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GOP Senate Majority Leader-Hopefuls Scramble To Address Trump Demands Ahead Of Inauguration

By Julianna Frieman Republican senators competing for the majority leader position vowed Sunday to address President-elect Donald Trump’s demands ahead of his inauguration. Trump revealed Sunday that the Senate leader of his GOP majority must support recess appointments to assure his Cabinet positions be confirmed expeditiously and unobstructed. The three senators contending for the leadership […]

The post GOP Senate Majority Leader-Hopefuls Scramble To Address Trump Demands Ahead Of Inauguration appeared first on Liberty Unyielding.



  • Law and Government

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'Everyone hopes to have different schedule in 2026'

Chief executive Guy Kinnings says the DP World Tour hopes "to have a different schedule in 2026" as golf's rulers continue to discuss a merger.




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Assisted dying bill dangerous, says Archbishop

His comments came ahead of an assisted dying bill being introduced to Parliament.




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Easy-fit prosthetics offer hope to thousands of Gaza amputees

Children are among the thousands to have lost limbs in Gaza, forcing them to learn a new way of life.




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'Norris' hopes crushed by Verstappen performance for the ages'

Lando Norris’ already slim world title hopes were crushed at the Sao Paulo Grand Prix by a performance for the ages from Max Verstappen.




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Archbishop of Canterbury Resigns

Justin Welby has stepped down over a church abuse scandal.




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Welch hopes to pass on legacy to female referees

Trailblazing referee Rebecca Welch says she hopes "somebody else picks up the legacy" as she is inducted into the National Football Museum's Hall of Fame.




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Iowa Pediatrician Blistered for Telling Trump Voters that He Hopes Their Children Die

A scumbag, left-wing (is there any other kind?) doctor in Iowa is facing an uncertain future at his hospital after he began posting obscene wishes on social media saying that he hopes the children of Trump voters are murdered. The creep is question is one Dr. Mayank Sharma, 35, a pediatric cardiology fellow for the […]

The post Iowa Pediatrician Blistered for Telling Trump Voters that He Hopes Their Children Die appeared first on The Lid.




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News24 | Archbishop of Canterbury Justin Welby announces resignation over abuse scandal

The leader of the world's Anglican communion, Archbishop of Canterbury Justin Welby, announced Tuesday he was resigning following a damning report that concluded the Church of England covered up a serial abuse case.





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Home Depot says shoplifting challenges aren't getting any easier

Home Depot's CFO said investments to combat retail theft are "paying off" but the operating environment is "getting harder and harder."




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Implementing Enterprise AI – Online workshop

Implementing Enterprise AI – Online workshop By Ajit Jaokar and Cheuk Ting Ho   Early bird discounted rate $599 USD     Introduction Launched for the first time, jointly delivered by Ajit Jaokar and Cheuk Ting Ho – Implementing Enterprise AI workshop is an online workshop targeting developers and strategists.  The workshop enables you to develop [...]




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Coding for #AI and #machinelearning – online course/workshop

Coding for #AI and #machinelearning – online course/workshop We are exploring a new way to learning how to code for AI and Machine Learning by applying ideas of  deliberate practise Starting Oct 2018 – the workshop has limited places Please contact info@futuretext.com if you want to sign up for our online workshop (300 USD)   [...]




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Sport | Marco Jansen hopes for better showing against spin as T20 series takes Highveld turn

Proteas all-rounder Marco Jansen, while acknowledging that spin has been a challenge for them in the ongoing T20 series against India, reckons things could be a bit different for Wednesday's third T20 in Centurion.




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Belt and Road Is Not a (Completely) Closed Shop

Belt and Road Is Not a (Completely) Closed Shop Expert comment sysadmin 22 March 2018

Though the infrastructure initiative will continue to be led in many places by Chinese investment, where there are benefits of scale, effectiveness and risk management, outside participation will be welcome.

Chinese Foreign Minister Wang Yi at the Belt and Road Forum in Yanqi Lake in May 2017. Photo: Getty Images.

First announced in 2013, President Xi Jinping’s Belt and Road Initiative promises, at a minimum, to improve infrastructure and connectivity between China and the rest of Eurasia. Any bold plan to finance infrastructure on a large-scale across so many low-income economies deserves a sympathetic ear and a positive reception. But many wonder how large the role can be for non-Chinese players in what is clearly an initiative of the Chinese government.

So far, Chinese state and policy banks account for the overwhelming majority of the financing – and this money then flows to Chinese enterprises, mainly state-owned. One study found that 89% of the work went to Chinese contractors on China-funded projects.

Yet, recently in Paris, Chinese Foreign Minister Wang Yi said the Belt and Road was a ‘sunshine initiative’ that was open and for all to benefit from. He declared that there were to be ‘no backroom deals. There is openness and transparency.’ The Belt and Road Initiative will ‘respect international rules’ and ‘will run according to market rules’.

