Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 289
Filter
1.
Sci Rep ; 14(1): 12429, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816436

ABSTRACT

Evapotranspiration (ETo) is an important component of the hydrological cycle and reliable estimates of ETo are essential for assessing crop water requirements and irrigation management. Direct measurement of evapotranspiration is both costly and involves complex and intricate procedures. Hence, empirical models are commonly utilized to estimate ETo using accessible meteorological data. Given that empirical methods operate on various assumptions, it is essential to assess their performance to pinpoint the most suitable methods for ETo calculation based on the availability of input data and the specific climatic conditions of a region. This study aims to evaluate different empirical methods of ETo in the tropical highland Udhagamandalam region of Tamil Nadu, India, utilizing sixty years of meteorological data from 1960-2020. In this study, 8 temperature-based and 10 radiation-based empirical models are evaluated against ETo estimates derived from pan evaporation observation and the FAO Penman-Monteith method (FAO-PM), respectively. Statistical error metrics indicate that both temperature and radiation-based models perform better for the Udhagamandalam region. However, radiation-based models performed better than the temperature based models. This is possibly due to the high humidity of the study region throughout the year. The results suggest that simple temperature and radiation-based models using minimum meteorological information are adequate to estimate ETo and thus find potential application in agricultural water practices, hydrological processes, and irrigation management.

2.
Nanoscale ; 16(20): 9819-9826, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38700382

ABSTRACT

We studied the electronic properties of a high-temperature superconductor in proximity to a ferromagnetic material in a bilayer film of La0.67Sr0.33MnO3 (LSMO)/YBa2Cu3O7 (YBCO). High-quality single-crystalline films of YBCO and LSMO/YBCO were grown epitaxially on an SrTiO3 (001) surface. Magnetization data of the LSMO/YBCO bilayer exhibit ferromagnetic transition at about 255 K, which is much smaller than the Curie temperature of bulk LSMO. Experimental data show the emergence of magnetic anisotropy with cooling, which becomes significantly stronger in the superconducting phase. The onset temperature of diamagnetism is observed at 86 K in the YBCO sample for the out-of-plane magnetization and at 89 K in the in-plane data. Interestingly, the diamagnetism sets in at about 86 K for both magnetization directions in the LSMO/YBCO film despite the presence of the ferromagnetic LSMO layer underneath. Ba 4d and Y 3d core-level spectra show different surface and bulk electronic structures. Surface contribution is reduced significantly in the LSMO/YBCO sample, suggesting enhanced bulk-like behavior due to an enhancement of electron density near the surface arising from charge transfer across the interface. These results reveal an outstanding platform for on-demand tuning of properties without affecting the superconductivity of the system for the exploration of fundamental science and applications in advanced technology.

3.
Cardiovasc Revasc Med ; 63: 1-7, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38423848

ABSTRACT

PURPOSE: To evaluate the safety and effectiveness of the novel, next-generation Myval Octacor - Transcatheter Heart Valve (THV) in patients with severe, symptomatic, native aortic stenosis (AS). METHODS: This multicenter, real-world observational registry included 123 patients with severe symptomatic AS, across 16 Indian centers who underwent treatment with the novel Myval Octacor THV. Study endpoints included all-cause mortality, all stroke, acute kidney injury (AKI), major vascular complications, moderate or severe paravalvular leakage (PVL) and new permanent pacemaker implantation (PPI) until 30 days follow-up. RESULTS: Of the 123 patients (average age 70.07 ± 8.33 years), 37.4 % (n = 46) were female and 39.84 % presented with bicuspid valves. The technical success rate of the procedure was 100 % and the device success rate at 30 days was 98.4 %. At 30 days (n = 123) after the procedure, the overall mortality was 1.6 %. AKI occurred in 1.6 % of patients and there was no incidence of stroke, bleeding (types 3 and 4), and major vascular complications. In an analysis of 31 patients whose echocardiographic parameters were available across all timepoints, there were significant improvements in the mean pressure gradient (54.31 ± 18.19 mmHg vs. 10.42 ± 4.24 mmHg; p < 0.0001) and effective orifice area (0.66 ± 0.21 cm2 vs. 1.80 ± 0.44 cm2; p < 0.0001) from baseline to the 30-day follow-up. None of the patients experienced severe PVL, while moderate PVL was observed in two patients (1.6 %). CONCLUSIONS: Early outcomes of the next-generation, novel Myval Octacor THV proved its safety and effectiveness in the treatment of severe AS.


