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The article focuses on the significant improvements achieved over the past year at the University of Illinois softball facility, attributed to a shift in culture and expectations regarding maintenance quality, including staff training, administrative education, agronomic program development, budget establishment, and the belief in consistently maintaining a high-quality field.

Magnesium alloys containing biocompatible components show tremendous promise for applications as temporary biomedical devices. However, to ensure their safe use as biodegradeable implants, it is essential to control their corrosion rates. In concentrated Mg alloys, a microgalvanic coupling between the α-Mg matrix and secondary precipitates exists which results in increased corrosion rate. To address this challenge, we engineered the microstructure of a biodegradable Mg–Zn–RE–Zr alloy by friction stir processing (FSP), improving its corrosion resistance and mechanical properties simultaneously. The FS processed alloy with refined grains and broken and uniformly distributed secondary precipitates showed a relatively uniform corrosion morphology accompanied with the formation of a stable passive layer on the alloy surface. In vivo corrosion evaluation of the processed alloy in a small animal model showed that the material was well-tolerated with no signs of inflammation or harmful by-products. Remarkably, the processed alloy supported bone until it healed till eight weeks with a low in vivo corrosion rate of 0.7 mm/year. Moreover, we analyzed blood and histology of the critical organs such as liver and kidney, which showed normal functionality and consistent ion and enzyme levels, throughout the 12-week study period. These results demonstrate that the processed Mg–Zn–RE–Zr alloy offers promising potential for osseointegration in bone tissue healing while also exhibiting controlled biodegradability due to its engineered microstructure. The results from the present study will have profound benefit for bone fracture management, particularly in pediatric and elderly patients.

Protein quality of the red kidney bean (RKB), a common source of dietary protein, has been assessed using the protein digestibility-corrected amino acid score (PDCAAS) determined in animal models using mainly oro-fecal digestibility. More recently, the FAO recommended to use digestible indispensable amino acid score (DIAAS) instead of PDCAAS but highlighted insufficient data on true ileal indispensable amino acid (IAA) digestibility of proteins because amino acids are absorbed in the ileum.

Scombroid poisoning, systemic mastocytosis, and hereditary alpha tryptasemia all present with episodes that resemble allergic reactions. Knowledge regarding systemic mastocytosis and hereditary alpha tryptasemia is quickly evolving. Epidemiology, pathophysiology, and strategies to identify and diagnose are discussed. Evidence-based management in the emergency setting and beyond is also explored and summarized. Key differences are described between these events and allergic reactions.

The article reviews the architectural design of the Art Gallery of New South Wales, designed by architectural firm SANAA.

DEEP-SEA DRILLING OPERATIONS often require hydraulic power at the seabed to actuate emergency blowout prevention (BOP) valves or other flow controls. Sometimes, large pre-charged accumulator arrays can be installed close [...]

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In this work, we present the influence of the irradiation temperature on electrical characterization of midwave infrared (MWIR) InAs/GaSb type-II superlattice (T2SL) photodetector, showing cutoff wavelength equal to 5 $\mu \text{m}$ at 90 K. The proton irradiations were performed with 60-MeV protons and fluences up to $8\times 10^{11}\,\,\text{H}^{+}$ /cm2 at cryogenic (100 K) or room temperature (300 K). The gamma irradiation, from a Cobalt-60 source, allows to reach a dose up to 50 krad(Si). We observed that degradation of the dark current under proton or gamma irradiations is strongly dependent on the temperature of the detector during irradiation but also on the protection layer used during the detector’s technological process.

Calreticulin (CALR) mutations present the main oncogenic drivers in JAK2wildtype (WT) myeloproliferative neoplasms (MPN), including essential thrombocythemia and myelofibrosis, where mutant (MUT) CALRis increasingly recognized as a suitable mutation-specific drug target. However, our current understanding of its mechanism-of-action is derived from mouse models or immortalized cell lines, where cross-species differences, ectopic over-expression and lack of disease penetrance are hampering translational research. Here, we describe the first human gene-engineered model of CALRMUT MPN using a CRISPR/Cas9 and adeno-associated viral vector-mediated knock-in strategy in primary human hematopoietic stem and progenitor cells (HSPCs) to establish a reproducible and trackable phenotype in vitro and in xenografted mice. Our humanized model recapitulates many disease hallmarks: thrombopoietin-independent megakaryopoiesis, myeloid-lineage skewing, splenomegaly, bone marrow fibrosis, and expansion of megakaryocyte-primed CD41+progenitors. Strikingly, introduction of CALRmutations enforced early reprogramming of human HSPCs and the induction of an endoplasmic reticulum stress response. The observed compensatory upregulation of chaperones revealed novel mutation-specific vulnerabilities with preferential sensitivity of CALRmutant cells to inhibition of the BiP chaperone and the proteasome. Overall, our humanized model improves purely murine models and provides a readily usable basis for testing of novel therapeutic strategies in a human setting.

