Glioblastoma Multiforme: Novel Therapeutic Approaches

The current therapy for glioblastoma multiforme involves total surgical resection followed by combination of radiation therapy and temozolomide. Unfortunately, the efficacy for such current therapy is limited, and newer approaches are sorely needed to treat this deadly disease. We have recently described the isolation of bacterial proteins and peptides with anticancer activity. In phase I human clinical trials, one such peptide, p28, derived from a bacterial protein azurin, showed partial and complete regression of tumors in several patients among 15 advanced-stage cancer patients with refractory metastatic tumors where the tumors were no longer responsive to current conventional drugs. An azurin-like protein called Laz derived from Neisseria meningitides demonstrates efficient entry and high cytotoxicity towards glioblastoma cells. Laz differs from azurin in having an additional 39-amino-acid peptide called an H.8 epitope, which allows entry and high cytotoxicity towards glioblastoma cells. Since p28 has been shown to have very little toxicity and high anti-tumor activity in advanced-stage cancer patients, it will be worthwhile to explore the use of H.8-p28, H.8-azurin, and Laz in toxicity studies and glioblastoma therapy in preclinical and human clinical trials

Assessment of risk factors and its fetal outcome of preterm birth: in rural tertiary care hospital, Karad, Maharashtra

Background: Preterm birth is an alarming cause of complication in pregnancy that leads to an immenseburden for imitation of children to their householders and health care providers. The present study was tofind out the functional relationship of preterm birth (PTB) and its study parameters at the Krishna Hospitaland Medical Research Centre Karad, Maharashtra from 2016–17. In SPSS (20.0), IBM, INDIA, multipleregression method was used to analyze the results.Methods: This was cross-sectional study done at rural tertiary care hospital, Karad. The examination wasdone in the ob-gyn. ward and various details were collected in the form of the questionnaire at presentthat ward with support of oral discussion of that patient.Results: Age and many more demographic variables were significantly associated with its fetal outcome ofpreterm birth. Also, it seems that pregnancy-induced hypertension, placenta diameter; numbers of meals,delivery mode, and those reasons were effective measures of risk factors of assessment of preterm birth.Conclusions: All the variables analyzed in this study were the part of the determinants of PTB needsto check time to time during the period of pregnancy. Heath care providers still need to take efforts forpregnancy-induced hypertension, placenta diameter

Doc2b Protects β-Cells Against Inflammatory Damage and Enhances Function

Loss of functional β-cell mass is an early feature of type 1 diabetes. To release insulin, β-cells require soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, as well as SNARE complex regulatory proteins like double C2 domain-containing protein β (Doc2b). We hypothesized that Doc2b deficiency or overabundance may confer susceptibility or protection, respectively, to the functional β-cell mass. Indeed, Doc2b+/- knockout mice show an unusually severe response to multiple-low-dose streptozotocin (MLD-STZ), resulting in more apoptotic β-cells and a smaller β-cell mass. In addition, inducible β-cell-specific Doc2b-overexpressing transgenic (βDoc2b-dTg) mice show improved glucose tolerance and resist MLD-STZ-induced disruption of glucose tolerance, fasting hyperglycemia, β-cell apoptosis, and loss of β-cell mass. Mechanistically, Doc2b enrichment enhances glucose-stimulated insulin secretion (GSIS) and SNARE activation and prevents the appearance of apoptotic markers in response to cytokine stress and thapsigargin. Furthermore, expression of a peptide containing the Doc2b tandem C2A and C2B domains is sufficient to confer the beneficial effects of Doc2b enrichment on GSIS, SNARE activation, and apoptosis. These studies demonstrate that Doc2b enrichment in the β-cell protects against diabetogenic and proapoptotic stress. Furthermore, they identify a Doc2b peptide that confers the beneficial effects of Doc2b and may be a therapeutic candidate for protecting functional β-cell mass

ANALYSIS AND DESIGN OF THREE LEGGED 400KV DOUBLE CIRCUIT STEEL TRANSMISSION LINE TOWERS

ABSTRACT Transmission line towers constitute about 28 to 42 percent of the cost of the transmission line. The increasing demand for electrical energy can be met more economically by developing different light weight configurations of transmission line towers. The present work describes the analysis and design of three legged self-supporting 400 kV double circuit steel transmission line towers models with an angle and tube sections. In this study constant loading parameters including wind forces as per IS: 802 (1995) are taken into account in both models. The efforts have been made to do 3D analysis of tower considering all the members of the space truss as primary members. STAAD. Pro program has been used to analysis and design the members of 400 kV double circuit tower have deviation angle 2 degree. The maximum sag and tension calculations of conductor and ground wire as per IS: 5613 (Part 3/ Sec 1) 1989. The comparative study is presented here with respective to axial forces, deflections, maximum sectional properties, critical loading conditions between both models of towers. The study shows that tower with tube sections are efficient and have better forceweight ratio including 20.6% saving in weight of steel with tubes against steel with angles in three legged transmission line tower

Nanomedicine-driven molecular targeting, drug delivery, and therapeutic approaches to cancer chemoresistance

Cancer cell resistance to chemotherapeutics (chemoresistance) poses a significant clinical challenge that oncology research seeks to understand and overcome. Multiple anticancer drugs and targeting agents can be incorporated in nanomedicines, in addition to different treatment modalities, forming a single nanoplatform that can be used to address tumor chemoresistance. Nanomedicine-driven molecular assemblies using nucleic acids, small interfering (si)RNAs, miRNAs, and aptamers in combination with stimuli-responsive therapy improve the pharmacokinetic (PK) profile of the drugs and enhance their accumulation in tumors and, thus, therapeutic outcomes. In this review, we highlight nanomedicine-driven molecular targeting and therapy combination used to improve the 3Rs (right place, right time, and right dose) for chemoresistant tumor therapies

Dissociating Slow Responses From Slow Responding

Increased Intra-Subject Variability (ISV) is a candidate endophenotype of ADHD. ISV's relationship with response speed is highly relevant for ADHD as patients are highly variable but typically no slower than controls. This brief report addresses the relationship between variability and speed by employing dimensional analyses for differentiated performance measures, with a particular focus on the ex-Gaussian measures, across relevant ADHD studies and in young healthy adults (N = 70). For both patients with ADHD and healthy adults, we found that reaction time standard deviation and mean reaction time were strongly correlated, thus failing to dissociate, but ex-Gaussian tau (tau) shared only little variance with Gaussian mu (mu), thus dissociating slow responses (tau) from response speed or-if given-slow responding (mu). Our results highlight the utility of employing the ex-Gaussian measures to disentangle ISV and speed, particularly for ADHD data as patients make more slow responses but are not overall slower than typical controls

Examining the Overlap Between ADHD and Autism Spectrum Disorder (ASD) Using Candidate Endophenotypes of ADHD

Objective: Recent discussions of aetiological overlap between ADHD and Autism Spectrum Disorder (ASD) require comparative studying of these disorders. Method: We examined performance of ASD patients with (ASD+) and without (ASD-) comorbid ADHD, ADHD patients, and controls for selected putative endophenotypes of ADHD: Intrasubject Variability (ISV) of reaction times, working memory (WM), inhibition, and temporal processing. Results: We found that patients with ADHD or ASD+, but not ASD-, had elevated ISV across the entire task battery and temporal processing deficits, and that none of the groups were impaired in WM or inhibition. High levels of ISV and generally poor performance in ASD+ patients were only partially due to additive effects of the pure disorders. Conclusion: Overall, we conclude that, within our limited but heterogeneous task battery, ISV and temporal processing deficits are most sensitive to ADHD symptomatology and that controlling for ADHD comorbidity is mandatory when assessing ISV in autism

Quantum noise limited microwave amplification using a graphene Josephson junction

Josephson junctions (JJ) and their tunable properties, including their nonlinearities, form the core of superconducting circuit quantum electrodynamics (cQED). In quantum circuits, low-noise amplification of feeble microwave signals is essential and the Josephson parametric amplifiers (JPA) are the widely used devices. The existing JPAs are based on Al-AlOx-Al tunnel junctions realized in a superconducting quantum interference device geometry, where magnetic flux is the knob for tuning the frequency. Recent experimental realizations of 2D van der Waals JJs provide an opportunity to implement various cQED devices with the added advantage of tuning the junction properties and the operating point using a gate potential. While other components of a possible 2D van der Waals cQED architecture have been demonstrated -- quantum noise limited amplifier, an essential component, has not been realized. Here we implement a quantum noise limited JPA, using a graphene JJ, that has linear resonance gate tunability of 3.5 GHz. We report 24 dB amplification with 10 MHz bandwidth and -130 dBm saturation power; performance on par with the best single-junction JPAs. Importantly, our gate tunable JPA works in the quantum-limited noise regime which makes it an attractive option for highly sensitive signal processing. Our work has implications for novel bolometers -- the low heat capacity of graphene together with JJ nonlinearity can result in an extremely sensitive microwave bolometer embedded inside a quantum noise-limited amplifier. In general, our work will open up exploration of scalable device architecture of 2D van der Waals materials by integrating a sensor with the quantum amplifier.Comment: 15 pages, 4 figures, and supplementary informatio