There are some notable instances of Belt and Road projects changing to conform more to international rules as they develop. For example, work on the Belgrade–Budapest high speed rail link originally ran into problems. Contracts were allegedly awarded to Chinese companies without following the EU-mandated competitive procurement processes. Now, the most recent round of contracts is to be awarded by tender.

Such a switch perhaps does not herald the unrestricted ‘market rules’ that Wang speaks of, but it does highlight that China is willing to turn Belt and Road towards openness in certain instances. These will be cases where it clearly brings benefits for China – but also where private sector players can be convinced of good commercial returns. These benefits are most likely to lie in three areas: scale and access, effectiveness and risk management.

Mutual benefits

Firstly, scale and access. Belt and Road can achieve greater scale if additional financing comes in alongside the current Chinese state and policy bank lending. This can come both by working together with multilateral institutions and with private sector institutions. This will in turn require defining projects or structuring financing with attractive risk-return trade-offs. In some cases, this will be feasible – in others not.

Getting bigger also necessitates initiating meaningful Belt and Road activity in more countries. As the Belgrade–Budapest rail experience has shown, approaches vary in terms of competitive tendering requirements and consideration of non-Chinese bidders. An approach that works in, say, Tajikistan, may not be effective in Poland. This is a pragmatic recognition of context that is quite separate from debates on what the ‘right’ approach to these standards should be. Both these elements suggest that a more open Belt and Road will be a larger and more far-reaching one.

Secondly, effectiveness. Despite extensive experience building infrastructure within China, many Chinese companies are much less familiar operating outside of China. Western, Japanese and Korean companies can bring their own experience to the table and help the success of these projects. By doing so, they also put competitive pressure on Chinese companies to improve and upgrade, while providing opportunities to learn. This in turn creates a stronger, more productive Chinese economy.

Beyond physical hardware, the ‘software’ is also critical to success. Again foreign companies have much to contribute. Areas such as maintenance, training, legal and accounting services are all in demand. Indeed, many such British and other companies are already actively engaged in working on projects with Chinese companies to help in these areas.

Finally, risk management. Beyond the usual project management risk of large projects, Belt and Road brings additional challenges. Many countries have weak governance, internal divisions and security issues, all within distinctively different cultures and traditions. Chinese companies with little experience of local conditions will struggle. Going it alone may provide what is an illusion of control, but exposure to social and political dynamics can rebound on China in unexpected ways.

Cooperating with others who have a history of in-country experience is a way to manage these risks. Examples would include British and Chinese cooperation both at company and governmental level in engaging in particular African countries, in partnership with the relevant country government.

Mixed system

Mechanisms that encourage competitive choices and restrain corruption are positive, but mechanisms that slow decision-making to a crawl also prevent countries from getting benefits of infrastructure projects. Conversely, continuing along the current path of Chinese-led investment does have some clear attractions in certain settings, at least to those directly involved. It combines the ability of Chinese policy banks to provide large-scale funding in even high-risk environments with the relevant experience and production capacity of Chinese state-owned businesses. It allows for government-to-government deals, pragmatic negotiations and all-encompassing accords, at times out of the public eye. In many cases, it is hard to make a commercial case for the investments.

But in cases where there is mutual benefit, engagement and will, there will be a role for international partnerships.




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The Indo-Pacific: Geostrategic Perspectives 2019-24 – Workshop 2

The Indo-Pacific: Geostrategic Perspectives 2019-24 – Workshop 2 24 September 2019 — 9:00AM TO 2:00PM Anonymous (not verified) 4 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

The roundtable brought together stakeholders within the UK strategic and policymaking communities to explore British perceptions of evolving strategic shifts in the Indo-Pacific until 2024.

The roundtable took place at Chatham House in London. The report below contains a summary of the discussions.

Read a summary




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The Indo-Pacific: Geostrategic Perspectives 2019-20 – Workshop 1

The Indo-Pacific: Geostrategic Perspectives 2019-20 – Workshop 1 11 September 2019 — 10:00AM TO 2:30PM Anonymous (not verified) 4 September 2019 East-West Center, 1819 L St., NW, Suite 600, Washington, DC 20036, USA

The roundtable brought together stakeholders within the US strategic and policymaking communities to explore American perceptions of evolving strategic shifts in the Indo-Pacific until 2024. The roundtable was organized in cooperation with, and was held at, the East-West Center in Washington D.C.

The report below contains a summary of the discussions and an essay by Satu Limaye, Vice President and Director of the East-West Center in Washington, DC.

Read a summary report and essay




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The Indo-Pacific: Geostrategic Perspectives to 2024 - Workshop 3

The Indo-Pacific: Geostrategic Perspectives to 2024 - Workshop 3 17 October 2019 — 9:30AM TO 2:00PM Anonymous (not verified) 14 October 2019 Institut Francais des Relations Internationales, 27 rue de la Procession, 75740 Paris Cedex 15, France

The roundtable brought together stakeholders within the French strategic and policymaking community to explore French perceptions of evolving strategic shifts in the Indo-Pacific until 2024. The roundtable was organized in cooperation with, and was held at, the Institut français des relations internationals in Paris.

