REGULATION OF ALC1'S SNF2 ATPASE: INTERPLAY BETWEEN THE SNF2 DOMAIN, THE MACRODOMAIN AND OTHER CONSERVED ELEMENTS

ALC1, also known as CHD1L, was originally identified as a gene present on a human chromosome 1q21 region amplified in ~50% of human hepatocellular carcinomas (HCC). ALC1 overexpressing cells form tumors in nude mice, and transgenic mice overexpressing ALC1 develop several types of spontaneous tumors. ALC1 has also been proposed as a novel candidate gene for congenital anomalies of the kidneys and urinary tract (CAKUT). ALC1, a member of the SNF2 family of ATPases, has an N-terminal SNF2-like ATPase that is most closely related to that of ISWI, and a C-terminal macrodomain that binds selectively to poly(ADP-ribose) (PAR). Between the ATPase and the macrodomain is an evolutionarily conserved region with no clear homology to any known domains. This "linker" region can be further divided into three sub-regions of greatest conservation. It was previously shown that wild type ALC1 possesses DNA-dependent ATPase and ATP-dependent nucleosome remodeling activities that are strongly dependent on the presence of poly(ADP-ribose) polymerase PARP1 (or the closely related PARP2) and its substrate NAD+. Importantly, a point mutation in the ALC1 macrodomain that interferes with PAR binding prevents PARP1- and NAD-dependent ALC1 activation. In this work, we dissected the mechanism by which PARP1 and NAD+ activate ALC1 nucleosome remodeling. We demonstrate that ALC1 activation depends on the formation of a stable ALC1·PARylated PARP1·nucleosome intermediate. In addition, by exploiting a novel PAR footprinting assay, we obtained evidence that the ALC1 macrodomain remains stably associated with PAR on autoPARylated PARP1 during the course of nucleosome remodeling reactions. Results of biochemical experiments described here argue (i) that stable binding of the ALC1 macrodomain to autoPARylated PARP1 is critical for ALC1 activation and (ii) that activation of ALC1 depends on formation of a stable ALC1-autoPARylated PARP1-nucleosome intermediate. In the course of this study, we also find that apart from being regulated by PARP and NAD+, ALC1 possesses and additional mode of intradomain control via conserved domains in the linker region and the macrodomain. First, we identified a region, NMAC (N-terminal to Macrodomain ATPase Coupling) domain needed to couple ATP hydrolysis to nucleosome remodeling. Deleting NMAC led to a robust PARP and NAD+-dependent ATPase, which lacked appreciable remodeling activity. In addition, we identified an additional mode of control via the macrodomain when we replaced ALC1's PAR binding macrodomain with another macrodomain from the variant histone macroH2A1.1 and discovered this chimeric protein was constitutively active independent of PARP and NAD+. Taken together our findings suggest a model of positive control of the SNF2 ATPase via the macrodomain and an additional level of control over its remodeling activities via the NMAC and other conserved linker elements

NOVEL SYNTHETIC METHODS AND APPLICATIONS OF POROUS MATERIALS: AEROGEL FOAMS, METALLIC AEROGELS, AMORPHOUS AND GRAPHITIC CARBON AEROGELS

We report novel methods for the synthesis of porous materials such as polymeric aerogel foams, pure metallic aerogels, amorphous and graphitic carbon aerogels, and their applications. I. Polyurethane based aerogel foams were synthesized with an aliphatic triisocyanate and ethylene glycol through a pressurized (7 bar) sol-gel method. The foam-like structure is prepared without any chemical foaming agents or templates, resulting in less expensive, more efficient, readily adaptable, and environmentally friendly process. Those materials exhibited lower thermal conductivity (by 25%) and higher oil adsorption capacity (by 36% w/w) than their corresponding aerogels. II. Monolithic, pure metallic Co(0) aerogels were synthesized from polyurea-crosslinked cobaltia xerogel powder compacts via carbothermal reduction, for application as thermites. III. Carbon aerogels were synthesized from compressed compacts of polyurea- and polyacrylonitrile-crosslinked silica xerogel powders. The process of making aerogels-via-xerogels allows to speed-up the solvent exchange process and bypasses supercritical fluid drying, resulting in time, energy, and materials efficient methodology. At their best, these carbon aerogels have high BET surface area (up to 1934 m2 g-1), porosities (up to 83% v/v) and good CO2 uptake (up to 9.15 mmol g-1) with high selectivity toward other gases (H2, N2 and CH4). IV. Sturdy, monolithic graphitic carbon aerogels with different nano-morphologies were synthesized at lower temperatures (800-1500 ºC) compared to conventional graphitization (2500-3300 ºC) from Fe- or Co-catalyzed free-radical surface-initiated polymerization of acrylonitrile monomer to polyacrylonitrile-crosslinked metal oxide xerogel powder compacts. These graphitic carbon aerogels were demonstrated as anodes for Li-ion batteries with good charge capacity --Abstract, p.

