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For a natural number $n\geq 2$, the function $\phi_{n\mathcal{L}}(z)=1+nz/(n+1)+z^n/(n+1)$ maps the open unit disk onto a domain bounded by an epicycloid with $(n-1)$ cusps. A class of starlike functions associated with $\phi_{n\mathcal{L}}$ is defined in the unit disk and its sharp bounds on initial coefficients, various inclusion relations and radii problems related to the other subclasses of starlike functions are investigated. As an application, the corresponding results are determined in the limiting case for the class of normalized analytic functions $f$ satisfying $|zf'(z)/f(z)-1

Infertility is one of the predominant health issues, affecting 10-15% of reproductive- aged couples. An infertility evaluation should be considered in any couple that has failed to conceive in one year. Infertility can be subdivided into primary infertility (no prior conception) and secondary infertility (infertility following at least 1 prior conception). Here it is the case of primary infertility. In Ayurveda it can be correlated with Anaptaya Vandhya (that is who never has conceived) and Apraja Vandhya (that lady who never have conceived but can conceive by eliminating the underlying cause). In this case study, Ayurvedic management successfully treat the primary infertility. Main clinical finding: A married Hindu female patient of 28 years of age visited to OPD of National institute of Ayurveda, Jaipur on 24 October 2020 with chief complaint of wants issue since 3 years. She had associated complaint of sometimes milk like discharge from breast since 3 years. Diagnosis: Her HSG scan suggestive of right fallopian tube fimbrial block & left fallopian tube cornual blockage. Her USG scan suggestive of bilateral polycystic ovary & a tiny echogenic polyp of size 3.7x2.3mm in mid part of endometrial cavity. Her prolactin level was found elevated. Interventions: Treatment given was Beejasamskara, Uttarbasti with Apamarga kshara tail & Shudah bala tail along with oral medication. Outcome: She conceived after taking 6 months of treatment. She was given proper antenatal care along with garbhsamskara. She delivered a healthy female baby of weight 3.03kg on 7th Jan 2022. Conclusion: This case study shows the potential of Beejasamskara, Uttarbasti in the management of infertility and the role of Garbhsamskara during the antenatal period.

Combined Supplementary Figures, Supplementary Tables, Legends and Key Resource Tables

Supplementary Material-1. Heatmap shows all the known ligand-receptor interactions between different cell types identified by CellPhoneDB in the OvD5-SS2 dataset.

SupplementaryMethods.docx from Oncostatin M Receptor–Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth

Although patients with advanced ovarian cancer may respond initially to treatment, disease relapse is common, and nearly 50% of patients do not survive beyond five years, indicating an urgent need for improved therapies. To identify new therapeutic targets, we performed single-cell and nuclear RNA-seq data set analyses on 17 human ovarian cancer specimens, revealing the oncostatin M receptor (OSMR) as highly expressed in ovarian cancer cells. Conversely, oncostatin M (OSM), the ligand of OSMR, was highly expressed by tumor-associated macrophages and promoted proliferation and metastasis in cancer cells. Ovarian cancer cell lines and additional patient samples also exhibited elevated levels of OSMR when compared with other cell types in the tumor microenvironment or to normal ovarian tissue samples. OSMR was found to be important for ovarian cancer cell proliferation and migration. Binding of OSM to OSMR caused OSMR–IL6ST dimerization, which is required to produce oncogenic signaling cues for prolonged STAT3 activation. Human monoclonal antibody clones B14 and B21 directed to the extracellular domain of OSMR abrogated OSM-induced OSMR–IL6ST heterodimerization, promoted the internalization and degradation of OSMR, and effectively blocked OSMR-mediated signaling in vitro. Importantly, these antibody clones inhibited the growth of ovarian cancer cells in vitro and in vivo by suppressing oncogenic signaling through OSMR and STAT3 activation. Collectively, this study provides a proof of principle that anti-OSMR antibody can mediate disruption of OSM-induced OSMR–IL6ST dimerization and oncogenic signaling, thus documenting the preclinical therapeutic efficacy of human OSMR antagonist antibodies for immunotherapy in ovarian cancer.Significance:This study uncovers a role for OSMR in promoting ovarian cancer cell proliferation and metastasis by activating STAT3 signaling and demonstrates the preclinical efficacy of antibody-based OSMR targeting for ovarian cancer treatment.

Introduction - Rifampin, isoniazid, pyrazinamide, and ethambutol are antitubercular drugs that have been licenced by the FDA for the treatment of Mycobacterium tuberculosis infections. Antitubercular medicines are drugs that are used to treat tuberculosis. The term "anthelmintic" refers to a medicine used to treat parasitic worm infestations in animals. This comprises both flat and round worms, such as flukes (trematodes) and tapeworms (cestodes) (nematodes). Aim of this study - The primary aim of this research is to develop and validate simple, fast, reliable, robustness and ruggedness analytical procedures for anthelmintics (ALB) and antitubercular (ETH) medicines. Material and Methods - Two CT reagents, iodine and picric acid, were used to produce two simple and somewhat sensitive Albendazole (ALB) and Ethionamide (ETN) techniques. The CT complex with the placebo blank had almost the same absorbance as the reagent blank, indicating that there was no interference by using Systronics model 166 digital spectrophotometer tools. Organic solvents were employed to dissolve all of the chemicals, which were of analytical reagent grade.

