The rental-car giant fell as much as 12% on Tuesday after posting a deeper-than-expected loss.

Marilyn Chinitz has worked with celebs like Tom Cruise, Michael Douglas, and Wendy Williams. She has been happily married for 38 years.

Donald Trump's proposed tariffs would hit the consumer tech sector, raising prices on US consumers' favorite gadgets, an October report found.

Jude Law added that people in middle age should start to reflect on their relationship patterns.

The collaboration comes amid skyrocketing demand for Nvidia chips, as companies scramble to secure supplies.

Today’s buyers are getting more demanding and selling online is getting more and more complex. Both B2B and B2C customers expect a seamless purchase experience and easy access to all the information, products and services they want, on any device and in any country.

Growth is top of mind for most companies, but it can be tricky to get started with developing a growth framework. For one thing, most companies aren’t organized around growth, so thinking about growth requires a lot of collaboration between teams. Additionally, companies often don’t have easy access to all of the data they need to understand growth.

First grade can bring a lot of changes! Even if your child had a great kindergarten year, there can be lots of new routines and expectations for first graders that can feel really different for students (and families). Here’s what you need to know.

Teacher question: One of my colleagues told us that we should not be teaching guided reading lessons or comprehension skills or strategies. We’re using a core reading program that includes those kinds of things. He says that the science of reading proves that we would get higher reading achievement by teaching more social studies and science (he’s our science teacher) and dropping the comprehension instruction that we are providing. He’s really vocal about this. Can you help us shut him up? Shanahan’s response

LG’s latest prototype screen is stretchy. Shown off at LG’s Science Park in Seoul, the company demonstrated the new type… Continue reading LG gives glimpse into the future with stretchy display

The post LG gives glimpse into the future with stretchy display appeared first on ReadWrite.

KwaZulu-Natal police commissioner Lieutenant General Nhlanhla Mkhwanazi has ordered an "immediate investigation" after a video went viral on social media of a police officer slapping and pulling around a man.

Plan a trip to Rome, and you’ll wish you were there for weeks! From the Colosseum to the Vatican Museums, there’s a lot in the Eternal City to check off your bucket list.  But if you can tear yourself away from Rome’s top attractions, there are plenty of excellent day trips from Rome. Rome is […]

The post 18 Fun Day Trips from Rome appeared first on Adventurous Kate.

Finding ways to save money is much easier than you think, because you’re probably spending money you don’t have to spend.

The article 3 Easy Steps to Save Money for Travel originated at EverInTransit.com

It was supposed to be a push to help her over the finish line. It ended up giving Trump a free shot with their audience instead.

The post OOPS: SNL Tried To Help Kamala… But Boosted TRUMP Instead (VIDEO) appeared first on Clash Daily.

When he first showed up, he was echoing the Jan-6-threat-to-democracy talking point. By the time he left, he had other considerations to chew over.

The post WATCH: Vivek Puts On A Clinic… Flips Bro From Kamala To MAGA In Just A Few Questions (VIDEO) appeared first on Clash Daily.

Shamelessly, Big Media doesn't even try to hide their Democrat preferences anymore. They are happy to lie. But even the lies they tell can point indirectly to the truth.

The post EPIC: When AI Swaps ‘Democracy’ For THIS Word, Journos Start Telling The Truth appeared first on Clash Daily.

Without a consequence-free hook-up culture, Planned Parenthood's business model collapses. The left's response to Trump's election is an existential threat... to itself!

The post OOPS: Planned Parenthood Sounds Alarm As Lefties Weaponize Abstinence appeared first on Clash Daily.

A few weeks ago we launched a new marketing project for HEY.com at dumpsterfire.email. If you haven’t seen it yet, it’s a flaming dumpster with a printer and conveyor. You email dumpsterfire@hey.com, it prints out your email, and drops it into the rolling flames on a livestream. Simple, right? What follows is far more than… keep reading

Bafana Bafana coach Hugo Broos has welcomed the number of young players who are given a chance and backed in the premier division, but has warned that to build on their progress, agents must prioritise players' development over their personal enrichment.

Rassie Erasmus' 7-1 variation of the Bomb Squad used against Scotland on Sunday set off a few tremors in the north, with Times writer Stephen Jones the latest to criticise the "dangerous" and "arrogant" tactic.

Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.

