The Impact of Neural Stem Cell Biology on CNS Carcinogenesis and Tumor Types

The incidence of gliomas is on the increase, according to epidemiological data. This increase is a conundrum because the brain is in a privileged protected site behind the blood-brain barrier, and therefore partially buffered from environmental factors. In addition the brain also has a very low proliferative potential compared with other parts of the body. Recent advances in neural stem cell biology have impacted on our understanding of CNS carcinogenesis and tumor types. This article considers the cancer stem cell theory with regard to CNS cancers, whether CNS tumors arise from human neural stem cells and whether glioma stem cells can be reprogrammed

Creation of Digital Elevated Model using lunar images of Chandrayan – 1

The present work discusses the technique and methodology of analysing and Terrain Mapping Camera (TMC) Images acquired during India’s first  Moon mission, Chandrayaan  – 1, launched on October, 2008  for generating Digital Elevated Model (DEM). The Terrain Mapping Camera (TMC) on India’s first satellite for lunar exploration, Chandrayaan-1, is intended for systematic topographic mapping of the entire lunar surface, including the far side and the polar regions. A high resolution imagery of the entire Moon will help detailed study of specific lunar regions of scientific interests and further our understanding of lunar evolution. The swath of the instrument is 20 km. The digital elevation model (DEM) is a computer representation of the moon’s surface. DEMs can be generated by traditional photogrammetry based on aerial photos if they are available and they are created very often more economically by the means of space images. A Digital Terrain Model (DEM) is a continuous representation of a ground surface landform that is commonly used to produce topographic maps. DEMs are created by integrating data obtained from a wide range of techniques including remote sensing and land surveying.DEM's are sampled arrays of elevation values representing ground positions at regularly spaced intervals. Digital Elevation Model (DEM) is the terminology adopted by the USGS to describe terrain elevation data sets in a digital raster form.  The normal orientation of data is by columns and rows. In this project work a DEM is created for each of the lunar images retrieved from the space craft using Triangulated Irregular Network (TIN)Key Words : Chandrayaan-1, DEM, Swath, TMC, TINDOI:http://dx.doi.org/10.11591/ijece.v1i2.8

Comparison of leaf volatile aroma constituents and phenolic acid profiles of the seedling originated polyembryonic mango (Mangifera indica L.) genotypes

In mango, leaf and fruit volatile aroma profiles are variety specific which can be used as fingerprint of a variety. Such biochemical markers can also discriminate the nucellar and zygotic seedlings in polyembryonic mango varieties. In order to validate the applicability of volatile as well as phenolic acid profiles as biomarkers, the open pollinated seedlings of three polyembryonic varieties of mango were compared with their mother trees. Leaf volatile and phenol acid profiling were done using Gas Chromatography/Mass Spectrometry (GCMS) and Liquid Chromatography/Mass Spectrometry (LCMS) methods respectively. The sesquiterpene hydrocarbons were the most abundant in all the genotypes studied. Monoterpenoids were the major compounds in cultivars Vellaikolumban and Olour, while the sesquiterpenoids were the major compounds in cv. Turpentine. While terpinolene was the major monoterpenoid compound in Vellaikolumban and limonene in cv. Olour, the sesquiterpene á-gurjunene was the major compound in cv. Turpentine. Volatile profiling showed clear differences between the varieties but was similar within a variety. Among the 15 phenolic acids quantified in the leaves, P-coumaric acid, gallic acid, and ferulic acids were predominant whereas, vanillic acid, syringic acid, gentisic acid, benzoic acid, and sinapic acids were low in quantity. Phenolic acid profile did not show significant diversity among the varieties and therefore cannot be used for identification of varieties. The volatile profiling can be used for the identification and differentiation of polyembryonic mango genotypes

Targeting the Ubiquitin System in Glioblastoma

Glioblastoma is the most common primary brain tumor in adults with poor overall outcome and 5-year survival of less than 5%. Treatment has not changed much in the last decade or so, with surgical resection and radio/chemotherapy being the main options. Glioblastoma is highly heterogeneous and frequently becomes treatment-resistant due to the ability of glioblastoma cells to adopt stem cell states facilitating tumor recurrence. Therefore, there is an urgent need for novel therapeutic strategies. The ubiquitin system, in particular E3 ubiquitin ligases and deubiquitinating enzymes, have emerged as a promising source of novel drug targets. In addition to conventional small molecule drug discovery approaches aimed at modulating enzyme activity, several new and exciting strategies are also being explored. Among these, PROteolysis TArgeting Chimeras (PROTACs) aim to harness the endogenous protein turnover machinery to direct therapeutically relevant targets, including previously considered “undruggable” ones, for proteasomal degradation. PROTAC and other strategies targeting the ubiquitin proteasome system offer new therapeutic avenues which will expand the drug development toolboxes for glioblastoma. This review will provide a comprehensive overview of E3 ubiquitin ligases and deubiquitinating enzymes in the context of glioblastoma and their involvement in core signaling pathways including EGFR, TGF-β, p53 and stemness-related pathways. Finally, we offer new insights into how these ubiquitin-dependent mechanisms could be exploited therapeutically for glioblastoma