The report below contains a summary of the discussions and an essay by Céline Pajon, Research Fellow, Center for Asian Studies, Institut français des relations internationals.

Read a summary and essay




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The Indo-Pacific: Geostrategic Outlook to 2024 - Workshop 4

The Indo-Pacific: Geostrategic Outlook to 2024 - Workshop 4 26 November 2019 — 9:30AM TO 12:00PM Anonymous (not verified) 9 January 2020 Gateway House, Stevens Street, Colaba

The roundtable brought together stakeholders within India’s strategic and policymaking communities to explore Indian perceptions of evolving strategic shifts in the Indo-Pacific until 2024. The roundtable was organized in cooperation with, and was held at, Gateway House in Mumbai.

The report below contains a summary of the discussions and an essay by the International Security Studies Programme at Gateway House.

Read a summary and essay




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The Indo-Pacific: Geostrategic Outlook From Now to 2024 - Workshop 5

The Indo-Pacific: Geostrategic Outlook From Now to 2024 - Workshop 5 18 February 2020 — 12:00PM TO 4:30PM Anonymous (not verified) 17 February 2020 Langafonua Centre

The roundtable brought together stakeholders within Tonga’s strategic and policymaking communities to explore Tongan perceptions of evolving strategic shifts in the Indo-Pacific until 2024. The roundtable took place in Nuku’alofa and was co-hosted by the Royal Oceania Institute in Tonga.

The report below contains a summary of the discussions and an essay by Lady Fane Fakafanua, Director of Operations at the Royal Oceania Institute.

Read a summary and essay




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Phosphoproteome Analysis of E. coli Reveals Evolutionary Conservation of Bacterial Ser/Thr/Tyr Phosphorylation

Boris Macek
Feb 1, 2008; 7:299-307
Research




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Quantitative Phosphoproteomics of Early Elicitor Signaling in Arabidopsis

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




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A Multidimensional Chromatography Technology for In-depth Phosphoproteome Analysis

Claudio P. Albuquerque
Jul 1, 2008; 7:1389-1396
Research




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Quantitative Phosphoproteomics Applied to the Yeast Pheromone Signaling Pathway

Albrecht Gruhler
Mar 1, 2005; 4:310-327
Research




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The ICC response to Russia’s war gives hope for justice

The ICC response to Russia’s war gives hope for justice Expert comment NCapeling 19 March 2023

The ICC’s arrest warrants against Putin and Lvova-Belova show the commission of international crimes is not without consequences.

Warrants of arrest for Russian president Vladimir Putin and Maria Alekseyevna Lvova-Belova, commissioner for children’s rights in the president’s office, have been issued because the Pre-Trial Chamber II of the International Criminal Court (ICC) has reasonable grounds to believe they have committed war crimes.

Following an independent investigation and evidence-gathering by the ICC prosecutor Karim Khan in his first new case since taking office, the pair are accused of committing two different war crimes – the unlawful deportation of children from Ukraine to Russia, and the unlawful transfer of children from occupied areas of Ukraine to the Russian Federation.

The focus on those two war crimes is likely due to clear evidence that deportation and forcible transfer of thousands of Ukrainian children have occurred, as the Russian government was overt about its policy of taking Ukrainian children to Russia and placing them in camps or putting them up for adoption by Russian families.

Furthermore, in line with the Office of the Prosecutor’s policy on children, crimes against children are prioritized given their particularly vulnerable status.

Jurisdiction and enforcement

The ICC does not have jurisdiction over crimes committed fully in Russia by Russian nationals, as Russia is not a party to the Rome Statute which created the ICC.

However, it does have jurisdiction over war crimes, crimes against humanity, and genocide committed in Ukraine irrespective of who committed them, pursuant to two declarations lodged by Ukraine in 2014 accepting the Court’s jurisdiction over its territory from November 2013.

Making the warrants public enables the ICC to reclaim itself as a key avenue for ensuring accountability for international crimes, following a wave of criticism and disenchantment about its work

Although a prosecution has been initiated, it is ultimately for the judges of the ICC to decide on the accused’s fate. But the chances of Putin getting arrested or tried for these offences are slim.

The ICC lacks enforcement or police powers and depends on state cooperation to execute arrest warrants. Also, because it cannot try individuals in their absence, a trial or conviction cannot occur without Putin and Lvova-Belova being in custody.

But by issuing and unsealing these arrest warrants, the ICC is relying on the symbolic function of international criminal law – it is publicly naming and shaming Putin and Lvova-Belova for the commission of serious atrocities, and it is sending a message to other leaders and the international community that such actions are not without consequence.

