96 research outputs found
Raltegravir, elvitegravir, and metoogravir: the birth of "me-too" HIV-1 integrase inhibitors
No full textAbstract Correction to Erik Serrao, Srinivas Odde, Kavya Ramkumar and Nouri Neamati: Raltegravir, elvitegravir, and metoogravir: the birth of "me-too" HIV-1 integrase inhibitors. Retrovirology 2009, 6:25. Since the recent publication of our article (Neamati, Retrovirology 2009, 6:25), we have noticed an error which we would like to correct and we would like to apologise to the readers for this mistake.</p
Endosomal receptor trafficking and signal transduction in Schwann cells: regulation of the Nrg1-induced PI3-kinase pathway
No full textNeuregulin1-ErbB signaling is important for various functions during Schwann cell development and myelination. Activation of the ErbB receptors also triggers myelin breakdown in mature myelinating Schwann cells. The mechanism by which the activated ErbB receptor complex elicits multiple biological functions in Schwann cells is unclear. In Charcot-Marie-Tooth (CMT) disease - the most common demyelinating neuropathy in the peripheral nervous system - many proteins involved in regulating intracellular vesicular trafficking and sorting through the endocytic pathway are found mutated. Endocytic pathways are also strongly implicated in the regulation of signal transduction by cell surface receptors. It is possible that aberrant regulation of the ErbB receptors and downstream signal activation by the impaired endocytic components contribute to the disease manifestation. The function of ErbB receptor trafficking and signal modulation in Schwann cells is largely unknown. We hypothesized that Nrg1-induced ErbB2 and ErbB3 receptor trafficking can differentially regulate signaling by spatially and temporally localizing receptors in different endocytic compartments. In this study, we show that following treatment with soluble Nrg1, internalized ErbB receptors are sorted into the late endosome/lysosome for degradation or transported to the recycling endosome and reappear on the cell surface. ErbB receptor recycling is also regulated by Nrg1 dose. Inhibition of receptor endocytosis by impairing dynamin activity blocked the Nrg1-induced Akt activation and abrogated the pro-myelinating effect in co-cultures. Interestingly, allowing receptor endocytosis but inhibiting the subsequent recycling from the early endosome enhanced Akt activation, indicating the importance of the early endosomal signaling for the Nrg1-induced Akt activity. Supporting this, sub-cellular fractionation showed that active Akt was enriched in the endosomal fraction in Schwann cells. We also investigated the mechanism by which membrane-bound Nrg1 Type III regulates ErbB receptor trafficking in Schwann cells. Binding of the axonal Nrg1 induced both ErbB2 and ErbB3 downregulation indicating receptor internalization. The membrane-bound Nrg1 Type III was also internalized into the Schwann cells, appearing in Rab5-positive early endosomes. The Nrg1-induced Akt activation, which is necessary for myelination was abrogated when receptor endocytosis in Schwann cells was blocked. Our results show that endocytic trafficking is important for the pro-myelinating function of Nrg1. The results also suggest that impaired endocytic pathways may contribute to the development of demyelinating neuropathy by resulting in aberrant regulation of the Nrg1-ErbB signaling in Schwann cells.Ph. D.Includes bibliographical referencesIncludes vitaby Kavya Redd
Effect of intravenous dexmedetomidine administered as bolus or as bolus-plus-infusion on subarachnoid anesthesia with hyperbaric bupivacaine
No full textBackground: Subarachnoid anesthesia is a widely practiced regional anesthetic for infraumbilical surgeries. Intravenous dexmedetomidine is known to prolong both sensory and motor blockade when administered along with subarachnoid anesthesia.
Material and Methods: Seventy-five patients scheduled to undergo elective infraumbilical surgeries under subarachnoid anesthesia were randomly allocated to one of the three groups. Group B received intravenous saline over 10 min followed by 12.5 mg intrathecal bupivacaine and then intravenous saline over 60 min. Group bupivacaine + dexmedetomidine bolus (BDexB) received intravenous dexmedetomidine (1 μg/kg) over 10 min followed by 12.5 mg intrathecal bupivacaine and then intravenous saline over 60 min. Group bupivacaine + dexmedetomidine bolus-plus-infusion (BDexBI) received intravenous dexmedetomidine (0.5 μg/kg) over 10 min followed by 12.5 mg intrathecal bupivacaine and then intravenous dexmedetomidine (0.5 μg/kg) over 60 min. Onset of analgesia (at T10), complete motor block (Bromage score 3), and highest level of analgesia were noted. Sensory and motor levels were checked periodically till sensory recovery (at S2–S4) and complete motor recovery (Bromage score 0). Ramsay sedation score and incidence of bradycardia/hypotension were noted.
Results: Sensory recovery was significantly longer in Group BDexB (303 min) and Group BdexBI (288 min) as compared to Group B (219.6 min). Motor recovery was also significantly prolonged in Group BDexB (321.6 min) and Group BDexBI (302.4 min) as compared to Group B (233.4 min). Patients receiving dexmedetomidine were sedated but were easily arousable.
