, which found native-like secondary structure in helices 1 and 4, a partial formation of helix 2, and the absence of a structured helix 3.[@bib20]
The data also allow benchmarking of the ensemble of intermediate states calculated using MD simulations.[@bib10 bib14] For Im7 H1H4 variants, there is excellent agreement; both techniques suggest that the arrangement of this helix pair is similar in both the native and intermediate states and there is little structural heterogeneity in this equilibrium ensemble. In this study, a similar result was observed for the Im7 H2H4 variants. This is in contrast to MD simulations of the intermediate ensemble that predicts a broader distribution of distances for the helix 2--4 pair than in the native state.[@bib14] Interestingly, however, comparison of the weight-averaged helix--helix distance for helices 2--4 calculated from the simulations demonstrates that these distances are identical for the native and folded intermediate state (17.7 and 17.6 Å, respectively). If the intermediate ensemble predicted by simulation is accurate, then this suggests that the conformational heterogeneity observed between helices 2--4 results from conformational exchange on a timescale faster than the timescale of the single-molecule experiment presented here.
The smFRET experiments also enabled the properties of the unfolded, intermediate, and native states to be determined as a function of the concentration of urea. Generally, the native and folded intermediate species were found to be only marginally compacted, as judged by the proximity ratio, as the denaturant concentration decreased, and were unaffected by the presence of 0.4 M Na~2~SO~4~ in agreement with previous studies using equilibrium denaturation.[@bib35 bib36] The peak width for the native and folded intermediate states was also generally found to be insensitive to denaturant concentration with the exception of Im7 I^eqm^ GlyH1H3 in the absence of 0.4 M Na~2~SO~4~. Introduction of cysteine pairs into Im7 resulted in destabilization of both the native state and the trapped intermediate state (I^eqm^ variants) by ≤ 4.5 and ≤ 3.3 kJ mol^− 1^, respectively. This proved to be advantageous, allowing the characterization of the unfolded state at very low concentrations of denaturant. This allowed observation of the equilibrium collapse (coil--globule transition) that is usually masked by the folding transition. Our data reveal that substantial compaction of the unfolded state occurs, as predicted by Alonso and Dill[@bib50] and observed previously for several other proteins using both single-molecule fluorescence[@bib25 bib27 bib42 bib44 bib45 bib51] and other techniques.[@bib51 bib52 bib53 bib54] Such data have been modeled as a continuum of substates[@bib25] or by using an analytical polymer model.[@bib51] In the latter approach, smFRET data reporting on the coil--globule transition were used to calculate the end-to-end distance probability distribution for several proteins as a function of interaction energy (or denaturant concentration). These data demonstrated a continuous contraction and narrowing of the distribution as denaturant concentration decreases. Conversion of these data to radii of gyration allowed the expansion of the denatured state relative to the native state to be extrapolated to the absence of denaturant where the unfolded state was found to be only 30% larger than that of the folded state,[@bib51] akin to the significant collapse observed in this study in the absence of urea. Furthermore, the free energy of denatured state collapse has a linear dependence on denaturant concentration with a similar gradient to that for the folding reaction, suggesting that the effect of denaturant is mediated through the collapse transition of the denatured state.[@bib55]
At low concentrations of denaturant, the proximity distribution width for the unfolded states of each variant is also dependent on the denaturant concentration ([Fig. 5](#fig5){ref-type="fig"}), possibly due to slower exchange between iso-energetic conformations in the unfolded energy basin at low chaotrope concentrations.
In the presence of 0.4 M Na~2~SO~4~, the unfolded states of Im7 I^eqm^ H1H4 and Im7 I^eqm^ Gly H1H3 are populated even in the absence of denaturant, and a striking new observation is possible ([Fig. 7](#fig7){ref-type="fig"}a and b, middle panel, triangles): After an initial increase in the width of the unfolded ensemble as described above, in mild denaturing conditions, the width narrows again as the urea concentration approaches zero ([Fig. 7](#fig7){ref-type="fig"}), reflecting the preferential population of a more homogeneous or less dynamic unfolded conformation. It is possible that both the compact unfolded state in 0.4 M Na~2~SO~4~ and the more expanded unfolded species in the absence of Na~2~SO~4~ belong to the same unfolded ensemble (i.e., they are not distinct thermodynamic states). In such a scenario, the addition of Na~2~SO~4~ would preferentially stabilize the more compact unfolded species, resulting in conformations with higher *P* ratios dominating the unfolded ensemble. The precise nature of the interactions that stabilize these compact states is still debated and could involve either specific or nonspecific hydrophobic interactions.[@bib51 bib53 bib55] Such highly compact, unfolded states could be favorable for efficient folding, limiting the conformational search to the native structure. Further studies by NMR will be needed to determine the properties of this state in atomistic detail, akin to the analyses of other nonnative species of Im7 and other proteins.[@bib18 bib20 bib56 bib57 bib58 bib59] Severely destabilized variants of Im7, where the unfolded state is populated in the presence of kosmotrope and in the absence of denaturant, may provide an ideal starting point for such studies.
Chemicals and reagents
Alexa Fluor 488 and 594 C-5 maleimide were purchased from Invitrogen (UK). Fluka brand reagents (Sigma-Aldrich, UK) were used for all single-molecule measurements. Urea was recrystallized in analytical-grade ethanol prior to use.
The desired mutations were introduced into hexahistidine-tagged Im7[@bib16] using QuikChange Site-Directed Mutagenesis Kit (Stratagene, UK). Im7 double-cysteine variants are named using the wild-type residue number (ignoring the His-tag) and the residue to which it has been mutated (e.g., K70C is lysine 70 mutated to cysteine). The proteins were purified to homogeneity as previously described[@bib36] and their identity was verified using mass spectrometry.
Characterization of the unlabeled protein
Fluorescence emission spectra were recorded in a Photon Technologies International Quantamaster C-61 spectrofluorimeter at 10 °C using protein at a concentration of ≈ 5 μM in 50 mM sodium phosphate buffer, pH 7.0, 0.4 M Na~2~SO~4~, 1 mM ethylenediaminetetraacetic acid, and 4 mM DTT and in the same buffer containing 8 M urea. The fluorescence of tryptophan and tyrosine residues was excited at 280 nm, and emission spectra were collected with a scan rate of 1 nm/s between 300 and 450 nm. Buffer blanks were subtracted and the spectra were normalized to the emission maximum of the unfolded state in 8 M urea.
Ensemble equilibrium denaturation of unlabeled protein
The stability of the Im7 double-cysteine variants was determined by equilibrium denaturation using urea titration. The samples were made from stock solutions of buffers containing 50 mM sodium phosphate buffer, pH 7.0, 0.4 M Na~2~SO~4~, 1 mM ethylenediaminetetraacetic acid, and 4 mM DTT in the absence or presence of 9 M urea. The solutions were mixed in appropriate proportions to give final urea concentrations ranging from 0 to 8 M (in 0.2-M increments) and a final protein concentration of ∼ 5 μM. Time-based fluorescence measurements were performed at 10 °C using a Photon Technologies International Quantamaster C-61 spectrofluorimeter. The samples were excited at 280 nm, and the emitted light at 360 nm was measured over a 60-s period. After signal averaging, we plotted the intensity as a function of urea concentration, and the data were fitted to a two-state transition as described previously.[@bib5] To compare the denaturation profiles of the variants, we converted the raw data to fraction population of native molecules.[@bib60]
Labeling with fluorophores
Each double-cysteine variant at a concentration of 3 mg/ml was first labeled with a 0.65 molar ratio of Alexa Fluor 594 C-5 maleimide in 50 mM sodium phosphate and 10% dimethyl sulfoxide, pH 7.3 (labeling buffer), for 45 min at room temperature. Singly labeled protein was separated from unlabeled and doubly labeled protein by anion-exchange chromatography using a prepacked 6 ml Resource Q anion-exchange column on an ÄKTA explorer system equilibrated with 50 mM sodium phosphate pH 7.3 (buffer A). Proteins were eluted with 0--50% gradient over 14 column volumes using buffer A with 1 M NaCl. Singly labeled protein at a concentration of 1 mg/ml in 6 M urea was then labeled with a 2-fold molar excess (over the thiol concentration) of Alexa Fluor 488 C-5 maleimide in labeling buffer for 2 h at room temperature. Double-labeled protein was separated from singly labeled protein by anion-exchange chromatography as described above. This procedure allows the preparation of highly pure proteins, each labeled with a single donor and acceptor pair, but results in an A/B, B/A mix. Remaining traces of unreacted dye were removed by gel filtration using a Superdex Peptide HR 10/30 column in 50 mM sodium phosphate buffer, pH 7.0. At each labeling step, the identity of the product was confirmed by electrospray ionization mass spectrometry.
Steady-state anisotropy data were measured using a HORIBA Jobin Yvon Fluorolog spectrophotometer with double-labeled protein solution at a concentration of 100 nM at 10 °C in 50 mM sodium phosphate buffer, pH 7.0 in the presence or absence of 8 M urea. Each sample was measured with excitation at both 488 and 594 nm, 60 times over the course of 1 min. This was repeated three times, and the mean anisotropy value was calculated.
Single-molecule experiments were performed using a custom-built confocal microscope described in Refs. [@bib21], [@bib30], and [@bib61]. Solutions contained 0--8 M urea (in increments of 0.5 M) in 50 mM sodium phosphate buffer, pH 7.0, 0.01% (w/v) Tween 20 with 0.4 M Na~2~SO~4~, unless otherwise stated. In addition, 1.5 mM [l-]{.smallcaps}carnosine, 2 mM mercaptoethanol, and 10 mM (1,4-diazabicyclo\[2,2,2\] octane were included as oxygen scavengers and to suppress blinking, to minimize the magnitude of the zero peak. Singlet oxygen and dark states (possible triplet-state population) are thought to be the main cause of premature photobleaching of the acceptor dye. Inclusion of these compounds at the stated concentrations has no effect on the thermodynamic parameters (*M*~un~ and Δ*G*~un~°) obtained for this protein.
The protein concentration of each sample was ≈ 50 pM, and all measurements were performed at 10 °C. Data were collected by observing the transient bursts of fluorescence produced by diffusion of single molecules into and out of the confocal detection volume, using an integration time of 0.5 ms. Ratiometric analysis of single-molecule data was performed as described in Ref. [@bib30] using custom algorithms written in the data analysis software package Igor Pro Version 5.06a (Wavemetrics Inc., USA). The proximity ratio, *P*, was calculated using;$$P = \frac{\left( {I_{\text{A}} - \left\langle B_{\text{A}} \right\rangle - \left\langle {\varphi I_{\text{D}}} \right\rangle} \right)}{\left( {I_{\text{A}} - \left\langle B_{\text{A}} \right\rangle - \left\langle {\varphi I_{\text{D}}} \right\rangle} \right) + \left( {I_{\text{D}} - \left\langle B_{\text{D}} \right\rangle} \right)}$$where *I*~A~ and *I*~D~ are the acceptor and donor signals in each 0.5-ms interval, respectively, 〈*B*~A~〉 and 〈*B*~D~〉 are the mean background signals for the acceptor and donor channels, respectively, and φ is the mean cross-talk (leakage) of fluorescence from the donor into the acceptor channel, determined to be ≈ 10% in a separate experiment using a concentrated donor-only sample (data not shown). Note that the FRET efficiency *E* is calculated from the ratio of the detected acceptor signal to the total signal (donor + acceptor) in the same integration time:$$E_{\text{FRET}} = \frac{I_{\text{A}}}{\gamma I_{\text{D}} + I_{\text{A}}}$$where *I*~A~ and *I*~D~ are the uncorrected number of donor and acceptor photon counts per counting interval. In this study, the ratio γ was assumed to be equal to 1. In this limit, a proximity ratio is the FRET efficiency and can be converted, if required to a distance (*R*~0~ = 54 Å for the dye pair used in this study).[@bib27]
A SUM threshold criterion was then applied to the data in order to select only integration times that contained valid single-molecule events and to reject the background;[@bib21 bib32]$$\left( {I_{\text{A}} - \left\langle B_{A} \right\rangle - \left\langle {\varphi I_{\text{D}}} \right\rangle} \right) + \left( {I_{\text{D}} - \left\langle B_{\text{D}} \right\rangle} \right) \geq T,$$where *T* is the particular threshold used. Histograms of the accepted proximity ratios were then constructed and fitted with the sum of two or three Gaussians with the following formularization:$$\text{Occurrence}\left( p \right) = \sum\limits_{n = 1}^{n = 3}{\frac{a_{n}}{w_{n}\sqrt{\pi/2}}\exp\left( \frac{- 2\left( p - p_{0,n} \right)^{2}}{w_{n}^{2}} \right)}$$where *a*~*n*~ is the area under the curve, from the baseline (fixed = 0) of curve *n*. *w*~*n*~ = 2σ~*n*~, where σ~*n*~ is the standard deviation of curve *n*. *p*~0,*n*~ is the mean proximity ratio (peak top for a Gaussian) of curve *n*. Fits were otherwise unconstrained. The mean proximity ratio values obtained from the fits were corrected for changes in the average refractive index of the solution (due to different urea concentrations) following Refs. [@bib27] and [@bib30].
Peak width analysis
Peak width analysis was performed as described in Ref. [@bib30] using a normalized formularization of the expected shot noise distribution with proximity ratio[@bib32] and using algorithms written in Igor 5. The predicted shot noise limited width of a given species is then:$$2\sigma\left( m,S \right) = 2N\frac{\sqrt{m\left( 1 - m \right)}}{\sqrt{S + 1}}$$where σ is the standard deviation, *m* is the mean proximity ratio of the species, *S* is the mean total signal of the identified single-molecule events in that species, obtained by analysis of the actual single-molecule bursts contributing to that species, and *N* is a normalization factor. Using *N* = 1, the width of the species of interest, in this case the folded peak, is underestimated, as previously described.[@bib30] Assuming that the native state of the labeled Im7 variants can be described as a homogeneous, static species, their width therefore represents the shot noise limit for our particular set of experimental conditions. Therefore, for each of the native peaks of the three variants, Im7 H1H4, Im7 H2H4, and Im7 Gly H1H3 in 0 M urea, a normalization pre-factor was generated. The pre-factor was then used to determine the expected shot noise contribution at all urea concentrations for both the native and denatured ensembles, of each Im7 helix pair, using Eq. ([5](#fd5){ref-type="disp-formula"}).[@bib30] In order to investigate the widths of the folded and unfolded peaks of the labeled trapped intermediate proteins as a function of urea concentration, we used the pre-normalization factor generated using the wild-type variant with fluorophores in identical locations. The reasoning behind this approach is that the intermediate may be heterogeneous and dynamic; therefore, the width of this species cannot be assumed to be due to shot noise alone.
We thank Graham Spence for construction of the glycine insertion wild-type variants, Joerg Gsponer for providing additional MD data, and Claire Friel for helpful discussions. S.D.P. was funded by a Wellcome Trust studentship (065520/Z/01/A), and C.G. was supported by the University of Leeds. D.J.B. is a White Rose Doctoral Training Centre lecturer founded by the Engineering and Physical Sciences Research Council.
::: {#fig1 .fig}
Schematic representation of the folding landscape of Im7 involving a populated on-pathway intermediate. Species on the folding pathway are indicated by the following: U, unfolded state; I, intermediate state; N, native state; TS~1~ and TS~2~, early and rate-determining transition states. Representative members of the ensembles calculated by MD simulations[@bib10 bib14] are shown for TS~1~, I, and TS~2~. The structure of native Im7 (Protein Data Bank code [1AYI](pdb:1AYI))[@bib13] is shown in the native well. The segments forming the four helices in the native state are colored red (helix 1), green (helix 2), purple (helix 3), and yellow (helix 4).
::: {#fig2 .fig}
\(a) Normalized fluorescence emission spectra of the folded and denatured states of the wild-type Im7 double-cysteine variants and Im7 I^eqm^ double-cysteine variants. The broken black, green, red, and gray lines correspond to Im7 GlyH1H3, Im7 H2H4, Im7 H1H4, and wild-type Im7 in 0 M urea, respectively. The continuous black, green, and red lines correspond to Im7 I^eqm^GlyH1H3, Im7 I^eqm^H2H4, and Im7 I^eqm^H1H4 in 0 M urea, respectively. The continuous blue lines correspond to the average of all the unfolded states in 8 M urea. All signals were normalized to the maximum signal of the denatured state in 8 M urea. (b) Urea-induced equilibrium unfolding curves of the wild-type Im7 double-cysteine variants and I^eqm^ Im7 double-cysteine variants. Denaturation was monitored by tryptophan fluorescence and normalized to the fraction of folded molecules present. Filled circles correspond to I^eqm^ double-cysteine variants, open circles correspond to the wild-type Im7 double-cysteine variants, and filled gray triangles correspond to wild-type Im7. Color coding of the different helical pairs is identical with that shown in (a). The continuous lines show the fits to a two-state transition.
::: {#fig3 .fig}
Proximity ratio histograms from smFRET measurements on Im7 and Im7 I^eqm^ species in 0 M urea with the fluorophores attached to (a) helices 1 and 4, (b) helices 1 and 3, and (c) helices 2 and 4 at pH 7, 10 °C with 0.4 M Na~2~SO~4~. Black lines show the fits obtained from summing one or two Gaussian distributions (red lines).
::: {#fig4 .fig}
Proximity ratio histograms showing the effect of pH and Na~2~SO~4~ on the distribution of populated species in the I^eqm^ Im7 double-cysteine variants at 10 °C. As the pH is decreased and the concentration of Na~2~SO~4~ is increased, the unfolded state is depopulated and the intermediate state is populated for all variants studied. Black lines show the fits obtained from summing one or more Gaussian distributions (red lines).
::: {#fig5 .fig}
Mean proximity ratio and mean peak width for the folded and unfolded states for (a) Im7 H1H4 and Im7 I^eqm^H1H4, (b) Im7 GlyH1H3 and Im7 I^eqm^ GlyH1H3, and (c) Im7 H2H4 and Im7 I^eqm^H2H4 as a function of urea concentration at pH 7.0, 10 °C in the absence of Na~2~SO~4~. Triangles and squares represent the unfolded and folded states, respectively, and filled and open symbols correspond to the Im7 I^eqm^ and Im7 variants, respectively. The dotted blue and red lines represent the shot noise predictions for the unfolded and folded species, respectively. The error bars are ± 1 SD.
::: {#fig6 .fig}
Selected proximity ratio histograms of the equilibrium urea denaturation of (a) Im7 I^eqm^H1H4 at pH 7 in the absence of Na~2~S0~4~ and (b) Im7 I^eqm^H1H4 and (c) Im7H1H4 at pH 7 and 0.4 M Na~2~S0~4,~ 10 °C monitored by smFRET. Black lines show the fits obtained from summing one or more Gaussian distributions (red lines).
::: {#fig7 .fig}
Mean proximity ratio and mean peak width for the folded and unfolded species of (a) Im7 H1H4 and Im7 I^eqm^H1H4 and (b) Im7 GlyH1H3 and Im7 I^eqm^ GlyH1H3 as a function of urea concentration at pH 7.0 and 0.4 M Na~2~SO~4~, 10 °C. Triangles and squares represent the unfolded and folded species, respectively, and filled and open symbols correspond to the Im7 I^eqm^ and Im7 variants, respectively. The dotted blue and red lines represent the shot noise predictions for the unfolded and folded species, respectively. The error bars are ± 1 SD.
::: {#tbl1 .table-wrap}
Biophysical characterization of the Im7 variants used in this study (at pH 7, 10 °C)
Variant Δ*G*~un~° (kJ mol^− 1^)[a](#tblfn1){ref-type="table-fn"} *M*~un~ (kJ mol^− 1^ M^− 1^)[a](#tblfn1){ref-type="table-fn"} Anisotropy
-------------------- ---------------------------------------------------------- --------------------------------------------------------------- ------------- ------------- ------------- -------------
Im7 24.6 ± 1.3 4.9 ± 0.7 ND ND ND ND
Im7 GlyH1H3 22.4 ± 0.8 5.6 ± 0.1[d](#tblfn4){ref-type="table-fn"} 0.11 ± 0.07 0.11 ± 0.03 0.17 ± 0.05 0.13 ± 0.08
Im7 H2H4 20.1 ± 0.8 4.7 ± 0.1 0.15 ± 0.07 0.12 ± 0.06 0.14 ± 0.02 0.12 ± 0.05
Im7 H1H4 20.8 ± 0.6 4.9 ± 0.1 0.10 ± 0.06 0.11 ± 0.05 0.14 ± 0.03 0.12 ± 0.04
Im7 I^eqm^ 10.1 ± 0.3[e](#tblfn5){ref-type="table-fn"} 3.4 ± 0.2[e](#tblfn5){ref-type="table-fn"} ND ND ND ND
Im7 I^eqm^ GlyH1H3 7.9 ± 0.9 4.5 ± 0.3[d](#tblfn4){ref-type="table-fn"} 0.12 ± 0.08 0.11 ± 0.05 0.17 ± 0.06 0.10 ± 0.05
Im7 I^eqm^ H2H4 7.8 ± 1.2 3.5 ± 0.3 0.18 ± 0.07 0.12 ± 0.03 0.17 ± 0.04 0.12 ± 0.03
Im7 I^eqm^ H1H4 6.8 ± 1.1 3.8 ± 0.2 0.19 ± 0.07 0.11 ± 0.06 0.17 ± 0.02 0.11 ± 0.03
The thermodynamic parameters (Δ*G*~un~° and *M*~un~) were calculated from chemical denaturant equilibrium unfolding experiments. Errors are those from fits of the data to a two-state equilibrium model.
Measured in the presence of 0.4 M Na~2~SO~4~.
Anisotropy of donor fluorophore measured at 488 nm.
Anisotropy of acceptor fluorophore measured at 594 nm.
*M* values for the two GlyH1H3 variants are significantly larger than their analogues without glycine insertions, consistent with the introduction of 15 glycine residues.
Taken from Ref. [@bib19].
S.D.P. and C.G. contributed equally to this work.
Present addresses: C. Gell, Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden, Germany; D. A. Smith, Avacta Group Plc, York Biocentre, Innovation Way, York YO10 5NY, UK.
|
Multiple conditionals with ng-show AngularJS
I have a ng-repeat that builds a table from a web service. I render 6 values like this: med:1 lab:1 pl:1 in one cell. I need to make a decision based on those 6 values. My ng-repeat code is like this:
<tr ng-repeat="(pid, value) in patient|groupBy:'pid'">
<td>{{pid}}</td>
<td ng-repeat="(disease, value) in patient|groupBy:'name'">
<span ng-repeat="item in value|filterBy:['pid']:pid" ng-model="disease-conditial">
{{item.src}}:{{item.total}}
</span>
<!--This is the code that I'm trying to make to work-->
<span class="label label-danger" ng-show="
(item.src == 'med' and item.total > 0) and
(item.src == 'lab' and item.total > 0 and
(item.src == 'pl' and item.total > 0))">Yes
</span>
</td>
</tr>
Please consider this sudo code. I need three conditions:
if src == med && total > 0
and
if src == lab && total > 0
and
if src == pl && total > 0
then Yes
if src == med && total == 0
if src == lab && total > 0
if src == pl && total > 0
then Maybe
if src == med && total == 0
if src == lab && total == 0
if src == pl && total == 0
then No
I was reading about ng-switch but this directive doesn't support conditionals with dynamic data $scope.something == 1
Does Angular has any built in directive where I can achieve this?
The data in the cell looks like this:
+-----------------+
|med:1 lab:1 pl:1 |
+-----------------+
I need to evaluate the value of med && the value of lab && the value of pl to make the decision of Yes, Maybe, No.
Update 7 SEP 2016
The data that comes from the object is as follow:
Array[50]
0:Object
$$hashKey:"object:18"
name:"Alcoholism"
pid:"1"
src:"lab"
total:"1"
__proto__:Object
1:Object
$$hashKey:"object:19"
name:"Alcoholism"
pid:"1"
src:"med"
total:"1"
__proto__:Object
2:Object
$$hashKey:"object:20"
name:"Alcoholism"
pid:"1"
src:"pl"
total:"0"
__proto__:Object
Once again, scenario 1. if med > 0 && lab >0 && pl >0 then Yes. Scenario 2. if med == 0 && lab > 0 && pl > 0 then Maybe. Scenario 3. if med == 0 && lab == 0 && pl == 0 then No.
First of all, you shouldnt be doing this at the view, you should use a function in ng-show: ng-show="showData()", and do the conditions in the controller... Second is not "And", is &&
What do you mean the condition maybe?????? Use && operators instead of and, and I agree with @GustavoGabriel, if you can create a function to define your logic in your controller, it will be much much easier.
Well if you remove the parentheses (operator precedence makes the parentheses useless when all conditions are 'and') you will see that item.src will never be 'med' and 'lab' and 'pl' at the same time, so the expression will always evaluate to false.
I change the and for && and doesn't work.
You can use a ng-switch with item.src like this:
<div class="animate-switch-container" ng-switch on="item.src" ng-show="item.total > 0">
<div ng-switch-when="med">med</div>
<div ng-switch-when="lab">lab</div>
<div ng-switch-when="pl">pl</div>
</div>
With the ng-show in the entire div will make the same and validation.
This is a good clean example of both the ngSwitch and ngShow directives
Fabio; the logic is as fallow... ng-switch-when="med" and the value for med == 1 then Yes.
Even though it can be a good example of the use of ngSwitch and ngShow, this is not the answer to the question. It does not follow the logic (barely) explained in the question.
I ill prefer you to get single value from controller which you want to display on view but ng-bind can also help you render required data
<span class="label label-danger" ng-bind="item.total>0 && (item.src === 'med' || item.src === 'lab' || item.src === 'pl')?'yes':'no'"> </span>
Muslim; let me try your solution.
Your code returns just two conditions, My problem has three instead.
I think you are just putting your conditions wrong. I'm doing some guessing here, but what I think you are trying to do is this:
<tr ng-repeat="(pid, value) in patient|groupBy:'pid'">
<td>{{pid}}</td>
<td ng-repeat="(disease, value) in patient|groupBy:'name'">
<span ng-repeat="item in value|filterBy:['pid']:pid" ng-model="disease-conditial">
{{item.src}}:{{item.total}}
</span>
<!--This is the code that I'm trying to make to work-->
<span class="label label-danger" ng-show="
((item.src == 'med' || item.src == 'lab' || item.src == 'pl') and item.total > 0)">
Yes
</span>
<span class="label label-danger" ng-show="
((item.src == 'med' && item.total == 0) || (item.src == 'lab' and item.total > 0) || (item.src == 'pl' and item.total > 0))">
Maybe
</span>
<span class="label label-danger" ng-show="
((item.src == 'med' || item.src == 'lab' || item.src == 'pl') and item.total == 0)">
No
</span>
</td>
</tr>
It is not a problem with the ng-show directive, it is a problem with the conditions inside it.
Let me try that Alvaro. I'm wondering why I got a -1 vote for this question?
I don't know, I'm not who gave the negative vote to you. Maybe because the problem itself does not relate to AngularJS but with the boolean condition but, honestly, I don't know. The best way to avoid downvotes is to follow StackOverflow's question guidelines. Good luck with your try!
Alvaro; I think you are missing a (. In the first line you are closing right after the 0 but I don't see where should opened. Any way, I tried that line of code and is rendering Yes in all my cells. I moved the missing ( right before item.total and at the very beggingitem.srcand got the same result, all cells withYes`
Please, try the solution now. There was a missing '(' at the very beggining of the fist condition.
Sorry again, there was another '(' at the beggining of the third condition :). I edited my answer.
It is rendering Yes, Maybe, No in all the cells. At some point in my code I had the same outcome. For some reason ng-show can't discriminate the values and create the conditions.
Now I have to go to bed, a little bit late here in Spain :), but it makes sense. Tomorrow I'll try to take a look if you didn't get any successfull answer. Kind regards.
In the meantime, try to get us a working plunker which reproduces the error with some representative data to make some testing.
Thank you Alvaro!!
Hi again Gilbert. I'm having a quick look at your question again and I notice that something must be wrong either with the logic or with de way you iterate over your data. The conditions I gave to you don't make much sense because if item.src === 'med' and item.total === 0, it will match two of the conditions. Please, edit your question adding a full example of the JSON object you are iterating over (I mean your 'patient' object/array) to take a look at it. Thanks.
|
Talk:US Navy Vessels (Contact '57)
what is the source of these images? Wingman1 01:31, April 21, 2013 (UTC)
|
Duplication of boards in Set Assignments?