Multiplier Based On Add And Shift Method By Passing Zero

In this paper, a low-power structure for shift-and-add multipliers is proposed. The architec-ture considerably lowers the switching activity of conventional multipliers. The modification to the multiplier which multiplies A by B include the removal of the shifting register, direct feeding of A to the adder, bypassing the adder whenever possible, using a ring counter instead of a binary counter and removal of the partial product shift. The architecture makes use of a low-power ring counter proposed in this work . The proposed multiplier can be used for low-power applications where the speed is not a primary design parameter

HLA-DR phenotypes and IgG, IgA and IgM antibody responses to Mycobacterium tuberculosis culture filtrate and 30 kDa antigens in pulmonary tuberculosis

The role of HLA-DR genetic make-up on the IgG, IgA and IgM antibody response to Mycobacterium tuberculosis culture filtrate and 30 kDa antigens was studied in pulmonary tuberculosis. The study was carried out in HLA-DR typed active pulmonary tuberculosis (ATB) patients (n = 37), inactive (cured) pulmonary tuberculosis (ITB) patients (n = 79) and normal healthy subjects (NHS; n = 46). In ATB and ITB (cured) patients, IgG antibody (optical density at 490 nm for 1 : 3200 dilution) as measured by enzyme-linked immunosorbent assay was the predominant one than IgA and IgM antibodies. Increased IgG antibody titre to culture filtrate (P = 0.03) and decreased titre to 30 kDa antigen were observed with HLA-DR1-positive ATB patients than non-DR1 (ATB) patients. Moreover, HLA-DR4- and HLA-DR6-positive ATB patients showed trends toward an increased IgG antibody response to 30 kDa antigen than HLA-DR4- and HLADR6- negative (ATB) patients respectively. Significantly increased IgA antibody to 30 kDa antigen was observed with HLA-DR1-positive ATB patients than non-DR1 patients (P = 0.03). The study suggests that multiple HLA-DR molecules may regulate the IgG and IgA antibody responses to various proteins of M. tuberculosis. Moreover, HLA-DR phenotypes and increased IgG and IgA antibody titres may be useful to differentiate M. tuberculosis-infected subjects from normal subjects and cured patients with the same HLA-DR phenotypes or genetic make-up

Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs

We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic

Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches

© 2019 H. P. Ellis et al. Glioblastoma is the most common primary adult brain tumour, and despite optimal treatment, the median survival is 12-15 months. Patients with matched recurrent glioblastomas were investigated to try to find actionable mutations. Tumours were profiled using a validated DNA-based gene panel. Copy number variations (CNVs) and single nucleotide variants (SNVs) were examined, and potentially pathogenic variants and clinically actionable mutations were identified. The results revealed that glioblastomas were IDH-wildtype (IDHWT; n = 38) and IDH-mutant (IDHMUT; n = 3). SNVs in TSC2, MSH6, TP53, CREBBP, and IDH1 were variants of unknown significance (VUS) that were predicted to be pathogenic in both subtypes. IDHWT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, WNT, SHH, NOTCH, Rb, and G-protein pathways. Many tumours had BRCA1/2 (18%) variants, including confirmed somatic mutations in haemangioblastoma. IDHWT recurrent tumours had fewer pathways impacted (RTK/Ras/PI(3)K, p53, WNT, and G-protein) and CNV gains (BRCA2, GNAS, and EGFR) and losses (TERT and SMARCA4). IDHMUT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, and WNT pathways. VUS in KLK1 was possibly pathogenic in IDHMUT. Recurrent tumours also had fewer pathways (p53, WNT, and G-protein) impacted by genetic alterations. Public datasets (TCGA and GDC) confirmed the clinical significance of findings in both subtypes. Overall in this cohort, potentially actionable variation was most often identified in EGFR, PTEN, BRCA1/2, and ATM. This study underlines the need for detailed molecular profiling to identify individual GBM patients who may be eligible for novel treatment approaches. This information is also crucial for patient recruitment to clinical trials

Studies on Composite Extrudable Propellant with varied Burning Rate Pressure Index 'n'

This paper discusses the development of composite propellantextrusion technique and the study of burning rate pressure indices nwith respect to compositional variations. The n is found to vary from0.35 to plateau and plateau to mesa by suitable compositionalmodifications. Compositional influence on burning rate with specificreference to plateau and mesaburning additives is described. Detailsof the process parameters like fluidity of the slurry, extrusion pressure,extrusion rate and die-swell are presented. This propellant is based onISRO-CTPB binder using ISRO-AP as oxidizer. Ammonium perchlorate (AP) particle size variation and inclusion of additives likePVC, lead stearate, ammonium sulphate, lithium fluoride etc. are foundto influence the burning rate pressure index n