Adrian Newey tells BBC Sport's Joe Wilson "it is easy to become stale", but his "passion has always been for trying to find ways to make the car go faster" after joining Aston Martin.

BBC F1 correspondent Andrew Benson answers your questions following the Sao Paulo Grand Prix.

Aston Martin technical director Dan Fallows leaves his role with the Formula 1 team.

Watch highlights as undefeated Manchester United are held to a 0-0 draw by Aston Villa in the WSL.

Former Premier League striker Chris Sutton discusses Manchester City’s recent form, and asks if this can be considered a crisis for manager Pep Guardiola.

Donald Trump's rocket fuel is rage and resentment, with a new and very detailed agenda to match. His country, this nation and the world await the full meaning and consequence of his second presidency, writes Tony Leon.

Denzel Washington may have let slip that director Ryan Coogler is working on a third "Black Panther" film, which Marvel has not yet announced.

"I think they say they want autonomy. I think their actions don't say the same thing," Airbnb CEO Brian Chesky recently said in an interview.

Paramount Plus, Peacock, and the Paramount Network all have a hand in the Yellowstone franchise, but it can be tricky to stream episodes.

Over the past decade, parent advocacy groups led a grassroots movement resulting in most states adopting dyslexia-specific legislation, with many states mandating the use of the Orton-Gillingham (OG) approach to reading instruction. Orton-Gillingham is a direct, explicit, multisensory, structured, sequential, diagnostic, and prescriptive approach to reading for students with or at risk for word-level reading disabilities (WLRD). Evidence from a prior synthesis and What Works Clearinghouse reports yielded findings lacking support for the effectiveness of OG interventions.

Many blog owners have recently started to monetize their websites by selling physical or digital products to their loyal customers from their sidebar. If you have a loyal following, perhaps you run a small blog from a WordPress website, there is no reason why you cannot try to make a little side cash by creating […]

The post Adding PayPal Payment Buttons to Your WordPress Sidebar Easily appeared first on Tips and Tricks HQ.

If you run an eCommerce website, you may prefer to use a graphic as the call-to-action button for your subscription-style products or services. Below you can find a number of different subscription buttons suitable for use on a website’s landing page or the product page. Want some Buy Now button or Add to Cart button […]

The post Subscription Button Graphics for eCommerce Websites appeared first on Tips and Tricks HQ.

In this blog post, you can find a range of different ‘Buy Now’ buttons that can be used on a website as the ‘call-to-action’ button for a product or service you are trying to sell. There is a range of different size buttons, in a number of different colors to fit with the aesthetics of […]

The post Buy Now Button Graphics for eCommerce Websites appeared first on Tips and Tricks HQ.

Time's arrow may not be as unidirectional as we were led to believe. According to Scientific American, a group of quantum physical researchers at the University of Toronto had observed evidence of what they're calling "negative time"—specifically, of photons exiting a material before they ever entered it, to begin with. — Read the rest

The post Physicists find evidence of "negative time" in photons appeared first on Boing Boing.

A Minnessota maker named Caleb Olson built the Poopcopter, an autonomous drone that seeks out dog-doo and retrieves it for disposal.

He describes it as the "world's first aerial bound self-guided dog poop removal system." See it in action below.

"The Poopcopter is capable of scanning areas defined by a user, your backyard for example, and as it scans it's performing real-time computer vision using the camera which is inside the drone," Olson says. — Read the rest

The post The Poopcopter is a DIY autonomous drone that finds and collects dog-doo appeared first on Boing Boing.

Have you heard of Locorotondo, Italy? Locorotondo is one of Southern Italy’s most beautiful villages, in my opinion, but it isn’t yet overwhelmed with tourist crowds. A true hidden gem, Locorotondo is just a 12-minute drive from busy Alberobello in the Puglia region, but feels like a world away. Planning your trip to Locorotondo last […]

The post Visiting Locorotondo, Italy – A Guide to the Trulli Town appeared first on Adventurous Kate.

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.

US and Europe Strategic Security Cooperation: The View from Washington 27 March 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 9 March 2023 Chatham House

As the US prepares to enter the next presidential election cycle, can the transatlantic alliance stay the course, especially against a deepening Russia-China partnership?

Thank you for your interest in joining our event. Please plan to arrive at Chatham House from 08:45 GMT as the event will begin promptly at 09:00.

