De novo identification of CD4+ T cell epitopes.

CD4+ T cells recognize peptide antigens presented on class II major histocompatibility complex (MHC-II) molecules to carry out their function. The remarkable diversity of T cell receptor sequences and lack of antigen discovery approaches for MHC-II make profiling the specificities of CD4+ T cells challenging. We have expanded our platform of signaling and antigen-presenting bifunctional receptors to encode MHC-II molecules presenting covalently linked peptides (SABR-IIs) for CD4+ T cell antigen discovery. SABR-IIs can present epitopes to CD4+ T cells and induce signaling upon their recognition, allowing a readable output. Furthermore, the SABR-II design is modular in signaling and deployment to T cells and B cells. Here, we demonstrate that SABR-IIs libraries presenting endogenous and non-contiguous epitopes can be used for antigen discovery in the context of type 1 diabetes. SABR-II libraries provide a rapid, flexible, scalable and versatile approach for de novo identification of CD4+ T cell ligands from single-cell RNA sequencing data using experimental and computational approaches.

Environmentally friendly and efficient TBHP-mediated catalytic reaction for the synthesis of substituted benzimidazole-2-ones: In-silico approach to pharmaceutical applications.

A novel method was used to synthesize benzimidazole-2-ones from the corresponding benzimidazolium salts. These salts were subsequently reacted with potassium tertiary butoxide (KOtBu), followed by oxidation using tertiary butyl hydrogen peroxide (TBHP) at room temperature in tetrahydrofuran (THF) to obtain the desired products in 1 h with excellent yields. After optimizing the reaction conditions, the study focused on preparing benzimidazole-2-ones with diverse substituents at N1 and N3 positions, including benzyl, 2',4',6'-trimethyl benzyl groups, and long-chain aliphatic substituents (hexyl, octyl, decyl, and dodecyl). The compounds were characterized by 1H and 13C NMR spectra, of which compound 2a is supported by single crystal XRD. Benzimidazole-2-one compounds exhibited promising anti-inflammatory and anti-cancer properties. The inhibition of mitochondrial Heat Shock Protein 60 (HSP60) of title compounds was also explored. Computational simulations were employed to assess anti-cancer properties of 19 benzimidazole-2-one derivatives (potential drugs). In-silico docking studies demonstrated promising binding interactions with HSP60, and these results were supported by molecular dynamics simulations. Notably, molecules 2b and 2d exhibited high affinity for HSP60 protein, highlighting their potential efficacy. The developed ligands were viable for the treatment of hepatocellular carcinoma (HCC). The findings provide valuable initial evidence supporting the efficacy of benzimidazole-2-ones as HSP60 inhibitors and lay the foundation for subsequent studies, including in-vitro assays.

Recent advances in sustainable N-heterocyclic carbene-Pd(II)-pyridine (PEPPSI) catalysts: A review.

Various catalysts in homogeneous or heterogeneous catalysis deploy unconventional reaction pathways by lowering the activation energy (AE) barrier, controlling the selectivity, and creating environmental impact, thereby bringing about economic viability. Hence, the study of these methodologies is of immense interest. To develop a new chemistry, there is much scope for the invention of brilliant candidates that could effectively catalyze diverse reaction methodologies. The palladium-catalyzed reactions motivate interesting applications on various organic transformations under mild reaction conditions. Although phosphorous designed ligands or catalysts have been used, despite their expensiveness, sensitivity and other properties, there is the necessity of developing even better cross-coupling ligands or catalysts such as N-heterocyclic carbene (NHC)-based palladium complexes. These palladium-NHCs (Pd-NHC) are novel and universal nucleophilic entities that have come into light as the most successful class of catalysts in organometallic chemistry. In the same class, a specific category of palladium-NHCs such as palladium-pyridine enhanced pre-catalyst preparation by the stabilization initiation (palladium-PEPPSI) complexes, are emerging as versatile alternatives to phosphine containing palladium complexes for various cross-coupling reactions due to their excellent catalytic activity. Further to mention that NHCs are recently extensively used as ancillary ligands in organometallic chemistry, which includes industrial-related catalytic transformations due to strong σ-donors to metal centres. Apart from this, many NHC-metal complexes are the fascinating consideration in material science as probable metallo-pharmaceuticals. The current review offers a brief exploration of palladium-PEPPSI complexes over the past few years. Further, the synthesis of a variety of these types of catalysts, their applications in Suzuki-Miyaura, Buchwald-Hartwig, Sonogashira, Negishi couplings direct C2-arylation, O-C(O) cleavage, α-arylation/alkylation of carbonyl compounds and trans-amidation reactions via cross-coupling methodologies, which are covered. Additionally, reported recent developments on reusable heterogeneous PdPEPPSI complexes and their catalytic applications are being covered. Finally, the chiral Pd complexes and their asymmetric transformations are discussed.

Feasibility and Utility of Routine Point-of-Care Gastric Ultrasonography in Patients Undergoing Upper Gastrointestinal Endoscopy Procedures: A Prospective Cohort Study.

OBJECTIVES: Previous studies have indicated that point-of-care ultrasonography (POCUS) of the gastric antrum can predict the adequacy of fasting before surgery and anesthesia. The aim of this study was to evaluate the utility of gastric POCUS in patients undergoing upper gastrointestinal (GI) endoscopy procedures. METHODS: We performed a single-center cohort study in patients undergoing upper GI endoscopy. Consenting patient's gastric antrum was scanned before anesthetic care for endoscopy to determine the cross-sectional area (CSA) and qualitatively determine safe and unsafe contents. Further, an estimate of residual gastric volume was determined using the formula and the nomogram methods. Subsequently, gastric secretions aspirated during endoscopy were quantified and further correlated with nomogram and formula-based assessments. No patient required a change in the primary anesthetic plan except for using rapid sequence induction in those with unsafe contents on POCUS scans. RESULTS: Qualitative ultrasound measurements consistently determined safe and unsafe gastric residual contents in 83 patients enrolled in the study. Unsafe contents were determined by qualitative scans in 4 out of 83 cases (5%) despite adequate fasting status. Quantitatively, only a moderate correlation was demonstrated between measured gastric volumes and nomogram (r = .40, 95% CI: 0.20, 0.57; P = .0002) or formula-based (r = .38, 95% CI: 0.17, 0.55; P = .0004) determinations of residual gastric volumes. CONCLUSION: In daily clinical practice, qualitative POCUS determination of residual gastric content is a feasible and useful technique to identify patients at risk of aspiration before upper GI endoscopy procedures.

Desidustat in Anemia due to Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-D).

BACKGROUND: A phase 3 study to assess the efficacy and safety of the desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, against the epoetin alfa for the treatment of anemia in patients with chronic kidney disease (CKD) with dialysis dependency. METHODS: DREAM-D was a phase 3, multicenter, open-label, randomized, active-controlled clinical study conducted across 38 centers in India. A total of 392 patients with clinical diagnosis of anemia due to CKD with dialysis need (Erythrocyte Stimulating Agent [ESA] naïve or prior ESA users) and with baseline hemoglobin levels of 8.0-11.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat oral tablets (thrice a week) or epoetin alfa subcutaneous injection for 24 weeks to maintain a hemoglobin level of 10-12 g/dL. The primary endpoint was to assess the change in the hemoglobin level between the desidustat and the epoetin alfa groups from the baseline to evaluation period week 16-24. The key secondary efficacy endpoint was the number of patients with hemoglobin response. RESULTS: The least square mean (standard error) change in hemoglobin from the baseline to week 16-24 was 0.95 (0.09) g/dL in the desidustat group and 0.80 (0.09) g/dL in the epoetin alfa group (difference: 0.14 [0.14] g/dL; 95% confidence interval: -0.1304, 0.4202), which met the prespecified noninferiority margin. The number of hemoglobin responders was significantly higher in the desidustat group (106 [59.22%]) when compared to the epoetin alfa group (89 [48.37%]) (p = 0.0382). The safety profile of the desidustat oral tablet was comparable with the epoetin alfa injection. There were no new risks or no increased risks seen with the use of desidustat compared to epoetin alfa. CONCLUSION: In this study, desidustat was found to be noninferior to epoetin in the treatment of anemia in CKD patients on dialysis and it was well-tolerated. Clinical Trial Registry Identifier: CTRI/2019/12/022312 (India).

Chitosan Encapsulated Meloxicam Nanoparticles for Sustained Drug Delivery Applications: Preparation, Characterization, and Pharmacokinetics in Wistar Rats.

Meloxicam (MLX) is currently used in the therapeutic management of both acute and chronic inflammatory disorders such as pain, injuries, osteoarthritis, and rheumatoid arthritis in both humans and animals. Gastrointestinal toxicity and occasional renal toxicity were observed in patients taking it for a long-term period. Meloxicam's late attainment of peak plasma concentration results in a slow onset of action. The goal of the current study was to prepare and characterize chitosan encapsulated meloxicam nanoparticles (CEMNPs) with high bioavailability and less gastro intestinal toxicity in order to prevent such issues. The size of the prepared CEMNPs was approximately 110-220 nm with a zetapotential of +39.9 mV and polydispersity index of 0.268, suggesting that they were uniformly dispersed nanoparticles. The FTIR and UV-Vis spectroscopy have confirmed the presence of MLX in the prepared CEMNPs. The pharmacokinetics have been studied with three groups of male Wistar rats receiving either of the treatments, viz., 4 mg·kg-1 of MLX and 1 or 4 mg·kg-1 of CEMNPs. Plasma samples were collected until 48 h post administration, and concentrations of MLX were quantified by using reverse (C18) phase HPLC. Non-compartmental analysis was applied to determine pharmacokinetic variables. Upon oral administration, the maximum concentration (Cmax) was reached in 4 h for CEMNPs and 6 h for MLX. The mean area under the plasma MLX concentration-time curve from 'zero' to infinity (AUC0-∞), half-life (t1/2ß), and mean resident time (MRT) of 1 mg·kg-1 of CEMNPs was 1.4-, 2-, and 1.8-fold greater than 4 mg·kg-1 of MLX. The prepared CEMNPs demonstrated quicker absorption and prolonged release along with a significant improvement in the bioavailability of MLX, paving a prospective path for the development of drugs with enhanced bioavailability with less side effects.

Comparative evaluation of nebulized ketamine and its combination with dexmedetomidine as premedication for paediatric patients undergoing surgeries under general anaesthesia.

Background: Various drugs have been endorsed but no standardised premedication protocol exists for paediatric patients. Nebulised form of drug not only results in better patient acceptability but also has improved clinical effectiveness. The present study delineates and evaluates the efficacy and safety of nebulised ketamine and combination of nebulised dexmedetomidine and ketamine for premedication in paediatric patients. Methods: Prospective randomised controlled study was planned in patients, 3-10 years of age, undergoing surgeries. Patients received either nebulised ketamine (2 mg/kg) (group X, n = 23) or dexmedetomidine 1 µg/kg plus ketamine (1 mg/kg) (group Y; n = 24), 30 min before shifting inside the operation theatre. The sedation level, haemodynamic response and ill-effects were recorded for 30 min. Results: The baseline haemodynamic (HR, MAP, RR and SpO2) parameters were normal and comparable in both the groups. There was no significant variation noticed in terms of HR, MAP, RR and SpO2% in either of the groups at 15 min (p < 0.15, p < 0.20, p < 0.85, p < 0.46) and 30 min (p < 0.21, p < 0.97, p < 0.75, p < 0.61) respectively, after receiving premedication. The level of sedation in group Y (score of 4 or less) was found to be better than that achieved by group X patients (p < 0.001). Face mask acceptance was satisfactory in group Y (score of 2 or less) as compared to group X patients (p < 0.001). The parental separation was comparable in both groups (p = 0.46). Conclusion: Nebulisation is a satisfactory method of premedication for children. A combination of nebulised ketamine with a dose of 1 mg/kg and dexmedetomidine with a dose of 1 µg/kg is capable of producing a satisfactory level of sedation in a more effective manner than sedation induced by nebulised ketamine alone (2 mg/kg).

Early liver transplantation after COVID-19 infection: The first report.

COVID-19 (coronavirus disease 2019) has impacted solid organ transplantation (SOT) in many ways. Transplant centers have initiated SOT despite the COVID-19 pandemic. Although it is suggested to wait for 4 weeks after COVID-19 infection, there are no data to support or refute the timing of liver transplant after COVID-19 infection. Here we describe the course and outcomes of COVID-19-infected candidates and healthy living liver donors who underwent transplantation. A total of 38 candidates and 33 potential living donors were evaluated from May 20, 2020 until October 30, 2020. Ten candidates and five donors were reverse transcriptase-polymerase chain reaction (RT-PCR) positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pretransplant. Four candidates succumbed preoperatively. Given the worsening of liver disease, four candidates underwent liver transplant after 2 weeks due to the worsening of liver disease and the other two candidates after 4 weeks. Only one recipient died due to sepsis posttransplant. Three donors underwent successful liver donation surgery after 4 weeks of COVID-19 infection without any postoperative complications, and the other two were delisted (as the candidates expired). This report is the first to demonstrate the feasibility of elective liver transplant early after COVID-19 infection.

