PEOPLE locked into high cost loans and rent-to-own schemes should be spared the extra fees charged if they fall behind with payments, says affordable provider Fair for You .

AT LAST there appears to be some momentum gathering behind what I have been saying for weeks: that it is wrong to lock down people on the grounds of age alone.

AT LAST there appears to be some momentum gathering behind what I have been saying for weeks: that it is wrong to lock down people on the grounds of age alone.

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

Ulrich Rothbauer
Feb 1, 2008; 7:282-289
Research

Jesper V. Olsen
Dec 1, 2005; 4:2010-2021
Technology

Invitation Only Research Event

Event participants

Sir Simon Fraser, Managing Partner of Flint Global; Deputy Chairman, Chatham House
Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and the Americas Programme, Chatham House

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6–2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (_CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of _CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.

Dorte B. Bekker-Jensen
Apr 1, 2020; 19:716-729
Technological Innovation and Resources

State-of-the-art proteomics-grade mass spectrometers can measure peptide precursors and their fragments with ppm mass accuracy at sequencing speeds of tens of peptides per second with attomolar sensitivity. Here we describe a compact and robust quadrupole-orbitrap mass spectrometer equipped with a front-end High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Interface. The performance of the Orbitrap Exploris 480 mass spectrometer is evaluated in data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes in combination with FAIMS. We demonstrate that different compensation voltages (CVs) for FAIMS are optimal for DDA and DIA, respectively. Combining DIA with FAIMS using single CVs, the instrument surpasses 2500 peptides identified per minute. This enables quantification of >5000 proteins with short online LC gradients delivered by the Evosep One LC system allowing acquisition of 60 samples per day. The raw sensitivity of the instrument is evaluated by analyzing 5 ng of a HeLa digest from which >1000 proteins were reproducibly identified with 5 min LC gradients using DIA-FAIMS. To demonstrate the versatility of the instrument, we recorded an organ-wide map of proteome expression across 12 rat tissues quantified by tandem mass tags and label-free quantification using DIA with FAIMS to a depth of >10,000 proteins.

Hyo Jung Kim
May 1, 2020; 61:722-733
Research Articles

1 February 2007 , Number 1

Russia is playing a risky game in Iran, continuing to build a nuclear power plant while supporting United Nations sanctions on Tehran for its nuclear policy. Moscow may be hoping for a deal with the west, but if restraint fails and Iran goes nuclear, the missiles would be too close for comfort. Equally a pre-emptive American or Israeli strike on Iranian nuclear sites might unleash serious consequences for Russia too.

14 February 2020

Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6–2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (_CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of _CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.

Invitation Only Research Event

Event participants

Sir Simon Fraser, Managing Partner of Flint Global; Deputy Chairman, Chatham House
Chair: Marianne Schneider-Petsinger, Senior Research Fellow, US and the Americas Programme, Chatham House

A study published by The BMJ today reports a possible association between intake of highly processed (“ultra-processed”) food in the diet and cancer. Ultra-processed foods include packaged baked goods and snacks, fizzy drinks, sugary cereals, ready meals and reconstituted meat products - often containing high levels of sugar, fat, and salt, but...

Gregory G. Schwartz
May 1, 2020; 43:1077-1084
Emerging Therapies: Drugs and Regimens

Nephron Pharmaceuticals, a drug manufacturing company in West Columbia, S.C., recently hired 650 current and retired teachers through a new program designed to provide educators with additional income.

Berlin : A. Hirschwald, 1893.

London (No. 32 Clipstone Street, Fitzroy Square) : Publish'd ... by S. Morgan, May 1st. 1802.

Assaf Rabinowicz, Saharon Rosset.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 272--301.

Abstract:
Common model selection criteria, such as $AIC$ and its variants, are based on in-sample prediction error estimators. However, in many applications involving predicting at interpolation and extrapolation points, in-sample error does not represent the relevant prediction error. In this paper new prediction error estimators, $tAI$ and $Loss(w_{t})$ are introduced. These estimators generalize previous error estimators, however are also applicable for assessing prediction error in cases involving interpolation and extrapolation. Based on these prediction error estimators, two model selection criteria with the same spirit as $AIC$ and Mallow’s $C_{p}$ are suggested. The advantages of our suggested methods are demonstrated in a simulation and a real data analysis of studies involving interpolation and extrapolation in linear mixed model and Gaussian process regression.

