Selective Reflection Spectroscopy at the Interface between a Calcium Fluoride Window and Cs Vapour

A special vapour cell has been built, that allows the measurement of the atom-surface van der Waals interaction exerted by a CaF2 window at the interface with Cs vapour. Mechanical and thermal fragility of fluoride windows make common designs of vapour cells unpractical, so that we have developed an all-sapphire sealed cell with an internal CaF2 window. Although impurities were accidentally introduced when filling-up the prototype cell, leading to a line-broadening and shift, the selective reflection spectrum on the Cs D1 line (894 nm) makes apparent the weak van der Waals surface interaction. The uncertainties introduced by the effects of these impurities in the van der Waals measurement are nearly eliminated when comparing the selective reflection signal at the CaF2 interface of interest, and at a sapphire window of the same cell. The ratio of the interaction respectively exerted by a sapphire interface and a CaF2 interface is found to be 0.55 $\pm$ 0.25, in good agreement with the theoretical evaluation of ~0.67.Comment: soumis \`a Appl Phys B MS 4734

Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin

Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mock-transfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor alpha 2 (IL-13R alpha 2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R alpha 2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R alpha 2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC(50) (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R alpha 2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38

Diet patterns are associated with demographic factors and nutritional status in south Indian children

The burden of non-communicable chronic disease (NCD) in India is increasing. Diet and body composition 'track' from childhood into adult life and contribute to the development of risk factors for NCD. Little is known about the diet patterns of Indian children. We aimed to identify diet patterns and study associations with body composition and socio-demographic factors in the Mysore Parthenon Study cohort. We collected anthropometric and demographic data from children aged 9.5 years (n = 538). We also administered a food frequency questionnaire and measured fasting blood concentrations of folate and vitamin B12. Using principal component analysis, we identified two diet patterns. The 'snack and fruit' pattern was characterised by frequent intakes of snacks, fruit, sweetened drinks, rice and meat dishes and leavened breads. The 'lacto-vegetarian' pattern was characterised by frequent intakes of finger millet, vegetarian rice dishes, yoghurt, vegetable dishes and infrequent meat consumption. Adherence to the 'snack and fruit' pattern was associated with season, being Muslim and urban dwelling. Adherence to the lacto-vegetarian pattern was associated with being Hindu, rural dwelling and a lower maternal body mass index. The 'snack and fruit' pattern was negatively associated with the child's adiposity. The lacto-vegetarian pattern was positively associated with blood folate concentration and negatively with vitamin B12 concentration. This study provides new information on correlates of diet patterns in Indian children and how diet relates to nutritional status. Follow-up of these children will be important to determine the role of these differences in diet in the development of risk factors for NCD including body composition

Endogenous tumor suppressor microRNA-193b: Therapeutic and prognostic value in acute myeloid leukemia

Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo. Results miR-193b exerted important, endogenous, tumor-suppressive functions on the hematopoietic system. miR-193b-3p was downregulated in several cytogenetically defined subgroups of pediatric and adult AML, and low expression served as an independent indicator for poor prognosis in pediatric AML (risk ratio 6 standard error, 20.56 6 0.23; P = .016). miR-193b-3p expression improved the prognostic value of the European LeukemiaNet risk-group stratification or a 17-gene leukemic stemness score. In knockout mice, loss of miR-193b cooperated with Hoxa9/Meis1 during leukemogenesis, whereas restoring miR-193b expression impaired leukemic engraftment. Similarly, expression of miR-193b in AML blasts from patients diminished leukemic growth in vitro and in mouse xenografts. Mechanistically, miR-193b induced apoptosis and a G1/S-phase block in various human AML subgroups by targeting multiple factors of the KIT-RAS-RAF-MEK-ERK (MAPK) signaling cascade and the downstream cell cycle regulator CCND1. Conclusion The tumor-suppressive function is independent of patient age or genetics; therefore, restoring miR-193b would assure high antileukemic efficacy by blocking the entire MAPK signaling cascade while preventing the emergence of resistance mechanisms

Development of new promising varieties of faba bean through traditional pedigree method for commercial cultivation in plain zone of India

A long term experiment was carried out in MAP Section, Department of Genetics & Plant Breeding,  CCS Haryana Agricultural University, Hisar from 2005-06 to 2018-19 on identification of elite genotypes from germplasm and their utilization in the development of high yielding variety through hybridization followed by traditional pedigree method to obtain desirable transgressive segregants in Faba bean. In the present investigation a number of germplasm lines were screened for seed yield and other related traits including national check Vikrant during 2005-06 under AICRN in augmented block design. As a result, ten elite genotypes identified i.e. EC117755, EC117799, EC248710, EC329675, HB123, HB180, HB430, HB204, HB 430, HB 502, HB 503 & one check variety, Vikrant. By using these elite genotypes, a number of F1 hybrids were made during 2005-06 and F2 to F6 generations were evaluated to identify the superior progenies during 2007-08 to 2011-12. After a long process of evaluation, rejection and selection, 20 superior transgressive segregant homozygous progenies were identified to make new entries. Later on, during 2012-2013, the superior entries (viz. HB12-1, HB12-5, HB12-8, HB12-9, HB12-11, HB12-12, HB12-13, HB12-14, HB12-15, HB12-26, HB12-28, HB12-29, HB12-30, HB12-31, HB12-34, HB12-36, HB12-37,HB12-38, HB12-39 and HB12-42) were evaluated at Hisar centre against Vikrant and found promising. Therefore, all these 20 genotypes were evaluated in SST during 2013-14, LST during 2014-15 and FYT during 2015-16. On the basis of above results, only five genotypes viz. HB12-8 (47.77q/ha), HB12-42 (47.70q/ha), HB12-15 (46.70q/ha), HB12-34 (46.14q/ha) and HB12-37 (45. 31q/ha) were found promising. These were further evaluated in multi-location trials at seven locations (i.e. Ambikpur, Delhi, Faizabad, Faridkot, Hisar, Ludhiana & Ranchi) for seed yield, quality and resistance against insect pest & disease in IVT and AVT during 2016-17 & 2017-18, respectively. Out of these, HB12-34 exhibited yield superiority over national checks,Vikrant and HFB-1 and free from insect pest and disease as well as low in vicine-covicine and high in protein content. Therefore, HB12-34 may be recommended for commercial cultivation in plain zone at national level

A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: A secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg −1 min −1 and peak oxygen consumption (VO 2 peak) >16 ml kg −1 min −1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg −1 min −1 and VO 2 peak>16 ml.kg −1min −1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg −1.min −1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO 2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO 2 peak>16 ml.kg −1.min −1 and VO 2 peak<16 ml.kg −1.min −1. Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management

Supernova neutrino detection in NOvA

The NOvA long-baseline neutrino experiment uses a pair of large, segmented, liquid-scintillator calorimeters to study neutrino oscillations, using GeV-scale neutrinos from the Fermilab NuMI beam. These detectors are also sensitive to the flux of neutrinos which are emitted during a core-collapse supernova through inverse beta decay interactions on carbon at energies of O(10 MeV). This signature provides a means to study the dominant mode of energy release for a core-collapse supernova occurring in our galaxy. We describe the data-driven software trigger system developed and employed by the NOvA experiment to identify and record neutrino data from nearby galactic supernovae. This technique has been used by NOvA to self-trigger on potential core-collapse supernovae in our galaxy, with an estimated sensitivity reaching out to 10 kpc distance while achieving a detection efficiency of 23% to 49% for supernovae from progenitor stars with masses of 9.6 M☉ to 27 M☉, respectively

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease