Platinum Assisted Vapor–Liquid–Solid Growth of Er–Si Nanowires and Their Optical Properties

We report the optical activation of erbium coated silicon nanowires (Er–SiNWs) grown with the assist of platinum (Pt) and gold (Au), respectively. The NWs were grown on Si substrates by using a chemical vapor transport process using SiCl4 and ErCl4 as precursors. Pt as well as Au worked successfully as vapor–liquid–solid (VLS) catalysts for growing SiNWs with diameters of ~100 nm and length of several micrometers, respectively. The SiNWs have core–shell structures where the Er-crystalline layer is sandwiched between silica layers. Photoluminescence spectra analyses showed the optical activity of SiNWs from both Pt and Au. A stronger Er3+ luminescence of 1,534 nm was observed from the SiNWs with Pt at room- and low-temperature (25 K) using the 488- and/or 477-nm line of an Ar laser that may be due to the uniform incorporation of more Er ions into NWs with the exclusion of the formation of catalyst-induced deep levels in the band-gap. Pt would be used as a VLS catalyst for high performance optically active Er–SiNWs

AhR transcriptional activity in serum of Inuits across Greenlandic districts

<p>Abstract</p> <p>Background</p> <p>Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-<it>p</it>-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors.</p> <p>Methods</p> <p>The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast), Qaanaaq (North Coast) and Tasiilaq (East Coast). The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors.</p> <p>Results</p> <p>In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ) of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk ≥ Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food.</p> <p>Conclusion</p> <p>i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain.</p

An Obligatory Role of Mind Bomb-1 in Notch Signaling of Mammalian Development

Background. The Notch signaling pathway is an evolutionarily conserved intercellular signaling module essential for cell fate specification that requires endocytosis of Notch ligands. Structurally distinct E3 ubiquitin ligases, Neuralized (Neur) and Mind bomb (Mib), cooperatively regulate the endocytosis of Notch ligands in Drosophila. However, the respective roles of the mammalian E3 ubiquitin ligases, Neur1, Neur2, Mib1, and Mib2, in mammalian development are poorly understood. Methodology/Principal Findings. Through extensive use of mammalian genetics, here we show that Neur1 and Neur2 double mutants and Mib2-1- mice were viable and grossly normal. In contrast, conditional inactivation of MW in various tissues revealed the representative Notch phenotypes: defects of arterial specification as deltalike4 mutants, abnormal cerebellum and skin development as jagged1 conditional mutants, and syndactylism as jagged2 mutants. Conclusions/Significance. Our data provide the first evidence that Mib1 is essential for Jagged as well as Deltalike ligand-mediated Notch signaling in mammalian development, while Neur1, Neur2, and Mib2 are dispensable.open504

A Buoyancy-Based Screen of Drosophila Larvae for Fat-Storage Mutants Reveals a Role for Sir2 in Coupling Fat Storage to Nutrient Availability

Obesity has a strong genetic component, but few of the genes that predispose to obesity are known. Genetic screens in invertebrates have the potential to identify genes and pathways that regulate the levels of stored fat, many of which are likely to be conserved in humans. To facilitate such screens, we have developed a simple buoyancy-based screening method for identifying mutant Drosophila larvae with increased levels of stored fat. Using this approach, we have identified 66 genes that when mutated increase organismal fat levels. Among these was a sirtuin family member, Sir2. Sirtuins regulate the storage and metabolism of carbohydrates and lipids by deacetylating key regulatory proteins. However, since mammalian sirtuins function in many tissues in different ways, it has been difficult to define their role in energy homeostasis accurately under normal feeding conditions. We show that knockdown of Sir2 in the larval fat body results in increased fat levels. Moreover, using genetic mosaics, we demonstrate that Sir2 restricts fat accumulation in individual cells of the fat body in a cell-autonomous manner. Consistent with this function, changes in the expression of metabolic enzymes in Sir2 mutants point to a shift away from catabolism. Surprisingly, although Sir2 is typically upregulated under conditions of starvation, Sir2 mutant larvae survive better than wild type under conditions of amino-acid starvation as long as sugars are provided. Our findings point to a Sir2-mediated pathway that activates a catabolic response to amino-acid starvation irrespective of the sugar content of the diet

Adverse Drug Reactions in Hospital In-Patients: A Prospective Analysis of 3695 Patient-Episodes

