After you submit a stored process from the SAS Stored Process Web Application, the generated URL is placed into a cell in a Microsoft Excel worksheet. When you click this URL, you expect that the stored process is sub

The Lady of Dancehall, D'Angel, says although her COVID-19 Relief Concert did not meet its US$200,000 target, she is overwhelmed by the support. The event, held via Instagram Live last Friday, saw performances from the likes of Beenie Man, G...

Numerous recent works highlight the limited utility of established tumor cell lines in recapitulating the heterogeneity of tumors in patients. More realistic preclinical cancer models are thought to be provided by transplantable, patient-derived tumor xenografts (PDX). Inter- and intra-tumor heterogeneity of PDX, however, present several challenges in developing optimal quantitative pipelines to assess response to therapy. The objective of this work was to develop and optimize image metrics of FDG-PET to assess response to combination docetaxel/carboplatin therapy in a co-clinical trial involving triple negative breast cancer (TNBC) PDX. We characterize the reproducibility of SUV metrics to assess response to therapy and optimize a preclinical PERCIST (µPERCIST) paradigm to complement clinical standards. Considerations in this effort included variability in tumor growth rate and tumor size; solid tumor vs. tumor heterogeneity and necrotic phenotype; and optimal selection of tumor slice versus whole tumor. A test-retest protocol was implemented to optimize the reproducibility of FDG-PET SUV thresholds, SUVpeak metrics, and µPERCIST parameters. In assessing response to therapy, FDG-PET imaging was performed at baseline and +4 days following therapy. The reproducibility, accuracy, variability, and performance of imaging metrics to assess response to therapy were determined. We defined an index—"Quantitative Response Assessment Score (QRAS)"—to integrate parameters of prediction and precision, and thus aid in selecting optimal image metrics of response to therapy. Our data suggests that a threshold value of 25% (SUV25) of SUVmax was highly reproducible (<9% variability). Concordance and reproducibility of µPERCIST were maximized at α=0.7 and β=2.8 and exhibited high correlation to SUV25 measures of tumor uptake. QRAS scores favor SUV25 followed by SUVP14 as optimal metrics of response to therapy. Additional studies are warranted to fully characterize the utility of SUV25 and µPERCIST SUVP14 as image metrics of response to therapy across a wide range of therapeutic regiments and PDX models.

Hosting duties fall to Henry Burrell this week as he discusses the deadline for the free Microsoft Windows 10 update with Chris Minasians, staff writer at PC Advisor. Scott Carey, online editor at Techworld.com jumps in to talk about why the Verizon deal for Yahoo is ridiculous and charts the missteps that got the company to this point (15:00). Finally, regular guest David Price discusses Apple's less than stellar financial results and if the iPhone is plateauing (26:00).  

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Campylobacter jejuni is a major cause of food-borne gastroenteritis. Proteomics by label-based two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) identified proteins associated with growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts), and system-wide validation was performed by data-independent acquisition (DIA-SWATH-MS). LC-MS/MS quantified 1326 proteins (~82% of the predicted C. jejuni proteome), of which 1104 were validated in additional biological replicates by DIA-SWATH-MS. DOC resulted in a profound proteome shift with 512 proteins showing significantly altered abundance. Induced proteins were associated with flagellar motility and antibiotic resistance; and these correlated with increased DOC motility and resistance to polymyxin B and ciprofloxacin. DOC also increased human Caco-2 cell adherence and invasion. Abundances of proteins involved in nutrient transport were altered by DOC and aligned with intracellular changes to their respective carbon sources. DOC increased intracellular levels of sulfur-containing amino acids (cysteine and methionine) and the dipeptide cystine (Cys-Cys), which also correlated with reduced resistance to oxidative stress. A DOC induced transport protein was Cj0025c, which has sequence similarity to bacterial Cys-Cys transporters. Deletion of cj0025c (cj0025c) resulted in proteome changes consistent with sulfur starvation, as well as attenuated invasion, reduced motility, atypical morphology, increased antimicrobial susceptibility and poor biofilm formation. Targeted metabolomics showed cj0025c was capable of utilizing known C. jejuni amino and organic acid substrates commensurate with wild-type. Medium Cys-Cys levels however, were maintained in cj0025c relative to wild-type. A toxic Cys-Cys mimic (selenocystine) inhibited wild-type growth, but not cj0025c. Provision of an alternate sulfur source (2 mM thiosulfate) restored cj0025c motility. Our data confirm that Cj0025c is a Cys-Cys transporter that we have named TcyP consistent with the nomenclature of homologous proteins in other species.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are emerging as leading causes of liver disease worldwide and have been recognized as one of the major unmet medical needs of the 21st century. Our recent translational studies in mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine kinase (STK)25 as a protein that coats intrahepatocellular lipid droplets (LDs) and critically regulates liver lipid homeostasis and progression of NAFLD/NASH. Here, we studied the mechanism-of-action of STK25 in steatotic liver by relative quantification of the hepatic LD-associated phosphoproteome from high-fat diet-fed Stk25 knockout mice compared with their wild-type littermates. We observed a total of 131 proteins and 60 phosphoproteins that were differentially represented in STK25-deficient livers. Most notably, a number of proteins involved in peroxisomal function, ubiquitination-mediated proteolysis, and antioxidant defense were coordinately regulated in Stk25^–/– versus wild-type livers. We confirmed attenuated peroxisomal biogenesis and protection against oxidative and ER stress in STK25-deficient human liver cells, demonstrating the hepatocyte-autonomous manner of STK25’s action. In summary, our results suggest that regulation of peroxisomal function and metabolic stress response may be important molecular mechanisms by which STK25 controls the development and progression of NAFLD/NASH.