The Biden administration’s response to Russia’s war in Ukraine and the rise of a globally assertive China, as articulated in the 2022 US national strategy, is to ‘constrain Russia and out-compete China’. It needs Europe as a partner and ally for both – yet Europe is also an object and a battleground in this era of strategic competition.

As the US prepares to enter the next presidential election cycle, can the transatlantic alliance stay the course, especially against a deepening Russia-China partnership? Can Europeans, in particular, move from deepening dependency to greater agency and self-reliance? What is the role for Germany – and for the UK?

Yue Chen
May 1, 2007; 6:812-819
Research

Lys234 is one of the residues present in class A β-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser130, it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant β-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome β-lactamase–mediated antibiotic resistance. Here we show that for CTX-M-14 β-lactamase, whereas Lys234 is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in kcat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser130, and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser130 and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance.

US election rhetoric on migration undermines Washington’s soft power in Latin America Expert comment jon.wallace 23 October 2024

As US public opinion hardens, the Democratic party takes a tougher stance, and Donald Trump proposes mass deportations, Latin American leaders note a lack of long-term policy.

The US’s broken immigration system has become a central theme of the 2024 election campaign. But the discussion on immigration, undocumented immigrants, and asylum seekers – increasingly lurching into dehumanizing rhetoric – extends beyond US borders. 

As one former senior director of the National Security Council told me, ‘when the president travels or meets with heads of state from Latin America what comes up –regardless of the country – isn’t US–Cuba policy or even trade. It’s immigration’. How the US talks about and treats citizens of Latin American and the Caribbean matters to elected politicians in the region. 

The roots of the US immigration debate go deep and will not be easily resolved, even with a sweeping reform of the system. 

According to a January 2024 Pew survey, 78 per cent of Americans ‘say the large number of migrants seeking to enter the country at the Mexico border is either a crisis (45 per cent) or a major problem (32 per cent)’. Worries about the border are not limited to Republican voters: 73 per cent of Democrats feel that the issue is either a crisis or major problem. 

Despite the heated popular temperature, the numbers of undocumented immigrants encountered at the US–Mexico border has actually dropped in recent months. US Customs and Border Protection (USCBP) reported 301,981 encounters with irregular border crossings in December 2023; by August 2024 this had dropped to 107,473.  

Nevertheless, illegal border crossings have increased under Biden. During his administration USCBP reported 8 million encounters along the Mexico border compared to 2.5 million under Donald Trump. 

Mexico

Any attempt to address the issue promises to affect US relations with Mexico, requiring the cooperation of newly elected president Claudia Sheinbaum. Her predecessor and founder of her Morena party, leftist Andres Manuel Lopez Obrador (AMLO), proved an unexpectedly cooperative partner for the previous Trump administration and Biden White House. 

But that came at a cost, particularly for Biden. In return for AMLO’s cooperation, the US soft-pedalled criticism over his failures to disrupt narcotics trafficking and criminal networks and for his steady weakening of checks on executive power. 

Mexico’s borders with other countries are also under pressure. Mexico remains the primary sending country to the US. But political repression and insecurity in countries including Cuba, Ecuador, Guatemala and Venezuela has pushed their citizens to travel across Mexico to the US. Economic collapse and humanitarian crises in Cuba and Venezuela have further fuelled the flight.

Rhetoric

The Kamala Harris and Trump campaigns have struck different positions on how to stem the flow of illegal immigration. But as US public opinion shifts, both parties are talking tougher. 

Harris is continuing Biden’s hardening stance, including the controversial move to bar those who cross the border illegally from applying for asylum. 

Biden’s early ‘roots’ strategy, to provide economic and security support in countries from where migrants are travelling, has fallen by the wayside. 

The Trump campaign is taking more extreme positions. The Republican presidential candidate mentions immigration in almost every campaign speech. 

He proposes to carry out the ‘largest deportation in US history’, using ICE personnel, the National Guard and local police forces to round up undocumented immigrants, including in their workplaces. 

The campaign has also pledged to end birth-right citizenship and Biden’s programme of parole for humanitarian reasons. Trump also plans to restore his first term policies including construction of the border wall. 

Trump’s proposals provide little opportunity for a broad, bipartisan consensus on immigration. Should he win in November he is likely, as he did in his first term, to attempt to push his policies via executive action, opening up challenges in federal court. 

A Harris victory would at least create space for the resurrection of the Biden administration’s 2024 immigration enforcement bill, originally supported by moderate Republican leadership in the Senate, but defeated following pressure from Trump. 