Many critics raise concerns about the prevalence of ‘echo chambers’ on social media and their potential role in increasing political polarization. However, the lack of available data and the challenges of conducting large-scale field experiments have made it difficult to assess the scope of the problem1,2. Here we present data from 2020 for the entire population of active adult Facebook users in the USA showing that content from ‘like-minded’ sources constitutes the majority of what people see on the platform, although political information and news represent only a small fraction of these exposures. To evaluate a potential response to concerns about the effects of echo chambers, we conducted a multi-wave field experiment on Facebook among 23,377 users for whom we reduced exposure to content from like-minded sources during the 2020 US presidential election by about one-third. We found that the intervention increased their exposure to content from cross-cutting sources and decreased exposure to uncivil language, but had no measurable effects on eight preregistered attitudinal measures such as affective polarization, ideological extremity, candidate evaluations and belief in false claims. These precisely estimated results suggest that although exposure to content from like-minded sources on social media is common, reducing its prevalence during the 2020 US presidential election did not correspondingly reduce polarization in beliefs or attitudes.

Therapy-related myeloid neoplasm (tMN) is considered a direct consequence of DNA damage in hematopoietic stem cells. Despite increasing recognition that altered stroma can also drive leukemogenesis, the functional biology of the tMN microenvironment remains unknown. We performed multiomic (transcriptome, DNA damage response, cytokine secretome and functional profiling) characterization of bone marrow stromal cells from tMN patients. Critically, we also compared (i) patients with myeloid neoplasm and another cancer but without cytotoxic exposure, (ii) typical primary myeloid neoplasm, and (iii) age-matched controls to decipher the microenvironmental changes induced by cytotoxics vs. neoplasia. Strikingly, tMN exhibited a profoundly senescent phenotype with induction of CDKN1Aand β-Galactosidase, defective phenotype, and proliferation. Moreover, tMN stroma showed delayed DNA repair and defective adipogenesis. Despite their dormant state, tMN stromal cells were metabolically highly active with a switch toward glycolysis and secreted multiple pro-inflammatory cytokines indicative of a senescent-secretory phenotype that inhibited adipogenesis. Critically, senolytics not only eliminated dormant cells, but also restored adipogenesis. Finally, sequential patient sampling showed senescence phenotypes are induced within months of cytotoxic exposure, well prior to the onset of secondary cancer. Our data underscores a role of senescence in the pathogenesis of tMN and provide a valuable resource for future therapeutics.

ABSTRACTFostering a sense of civic engagement is considered an essential purpose of social studies education. However, given the ways in which formal civic curricula and standards decenter the impact of racial membership on civic status, Black teachers are turning to alternative, out-of-school sites to enact critical approaches to teaching civics. Interscholastic athletics serves as one locale for such revisionist practices. This multiple case study troubles the centrality of Whiteness and deficit notions within the teacher-coach discourse by explicating the civic practices of five Black male teacher-coaches who served in schools that were not predominantly Black. Drawing on a conceptual framework rooted in Black critical theories, their civic mindedness of coaching ideologies and civic-oriented activities fostered a sense of liberatory fantasy while immersed within an anti-Black milieu.

Reality has returned to retail with a surge in profit warnings, slowing sales figures and renewed rounds of administrations as British shoppers tighten their belts. Surprisingly benign economic conditions delayed [...]

The property industry is starting its recovery from the unfettered spending spree during the boom years, shows De Montfort's authoritative account of real estate debt in the UK. There is [...]

The bloodshed may have abated on the high street, with fewer signs of distress among retailers, but there are worries of a thousand smaller cuts to come, as consumers tighten [...]

Banks are back in business, but the extent of legacy problems from the wasteful lending of the previous boom is only just being recognised, the annual De Montfort report into [...]

Opinion about the property investment market stands finely balanced in the run-up to the summer. There are as many experts who predict a continued recovery as there are those who [...]

AFTER A LONG PERIOD WHEN THERE HAS BEEN little to be cheerful about in the retail property sector, Colliers CRE's well-regarded Midsummer Retail Report arrives with a few reasons--at least [...]

KID GLOVES OR AN IRON FIST. DEPENDING ON WHO you are, the latest De Montfort University survey into real estate bank lending shows that most property investors have seen one [...]

