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The Venezuelan military defector identified as the ringleader of the botched coup attempt in Venezuela was likely working as a "double agent" for the same man he allegedly attempted to overthrow, socialist narco-dictator Nicolás Maduro, Breitbart News has learned.

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An officer was shot and killed.

The square root cancellation heuristic, briefly mentioned in the preceding set of notes, predicts that if a collection of complex numbers have phases that are sufficiently “independent” of each other, then similarly, if are a collection of functions in a Lebesgue space that oscillate “independently” of each other, then we expect We have already seen […]

By Luis Prada  Published: May 08th, 2020 

An L.A. woman was to fly from LAX to Toronto and back. The airline canceled the flight. It won't give her a refund nor will the booking agency.

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YOU might say the odds have always been stacked against age-gap relationships. The tut-tutters predict doom the moment they so much as sniff a union between May and December. "What does that old fool possibly think that beautiful damsel sees in him?" they ask. "How could that ancient crone believe that hunky young buck finds her attractive?"

YOU might say the odds have always been stacked against age-gap relationships. The tut-tutters predict doom the moment they so much as sniff a union between May and December. "What does that old fool possibly think that beautiful damsel sees in him?" they ask. "How could that ancient crone believe that hunky young buck finds her attractive?"

Police are investigating a house robbery in which a couple in Amanzimtoti, on the south coast of KwaZulu-Natal, believed to be in their 50s was stabbed.

Allostery exploits the conformational dynamics of enzymes by triggering a shift in population ensembles toward functionally distinct conformational or dynamic states. Allostery extensively regulates the activities of key enzymes within biosynthetic pathways to meet metabolic demand for their end products. Here, we have examined a critical enzyme, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS), at the gateway to aromatic amino acid biosynthesis in Mycobacterium tuberculosis, which shows extremely complex dynamic allostery: three distinct aromatic amino acids jointly communicate occupancy to the active site via subtle changes in dynamics, enabling exquisite fine-tuning of delivery of these essential metabolites. Furthermore, this allosteric mechanism is co-opted by pathway branchpoint enzyme chorismate mutase upon complex formation. In this study, using statistical coupling analysis, site-directed mutagenesis, isothermal calorimetry, small-angle X-ray scattering, and X-ray crystallography analyses, we have pinpointed a critical node within the complex dynamic communication network responsible for this sophisticated allosteric machinery. Through a facile Gly to Pro substitution, we have altered backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallosteric enzyme that retains full catalytic activity. We also identified a second residue of prime importance to the inter-enzyme communication with chorismate mutase. Our results reveal that highly complex dynamic allostery is surprisingly vulnerable and provide further insights into the intimate link between catalysis and allostery.

10 August 2016

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.

Sophie Rousset
Feb 1, 2004; 53:S130-S135
Section III: Mitochondria, Beta-Cell Function, and Type 2 Diabetes

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(Printed in Austria)

Mingjie Liang, René L. Schilling, Jian Wang.

Source: Bernoulli, Volume 26, Number 1, 664--693.

Abstract:
We present a general method to construct couplings of stochastic differential equations driven by Lévy noise in terms of coupling operators. This approach covers both coupling by reflection and refined basic coupling which are often discussed in the literature. As applications, we prove regularity results for the transition semigroups and obtain successful couplings for the solutions to stochastic differential equations driven by additive Lévy noise.

Antony Overstall, James McGree.

Source: Bayesian Analysis, Volume 15, Number 1, 103--131.

Abstract:
A Bayesian design is given by maximising an expected utility over a design space. The utility is chosen to represent the aim of the experiment and its expectation is taken with respect to all unknowns: responses, parameters and/or models. Although straightforward in principle, there are several challenges to finding Bayesian designs in practice. Firstly, the utility and expected utility are rarely available in closed form and require approximation. Secondly, the design space can be of high-dimensionality. In the case of intractable likelihood models, these problems are compounded by the fact that the likelihood function, whose evaluation is required to approximate the expected utility, is not available in closed form. A strategy is proposed to find Bayesian designs for intractable likelihood models. It relies on the development of an automatic, auxiliary modelling approach, using multivariate Gaussian process emulators, to approximate the likelihood function. This is then combined with a copula-based approach to approximate the marginal likelihood (a quantity commonly required to evaluate many utility functions). These approximations are demonstrated on examples of stochastic process models involving experimental aims of both parameter estimation and model comparison.

Jozsef Csicsvari
Jan 1, 1999; 19:274-287
Articles

French translation of the BIS press release about the BIS Quarterly Review, December 2018

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A B.C. couple who shaved their eyebrows off in the spirit of forcing themselves to stay at home has tackled another isolation challenge — home haircuts. 

A search warrant executed by Hamilton police vice and drugs officers at an address in the city’s east end has resulted in the arrest of a couple and multiple charges, police said in a Friday release.

AppleInsider has rounded up the best 16-inch MacBook Pro deals going on right now, with coupon savings knocking up to $450 off every single model. Whether you're in the market for a standard config or looking for a loaded Core i9 model, it pays to check out the cash discounts.

A Special Purpose Machine, which is intended to perform a specific task, have a wide range of scope in the Industrial Applications like quantity packaging and bottle filling. It includes limit switches, sensors, logic controls where the process can be

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The post Effect of Distributed Coupling on SPM appeared first on SOLIDWORKS Tech Blog.

One of the country's most-loved couples returned to Channel 4 this week with Richard & Judy: Keep Reading And Carry On. The presenters talk to Georgia Humphreys about marriage, their love of books, and filming in lockdown.

Drs. William and Jean Lovrinic have made an estate commitment to Penn State that will establish a $100,000 scholarship fund at Penn State Hazleton.

A proposal to make civil partnerships available to different sex couples will strengthen equality and advance human rights in Scotland, according to a Holyrood Committee.

Others face prison on assault and resisting arrest charges Steven Snell, the Millsboro man who kidnapped and robbed an elderly Rehoboth Beach couple has been sentenced to prison. In July 2018, Snell, 30, went to a home on Cornwall Road asking to use the phone. Once inside, Snell threatened the couple with a box cutter, […]

The 2020 BMW 8 Series Gran Coupe has been launched in India, with prices starting at Rs. 1.29 crore (ex-showroom India). The four-door coupe is being offered in two variants - 840i Gran Coupe and 840i...