Resistance of Common Circulating Enteric Bacterial Pathogens to Prescribed Antibiotics Among Under Five Years in Selected Public Hospitals in Kenya

No Abstract

The Eliashberg Function of Amorphous Metals

A connection is proposed between the anomalous thermal transport properties of amorphous solids and the low-frequency behavior of the Eliashberg function. By means of a model calculation we show that the size and frequency dependence of the phonon mean-free-path that has been extracted from measurements of the thermal conductivity in amorphous solids leads to a sizeable linear region in the Eliashberg function at small frequencies. Quantitative comparison with recent experiments gives very good agreement.Comment: 4pp., REVTeX, 1 uuencoded ps fig. Original posting had a corrupted raw ps fig appended. Published as PRB 51, 689 (1995

SINEUPs: A novel toolbox for RNA therapeutics

RNA molecules have emerged as a new class of promising therapeutics to expand the range of druggable targets in the genome. In addition to 'canonical' protein-coding mRNAs, the emerging richness of sense and antisense long non-coding RNAs (lncRNAs) provides a new reservoir of molecular tools for RNA-based drugs. LncRNAs are composed of modular structural domains with specific activities involving the recruitment of protein cofactors or directly interacting with nucleic acids. A single therapeutic RNA transcript can then be assembled combining domains with defined secondary structures and functions, and antisense sequences specific for the RNA/DNA target of interest. As the first representative molecules of this new pharmacology, we have identified SINEUPs, a new functional class of natural antisense lncRNAs that increase the translation of partially overlapping mRNAs. Their activity is based on the combination of two domains: An embedded mouse inverted SINEB2 element that enhances mRNA translation (effector domain) and an overlapping antisense region that provides specificity for the target sense transcript (binding domain). By genetic engineering, synthetic SINEUPs can potentially target any mRNA of interest increasing translation and therefore the endogenous level of the encoded protein. In this review, we describe the state-of-the-art knowledge of SINEUPs and discuss recent publications showing their potential application in diseases where a physiological increase of endogenous protein expression can be therapeutic

Observation of the Bs0→J/ψϕϕB_s^0 \rightarrow J/\psi \phi \phi decay

The $B_s^0 \rightarrow J/\psi \phi \phi$ decay is observed in $pp$ collision data corresponding to an integrated luminosity of 3 fb$^{-1}$ recorded by the LHCb detector at centre-of-mass energies of 7 TeV and 8 TeV. This is the first observation of this decay channel, with a statistical significance of 15 standard deviations. The mass of the $B_s^0$ meson is measured to be $5367.08\,\pm \,0.38\,\pm\, 0.15$ MeV/c$^2$. The branching fraction ratio $\mathcal{B}(B_s^0 \rightarrow J/\psi \phi \phi)/\mathcal{B}(B_s^0 \rightarrow J/\psi \phi)$ is measured to be 0.0115\,\pm\, 0.0012\, ^{+0.0005}_{-0.0009}. In both cases, the first uncertainty is statistical and the second is systematic. No evidence for non-resonant $B_s^0 \rightarrow J/\psi \phi K^+ K^-$ or $B_s^0 \rightarrow J/\psi K^+ K^- K^+ K^-$ decays is found.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-033.htm

Interactions between hypoxia tolerance and food deprivation in Amazonian oscars, Astronotus ocellatus

Oscars are often subjected to a combination of low levels of oxygen and fasting during nest-guarding on Amazonian floodplains. We questioned whether this anorexia would aggravate the osmo-respiratory compromise. We compared fed and fasted oscars (1014 days) in both normoxia and hypoxia (1020 Torr, 4 h). Routine oxygen consumption rates (MO2) were increased by 75% in fasted fish, reflecting behavioural differences, whereas fasting improved hypoxia resistance and critical oxygen tensions (Pcrit) lowered from 54 Torr in fed fish to 34 Torr when fasting. In fed fish, hypoxia reduced liver lipid stores by approximately 50% and total liver energy content by 30%. Fasted fish had a 50% lower hepatosomatic index, resulting in lower total liver protein, glycogen and lipid energy stores under normoxia. Compared with hypoxic fed fish, hypoxic fasted fish only showed reduced liver protein levels and even gained glycogen (+50%) on a per gram basis. This confirms the hypothesis that hypoxia-tolerant fish protect their glycogen stores as much as possible as a safeguard for more prolonged hypoxic events. In general, fasted fish showed lower hydroxyacylCoA dehydrogenase activities compared with fed fish, although this effect was only significant in hypoxic fasted fish. Energy stores and activities of enzymes related to energy metabolism in muscle or gills were not affected. Branchial Na+ uptake rates were more than two times lower in fed fish, whereas Na+ efflux was similar. Fed and fasted fish quickly reduced Na+ uptake and efflux during hypoxia, with fasting fish responding more rapidly. Ammonia excretion and K+ efflux were reduced under hypoxia, indicating decreased transcellular permeability. Fasted fish had more mitochondria-rich cells (MRC), with larger crypts, indicating the increased importance of the branchial uptake route when feeding is limited. Gill MRC density and surface area were greatly reduced under hypoxia, possibly to reduce ion uptake and efflux rates. Density of mucous cells of normoxic fasted fish was approximately fourfold of that in fed fish. Overall, a 1014 day fasting period had no negative effects on hypoxia tolerance in oscars, as fasted fish were able to respond more quickly to lower oxygen levels, and reduced branchial permeability effectively. © 2013. Published by The Company of Biologists Ltd

Regulation of gill transcellular permeability and renal function during acute hypoxia in the Amazonian oscar (Astronotus ocellatus): New angles to the osmorespiratory compromise

