SUPERNATANT PROTEIN FACTOR: INSIGHTS INTO ITS REGULATION AND ABILITY TO STIMULATE CHOLESTEROL SYNTHESIS IN VITRO AND IN CELL CULTURE

Supernatant protein factor (SPF) is a 46-kDa cytosolic protein that stimulates squalene monooxygenase, which catalyses the second committed step in cholesterol biosynthesis. The mechanism by which SPF stimulates this enzyme is not understood and the goal of these studies was to see if SPF affected cholesterol synthesis in cultured cells. Rat supernatant protein factor-like protein (SPF2) shares 77% sequence identity with human SPF. In my studies SPF2 also stimulated squalene monooxygenase in vitro and incubation of SPF2 with protein kinase A (PKA) and C increased its activity by about 2-fold, as shown earlier with SPF. GTP and GDP prevented the stimulation of squalene monooxygenase by SPF2, suggesting that binding of these nucleotides inhibits SPF2. This inhibition could be prevented by the addition of -tocopherol, although -tocopherol alone had no effect on SPF2 activity in vitro. Expression of human SPF in hepatoma cells, which lack expression of endogenous SPF, increased cholesterol synthesis by 2-fold and addition of dibuytrylcAMP, a PKA activator, to these cells yielded an additional 62% increase whereas addition of a PKA inhibitor completely blocked the ability of SPF to stimulate cholesterol synthesis. To further confirm a role for phosphorylation in the regulation of SPF, substitution of alanine for serine-289 (a putative PKA recognition site) reduced the PKA-mediated activation of SPF in vitro by 50%, as measured with microsomal squalene monooxygenase and completely blocked the ability of SPF to stimulate cholesterol synthesis in hepatoma cells. In further structure-function studies, deletion of the carboxy-terminal Golgi-dynamics domain greatly increased the ability of SPF to stimulate squalene monooxygenase in microsomes, but, paradoxically prevented SPF from stimulating cholesterol synthesis in cell culture. Addition of brefeldin A, which disrupts Golgi formation, also abolished the ability of SPF to stimulate cholesterol synthesis, supporting a role for the Golgi in SPF function. Since squalene monooxygenase is not thought to be rate-limiting with regard to cholesterol synthesis, the possibility that SPF might stimulate other enzymes in the cholesterol biosynthetic pathway was investigated. The substitution of 14Cmevalonate for 14C-acetate completely blocked an SPF-induced 1.5-fold increase in squalene synthesis, suggesting that SPF stimulated mevalonate synthesis at HMGCoA reductase. 2,3-Oxidosqualene synthesis from 14C-mevalonate remained elevated (1.3-fold) with mevalonate demonstrating that SPF also stimulated squalene monooxygenase in hepatoma cells. SPF did not increase HMG-CoA reductase or squalene monooxygenase enzyme levels in cells, indicating that SPF directly activated these enzymes. Indeed, addition of purified recombinant SPF to rat liver microsomes stimulated HMG-CoA reductase by about 1.5-fold. These results reveal that SPF directly stimulates HMG-CoA reductase, the rate-limiting step of the cholesterol biosynthetic pathway, as well as squalene monooxygenase, and, coupled with the ability of PKA-mediated phosphorylation to regulate SPF activity, suggest a new means by which cholesterol synthesis can be rapidly modulated in response to hormonal and environmental signals

RIXA - Explaining Artificial Intelligence in Natural Language

Natural language is the instinctive form of communication humans use among each other. Recently large language models have drastically improved and made natural language interfaces viable for all kinds of applications. We argue that the use of natural language is a great tool to make explainable artificial intelligence (XAI) accessible to end users. We present our concept and work in progress implementation of a new kind of XAI dashboard that uses a natural language chat. We specify 5 design goals for the dashboard and show the current state of our implementation. The natural language chat is the main form of interaction for our new dashboard. Through it the user should be able to control all important aspects of our dashboard. We also define success metrics we want to use to evaluate our work. Most importantly we want to conduct user studies because we deem them to be the best method of evaluation for end-user-centered application

Scratchpad Sharing in GPUs

GPGPU applications exploit on-chip scratchpad memory available in the Graphics Processing Units (GPUs) to improve performance. The amount of thread level parallelism present in the GPU is limited by the number of resident threads, which in turn depends on the availability of scratchpad memory in its streaming multiprocessor (SM). Since the scratchpad memory is allocated at thread block granularity, part of the memory may remain unutilized. In this paper, we propose architectural and compiler optimizations to improve the scratchpad utilization. Our approach, Scratchpad Sharing, addresses scratchpad under-utilization by launching additional thread blocks in each SM. These thread blocks use unutilized scratchpad and also share scratchpad with other resident blocks. To improve the performance of scratchpad sharing, we propose Owner Warp First (OWF) scheduling that schedules warps from the additional thread blocks effectively. The performance of this approach, however, is limited by the availability of the shared part of scratchpad. We propose compiler optimizations to improve the availability of shared scratchpad. We describe a scratchpad allocation scheme that helps in allocating scratchpad variables such that shared scratchpad is accessed for short duration. We introduce a new instruction, relssp, that when executed, releases the shared scratchpad. Finally, we describe an analysis for optimal placement of relssp instructions such that shared scratchpad is released as early as possible. We implemented the hardware changes using the GPGPU-Sim simulator and implemented the compiler optimizations in Ocelot framework. We evaluated the effectiveness of our approach on 19 kernels from 3 benchmarks suites: CUDA-SDK, GPGPU-Sim, and Rodinia. The kernels that underutilize scratchpad memory show an average improvement of 19% and maximum improvement of 92.17% compared to the baseline approach

Endometriosis and its Ayurvedic perspective

Endometriosis defined as the presence of functioning endometrium, in sights other than uterus. It can be either the endometriosis externa or interna. Externa refers to endometriosis of any part of the body except the myometrium. In interna, the endometriosis is found in the muscle wall of the uterus. All though endometriosis is not considered as a life threatening disease, is a life altering disease that requires timely diagnosis and treatment. This paper intends to review on endometriosis and its Ayurvedic perspective in detail

Open source Software ADOPTION: an academic perspective

Open Source Software (OSS) is defined as a computer software that is freely provided and which permits users to use, change, and improve the software, and to redistribute it in a modified or an unmodified forms. OSS is developed in a highly social online environment where developers are dispersed in space and time, but rarely interact in a face-to-face manner. Literature in this field specifies many successful OSS implementations in Academic Institutions globally. Educational Institutions have diverse opinion on the academic use of OSS. The concept of open access and the proliferation of academic blogs have broken down many barriers in the educational sector. With the reference of studies conducted in various countries such as Switzerland, USA, Australia, UK etc., it can be said that there are two distinct views on the academic acceptance of OSS. One view is in favor of the use of OSS, while the other is hesitant about OSS thinking that it could suppress the creativity of individuals. OSS represents a social dimension of Learning through a Persistent, Unified, Massively Multi-User, and Self-Organizing Virtual Environment extending beyond the traditional classroom into the universities common areas where learners build knowledge and understanding through serendipitous and collaborative exchanges both within and across subject area boundaries. The digitization of education is a relatively new phenomenon but has already transformed the education sector .Most Educational Institutions are operated on a non-profit basis and many of them are government funded. Open Source Software’s are freely available on well-known OSS Project community providers such as www.SourceForge.net and hence can be implemented in Educational Institutions at no procurement costs. This research is an attempt to examine the differences between the implementation of OSS and Proprietary software’s in Educational Institutions. Findings of this study could facilitate Universities and Educational Institutions to evaluate the options of using OSS for their Information Technology or Information Systems requirements

Modelling and Simulation of Solar PV Array Field Incorporated with Solar Irradiance and Temperature Variation to Estimate Output Power of Solar PV Field

Photovoltaic systems are designed to feed either to grid or direct consumption. Due to global concerns, significant growth is being observed in Grid connected solar PV Plants. Since the PV module generates DC power, inverter is needed to interface it with grid. The power generated by a solar PV module depends on surrounding such as irradiance and temperature. This paper presents modelling of solar PV arrays connected to grid-connected plant incorporated with irradiance and temperature variation, to design simulator to study and analyse effect on output power of solar PV arrays with irradiance and temperature variation, also to estimate the output power generated by PV arrays. The mathematical model is designed implemented separately on simulator for each PV components connected in PV systems, which are PV cell, Module, sting, array and field of arrays. The results from simulation based on model are verified by the data collected from power plants and experiments done on solar PV cell