Persistent transcriptional changes in cardiac adaptive immune cells following myocardial infarction: New evidence from the re-analysis of publicly available single cell and nuclei RNA-sequencing data sets.

INTRODUCTION: Chronic immunopathology contributes to the development of heart failure after a myocardial infarction. Both T and B cells of the adaptive immune system are present in the myocardium and have been suggested to be involved in post-MI immunopathology. METHODS: We analyzed the B and T cell populations isolated from previously published single cell RNA-sequencing data sets (PMID: 32130914, PMID: 35948637, PMID: 32971526 and PMID: 35926050), of the mouse and human heart, using differential expression analysis, functional enrichment analysis, gene regulatory inferences, and integration with autoimmune and cardiovascular GWAS. RESULTS: Already at baseline, mature effector B and T cells are present in the human and mouse heart, having increased activity in transcription factors maintaining tolerance (e.g. DEAF1, JDP2, SPI-B). Following MI, T cells upregulate pro-inflammatory transcript levels (e.g. Cd11, Gzmk, Prf1), while B cells upregulate activation markers (e.g. Il6, Il1rn, Ccl6) and collagen (e.g. Col5a2, Col4a1, Col1a2). Importantly, pro-inflammatory and fibrotic transcription factors (e.g. NFKB1, CREM, REL) remain active in T cells, while B cells maintain elevated activity in transcription factors related to immunoglobulin production (e.g. ERG, REL) in both mouse and human post-MI hearts. Notably, genes differentially expressed in post-MI T and B cells are associated with cardiovascular and autoimmune disease. CONCLUSION: These findings highlight the varied and time-dependent dynamic roles of post-MI T and B cells. They appear ready-to-go and are activated immediately after MI, thus participate in the acute wound healing response. However, they subsequently remain in a state of pro-inflammatory activation contributing to persistent immunopathology.

PPMS: A framework to Profile Primary MicroRNAs from Single-cell RNA-sequencing datasets.

MOTIVATION: Single-cell/nuclei RNA-sequencing (scRNA-seq) technologies can simultaneously quantify gene expression in thousands of cells across the genome. However, the majority of the noncoding RNAs, such as microRNAs (miRNAs), cannot currently be profiled at the same scale. MiRNAs are a class of small noncoding RNAs and play an important role in gene regulation. MiRNAs originate from the processing of primary transcripts, known as primary-microRNAs (pri-miRNAs). The pri-miRNA transcripts, independent of their cognate miRNAs, can also function as long noncoding RNAs, code for micropeptides or even interact with DNA, acting like enhancers. Therefore, it is apparent that the significance of scRNA-seq pri-miRNA profiling expands beyond using pri-miRNA as proxies of mature miRNAs. However, there are no computational methods that allow profiling and quantification of pri-miRNAs at the single-cell-type resolution. RESULTS: We have developed a simple yet effective computational framework to profile pri-MiRNAs from single-cell RNA-sequencing datasets (PPMS). Based on user input, PPMS can profile pri-miRNAs at cell-type resolution. PPMS can be applied to both newly produced and publicly available datasets obtained via single cell or single-nuclei RNA-seq. It allows users to (i) investigate the distribution of pri-miRNAs across cell types and cell states and (ii) establish a relationship between the number of cells/reads sequenced and the detection of pri-miRNAs. Here, to demonstrate its efficacy, we have applied PPMS to publicly available scRNA-seq data generated from (i) individual chambers (ventricles and atria) of the human heart, (ii) human pluripotent stem cells during their differentiation into cardiomyocytes (the heart beating cells) and (iii) hiPSCs-derived cardiomyocytes infected with severe acute respiratory syndrome coronavirus 2.

Exploring Hopf-bifurcations and endemic bubbles in a tuberculosis model with behavioral changes and treatment saturation.