The bill would have toughened enforcement at the border – increasing funding for detention centres, asylum hearings and for local governments and border patrols. It would also permit ICE to shut down the border when crossings surpassed an average of 5,000 per day or 8,500 on a single day.

Undermining US influence

But such legislation, while promising to address domestic US perceptions of the crisis, threatens to reduce US soft power in Latin America. That would be counterproductive at a time when the US is attempting to consolidate global support in its competition with China and conflict with Russia. 

For Latin American leaders, US rhetoric on immigration rankles. The priorities of Latin American and Caribbean leaders and their voters are long term: economic growth, improved security, and climate change. These issues require investment and commitment from an engaged and reliable US partner. Sadly, Latin Americans can see such issues are not on the domestic agenda in US politics. 

To improve regional perceptions of US intentions after the election, new policy should seek to address the root causes of migration. That will require a multi-pronged, bipartisan approach that focuses attention and resources on US neighbours south of the border.  

The US’s immigration system will need to broaden paths for legal immigration to meet US labour needs, while delivering increased support for border security, and accelerated (and humane) processes for detaining and repatriating illegal border crossers and asylum claims.  

But any sustainable answer also requires addressing the multifaceted reasons driving migrants north. Any future US administration will need to risk unpopularity with some voters at home and engage with sending countries and their neighbours. 

Linda J. Pike
Jul 1, 2006; 47:1597-1598
Report

Chatham House appoints Tim Benton as Research Director for Energy, Environment and Resources News Release sysadmin 30 May 2019

Chatham House is pleased to announce that Professor Tim Benton has been appointed as research director of the Energy, Environment and Resources Department.

The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN–GAA–Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by ∼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4–7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA.

Histone recognition by “reader” modules serves as a fundamental mechanism in epigenetic regulation. Previous studies have shown that Spindlin1 is a reader of histone H3K4me3 as well as “K4me3-R8me2a” and promotes transcription of rDNA or Wnt/TCF4 target genes. Here we show that Spindlin1 also acts as a potent reader of histone H3 “K4me3-K9me3/2” bivalent methylation pattern. Calorimetric titration revealed a binding affinity of 16 nm between Spindlin1 and H3 “K4me3-K9me3” peptide, which is one to three orders of magnitude stronger than most other histone readout events at peptide level. Structural studies revealed concurrent recognition of H3K4me3 and H3K9me3/2 by aromatic pockets 2 and 1 of Spindlin1, respectively. Epigenomic profiling studies showed that Spindlin1 colocalizes with both H3K4me3 and H3K9me3 peaks in a subset of genes enriched in biological processes of transcription and its regulation. Moreover, the distribution of Spindlin1 peaks is primarily associated with H3K4me3 but not H3K9me3, which suggests that Spindlin1 is a downstream effector of H3K4me3 generated in heterochromatic regions. Collectively, our work calls attention to an intriguing function of Spindlin1 as a potent H3 “K4me3-K9me3/2” bivalent mark reader, thereby balancing gene expression and silencing in H3K9me3/2-enriched regions.

L. Oeding
Trans. Moscow Math. Soc. 83 (), 227-250.
Abstract, references and article information

Jan Goedgebeur, Jorik Jooken, On-Hei Solomon Lo, Ben Seamone and Carol T. Zamfirescu
Math. Comp. 93 (), 3059-3082.
Abstract, references and article information

Carolyn S. Gordon and Michael R. Jablonski
Trans. Amer. Math. Soc. 377 (), 5673-5704.
Abstract, references and article information

Kadian Morgan was overwhelmed with grief as she leaned against a wall outside her gate on Jackson Lane, East Kingston, yesterday, tears streaming down her face. Her 19-year-old son, Kayshan 'Bem Bem' Smith, was lying in the morgue after being...

15 July 2020

Congcong Lu
Nov 17, 2020; 0:R120.002257v1-mcp.R120.002257
Review

Histone post-translational modifications (PTMs) are one of the main mechanisms of epigenetic regulation. Dysregulation of histone PTMs leads to many human diseases, such as cancer. Due to its high-throughput, accuracy, and flexibility, mass spectrometry (MS) has emerged as a powerful tool in the epigenetic histone modification field, allowing the comprehensive and unbiased analysis of histone PTMs and chromatin-associated factors. Coupled with various techniques from molecular biology, biochemistry, chemical biology and biophysics, MS has been employed to characterize distinct aspects of histone PTMs in the epigenetic regulation of chromatin functions. In this review we will describe advancements in the field of MS that have facilitated the analysis of histone PTMs and chromatin biology.  

