819 research outputs found

    Low temperature mobility in hafnium-oxide gated germanium p-channel metal-oxide-semiconductor field-effect transistors

    Get PDF
    Effective mobility measurements have been made at 4.2 K on high performance high-k gated germanium p-type metal-oxide-semiconductor field effect transistors with a range of Ge/gate dielectric interface state densities. The mobility is successfully modelled by assuming surface roughness and interface charge scattering at the SiO2 interlayer/Ge interface. The deduced interface charge density is approximately equal to the values obtained from the threshold voltage and subthreshold slope measurements on each device. A hydrogen anneal reduces both the interface state density and the surface root mean square roughness by 20%

    The effect of review writing on learning engagement in channel partner relationship management

    Get PDF
    To develop the knowledge and skill sets of channel partner firms, firms increasingly introduce learning programs as part of their relationship management strategies. Yet, the engagement of channel partners in these programs tends to be low though. The current research, conducted in collaboration with a Fortune 100 information technology company, examines ways to strengthen learning engagement. In accordance with self-regulated learning theory, the authors propose and demonstrate that when channel partners write reviews of a learning module that they attended, beyond providing ratings,they are better able to reflect on the relevance of their learning experience and they are further engaged in learning activities. The audience and focus of these written reviews determine the engagement of the channel partner sales personnel. Therefore, review writing is a valuable, informal mechanism to motivate them. These effects are moderated by characteristics of both the channel partner (learning orientation of the salesperson, identification with the manufacturer) and the relationship with the manufacturer (length and exclusivity)

    Integrating youth mental health into cash transfer programmes in response to the COVID-19 crisis in low-income and middle-income countries

    Get PDF
    Social protection measures can play an important part in securing livelihoods and in mitigating short-term and longterm economic, social, and mental health impacts of the COVID-19 pandemic. In particular, cash transfer programmes are currently being adapted or expanded in various low-income and middle-income countries to support individuals and families during the pandemic. We argue that the current crisis offers an opportunity for these programmes to focus on susceptible young people (aged 15–24 years), including those with mental health conditions. Young people living in poverty and with mental health problems are at particular risk of experiencing adverse health, wellbeing, and employment outcomes with long-term consequences. They are also at risk of developing mental health conditions during this pandemic. To support this population, cash transfer programmes should not only address urgent needs around food security and survival but expand their focus to address longer-term mental health impacts of pandemics and economic crises. Such an approach could help support young people’s future life chances and break the vicious cycle between mental illness and poverty that spirals many young people into both socioeconomic and mental health disadvantage

    Examining the dynamics between young people’s mental health, poverty and life chances in six low- and middle-income countries: protocol for the CHANCES-6 study

    Get PDF
    PURPOSE: Poverty and poor mental health are closely related and may need to be addressed together to improve the life chances of young people. There is currently little evidence about the impact of poverty-reduction interventions, such as cash transfer programmes, on improved youth mental health and life chances. The aim of the study (CHANCES-6) is to understand the impact and mechanisms of such programmes. METHODS: CHANCES-6 will employ a combination of quantitative, qualitative and economic analyses. Secondary analyses of longitudinal datasets will be conducted in six low- and middle-income countries (Brazil, Colombia, Liberia, Malawi, Mexico and South Africa) to examine the impact of cash transfer programmes on mental health, and the mechanisms leading to improved life chances for young people living in poverty. Qualitative interviews and focus groups (conducted among a subset of three countries) will explore the views and experiences of young people, families and professionals with regard to poverty, mental health, life chances, and cash transfer programmes. Decision-analytic modelling will examine the potential economic case and return-on-investment from programmes. We will involve stakeholders and young people to increase the relevance of findings to national policies and practice. RESULTS: Knowledge will be generated on the potential role of cash transfer programmes in breaking the cycle between poor mental health and poverty for young people, to improve their life chances. CONCLUSION: CHANCES-6 seeks to inform decisions regarding the future design and the merits of investing in poverty-reduction interventions alongside investments into the mental health of young people

    Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy

    Get PDF
    Background Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, disarray, fibrosis, and increased risk for ventricular arrhythmias. Increased QT dispersion has been reported in patients with HCM, but the underlying mechanisms have not been completely elucidated. In this study, we examined the relationship between diffuse interstitial fibrosis, replacement fibrosis, QTc dispersion and ventricular arrhythmias in patients with HCM. We hypothesized that fibrosis would slow impulse propagation and increase dispersion of ventricular repolarization, resulting in increased QTc dispersion on surface electrocardiogram (ECG) and ventricular arrhythmias. Methods ECG and cardiac magnetic resonance (CMR) image analyses were performed retrospectively in 112 patients with a clinical diagnosis of HCM. Replacement fibrosis was assessed by measuring late gadolinium (Gd) enhancement (LGE), using a semi-automated threshold technique. Diffuse interstitial fibrosis was assessed by measuring T1 relaxation times after Gd administration, using the Look?Locker sequence. QTc dispersion was measured digitally in the septal/anterior (V1?V4), inferior (II, III, and aVF), and lateral (I, aVL, V5, and V6) lead groups on surface ECG. Results All patients had evidence of asymmetric septal hypertrophy. LGE was evident in 70 (63%) patients; the median T1 relaxation time was 411±38æms. An inverse correlation was observed between T1 relaxation time and QTc dispersion in leads V1?V4 (p\u3c 0.001). Patients with HCM who developed sustained ventricular tachycardia had slightly higher probability of increased QTc dispersion in leads V1?V4 (odds ratio, 1.011 [1.004?1.0178, p=0.003). We found no correlation between presence and percentage of LGE and QTc dispersion. Conclusion Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1?V4

