86 research outputs found

    Solid-state metathesis reactions under pressure: A rapid route to crystalline gallium nitride

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    High pressure chemistry has traditionally involved applying pressure and increasing temperature until conditions become thermodynamically favorable for phase transitions or reactions to occur. Here, high pressure alone is used as a starting point for carrying out rapid, self-propagating metathesis reactions. By initiating chemical reactions under pressure, crystalline phases, such as gallium nitride, can be synthesized which are inaccessible when initiated from ambient conditions. The single-phase gallium nitride made by metathesis reactions under pressure displays significant photoluminescence intensity in the blue/ultraviolet region. The absence of size or surface-state effects in the photoluminescence spectra show that the crystallites are of micron dimensions. The narrow lines of the x-ray diffraction patterns and scanning electron microscopy confirm this conclusion. Brightly luminescent thin films can be readily grown using pulsed laser deposition

    Exclusive breastfeeding rates and associated factors in 13 "Economic Community of West African States" (ECOWAS) countries

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    Exclusive breastfeeding (EBF) has important protective effects on child survival and also increases the growth and development of infants. This paper examined EBF rates and associated factors in 13 “Economic Community of West African States” (ECOWAS) countries. A weighted sample of 19,735 infants from the recent Demographic and Health Survey dataset in ECOWAS countries for the period of 2010–2018 was used. Survey logistic regression analyses that adjusted for clustering and sampling weights were used to determine the factors associated with EBF. In ECOWAS countries, EBF rates for infants 6 months or younger ranged from 13.0% in Côte d’Ivoire to 58.0% in Togo. EBF decreased significantly by 33% as the infant age (in months) increased. Multivariate analyses revealed that mothers with at least primary education, older mothers (35–49 years), and those who lived in rural areas were significantly more likely to engage in EBF. Mothers who made four or more antenatal visits (ANC) were significantly more likely to exclusively breastfeed their babies compared to those who had no ANC visits. Our study shows that EBF rates are still suboptimal in most ECOWAS countries. EBF policy interventions in ECOWAS countries should target mothers with no schooling and those who do not attend ANC. Higher rates of EBF are likely to decrease the burden of infant morbidity and mortality in ECOWAS countries due to non-exposure to contaminated water or other liquids

    Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

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    BACKGROUND: We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. METHODS: Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-alpha (ERalpha)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERalpha or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. RESULTS: Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2alpha and CAIX, but not to HIF-1alpha or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERalpha or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. CONCLUSION: We conclude that in breast cancer, Mb is co-expressed with ERalpha and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours

    A Novel Small Molecule Inhibitor of Hepatitis C Virus Entry

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    Small molecule inhibitors of hepatitis C virus (HCV) are being developed to complement or replace treatments with pegylated interferons and ribavirin, which have poor response rates and significant side effects. Resistance to these inhibitors emerges rapidly in the clinic, suggesting that successful therapy will involve combination therapy with multiple inhibitors of different targets. The entry process of HCV into hepatocytes represents another series of potential targets for therapeutic intervention, involving viral structural proteins that have not been extensively explored due to experimental limitations. To discover HCV entry inhibitors, we utilized HCV pseudoparticles (HCVpp) incorporating E1-E2 envelope proteins from a genotype 1b clinical isolate. Screening of a small molecule library identified a potent HCV-specific triazine inhibitor, EI-1. A series of HCVpp with E1-E2 sequences from various HCV isolates was used to show activity against all genotype 1a and 1b HCVpp tested, with median EC50 values of 0.134 and 0.027 µM, respectively. Time-of-addition experiments demonstrated a block in HCVpp entry, downstream of initial attachment to the cell surface, and prior to or concomitant with bafilomycin inhibition of endosomal acidification. EI-1 was equally active against cell-culture adapted HCV (HCVcc), blocking both cell-free entry and cell-to-cell transmission of virus. HCVcc with high-level resistance to EI-1 was selected by sequential passage in the presence of inhibitor, and resistance was shown to be conferred by changes to residue 719 in the carboxy-terminal transmembrane anchor region of E2, implicating this envelope protein in EI-1 susceptibility. Combinations of EI-1 with interferon, or inhibitors of NS3 or NS5A, resulted in additive to synergistic activity. These results suggest that inhibitors of HCV entry could be added to replication inhibitors and interferons already in development

    How the "Northern Irish" national identity is understood and used by young people and politicians

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    The conventional understanding of the nation within social psychology is as a category of people or "imagined community." However, work within the discursive tradition shows that citizens tend to discuss nationhood in a variety of modes, including the use of nonhuman categories such as references to the physical landscape of the country. This article aims to give a more comprehensive overview of how young people understand the Northern Irish identity, a new and potentially inclusive national category in a divided society, and how politicians articulate it in rhetoric. In Study 1, students (N = 286) discussed this identity in 44 peer‐led focus groups. Thematic analysis of their discussions shows four distinct ways in which it is constructed: as a distinctive people, as an identity claim, as a "hot" political project, and as a "cold" or banal indicator of place. In Study 2, Members of the Legislative Assembly at Stormont (N = 49) responded to open‐ended questions about the Northern Irish identity. Each of the parties used different conceptualizations for rhetorical effect. These results give a deeper understanding of the multifaceted nature of national identity and its ability to promote political agendas

    Epigenetics and developmental programming of welfare and production traits in farm animals

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    The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the ‘developmental origins of health and disease’ or ‘DOHaD’ hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems

    Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

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    Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant
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