Stem Cell Therapeutics: Exploring Newer Alternatives to Human Embryonic Stem Cells

Stem cells therapeutics has come a long way since stem cells and their potential was discovered for the first time. Intense research into cellular biology of stem cells has revealed that they possess immense potential for curing many human diseases. Research done in last couple of decades revealed that a particular class of stem cells called, “Human embryonic stem cells (HESCs)” possessed exceptional self-renewal and pluripotency properties. There ability to differentiate into specialized cell lineages of all three embryonic germ layers contributed further towards their popularity. However, in recent times HESCs have come under the cross-hairs of critics, politicians and religious groups due to certain technical and ethical concerns related to them. Such problems with HESCs research have forced stem cell researchers to start exploring the prospects of using alternatives to HESCs for regenerative medicine and therapeutics. In the present review, various sources of stem cells have been described, which in near future, have the potential to replace HESCs in regenerative medicine

Generalizing Permissive-Upgrade in Dynamic Information Flow Analysis

Preventing implicit information flows by dynamic program analysis requires coarse approximations that result in false positives, because a dynamic monitor sees only the executed trace of the program. One widely deployed method is the no-sensitive-upgrade check, which terminates a program whenever a variable's taint is upgraded (made more sensitive) due to a control dependence on tainted data. Although sound, this method is restrictive, e.g., it terminates the program even if the upgraded variable is never used subsequently. To counter this, Austin and Flanagan introduced the permissive-upgrade check, which allows a variable upgrade due to control dependence, but marks the variable "partially-leaked". The program is stopped later if it tries to use the partially-leaked variable. Permissive-upgrade handles the dead-variable assignment problem and remains sound. However, Austin and Flanagan develop permissive-upgrade only for a two-point (low-high) security lattice and indicate a generalization to pointwise products of such lattices. In this paper, we develop a non-trivial and non-obvious generalization of permissive-upgrade to arbitrary lattices. The key difficulty lies in finding a suitable notion of partial leaks that is both sound and permissive and in developing a suitable definition of memory equivalence that allows an inductive proof of soundness

Information Flow Control in WebKit's JavaScript Bytecode

Websites today routinely combine JavaScript from multiple sources, both trusted and untrusted. Hence, JavaScript security is of paramount importance. A specific interesting problem is information flow control (IFC) for JavaScript. In this paper, we develop, formalize and implement a dynamic IFC mechanism for the JavaScript engine of a production Web browser (specifically, Safari's WebKit engine). Our IFC mechanism works at the level of JavaScript bytecode and hence leverages years of industrial effort on optimizing both the source to bytecode compiler and the bytecode interpreter. We track both explicit and implicit flows and observe only moderate overhead. Working with bytecode results in new challenges including the extensive use of unstructured control flow in bytecode (which complicates lowering of program context taints), unstructured exceptions (which complicate the matter further) and the need to make IFC analysis permissive. We explain how we address these challenges, formally model the JavaScript bytecode semantics and our instrumentation, prove the standard property of termination-insensitive non-interference, and present experimental results on an optimized prototype

DAMPs and PDT-mediated photo-oxidative stress: exploring the unknown

Damage-associated molecular patterns (DAMPs) or cell death associated molecular patterns (CDAMPs) are a subset of endogenous intracellular molecules that are normally hidden within living cells but become either passively released by primary and secondary necrotic cells or actively exposed and secreted by the dying cells. Once released, DAMPs are sensed by the innate immune system and act as activators of antigen-presenting cells (APCs) to stimulate innate and adaptive immunity. Cancer cells dying in response to a subset of conventional anticancer modalities exhibit a particular composition of DAMPs at their cell surface, which has been recently shown to be vital for the stimulation of the host immune system and the control of residual disease. Photodynamic therapy (PDT) for cancer has long been shown to be capable of killing malignant cells and concomitantly stimulate the host immune system, properties that are likely linked to its ability of inducing exposure/release of certain DAMPs. PDT, by evoking oxidative stress at specific subcellular sites through the light activation of organelle-associated photosensitizers, may be unique in incorporating tumour cells destruction and antitumor immune response in one therapeutic paradigm. Here we review the current knowledge about mechanisms and signalling cascades leading to the exposure of DAMPs at the cell surface or promoting their release, the cell death mechanism associated to these processes and its immunological consequences. We also discuss how certain PDT paradigms may yield therapies that optimally stimulate the immune system and lead to the discovery of new DAMPs

Antimicrobial activity of skin secretions isolated from Indian toad, Bufo melanostictus Schneider 1799

Amphibians like toads have been known to secrete antimicrobial secretions outside their body into their environments, through skin pores and parotid glands. Toad skin-secretions contain four types of compounds namely, biogenic amines, bufadienolides, alkaloids & steroids and peptides & proteins. Bulk of research relating to amphibian antimicrobial secretions has been done on frogs. In toads, such research has only been done in South America, Europe and China. Antimicrobial secretions vary considerably from specie-to-specie and drastically across various biomes. This prompted us to examine and confirm presence of antimicrobial activity (if any) in Indian Common Toad (Bufo melanostictus Schneider 1799) skin secretions since; no such analysis had been previously done on this toad which is found all across the South-east Asia. The antibacterial potency of toad skin secretions was tested against the bacteria, Escherichia coli. After running preliminary antibacterial analysis assays, we found that these cutaneous secretions retrieved from Indian Common Toad possessed potential bactericidal activity. The results that we got confirmed that some unexplored bactericidal components were present in skin secretions of these toads. These conclusions call for further research into biochemistry and molecular characterization of these components

Immediate versus delayed percutaneous coronary intervention for patients with non-ST elevation-acute coronary syndrome : a meta-analysis of randomised trials [abstract]

Studies have indicated that an early invasive strategy is favorable over a selective invasive strategy for Non-ST segment elevation acute coronary syndromes (NSTE-ACS). However, there is no general consensus on precisely how early should the revascularization be performed. Randomized controlled trials (RCTs) performed to compare the outcomes of revascularization less than 24 hours of presentation (Group A) versus greater than 24 hours of presentation (Group B) for NSTE-ACS have shown conflicting results. Based on a systematic search seven RCTs (13,762 patients) comparing the composite of death and myocardial infarctions (MI) within 30 days of revascularization were included. The effects of both methods were analyzed by calculating pooled estimates for composite of death and MI, death, MI and revascularization

Cardiopulmonary Resuscitation: Recent Advances

Cardiac arrest is the most significant reason for mortality and morbidities worldwide. With a better understanding of the pathophysiology of cardiac arrest, simple adaptations in basic life support to upcoming modifications in post-resuscitation care have been proposed by various resuscitation councils throughout the globe. Role of point of care cardiac ultrasound during cardiopulmonary resuscitation (CPR) has been explored and its contribution for identifying reversible causes and its real time management has been explored. A higher blood and tissue oxygenation levels contributed to an increased rate of return of spontaneous circulation (ROSC) which has to lead us to explore more options to increase the oxygenation. Starting from the CPR training, the use of sensors for spirometric feedback in ventilation maneuvers can help improve the quality of CPR. High flow nasal oxygenation during CPR has shown promising results. Extracorporeal CPR is another entity that has shown survival benefits in a selected group of patients. The aim of the newer advances has always been to decrease the morbidity and improve survival outcomes in terms of neurological deficit as well. These guidelines are reviewed and updated regularly to improve knowledge and training based on the current evidence. This chapter shall focus on recent advances in cardiopulmonary resuscitation

FEEDBACK INHIBITION OF IL-17 RECEPTOR SIGNAL TRANSDUCTION

IL-17 is a proinflammatory cytokine that mediates host defense against extracellular pathogens but also contributes to the pathogenesis of various autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and psoriasis. Despite some homology with the toll-like receptors, IL-17 receptor subunits (IL-17RA and IL-17RC) do not recruit adaptors such as MyD88, but instead associate with and signal through the E3 ubiquitin ligase Act1. Upon recruitment, Act1 ubiquitinates tumor necrosis factor receptor associated factor 6 (TRAF6), resulting in the activation of downstream transcription factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), CCAAT-enhancer binding proteins (C/EBPs) and mitogen-activated protein kinases (MAPKs). Despite advances in our understanding IL-17 signaling, the details of molecular events involved in negative regulation of IL-17 signaling still remain unclear. Therefore, we focused our attention on feedback inhibitory mechanisms mediated by proteins that are regulated by IL-17. Here we describe three novel inhibitors of IL-17 signal transduction, A20, anaphase promoting complex subunit 5 (AnapC5) and monocyte chemotactic protein 1 induced protein 1 (MCPIP1). We uncovered non-overlapping function of these proteins in IL-17 pathway, signifying their importance in inhibiting inflammatory signaling. A20 is a deubiquitinating enzyme that restricts IL-17-induced TRAF6 ubiquitination, whereas AnapC5 associates with A20 and appears to function as an adaptor protein in the A20/IL-17 pathway. MCPIP1, on the other hand, is an RNase that degrades Il17ra and Il17rc mRNA, thereby restraining IL-17 signaling. Notably, gene expression of A20 and MCPIP1 is regulated by IL-17, indicating feedback inhibition of IL-17 signaling pathway. In summary, our findings have advanced the understanding of IL-17 signaling inhibition, may provide a novel mechanistic approach for controlling IL-17-induced inflammation and ultimately treating IL-17 mediated autoimmune diseases

Design and Implementation of Analog Controller Based Single Phase Full Bridge Inverter for Photovoltaic Applications

This paper presents a low-cost design of the analog controller for the photovoltaic driven single-phase inverter to generate desired output voltage. The hardware set-up mainly consists of an inverter and an analog controller. The developed controller controls the output voltage of the inverter using SPWM (Sinusoidal Pulse Width Modulation) technique. The inverter, which is designed using Metal-Oxide-Semiconductor Field Effect Transistor (MOSFET) as a switch, generates high-quality output with reduced ripple content and less filtering requirement, making the whole setup cost-effective and efficient. A gate driver circuit is also employed to provide isolation between the inverter and the analog controller. The closed loop analog controller for the photovoltaic driven inverter is implemented and tested for various loads. In all these cases, the output voltage waveforms are of high quality with a lesser number of lower order harmonics. In this way, the paper presents a low-cost design of the inverter that can be used for low-power domestic applications.Citation: Ranjan, A., Jalutharia, S., GARG, H., and Gupta, N. (2018). Design and Implementation of Analog Controller Based Single Phase Full Bridge Inverter for Photovoltaic Applications. Trends in Renewable Energy, 4, 102-113. DOI: 10.17737/tre.2018.4.3.006