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On 3 April 2020, the Basel Committee on Banking Supervision (“BCBS”) and the International Organization of Securities Commissions (“IOSCO”) issued a statement recommending an extension to Phases 5 and 6 of the initial margin ...

Phosphoglycerate kinase 1 (PGK1) plays important roles in glycolysis, yet its forward reaction kinetics are unknown, and its role especially in regulating cancer cell glycolysis is unclear. Here, we developed an enzyme assay to measure the kinetic parameters of the PGK1-catalyzed forward reaction. The Km values for 1,3-bisphosphoglyceric acid (1,3-BPG, the forward reaction substrate) were 4.36 μm (yeast PGK1) and 6.86 μm (human PKG1). The Km values for 3-phosphoglycerate (3-PG, the reverse reaction substrate and a serine precursor) were 146 μm (yeast PGK1) and 186 μm (human PGK1). The Vmax of the forward reaction was about 3.5- and 5.8-fold higher than that of the reverse reaction for the human and yeast enzymes, respectively. Consistently, the intracellular steady-state concentrations of 3-PG were between 180 and 550 μm in cancer cells, providing a basis for glycolysis to shuttle 3-PG to the serine synthesis pathway. Using siRNA-mediated PGK1-specific knockdown in five cancer cell lines derived from different tissues, along with titration of PGK1 in a cell-free glycolysis system, we found that the perturbation of PGK1 had no effect or only marginal effects on the glucose consumption and lactate generation. The PGK1 knockdown increased the concentrations of fructose 1,6-bisphosphate, dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, and 1,3-BPG in nearly equal proportions, controlled by the kinetic and thermodynamic states of glycolysis. We conclude that perturbation of PGK1 in cancer cells insignificantly affects the conversion of glucose to lactate in glycolysis.

A significant part of mélanges recognized in exhumed convergent margins around the world has been recently documented to have chiefly originated from masse transport and subsurface remobilization and disruption (i.e. mélanges, from sedimentary and mud–serpentinite diapiric processes and from in situ fluidification–disruption). Tectonic and/or sedimentary processes occurring during subsequent multiple deformational events of convergent margin evolution commonly overprint and significantly rework the primary (sedimentary or diapiric) mélange fabric, forming polygenetic mélanges. This ultimately complicates their distinction from true tectonic mélanges, masking part of the recorded tectono-sedimentary evolution of the associated convergent margin. The contributions gathered in this thematic collection explore with different approaches (from field structural and stratigraphic observations to geophysical analyses) different types of polygenetic mélange, at various scales, around the world. These studies conclude that the understanding of this type of mélange may provide crucial insights for a more detailed interpretation of the evolution of ancient and modern convergent margins, and of processes and mechanisms triggering potential natural hazards (earthquakes and tsunamis). Case studies include the Apennines in the Central Mediterranean region, the Carpathians in Central Europe and the Nankai Prism in Japan.

Thematic collection: This article is part of the ‘Polygenetic mélanges: a glimpse on tectonic sedimentary and diapiric recycling in convergent margins’ collection available at https://www.lyellcollection.org/cc/polygenetic-melanges

The Tabaquito batholith (Frontal Cordillera, western Argentina), is mainly composed of shallowly emplaced granodiorite to minor monzogranite with abundant mafic microgranular enclaves. New sensitive high-resolution ion microprobe U–Pb zircon ages of c. 337 Ma (biotite granodiorite) and c. 284 Ma (mafic dyke) along with previously published geochronological data suggest that a long-lived magmatic system formed through at least two magmatic pulses at c. 337 and c. 322 Ma with later superimposition of Permian magmatism. The Tabaquito granitoids are metaluminous, calc-alkalic and magnesian with I-type affinity. Elevated Th/Nb, Y/Nb and La/Nb ratios along with negative Nb–Ta and positive Pb anomalies are consistent with a continental arc setting. Hf, Nd and Sr isotopic composition of the Tabaquito granitoids suggests that their source could result from mixing of an old felsic crustal component and a juvenile mafic to intermediate component. New geochronological and geochemical data together with published data reveal a continuous arc setting from the Carboniferous to the Permian in Argentina, and important magmatic compositional variations through time and space controlled by episodic fluctuations in the subduction angle of the oceanic plate. Reported and compiled data allow us to infer the continuity of the Carboniferous magmatic arc along the west margin of Gondwana.