To manage risks and minimize the transmission of contagious diseases, individuals may reduce their contact with each other and take other precautions as much as possible in their daily lives and workplaces. As a result, the transmission of the infection reduces due to the behavioral changes. These behavioral changes are incorporated into models by introducing saturation in disease incidence. In this article, we propose and analyze a tuberculosis model that incorporates saturated exogenous reinfection and treatment. The stability analysis of the model's steady states is rigorously examined. We observe that the disease-free equilibrium point and the endemic equilibrium point (EEP) are globally asymptotically stable if the basic reproduction number (R0) is less than 1 and greater than 1, respectively, only when exogenous reinfection is not present (p=0) and when treatment is available for all (ω=0). However, even when R0 is less than 1, tuberculosis may persist at a specific level in the presence of exogenous reinfection and treatment saturation, leading to a backward bifurcation in the system. The existence and direction of Hopf-bifurcations are also discussed. Furthermore, we numerically validate our analytical results using different parameter sets. In the numerical examples, we study Hopf-bifurcations for parameters such as ß, p, α, and ω. In one example, we observe that increasing ß leads to the loss of stability of the unique EEP through a forward Hopf-bifurcation. If ß is further increased, the unique EEP restores its stability, and the bifurcation diagram exhibits an interesting structure known as an endemic bubble. The existence of an endemic bubble for the saturation constant ω is also observed.

Crop type discrimination using Geo-Stat Endmember Extraction and machine learning algorithms.

The identification of crop diversity in today's world is very crucial to ensure adaptation of the crop with changing climate for better productivity as well as food security. Towards this, Hyperspectral Remote Sensing (HRS) is an efficient technique based on imaging spectroscopy that offers the opportunity to discriminate crop types based on morphological as well as physiological features due to availability of contiguous spectral bands. The current work utilized the benefits of Airborne Visible Infrared Imaging spectrometer- New Generation (AVIRIS-NG) data and explored the techniques for classification and identification of crop types. The endmembers were identified using the Geo-Stat Endmember Extraction (GSEE) algorithm for pure pixels identification and to generate the spectral library of the different crop types. Spectral feature comparison was done among AVIRIS-NG, Analytical Spectral Device (ASD)-Spectroradiometer and Continuum Removed (CR) spectra. The best-fit spectra obtained with the Reference ASD-Spectroradiometer and Pure Pixel spectral library were then used for crop discrimination using the ten supervised classifiers namely Spectral Angle Mapper (SAM), Spectral Information Divergence (SID), Support Vector Machine (SVM), Minimum Distance Classifier (MDC), Binary Encoding, deep learning-based Convolution Neural Network (CNN) and different algorithms of Ensemble learning such as Tree Bag, AdaBoost (Adaptive Boosting), Discriminant and RUSBoost (Random Under Sampling). In total, nine crop types were identified, namely, wheat, maize, tobacco, sorghum, linseed, castor, pigeon pea, fennel and chickpea. The performance evaluation of the classifiers was made using various metrics like Overall Accuracy, Kappa Coefficient, Precision, Recall and F1 score. The classifier 2D-CNN was found to be the best with Overall Accuracy, Kappa Coefficient, Precision, Recall and F1 score values of 89.065 %, 0.871,87.565%, 89.541% and 88.678% respectively. The output of this work can be utilized for large scale mapping of crop types at the species level in a short interval of time of a large area with high accuracy.

Integration of epigenetic regulatory mechanisms in heart failure.

The number of "omics" approaches is continuously growing. Among others, epigenetics has appeared as an attractive area of investigation by the cardiovascular research community, notably considering its association with disease development. Complex diseases such as cardiovascular diseases have to be tackled using methods integrating different omics levels, so called "multi-omics" approaches. These approaches combine and co-analyze different levels of disease regulation. In this review, we present and discuss the role of epigenetic mechanisms in regulating gene expression and provide an integrated view of how these mechanisms are interlinked and regulate the development of cardiac disease, with a particular attention to heart failure. We focus on DNA, histone, and RNA modifications, and discuss the current methods and tools used for data integration and analysis. Enhancing the knowledge of these regulatory mechanisms may lead to novel therapeutic approaches and biomarkers for precision healthcare and improved clinical outcomes.

