Reconstruction of the Disassembly Pathway of an Icosahedral Viral Capsid and Shape Determination of Two Successive Intermediates

Viral capsids derived from an icosahedral plant virus widely used in physical and nanotechnological investigations were fully dissociated into dimers by a rapid change of pH. The process was probed in vitro at high spatiotemporal resolution by time-resolved small-angle X-ray scattering using a high brilliance synchrotron source. A powerful custom-made global fitting algorithm allowed us to reconstruct the most likely pathway parametrized by a set of stoichiometric coefficients and to determine the shape of two successive intermediates by ab initio calculations. None of these two unexpected intermediates was previously identified in self-assembly experiments, which suggests that the disassembly pathway is not a mirror image of the assembly pathway. These findings shed new light on the mechanisms and the reversibility of the assembly/disassembly of natural and synthetic virus-based systems. They also demonstrate that both the structure and dynamics of an increasing number of intermediate species become accessible to experiments.

Part II: A Fully Integrated RF PA in 28-nm CMOS With Device Design for Optimized Performance and ESD Robustness

In this paper, we report drain-extended MOS device design guidelines for the RF power amplifier (RF PA) applications. A complete RF PA circuit in a 28-nm CMOS technology node with the matching and biasing network is used as a test vehicle to validate the RF performance improvement by a systematic device design. A complete RF PA with 0.16-W/mm power density is reported experimentally. By simultaneous improvement of device-circuit performance, 45% improvement in the circuit RF power gain, 25% improvement in the power-added efficiency at 1-GHz frequency, and 5x improvement in the electrostatic discharge robustness are reported experimentally.

MPTP activates ASK1-p38 MAPK signaling pathway through TNF-dependent Trx1 oxidation in parkinsonism mouse model

Activation of apoptosis signal regulating kinase 1 (ASK1)-p38 MAPK death signaling cascade is irn plicated in the death of dopaminergic neurons in substantia nigra in Parkinson's disease (PD). We investigated upstream activators of ASK1 using an MPTP mouse model of parkinsonism and assessed the temporal cascade of death signaling in ventral midbrain (VMB) and striatum (ST). MPTP selectively activated ASK1 and downstream 1)38 MAPK in a time dependent manner in VMB alone. This occurred through selective protein thiol oxidation of the redox-sensitive thiol disulfide oxidoreductase, thiorcdoxin (Trxl), resulting in release of its inhibitory association with ASK1, while glutathione-S-transferase ji 1 (GSTM1) remained in reduced form in association with ASK1. Levels of tumor necrosis factor (TNF), a known activator of ASK1, increased early after MPTP in VMB. Protein ovariation netvvork analysis (PCNA) using protein states as nodes revealed TNF to be an important node regulating the ASK1 signaling cascade. In confirmation, blocking MPTP-mecliated TNF signaling through intrathecal administration of TNFneutralizing antibody prevented Trxl oxidation and downstream ASK1-p38 MAPK activation. Averting an early increase in TNF, which leads to protein thiol oxidation resulting in activation of ASK1-p38 signaling, may be critical for neuroprotection in PD. Importantly, network analysis can help in understanding the cause/effect relationship within protein networks in complex disease states. (C) 2015 Published by Elsevier Inc.

Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection

Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long-term survival of engrafting cells in the body, not only do the cells have to execute liver-specific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 post-differentiation), hepatoblast (day 15) and hepatocyte-like cells (day 21) from human embryonic stem cells (hESCs). Day 5, 15 and 21 cells were stimulated with IFN-alpha and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-alpha treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFN-stimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatic cells upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs - LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival. (C) 2015 The Authors. Published by Elsevier B.V.

Effect of Magnetic Field on Photoresponse of Cobalt Integrated Zinc Oxide Nanorods

Cobalt integrated zinc oxide nanorod (Co-ZnO NR) array is presented as a novel heterostructure for ultraviolet (UV) photodetector (PD). Defect states in Co-ZnO NRs surface induces an enhancement in photocurrent as compared to pristine ZnO NRs PD. Presented Co-ZnO NRs PD is highly sensitive to external magnetic field that demonstrated 185.7% enhancement in response current. It is concluded that the opposite polarizations of electron and holes in the presence of external magnetic field contribute to effective separation of electron hole pairs that have drifted upon UV illumination. Moreover, Co-ZnO NRs PD shows a faster photodetection speed (1.2 s response time and 7.4 s recovery time) as compared to the pristine ZnO NRs where the response and recovery times are observed as 38 and 195 s, respectively.

Fabrication of Microfluidic-Nanofluidic Channels with Integrated Electrodes

We report on the fabrication of microfluidc-nanofluidic channels on Si incorporated with embedded metallic interconnects. The device aids the study of motion of dispersed particles relative to the fluid under the influence of spatially uniform electric field. Optical lithography in combination with focused ion beam technique was used to fabricate the microfluidic-nanofluidic channels, respectively. Focused ion beam technique was also used for embedding the electrodes in the nanochannel. Gold contact pads were deposited using sputtering. The substrate was finally anodically bonded to a glass substrate.

Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis

Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to -5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy.

SMO: An Integrated Approach to Intra-array and Inter-array Storage Optimization

The polyhedral model provides an expressive intermediate representation that is convenient for the analysis and subsequent transformation of affine loop nests. Several heuristics exist for achieving complex program transformations in this model. However, there is also considerable scope to utilize this model to tackle the problem of automatic memory footprint optimization. In this paper, we present a new automatic storage optimization technique which can be used to achieve both intra-array as well as inter-array storage reuse with a pre-determined schedule for the computation. Our approach works by finding statement-wise storage partitioning hyper planes that partition a unified global array space so that values with overlapping live ranges are not mapped to the same partition. Our heuristic is driven by a fourfold objective function which not only minimizes the dimensionality and storage requirements of arrays required for each high-level statement, but also maximizes inter statement storage reuse. The storage mappings obtained using our heuristic can be asymptotically better than those obtained by any existing technique. We implement our technique and demonstrate its practical impact by evaluating its effectiveness on several benchmarks chosen from the domains of image processing, stencil computations, and high-performance computing.