An Eddie Murphy comedy that Eddie Murphy would probably prefer for everyone to forget is dominating the streaming charts on Prime Video.

What it is: GeoGuessr is a fun map-based game where students get virtually “dropped” somewhere in the world, and must explore the landscape around them through Google Street View to determine where in the world they are. When they’ve determined where in the world they are, they click on the world map to make a...

In this session, Monroe Porter will review some of the more common problem areas roofing contractors should consider when running their business.

FourKites has announced that Teva, a global provider of generic medicines, has achieved a 0.005% incident rate by leveraging FourKites’ global carrier visibility solution, NIC-Place.

Itron, Inc. has released its 2024 Resourcefulness Insight Report (“the report”) that explores the current trends and future expectations of artificial intelligence (AI) and machine learning (ML) on utility operations and strategies.

Manufacturers now expect logistics suppliers to further integrate with their operating systems DANX Carousel Chief Information Officer, Mohan Palaniandy, has told delegates at a recent supply chain transparency conference.

The Supreme Court has stripped the Securities and Exchange Commission of a major tool in fighting securities fraud.

The post The Supreme Court strips the SEC of a critical enforcement tool in fraud cases first appeared on Federal News Network.

Officials on President-elect Donald Trump’s transition team said this year’s transition planning efforts will be “about as different as possible” from 2016.

The post Trump still forgoing ‘critical’ agreements for transition planning first appeared on Federal News Network.

Location: Main Oversize- BQ3080.S455S45 2014

Location: Electronic Resource- 

While we all debate what critical race theory is and whether lawmakers should ban it from public schools, every honest person should agree on one thing: This theory is behind the curricula in school districts all over the country, shaping the minds of unsuspecting, malleable children.

Gio Gonzalez threw strikes on Thursday night – 78 to be exact, on 112 pitches — keying his one-hit work over eight dominant innings in the Nats’ 8-1 victory over the Reds. Gonzalez (2-1), the Nats’ starter most susceptible to wildness, had walked 11 in 20 innings, lasting no more than six innings in any of his previous four starts. But with the lead from the third inning on, Gonzalez was able to attack.

After a tough loss at Texas, the Zags bounced back in a big way On Sunday evening, all eyes in college basketball were on Spokane Arena, where a battle between “new blood” Gonzaga and the bluest of blue bloods Kentucky went down. A fervent fanbase stoked on by two-plus decades of increasing success, against a team that has been at the top of the sport since time immemorial…

Historically abundant predatory fish such as groupers and snappers remain at critically low numbers on Bermuda’s reefs based on international standards, according to a recently released report that monitored their status and trends by Bermudian scientist Dr Thaddeus Murdoch and his local team of research associates through the Bermuda Reef Ecosystem Assessment and Mapping [BREAM] […]

Knowing that today’s homes burn faster than ever, the National Fire Protection Association (NFPA) announced “Every Second Counts: Plan Two Ways Out” as the official theme for this year’s Fire Prevention Week campaign, October 8-14, 2017. Experts say you may have as little as two minutes (or even less) to safely escape a typical home fire from the time the smoke alarm sounds.

Cybersecurity researchers have disclosed six security flaws in the Ollama artificial intelligence (AI) framework that could be exploited by a malicious actor to perform various actions, including denial-of-service, model poisoning, and model theft. "Collectively, the vulnerabilities could allow an attacker to carry out a wide-range of malicious actions with a single HTTP request, including

Taiwanese network-attached storage (NAS) appliance maker Synology has addressed a critical security flaw impacting DiskStation and BeePhotos that could lead to remote code execution. Tracked as CVE-2024-10443 and dubbed RISK:STATION by Midnight Blue, the zero-day flaw was demonstrated at the Pwn2Own Ireland 2024 hacking contest by security researcher Rick de Jager. RISK:STATION is an "

Cisco has released security updates to address a maximum severity security flaw impacting Ultra-Reliable Wireless Backhaul (URWB) Access Points that could permit unauthenticated, remote attackers to run commands with elevated privileges. Tracked as CVE-2024-20418 (CVS score: 10.0), the vulnerability has been described as stemming from a lack of input validation to the web-based management

The U.S. Cybersecurity and Infrastructure Security Agency (CISA) on Thursday added a now-patched critical security flaw impacting Palo Alto Networks Expedition to its Known Exploited Vulnerabilities (KEV) catalog, citing evidence of active exploitation. The vulnerability, tracked as CVE-2024-5910 (CVSS score: 9.3), concerns a case of missing authentication in the Expedition migration tool that