HCG18, LEF1AS1 and lncCEACAM21 as biomarkers of disease severity in the peripheral blood mononuclear cells of COVID-19 patients.

BACKGROUND: Even after 3 years from SARS-CoV-2 identification, COVID-19 is still a persistent and dangerous global infectious disease. Significant improvements in our understanding of the disease pathophysiology have now been achieved. Nonetheless, reliable and accurate biomarkers for the early stratification of COVID-19 severity are still lacking. Long noncoding RNAs (LncRNAs) are ncRNAs longer than 200 nucleotides, regulating the transcription and translation of protein-coding genes and they can be found in the peripheral blood, thus holding a promising biomarker potential. Specifically, peripheral blood mononuclear cells (PBMCs) have emerged as a source of indirect biomarkers mirroring the conditions of tissues: they include monocytes, B and T lymphocytes, and natural killer T cells (NKT), being highly informative for immune-related events. METHODS: We profiled by RNA-Sequencing a panel of 2906 lncRNAs to investigate their modulation in PBMCs of a pilot group of COVID-19 patients, followed by qPCR validation in 111 hospitalized COVID-19 patients. RESULTS: The levels of four lncRNAs were found to be decreased in association with COVID-19 mortality and disease severity: HLA Complex Group 18-242 and -244 (HCG18-242 and HCG18-244), Lymphoid Enhancer Binding Factor 1-antisense 1 (LEF1-AS1) and lncCEACAM21 (i.e. ENST00000601116.5, a lncRNA in the CEACAM21 locus). Interestingly, these deregulations were confirmed in an independent patient group of hospitalized patients and by the re-analysis of publicly available single-cell transcriptome datasets. The identified lncRNAs were expressed in all of the PBMC cell types and inversely correlated with the neutrophil/lymphocyte ratio (NLR), an inflammatory marker. In vitro, the expression of LEF1-AS1 and lncCEACAM21 was decreased upon THP-1 monocytes exposure to a relevant stimulus, hypoxia. CONCLUSION: The identified COVID-19-lncRNAs are proposed as potential innovative biomarkers of COVID-19 severity and mortality.

Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability.

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. We assessed the effect of gestational VPA on foetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses that are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied-inbred Genetic Absence Epilepsy Rats from Strasbourg, a model of genetic generalized epilepsy, and inbred non-epileptic control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Foetuses were extracted via C-section on gestational Day 21 (1 day prior to birth) and foetal brains were snap-frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes downregulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic foetal VPA exposure and neurodevelopmental disability mediated by VPA-induced transcriptional dysregulation.

Seeing from space makes sense: Novel earth observation variables accurately map species distributions over Himalaya.

Topical advances in earth observation have enabled spatially explicit mapping of species' fundamental niche limits that can be used for nature conservation and management applications. This study investigates the possibility of applying functional variables of ecosystem retrieved from Moderate Resolution Imaging Spectroradiometer (MODIS) onboard sensor data to map the species distribution of two alpine treeline species, namely Betula utilis D.Don and Rhododendron campanulatum D.Don over the Himalayan biodiversity hotspot. In this study, we have developed forty-nine Novel Earth Observation Variables (NEOVs) from MODIS products, an asset to the present investigation. To determine the effectiveness and ecological significance of NEOVs combinations, we built and compared four different models, namely, a bioclimatic model (BCM) with bioclimatic predictor variables, a phenology model (PhenoM) with earth observation derived phenological predictor variables, a biophysical model (BiophyM) with earth observation derived biophysical predictor variables, and a hybrid model (HM) with a combination of selected predictor variables from BCM, PhenoM, and BiophyM. All models utilized topographical variables by default. Models that include NEOVs were competitive for focal species, and models without NEOVs had considerably poor model performance and explanatory strength. To ascertain the accurate predictions, we assessed the congruence of predictions by pairwise comparisons of their performance. Among the three machine learning algorithms tested (artificial neural networks, generalised boosting model, and maximum entropy), maximum entropy produced the most promising predictions for BCM, PhenoM, BiophyM, and HM. Area under curve (AUC) and true skill statistic (TSS) scores for the BCM, PhenoM, BiophyM, and HM models derived from maximum entropy were AUC ≥0.9 and TSS ≥0.6 for the focal species. The overall investigation revealed the competency of NEOVs in the accurate prediction of species' fundamental niches, but conventional bioclimatic variables were unable to achieve such a level of precision. A principal component analysis of environmental spaces disclosed that niches of focal species substantially overlapped each other. We demonstrate that the use of satellite onboard sensors' biotic and abiotic variables with species occurrence data can provide precision and resolution for species distribution mapping at a scale that is relevant ecologically and at the operational scale of most conservation and management actions.

Quantifying the landscape changes within and outside the Dachigam National Park, Kashmir Himalaya, India using observations and models.

Protected areas are the cornerstone of biodiversity and serve as a haven for biodiversity conservation. However, due to immense anthropic pressures and ongoing changes in climate, the protected reserves are under immense threat. Human interference through land system changes is a major precusor of fragmentation of landscapes resulting in the decline of Himalayan biodiversity. In this context, this research assessed land use land cover changes (LULCCs) and fragmentation within and outside the Dachigam National Park (DNP) using remote sensing data, GIS-based models and ground truth over the past 55 years (1965-2020). Landscape Fragmentation Tool (LFT) helped to compute edge effect, patchiness, perforation and core areas. The Land Change Modeller (LCM) of IDRISI TerrSet was used for simulating the future LULC for the years 2030, 2050, 2700 and 2100. The analysis of LULCCs showed that built-up and aquatic vegetation expanded by 326% and 174%, respectively in the vicinity of the DNP. The area under agriculture, scrub and pasture decreased primarily due to intensified land use activities. Within the DNP, the area under forest cover declined by 7%. A substantial decrease was observed in the core zone both within (39%) and outside (30%) the DNP indicative of fragmentation of natural habitats. LCM analysis projected 10% increase in the built-up extents besides forests, shrublands and pastures. This knowledge generated in this study shall form an important baseline for understanding and characterising the human-wildlife relationship, initiating long-term ecological research (LTER) on naturally vegetated and aquatic ecosystems (primarily Dal Lake) of the region.

Nitrogen dioxide as proxy indicator of air pollution from fossil fuel burning in New Delhi during lockdown phases of COVID-19 pandemic period: impact on weather as revealed by Sentinel-5 precursor (5p) spectrometer sensor.

There has been a long-lasting impact of the lockdown imposed due to COVID-19 on several fronts. One such front is climate which has seen several implications. The consequences of climate change owing to this lockdown need to be explored taking into consideration various climatic indicators. Further impact on a local and global level would help the policymakers in drafting effective rules for handling challenges of climate change. For in-depth understanding, a temporal study is being conducted in a phased manner in the New Delhi region taking NO2 concentration and utilizing statistical methods to elaborate the quality of air during the lockdown and compared with a pre-lockdown period. In situ mean values of the NO2 concentration were taken for four different dates, viz. 4th February, 4th March, 4th April, and 25th April 2020. These concentrations were then compared with the Sentinel (5p) data across 36 locations in New Delhi which are found to be promising. The results indicated that the air quality has been improved maximum in Eastern Delhi and the NO2 concentrations were reduced by one-fourth than the pre-lockdown period, and thus, reduced activities due to lockdown have had a significant impact. The result also indicates the preciseness of Sentinel (5p) for NO2 concentrations.

Nano-cryospray: An adjuvant assisted approach to increase the efficacy of cryospray.

The present study proposes a novel approach to treat skin cancer. It is an amalgamation of two techniques; (i) Cryospray in which necrosis is achieved through local application of liquid nitrogen spray on lesions (occurring on superficial skin) and (ii) Transdermal Drug Delivery systems (TDDS) in which drugs are administered through the superficial skin. It focuses on increasing the cryoablation through the administration of nanoparticles in the skin. Biodegradable Magnesium Oxide (MgO) nanoparticles are selected to make nano-phantom. TEM and XRD results reveal the crystalline nature of MgO nanoparticle with particle diameter 10-40 nm. A comparative study of cryoablation is carried out between the nano-phantom and the normal-phantom while spraying liquid nitrogen through a commercial 0.8 mm diameter single hole nozzle. Quantitative and qualitative improvements in cryoablation are observed due to the presence of nanoparticle. Necrotic zone in nano-phantom is twice larger than in the normal-phantom up to an axial depth of 2 mm from the centre of spray for the same spraying distance. Minimum spraying distance for nano-phantom is estimated to be 13 mm. Among the three spraying distances selected for the study, it has been observed that cryoablation decreases as the spraying distance increases. The proposed approach can be used to enhance the scope of cryospray in the treatment of larger lesions like Squamous cell carcinoma, keloids etc. without incorporating the device modifications.

Synergistic Evaluation of Passive Microwave and Optical/IR Data for Modelling Vegetation Transmissivity towards Improved Soil Moisture Retrieval.

Vegetation cover and soil surface roughness are vital parameters in the soil moisture retrieval algorithms. Due to the high sensitivity of passive microwave and optical observations to Vegetation Water Content (VWC), this study assesses the integration of these two types of data to approximate the effect of vegetation on passive microwave Brightness Temperature (BT) to obtain the vegetation transmissivity parameter. For this purpose, a newly introduced index named Passive microwave and Optical Vegetation Index (POVI) was developed to improve the representativeness of VWC and converted into vegetation transmissivity through linear and nonlinear modelling approaches. The modified vegetation transmissivity is then applied in the Simultaneous Land Parameters Retrieval Model (SLPRM), which is an error minimization method for better retrieval of BT. Afterwards, the Volumetric Soil Moisture (VSM), Land Surface Temperature (LST) as well as canopy temperature (TC) were retrieved through this method in a central region of Iran (300 × 130 km2) from November 2015 to August 2016. The algorithm validation returned promising results, with a 20% improvement in soil moisture retrieval.

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.

Impact of extreme weather events on cropland inundation over Indian subcontinent.

Cyclonic storms and extreme precipitation lead to loss of lives and significant damage to land and property, crop productivity, etc. The "Gulab" cyclonic storm formed on the 24th of September 2021 in the Bay of Bengal (BoB), hit the eastern Indian coasts on the 26th of September and caused massive damage and water inundation. This study used Integrated Multi-satellite Retrievals for GPM (IMERG) satellite precipitation data for daily to monthly scale assessments focusing on the "Gulab" cyclonic event. The Otsu's thresholding approach was applied to Sentinel-1 data to map water inundation. Standardized Precipitation Index (SPI) was employed to analyze the precipitation deviation compared to the 20 years mean climatology across India from June to November 2021 on a monthly scale. The water-inundated areas were overlaid on a recent publicly available high-resolution land use land cover (LULC) map to demarcate crop area damage in four eastern Indian states such as Andhra Pradesh, Chhattisgarh, Odisha, and Telangana. The maximum water inundation and crop area damages were observed in Andhra Pradesh (~2700 km2), followed by Telangana (~2040 km2) and Odisha (~1132 km2), and the least in Chhattisgarh (~93.75 km2). This study has potential implications for an emergency response to extreme weather events, such as cyclones, extreme precipitation, and flood. The spatio-temporal data layers and rapid assessment methodology can be helpful to various users such as disaster management authorities, mitigation and response teams, and crop insurance scheme development. The relevant satellite data, products, and cloud-computing facility could operationalize systematic disaster monitoring under the rising threats of extreme weather events in the coming years.

Cross-platform transcriptional profiling identifies common and distinct molecular pathologies in Lewy body diseases.

Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms underlying PDD and DLB remain largely unknown, a knowledge gap that presents an impediment to the discovery of disease-modifying therapies. Transcriptomic profiling can contribute to addressing this gap, but remains limited in the LBDs. Here, we applied paired bulk-tissue and single-nucleus RNA-sequencing to anterior cingulate cortex samples derived from 28 individuals, including healthy controls, PD, PDD and DLB cases (n = 7 per group), to transcriptomically profile the LBDs. Using this approach, we (i) found transcriptional alterations in multiple cell types across the LBDs; (ii) discovered evidence for widespread dysregulation of RNA splicing, particularly in PDD and DLB; (iii) identified potential splicing factors, with links to other dementia-related neurodegenerative diseases, coordinating this dysregulation; and (iv) identified transcriptomic commonalities and distinctions between the LBDs that inform understanding of the relationships between these three clinical disorders. Together, these findings have important implications for the design of RNA-targeted therapies for these diseases and highlight a potential molecular "window" of therapeutic opportunity between the initial onset of PD and subsequent development of Lewy body dementia.

Optimizing the spray parameters of a cryospray process.

Smaller spray zone of single-hole nozzle (SHN) constrains cryospray as a treatment method suitable for lesions having diameter larger than 15 mm on the skin surface. The present study is an attempt to resolve this issue, through the improvement in conventional technique of spraying liquid nitrogen on cancerous lesion. A multi-hole nozzle (MHN) with 5 holes is fabricated to demarcate the variation in outcome when cryogen is sprayed through customised MHN instead of conventional SHN. Special emphasis is placed on reducing the number of sitting required for completion of treatment and increasing the feasibility of cryospray process for larger lesions. Commercial SHN having a hole diameter of 0.8 mm is selected to compare results with the customised MHN having 5 holes of 0.8 mm diameter (4 holes are arranged in a circle of radius 2 mm around the central hole). Single freeze-thaw cycle is carried out to spray liquid nitrogen on tissue mimicking gel. Temperature profile accessed through infrared images advocates that lethal area formed through application of MHN is twice larger than the lethal area formed through the application of SHN on the surface of gel for same spraying distance (z). Thermocouples placed at various locations strengthen the fact that higher cooling rate (CR) corresponding to MHN ensures 15 mm spread of necrotic zone from the centre of spray (CS) and up to a depth of 2 mm from the gel surface while in case of SHN, it is limited to the vicinity of CS. On the basis of observations made through thermal images and digital images, it can be said that the ratio of lateral spread to penetration depth of ice ball remains almost same for SHN and MHN. However, the lateral spread of ice ball formed through the application of MHN is twice larger than SHN while the axial depth of ice ball does not record such increment. This reflects that MHN provides more destruction to superficial skin than SHN. Among the three spraying distances selected (i.e. z = 13 mm, 18 mm and 23 mm), the most optimised spraying distance (z) for MHN is also explored in this study. It has been found that cryoablation is not inversely proportional to the spraying distance. Spraying distance of z = 18 mm provided the most optimised result in terms of cryoablation.

Nonlinear dynamical behavior of an SEIR mathematical model: Effect of information and saturated treatment.

When a disease spreads in a population, individuals tend to change their behavior due to the presence of information about disease prevalence. Therefore, the infection rate is affected and incidence term in the model should be appropriately modified. In addition, a limitation of medical resources has its impact on the dynamics of the disease. In this work, we propose and analyze an Susceptible-Exposed-Infected-Recovered (SEIR) model, which accounts for the information-induced non-monotonic incidence function and saturated treatment function. The model analysis is carried out, and it is found that when R0 is below one, the disease may or may not die out due to the saturated treatment (i.e., a backward bifurcation may exist and cause multi-stability). Further, we note that in this case, disease eradication is possible if medical resources are available for all. When R0 exceeds one, there is a possibility of the existence of multiple endemic equilibria. These multiple equilibria give rise to rich and complex dynamics by showing various bifurcations and oscillations (via Hopf bifurcation). A global asymptotic stability of a unique endemic equilibrium (when it exists) is established under certain conditions. An impact of information is shown and also a sensitivity analysis of model parameters is performed. Various cases are considered numerically to provide the insight of model behavior mathematically and epidemiologically. We found that the model shows hysteresis. Our study underlines that a limitation of medical resources may cause bi(multi)-stability in the model system. Also, information plays a significant role and gives rise to a rich and complex dynamical behavior of the model.

