34 research outputs found

    Mechanistic and synthetic studies on the prochlorosin and cytolysin families of lanthipeptides

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    Peptides are an attractive class of therapeutics, occupying a niche between small molecules and biologics. Research in the van der Donk lab focuses on lanthipeptides, a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that commonly feature antibacterial activity and contain the characteristic thioether residues lanthionine (Lan) and methyllanthionine (MeLan). Installation of thioether crosslinks in lanthipeptide biosynthesis is carried out by designated synthetases and involves dehydration of Ser/Thr residues and cyclization via Michael-type addition. The remarkably broad substrate scope of the synthetase ProcM inspired us to explore its mechanism in detail (chapter 2). My studies on ProcM revealed the directionality of dehydration, the order of cyclization, and that, despite the impressive substrate scope, none of the cyclizations are non-enzymatic. In collaboration, we established the irreversibility of the Michael-type addition and proposed that the topology of the thioether rings is under kinetic control. Solid phase peptide synthesis (SPPS) was used to generate the substrates to study ProcM, and is also a flexibile tool to access non-native lanthipeptide analogues. Interestingly, a lanthipeptide, cytolysin S (CylLS”), exhibited cytolytic activity in synergy with cytolysin L (CylLL”). Given that a thioether crosslink in CylLS” has an unusual LL-stereochemistry, the synthesis of a diastereomer of CylLS” with the more common DL-stereochemistry was achieved by SPPS (chapter 3). We probed whether the cytolytic activity depended on the LL-stereochemistry observed in CylLS”. Surprisingly, the unusual LL-stereochemistry was found to be important for the antibacterial activity, but not necessary for the hemolytic activity of CylLS”. I have also synthesized another hydrophobic lanthipeptide analogue, the portion of microbisporicin that contains the A and B ring (chapter 4). We established that this motif is not recognized by the halogenase MibH, and that the C terminus of microbisporicin is necessary for the chlorination by MibH. During my graduate studies, I had the opportunity to collaborate in a different area of research in our laboratory, the phosphonates. My efforts in the syntheses of various substrates and intermediates were instrumental in elucidating the biosynthetic pathways of dehydrophos, fosfazinomycin, and rhizocticin (chapter 5).Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2017-12-01The student, Subha Mukherjee, accepted the attached license on 2015-09-16 at 09:51.The student, Subha Mukherjee, submitted this Dissertation for approval on 2015-09-16 at 10:30.This Dissertation was approved for publication on 2015-09-17 at 16:49.DSpace SAF Submission Ingestion Package generated from Vireo submission #8689 on 2016-03-02 at 14:12:02Made available in DSpace on 2016-03-02T20:57:20Z (GMT). No. of bitstreams: 5 MUKHERJEE-DISSERTATION-2015.pdf: 14612785 bytes, checksum: c3aad023f3a2d3da85edae724ae51b88 (MD5) Mukherjee-Thesis-2015 - 091715.doc: 25670656 bytes, checksum: 88f5972e2608967d36a5e52fcb12b231 (MD5) LICENSE.txt: 4212 bytes, checksum: 3ebdb6fc336f6e901085f9a33daed6a0 (MD5) Subha Mukherjee Supplemental Document 1.pdf: 121941 bytes, checksum: 10c928dd46159e58e97e53d5f8717860 (MD5) Subha Mukherjee Supplemental Document 2.pdf: 75174 bytes, checksum: feaa03abb42ec3030dbdaca58be5c4a8 (MD5) Previous issue date: 2015-09-17Embargo set by: Seth Robbins for item 91376 Lift date: 2018-03-02T20:57:40Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 91376 Lift date: 2018-03-02T21:07:27Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 91376 on 2018-03-03T10:15:22Z

    Magnetic field threshold for accurate electrocardiography in the MRI environment

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    Although the electrocardiogram is known to be nondiagnostic within the bore of any high-field magnet due to the magnetohydrodynamic effect, there are an increasing number of applications that require accurate electrocardiogram monitoring of a patient inside the MRI room but outside of the magnet bore. Magnetohydrodynamic effects on the ST segment of the electrocardiogram waveform were investigated in six subjects at magnetic field strengths ranging from 6.4 mT to 652 mT at the aortic midarch, and the electrocardiogram was found to be accurate at magnetic fields below 70 mT. This corresponds to a distance of 160 cm from the isocenter and 80 cm from the bore entrance for the 1.5-T MRI system used in this study. These results can be translated to any MRI system, with knowledge of the fringe field. Accurate electrocardiogram monitoring is feasible in close proximity to the MRI magnet, such as during and after pharmacologic or exercise stress, or interventional or surgical procedures performed in the MRI room

    The bard in Bharadwaj: Politics of transculturation in the cinematic adaptations of Shakespeare by Vishal Bharadwaj

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    Cinema adaptations play a vital role in recreating the imaginations. When the author scripts his ideas into a text, again the text in converted into visual by the director, where he is both an author and an adopter. This paper investigates the three adaptations of Shakespeare by Vishal Bharadwaj – Maqbool, Omkara and Haider. It argues that the adaptations are transculturating Shakespeare in the Indian context and like Shakespeare was a cultural commodity propagated by British imperialism, Bollywood is a cultural commodity of the hegemonic discourse of Indian Nationhood. Thus, the paper aims to study if by transculturating Shakespeare, Bharadwaj dismantles the narrative of Indian Nationhood or if he merely reinforces it despite situating it in the uncomfortable margins that threaten it. Finally, the paper locates the struggle between the narrative of nationhood and the counter narratives on the body of the female subject and studies the leads in 10 100 Identity and Marginalisation in South Asian Literature and Media Shakespeare’s plays transculturated onto Bharadwaj’s screen in this ligh

    A comment on Liao’s Homotopy analysis method

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    Liao’s Homotopy analysis method is discussed. The authors introduced the new approach on which they claim makes the calculation of Homotopy analysis method easy. The analytical solutions for non-linear reaction diffusion equations using Homotopy analysis method and new Homotopy analysis method were discussed with examples. We also prove analytically that the methods given by Liao is equivalent to the present method

    Queerness, Sex Work, and Refugee Status in Nairobi: A conversation with Queer Sex Workers Initiative for Refugees

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    In this interview, the author speaks with Queer Sex Workers Initiative for Refugees: a Nairobi-based grassroots service-provision and advocacy group formed by queer refugees in Kenya who are engaged in sex work. The interview explores the question of how queer identity experiences interact with the policing of borders, labour issues, and refugee status. It teases out the ramifications of the compounding factors of migration and criminalisation of sex work and gender diversity, across borders, to show how these produce discrimination, loss of livelihood, and vulnerability to violence

    Machine learning based prediction of production using real time data of a point bottom sealing and cutting machine

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    The packaging sector utilizes polypropylene based flexible materials for diverse product packaging with customization options in size and design achieved through advanced flexographic printing and point bottom sealing and cutting machines. Accurately estimating production time and quantity is vital for efficient planning and cost estimation, with factors like material dimensions, thickness, and cutting machine speed influencing production output. Understanding the intricate relationship between these parameters is essential for comprehending their impact on production time and quantity. Predicting production quantity before production begins helps in determining machine runtime and associated costs. In large-scale production systems, machine learning (ML) has proven to be a useful tool for resource allocation and predictive scheduling. An attempt has been made in this paper to develop an intelligent model for predicting the yield of a cutting machine using artificial neural network (ANN), support vector regression (SVR), regression tree ensemble (RTE) and gaussian process regression (GPR). The most crucial features for prediction were identified and the hyperparameters of the ML models were optimized to create efficient models for prediction. A comparative analysis of the four models revealed that the GPR model was simple and effective with least training time and prediction error

    Development of Self-Powered Energy-Harvesting Electronic Module and Signal-Processing Framework for Wearable Healthcare Applications

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    A battery-operated biomedical wearable device gradually assists in clinical tasks to monitor patients’ health states regarding early diagnosis and detection. This paper presents the development of a self-powered portable electronic module by integrating an onboard energy-harvesting facility for electrocardiogram (ECG) signal processing and personalized health monitoring. The developed electronic module provides a customizable approach to power the device using a lithium-ion battery, a series of silicon photodiode arrays, and a solar panel. The new architecture and techniques offered by the developed method include an analog front-end unit, a signal processing unit, and a battery management unit for the acquiring and processing of real-time ECG signals. The dynamic multi-level wavelet packet decomposition framework has been used and applied to an ECG signal to extract the desired features by removing overlapped and repeated samples from an ECG signal. Further, a random forest with deep decision tree (RFDDT) architecture has been designed for offline ECG signal classification, and experimental results provide the highest accuracy of 99.72%. One assesses the custom-developed sensor by comparing its data with those of conventional biosensors. The onboard energy-harvesting and battery management circuits are designed with a BQ25505 microprocessor with the support of silicon photodiodes and solar cells which detect the ambient light variations and provide a maximum of 4.2 V supply to enable the continuous operation of an entire module. The measurements conducted on each unit of the proposed method demonstrate that the proposed signal-processing method significantly reduces the overlapping samples from the raw ECG data and the timing requirement criteria for personalized and wearable health monitoring. Also, it improves temporal requirements for ECG data processing while achieving excellent classification performance at a low computing cost

    EXTRUSION TECHNIQUE IN FOOD PROCESSING AND A REVIEW ON ITS VARIOUS TECHNOLOGICAL PARAMETERS

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    *Author for Correspondence Extrusion technique is a process in food processing technology which combines several unit operations including mixing, cooking, kneading, shearing, shaping and forming. Food extrusion is a form of extrusion used in food processing. It is a process by which a set of mixed ingredients are forced through an opening in a perforated plate or die with a design specific to the food, and is then cut to a specified size by blades. The machine which forces the mix through the die is an extruder, and the mix is known as the extrudate. The extruder consists of a large, rotating screw tightly fitting within a stationary barrel, at the end of which is the die. Key Words: Extrudate, Extrusion and Food Processin
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