I seem to have the same board appearing twice in set assignments (this is the<EMAIL_ADDRESS>account). Not sure if this is a recurring problem:
It's worth noting that these are definitely the same board as when I assign a group to one instance, it also appears on the other instance
So I'm pretty confident this is just the list of boards changing between page load and "Load more" being clicked. The server has had a new board added to the top of its list, but the client doesn't know about this. So it asks for boards 6-12 and gets the 6th-become-7th board twice.
It's perfectly correct behaviour from the server, but I agree the front end might do something smart like hide the duplicate.
|
Angular 6 validators pattern for latin characters is not working
I am using reactive forms with validators. For the arabic name field I am using:
Validators.pattern('[\u0600-\u06FF ]*')
But I can't figure out the pattern for latin letters of A-Z and a-z.
I tried:
Validators.pattern(/^-?([a-z]\d*)?$/)
But it didn't work.
regexr is awesome for working out regular expressions
try to apply this pattern: /^[ءآأؤإئابةتثجحخدذرزسشصضطظعغفقكلمنهوىيًٌٍَُِّْٰ]*$/
for arabic :https://stackoverflow.com/questions/12847333/include-arabic-characters-in-javascript-regular-expression
i use this regex:
Validators.pattern('^[a-zA-Z][a-zA-Z0-9-_@\.]{2,20}$')
And
Validators.pattern(/[\u0600-\u06FF-/ ]/) for arabic
The answer was by simply using:
Validators.pattern('[a-zA-Z ]*')
To allow numbers with them:
Validators.pattern('[a-zA-Z0-9 ]*')
|
Protein sequence pattern-matching python
I'm working on a matching algorithm for protein sequences. I'm starting with an aligned protein sequence, and I am attempting to convert a mis-aligned sequence into the correctly aligned one. Here is an example:
original aligned sequence: ----AB--C-D-----
mis-aligned sequence: --A--BC---D-
The expected output should look like this:
original aligned sequence: ----AB--C-D-----
mis-aligned sequence: ----AB--C-D----- (both are now the same)
I'm told to be very specific about my problem, but the sequences I'm trying to match are >4000 characters long, and look ridiculous when pasted here. I'll post two sequences representative of my problem, though, and that should do.
seq="---A-A--AA---A--"
newseq="AA---A--A-----A-----"
seq=list(seq) #changing maaster sequence from string to list
newseq=list(newseq) #changing new sequence from string to list
n=len(seq) #obtaining length of master sequence
newseq.extend('.') #adding a tag to end of new sequence to account for terminal gaps
print(seq, newseq,n) #verification of sequences in list form and length
for i in range(n)
if seq[i]!=newseq[i]:
if seq[i] != '-': #gap deletion
del newseq[i]
elif newseq[i] != '-':
newseq.insert(i,'-') #gap insertion
elif newseq[i] == '-':
del newseq[i]
old=''.join(seq) #changing list to string
new=''.join(newseq) #changing list to string
new=new.strip('.') #removing tag
print(old) #verification of master-sequence fidelity
print(new) #verification of matching sequence
The output I get from this particular code and set of sequences is:
---A-A--AA---A--
---A-A--A----A-----A-----
I can't seem to get the loop to correctly delete unwanted dashes in between the letters more than once, because the rest of the loop iterations are used in an add dash/delete dash pair.
This is a good start to the problems here.
How can I write this loop successfully to obtain my desired output (two identical sequences)
There is no loop in this code sample
Thanks for pointing that out! I guess I lost the loop command in the shuffle
I edited your code and it is giving correct output now:
seq="----AB--C-D-----"
newseq="--A--BC---D-"
seq=list(seq) #changing maaster sequence from string to list
newseq=list(newseq) #changing new sequence from string to list
n=len(seq) #obtaining length of master sequence
newseq.extend('.') #adding a tag to end of new sequence to account for terminal gaps
print(seq, newseq,n) #verification of sequences in list form and length
for i in range(len(seq)):
if seq[i]!=newseq[i]:
if seq[i]=='-':
newseq.insert(i,'-')
elif newseq[i]=='-':
newseq.insert(i,seq[i])
else:
newseq.insert(i,seq[i])
else:
newseq=newseq[0:len(seq)]
old=''.join(seq) #changing list to string
new=''.join(newseq) #changing list to string
new=new.strip('.') #removing tag
print(old) #verification of master-sequence fidelity
print(new) #verification of matching sequence
output:
----AB--C-D-----
----AB--C-D-----
and for AA---A--A-----A-----:
---A-A--AA---A--
---A-A--AA---A--
This algorithm, as the previous one, does not consider the possible mismatch between specific positions, different size strings and has no backtracking if a better solution arises afterwards. Please consider looking into dynamic programming.
I will definitely pursue dynamic programming for future work. This code works in general for my immediate purposes, though (the sequences are always the same order, there is only one solution, and this code works for different size strings). Thanks!
The problem of sequence alignment is well known and its solution is well described. For an introductory text, see the Wikipedia. The best solution I know involves Dynamic programming, and you can see an example implementation in Java at this site.
|
Adopt use of black instead of yapf
This change is switching our code-formatter from yapf to black, which
become far more popular, mainly because it is not configurable. This
means that project maintainers no longer have the option to introduce
their own oppionated settings.
Black is now hosted under official Python Foundation GitHub organization
and was already adopted by major projects like pytest and django.
Another serious benefit is speed, black is incomparebly faster than yapf
and can be used as a pre-commit hook.
Please review this, is only reformated by black, the faster we do the switch the easier it will be.
Add a pyproject.toml with the following:
[tool.black]
skip-string-normalization = true
@decentral1se Addressed your concerns but I will make another change to also change the quotes as I think that one would be useful too (for consistency). Still, it makes no sense to delay adopting your suggestion as the first step.
Regarding existing PRs, we have only 30 now and their authors can easily rebase them and re-run linting, not a real deal. We used to have >100 ones so now we are much better.
@decentral1se Addressed your concerns but I will make another change to also change the quotes as I think that one would be useful too (for consistency). Still, it makes no sense to delay adopting your suggestion as the first step.
Huh!? The whole point is to not change the quotes to reduce the diff. I have no idea what you mean by "consistency" in this context. My concern is to address consistency (keep using single quote style we already have) while yours is to break consistency and increase the diff size. Please spare me this purism of "not having a config" because Black's "philopsophy" or whatever..
@decentral1se please re-review, the current code followed all your comments. I just want to merge it ASAP because otherwise I will have to rebase it after each other PR merged.
|
138 The Twentieth General Meeting.
trigonia, &c., &c. The shells recorded as occurring at Swindon were not numerous^ only reaching twenty species. But he found that in his own collection he had increased the number to something like eighty species : some of them of very great interest. After passing through the Portland beds, which formed the greatest thickness of the quarries, they came to the series of beds called the Purbeck, also largely developed on the coast near Swanage. In passing from the Portland to the Purbeck, they as it were passed from one world into another. The Portland beds were marine formations, and the Purbeck were fresh- water deposits. The bed of most especial interest in the quarries here, was about 18 inches in thickness. If he said that it was full of interesting things, .that would be an exaggeration, but great care and time were required for their discovery. At Swindon the beds were horizontal, but at Swanage they were disturbed. At Swanage twenty-three species of Purbeck mammalia had been taken, very nearly all of them little kanga roos. The remains were almost all lower jaws, and very small. The strata at Swanage were vertical, but at the top of the cliff they lapped over ; and here, himself and some friends had executed a work not unattended with danger. While detaching a stone it gave way suddenly, and struck one of his friends, who was thrown over the edge of the cliff, and rolled down seventy feet. Just below that, there was a sheer precipice of one hundred feet. They had to go round a quarter of a mile to get at him, and of course anticipated that he had been killed. What was their astonishment when after shaking himself together a little he asked if he was much hurt? They carried him home, and actually in four days he had not only recovered, but was at work at the same spot again ! That, however, was a digression. Some years ago he had examined the similar bed at Swindon, and found fom* of the genera of mammals which occur at Swanage. These four were small insectivorous mammals — little kangaroos. There were also six or seven reptiles, one possessing teeth of remarkable form.
But now he had shown them that ages ago Swindon was actually the home of a species of small kangaroos, they might ask him if there were any traces of the food of these creatures. There were
|
package com.cameron.test;
import android.graphics.Color;
import android.os.Bundle;
import android.support.annotation.ColorInt;
import android.support.v4.content.ContextCompat;
import android.support.v7.app.AppCompatActivity;
import android.util.Log;
import android.view.View;
import android.widget.Button;
import android.widget.Toast;
import com.cameron.materialcolorpicker.ColorPicker;
import com.cameron.materialcolorpicker.ColorPickerCallback;
public class MainActivity extends AppCompatActivity implements ColorPickerCallback {
private final String COLOR_VALUE = "colorValue";
private ColorPicker colorPicker;
private View colorView;
private int currentColor;
@Override
protected void onCreate(Bundle savedInstanceState) {
super.onCreate(savedInstanceState);
setContentView(R.layout.activity_main);
setTitle(getString(R.string.toolbar_title));
Button openColorDialog = findViewById(R.id.open_color_picker);
int defaultColor = ContextCompat.getColor(this, R.color.colorPrimary);
currentColor = savedInstanceState != null ? savedInstanceState.getInt(COLOR_VALUE) : defaultColor;
colorView = findViewById(R.id.color_image);
colorPicker = new ColorPicker(
this, // Context
0, // Default Alpha value, this can be omitted
0, // Default Red value
0, // Default Green value
0 // Default Blue value
);
// Various configurations, all of the below are optional
colorPicker.setCloseOnDialogButtonPressed(true)
.setDialogButtonText("CONFIRM")
.setCloseOnBackPressed(false)
.showButtonAsTransparent(true)
// Since this activity already implements the ColorPickerCallback,
// this last configuration is technically unnecessary
.setCallback(this);
// The dialog will be reset on orientation change. This is an
// example of how to retain the color value in such a case
colorPicker.setColor(savedInstanceState == null ? defaultColor : currentColor);
colorView.setBackgroundColor(savedInstanceState == null ? defaultColor : currentColor);
openColorDialog.setOnClickListener(new View.OnClickListener() {
@Override
public void onClick(View v) {
colorPicker.show();
}
});
}
@Override
protected void onSaveInstanceState(Bundle outState) {
super.onSaveInstanceState(outState);
outState.putInt(COLOR_VALUE, currentColor);
}
/**
* Thanks to android's window leaks, we need to dismiss the
* dialog when the device is rotated
*/
@Override
protected void onStop() {
super.onStop();
if (colorPicker != null) colorPicker.dismiss();
}
/**
* One way to get values from the Color Picker is by implementing the
* {@link ColorPickerCallback} on a class level, as can be seen here.
*/
@Override
public void onColorChosen(@ColorInt int color, String hex, String hexNoAlpha) {
Log.d("Pure color", String.valueOf(color));
Log.d("Alpha", Integer.toString(Color.alpha(color)));
Log.d("Red", Integer.toString(Color.red(color)));
Log.d("Green", Integer.toString(Color.green(color)));
Log.d("Blue", Integer.toString(Color.blue(color)));
Log.d("Hex with alpha", hex);
Log.d("Hex no alpha", hexNoAlpha);
// Once the dialog's select button has been pressed, we
// can get the selected color and use it for the
// background of our view
colorView.setBackgroundColor(color);
Toast.makeText(this, "ARGB: " + hex + " | RGB: " + hexNoAlpha, Toast.LENGTH_LONG).show();
}
/**
* When the color values from the dialog are changed, this method will
* be called. Here, we'll just change the color of the dialog's button.
*/
@Override
public void onColorChanged(@ColorInt int color, String hex, String hexNoAlpha) {
Log.d("Color", String.valueOf(color));
Log.d("Hex", hex);
Log.d("Hex no alpha", hexNoAlpha);
// Save the color selected so we can retrieve it again
// when the device is rotated
currentColor = color;
colorPicker.setDialogButtonTextColor(color);
}
}
|
Multilevel analysis of anemia and associated factors among women of reproductive age (15–49 years) in Liberia: Evidence from the 2019/20 Liberia demographic and health survey data
Background Anemia is a global public health problem, principally affecting young children and reproductive-age mothers. Although anemia is a main public health concern in low-income countries, there is no evidence about its prevalence and associated factors among women of reproductive age in Liberia. Thus, the purpose of this study was to identify the prevalence and associated factors of anemia among women of reproductive age in Liberia. Methods We used the data extracted from the fifth Liberia Demographic and Health Survey (LDHS-V) that were carried out between October 2019 and February 2020. The sample was chosen using a stratified two-stage cluster sampling procedure. Overall weighted samples of 4027 women of reproductive age were used in the analysis. Data weighting was carried out to obtain reliable estimates and standard errors as well as to restore the representativeness of the data. Stata version 14 software was used for data extraction, coding, and analysis. We used multilevel analysis to identify the significant factors associated with anemia among women of reproductive age. Results The prevalence of anemia among women of reproductive age in Liberia was 44.51 (95% CI: 42.97–46.04). From these, about 23.10% of women of reproductive age were mildly anemic, 20.63% were moderately anemic and 0.78% was severely anemic. In multivariable analysis; women with the groups of 20–24 years (adjusted odds ratio (AOR) = 0.72, 95% CI: 0.56, 0.92), 25–29 years (AOR = 0.57, 95% CI: 0.43, 0.77), 30–34 years (AOR = 0.59, 95% CI: 0.43, 0.83), 35–39 years (AOR = 0.56, 95% CI: 0.41, 0.79), 40–44 years (AOR = 0.61, 95% CI: 0.43,0.87), 45–49 years (AOR = 0.57, 95% CI: 0.39,0.82), overweight (AOR = 0.83; 95% CI: 0.70, 0.98), obese (AOR = 0.72; 95% CI: 0.58, 0.88), using modern contraceptive methods (AOR = 0.61; 95% CI: 0.52, 0.72), and being from the Northcentral region (AOR = 0.55; 95% CI: 0.43, 0.72) were significantly associated with lower odds of anemia. However, being pregnant (AOR = 1.34; 95% CI: 1.04, 1.73) and having higher parity (3 children or more) (AOR = 1.40; 95% CI: 1.03, 1.93) were significantly associated with higher odds of anemia. Conclusion In the present study, the prevalence of anemia in women of reproductive age was relatively high. Therefore, it is better to provide special emphasis on high-risk groups such as pregnant and multiparous women.
Introduction
Anemia is a disorder in which the number of erythrocyte cells (hemoglobin levels) is inadequate to meet the physiologic desires of the body tissue [1].It is a main worldwide public health problem, principally affecting young children and reproductive-age mothers [2][3][4].Globally, over 500 million (33%) women of reproductive age suffer from anemia which has a long-term negative impact on both the health of mothers and their children as well as economic development [5].However, the highest-burden (49.7%) of anemia in women of reproductive age is found in sub-Saharan Africa [6].
Anemia has significant long-term adverse impacts on the health of general populations; especially women are among the vulnerable groups because of their experiences of menstruation, pregnancy, and childbirth-related hemorrhage [7].Anemia in women of childbearing age causes low productivity because of decreased work capacity, high infection risk because of its effect on immunity, termination of pregnancy, and maternal death [8][9][10][11].Furthermore, maternal anemia is associated with adverse neonatal health outcomes like premature birth, mental retardation, small birth weight, and decreased baby iron stores, which may ultimately lead to child death [10][11][12][13].
Even though the etiologies of anemia are multifactorial, it may be caused by nutritional and non-nutritional causes [14][15][16].Due to the high demand for iron during pregnancy, breastfeeding, and menstrual period, iron deficiency is the most common cause of anemia in women of childbearing age [10,17].
The world health organization (WHO) considers anemia a serious public health problem when its prevalence is above 5% [38]; however, the majority of the evidence shown above indicates that the burden of anemia among mothers of reproductive age is greater than 20%.WHO has established a worldwide aim of accomplishing a 50% decrease in anemia prevalence among women of reproductive age by 2025 [11], even though it is difficult to achieve this aim in the recent trend.Although anemia is a main public health concern in low-income countries, there is no evidence about its prevalence and associated factors among women of reproductive age in Liberia.Thus, the purpose of this study was to identify the prevalence and associated factors of anemia among women of reproductive age in Liberia.
Data source, sampling technique, and population
We used the data extracted from the fifth Liberia Demographic and Health Survey (LDHS-V) that was carried out between October 2019 and February 2020.The LDHS has performed a stratified, two-stage cluster sampling technique.In the first stage, a total of 325 clusters were selected using a stratified two-stage cluster sampling technique.In the second stage, a fixed number of households (30 households for each cluster) were selected using a systematic sampling technique.For this study, we used the woman's data (IR) file and an overall weighted sample of 4027 women of reproductive age.
Variables of the study
Outcome variable.The dependent variable for this study was anemia level, which was determined by the mother's pregnancy status; when non-pregnant a hemoglobin level <12.0 g per deciliter (g/dl), and when pregnant a hemoglobin concentration <11.0 g/dl were considered as anemia.Based on severity, anemia was also categorized as mild (if hemoglobin levels were between 10.0 and 10.9 g/dl and 10.0 and11.9g/dl for pregnant women and non-pregnant women, respectively); moderate (if hemoglobin values were between 7.0 and 9.9 g/dl); and severe (if hemoglobin level <7.0 g/d) for both pregnant and non-pregnant women.In our study, we re-classified anemia status as anemic, which was coded as "1" and non-anemic, coded as "0".Independent variables.According to different literature, the explanatory variables included in the study were individual-level and community-level factors.Individual-level variables considered were classified as maternal-related factors and household-related factors.The maternal-related factors were age of the mothers (categorized as 15-19 years, 20-24 years, 25-29 years, 30-34 years, 35-39 years, 40-44 years, and 45-49 years), educational status (no primary education, primary education, and secondary and above), occupational status (working and not working), marital status, having ever had a terminated pregnancy (yes and no), parity, perception of distance from the health facility, modern contraceptive use, current pregnancy (yes and no) status, breastfeeding, body mass index, and respondents slept under the mosquito net.The household-level factors include wealth index (poorest, poorer, middle, richer, and richest), sex of household head, household size, media exposure (made from 3 factors: frequency of listening to radio, frequency of watching television, and frequency of reading newspapers), type of toilet facility (improved and non-improved), and source of drinking water.The community level factors were residence (urban and rural) and region (Northwestern, Southcentral, Southeastern-a, Southeastern-b, and Northeastern).
Data management and analysis
Data extraction, coding, and analysis were done using Stata version 14 software.Data weighting was carried out throughout the analysis to obtain reliable estimates and standard errors as well as to restore the representativeness of the data.Descriptive statistics were done using frequencies and percentages.A multilevel binary logistic regression model was fitted to determine associated factors of anemia because of the hierarchical nature of LDHS data.In LDHS, study participants were nested within clusters, and we assume that participants within the same cluster are more likely to share similar characteristics than participants in another cluster.The independent and equal variance assumptions of the traditional logistic regression model are violated in this situation.As a result, a sophisticated model must be used to account for the heterogeneity between clusters.Four models were developed during the multilevel analysis: the first (null model), which only incorporated the dependent variable; the second (Model I), which only included individual-level factors; the third (Model II), which only included community-level variables; and the fourth (Model III), which included both individual and community-level variables.To detect the clustering effect or variability, the intraclass correlation coefficient (ICC), median odds ratio (MOR), and proportional change in variance (PCV) were checked.Model comparison was done using deviance (-2 log-likelihood (LL)), and the model with the lowest deviance was declared to be the best-fitted model.To select the variables for the multivariable logistic regression analysis, a binary bivariable logistic regression analysis was initially performed, and variables with a p-value of less than 0.20 were selected as candidates for the multivariable logistic regression analysis.Variables with a P-value of less than 0.05 in the multivariable logistic regression analysis were considered significant factors associated with anemia among women of reproductive age, and an adjusted odds ratio (AOR) with a 95% confidence interval (CI) was reported.
Ethical considerations
Ethical approval and participant consent were not required for this study because it was a secondary data analysis of publically accessible survey data from the MEASURE DHS Program.The authors requested DHS Program and permission was obtained to download and utilize the data for this study from https://www.dhsprogram.com/data/dataset_admin/login_main.cfm.The datasets contain neither household addresses nor names of individuals.There are no names of participants or household addresses recorded in these data sets.
Sociodemographic characteristics of women in Liberia
An overall weighted sample of 4027 reproductive-age women (15-49 years) was included in the final analysis.The mean [±SD] age of the women was 29.2 (±10.01)years.The highest proportion (21.66%) of women was in the age group of 15-19 years and nearly 39.26% of the respondents were unmarried.About 45.87% of respondents had secondary education and above.Around 64.77% of women had media exposure, and 63.04% of them had no job or were currently not working.Most (84.74%) of women were from households with an improved source of drinking water, and about half (50.98%) were from households with an unimproved type of toilet facility.About three-quarters (74.60%) of women did not use modern contraceptives.Concerning residence and sex of household heads, about 62.46% and 60.02% of respondents were urban dwellers and male-headed households, respectively.Regarding region, about half (50.70%) of respondents were from the Southcentral region (Table 1).
Anemia prevalence among women of childbearing age (15-49 years) in Liberia
In our study, the prevalence of anemia among women of reproductive age in Liberia was 44.51% (95% CI: 42.97-46.04).The study revealed that 23.10% of women of reproductive age had mild anemia, 20.63% had moderate anemia, and 0.78% had severe anemia.The prevalence of anemia was higher in women from the Northwestern region (52.36%) and lower in those from the Northcentral region (37.27%)(Fig 1).
Results of the random effect analysis and model selection
In this study, ICC, MOR, and PCV were used to assess the random-effects model analysis.The community-level variability was measured by both ICC and MOR.The ICC value in the null ).We used the last model to identify the significant factors associated with anemia among women of reproductive age in Liberia (Table 2).
Discussion
Anemia among women of reproductive age is a significant public health concern in developing countries due to their increased need for iron during pregnancy, breastfeeding, and menstrual blood loss [10].In the current study, the prevalence of anemia among women of reproductive age in Liberia was 44.51% (95% CI: 42.97-46.04),which is consistent with a systematic review conducted in developing countries [39].The prevalence of anemia in this study was higher than in a previous study conducted in Ethiopia [40], Rwanda [24], Democratic Republic of Congo [19], East Africa [5], Nepal [25], and South and Southeast Asian countries [41].However, the prevalence in this study was lower than in studies carried out in India [42] and Vietnam [43].The variation in anemia prevalence across countries is likely due to the differences in sociocultural, geographical, and dietary-related factors between countries.Moreover, the high burden of anemia among mothers in Liberia might be due to their social and biological vulnerability to anemia.Furthermore, in low-income countries, particularly Liberia, access to iron-rich food is insufficient because of their low socioeconomic status and limited access to and underutilization of health care, which may contribute to anemia.
Our study indicated that respondent age, body mass index, modern contraceptive use, current pregnant status, parity, and being from the Northcentral region of Liberia were significantly associated with anemia.Older age groups of women had lower odds of anemia than younger age groups (15-19 years).This finding is in agreement with different studies done elsewhere [5,18,19,44].An increased risk of anemia in relatively younger women might be because of the adverse effects of poor dietary iron intake and the increased demand for iron imposed by iron loss during menstrual blood loss, pregnancy, and lactation [17].We also found that overweight and obese women had lower odds of anemia as compared to women with normal body weight, and this is in agreement with other studies [24,25,41,45].A study conducted in China indicated that overweight and obese mothers had higher iron consumption rates than normal body weight mothers [46].Previous studies revealed that a higher socioeconomic status is associated with good nutritional status [47], preventing infection [48], better access to health care services, and improving other living conditions [47,49], all of which in turn increase iron intake and prevent anemia.
This study also showed that the use of modern contraceptive methods was significantly associated with anemia.A woman who used modern contraceptive methods had a lower risk of developing anemia as compared to women who did not use any contraceptive, and this is supported by different studies [5,6,24,25].This might be due to the preventive effects of modern contraceptives on menstrual blood loss, pregnancy, and birth-related complications, which in turn, reduce the burden of anemia due to recurrent blood loss [50,51].Simultaneous iron supplementation is also obtained, especially in those mothers who have taken oral hormonal contraceptives, and this could prevent anemia [52].
In this study, we also found that pregnant women had higher odds of anemia as compared with non-pregnant women, and this is in agreement with other studies reported elsewhere [5,19,21,26,33].This is because pregnant women need more iron to support their intrauterine fetal development.The second probable reason could be that anemia during pregnancy may result from micronutrient deficiencies, infections, or genetic disorders of the erythrocytes such as thalassemia; all of these are common during pregnancy [53].Women with a higher parity (3 children or more) had a higher odds of developing anemia as compared to women with no children and this is consistent with other previous studies done elsewhere [54,55].This is because the prevalence of anemia increases with the number of pregnancies.
Furthermore, in our study, the region was significantly associated with anemia among women of reproductive age.The odds of anemia were lower among women who were living in the Northcentral region as compared to women from the Southeastern-b region of Liberia.The first possible explanation for the difference in the proportion of anemia could be variation in sociocultural status, availability and accessibility of health care services, economic status, and dietary-related factors between regions within the same country [56].Additionally, variation in the prevalence of anemia could be due to the discrepancy in the proportion of women taking iron supplements and getting dewormed between regions [57].
Strengths and limitations of the study
The study has several strengths.Firstly, it was based on a large weighted sample size of nationally representative data.Secondly, appropriate statistical analysis was performed using multilevel analysis to consider the hierarchical nature of the LDHS data and get a reliable estimate.Thirdly, we strongly believe that the study has the potential to provide insight for policymakers and program managers to design appropriate intervention strategies for the problem both at regional and national levels since it is based on the national survey data.Conversely, the study has limitations.Since LDHS data was based on participants' self-report of variables, there might be a probability of recall bias.Also, since this study was cross-sectional, it is difficult to show the temporal relationship between outcome and explanatory variables.We didn't address some independent variables like parasitic infection (such as malaria and intestinal parasitic infestation) in the analysis since these variables are not available in the LDHS data.
Conclusion
In the present study, the prevalence of anemia in women of reproductive age was relatively high.We found that older age, a higher body mass index, the use of modern contraceptive methods, and being from the Northcentral region of Liberia were significantly associated with lower odds of anemia in women of reproductive age.However, being pregnant and having higher parity were significantly associated with a higher prevalence of anemia.Therefore, it is better to provide special emphasis on high-risk groups such as pregnant and multiparous women.
Table 1 .
(Continued) was 5.9%, revealing that 5.9% of the total variability of the level of anemia in women of reproductive age was because of differences between clusters whereas the remaining unexplained 94.1% of the total variability of the level of anemia was due to individual differences.
https://doi.org/10.1371/journal.pone.0296747.t001Fig1.The prevalence of anemia among women of reproductive age in Liberia.https://doi.org/10.1371/journal.pone.0296747.g001modelAdditionally,thehighest MOR value(1.16) in the null model supports the fact that there was significant clustering of anemia in women of reproductive age.Moreover, the highest PCV value (0.28) in the last model (model III) indicated that 28% of the variation in anemia among reproductive-age women was explained by both individual-level and community-level variables.The final model (model III), which contains both individual and community-level factors simultaneously, was chosen as the best-fitted model for the data as it had the lowest deviance value (5432.10
|
Board Thread:General Discussion/@comment-30714040-20170922183405/@comment-25516840-20170922194500
Coolan28 wrote: HEIL JOPEDE wrote: I don't think you have a ego.
|
import { Slider } from "./shape";
/*
* @Author: Shirtiny
* @Date: 2021-06-23 17:21:45
* @LastEditTime: 2021-06-24 22:56:47
* @Description:
*/
export enum Colors {
red = "#e72528",
blue = "#2a79af",
weakBlue = "#6eb6f4",
geekblue = "#85a5ff",
gold = "#ffd666",
orange = "#ffa940",
cyan = "#13c2c2",
green = "#52c41a",
volcano = "#fa541c",
lime = "#389e0d",
pink = "#eb2f96",
purple = "#722ed1",
darkPurple = "#292F4C",
gray = "#8c8c8c",
}
export class Theme {
colors: typeof Colors;
shapes: {
slider: Slider;
};
constructor() {
this.colors = Colors;
this.shapes = {
slider: new Slider()
}
}
}
|
also to a sinus or vessel acting as a ventral heart. Supra-spiracular line: in caterpillars, margins the spiracles superiorly. Supra-stigmatal line: = supra-spiracular lines.