Target of vision 2020- right to sight is to control blindness. Blindness in children affects their psychological and social growth. Various research were done on community and in blind school to know about the prevalence and causes of blindness in children. Total five- community based studies were done for knowing about the prevalence of blindness that also includes two refractive error studies for the children below 16 years of age in India. Result of data collected from blind school showed that blindness in children shifted from corneal causes to whole globe abnormalities. Blindness in children has different impact in different region based upon the socioeconomic development of that region, primary health care centre present in that region and also the eye care services provided to the people. The strategies to control blindness should be region specific. Solution has to be drafted based on regional challenges, in such a way that it helps to cure the blindness and also help to reduce the chances of blindness in future. Prevention strategies is targeted towards proper and timely immunization, control of Vit A deficiency by providing healthy and balanced diet and to educate people about the outcome of blindness and also providing tertiary level care to treat the causes. No available data is present to know about the causes and incidence of blindness in children. Rehabilitation programme done on community level help to identify the incidence and causes of blindness in children present in India. In this article we have discussed about childhood blindness, prevalence of childhood blindness, causes of childhood blindness, prevention of childhood blindness, control of childhood blindness, programmes running for childhood blindness. Refractive error such as myopia leads to blindness in children. School going children are at increase risk for developing blindness due to refractive error that is not corrected. Control of blindness in children is very important because a child suffer more years from blindness than adults. Around 1.4 million are affected by childhood blindness globally. Per year approx 500000 children are affected and became blind. The cause that is most common and in fact single for childhood blindness worldwide is vit A deficiency. By the year 2020, WHO has took the initiative to eliminate blindness. Some of the factors that can help are good nutrition to child, taking proper care of mother and child, proper immunization of mother and child, health education etc.

Out of all the cranial nerves “Trigeminal Nerve” is the fifth cranial nerve. Trigeminal nerve possesses both the components i.e. mixed components as well as sensitive components that’s why trigeminal nerve is known as a mixed nerve. The sensitive component of the trigeminal nerve takes up the sensation from most of the part of the face and the mucous membrane to the central nervous system and that’s why it is responsible for the disease which is known as trigeminal neuralgia. The characteristic feature of the trigeminal neuralgia is the sudden onset of pain which is sharp and lacerating, and that may last from few of the seconds to few minutes. Trigeminal neuralgia more frequently affects the female as compared to the male.

The ongoing COVID-19 pandemic has seriously impacted countries across the globe. The pandemic has created a completely new teaching-learning environment of interaction for early childhood educators. In many countries, face-to-face teaching has been replaced by remote teaching, while in others, there have been intermittent lockdowns and limited interruptions to regular teaching norms. Given the play-based nature of preschool teaching-learning activities in most countries, educators are required to reimagine the sociocultural relationships to their pedagogical practices in their everyday teaching-learning contexts. This paper sheds light on educators' experiences and the dramatic shift in their indoor-outdoor teaching-learning environment due to the evolving health measures. The study draws on notions of teachers' identities and Vygotsky's cultural-historical concept of social situation of development (Vygotsky, 1994) to capture the new forms of relationships that early childhood educators experienced with their pedagogical environments across different countries during the pandemic. Data were collected from preschool teachers across five countries-Australia, Bangladesh, Norway, Singapore and India using online surveys which included open- and close-ended questions. Findings reveal the on-ground realities and teachers' adaptations to new pedagogies emerging across the five countries. The new digital environments provided an equally new dimension for change. These changes were seen in interactions, relationships within the everyday pedagogical contexts, as well as the shifting physical and social environment of early years educators.La pandémie actuelle de COVID-19 a gravement touché les pays du monde entier. La pandémie a créé un tout nouvel environnement d'interaction enseignement-apprentissage pour les éducateurs de la petite enfance. Dans de nombreux pays, l'enseignement en face à face a été remplacé par l'enseignement à distance, tandis que dans d'autres, il y a eu des blocages intermittents et des interruptions limitées des normes d'enseignement régulières. Étant donné la nature ludique des activités d'enseignement-apprentissage préscolaires dans la plupart des pays, les éducateurs sont tenus de réimaginer les relations socioculturelles avec leurs pratiques pédagogiques dans leurs contextes d'enseignement-apprentissage quotidiens. Cet article met en lumière les expériences des éducateurs et le changement radical de leur environnement d'enseignement-apprentissage intérieur-extérieur en raison de l'évolution des mesures de santé. L'étude s'appuie sur les notions d'identité des enseignants et le concept culturel et historique de Vygotsky de situation sociale de développement (Vygotsky, 1994) pour saisir les nouvelles formes de relations que les éducateurs de la petite enfance ont vécues avec leurs environnements pédagogiques dans différents pays pendant la pandémie. Les données ont été recueillies auprès d'enseignants du préscolaire dans cinq pays—Australie, Bangladesh, Norvège, Singapour et Inde à l'aide d'enquêtes en ligne comprenant des questions ouvertes et fermées. Les résultats révèlent les réalités sur le terrain et les adaptations des enseignants aux nouvelles pédagogies émergentes dans les cinq pays. Les nouveaux environnements numériques ont fourni une dimension tout aussi nouvelle pour le changement. Ces changements ont été observés dans les interactions, les relations au sein des contextes pédagogiques quotidiens, ainsi que dans l'environnement physique et social changeant des éducateurs de la petite enfance.La pandemia de COVID-19 en curso ha afectado gravemente a países de todo el mundo. La pandemia ha creado un entorno de interacción de enseñanza-aprendizaje completamente nuevo para los educadores de la primera infancia. En muchos países, la enseñanza presencial ha sido reemplazada por la enseñanza a distancia, mientras que en otros, ha habido bloqueos intermitentes e interrupciones limitadas de las normas de enseñanza regulares. Dada la naturaleza basada en el juego de las actividades de enseñanza-aprendizaje preescolar en la mayoría de los países, los educadores deben reinventar las relaciones socioculturales con sus prácticas pedagógicas en sus contextos cotidianos de enseñanza-aprendizaje. Este documento arroja luz sobre las experiencias de los educadores y el cambio dramático en su entorno de enseñanza-aprendizaje interior y exterior debido a la evolución de las medidas de salud. El estudio se basa en las nociones de las identidades de los maestros y el concepto histórico-cultural de Vygotsky sobre la situación social del desarrollo (Vygotsky, 1994) para capturar las nuevas formas de relaciones que los educadores de la primera infancia experimentaron con sus entornos pedagógicos en diferentes países durante la pandemia. Se recopilaron datos de maestros de preescolar en cinco países: Australia, Bangladesh, Noruega, Singapur e India mediante encuestas en línea que incluían preguntas abiertas y cerradas. Los hallazgos revelan las realidades sobre el terreno y las adaptaciones de los profesores a las nuevas pedagogías que surgen en los cinco países. Los nuevos entornos digitales proporcionaron una dimensión igualmente nueva para el cambio. Estos cambios se observaron en las interacciones, las relaciones dentro de los contextos pedagógicos cotidianos, así como en el entorno físico y social cambiante de los educadores de la primera infancia.

While trade opening is generally welfare enhancing, it requires a reallocation of capital and labor across sectors and firms. The empirical evidence on how this reallocation works is still relative...

Multiple primary cancers are gradually becoming a regular condition and frequently result in many diagnostic and therapeutic difficulties. In our case report we present a 68-year female with breast lump who was incidentally diagnosed with chronic myeloid leukemia. The fine needle aspiration biopsy (FNAC) of the breast lump lead to the diagnosis of Invasive ductal carcinoma.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of primary gastrointestinal lymphomas. It is a clinically heterogenous disease as most patients respond well to therapy, however a significant proportion of these patients become refractory or eventually relapse. Different prognostic factors for response and survival have been described for DLBCL. Immunophenotypic algorithms with small panels of biomarkers have been developed to translate the robust information from molecular studies into a routine clinical. platform. One of these biomarkers is MUM-1 which is used as a marker for classification of diffuse large B cell lymphoma into ABC type and its expression is associated with poorer overall survival as stated by various studies. We aim to study the expression pattern of MUM-1 IHC in primary gastrointestinal diffuse large B cell lymphomas and its role in prognosis and survival outcome. Materials and Methods: It was a five-year retrospective study where 40 cases of primary gastrointestinal DLBCL were identified, and MUM-1 IHC was done in 29 cases. Follow up and subsequent survival analysis was done. Results: MUM-1 was positive in 7 (24%) and negative in 22 (76%) cases of primary gastrointestinal DLBCL. The overall survival of patients with DLBCL with MUM-1 [removed]42.9%) was shorter than those without MUM-1 [removed]72.7%). This suggested that MUM-1 expression in cases with DLBCL is associated with poorer prognosis. Conclusion: Multicentre large studies are warranted to study the role of MUM-1 IHC in prognosis of primary gastrointestinal DLBCL. Keywords: Activated B cell type, Gastrointestinal lymphoma, Gene expression profiling, Germinal centre B-cell, Immunohistochemistry.

We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low-intermediate shear viscous flow, in which aggregation is mediated by the interaction of α(IIb)β(3) receptors on the platelets membrane and fibrinogen (Fg). This multiscale model uses coarse grained molecular dynamics (CGMD) for platelets at the microscales, and dissipative particle dynamics (DPD) for the shear flow at the macroscales, employing our hybrid aggregation force field for modeling molecular level receptor ligand bonds. We define an aggregation tensor and use it to quantify the molecular level contact characteristics between platelets in an aggregate. We perform numerical studies under different flow conditions for platelet doublets and triplets and evaluate the contact area, detaching force, and minimum distance between different pairs of platelets in an aggregate. We also present the dynamics of applied stress and velocity magnitude distributions on the platelet membrane during aggregation and quantify the increase in stress in the contact region under different flow conditions. Integrating the knowledge from our previously validated models, together with new aggregation scenarios, our model can dynamically quantify aggregation characteristics and map stress and velocity distribution on the platelet membrane which are difficult to measure in vitro, thus providing an insight into mechanotransduction bond formation response of platelets to flow induced shear stresses. This modeling framework, together with the tensor method for quantifying inter-platelet contact, can be extended to simulate and analyze larger aggregates and their adhesive properties.