Conclusion: Intravenous dexmedetomidine given as bolus or bolus-plus-infusion with intrathecal hyperbaric bupivacaine prolongs both sensory and motor blockade
Concrete particle characterization using impedance cytometry
No full textWe demonstrate a novel method to detect and characterize the size and number of Wollastonite particles using microfluidic impedance cytometry. The fabricated device which consists of gold electrodes micro-fabricated in a microchannel is capable of detecting particles >1 micron. Particle characterization is often carried out across a wide range of industries and is a critical parameter in the manufacture of various products to help improve the characteristics, performance or quality of powders or particles. There are a number of commercially available particle characterization techniques like laser diffraction, dynamic light scattering, electrophoretic light scattering, automated imaging, sedimentation etc that can be used to measure particulate samples and each has its relative strengths and limitations-there is no universally applicable technique for all samples. Our approach uses electrical impedance spectroscopy which measures the change in impedance as the particles in suspension pass through the sensor. It is a highly precise, low cost alternative for particle size characterization with a smaller footprint offering quick analysis time and is suitable for relatively broad range of particle sizes.M.S.Includes bibliographical referencesby Kavya Vasudevamurth
Costs and consequences of unmet early child care needs among parents working at academic institutions across the United States
No full textThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: M.C.P., Massachusetts Institute of Technology, Department of Urban Studies and Planning, 2019Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 200-216).Cities across the United States are saddled with a burgeoning child care conundrum, a mismatch between the skyrocketing need for child care and the fundamental insufficiency of child care infrastructure and policies to address the growing demand. To be sure, the broken child care market -- characterized by too few spots, mediocre quality, and exorbitant costs -- forces parents to make tradeoffs in order to fully meet their child care needs. These tradeoffs not only perpetuate deep-seated gender inequalities and compromise family economic security, but they also have broader social and economic consequences. Though research shows that large public investments could go a long way in fixing the child care conundrum and its pernicious effects, current political gridlock has hindered efforts to create universal child care programs and policies. In the absence of large public investments in child care, this thesis builds a case for local employers and institutions to be held accountable for filling the early child care needs of their workforce. One such employer primed to tackle the child care conundrum is the American academe. I use the results of an original online survey of parents working, teaching, researching, or studying in academia with a child under the age of five to develop a deterministic model that quantifies the total cost of unmet child care needs to academic parents and academic institutions. The findings suggest that a variety of small investments in child care by academic institutions could generate substantial savings for parents and institutions alike, contribute to local economic development, and set the stage for innovative child care policy.by Kavya Vaghul.M.C.P.M.C.P. Massachusetts Institute of Technology, Department of Urban Studies and Plannin
Buddhaghosa
No full textThis entriy is about Buddhaghosa or Buddhaghosacarya, a poet of unknown date known for being the author of the Padyacudamani (The Crest-Jewel of Verses), a Sanskrit mahakavya (great kavya) or sargabandha (canto composition) poem
Regulatory mechanisms underlying C3 carbon and nitrogen metabolism under elevated CO2
No full textRising atmospheric CO2 concentration will affect species-specific responses to carbon (C) gain in plants, in turn impacting plant productivity in natural and agro-ecosystems in the future. Several interacting environmental and genetic factors affect species-specific response to C gain under elevated atmospheric CO2 concentration (eCO2). One of the many challenges faced in understanding these interaction responses is efficiently predicting genotype to phenotype relationships that are also needed to design future crop idiotypes. Hence this thesis aims to partly address this fundamental knowledge gap by using mathematical modeling and systems biology approaches to identify regulatory factors influencing carbon (C) and nitrogen (N) metabolism in C3 plants under eCO2 through inferences made in Soybean and Arabidopsis. This aim is achieved threefold.
The first aim involves optimizing protein translation dynamics in C3 plants. It is essential to understand the processes underlying changes in protein abundance in a gene under varying physiological and developmental conditions to model and rationally engineer plants. Several protein translation models have been developed in the past that utilize genome-wide transcriptomic datasets to make predictions on protein levels in eukaryotes. Still, very few have successfully incorporated post-transcriptional and post-translational modifications in making these predictions, especially in plants, owing to the lack of experimental data capturing these mechanisms. Moreover, a large proportion of genes in plants undergo complex regulatory dynamics, some of which are different from other eukaryotes that cause a large discrepancy between mRNA expression and protein levels of individual genes, and this discrepancy changes based on the severity of the stress condition. Hence, to partly address this issue, genome-wide proteome and transcriptome datasets in Arabidopsis are utilized as a benchmark to optimize a protein transition model represented by a non-linear ordinary differential equation.