Subject(s)
Aortic Valve Stenosis , Aortic Valve , Heart Valve Prosthesis , Prosthesis Design , Registries , Severity of Illness Index , Transcatheter Aortic Valve Replacement , Humans , Female , Male , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/physiopathology , Treatment Outcome , Aged , India , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/instrumentation , Transcatheter Aortic Valve Replacement/mortality , Time Factors , Aged, 80 and over , Middle Aged , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve/physiopathology , Risk Factors , Recovery of Function , Postoperative Complications , Retrospective Studies , Hemodynamics
4.
Med Phys ; 50(11): 7003-7015, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37272198

ABSTRACT

BACKGROUND: The calculation of the net administered activity (Aadmin ) in patients undergoing 90 Y-radioembolization is essential for dosimetry and radiation safety, yet current methods for measuring residual 90 Y activity are often associated with high uncertainty. Therefore, an accurate, robust, and clinically viable method for the determination of Aadmin across approved 90 Y microsphere devices is desirable. PURPOSE: We report on a novel method to determine Aadmin by leveraging the quantitative capabilities of SPECT/CT to measure 90 Y-emission in vivo from patients following 90 Y-radioembolization with glass or resin microspheres. METHODS: 90 Y-SPECT/CT attenuation-corrected count data from 147 sequential 90 Y-radioembolization patients was used for this analysis. Aadmin was calculated as part of routine clinical practice via the exposure rate differences between the initial 90 Y-vial and the 90 Y-residual jar. This served as our gold standard measure of Aadmin . Patient data for each microsphere device were separated into training and testing cohorts to first develop regression models and then to independently assess model performance. The training cohorts were divided into four groups: first, based on the microsphere device (glass or resin), and second, based on the SPECT volume used to calculate counts (the full SPECT field of view (FOV) or liver only (VOIliver )). Univariate linear regression models were generated for each group to predict Aadmin based on 90 Y-SPECT data from the training cohorts. Leave-one-out cross validation was implemented to estimate variability in model parameters. To assess performance, linear models derived from the training cohort were applied to 90 Y-SPECT data from the testing cohort. A comparison of the models between microspheres devices was also performed. RESULTS: Linear models derived from the glass and resin training cohorts demonstrated a strong, positive correlation between 90 Y-SPECT image counts and Aadmin for VOIliver and FOV with R2  > 0.98 in all cases. In the glass training cohort, model accuracy (100%-absolute mean prediction error) and precision (95% prediction intervals of mean prediction error) were 99.0% and 15.4% for the VOIliver and 99.7% and 17.5% for the FOV models, respectively. In the resin training cohort, the corresponding values were 98.6% and 16.7% for VOIliver and > 99.9% and 11.4% for the FOV models, respectively. The application of these linear models to 90 Y-SPECT data from the testing cohort showed Aadmin prediction errors to have high accuracy and precision for both microsphere devices. For the glass testing cohort, accuracy (precision) was 96.9% (19.6%) and 98.8% (21.1%) for the VOIliver and FOV models, respectively. The corresponding values for the resin training cohort were 97.3% (26.2%) and 98.5% (25.7%) for the VOIliver and FOV models, respectively. The slope of the linear models between the two microsphere devices was observed to be significantly different with resin microspheres generating 48%-49% more SPECT counts for equivalent 90 Y activity based on each device manufacturer's activity calibration process. CONCLUSION: 90 Y-SPECT image counts can reliably predict (accuracy > 95% and precision < 18%) Aadmin after 90 Y-radioembolization, with performance characteristics essentially equivalent for both glass and resin microspheres. There is a clear indication that activity calibrations are fundamentally different between the two microsphere devices.


