On-Board Oxygen Generation Using High Performance Molecular Sieve

The majority of high performance combat aircrafts presently being operated by Indian air Force are fitted with conventional oxygen systems in which a replenishable store of oxygen is carried, most often as liquid oxygen and the flow of gas to each crew member is controlled by an individual pressure demand regulator in which the oxygen is diluted with cabin air to provide breathing gas.Moreover, in-flight refueling capability of present generation fighter aircraft has made it possible to fly for long durations (6 to 8 hours). In such case, the oxygen source becomes one of the limiting factors. In order to meet this requirement, a large supply of Gaseous Oxygen (GASOX) or Liquid Oxygen (LOX) have proven to be a costly affair and the Onboard Oxygen Generating System (OBOGS) has become a very convenient and attractive proposal. The OBOGS employs molecular sieves to adsorb nitrogen from engine bleed air using pressure swing adsorption (PSA) technique, wherein two molecular sieve beds are continuously cycled between steps of pressurization (adsorption) and depressurization (desorption) to generate oxygen enriched breathing gas for aircrew. This paper describes the design of OBOGS using high performance Lithium based Low Silica X-type (Li-LSX) molecular sieves and its performance characteristics. It consists of two Zeolite beds filled with Li-LSX material which adsorbs nitrogen fromengine bleed air tapped from Environmental Control System pipe line. The two beds are cycled by a 5/2 way solenoid valve. The input air is supplied to the solenoid valve through a coalescent filter to reduce moisture from it and a pressure regulator is fitted at the upstream of solenoid valve to regulate the system pressure. The experimental setup for evaluation of OBOGS is also discussed. The OBOGS, presented in this paper, meets all the performance requirements as specified in MIL-C-85521 (AS).

Pathogenic variability in Exserohilum turcicum and identification of resistant sources to turcicum leaf blight of maize (Zea mays L.)

Turcicum leaf blight of maize incited by Exserohilum turcicum (Pass.) Leonard and Suggs is the major limiting factor of maize production in temperate agro-ecologies. Disease management through host plant resistance is the most effective strategy. In the present study among 26 maize genotypes which were initially screened for resistance against E. turcicum under field conditions, 8 genotypes viz., PS 39, CML 451, CML 470, CML 472, VL 1030, VL 1018140, VL1018527 and SMI178-1 were found resistant when screened against twelve isolates of E. turcicum under artificial epiphytotic conditions. Eight genotypes viz., PS45, CML165, CML459, VL1249, VL0536, SMC-5, SMC-3 and KDL 211 were found moderately resistant with disease grade ranged from 2.1-2.5. These maize genotypes possess resistance to turcicum leaf blight can be used successfully in developing high yielding early maturing varieties for high altitude temperate agro-ecologies. The fungus E. turcicum is highly variable in nature. Variability studies on pathogenicity were conducted on twelve isolates of E. turcicum on eleven putative differential maize lines. During the present study a wide pathogenic variation was observed among the twelve isolates of E. turcicum. Cluster analysis on the basis of similarity or dissimilarity in reaction types exhibited by the differential hosts, clustered the isolates into 6 pathogenic groups. The isolates belonged to higher altitudes (Kti 10, Kti11, Kti5) were found to be more aggressive as compared to the isolates of low altitude areas

Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anti-cancer drug resistance.

The tumor microenvironment represents a complex network, in which tumor cells not only communicate with each other but also with stromal and immune cells. Current research has demonstrated the vital role of the tumor microenvironment in supporting tumor phenotype via a sophisticated system of intercellular communication through direct cell-to-cell contact or by classical paracrine signaling loops of cytokines or growth factors. Recently, extracellular vesicles have emerged as an important mechanism of cellular interchange of bioactive molecules. Extracellular vesicles isolated from tumor and stromal cells have been implicated in various steps of tumor progression, such as proliferation, angiogenesis, metastasis, and drug resistance. Inhibition of extracellular vesicles secretion, and thus of the transfer of oncogenic molecules, holds promise for preventing tumor growth and drug resistance. This review focuses on the role of extracellular vesicles in modulating the tumor microenvironment by addressing different aspects of the bidirectional interactions among tumor and tumor-associated cells. The contribution of extracellular vesicles to drug resistance will also be discussed as well as therapeutic strategies targeting extracellular vesicles production for the treatment of cancer

Liquid Biopsy: A Step Closer to Transform Diagnosis, Prognosis and Future of Cancer Treatments

Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes

Ubiquitin-specific peptidase 37: an important cog in the oncogenic machinery of cancerous cells.

