Magnetically-controlled velocity selection in a cold atom sample using stimulated Raman transitions

We observe velocity-selective two-photon resonances in a cold atom cloud in the presence of a magnetic field. We use these resonances to demonstrate a simple magnetometer with sub-mG resolution. The technique is particularly useful for zeroing the magnetic field and does not require any additional laser frequencies than are already used for standard magneto-optical traps. We verify the effects using Faraday rotation spectroscopy.Comment: 5 pages, 6 figure

Cold atom confinement in an all-optical dark ring trap

We demonstrate confinement of $^{85}$Rb atoms in a dark, toroidal optical trap. We use a spatial light modulator to convert a single blue-detuned Gaussian laser beam to a superposition of Laguerre-Gaussian modes that forms a ring-shaped intensity null bounded harmonically in all directions. We measure a 1/e spin-relaxation lifetime of ~1.5 seconds for a trap detuning of 4.0 nm. For smaller detunings, a time-dependent relaxation rate is observed. We use these relaxation rate measurements and imaging diagnostics to optimize trap alignment in a programmable manner with the modulator. The results are compared with numerical simulations.Comment: 5 pages, 4 figure

Fecal carriage and clonal dissemination of blaNDM-1 carrying Klebsiella pneumoniae sequence type 147 at an intensive care unit in Lao PDR

OBJECTIVES: Carbapenemase-producing Enterobacterales (CPE) are high priority targets of global antimicrobial surveillance. Herein, we determined the colonization rate of CPE on admission to intensive care units in Vientiane, Lao PDR in August-September 2019. METHODS: Data regarding clinical conditions, infection control, and antibiotic usage were collected during admission. Rectal swab samples (n = 137) collected during admission were inoculated to selective chromogenic agars, followed by confirmatory tests for extended-spectrum beta-lactamases and carbapenemases. All CPE isolates were sequenced on Illumina (HiSeq2500), reads assembled using SPAdes 3.13, and the draft genomes used to query a database (https://www.genomicepidemiology.org) for resistome, plasmid replicons, and sequence types (ST). Optical DNA mapping (ODM) was used to characterize plasmids and to determine location of resistance genes. Minimum spanning tree was generated using the Bacterial Isolate Genome Sequence database (BIGSdb) and annotated using iTOL. RESULT: From 47 Enterobacterales isolated on selective agars, K. pneumoniae (25/47) and E. coli (12/47) were the most prevalent species, followed by K aerogenes (2/47), K. variicola (1/47), and K. oxytoca (1/47). The overall prevalence of ESBLs was 51.0%; E. coli 83.3% (10/12) and Klebsiella spp. 41.3% (12/29). Twenty percent of the K. pneumoniae (5/25) isolates were carbapenem-resistant, and 4/5 contained the blaNDM-1 gene. All blaNDM-1 isolates belonged to ST147 and were indistinguishable with cgMLST. ODM showed that the blaNDM-1 gene was located on identical plasmids in all isolates. CONCLUSION:\ua0The prevalence of ESBL-producing Enterobacterales was high, while carbapenemases were less common. However, the detection of clonal dissemination of blaNDM-1-producing K. pneumoniae isolates in one of the intensive care units calls for vigilance. Stringent infection prevention and antimicrobial stewardship strategies are highly important measures

Post hoc Analysis for Detecting Individual Rare Variant Risk Associations Using Probit Regression Bayesian Variable Selection Methods in Case-Control Sequencing Studies

Rare variants (RVs) have been shown to be significant contributors to complex disease risk. By definition, these variants have very low minor allele frequencies and traditional single-marker methods for statistical analysis are underpowered for typical sequencing study sample sizes. Multimarker burden-type approaches attempt to identify aggregation of RVs across case-control status by analyzing relatively small partitions of the genome, such as genes. However, it is generally the case that the aggregative measure would be a mixture of causal and neutral variants, and these omnibus tests do not directly provide any indication of which RVs may be driving a given association. Recently, Bayesian variable selection approaches have been proposed to identify RV associations from a large set of RVs under consideration. Although these approaches have been shown to be powerful at detecting associations at the RV level, there are often computational limitations on the total quantity of RVs under consideration and compromises are necessary for large-scale application. Here, we propose a computationally efficient alternative formulation of this method using a probit regression approach specifically capable of simultaneously analyzing hundreds to thousands of RVs. We evaluate our approach to detect causal variation on simulated data and examine sensitivity and specificity in instances of high RV dimensionality as well as apply it to pathway-level RV analysis results from a prostate cancer (PC) risk case-control sequencing study. Finally, we discuss potential extensions and future directions of this work

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.

UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.The Breast Cancer Association Consortium (BCAC), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), and the Ovarian Cancer Association Consortium (OCAC) that contributed breast, prostate, and ovarian cancer data analyzed in this study were in part funded by Cancer Research UK [C1287/A10118 and C1287/A12014 for BCAC; C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135 for PRACTICAL; and C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689 for OCAC]. Funding for the Collaborative Oncological Gene-environment Study (COGS) infrastructure came from: the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the US National Institutes of Health (CA128978) and the Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112), the US Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund [with donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07)]. Additional financial support for contributing studies is documented under Supplementary Financial Support.This is the author accepted manuscript. The final version is available from the American Association for Cancer Research via http://dx.doi.org/10.1158/2159-8290.CD-15-122

Alterations of mucin O-glycosylation in response to intestinal infection. Importance of specific glycosyltransferases

Mucins are large glycoproteins constituting the major protein component of the mucus layer covering the epithelial surfaces. The mucins are characterised by a dense and heterogeneous O-glycosylation, important for their chemical and physiological properties. The mucus layer forms a selective physical barrier serving to protect the epithelium from physical and chemical stress. With their heterogeneous glycosylation, the mucins probably have a role in the interplay with microbes dwelling at the epithelia, by constituting the targets for microbial adhesins. An increased understanding of mucin O-glycosylation and its biosynthesis would aid in exploring the mechanisms and occurrence of such an interplay.We have studied the O-glycosylation of rat small intestinal mucins, mainly Muc2, during an infection with the parasitic nematode Nippostrongylus brasiliensis. Mucins were collected from the rats at different stages of the infection, and oligosaccharides were released from the protein backbone and separated into neutral, sialylated and sulphated species. The oligosaccharides were structurally analysed, using gas chromatography-mass spectrometry, NMR and high pH anion exchange chromatography. The comparison of the oligosaccharides from normal and infected rats revealed three specific alterations appearing transiently during the infection, indicating a dynamic regulation of mucin O-glycosylation. The alterations were 1) an increased amount of N-acetylneuraminic acid relative to N-glycolylneuraminic acid, 2) the appearance of blood group A terminal epitopes and 3) the appearance of blood group Sda/Cad terminal epitopes. The enzymes responsible for the two first alterations were by northern blotting identified as the CMP-NeuAc hydroxylase and the blood group A GalNAc-transferase, respectively. The rat blood group A glycosyltransferase was cloned and sequenced at the genomic and cDNA levels. The gene was mapped to chromosome 3q11-12 by fluorescence in-situ hybridisation and radiation hybrid mapping. During the cDNA cloning, two similar sequences with 95 percent similarity were identified, both encoding active transferases. By PCR studies on inbred, outbred and interbred rats, the two sequences were shown to be allelic. The unusually large difference between the alleles might indicate an evolutionary pressure in favour of a high mutation frequency for this gene.An aspect of mucin glycosylation that has been difficult to address is the glycosylation of specific O-glycan sites, partly due to the large number of such sites in the mucins. As a step towards such an analysis, a short recombinant reporter protein was constructed, based on sequence from the glycosylated domain of MUC1 and containing only eight O-glycan sites. When this protein was produced in CHO K1 cells, the major oligosaccharides present were mono- and disialylated core 1 glycans, as determined by liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) and LC-ESI-MS/MS on released oligosaccharides. N-terminal peptide sequencing showed that all individual O-glycan sites were glycosylated, to an extent of 75-95 percent at the different sites. The occupancy of the O-glycan sites could be increased by co-expression with polypeptide-GalNAc-T4, which in vitro has been shown to add GalNAc to the polypeptide backbone of MUC1 glycopeptides. Our results confirmed the proposed activity of GalNAc-T4 in vivo

Dissonant futures : Occupational trajectories, gender and class in contemporary municipal adult education in Sweden

The aim of this article is to problematize the ways class and gender are played out in adult students’ narratives about their occupational choice and future. Drawing on Beverly Skeggs, we analyse how students think about future occupations, what motivates them towards these and how they are able to form their future in relation to them. Taking on Sweden as a case, our results show that students’ narratives on their future occupations are classed as well as gendered. In their vision of future occupations, working-class students tend to focus on occupations helping and caring for others, while middleclass students tend to focus on work more as a means of fulfilling themselves as individuals. These differences are also gendered. Female students are more likely than their male counterparts to picture their future occupations in relation to having children and a family. This tells us that in the female students’ narratives, there tends to be a strong focus on caring – for their families as well as in future occupations

Adult education as a heterotopia of deviation : A dwelling for the abnormal citizen

We argue that municipal adult education (MAE) can be seen as a place for displaced and abnormal citizens to gain temporary stability, enabling their shaping into desirable subjects. Drawing on a poststructural discursive analysis, we analyse policy texts and interviews with teachers and students. Our analysis illustrates how two distinct student subjectivities are shaped: the rootless, unmotivated and irresponsible student and the responsible, motivated and goal-oriented one. The difference is that the latter of these subjectivities is positioned as desirable. MAE provides a temporary place in time, a heterotopia of deviation, allowing students to escape precarious employment. The heterotopia places the students in a positive utopian dream of the future. A utopia is not a real place, and what is to become of the students after finishing MAE is not determined; the students themselves should shape it. If they fail, in line with a neoliberal governmentality, it is their own fault.  

Medborgarskap och utbildning för vuxna : Om komvux, folkhögskola och medborgarskapandets praktiker

Utbildning för vuxna lyfts ofta fram som en lösning på en rad aktuella samhällsutmaningar. Allt från miljöfrågor till den mer övergripande målsättningen att skapa ekonomisk tillväxt. Men vuxenutbildningen har också ett tydligt demokratiskt och medborgerligt uppdrag och i denna bok utforskas detta medborgerliga uppdrag utifrån dess grundläggande antaganden, verkningssätt och konsekvenser. Det är en berättelse som å ena sidan handlar om inkludering, erkännande, framtidstro och realiserandet av drömmar, å andra sidan om normalisering, exkludering och villkorad gemenskap. Med andra ord, att bli en god samhällsmedborgare handlar inte enbart om att tillägna sig relevant kunskap