Background: Communication between cancer cells and surrounding cells in the tumor microenvironment (TME) is critical for tumor metastasis. There has been an increasing focus on how tumor-derived extracellular vesicles (EVs) contribute to the complex intracellular communications within the TME. More recent characterizations in both mice and humans have demonstrated that expression of the immune checkpoint molecule, programmed death ligand-1 (PD-L1) on EVs contributes to systemic immunosuppression, higher overall tumor burdens, and decreased survival of a variety of cancer types. In ovarian carcinoma, macrophages are reprogrammed toward pro-tumorigenic phenotypes, including the release of anti-inflammatory cytokines and expression of immunosuppressive molecules such as arginase-1 and PD-L1. However, a detailed mechanism that explains how tumor-derived EVs induce immunosuppressive phenotype in macrophages is necessary to develop novel immunotherapy strategies for advanced ovarian cancer treatment. The present study aimed to examine the effect of EVs derived from ovarian cancer cells on macrophage functions. Methods: We isolated murine peritoneal macrophages from naïve C57BL/6 female mice and co-cultured the macrophages with EVs derived from ovarian cancer (ID8-Trp53-/-Brca2-/-) cell lines. The expression of PD-L1, CD206, interleukin-6 (IL-6), and other inflammatory cytokines on EVs treated macrophages was evaluated using flow cytometry and a cytokine array kit. Further, we created Rab27aKO ID8 cell lines to generate ovarian cancer in vivo mouse models for studying the effect of exogenous EVs on the immunosuppressive ability of macrophages and tumor progression. Results: Our results indicate that EVs uptake efficiency of macrophages is higher than fibroblast, endothelial, and mesothelial cells. We found that tumor-derived EVs can significantly upregulate the expressions of PD-L1, CD206, and IL-6 on macrophages to support tumor growth. Treatment of macrophages with EVs also decreased their phagocytic ability. In addition, our data show that in the Rab27aKO ovarian cancer in vivo mouse model, intravenous injection of tumor-derived EVs increased the tumor burden, metastasis, and ascites accumulation as compared to PBS control. EVs treatment increased the infiltration of tumor-associated macrophages (TAM) in ascites. We also found increased expression of PD-L1 and CD206 on TAM isolated from ascites. Conclusion: We uncover a tumor-promoting role of ovarian cancer-derived EVs on reprogramming TAM towards pro-tumor phenotype. Our data suggest that tumor-derived EVs contribute to the formation of an immunosuppressive microenvironment to promote ovarian cancer growth. Citation Format: Sonam Mittal, Ishaque Pulikkal Kadamberi, Prachi Gupta, Sudhir Kumar, Jasmine George, Anjali Geethadevi, Pradeep Chaluvally-Raghavan, Sunila Pradeep. Tumor-derived extracellular vesicles induce macrophages immunosuppressive polarization to promote ovarian cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2321.

Introduction: Head and neck lesions are very common in day to day practice. These diseases range from common cold to the uncommon, malignant neoplasms. These lesions are responsible for very high morbidity and mortality. Factors known to contribute to the risk of developing head and neck cancer are smokeless tobacco (Pan masala, soda), alcohol, HPV viral infections, etc. Smokeless tobacco is commonly used in Northern part of India, especially in Uttar Pradesh. Aim: To evaluate the diagnosis, frequency and histopathological subtypes of head and neck lesions and their distribution in different age groups and sex in Western Uttar Pradesh. Settings and Design: A retrospective study of 3 years from March 2014 to February 2017 was conducted and the data were collected from the archives of the department. The data were analyzed using SPSS version 15.0. Materials and Methods: All the biopsies from the head and neck region, which were submitted for histopathology in the Post Graduate department of Pathology, Rohilkhand Medical College and Hospital, Bareilly, were reviewed and analyzed for their demographic profile, age, gender, site and diagnosis. The lesions were then categorized accordingly as inflammatory, benign and malignant. Results: All the lesions of head and neck region, diagnosed on histopathology were included in the present study. A total of three hundred twenty one biopsies were studied, including 212 (66%) males and 109 (34%) females (M: F=1.9:1). 197 (61%) of the cases were benign, followed by 69 (22%) malignant and 55 (17%) inflammatory lesions. The maximum numbers of malignant cases were in the age group of 41 to 50 years with Squamous cell carcinoma as the most common histopathological type. The most common site of malignant lesions was the oral cavity. The maximum benign lesions were in the 11-20 years age group. Conclusions: The present study helped us in assessing the frequency as well as the different histopathological types of head and neck lesio

In this work, a simple procedure for the preparation of an inkjet printed disposable graphene electrode is reported. Commercial graphene ink was printed on a kapton substrate and the resulting electrode was 30 min treated by oxygen plasma, then modified by a bismuth salt. The as prepared electrode was characterized by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), laser scanning microscopy (LSM) and scanning electron microscopy (SEM) coupled to energy-dispersive X-ray spectroscopy (EDX). The sensing properties of the characterized electrodes were then investigated using cyclic voltammetry and Electrochemical Impedance Spectroscopy (EIS). After-wards, these electrodes were exploited in a comparative way for the electroa-nalysis of Cadmium(II) and Lead(II) ions. An increase in the electrode sensi-tivity due to its modification and to the presence of bismuth was observed. Some preliminary experiments based on stripping square wave voltammetry highlighted the interest of using the proposed disposable inkjet printed elec-trodes for the electrochemical detection of heavy metals in tap water.

Data centers (DCs) have become the critical and irreplaceable infrastructure to drive this ever-growing trend because of the exponential expansion of Internet services. In general, DC has several data & storage nodes connected by a network that is specially built, called Data Center Network (DCN). DCN functions as a communications backbone also play a significant role in maximizing the operation of DC. However, the infrastructure and operations are very difficult in comparison with the conventional network compared with unique DCN specifications, including a wide range of applications, high power density, and high reliability. In this paper, the Bellmanford MST algorithm is used for FAT-tree-based routing. The main characteristic of the FAT Tree is that the links which are used for connecting nodes from different levels may have different bandwidth. The Bellmanford algorithm used here is the shortest path algorithm which provides a reliable and short path for the route nodes to travel which provides fewer time complexities in data center networking.

Merging polymer-supported asymmetric organocatalysis with continuous flow in a packed bed reactor has been used as the key, enantiodetermining step in a short synthesis of indoloquinolizidines. Using this approach, a highly enantioselective, solvent-free and rapid conjugate addition of dimethyl malonate to a diverse family of cinnamaldehydes in continuous flow, allowing the preparation of relevant oxodiesters in multigram amounts has been developed. The obtained Michael adducts have been used to complete an expedient diastereoselective synthesis of indoloquinolizidine

Metal–insulator–semiconductor (MIS)-based Pt/La2O3/SiOXNY/p-Si/Pt structures are fabricated using ultrathin silicon oxynitride (SiOXNY ~ 4 nm) interfacial layer underneath of lanthanum (III) oxide (La2O3 ~ 7.8 nm) with Pt as gate electrode for CMOS applications. Capacitance–voltage (C–V) characteristics of Pt/La2O3/SiOXNY/p-Si/Pt at 500 kHz showed a positive gate bias threshold voltage (Vth) shift of ~ 0.43 V (~ 43.8%) and flat-band (Vfb) shift of ~ 1.24 V (~ 42.3%) as compared to Pt/La2O3/p-Si/Pt MIS structures, attributing to the reduction in effective positive oxide charges at La2O3/SiOXNY/Si gate stack. Likewise, conductance–voltage (G–V) characteristics show ~ 0.56 (~ 44.4%) reduction in FWHM for Pt/La2O3/SiOXNY/p-Si/Pt as compared to Pt/La2O3/p-Si/Pt MIS structures revealing the reduction in interface states at La2O3/SiOXNY/Si interface. There is a considerable reduction of effective oxide charge concentration (Neff) ~ 3.99 × 1010 cm−2 by (~ 15.2%) and ~ 56.8% lower gate leakage current density ~ 4.47 × 10−7 A/cm2 (|J|–V) at − 1 V for SiOXNY based MIS structures w.r.t its counterpart. Capacitance–time (C–t) characteristics, constant voltage stress (CVS) and temperature measurements for C–V and |J|–V demonstrate the considerable retention ~ 12 years, electrical improvement and reliability of MIS structures. The depth profile analysis X-ray photoelectron spectroscopy (XPS) for SiOXNY/Si gate stack clearly reveals that less nitrogen concentration in bulk than SiOXNY/Si interface. Atomic force microscopy (AFM) micrographs of La2O3/Si and SiOXNY/Si showed the significantly lesser r.m.s roughness of ~ 1.11 ± 0.39 nm and ~ 0.97 ± 0.11 nm, respectively. Thus, the ultrathin SiOXNY interfacial layer underneath of La2O3 demonstrates a significantly improved electrical performance and prelude the gate stack strong potential for reliable CMOS logic devices and integrated circuits.

The recent increase in dataset size has brought about significant advances in natural language understanding. These large datasets are usually collected through automation (search engines or web crawlers) or crowdsourcing which inherently introduces incorrectly labeled data. Training on these datasets leads to memorization and poor generalization. Thus, it is pertinent to develop techniques that help in the identification and isolation of mislabelled data. In this paper, we study the applicability of the Area Under the Margin (AUM) metric to identify and remove/rectify mislabelled examples in NLP datasets. We find that mislabelled samples can be filtered using the AUM metric in NLP datasets but it also removes a significant number of correctly labeled points and leads to the loss of a large amount of relevant language information. We show that models rely on the distributional information instead of relying on syntactic and semantic representations., EMNLP BlackBoxNLP 2021