Inducing cell death by the sphingolipid ceramide is a potential anticancer strategy, but the underlying mechanisms remain poorly defined. In this study, triggering an accumulation of ceramide in acute myeloid leukemia (AML) cells by inhibition of sphingosine kinase induced an apoptotic integrated stress response (ISR) through protein kinase R–mediated activation of the master transcription factor ATF4. This effect led to transcription of the BH3-only protein Noxa and degradation of the prosurvival Mcl-1 protein on which AML cells are highly dependent for survival. Targeting this novel ISR pathway, in combination with the Bcl-2 inhibitor venetoclax, synergistically killed primary AML blasts, including those with venetoclax-resistant mutations, as well as immunophenotypic leukemic stem cells, and reduced leukemic engraftment in patient-derived AML xenografts. Collectively, these findings provide mechanistic insight into the anticancer effects of ceramide and preclinical evidence for new approaches to augment Bcl-2 inhibition in the therapy of AML and other cancers with high Mcl-1 dependency.

* THE WORST RETAIL MARKET SINCE' EARLY 1990S' * INVESTMENT VOLUMES DOWN 40% * VALUES HAVE FALLEN BY 20% AND WILL FALL A FURTHER 10% IN 12 MONTHS * RENTS [...]

NO ONE IN THE PROPERTY INDUSTRY WILL NEED telling that last year was split into two halves. Property values were ramped up to breaking point before an inevitable crash in [...]

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Byline: Daniel Thomas If Britain's exit from the EU goes horribly wrong, the U.K. government has hinted at a contingency plan: radically reduce corporate tax rates, turning Britain into an [...]

IN MANCHESTER'S PICCADILLY GARDENS THERE stands a condemned building. The scaffolding around the Pound Empire shop masks what once might have been an eight-storey trophy building for one of the [...]

PRUDENTIAL CHAIRMAN AND FORMER DEPUTY governor of the Bank of England Sir David Clementi is no stranger to the property/industry/. But his speech at this week's Investment Property Forum annual [...]

I. INTRODUCTION In 1994, a District Court of New Mexico awarded a woman $160,000 in compensatory damages and $2.7 million in punitive damages because of the burns caused after the [...]

IT IS A LANDLORD'S WORST NIGHTMARE: the occupier of its flagship building goes bust, leaving a long lease void in a difficult leasing market. This is precisely what happened in [...]

Background: Recently, two new indexes based on the ratio of transmitral early diastolic velocity (E) to tissue Doppler imaging (TDI), and early diastolic velocity of mitral annulus (E') and E [...]

Objective: The objective of this study was to characterize the resurgence of infectious syphilis in the United Kingdom between 1997 and 2003. Study: The authors conducted a retrospective analysis of routine surveillance data from genitourinary medicine clinics and data collected through enhanced surveillance. Results: Between 1997 and 2002, diagnoses of primary, secondary, and early latent syphilis made at genitourinary medicine clinics increased by 213% in heterosexual males, 1412% in men who have sex with men (MSM), and 22% in females. These increases have been driven by a series of outbreaks, the largest of which were seen in Manchester (528) and London (1222) up to the end of October 2003. All the outbreaks have been geographically localized and the majority of cases occurred in MSM. A high percentage of concurrent HIV infection was reported, and oral sex was often reported as a route of transmission. Conclusions: Syphilis has re-emerged in response to behavior change, probably driven by changes in the HIV epidemic. The future course of the epidemic is difficult to predict and control remains elusive.

The race to host the 2012 Olympic Games has entered its final stages, with the technical bid documents completed and submitted by the five short-listed cities. Many observers have already [...]

Marketers can spend millions of pounds and countless years developing a brand only to find that inadequate intellectual property protection has allowed an opportunistic imitator to steal its identity. A […]

While hair fashions constantly change, the market that produces hair products has traditionally been a bit of a millpond. Rarely has it seen so much upheaval as in recent years, […]

With the rumour mill linking Chelsea to football superstar David Beckham once more, Roman Abramovich's millionaire army could be on the verge of signing a brand leader to help shape […]

Blood is about to be drawn in the increasingly tense razor war between male grooming super power Gillette and a rejuvenated Wilkinson Sword. In preparation, Wilkinson Sword is sharpening its […]

It is supposed to be the job of ad agencies to excel in creativity and that of marketers to demand it. But as ad campaigns increasingly mine the same tired […]

The odds that Camelot will face significant competition for the first time in the lottery market are narrowing. Las week, Novamedia, which claims to be the largest charity lottery operator […]

Niall FitzGerald, whose influence as head of Unilever has irrevocably changed how consumer goods are marketed from Brazil to Bangalore, caused many to raise their eyebrows last week by step [...]

Failure is a word that rarely trips off a marketer's tongue. Few want to dwell on their mistakes or oversights, preferring instead to trumpet their successes. But some brave marketers […]

Just in case you've missed it, England has won the World Cup--but this time it's rugby. It's the first time since 1966 that the country has picked up a World […]

Formula One has been hit by a series of sponsorship losses in recent weeks that has left spectators wondering whether the sport has hit the skids. And with Ferrari's Michael […]