Denoising AVIRIS-NG Data for Generation of New Chlorophyll Indices.

The availability of Airborne Visible and Infrared Imaging Spectrometer-Next Generation (AVIRIS-NG) data has enormous possibilities for quantification of Leaf Chlorophyll Content (LCC). The present study used the AVIRIS-NG campaign site of Western India for generation and validation of new chlorophyll indices by denoising the AVIRIS-NG data. For validation, concurrent to AVIRIS-NG flight overpass, field samplings were performed. The acquired AVIRIS-NG was subjected to Spectral Angle Mapper (SAM) classifier for discriminating the crop types. Three smoothing techniques i.e., Fast-Fourier Transform (FFT), Mean and Savitzky-Golay filters were evaluated for their denoising capability. Raw and filtered data was used for developing new chlorophyll indices by optimizing AVIRIS-NG bands using VIs based on parametric regression algorithms. In total, 20 chlorophyll indices and corresponding 20 models were developed for mapping LCC in the area. SAM identified 17 crop types in the area, while FFT found to be the best for filtering. Performance of these models when checked based on Pearson correlation coefficient (r) and Centered Root Mean Square Difference (CRMSD), indicated that LCC-CCI10 based on normalized difference type index formed through Near Infrared band and blue band is the best estimator of LCC (rcal = 0.73, rval = 0.66, CRMSD = 4.97). The approach was also tested using AVIRIS-NG image of the year 2018, which also showed a promising correlation (r = 0.704, CRSMD = 8.98, Bias = -0.5) between modeled and field LCC.

The Influence of a Changing Local Environment during Photoinduced CO2 Dissociation.

Though largely influencing the efficiency of a reaction, the molecular-scale details of the local environment of the reactants are experimentally inaccessible hindering an in-depth understanding of a catalyst's reactivity, a prerequisite to maximizing its efficiency. We introduce a method to follow individual molecules and their largely changing environment during a photochemical reaction. The method is illustrated for a rate-limiting step in a photolytic reaction, the dissociation of CO2 on two catalytically relevant surfaces, Ag(100) and Cu(111). We reveal with a single-molecule resolution how the reactant's surroundings evolve with progressing laser illumination and with it their propensity for dissociation. Counteracting processes lead to a volcano-like reactivity. Our unprecedented local view during a photoinduced reaction opens the avenue for understanding the influence of the products on reaction yields on the nanoscale.

Proof-of-concept that network pharmacology is effective to modify development of acquired temporal lobe epilepsy.

Epilepsy is a complex network phenomenon that, as yet, cannot be prevented or cured. We recently proposed network-based approaches to prevent epileptogenesis. For proof of concept we combined two drugs (levetiracetam and topiramate) for which in silico analysis of drug-protein interaction networks indicated a synergistic effect on a large functional network of epilepsy-relevant proteins. Using the intrahippocampal kainate mouse model of temporal lobe epilepsy, the drug combination was administered during the latent period before onset of spontaneous recurrent seizures (SRS). When SRS were periodically recorded by video-EEG monitoring after termination of treatment, a significant decrease in incidence and frequency of SRS was determined, indicating antiepileptogenic efficacy. Such efficacy was not observed following single drug treatment. Furthermore, a combination of levetiracetam and phenobarbital, for which in silico analysis of drug-protein interaction networks did not indicate any significant drug-drug interaction, was not effective to modify development of epilepsy. Surprisingly, the promising antiepileptogenic effect of the levetiracetam/topiramate combination was obtained in the absence of any significant neuroprotective or anti-inflammatory effects as indicated by multimodal brain imaging and histopathology. High throughput RNA-sequencing (RNA-seq) of the ipsilateral hippocampus of mice treated with the levetiracetam/topiramate combination showed that several genes that have been linked previously to epileptogenesis, were significantly differentially expressed, providing interesting entry points for future mechanistic studies. Overall, we have discovered a novel combination treatment with promise for prevention of epilepsy.