Nenroptera, serving as oars or organs of locomotion. Swimming paddles: terminal appendages of mosquito pupae. Swoked: smoky, suffused with gray or blackish. Sylvan: species inhabiting forests or woodland areas. Symbiogenesis: the method of origin of social symbiotic relation among ants
|
Centaurea, Michell’s Blue Bonnet Special Florists’ Super-Giant Strain. Blooms are fully double, with clear color and Jong stems, making this strain extra fine for florists’ cut-flower purposes. Large, deep blue. Trade pkt. 25c; 0z. 75c; I4lb. $2.50; Ib. $7.5 Cyclamen,
All-America Selection for 1948—Silver Medal Award A striking new color combination never before seen in Sensation Cosmos—deep rose petals overlaid with a large, well-defined zone of rich crimson, the first bicolor Cosmos to be developed. Destined for immediate popularity in the nation’s gardens, it is the first postwar novelty. Trade pkt. 50c; 140z. 90c; oz. $3.00. HENRY F. MICHELL CO., 516-518 Market st., PHILADELPHIA 5, PA.
|
import sys
from main import return_minizers, parse_fasta_file, Minimizer
def load_hashtable(hash_file):
"""
Function that will receive data from minimizer_table
and write it in the file on disk. This will include
parsing of existing data in dictionary minimizer_table
in specific format.
:param minimizer_table: dict (dictionary of minimizers)
:param hash_file: str (path to the file in which you want to save hash table
:return:
"""
minimizer_table = dict()
with open(hash_file, "r") as file:
for line in file:
parsed_line = line.split(":")
key = parsed_line[0]
positions = parsed_line[1]
mini = Minimizer(positions, key)
minimizer_table[key] = mini
return minimizer_table
if __name__ == "__main__":
"""
Argument for this script should be path to the file
where hashtable is saved and string which you want to
be found (which is a minimizer saved in hash.txt).
For example:
python MinimizerHashTableQuery.py hash.txt TTTCA
"""
hash_file, string_to_find = sys.argv[1], sys.argv[2]
minimizer_dictionary = load_hashtable(hash_file)
output_file = "out.txt"
try:
with open(output_file, "w") as out:
out.write("Found string: {}, Positions: {}".format(string_to_find, minimizer_dictionary[string_to_find].position))
except KeyError:
with open(output_file, "w") as out:
out.write("Minimizer string {} not found".format(string_to_find))
|
export function selectBook(book) {
// selectBook is an ActionCreator, it needs to return an action,
// an object with a type property.
// every action has a type (describe the purpose of the action) and payload (data that describes the action taken )
// BOOK_SELECTED - keep it uppercase
return {
type: "BOOK_SELECTED",
payload: book
};
}
|
John H. Kassing v. John M. Durand and Henry C. Durand.
Real Property—Secret Trust—Fraud.
1. He who goes into a court of equity seeking relief, must do so with clean hands.
•2. A secret trust in real estate resting upon an agreement to hinder or delay creditors, will not be enforced.
3. A court of equity will afford no relief to a debtor who has transferred his property for the purpose of defrauding his creditors, and subsequently seeks as against the transferees to recover back the same.
[Opinion filed June 25, 1891.]
Appeal from the Circuit Court of Cook County; the Hon. Loein C. Collins, Judge, presiding.
John H. Kassing filed his bill in the court below setting forth that about the first of September, 1876, he was the owner in fee simple of lots 4, 5 and 9, in block 14, in Hewbury’s addition to Chicago, subject to a mortgage to secure the payment of about $10,000, with interest thereon at the rate of nine per cent per annum, payable semi-annually; that at said time he was indebted to different people, which indebtedness he had not at that time the ready money to pay, although he was the owner of property worth more than enough to pay such indebtedness; that he was at that time acquainted with appellees, John M. and Henry C. Durand, who were then engaged in the wholesale grocery business in the city of Chicago, and he was then indebted to them, or the firm of which they were members, and that said firm held his promissory note therefor for the sum of $550; that being so indebted to appellees, and not having the ready cash at that time to pay the same, he went to them for the purpose of securing the payment of the note to them, and borrowing money from them to pay his indebtedness, and to take and follow their advice in the matter of giving them security; and that he told them exactly how he was financially situated; what property he owned; that he wished to secure the payment of the note to them aforesaid, and to borrow money from them to pay 'his indebtedness; that it was then understood by them that he was the owner of the real estate heretofore mentioned and that there was then no money due on the said mortgage; and it was then suggested by a lawyer employed by said appellees, that the best way for them to obtain security for the payment of the promissory note held by them and the repayment of any money that they might loan to him, would be for appellees’ firm to enter up judgment trpon said note, to issue execution thereon, levy the same upon the real estate hereinbefore mentioned and sell the interest of appellant in said real estate and bid it in in the name of one or both of said appellees^ and to wait until there was interest due upon the mortgage and not to pay the same, but to have the mortgage foreclosed, and at the foreclosure sale either one or the other of appellees should bid off said lots covered by the mortgage, in the name of one or the other of them, and take a deed therefor; and it was also suggested by said lawyer that appellant should file a petition in bankruptcy in the District Court of the United States for the Northern District of Illinois, to be declared bankrupt, and to have an assignee appointed, and that said assignee in bankruptcy should sell and convey all the interest of appellant in said real estate, and that appellees, or one of them, would attend the sale thereof to be made by the assignee in bankruptcy and bid off said property and receive a deed therefor, and in that way appellees would be able to have in their own hands the legal title to said real estate, and it could be held by them as security to them for the payment of said note, and for the repayment of any and all moneys they should loan and advance for and on behalf of appellant; and it was then and there agreed between appellant and appellees that the aforesaid things suggested and advised by said lawyer should be done.
That accordingly appellant permitted appellees to obtain the title to said real property in the manner suggested; that in pursuance of said arrangement on the 14tli day of October, 1876, a judgment was entered in the Circuit Court of Cook County in favor of John M. Durand and Henry C. Durand, Calvin Durand and Cornelius E. Connolly, as plaintiffs, and against appellant as defendant, for the sum of §562 and costs; that execution was issued upon said judgment, and delivered to the sheriff of Cook County, and the sheriff thereupon levied upon the said real property on the 27th day of November, 1876, and sold appellant’s interest in the same and improvements thereon for the nominal sum of $594, and issued to said John M. Durand a certificate of sale thereof; that afterward appellant, acting under the advice of said appellees and their lawyer, on the 4th day of November, 1876, filed his petition in bankruptcy in the District Court of the United States for the Northern District of Illinois, and was declared a bankrupt, and Eobert E. Jenkins was, on or about the 6th day of January, appointed assignee in bankruptcy of appellant’s estate; and that thereafter, to carry out the arrangement with appellees, the interest coupon on said mortgage which next fell due wras not paid, payment being withheld for the purpose of creating an excuse for foreclosing the said mortgage, and thereupon the United States Mortgage Company took steps to foreclose said mortgage; advertised for sale the property covered thereby, and sold the same on or about the 28th day of February, 1877; and that upon the suggestion of said appellees and their lawyer, appellant procured one Bernard Niggemyer to attend the sale, and as he is informed and believes, the. said Niggemyer, and the said John M. Durand, and the lawyer of appellees, attended the sale, and the said John M. Durand bid off the said property at said sale, with all the improvements thereon, for the sum of §12,800, in the name of the said Henry C. Durand, said JohnM. Durand being the only bidder therefor, and that thereafter on the 28th day of February, 1877, the said United States Mortgage Company executed and delivered to said Henry C. Durand a warranty deed of the premises so sold at said foreclosure sale, and that thereafter, on or about the 26th day of March, 1877, the said Eobert E. Jenkins, as assignee in bankruptcy, sold appellant’s interest in the real estate hereinbefore described, together with appellant’s interest in other real estate, at public auction, to Henry C. Durand, for the sum of $315, and executed and delivered to said Henry C. Durand a deed of the premises so sold. The bill sets forth that after this was done the proceedings in bankruptcy were dismissed, but when is not stated. The bill further alleges that thereafter, on the 19tli day of March, 1878, the said premises sold under said execution, not having been redeemed from the said sale made by the sheriff of Cook County, the said sheriff executed and delivered'to the said John M. Durand a sheriff’s deed of the premises so sold.
Appellant further sets forth in his bill that all of the aforesaid transactions were made under an arrangement with appellees for the purpose merely of placing the title to appellant’s said real estate in the said appellees as security for the indebtedness of appellant to appellees’firm, and the money advanced by appellees to make said purchase, and such other moneys as appellees might have to advance for taxes and to protect their lien upon said property, and that lots 4 and 5 were, when he made the arrangement, worth $30,000, and lot 9 was then worth $2,000.
The bill'sets forth that appellant remained in possession and control of said premises, rented the same, collected the rents, made repairs on them and paid appellees large sums of money down to the year 1886; that from some time in the year 1876 or 1877 down to 1886 he paid to appellees a large sum of money, the exact amount of which he is unable to state as he kept no account of the same, but trusted entirely to appellees’ keeping a correct account thereof: that, such payments were made by him to apply on the indebtedness he was owing to appellees for their advances as aforesaid; that how much money appellees advanced and paid out on account of said premises under their arrangement with appellant, appellant does not know, but that appellees have a full and complete account of the same; that in 1886, appellees notified appellant that he could collect no more rents from said premises, but they would employ a real estate agent to manage the property for them, and that since 1886 appellant has not been allowed by appellees to have anything to do with the premises, but the rents have been collected and paid to appellees, and they are now in possession of the premises to the exclusion of appellant; and they now repudiate the arrangement which they made with him and insist that they took the title to said premises entirely for their own use and benefit and that appellant has no interest or right in or to said premises or claim upon them in any way whatever.
The bill prays for an accounting by appellees as to their receipts and expenditures on account of such premises, and that appellees be compelled to convey said premises to appellant, and to surrender to him all deeds, leases, writings and tax receipts which they or either of them have pertaining to said premises.
A demurrer to the bill was sustained and the bill dismissed; from the decree sustaining the demurrer and dismissing the bill, the complainant below has appealed.
Mr. A. B. Jenks, for appellant.
The first question is, can an absolute conveyance in equity be proven by oral testimony to be a mortgage ?
That proof can be so made seems to be positively settled by the following authorities: 1 Jones on Mortgages, Sec. 293; Miller v. Thomas, 14 Ill. 428; Tillson v. Moulton, 23 Ill. 600; Shaver v. Woodward, 28 Ill. 277; Smith v. Cremer, 71 Ill. 185; Union Mutual Life Insurance Co. v. White, 106 Ill. 67; Workman v. Greening, 115 Ill. 477; Slee v. Manhattan Company, 1 Paige Chy. 48.
Has the statute of frauds any application to a case of this kind, in equity, where a fraud was perpetrated by the persons in obtaining the legal title to real estate from the owner, and who now seek to maintain such legal title as against the owner of the property ?
It is said that “ the correct view appears to be that equity will at all times lend its aid to defeat a fraud notwithstanding the statute of frauds.” Browne on Statute of Frauds, 3d Ed., Sec. 438.
“A simple illustration of the rule that when the statute of frauds has been used as a cover to a fraud, equity will relieve against the fraud, notwithstanding its provisions, is found in a case reported by Yiner, and stated by him to have occurred in Lord Nottingham’s time, and to have been the first instance in which any equitable exception to the statute appears. There was a verbal agreement for an absolute conveyance of land, and for a defeasance to be executed by the grantee; but he, having obtained the conveyance, refused to execute the defeasance, and relied upon the statute; but his plea was overruled and he was compelled to execute according to his agreement. Here the attempted fraud consisted, not merely in refusing to do what he agreed, but in deceiving the plaintiff out of his property.” Browne on Stat. of Frauds, 3d Ed., Sec. 441.
“ It was not intended by the adoption of the statute (frauds) to facilitate the perpetration of and to protect fraud, but to prevent it; and the courts have never lent themselves to assist or protect fraud, which the statute did not sanction by its adoption. The courts will not permit the statute to be used as an engine of fraud, as its purpose was its suppression.” Union Mutual Life Ins. Co. v. White, 106 Ill. 67.
“ The question is presented on this record whether, as the transaction has assumed the form of a sale, a court of equity can effectuate the original intention of the parties, by declaring it a mortgage. It is objected that the agreement, resting alone in parol, the statute of frauds will prevent it from being carried into effect. Under Sec. 12 of our Conveyance Act, and "upon general equitable principles, this court repeatedly held that deeds in form absolute, might be shown to be mortgages in fact. Such has been repeatedly held, as in the case of Wynkoop v. Corning, 21 Ill. 570, it was said that courts are not estopped from looking into all the facts and circumstances of a deed absolute on its face, to ascertain whether a Joan of, and security for, money was really intended.” Reigard v. McNeil, 38 Ill. 400.
“ Courts of equity strongly incline to treat all securities for money, or to indemnify, as mortgages; and when a purchaser of lands, at or before a judicial sale, promises to extend the redemption beyond the time allowed by law, the transaction will be treated as a mortgage of the land sold, the real right of the creditor extending no further than full satisfaction of his debt. All such cases, however, are controlled by the circumstances attending them.” Pensoneau v. Pulliam et al., 47 Ill. 58.
In the case of Slee v. The President and Directors of the Manhattan Company, 1 Paige Chy. Rep. 47, it is said by Judge Betts (page 55): “It is unquestionably the rule of this court and at law, that a deed, however absolute the terms may be upon its face, if really only intended to secure a debt, will be deemed a mortgage, though the defeasance is by parol. 1 Johns. Chy. R. 594; 4 Id. 167; 6 Id. 417; 7 Id. 40. It never loses the character and quality of a mortgage, and the right of redemption, as an inseparable incident, can not be restrained or clogged, even by the stipulation of the parties. Clark v. Henry, 2 Cowen, 324, in error. Lapse of time, in this case, can not affect the remedy; for as against the mortgagor, possession by the mortgagee for any period short of twenty years will not bar the equity of redemption. Anon. 3 Atk. 213; Moore v. Cable, 1 Johns. Chy. R. 385.”
