393 research outputs found
Highly selective and sensitive fluorescent chemosensor for femtomolar detection of silver ion in aqueous medium
AbstractThe chemical sensing for the trace level detection of silver ion in aqueous solution still remains a challenge using simple, rapid, and inexpensive method. We report that thionine can be used as a fluorescent probe for the detection of Ag+ ion. The successive addition of Ag+ ion to the solution containing thionine quenches (turns-off) the fluorescence intensity of thionine. Association and quenching constants have been estimated by the BenesiâHildebrand method and SternâVolmer plot, respectively. From the plot, the nature of the fluorescence quenching was confirmed as static quenching. An important feature of our chemosensor is high selectivity towards the determination of silver ion in aqueous solution over the other competitive metal ions. The detection limit of the sensor achieved 5fM for Ag+ ion, which is superior to all previously reported chemosensors. The NMR and FT-IR studies were also carried out to support the complex formation between thionine and Ag+ ion. The practicality of the proposed chemosensor for determination of Ag+ ion was carried in untreated water samples
Unraveling the Allosteric Mechanism of Serine Protease Inhibition by an Antibody
SummaryRecent structural studies have outlined the mechanism of protease inhibition by active site-directed antibodies. However, the molecular basis of allosteric inhibition by antibodies has been elusive. Here we report the 2.35 Ă
resolution structure of the trypsin-like serine protease hepatocyte growth factor activator (HGFA) in complex with the allosteric antibody Ab40, a potent inhibitor of HGFA catalytic activity. The antibody binds at the periphery of the substrate binding cleft and imposes a conformational change on the entire 99-loop (chymotrypsinogen numbering). The altered conformation of the 99-loop is incompatible with substrate binding due to the partial collapse of subsite S2 and the reorganization of subsite S4. Remarkably, a single residue deletion of Ab40 abolished inhibition of HGFA activity, commensurate with the reversal of the 99-loop conformation to its âcompetentâ state. The results define an âallosteric switchâ mechanism as the basis of protease inhibition by an allosteric antibody
A Multi-hop Mobile Networking Test-bed for Telematics
An onboard vehicle-to-vehicle multi-hop wireless networking system has been developed to test the realworld performance of telematics applications. The system targets emergency and safety messaging, traffic updates, audio/video streaming and commercial announcements. The test-bed includes a Differential GPS receiver, an IEEE 802.11a radio card modified to emulate the DSRC standard, a 1xRTT cellular-data connection, an onboard computer and audio-visual equipment. Vehicles exchange data directly or via intermediate vehicles using a multi-hop routing protocol. The focus of the test-bed is to (a) evaluate the feasibility of high-speed inter-vehicular networking, (b) characterize 5.8GHz signal propagation within a dynamic mobile ad hoc environment, and (c) develop routing protocols for highly mobile networks. The test-bed has been deployed across five vehicles and tested over 400 miles on the road
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Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial
Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events
Incidence of type 2 diabetes in people with a history of hospitalisation for major mental illness in Scotland 2001-2015: a retrospective cohort study
Objective: To determine the incidence of type 2 diabetes in people with a history of hospitalization for major mental illness versus no mental illness in Scotland by time period and sociodemographics.
Research Design and Methods: We used national Scottish population-based records to create cohorts with a hospital record of schizophrenia, bipolar disorder, or depression or no mental illness and to ascertain diabetes incidence. We used quasi-Poisson regression models including age, sex, time period, and area-based deprivation to estimate incidence and relative risks (RRs) of diabetes by mental illness status. Estimates are illustrated for people aged 60 years and in the middle deprivation quintile in 2015.
Results: We identified 254,136 diabetes cases during 2001â2015. Diabetes incidence in 2015 was 1.5- to 2.5-fold higher in people with versus without a major mental disorder, with the gap having slightly increased over time. RRs of diabetes incidence were greater among women than men for schizophrenia (RR 2.40 [95% CI 2.01, 2.85] and 1.63 [1.38, 1.94]), respectively) and depression (RR 2.10 [1.86, 2.36] and 1.62 [1.43, 1.82]) but similar for bipolar disorder (RR 1.65 [1.35, 2.02] and 1.50 [1.22, 1.84]). Absolute and relative differences in diabetes incidence associated with mental illness increased with increasing deprivation.
Conclusions: Disparities in diabetes incidence between people with and without major mental illness appear to be widening. Major mental illness has a greater effect on diabetes risk in women and people living in more deprived areas, which has implications for intervention strategies to reduce diabetes risk in this vulnerable population
Partnering with women collectives for delivering essential women\u2019s nutrition interventions in tribal areas of eastern India: a scoping study
Background: We examined the feasibility of engaging women collectives
in delivering a package of women\u2019s nutrition messages/services as
a funded stakeholder in three tribal-dominated districts of Odisha,
Jharkhand and Chhattisgarh States, in eastern India. These districts
have high prevalence of child stunting and poor government service
outreach. Methods: Conducted between July 2014 and March 2015, an
exploratory mix-methods design was adopted (review of coverage data and
government reports, field interviews and focus group discussion with
multiple stakeholders and intended communities) to assess coverage of
women\u2019s nutrition services. A capacity assessment tool was
developed to map all types of community collectives and assess their
awareness, institutional and programme capacity as a funded stakeholder
for delivering women\u2019s nutrition services/behaviour promotion.