A review on multicomponent reactions catalysed by zero-dimensional/one-dimensional titanium dioxide (TiO2) nanomaterials: Promising green methodologies in organic chemistry.

Heterogeneous catalysis has currently become an emerging tool for the design and development of sustainable manufacturing processes in order to obtain advanced intermediates, fine chemicals, and bioactive molecules. This field has been considered efficient and eco-friendly, as it investigates the utilization of non-hazardous metals for atom-economical reactions. Nanomaterials have created a significant impact on scientific and engineering advancements due to their tunable properties with superior performance over their massive counterparts. Due to the increased demand for heterogeneous catalysts in industries and academia, different transition metal oxides have been made into substantial nanostructures. Among them, titanium dioxide (TiO2) nanomaterials have received more attention on account of their chemical stability, low cost, dual acid-base properties, good oxidation rate and refractive index. Different modifications of TiO2 extend their applications as active catalysts or catalyst supports in diverse catalytic processes, such as photovoltaics, lithium batteries, pigments and others. One-dimensional (1-D) TiO2 nanostructures such as nanotubes, nanowires and nanorods have achieved greater importance owing to the unique properties of improved porosity, decreased inter-crystalline contacts, large surface-to-volume ratio, superior dispersibility, amplified accessibility of hydroxyl (-OH) groups and presence of good concentrations of Brønsted/Lewis acid sites. Since the discovery, 1-D TiO2 nanostructures have served good photocatalytic applications, but were less explored in organic transformations. While many articles and reviews have covered the applications of 0-D and 1-D TiO2 nanostructured materials (NSMs) in photoelectrochemical reactions and solar cells, there are other interesting applications of these as well. In contrast to the conventional multi-step processes that utilise the stepwise formation of individual bonds, one-pot conversions based on multicomponent reactions (MCRs) have acquired much significance in contemporary organic synthesis. This paper presents a critical review on history, classification, design and synthetic utility of titania-based nanostructures, which could be used as robust solid-acid catalysts and catalyst supports for MCRs. Further, to put ideas into perspective, the introduction and applications of MCRs for various organic transformations have been discussed.

Synthesis of some novel methyl ß-orsellinate based 3, 5-disubstituted isoxazoles and their anti-proliferative activity: Identification of potent leads active against MCF-7 breast cancer cell.

A series of sixteen novel methyl ß-orsellinate based 3, 5-disubstituted isoxazole hybrids (3-18) were synthesized in excellent yields by employing 1,3-dipolar cycloaddition reaction of terminal alkyne and corresponding nitriloxides as the key step. The structures of all the synthesized compounds were elucidated by spectroscopic data such as 1H &13C NMR and HRMS. The anti-proliferative activity of newly synthesized compounds were assessed in vitro against a panel of four human cancer cell lines, namely IMR-32 (neuroblastoma), DU-145 (prostate), MIAPACA (pancreatic), MCF-7 (breast) along with a normal cell line HEK-293T (embryonic kidney) by employing Sulforhodamine B (SRB) assay. The biological results revealed that majority of synthesized compounds exhibited anti-proliferative activity. In particular, compound 12 was found to be the most potent one as it exhibited five fold higher activity (IC50: 7.9 ± 0.07 µM) than parent compound 1 (IC50: 40.63 ± 0.11 µM) against MCF-7 breast cancer cell line. Flow cytometric analysis of compound 12 revealed that it induced apoptosis and arrested cell cycle in G2/M phase. Mechanistic studies have shown the compound as a potent activator of pro-apoptotic proteins, Bax and Cytochrome-c via the upregulation of tumour suppressor proteins, p53 and PTEN. From the docking studies, it can be inferred that Compound 12 acts as a novel and attractive anti-cancer therapeutic inhibiting the CDK1-Cyclin B complex.