Subject(s)
Embolization, Therapeutic , Liver Neoplasms , Humans , Technetium Tc 99m Aggregated Albumin , Yttrium Radioisotopes/therapeutic use , Single Photon Emission Computed Tomography Computed Tomography , Tomography, Emission-Computed, Single-Photon , Radiometry , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapy , Microspheres
5.
Rheumatol Int ; 43(10): 1835-1840, 2023 10.
Article in English | MEDLINE | ID: mdl-37310437

ABSTRACT

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with varied dermatological manifestations that are almost universal. Overall, lupus disease has a major effect on the quality of life in these patients. We assessed the extent of cutaneous disease in early lupus and correlated it with the SLE quality-of-life (SLEQoL) index and disease activity measures. Patients diagnosed as SLE with the skin involved were recruited at the first presentation and were assessed for cutaneous and systemic disease activity using the cutaneous lupus erythematosus disease area and severity index (CLASI) and the Mexican-SLE disease activity index (Mex-SLEDAI), respectively. Quality of life was assessed with the SLEQoL tool while systemic damage was captured by the SLICC damage index. Fifty-two patients with SLE who had cutaneous involvement were enrolled (40, 76.9% females) with a median disease duration of 1 month (1-3.7). The median age was 27.5 years (IQR: 20-41). Median Mex-SLEDAI and SLICC damage index were 8(IQR: 4.5-11) and 0 (0-1), respectively. The median CLASI activity and damage scores were 3 (1-5) and 1 (0-1), respectively. Overall, there was no correlation between SLEQoL with CLASI or CLASI damage. Only the self-image domain of SLEQoL correlated with total CLASI (ρ = 0.32; p = 0.01) and CLASI-D (ρ = 0.35; p = 0.02). There was a weak correlation of CLASI with the Mexican-SLEDAI score (ρ = 0.30; p = 0.03) but not with the SLICC damage index. In this cohort of early lupus, cutaneous disease activity in lupus had a weak correlation with systemic disease. Cutaneous features did not appear to influence the quality of life except in the self-image domain.


Subject(s)
Lupus Erythematosus, Cutaneous , Lupus Erythematosus, Systemic , Female , Humans , Adult , Male , Quality of Life , Cross-Sectional Studies , Skin , Lupus Erythematosus, Cutaneous/diagnosis , Lupus Erythematosus, Systemic/diagnosis , Severity of Illness Index
6.
Environ Technol ; 44(6): 817-831, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34559029

ABSTRACT

In the present study, endophytic fungus, Penicillium simplicissimum isolated from Loranthus micranthus was used to analyze phytochemical studies by qualitative and GC-MS methods. The endophytic fungus P. simplicissimum yielded novel compound penisimplicissin identified through GC-MS studies. Further, P. simplicissimum was conjugated with C60 fullerene nanoparticles (Ps-FNPs) were verified using UV-vis spectra, XRD, FTIR, DLS, EDX and SEM. Ps-FNPs was confirmed using UV-visible spectra with a peak at 260 nm. The IR bands were recorded at 2085, 1428, 1181, 661, 652, 644, 628, and 604 cm-1. The Ps-FNPs treated cells showed a nucleolar shrinkage and cell arrest atprophase, binuclear and multinucleolar cells, a chromosomal bridge and diversion at anaphase was observed, whereas, chromosomal fragment and abnormal distribution at metaphase stage. The Ps-FNPs exhibited a noteworthy anticancer activity on lung cancer cell line H1975 through cytotoxicity. The cytotoxicity was induced by increasing caspase-3, 7, and 9 activities and also showed highest inhibition in xanthine oxidase and COX-II assay proved good anti-inflammatory activity. Ps-FNPs have been extensively studied for photocatalytic activity test against Rhodamine B, Methylene blue and nigrosine showed potential dye degradation in the presence of sunlight proved to be novel photocatalysts. With all the results recorded, Ps-FNPs also have a synergetic effect having on anti-mitotic, anticancer, anti-inflammation potential and photocatalytic degradation of dyes. Hence, the conjugated Ps-FNPs could be one of the potent nano-drug formulations in future. Thus, the present study gives a clear idea of the multifaceted therapeutic and photocatalytic applications.


Subject(s)
Antimitotic Agents , Photolysis , Fungi
7.
Nat Methods ; 20(2): 295-303, 2023 02.
Article in English | MEDLINE | ID: mdl-36585455

ABSTRACT

We present an auxiliary learning task for the problem of neuron segmentation in electron microscopy volumes. The auxiliary task consists of the prediction of local shape descriptors (LSDs), which we combine with conventional voxel-wise direct neighbor affinities for neuron boundary detection. The shape descriptors capture local statistics about the neuron to be segmented, such as diameter, elongation, and direction. On a study comparing several existing methods across various specimen, imaging techniques, and resolutions, auxiliary learning of LSDs consistently increases segmentation accuracy of affinity-based methods over a range of metrics. Furthermore, the addition of LSDs promotes affinity-based segmentation methods to be on par with the current state of the art for neuron segmentation (flood-filling networks), while being two orders of magnitudes more efficient-a critical requirement for the processing of future petabyte-sized datasets.


Subject(s)
Image Processing, Computer-Assisted , Neurons , Image Processing, Computer-Assisted/methods
8.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 2): 1683-1689, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36452524

ABSTRACT

The Onodi cell is defined as the posterior-most ethmoid cell. Haller cells are defined as infraorbital ethmoid cells. HRCT scanning provides excellent bone detail and accurate soft tissue mapping. The aim of this study is to know the prevalence of Haller cells and Onodi cells and to find variations in them on HRCT. Also to find co-relation between HRCT findings and Intra operative findings. A Hospital based prospective and cross-sectional study which included 30 patients above 15 years of age coming to ENT OPD with complaints related to sinonasal disease and polyposis;willing for HRCT followed by operative procedures. A total of 30 patients are included in the study. The mean age was found to be 38.70 ± 14.37. Prevalence of haller cells and onodi cells was 30% and 33.3% respectively. Statistical significance was found between association of haller cells with sinusitis. Intra-operative findings corresponded to 8 out of 9 HRCT findings (p-value = 0.001). We conclude that the actual prevalence of haller cell and onodi cell is best noted on HRCT-PNS and this holds a significant role in imparting thorough knowledge of the anatomical variations of PNS and hence preventing intraoperative complications due to presence of these variant cells.

9.
J Environ Radioact ; 255: 107029, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36265399

ABSTRACT

A Gaussian Plume based simple numerical model, named DIFFUSE is developed to simulate the long-term sector-average plume gamma dose due to radioactive plume released during normal operation of nuclear facilities. DIFFUSE calculates site specific joint frequency distributions of wind speed, wind direction and atmospheric stability using micrometeorological observations. It performs the finite sector-average dose integration for any stack height and gamma energy using Simpson's 1/3rd method with sufficient computational efficiency within the site boundary up to 2 km. Plume dose contribution to the main plume sector from nearest and next nearest side plume sectors is also calculated. DIFFUSE is validated with a 3-month long, starting from February 2021 to April 2021, dose rate observation data during operational releases from 100 m stack of Madras Atomic Power Station, Kalpakkam, India. Meteorological data from onsite 50 m tower and continuous dose rate observation from two sets of Autonomous Gamma Dose Logger (AGDL) detectors, namely n-AGDLs and r-AGDLs, placed in two different configurations along the geometric arcs of wind sectors around the stack are used. Simulated doses are compared with look-up table based dose estimates by Hukkoo et al. (1988). Linear spatial averaging of cumulative AGDL doses on a sector arc is used as measured sector-average dose for model validation. Simulations performed for both n-AGDL and r-AGDL configurations show DIFFUSE estimated doses are ∼37% lower and Hukkoo estimated doses are at least ∼50% lower than the measured doses. Statistical analysis of DIFFUSE simulated doses shows a statistical correlation of R2∼98.3%, slope of the fit ∼1.36 for n-AGDL setup and R2∼75.3%, slope of the fit ∼1.57 for r-AGDL setup. Overall, DIFFUSE produces conservative doses compared to look-up table based doses as required by regulatory bodies.


Subject(s)
Radiation Monitoring , Radiation Monitoring/methods , India , Wind , Gamma Rays
10.
Sci Rep ; 12(1): 16985, 2022 10 10.
Article in English | MEDLINE | ID: mdl-36216959

ABSTRACT

This study evaluated the effects of water stress on rice yield over Punjab and Haryana across North India by integrating Weather Research Forecasting (WRF) and Decision Support System for Agrotechnology Transfer (DSSAT) models. Indian Remote Sensing Satellite datasets were used to define land use/land cover in WRF. The accuracy of simulated rainfall and temperature over Punjab and Haryana was evaluated against Tropical Rainfall Measuring Mission and automated weather station data of Indian Space Research Organization, respectively. Data from WRF was used as weather input to DSSAT to simulate rice yield in Punjab and Haryana for 2009 and 2014. After simulated yield has been evaluated against district-level observed yield, the water balance components within the DSSAT model were used to analyze the impact of water stress on rice yield. The correlation (R2) between the crop water stress factor and the rice yield anomaly at the vegetative and reproductive stage was 0.64 and 0.52 for Haryana and 0.73 and 0.68 for Punjab, respectively. Severe water stress during the flowering to maturity stage inflicted devastating effects on yield. The study concludes that the regional climate simulations can be potentially used for early water stress prediction and its impact on rice yield.