Next steps for EU-US cooperation on trade and technology 8 December 2022 — 3:00PM TO 4:00PM Anonymous (not verified) 21 November 2022 Online

How can the EU and US increase cooperation on AI, semi-conductors and funding information communication technology services?

On trade and technology policy, the EU and the US are making meaningful progress towards cooperation while at the same time navigating tensions. As senior officials meet on 5 December for the third meeting of the Trade and Technology Council (TTC), both sides have vowed to move towards concrete results. But can the US and EU increase cooperation on artificial intelligence, semiconductors, and funding information communication technology services? 

This event draws on insights from a forthcoming Briefing Paper by Marianne Schneider-Petsinger that explores next steps for US-EU cooperation on trade and technology, which is part of a project supported by the Hanns Seidel Foundation. 

SVB collapse shows interest rate financial stability threat Expert comment LJefferson 15 March 2023

Governments must resist pressure to relax post-financial crisis regulation, while central banks should moderate their attack on inflation if financial stability is at risk.

The collapse of California’s Silicon Valley Bank (SVB) on 10 March has triggered a wave of volatility in global bank equity prices, raised questions about whether US bank regulation and its tech industry funding model are fit for purpose, and forced a rethink on the extent and pace of monetary policy tightening appropriate for the US and other advanced economies.

SVB was the US’s 16th largest bank with total assets of $212bn at the end of 2022 and a presence in eight countries around the world, including the UK. Since it was founded 40 years ago, it has maintained a strong focus on the technology sector, claiming recently that nearly half of all US venture-backed technology and life science companies banked with it. Partly as a consequence, some 95 per cent of its deposits came from corporates and hedge funds, far higher than the one-third typical of similarly sized banks.

What led to SVB’s collapse?

Ironically, SVB’s failure did not result from its core business model of serving a relatively high-risk and fast-growing sector, but rather from a dramatic failure in liquidity management. During the pandemic, SVB saw a very large inflow of corporate deposits. But rather than disincentivizing depositors or investing the funds attracted in assets of matching maturity, it chose to invest them in low credit risk, but long maturity bonds attracted by a small pick-up in return over shorter-term assets. 

When US interest rates began to rise rapidly in 2022 following Russia’s invasion of Ukraine, the value of SVB’s long-term bond portfolio declined sharply. It was left facing a large capital loss of some $15bn, roughly equivalent to its total shareholder funds. The management attempted to repair SVB’s balance sheet last week by crystalizing some of the loss and raising new capital.

But when this failed, the US supervisory authorities had no choice but to step in and close the institution.  This action was quickly followed by emergency action from other regulators vis-a-vis SVB subsidiaries and offices around the world.

The US entity has formally been taken over by the FDIC and a bridge bank established. All depositors have had their funds guaranteed, going beyond the normal federal deposit insurance limit of $250,000 per customer. However, bond holders and equity holders have been wiped out. The authorities have said that any loss will be covered by the industry as a whole via the FDIC.

In the UK, the Bank of England was able to sell the ring-fenced UK subsidiary of SVB to HSBC for £1 over the weekend, so that all its depositors and other liability holders have effectively had their funds guaranteed. In contrast to previous Bank of England rescues (such as Johnson Matthey Bank in 1984, the ‘small banks’ crisis in 1991 and the global financial crisis in 2008-9) no public money has been put at risk.

Four key questions

SVB’s rapid collapse raises four central questions:

First, how was it that the bank was able to take on such a risky interest rate maturity mismatch in its US operations? Maturity transformation is standard banking industry practice, but it is usually closely monitored by regulators who place limits on the extent of interest rate maturity mismatch and require liquidity buffers to offset the risk of deposit flight and forced asset sales.

SVB’s very high concentration of corporate deposits as compared to ‘sticky’ retail deposits, means that the risk of deposit flight was unusually high and so the bank should have been more, not less, cautious in its liquidity policy. SVB was classed as a regional bank in the US which means that it did not have to meet international regulatory standards under Basle III. And in 2018, the Trump administration approved legislation removing the post-financial crisis requirement that banks with assets under $250bn submit to stress testing and relaxing liquidity buffer requirements.

But it is still hard to understand why regulators allowed SVB to commit such a classic banking error. On Monday, the Federal Reserve ordered an inquiry into what it has correctly described as a regulatory failure. This should look at the role played by all the elements of the oversight system including the auditors, KPMG.

