66 research outputs found
Understanding ubiquitin chain interactions and mechanisms of deubiquitinases
No full textZhuang, ZhihaoIn the past 15 years following the recognition of Ciechanover, Hershko, and Rose’s discovery of ubiquitin in signaling protein degradation, we have made much progress in understanding ubiquitination and deubiquitination as critical cellular signaling processes. Ubiquitination is catalyzed by a cascade of three enzymes (E1, E2 and E3) resulting in site- and linkage-specific ubiquitination of target protein. Deubiquitinases (DUBs) counter the ubiquitin ligases’ activity and reverse this process. It is increasingly realized that DUBs, in addition to linkage specificity to polyubiquitin chains, also exhibit target protein and site specificity. Understanding the source of linkage specificity is critical to understanding cellular signaling pathways including DNA damage response, immune response, and cell cycle progression. Dysregulation of the ubiquitin pathway enzymes are often associated with human diseases like cancer and neurological disorder. ☐ In Chapter 2, I detail the development and utilization of di- and tri-ubiquitin probes/ substrates in understanding DUB activity and specificity. I prepared both terminal and internal warhead-containing chemically linked diubiquitin probes. I generated a new terminal fluorophore-containing diubiquitin probe of K11, K48 and K63 linkages resistant to internal cleavage by DUBs. I also successfully generated hybrid triubiquitin probes bearing a chemical linkage through a non-cleavable or Michael acceptor-containing linker. Finally I created a heterotypic branched triubiquitin chain probes resistant to internal cleavage and containing a terminal warhead. These di-and tri-ubiquitin probes enabled extensive interrogation the linkage specificity of DUBs and polyUb chain reader proteins. ☐ In Chapter 3, I present proteomic study and identification of DUBs and reader proteins specific for branched ubiquitin probes from HEK-293T cell lysates. Branched ubiquitin chains represent a new frontier in understanding of polyubiquitin signaling in the cell with very little known about the roles and functions. These probes show some branched linkage specific to pathways like DNA damage response and mitophagy. While certain ubiquitin binding domains were shown to exhibit specificity to branched triubiquitin chains. ☐ In Chapter 4, I discuss the crystal structure of a USP family DUB, USP9X, catalytic core as well as the structural elements responsible for recognition of polyubiquitin chains of different linkages. Using polyubiquitin probes discussed in Chapter 1, we investigated the linkage dependent endo/exo cleavage selectivity of USP9X towards different polyubiquitin chains. Furthermore, we explore K11 diubiquitin binding dynamics to USP9X catalytic core through high resolution mass spectrometry demonstrating the power of activity-based polyubiquitin probes. ☐ Parts of chapter 2 and most of chapter 4 are adapted from texts and figures published in Paudel et. al. (2019). PNAS. 116(15) 7288-7297. Parts of chapter 2 also contain adapted text and figures from Gui et. al. (2019) Ref Mod Chem. Mol Sci Chem. 14672.University of Delaware, Department of Chemistry and BiochemistryPh.D
Topics on electron,neutrino and axion scattering
No full textThesis: S.M., Massachusetts Institute of Technology, Department of Physics, 2015.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from PDF version of thesis.Includes bibliographical references (pages 61-64).Under the broad topic of scattering, in this thesis we particularly investigate Lorentz invariance using Compton Scattering at the Compton Polarimeter located in Hall-C at Thomas Jefferson National Accelerator Facility. The Mississippi State Axion Search, an axion search experiment which uses light shining through a wall technique is described in detail, including its instrumentation, initial tests and future impact. Furthermore, a novel method of detection of solar anti-neutrinos based on coherent neutrino scattering is described. Additionally, on the instrumentation side, development of a multi-purpose beam instrument based on synchrotron light to measure the electron beam polarization, beam profile and intensity at the future Electron Ion Collider is presented.by Prajwal Mohanmurthy.S.M
Leaf Essential Oil Composition of Citrus Japonica from Biratnagar, Nepal
No full texthttps://louis.uah.edu/rceu-hcr/1246/thumbnail.jp
MDO framework for university research collaboration: AGILE academy initiatives & outcomes
No full textAGILE Project is developing the 3rd generation MDO processes, which will support the development of the next generation aerospace products. The establishment of effective collaborative design methodologies is currently acknowledged as the key enabler for future product development processes. At the same time, the need to introduce collaborative design techniques within educational activities is also well recognized by the Academic, Research and Industrial communities. AGILE project supported by European Commission’s H2020 Programme, is setting the “AGILE Paradigm”, a conceptual framework which contains all the elements to implement a multidisciplinary collaborative design network. The AGILE Academy initiative is conceived to infuse into the Academic organizations and educational environments the “AGILE Paradigm”, and make available all the technologies developed within the AGILE Project, which support the implementation of such a Paradigm. This paper focus is on the inception, approach and results of the AGILE Academy participants from several universities around the world
Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study
No full textBACKGROUND: The COVID-19 pandemic response is affecting maternal and neonatal health services all over the world. We aimed to assess the number of institutional births, their outcomes (institutional stillbirth and neonatal mortality rate), and quality of intrapartum care before and during the national COVID-19 lockdown in Nepal. METHODS: In this prospective observational study, we collected participant-level data for pregnant women enrolled in the SUSTAIN and REFINE studies between Jan 1 and May 30, 2020, from nine hospitals in Nepal. This period included 12·5 weeks before the national lockdown and 9·5 weeks during the lockdown. Women were eligible for inclusion if they had a gestational age of 22 weeks or more, a fetal heart sound at time of admission, and consented to inclusion. Women who had multiple births and their babies were excluded. We collected information on demographic and obstetric characteristics via extraction from case notes and health worker performance via direct observation by independent clinical researchers. We used regression analyses to assess changes in the number of institutional births, quality of care, and mortality before lockdown versus during lockdown. FINDINGS: Of 22 907 eligible women, 21 763 women were enrolled and 20 354 gave birth, and health worker performance was recorded for 10 543 births. From the beginning to the end of the study period, the mean weekly number of births decreased from 1261·1 births (SE 66·1) before lockdown to 651·4 births (49·9) during lockdown-a reduction of 52·4%. The institutional stillbirth rate increased from 14 per 1000 total births before lockdown to 21 per 1000 total births during lockdown (p=0·0002), and institutional neonatal mortality increased from 13 per 1000 livebirths to 40 per 1000 livebirths (p=0·0022). In terms of quality of care, intrapartum fetal heart rate monitoring decreased by 13·4% (-15·4 to -11·3; p<0·0001), and breastfeeding within 1 h of birth decreased by 3·5% (-4·6 to -2·6; p=0·0032). The immediate newborn care practice of placing the baby skin-to-skin with their mother increased by 13·2% (12·1 to 14·5; p<0·0001), and health workers' hand hygiene practices during childbirth increased by 12·9% (11·8 to 13·9) during lockdown (p<0·0001). INTERPRETATION: Institutional childbirth reduced by more than half during lockdown, with increases in institutional stillbirth rate and neonatal mortality, and decreases in quality of care. Some behaviours improved, notably hand hygiene and keeping the baby skin-to-skin with their mother. An urgent need exists to protect access to high quality intrapartum care and prevent excess deaths for the most vulnerable health system users during this pandemic period. FUNDING: Grand Challenges Canada
Cutaneous Manifestations of Covid-19 in Nepal: A Series of Case Reports
No full textCoronavirus Disease 2019 (COVID-19) is an illness caused by SARS-CoV-2. Case series of large population on cutaneous manifestations of COVID-19 are yet to be reported from Nepal. Among the cases in our study, onset of urticarial rash prior to onset of fever and systemic symptoms can be very important in preventing the chain of transmission of COVID-19 infection. Knowledge among medical practitioners of varied cutaneous features of COVID-19 can lead to testing COVID-19 in these cases and an early diagnosis
Low-cost uni-directional PFC for 3-phase systems
No full textPower consumed by any equipment connected to the grid must be regulated to facilitate the reliable and efficient operation of the grid and for smooth equipment operation of other consumers. Power factor is one of the major power quality measurement tool. All the electrical equipment connected to the grid must comply with the power factor limits as specified under various standards. This thesis aims at the development of a cost-effective power factor correction converter for a motor drive with a power range up to 10 kW, which is also robust for line and load transients.Electrical Engineerin
Quality of Life in Nepalese Patients with Non-Scarring Alopecia: A Cross-Sectional Observational Study at a Tertiary Center
No full textIntroduction: Alopecia is a dermatological condition characterized by the loss or reduction of hair. Alopecia areata and androgenetic alopecia are fairly common hair disorders. Hair loss causes a significant impact in person’s life which may lead to loss of self-confidence and distorted body image.