Adverse drug reactions (ADRs) are a major cause of hospital admissions, but recent data on the incidence and clinical characteristics of ADRs which occur following hospital admission, are lacking. Patients admitted to twelve wards over a six-month period in 2005 were assessed for ADRs throughout their admission. Suspected ADRs were recorded and analysed for causality, severity and avoidability and whether they increased the length of stay. Multivariable analysis was undertaken to identify the risk factors for ADRs. The 5% significance level was used when assessing factors for inclusion in multivariable models. Out of the 3695 patient episodes assessed for ADRs, 545 (14.7%, 95% CI 13.6–15.9%) experienced one or more ADRs. Half of ADRs were definitely or possibly avoidable. The patients experiencing ADRs were more likely to be older, female, taking a larger number of medicines, and had a longer length of stay than those without ADRs. However, the only significant predictor of ADRs, from the multivariable analysis of a representative sample of patients, was the number of medicines taken by the patient with each additional medication multiplying the hazard of an ADR episode by 1.14 (95% CI 1.09, 1.20). ADRs directly increased length of stay in 147 (26.8%) patients. The drugs most frequently associated with ADRs were diuretics, opioid analgesics, and anticoagulants. In conclusion, approximately one in seven hospital in-patients experience an ADR, which is a significant cause of morbidity, increasing the length of stay of patients by an average of 0.25 days/patient admission episode. The overall burden of ADRs on hospitals is high, and effective intervention strategies are urgently needed to reduce this burden

Efficacy of fixed-dose amlodipine and losartan combination compared with amlodipine monotherapy in stage 2 hypertension: a randomized, double blind, multicenter study

<p>Abstract</p> <p>Background</p> <p>The objective of this trial was to compare the blood-pressure lowering efficacy of amlodipine/losartan combination with amlodipine monotherapy after 6 weeks of treatment in Korean patients with stage 2 hypertension.</p> <p>Results</p> <p>In this multi-center, double-blind, randomized study, adult patients (n = 148) with stage 2 hypertension were randomized to amlodipine 5 mg/losartan 50 mg or amlodipine 5 mg. After 2 weeks, patients with systolic blood pressure (SBP) > 140 mmHg were titrated to amlodipine 10 mg/losartan 50 mg or amlodipine 10 mg. After 4 weeks of titration, hydrochlorothiazide 12.5 mg could be optionally added to both groups. The change from baseline in SBP was assessed after 6 weeks. The responder rate (defined as achieving SBP < 140 mmHg or DBP < 90 mmHg) was also assessed at 2, 6 and 8 weeks as secondary endpoints. Safety and tolerability were assessed through adverse event monitoring and laboratory testing. Baseline demographics and clinical characteristics were generally similar between treatment groups. Least-square mean reduction in SBP at 6 weeks (primary endpoint) was significantly greater in the combination group (36.5 mmHg vs. 31.6 mmHg; p = 0.0117). The responder rate in SBP (secondary endpoints) was significantly higher in the combination group at 2 weeks (52.1% vs. 33.3%; p = 0.0213) but not at 6 weeks (p = 0.0550) or 8 weeks (p = 0.0592). There was no significant difference between groups in the incidence of adverse events.</p> <p>Conclusion</p> <p>These results demonstrate that combination amlodipine/losartan therapy provides an effective and generally well-tolerated first line therapy for reducing blood pressure in stage 2 hypertensive patients.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01127217">NCT01127217</a></p

Origination of New Immunological Functions in the Costimulatory Molecule B7-H3: The Role of Exon Duplication in Evolution of the Immune System

B7-H3, a recently identified B7 family member, has different isoforms in human and mouse. Mouse B7-H3 gene has only one isoform (2IgB7-H3) with two Ig-like domains, whereas human B7-H3 has two isoforms (2IgB7-H3 and 4IgB7-H3). In this study a systematic genomic survey across various species from teleost fishes to mammals revealed that 4IgB7-H3 isoform also appeared in pigs, guinea pigs, cows, dogs, African elephants, pandas, megabats and higher primate animals, which resulted from tandem exon duplication. Further sequence analysis indicated that this duplication generated a new conserved region in the first IgC domain, which might disable 4IgB7-H3 from releasing soluble form, while 2IgB7-H3 presented both membrane and soluble forms. Through three-dimensional (3D) structure modeling and fusion-protein binding assays, we discovered that the duplicated isoform had a different structure and might bind to another potential receptor on activated T cells. In T cell proliferation assay, human 2IgB7-H3 (h2IgB7-H3) and mouse B7-H3 (mB7-H3) both increased T cell proliferation and IL-2, IFN-γ production, whereas human 4IgB7-H3 (h4IgB7-H3) reduced cytokine production and T cell proliferation compared to control. Furthermore, both h2IgB7-H3 and mB7-H3 upregulated the function of lipopolysacharide (LPS)-activated monocyte in vitro. Taken together, our data implied that during the evolution of vertebrates, B7-H3 exon duplication contributed to the generation of a new 4IgB7-H3 isoform in many mammalian species, which have carried out distinct functions in the immune responses