Second, does SVB’s failure reflect a much bigger underlying risk in the US banking sector, and potentially other banking systems around the world, built up over the prolonged period of ultra-low interest rates? SVB’s collapse was followed by the failure of the $110bn Signature Bank in New York, as well as sharp falls in US regional bank stock prices – by close of play on 14 March, the S&P Regional Bank Index was down 22 per cent on a week before, with some individual bank stocks seeing much sharper falls.  

To the extent that banks have been covered by international bank regulatory requirements, the risk of a much broader problem should be limited because stress testing and other regulatory tests would have looked at precisely the scenario that has happened. Even where large market losses have been incurred, capital buffers should be sufficient to cover them. But as SVB has shown, there are some large banks that are seemingly not required to follow international rules, while the latest developments at Credit Suisse indicate that market concerns may still arise when other factors are in play.

Third, how far, in the light of the potential vulnerability in banking systems, should central banks in advanced countries moderate their efforts to squeeze out inflationary pressures? While inflation already appears to have peaked in many economies and the pace of interest rate rises was expected to slow, inflation is far from vanquished, as recent data in the US has demonstrated.

Fourth, does the failure of SVB tell us something new about the financial risks facing the high technology sector?  It was remarkable that a single (and not particularly large, by international standards) financial institution could have played such a central role in the tech sector in both the US and UK. 

Why was this the case and does it reflect special features of the tech/start-up sector (e.g. the need for substantial cash deposits to cover relatively large negative cash flows in the early years of operation, or the need for highly specialized lending expertise). If so, should governments take steps to mitigate such risks, given the outsized importance of this sector in many national economic strategies? 

Jonathan C. Trinidad
Aug 1, 2012; 11:215-229
Research

Joris J. Benschop
Jul 1, 2007; 6:1198-1214
Research

Jesper V. Olsen
Jun 1, 2004; 3:608-614
Technology

Yu Xue
Sep 1, 2008; 7:1598-1608
Research

How Beijing is closing surveillance gaps in the South China Sea The World Today iallan.drupal 15 October 2024

The discovery of a new radar system on China’s Triton Island military base shows that Beijing is rapidly developing its intelligence capacities in contested waters, write John Pollock and Damien Symon.

New satellite images reveal how the Chinese military is dramatically expanding its capabilities on Triton Island, which looks set to become a one of Beijing’s key signal intelligence bases in the South China Sea.

Once completed, the radar system would significantly increase China’s signals intercept and electronic warfare capabilities across the disputed Paracel Islands archipelago and add to a wider surveillance network spanning much of the South China Sea.

The enhanced facility on Triton is likely to offer a challenge to China’s competitors in the region and internationally.

China seized control of the Paracels from Vietnam in a 1974 naval battle, and competition for access to it waters has intensified since the recent discovery of oil and gas reserves. Chinese and Vietnamese maritime militia clashed off the coast of Triton in 2014.

In addition, American, British and Australian naval forces have for the past decade patrolled the waters to collectively challenge China’s contested ‘nine-dash-line’ claim to large stretches of the South China Sea. 

Overlapping anti-stealth network

A year after work was first identified on Triton, satellite images from Maxar have helped build a clearer picture of Beijing’s efforts to defend this strategic waterway.

The most striking development is the construction of a new radar system, known as SIAR – synthetic impulse and aperture radar – which purportedly detects stealth aircraft. The counter-stealth radar on Triton is characterized by its distinctive octagonal structure, which resembles another SIAR system built by China on Subi Reef in the Spratly Islands, south of the Paracels, in 2017. A half-completed tower also sits near the SIAR radar on Triton, which is likely to be the operations centre.

Once completed, the radar on Triton will form what is believed to be a wider network of at least three overlapping counter-stealth radars built across Chinese bases in the South China Sea over the past decade, including on Hainan Island, home to several Chinese naval bases. 

The positioning of the radar on Triton, 320km south of Hainan, is telling, says J. Michael Dahm, Senior Resident Fellow for Aerospace and China Studies at the Mitchell Institute. 

‘SIAR radars cannot see over the curve of the Earth, which means there is a gap in China’s air surveillance coverage between Subi Reef and Hainan Island. The Triton Island site will help close that gap’, said Dahm.