Results: Limited targeting of pre-pregnancy period, delays in first
trimester registration of pregnant women, and low micronutrient
supplementation supply and awareness issues emerged as key bottlenecks
in improving women\u2019s nutrition in these districts. Amongst the 18
different types of community collectives mapped, Self Help Groups
(SHGs) and their federations (tier 2 and tier 3), with total membership
of over 650,000, emerged as the most promising community collective due
to their vast network, governance structure, bank linkage, and regular
interface. Nearly 400,000 (or 20% of women) in these districts can be
reached through the mapped 31,919 SHGs. SHGs with organisational
readiness for receiving and managing grants for income generation and
community development activities varied from 41 to 94% across study
districts. Stakeholders perceived that SHGs federations managing grants
from government and be engaged for nutrition promotion and service
delivery and SHG weekly meetings can serve as community interface for
discussing/resolving local issues impeding access to services.
Conclusions: Women SHGs (with tier 2 and tier 3) can become direct
grantees for strengthening coverage of women\u2019s nutrition
interventions in these tribal districts/pockets, provided they are
capacitated, supervised and given safe guards against exploitation and
violence
Experimental verification of smart grid control functions on international grids using a real-time simulator
The drastic increase in distributed energy resources (DERs) leads to challenges in the operation of distribution systems worldwide. While several solutions for grid monitoring and control are available on the market and in literature, this research is the first of its kind aiming to supervise the grid by providing a modular configurable unified hardware and software architecture. The control algorithms are configured using data models according to IEC 61850-7-3 and IEC 61850-7-4. The novel system architecture is a portable, modular and flexible architecture that aggregates smart grid control functions onto a standardised hardware platform, emphasising the need for hardware independence. The central controller contains several smart grid control functions and the various field devices are distributed across the distribution grid. This paper deals with the simulation of different real-world distribution grids on the Real-Time Simulator (RTS) and experimental verification of the control algorithms. Smart grid control functions such as Coordinated Voltage Control (CVC) and Optimal Power Flow (OPF) are experimentally verified on a German grid. The grid dynamics are compared when the central controller executes the CVC against the OPF implementations. The experimental results, advantages and challenges of each control are presented here. The results also showed the variation in grid behaviour when the control parameters were varied. The paper also shows that the algorithm and the choice of the control parameters depend upon the distribution grid's complexity and the system operator's individual needs. The results illustrate the potential of such a universal distribution automation solution for system operators worldwide
Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models
INTRODUCTION: The experiments reported here address the question of whether a short-term hormone treatment can prevent mammary tumorigenesis in two different genetically engineered mouse models. METHODS: Two mouse models, the p53-null mammary epithelial transplant and the c-neu mouse, were exposed to estrogen and progesterone for 2 and 3 weeks, respectively, and followed for development of mammary tumors. RESULTS: In the p53-null mammary transplant model, a 2-week exposure to estrogen and progesterone during the immediate post-pubertal stage (2 to 4 weeks after transplantation) of mammary development decreased mammary tumorigenesis by 70 to 88%. At 45 weeks after transplantation, analysis of whole mounts of the mammary outgrowths demonstrated the presence of premalignant hyperplasias in both control and hormone-treated glands, indicating that the hormone treatment strongly affects the rate of premalignant progression. One possible mechanism for the decrease in mammary tumorigenesis may be an altered proliferation activity as the bromodeoxyuridine labeling index was decreased by 85% in the mammary glands of hormone-treated mice. The same short-term exposure administered to mature mice at a time of premalignant development also decreased mammary tumorigenesis by 60%. A role for stroma and/or systemic mediated changes induced by the short-term hormone (estrogen/progesterone) treatment was demonstrated by an experiment in which the p53-null mammary epithelial cells were transplanted into the cleared mammary fat pads of previously treated mice. In such mice, the tumor-producing capabilities of the mammary cells were also decreased by 60% compared with the same cells transplanted into unexposed mice. In the second set of experiments using the activated Her-2/neu transgenic mouse model, short-term estradiol or estradiol plus progesterone treatment decreased mammary tumor incidence by 67% and 63%, and tumor multiplicity by 91% and 88%, respectively. The growth rate of tumors arising in the hormone-treated activated Her-2/neu mice was significantly lower than tumors arising in non-hormone treated mice. CONCLUSION: Because these experiments were performed in model systems that mimic many essential elements of human breast cancer, the results strengthen the rationale for translating this prevention strategy to humans at high risk for developing breast cancer
Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS
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