Fábio P. Lima, Francisco Cribari-Neto.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 1, 18--34.

Abstract:
We address the issue of performing testing inference in small samples in the class of beta regression models. We consider the likelihood ratio test and its standard bootstrap version. We also consider two alternative resampling-based tests. One of them uses the bootstrap test statistic replicates to numerically estimate a Bartlett correction factor that can be applied to the likelihood ratio test statistic. By doing so, we avoid estimation of quantities located in the tail of the likelihood ratio test statistic null distribution. The second alternative resampling-based test uses a fast double bootstrap scheme in which a single second level bootstrapping resample is performed for each first level bootstrap replication. It delivers accurate testing inferences at a computational cost that is considerably smaller than that of a standard double bootstrapping scheme. The Monte Carlo results we provide show that the standard likelihood ratio test tends to be quite liberal in small samples. They also show that the bootstrap tests deliver accurate testing inferences even when the sample size is quite small. An empirical application is also presented and discussed.

Zeinab Mashreghi, David Haziza, Christian Léger.

Source: Statistics Surveys, Volume 10, 1--52.

Abstract:
We review bootstrap methods in the context of survey data where the effect of the sampling design on the variability of estimators has to be taken into account. We present the methods in a unified way by classifying them in three classes: pseudo-population, direct, and survey weights methods. We cover variance estimation and the construction of confidence intervals for stratified simple random sampling as well as some unequal probability sampling designs. We also address the problem of variance estimation in presence of imputation to compensate for item non-response.

Han Hong, Jessie Li.

Source: The Annals of Statistics, Volume 48, Number 1, 397--412.

Abstract:
This paper proposes a numerical bootstrap method that is consistent in many cases where the standard bootstrap is known to fail and where the $m$-out-of-$n$ bootstrap and subsampling have been the most commonly used inference approaches. We provide asymptotic analysis under both fixed and drifting parameter sequences, and we compare the approximation error of the numerical bootstrap with that of the $m$-out-of-$n$ bootstrap and subsampling. Finally, we discuss applications of the numerical bootstrap, such as constrained and unconstrained M-estimators converging at both regular and nonstandard rates, Laplace-type estimators, and test statistics for partially identified models.

Stephen M. S. Lee, Puyudi Yang.

Source: The Annals of Statistics, Volume 48, Number 1, 274--299.

Abstract:
Suppose that a confidence region is desired for a subvector $ heta $ of a multidimensional parameter $xi =( heta ,psi )$, based on an M-estimator $hat{xi }_{n}=(hat{ heta }_{n},hat{psi }_{n})$ calculated from a random sample of size $n$. Under nonstandard conditions $hat{xi }_{n}$ often converges at a nonregular rate $r_{n}$, in which case consistent estimation of the distribution of $r_{n}(hat{ heta }_{n}- heta )$, a pivot commonly chosen for confidence region construction, is most conveniently effected by the $m$ out of $n$ bootstrap. The above choice of pivot has three drawbacks: (i) the shape of the region is either subjectively prescribed or controlled by a computationally intensive depth function; (ii) the region is not transformation equivariant; (iii) $hat{xi }_{n}$ may not be uniquely defined. To resolve the above difficulties, we propose a one-dimensional pivot derived from the criterion function, and prove that its distribution can be consistently estimated by the $m$ out of $n$ bootstrap, or by a modified version of the perturbation bootstrap. This leads to a new method for constructing confidence regions which are transformation equivariant and have shapes driven solely by the criterion function. A subsampling procedure is proposed for selecting $m$ in practice. Empirical performance of the new method is illustrated with examples drawn from different nonstandard M-estimation settings. Extension of our theory to row-wise independent triangular arrays is also explored.

Alessandro Rinaldo, Larry Wasserman, Max G’Sell.

Source: The Annals of Statistics, Volume 47, Number 6, 3438--3469.

Abstract:
Several new methods have been recently proposed for performing valid inference after model selection. An older method is sample splitting: use part of the data for model selection and the rest for inference. In this paper, we revisit sample splitting combined with the bootstrap (or the Normal approximation). We show that this leads to a simple, assumption-lean approach to inference and we establish results on the accuracy of the method. In fact, we find new bounds on the accuracy of the bootstrap and the Normal approximation for general nonlinear parameters with increasing dimension which we then use to assess the accuracy of regression inference. We define new parameters that measure variable importance and that can be inferred with greater accuracy than the usual regression coefficients. Finally, we elucidate an inference-prediction trade-off: splitting increases the accuracy and robustness of inference but can decrease the accuracy of the predictions.

