SARS-CoV-2 detection with aptamer-functionalized gold nanoparticles

A rapid detection test for SARS-CoV-2 is urgently required to monitor virus spread and containment. Here, we describe a test that uses nanoprobes, which are gold nanoparticles functionalized with an aptamer specific to the spike membrane protein of SARS-CoV-2. An enzyme-linked immunosorbent assay confirms aptamer binding with the spike protein on gold surfaces. Protein recognition occurs by adding a coagulant, where nanoprobes with no bound protein agglomerate while those with sufficient bound protein do not. Using plasmon absorbance spectra, the nanoprobes detect 16 nM and higher concentrations of spike protein in phosphate-buffered saline. The time-varying light absorbance is examined at 540 nm to determine the critical coagulant concentration required to agglomerates the nanoprobes, which depends on the protein concentration. This approach detects 3540 genome copies/μl of inactivated SARS-CoV-2

Post-outburst evolution of bonafide FUor V2493 Cyg: A Spectro-photometric monitoring

We present here the results of eight years of our near-simultaneous optical/near-infrared spectro-photometric monitoring of bonafide FUor candidate `V2493 Cyg' starting from 2013 September to 2021 June. During our optical monitoring period (between October 16, 2015 and December 30, 2019), the V2493 Cyg is slowly dimming with an average dimming rate of $\sim$26.6 $\pm$ 5.6 mmag/yr in V band. Our optical photometric colors show a significant reddening of the source post the second outburst pointing towards a gradual expansion of the emitting region post the second outburst. The mid infra-red colors, on the contrary, exhibits a blueing trend which can be attributed to the brightening of the disc due to the outburst. Our spectroscopic monitoring shows a dramatic variation of the H$\alpha$ line as it transitioned from absorption feature to the emission feature and back. Such transition can possibly be explained by the variation in the wind structure in combination with accretion. Combining our time evolution spectra of the Ca II infra-red triplet lines with the previously published spectra of V2493 Cyg, we find that the accretion region has stabilised compared to the early days of the outburst. The evolution of the O I $\lambda$7773 \AA~ line also points towards the stabilization of the circumstellar disc post the second outburst.Comment: 34 pages, 12 figures, 6 tables, accepted for publication in Ap

Draft genome sequence of Sclerospora graminicola, the pearl millet downy mildew pathogen:Genome sequence of pearl millet downy mildew pathogen

Sclerospora graminicola pathogen is one of the most important biotic production constraints of pearl millet worldwide. We report a de novo whole genome assembly and analysis of pathotype 1. The draft genome assembly contained 299,901,251 bp with 65,404 genes. Pearl millet [Pennisetum glaucum (L.) R. Br.], is an important crop of the semi-arid and arid regions of the world. It is capable of growing in harsh and marginal environments with highest degree of tolerance to drought and heat among cereals (1). Downy mildew is the most devastating disease of pearl millet caused by Sclerospora graminicola (sacc. Schroet), particularly on genetically uniform hybrids. Estimated annual grain yield loss due to downy mildew is approximately 10?80 % (2-7). Pathotype 1 has been reported to be the highly virulent pathotype of Sclerospora graminicola in India (8). We report a de novo whole genome assembly and analysis of Sclerospora graminicola pathotype 1 from India. A susceptible pearl millet genotype Tift 23D2B1P1-P5 was used for obtaining single-zoospore isolates from the original oosporic sample. The library for whole genome sequencing was prepared according to the instructions by NEB ultra DNA library kit for Illumina (New England Biolabs, USA). The libraries were normalised, pooled and sequenced on Illumina HiSeq 2500 (Illumina Inc., San Diego, CA, USA) platform at 2 x100 bp length. Mate pair (MP) libraries were prepared using the Nextera mate pair library preparation kit (Illumina Inc., USA). 1 ?g of Genomic DNA was subject to tagmentation and was followed by strand displacement. Size selection tagmented/strand displaced DNA was carried out using AmpureXP beads. The libraries were validated using an Agilent Bioanalyser using DNA HS chip. The libraries were normalised, pooled and sequenced on Illumina MiSeq (Illumina Inc., USA) platform at 2 x300 bp length. The whole genome sequencing was performed by sequencing of 7.38 Gb with 73,889,924 paired end reads from paired end library, and 1.15 Gb with 3,851,788 reads from mate pair library generated from Illumina HiSeq2500 and Illumina MiSeq, respectively. The sequences were assembled using various assemblers like ABySS, MaSuRCA, Velvet, SOAPdenovo2, and ALLPATHS-LG. The assembly generated by MaSuRCA (9) algorithm was observed superior over other algorithms and hence used for scaffolding using SSPACE. Assembled draft genome sequence of S. graminicola pathotype 1 was 299,901,251 bp long, with a 47.2 % GC content consisting of 26,786 scaffolds with N50 of 17,909 bp with longest scaffold size of 238,843 bp. The overall coverage was 40X. The draft genome sequence was used for gene prediction using AUGUSTUS. The completeness of the assembly was investigated using CEGMA and revealed 92.74% proteins completely present and 95.56% proteins partially present, while BUSCO fungal dataset indicated 64.9% complete, 12.4% fragmented, 22.7% missing out of 290 BUSCO groups. A total of 52,285 predicted genes were annotated using BLASTX and 38,120 genes were observed with significant BLASTX match. Repetitive element analysis in the assembly revealed 8,196 simple repeats, 1,058 low complexity repeats and 5,562 dinucleotide to hexanucleotide microsatellite repeats.publishersversionPeer reviewe