The interaction between tumor cells and macrophages in the tumor microenvironment plays an essential role in metabolic changes in macrophages and reprograms them towards a pro-tumorigenic phenotype. Increasing evidence indicates that macrophage metabolism is a highly complex process and may not be as simple as previously thought. Pro-inflammatory stimuli switch macrophages towards an M1-like phenotype and rely mainly on aerobic glycolysis and fatty acid synthesis, whereas anti-inflammatory stimuli switch macrophages towards an M2-like phenotype. M2-like macrophages depend more on oxidative phosphorylation (OXPHOS) and fatty acid oxidation. However, this metabolically reprogrammed phenotypic switch in macrophages remained a mystery for a while. Therefore, through this review, we tend to describe how macrophage immunometabolism determines macrophage phenotypes and functions in tumor microenvironments (TMEs). Furthermore, we have discussed how metabolic reprogramming in TAM can be used for therapeutic intervention and drug resistance in ovarian cancer.

Although patients with advanced ovarian cancer may respond initially to treatment, disease relapse is common, and nearly 50% of patients do not survive beyond five years, indicating an urgent need for improved therapies. To identify new therapeutic targets, we performed single-cell and nuclear RNA-seq data set analyses on 17 human ovarian cancer specimens, revealing the oncostatin M receptor (OSMR) as highly expressed in ovarian cancer cells. Conversely, oncostatin M (OSM), the ligand of OSMR, was highly expressed by tumor-associated macrophages and promoted proliferation and metastasis in cancer cells. Ovarian cancer cell lines and additional patient samples also exhibited elevated levels of OSMR when compared with other cell types in the tumor microenvironment or to normal ovarian tissue samples. OSMR was found to be important for ovarian cancer cell proliferation and migration. Binding of OSM to OSMR caused OSMR–IL6ST dimerization, which is required to produce oncogenic signaling cues for prolonged STAT3 activation. Human monoclonal antibody clones B14 and B21 directed to the extracellular domain of OSMR abrogated OSM-induced OSMR–IL6ST heterodimerization, promoted the internalization and degradation of OSMR, and effectively blocked OSMR-mediated signaling in vitro. Importantly, these antibody clones inhibited the growth of ovarian cancer cells in vitro and in vivo by suppressing oncogenic signaling through OSMR and STAT3 activation. Collectively, this study provides a proof of principle that anti-OSMR antibody can mediate disruption of OSM-induced OSMR–IL6ST dimerization and oncogenic signaling, thus documenting the preclinical therapeutic efficacy of human OSMR antagonist antibodies for immunotherapy in ovarian cancer. Significance: This study uncovers a role for OSMR in promoting ovarian cancer cell proliferation and metastasis by activating STAT3 signaling and demonstrates the preclinical efficacy of antibody-based OSMR targeting for ovarian cancer treatment.

The corrosion inhibition of mild steel in 0.5 M H2SO4 solution by the extract of litchi peel (Litchi chinensis) was studied by weight loss method, potentiodynamics polarization and electrochemical impedance spectroscopy (EIS). The results show that the litchi peels extract acts as mixed-type inhibitor. The inhibition of corrosion is found to be due to adsorption of the extract on metal surface, which is in conformity with Langmuir’s adsorption isotherm. UV–Vis, Fourier transform infrared (FT-IR) spectroscopy and Scanning electron microscopy (SEM) studies confirm that the inhibition of corrosion of mild steel occurs through adsorption of the inhibitor molecules. Keywords: A. Mild steel, B. EIS, SEM, IR spectroscopy, C. Acid corrosion

INTRODUCTION: We developed a multiscale model to simulate the dynamics of platelet aggregation by recruitment of unactivated platelets flowing in viscous shear flows by an activated platelet deposited onto a blood vessel wall. This model uses coarse grained molecular dynamics for platelets at the microscale and dissipative particle dynamics for the shear flow at the macroscale. Under conditions of relatively low shear, aggregation is mediated by fibrinogen via αIIbβ3 receptors. METHODS: The binding of αIIbβ3 and fibrinogen is modeled by a molecular-level hybrid force field consisting of Morse potential and Hooke law for the nonbonded and bonded interactions, respectively. The force field, parametrized in two different interaction scales, is calculated by correlating with the platelet contact area measured in vitro and the detaching force between αIIbβ3 and fibrinogen. RESULTS: Using our model, we derived, the relationship between recruitment force and distance between the centers of mass of two platelets, by integrating the molecular-scale inter-platelet interactions during recruitment aggregation in shear flows. Our model indicates that assuming a rigid-platelet model, underestimates the contact area by 89% and the detaching force by 93% as compared to a model that takes into account the platelet deformability leading to a prediction of a significantly lower attachment during recruitment. CONCLUSIONS: The molecular-level predictive capability of our model sheds a light on differences observed between transient and permanent platelet aggregation patterns. The model and simulation framework can be further adapted to simulate initial thrombus formation involving multiple flowing platelets as well as deposition and adhesion onto blood vessels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12195-019-00583-2) contains supplementary material, which is available to authorized users.