The arrest warrants also give victims some form of vindication or recognition for their suffering and hope for justice in the future. And making the warrants public enables the ICC to reclaim itself as a key avenue for ensuring accountability for international crimes, following a wave of criticism and disenchantment about its work in Africa and delays in advancing its investigation on Afghanistan.

International courts gearing into action

This ICC case is the latest in a series of ongoing cases related to Russia’s war in Ukraine before different international courts and tribunals. Others include at least four cases before the European Court of Human Rights for events that occurred before Russia was excluded from the Council of Europe, such as the MH17 flight case and the annexation of Crimea.

They showcase an important feature of the global legal system and its judicial architecture that cannot be underestimated – the ability to quickly swing into action in response to violations of international law

Two cases have also been brought by Ukraine against Russia before the International Court of Justice – in 2017 and 2022 – with hearings scheduled for June. An unprecedented number of states parties have sought to intervene in one or more of these cases.

Each case must be considered on its own merits and the decisions cannot be prejudged. But they showcase an important feature of the global legal system and its judicial architecture that cannot be underestimated – the ability to quickly swing into action in response to violations of international law. In this case, the response was prompted by Russia’s aggression against Ukraine in breach of the United Nations Charter and fundamental principles of international law.

A starting point for a bigger case

The ICC prosecutor already has a broader investigation into other international crimes committed in Ukraine since 21 November 2013. So this is likely to be just the starting point of a much bigger case against Putin and other senior Russian officials for international crimes committed in the context of the war in Ukraine and within the ICC’s jurisdiction.

These potentially include other war crimes such as the indiscriminate or disproportionate targeting of civilians, crimes against humanity, and genocide.




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ROCKING HORSE SHOP .Diorama By Me!

Photo- Roy posted a photo:




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Quantitative phosphoproteomic analysis reveals involvement of PD-1 in multiple T cell functions [Signal Transduction]

Programmed cell death protein 1 (PD-1) is a critical inhibitory receptor that limits excessive T cell responses. Cancer cells have evolved to evade these immunoregulatory mechanisms by upregulating PD-1 ligands and preventing T cell–mediated anti-tumor responses. Consequently, therapeutic blockade of PD-1 enhances T cell–mediated anti-tumor immunity, but many patients do not respond and a significant proportion develop inflammatory toxicities. To improve anti-cancer therapy, it is critical to reveal the mechanisms by which PD-1 regulates T cell responses. We performed global quantitative phosphoproteomic interrogation of PD-1 signaling in T cells. By complementing our analysis with functional validation assays, we show that PD-1 targets tyrosine phosphosites that mediate proximal T cell receptor signaling, cytoskeletal organization, and immune synapse formation. PD-1 ligation also led to differential phosphorylation of serine and threonine sites within proteins regulating T cell activation, gene expression, and protein translation. In silico predictions revealed that kinase/substrate relationships engaged downstream of PD-1 ligation. These insights uncover the phosphoproteomic landscape of PD-1–triggered pathways and reveal novel PD-1 substrates that modulate diverse T cell functions and may serve as future therapeutic targets. These data are a useful resource in the design of future PD-1–targeting therapeutic approaches.




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Market Rally Contains Hopeful Message for the Economy

21 August 2020

Dame DeAnne Julius DCMG CBE

Senior Adviser, Chatham House; Distinguished Fellow, Global Economy and Finance Programme
There are good reasons for soaring stocks, despite a seeming disconnect from the recession.

2020-08-21-Stock-Exchange-New-York-US

Fearless Girl statue outside the New York Stock Exchange. Photo by Noam Galai/Getty Images.

Among the many unusual features of the pandemic-induced downturn is the disconnect between depressed real economies and buoyant financial markets. This is particularly evident in the US, where output fell 9.5% in the second quarter while the S&P 500 index rose by one-fifth.

This may suggest a huge financial bubble is in the making, or at least a highly optimistic view of a COVID-19 vaccine and treatments. Another possibility is that markets have a better grasp of the economic dynamics of a post-pandemic world than most nervous consumers and governments.

Certainly, markets have been helped by central bank largesse. In March, major central banks reacted forcefully to the possibility of a serious credit crunch with lending guarantees and bond purchases. Such liquidity interventions soothe troubled markets, but they also raise asset prices — potentially into bubble territory. This partly explains the markets’ strength. But it may not be the whole story.

A closer look at market performance suggests they may be on to something more interesting. Compare the US’s broad-based S&P 500 equity index with the tech-focused Nasdaq 100. Since the start of the year, the Nasdaq has risen 24% while the S&P is up just 5%. In the S&P itself, it has been the dramatic rise of the so-called Faang companies — Facebook, Amazon, Apple, Netflix and Google/Alphabet — that offset lesser performances by the other 495 companies. This sharp difference reflects two forces.