The aim, he suggests, is to give China contiguous counter-stealth radar coverage of the South China Sea.

More construction underway

The satellite images reveal other building projects on Triton. One is a large pad at the end of the road network which will probably be used as a launching point for a mobile anti-ship missile battery. The building at the northeast end of the road is probably a storage building for missile transport vehicles. 

Diminishing Vietnam’s options

The development of a new counter-stealth radar system and other suspected signals intercept structures on Triton represents a notable increase in China’s intelligence capabilities in the Paracels. The Chinese Communist Party has not disclosed the purpose of the building work on Triton, but its effects on regional and global competitors are likely to be wide ranging.

For Vietnam, which is rapidly expanding its own bases in the South China Sea, the intelligence structures on Triton would significantly diminish its capacity to operate undetected in the area. Alongside existing radar on Triton which can detect sea-going vessels, Beijing now has the potential to track Vietnamese air movements and gain forewarning of Hanoi’s manoeuvres in the area, including efforts to access oil and gas deposits.

The desire to strengthen control over these resources may explain why China is fortifying Triton Island, says Bill Hayton, Associate Fellow in the Asia-Pacific Programme, Chatham House. ‘The developments might be a warning that China is planning to mount another drilling expedition’, he suggests.

Independent Thinking: Why is North Korea sending troops to Russia? Audio john.pollock 31 October 2024

Orysia Lutsevych, Edward Howell and Yossi Mekelberg discuss North Korean troops fighting with Russian forces against Ukraine, as well as the issue of military conscription.

On this episode

North Korea is sending troops to Russia, but what is Kim Jong-Un hoping to get from Vladmir Putin for this military assistance against Ukraine? The panel also discuss the role military conscription plays in Israel, South Korea and Ukraine’s defence.

Bronwen Maddox is joined by Edward Howell, the Korea Foundation fellow at Chatham House, Orysia Lutsevych, the head of our Ukraine Forum and Yossi Mekelberg, a senior consulting fellow with our Middle East and North Africa Programme.

About Independent Thinking

Independent Thinking is a weekly international affairs podcast hosted by our director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

More ways to listen: Apple Podcasts, Spotify.

Mohamad Navab
Sep 1, 2000; 41:1495-1508
Articles

Mohamad Navab
Sep 1, 2000; 41:1481-1494
Articles

Phospholipase Cε (PLCε) is activated downstream of G protein–coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core.

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.

Artificial Intelligence Apps Risk Entrenching India’s Socio-economic Inequities Expert comment sysadmin 14 March 2018

Artificial intelligence applications will not be a panacea for addressing India’s grand challenges. Data bias and unequal access to technology gains will entrench existing socio-economic fissures.

Artificial intelligence (AI) is high on the Indian government’s agenda. Some days ago, Prime Minister Narendra Modi inaugurated the Wadhwani Institute for Artificial Intelligence, reportedly India’s first research institute focused on AI solutions for social good. In the same week, Niti Aayog CEO Amitabh Kant argued that AI could potentially add $957 billion to the economy and outlined ways in which AI could be a ‘game changer’.

During his budget speech, Finance Minister Arun Jaitley announced that Niti Aayog would spearhead a national programme on AI; with the near doubling of the Digital India budget, the IT ministry also announced the setting up of four committees for AI-related research. An industrial policy for AI is also in the pipeline, expected to provide incentives to businesses for creating a globally competitive Indian AI industry.

Narratives on the emerging digital economy often suffer from technological determinism — assuming that the march of technological transformation has an inner logic, independent of social choice and capable of automatically delivering positive social change. However, technological trajectories can and must be steered by social choice and aligned with societal objectives. Modi’s address hit all the right notes, as he argued that the ‘road ahead for AI depends on and will be driven by human intentions’. Emphasising the need to direct AI technologies towards solutions for the poor, he called upon students and teachers to identify ‘the grand challenges facing India’ – to ‘Make AI in India and for India’.

To do so, will undoubtedly require substantial investments in R&D, digital infrastructure and education and re-skilling. But, two other critical issues must be simultaneously addressed: data bias and access to technology gains.