Subject(s)
Oryza , Agriculture , Climate Change , Crops, Agricultural , Dehydration , Forecasting , Weather
11.
J Chem Inf Model ; 62(1): 116-128, 2022 01 10.
Article in English | MEDLINE | ID: mdl-34793155

ABSTRACT

Despite the recent availability of vaccines against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the search for inhibitory therapeutic agents has assumed importance especially in the context of emerging new viral variants. In this paper, we describe the discovery of a novel noncovalent small-molecule inhibitor, MCULE-5948770040, that binds to and inhibits the SARS-Cov-2 main protease (Mpro) by employing a scalable high-throughput virtual screening (HTVS) framework and a targeted compound library of over 6.5 million molecules that could be readily ordered and purchased. Our HTVS framework leverages the U.S. supercomputing infrastructure achieving nearly 91% resource utilization and nearly 126 million docking calculations per hour. Downstream biochemical assays validate this Mpro inhibitor with an inhibition constant (Ki) of 2.9 µM (95% CI 2.2, 4.0). Furthermore, using room-temperature X-ray crystallography, we show that MCULE-5948770040 binds to a cleft in the primary binding site of Mpro forming stable hydrogen bond and hydrophobic interactions. We then used multiple µs-time scale molecular dynamics (MD) simulations and machine learning (ML) techniques to elucidate how the bound ligand alters the conformational states accessed by Mpro, involving motions both proximal and distal to the binding site. Together, our results demonstrate how MCULE-5948770040 inhibits Mpro and offers a springboard for further therapeutic design.


Subject(s)
COVID-19 , Protease Inhibitors , Antiviral Agents , Coronavirus 3C Proteases , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Orotic Acid/analogs & derivatives , Piperazines , SARS-CoV-2
12.
Mar Pollut Bull ; 173(Pt B): 113147, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34808544

ABSTRACT

Seafood, intertidal biota, beach sediment, and seawater from Kalpakkam coast, Bay of Bengal were analyzed for 210Po to evaluate the internal exposure and other radiological safety aspects. Kalpakkam houses various nuclear power generation facilities on its coast. The activity concentration of 210Po was more pronounced in the intertidal organisms. Pelagic planktivorous fishes have the highest activity of the non-technogenic radionuclide, followed by the detrital feeders, benthic planktivores, benthic carnivores, and pelagic carnivore fishes. The affinity of 210Po to organic detrital matter and planktonic organisms has led to a higher accumulation of radionuclide in planktivorous fishes. Activity concentration of 210Po in seafood ranged between 1.13 ± 0.3 and 96.71 ± 1.6 Bq kg-1 (Becquerel/kilogram). In seaweeds and gastropods, it ranged from 2.09 ± 0.2 to 8.21 ± 0.6 and from 9.31 ± 0.7 to 21.58 ± 1.2 Bq kg-1, respectively. The committed effective dose (CED) of 210Po in seafood varied from 31.18 to 456.68 µSv yr-1 (microSievert/year). Radiological hazard parameters, such as activity intake, CED in consumption, of the seafood from this coast are within the acceptable levels prescribed by the International Commission on Radiological Protection and US Environmental Protection Agency.


Subject(s)
Polonium , Radiation Monitoring , Water Pollutants, Radioactive , Animals , Bays , Biota , Polonium/analysis , Seafood/analysis , Water Pollutants, Radioactive/analysis
14.
Nat Methods ; 18(9): 1082-1090, 2021 09.
Article in English | MEDLINE | ID: mdl-34480155

ABSTRACT

Single-molecule localization microscopy (SMLM) has had remarkable success in imaging cellular structures with nanometer resolution, but standard analysis algorithms require sparse emitters, which limits imaging speed and labeling density. Here, we overcome this major limitation using deep learning. We developed DECODE (deep context dependent), a computational tool that can localize single emitters at high density in three dimensions with highest accuracy for a large range of imaging modalities and conditions. In a public software benchmark competition, it outperformed all other fitters on 12 out of 12 datasets when comparing both detection accuracy and localization error, often by a substantial margin. DECODE allowed us to acquire fast dynamic live-cell SMLM data with reduced light exposure and to image microtubules at ultra-high labeling density. Packaged for simple installation and use, DECODE will enable many laboratories to reduce imaging times and increase localization density in SMLM.