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Simple Summary Accumulating evidence has reported that extracellular vesicles secreted by different tumor microenvironment cells can interfere with the host immune system. These vesicles transmit the signals in the tumor microenvironment that affect the proliferation, apoptosis, activation, and, metabolism of immune cells such as dendritic cells, T cells, macrophages, and natural killer cells, creating a pro-tumoral environment for tumor progression and survival. In this review, we summarize the recent literature on the function of extracellular vesicles derived from tumor cells and immune cells in regulating the critical processes associated with cancer progression. Besides, we also provide insights on how the extracellular vesicles are employed as diagnostic and prognostic biomarkers and drug carriers in cancer. Abstract The development of effective therapies for cancer treatment requires a better understanding of the tumor extracellular environment and a dynamic interaction between tumor cells, the cells of the immune system, and the tumor stroma. Increasing evidence suggests that extracellular vesicles play an important role in this interaction. Extracellular vesicles are nanometer-sized membrane-bound vesicles secreted by various types of cells that facilitate intracellular communication by transferring proteins, various lipids, and nucleic acids, especially miRNAs, between cells. Extracellular vesicles play discrete roles in the immune regulatory functions, such as antigen presentation, and activation or suppression of immune cells. Achieving therapeutic intervention through targeting of extracellular vesicles is a crucial area of research now. Thus, a deeper knowledge of exosome biology and the molecular mechanism of immune regulation is likely to provide significant insight into therapeutic intervention utilizing extracellular vesicles to combat this dreadful disease. This review describes the recent updates on immune regulation by extracellular vesicles in cancer progression and possible use in cancer therapy.

SUMMARY Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3′ untranslated region (3′UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover a mechanism by which FXR1 promotes cMYC levels in cancer cells., Graphical abstract, In brief George et al. demonstrate that FXR1 binds to the AREs within the 3′UTR of MYC mRNA and improves its stability. The authors also show that the RGG domain of FXR1 interacts with eIF4A1 and eIF4E and facilitates recruitment of the eIF4F complex to translation initiation sites for cMYC translation.

BackgroundThe RNA-binding protein FXR1 (fragile X-related protein 1) has been implicated as an important regulator of post-transcriptional changes of mRNAs. However, its role in mRNA circularization and recruitment of eukaryotic translation initiation factors for protein translation remains obscure. Here, we aimed to investigate the molecular mechanisms and potential clinical applications of FXR1 in ovarian cancer growth and progression.MethodsFXR1 copy number variation, mRNA expression, protein levels, and their association with prognosis were determined in clinical datasets. An orthotopic ovarian cancer model and bioluminescence imaging were used for preclinical evaluation of FXR1 in vivo. Reverse phase protein arrays (RPPA) and qPCR arrays were performed to identify FXR1’s key targets and downstream effects. SUnSET and polysome profiling were used to determine the translational effects of FXR1. Immunoprecipitation and immunofluorescence were performed to identify the interaction between FXR1 and cMYC mRNA and eIF4F complex. RNA-immunoprecipitation (RIP), RNA electrophoretic mobility shift assays (REMSA), proximity ligation assays (PLA), and biochemical assays were used to identify the specific site on cMYC mRNA to which FXR1 binds to promote mRNA circularization and translation.ResultsWe found that amplification and copy-gain of FXR1 increased the expression of FXR1 mRNA and FXR1 protein in ovarian cancer patients, and these events associated with poor prognosis. We demonstrated that FXR1 binds to AU-rich elements (ARE) within the 3’ untranslated region (3’UTR) of cMYC. As a consequence, FXR1 binding to cMYC 3’UTR leads to the circularization of mRNA and facilitated the recruitment of eukaryotic translation initiation factors (eIFs) to translation start site for improving protein synthesis.ConclusionWe found that FXR1 upregulates a known oncogene, cMYC, by binding to AU-rich elements within the 3’UTR, leading to the recruitment of the eIF4F complex for cMYC translation. Our findings uncover a novel mechanism of action of FXR1 in tumorigenesis and provides opportunities to use FXR1 and its downstream effectors as biomarkers or therapeutic targets in ovarian and other cancers.

Under type-2 diabetes, insulin resistance develops in skeletal muscles as a key defect and to study the disorder, its manifestation, and possible solution, measurement of glucose uptake is a fundamental necessity. Of various approaches (i.e. scintillation counting, flow cytometry, fluorometry and spectrophotometry) fluorescent labelled glucose analogue, 2-NBDG solution is the most popular one. Although 2-NBDG based assay is the most widely used approach in various cells including skeletal muscle, even then all available protocols possess huge variability which impacts the overall data reproducibility. Moreover, starvation (use of glucose/serum free medium), one of the prerequisite condition for glucose uptake assay, itself induces stress specifically during longer pre-incubation periods and alters muscle cell metabolism and morphology, but the fact has not been duly considered. Therefore in the present article, using specific skeletal muscle cells i.e. C2C12 myotubes, we have re-established the conditions like pre-incubation time period, concentrations of insulin, glucose and serum/BSA while maintaining the cultured myotubes in morphologically healthy state. Our lab standardized protocols were observed to be effective in studying insulin resistance condition induced by diverse stresses (oxidative & inflammation) in myotubes. Comparative study conducted with already established protocols demonstrates that the present method is more efficient, effective and better improvised for studying glucose uptake in C2C12.

