287 research outputs found

    Structure-Function and Behavioral Studies on the Glutamate Delta-1 Receptor

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    The delta family of ionotropic glutamate receptors (iGluRs) consists of glutamate delta-1 (GluD1) and glutamate delta-2 (GluD2) receptors. The function of GluD1 in the central nervous system (CNS) remains elusive. As a first step we conducted electrophysiological studies on the rat clone of GluD1 to study the activation gate and ligand binding domain of GluD1 receptor. Site directed mutagenesis in the SYTANLAAF region resulted in four constitutively open mutants GluD1A650C, GluD1L652A, GluD1A654C, and GluD1F655A. Channel blockers pentamidine and NASP inhibited currents through the GluD1 mutant receptors. D-serine and extracellular calcium had opposing effects on GluD1 mutants and a chimeric GluD1-D2 lurcher. D-serine decreased currents through GluD1F655A and chimeric GluD1-D2 lurcher while calcium increased currents through GluD1F655A. These results suggest, GluD1 receptors have a conserved activation gate. In addition conformational changes brought about by D-serine and calcium are conserved among GluD1 and GluD2 receptors. GluD1 functions in synapse formation. Addtionally the GRID1 gene has been implicated in neuropsychiatric disorders. We hypothesize that synaptic abnormalities due to GluD1 deletion would lead to aberrant behaviors. Thus we performed tests in GluD1 knockout (GluD1 KO) mice to study the functional significance of the GluD1 receptor. GluD1 KO mice showed hyperactivity, lower anxiety-like behavior, hyperaggression, depression-like behavior, and social interaction deficits. Altered levels of synaptic proteins and iGluR subunits were seen in prefrontal cortex and amygdala. Few aberrant behaviors were rescued by chronic lithium and D-cycloserine (DCS) treatment. Amygdala functions in associative fear learning while prefrontal cortex plays a role in working memory. We found molecular abnormalities in amygdala and prefrontal cortex. Thus we tested the effect of GluD1 deletion on amygdalar and prefrontal cortex associated learning tasks. We observed normal or enhanced learning for prefrontal cortex associated tasks. However we found deficits in fear learning. iGluR expression was altered in the hippocampus along with synaptic anomalies in the amygdala, prefrontal cortex and hippocampus. These data suggest GluD1 functions in regulation of behavior and synaptic physiology. In addition GluD1 KO mice manifest symptoms related to neuropsychiatric disorders with which GRID1 has been associated.ProQuest Traditional Publishing Optionxv, 159 page

    Role of transcriptional regulation in auxin-mediated response to abiotic stresses

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    Global climate change (GCC) is posing a serious threat to organisms, particularly plants, which are sessile. Drought, salinity, and the accumulation of heavy metals alter soil composition and have detrimental effects on crops and wild plants. The hormone auxin plays a pivotal role in the response to stress conditions through the fine regulation of plant growth. Hence, rapid, tight, and coordinated regulation of its concentration is achieved by auxin modulation at multiple levels. Beyond the structural enzymes involved in auxin biosynthesis, transport, and signal transduction, transcription factors (TFs) can finely and rapidly drive auxin response in specific tissues. Auxin Response Factors (ARFs) such as the ARF4, 7, 8, 19 and many other TF families, such as WRKY and MADS, have been identified to play a role in modulating various auxin-mediated responses in recent times. Here, we review the most relevant and recent literature on TFs associated with the regulation of the biosynthetic, transport, and signalling auxin pathways and miRNA-related feedback loops in response to major abiotic stresses. Knowledge of the specific role of TFs may be of utmost importance in counteracting the effects of GCC on future agriculture and may pave the way for increased plant resilience

    The Needs of the Stakeholders are the Seeds of Growth for the Organisation (Interview with Mr. G. Narayana)

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    A rare interview with a well-regarded leader of commerce in India is presented by the author, Dr. Shashank Shah. The interviewee, Mr. G. Narayana, is Chairman Emeritus of Excel Industries Ltd. (Excel). Mr. Narayana is noted for his ability to positively motivate people through kindness and the integration of spirituality in the workplace. His brand of leadership is characterized by a type of management philosophy that integrates the scientific principles of the West with the profound thought of Indian scriptures

    Professional NoSQL

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    A hands-on guide to leveraging NoSQL databases NoSQL databases are an efficient and powerful tool for storing and manipulating vast quantities of data. Most NoSQL databases scale well as data grows. In addition, they are often malleable and flexible enough to accommodate semi-structured and sparse data sets. This comprehensive hands-on guide presents fundamental concepts and practical solutions for getting you ready to use NoSQL databases. Expert author Shashank Tiwari begins with a helpful introduction on the subject of NoSQL, explains its characteristics and typical uses, and looks at wher

    FastRecover: simple and effective fault recovery in a distributed operator-based stream processing engine