Hewlett Packard Enterprise (HPE) has released security updates to address multiple vulnerabilities impacting Aruba Networking Access Point products, including two critical bugs that could result in unauthenticated command execution. The flaws affect Access Points running Instant AOS-8 and AOS-10 - AOS-10.4.x.x: 10.4.1.4 and below Instant AOS-8.12.x.x: 8.12.0.2 and below Instant AOS-8.10.x.x:

New evidence suggests that the larger system the Gulf Stream is part of is approaching a tipping point that could cause dramatic shifts in global weather patterns.

The Critical Transition: China’s Priorities for 2021 Research paper sysadmin 31 January 2017

This paper sets out the core issues for the Xi leadership, and focuses on what these might mean for the UK, particularly in the post-Brexit world and with the election of Donald Trump as US president.

In 2017 Xi Jinping will complete his first full five-year term as China’s leader. Towards the end of the year, in autumn, the country is due to hold its 19th Party Congress. This major meeting usually marks the moment when the Communist Party of China (CPC) assesses its performance over the previous five years, sets out political goals for the coming five-year period and makes new appointments.

Xi Jinping’s leadership has been characterized by a number of significant domestic and international policy strategies. China’s economic growth rate is slowing, and the country’s economy is undergoing major restructuring. Export-led manufacturing growth and capital investment in fixed assets are now being replaced by consumer-led and service-dominated expansion. Meanwhile, the role of the CPC has been rearticulated with a major anti-corruption struggle since 2013 that has sought to clear away a raft of different networks and senior officials and connected business people. Xi has proved a more communicative, more populist and more nationalistic leader than his predecessors. He is also crafting an image of himself as a more visionary leader.

Internationally, China is striving for a relevance and role that it has never had before. Its reach is felt in international organizations, regionally, and through its economic and resource needs. It has a role in global affairs that embraces places once considered on its periphery, such as Latin America, the Arctic and Antarctic Circles, and the Middle East. Its impact in Asia is particularly striking, marked by activity in the South China Sea, and a new kind of relationship with Russia, India and the US. The major Belt and Road Initiative, in particular, has started to outline a new expansiveness in China’s relations with the outside world, despite the largely abstract nature of its overall shape and form at the moment.

The themes and viewpoints in this collection of essays are particularly geared towards those with an interest in policy engagement with China. While setting out the core issues for the Xi leadership, it also focuses on what these might mean for the UK, particularly in the post-Brexit world and with the election of Donald Trump as US president. As the UK seeks a new kind of relationship with a rapidly changing China, this group of expert opinions maps out the key markers in the run up to 2021, when China is due to celebrate achieving the first of its centennial goals: the delivery of middle-income status and a moderately prosperous society.

Critical elections and the future of American politics 14 December 2022 — 9:00AM TO 10:15AM Anonymous (not verified) 8 December 2022 Chatham House

This event explores whether the United States is undergoing a critical change in the composition of the Republican and Democratic parties.

Drawing on current and historical events, Paul E. Peterson joins us to examine whether the United States is undergoing a critical change in the composition of the Republican and Democratic parties.

Key questions to consider include:

• What factors might be driving such an evolution within both parties?

• How could these dynamics affect the balance of power in Washington and in states?

This event is co-hosted with the Centre on US Politics at UCL, and the US and Americas programme at Chatham House would like to thank the British Association for American Studies for their generous support of this event.

Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology.

WS Harris
Jun 1, 1989; 30:785-807
Reviews

Lasse L. Wolf and Hong-Wei Zhang
Proc. Amer. Math. Soc. 152 (), 5445-5453.
Abstract, references and article information