While computers have been mimicking human intelligence for some decades now, a massive increase in computational power and the quantity of available data are enabling a process of ‘machine learning.’ Instead of coding software with specific instructions to accomplish a set task, machine learning involves training an algorithm on large quantities of data to enable it to self-learn; refining and improving its results through multiple iterations of the same task. The quality of data sets used to train machines is thus a critical concern in building AI applications.

Much recent research shows that applications based on machine learning reflect existing social biases and prejudice. Such bias can occur if the data set the algorithm is trained on is unrepresentative of the reality it seeks to represent. If for example, a system is trained on photos of people that are predominantly white, it will have a harder time recognizing non-white people. This is what led a recent Google application to tag black people as gorillas.

Alternatively, bias can also occur if the data set itself reflects existing discriminatory or exclusionary practices. A recent study by ProPublica found for example that software that was being used to assess the risk of recidivism in criminals in the United States was twice as likely to mistakenly flag black defendants as being at higher risk of committing future crimes.

The impact of such data bias can be seriously damaging in India, particularly at a time of growing social fragmentation. It can contribute to the entrenchment of social bias and discriminatory practices, while rendering both invisible and pervasive the processes through which discrimination occurs. Women are 34 per cent less likely to own a mobile phone than men – manifested in only 14 per cent of women in rural India owning a mobile phone, while only 30 per cent of India’s internet users are women.

Women’s participation in the labour force, currently at around 27 per cent, is also declining, and is one of the lowest in South Asia. Data sets used for machine learning are thus likely to have a marked gender bias. The same observations are likely to hold true for other marginalized groups as well.

Accorded to a 2014 report, Muslims, Dalits and tribals make up 53 per cent of all prisoners in India; National Crime Records Bureau data from 2016 shows in some states, the percentage of Muslims in the incarcerated population was almost three times the percentage of Muslims in the overall population. If AI applications for law and order are built on this data, it is not unlikely that it will be prejudiced against these groups.

(It is worth pointing out that the recently set-up national AI task force is comprised of mostly Hindu men – only two women are on the task force, and no Muslims or Christians. A recent article in the New York Times talked about AI’s ‘white guy problem’; will India suffer from a ‘Hindu male bias’?)

Yet, improving the quality, or diversity, of data sets may not be able to solve the problem. The processes of machine learning and reasoning involve a quagmire of mathematical functions, variables and permutations, the logic of which are not readily traceable or predictable. The dazzle of AI-enabled efficiency gains must not blind us to the fact that while AI systems are being integrated into key socio-economic systems, their accuracy and logic of reasoning have not been fully understood or studied.

The other big challenge stems from the distribution of AI-led technology gains. Even if estimates of AI contribution to GDP are correct, the adoption of these technologies is likely to be in niches within the organized sector. These industries are likely to be capital- rather than labour-intensive, and thus unlikely to contribute to large-scale job creation.

At the same time, AI applications can most readily replace low- to medium-skilled jobs within the organized sector. This is already being witnessed in the outsourcing sector – where basic call and chat tasks are now automated. Re-skilling will be important, but it is unlikely that those who lose their jobs will also be those who are being re-skilled – the long arch of technological change and societal adaptation is longer than that of people’s lives. The contractualization of work, already on the rise, is likely to further increase as large industries prefer to have a flexible workforce to adapt to technological change. A shift from formal employment to contractual work can imply a loss of access to formal social protection mechanisms, increasing the precariousness of work for workers.

The adoption of AI technologies is also unlikely in the short- to medium-term in the unorganized sector, which engages more than 80 per cent of India’s labor force. The cost of developing and deploying AI applications, particularly in relation to the cost of labour, will inhibit adoption. Moreover, most enterprises within the unorganized sector still have limited access to basic, older technologies – two-thirds of the workforce are employed in enterprises without electricity. Eco-system upgrades will be important but incremental. Given the high costs of developing AI-based applications, most start-ups are unlikely to be working towards creating bottom-of-the-pyramid solutions.

Access to AI-led technology gains is thus likely to be heavily differentiated – a few high-growth industries can be expected, but these will not necessarily result in the welfare of labour. Studies show that labour share of national income, especially routine labour, has been declining steadily across developing countries.

We should be clear that new technological applications themselves are not going to transform or disrupt this trend – rather, without adequate policy steering, these trends will be exacerbated.