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Fluid Mechanics of Nano-textured Coalescing Filters

The work deals with the different stages of filtration within the coalescing filters on the physical level. The main stages involved in separation of airborne liquid drops brought by a gas flux onto a coalescing filter were separated into several fundamental problems studied experimentally and theoretically. Novel experimental setups were designed for conducting the experiments and theoretical modeling was used to explain, rationalize and predict the observations. The effect of static wettability under dynamic drop impact was found to be negligible after the drop crosses a certain threshold velocity. The hydrodynamic focusing of the liquid drop into the pores of the membrane overcomes the static wettability. It has been shown that the superhydrophobicity does not prevent water from being delivered into a filter if the impact velocity surpasses a threshold value of the order of 3 m/s, and the hydrodynamic focusing becomes important. As the liquid drops get inside the filter, it gets intercepted with the fiber matrix inside. As the air keeps blowing the intercepted liquid drops move over the fibers in different directions depending on the direction of air blowing with respect to the fiber axis. The different breakup modes observed during cross blowing was mapped onto the We-Oh plane. Drop hopping between the fibers was also observed. Liquid drops were observed to reach a significant depth of its thickness due to the hydrodynamic focusing. In addition, propagation of liquid fronts associated with drop boundaries inside non-wettable nonwovens was studied experimentally and theoretically, as well as the entrainment of nanoparticles by such fronts. As the usage of nanofibers is steadily increasing in the filtration industry, the mechanically-driven rearrangement of nanofiber membranes under the action of drop evaporation at the front surface becomes very important. The formation of big holes on the suspended nanofiber mat is addressed in the experiments of the present work. Void formation was uncovered and quantitatively described. The findings of the present work reported are useful for development of novel coalescing filters and proper understanding of their operation

Pseudocapacitive behavior of ferrimagnetic NiFe2O4-carbon nanotube electrodes prepared with a multifunctional dispersing agent

We investigate the pseudocapacitive properties of ferrimagnetic NiFe2O4 ceramics in a 0.5 ​M Na2SO4 aqueous electrolyte. These ceramics have a high capacitance of 2.33 Fcm−2 since a more efficient colloidal technique is applied, which enhances the current response of the electrode in the negative potential range. NiFe2O4 is co-dispersed with multiwalled carbon nanotubes (MWCNTs) using Celestine Blue (CB) dye as a multifunctional co-dispersant. The capacitance measurements are performed by cyclic voltammetry, impedance spectroscopy and galvanostatic charge-discharge. The experiments reveal the synergistic effects of NiFe2O4 and conductive MWCNTs additives and the benefit they provide through co-dispersion with CB, which acts as an electron transfer mediator, enhancing pseudocapacitance. The mass ratio of NiFe2O4 and MWCNTs in the composite electrodes is varied to optimize the capacitance enhancement, lower electrical resistance at a high active mass loading of 40 ​mg ​cm−2, and achieve favorable capacitance retention at high charge-discharge rates. The results reveal a path for the development of pseudocapacitive ferrimagnetic ceramic composites that have advanced functionality

Influence of conductive porous electrodes on the apparent electrode kinetics of fenitrothion

Planar bare electrodes fabricated with surface-modified multiwalled carbon nanotubes (MWCNT) are used to detect organophosphate (OP) compounds, which are used as herbicides and fungicides but are harmful to human health. Deposition of carbon nanotubes on the surfaces of bare electrodes enhances electrocatalysis, increasing the electrode to analyte current response and narrowing peak-to-peak potential separation during cyclic voltammetry (CV). We hypothesize that, as the thickness of the deposited MWCNT layer decreases, Fenitrothion (FT, an OP) mass transport between the layers of porous multiwalled carbon nanotubes changes from semi-infinite to thin-layer diffusion. This influences the electrode electrochemical response to the analyte. Using simulations and experiments, we show that when porous MWCNT are deposited on a conductive glassy carbon electrode the mass transport of FT changes from semi-infinite to thin-layer diffusion during CV. This alters the electrochemical response of the electrode and reduces peak-to-peak potential separation. To simulate CV response to multi-step and multi-electron electrochemical reactions of FT, both the semi-infinite and thin-layer diffusion models are employed for the planar bare and modified porous surface electrodes. The transition from thin layer to semi-infinite diffusion is clear when the nanotube layer thickness on the bare electrode increases. The model is applicable to other toxic chemicals, such as 4-nitrophenol, parathion, or methyl parathion that have similar electrode kinetics