First, the COVID-19 crisis has had vastly different effects on different sectors. Lockdown brought a sudden increase in demand for the technology services that enable home learning (with school closures), homeworking (especially by office workers), home entertainment (instead of cinemas and theatres), home shopping (instead of physical shops), and home deliveries of almost everything else, including food. The Faang companies benefited disproportionally from this surge in demand as their production is scalable. Much of it could also be delivered by employees who themselves worked from home. The rise in their share prices reflects this.

Meanwhile, other sectors suffered massively. In the UK, the overall drop in gross domestic product of 20% in the second quarter was led by a fall of 87% in the accommodation and food services sector, which was severely affected by government restrictions. About one-quarter of the UK workforce, according to official figures, was also furloughed or temporarily off work without pay during lockdown. The fall in the share prices of hotels, restaurant franchises and airlines reflects such factors. 

The second driver of rising markets is that they are forward-looking while economic statistics reflect the past. For example, that UK GDP shrank during the second quarter is less interesting to a financial investor than the fact that during two months (May and June) GDP expanded by 2.4% and 8.7% respectively. In other words, output troughed in April but recovery began in May and accelerated in June as lockdown restrictions were eased. 

It is likely that rapid adaptations by companies and consumers to the pandemic-supercharged trends are already under way. In Britain, the share of retail sales (excluding fuel) made by ecommerce rose from around 7% in 2010 to 20% at the beginning of 2020 — it has since jumped to more than 30%. 

One-third of those officially working from home meanwhile say that they would like to do that permanently, according to the Centre for Economics and Business Research, and many large companies have offered their staff this choice.

Even in labour-intensive sectors such as healthcare and government services there has been a replacement of face-to-face delivery with digital booking and screen-based consultations.

Still, while this may help some companies in certain sectors, it does not imply a smooth recovery for the whole economy. Rather, it augurs a period of disruption as new companies, new business models and new job openings emerge. If the pandemic has ignited a Schumpeterian process of creative destruction, that is likely to continue whether or not effective vaccines and treatments ever come. 

Governments should ease the pain of this disruption with supportive fiscal and monetary policies, but they should not try to slow it down. The hopeful market message is that one lasting consequence of COVID-19 may be the rejuvenation of productivity growth that eventually spreads far beyond tech. 

This article was originally published in the Financial Times.




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Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury

Yi-Han Lin
Dec 1, 2020; 19:2030-2046
Research




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In depth characterization of the Staphylococcus aureus phosphoproteome reveals new targets of Stk1

Nadine Prust
Dec 17, 2020; 0:RA120.002232v1-mcp.RA120.002232
Research




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Sterol regulatory element-binding protein Sre1 regulates carotenogenesis in the red yeast Xanthophyllomyces dendrorhous

Melissa Gómez
Dec 1, 2020; 61:1658-1674
Research Articles




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Sterol regulatory element-binding protein Sre1 regulates carotenogenesis in the red yeast Xanthophyllomyces dendrorhous [Research Articles]

Xanthophyllomyces dendrorhous is a basidiomycete yeast that produces carotenoids, mainly astaxanthin. Astaxanthin is an organic pigment of commercial interest due to its antioxidant and coloring properties. X. dendrorhous has a functional SREBP pathway, and the Sre1 protein is the SREBP homolog in this yeast. However, how sterol regulatory element (Sre)1 promotes the biosynthesis of sterols and carotenoids in X. dendrorhous is unknown. In this work, comparative RNA-sequencing analysis between modified X. dendrorhous strains that have an active Sre1 protein and the WT was performed to identify Sre1-dependent genes. In addition, Sre1 direct target genes were identified through ChIP combined with lambda exonuclease digestion (ChIP-exo) assays. SRE motifs were detected in the promoter regions of several Sre1 direct target genes and were consistent with the SREs described in other yeast species. Sre1 directly regulates genes related to ergosterol biosynthesis as well as genes related to the mevalonate (MVA) pathway, which synthesizes the building blocks of isoprenoids, including carotenoids. Two carotenogenic genes, crtE and crtR, were also identified as Sre1 direct target genes. Thus, carotenogenesis in X. dendrorhous is regulated by Sre1 through the regulation of the MVA pathway and the regulation of the crtE and crtR genes. As the crtR gene encodes a cytochrome P450 reductase, Sre1 regulates pathways that include cytochrome P450 enzymes, such as the biosynthesis of carotenoids and sterols. These results demonstrate that Sre1 is a sterol master regulator that is conserved in X. dendrorhous.




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Conserved biophysical features of the CaV2 presynaptic Ca2+ channel homologue from the early-diverging animal Trichoplax adhaerens [Membrane Biology]

The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts toward dependence on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for CaV1–CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage–activated currents that are larger in external Ba2+ than in Ca2+; voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of presynaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis.




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Radiosensitization by Kinase Inhibition Revealed by Phosphoproteomic Analysis of Pancreatic Cancer Cells [Research]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers and known for its extensive genetic heterogeneity, high therapeutic resistance, and strong variation in intrinsic radiosensitivity. To understand the molecular mechanisms underlying radioresistance, we screened the phenotypic response of 38 PDAC cell lines to ionizing radiation. Subsequent phosphoproteomic analysis of two representative sensitive and resistant lines led to the reproducible identification of 7,800 proteins and 13,000 phosphorylation sites (p-sites). Approximately 700 p-sites on 400 proteins showed abundance changes after radiation in all cell lines regardless of their phenotypic sensitivity. Apart from recapitulating known radiation response phosphorylation markers such as on proteins involved in DNA damage repair, the analysis uncovered many novel members of a radiation-responsive signaling network that was apparent only at the level of protein phosphorylation. These regulated p-sites were enriched in potential ATM substrates and in vitro kinase assays corroborated 10 of these. Comparing the proteomes and phosphoproteomes of radiosensitive and -resistant cells pointed to additional tractable radioresistance mechanisms involving apoptotic proteins. For instance, elevated NADPH quinine oxidoreductase 1 (NQO1) expression in radioresistant cells may aid in clearing harmful reactive oxygen species. Resistant cells also showed elevated phosphorylation levels of proteins involved in cytoskeleton organization including actin dynamics and focal adhesion kinase (FAK) activity and one resistant cell line showed a strong migration phenotype. Pharmacological inhibition of the kinases FAK by Defactinib and of CHEK1 by Rabusertib showed a statistically significant sensitization to radiation in radioresistant PDAC cells. Together, the presented data map a comprehensive molecular network of radiation-induced signaling, improves the understanding of radioresistance and provides avenues for developing radiotherapeutic strategies.




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Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury [Research]

Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, although AKI has been recognized as a disease with long-term sequelae, partly because of the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including the transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively, by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2950 phosphosites through multi-proteomics analyses. Among them, we identified an array of highly promising candidate marker proteins indicative of disease onset and progression accompanied by immunoblot validations, and further denoted the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.




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In depth characterization of the Staphylococcus aureus phosphoproteome reveals new targets of Stk1 [Research]

Staphylococcus aureus is a major cause of infections worldwide and infection results in a variety of diseases. As of no surprise, protein phosphorylation is an important game player in signaling cascades and has been shown to be involved in S. aureus virulence. Albeit long neglected, eukaryotic-type serine/threonine kinases in S. aureus have been implicated in this complex signaling cascades. Due to the sub-stoichiometric nature of protein phosphorylation and a lack of suitable analysis tools, the knowledge of these cascades is however, to date, still limited.

Here, were apply an optimized protocol for efficient phosphopeptide enrichment via Fe3+-IMAC followed by LC-MS/MS to get a better understanding of the impact of protein phosphorylation on the complex signaling networks involved in pathogenicity. By profiling a serine/threonine kinase and phosphatase mutant from a methicillin-resistant S. aureus mutant library, we generated the most comprehensive phosphoproteome dataset of S. aureus to date, aiding a better understanding of signaling in bacteria. With the identification of 3800 class I p-sites we were able to increase the number of identifications by more than 21 times compared to recent literature. In addition, we were able to identify 74 downstream targets of the only reported eukaryotic-type Ser/Thr kinase of the S. aureus strain USA300, Stk1. This work allowed an extensive analysis of the bacterial phosphoproteome and indicates that Ser/Thr kinase signaling is far more abundant than previously anticipated in S. aureus.




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Angels' hope: Ohtani returns as DH in May

Brad Ausmus held his first media session of the spring on the day pitchers and catchers officially reported on Tuesday, giving updates on rehabbing players such as Shohei Ohtani, Albert Pujols and Zack Cozart.




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HIV: Breakthrough study raises hopes of effective prevention if drug’s cost can be lowered




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Anti-bullying programme is launched by orthopaedic trainees




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Hope, Peace and Reconciliation: Pope Francis in Mozambique

Hope, Peace and Reconciliation: Pope Francis in Mozambique Expert comment sysadmin 4 September 2019

A papal visit will highlight the importance of the recently signed peace agreement between the government and opposition.

Sales of papal-pictured capulanas have been brisk. Photo: Chatham House.

Pope Francis’ visit to Mozambique on 4–6 September comes at a critical political moment. The theme for the papal Africa trip (which also includes Madagascar and Mauritius) is ‘pilgrim of hope, peace and reconciliation’. This is especially relevant for Mozambique, as this is the first week of the official campaign for Mozambique’s sixth national elections on 15 October.

It is also the one-month anniversary of the Maputo Accords for Peace and Reconciliation between the government and the armed opposition, RENAMO (and the fifth anniversary of the previous such agreement in 2014).