Messrs. M. B. & F. S. Looms, for appellees.
The transaction, being in fraud of creditors, can not be successfully assailed by either of the parties thereto.
In the case of Dunaway v. Robertson et al., 95 Ill. 419, the court say (at page 426): “ The rule is familiar that no man can be permitted to found a claim on his own iniquity—Frustra legis auxilium quaerit qui in legem comittitP The court continues to say: “It was held by this court in Miller v. Marckle, 21 Ill. 152, that where a transaction was tainted with fraud, as between the parties to it, a court will not assist either, but will leave them in the position in which they have placed themselves.” In support .of the decision the case of Smith et al. v. Hubbs, 10 Me. (1 Fairfield) 71, was cited, where Mellen, C. J., says: “ Whatever the parties to an action have executed for fraudulent or illegal purposes, the law refuses to lend its aid to enable either party to disturb. Whatever the parties fraudulently or illegally contracted to execute, the law refuses to compel the contractor to execute or pay damages for not executing; but in both cases leaves the parties where it finds them.” The object of the law in the latter case is, as far as possible, to prevent the contemplated wrong, and in the former, to punish the wrongdoer by leaving him to the consequences of his own folly or misconduct. Bolt v. Rogers, 3 Paige, 154, was also cited, where the court say: “Whenever two or more persons are engaged in a fraudulent transaction to injure another, neither law nor equitjT will interfere to relieve either of those persons, as against the other, from the consequences of their own misconduct.” In conclusion, in the case of Miller v. Marckle, it was "said: “The rule we have adopted seems best calculated to frustrate the designs of parties who engage in transactions of a fraudulent character, saying to them most emphatically, keep what you have got, be it notes or mortgages, but seek not our aid to enforce the one or the other, or, on the other hand, to relieve against them.”
The case above cited (Dunaway v. Robertson et al.), like the case at bar, was heard and decided on demurrer to bill of complaint. The bill was filed for the purpose of setting aside certain deeds which the complainant had executed to his father, in the lifetime of the latter, or to compel the other heirs to make a re-conveyance, alleging that “ fearing he (complainant) might in the then future become involved in litigation, which, because of its tediousness and =expensiveness, would probably embarrass him, hut not for the purpose of avoiding the payment of any debt or obligation, legal or equitable, due from him, or previously contracted by him,” complainant made the deeds. It was held that averment in the bill that the deeds were not made for the purpose of avoiding the payment of any debt or obligation, was but the statement of a conclusion, and did not relieve the conveyances of the fraudulent character attributable to them by reason of their being made under an apprehension of embarrassment from anticipated litigation.
So in the case at bar, the assertion of appellant in his bill “ that he had no intention whatever of hindering or delaying his other creditors,” is but the statement of a conclusion and does not relieve the transaction narrated of the fraudulent character attributable to it by reason of its evident intention to defraud the creditors of appellant. It is not necessary there should be any actual defrauding of creditors intended. It is sufficient if there was an intention to place property beyond their reach for the time being. Phelps v. Curts, 80 Ill. 109; Nesbitt et al. v. Digby et al., 13 Ill. 387; Fitzgerald v. Forristal, 48 Ill. 228; Ryan v. Ryan, 97 Ill. 38.
A debtor in failing circumstances is only allowed to place his property beyond the reach of his creditors by making a general assignment of it; by devoting it unreservedly to the payment of his debts; and not with a view to his advantage in delaying until a favorable time the appropriation of the property for such purposes. Nesbitt et al. v. Digby et al., supra; Phelps v. Curtis, supra.
A transaction consisting of a purchase, through a third person, of mortgaged premises at a foreclosure sale, may be deemed fraudulent as to the mortgagor’s creditors, the evidence showing a scheme to keep the land from them by means of the foreclosure and purchase. Simmons v. Johnson, 48 Hun (N. Y.), 131.
A party to a covinous transaction intended to cover the property from creditors, shall not give in evidence his own fraud, whether it be an absolute deed or a mortgage, or however it be mingled with other arrangements between the parties. Gill v. Henry, 95 Pa. St. 388.
An intent to delay creditors must be conclusively presumed from a conveyance which does delay, them. In re Smith, 4 Ben. 1.
A secret trust in real estate, resting upon an agreement made to hinder and delay creditors, will not be enforced. Fast v. McPherson, 98 Ill. 496; Moore, Adm’r, etc., v. Wood, 100 Ill. 451; Tyler v. Tyler, 126 Ill. 525.
The grantor of a deed made to baffle creditors, can not be relieved against its operation, though it was in fact intended as a mortgage. Ybarra v. Lorenzana, 53 Cal. 197; Lill v. Brant, 6 Ill. App. 366.
A conveyance of land made by a debtor to his attorney at the suggestion of the latter, with mutual intent to defraud the. client’s creditors, vests the legal estate as between the parties to the deed. York v. Merritt, 80 N. C. 285.
The fact that judgments were confessed for bona fide debts, does not exclude fraudulent intent, especially where the manner in which the judgments were confessed, the agency resorted to, and the use made of them, stamp the transaction as an attempt to keep creditors at arm’s length, and to enable the debtor to retain possession and control the property. Abey v. Schwab, 31 N. Y. S. R. 139.
If a man, knowing that a scheme is fraudulent, and that the natural outcome of it will be to defraud some innocent person, goes into it solely for the purpose of making money out of it, though he may not be equally in fault with another who is the moving party in the fraud, and influences him by his persuasions and representations, a court will, on the ground of public policy, deny him any relief against the other party. Knight v. Linzey (Mich.), 45 N. W. Rep. 337.
Kumerous other cases to the same effect as those already referred to might be cited, establishing beyond question the doctrine that, while transactions of the kind narrated in appellant’s bill of complaint, are, or may be void as to existing creditors, they are perfect and effectual as between the parties, and can not be set aside by either of them in case they become dissatisfied with the transaction.
The alleged agreement of appellees to re-convey constituted an express trust, and, being verbal, was void under the statute of frauds.
The bill of complaint sets up, in direct and express words, a positive verbal agreement on the part of appellees to re-convey to appellant the premises in question; there is no pretense that any contract, agreement or memorandum in writing of any kind was ever made or signed by them, or either of them, to that effect; and nothing is shown to take the case out of the operation'of the statute*
The statute provides (Sec. 9, Chap. 59) that “ All declarations or creations of trusts or confidences of any lauds, tenements or hereditaments shall be manifested and proved by some writing signed by the party, * * * or else they shall be utterly void and of no effect. Provided, that resulting trust or trusts, created by construction, implication or operation of law, need not be in writing, and the same may be proved by parol.”
There can be no pretense in this case that there was a resulting trust within the exception of the statute, as a resulting trust can not be created unless the money of the eestui que trust (appellant) was used in acquiring title to the property. It can not be created by agreement or contract. Remington v. Campbell, 60 Ill. 516; Sheldon v. Harding, 44 Ill. 68; Holmes v. Holmes, 44 Ill. 168; Roberts v. Ware, 40 Cal. 634.
It must, moreover, be shown that the money was actually paid, directly or indirectly, by appellant. It is not sufficient to show that he requested appellees to do so, and promised to repay them what they paid for the same. Kendall v. Mann, 11 Allen 17, 546; Baxter v. Baxter, 22 Cal. 579.
r Appellant does not claim that any of his own money was used in the purchase, either at the sheriff’s sale, the mortgagee’s sale, or the sale under the bankruptcy proceedings, through which several proceedings appellees acquired title, but concedes that appellees furnished the money, but agreed verbally to re-convey on being reimbursed therefor by him.
In the case of Stephenson v. Thompson, 13 Ill. 186, where an agreement existed in parol between A and B, that A should pay for certain lands, and on being reimbursed by B therefor, A should convey them toB, and the lands were sold at sheriff’s sale and bought by A with his own money, and conveyed to him by the sheriff, it was held that the contract between A and B, being verbal, was void under the statute of frauds.
If the bill had sought to establish a resulting trust, by construction, implication or operation of law, it would have been no defense to have alleged that the trust was not created by some instrument in writing. But, as stated, the bill alleges an express trust, and to this allegation the defense that the agreement to re-convey—or declaration of trust—-is not in writing, is applicable. Scott v. Harris, 113 Ill. 447; Biggins v. Biggins, 133 Ill. 211; Adams v. Adams, 79 Ill. 517; Wilson v. McDowell, 78 Ill. 514; Lill v. Brant, 6 Ill. App. 372; Green v. Coates, 73 Mo. 115.
Waterman, J.
The bill filed by appellant is for the enforcement of a contract alleged to have been made by him with appellees.
The first question that arises is, whether the contract as stated is one which a court of equity will enforce. The rule that no one should be permitted to take advantage of his own wrong—JWullus cowmodum eapere potest de injuria sua propria—is familiar.
We are therefore called upon to inquire what it really was that appellant alleges was agreed to be done, and what has been done in pursuance of such agreement.
The allegation is made that he told appellees that he wished among other things to borrow money of them with which to pay his debts, and that they expressed a willingness to loan him money for such purpose; but it does not appear that any attempt to obtain money for such purpose was actually ever made. Practically, according to the bill, the advances and the application for advances were confined to the money necessary to buy in for the use of appellant his property when offered for sale.
That the scheme was one well calculated to enable appellant to defraud his creditors, is apparent.
Lots 4 and 5 were at the time he made this arrangement, worth §30,000, and lot 9 was then worth §2,000. Upon these the only incumbrance shown to have existed was for the sum of §10,620. In this property appellant had an equity of over §20,000, yet he arranges to have it sold, and it was sold to appellees, first on a judgment for §562, then two of the lots were sold for §12,800 on the mortgage. A secret trust, as appellant says, was created in his favor, he apparently having lost this valuable equity.
Next, as a part of the arrangement, and lest some of his creditors might redeem from the judgment sale or seek to reach his secret equity, he filed a petition in bankruptcy. By this last proceeding appellant practically stayed the hands of his creditors, suspended the operation of the ordinary remedies they possessed, and compelled them to go into the bankrupt court in order to reach his property.
By the adjudication of bankruptcy the valuable secret equity which he had in this property passed to his assignee, became a bankrupt asset to be sold, the proceeds thereof to be divided among his creditors.
Appellant also, by the filing of his petition in bankruptcy, placed himself in a position where he might, by the payment of but a percentage upon the claims against him, obtain a discharge that would free him from all his indebtedness.
In this proceeding, in which, under his solemn oath, he summoned his creditors into a court of his own choosing and compelled them there alone to look for the ascertainment and payment of their claims, he was bound to the exercise of the utmost good faith. It nowhere appears in the bill he has filed in this cause, that in the bankruptcy court he at any time disclosed the fact of his ownership of the valuable equity in this property, he now tells us that he then had. So far as appears, his creditors and his assignee were suffered to remain in ignorance of this, a fact which it was his moral and legal duty to at once make known.
That he did not do so, and that his creditors were defrauded by his action and his silence, is apparent from- the fact that this valuable equity, amounting to over §20,000, was on the 26th day of March, 1877, sold by Robert E. Jenkins, his assignee, to Henry C. Durand, for his, appellant’s, use and benefit, for the sum of §315.
And the arrangement for this proceeding under which his creditors were swindled out of this great sum, a court of equity is now'asked to lend its aid in carrying out.
As to the lots alleged to have been worth the sum of §30,000, the work of secreting all evidence of appellant’s title and interest seems to have been complete February 27, 1877. As to the remaining lot, then worth §2,000, the right of creditors to redeem was finally cut off March 19, 1878.
Appellant began, as he says, to collect rents and pay them over to appellees ; this continued until 1886 ; appellant keeping no account of how much he thus paid over, as he neither kept nor asked for an account of what appellees had paid for or kept on behalf of the premises. Twelve years thus passed away, when appellee saw fit to, as they told him, employ another real estate agent to look after the property; nearly four years after this he filed his bill.
It is a fundamental principle that he who goes into a court of equity seeking relief, must do so with clean hands.
The allegation in the bill that appellant had no intention of hindering or delajdng his creditors, is similar to that made in the case of Dunaway v. Robertson, 95 Ill. 419, concerning which the court say: “ This is but the statement of a collusion and does not control in the case.”
The arrangement for an actual sale of appellant’s property under the circumstances described would be for a fraudulent purpose as regards creditors, notwithstanding any assertions to the contrary. Dunaway v. Robertson, supra.
One of the most common occasions for the enforcement of the rule that he who comes into equity must do so with clean hands, arises in cases -where a debtor has in any manner transferred his property for the purpose of defrauding his creditors and afterward seeks as against the transferee to recover back the property. The door of a court of equity is always shut against such a claimant. Pomeroy’s Equity Jurisprudence, Sec. 401; Wheeler v. Sage, 1 Wall. 518 ; Bolt v. Rogers, 3 Paige, 156 ; Riedle v. Mulhausen, 20 Ill. App. 68; Ryan v. Ryan, 97 Ill. 38; Fitzgerald v. Forristall, 48 Ill. 228 ; Phelps et al. v. Curts et al., 80 Ill. 109 ; Nesbit v. Digby, 13 Ill. 387.
It it true that according to the allegations of the bill, appellees were engaged with appellant in a fraudulent scheme, but in such case the rule is in pari delicto potior est conditio defendeniis. Miller v. Marckle, 21 Ill. 152.
A secret trust in real estate resting upon an agreement to hinder or delay creditors, will not be enforced. Fast v. McPherson, 98 Ill. 468; Moore v. Wood, 100 Ill. 451.
The agreement as stated was one which could not fail to hinder and delay creditors; the bankruptcy proceeding alone hindered and delayed them.
Appellant did not make or state in his bill a cause entitling him to relief in a court of equity, and the bill was properly dismissed. Judgment affirmed.
|
User:Ttocserp/sandbox
According to connoisseurs
In a paper for the 2013 Oxford Food Symposium, Tan and Bursa identified the features of the art or craft of making and serving Turkish coffee, according to the traditional procedures:
* Roasting. Ideally the best green Arabica beans are medium-roasted in small quantities over steady heat in a shallow, wrought-iron roasting pan. It is crucial to stop at the right moment, then transfer the beans to the next stage:
* Cooling. The beans are allowed to cool down in a wooden box and absorb excess oil. The kind of wood is claimed to affect the taste, walnut being the best.