Subject(s)
Deep Learning , Image Processing, Computer-Assisted/methods , Single Molecule Imaging/methods , Animals , COS Cells , Chlorocebus aethiops , Databases, Factual , Software
16.
Nat Methods ; 18(7): 771-774, 2021 07.
Article in English | MEDLINE | ID: mdl-34168373

ABSTRACT

We develop an automatic method for synaptic partner identification in insect brains and use it to predict synaptic partners in a whole-brain electron microscopy dataset of the fruit fly. The predictions can be used to infer a connectivity graph with high accuracy, thus allowing fast identification of neural pathways. To facilitate circuit reconstruction using our results, we develop CIRCUITMAP, a user interface add-on for the circuit annotation tool CATMAID.


Subject(s)
Brain/physiology , Image Processing, Computer-Assisted/methods , Synapses/physiology , Animals , Brain/cytology , Databases, Factual , Drosophila melanogaster , Microscopy, Electron , Neural Pathways
17.
Preprint in English | bioRxiv | ID: ppbiorxiv-437323

ABSTRACT

Despite the recent availability of vaccines against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the search for inhibitory therapeutic agents has assumed importance especially in the context of emerging new viral variants. In this paper, we describe the discovery of a novel non-covalent small-molecule inhibitor, MCULE-5948770040, that binds to and inhibits the SARS-Cov-2 main protease (Mpro) by employing a scalable high throughput virtual screening (HTVS) framework and a targeted compound library of over 6.5 million molecules that could be readily ordered and purchased. Our HTVS framework leverages the U.S. supercomputing infrastructure achieving nearly 91% resource utilization and nearly 126 million docking calculations per hour. Downstream biochemical assays validate this Mpro inhibitor with an inhibition constant (Ki) of 2.9 {micro}M [95% CI 2.2, 4.0]. Further, using room-temperature X-ray crystallography, we show that MCULE-5948770040 binds to a cleft in the primary binding site of Mpro forming stable hydrogen bond and hydrophobic interactions. We then used multiple {micro}s-timescale molecular dynamics (MD) simulations, and machine learning (ML) techniques to elucidate how the bound ligand alters the conformational states accessed by Mpro, involving motions both proximal and distal to the binding site. Together, our results demonstrate how MCULE-5948770040 inhibits Mpro and offers a springboard for further therapeutic design. O_TEXTBOXSignificance StatementThe ongoing novel coronavirus pandemic (COVID-19) has prompted a global race towards finding effective therapeutics that can target the various viral proteins. Despite many virtual screening campaigns in development, the discovery of validated inhibitors for SARS-CoV-2 protein targets has been limited. We discover a novel inhibitor against the SARS-CoV-2 main protease. Our integrated platform applies downstream biochemical assays, X-ray crystallography, and atomistic simulations to obtain a comprehensive characterization of its inhibitory mechanism. Inhibiting Mpro can lead to significant biomedical advances in targeting SARS-CoV-2 treatment, as it plays a crucial role in viral replication. C_TEXTBOX

