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Current approaches for points-of-interest (POI) recommendation learn the preferences of a user via the standard spatial features such as the POI coordinates, the social network, etc. These models ignore a crucial aspect of spatial mobility -- every user carries their smartphones wherever they go. In addition, with growing privacy concerns, users refrain from sharing their exact geographical coordinates and their social media activity. In this paper, we present REVAMP, a sequential POI recommendation approach that utilizes the user activity on smartphone applications (or apps) to identify their mobility preferences. This work aligns with the recent psychological studies of online urban users, which show that their spatial mobility behavior is largely influenced by the activity of their smartphone apps. In addition, our proposal of coarse-grained smartphone data refers to data logs collected in a privacy-conscious manner, i.e., consisting only of (a) category of the smartphone app and (b) category of check-in location. Thus, REVAMP is not privy to precise geo-coordinates, social networks, or the specific application being accessed. Buoyed by the efficacy of self-attention models, we learn the POI preferences of a user using two forms of positional encodings -- absolute and relative -- with each extracted from the inter-check-in dynamics in the check-in sequence of a user. Extensive experiments across two large-scale datasets from China show the predictive prowess of REVAMP and its ability to predict app- and POI categories., Comment: IEEE Transactions on Big Data

The present paper investigated the electrochemical behaviour of Schiff base and its zinc complex at a working electrode by cyclic voltammetry technique. In the phosphate and Britton-Robinson buffers, the electrochemical study of Schiff base was performed within various pH values 5-9. Cyclic voltammograms of the examined Schiff base exhibited irreversible and diffusion controlled waves at different sweep rates, which is associated with the two electron reduction process of azomethine group. The symmetry transfer coefficient (αn), the diffusion coefficient (D01/2) and rate constant (k°f,h) of the reactant species were calculated. Cyclic voltammetric study of zinc complex showed one electron diffusion controlled, quasi-reversible peaks at 50-250 mV/s sweep rates. Antimicrobial study of zinc complex showed that zinc complex found to be more potent than uncoordinated Schiff base.

Dysregulation of lipid metabolism is associated with cardiovascular/metabolic diseases, including atherosclerosis, liver diseases and type 2 diabetes mellitus (T2DM). Several miRNAs have been reported as regulators of different stages of lipid homeostasis, including cholesterol/fatty acid biosynthesis, degradation, transport, storage, and low-density (LDL) and high-density lipoprotein (HDL) formation. Indeed, various miRNAs are emerging as attractive therapeutic candidates for metabolic/cardiovascular disease (CVD). Here, we summarize the roles of miR-19b, miR-20a, miR-21, miR-27, miR-29, miR-34a, miR-144, miR-148a, and miR-199a in post-transcriptional regulation of genes involved in lipid homeostasis and their therapeutic potential. We also discuss experimental strategies for further development of these miRNAs as novel cardiometabolic therapeutics.

Though chlorine is a cost-effective disinfectant for water and wastewaters, the bacteria surviving after chlorination pose serious public health and environmental problems. This review critically assesses the mechanism of chlorine disinfection as described by various researchers; factors affecting chlorination efficacy; and the re-growth potential of microbial contaminations in treated wastewater post chlorination to arrive at meaningful doses for ensuring health safety. Literature analysis shows procedural inconsistencies in the assessment of chlorine tolerant bacteria, making it extremely difficult to compare the tolerance characteristics of different reported tolerant bacteria. A comparison of logarithmic reduction after chlorination and the concentration-time values for prominent pathogens led to the generation of a standard protocol for the assessment of chlorine tolerance. The factors that need to be critically monitored include applied chlorine doses, contact time, determination of chlorine demands of the medium, and the consideration of bacterial counts immediately after chlorination and in post chlorinated samples (regrowth). The protocol devised here appropriately assesses the chlorine-tolerant bacteria and urges the scientific community to report the regrowth characteristics as well. This would increase the confidence in data interpretation that can provide a better understanding of chlorine tolerance in bacteria and aid in formulating strategies for effective chlorination.

3-Hydroxy-3-methyl glutaryl-coenzyme A reductase (Hmgcr) encodes the rate-limiting enzyme in the cholesterol biosynthesis pathway. The regulation of Hmgcr in rat models of genetic hypertension (viz. Spontaneously Hypertensive Rat [SHR] and its normotensive control Wistar/Kyoto [WKY] strain) is unclear. Interestingly, Hmgcr transcript and protein levels are diminished in liver tissues of SHR as compared to WKY. This observation is consistent with the diminished plasma cholesterol level in SHR animals. However, the molecular basis of these apparently counter-intuitive findings remains completely unknown. Sequencing of the Hmgcr promoter in SHR and WKY strains reveals three variations: A-405G, C-62T and a 11 bp insertion (‐398_-388insTGCGGTCCTCC) in SHR. Among these variations, A-405G occurs at an evolutionarily-conserved site among many mammals. Moreover, SHR-Hmgcr promoter displays lower activity than WKY-Hmgcr promoter in various cell lines. Transient transfections of Hmgcr-promoter mutants and in silico analysis suggest altered binding of Runx3 and Srebf1 across A-405G site. On the other hand, C-62T and -398_-388insTGCGGTCCTCC variations do not appear to contribute to the reduced Hmgcr promoter activity in SHR as compared to WKY. Indeed, chromatin immunoprecipitation assays confirm differential binding of Runx3 and Srebf1 to Hmgcr promoter leading to reduced expression of Hmgcr in SHR as compared to WKY under basal as well as cholesterol-modulated conditions. Taken together, this study provides, for the first time, molecular basis for diminished Hmgcr expression in SHR animals, which may account for the reduced circulating cholesterol level in this widely-studied model for cardiovascular diseases.

Laser printers and writing instruments are being exploited by the forgers to produce fabricated documents. They often produce such documents by appending genuine signature on a blank sheet and later printing on it. Often these fabricated documents do not contain intersection of strokes and may pose a difficulty to forensic document examiners in analyzing cases related to such documents. Keeping in mind the limited research work done on nonintersecting strokes, the present study has been conducted with an aim to determine the sequence of nonintersecting strokes of gel pens and laser printers. Three hundred samples of nonintersecting strokes of gel pen ink and laser printing were prepared. Of these 300, 150 had laser-printed text below the gel pen strokes and the remaining 150 were prepared with gel pen stokes below the laser-printed text. The samples have been analyzed using Nikon SMZ 800N stereomicroscope. Three micro-conformation features, that is, pattern of toner distribution, ink distribution, and fiber distribution have been observed in the samples. The results demonstrate the successful establishment of sequence of nonintersecting strokes in case of gel pen and laser-printed documents by the determination of micro-conformation features.

Background: Ets transcription factors function as important developmental regulators and are known to be modulators of cell fate. Previously, in conjunction with co-factors, we have described Ets variant 2 (Etv2) as an essential regulator of the hematopoietic and endothelial lineages. But the mechanism and the Etv2 interacting partners involved in achieving this critical function remains poorly understood. Results: Using a yeast two-hybrid assay, we identified Vascular Endothelial Zinc Finger 1 (Vezf1) as an interacting factor with Etv2. Vezf1 is a conserved C2H2 zinc finger transcription factor known to regulate the formation, proliferation, and migration of endothelial cells. We verified Vezf1 as a binding partner of Etv2 through co-immunoprecipitation and GST-pull down studies. Bioinformatics analysis of ChIP-seq and Etv2-expressing single cell RNA sequencing was conducted to identify candidate genes containing both Etv2 and Vezf1 binding motifs in their regulatory regions. Histone deacetylase 7 (Hdac7) and angiomotin like protein 2 (Amotl2) were identified as candidate genes and have previously been shown to function as regulators of endothelial development. RT-qPCR analysis showed upregulation of Hdac7 and Amotl2 in response to doxycycline inducible Etv2 and Vezf1; whereas significant reduction of expression of these two genes was observed in the Etv2 and Vezf1 knockout cells. Chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assays (EMSA) confirmed Etv2-Vezf1 adjacent binding sites in the promoters of Hdac7 and Amotl2. Histone Acetyl transferase (HAT) assays was performed to investigate Etv2-Vezf1 on global histone acetylation conditions in doxycycline inducible embryoid bodies. Vezf1 overexpression results in a significant reduction of acetylated histones. Additionally, we have undertaken ATAC-Seq (Assay for Transposase-Accessible Chromatin using sequencing) and Vezf1 ChIP-Seq studies to profile the epigenetic modifications and genome-wide occupancy of Vezf1 in the presence or absence of Etv2 in endothelial progenitor cells. Conclusion: In summary, this study identifies Vezf1 as a novel binding partner of Etv2 and we further demonstrate their combined role in the regulation of downstream target genes, Amotl2 and Hdac7, during endothelial development.

Skin diseases have become prevalent in the present times. It has been observed in a study that every year the percentage of global population suffering from skin diseases is 1.79%. These diseases have a potential to become extremely dangerous if they are not treated in the nascent stages. It is extremely important that skin diseases are detected and diagnosed at the starting stages so that serious risks to life are avoided. Often, exhaustive tests are required so as to arrive on a conclusion regarding skin condition, the patient may be affected with. Thus, an expert system is required that has the ability to identify diseases and propose the required diagnosis. Presently, only a few solutions are available for diagnosis of skin diseases using computerized system but this is an era which is under extensive research and can be developed further. As the existing system has certain loopholes, this system attempts to override the present problems by applying a different approach. As a result of comparison of results from numerous research papers, an expert system has been developed by choosing residual neural networks (ResNet) and this system can be used to aid skin specialists in identifying and diagnosing various major diseases of skin like (Eczema, Psoriasis & Lichen Planus, Benign Tumors, Fungal Infections and Viral Infections) in more effective and efficient manner. The causes for identified skin disease can be outlined through this system and treatment can be provided. We have used Python language for implementing the proposed expert system that uses a 50-layer ResNets for training a dataset that has been taken from DERMNET. We achieved an accuracy of 95% using ResNet for training of the model and prediction of results at an epoch value of 10.

Hypercholesterolemia is a strong predictor of cardiovascular diseases. The 3-hydroxy-3-methylglutaryl coenzyme A reductase gene (Hmgcr) coding for the rate-limiting enzyme in the cholesterol biosynthesis pathway is a crucial regulator of plasma cholesterol levels. However, the posttranscriptional regulation of Hmgcr remains poorly understood. The main objective of this study was to explore the role of microRNAs (miRNAs) in the regulation of Hmgcr expression. Systematic in silico predictions and experimental analyses reveal that miRNA 27a (miR-27a) specifically interacts with the Hmgcr 3′ untranslated region in murine and human hepatocytes. Moreover, our data show that Hmgcr expression is inversely correlated with miR-27a levels in various cultured cell lines and in human and rodent tissues. Actinomycin D chase assays and relevant experiments demonstrate that miR-27a regulates Hmgcr by translational attenuation followed by mRNA degradation. Early growth response 1 (Egr1) regulates miR-27a expression under basal and cholesterol-modulated conditions. miR-27a augmentation via tail vein injection of miR-27a mimic in high-cholesterol-diet-fed Apoe(−/−) mice shows downregulation of hepatic Hmgcr and plasma cholesterol levels. Pathway and gene expression analyses show that miR-27a also targets several other genes (apart from Hmgcr) in the cholesterol biosynthesis pathway. Taken together, miR-27a emerges as a key regulator of cholesterol biosynthesis and has therapeutic potential for the clinical management of hypercholesterolemia.

Durability is one of the primary concern in new buildings and also for the old existing infrastructures. This paper deals with the durability properties of concrete containing sandstone slurry as a filler material. A significant quantity of sandstone slurry gets deposited, and their disposal problem becomes acuter. In order to utilize these wastes and to practice a sustainable construction, the ultimate solution is to use these types of sandstone slurry in concrete. Since durability plays an enormous role in maintaining the infrastructure for years, various tests such as compressive strength, flexural strength, water absorption, sulfate attack, acid attack, carbonation, DIN-Permeability, sorptivity are done to get the durability of the sandstone slurry mix in concrete. This paper presents the result of experimental research to examine the suitability of sandstone slurry as a partial replacement of total aggregates in cement concrete. It was observed that up to a certain level of substitution, compressive and flexural strength show a comparable result to that of control concrete. Also, it shows a good result with a controlled replacement towards acid-attack as well as sulfate attack and are equivalent to that of Portland cement concrete. Similar effect were also observed towards carbonation and permeability. From the results, it can be said that there is a promising future for the use of sandstone slurry as a partial replacement of total aggregate, which can lead to more significant environmental and sustainable benefits.