* Pounding or grinding. The beans must be reduced into a very fine powder. The fineness of the powder is crucial to the success of Turkish coffee since it affects the foam and mouth feel. (According to one source, the particle size should be 75-125 microns.) Strict connoisseurs insist that they must be hand-pounded in a wooden mortar, although it is difficult to do this while achieving an uniform fineness. Consequently it has become more usual to grind them in a brass or copper mill, though it does make for drier particles.
* Brewing. It is essential to use a proper cezve. This vessel is a conical flask, being wider at the base than at the neck, and is made of thick forged copper. (A common sized cezve will make one cup of coffee, and they can easily be ordered online in many western countries.) Cold water, several teaspoons of the ground coffee (at least 7 grams per person) and any sugar are put in the cezve and it is put on the fire. The tapering shape of the vessel encourages the formation of foam and retains the volatile aromas. The coffee should never be allowed to come to a rolling boil, and must not be over-done. "This stage requires close monitoring and delicate timing since a good Turkish coffee has the thickest possible layer of froth at the top". Some think that the metallic copper helps tp improve the taste.
* Serving. The cezve has a spout by which it is poured into the serving cup. While the cup design might not seem to have anything to do with the taste of the beverage, connoisseurs say it makes a difference. The best cups are made of porcelain with a thin rim: it affects mouth feel A long cultural tradition emphasises the pleasure of being served coffee in beautiful cups, which are family heirlooms. The beverage is served together with a glass of water which should be sipped first to cleanse the mouth. Other cultural traditions affect the guest's appreciation of the beverage and the conviviality of the occasion, including story-telling, fortune-telling, and so forth.
While some of these stages may be curtailed in modern coffee drinking, for example the coffee might be purchased already roasted and ground, the rituals and paraphernalia (e.g. the anticipatory smell of the roasting beans) do act on the imagination and have a psychological effect.
xxx
La pelota era un barco improvisado de cuero utilizado en América del Sur y Central para cruzar ríos. Era similar en algunos aspectos al bull boat (bote de cuero) de América del Norte o al coracle de las Islas Británicas, pero a menudo no tenía armazón de madera ni estructura de soporte interna, y dependía enteramente de la rigidez del cuero para mantenerlo a flote. Por lo tanto, podía transportarse a caballo y montarse rápidamente en caso de emergencia, y era una habilidad rural común. El barco era remolcado por un animal o un nadador humano, siendo las mujeres consideradas especialmente diestras. Las pelotas podían transportar cargas sustanciales (lo común era alrededor de un cuarto de tonelada) e incluso pequeñas piezas de artillería. Continuaron utilizándose hasta bien entrado el siglo XX.
Necesidad
General Manuel Belgrano recalled taking a small revolutionary army across the Corriente River in 1811 with nothing but two bad canoes and some pelotas. The river was about a cuadra (80 metres) wide, and unfordable. He noted that most of his men knew how to use a pelota, implying that it was standard rural knowhow.
Not all countrymen knew how to swim, however: it depended on the region. The cavalry troopers of General Paz were from the Province of Corrientes, where everyone did. Crossing a river at night, holding on to the mains or tails of their swimming horses - their arms, ammunition, uniforms and saddles safely dry in pelotas, which they had improvised from rawhide saddle blankets - they surprised and defeated the enemy at the Battle of Caaguazú.
at 350-1
pp. 37, 39, 54, 168-9
==Fuentes=
Professional pelota towers
The Spanish Empire established a postal service linking Buenos Aires in the Atlantic world with Lima in the Pacific. At intervals along this 3,000 mile route, posts were set up at where fresh horses could be obtained and there was (very) basic sleeping accommodation. These posts were often beside rivers. At each place a person was put in charge who got no salary but was rewarded with valuable legal exemptions. Private voyagers were encouraged to travel with the mail, being forbidden to take their own horses.
Where the rivers were too deep to be forded the postal service appointed pasadores whose function was to carry passengers and mail across in pelotas. They were not allowed to charge much for the mail but were able to recoup themselves from the private travellers. Thus, at some places there were official pelota towers - persons who swam across rivers and pulled the boat with their teeth - whose charges were regulated by law.
The most notable crossing was at the Río del Pasage (today called the Juramento River), which lay on the road between Tucumán and Salta. It could be forded quite easily in the dry season, but when the waters rose it grew wide and deep, with strong currents and eventually, turbulent waves. An artillery officer wrote that the river brought down logs that endangered pelota and swimmer alike; the latter had to be adept to dodge them. He recorded that the service was still functioning in 1833, despite the need for a bridge, for none had been built owing to bureaucratic inertia. At this spot Indian women were celebrated pelota towers. It is not clear when the service ceased to function.
Pelotas in reality, and in European art
Surviving images of pelotas drawn by European artists always depict them with some form of wooden bracing, as if they assumed one must be necessary to give them rigidity. Verbal descriptions by reputable observers, like Azara or Dobrizhoffer, make it clear they seldom possessed one; it would have defeated the object
Rosas
Shumway, Jeffrey. "A veces saber olvidar es también tener memoria”: La repatriación de Juan Manuel de Rosas, el menemismo, y las heridas de la memoria Argentina." O. Barreneche y A. Bisso (Comps.), El tiempo pasa, la historia queda. Ayer, hoy y mañana son contemporáneos (2010): 93-132.
xxx
1. "Paraguayan War" is the preferred usage in the English language, certainly in serious scholarly writing.
The JSTOR library is a database of nearly all recent high-quality scholarly articles in the English language. The facts speak for themselves:
(Source: JSTOR, interrogation of search engine provided, 29 April 2024, all articles.)
The larger (albeit lower quality) Google Scholar database paints a broadly similar picture:
Likewise, there are clearly more books with "Paraguayan War" in the title, than "War of the Triple Alliance. (Source: Google Books, interrogate intitle:field.)
2. The 1864-1870 war is little known outside South America. By itself, the title "War of the Triple Alliance" doesn't tell the international reader anything. Which triple alliance? There have been quite a few in human history. To suppose "Triple Alliance", without context, must mean the South American one, is parochial. "Paraguayan War" at least points the reader to the right continent.
3. The title "War of the Triple Alliance" can be ideologically loaded. It was increasingly hijacked by the revisionists of the 1970s, with their conspiracy theories of an invisible plot to "get" Paraguay. But it was the war that caused the triple alliance, not the other way round. The war actually began and developed in 1864, between Paraguay and Brazil alone; there was no triple alliance then, just a Paraguayan army sacking the Mato Grosso's capital. Not until after Argentina's province of Corrientes was invaded in April 1865 did Argentina make an alliance with Brazil - its traditional enemy.
|
Talk:Kwamibuster/@comment-37547855-20191012073538
so basically...?
all went back to the box and cat noir now thinks marinette isn't ladybug Xc
|
package org.lilyproject.indexer.model.indexerconf;
import java.util.HashMap;
import java.util.Map;
public class DynamicFieldNameTemplateResolver implements NameTemplateResolver {
private Map<String, Object> values = new HashMap<String, Object>();
public DynamicFieldNameTemplateResolver(Map<String, Object> values) {
this.values = values;
}
@Override
public Object resolve(TemplatePart part) {
if (part instanceof ConditionalTemplatePart) {
ConditionalTemplatePart cPart = (ConditionalTemplatePart)part;
Object condVal = values.get(cPart.getConditional());
if (condVal == null) {
throw new NameTemplateEvaluationException("Variable does not evaluate to a value: " + cPart.getConditional());
}
if (!(condVal instanceof Boolean)) {
throw new NameTemplateEvaluationException("Variable is not a boolean: " + cPart.getConditional());
}
if ((Boolean)condVal) {
return cPart.getTrueString();
} else {
return cPart.getFalseString();
}
} else if (part instanceof VariableTemplatePart) {
VariableTemplatePart varPart = (VariableTemplatePart) part;
Object value = values.get(varPart.getVariable());
if (value == null) {
throw new NameTemplateEvaluationException("Variable does not evaluate to a value: " + varPart.getVariable());
}
return value;
} else if (part instanceof LiteralTemplatePart) {
return ((LiteralTemplatePart)part).getString();
} else {
throw new NameTemplateEvaluationException("Unsupported TemplatePart class: " + part.getClass().getName());
}
}
}
|
Accepted the offer but no response from Human Resources Manager
I have been interviewd with XYZ Company, and got the offer letter. I signed and sent it back the same day evening
There were 6-8 documents which needed to be filled, signed and send. I did fill all the documents online but the one document I initially filled it hand written and later did filled it in pdf and while sending email I attached the hand written one. Immediately sent a mail stating that ignore the previously attached attachments as one of the file is not so clean so consider the attached in the next email.
Does doing this give a negative impact to human resources manager? Will they revoke the offer for this? I called them this morning and left voicemail and no response.
How long ago did you send them the documents? Resending the documents shouldn't reflect badly on you at all, and they definitely shouldn't pull back the offer over something so inconsequential.
I received the documents on friday sent them on monday evening. Does human resource managers have right to revoke offer or is it hiring manager who must make it? I emailed monday and called them this morning left a voicemail. Does that calling immediately make any negative impact. @David
Breathe Nikhil, you're panicking. So far you have not done anything that I would say warrants revoking an offer. Mailing one evening and calling the next morning for an update is an overreaction though, and if you constantly contact them it will certainly look bad. Give them a week to get back to you - 8 documents is not a small amount and they probably have a good deal of paperwork to do before anything else can happen.
Thank you David. Yea I know its an overreaction, but I didn't call for update just called and left a note saying just giving a call to check if you need anything else from me.
Does doing this give a negative impact to human resources manager?
Would be guessing but I don't see how this can cause such negative impact.
Will they revoke the offer for this?
I seriously doubt it.
You already went through all the interview process and were successfully accepted; sending a sub-optimal document is hardly something that disqualifies someone for a job position.
I know you are excited for this new job but don't torture yourself. At this point you are already in, so don't let this minor incident make you doubt of yourself.
|
Program stuck on startup
After the environment is set up, I use only one GPU GeForce RTX 3080 to run the script.sh in the startup manual, and I find that the program will be stuck on this page for more than ten minute:
and Then the program reports an error
I don't know why this happens, can you help me bro?
@MLuminous I'm sorry to bother you. Have you successfully run the program now? Is it a program running on windows?
@MLuminous @charlesCXK @ChrisLiang2020 I'm sorry to bother you, has this problem been resolved? I also encountered an error similar to yours. I need your help, thanks.
|
package com.genexus.specific.java;
import com.genexus.common.interfaces.IExtensionNativeFunctions;
import com.genexus.platform.INativeFunctions;
import com.genexus.util.IThreadLocal;
import com.genexus.util.IThreadLocalInitializer;
public class NativeFunctions implements IExtensionNativeFunctions {
@Override
public IThreadLocal newThreadLocal(IThreadLocalInitializer initializer) {
return new InheritableThreadLocalSun(initializer);
}
class InheritableThreadLocalSun extends ThreadLocal implements com.genexus.util.IThreadLocal
{
private IThreadLocalInitializer initializer;
public InheritableThreadLocalSun()
{
}
public InheritableThreadLocalSun(IThreadLocalInitializer initializer)
{
this.initializer = initializer;
}
@SuppressWarnings("unchecked")
public Object get()
{
Object obj = super.get();
if(obj == null && initializer != null)
{
set(initializer.initialValue());
return super.get();
}
return obj;
}
}
@Override
public INativeFunctions getInstance() {
return com.genexus.platform.NativeFunctions.getInstance();
}
}
|
// Copyright (c) 2021 AccelByte Inc. All Rights Reserved.
// This is licensed software from AccelByte Inc, for limitations
// and restrictions contact your company contract manager.
// Code generated; DO NOT EDIT.
package public_player_binary_record
import (
"encoding/json"
"fmt"
"io"
"io/ioutil"
"strings"
"github.com/go-openapi/runtime"
"github.com/go-openapi/strfmt"
"github.com/AccelByte/accelbyte-go-sdk/cloudsave-sdk/pkg/cloudsaveclientmodels"
)
// GetPlayerPublicBinaryRecordsV1Reader is a Reader for the GetPlayerPublicBinaryRecordsV1 structure.
type GetPlayerPublicBinaryRecordsV1Reader struct {
formats strfmt.Registry
}
// ReadResponse reads a server response into the received o.
func (o *GetPlayerPublicBinaryRecordsV1Reader) ReadResponse(response runtime.ClientResponse, consumer runtime.Consumer) (interface{}, error) {
switch response.Code() {
case 200:
result := NewGetPlayerPublicBinaryRecordsV1OK()
if err := result.readResponse(response, consumer, o.formats); err != nil {
return nil, err
}
return result, nil
case 401:
result := NewGetPlayerPublicBinaryRecordsV1Unauthorized()
if err := result.readResponse(response, consumer, o.formats); err != nil {
return nil, err
}
return result, nil
case 404:
result := NewGetPlayerPublicBinaryRecordsV1NotFound()
if err := result.readResponse(response, consumer, o.formats); err != nil {
return nil, err
}
return result, nil
case 500:
result := NewGetPlayerPublicBinaryRecordsV1InternalServerError()
if err := result.readResponse(response, consumer, o.formats); err != nil {
return nil, err
}
return result, nil
default:
data, err := ioutil.ReadAll(response.Body())
if err != nil {
return nil, err
}
return nil, fmt.Errorf("Requested GET /cloudsave/v1/namespaces/{namespace}/users/{userId}/binaries/{key}/public returns an error %d: %s", response.Code(), string(data))
}
}
// NewGetPlayerPublicBinaryRecordsV1OK creates a GetPlayerPublicBinaryRecordsV1OK with default headers values
func NewGetPlayerPublicBinaryRecordsV1OK() *GetPlayerPublicBinaryRecordsV1OK {
return &GetPlayerPublicBinaryRecordsV1OK{}
}
/*GetPlayerPublicBinaryRecordsV1OK handles this case with default header values.
