280 research outputs found

    Isolating the photovoltaic junction: atomic layer deposited TiO2-RuO2 alloy Schottky contacts for silicon photoanodes

    Get PDF
    We synthesized nanoscale TiO2-RuO2 alloys by atomic layer deposition (ALD) that possess a high work function and are highly conductive. As such, they function as good Schottky contacts to extract photogenerated holes from n-type silicon while simultaneously interfacing with water oxidation catalysts. The ratio of TiO2 to RuO2 can be precisely controlled by the number of ALD cycles for each precursor. Increasing the composition above 16% Ru sets the electronic conductivity and the metal work function. No significant Ohmic loss for hole transport is measured as film thickness increases from 3 to 45 nm for alloy compositions >= 16% Ru. Silicon photoanodes with a 2 nm SiO2 layer that are coated by these alloy Schottky contacts having compositions in the range of 13-46% Ru exhibit average photovoltages of 525 mV, with a maximum photovoltage of 570 mV achieved. Depositing TiO2-RuO2 alloys on nSi sets a high effective work function for the Schottky junction with the semiconductor substrate, thus generating a large photovoltage that is isolated from the properties of an overlying oxygen evolution catalyst or protection layer

    Where do children die and what are the causes? Under-5 deaths in the Metro West geographical service area of the Western Cape, South Africa, 2011

    Get PDF
    Background. Accurate child mortality data are essential to plan health interventions to reduce child deaths.Objectives. To review the deaths of children aged <5 years during 2011 in the Metro West geographical service area (GSA) of the Western Cape Province (WC), South Africa, from routine data sources.Methods. A retrospective study of under-5 deaths in the Metro West GSA was done using the WC Local Mortality Surveillance System (LMSS), the Child Healthcare Problem Identification Programme (Child PIP) and the Perinatal Problem Identification Programme (PPIP), and linking where possible.Results. The LMSS reported 700 under-5 deaths, Child PIP 99 and PPIP 252, with an under-5 mortality rate of 18 deaths per 1 000 live births. The leading causes of death were pneumonia (25%), gastroenteritis (10%), prematurity (9%) and injuries (9%). There were 316 in-hospital deaths (45%) and 384 out-of-hospital deaths (55%). Among children aged <1 year, there were significantly more pneumonia deaths out of hospital than in hospital (144 (49%) v. 16 (6%); p<0.001). Among children aged 1 - 4 years there were significantly more injury-related deaths out of hospital than in hospital (43 (47%) v. 4 (9%); p<0.001). In 56 (15%) of the cases of out-of-hospital death the child had visited a public healthcare facility within 1 week of death. Thirty-six (64%) of these children had died of pneumonia or gastroenteritis.Conclusions. Health interventions targeted at reducing under-5 deaths from pneumonia, gastroenteritis, prematurity and injuries need to be implemented across the service delivery platform in the Metro West GSA. It is important to consider all routine data sources in the evaluation of child mortality

    Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants

    Get PDF
    Iron supplementation may have adverse health effects in infants, probably through manipulation of the gut microbiome. Previous research in low-resource settings have focused primarily on anemic infants. This was a double blind, randomized, controlled trial of home fortification comparing multiple micronutrient powder (MNP) with and without iron. Six-month-old, non- or mildly anemic, predominantly-breastfed Kenyan infants in a rural malaria-endemic area were randomized to consume: (1) MNP containing 12.5 mg iron (MNP+Fe, n = 13); (2) MNP containing no iron (MNP−Fe, n = 13); or (3) Placebo (CONTROL, n = 7), from 6–9 months of age. Fecal microbiota were profiled by high-throughput bacterial 16S rRNA gene sequencing. Markers of inflammation in serum and stool samples were also measured. At baseline, the most abundant phylum was Proteobacteria (37.6% of rRNA sequences). The proteobacterial genus Escherichia was the most abundant genus across all phyla (30.1% of sequences). At the end of the intervention, the relative abundance of Escherichia significantly decreased in MNP−Fe (−16.05 ± 6.9%, p = 0.05) and CONTROL (−19.75 ± 4.5%, p = 0.01), but not in the MNP+Fe group (−6.23 ± 9%, p = 0.41). The second most abundant genus at baseline was Bifidobacterium (17.3%), the relative abundance of which significantly decreased in MNP+Fe (−6.38 ± 2.5%, p = 0.02) and CONTROL (−8.05 ± 1.46%, p = 0.01), but not in MNP-Fe (−4.27 ± 5%, p = 0.4445). Clostridium increased in MNP-Fe only (1.9 ± 0.5%, p = 0.02). No significant differences were observed in inflammation markers, except for IL-8, which decreased in CONTROL. MNP fortification over three months in non- or mildly anemic Kenyan infants can potentially alter the gut microbiome. Consistent with previous research, addition of iron to the MNP may adversely affect the colonization of potential beneficial microbes and attenuate the decrease of potential pathogens

    Characterising molecules for fundamental physics: an accurate spectroscopic model of methyltrioxorhenium derived from new infrared and millimetre-wave measurements

    Full text link
    Precise spectroscopic analysis of polyatomic molecules enables many striking advances in physical chemistry and fundamental physics. We use several new high-resolution spectroscopic devices to improve our understanding of the rotational and rovibrational structure of methyltrioxorhenium (MTO), the achiral parent of a family of large oxorhenium compounds that are ideal candidate species for a planned measurement of parity violation in chiral molecules. Using millimetre-wave and infrared spectroscopy in a pulsed supersonic jet, a cryogenic buffer gas cell, and room temperature absorption cells, we probe the ground state and the Re=O antisymmetric and symmetric stretching excited states of both CH3 187 ReO3 and CH3 185 ReO3 isotopologues in the gas phase with unprecedented precision. By extending the rotational spectra to the 150-300 GHz range, we characterize the ground state rotational and hyperfine structure up to J = 43 and K = 41, resulting in refinements to the rotational, quartic and hyperfine parameters, and the determination of sextic parameters and a centrifugal distortion correction to the quadrupolar hyperfine constant. We obtain rovibrational data for temperatures between 6 and 300 K in the 970-1015 cm-1 range, at resolutions down to 8 MHz and accuracies of 30 MHz. We use these data to determine more precise excited-state rotational, Coriolis and quartic parameters, as well as the ground-state centrifugal distortion parameter D K of the 187 Re isotopologue. We also account for hyperfine structure in the rovibrational transitions and hence determine the upper state rhenium atom quadrupole coupling constant eQq'

    The Vaginal Microbiome: Disease, Genetics and the Environment

    Get PDF
    The vagina is an interactive interface between the host and the environment. Its surface is covered by a protective epithelium colonized by bacteria and other microorganisms. The ectocervix is nonsterile, whereas the endocervix and the upper genital tract are assumed to be sterile in healthy women. Therefore, the cervix serves a pivotal role as a gatekeeper to protect the upper genital tract from microbial invasion and subsequent reproductive pathology. Microorganisms that cross this barrier can cause preterm labor, pelvic inflammatory disease, and other gynecologic and reproductive disorders. Homeostasis of the microbiome in the vagina and ectocervix plays a paramount role in reproductive health. Depending on its composition, the microbiome may protect the vagina from infectious or non-infectious diseases, or it may enhance its susceptibility to them. Because of the nature of this organ, and the fact that it is continuously colonized by bacteria from birth to death, it is virtually certain that this rich environment evolved in concert with its microbial flora. Specific interactions dictated by the genetics of both the host and microbes are likely responsible for maintaining both the environment and the microbiome. However, the genetic basis of these interactions in both the host and the bacterial colonizers is currently unknown. _Lactobacillus_ species are associated with vaginal health, but the role of these species in the maintenance of health is not yet well defined. Similarly, other species, including those representing minor components of the overall flora, undoubtedly influence the ability of potential pathogens to thrive and cause disease. Gross alterations in the vaginal microbiome are frequently observed in women with bacterial vaginosis, but the exact etiology of this disorder is still unknown. There are also implications for vaginal flora in non-infectious conditions such as pregnancy, pre-term labor and birth, and possibly fertility and other aspects of women’s health. Conversely, the role of environmental factors in the maintenance of a healthy vaginal microbiome is largely unknown. To explore these issues, we have proposed to address the following questions:

*1.	Do the genes of the host contribute to the composition of the vaginal microbiome?* We hypothesize that genes of both host and bacteria have important impacts on the vaginal microbiome. We are addressing this question by examining the vaginal microbiomes of mono- and dizygotic twin pairs selected from the over 170,000 twin pairs in the Mid-Atlantic Twin Registry (MATR). Subsequent studies, beyond the scope of the current project, may investigate which host genes impact the microbial flora and how they do so.
*2.	What changes in the microbiome are associated with common non-infectious pathological states of the host?* We hypothesize that altered physiological (e.g., pregnancy) and pathologic (e.g., immune suppression) conditions, or environmental exposures (e.g., antibiotics) predictably alter the vaginal microbiome. Conversely, certain vaginal microbiome characteristics are thought to contribute to a woman’s risk for outcomes such as preterm delivery. We are addressing this question by recruiting study participants from the ~40,000 annual clinical visits to women’s clinics of the VCU Health System.
*3.	What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions?* We hypothesize that susceptibility to infectious disease (e.g. HPV, _Chlamydia_ infection, vaginitis, vaginosis, etc.) is impacted by the vaginal microbiome. In turn, these infectious conditions clearly can affect the ability of other bacteria to colonize and cause pathology. Again, we are exploring these issues by recruiting participants from visitors to women’s clinics in the VCU Health System.