Earlier studies demonstrated that oscars, endemic to ion-poor Amazonian waters, are extremely hypoxia tolerant, and exhibit a marked reduction in active unidirectional Na+ uptake rate (measured directly) but unchanged net Na+ balance during acute exposure to low Po2, indicating a comparable reduction in whole body Na+ efflux rate. However, branchial O2 transfer factor does not fall. The present study focused on the nature of the efflux reduction in the face of maintained gill O 2 permeability. Direct measurements of 22Na appearance in the water from bladder-catheterized fish confirmed a rapid 55% fall in unidirectional Na+ efflux rate across the gills upon acute exposure to hypoxia (PO2=10-20torr; 1 torr=133.3 Pa), which was quickly reversed upon return to normoxia. An exchange diffusion mechanism for Na + is not present, so the reduction in efflux was not directly linked to the reduction in Na+ influx. A quickly developing bradycardia occurred during hypoxia. Transepithelial potential, which was sensitive to water [Ca2+], became markedly less negative during hypoxia and was restored upon return to normoxia. Ammonia excretion, net K+ loss rates, and 3H2O exchange rates (diffusive water efflux rates) across the gills fell by 55-75% during hypoxia, with recovery during normoxia. Osmotic permeability to water also declined, but the fall (30%) was less than that in diffusive water permeability (70%). In total, these observations indicate a reduction in gill transcellular permeability during hypoxia, a conclusion supported by unchanged branchial efflux rates of the paracellular marker [3H]PEG-4000 during hypoxia and normoxic recovery. At the kidney, glomerular filtration rate, urine flow rate, and tubular Na+ reabsorption rate fell in parallel by 70% during hypoxia, facilitating additional reductions in costs and in urinary Na+, K+ and ammonia excretion rates. Scanning electron microscopy of the gill epithelium revealed no remodelling at a macro-level, but pronounced changes in surface morphology. Under normoxia, mitochondria-rich cells were exposed only through small apical crypts, and these decreased in number by 47% and in individual area by 65% during 3 h hypoxia. We suggest that a rapid closure of transcellular channels, perhaps effected by pavement cell coverage of the crypts, allows conservation of ions and reduction of ionoregulatory costs without compromise of O2 exchange capacity during acute hypoxia, a response very different from the traditional osmorespiratory compromise

Continuous and transparent multimodal authentication: reviewing the state of the art

Individuals, businesses and governments undertake an ever-growing range of activities online and via various Internet-enabled digital devices. Unfortunately, these activities, services, information and devices are the targets of cybercrimes. Verifying the user legitimacy to use/access a digital device or service has become of the utmost importance. Authentication is the frontline countermeasure of ensuring only the authorized user is granted access; however, it has historically suffered from a range of issues related to the security and usability of the approaches. They are also still mostly functioning at the point of entry and those performing sort of re-authentication executing it in an intrusive manner. Thus, it is apparent that a more innovative, convenient and secure user authentication solution is vital. This paper reviews the authentication methods along with the current use of authentication technologies, aiming at developing a current state-of-the-art and identifying the open problems to be tackled and available solutions to be adopted. It also investigates whether these authentication technologies have the capability to fill the gap between high security and user satisfaction. This is followed by a literature review of the existing research on continuous and transparent multimodal authentication. It concludes that providing users with adequate protection and convenience requires innovative robust authentication mechanisms to be utilized in a universal level. Ultimately, a potential federated biometric authentication solution is presented; however it needs to be developed and extensively evaluated, thus operating in a transparent, continuous and user-friendly manner

CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

<p>Abstract</p> <p>Background</p> <p>Design of effective vaccines against the human immunodeficiency virus (HIV-1) continues to present formidable challenges. However, individuals who are exposed HIV-1 but do not get infected may reveal correlates of protection that may inform on effective vaccine design. A preliminary gene expression analysis of HIV resistant female sex workers (HIV-R) suggested a high expression CD26/DPPIV gene. Previous studies have indicated an anti-HIV effect of high CD26/DPPIV expressing cells in vitro. Similarly, high CD26/DPPIV protein levels in vivo have been shown to be a risk factor for type 2 diabetes. We carried out a study to confirm if the high CD26/DPPIV gene expression among the HIV-R were concordant with high blood protein levels and its correlation with clinical type 2 diabetes and other perturbations in the insulin signaling pathway.</p> <p>Results</p> <p>A quantitative CD26/DPPIV plasma analysis from 100 HIV-R, 100 HIV infected (HIV +) and 100 HIV negative controls (HIV Neg) showed a significantly elevated CD26/DPPIV concentration among the HIV-R group (mean 1315 ng/ml) than the HIV Neg (910 ng/ml) and HIV + (870 ng/ml, p < 0.001). Similarly a FACs analysis of cell associated DPPIV (CD26) revealed a higher CD26/DPPIV expression on CD4+ T-cells derived from HIV-R than from the HIV+ (90.30% vs 80.90 p = 0.002) and HIV Neg controls (90.30% vs 82.30 p < 0.001) respectively. A further comparison of the mean fluorescent intensity (MFI) of CD26/DPPIV expression showed a higher DPP4 MFI on HIV-R CD4+ T cells (median 118 vs 91 for HIV-Neg, p = 0.0003). An evaluation for hyperglycemia, did not confirm Type 2 diabetes but an impaired fasting glucose condition (5.775 mmol/L). A follow-up quantitative PCR analysis of the insulin signaling pathway genes showed a down expression of NFκB, a central mediator of the immune response and activator of HIV-1 transcription.</p> <p>Conclusion</p> <p>HIV resistant sex workers have a high expression of CD26/DPPIV in tandem with lowered immune activation markers. This may suggest a novel role for CD26/DPPIV in protection against HIV infection in vivo.</p

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark