We performed an in-depth characterization and comparison of the pediatric and adult urinary glycomes using a nanoLC-MS/MS based glycomics method, which included normal healthy pediatric (1–10 years, n = 21) and adult (21–50 years, n = 22) individuals. A total of 116 N-glycan compositions were identified, and 46 of them could be reproducibly quantified. We performed quantitative comparisons of the 46 glycan compositions between different age and sex groups. The results showed significant quantitative changes between the pediatric and adult cohorts. The pediatric urinary N-glycome was found to contain a higher level of high-mannose (HM), asialylated/afucosylated glycans (excluding HM), neutral fucosylated and agalactosylated glycans, and a lower level of trisialylated glycans compared with the adult. We further analyzed gender-associated glycan changes in the pediatric and adult group, respectively. In the pediatric group, there was almost no difference of glycan levels between males and females. In adult, the majority of glycans were more abundant in males than females, except the high-mannose and tetrasialylated glycans. These findings highlight the importance to consider age-matching and adult sex-matching for urinary glycan studies. The identified normal pediatric and adult urinary glycomes can serve as a baseline reference for comparisons to other disease states affected by glycosylation.

Endometrial carcinoma (EC) is the most common gynecologic malignancy in the United States, with limited effective targeted therapies. Endometrial tumors exhibit frequent alterations in protein kinases, yet only a small fraction of the kinome has been therapeutically explored. To identify kinase therapeutic avenues for EC, we profiled the kinome of endometrial tumors and normal endometrial tissues using Multiplexed Inhibitor Beads and Mass Spectrometry (MIB-MS). Our proteomics analysis identified a network of kinases overexpressed in tumors, including Serine/Arginine-Rich Splicing Factor Kinase 1 (SRPK1). Immunohistochemical (IHC) analysis of endometrial tumors confirmed MIB-MS findings and showed SRPK1 protein levels were highly expressed in endometrioid and uterine serous cancer (USC) histological subtypes. Moreover, querying large-scale genomics studies of EC tumors revealed high expression of SRPK1 correlated with poor survival. Loss-of-function studies targeting SRPK1 in an established USC cell line demonstrated SRPK1 was integral for RNA splicing, as well as cell cycle progression and survival under nutrient deficient conditions. Profiling of USC cells identified a compensatory response to SRPK1 inhibition that involved EGFR and the up-regulation of IGF1R and downstream AKT signaling. Co-targeting SRPK1 and EGFR or IGF1R synergistically enhanced growth inhibition in serous and endometrioid cell lines, representing a promising combination therapy for EC.

Complex protein glycosylation occurs through biosynthetic steps in the secretory pathway that create macro- and microheterogeneity of structure and function.  Required for all life forms, glycosylation diversifies and adapts protein interactions with binding partners that underpin interactions at cell surfaces and pericellular and extracellular environments. Because these biological effects arise from heterogeneity of structure and function, it is necessary to measure their changes as part of the quest to understand nature.  Quite often, however, the assumption behind proteomics that post-translational modifications are discrete additions that can be modeled using the genome as a template does not apply to protein glycosylation.  Rather, it is necessary to quantify the glycosylation distribution at each glycosite and to aggregate this information into a population of mature glycoproteins that exist in a given biological system.  To date, mass spectrometric methods for assigning singly glycosylated peptides are well-established.  But it is necessary to quantify glycosylation heterogeneity accurately in order to gauge the alterations that occur during biological processes.  The task is to quantify the glycosylated peptide forms as accurately as possible and then apply appropriate bioinformatics algorithms to the calculation of micro- and macro-similarities.  In this review, we summarize current approaches for protein quantification as they apply to this glycoprotein similarity problem.

Dance of the Trillions: Developing Countries and Global Finance Book sysadmin 6 July 2018

David Lubin tells the story of what makes money flow from high-income countries to lower-income ones; what makes it flow out again; and how developing countries have sought protection against the volatility of international capital flows.

Selected by the Financial Times as one of the best economics books of 2018, Dance of the Trillions traces an arc from the 1970s, when developing countries first gained access to international financial markets, to the present day.

Underlying this story is a discussion of how the relationship between developing countries and global finance appears to be moving from one governed by the ‘Washington Consensus’ to one more likely to be shaped by Beijing.

This book is part of the Insights series.

Praise for Dance of the Trillions

About the author

David Lubin is managing director and head of emerging markets economics at Citi, an American bank, where he is responsible for a team of more than 30 economists in 15 locations globally.