Distinct cell types emerge from embryonic stem cells through a precise and coordinated execution of gene expression programs during lineage commitment. This is established by the action of lineage specific transcription factors along with chromatin complexes. Numerous studies have focused on epigenetic factors that affect embryonic stem cells (ESC) self-renewal and pluripotency. However, the contribution of chromatin to lineage decisions at the exit from pluripotency has not been as extensively studied. Using a pooled epigenetic shRNA screen strategy, we identified chromatin-related factors critical for differentiation toward mesodermal and endodermal lineages. Here we reveal a critical role for the chromatin protein, ARID4B. Arid4b-deficient mESCs are similar to WT mESCs in the expression of pluripotency factors and their self-renewal. However, ARID4B loss results in defects in up-regulation of the meso/endodermal gene expression program. It was previously shown that Arid4b resides in a complex with SIN3A and HDACS 1 and 2. We identified a physical and functional interaction of ARID4B with HDAC1 rather than HDAC2, suggesting functionally distinct Sin3a subcomplexes might regulate cell fate decisions Finally, we observed that ARID4B deficiency leads to increased H3K27me3 and a reduced H3K27Ac level in key developmental gene loci, whereas a subset of genomic regions gain H3K27Ac marks. Our results demonstrate that epigenetic control through ARID4B plays a key role in the execution of lineage-specific gene expression programs at pluripotency exit.

A critical juncture for Sudan’s democratic transition Expert comment LJefferson 28 March 2023

International pressure is essential to reach an agreement that establishes a credible civilian government.

The signing of the Framework Agreement (FA) on 5 December 2022 between Sudan’s military leaders and its leading pro-democracy parties is a major step to reversing the damage done by the disastrous military coup in October 2021.

The FA removes any formal role for the military in Sudan’s politics. A civilian head of state and prime minister will select the cabinet and chair the Defence and Security Council. The armed forces will be prohibited from non-military business activities and security sector reform will lead to a unified, professional and non-partisan national army. Elections are due to take place at the end of a two-year transitional period. 

Signatories included General Abdel Fatah Al Burhan, chair of the Sovereign Council and head of the Sudanese Armed Forces (SAF), General Mohamed Hamdan Dagalo (known as Hemedti), his deputy and Commander of the paramilitary Rapid Support Forces (RSF) and more than 40 civilian entities, including the Forces of Freedom and Change- Central Council (FFC-CC), a few other political parties, former armed movements, civil society organizations and professional associations. However, the agreement has faced criticism from the street for not being sufficiently radical, has been overshadowed at times by heightened tension between the two military leaders, and has seen sabotage attempts by supporters of the Bashir regime.

Building consensus on the Framework Agreement

The agreement meets most of the demands of the anti-coup camp, at least on paper. Yet doubts persist as to whether the military are genuine about handing over power, particularly among the neighbourhood-based resistance committees – the heart of the youth-led mobilization that forced the military to recognize the failure of their power grab. Peaceful protests against the coup have seen 125 killed and over 8,000 injured by government security forces. Many want to see Burhan and Hemedti held accountable.

Recognizing the need to expand popular support, FFC-CC leaders have been reaching out to other pro-democracy forces to build a united civilian front. They report increased buy-in from some resistance committees in the last few months, recognizing that street protests alone were not sufficient to overthrow the coup, and that engagement with the military is necessary to find a way out of the impasse.

The FA offers the only currently available path to embedding civilian politics in Sudan and has received active diplomatic support from UNITAMS, AU and IGAD (who form the Tripartite Mechanism), the Troika of the US, UK and Norway, alongside the EU, as well as Saudi Arabia and the UAE (who are members of ‘the Quad’ with the US and UK).

Broader public participation has also been developed through a series of conferences, facilitated by the Tripartite Mechanism, on five contentious issues – dismantling the old regime, the Juba Peace Agreement, Eastern Sudan, Transitional Justice and Security Sector Reform. Recommendations will be incorporated in a final political agreement. 

The political process has been overshadowed by increasingly visible tension between Burhan and Hemedti, seen in parallel foreign visits, conflicting public statements, and a heavy military presence in Khartoum. But concerns that SAF and the RSF were heading towards confrontation appear to have been assuaged thanks to international pressure and preliminary agreements reached between military and civilian signatories of the FA on security sector reform and integration. In a significant breakthrough, both sides have now agreed to draft the final agreement and transitional constitution, with the aim of forming a civilian government by 11 April.  

Potential spoilers and interests from Sudan’s regions

Progress has been made, but significant challenges remain, notably from supporters of the former Bashir regime in ‘the deep state’ and from Sudan’s historically marginalized peripheries. Old regime elements have been intensifying social media campaigns to derail the agreement and drive a wedge between the SAF and RSF, and have been accused of deliberately inciting instability in the peripheries to undermine the democratic transition. 

The Popular Defence Forces, established by the National Islamic Front in the 1990s, have been reactivated under different names in several parts of the country and there are reports of mobilization and recruitment of armed militias in Darfur. The recent public appearance of Ali Karti, the Secretary-General of the Islamic Movement, who has close relations with Islamists in SAF, has also caused renewed concern.

Two Darfuri armed movement leaders who signed the October 2020 Juba Peace Agreement (JPA) and are members of the current military-led government, have not signed the FA, allegedly due to concerns about their representation in the next government.

Despite intensive efforts to bring them on board, there is continuing disagreement over the inclusion of other members of ‘the Democratic Bloc’, a political alliance backed by Sudan’s influential neighbour Egypt, which is reportedly angry at being excluded from the Quad. The FFC-CC say that the door is open for the two Darfuri leaders and some other political parties, but they will not allow the agreement to be ‘diluted’ with political forces who intend to torpedo the transition, including by imposing a weak prime minister.

Both Burhan and Hemedti have courted support from the regions. Burhan used the 2020 SAF takeover of Al Fashaga in the contested eastern border region with Ethiopia to boost his national standing and secure backing from local tribal leaders; while Hemedti has sought to position himself as a champion of the peripheries, particularly in his Darfur heartlands, while simultaneously advancing his business interests.

Competition between them in building domestic powerbases, as well as alliances with neighbouring states, risks reigniting tensions, particularly given deep grievances and contrasting ambitions between and among Sudan’s diverse regional leaders and communities.

RAS genes are the most commonly mutated in human cancers and play critical roles in tumor initiation, progression, and drug resistance. Identification of targets that block RAS signaling is pivotal to develop therapies for RAS-related cancer. As RAS translocation to the plasma membrane (PM) is essential for its effective signal transduction, we devised a high-content screening assay to search for genes regulating KRAS membrane association. We found that the tyrosine phosphatase PTPN2 regulates the plasma membrane localization of KRAS. Knockdown of PTPN2 reduced the proliferation and promoted apoptosis in KRAS-dependent cancer cells, but not in KRAS-independent cells. Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling. Consistently, analysis of the TCGA database demonstrates that high expression of PTPN2 is significantly associated with poor prognosis of patients with KRAS-mutant pancreatic adenocarcinoma. These results indicate that PTPN2 is a key regulator of KRAS and may serve as a new target for therapy of KRAS-driven cancer.

Priyanka Tripathi
Dec 30, 2020; 0:jlr.RA120001190v1-jlr.RA120001190
Research Articles

Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) emerges as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide-1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.

Microtubules are polymers composed of αβ-tubulin subunits that provide structure to cells and play a crucial role in in the development and function of neuronal processes and cilia, microtubule-driven extensions of the plasma membrane that have sensory (primary cilia) or motor (motile cilia) functions. To stabilize microtubules in neuronal processes and cilia, α tubulin is modified by the posttranslational addition of an acetyl group, or acetylation. We discovered that acetylated tubulin in microtubules interacts with the membrane sphingolipid, ceramide. However, the molecular mechanism and function of this interaction are not understood. Here, we show that in human iPS cell-derived neurons, ceramide stabilizes microtubules, which indicates a similar function in cilia. Using proximity ligation assays, we detected complex formation of ceramide with acetylated tubulin in C. reinhardtii flagella and cilia of human embryonic kidney (HEK293T) cells, primary cultured mouse astrocytes, and ependymal cells. Using incorporation of palmitic azide and click chemistry-mediated addition of fluorophores, we show that a portion of acetylated tubulin is S-palmitoylated. S-palmitoylated acetylated tubulin is colocalized with ceramide-rich platforms (CRPs) in the ciliary membrane, and it is coimmunoprecipitated with Arl13b, a GTPase that mediates transport of proteins into cilia. Inhibition of S-palmitoylation with 2-bromo palmitic acid or inhibition of ceramide biosynthesis with fumonisin B1 reduces formation of the Arl13b-acetylated tubulin complex and its transport into cilia, concurrent with impairment of ciliogenesis. Together, these data show, for the first time, that CRPs mediate membrane anchoring and interaction of S-palmitoylated proteins that are critical for cilium formation, stabilization, and function. 

Concerns about local school systems can pose recruitment and retention hurdles for the armed services as they seek to meet the needs of military families.

