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Introduction: Pulmonary arterial compliance, the dynamic component of pulmonary vasculature, remains inadequately studied in patients with left to right shunts. We sought to study the pulmonary arterial compliance in patients with left to right shunt lesions and its utility in clinical decision-making. Materials and methods: In this single-centre retrospective study, we reviewed cardiac catheterisation data of consecutive patients of left to right shunt lesions catheterised over one year. In addition to the various other parameters, pulmonary arterial compliance was calculated, as indexed pulmonary flow (Qpi) / (Heart rate × pulse pressure in the pulmonary artery). RC time was also calculated, as the product of pulmonary arterial compliance and pulmonary vascular resistance index. Patients were divided into “operable,” “borderline,” and “inoperable” based on the decision of the treating team, and the pulmonary arterial compliance values were evaluated in these groups to study if it can be utilised to refine the operability decision. Results: 298 patients (Median age 16 years, 56% 2 (IQR 3.2). The median pulmonary arterial compliance for operable patients was 2.67 ml/mmHg/m2 (IQR 2.2). Median pulmonary arterial compliance was significantly lower in both inoperable (0.52 ml/mmHg/m2, IQR 0.34) and borderline (0.80 ml/mmHg/m2, IQR 0.36) groups when compared to operable patients (p < 0.001). A pulmonary arterial compliance value lower than 1.18 ml/mmHg/m2 identified inoperable patients with high sensitivity and specificity (95%, AUC 0.99). However, in borderline cases, assessment by this value did not agree with empirical clinical assessment. The median RC time for the entire study population was 0.47 S (IQR 0.30). RC time in operable patients was significantly lower than that in the inoperable patients (Median 0.40 IQR 0.23 in operable, 0.73 0.25 in inoperable patients (p < 0.001). Conclusions: Addition of pulmonary arterial compliance to the routine haemodynamic assessment of patients with shunt lesions may improve our understanding of the pulmonary circulation and may have clinical utility.

Objective Accumulating evidence suggests increased cardiovascular risk in women with polycystic ovarian syndrome (PCOS) due to a cluster of factors, such as obesity, lipid abnormalities, impaired glucose tolerance (IGT), and hypertension. Markers such as high-sensitivity C-reactive protein (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) can provide an adjunctive method for the assessment of cardiovascular risk and can indicate future coronary heart diseases in women with lean PCOS. Materials and Methods In this prospective case-control study, women clinically diagnosed with PCOS (n = 25) with normal body mass index (BMI) and age and BMI-matched healthy controls (n = 75) were enrolled. The quantitative data were expressed as mean ± standard deviation (SD). Unpaired Student's t-test was used to compare the values (PCOS vs. controls) and Pearson's correlation coefficient was used to elucidate the relationship between the variables. Results The mean level of fasting blood sugar, serum total cholesterol, low-density lipoprotein (LDL), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), hs-CRP, and PAI-1 were significantly increased in PCOS patients (p Conclusion Women with lean phenotype of PCOS suffer from many metabolic abnormalities such as abdominal obesity, dyslipidemia, hyperandrogenemia, and insulin resistance. The findings of the study suggest that environment of ongoing low-grade inflammation due to infiltration further exacerbates the metabolic derangements and cardiovascular risk. The investigations as hs-CRP and PAI-1 will help in early identification, diagnosis, and management of cardiovascular diseases associated with lean type of PCOS. These markers can prove to be beneficial in monitoring any unfavorable changes in cardiometabolic profile of such patients.

Incorporation of the standard model Yukawa interactions in a grand unified theory (GUT) often predicts varieties of new scalars that couple to the fermions and lead to some novel observational effects. We assess such a possibility for the colour sextet diquark scalars within the realistic renormalizable models based on $SO(10)$ GUT. The spectrum consists of five sextets: $\Sigma \sim (6,1,-\frac{2}{3})$, $S \sim (6,1,\frac{1}{3})$, $\overline{S}\sim(\overline{6},1,-\frac{1}{3})$, ${\cal S}\sim(6,1,\frac{4}{3})$ and $\mathbb{S}\sim(\overline{6},3,-\frac{1}{3})$. Computing explicitly their couplings with the quarks, we evaluate their contributions to the neutral meson-antimeson mixing and baryon number-violating processes like neutron-antineutron oscillation. The latter arises because of a $B-L$ violating trilinear coupling between the sextets which also contributes to some of the quartic couplings and perturbativity of the same leads to strong limits on the sextet masses. Using the values of the $B-L$ breaking scale and Yukawa couplings permitted in the realistic models, we derive constraints on the masses of these scalars. It is found that $\Sigma$ along with any of the remaining sextets cannot be lighter than the $B-L$ breaking scale, simultaneously. In the realm of realistic models, this implies no observable $n$-$\bar{n}$ oscillation in near future experiments. We also point out a possibility in which sub-GUT scale $\Sigma$ and a pair of $S$, allowed by the other constraints, can viably produce the observed baryon asymmetry of the universe., Comment: 25 Pages, 7 Captioned Figures, 1 Table, V2: published in PRD

The pathogenesis of COVID-19 is complicated by immune dysfunction. The impact of immune-based therapy in COVID-19 patients has been well documented, with some notable studies on the use of anti-cytokine medicines. However, the complexity of disease phenotypes, patient heterogeneity and the varying quality of evidence from immunotherapy studies provide problems in clinical decision-making. This review seeks to aid therapeutic decision-making by giving an overview of the immunological responses against COVID-19 disease that may contribute to the severity of the disease. We have extensively discussed theranostic methods for COVID-19 detection. With advancements in technology, bioinformatics has taken studies to a higher level. The paper also discusses the application of bioinformatics and machine learning tools for the diagnosis, vaccine design and drug repurposing against SARS-CoV-2.

This paper summarizes the design and analysis of Jet Wind Turbine blades, CATIA is used for design and analysis for model generated by applying boundary condition; this paper also includes specific post processing and life assessment of blade. We take an opportunity to present this report on “Design and Analysis of Jet Wind Turbine Blades” and put before readers some useful information regarding this project. Drawn by list of priorities progress in the design and structural analysis of jet wind turbine blades is reviewed and presented for generating 100 watt power. This article is motivated by the key role of blades in the performance of jet wind turbine. The fundamentals of the associated physics are emphasized. Recent developments and advancements have led to an increase and improvement in blade aerodynamics, stability and reliability. This article is intended as a high level review of design of the blade environment and current state of structural design to aid further research in developing new and innovative blade technologies.

Mathematical and computer modeling have been playing an increasingly important role in the computer aided engineering (CAE) process of many products since last 60 years. The present work consists of a leaf spring involving two supporting leafs with the main Leaf. Main leaf and the centre leaf are having a uniform cross section throughout the length of the blade, while the bottom leaf having a thickness of around 1.5 times of that of the other two. Moreover a central bolt and two supporting U-Bolts are provided to hold leafs together. The load is applied axially downwards at the eye ends of the main leaf and a double magnitude load is applied at the bottom of the bolt. Here in the present model we have taken the steel material for the analysis purpose and the nut is firmly fixed by giving a fully constrained boundary condition on it. An octree 10 node modified tetrahedron mesh element is used for the discretization of the spring model. For the whole work i.e., from the modeling to the result generation CATIA V5R12 software is used and the obtained results are finally compared with the numerically obtained result of stress and deflection to validate the simulation results. Vehicle whose, leaf spring dimension are taken is light commercial vehicle (Ashok Leland Dost).

NDI derivatives have been synthesized via Michael addition reaction with uplifted HOMO–LUMO energy levels and strong CT interaction in MA products generally not achieved by simple imide-N substitutions.