Purchase

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

The faithful segregation, or “partition,” of many low-copy number bacterial plasmids is driven by plasmid-encoded ATPases that are represented by the P1 plasmid ParA protein. ParA binds to the bacterial nucleoid via an ATP-dependent nonspecific DNA (nsDNA)-binding activity, which is essential for partition. ParA also has a site-specific DNA-binding activity to the par operator (parOP), which requires either ATP or ADP, and which is essential for it to act as a transcriptional repressor but is dispensable for partition. Here we examine how DNA binding by ParA contributes to the relative distribution of its plasmid partition and repressor activities, using a ParA with an alanine substitution at Arg351, a residue previously predicted to participate in site-specific DNA binding. In vivo, the parAR351A allele is compromised for partition, but its repressor activity is dramatically improved so that it behaves as a “super-repressor.” In vitro, ParAR351A binds and hydrolyzes ATP, and undergoes a specific conformational change required for nsDNA binding, but its nsDNA-binding activity is significantly damaged. This defect in turn significantly reduces the assembly and stability of partition complexes formed by the interaction of ParA with ParB, the centromere-binding protein, and DNA. In contrast, the R351A change shows only a mild defect in site-specific DNA binding. We conclude that the partition defect is due to altered nsDNA binding kinetics and affinity for the bacterial chromosome. Furthermore, the super-repressor phenotype is explained by an increased pool of non-nucleoid bound ParA that is competent to bind parOP and repress transcription.

Zimbabwe Futures 2030: Policy Priorities for Industrialization, Agri-Business and Tourism 6 June 2019 — 9:30AM TO 1:15PM Anonymous (not verified) 21 June 2019 Bulawayo, Zimbabwe

An employment judge has cleared the way for Farah Jameel, a former chair of the BMA’s General Practitioners Committee for England (GPCE), to go ahead with claims of discrimination and unfair dismissal against the association over her removal from the post during maternity leave.Jameel, who was elected the first female chair in November 2021, was put on temporary suspension in 2022 after complaints by BMA staff. The BMA told her in August 2023 that her contract was being terminated.The contract described her as a contractor providing consultancy services rather than an employee. But in a preliminary ruling the employment judge Natasha Joffe has held that Jameel was in reality an office holder and an employee, opening the way for her claims to proceed to a full hearing by an employment tribunal.The GPCE passed a vote of no confidence in Jameel in July 2023, as a means of electing a new...

The National Institute for Health and Care Excellence (NICE) has recommended that all women with suspected endometriosis be offered an early transvaginal ultrasound scan, even if the pelvic or abdominal examination is normal.In its updated guideline1 on the diagnosis and management of endometriosis, NICE recommends specialist ultrasound as an alternative to magnetic resonance imaging for investigating suspected cases of the condition in secondary care.The updated guideline follows recent reports from both the National Confidential Enquiry into Patient Outcome and Death2 and Endometriosis UK which highlighted problems with delayed diagnoses, partly owing to a lack of awareness among healthcare professionals of the condition and how it presents. Such delays can result in prolonged suffering, ill health, and risks to fertility, the reports warned.Other new and updated recommendations include asking women with suspected endometriosis if any first degree relatives have a history of the condition, and considering neurodiversity when taking into account...

Ukraine crisis could trigger cascading risks globally Expert comment NCapeling 16 March 2022

The effects on the wider world from the Ukraine invasion go far beyond the waves of shock and horror being felt from this escalating conflict.

Russia and Ukraine rank 11th and 55th respectively in terms of their national economies but, for the global supply of critical resources such as energy, food, and minerals, these two countries together are far bigger hitters – and both the threat and reality of resource flows from them being reduced have already driven up global prices.

The world is already facing a cost-of-living squeeze coming out of the COVID-19 pandemic, so further price spikes or supply constraints have the potential to seriously undermine food and energy security, equitable access to basic goods and services, and social stability around the world – which can then potentially create systemic risks for economies and societies.

The global implications of the Ukraine conflict are only just beginning to be explored fully but the immediate impacts of the crisis on global markets are already well-documented. In the first few days after Russia’s invasion, energy prices spiked, triggering further fertilizer price rises – as fertilizer production is highly energy intensive – which in turn is contributing to food price rises because fertilizer costs are an important factor in food production.

Interruptions to shipping in the region around Ukraine – as well as globally – have impeded the flow of goods which pushed prices up even further, while economic sanctions on cross-border flows of goods and finance are further adding to market pressures. But this is just the start – these impacts will bring ripple effects which propagate far beyond their point of origin, known as ‘cascading risks’.

Risk is a combination of hazard, exposure, and vulnerability – in terms of the Ukraine invasion, the hazard is the conflict and its immediate impacts on the societies and economies of Ukraine and Russia, while exposure relates to the degree to which other countries are likely to be affected depending on how much they are integrated into the global economy or the ‘just in time’ nature of their supply chains.