Synthesis, 18F-radiolabeling and apoptosis inducing studies of novel 4, 7-disubstituted coumarins.

In present study, a new series of 4, 7-disubstituted coumarin derivatives (7a-y) have been synthesized as galectin-1 targeting apoptosis inducing agents and evaluated for their in vitro cytotoxic potentials against a panel of selected human cancer cell lines namely, Brest (MCF7), Ovarian (SKOV3), Prostate (PC-3 & DU145) and normal embryonic kidney (HEK293T) cells, using MTT assay. Most of the compounds exhibited potent growth inhibitory action against the treated cancer cell lines with an IC50 range of 10-30 µM. Compound 7q exhibited a significant growth inhibition against prostate cancer (PC-3 & DU145) cell lines with an IC50 value of 7.45 ± 0.03 µM, 8.95 ± 0.17 µM respectively. Further, the target compound 7q was radiolabeled with fluorine-18 [18F] to be used as a novel PET radiotracer for imaging of tumors via targeting galectin-1, using appropriate reaction conditions in the GE Tracer-lab FX2N synthesis module. The purification of the [18F] radiolabeled compound [18F]-7q was successfully achieved with 60% ethanol. The radiochemical purity was>85% and residual solvent limits of DMF was 65 ± 3 ppm as analysed by HPLC, TLC & GC analytical methods. The apoptosis studies confirm the inhibition of cell proliferation with morphological changes like cell shrinkage, blebbing and cell wall deformation, increasing the ROS levels, and loss of mitochondrial membrane potential by Acridine orange/Ethidium bromide staining, Hoechst-33342 staining, H2DCFDA staining, annexin V-FITC/PI, and JC-1 staining methods. In flow cytometric analysis, 7q selectively arrested the sub-G1 phase of the cell cycle in a dose-dependent manner. In Gal-1 ELISA studies, compound 7q efficiently reduced the levels of Gal-1 protein in dose-dependent manner with an IC50 value of 100 µM. The binding constant (Ka) of 7q with Gal-1 was observed as 1.3 × 104 M-1 by fluorescence spectroscopy. The molecular docking studies clearly showed possible interactions and the pharmacokinetic (ADMET) properties of compound 7q with Gal-1. Hence, the novel 4, 7-disubstituted coumarins could be a potential cytotoxic and PET imaging agents via Gal-1.

Undoped and Nickel-Doped Zinc Oxide Thin Films Deposited by Dip Coating and Ultrasonic Spray Pyrolysis Methods for Propane and Carbon Monoxide Sensing Applications.

Undoped and nickel-doped zinc oxide thin films were deposited on sodalime glass substrates by utilizing dip coating and ultrasonic spray pyrolysis deposition techniques. In both cases zinc acetate and nickel acetylacetonate were used as zinc precursor and nickel dopant source, respectively. XRD analysis confirms the ZnO wurtzite structure with (002) as the preferential orientation.SEM studies show the formation of two types of morphologies, primarily a porous spherical grains with a grain size distribution from 40 to 150 nm and another, rose-like structures with size distribution from 30 to 200 nm, based on different deposition techniques utilized. The elemental depth profiles across the films were investigated by the secondary-ion mass spectrometry (SIMS). Different gas sensing responses of all ZnO films were obtained for both propane and carbon monoxide gases, at different gas concentrations and operating temperatures. The highest sensing response (~6) for undoped ZnO films was obtained for films deposited by ultrasonic spray pyrolysis (USP). Nevertheless, the highest sensing response (~4 × 104) for doped ZnO films was obtained for films deposited by dip coating method. The behavior of sensing responses is explained in detail based on the morphological properties and the amount of Ni impurities incorporated into the crystal lattice.

Recent perspectives on the virulent factors and treatment options for multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii (AB) is one of the most notorious and opportunistic pathogens, which caused high morbidity and mortality rate and World Health Organization (WHO) declared this bacterium as priority-1 pathogen in 2017. The current antibacterial agents, such as colistins, carbapenems, and tigecyclines have limited applications, which necessitate novel and alternative therapeutic remedies. Thus, the understanding of recent perspectives on the virulent factors and antibiotic resistance mechanism exhibited by the bacteria are extremely important. In addition to many combinatorial therapies of antibacterial, there is several natural compounds demonstrated significant antibacterial potential towards these bacteria. The computational systems biology and high throughput screening approaches provide crucial insights in identifying novel drug targets and lead molecules with therapeutics potential. Hence, this review provides profound insight on the recent aspects of the virulent factors associated with AB, role of biofilm formation in drug resistance and the mechanisms of multidrug resistance. This review further illustrates the status of current therapeutic agents, scope, and applications of natural therapeutics, such as herbal medicines and role of computational biology, immunoinformatics and virtual screening in novel lead developments. Thus, this review provides novel insight on latest developments in drug-resistance mechanism of multidrug-resistant A. baumannii (MDRAB) and discovery of probable therapeutic interventions.