Three kinds of sequence data are generated in this project: i) rDNA sequences from vaginal microbes; ii) whole metagenome shotgun sequences from vaginal samples; and iii) whole genome shotgun sequences of bacterial clones selected from vaginal samples. The study includes samples from three vaginal sites: mid-vaginal, cervical, and introital. The data sets also include buccal and perianal samples from all twin participants. Samples from these additional sites are used to test the hypothesis of a per continuum spread of bacteria in relation to vaginal health. An extended set of clinical metadata associated with these sequences are deposited with dbGAP. We have currently collected over 4,400 samples from ~100 twins and over 450 clinical participants. We have analyzed and deposited data for 480 rDNA samples, eight whole metagenome shotgun samples, and over 50 complete bacterial genomes. These data are available to accredited investigators according to NIH and Human Microbiome Project (HMP) guidelines. The bacterial clones are deposited in the Biodefense and Emerging Infections Research Resources Repository ("http://www.beiresources.org/":http://www.beiresources.org/). 

In addition to the extensive sequence data obtained in this study, we are collecting metadata associated with each of the study participants. Thus, participants are asked to complete an extensive health history questionnaire at the time samples are collected. Selected clinical data associated with the visit are also obtained, and relevant information is collected from the medical records when available. This data is maintained securely in a HIPAA-compliant data system as required by VCU’s Institutional Review Board (IRB). The preponderance of these data (i.e., that judged appropriate by NIH staff and VCU’s IRB are deposited at dbGAP ("http://www.ncbi.nlm.nih.gov/gap":http://www.ncbi.nlm.nih.gov/gap). Selected fields of this data have been identified by NIH staff as ‘too sensitive’ and are not available in dbGAP. Individuals requiring access to these data fields are asked to contact the PI of this project or NIH Program Staff. 
&#xa

    The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.

    Get PDF
    Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids1,2. The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols3,4. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions2, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death5. However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines6, which suggests that additional factors govern resistance to ferroptosis. Here, using a synthetic lethal CRISPR-Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2)) as a potent ferroptosis-resistance factor. Our data indicate that myristoylation recruits FSP1 to the plasma membrane where it functions as an oxidoreductase that reduces coenzyme Q10 (CoQ) (also known as ubiquinone-10), which acts as a lipophilic radical-trapping antioxidant that halts the propagation of lipid peroxides. We further find that FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse tumour xenografts. Thus, our data identify FSP1 as a key component of a non-mitochondrial CoQ antioxidant system that acts in parallel to the canonical glutathione-based GPX4 pathway. These findings define a ferroptosis suppression pathway and indicate that pharmacological inhibition of FSP1 may provide an effective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutic agents

    Sonic Hedgehog Is a Chemoattractant for Midbrain Dopaminergic Axons

    Get PDF
    Midbrain dopaminergic axons project from the substantia nigra (SN) and the ventral tegmental area (VTA) to rostral target tissues, including the striatum, pallidum, and hypothalamus. The axons from the medially located VTA project primarily to more medial target tissues in the forebrain, whereas the more lateral SN axons project to lateral targets including the dorsolateral striatum. This structural diversity underlies the distinct functions of these pathways. Although a number of guidance cues have been implicated in the formation of the distinct axonal projections of the SN and VTA, the molecular basis of their diversity remains unclear. Here we investigate the molecular basis of structural diversity in mDN axonal projections. We find that Sonic Hedgehog (Shh) is expressed at a choice point in the course of the rostral dopaminergic projections. Furthermore, in midbrain explants, dopaminergic projections are attracted to a Shh source. Finally, in mice in which Shh signaling is inactivated during late neuronal development, the most medial dopaminergic projections are deficient

    A new view of electrochemistry at highly oriented pyrolytic graphite

    Get PDF
    Major new insights on electrochemical processes at graphite electrodes are reported, following extensive investigations of two of the most studied redox couples, Fe(CN)64–/3– and Ru(NH3)63+/2+. Experiments have been carried out on five different grades of highly oriented pyrolytic graphite (HOPG) that vary in step-edge height and surface coverage. Significantly, the same electrochemical characteristic is observed on all surfaces, independent of surface quality: initial cyclic voltammetry (CV) is close to reversible on freshly cleaved surfaces (>400 measurements for Fe(CN)64–/3– and >100 for Ru(NH3)63+/2+), in marked contrast to previous studies that have found very slow electron transfer (ET) kinetics, with an interpretation that ET only occurs at step edges. Significantly, high spatial resolution electrochemical imaging with scanning electrochemical cell microscopy, on the highest quality mechanically cleaved HOPG, demonstrates definitively that the pristine basal surface supports fast ET, and that ET is not confined to step edges. However, the history of the HOPG surface strongly influences the electrochemical behavior. Thus, Fe(CN)64–/3– shows markedly diminished ET kinetics with either extended exposure of the HOPG surface to the ambient environment or repeated CV measurements. In situ atomic force microscopy (AFM) reveals that the deterioration in apparent ET kinetics is coupled with the deposition of material on the HOPG electrode, while conducting-AFM highlights that, after cleaving, the local surface conductivity of HOPG deteriorates significantly with time. These observations and new insights are not only important for graphite, but have significant implications for electrochemistry at related carbon materials such as graphene and carbon nanotubes
    corecore