Robbert Havekes
Dec 12, 2012; 32:18137-18149
BehavioralSystemsCognitive

The capabilities of the human ear are remarkable. We can normally detect acoustic stimuli down to a threshold sound-pressure level of 0 dB (decibels) at the entrance to the external ear, which elicits eardrum vibrations in the picometer range. From this threshold up to the onset of pain, 120 dB, our ears can encompass sounds that differ in power by a trillionfold. The comprehension of speech and enjoyment of music result from our ability to distinguish between tones that differ in frequency by only 0.2%. All these capabilities vanish upon damage to the ear's receptors, the mechanoreceptive sensory hair cells. Each cochlea, the auditory organ of the inner ear, contains some 16,000 such cells that are frequency-tuned between ~20 Hz (cycles per second) and 20,000 Hz. Remarkably enough, hair cells do not simply capture sound energy: they can also exhibit an active process whereby sound signals are amplified, tuned, and scaled. This article describes the active process in detail and offers evidence that its striking features emerge from the operation of hair cells on the brink of an oscillatory instability—one example of the critical phenomena that are widespread in physics.

The small town of Spruce Pine, North Carolina, is one of the only sources of high-purity quartz on Earth, but it has been left battered by the storm's heavy rains

A federal audit of Canada’s strategy to promote the extraction of critical minerals says the government isn’t giving due consideration to the potential impact of mining on the environment, biodiversity and Indigenous people.

President Trump and the U.S. Department of Education are wrong to target the valuable toolkit, argue David E. DeMatthews and Terri N. Watson.

Students who were chronically absent or at risk of dropping out before the coronavirus outbreak are even more at risk now that schools are closed, experts say.

Mining expert Barbara Arnold, professor of practice in mining engineering, joined a panel of experts to discuss how the United States will need to make dramatic advances to increase its technical- and skilled-labor workforce to power its green energy future and to become less reliant on foreign nations for securing materials used in both everyday devices and critical national security applications.

The government on Wednesday said 125 new projects have been taken up in the current financial year for exploration of critical minerals.

Every five years, the U.S. Department of Agriculture’s (USDA) National Agricultural Statistics Service (NASS) surveys every agricultural producer across the country and in Puerto Rico to obtain a complete account of the industry, its changes, and emerging trends. Less than 25 percent of Delaware producers have responded to the 2022 Ag Census, which could jeopardize farm policy and decision-making about disaster relief, community planning, technology development, and more.

AI is no longer a futuristic concept – it’s a mainstay in our daily lives, both personally and professionally. In the business world, AI is revolutionizing workflows, driving efficiency and speeding up processes. However, as organizations rush to benefit from this modern technology, they must prioritize the ethical and transparent [...]

Critical areas for productivity gains with data and AI was published on SAS Voices by Manisha Khanna

Critical Conversations on Islam and Asia Critical Conversations on Islam and Asia

TORONTO, canada — A teenager is in critical condition in a British Columbia children's hospital, sick with Canada's first presumptive human case of avian influenza. "This was a healthy teenager prior to this, so no underlying conditions," said provincial health officer Bonnie Henry in a news conference on Tuesday. "It just reminds us that in young people this is a virus that can progress and cause quite severe illness, and the deterioration that I mentioned was quite rapid." British Columbia health officials said on Saturday the province had detected Canada's first human case of H5 bird flu in a teenager. Henry said the province is still identifying the exact strain but assumes the case is H5N1. The World Health Organization says H5N1's risk to humans is low because there is no evidence of human transmission, but the virus has been found in an increasing number of animals, including cattle in the United States. Henry would not disclose the teen's gender or age but said the patient had first developed symptoms on November 2 and was tested on November 8, when admitted to a hospital. Symptoms included conjunctivitis, fever and coughing. As of Tuesday, the teen was hospitalized with acute respiratory distress syndrome, she said. The teen had no farm exposure but had been exposed to dogs, cats and reptiles, Henry said. No infection source had been identified. "That is absolutely an ongoing investigation." More severe illness takes place when the virus binds to receptors deep in the lungs, she said. Public health officials had identified and tested about three dozen contacts and had not found anyone infected with the virus. There has been no evidence that the disease is easily spread between people. But if that were to happen, a pandemic could unfold, scientists have said. Earlier in November, the U.S. Centers for Disease Control and Prevention asked that farm workers exposed to animals with bird flu be tested for the virus even if they did not have symptoms. Bird flu has infected nearly 450 dairy farms in 15 U.S. states since March, and the CDC has identified 46 human cases of bird flu since April. In Canada, British Columbia has identified at least 26 affected premises across the province, Henry said Tuesday, and numerous wild birds have tested positive. Canada has had no cases reported in dairy cattle and no evidence of bird flu in samples of milk.

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