Record retrieved
*/
type GetPlayerPublicBinaryRecordsV1OK struct {
Payload *cloudsaveclientmodels.ModelsPlayerBinaryRecordResponse
}
func (o *GetPlayerPublicBinaryRecordsV1OK) Error() string {
return fmt.Sprintf("[GET /cloudsave/v1/namespaces/{namespace}/users/{userId}/binaries/{key}/public][%d] getPlayerPublicBinaryRecordsV1OK %+v", 200, o.ToJSONString())
}
func (o *GetPlayerPublicBinaryRecordsV1OK) ToJSONString() string {
if o.Payload == nil {
return "{}"
}
b, err := json.Marshal(o.Payload)
if err != nil {
fmt.Println(err)
return fmt.Sprintf("Failed to marshal the payload: %+v", o.Payload)
}
return fmt.Sprintf("%+v", string(b))
}
func (o *GetPlayerPublicBinaryRecordsV1OK) GetPayload() *cloudsaveclientmodels.ModelsPlayerBinaryRecordResponse {
return o.Payload
}
func (o *GetPlayerPublicBinaryRecordsV1OK) readResponse(response runtime.ClientResponse, consumer runtime.Consumer, formats strfmt.Registry) error {
// handle file responses
contentDisposition := response.GetHeader("Content-Disposition")
if strings.Contains(strings.ToLower(contentDisposition), "filename=") {
consumer = runtime.ByteStreamConsumer()
}
o.Payload = new(cloudsaveclientmodels.ModelsPlayerBinaryRecordResponse)
// response payload
if err := consumer.Consume(response.Body(), o.Payload); err != nil && err != io.EOF {
return err
}
return nil
}
// NewGetPlayerPublicBinaryRecordsV1Unauthorized creates a GetPlayerPublicBinaryRecordsV1Unauthorized with default headers values
func NewGetPlayerPublicBinaryRecordsV1Unauthorized() *GetPlayerPublicBinaryRecordsV1Unauthorized {
return &GetPlayerPublicBinaryRecordsV1Unauthorized{}
}
/*GetPlayerPublicBinaryRecordsV1Unauthorized handles this case with default header values.
Unauthorized
*/
type GetPlayerPublicBinaryRecordsV1Unauthorized struct {
Payload *cloudsaveclientmodels.ModelsResponseError
}
func (o *GetPlayerPublicBinaryRecordsV1Unauthorized) Error() string {
return fmt.Sprintf("[GET /cloudsave/v1/namespaces/{namespace}/users/{userId}/binaries/{key}/public][%d] getPlayerPublicBinaryRecordsV1Unauthorized %+v", 401, o.ToJSONString())
}
func (o *GetPlayerPublicBinaryRecordsV1Unauthorized) ToJSONString() string {
if o.Payload == nil {
return "{}"
}
b, err := json.Marshal(o.Payload)
if err != nil {
fmt.Println(err)
return fmt.Sprintf("Failed to marshal the payload: %+v", o.Payload)
}
return fmt.Sprintf("%+v", string(b))
}
func (o *GetPlayerPublicBinaryRecordsV1Unauthorized) GetPayload() *cloudsaveclientmodels.ModelsResponseError {
return o.Payload
}
func (o *GetPlayerPublicBinaryRecordsV1Unauthorized) readResponse(response runtime.ClientResponse, consumer runtime.Consumer, formats strfmt.Registry) error {
// handle file responses
contentDisposition := response.GetHeader("Content-Disposition")
if strings.Contains(strings.ToLower(contentDisposition), "filename=") {
consumer = runtime.ByteStreamConsumer()
}
o.Payload = new(cloudsaveclientmodels.ModelsResponseError)
// response payload
if err := consumer.Consume(response.Body(), o.Payload); err != nil && err != io.EOF {
return err
}
return nil
}
// NewGetPlayerPublicBinaryRecordsV1NotFound creates a GetPlayerPublicBinaryRecordsV1NotFound with default headers values
func NewGetPlayerPublicBinaryRecordsV1NotFound() *GetPlayerPublicBinaryRecordsV1NotFound {
return &GetPlayerPublicBinaryRecordsV1NotFound{}
}
/*GetPlayerPublicBinaryRecordsV1NotFound handles this case with default header values.
Not Found
*/
type GetPlayerPublicBinaryRecordsV1NotFound struct {
Payload *cloudsaveclientmodels.ModelsResponseError
}
func (o *GetPlayerPublicBinaryRecordsV1NotFound) Error() string {
return fmt.Sprintf("[GET /cloudsave/v1/namespaces/{namespace}/users/{userId}/binaries/{key}/public][%d] getPlayerPublicBinaryRecordsV1NotFound %+v", 404, o.ToJSONString())
}
func (o *GetPlayerPublicBinaryRecordsV1NotFound) ToJSONString() string {
if o.Payload == nil {
return "{}"
}
b, err := json.Marshal(o.Payload)
if err != nil {
fmt.Println(err)
return fmt.Sprintf("Failed to marshal the payload: %+v", o.Payload)
}
return fmt.Sprintf("%+v", string(b))
}
func (o *GetPlayerPublicBinaryRecordsV1NotFound) GetPayload() *cloudsaveclientmodels.ModelsResponseError {
return o.Payload
}
func (o *GetPlayerPublicBinaryRecordsV1NotFound) readResponse(response runtime.ClientResponse, consumer runtime.Consumer, formats strfmt.Registry) error {
// handle file responses
contentDisposition := response.GetHeader("Content-Disposition")
if strings.Contains(strings.ToLower(contentDisposition), "filename=") {
consumer = runtime.ByteStreamConsumer()
}
o.Payload = new(cloudsaveclientmodels.ModelsResponseError)
// response payload
if err := consumer.Consume(response.Body(), o.Payload); err != nil && err != io.EOF {
return err
}
return nil
}
// NewGetPlayerPublicBinaryRecordsV1InternalServerError creates a GetPlayerPublicBinaryRecordsV1InternalServerError with default headers values
func NewGetPlayerPublicBinaryRecordsV1InternalServerError() *GetPlayerPublicBinaryRecordsV1InternalServerError {
return &GetPlayerPublicBinaryRecordsV1InternalServerError{}
}
/*GetPlayerPublicBinaryRecordsV1InternalServerError handles this case with default header values.
Internal Server Error
*/
type GetPlayerPublicBinaryRecordsV1InternalServerError struct {
Payload *cloudsaveclientmodels.ModelsResponseError
}
func (o *GetPlayerPublicBinaryRecordsV1InternalServerError) Error() string {
return fmt.Sprintf("[GET /cloudsave/v1/namespaces/{namespace}/users/{userId}/binaries/{key}/public][%d] getPlayerPublicBinaryRecordsV1InternalServerError %+v", 500, o.ToJSONString())
}
func (o *GetPlayerPublicBinaryRecordsV1InternalServerError) ToJSONString() string {
if o.Payload == nil {
return "{}"
}
b, err := json.Marshal(o.Payload)
if err != nil {
fmt.Println(err)
return fmt.Sprintf("Failed to marshal the payload: %+v", o.Payload)
}
return fmt.Sprintf("%+v", string(b))
}
func (o *GetPlayerPublicBinaryRecordsV1InternalServerError) GetPayload() *cloudsaveclientmodels.ModelsResponseError {
return o.Payload
}
func (o *GetPlayerPublicBinaryRecordsV1InternalServerError) readResponse(response runtime.ClientResponse, consumer runtime.Consumer, formats strfmt.Registry) error {
// handle file responses
contentDisposition := response.GetHeader("Content-Disposition")
if strings.Contains(strings.ToLower(contentDisposition), "filename=") {
consumer = runtime.ByteStreamConsumer()
}
o.Payload = new(cloudsaveclientmodels.ModelsResponseError)
// response payload
if err := consumer.Consume(response.Body(), o.Payload); err != nil && err != io.EOF {
return err
}
return nil
}
|
package no.kartverket.glrenderer;
import java.util.ArrayList;
import no.kartverket.geometry.Line;
import no.kartverket.geometry.Pos;
/**
* Created by janvin on 11/05/17.
*/
public class GlLines {
ArrayList<GlLine> lines = new ArrayList<GlLine>();
public GlLines(){
}
/**
*
* @param lines
*/
public void setLines(Line[] lines){
this.lines.clear();
for(int i = 0; i<lines.length;i++){
GlLine l= new GlLine();
Line line = lines[i];
l.setPositions(line.p1,line.p2);
l.setColor(ArScene.LINE_COLOR);
l.setWidth(ArScene.LINE_WIDTH);
this.lines.add(l);
}
}
/**
*
* @param lines
*/
public void setLines(ColorLine[] lines){
this.lines.clear();
for(int i = 0; i<lines.length;i++){
GlLine l= new GlLine();
ColorLine line = lines[i];
l.setPositions(line.p1,line.p2);
l.setColor(line.color);
l.setWidth(line.width);
this.lines.add(l);
}
}
/**
*
* @param mvpMatrix
*/
public void draw(float[] mvpMatrix) {
for (GlLine line: lines) {
line.draw(mvpMatrix);
}
}
}
|
// +build !windows
package minikube
import (
"bytes"
"fmt"
"os/exec"
"github.com/kyma-project/cli/internal/cli"
"github.com/kyma-project/cli/internal/root"
"github.com/kyma-project/cli/internal/step"
)
func addDevDomainsToEtcHostsOSSpecific(domain string, s step.Step, hostAlias string) error {
notifyUserFunc := func(err error) {
if err != nil {
s.LogInfof("Error: %s", err.Error())
}
s.LogInfof("Execute the following command manually to add domain entries:\n###\n sudo sed -i.bak \"/"+domain+"/d\" "+hostsFile+" && echo '%s' | sudo tee -a /etc/hosts\r\n###\n", hostAlias)
}
s.LogInfo("Adding domain mappings to your 'hosts' file")
if root.IsWithSudo() {
s.LogInfo("You're running CLI with sudo. CLI has to add Kyma domain entries to your 'hosts'. Type 'y' to allow this action")
if !root.PromptUser() {
notifyUserFunc(nil)
return nil
}
}
_, err := cli.RunCmd("sudo",
"sed", "-i.bak",
fmt.Sprintf("/%s/d", domain),
hostsFile)
if err != nil {
notifyUserFunc(err)
return nil
}
cmd := exec.Command("sudo", "tee", "-a", hostsFile)
buf := &bytes.Buffer{}
_, err = fmt.Fprint(buf, hostAlias)
if err != nil {
notifyUserFunc(err)
return nil
}
cmd.Stdin = buf
err = cmd.Run()
if err != nil {
notifyUserFunc(err)
return nil
}
return nil
}
|
End of preview. Expand
in Data Studio
Comma v0.1 Training Dataset (1 Billion Token Sample)
This is a 1 billion token subset of the Comma v0.1 Training Set intended as a convenience for small deep learning experiments. It is similar in spirit to the 1 billion token RedPajama sample which is no longer functioning with HuggingFace transformers due to involving the execution of arbitrary code at load time.
Method
The subset was created using a single item batch version of the following script which I no longer have:
import os
import json
import random
import requests
from datasets import load_dataset
from transformers import AutoTokenizer
from argparse import ArgumentParser
parser = ArgumentParser()
parser.add_argument("--tokens", default=10**9, type=int,
help="The number of tokens to subset.")
args = parser.parse_args()
tokenizer = AutoTokenizer.from_pretrained("common-pile/comma-v0.1-1t")
dataset = load_dataset("common-pile/comma_v0.1_training_dataset")
used = set()
token_count = 0
split = {"train":[]}
if os.path.exists("subset_resume.json"):
with open("subset_resume.json") as infile:
data = json.load(infile)
spans = set(data["used"])
token_count = data["token_count"]
split = data["split"]
milestone = 10 ** 6
while token_count < args.tokens:
choices = set()
for i in range(64):
choice = random.randrange(dataset["train"].num_rows)
while choice in used:
choice = random.randrange(dataset["train"].num_rows)
used.add(choice)
choices.add(choice)
assert len(choices) == 64
items = []
for choice in choices:
items.append(dataset["train"][choice])
texts = [item["text"] for item in items]
token_count += sum([len(i) for i in tokenizer(texts)["input_ids"]])
split["train"].extend(items)
if token_count > milestone:
with open("subset_resume.json", "w") as outfile:
serial_used = list(used)
json.dump({"used":serial_used, "token_count":token_count, "split":split}, outfile)
milestone += 10 ** 6
print(token_count, f"{(token_count / args.tokens) * 100}%")
with open(f"subset_{args.tokens}.json", "w") as outfile:
json.dump(split, outfile)
Feel free to modify and use this script to create subsets of other datasets.
The dataset was sharded using the following script:
import json
import gzip
import math
from pathlib import Path
def shard_dataset(input_file, output_dir, num_shards=4):
"""
Shard a JSON dataset into multiple gzipped JSON lines files.
Args:
input_file (str): Path to the input JSON file
output_dir (str): Directory where shards will be saved
num_shards (int): Number of shards to create
"""
# Create output directory if it doesn't exist
Path(output_dir).mkdir(parents=True, exist_ok=True)
# Load the dataset
print(f"Loading dataset from {input_file}...")
with open(input_file, 'r') as f:
data = json.load(f)
# Extract the training examples
train_examples = data["train"]
total_examples = len(train_examples)
examples_per_shard = math.ceil(total_examples / num_shards)
print(f"Found {total_examples} examples, splitting into {num_shards} shards")
# Create each shard
for shard_idx in range(num_shards):
# Calculate start and end indices for this shard
start_idx = shard_idx * examples_per_shard
end_idx = min((shard_idx + 1) * examples_per_shard, total_examples)
# Format the filename with zero-padding
filename = f"train-{shard_idx:05d}-of-{num_shards:05d}.jsonl.gz"
filepath = Path(output_dir) / filename
print(f"Creating shard {shard_idx+1}/{num_shards}: {filename}")
# Write the shard as gzipped JSON lines
with gzip.open(filepath, 'wt', encoding='utf-8') as f:
for i in range(start_idx, end_idx):
# Write each example as a JSON line
json_line = json.dumps(train_examples[i])
f.write(json_line + '\n')
print(f"Finished creating {num_shards} shards in {output_dir}")
if __name__ == "__main__":
# Configuration - update these paths as needed
input_json_file = "1B_sample/train.json" # Update this path
output_directory = "1B_sample/sharded_dataset" # Update this if needed
# Shard the dataset into 4 parts
shard_dataset(input_json_file, output_directory, num_shards=4)
- Downloads last month
- 90