    Middle and Late Pleistocene environmental history of the Marsworth area, south-central England

    Get PDF
    To elucidate the Middle and Late Pleistocene environmental history of south-central England, we report the stratigraphy, sedimentology, palaeoecology and geochronology of some deposits near the foot of the Chiltern Hills scarp at Marsworth, Buckinghamshire. The Marsworth site is important because its sedimentary sequences contain a rich record of warm stages and cold stages, and it lies close to the Anglian glacial limit. Critical to its history are the origin and age of a brown pebbly silty clay (diamicton) previously interpreted as weathered till. The deposits described infill a river channel incised into chalk bedrock. They comprise clayey, silty and gravelly sediments, many containing locally derived chalk and some with molluscan, ostracod and vertebrate remains. Most of the deposits are readily attributed to periglacial and fluvial processes, and some are dated by optically stimulated luminescence to Marine Isotope Stage (MIS) 6. Although our sedimentological data do not discriminate between a glacial or periglacial interpretation of the diamicton, amino-acid dating of three molluscan taxa from beneath it indicates that it is younger than MIS 9 and older than MIS 5e. This makes a glacial interpretation unlikely, and we interpret the diamicton as a periglacial slope deposit. The Pleistocene history reconstructed for Marsworth identifies four key elements: (1) Anglian glaciation during MIS 12 closely approached Marsworth, introducing far-travelled pebbles such as Rhaxella chert and possibly some fine sand minerals into the area. (2) Interglacial environments inferred from fluvial sediments during MIS 7 varied from fully interglacial conditions during sub-stages 7e and 7c, cool temperate conditions during sub-stage 7b or 7a, temperate conditions similar to those today in central England towards the end of the interglacial, and cool temperate conditions during sub-stage 7a. (3) Periglacial activity during MIS 6 involved thermal contraction cracking, permafrost development, fracturing of chalk bedrock, fluvial activity, slopewash, mass movement and deposition of loess and coversand. (4) Fully interglacial conditions during sub-stage 5e led to renewed fluvial activity, soil formation and acidic weathering

    Why Did Ancient People Have Atherosclerosis?: From Autopsies to Computed Tomography to Potential Causes

    Get PDF
    Computed tomographic findings of atherosclerosis in the ancient cultures of Egypt, Peru, the American Southwest and the Aleutian Islands challenge our understanding of the fundamental causes of atherosclerosis. Could these findings be true? Is so, what traditional risk factors might be present in these cultures that could explain this apparent paradox? The recent computed tomographic findings are consistent with multiple autopsy studies dating as far back as 1852 that demonstrate calcific atherosclerosis in ancient Egyptians and Peruvians. A nontraditional cause of atherosclerosis that could explain this burden of atherosclerosis is the microbial and parasitic inflammatory burden likely to be present in ancient cultures inherently lacking modern hygiene and antimicrobials. Patients with chronic systemic inflammatory diseases of today, including systemic lupus erythematosus, rheumatoid arthritis, and human immunodeficiency virus infection, experience premature atherosclerosis and coronary events. Might the chronic inflammatory load of ancient times secondary to infection have resulted in atherosclerosis? Smoke inhalation from the use of open fires for daily cooking and illumination represents another potential cause. Undiscovered risk factors could also have been present, potential causes that technologically cannot currently be measured in our serum or other tissue. A synthesis of these findings suggests that a gene-environmental interplay is causal for atherosclerosis. That is, humans have an inherent genetic susceptibility to atherosclerosis, whereas the speed and severity of its development are secondary to known and potentially unknown environmental factors

    The LIGO HET Response (LIGHETR) Project to Discover and Spectroscopically Follow Optical Transients Associated with Neutron Star Mergers

    Full text link
    The LIGO HET Response (LIGHETR) project is an enterprise to follow up optical transients (OT) discovered as gravitational wave merger sources by the LIGO/Virgo collaboration (LVC). Early spectroscopy has the potential to constrain crucial parameters such as the aspect angle. The LIGHETR collaboration also includes the capacity to model the spectroscopic evolution of mergers to facilitate a real-time direct comparison of models with our data. The principal facility is the Hobby-Eberly Telescope. LIGHETR uses the massively-replicated VIRUS array of spectrographs to search for associated OTs and obtain early blue spectra and in a complementary role, the low-resolution LRS-2 spectrograph is used to obtain spectra of viable candidates as well as a densely-sampled series of spectra of true counterparts. Once an OT is identified, the anticipated cadence of spectra would match or considerably exceed anything achieved for GW170817 = AT2017gfo for which there were no spectra in the first 12 hours and thereafter only roughly once daily. We describe special HET-specific software written to facilitate the program and attempts to determine the flux limits to undetected sources. We also describe our campaign to follow up OT candidates during the third observational campaign of the LIGO and Virgo Scientific Collaborations. We obtained VIRUS spectroscopy of candidate galaxy hosts for 5 LVC gravitational wave events and LRS-2 spectra of one candidate for the OT associated with S190901ap. We identified that candidate, ZTF19abvionh = AT2019pip, as a possible Wolf-Rayet star in an otherwise unrecognized nearby dwarf galaxy.Comment: 26 pages, 15 figure

    Prediction of peptide and protein propensity for amyloid formation

    Get PDF
    Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

    Extreme genetic fragility of the HIV-1 capsid

    Get PDF
    Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies
    • …
    corecore