Delta-Sigma Modulator based Compact Sensor Signal Acquisition Front-end System

The proposed delta-sigma modulator ($\Delta\Sigma$M) based signal acquisition architecture uses a differential difference amplifier (DDA) customized for dual purpose roles, namely as instrumentation amplifier and as integrator of $\Delta\Sigma$M. The DDA also provides balanced high input impedance for signal from sensors. Further, programmable input amplification is obtained by adjustment of $\Delta\Sigma$M feedback voltage. Implementation of other functionalities, such as filtering and digitization have also been incorporated. At circuit level, a difference of transconductance of DDA input pairs has been proposed to reduce the effect of input resistor thermal noise of front-end R-C integrator of the $\Delta\Sigma$M. Besides, chopping has been used for minimizing effect of Flicker noise. The resulting architecture is an aggregation of functions of entire signal acquisition system within the single block of $\Delta\Sigma$M, and is useful for a multitude of dc-to-medium frequency sensing and similar applications that require high precision at reduced size and power. An implementation of this in 0.18-$\mu$m CMOS process has been presented, yielding a simulated peak signal-to-noise ratio of 80 dB and dynamic range of 109dBFS in an input signal band of 1 kHz while consuming 100 $\mu$W of power; with the measured signal-to-noise ratio being lower by about 9 dB.Comment: 13 pages, 16 figure

Synthesis and Characterization of Some Triphenyltin(IV) Complexes from Sterically Crowded [(( E )-1-{2-Hydroxy-5-[( E )-2-(aryl)-1-diazenyl]phenyl}methylidene)amino]acetate Ligands and Crystal Structure Analysis of a Tetrameric Triphenyltin(IV) Compound

Four new triphenyltin(IV) complexes containing [((E)-1-{2-hydroxy-5-[(E)-2-(aryl)-1-diazenyl]phenyl}methylidene)amino]acetate ligands (L) have been synthesized with formulations of Ph3SnLH. They have been studied by multinuclear (1H, 13C, 119Sn) NMR, 119Sn Mössbauer and IR spectroscopy. A full characterization of one complex, Ph3SnL1H (1), was accomplished by single crystal X-ray crystallography, which revealed the compound to be a macrocyclic tetramer. In the tetramer, the five coordinate tin atoms have distorted trigonal bipyramidal geometries with the three phenyl groups occupying equatorial positions, while an oxygen atom of the carboxylate group of one L ligand and the oxide O-atom (formerly the hydroxy group) of a second L ligand in an apical positions. The carboxylate ligands bridge adjacent tin atoms and coordinate in the zwitterionic form with the phenolic proton moved to the nearby nitrogen atom. 119Sn NMR results indicate that the tetrameric structures of the complexes in the solid state, in which the tin atoms are five-coordinated, dissociate in solution to yield four coordinate monomeric specie

Implications of importance factor on seismic design from 2000 SAC-FEMA perspective

The seismic design of buildings uses global ductility factor and occupancy importance factor (IF) as two major fixed parameters in defining the safety of the structure. The study of performance variation of the structure with global ductility factor is available but there is hardly any study that provides information regarding the increase in the level of safety achieved by increasing the IF values. Being a building categorical dependent parameter, IF is used by the international seismic design codes for increasing the design loads of the structure. The change in the level of safety achieved through the variation in the value of the IFs for reinforced concrete (RC)–framed buildings will perhaps be an important and useful representation of the stakeholders for the approximate damage cost estimation. This article performs the structural safety assessment against seismic load using a standard structural reliability method with second-order hazard approximation to evaluate the effect of the IF on the level of safety and the cost associated with the building. Results show that an overall reduction of 50%–60% in the damage index of the selected buildings can be achieved by increasing the IF from a value of 1.0–2.0 with a consequent increase in the cost of the building

Characterization of non-membrane-damaging cytotoxin of non-toxigenic Vibrio cholerae O1 and its relevance to disease

The non-membrane-damaging cytotoxin which causes dramatic cell rounding of cultured HeLa cells was purified to homogeneity from a clinical strain (WO5) of non-toxigenic Vibrio cholerae O1 Inaba belonging to the El Tor biotype. The purified protein has a denatured molecular weight of 35 kDa and a native molecular weight of approximately 37 kDa indicating the monomeric nature of the protein. The 15 N-terminal amino acid sequence of non-membrane-damaging cytotoxin showed complete homology to the hemagglutinin protease previously purified and characterized from V. cholerae O1. Purified non-membrane-damaging cytotoxin from V. cholerae O1 was immunologically and biochemically identical to that previously purified from V. cholerae O26. Non-membrane-damaging cytotoxin was found to be enterotoxic in rabbit ileal loop assay inducing accumulation of non-hemorrhagic fluid at 100 μg and elicited a concentration dependent increase in short circuit current and tissue conductance of rabbit ileal mucosa mounted on Ussing chambers. A significant serum immunoglobulin G response against non-membrane-damaging cytotoxin was elicited by patients infected with V. cholerae O139 but not with V. cholerae O1. These properties make non-membrane-damaging cytotoxin a potential virulence factor of V. cholerae which should be taken into consideration while making live, attenuated recombinant vaccine strains against cholera

Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation

The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (SbRLD) and antimony-sensitive (SbSLD) was compared in vitro. Unlike SbSLD, infection of DCs with SbRLD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. SbRLD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-κB pathways. In contrast, SbSLD failed to block activation of SAG (20 µg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-κB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with SbSLD also inhibited SAG (20 µg/ml)-induced activation of PI3K/AKT and NF-κB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 µg/ml. In contrast, SbRLD inhibited these SAG-induced events regardless of duration of DC exposure to SbRLD or dose of SAG. Interestingly, the inhibitory effects of isogenic SbSLD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of SbRLD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-κB was found to transcriptionally regulate expression of murine γglutamylcysteine synthetase heavy-chain (mγGCShc) gene, presumably an important regulator of antimony resistance. Importantly, SbRLD but not SbSLD blocked SAG-induced mγGCS expression in DCs by preventing NF-κB binding to the mγGCShc promoter. Our findings demonstrate that SbRLD but not SbSLD prevents SAG-induced DC activation by suppressing a PI3K-dependent NF-κB pathway and provide the evidence for differential host-pathogen interaction mediated by SbRLD and SbSLD

Clinical outcome after high dose rate intracavitary brachytherapy with traditional point ‘A’ dose prescription in locally advanced carcinoma of uterine cervix: dosimetric analysis from the perspective of computed tomography imaging-based 3-dimensional treatment planning

Objective To analyze tumour response and toxicity with respect to cumulative radiotherapy dose to target and organs at risk (OARs) with computed tomography (CT)-based image guided adaptive brachytherapy planning for locally advanced carcinoma cervix. Methods Patients were treated with two-dimensional concurrent chemoradiotherapy to whole pelvis followed by intracavitary brachytherapy (ICBT) with dose prescription to point ‘A’. CT image-based delineation of high-risk clinical target volume (HR-CTV), urinary bladder, rectum and sigmoid colon was done with generation of dose-volume histogram (DVH) data and optimization of doses to target and OARs. Follow up assessments were done for response of disease and toxicity with generation of data for statistical analysis. Results One hundred thirty-six patients were enrolled in the study. Delineated volume of HR-CTV ranged from 20.9 to 37.1 mL, with median value of 30.2 mL. The equivalent dose in 2 Gy per fraction (EQD2) for point ‘A’ ranged from 71.31 to 79.75 Gy with median value of 75.1 Gy and EQD2 HR-CTV D90 ranged from 71.9 to 89.7 Gy with median value of 85.1 Gy. 69.2% of patients showed complete response and after median follow-up of 25 months, 50 patients remained disease free, of whom, 74.0% had received ≥85 Gy to HR-CTV D90 versus 26.0% receiving <85 Gy to HR-CTV D90. Conclusions Amidst the unavailability of magnetic resonance imaging facilities in low middle income countries, incorporation of CT-image based treatment planning into routine practice for ICBT provides the scope to delineate volumes of target and OARs and to generate DVH data, which can prove to be a better surrogate for disease response and toxicity

A Multi-centre Study to Evaluate the Long-Term Efficacy and Safety of Biosimilar Infliximab (Infimab™) in Ankylosing Spondylitis in Real-world Clinical Settings - A perspective from Eastern India

Introduction: Owing to dearth of data on infliximab biosimilars in Indian patients, a pan-India case database-based study with infliximab biosimilar BOW015 (Infimab™) was carried out to capture its efficacy and safety in real world clinical settings in India. Here, we assessed its efficacy and safety in ankylosing spondylitis (AS) among patients in the East India cohort. Materials and methods: Data were collected from multiple centers across the eastern region of India. Patients diagnosed with AS, within the preceding 4-6 months during the preceding one year were included in the study. Patients who were given BOW015 for other indications, prior innovator infliximab or other biologics were excluded from the study. Primary variable was Ankylosing Spondylitis Disease Activity Scale (ASDAS) response defined as change of &gt; 2 in the ASDAS score from the baseline by 4-6 months of follow up. Results: The cohort consisted of 149 patients, predominantly male (69.8%), with mean (±SD) age of 36.75 (±11.11) years and mean (±SD) body weight of 58.26 (±15.4) kgs. Of the treated patients, 91 (61.1%) patients were administered four doses, 10 (6.7%) patients were administered three doses, 37 (24.8%) patients were administered two doses and 11 (7.4%) patients were administered only a single dose of BOW015. In the final analysis set, 81 patients had data at baseline and 4th visit. Among the 81 patients, 74 (91%) patients achieved major improvement, 5 (6%) patients achieved clinically important improvement and 2 (3%) were non-responders at 4th visit. Secondarily, cross categorization of the cohort into disease activity categories by number of infusions administered from baseline to 4th visit and assessment of trends in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were also carried out and these too confirmed the efficacy of BOW015. Conclusion: Infimab™ (BOW015) showed significant improvement in ASDAS and BASDAI in patients with AS at the end of 4-6 months of follow up with its clinical benefits being apparent as early as first dose of BOW015

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.publishedVersio

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe