Membrane Fluctuation Model for Understanding the Effect of Receptor Nanoclustering on the Activation of Natural Killer Cells through Biomechanical Feedback.

We investigated the role of ligand clustering and density in the activation of natural killer (NK) cells. To that end, we designed reductionist arrays of nanopatterned ligands arranged with different cluster geometries and densities and probed their effects on NK cell activation. We used these arrays as an artificial microenvironment for the stimulation of NK cells and studied the effect of the array geometry on the NK cell immune response. We found that ligand density significantly regulated NK cell activation while ligand clustering had an impact only at a specific density threshold. We also rationalized these findings by introducing a theoretical membrane fluctuation model that considers biomechanical feedback between ligand-receptor bonds and the cell membrane. These findings provide important insight into NK cell mechanobiology, which is fundamentally important and essential for designing immunotherapeutic strategies targeting cancer.

A Novel Approach for Colloidal Lithography: From Dry Particle Assembly to High-Throughput Nanofabrication.

We introduce a novel approach for colloidal lithography based on the dry particle assembly into a dense monolayer on an elastomer, followed by mechanical transfer to a substrate of any material and curvature. This method can be implemented either manually or automatically and it produces large area patterns with the quality obtained by the state-of-the-art colloidal lithography at a very high throughput. We first demonstrated the fabrication of nanopatterns with a periodicity ranging between 200 nm and 2 µm. We then demonstrated two nanotechnological applications of this approach. The first one is antireflective structures, fabricated on silicon and sapphire, with different geometries including arrays of bumps and holes and adjusted for different spectral ranges. The second one is smart 3D nanostructures for mechanostimulation of T cells that are used for their effective proliferation, with potential application in cancer immunotherapy. This new approach unleashes the potential of bottom-up nanofabrication and paves the way for nanoscale devices and systems in numerous applications.

TiO2 Nano-Biopatterning Reveals Optimal Ligand Presentation for Cell-Matrix Adhesion Formation.

Nanoscale organization of transmembrane receptors is critical for cellular functions, enabled by the nanoscale engineering of bioligand presentation. Previously, a spatial threshold of ≤60 nm for integrin binding ligands in cell-matrix adhesion is demonstrated using monoliganded gold nanoparticles. However, the ligand geometric arrangement is limited to hexagonal arrays of monoligands, while plasmonic quenching limits further investigation by fluorescence-based high-resolution imaging. Here, these limitations are overcome with dielectric TiO2 nanopatterns, eliminating fluorescence quenching, thus enabling super-resolution fluorescence microscopy on nanopatterns. By dual-color super-resolution imaging, high precision and consistency among nanopatterns, bioligands, and integrin nanoclusters are observed, validating the high quality and integrity of both nanopattern functionalization and passivation. By screening TiO2 nanodiscs with various diameters, an increase in fibroblast cell adhesion, spreading area, and Yes-associated protein (YAP) nuclear localization on 100 nm diameter compared with smaller diameters was observed. Focal adhesion kinase is identified as the regulatory signal. These findings explore the optimal ligand presentation when the minimal requirements are sufficiently fulfilled in the heterogenous extracellular matrix network of isolated binding regions with abundant ligands. Integration of high-fidelity nano-biopatterning with super-resolution imaging allows precise quantitative studies to address early signaling events in response to receptor clustering and their nanoscale organization.

Comprehensive analysis of spatiotemporal variability of rainfall-based extremes and their implications on agriculture in the Upper Ganga Command Area.

The agricultural sector in India primarily relies on monsoon rains, making it necessary for agricultural water managers to study variations in water availability by analyzing rainfall patterns. This information is critical for deciding cropping patterns and irrigation approaches, managing water resources, and improving crop water productivity. The long-term spatiotemporal variability over the command area, India Meteorological Department (IMD) based selection of thresholds for extremes indices, and thorough analysis of the consequences of extreme on agriculture make the study unique. These aspects collectively enhance the perception of the climate-agriculture relationship, which is essential for promoting agriculture resilience under changing rainfall patterns. This type of research is very limited in the literature. Therefore, the present study focuses on comprehensively analyzing the spatiotemporal variability of rainfall and extreme precipitation indices and their implications on agriculture. The study is carried out in the Upper Ganga Command Area (UGCA), India's oldest irrigation canal system, by using long-term (1901-2021) high-resolution (0.25 × 0.25°) daily rainfall gridded data obtained from IMD, Pune. Eight different extreme rainfall indices are used to assess spatiotemporal variations. The Mann-Whitney-Pettitt test identified 1970 as a significant change point. Rainfall trends and extreme indices for pre- and post-1970 periods were examined using the non-parametric modified Mann-Kendall test. The results show significant increases in rainfall trends for the annual, monsoon, and kharif seasons from 1901 to 1970, but significant decreases were observed during 1971-2021. This difference resulted in a noticeable decrease in average precipitation in the latter period, approximately 62 mm less than in 1901-1970. Similarly, extreme precipitation indices, including the number of rainy days (NxRainy), consecutive dry days (CWD), simple daily intensity index (SDII), and total precipitation (PRCPTOT), exhibited increasing trends in 1901-1970, but they showed significant decreasing trends in 1971-2021. In addition, there is a strong positive correlation between these indices and total precipitation. The study also found that geographical factors influence these trends, with all indices, except SDII, strongly correlated with latitude and elevation, but not with longitude. The implications of these negative rainfall and extreme rainfall trends were further analyzed, and the results indicate a significant impact on the cropping patterns in the study area. The present research findings will be beneficial for regional water resource managers and policymakers in better understanding the existing trends in rainfall distribution over the UGCA.

Multifunctional Nanoscale Platform for the Study of T Cell Receptor Segregation.

T cells respond not only to biochemical stimuli transmitted through their activating, costimulatory, and inhibitory receptors but also to biophysical aspects of their environment, including the receptors' spatial arrangement. While these receptors form nanoclusters that can either colocalize or segregate, the roles of these colocalization and segregation remain unclear. Deciphering these roles requires a nanoscale platform with independent and simultaneous spatial control of multiple types of receptors. Herein, using a straightforward and modular fabrication process, we engineered a tunable nanoscale chip used as a platform for T cell stimulation, allowing spatial control over the clustering and segregation of activating, costimulatory, and inhibitory receptors. Using this platform, we showed that, upon blocked inhibition, cells became sensitive to changes in the nanoscale ligand configuration. The nanofabrication methodology described here opens a pathway to numerous studies, which will produce an important insight into the molecular mechanism of T cell activation. This insight is essential for the fundamental understanding of our immune system as well as for the rational design of future immunotherapies.

Debris flow simulation and modeling of the 2021 flash flood hazard caused by a rock-ice avalanche in the Rishiganga River valley of Uttarakhand.

The high mountain ecosystem of the Indian Himalayas has frequently been experiencing primary hazards (like earthquakes, avalanches, and landslides). Often, these events are followed by the triggering of secondary hazards (like landslide dams, debris flows, and flooding), thereby posing massive risks to infrastructure and residents in the region. This study was taken up to understand the dynamics of an extraordinary debris flood disaster in the Rishiganga River valley, Chamoli district of Uttarakhand on 7th February 2021. Rapid mass movements (RAMMS)-debris flow software was employed to recreate the entire sequence of the hazard consisting of a rock-ice slide, mass deposition and erosion along the channel, and subsequent debris flood. Forty-nine scenarios were analyzed for accurate calibration of dry-Coulomb type friction coefficient (µ) and viscous-turbulent friction coefficient (ξ). Consequently, the geomorphologic characteristics of the debris flow were validated using high-resolution satellite image interpretation and field photographs. The volume of detached rock-ice mass was estimated to be 26.42 × 106 m3. At the same time, the RAMMS-derived model outputs for velocity, flow depth, and momentum were found in good agreement with the extent and height of actual debris on the ground. The study highlights an urgent need to identify the glaciers with a high risk of ice avalanches in the Indian Himalayas. The presented modeling approach may be applied in dynamic mountain ecosystems to simulate potential flash floods due to avalanches. Moreover, the information reported in this study can be vital input for improving the district-level disaster management plan.

Sediment modeling using laboratory-scale rainfall simulator and laser precipitation monitor.

The characterization of a rainfall simulator provides an excellent opportunity to study the potential of soil erosivity without waiting for natural rain. But, precise instrumentation is required to estimate the parameters, which is seldom available. To overcome this problem, the empirical and conceptual relationships obtained through physically-based modeling help to correlate the rain parameters contributing to soil erosion. The present laboratory study used five pressurized nozzles of different capacities and a Laser Precipitation Monitor (LPM) to generate different rain intensities (21.0-79.0 mm h-1) and to register drop size distribution, respectively. The sediment transportation induced by rain and runoff was measured with an erosion flume of 2.50 × 1.25 × 0.56 m with an adjustable longitudinal slope. The spatial uniformity, drop size distribution, drop velocity, and kinetic energy were used to evaluate the simulator's performance. The different rain erosivity parameters were correlated and tested statistically using linear and non-linear regression analysis. The rain simulation experiments of different intensities at different pressure ranges were performed on flat, 5, 10, and 15% slopes of the erosion flume to evaluate rain characteristics and record the surface runoff and sediment yield. The median drop sizes produced during the simulator ranged from 0.38 to 2.11 mm, coinciding with natural rain. The empirical relationships were developed to correlate surface discharge and sediment yield with rain intensity by optimizing the parameters for further study of experimental field plots of different slopes. The observed and estimated rain erosivity parameters showed a significant relationship (R2 = 0.75 to 0.93; P < 0.001) in multiple regression analysis, and the metrics used to test the developed regression equations showed lower MAE, MSE, and RMSE errors indicating the adequacy of the relationships. The results indicated that the simulator helps to understand the complex task of soil erosion with hydrologic and geomorphic processes in laboratory experimentation with sufficient accuracy in measuring sediment transport events.

Elastic Microstructures: Combining Biochemical, Mechanical, and Topographical Cues for the Effective Activation and Proliferation of Cytotoxic T Cells.

The ex vivo activation and proliferation of cytotoxic T cells are critical steps in adoptive immunotherapy. Today, T cells are activated by stimulation with antibody-coated magnetic beads, traditionally used for cell separation. Yet, efficient and controlled activation and proliferation of T cells require new antibody-bearing materials, which, in particular, deliver mechanical and topographic cues sensed by T cells. Here, we demonstrate a new approach for the activation and proliferation of human cytotoxic T cells using an elastic microbrush coated with activating and costimulatory antibodies. We found that the microbrush topography affects the protrusion of the cell membrane and the elastic response to the forces applied by cells and can be optimized to yield the strongest activation of T cells. In particular, T cells stimulated by a microbrush showed a three-fold increase in degranulation and release of cytokines over T cells stimulated with state-of-the-art magnetic beads. Furthermore, the microbrush induced a T-cell proliferation of T cells that was more prolonged and yielded much higher cell doubling than that done by the state-of-the-art methods. Our study provides an essential insight into the physical mechanism of T-cell activation and proliferation and opens the floodgates for the design of novel stimulatory materials for T-cell-based immunotherapy.

Characterization and assessment of hydrological droughts using GloFAS streamflow data for the Narmada River Basin, India.

Hydrological droughts severely affect the demand of water for domestic water supply, irrigation, hydropower generation, and several other purposes. The pervasiveness and consequences of hydrological droughts necessitate a thorough investigation of their characteristics, which is hindered due to unavailability of continuous streamflow records at desirable resolutions. This study aims to assess the hydrological drought characteristics and their spatial distribution using high-resolution Global Flood Awareness System (GloFAS) v3.1 streamflow data for the period 1980 to 2020. Streamflow Drought Index (SDI) was used to characterize droughts at 3-, 6-, 9-, and 12-monthly timescales starting from June, i.e., the start of water year in India. GloFAS is found to capture the spatial distribution of streamflow and its seasonal characteristics. The number of hydrological drought years over the basin varied from 5 to 11 during the study duration, implying that the basin is prone to frequent abnormal water deficits. Interestingly, the hydrological droughts are more frequent in the eastern portion of the basin, i.e., the Upper Narmada Basin. The trend analysis of multi-scalar SDI series using non-parametric Spearman's Rho test exhibited increasing drying trends in the easternmost portions. The results were not similar for the middle and western portions of the basin, which may be due to presence of a large number of reservoirs in these regions and their systematic operations. This study highlights the importance of open-access global products that can be used for monitoring hydrological droughts, especially over ungauged catchments.

Assessment of drought trends and variabilities over the agriculture-dominated Marathwada Region, India.

Drought is considered among the most perilous events with catastrophic consequences, particularly from the agro-economic point of view. These consequences are expected to exacerbate under the increasing meteorological aberrations due to changing climate, which necessitates investigating drought variabilities. This study presents a thorough spatiotemporal assessment of drought trends and variabilities over the agriculture-dominated Marathwada Region, Maharashtra, India. The precipitation data is extracted from the India Meteorological Department (IMD) gridded product, whereas actual evapotranspiration (ET) and Evaporative Stress Index (ESI) are obtained from Global Land Evaporation Amsterdam Model (GLEAM) datasets. Standardized Precipitation Index (SPI) is used to characterize drought occurrences at multiple time frames, whereas non-parametric tests, i.e., modified Mann-Kendall (MMK) and Sen's slope (SS) tests, are employed to detect trends. The results reveal the region to be prone to droughts, and SPI at a longer time frame (i.e., 12-monthly moving frame) can capture drought occurrences better than the shorter time frames, which can be attributed to the lesser randomness in the time series in the longer frame. A mix of positive/negative trends of SPI series are found for the monsoonal months; however, they are relatively more concentrated towards negative ZMMK. Hence, the Marathwada Region can be inferred to have exhibited a relatively increased tendency towards drought occurrences. The seasonal differences in mean values and trends of rainfall, ET, and ESI are discussed in detail. Since the Marathwada Region has a monsoon-dominated climate with high agricultural importance, the information reported in this study will help in devising water management strategies to minimize the repercussions of droughts.

Appraisal of historical trends in maximum and minimum temperature using multiple non-parametric techniques over the agriculture-dominated Narmada Basin, India.

In this study, the long-term trends in climatological parameters, viz., maximum temperature (TMAX) and minimum temperature (TMIN), are determined over 68 years (i.e., June 1951 to May 2019) using the gridded observation datasets (1° × 1° spatial resolution) of India Meteorological Department over the Narmada river basin, India. Multiple non-parametric techniques, viz., modified Mann-Kendall (MMK), Sen's slope (SS), and Spearman's rho (SR) tests, are used to determine monthly, seasonal, and annual trends over individual grids. The trends are also analyzed for the climatic variables spatially averaged over the entire basin to draw general conclusions on historical climate change. The results reveal a significant spatiotemporal variation in trends of TMAX and TMIN over the basin. In general, both the parameters are found to be increasing. Furthermore, the hottest months (April and May) have become hotter, and the coldest month (January) has become colder, implying a higher probability of increasing temperature extremes. Furthermore, the entire duration of 68 years is divided into two epochs of 34 years, i.e., 1951-1984 and 1985-2018, and the trend analysis of TMAX and TMIN is also carried out epoch-wise to better understand/assess the signals of climate change in recent years. In general, a relatively higher warming trend was observed in the latter epoch. As a majority of the basin area is dominated by agricultural lands, the implications of the temperature trends and their impacts on agriculture are succinctly discussed. The information reported in this study will be helpful for proper planning and management of water resources over the basin under the changing climatic conditions.

A case of bilateral sclerouveitis with secondary glaucoma right eye.

Infectious scleritis is rare and most commonly herpetic in origin. We report an unusual bilateral subacute presentation of scleritis with uveitis and glaucoma which responded to treatment with acyclovir. A 47-year-old male coast guard personnel presented with 2 months history of bilateral red eye. He was initially managed elsewhere as conjunctivitis, and on examination had bilateral diffuse redness of the eyes persisting with phenylephrine, with scleral edema and mild globe tenderness. Investigations for underlying autoimmune systemic illness were normal. He showed inadequate response to topical steroids and cycloplegics and developed uveitis and glaucoma while on steroids. He was then given tablet acyclovir with antiglaucoma topical medications with which he showed rapid response and complete resolution. The case is being reported for highlighting this unusual bilateral presentation of scleritis with uveitis and glaucoma with possible viral etiology.

Nanocomposite coatings for the prevention of surface contamination by coronavirus.

The current Covid-19 pandemic has a profound impact on all aspects of our lives. Aside from contagion by aerosols, the presence of the SARS-CoV-2 is ubiquitous on surfaces that millions of people handle daily. Therefore, controlling this pandemic involves the reduction of potential infections via contaminated surfaces. We developed antiviral surfaces by preparing suspensions of copper and cupric oxide nanoparticles in two different polymer matrices, poly(methyl methacrylate) and polyepoxide. For total copper contents as low as 5%, the composite material showed remarkable antiviral properties against the HCoV-OC43 human coronavirus and against a model lentivirus and proved well-resistant to accelerated aging conditions. Importantly, we showed that the Cu/CuO mixture showed optimal performances. This product can be implemented to produce a simple and inexpensive coating with long-term antiviral properties and will open the way to developing surface coatings against a broad spectrum of pathogens including SARS-CoV-2.

Leveraging the potential of silver nanoparticles-based materials towards sustainable water treatment.

Increasing demand of pure and accessible water and improper disposal of waste into the existing water resources are the major challenges for sustainable development. Nanoscale technology is an effective approach that is increasingly being applied to water remediation. Compared to conventional water treatment processes, silver nanotechnology has been demonstrated to have advantages due to its anti-microbial and oligodynamic (biocidal) properties. This review is focused on environmentally friendly green syntheses of silver nanoparticles (AgNPs) and their applications for the disinfection and microbial control of wastewater. A bibliometric keyword analysis is conducted to unveil important keywords and topics in the utilisation of AgNPs for water treatment applications. The effectiveness of AgNPs, as both free nanoparticles (NPs) or as supported NPs (nanocomposites), to deal with noxious pollutants like complex dyes, heavy metals as well as emerging pollutants of concern is also discussed. This knowledge dataset will be helpful for researchers to identify and utilise the distinctive features of AgNPs and will hopefully stimulate the development of novel solutions to improve wastewater treatment. This review will also help researchers to prepare effective water management strategies using nano silver-based systems manufactured using green chemistry.

Microwave-assisted extraction of lignin from coconut coir using deep eutectic solvents and its valorization to aromatics.

Lignin is a rich renewable source of aromatics present in lignocellulosic biomass (LCB). The extraction of lignin from the intricate LCB network is a challenging task for successful commercialization of sustainable biorefineries. In the present study, a series of choline chloride (ChCl)-carboxylic acid based deep eutectic solvents (DESs) were used for the extraction of lignin from coconut coir under microwave irradiation. Among the synthesized DESs, ChCl: lactic acid (LA) (1:4) gave the highest lignin yield of 82% with >95% purity. Interestingly, the severity factor (H factor) for the pretreatment process was found to be a significantly lower (55.5) as compared to reported studies due to efficient microwave heating. Moreover, the DES showed good recyclability for four recycle runs thus making it a promising candidate for the delignification of LCB. Finally, the extracted lignin was converted to aromatics via catalytic transfer hydrogenation (CTH) using Ru/C and isopropanol as in-situ hydrogen donor.

Tobacco retailer density and tobacco retailers near schools in two cities of East India, Ranchi and Siliguri.

BACKGROUND: Passive and active exposure to tobacco smoke is associated with tuberculosis infection and tuberculosis disease. Addressing tobacco use is a critical strategy to address tuberculosis (TB). Studies conducted globally demonstrate that the physical presence and density of tobacco vendors can increase tobacco use in both youth and adults. Little is known about the number and density of tobacco vendors in India, where there are approximately 267 million tobacco users. In India, a national tobacco control law (COTPA, 2003) prohibits the sale of tobacco within 100-yards of an educational institution. Little is known about the number of tobacco vendors operating within 100-yards of schools. This study assesses the number and density of tobacco vendors in the cities of Ranchi (Jharkhand) and Siliguri (West Bengal), and the number of retailers selling tobacco near schools. Both of these jurisdictions have passed local tobacco vendor licensing laws. METHODS: Data collectors conducted a census of tobacco vendors within select wards in each city. Each tobacco vendor was classified as either an independent store, permanent kiosk, temporary kiosk, or street vendor. The location of each tobacco vendor was recorded. Data collectors also noted the location of any school/educational institution. Spatial analysis was conducted using GIS software (QGIS 10.5). 100-yard buffers were mapped around school premises. Tobacco vendor density was calculated by area, by road distance, and by population. Tobacco vendors within 100-yards of school properties were counted. RESULTS: The study identified 559 tobacco vendors in Ranchi, across three wards, and 367 tobacco vendors in Siliguri, across five wards. When considering the three wards in Ranchi, tobacco vendor density was 68 vendors/km2, 06 vendors/km road, and 08 vendors/1000 population. In Siliguri, the tobacco vendor density was 99 vendors/km2, 05 vendors/km road, and 07 vendors/1000 population. The study found that 19% (n = 105) of vendors observed in Ranchi and 23% (n = 84) of vendors in Siliguri were located within 100-yards of one or more schools. The most common vendor-type in Ranchi was an independent store (58%) and in Siliguri was a permanent kiosk (52%). CONCLUSION: Tobacco vendor density was remarkably high in each of the surveyed wards. The study identified tobacco vendors operating within 100-yards of schools. Fully implementing COTPA, 2003 could reduce vendor density in Ranchi and Siliguri. Each city's tobacco vendor licensing laws could further reduce tobacco vendor density. Other strategies should be considered to further reduce density, including setting limits on tobacco vendor type, area or population. The data from this study can be used to inform future tobacco control strategies for these cities and others in the region.

Instructive analysis of engineered carbon materials for potential application in water and wastewater treatment.

Water remediation is an essential component for sustainable development. Increasing population and rapid industrialization have contributed to the deterioration of water resources. In particular, effluents from chemical, pharmaceutical, petroleum industries, and anthropogenic activities have led to severe ecological degradation. Many of these detrimental pollutants are highly toxic even at low concentrations, acting as carcinogens and inflicting severe long-lasting effects on human health. This review underscores the potential applications of engineered carbon-based materials for effective wastewater treatment. It focuses on the performance as well as efficiency of activated carbon, graphene nanomaterial, and carbon nanotubes, both with and without chemical functionalization. Plausible mechanisms of action between the chemically functionalized adsorbent and pollutants are also discussed. Based on the keywords from the literature published in the recent five years, a statistical practicality-vs-applicability analysis of these three materials is also provided. The review will provide a deep understanding of the physical or chemical interactions of the wastewater pollutants with carbon materials.

Comparison of clinical characteristics and outcomes between alcohol-induced and gallstone-induced acute pancreatitis: An Australian retrospective observational study.

OBJECTIVES: To compare the characteristics and outcomes of patients presenting to hospital with alcohol-induced and gallstone-induced acute pancreatitis. METHODS: Retrospective study of all patients with alcohol-induced or gallstone-induced pancreatitis during the period 1 June 2012 to 31 May 2016. The primary outcome measure was hospital mortality. Secondary outcome measures included hospital length of stay, requirements for intensive care unit admission, intensive care unit mortality, mechanical ventilation, renal replacement therapy, requirement of inotropes and total parenteral nutrition. RESULTS: A total of 642 consecutive patients (49% alcohol; 51% gallstone) were included. No statistically significant differences were found between alcohol-induced and gallstone-induced acute pancreatitis with respect to hospital mortality, requirement for intensive care unit admission, intensive care unit mortality and requirement for mechanical ventilation, renal replacement therapy, inotropes or total parenteral nutrition. There was significant difference in hospital length of stay (3.07 versus 4.84; p < 0.0001). On multivariable regression analysis, Bedside Index of Severity in Acute Pancreatitis score (estimate: 0.393; standard error: 0.058; p < 0.0001) and admission haematocrit (estimate: 0.025; standard error: 0.008; p = 0.002) were found to be independently associated with prolonged hospital length of stay. CONCLUSION: Hospital mortality did not differ between patients with alcohol-induced and gallstone-induced acute pancreatitis. The duration of hospital stay was longer with gallstone-induced pancreatitis. Bedside Index of Severity in Acute Pancreatitis score and admission haematocrit were independently associated with hospital length of stay.