Random k-Body Ensembles for Chaos and Thermalization in Isolated Systems.

Embedded ensembles or random matrix ensembles generated by k-body interactions acting in many-particle spaces are now well established to be paradigmatic models for many-body chaos and thermalization in isolated finite quantum (fermion or boson) systems. In this article, briefly discussed are (i) various embedded ensembles with Lie algebraic symmetries for fermion and boson systems and their extensions (for Majorana fermions, with point group symmetries etc.); (ii) results generated by these ensembles for various aspects of chaos, thermalization and statistical relaxation, including the role of q-hermite polynomials in k-body ensembles; and (iii) analyses of numerical and experimental data for level fluctuations for trapped boson systems and results for statistical relaxation and decoherence in these systems with close relations to results from embedded ensembles.

Down-regulation of BORIS/CTCFL efficiently regulates cancer stemness and metastasis in MYCN amplified neuroblastoma cell line by modulating Wnt/ß-catenin signaling pathway.

BORIS/CTCFL is a vital nucleotide binding protein expressed during embryogenesis and gametogenesis. BORIS/CTCFL is the paralogue of transcriptional repressor protein CTCF, which is aberrantly expressed in various malignancies and primarily re-expressed in cancer stem cells (CSCs). The mechanism behind regulation of BORIS in various cancer conditions and tumor metastases is so far not explored in detail. The aim of the study was to understand the influence of BORIS/CTCFL on stemness and metastasis by regulating well-known oncogenes and related signaling pathways. In our study, we have identified a cross-talk between expression of BORIS/CTCFL and Wnt/ß-catenin signaling pathway, which plays a crucial role in various processes including ontogenesis, embryogenesis and maintenance of stem cell properties. Upon knockdown of BORIS/CTCFL, we observed an upregulation of Mesenchymal to Epithelial transition markers such as E-cad and downregulation of Epithelial to Mesenchymal transition markers such as N-CAD, Vimentin, SNAIL, etc. This transition was accomplished by activation of Wnt/ß-catenin signaling pathway by regulating upstream and downstream Wnt associated proteins including ß-catenin, Wnt3a/5a, CD44, MYC etc. We also identified that BMI1, an oncogene belonging to polycomb group expressed positively with levels of BORIS/CTCFL. Our study implicates the role of BORIS/CTCFL in maintenance of stemness and in transition from mesenchymal to epithelial state in MYC amplified neuroblastoma IMR-32 cells. Effectively controlling BORIS/CTCFL levels can inhibit disease establishment and hence can be considered as a potent target for cancer therapy.

A Study of the CO Sensing Responses of Cu-, Pt- and Pd-Activated SnO2 Sensors: Effect of Precipitation Agents, Dopants and Doping Methods.

In this work, we report the synthesis of Cu, Pt and Pd doped SnO2 powders and a comparative study of their CO gas sensing performance. Dopants were incorporated into SnO2 nanostructures using chemical and impregnation methods by using urea and ammonia as precipitation agents. The synthesized samples were characterized using X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HR-TEM). The presence of dopants within the SnO2 nanostructures was evidenced from the HR-TEM results. Powders doped utilizing chemical methods with urea as precipitation agent presented higher sensing responses compared to the other forms, which is due to the formation of uniform and homogeneous particles resulting from the temperature-assisted synthesis. The particle sizes of doped SnO2 nanostructures were in the range of 40-100 nm. An enhanced sensing response around 1783 was achieved with Cu-doped SnO2 when compared with two other dopants i.e., Pt (1200) and Pd:SnO2 (502). The high sensing response of Cu:SnO2 is due to formation of CuO and its excellent association and dissociation with adsorbed atmospheric oxygen in the presence of CO at the sensor operation temperature, which results in high conductance. Cu:SnO2 may thus be an alternative and cost effective sensor for industrial applications.

A Rare Case Series of Ischemic Stroke Following Russell's Viper Snake Bite in India.

Snakebite is an important medical problem in India. Among their various manifestations, cerebral complications are uncommonly found in literature. Moreover, Ischemic stroke following snake bite is quite rare. Here we report a case series of two such cases that developed neurological manifestations following Russell's viper bite. On computerized tomography (CT) scan of brain; cerebral infarcts were revealed. Their likely mechanisms are discussed in present study which include disseminated intravascular coagulation, toxin induced vasculitis and endothelial damage.

CO Gas Sensing Properties of Pure and Cu-Incorporated SnO2 Nanoparticles: A Study of Cu-Induced Modifications.

Pure and copper (Cu)-incorporated tin oxide (SnO2) pellet gas sensors with characteristics provoking gas sensitivity were fabricated and used for measuring carbon monoxide (CO) atmospheres. Non-spherical pure SnO2 nano-structures were prepared by using urea as the precipitation agent. The resultant SnO2 powders were ball milled and incorporated with a transition metal, Cu, via chemical synthesis method. The incorporation is confirmed by high-resolution transmission electron microscope (HRTEM) analysis. By utilizing Cu-incorporated SnO2 pellets an increase in the CO sensitivity by an order of three, and a decrease in the response and recovery times by an order of two, were obtained. This improvement in the sensitivity is due to two factors that arise due to Cu incorporation: necks between the microparticles and stacking faults in the grains. These two factors increased the conductivity and oxygen adsorption, respectively, at the pellets' surface of SnO2 which, in turn, raised the CO sensitivity.

Automated Lung Segmentation from HRCT Scans with Diffuse Parenchymal Lung Diseases.

Performing accurate and fully automated lung segmentation of high-resolution computed tomography (HRCT) images affected by dense abnormalities is a challenging problem. This paper presents a novel algorithm for automated segmentation of lungs based on modified convex hull algorithm and mathematical morphology techniques. Sixty randomly selected lung HRCT scans with different abnormalities are used to test the proposed algorithm, and experimental results show that the proposed approach can accurately segment the lungs even in the presence of disease patterns, with some limitations in the apices and bases of lungs. The algorithm demonstrates a high segmentation accuracy (dice similarity coefficient = 98.62 and shape differentiation metrics dmean = 1.39 mm, and drms = 2.76 mm). Therefore, the developed automated lung segmentation algorithm is a good candidate for the first stage of a computer-aided diagnosis system for diffuse lung diseases.

Active and Repressive Chromatin-Associated Proteome after MPA Treatment and the Role of Midkine in Epithelial Monolayer Permeability.

UNLABELLED: Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported that MPA altered the tight junction (TJ)-mediated barrier function in a Caco-2 cell monolayer model system. This study investigates whether MPA induces epigenetic changes which lead to GI complications, especially diarrhea. METHODS: We employed a Chromatin Immunoprecipitation-O-Proteomics (ChIP-O-Proteomics) approach to identify proteins associated with active (H3K4me3) as well as repressive (H3K27me3) chromatin histone modifications in MPA-treated cells, and further characterized the role of midkine, a H3K4me3-associated protein, in the context of epithelial monolayer permeability. RESULTS: We identified a total of 333 and 306 proteins associated with active and repressive histone modification marks, respectively. Among them, 241 proteins were common both in active and repressive chromatin, 92 proteins were associated exclusively with the active histone modification mark, while 65 proteins remained specific to repressive chromatin. Our results show that 45 proteins which bind to the active and seven proteins which bind to the repressive chromatin region exhibited significantly altered abundance in MPA-treated cells as compared to DMSO control cells. A number of novel proteins whose function is not known in bowel barrier regulation were among the identified proteins, including midkine. Our functional integrity assays on the Caco-2 cell monolayer showed that the inhibition of midkine expression prior to MPA treatment could completely block the MPA-mediated increase in barrier permeability. CONCLUSIONS: The ChIP-O-Proteomics approach delivered a number of novel proteins with potential implications in MPA toxicity. Consequently, it can be proposed that midkine inhibition could be a potent therapeutic approach to prevent the MPA-mediated increase in TJ permeability and leak flux diarrhea in organ transplant patients.