What is unusual is that the pope accepted to visit Mozambique just after a peace accord and in the run-up to national elections. Something similar has happened only once, when Pope John Paul II visited Angola in June 1992 (following the Bicesse Accords) prior to the country’s first ever national elections in September. Unfortunately Pope John Paul’s preaching of reconciliation and pluralism failed and civil war resumed some months later, following rejection of the preliminary election results. Angola’s civil war only finally ended a decade later in 2002.

The last papal visit to Mozambique was also by Pope John Paul II in 1988, when civil war was still ongoing, and the country was still a single party state. Despite the war, massive congregations attended and RENAMO reached local ceasefires and agreements to maintain electricity supply to honour the visit. Some of the seeds for the Rome peace process were laid during this trip – especially as it also represented a formal reconciliation of FRELIMO, the ruling party, with the Catholic Church.

This papal visit to Mozambique is equally anticipated, as was highlighted several times during speeches at the 6 August peace agreement signing in Maputo. When I was in Maputo last month, sales of papal-pictured capulanas (a Mozambican sarong) were brisk and Mozambican television carried countdown clocks on many programmes for the touchdown of Pope Francis on national soil.

The Catholic Church has played an instrumental role in promoting peace in Mozambique over the years. The 1977–92 civil war ended through negotiations hosted at the Sant’ Egidio lay community in Rome, and the current Archbishop of Bologna, Dom Matteo Zuppi (who led the Sant’ Egido negotiations in 1992 and is soon to be made a cardinal) was an official witness to 6 August accords signing.

When targeted armed conflict resumed in 2013, faith groups once more re-engaged and in 2016 Sant’ Egidio once more co-led mediation efforts, less successfully than in 1991–92. Sant’ Egidio (including during a presidential visit to Rome in July) contributed to convincing the Vatican that this papal visit should occur before the October elections.

President Filipe Nyusi anxiously wanted this visit to occur before the elections. He is seeking re-election for his second and final term and a papal visit should help win some votes. His party, FRELIMO, is also worried about securing a majority in the national assembly, as it has been weakened by patchy delivery of services and ongoing high-level corruption scandals.

This year, President Nyusi’s priorities have been to show that he can attract international investment (such as Andarko’s recently announced final investment decision on its gas project), a peace agreement with RENAMO (the August agreements) and a papal visit, so a successful trip would complete his goals.

The pope’s ‘hope, peace and reconciliation’ message of his visit is important. Twice previously, the FRELIMO-led government and RENAMO have reached definitive agreements, in Rome (1992) and Maputo (2014), but failed to fully end bloodshed. This new August 2019 agreement is the third attempt, and if it is to last, it will require political goodwill, compromise and an acceptance of more inclusive national politics by both parties.

There are two immediate threats to this agreement. The first is the forthcoming 15 October elections and their conduct could make or break it. Accepting reconciliation and greater pluralism underpins this agreement, but RENAMO expects to increase its share of the parliamentary vote and win a majority in some provinces (and therefore indirectly elect their choice for governor).

A second threat is the ‘Military Junta’, a RENAMO splinter group that claims to be 500 strong, but probably accounts for 80 armed persons. It rejects the 6 August agreement and warns that it could disrupt the elections. This group has asked for mediation, and hopefully can be accommodated in a side deal to the main one agreed in August, which already provides for the reintegration of over 5,000 RENAMO supporters and combatants.

A recent Chatham House research paper on elite bargains in Mozambique concluded that the October elections will be the first immediate test of the August agreement. If the elections pass without significant electoral manipulation or violence and this August deal sticks on the third attempt, the domestic focus should then move onto poverty reduction, combating inequality, education and solving the new security crisis with Islamic militants in Cabo Delgado province.




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2025 Luis J. Alvarez and Admiral Grace M. Hopper Postdoc Fellowship in Computing Sciences