Astrocytic hamartoma is a benign glial tumor. It may be associated with tuberous sclerosis and can also be found incidentally on retinal examination as an isolated presentation. Here, we describe multimodal imaging characteristics of astrocytic hamartoma in a patient with retinitis pigmentosa. Spectral domain optical coherence tomography of both eyes showed moth-eaten optically empty spaces and hyperreflective dots along with foveal thinning. Multicolor image highlighted mulberry appearance of the lesion with green shift signifying elevated lesion. In infrared reflectance, lesion was hyporeflective with its margins well delineated. Green reflectance and blue reflectance highlighted calcification as multiple hyperreflective dots. Autofluorescence showed typical hyperautofluorescence.

Chylothorax is an infrequent cause of pleural effusion that is most commonly caused by the obstruction or disruption of the thoracic duct. Chylothorax is rare in nephrotic syndrome. Unilateral chylothorax of the right side is due to the transdiaphragmatic shunting of chylous ascites. It is usually transient and self-limiting but a massive chylothorax requiring therapeutic thoracentesis can also be encountered. Here, we present a rare cause of chylous ascites-nephrotic syndrome resulting in chylothorax, where initially therapeutic thoracentesis is done followed by the management of nephrotic syndrome with modified Ponticelli regimen. This case highlights the need to consider chylous ascites as a cause of chylothorax via transdiaphragmatic shunting in patients with nephrotic syndrome to institute the appropriate treatment.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg ...

Early studies in mouse neurodevelopment led to the discovery of the RE1 Silencing Transcription Factor (REST) and its role as a master repressor of neuronal gene expression. Recently, REST was reported to also repress neuronal genes in the human adult brain. These genes were found to be involved in pro-apoptotic pathways; and their repression, associated with increased REST levels during aging, were found to be neuroprotective and conserved across species. However, direct genome-wide REST binding profiles for REST in adult brain have not been identified for any species. Here, we apply this approach to mouse and human hippocampus. We find an expansion of REST binding sites in the human hippocampus that are lacking in both mouse hippocampus and other human non-neuronal cell types. The unique human REST binding sites are associated with genes involved in innate immunity processes and inflammation signaling which, on the basis of histology and recent public transcriptomic analyses, suggest that these new target genes are repressed in glia. We propose that the increases in REST expression in mid-adulthood presage the beginning of brain aging, and that human REST function has evolved to protect the longevity and function of both neurons and glia in human brain. SIGNIFICANCE STATEMENT The RE1 Silencing Transcription Factor (REST) repressor has served historically as a model for gene regulation during mouse neurogenesis. Recent studies of REST have also suggested a conserved role for REST repressor function across lower species during aging. However, direct genome-wide studies for REST have been lacking for human brain. Here, we perform the first genome-wide analysis of REST binding in both human and mouse hippocampus. The majority of REST-occupied genes in human hippocampus are distinct from those in mouse. Further, the REST-associated genes unique to human hippocampus represent a new set related to innate immunity and inflammation, where their gene dysregulation has been implicated in aging-related neuropathology, such as Alzheimer's disease.

Realistic models based on the renormalizable grand unified theories have varieties of scalars, many of which are capable of mediating baryon ($B$) and lepton ($L$) number non-conserving processes. We identify all such scalar fields residing in ${\bf 10}$, $\overline{\bf 126}$ and ${\bf 120}$ dimensional irreps of $SO(10)$ which can induce baryon and lepton number violating interactions through the leading order $d=6$ and $d=7$ operators. Explicitly computing their couplings with the standard model fermions, we derive the effective operators including the possibility of mixing between the scalars stemming from a given representation. We find that such interactions at $d=6$ are mediated by only three sets of scalars: $T(3,1,-1/3)$, ${\cal T} (3,1,-4/3)$ and $\mathbb{T}(3,3,-1/3)$ and their conjugates. In the models with ${\bf 10}$ and $\overline{\bf 126}$, only the first has appropriate couplings to mediate the proton decay. While ${\cal T}$ and $\mathbb{T}$ can induce baryon number violating interactions when ${\bf 120}$ is present, ${\cal T}$ does not contribute to the proton decay at tree level because of its flavour antisymmetric coupling. Three additional colour triplets and their conjugates can mediate nucleon decay via $d=7$ operators which violate also the $B-L$. We give general expressions for partial widths of proton in terms of the fundamental Yukawa couplings and use these results to explicitly compute the proton lifetime and branching ratios for the minimal non-supersymmetric $SO(10)$ model based on ${\bf 10}$ and $\overline{\bf 126}$ Higgs. We find that the proton preferably decays into $\overline{\nu}\, K^+$ or $\mu^+\, K^0$ and list several distinct features of scalar mediated proton decay. If the latter dominates over the gauge mediated contributions, the proton decay spectrum provides a direct probe to the flavour structure of the underlying grand unified theory., Comment: 34 pages, 4 tables, 3 captioned figures. Version published in JHEP

A convenient and metal-free synthesis of vinyloxyimidazopyridine derivatives has been attained via BF3.OEt2 promoted one-pot multicomponent approach. This procedure involves a facile coupling of 2-aminopyridine derivatives with arylglyoxal and alkyne derivatives. BF3.OEt2 complexation has successfully catalyzed the reaction at room temperature. Utilization of transition metal-free catalyst, mild reaction conditions, easy handling and operational simplicity are key features of developed process.

Aim and Objective:: At present, the world is facing a global pandemic threat of SARSCoV- 2 or COVID-19 and to date, there are no clinically approved vaccines or antiviral drugs available for the treatment of coronavirus infections. Studies conducted in China recommended the use of liquorice (Glycyrrhiza species), an integral medicinal herb of traditional Chinese medicine, in the deactivation of COVID-19. Therefore, the present investigation was undertaken to identify the leads from the liquorice plant against COVID-19 using molecular docking simulation studies. Materials and Methods:: A set of reported bioactive compounds of liquorice were investigated for COVID-19 main protease (Mpro) inhibitory potential. The study was conducted on Autodock vina software using COVID-19 Mpro as a target protein having PDB ID: 6LU7. Results: Out of the total 20 docked compounds, only six compounds showed the best affinity towards the protein target, which included glycyrrhizic acid, isoliquiritin apioside, glyasperin A, liquiritin, 1-methoxyphaseollidin and hedysarimcoumestan B. From the overall observation, glycyrrhizic acid followed by isoliquiritin apioside demonstrated the best affinity towards Mpro representing the binding energy of -8.6 and -7.9 Kcal/mol, respectively. Nevertheless, the other four compounds were also quite comparable with the later one. Conclusion:: From the present investigation, we conclude that the compounds having oxane ring and chromenone ring substituted with hydroxyl 3-methylbut-2-enyl group could be the best alternative for the development of new leads from liquorice plant against COVID-19.

Although Ipilimumab (anti-CTLA-4) is FDA-approved for stage III/IV melanoma adjuvant treatment, it is not used clinically in first-line therapy, given the superior relapse-free survival (RFS)/toxicity benefits of anti-PD-1 therapy. However, it is important to understand anti-CTLA-4’s mechanistic contribution to combination anti-PD-1/CTLA-4 therapy and investigate anti-CTLA-4 therapy for BRAF-wild type melanoma cases reresected after previous adjuvant anti-PD-1 therapy. Our group published that nitric oxide (NO) increased within the immune effector cells among patients with longer RFS after adjuvant ipilimumab, whereas NO increased within the immune suppressor cells among patients with shorter RFS. Herein, we measured the post-translational modifications of STAT1 (nitration-nSTAT1 and phosphorylation-pSTAT1) that are important for regulating its activity via flow cytometry and mass spectrometry approaches. PBMCs were analyzed from 35 patients undergoing adjuvant ipilimumab treatment. Shorter RFS was associated with higher pSTAT1 levels before (p = 0.007) and after (p = 0.036) ipilimumab. Ipilimumab-treated patients with high nSTAT1 levels before and after therapy in PBMCs experienced decreased RFS, but the change in nSTAT1 levels before and after ipilimumab therapy was associated with longer RFS (p = 0.01). The measurement of post-translational modifications in STAT1 may distinguish patients with prolonged RFS from ipilimumab and provide mechanistic insight into responses to ipilimumab combination regimens.

Physical systems that exhibit brain-like behaviour are currently under intense investigation as platforms for neuromorphic computing. We show that discontinuous metal films, comprising irregular flat islands on a substrate and formed using simple evaporation processes, exhibit correlated avalanches of electrical signals that mimic those observed in the cortex. We further demonstrate that these signals meet established criteria for criticality. We perform a detailed experimental investigation of the atomic-scale switching processes that are responsible for these signals, and show that they mimic the integrate-and-fire mechanism of biological neurons. Using numerical simulations and a simple circuit model, we show that the characteristic features of the switching events are dependent on the network state and the local position of the switch within the complex network. We conclude that discontinuous films provide an interesting potential platform for brain-inspired computing.

Over the last 3 decades ATP-dependent chromatin remodelers have been thought to recognize chromatin at the level of single nucleosomes rather than higher-order organization of more than one nucleosome. We show the yeast ISW1a remodeler has such higher-order structural specificity, as manifested by large allosteric changes that activate the nucleosome remodeling and spacing activities of ISW1a when bound to dinucleosomes. Although the ATPase domain of Isw1 docks at the SHL2 position when ISW1a is bound to either mono- or di-nucleosomes, there are major differences in the interactions of the catalytic subunit Isw1 with the acidic pocket of nucleosomes and the accessory subunit Ioc3 with nucleosomal DNA. By mutational analysis and uncoupling of ISW1a’s dinucleosome specificity, we find that dinucleosome recognition is required by ISW1a for proper chromatin organization at promoters; as well as transcription regulation in combination with the histone acetyltransferase NuA4 and histone H2A.Z exchanger SWR1., Here the authors show that the preference of yeast chromatin remodeler ISW1a for dinucleosomes hinges on conformational changes that occur in the transition from binding mononucleosomes to dinucleosomes. These changes are critical for ISW1a organizing chromatin at promoters and regulating transcription in conjunction with other chromatin remodelers.

COVID-19 has ravaged the world and is the greatest of pandemics in human history, in the absence of treatment or vaccine the mortality and morbidity rates are very high. The present investigation was undertaken to screen and identify the potent leads from the Indian Ayurvedic herb, Asparagus racemosus (Willd.) against SARS-CoV-2 using molecular docking and dynamics studies. The docking analysis was performed on the Glide module of Schrödinger suite on two different proteins from SARS-CoV-2 viz. NSP15 Endoribonuclease and spike receptor-binding domain. Asparoside-C, Asparoside-D and Asparoside -F were found to be most effective against both the proteins as confirmed through their docking score and affinity. Further, the 100 ns molecular dynamics study also confirmed the potential of these compounds from reasonably lower root mean square deviations and better stabilization of Asparoside-C and Asparoside-F in spike receptor-binding domain and NSP15 Endoribonuclease respectively. MM-GBSA based binding free energy calculations also suggest the most favourable binding affinities of Asparoside-C and Asparoside-F with binding energies of −62.61 and −55.19 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease. HighlightsAsparagus racemosus have antiviral potentialPhytochemicals of Shatavari showed promising in-silico docking and MD resultsAsparaoside-C and Asparoside-F has good binding with target proteinsAsparagus racemosus holds promise as SARS-COV-2 (S) and (N) proteins inhibitor Communicated by Ramaswamy H. Sarma

An eco-compatible, facile and clean strategy for the synthesis of 1, 4-dihydropyridine (1, 4-DHP) derivatives has been reported through one pot multi-component Hantzsch reaction using glycerol as a...

The Public Health Emergency of International Concern declared the widespread outbreak of SARS-CoV-2 as a global pandemic emergency, which has resulted in 1,773,086 confirmed cases including 111,652 human deaths, as on 13 April 2020, as reported to World Health Organization. As of now, there are no vaccines or antiviral drugs declared to be officially useful against the infection. Saikosaponin is a group of oleanane derivatives reported in Chinese medicinal plants and are described for their anti-viral, anti-tumor, anti-inflammatory, anticonvulsant, antinephritis and hepatoprotective activities. They have also been known to have anti-coronaviral property by interfering the early stage of viral replication including absorption and penetration of the virus. Thus, the present study was undertaken to screen and evaluate the potency of different Saikosaponins against different sets of SARS-CoV-2 binding protein via computational molecular docking simulations. Docking was carried out on a Glide module of Schrodinger Maestro 2018-1 MM Share Version on NSP15 (PDB ID: 6W01) and Prefusion 2019-nCoV spike glycoprotein (PDB ID: 6VSB) from SARS-CoV-2. From the binding energy and interaction studies, the Saikosaponins U and V showed the best affinity towards both the proteins suggesting them to be future research molecule as they mark the desire interaction with NSP15, which is responsible for replication of RNA and also with 2019-nCoV spike glycoprotein which manage the connection with ACE2. [Formula: see text] Communicated by Ramaswamy H. Sarma.

The present research work was designed to examine the neuroprotective effect of ethanolic extract of Solanum virginianum Linn. (SV) in chronic construction injury (CCI) of sciatic nerve–induced neuropathic pain in rats. The extract was initially standardized by high-performance thin-layer chromatography using solasodine as a biomarker and was then subjected to assess the degree of mechanical allodynia, thermal allodynia, mechanical hyperalgesia, thermal hyperalgesia and biochemical evaluations. Administration of SV (100 and 200 mg/kg; p.o.) and pregabalin (10 mg/kg; p.o.) as a reference standard significantly debilitated hyperalgesia and allodynia and notably restored the altered antioxidant level and pro-inflammatory cytokine (IL-1β and TNF-α) expression in a dose-dependent manner. Further, to appraise the mechanistic approach of solasodine, docking simulation studies were done on the 3D structure of the voltage-gated N-type calcium channel (Cav 2.2), R-type calcium channel (Cav 2.3) and sodium channel (Nav 1.7), and the results revealed that solasodine properly positioned into Phe 19, Leu 32, Met 51 and Met 71 (FLMM pocket) of Cav 2.2 and Cav 2.3 and being a competitor of Ca2+/N-lobe it may inactivate these calcium channels but did not bind into the desired binding pocket of Nav 1.7. Thus, the study confirmed the role of solasodine as a major biomarker for the observed neuroprotective nature of Solanum virginianum.

A visible-light-mediated, mild and one-pot three-component reaction in the presence of organophotoredox catalyst Eosin Y using EtOH:H2O as reaction medium for the synthesis of 3-functionalized indole derivatives was developed. Visible light used in the protocol is green, inexpensive, readily available energy source. The sustainable reagents make the protocol compatible with green chemistry demands.

The specially designed pyrazole and pyrazole fused pyrimidines were subjected to the molecular docking studies with aurora kinase A, Hematopoietic cell kinase (hck) and anaplastic lymphoma kinase. The good interactions prompted us to synthesize the newer pyrazole and pyrazolo[3,4-d]pyrimidines. To prove the hypothesis about anticancer activity, the compounds were screened for their cytotoxicity against human cancer cell lines (MCF-7, K-562 and A-549) and compared with standard drugs. The hypothesis was supported as the IC50 values are found in lower micromolar ranges for six compounds and more potent in the case of chronic myeloid leukemia and lung carcinoma.

The purpose of this study was to describe the development of a solar-powered submersible pump system without the use of batteries in agriculture. The submersible pump system used a solar drive to run it. The implementation uses a combination of solar trackers, water storage tanks, power converters, and stabilizers. The results of the study explained that solar trackers increased the efficiency of solar units that track the sun throughout the day and convert solar energy into DC electrical power.