Supplementary material: Detailed petrography, analytical methods and data, zircon cathodoluminescence images and supplementary figures are available at https://doi.org/10.6084/m9.figshare.c.4763993

Negative circumferential resection margins (CRM) are the cornerstone for the curative treatment of locally advanced rectal cancer (LARC). However, in up to 18.6% of patients, tumor-positive resection margins are detected on histopathology. In this proof-of-concept study, we investigated the feasibility of optical molecular imaging as a tool for evaluating the CRM directly after surgical resection to improve tumor-negative CRM rates. Methods: LARC patients treated with neoadjuvant chemoradiotherapy received an intravenous bolus injection of 4.5 mg of bevacizumab-800CW, a fluorescent tracer targeting vascular endothelial growth factor A, 2–3 d before surgery (ClinicalTrials.gov identifier: NCT01972373). First, for evaluation of the CRM status, back-table fluorescence-guided imaging (FGI) of the fresh surgical resection specimens (n = 8) was performed. These results were correlated with histopathology results. Second, for determination of the sensitivity and specificity of bevacizumab-800CW for tumor detection, a mean fluorescence intensity cutoff value was determined from the formalin-fixed tissue slices (n = 42; 17 patients). Local bevacizumab-800CW accumulation was evaluated by fluorescence microscopy. Results: Back-table FGI correctly identified a tumor-positive CRM by high fluorescence intensities in 1 of 2 patients (50%) with a tumor-positive CRM. For the other patient, low fluorescence intensities were shown, although (sub)millimeter tumor deposits were present less than 1 mm from the CRM. FGI correctly identified 5 of 6 tumor-negative CRM (83%). The 1 patient with false-positive findings had a marginal negative CRM of only 1.4 mm. Receiver operating characteristic curve analysis of the fluorescence intensities of formalin-fixed tissue slices yielded an optimal mean fluorescence intensity cutoff value for tumor detection of 5,775 (sensitivity of 96.19% and specificity of 80.39%). Bevacizumab-800CW enabled a clear differentiation between tumor and normal tissue up to a microscopic level, with a tumor-to-background ratio of 4.7 ± 2.5 (mean ± SD). Conclusion: In this proof-of-concept study, we showed the potential of back-table FGI for evaluating the CRM status in LARC patients. Optimization of this technique with adaptation of standard operating procedures could change perioperative decision making with regard to extending resections or applying intraoperative radiation therapy in the case of positive CRM.

A COVID-19 mass testing effort within San Francisco's Mission District  — which aimed to broadly test individuals regardless of symptoms  — found stark inequalities in how the virus is affecting different groups. About 95% of the people who tested positive were Latino, and the vast majority could not work from home. Not a single white person tested positive, despite making up about a third of the people who were tested. 

While oil and wholesale fuel prices have been at two-decade lows, pump prices have not come down so quickly or consistently across the country. But service station owners say they too are struggling to survive the COVID-19 downturn.

The Department of Justice and the U.S. Department of Agriculture (USDA) announced today the agenda and panelists for the Dec. 8, 2010, joint public workshop on margins in agriculture.

The Department of Justice and the U.S. Department of Agriculture (USDA) today held the fifth of five joint public workshops to explore the appropriate role for antitrust and regulatory enforcement in American agriculture.

Lewis Hamilton secured pole position in the opening qualifying round of his title defence, dominating the session and setting a time nearly 0.6s faster than his Mercedes team-mate Nico Rosberg

As the coronavirus outbreak rapidly spreads, existing social and economic inequalities in society have been exposed and exacerbated. State and local governments across the country, on the advice of public health officials, have shuttered businesses of all types and implemented other social distancing recommendations. Such measures assume a certain basic level of affluence, which many…

On March 15, 2020, the Kenyan government abruptly closed schools and colleges nationwide in response to COVID-19, disrupting nearly 17 million learners countrywide. The social and economic costs will not be borne evenly, however, with devastating consequences for marginalized learners. This is especially the case for girls in rural, marginalized communities like the Maasai, Samburu,…

On March 15, 2020, the Kenyan government abruptly closed schools and colleges nationwide in response to COVID-19, disrupting nearly 17 million learners countrywide. The social and economic costs will not be borne evenly, however, with devastating consequences for marginalized learners. This is especially the case for girls in rural, marginalized communities like the Maasai, Samburu,…

On March 15, 2020, the Kenyan government abruptly closed schools and colleges nationwide in response to COVID-19, disrupting nearly 17 million learners countrywide. The social and economic costs will not be borne evenly, however, with devastating consequences for marginalized learners. This is especially the case for girls in rural, marginalized communities like the Maasai, Samburu,…

On March 15, 2020, the Kenyan government abruptly closed schools and colleges nationwide in response to COVID-19, disrupting nearly 17 million learners countrywide. The social and economic costs will not be borne evenly, however, with devastating consequences for marginalized learners. This is especially the case for girls in rural, marginalized communities like the Maasai, Samburu,…

As the coronavirus outbreak rapidly spreads, existing social and economic inequalities in society have been exposed and exacerbated. State and local governments across the country, on the advice of public health officials, have shuttered businesses of all types and implemented other social distancing recommendations. Such measures assume a certain basic level of affluence, which many…

On March 15, 2020, the Kenyan government abruptly closed schools and colleges nationwide in response to COVID-19, disrupting nearly 17 million learners countrywide. The social and economic costs will not be borne evenly, however, with devastating consequences for marginalized learners. This is especially the case for girls in rural, marginalized communities like the Maasai, Samburu,…

Last month, Senator Bernie Sanders spoke in a notably all-white panel at a Sanders Institute conference, and reiterated a frequent talking point of his, as well as many in his sect of often white, male progressive thinkers who reject what they call “identity politics” and “social issues.” According to Sanders, the experiences of rural Trump […]

On #CricketConnected, Star Sports’ new show the Greatest Of All Time (G.O.A.T) – Captain was a tie between MS Dhoni and Rohit Sharma based on the jury's votes, but then the selection panel on the show picked Dhoni ahead of Rohit by the slimmest of margins.