Protein ubiquitination is one of the most crucial posttranslational modifications responsible for regulating the stability and activity of proteins involved in homeostatic cellular function. Inconsistencies in the ubiquitination process may lead to tumorigenesis. Ubiquitin-specific peptidases are attractive therapeutic targets in different cancers and are being evaluated for clinical development. Ubiquitin-specific peptidase 37 (USP37) is one of the least studied members of the USP family. USP37 controls numerous aspects of oncogenesis, including stabilizing many different oncoproteins. Recent work highlights the role of USP37 in stimulating the epithelial-mesenchymal transition and metastasis in lung and breast cancer by stabilizing SNAI1 and stimulating the sonic hedgehog pathway, respectively. Several aspects of USP37 biology in cancer cells are yet unclear and are an active area of research. This review emphasizes the importance of USP37 in cancer and how identifying its molecular targets and signalling networks in various cancer types can help advance cancer therapeutics.This study was supported by AIIMS Intramural grant (Grant number: A514) and AIIMS IITD Grant (AI-34) from All India Institute of Medical Sciences (AIIMS) New Delhi, Delhi India to Mayank singh. Sidra Medicine Precision Program provides research funding to Mohammad Haris (5081012002). Muzafar A. Macha is supported by Ramalingaswami Fellowship (Grant number: D.O. NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi

Association of genes with phenotype in autism spectrum disorder.

Autism spectrum disorder (ASD) is a genetic heterogeneous neurodevelopmental disorder that is characterized by impairments in social interaction and speech development and is accompanied by stereotypical behaviors such as body rocking, hand flapping, spinning objects, sniffing and restricted behaviors. The considerable significance of the genetics associated with autism has led to the identification of many risk genes for ASD used for the probing of ASD specificity and shared cognitive features over the past few decades. Identification of ASD risk genes helps to unravel various genetic variants and signaling pathways which are involved in ASD. This review highlights the role of ASD risk genes in gene transcription and translation regulation processes, as well as neuronal activity modulation, synaptic plasticity, disrupted key biological signaling pathways, and the novel candidate genes that play a significant role in the pathophysiology of ASD. The current emphasis on autism spectrum disorders has generated new opportunities in the field of neuroscience, and further advancements in the identification of different biomarkers, risk genes, and genetic pathways can help in the early diagnosis and development of new clinical and pharmacological treatments for ASD

Chemokine-cytokine networks in the head and neck tumor microenvironment

Head and neck squamous cell carcinomas (HNSCCs) are aggressive diseases with a dismal patient prognosis. Despite significant advances in treatment modalities, the five-year survival rate in patients with HNSCC has improved marginally and therefore warrants a comprehensive understanding of the HNSCC biology. Alterations in the cellular and non-cellular components of the HNSCC tumor micro-environment (TME) play a critical role in regulating many hallmarks of cancer development including evasion of apoptosis, activation of invasion, metastasis, angiogenesis, response to therapy, immune escape mechanisms, deregulation of energetics, and therefore the development of an overall aggressive HNSCC phenotype. Cytokines and chemokines are small secretory proteins produced by neoplastic or stromal cells, controlling complex and dynamic cell–cell interactions in the TME to regulate many cancer hallmarks. This review summarizes the current understanding of the complex cytokine/chemokine networks in the HNSCC TME, their role in activating diverse signaling pathways and promoting tumor progression, metastasis, and therapeutic resistance development.This study was supported by Ramalingaswami Fellowship (Grant number: D.O.NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi to Muzafar A. Macha. Sidra Medicine Precision Program funded this research to Mohammad Haris (5081012001, 5081012001) and Ajaz A. Bhat (5081012003)

Anticancer activity of Neosetophomone B by targeting AKT/SKP2/MTH1 axis in leukemic cells

Neosetophomone B (NSP–B), a meroterpenoid fungal secondary metabolite, was investigated for its anticancer potential in leukemic cell lines (K562 and U937). NSP-B treatment of leukemic cells suppressed cell viability by triggering apoptotic cell death. Apoptosis induced by NSP-B is triggered by mitochondrial signaling and caspase activation. Additionally, NSP-B treatment of leukemic cells causes AKT's inactivation accompanied by downregulation of SKP2 oncogene and MTH1 with a concomitant increase of p21Cip1and p27Kip1. Furthermore, NSP-B causes suppression of antiapoptotic proteins, including cIAP1, cIAP2, XIAP, survivin and BCl-XL. Overall, NSP-B reduces cell viability by mitochondrial and caspase-dependent apoptosis. The inhibition of AKT and SKP2 axis could be a promising therapeutic target for leukemia treatment.This work was supported by grant funded by the Medical Research Center (MRC), Hamad Medical Corporation, Doha, Qatar (MRC-01-21-301). The authors thank Qatar National Library for open access support of this article

Genetics of structural and functional brain changes in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social impairment and restricted interactive and communicative behaviors. It may occur as an isolated disorder or in the context of other neurological, psychiatric, developmental, and genetic disorders. Due to rapid developments in genomics and imaging technologies, imaging genetics studies of ASD have evolved in the last few years. Increased risk for ASD diagnosis is found to be related to many specific single-nucleotide polymorphisms, and the study of genetic mechanisms and noninvasive imaging has opened various approaches that can help diagnose ASD at the nascent level. Identifying risk genes related to structural and functional changes in the brain of ASD patients provide a better understanding of the disease's neuropsychiatry and can help identify targets for therapeutic intervention that could be useful for the clinical management of ASD patients.This study was supported by a PI grant from Sidra Medicine (5071012001) to M.H. A.A.B. is supported by Sidra Medicine internal grant (5011041002)