Exploiting Locally Imposed Anisotropies in (Ga,Mn)As: a Non-volatile Memory Device

Progress in (Ga,Mn)As lithography has recently allowed us to realize structures where unique magnetic anisotropy properties can be imposed locally in various regions of a given device. We make use of this technology to fabricate a device in which we study transport through a constriction separating two regions whose magnetization direction differs by 90 degrees. We find that the resistance of the constriction depends on the flow of the magnetic field lines in the constriction region and demonstrate that such a structure constitutes a non-volatile memory device

Supporting frail older people with depression and anxiety: a qualitative study

Objectives: Depression and anxiety are common in later life, particularly when people are frail. This leads to reduced quality of life, faster decline in physical health and increased health/social care use. Available treatments are commonly not tailored to people with frailty. We explored frail older peoples’ experiences of depression and/or anxiety and how services could be adapted to their needs. / Methods: Semi-structured interviews with 28 older people in the UK purposively sampled for practice location and severity of frailty and anxiety/depression. We asked about symptoms, interactions with physical health, help-seeking, treatments and what might help in future. We audio-recorded and transcribed interviews, using thematic analysis to inductively derive themes. / Results: Frail older people had low expectations of their wellbeing at this point in life due to multiple physical health issues and so anxiety and mild depressive symptoms were normalised. There was a particular reluctance and uncertainty regarding help-seeking for anxiety. Treatments were considered appropriate where they aligned with coping skills developed over their lifetime, and facilitated independence and problem-solving skills. Most older people felt their knowledge of mental health was limited and relied upon information about and endorsement of therapies from an expert. This was usually their GP, but access was often problematic. Online methods of accessing information and therapies were not popular. / Conclusion: Mental health support for frail older people needs to address late-life anxieties as well as depression, account for physical health issues, align with older people’s need for independence and facilitate coping skills

Evaluation of Pneumococcal Serotyping of Nasopharyngeal-Carriage Isolates by Latex Agglutination, Whole-Genome Sequencing (PneumoCaT), and DNA Microarray in a High-Pneumococcal-Carriage-Prevalence Population in Malawi.

Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations. Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine [PCV13] as part of the Expanded Program on Immunization [EPI]), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut [SSI], Denmark). For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. A total of 1,347 samples were analyzed. Concordance was 90.7% (95% confidence interval [CI], 89.0 to 92.2%) between latex agglutination and PneumoCaT, 95.2% (95% CI, 93.9 to 96.3%) between latex agglutination and the microarray, and 96.6% (95% CI, 95.5 to 97.5%) between the microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococci carried at low relative abundances (median, 8%), the microarray increased VT detection by 31.5% over that by latex serotyping. To conclude, all three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine serotypes and requires the least expertise and resources for field implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories for investigating the importance of vaccine serotypes at low relative abundances in transmission and disease

Evaluation of pneumococcal serotyping in nasopharyngeal carriage isolates by latex agglutination, whole genome sequencing (PneumoCaT) and DNA microarray in a high pneumococcal carriage prevalence population in Malawi

BACKGROUND: Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for the evaluation and formulation of pneumococcal vaccines and informing vaccine policy. METHODS: We evaluated pneumococcal serotyping concordance between latex agglutination, PneumoCaT by whole genome sequencing (WGS) and DNA microarray using samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected, following WHO recommendations, between 2015 and 2017, using stratified random sampling among study populations. Participants included healthy children 3–6 years old (PCV13 vaccinated as part of EPI), healthy children 5–10 years (age-ineligible for PCV13), and HIV-infected adults (18–40yrs) on ART. For phenotypic serotyping we used a 13-valent latex kit (SSI, Denmark). For genomic serotyping we applied PneumoCaT pipeline to whole genome sequence libraries. For molecular serotyping by microarray we used the BUGS Bioscience Senti-SP microarray. RESULTS: 1347 samples were analysed. Concordance was 90.7% (95% CI: 89.0–92.2) between latex and PneumoCaT; 95.2% (93.9–96.3) between latex and microarray; and 96.6% (95.5–97.5) between microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococcus carried at low relative abundance (median 8%), microarray increased VT detection by 31.5% compared to latex serotyping. CONCLUSION: All three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine-serotypes and requires the least expertise and resources for field-implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories while investigating the importance of VT in low relative abundance in transmission and disease

A novel hybrid promoter responsive to pathophysiological and pharmacological regulation

The aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic conditions or through pharmacological induction, and also show pharmacological repression. In vivo studies utilised electroporation of plasmid to mouse paws, a delivery method shown to be effective by bioluminescence imaging. For gene therapy, the promoter was used to drive expression of IL-1Ra in a paw inflammation model with therapeutic effect observed which was further enhanced when the promoter was additionally induced with a pharmacological activator. One of the most important observations from this study was that promoter induction by hypoxia or inflammation could be prevented by the pharmacological repressor in the absence of doxycycline. These studies demonstrate that hybrid promoters enable pharmacological adjustment to the pathophysiological level of gene expression and, importantly, that they allow termination of gene expression even in the presence of pathophysiological stimuli

Virulence profiling and quantification of verocytotoxin-producing Escherichia coli O145:H28 and O26:H11 isolated during an ice cream-related hemolytic uremic syndrome outbreak

In September-October 2007, a mixed-serotype outbreak of verocytotoxin-producing Escherichia coli (VTEC) O145:H28 and O26:H11 occurred in the province of Antwerp, Belgium. Five girls aged between 2 and 11 years developed hemolytic uremic syndrome, and seven other coexposed persons with bloody diarrhea were identified. Laboratory confirmation of O145:H28 infection was obtained for three hemolytic uremic syndrome patients, one of whom was coinfected with O26:H11. The epidemiological and laboratory investigations revealed ice cream as the most likely source of the outbreak. The ice cream was produced at a local dairy farm using pasteurized milk. VTEC of both serotypes with indistinguishable pulsed-field gel electrophoresis patterns were isolated from patients, ice cream, and environmental samples. Quantitative analysis of the ice cream indicated concentrations of 2.4 and 0.03 CFU/g for VTEC O145 and O26, respectively. Virulence typing revealed that the repertoire of virulence genes carried by the O145:H28 outbreak strain was comparable to that of O157 VTEC and more exhaustive as compared to the O26:H11 outbreak strain and nonrelated clinical strains belonging to these serotypes. Taken together, these data suggest that O145:H28 played the most important role in this outbreak

Colony-level differences in the scaling rules governing wood ant compound eye structure

Differential organ growth during development is essential for adults to maintain the correct proportions and achieve their characteristic shape. Organs scale with body size, a process known as allometry that has been studied extensively in a range of organisms. Such scaling rules, typically studied from a limited sample, are assumed to apply to all members of a population and/or species. Here we study scaling in the compound eyes of workers of the wood ant, Formica rufa, from different colonies within a single population. Workers' eye area increased with body size in all the colonies showing a negative allometry. However, both the slope and intercept of some allometric scaling relationships differed significantly among colonies. Moreover, though mean facet diameter and facet number increased with body size, some colonies primarily increased facet number whereas others increased facet diameter, showing that the cellular level processes underlying organ scaling differed among colonies. Thus, the rules that govern scaling at the organ and cellular levels can differ even within a single population

Classic yin and yang tonic formula for osteopenia: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is a growing worldwide problem, with the greatest burden resulting from fractures. Nevertheless, the majority of fractures in adults occur in those with "osteopenia" (bone mineral density (BMD) only moderately lower than young normal individuals). Since long-term drug therapy is an expensive option with uncertain consequences and side effects, natural herbal therapy offers an attractive alternative. The purpose of this study is to evaluate the effect on BMD and safety of the Classic Yin and Yang Tonic Formula for treatment of osteopenia and to investigate the mechanism by which this efficacy is achieved.</p> <p>Methods/design</p> <p>We propose a multicenter double-blind randomized placebo-controlled trial to evaluate the efficacy and safety of the Classic Yin and Yang Tonic Formula for the treatment of osteopenia. Participants aged 55 to 75 with low bone mineral density (T-score between -1 and -2.5) and kidney deficiency in TCM will be included and randomly allocated into two groups: treatment group and control group. Participants in the treatment group will be treated with Classic Yin and Yang Tonic Granule, while the controlled group will receive placebo. Primary outcome measure will be BMD of the lumbar spine and proximal femur using dual-energy X-ray absorptiometry. Secondary outcomes will include pain intensity measured with visual analogue scales, quality of life, serum markers of bone metabolism, indices of Neuro-endocrino-immune network and safety.</p> <p>Discussion</p> <p>If the Classic Yin and Yang Tonic Formula can increase bone mass without adverse effects, it may be a novel strategy for the treatment of osteoporosis. Furthermore, the mechanism of the Chinese medical formula for osteoporosis will be partially elucidated.</p> <p>Trial registration</p> <p>This study is registered at ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01271647">NCT01271647</a>.</p

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

A structure filter for the Eukaryotic Linear Motif Resource

<p>Abstract</p> <p>Background</p> <p>Many proteins are highly modular, being assembled from globular domains and segments of natively disordered polypeptides. Linear motifs, short sequence modules functioning independently of protein tertiary structure, are most abundant in natively disordered polypeptides but are also found in accessible parts of globular domains, such as exposed loops. The prediction of novel occurrences of known linear motifs attempts the difficult task of distinguishing functional matches from stochastically occurring non-functional matches. Although functionality can only be confirmed experimentally, confidence in a putative motif is increased if a motif exhibits attributes associated with functional instances such as occurrence in the correct taxonomic range, cellular compartment, conservation in homologues and accessibility to interacting partners. Several tools now use these attributes to classify putative motifs based on confidence of functionality.</p> <p>Results</p> <p>Current methods assessing motif accessibility do not consider much of the information available, either predicting accessibility from primary sequence or regarding any motif occurring in a globular region as low confidence. We present a method considering accessibility and secondary structural context derived from experimentally solved protein structures to rectify this situation. Putatively functional motif occurrences are mapped onto a representative domain, given that a high quality reference SCOP domain structure is available for the protein itself or a close relative. Candidate motifs can then be scored for solvent-accessibility and secondary structure context. The scores are calibrated on a benchmark set of experimentally verified motif instances compared with a set of random matches. A combined score yields 3-fold enrichment for functional motifs assigned to high confidence classifications and 2.5-fold enrichment for random motifs assigned to low confidence classifications. The structure filter is implemented as a pipeline with both a graphical interface via the ELM resource <url>http://elm.eu.org/</url> and through a Web Service protocol.</p> <p>Conclusion</p> <p>New occurrences of known linear motifs require experimental validation as the bioinformatics tools currently have limited reliability. The ELM structure filter will aid users assessing candidate motifs presenting in globular structural regions. Most importantly, it will help users to decide whether to expend their valuable time and resources on experimental testing of interesting motif candidates.</p