New Opportunities for Air Cathode Batteries; in-Situ Neutron Diffraction Measurements

Batteries with air electrodes are gaining interest as Energy Storage Systems (ESSs) for Electrical Vehicles (EVs) because of their high specific energy density. The electrochemical performance of these batteries is limited by the metallic electrode, which suffers structural transformations and corrosion during cycling that reduces the cycle life of the battery. In this context, relevant information on the discharge products may be obtained by in-situ neutron diffraction, a suitable technique to study electrodes that contain light elements or near neighbor elements in the periodic table. Case studies of MH-air and Fe-air batteries are highlighted

Tuberculosis incidence among migrants according to migrant status: a cohort study, Denmark, 1993 to 2015.

Background Migrants account for the majority of tuberculosis (TB) cases in low-incidence countries in western Europe. TB incidence among migrants might be influenced by patterns of migration, but this is not well understood.Aim To investigate differences in TB risk across migrant groups according to migrant status and region of origin. Methods This prospective cohort study included migrants ≥ 18 years of age who obtained residency in Denmark between 1 January 1993 and 31 December 2015, matched 1:6 to Danish-born individuals. Migrants were grouped according to legal status of residency and region of origin. Incidence rates (IR) and incidence rate ratios (IRR) were estimated by Poisson regression. Results The cohort included 142,314 migrants. Migrants had significantly higher TB incidence (IR: 120/100,000 person-years (PY); 95% confidence interval (CI): 115–126) than Danish-born individuals (IR: 4/100,000 PY; 95% CI: 3–4). The IRR was significantly higher in all migrant groups compared with Danish-born (p < 0.01). A particularly higher risk was seen among family-reunified to refugees (IRR: 61.8; 95% CI: 52.7–72.4), quota refugees (IRR: 46.0; 95% CI: 36.6–57.6) and former asylum seekers (IRR: 45.3; 95% CI: 40.2–51.1), whereas lower risk was seen among family-reunified to Danish/Nordic citizens (IRR 15.8; 95% CI: 13.6–18.4) and family-reunified to immigrants (IRR: 16.9; 95% CI: 13.5–21.3). Discussion All migrants had higher TB risk compared with the Danish-born population. While screening programmes focus mostly on asylum seekers, other migrant groups with high risk of TB are missed. Awareness of TB risk in all high-risk groups should be strengthened and screening programmes should be optimised

Mapping translocation breakpoints using a wheat microarray

We report mapping of translocation breakpoints using a microarray. We used complex RNA to compare normal hexaploid wheat (17 000 Mb genome) to a ditelosomic stock missing the short arm of chromosome 1B (1BS) and wheat-rye translocations that replace portions of 1BS with rye 1RS. Transcripts detected by a probe set can come from all three Triticeae genomes in ABD hexaploid wheat, and sequences of homoeologous genes on 1AS, 1BS and 1DS often differ from each other. Absence or replacement of 1BS therefore must sometimes result in patterns within a probe set that deviate from hexaploid wheat. We termed these ‘high variance probe sets’ (HVPs) and examined the extent to which HVPs associated with 1BS aneuploidy are related to rice genes on syntenic rice chromosome 5 short arm (5S). We observed an enrichment of such probe sets to 15–20% of all HVPs, while 1BS represents ∼2% of the total genome. In total 257 HVPs constitute wheat 1BS markers. Two wheat-rye translocations subdivided 1BS HVPs into three groups, allocating translocation breakpoints to narrow intervals defined by rice 5S coordinates. This approach could be extended to the entire wheat genome or any organism with suitable aneuploid or translocation stocks

Suppression of type 1 pilus assembly in uropathogenic Escherichia coli by chemical inhibition of subunit polymerization

OBJECTIVES: To identify and to characterize small-molecule inhibitors that target the subunit polymerization of the type 1 pilus assembly in uropathogenic Escherichia coli (UPEC). METHODS: Using an SDS-PAGE-based assay, in silico pre-filtered small-molecule compounds were screened for specific inhibitory activity against the critical subunit polymerization step of the chaperone-usher pathway during pilus biogenesis. The biological activity of one of the compounds was validated in assays monitoring UPEC type 1 pilus biogenesis, type 1 pilus-dependent biofilm formation and adherence to human bladder epithelial cells. The time dependence of the in vivo inhibitory activity and the overall effect of the compound on UPEC growth were determined. RESULTS: N-(4-chloro-phenyl)-2-{5-[4-(pyrrolidine-1-sulfonyl)-phenyl]-[1,3,4]oxadiazol-2-yl sulfanyl}-acetamide (AL1) inhibited in vitro pilus subunit polymerization. In bacterial cultures, AL1 disrupted UPEC type 1 pilus biogenesis and pilus-dependent biofilm formation, and resulted in the reduction of bacterial adherence to human bladder epithelial cells, without affecting bacterial cell growth. Bacterial exposure to the inhibitor led to an almost instantaneous loss of type 1 pili. CONCLUSIONS: We have identified and characterized a small molecule that interferes with the assembly of type 1 pili. The molecule targets the polymerization step during the subunit incorporation cycle of the chaperone-usher pathway. Our discovery provides new insight into the design and development of novel anti-virulence therapies targeting key virulence factors of bacterial pathogens

Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA

Distinct families of multipotent heart progenitors play a central role in the generation of diverse cardiac, smooth muscle and endothelial cell lineages during mammalian cardiogenesis. The identification of precise paracrine signals that drive the cell-fate decision of these multipotent progenitors, and the development of novel approaches to deliver these signals in vivo, are critical steps towards unlocking their regenerative therapeutic potential. Herein, we have identified a family of human cardiac endothelial intermediates located in outflow tract of the early human fetal hearts (OFT-ECs), characterized by coexpression of Isl1 and CD144/vWF. By comparing angiocrine factors expressed by the human OFT-ECs and non-cardiac ECs, vascular endothelial growth factor (VEGF)-A was identified as the most abundantly expressed factor, and clonal assays documented its ability to drive endothelial specification of human embryonic stem cell (ESC)-derived Isl1+ progenitors in a VEGF receptor-dependent manner. Human Isl1-ECs (endothelial cells differentiated from hESC-derived ISL1+ progenitors) resemble OFT-ECs in terms of expression of the cardiac endothelial progenitor- and endocardial cell-specific genes, confirming their organ specificity. To determine whether VEGF-A might serve as an in vivo cell-fate switch for human ESC-derived Isl1-ECs, we established a novel approach using chemically modified mRNA as a platform for transient, yet highly efficient expression of paracrine factors in cardiovascular progenitors. Overexpression of VEGF-A promotes not only the endothelial specification but also engraftment, proliferation and survival (reduced apoptosis) of the human Isl1+ progenitors in vivo. The large-scale derivation of cardiac-specific human Isl1-ECs from human pluripotent stem cells, coupled with the ability to drive endothelial specification, engraftment, and survival following transplantation, suggest a novel strategy for vascular regeneration in the heart

A prospective pilot clinical trial evaluating the utility of a dynamic near-infrared imaging device for characterizing suspicious breast lesions

Introduction: Characterizing and differentiating between malignant tumors, benign tumors, and normal breast tissue is increasingly important in the patient presenting with breast problems. Near-infrared diffuse optical imaging and spectroscopy is capable of measuring multiple physiologic parameters of biological tissue systems and may have clinical applications for assessing the development and progression of neoplastic processes, including breast cancer. The currently available application of near-infrared imaging technology for the breast, however, is compromised by low spatial resolution, tissue heterogeneity, and interpatient variation. Materials and methods: We tested a dynamic near-infrared imaging schema for the characterization of suspicious breast lesions identified on diagnostic clinical ultrasound. A portable handheld near-infrared tissue imaging device (P-Scan; ViOptix Inc., Fremont, CA, USA) was utilized. An external mechanical compression force was applied to breast tissue. The tissue oxygen saturation and hemoglobin concentration were recorded simultaneously by the handheld near-infrared imaging device. Twelve categories of dynamic tissue parameters were derived based on real-time measurements of the tissue hemoglobin concentration and the oxygen saturation. Results: Fifty suspicious breast lesions were evaluated in 48 patients. Statistical analyses were carried out on 36 out of 50 datasets that satisfied our inclusion criteria. Suspicious breast lesions identified on diagnostic clinical ultrasound had lower oxygenation and higher hemoglobin concentration than the surrounding normal breast tissue. Furthermore, histopathologic-proven malignant breast tumors had a lower differential hemoglobin contrast (that is, the difference of hemoglobin concentration variability between the suspicious breast lesion and the normal breast parenchyma located remotely elsewhere within the ipsilateral breast) as compared with histopathologic-proven benign breast lesions. Conclusion: The proposed dynamic near-infrared imaging schema has the potential to differentiate benign processes from those of malignant breast tumors. Further development and refinement of the dynamic imaging device and additional subsequent clinical testing are necessary for optimizing the accuracy of detection

Country Concepts and the Rational Actor Trap: Limitations to Strategic Management of International NGOs

Growing criticism of inefficient development aid demanded new planning instruments of donors, including international NGOs (INGOs). A reorientation from isolated project-planning towards holistic country concepts and the increasing rationality of a result-orientated planning process were seen as answer. However, whether these country concepts - newly introduced by major INGOs too - have increased the efficiency of development cooperation is open to question. Firstly, there have been counteracting external factors, like the globalization of the aid business, that demanded structural changes in the composition of INGO portfolios towards growing short-term humanitarian aid; this was hardly compatible with the requirements of medium-term country planning. Secondly, the underlying vision of rationality as a remedy for the major ills of development aid was in itself a fallacy. A major change in the methodology of planning, closely connected with a shift of emphasis in the approach to development cooperation, away from project planning and service delivery, towards supporting the socio-cultural and political environment of the recipient communities, demands a reorientation of aid management: The most urgent change needed is by donors, away from the blinkers of result-orientated planning towards participative organizational cultures of learning.Des critiques croissantes de l'aide au développement inefficace exigent de nouveaux instruments de planification des bailleurs de fonds, y compris les ONG internationales (ONGI). Une réorientation de la planification des projets isolés vers des concepts holistiques de la planification de l’aide par pays ainsi que la rationalité croissante d'un processus de planification orientée vers les résultats ont été considérés comme réponse. Toutefois, si ces concepts de pays - nouvellement introduites par les grandes OING eux aussi - ont augmenté l'efficacité de la coopération au développement est ouvert à la question. Tout d'abord, il y a eu l’impact des facteurs externes, comme la mondialisation de l'entreprise de l'aide, qui a exigé des changements structurels dans la composition des portefeuilles des OING vers la croissance de l'aide humanitaire à court terme. Cela était difficilement compatible avec les exigences de l'aménagement du territoire à moyen terme. Deuxièmement, la vision sous-jacente de la rationalité accrue de la planification, concentré sur les resultats, comme un remède pour les grands maux de l'aide au développement était en soi une erreur. Un changement majeur dans la méthodologie de la planification, étroitement liée à un changement d'orientation dans l'approche de la coopération au développement, qui n’est pas concentrer sur planification du projet et la prestation de services, mais qui soutienne l'environnement socio-culturel et politique des communautés bénéficiaires, exige une réorientation de la gestion de l’aide: Le changement le plus urgent est un changement par les donateurs eux-mêmes, qui devrait implanter des cultures de collaboration étroit avec les partenaires et la population locale

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms