Novel carbamodithioate regulates cellular hypoxia through chemical activation of prolyl hydroxylase-2 for breast cancer chemoprevention.

Inhibition of prolylhydroxylase-2 (PHD-2) in both normoxic and hypoxic cells is a critical component of solid tumours. The present study aimed to identify small molecules with PHD-2 activation potential. Virtually screening 4342 chemical compounds for structural similarity to R59949 and docking with PHD-2. To find the best drug candidate, hits were assessed for drug likeliness, antihypoxic and antineoplastic potential. The selected drug candidate's PHD-2 activation, cytotoxic and apoptotic potentials were assessed using 2-oxoglutarate, MTT, AO/EtBr and JC-1 staining. The drug candidate was also tested for its in-vivo chemopreventive efficacy against DMBA-induced mammary gland cancer alone and in combination with Tirapazamine (TPZ). Virtual screening and 2-oxoglutarate assay showed BBAP-6 as lead compound. BBAP-6 exhibited cytotoxic and apoptotic activity against ER+ MCF-7. In carmine staining and histology, BBAP-6 alone or in combination with TPZ restored normal surface morphology of the mammary gland after DMBA produced malignant alterations. Immunoblotting revealed that BBAP-6 reduced NF-κB expression, activated PHD-2 and induced intrinsic apoptotic pathway. Serum metabolomics conducted with 1H NMR confirmed that BBAP-6 prevented HIF-1α and NF-κB-induced metabolic changes in DMBA mammary gland cancer model. In a nutshell, it can be concluded that BBAP-6 activates PHD-2 and exhibits anticancer potential.

Elucidating the impact of sanitary waste on the formation of fat, oil and grease deposits in sewer systems.

The accumulation of fat, oil and grease (FOG) deposits in sanitary sewer systems is a significant cause of sewer overflows, mainly due to their tendency to adhere to pipe walls. The aim of this study is to (i) develop laboratory-prepared FOG deposits using a mixture of iron (Fe) and aluminium (Al) metal ions, fatty acids, saccharides and cooked oils, in addition to various sanitary waste materials such as paper towels, wipes and pads and (ii) examine the characteristics of these FOG deposits. The goals of this study were to (i) gain a deeper understanding of the impact of sanitary waste on the formation of FOG deposits and (ii) discuss the detailed physiochemical properties of these FOG deposits. The findings revealed that FOG deposits can vary in nature, appearing as either a smooth, paste-like substance or a coarse, semi-solid material, depending on the types of waste present in the sewer. Analysis of the fatty acid profile indicated that the FOG deposits with wipes have the highest viscosity (3.2 × 104 Pa s) and larger composition of smaller chain saturated fatty acids (caprylic acid 0.64%, undecanoic acid 5.61%, lauric acid 4.65%, myristic acid 3.21% and palmitic 8.38%). In contrast, FOG deposits with Fe and Al metal impurities have higher heat resistance and thermal stability (melting point of 125 °C) and have larger composition of long chain fatty acids. Furthermore, FTIR analysis confirmed that these FOG deposits are composed of metallic salts of fatty acids, aligning with samples from sewer lines. Our results suggest that FOG deposit formation involves the aggregation of excess calcium, which compresses free fatty acid micelles, and a saponification reaction between the calcium aggregates and free fatty acids. This research illuminates the complex processes behind FOG deposit formation and their varied characteristics, providing valuable insights into potential strategies for preventing FOG-related sewer blockages.

NMR based Serum metabolomics revealed metabolic signatures associated with oxidative stress and mitochondrial damage in brain stroke.

Brain stroke (BS, also known as a cerebrovascular accident), represents a serious global health crisis. It has been a leading cause of permanent disability and unfortunately, frequent fatalities due to lack of timely medical intervention. While progress has been made in prevention and management, the complexities and consequences of stroke continue to pose significant challenges, especially, its impact on patient's quality of life and independence. During stroke, there is a substantial decrease in oxygen supply to the brain leading to alteration of cellular metabolic pathways, including those involved in mitochondrial-damage, leading to mitochondrial-dysfunction. The present proof-of-the-concept metabolomics study has been performed to gain insights into the metabolic pathways altered following a brain stroke and discover new potential targets for timely interventions to mitigate the effects of cellular and mitochondrial damage in BS. The serum metabolic profiles of 108 BS-patients were measured using 800 MHz NMR spectroscopy and compared with 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of glutamate, TCA-cycle intermediates (such as citrate, succinate, etc.), and membrane metabolites (betaine, choline, etc.) were found to be decreased BS patients, whereas those of methionine, mannose, mannitol, phenylalanine, urea, creatine and organic acids (such as 3-hydroxybutyrate and acetone) were found to be elevated in BS patients. These metabolic changes hinted towards hypoxia mediated mitochondrial dysfunction in BS-patients. Further, the area under receiver operating characteristic curve (ROC) values for five metabolic features (methionine, mannitol, phenylalanine, mannose and urea) found to be more than 0.9 suggesting their high sensitivity and specificity for differentiating BS from NC subjects.

Granularity mediated multiple reentrances with negative magnetoresistance in disordered TiN thin films.

Granular superconductors are the common examples of experimentally accessible model systems which can be used to explore various fascinating quantum phenomena that are fundamentally important and technologically relevant. One such phenomenon is the occurrence of reentrant resistive states in granular superconductors. Here, we report the observation of multiple reentrant resistive states for a disordered TiN thin film in its temperature and magnetic field dependent resistance measurements, R(T) and R(B), respectively. At each of the peak-temperatures corresponding to the zero-field R(T), a resistance peak appears in the R(B) around zero field which leads to a negative magnetoresistance (MR) region in its surrounding. These low-field negative MR regions appear for both perpendicular and parallel field directions with relatively higher amplitude and larger width for the parallel field. By adopting a granularity-based model, we show that the superconducting fluctuations in granular superconductors may lead to the observed reentrant states and the corresponding negative MR. Here, we propose that the reduction in the density of states in the fermionic channel due to the formation of Cooper pairs leads to the reentrant resistive state and the competition between the conduction processes in the single particle and Cooper channels result into the multiple resistive reentrances.

Clinical metabolomics by NMR revealed serum metabolic signatures for differentiating sarcoidosis from tuberculosis.

BACKGROUND: Pulmonary sarcoidosis (SAR) and tuberculosis (TB) are two granulomatous lung-diseases and often pose a diagnostic challenge to a treating physicians. OBJECTIVE: The present study aims to explore the diagnostic potential of NMR based serum metabolomics approach to differentiate SAR from TB. MATERIALS AND METHOD: The blood samples were obtained from three study groups: SAR (N = 35), TB (N = 28) and healthy normal subjects (NC, N = 56) and their serum metabolic profiles were measured using 1D 1H CPMG (Carr-Purcell-Meiboom-Gill) NMR spectra recorded at 800 MHz NMR spectrometer. The quantitative metabolic profiles were compared employing a combination of univariate and multivariate statistical analysis methods and evaluated for their diagnostic potential using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared to SAR, the sera of TB patients were characterized by (a) elevated levels of lactate, acetate, 3-hydroxybutyrate (3HB), glutamate and succinate (b) decreased levels of glucose, citrate, pyruvate, glutamine, and several lipid and membrane metabolites (such as very-low/low density lipoproteins (VLDL/LDL), polyunsaturated fatty acids, etc.). CONCLUSION: The metabolic disturbances not only found to be well in concordance with various previous reports, these further demonstrated very high sensitivity and specificity to distinguish SAR from TB patients suggesting serum metabolomics analysis can serve as surrogate method in the diagnosis and clinical management of SAR.

Synthesis and characterization of nanostructured graphene-doped selenium.

In this work, we explore various properties of elemental selenium glass (g-Se) by doping with graphene through the facile melt-quench technique. The structural information of the synthesized sample was found by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Raman spectroscopy. The analyses confirm that the graphene-doped g-Se behaves like a glass-ceramic material. Electrical and dielectric measurements were performed to discover the consequences of graphene incorporation on the nano-structure of g-Se. The electrical measurements of the dielectric parameters (i.e., dielectric constant ε' and loss ε'') and conductivity (σ ac) reveal that graphene incorporation causes a rise in the dielectric constant but simultaneously increases dielectric loss. The enhancement in ε' and ε'' values is thought to be a consequence of the interface effect between graphene and the host selenium glass. Calorimetric experiments were performed in a standard differential scanning calorimetry (DSC) unit on the glassy nanocomposite in non-isothermal mode. By measuring the kinetic temperatures at four heating rates, the kinetics of the crystallization/glass transition were studied. The results were examined to understand the role of graphene doping on the well-known phase transitions (i.e., glass transition and crystallization) of g-Se.

Selective-Area Epitaxy of InGaAsP Buffer Multilayer for In-Plane InAs Nanowire Integration.

In order to use III-V compound semiconductors as active channel materials in advanced electronic and quantum devices, it is important to achieve a good epitaxial growth on silicon substrates. As a first step toward this, we report on the selective-area growth of GaP/InGaP/InP/InAsP buffer layer nanotemplates on GaP substrates which are closely lattice-matched to silicon, suitable for the integration of in-plane InAs nanowires. Scanning electron microscopy reveals a perfect surface selectivity and uniform layer growth inside 150 and 200 nm large SiO2 mask openings. Compositional and structural characterization of the optimized structure performed by transmission electron microscopy shows the evolution of the major facet planes and allows a strain distribution analysis. Chemically uniform layers with well-defined heterointerfaces are obtained, and the topmost InAs layer is free from any dislocation. Our study demonstrates that a growth sequence of thin layers with progressively increasing lattice parameters is effective to efficiently relax the strain and eventually obtain high quality in-plane InAs nanowires on large lattice-mismatched substrates.

ECM Mimicking Biodegradable Nanofibrous Scaffold Enriched with Curcumin/ZnO to Accelerate Diabetic Wound Healing via Multifunctional Bioactivity.

Introduction: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15-24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action. Purpose: This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats. Results: In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 - 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ-induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing. Discussion: CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively.

Monolithic Integration of Nano-Ridge Engineered InGaP/GaAs HBTs on 300 mm Si Substrate.

Nano-ridge engineering (NRE) is a novel method to monolithically integrate III-V devices on a 300 mm Si platform. In this work, NRE is applied to InGaP/GaAs heterojunction bipolar transistors (HBTs), enabling hybrid III-V/CMOS technology for RF applications. The NRE HBT stacks were grown by metal-organic vapor-phase epitaxy on 300 mm Si (001) wafers with a double trench-patterned oxide template, in an industrial deposition chamber. Aspect ratio trapping in the narrow bottom part of a trench results in a threading dislocation density below 106∙cm-2 in the device layers in the wide upper part of that trench. NRE is used to create larger area NRs with a flat (001) surface, suitable for HBT device fabrication. Transmission electron microscopy inspection of the HBT stacks revealed restricted twin formation after the InGaP emitter layer contacts the oxide sidewall. Several structures, with varying InGaP growth conditions, were made, to further study this phenomenon. HBT devices-consisting of several nano-ridges in parallel-were processed for DC and RF characterization. A maximum DC gain of 112 was obtained and a cut-off frequency ft of ~17 GHz was achieved. These results show the potential of NRE III-V devices for hybrid III-V/CMOS technology for emerging RF applications.

A robust nitridation technique for fabrication of disordered superconducting TiN thin films featuring phase slip events.

Disorder induced phase slip (PS) events appearing in the current voltage characteristics (IVCs) are reported for two-dimensional TiN thin films produced by a robust substrate mediated nitridation technique. Here, high temperature annealing of Ti/Si3N4 based metal/substrate assembly is the key to produce majority phase TiN accompanied by TiSi2 & elemental Si as minority phases. The method itself introduces different level of disorder intrinsically by tuning the amount of the non-superconducting minority phases that are controlled by annealing temperature (Ta) and the film thickness. The superconducting critical temperature (Tc) strongly depends on Ta and the maximum Tc obtained from the demonstrated technique is about 4.8 K for the thickness range ~ 12 nm and above. Besides, the dynamics of IVCs get modulated by the appearance of intermediated resistive steps for decreased Ta and the steps get more prominent for reduced thickness. Further, the deviation in the temperature dependent critical current (Ic) from the Ginzburg-Landau theoretical limit varies strongly with the thickness. Finally, the Tc, intermediate resistive steps in the IVCs and the depairing current are observed to alter in a similar fashion with Ta and the thickness indicating the robustness of the synthesis process to fabricate disordered nitride-based superconductor.

Image fusion using hybrid methods in multimodality medical images.

An image fusion based on multimodal medical images renders a considerable enhancement in the quality of fused images. An effective image fusion technique produces output images by preserving all the viable and prominent information gathered from the source images without any introduction of flaws or unnecessary distortions. This review paper intends to bring out the process of image fusion, its utilization in the medical domain, merits, and demerits and reviews the perspective of multimodal medical image fusion. It also discusses the involvement of various medical entities like medical resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The usefulness of such modalities is presented, suggesting plausible hybrid modality combinations which could greatly enhance image fusion. This review also discusses innovative dispositions in the medical image fusion techniques for the achievement of incisively desired, quality images focused on fusion with wavelet transform and use of independent component analysis (ICA) and principal component analysis (PCA) techniques for the purpose denoising and data dimension reductions. Additionally, the future-prospects of an ideal technique for medical image fusion through the utilization of various medical modalities have been also discussed in this review paper. Graphical abstract.

Substrate mediated nitridation of niobium into superconducting Nb2N thin films for phase slip study.

Here we report a novel nitridation technique for transforming niobium into hexagonal Nb2N which appears to be superconducting below 1K. The nitridation is achieved by high temperature annealing of Nb films grown on Si3N4/Si (100) substrate under high vacuum. The structural characterization directs the formation of a majority Nb2N phase while the morphology shows granular nature of the films. The temperature dependent resistance measurements reveal a wide metal-to-superconductor transition featuring two distinct transition regions. The region close to the normal state varies strongly with the film thickness, whereas, the second region in the vicinity of the superconducting state remains almost unaltered but exhibiting resistive tailing. The current-voltage characteristics also display wide transition embedded with intermediate resistive states originated by phase slip lines. The transition width in current and the number of resistive steps depend on film thickness and they both increase with decrease in thickness. The broadening in transition width is explained by progressive establishment of superconductivity through proximity coupled superconducting nano-grains while finite size effects and quantum fluctuation may lead to the resistive tailing. Finally, by comparing with Nb control samples, we emphasize that Nb2N offers unconventional superconductivity with promises in the field of phase slip based device applications.

Cholera Outbreak in Gaidataar: A Lesson for Further Strengthening the Task Force for Epidemic Management in Nepal.

Cholera is an acute enteric infection caused by the ingestion of bacterium Vibrio cholerae(1). Cholera is transmitted through contaminated food and water. Prevention and preparedness of cholera require a coordinated multi-disciplinary approach. The extremely short incubation period enhances the potentially explosive pattern of outbreaks. Cholera can lead to severe dehydration and death if left untreated. The laboratory testing is required for antimicrobial sensitivity testing and for confirming the end of an outbreak. Provision of safe drinking water, proper sanitation, and food safety are critical for preventing occurrence of cholera. Health education aims at communities adopting preventive behavior for averting contamination. Specific training for all the staffs about proper case management including avoidance of noso-comial infection (like face masks, gloves, antiseptic solution, hand scrubs). Sufficient pre-positioned medical supplies for case management (diarrhoeal disease kits, iv fluids, antibiotics, safety measures). Improved access to water, effective sanitation, proper waste management and vector control. Improved communication and public information. Oral Rehydration Salts can treat 80% of cholera1. Appropriate antibiotics can reduce the duration of purging. With a well and properly managed team of health experts with all essential medicines and a good rapid response team, any outbreak can be prevented, controlled and managed.

Integration of InGaAs MOSFETs and GaAs/ AlGaAs lasers on Si Substrate for advanced opto-electronic integrated circuits (OEICs).

Lasers monolithically integrated with high speed MOSFETs on the silicon (Si) substrate could be a key to realize low cost, low power, and high speed opto-electronic integrated circuits (OEICs). In this paper, we report the monolithic integration of InGaAs channel transistors with electrically pumped GaAs/AlGaAs lasers on the Si substrate for future advanced OEICs. The laser and transistor layers were grown on the Si substrate by molecular beam epitaxy (MBE) using direct epitaxial growth. InGaAs n-FETs with an ION/IOFF ratio of more than 106 with very low off-state leakage and a low subthreshold swing with a minimum of 82 mV/decade were realized. Electrically pumped GaAs/AlGaAs quantum well (QW) lasers with a lasing wavelength of 795 nm at room temperature were demonstrated. The overall fabrication process has a low thermal budget of no more than 400 °C.

Knowledge Attitude and Perception of Sex Education among School Going Adolescents in Ambala District, Haryana, India: A Cross-Sectional Study.

INTRODUCTION: Adolescence is a highly dynamic period characterised by rapid growth and development. Adolescents have limited knowledge about sexual and reproduction health, and know little about the natural processes of puberty, sexual health, pregnancy or reproduction. Sex education should be an integral part of the learning process beginning in childhood and continuing into adult life, because it is lifelong process. AIM: This study was carried out to identify the knowledge and attitude of imparting sex education in school going adolescents in rural and urban area of Ambala district. MATERIALS AND METHODS: A cross sectional study design was used to study the knowledge of reproductive and sexual health among school going children. A total of 743 adolescents from age group of 13-19 year were studied, using self designed semi-structured questionnaire to assess the knowledge regarding reproductive and sexual health among adolescents. RESULTS: The mean age of study subjects was 15.958±1.61 years, majority of adolescents i.e., 93.5% favour sex education. An 86.3% said sex education can prevent the occurrence of AIDS and 91.5% of adolescents prefer doctors should give them sex education followed by 83.0% school/teacher and least preference was parents 37.3%. CONCLUSION: There were substantial lacunae in the knowledge about reproductive and sexual health. Students felt that sex education is necessary and should be introduced in the school curriculum.

Light Induced Electron-Phonon Scattering Mediated Resistive Switching in Nanostructured Nb Thin Film Superconductor.

The elemental Nb is mainly investigated for its eminent superconducting properties. In contrary, we report of a relatively unexplored property, namely, its superior optoelectronic property in reduced dimension. We demonstrate here that nanostructured Nb thin films (NNFs), under optical illumination, behave as room temperature photo-switches and exhibit bolometric features below its superconducting critical temperature. Both photo-switch and superconducting bolometric behavior are monitored by its resistance change with light in visible and near infrared (NIR) wavelength range. Unlike the conventional photodetectors, the NNF devices switch to higher resistive states with light and the corresponding resistivity change is studied with thickness and grain size variations. At low temperature in its superconducting state, the light exposure shifts the superconducting transition towards lower temperature. The room temperature photon sensing nature of the NNF is explained by the photon assisted electron-phonon scattering mechanism while the low temperature light response is mainly related to the heat generation which essentially changes the effective temperature for the device and the device is capable of sensing a temperature difference of few tens of milli-kelvins. The observed photo-response on the transport properties of NNFs can be very important for future superconducting photon detectors, bolometers and phase slip based device applications.

Monolithic integration of InGaAs n-FETs and lasers on Ge substrate.

We report the first monolithic integration of InGaAs channel field-effect transistors with InGaAs/GaAs multiple quantum wells (MQWs) lasers on a common platform, achieving a milestone in the path of enabling low power and high speed opto-electronic integrated circuits (OEICs). The III-V layers used for realizing transistors and lasers were grown epitaxially on the Ge substrate using molecular beam epitaxy (MBE). A Si-CMOS compatible process was developed to realize InGaAs n-FETs with subthreshold swing SS of 93 mV/decade, ION/IOFF ratio of more than 4 orders of magnitude with very low off-state leakage current, and a peak effective mobility of more than 2000 cm2/V·s. In addition, fabrication process uses a low overall processing temperature (≤ 400 °C) to maintain the high quality of the InGaAs/GaAs MQWs for the laser. Room temperature electrically-pumped lasers with a lasing wavelength of 1.03 µm and a linewidth of less than 1.7 nm were realized.

An Epidemiological Study of Malnutrition Among Under Five Children of Rural and Urban Haryana.

INTRODUCTION: A child is future of nation. Malnutrition is a big public health problem in India as it can be attributed for more than half (54 percent) of all under five mortality in India. AIM: To assess prevalence of malnutrition among urban and rural population of Haryana using newly developed WHO growth standards. SETTINGS AND DESIGN: A community based cross-sectional survey was conducted in children of 3-60 months age living in the urban and rural field practice areas of Department of Community Medicine MMIMSR, Mullana, Ambala during January 2012 to December 2012. MATERIALS AND METHODS: Seven hundred and fifty children, aged 3-60 months, were studied for nutritional status, socio-demographic measures were obtained from structured questionnaire and followed by anthropometric assessment using standards methods. Z score for Anthropometric data was calculated by WHO Anthro 2010 software (beta version). STATISTICAL ANALYSIS: Descriptive statistics as well as simple proportion were calculated with SPSS 20. RESULTS: We found that 41.3% children were underweight and 14% were severe underweight. Female children were more nutritionally deprived than males. Among sociodemographic factors maternal educational and working status as well as SES class and rural background of family had greater impact on nutritional status of child. CONCLUSION: We found that almost half of our under five children are underweight, girl child being affected more. For attainment of best possible nutrition and growth in children, targeted short-term strategies addressing underlying risk factors and more long-term poverty alleviation strategies may be needed.