Materials and Methods: All consenting patients with alopecia areata and androgenetic alopecia, presenting to the out-patient department from September 2020 to August 2021 were enrolled based on convenience sampling method in this observational study. Ethical clearance was obtained from the ethical review committee of same institute (IRC protocol no.9/2021). All patients completed the Nepali Dermatology Life Quality Index questionnaire. Statistical Package for Social Studies version 25 was used for statistical analysis. Mean scores between groups were compared with Mann-Whitney U test.
Results: Out of 142 patients, there were 79 (55.6%) males and 63 (44.4%) females. There were 48 (33.8%) patients of alopecia areata while ninety-four (66.2%) had androgenetic alopecia. The mean total of Dermatology Life Quality Index score was 8.16 (±6.126). Mean score of females was 9.16±5.858 which was significantly higher than that of males 7.37±6.258 (p<0.05) and the score of the androgenetic patients (9.45±6.094) was significantly higher than that of areata patients (5.65±5.417) (p<0.001). All sub-domains of the questionnaire were impaired more in female. Increasing duration of the disease and hair loss in any first degree relative increased the impairment in quality of life significantly.
Conclusion: The quality of life in females were more affected as compared to males in both kinds of hair loss. However, patients with androgenetic alopecia had a greater impairment than patients with alopecia areata in our population
Cylinder Drag Reduction Using Discrete Surface Roughness: An Experimental Investigation Into the Effect of Cylindrical Roughness Elements
No full textThis thesis investigates the influence of Cylindrical Distributed Roughness Elements (polka-dots) on cylinder flow, with a focus on potential applications in sports aerodynamics. The primary goals are twofold: to explore the mechanism behind tripping and to analyse how the dimensions (height, width, spacing) of polka-dots affect flow characteristics. The research employs an experimental approach, utilising balance measurements to quantify drag within the relevant Reynolds number range experienced by the limbs of speed-skaters. Additionally, Particle Image Velocimetry (PIV) measurements are conducted to examine the boundary layer and wake flow, revealing insights into how different polka-dot geometries impact flow characteristics.11 polka-dot configurations were tested wherein the polka-dot height, diameter and spanwise (flow-normal) spacing was varied. Two PIV domains were imaged: the boundary layer flow before and after the polka-dot (covering an azimuthal range of about 40◦ of the circular profile), and the wake domain of the cylinder (about 2 diameters into the downstream flow). The boundary layer flow images were used to characterise the flow seen by the polka-dot array, and how it is affected by changes in the polka-dot geometry. The wake domain PIV imagery was used to examine the shape and dimensions of the cylinder wake.Among the 11 tested polka-dot configurations, 10 effectively triggered drag reduction to varying extents within the relevant regime. The minimum drag coefficient was achieved by the configuration with the polka-dots of greatest diameter. It was also seen that increasing polka-dot height is likely to cause premature separation which is further exacerbated by a narrower polka-dot spacing. In general, results indicate that shorter and wider polka-dots cause transition at lower Reynolds numbers, and a greater reduction in drag occurs when transition takes place at higher Reynolds numbers. Polka-dots placed in closer proximity initiate flow tripping earlier, while wider spacing results in more substantial drag reduction. However, it is observed that the polka-dots, when spaced closer together, see a lower flow velocity for the same polka-dot height and may lead to premature separation.In terms of the wake width, a high linear correlation is seen between the measured wake width and the measured coefficient of drag (r2 ≈ 0.9). It is also seen that for drag coefficient values close to the minimum drag coefficient value, the wake width sees minimal change. The change in wake geometry is then seen as a change in the wake tapering (downstream decrease of the wake width) and the streamwise wake length. Therefore, a larger wake imaging domain in the streamwise direction is likely to allow for a more accurate correlation of the wake geometry and the drag coefficient.While the study offers valuable insights, several recommendations are put forth for further research. Expanding the wake imaging domain is suggested to enhance correlations with the drag coefficient, and investigating spanwise flow variations would provide deeper insight into the tripping mechanism.Aerospace Engineering | Aerodynamic
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