2025 Luis J. Alvarez and Admiral Grace M. Hopper Postdoc Fellowship in Computing Sciences - 102564 Division: AC-Computing Luis J. Alvarez Postdoctoral Fellowship and Admiral Grace M. Hopper Postdoctoral Fellowship in Computing Sciences The Computing Sciences Area (https://cs.lbl.gov/) at Lawrence Berkeley National Laboratory (https://www.lbl.gov) is now accepting applications for two distinguished postdoctoral fellowships in Computing Sciences: • Luis W. Alvarez Postdoctoral Fellowship, and • Admiral Grace M. Hopper Postdoctoral Fellowship. Researchers in computer science, mathematics, data science, or any computational science discipline who have received their Ph.D. no earlier than January 1, 2022 but no later than September 30, 2025 are encouraged to apply. Only one (1) application is needed and it will be considered for both postdoctoral fellowships. The successful candidates will participate in research activities in computer science, mathematics, data science, or any computational science discipline of interest to the Computing Sciences Area and Berkeley Lab. Alvarez Fellows apply advances in computer science, mathematics, computational science, data science, machine learning or AI to computational modeling, simulations, and advanced data analytics for scientific discovery in materials science, biology, astronomy, environmental science, energy, particle physics, genomics, and other scientific domains. Hopper Fellows concentrate on the development and optimization of scientific and engineering applications leveraging high-speed network capability provided by the Energy Sciences Network or run on next-generation high performance computing and data systems hosted by the National Energy Research Scientific Computing Center at Berkeley Lab. Since its founding in 2002, Berkeley Lab’s Luis W. Alvarez Postdoctoral Fellowship (go.lbl.gov/alvarez) has cultivated exceptional early career scientists who have gone on to make outstanding contributions to computer science, mathematics, data science, and computational sciences. The Admiral Grace Hopper Postdoctoral Fellowship (go.lbl.gov/hopper) was first awarded in 2015 with the goal of enabling early career scientists to make outstanding contributions in computer science and high performance computing (HPC) research. About Computing Sciences at Berkeley Lab: Whether running extreme-scale simulations on a supercomputer or applying machine-learning or data analysis to massive datasets, scientists today rely on advances in and integration across applied mathematics, computer science, and computational science, as well as large-scale computing and networking facilities, to increase our understanding of ourselves, our planet, and our universe. Berkeley Labs Computing Sciences Area researches, develops, and deploys new tools and technologies to meet these needs and to advance research in our core capabilities of applied mathematics, computer science, data science, and computational science. In addition to fundamental advances in our core capabilities, we impact such areas as astrophysics and cosmology, accelerator physics, chemical science and materials science, combustion, fusion energy, nuclear physics, biology, climate change, and HPC systems and network technology. Research areas in Computing Sciences include but are not limited to: • Developing scientific applications and software technologies for extreme-scale and energy-efficient • Developing mathematical modeling for complex scientific problems • Designing algorithms to improve the performance of scientific applications • Researching digital and post-digital computer architectures for science • Developing and advancing extreme-scale scientific data management, analysis, and visualization • Developing and advancing next-generation machine learning, AI, and data science approaches for science • Advancing quantum computing and networking technologies, software, algorithms and applications • Evaluating or developing new and promising HPC systems and networking technologies • Researching methods to control and manage next-generation networks • Managing scientific data and workflows in distributed environments Qualifications: • Requires a Ph.D. in computer science, mathematics, computational science, or related discipline. • Candidates must have no more than 3 years of Postdoctoral Researcher or similar experience. • Expertise with advanced algorithms, software techniques, HPC systems and/or networking in a related research field. • Demonstrated creativity and the ability to perform independent research. • Demonstrated excellence in a related research field. • Ability to develop new cross-disciplinary partnerships that use advanced computational and/or mathematical techniques to produce unique lab capabilities. • Excellent communication skills with the ability to facilitate communications and collaborations with internal and external stakeholders. Additional Desired Qualifications: • Knowledge of advanced computing and high-performance computing. Application Process: 1. As part of your application process, you must upload and submit the following materials with your online application. 1. Cover letter 2. CV, with publication list included 3. Research Statement (no more than five (5) pages in length when printed using standard letter-size (8.5 inch x 11 inch) paper with 1-inch margins (top, bottom, left, and right) and a font size not smaller than 11 point; figures and references cited, if included, must fit within the five-page limit) 4. Contact information (name, affiliation, and email address) of at least three (3) individuals who will be able to provide letters of reference. 2. Application deadline: October 31, 2024. * It is highly advisable that you have all the required application materials and information ready and available prior to completing and submitting your application. Your application will not be considered complete if any of the above information is missing. Tentative Application Timeline: The Computing Sciences Fellowship Selection Committee is made up of a diverse representation of scientists and engineers across Berkeley Lab’s Computing Sciences Area who will conduct a thorough review of all applications received. • Application deadline: October 31, 2024 • Review and Selection: October 2024 - December 2024 • Decisions made: January/February 2025 Want to learn more about working at Berkeley Lab? Please visit: careers.lbl.gov How To Apply Apply directly online at http://50.73.55.13/counter.php?id=290341 and follow the on-line instructions to complete the application process. Berkeley Lab is committed to inclusion, diversity, equity and accessibility and strives to continue building community with these shared values and commitments. Berkeley Lab is an Equal Opportunity and Affirmative Action Employer. We heartily welcome applications from women, minorities, veterans, and all who would contribute to the Labs mission of leading scientific discovery, inclusion, and professionalism. In support of our diverse global community, all qualified applicants will be considered for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, or protected veteran status. Equal Opportunity and IDEA Information Links: Know your rights, click here (http://www.dol.gov/ofccp/regs/compliance/posters/ofccpost.htm) for the supplement: Equal Employment Opportunity is the Law and the Pay Transparency Nondiscrimination Provision (https://www.dol.gov/sites/dolgov/files/ofccp/pdf/pay-transp_%20English_formattedESQA508c.pdf) under 41 CFR 60-1.4.




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