Islet transplantation is an emerging therapy for type 1 diabetes (T1D) and hypoglycaemic unawareness. However, a key challenge for islet transplantation is cellular rejection and the requirement for long-term immunosuppression. In this study we established a diabetic-humanized NOD-scidIL2R^null(NSG) mouse model of T cell mediated human islet-allograft rejection and developed a therapeutic regimen of low-dose recombinant human interleukin2(IL-2) combined with low-dose rapamycin to prolong graft survival. NSG-mice that had received renal-subcapsular human islet-allografts and were transfused with 1x10⁷ of human-spleen-mononuclear-cells (hSPMCs), reconstituted human CD45⁺ cells that were predominantly CD3⁺ T cells and rejected their grafts with a median survival time of 27 days. IL-2 alone (0.3x10⁶ IU/m² or 1x10⁶ IU/m²), or rapamycin alone (0.5-1mg/kg) for 3 weeks did not prolong survival. However, the combination of rapamycin with IL-2 for 3 weeks significantly prolonged human islet-allograft survival. Graft survival was associated with expansion of CD4⁺CD25⁺FOXP3⁺ Tregs and enhanced TGF-β production by CD4⁺ T cells. CD8⁺ T cells showed reduced IFN- production and reduced expression of perforin-1. The combination of IL-2 and rapamycin has the potential to inhibit human islet-allograft rejection by expanding CD4⁺FOXP3⁺ Tregs in vivo and supressing effector cell function, and could be the basis of effective tolerance-based regimens.

The Open Arms Development Centre, a homeless shelter in downtown Kingston, and Jamaica’s COVID-19 Response Fund Food Relief are among 25 charitable and community organisations across the island to benefit from the latest round of grants from US-...

Led by vice president of home clubhouse operations Rick Stowe, who began working for the club in 1981 and became head of the clubhouse in 1997, the Reds have a well-oiled machine with regard to packing up and moving out.

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, ⁶⁴Cu (half-life, 12.7 h) and ²²⁵Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n = 12; MIA PaCa-2, n = 8). Tumor xenograft mice were investigated after the intravenous injection of ⁶⁴Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of ⁶⁸Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice (n = 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, ²²⁵Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice (n = 6). Tumor size was monitored and compared with that of control mice (n = 6). Results: Dynamic imaging of ⁶⁴Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of ⁶⁴Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for ⁶⁴Cu-FAPI-04 than for ⁶⁸Ga-FAPI-04, except in the heart, and excretion in the urine was higher for ⁶⁸Ga-FAPI-04 than for ⁶⁴Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. ²²⁵Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that ⁶⁴Cu-FAPI-04 and ²²⁵Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.