The second aim of this thesis involves multiscale modeling to gain a mechanistic understanding of the regulation of photosynthesis in soybean under eCO2. Multiscale models can predict emergent plant responses to environmental perturbations by mimicking the biological flow of information across scales. Soybean is one of the major sources of plant protein and oil. Specific genotypes of soybean have shown a lower than theoretically anticipated stimulation of photosynthesis under eCO2. It is hypothesized that a guided genetic manipulation could alter the photosynthesis machinery in soybean under eCO2, which might, in turn, affect its productivity under future “C” fertilization conditions as photosynthesis is one of the fundamental processes for sustaining plant growth. Hence, to test this hypothesis, chapter 3 utilizes a multiscale modeling approach that scales from gene expression to organ-level physiology to predict robust transcription factor candidates that might influence soybean photosynthesis under eCO2.
The third aim of this thesis involves the investigation of regulatory mechanisms controlling the coordination of C and N metabolism in C3 plants under eCO2. Among the many interacting environmental factors, N availability has been shown to significantly influence the extent of photosynthetic stimulation, photosynthetic acclimation, leaf N status as well as productivity in selected C3 plants under eCO2. Chapter 4 draws inferences from a C-N interaction significant gene regulatory network to predict key transcription factors that could fine-tune the genetic changes in C3 plants to coordinate C and N metabolism under eCO2. Transcription factors thus predicted could provide additional insights on regulatory mechanisms underlying C3 plant quality and productivity in a future “C” fertilization environment.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01The student, Kavya Kannan, accepted the attached license on 2020-04-30 at 21:03.The student, Kavya Kannan, submitted this Dissertation for approval on 2020-04-30 at 23:26.This Dissertation was approved for publication on 2020-05-03 at 15:11.DSpace SAF Submission Ingestion Package generated from Vireo submission #15136 on 2020-08-25 at 17:42:23Made available in DSpace on 2020-08-27T00:50:15Z (GMT). No. of bitstreams: 4
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Effects of a Single Bout of Exercise on Lipoprotein Fractions in Hypercholesterolemic Women
No full textEffects of a Single Bout of Exercise on Lipoprotein Fractions in Hypercholesterolemic Women
Allen Sexton, Kavya Chelikani, and Yunsuk Koh
Department of Health and Kinesiology, Lamar University, Beaumont, TX 77710
Classification of First Author: Master’s
Background: Abnormal lipoprotein profiles are strongly associated with premature cardiovascular disease. Sedentary lifestyle and menopause may accelerate abnormal lipid and lipoprotein metabolism in women. A single bout of aerobic exercise at moderate intensity may positively alter serum lipoprotein fractions in postmenopausal women with high cholesterol levels.
Objectives: The current study investigated how a single bout of exercise affects lipoprotein fractions in sedentary, postmenopausal women with hypercholesterolemia.
Methods: Thirteen (N=13) sedentary, hypercholesterolemic (defined as total cholesterol \u3e 200 mg/dl; average TC = 241.7 ± 5.8 mg/dl) postmenopausal women (age = 57.4 ± 2.0 years) randomly performed both exercise and rest trials. For the exercise trial, participants performed a single bout of exercise at 60% of heart rate reserve on a treadmill until 400 kcal were expended. Serum samples were collected at pre (0), 24, and 48 hours following each trial to analyze the lipoprotein fractions (α, pre-β, and β) using electrophoresis. A 2 (trial: rest and exercise) x 3 (time: 0, 24, and 48 hours) repeated ANOVA was employed to determine the significant changes in serum lipoprotein fractions. The p value \u3c .05 was considered to be statistically significant.
Results: The α-lipoprotein fraction in the exercise trial was significantly higher than the rest trial (35.7 vs. 34.9%, p=.006), while the β-lipoprotein fraction in the exercise trial was significantly lower than the rest trial (56.8 vs. 57.6%, p=.001). Additionally, the β-lipoprotein fraction at 24 hours (56.3%) was significantly lower (p=.008) than 0 (57.8%) or 48 hours (57.5%). The pre-β fraction remained unchanged.
Conclusion: A single bout of moderate intensity aerobic exercise can favorably alter serum α- and β- lipoprotein fractions in postmenopausal women with hypercholesterolemia
Developing an Integrated and Contextualized Planning and Design Framework for Livable Patterns of Urbanization in Chennai
No full textThis article analyses the urban conditions of Chennai, India, and takes a critical look at its planning framework by considering four main aspects: the ecological structures, urban morphology, mobility, and livability. To do so, the article examines policy documents, urban form, public perceptions, and daily mobility patterns. Specific attention is focused on three layers of the urban fabric: water and ecology, transport infrastructure, and housing. First, the city’s river restoration is critically assessed, with a focus on integrating the social dimension into the process. Second, the metro network is analyzed, specifically understanding its usage with respect to different user groups. Third, the densification pattern in different parts of the city is analyzed. Considering the layers of water, transport infrastructure, and housing together, the article sets out an alternative integrated approach to strategic design and planning in the city towards the goal of creating a more livable public realm. The proposed integrated framework, termed “supergrids” is a city-scale strategy that enables a large reconfiguration of the existing networks in the city, integration of ecological systems into the public space network, and a restructuring of movement patterns by upscaling the vehicular network, and aligning pedestrian connections with green networks, public transit, and important functions.Urban DesignSpatial Planning and Strateg
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