Loss Model for Gallium Nitride DC-DC Buck Converter

In recent years, more research has been done on Enhancement Mode Gallium Nitride (eGaN) converters, as the world is moving towards more power efficient converters. Power converters play a major role in efficiently controlling and converting electric energy used by machines, systems, and everyday products. The process to make converters more efficient was complicated and slow in the twentieth century. One of the important aspects in power electronics is to evaluate different losses and minimize losses to achieve high efficiency of the converter. With help of simulation tools such as MATLAB and LTspice, this process has become much faster and reliable in the modern era. A model for estimating power losses for eGaN DC-DC buck converter (12V/1.2V) is illustrated in this paper. This loss model was calculated for different frequencies, and compared experimentally and theoretically. This paper also investigated the constant variables, which help realize the difference between theoretical and experimental losses in eGaN DC-DC buck converter. Pre-prints of this article have been previously made available [1-4]

Questioning the Utility of Self‐Efficacy Measurements for Indians

This study examined the influence of academic self‐efficacy and social support on the academic success of Indian‐American and Caucasian‐American undergraduate students. 200 Indian‐American and Caucasian‐American students completed a demographic form and five surveys. The data showed that academic self‐efficacy had a significant effect on college grade point averages (GPA) for Caucasians, but not for Indians. Regarding social support, the quality of mentoring relationships was found to be twice as high for Indians than Caucasians. The total number of mentors, however, was significantly higher for Caucasians. The results of this study support theories that highlight the importance of social support on Indians’ academic success, and of academic self‐efficacy on Caucasians’ academic success. This study also provides support of the existing literature that the construct of self‐efficacy is culturally biased, and questions the utility of self‐efficacy measurements for the Indian ethnicity

In-situ measurements of the elastic modulus of Zirconia polycrystals held in a state of flash induced by an electric field

Partially Stabilized zirconia is known to show the phenomenon of flash under applied electric fields. A proposed mechanism for flash is the introduction of nonlinear lattice vibrations at the onset of flash which may further soften the shear modulus of the lattice. This softening would in turn lower the energy barrier for the formation of defects. Here, in-situ measurements of elastic modulus of 3Y-TZP during flash for different current densities is estimated by comparing the modal response from the experiments against the simulations. Results in Figure 1 compare the modulus with and without (baseline) flash showing a lower modulus during flash for that corresponding sample temperature. Hence, supporting a scientific explanation behind flash. Please click Additional Files below to see the full abstract

Computation off loading to Cloud let and Cloud in Mobile Cloud Computing

Computation offloading in mobile cloud computing means transfer of execution of mobile application in the mobile device to the virtual mobile device in the Cloud or the Cloudlet. Intensive application like Nqueens puzzle, tower of hanoi when they execute on the Compute mobile device they consume more time because of the low computational power and limited battery capacity of mobile devices. By offloading computation to resource rich Cloud, energy consumption on the mobile device can be saved considerably and limitations of mobile devices can be overcomed. However offloading becomes difficult, when internet connectivity is interrupted due to hostile environment. Hence we offload compute intensive task from mobile device to resource rich surrogate machines in local network and overcome limitations of mobile devices when the internet connection is missing