Andrés F. Barrientos, Víctor Peña.

Source: Bayesian Analysis, Volume 15, Number 2, 363--388.

Abstract:
In this article, we present data-subsetting algorithms that allow for the approximate and scalable implementation of the Bayesian bootstrap. They are analogous to two existing algorithms in the frequentist literature: the bag of little bootstraps (Kleiner et al., 2014) and the subsampled double bootstrap (Sengupta et al., 2016). Our algorithms have appealing theoretical and computational properties that are comparable to those of their frequentist counterparts. Additionally, we provide a strategy for performing lossless inference for a class of functionals of the Bayesian bootstrap and briefly introduce extensions to the Dirichlet Process.

Jamie D. Roitman
Nov 1, 2002; 22:9475-9489
Behavioral

Exiting low inflation traps by "consensus": nominal wages and price stability - Speech by Luiz A Pereira da Silva and Benoît Mojon, based on the keynote speech at the Eighth High-level Policy Dialogue between the Eurosystem and Latin American Central Banks, Cartagena de Indias, Colombia, 28-29 November 2019.

The liquidity trap is synonymous with ineffective monetary policy. The common wisdom is that, as the short-term interest rate nears its effective lower bound, monetary policy cannot do much to stimulate the economy. However, central banks have resorted to alternative instruments, such as QE, credit easing and forward guidance.

Behind the glow of city lights, a group of people easily go unnoticed—lost sheep in desperate need of the hope of the gospel.

Entrepreneurship is a powerful tool that can be used within an established institution to foster innovation and accelerate promising initiatives. Leading a startup project within an organization is called "intrapreneurship" and there are many ways to do that within a school setting.

Previous observational studies and randomized trials have reported an association between the use of epidural analgesia for pain relief in labor and intrapartum maternal fever. Studies have also reported an increase in adverse neonatal outcomes with intrapartum maternal fever.

Among low-risk women receiving epidural analgesia, intrapartum maternal temperature >99.5°F was associated with adverse neonatal outcomes, with the rate of adverse outcomes increasing directly with maximum maternal temperature. Without temperature elevation, epidural use was not associated with adverse neonatal outcomes. (Read the full article)

Etiology and timing of onset of neonatal hypoxic-ischemic encephalopathy continue to be controversial. Previous studies suggest antepartum events are the main contributing factors, but have used a broad definition of encephalopathy and included infants with genetic, congenital, and developmental abnormalities.

Our study suggests that when strict criteria defining hypoxic-ischemic encephalopathy are applied with supporting neuroimaging evidence of an acute hypoxic-ischemic insult, intrapartum events are the final and necessary pathway leading to this condition. (Read the full article)

Using performance tables is not the way to choose funds.

If you have lost your income due to the lockdown, your options are limited.

Need a featherweight laptop that lasts all day on a single battery charge? Thin, light, and power-efficient, these ultraportables are our top performers in testing.

Here Mudassar Ahmed Khan has explained with an example, how to show jQuery DatePicker Calendar when the Bootstrap FontAwesome Glyphicon Icon is clicked. Basically, this article will explain how to replace the jQuery DatePicker Calendar Icon with Bootstrap FontAwesome Glyphicon Icon so that when the Bootstrap FontAwesome Glyphicon Icon is clicked, the jQuery DatePicker Calendar is shown.

Here Mudassar Ahmed Khan has explained with an example, how to set dd/MM/yyyy Date format in Bootstrap DatePicker (Calendar). The Bootstrap DatePicker supports multiple Date formats and in order to set the dd/MM/yyyy Date format, the format property needs to be set.

Here Mudassar Ahmed Khan has explained with an example, how to show Calendar Icon (Image) next to TextBox using Bootstrap DatePicker (Calendar) plugin. The Calendar Icon (Image) will be displayed using Calendar Icon with Bootstrap FontAwesome Glyphicon Icon. When the Bootstrap FontAwesome Glyphicon Icon is clicked, the Bootstrap DatePicker Calendar is shown.

The development is likely to increase pressure on the government to adjourn the Parliament session, which the Opposition has been demanding.