Tectonic Politics: Global Political Risk in an Age of Transformation Book sysadmin 7 May 2019

Political risk now affects more markets and countries than ever before and that risk will continue to rise. But traditional methods of managing political risk are no longer legitimate or effective.

In Tectonic Politics, Nigel Gould-Davies explores the complex, shifting landscape of political risk and how to navigate it. He analyses trends in each form of political risk: the power to destroy, seize, regulate, and tax.

He shows how each of these forms reflects a deeper transformation of the global political economy that is reordering the relationship between power, wealth, and values. In a world where everything is political, the craft of engagement is as important as the science of production and the art of the deal.

The successful company must integrate that craft—the engager’s way of seeing and doing—into strategy and culture.

Drawing on a career in academia, business, and diplomacy, Gould-Davies provides corporate leaders, scholars, and engaged citizens with a groundbreaking study of the fastest-rising political risk today. ‘As tectonic plates shape the earth,’ he writes, ‘so tectonic politics forges its governance.’

The book is published as part of the Insights series.

Praise for Tectonic Politics

About the author

Nigel Gould-Davies was an associate fellow of the Russia and Eurasia Programme at Chatham House.

Purchase

• UK (via Amazon)
• Rest of world (via Brookings Institution Press)
• Students (via Browns Books)

The Angels will be without left fielder Justin Upton early in Spring Training, as he's dealing with right knee patellar tendinitis but is expected to be ready for Opening Day, manager Brad Ausmus said on Monday.

CAMBRIDGE, England, Oct. 15, 2024 — Nu Quantum has announced a proof-of-principle prototype that advances the development of modular, distributed quantum computers by enabling connections across different qubit modalities and […]

The post Nu Quantum Unveils Qubit-Photon Interface to Enable Distributed Quantum Computing Networks appeared first on HPCwire.

A struggling Detroit Lions offense awoke late, scoring 19-unanswered points to rally past the Houston Texans and improve to 8-1 this season. The Lions overcame a career-high five interceptions Jared Goff threw.

All-Pro left tackle Tristan Wirfs and tight ends Sam LaPorta and Dalton Kincaid were among key players injured in Week 10 of the NFL season.

The Miami Marlins officially hired former Los Angeles Dodgers first base coach Clayton McCullough as their new manager, the franchise announced Monday.

PITTSBURGH, Sept. 24, 2024 — Ansys and TSMC today announced a successful pilot with Microsoft that significantly speeds-up the simulation and analysis of silicon photonic components. Together, the companies achieved […]

The post TSMC Collaborates with Ansys and Microsoft to Accelerate Photonic Simulations appeared first on HPCwire.

SANTA CLARA, Calif., Oct. 22, 2024 — Celestial AI today announced the acquisition of silicon photonics intellectual property from Rockley Photonics, including worldwide issued and pending patents. The combination of Celestial […]

The post Celestial AI Acquires Rockley Photonics Patent Portfolio, Strengthening Photonic Fabric IP appeared first on HPCwire.

Oct. 25, 2024 — Aggregation of proteins underlies many human disorders, including Alzheimer’s. Teams from the New Jersey Institute of Technology and Princeton University joined forces to study how the amyloid […]

The post PSC: Anton Simulations Reveal How Alzheimer’s Fibril Growth May Accelerate appeared first on HPCwire.

Australian Defense Minister Peter Dutton called for alliances to protect the nations and people of the Indo-Pacific region.

COLLEGE PARK, Md., Nov. 8, 2024 — IonQ, a leader in the quantum computing industry, has announced a partnership with NKT Photonics, a subsidiary of Hamamatsu Photonics, to procure next-generation laser […]

The post IonQ and NKT Photonics Collaborate on Next-Gen Laser Tech for Quantum Data Centers appeared first on HPCwire.

COLLEGE PARK, Md., Nov. 11, 2024 — IonQ, a leader in the quantum computing industry, has announced that it is developing photonic integrated circuits (PICs) and chip-scale ion trap technology for […]

The post IonQ Partners with imec to Advance Quantum Computers with Photonic Integrated Circuits appeared first on HPCwire.

It will cost $55.7 million to repair Tropicana Field, home to the MLB Tampa Bay Rays, in time for the 2026 home opener, St. Petersburg., Fla., city officials said Tuesday.