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    Fault tolerance is a key requirement in large-scale distributed stream processing engines (SPEs), especially those that run atop commodity hardware. Currently, fault tolerance in popular distributed SPEs is either inadequate (e.g., those without automatic recovery of operator states) or complex and inefficient (e.g., those with transactional semantics). There are two major considerations in the design of an effective fault tolerance mechanism: the overhead of additional checkpointing operations during normal processing, and the time required to recover and return to normal processing when a failure happens. The main challenge lies in that faster recovery requires higher checkpointing overhead, and vice versa. This thesis presents FastRecover, a novel fault tolerance mechanism for distributed SPEs that strikes a balance between recovery time and checkpointing overhead. Specifically, given an application topology consisting of interconnected operators, and an upper bound on checkpoint overhead, FastRecover computes the optimal expected recovery time, as well as the strategy used for checkpointing and recovery in each operator. The main idea of FastRecover is to compute an optimal partitioning of the streaming operator topology into independent segments; for each segment, FastRecover backs up its input tuples and periodically checkpoints the states of operators therein. During recovery for a particular segment, FastRecover restores each affected operator state in the segment to the latest checkpoint, and replays the inputs of the segment since then. Both checkpointing and recovery utilize the parallel processing capabilities of the distributed SPE. Extensive experiments demonstrate that FastRecover achieves an average of 50% reduction in expected recovery time compared to simple solutions. The experiments also show that the total expected recovery time varies proportionally to the total computational recovery time and recovery latency in tests with simulated failures, and hence is a good measure to optimize.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2018-05-01The student, Shashank Yaduvanshi, accepted the attached license on 2016-04-26 at 10:44.The student, Shashank Yaduvanshi, submitted this Thesis for approval on 2016-04-26 at 10:47.This Thesis was approved for publication on 2016-04-27 at 09:19.DSpace SAF Submission Ingestion Package generated from Vireo submission #9498 on 2016-07-07 at 13:50:55Made available in DSpace on 2016-07-07T20:35:17Z (GMT). No. of bitstreams: 2 YADUVANSHI-THESIS-2016.pdf: 518533 bytes, checksum: 30ba3a4a00e435d068849e201c1c0d3e (MD5) LICENSE.txt: 4216 bytes, checksum: 241d02c3815a86bdd56f127b07578308 (MD5) Previous issue date: 2016-04-27Embargo set by: Seth Robbins for item 93185 Lift date: 2018-07-07T20:35:34Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 93185 on 2018-07-08T09:15:20Z

    The surprising effectiveness of explicit semantic analysis in dataless classification

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    Organizing textual content into broad labels is one of the most basic tasks that some people carry out on a regular basis. This simple task helps people navigate through large document collections by exposing the labels of the documents, which can then be used for selecting the documents of interest. Currently, the most popular techniques for providing this basic functionality are supervised in nature, wherein someone has to annotate a collection of documents with the labels of interest. However, it might not always be possible to create a sizeable labeled dataset for every scenario or domain of interest. Thus, techniques like “Dataless Classification” have been proposed in the past that are able to bootstrap the creation of a classifier by only requiring semantic descriptions of the labels. However, despite the encouraging performance of Dataless Classification on Text Classification tasks, there is still a room for large improvement. In this thesis, we identify the limitations of ESA-driven Dataless Classification and systematically design techniques for addressing each limitation. In the process, we end up developing 4 new embeddings – EntityESA, Entity2Vec, Topic2Vec and Word2Concept. However, despite our best efforts, we found it difficult to outperform the original Dataless Classification system. For some of the techniques we provide an explanation for this observed behavior, however we also attribute some of these observations to the datasets that are being used for evaluation purposes. We then propose a way to create a new dataset that can used for future Dataless evaluations. The new embedding methods proposed in this work are generic enough that they can be of independent interest as well.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-08-01The student, Shashank Gupta, accepted the attached license on 2019-07-15 at 16:16.The student, Shashank Gupta, submitted this Thesis for approval on 2019-07-15 at 16:30.This Thesis was approved for publication on 2019-07-16 at 09:00.DSpace SAF Submission Ingestion Package generated from Vireo submission #14330 on 2019-11-26 at 13:05:59Made available in DSpace on 2019-11-26T20:49:31Z (GMT). No. of bitstreams: 2 GUPTA-THESIS-2019.pdf: 2559723 bytes, checksum: 627d25e8a76ba33bd36b7f7048a8e3c7 (MD5) LICENSE.txt: 4211 bytes, checksum: c89953f4374346e995fc10a787018c72 (MD5) Previous issue date: 2019-07-16Embargo set by: Seth Robbins for item 112971 Lift date: 2021-11-26T20:49:41Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 112971 on 2021-11-27T10:15:20Z
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