Vulnerability relates to a society’s capacity to mitigate the harmful impacts of the conflict, such as controlling borders, sourcing alternative goods from suppliers, or protecting against price or supply shocks.

Risk cascades – the second- and third-order impacts of the original hazard and of responses to that hazard – can interact across sectoral boundaries – as with energy and food, for example – and their compound effect can lead to overall systemic risks for society.

Anticipating this potential is essential to understanding the nature and scale of the global ramifications being felt from the Ukraine conflict. Recent work in the UK to assess levels of cascading risks resulting from a changing climate – the UK Climate Change Risk Assessment – provides a valuable framework for thinking about this area.

It examines key pathways for risk to cascade through global systems – when applied to the situation in Ukraine, these pathways and their interactions offer an indication of the scale of crisis that citizens face far beyond Ukraine’s and Russia’s borders.

Interruptions to the flows of goods and energy

In globalized trade networks, localized disruption to supply chains rapidly yields widespread international impacts – of particular concern is the immediate supply of food because most countries rely on lean supply chains and some may only have a few days food within their own borders.

Experience from previous food price crises indicate even small interruptions to trade can result in runs on the market and rapid price inflation. In the case of this conflict, the trade interruption will be far from small because, between them, Russia and Ukraine export around one-quarter of all traded wheat, more than three-quarters of traded sunflower oil, and one-sixth of traded maize.

Energy markets are also a concern because many countries use more energy than they produce and therefore rely on imports of energy or fuel for domestic use. Russia produces around ten per cent of the world’s commercial energy with a concentration of sales in major regions such as the European Union (EU) and China.

As with food, a shortfall in energy provision leads to market runs and rapid inflation as actors compete in a tightening space, while poorly designed policy interventions by nations trying to ensure their own security add further pressure to global supply and worsen price rises. In addition, the closely interconnected nature of energy markets means disruption to one fuel – such as gas in this case – affects global prices for other forms of energy.

The impact of moving people and money

As the last decade richly illustrates, the cross-border flows of people impact those societies absorbing them – for example, contributing to a rise in nationalism – as well as increase the costs of supplying essential resources. Given many people are understandably fleeing this conflict, other countries may struggle to cope as the cost-of-living crisis and urgent efforts to bolster national security infrastructure may squeeze available public funds.

Financial flows are crucial to the functioning of global economies, whether for inward investment or insurance and – as Russian citizens may be about to discover – restricting the global flow of money has a serious impact on households. Beyond Russia, the outflow of money from major financial centres such as London to meet insurance claims or to enable infrastructure reinvestment post-conflict may also have severe knock-on economic impacts.

The impact on governance and health

The global spikes in energy and food prices resulting from these supply chain disruptions will see many countries struggle with rising food and energy insecurity as well as increased inequality. Taken together these conditions create many issues beyond immigration pressures and the associated politics, including increased inequality and civil unrest.

This potentially destabilizes governments which has consequences for the stability of an entire region such as interrupted supply chains, the need to deploy peacekeeping forces, or significant flows of aid – all with global consequences far beyond the countries in question.

Populations may suffer mental health impacts arising from the Ukraine invasion, whether from the trauma of being forced to leave home to escape conflict, anxiety for the wellbeing and safety of families and friends caught up in it, or a more general anxiety arising from the perception of living in an unstable world.

Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [¹⁷⁷Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [¹⁷⁷Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (TBS) and changes in normalized peak count (nPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in TBS_second-first, TBS_third-first, and TBS_fourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [¹⁷⁷Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. –0.049, 0.08 vs. –0.116, and 0.109 vs. –0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). nPC_second-first showed significant group differences (mean, –0.107 vs. –0.282; P = 0.033); nPC_third-first and nPC_fourth-first did not reach statistical significance (mean, –0.122 vs. –0.312 and –0.183 vs. –0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, TBS_fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. TBS_second-first and TBS_third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. nPC_second-first, nPC_third-first, and nPC_fourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: TBS and nPC can predict [¹⁷⁷Lu]Lu-DOTATATE response by the second treatment session.

Tens of thousands of striking Boeing machinists voted Monday to ratify a new contract, ending their seven-week work stoppage.

About 1,100 workers will be laid off indefinitely in January from the Jeep Gladiator plant in Toledo, Ohio, Stellantis officials announced Wednesday.

Tesla Friday reached a $1 trillion market capitalization value for the first time since 2022 in a post-election stock rally.