Concrete production has a lot of environmental impacts causing damage to the most fertile layer of the earth. Cement industry often uses unethical methods in obtaining resources by breaking river stones from the most alluring areas of the world for the production of cement concrete. Due to various environmental hazards associated with cement concrete production industries, most of the government re-forces and subsides the use of cement and also encourages to find a sustainable replacement material for the manufacture of cement concrete. Sandstones are a type of sedimentary rock which is composed of silt-sized minerals, rock grains and clay components. Some of the minerals like quartz and feldspar are the most occurred in earth surface and are found in sandstones. Since sandstones are highly porous when compared to magmatic rocks, they allow water to percolate and form aquifers and petroleum reservoirs. Even though sandstones were widely used in historical constructions around the globe, at present the use of such sedimentary rocks are not traditional in the field of building technology. There are many types of sandstones occurring in earth's surface and can be classified based on their elemental composition, clay content and sometimes based on their colour. Also, mining and quarrying generate a lot of these sandstone wastes which leads to excessive dumping without any utilisation. Although sandstones are a weaker type of aggregates that can be used in concrete, some of the studies have utilised them efficiently depending on the output needed for the use of such sedimentary materials. This paper presents the overview on the possible use of sandstones in cement concrete and some of the properties of such concrete in fresh and hardened states. Studies indicate that there is a promising future for the use of some selected sandstones in the production of cement concrete. The summary and information provided in this paper would provide new information and knowledge on the sustainable use of sandstone and its wastes for a greener concrete production.

Ets transcription factors function as important developmental regulators and are known to be modulators of cell fate. Previously, in conjunction with co-factors, we have described Ets variant 2 (Etv2) as an essential regulator of the hematopoietic and endothelial lineages. But the mechanism and the Etv2 interacting partners involved in achieving this critical function remains poorly understood. Through Yeast two-hybrid analysis we identified Vascular Endothelial Zinc Finger 1 (Vezf1) as an interacting factor with Etv2. Vezf1 is a conserved C2H2 zinc finger transcription factor known to regulate the formation, proliferation, and migration of endothelial cells through several gene targets. We verified Vezf1 as a binding partner of Etv2 through co-immunoprecipitation and GST-pull down studies. Bioinformatic analysis of ChIP-seq and Etv2-expressing single cell RNA sequencing was conducted to identify candidate genes containing both Etv2 and Vezf1 binding motifs in their regulatory regions. Histone deacetylase 7 (Hdac7) and angiomotin like protein 2 (Amotl2) were identified as genes of interest involved in endothelial development. Hdac7 is a conserved class II deacetylase that functions in endothelial cell adhesion and vascular integrity. Amotl2 is a Motin family protein that functions in angiogenesis, endothelial cell polarity and migration. RT-qPCR analysis showed upregulation of Hdac7 and Amotl2 in response to doxycycline inducible Etv2 and Vezf1; whereas significant reduction of expression of these two genes was observed in the Etv2 and Vezf1 knockout cells. Chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assays (EMSA) confirmed Etv2-Vezf1 adjacent binding sites in the promoters of Hdac7 and Amotl2. Histone Acetyl transferase (HAT) assays was performed to investigate Etv2-Vezf1 on global histone acetylation conditions in doxycycline inducible embryoid bodies. Vezf1 overexpression results in a significant reduction of acetylated histone. In summary, this study identifies Vezf1 as a novel binding partner of Etv2 and their combined role in regulating downstream target genes Amotl2 and Hdac7 in hematoendothelial development.

3-Hydroxy-3-methyl glutaryl-coenzyme A reductase (Hmgcr) encoding the rate-limiting enzyme in the cholesterol biosynthesis pathway is a candidate gene for essential hypertension (EH). However, the regulation ofHmgcrin rat models of hypertension (viz. Spontaneously Hypertensive Rats [SHR] and its normotensive control Wistar/Kyoto [WKY] strain) is unknown. Here, we show that Hmgcr transcript and protein levels are diminished in liver tissues of SHR as compared to WKY. Consistently, a number of other rat models of hypertension display diminished cholesterol levels as compared to corresponding control strains. Sequencing of theHmgcrpromoter in SHR/WKY reveals three variations: A-405G, C-62T and a 11 bp insertion (-393_-382insTGCGGTCCTCC) in SHR. Moreover, SHR-Hmgcrpromoter displays higher activity than WKY-Hmgcrpromoter in various cell lines. Transient transfections ofHmgcr-promoter mutants andin silicoanalysis suggest altered binding of Runx3 and Srebf1 across A-405G and -393_-382insTGCGGTCCTCC sites. Indeed, chromatin immunoprecipitation assays confirm differential binding of Runx3/Srebf1 toHmgcrpromoter leading to diminished expression ofHmgcrin SHR as compared to WKY under basal/cholesterol-modulated conditions. Taken together, this study provides mechanistic insights for the alteredHmgcrexpression in these models of EH, thereby unravelling the links of this gene to hypertension and associated cardiovascular disease states.

Despite the well-known role of cystathionine γ-lyase (Cth) in cardiovascular pathophysiology, transcriptional regulation of Cth remains incompletely understood. Sequencing of the Cth promoter region in mouse models of genetic/essential hypertension (viz. Blood Pressure High [BPH], Blood Pressure Low [BPL] and Blood Pressure Normal [BPN] mice) identified several genetic variations. Transient transfections of BPH/BPL-Cth promoter-reporter plasmids into various cell types revealed higher promoter activity of BPL-Cth than that of BPH-Cth. Corroboratively, endogenous Cth mRNA levels in kidney and liver tissues were also elevated in BPL mice. Computational analysis of the polymorphic Cth promoter region predicted differential binding affinity of c-Rel, HOXA3 and IRF1 with BPL/BPH-Cth promoter domains. Over-expression of c-Rel/HOXA3/IRF1 modulated BPL/BPH-Cth promoter activities in a consistent manner. Gel shift assays using BPH/BPL-Cth-promoter oligonucleotides with/without binding sites for c-Rel/HOXA3/IRF1 displayed formation of specific complexes with c-Rel/HOXA3/IRF1; addition of antibodies to reaction mixtures resulted in supershifts/inhibition of Cth promoter-transcription factor complexes. Furthermore, chromatin immunoprecipitation (ChIP) assays proved differential binding of c-Rel, HOXA3 and IRF1 with the polymorphic promoter region of BPL/BPH-Cth. Tumor necrosis factor-α (TNF-α) reduced the activities of BPL/BPH-Cth promoters to different extents that were further declined by ectopic expression of IRF1; on the other hand, siRNA-mediated down-regulation of IRF1 rescued the TNF-α-mediated suppression of the BPL/BPH-Cth promoter activities. In corroboration, ChIP analysis revealed enhanced binding of IRF1 with BPH/BPL-Cth promoter following TNF-α treatment. BPL/BPH-Cth promoter activity was diminished upon exposure of hepatocytes and cardiomyoblasts to ischemia-like pathological condition due to reduced binding of c-Rel with BPL/BPH-Cth-promoter. Taken together, this study reveals the molecular basis for the differential expression of Cth in mouse models of essential hypertension under basal and pathophysiological conditions.

The comparative reaction efficiencies of currently used nucleophilic and electrophilic probes towards cysteine sulfenic acid have been thoroughly evaluated in two different settings – (i) a small molecule dipeptide based model and, (ii) a recombinant protein model. We further evaluated the stability of corresponding thioether and sulfoxide adducts under reducing conditions which are commonly encountered during proteomic protocols and in cell analysis. Powered by the development of new cyclic and linear C-nucleophiles, the unsurpassed efficiency in the capture of sulfenic acid under competitive conditions is achieved and thus holds great promise as highly potent tools for activity-based sulfenome profiling.

Monoamine oxidases (MAOs) are flavoenzymes that metabolize biogenic amines, dietary amines, and catecholamines in the brain and peripheral tissues. While MAOs are known to contribute to psychiatric and neurodegenerative (Parkinson’s and Alzheimer’s) diseases for a long time, recent studies have established their role in heart diseases as these enzymes potently generate reactive oxygen species (ROS) in cardiomyocytes via oxidative deamination of mainly norepinephrine and serotonin. Indeed, MAOs have emerged as important regulators of mitochondrial/endothelial/cardiac dysfunction, essential hypertension, ventricular hypertrophy, myocardial infarction, cardiomyocyte apoptosis, postischemic cardiac damage, and heart failure. Transcriptional and posttranscriptional regulation of MAOs (via certain transcription factors or microRNAs) may emerge as new therapeutic strategies for treatment of cardiovascular pathological conditions. The next-generation MAO inhibitors (that do not cause irreversible inhibition of MAOs) may also be useful for management of cardiovascular disease states involving dysregulated expression/activity of MAOs.