Justifying the pick Former England batsman Kevin Pietersen said, “His relationship with Fleming the consistency at the franchise and the wicket they play on so it would be hard to go against MS and he will probably get my vote, I like what Rohit Sharma does and I love the Mumbai Indians and their approach to the game. However, for consistency and weight of expectation down there in Chennai MS is my guy.”

Former New Zealand fast bowler Danny Morrison added, “Looking at the vibe and the inspiration of that fellow (MS Dhoni) in yellow and what he did for India in blue and variably that helicopter shot which changes the course of the game, yes he is a lot older and finishing up Rohit got more time. But for me, Dhoni takes the pressure like no one else.”

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Blog examining how corruption can have a negative impact on citizens health, and underlines the difficulties of controlling trade networks and examines how illicit trade continues to evolve.

Euro Area Marginal Lending Rate was at 0.25 percent on Friday May 8. Lending Rate in the Euro Area averaged 2.42 percent from 1999 until 2020, reaching an all time high of 5.75 percent in October of 2000 and a record low of 0.25 percent in March of 2016. In the Euro Area, the marginal lending facility aims to provide overnight liquidity, signal the general stance of monetary policy and normally provides a ceiling for the overnight market interest rate. This facility is available to eligible counterparties on their own initiative, subject to their fulfilment of certain operational access conditions. Counterparties can use the marginal lending facility to obtain overnight liquidity from the national central banks against eligible assets. Under normal circumstances, there are no credit limits or other restrictions on counterparties' access to the facility, apart from the requirement to present sufficient underlying assets. The marginal lending facility is administered in a decentralised manner by the national central banks. This page provides - Euro Area Lending Rate- actual values, historical data, forecast, chart, statistics, economic calendar and news.

Margin Call, the latest in a line of films on the crash of 2008, depicts a Wall Street investment bank’s last ditch attempts to save itself from impending disaster. Written and directed by first time feature director J.C.Chandor – and starring Kevin Spacey, Demi Moore and Jeremy Irons – The New Yorker called it “the best Wall Street movie ever made”. It’s been marketed as a thriller – but how do you create excitement when the action consists of men in suits peering at computer screens and talking on Blackberries? Does Margin Call have anything new to say on the much-debated causes of the collapse? Andrew Hill, FT management editor, puts these questions to Alex Preston, ex-City trader and author of This Bleeding City; Peter Aspden, FT arts writer; and Leo Robson, film and television critic. Produced by Griselda Murray Brown  

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German supplier scraps outlook and warns smaller contractors could go out of business

Australia’s four major banks delivered combined underlying cash earnings of $15.5 billion for the first-half to March 2015.

A new data set from Silicon Valley Bank (SVB) details how startups are reacting to the post-unicorn era as COVID-19-related disruptions upset the global economy and remake the risk tolerance of private investors. What SVB’s new report shows is unsurprising: venture capital deal volumes are falling, startups are tapping existing debt capacities to add cash […]

The day before the election and the presidential race is on a knife edge. Hillary Clinton leads Donald Trump in most polls by three or four points, according to data published Monday.

75628596Julia Taylor Kennedy and Pooja Jain-Link are executive vice presidents and lead researchers at the Center for Talent Innovation.They write that COVID-19 has had greater consequences for marginalized populations.But employers can consciously create a more diverse and inclusive workplace in the midst of the pandemic.Employers should put in place sponsorship programs and flexible workplaces — and acknowledge any fears workers have right now.Visit Business Insider's homepage for more stories.We've all seen the headlines: instead of being the "great equalizer," this pandemic has revealed that if you are lower-income, black, Latinx, Asian, or a woman, you are likely to face deeper consequences from the coronavirus and the attendant economic downturn.In its spread, COVID-19 has revealed much

Voters under 35 years old are just not that into Donald Trump, a new USA Today/Rock the Vote poll finds, with just 20 percent saying they planned to vote for the Republican nominee.

The former Tory Party adviser has taken unpaid leave to tour the UK electioneering for young female Conservative candidates in marginal seats in the run up to December 12.

Khan amassed 130,367 votes decimating his BJP rival to 58,540 votes, while Congress's Parvez Hashmi could manage just 5,123

BJP leadership had exuded confidence after exit polls had come out; EC data shows that there was no reason to

In the poorest part of Jharkhand, community radio has become an important instrument for the development of neglected communities. If access to their own media were freer, the villagers believe, things could be even better. Pratibha Jyoti reports on the progress made even without government support for community stations.