18.
Indian J Surg Oncol ; 11(4): 653-661, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33281405

ABSTRACT

Emerging techniques in minimally invasive rectal resection include robotic total mesorectal excision (R-TME). The Da Vinci Surgical System offers precise dissection in narrow and deep confined spaces and is gaining increasing acceptance during recent times. The aim of this study is to analyse our initial experience of R-TME with Da Vinci Xi platform in terms of perioperative and oncological outcomes in the context of data from recently published randomised ROLARR trial amongst minimally invasive novice surgeons. Patients who underwent R-TME or tumour specific mesorectal excision for rectal cancer between May 2016 and November 2019 were identified from a prospectively maintained single institution colorectal database. Demographic, clinical-pathological and short-term oncological outcomes were analysed. Of the 178 patients, 117 (65.7%) and 31 (17.4%) patients had lower and mid third rectal cancer. Most of the tumours were locally advanced, cT3-T4: 138 (77.5%). One hundred/178 (56.2%) underwent sphincter preserving TME. Eighty-seven (48.8%) were grade II adenocarcinoma. Nonmucinous adenocarcinoma was the predominant histology, 138 (78.4%). One hundred one cases (56.7%) were pT3. The mean number of lymph node yield was 13 ± 5. Distal resection margin and circumferential resection margin were positive in 2 (1.12%), 12 cases (6.74%) respectively. Eleven cases (6.7%) had to be converted to open TME. Mean blood loss and duration of surgery was 170 ± 60 ml and 286 ± 45 min respectively. Five percent cases had an anastomotic leak. Grade IIIa-IIIb Clavien Dindo (CD) morbidity score was reported to be in 12 (6.75%) and 10 (5.61%) cases. Median length of hospitalisation was 7 days (range 4-14 days). Perioperative and pathologic outcomes following robotic rectal resection is associated with good short-term oncological outcomes and is safe, effective, and reproducible by a minimally invasive novice surgeon.

19.
Int J Trichology ; 12(3): 114-117, 2020.
Article in English | MEDLINE | ID: mdl-33223735

ABSTRACT

INTRODUCTION: Indirect immunofluorescence (IIF) is used to determine the circulating autoantibodies in cases of Pemphigus. For IIF in Pemphigus several substrates had been used. This study was done to determine whether plucked hair can be utilized as a substrate for IIF in cases of Pemphigus. Aim & Objectives: To determine the efficacy of utilizing the plucked hair as a substrate for indirect immunofluorescence among patients with Pemphigus vulgaris. METHODOLOGY: Thirty two consecutive patients with active and fresh diagnosed cases of pemphigus vulgaris (PV) who did not undergo any treatment and those patients who had positive DIF findings of characteristic fish net or chicken wire pattern of intercellular IgG deposits in the epidermis of perilesional skin were included in the study. A total of 32 control subjects without any auto immune disorders were selected and the blood samples were taken from these patients for IIF analysis. Anagen hair were collected from the healthy volunteers without pemphigus in the same way as for trichogram. Telogen hair were obtained by combing the hair and collecting the loose strands of hair on the comb and further confirmed under microscope. Three hairs each of anagen and telogen stage were collected from each subject to be utilized as a substrate for IIF. RESULTS: Out of 32 samples 20 samples showed positive results for Ig G alone and 5 samples showed positivity for Ig G and C3. One sample showed positivity for C3alone. All these 26 samples were considered to have positive IIF test based on the intercellular pattern of deposit. Positive IIF results were observed in anagen hair samples and were negative in all the telogen hair samples. Six anagen hair samples did not show any positive findings in IIF for the study group. All the 32 control samples showed negative reports in IIF. CONCLUSION: In conclusion, IIF microscopy on plucked hair as a substrate is a more sensitive immunoassay for the detection of circulating intercellular autoantibodies in PV and the lower negative predictive value of this substrate is a limitation. Further large scale studies might provide better information regarding the practical utility.

20.
Science ; 370(6514)2020 10 16.
Article in English | MEDLINE | ID: mdl-33060330

ABSTRACT

Brains encode behaviors using neurons amenable to systematic classification by gene expression. The contribution of molecular identity to neural coding is not understood because of the challenges involved with measuring neural dynamics and molecular information from the same cells. We developed CaRMA (calcium and RNA multiplexed activity) imaging based on recording in vivo single-neuron calcium dynamics followed by gene expression analysis. We simultaneously monitored activity in hundreds of neurons in mouse paraventricular hypothalamus (PVH). Combinations of cell-type marker genes had predictive power for neuronal responses across 11 behavioral states. The PVH uses combinatorial assemblies of molecularly defined neuron populations for grouped-ensemble coding of survival behaviors. The neuropeptide receptor neuropeptide Y receptor type 1 (Npy1r) amalgamated multiple cell types with similar responses. Our results show that molecularly defined neurons are important processing units for brain function.


Subject(s)
Behavior, Animal , Calcium/metabolism , Gene Expression , Paraventricular Hypothalamic Nucleus/metabolism , RNA/metabolism , Animals , Gene Expression Profiling , Genetic Markers , Male , Mice , Neurons/metabolism , RNA-Seq , Receptors, Neuropeptide Y/genetics , Single-Cell Analysis
SELECTION OF CITATIONS
SEARCH DETAIL
...