The global pandemic Novel Coronavirus Disease (COVID-19), which originated in Wuhan, has affected the countries worldwide and has been declared as a public health emergency by World Health Organisation. Because of the exclusive features of dental healthcare set-ups, risk of cross-contamination is greater between patients and dental personnel due to high chances of getting in contact with suspected or asymptomatic COVID-19 patients. Preventive measures are essential to be taken for prevention of furthermore spread of nosocomial infection. The present article provides a brief overview on COVID-19 in dental settings and recommended protocols for screening/assessment, patient management and precautions for dental health care professionals.

As the technology feature size shrinks, leakage power is dominating in the total chip power consumption of VLSI circuits. In this work to reduce the leakage power, sleepy transistor technique is used for differential ring oscillator (RO). First design is proposed using CMOS inverter stage in a differential manner to form ring oscillator with sleepy NMOS and sleepy PMOS transistors. Second design of differential ring oscillator is proposed with CMOS cross-coupled cell with sleepy NMOS and PMOS transistors. Further, substrate-biasing concept has been applied to proposed design for improvement in the power consumption. The power consumption for sleepy NMOS inverter stage differential ring oscillator (RO) is 0.696–0.953 mW and the frequency of operation is 3.09–4.56 GHz. Sleepy NMOS cross-coupled based ring oscillator design shows the power consumption of 0.78–1.21 mW at an operating frequency of 2.23–4.25 GHz. The power consumption for sleepy PMOS inverter stage differential RO design is 1.95–2.04 mW and the frequency of operation is 4.41–4.63 GHz. Further, sleepy PMOS cross-coupled RO design shows power consumption of 0.97–1.06 mW at an operating frequency of 2.26–2.41 GHz. The substrate biasing of sleepy NMOS inverter stage ring oscillator design gives power consumption of 0.862–0.924 mW and the frequency of operation is 4.16–4.45 GHz. Substrate biasing of sleepy NMOS cross-coupled ring oscillator design shows power consumption of 1.06–1.16 mW and output frequency varies from 1.86–2.05 GHz. The simulations have been performed using SPICE in 0.18 µm CMOS technology. Results of power consumption, tuning range, phase noise, FoM and output frequency have been compared with earlier circuits and proposed circuits show improvement in results.

Recently, biomaterials have been designed to contain redox-sensitive moieties, such as thiols and disulfides, to impart responsive degradation and/or controlled release. However, due to the high sensitivity of cellular redox-based systems which maintain free-radical homeostasis (e.g. glutathione/glutathione disulfide), if these biomaterials modify the cellular redox environment, they may inadvertently affect cellular compatibility and/or oxidative stress defenses. In this work, we hypothesize that the degradation products of a poly(β-amino ester) (PBAE) hydrogel formed with redox sensitive disulfide (cystamine) crosslinking could serve as a supplement to the environmental cellular antioxidant defenses. Upon introduction into a reducing environment, these disulfide-containing hydrogels cleave to present bound-thiol groups, yet remain in the bulk form at up to 66 mol% cystamine of the total amines. By controlling the molar fraction of cystamine, it was apparent that the thiol content varied human umbilical vein endothelial cell (HUVEC) viability IC50 values across an order of magnitude. Further, upon introduction of an enzymatic oxidative stress generator to the cell culture (HX/XO), pre-incubated thiolated hydrogel degradation products conferred cellular and mitochondrial protection from acute oxidative stress, whereas non-reduced disulfide-containing degradation products offered no protection. This polymer may be an advantageous implantable drug delivery system for use in acute oxidative stress prophylaxis and/or chronic oxidative stress cell therapies due to its solid/liquid reversibility in a redox environment, controlled thiolation, high loading capacity through covalent drug-addition, and simple post-synthesis modification which bound-thiols introduce. Statement of Significance In this work, we demonstrate a unique property of disulfide containing degradable biomaterials. By changing the redox state of the degradation products (from oxidized to reduced), it is possible to increase the IC50 of the material by an order of magnitude. This dramatic shift is linked directly to the oxidative stress response of the cells and suggests a possible mechanism by which one can tune the cellular response to degradable biomaterials.

We decompose India's export performance in manufactured products during 2000–15 into changes at the intensive and extensive margins. India's performance, along different margins, is compared and contrasted with that of China. The results show that while China outperforms India at both the margins, the gap is particularly wide at the intensive margin. Decomposition of intensive margin along quantity and price margins shows that Chinese products are generally sold cheaper than Indian products. Higher price margin, however, has not translated into high intensive margin for India due to its abysmally low quantity margin. We examine different explanations for China's superior performance relative to India, along different margins, using a gravity model. Our results suggest that China's exchange rate policy was not the prime reason for its export success. Neither do we find that FDI inflows were significant in explaining the export performance gap between them. The results show that China's export relationship bias towards high†income partner countries holds the key in understanding its superior performance. This bias is a natural consequence of China's high degree of specialization in labor†intensive activities. India, by contrast, due to an idiosyncratic pattern of specialisation, has failed to exploit its export potential in high income countries.