Invitation Only Research Event

HE Raffaele Trombetta, Italian Ambassador to the UK, Co-Host, COP 26
Archie Young, UK Lead Climate Negotiator, Cabinet Office 
Peter Betts, Associate Fellow, Energy, Environment and Resources Department, Chatham House
Chair: Professor Tim Benton, Research Director, Energy, Environment and Resources, Chatham House  

The recent rise in xenophobia in Hungary stands in marked contrast with the country's rich migration history. After 390,000 migrants and asylum seekers arrived in 2015, the government of Viktor Orbán issued policies to significantly limit migration and enacted a law criminalizing humanitarian assistance to migrants. This country profile examines Hungary’s migration past and present, tracing the country’s multicultural heritage to the current wave of anti-immigrant sentiment.

A South Carolina man had extra trouble convincing his wife that his $250,000 lottery win was legitimate due to her memories of a past prank.

Massimo Cigolini
Mar 1, 2006; 29:722-724
BR Cardiovascular and Metabolic Risk

Raytheon was awarded a $325 million contract for repair of the Advanced Targeting Forward Looking Infrared System in the F/A-18 Super Hornet aircraft Tuesday, according to the Pentagon.

On her first official trip to Washington, DC, Secretary of the Interior Olga Sánchez Cordero offered a public address on Mexico’s new approach to migration policy at MPI. Her remarks and the event discussion were mostly conducted in Spanish, and this recording is of the simultaneous English interpretation. 

Durante su primera visita oficial a Washington, DC, la Secretaria de Gobierno Olga Sánchez Cordero presento un discurso público sobre la nueva política migratoria de México en el Instituto de Políticas Migratorias.

WASHINGTON – A pesar de que los gobiernos de América Latina y el Caribe han tomado medidas generosas e innovadoras para lidiar con el desplazamiento forzado desde Venezuela y más recientemente desde Nicaragua, la cálida bienvenida se ha enfriado en algunos lugares a medida que el número de entradas, la presión sobre los servicios públicos y la preocupación del público aumenta.

Responsables de políticos principales y partes interesadas de América Latina, así como representantes de instituciones internacionales claves, ofrecen sus puntos de vista sobre los desafíos futuros mientras gobiernos latinoamericanos buscan establecer las estrategias para responder a flujos migratorios forzados a gran escala, como los de Venezuela y Nicaragua.

Aunque colombianos encontraron un refugio cálido en Ecuador después de ser desplazados de su país por una guerra civil que duro décadas, la vida se ha vuelto más difícil para ellos en los últimos años, en parte como resultado del flujo de venezolanos que buscan seguridad. Este artículo se basa en encuestas de migrantes en Quito, comparando y contrastando las experiencias de colombianos y venezolanos, y evaluando sus percepciones de discriminación, victimización y esperanzas para el futuro.

MPI llevó a cabo un seminario en línea para marcar el lanzamiento de: Un portal sobre Migración en América Latina y el Caribe; y un informe que examina los efectos de las políticas migratorias y de integración en 11 países en América Latina y el Caribe ante el aumento de la migración venezolana y nicaragüense.

El gran desplazamiento forzado de personas en Venezuela y Nicaragua está transformando el panorama migratorio en gran parte de América Latina y el Caribe. Este informe examina las respuestas de las políticas de inmigración e integración de once países, incluyendo vías de regularización y medidas para integrar a los recién llegados en las escuelas y mercados laborales. Este informe acompaña el lanzamiento de un Portal Sobre Migración que ofrece investigación y análisis actualizados sobre tendencias y políticas de inmigración en la región.

Responsables de políticos principales y partes interesadas de América Latina, así como representantes de instituciones internacionales claves, ofrecen sus puntos de vista sobre los desafíos futuros mientras gobiernos latinoamericanos buscan establecer las estrategias para responder a flujos migratorios forzados a gran escala, como los de Venezuela y Nicaragua.

MPI llevó a cabo un seminario en línea para marcar el lanzamiento de: Un portal sobre Migración en América Latina y el Caribe; y un informe que examina los efectos de las políticas migratorias y de integración en 11 países en América Latina y el Caribe ante el aumento de la migración venezolana y nicaragüense.

This Quality Counts 2019 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes.

Australia -- History -- 1901-1945.

Wiesbaden : J.F. Bergmann, 1907.

Leipzig : G. Thieme, 1890-1891.

Wien : M. Perles, 1878.

Berlin : Hirschwald, 1902.

Leipzig : F.C.W. Vogel, 1888.