Canada ordered striking dock workers back to the ports of Vancouver, Prince Rupert and Montreal on Tuesday to clear out more than a week of container congestion bound for the United States and Canada.

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

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

Ukraine launched a massive drone attack on Moscow overnight, the largest on the Russian capital since the Russian invasion more than two years ago, forcing three airports to divert traffic and causing casualties.

A pair of strong earthquakes has struck off the southern coast of Cuba, inflicting damage and causing landslides.

Dozens of people were killed in Israeli military strikes on northern Lebanon and the Gaza strip, including as many as 20 children, authorities said.

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

Veteran quarterback Dak Prescott will undergo season-ending surgery to repair his injured hamstring, Dallas Cowboys owner Jerry Jones announced Tuesday.

The USS Frank E. Petersen Jr. cleared another hurdle toward joining the Navy's fleet after it completed acceptance trials on Thursday.

The Rapid Trident 21 exercise to enhance interoperability between Ukraine, U.S. and NATO partners started Monday, with an opening ceremony, and will run through Oct. 1.

The U.S. Navy conducted a two-missile test flight of unarmed life-extended Trident II-D5LE missiles from the USS Wyoming in the Eastern Test Range off the coast of Cape Canaveral, Fla, the Navy announced.

Divergent Technologies developed a digital production system that can revolutionize automotive and industrial scale manufacturing. Divergent uses new manufacturing solutions and their Divergent Adaptive Production System (DAPS™) software to make […]

The post Transforming Industrial and Automotive Manufacturing appeared first on HPCwire.

A former Jeopardy! winner led a new study that probes how linked memory systems may give trivia buffs an edge in their game

Research shows rough sex is becoming more common. Dominatrices are helping the general public catch up.

Nutritional supplements that contain curcumin -- a natural anti-inflammatory compound -- may protect the eyes from the development and progression of age-related macular degeneration, a new study suggests.

One of the most difficult problems with quantum computing relates to increasing the size of the quantum computer. Researchers globally are seeking to solve this “challenge of scale.” To bring […]

The post Recipe for Scaling: ARQUIN Framework for Simulating a Distributed Quantum Computing System appeared first on HPCwire.

MTV's Europe Music Awards included a heartfelt tribute to late musician Liam Payne.

Canada ordered striking dock workers back to the ports of Vancouver, Prince Rupert and Montreal on Tuesday to clear out more than a week of container congestion bound for the United States and Canada.

The U.S. military conducted retaliatory airstrikes Tuesday in Syria, targeting facilities of Iran-backed militias following rockets launched at U.S. forces in the Middle Eastern country.

Around 3% of people are thought to hear voices when there is no one talking.

You might be seconds away from regaining your focus with this scientifically backed method.

These little treats may be the secret to boosting someone’s mood.

Many people who want to be healthy often try to eat a balanced diet and get regular exercise. However, most foods today simply do not contain the nutrition they did in the past. If your goal is to improve your physical and mental health, your body may still require essential nutrients. IV nutrition therapy is […]

The post Exploring the Impact of IV Nutrition Therapy on Mental Health first appeared on What is Psychology?.

Although common ‘disorders’ (e.g., eating disorders, anxiety, and depression) look different on the surface, there are some common underlying mechanisms. One of these is checking. I’m going to go explain the role of checking in a selection of common mental health problems. Checking in Health Anxiety Examples: – Person goes to the Dr for blood […]

The post CBT: How Checking Contributes to Mental Health Problems (Eating Disorders, Depression, Anxiety) appeared first on Dr Alice Boyes.

Montana's highest court has struck down a tuition tax-credit program which, as enacted by that state's legislature, allowed tuition scholarships to benefit students at private religious schools as well as secular schools.

The lawsuit, filed in 2014, alleges that the state was severely underfunding schools, forcing school districts to lean heavily on property taxes, which especially disadvantages students in property-poor areas.

Fed up with their district’s unmet pledges to stop steering African American students into low-level classes, parents take action.

Facing big transportation costs due to the COVID-19 pandemic, some school districts will pay parents or caregivers to get their kids to school, or charge them for the bus ride.

Democratic Gov. Gina Raimondo proposes to allow traditional public schools to be free of certain regulations, including opening up enrollment outside their neighborhoods.

The move to assume broad powers over the Providence school system illustrates both the attraction and challenges of high-profile approaches to troubled or low-performing schools and districts.

New report on Oregon's tribal students show they start out behind, miss more school, and are more likely to drop out.

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.

A federal appeals court rejected a multi-pronged challenge to a school district plan allowing transgender students to use restrooms and other facilities that match their gender identity.

Two rural North Dakota school districts will switch to a four-day school week to save costs and improve student and teacher morale.