Policy debates about AI applications in India need to take these two issues seriously. AI applications will not be a panacea for addressing ‘India’s grand challenges’. Data bias and unequal access to technology gains will entrench existing socio-economic fissures, even making them technologically binding.

In addition to developing AI applications and creating a skilled workforce, the government needs to prioritize research that examines the complex social, ethical and governance challenges associated with the spread of AI-driven technologies. Blind technological optimism might entrench rather than alleviate the grand Indian challenge of inequity and growth.

This article was originally published in the Indian Express.

Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu
Math. Comp. 93 (), 3027-3058.
Abstract, references and article information

Ahmed Elshafei, Ana Cristina Ferreira, Miguel Sánchez and Abdelghani Zeghib
Trans. Amer. Math. Soc. 377 (), 5837-5862.
Abstract, references and article information

Rubén Medina and Andrés Quilis
Proc. Amer. Math. Soc. 152 (), 5137-5148.
Abstract, references and article information

E. Voronetsky
St. Petersburg Math. J. 35 (), 433-443.
Abstract, references and article information

Reggae artiste Jah Kettle says he was pleased with his recently concluded Canada tour and is now excited to release a new single, titled Nothing Gonna Take Your Love Away, done with fellow reggae act Ras Penco. "The fans were riveting and showed...

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...

Infiltration of peripheral immune cells after blood-brain barrier dysfunction causes severe inflammation after a stroke. Although the endothelial glycocalyx, a network of membrane-bound glycoproteins and proteoglycans that covers the lumen of endothelial cells, functions as a barrier to circulating cells, the relationship between stroke severity and glycocalyx dysfunction remains unclear. In this study, glycosaminoglycans, a component of the endothelial glycocalyx, were studied in the context of ischemic stroke using a photochemically induced thrombosis mouse model. Decreased levels of heparan sulfate and chondroitin sulfate and increased activity of hyaluronidase 1 and heparanase (HPSE) were observed in ischemic brain tissues. HPSE expression in cerebral vessels increased after stroke onset and infarct volume greatly decreased after co-administration of N-acetylcysteine + glycosaminoglycan oligosaccharides as compared with N-acetylcysteine administration alone. These results suggest that the endothelial glycocalyx was injured after the onset of stroke. Interestingly, scission activity of proHPSE produced by immortalized endothelial cells and HEK293 cells transfected with hHPSE1 cDNA were activated by acrolein (ACR) exposure. We identified the ACR-modified amino acid residues of proHPSE using nano LC–MS/MS, suggesting that ACR modification of Lys139 (6-kDa linker), Lys107, and Lys161, located in the immediate vicinity of the 6-kDa linker, at least in part is attributed to the activation of proHPSE. Because proHPSE, but not HPSE, localizes outside cells by binding with heparan sulfate proteoglycans, ACR-modified proHPSE represents a promising target to protect the endothelial glycocalyx.

α1-antitrypsin (AAT) regulates the activity of multiple proteases in the lungs and liver. A mutant of AAT (E342K) called ATZ forms polymers that are present at only low levels in the serum and induce intracellular protein inclusions, causing lung emphysema and liver cirrhosis. An understanding of factors that can reduce the intracellular accumulation of ATZ is of great interest. We now show that calreticulin (CRT), an endoplasmic reticulum (ER) glycoprotein chaperone, promotes the secretory trafficking of ATZ, enhancing the media:cell ratio. This effect is more pronounced for ATZ than with AAT and is only partially dependent on the glycan-binding site of CRT, which is generally relevant to substrate recruitment and folding by CRT. The CRT-related chaperone calnexin does not enhance ATZ secretory trafficking, despite the higher cellular abundance of calnexin-ATZ complexes. CRT deficiency alters the distributions of ATZ-ER chaperone complexes, increasing ATZ-BiP binding and inclusion body formation and reducing ATZ interactions with components required for ER-Golgi trafficking, coincident with reduced levels of the protein transport protein Sec31A in CRT-deficient cells. These findings indicate a novel role for CRT in promoting the secretory trafficking of a protein that forms polymers and large intracellular inclusions. Inefficient secretory trafficking of ATZ in the absence of CRT is coincident with enhanced accumulation of ER-derived ATZ inclusion bodies. Further understanding of the factors that control the secretory trafficking of ATZ and their regulation by CRT could lead to new therapies for lung and liver diseases linked to AAT deficiency.