13 results on '"Kumar, Bhaskar"'
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2. GlcNAc-1,6-anhydro-MurNAc Moiety Affords Unusual Glycosyl Acceptor that Terminates Peptidoglycan Elongation
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Zhang, Xiao-Lin, Báti, Gábor, Li, Chenyu, Guo, Aoxin, Yeo, Claresta, Ding, Han, Pal, Kumar Bhaskar, Xu, Yuan, Qiao, Yuan, and Liu, Xue-Wei
- Abstract
Peptidoglycan (PG), an essential exoskeletal polymer in bacteria, is a well-known antibiotic target. PG polymerization requires the action of bacterial transglycosylases (TGases), which couple the incoming glycosyl acceptor to the donor. Interfering with the TGase activity can interrupt the PG assembly. Existing TGase inhibitors like moenomycin and Lipid II analogues always occupy the TGase active sites; other strategies to interfere with proper PG elongation have not been widely exploited. Inspired by the natural 1,6-anhydro-MurNAc termini that mark the ends of PG strands in bacteria, we hypothesized that the incorporation of an anhydromuramyl-containing glycosyl acceptor by TGase into the growing PG may effectively inhibit PG elongation. To explore this possibility, we synthesized 4-O-(N-acetyl-β-d-glucosaminyl)-1,6-anhydro-N-acetyl-β-d-muramyl-l-Ala-γ-d-Glu-l-Lys-d-Ala-d-Ala, 1, within 15 steps, and demonstrated that this anhydromuropeptide and its analogue lacking the peptide, 1-deAA, were both utilized by bacterial TGase as noncanonical anhydro glycosyl acceptors in vitro. The incorporation of an anhydromuramyl moiety into PG strands by TGases afforded efficient termination of glycan chain extension. Moreover, the preliminary in vitrostudies of 1-deAAagainst Staphylococcus aureusshowed that 1-deAAserved as a reasonable antimicrobial adjunct of vancomycin. These insights imply the potential application of such anhydromuropeptides as novel classes of PG-terminating inhibitors, pointing toward novel strategies in antibacterial agent development. more...
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- 2024
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3. Prediction of battery critical parameters using machine learning algorithms for electric vehicles
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Hegde, Vasudha, Sohal, Jaskaran Singh, Balaraman, Gopi, Karn, Aayush, and Pandey, Kumar Bhaskar
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To enhance the adaptability of electric vehicles (EVs) and mitigate the intermittent nature of renewable energy sources, energy storage via batteries is imperative. Accurate forecasting of battery performance parameters is vital for optimal utilisation. This study introduces a machine learning algorithm for electric vehicle battery management systems (BMS), focusing on predicting state of charge (SoC) efficiently and precisely. Utilising linear regression and long short-term memory (LSTM) models, the algorithm constructs and deploys predictions. Training data, obtained from Li-ion battery packs during charge-discharge cycles via smart BMS, enables precise modelling. Predicted values are validated against empirical results, and the resultant error guides algorithm refinement for enhanced accuracy. The algorithm, integrated into a web application using Streamlit, achieved a remarkable 99% R2_score, indicating its robust performance. This framework advances EV battery management, facilitating informed decision-making and optimising energy utilisation in conjunction with renewable sources. more...
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- 2024
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4. Ligand Sulfur Oxidation State Progressively Alters Galectin-3-Ligand Complex Conformations To Induce Affinity-Influencing Hydrogen Bonds
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Mahanti, Mukul, Pal, Kumar Bhaskar, Kumar, Rohit, Schulze, Markus, Leffler, Hakon, Logan, Derek T., and Nilsson, Ulf J.
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Galectins play biological roles in immune regulation and tumor progression. Ligands with high affinity for the shallow, hydrophilic galectin-3 ligand binding site rely primarily on a galactose core with appended aryltriazole moieties, making hydrophobic interactions and π-stacking. We designed and synthesized phenyl sulfone, sulfoxide, and sulfide-triazolyl thiogalactoside derivatives to create affinity-enhancing hydrogen bonds, hydrophobic and π-interactions. Crystal structures and thermodynamic analyses revealed that the sulfoxide and sulfone ligands form hydrogen bonds while retaining π-interactions, resulting in improved affinities and unique binding poses. The sulfoxide, bearing one hydrogen bond acceptor, leads to an affinity decrease compared to the sulfide, whereas the corresponding sulfone forms three hydrogen bonds, two directly with Asn and Arg side chains and one water-mediated to an Asp side chain, respectively, which alters the complex structure and increases affinity. These findings highlight that the sulfur oxidation state influences both the interaction thermodynamics and structure. more...
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- 2023
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5. A Comparative Study of Machine Learning Models for Predicting Single Bead Geometry of SS316L Depositions by GTAW Wire Arc Additive Manufacturing Process
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kumar, Bhaskar and Rajak, Sonu
- Abstract
Machine learning (ML) has recently gained popularity as a computational method in the manufacturing sector. The current study compared three ML techniques, namely support vector machine (SVM), artificial neural network (ANN), and adaptive neuro-fuzzy inference system (ANFIS), for predicting bead geometry in wire arc additive manufacturing (WAAM). Single beads of stainless-steel 316L (SS316L) material were deposited in the WAAM process using a gas tungsten arc welding (GTAW) machine. Statistical metrics including the mean square error (MSE), mean absolute error (MAE), coefficient of determination (R2value), index of merit (IM), and root mean square error (RMSE) were used to evaluate the effectiveness of ML models. The result revealed that the ANFIS model showed the best results, having minimum RMSE and IM values of 0.28 and 0.60, respectively, for the prediction of bead height, while for predicting bead width, RMSE and IM values were found to be 0.11 and 0.60, respectively. more...
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- 2025
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6. Completely minimally invasive versus hybrid Ivor-Lewis oesophagectomy for oesophageal and gastro-oesophageal junctional cancer: a UK multi-centre comparative study
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Patel, Krashna, Askari, Alan, Abbassi, Omar, Jayanthi, Naga Venkatesh, Claydon, Oliver, Laycock, James, Ramalingam, Aravindh, Kumar, Bhaskar, Wong, Joshua, Aly, Mohamed, and Jambulingam, Periyathambi
- Abstract
Background: Limited robust evidence exists comparing outcomes following completely minimally invasive oesophagectomy (CMIO) to hybrid oesophagectomy (HO) in the treatment of resectable oesophageal and gastro-oesophageal junctional (GOJ) cancer. This multi-centre study aims to assess postoperative morbidity between HO and CMIO according to the full Esophagectomy Complications Consensus Group (ECCG) complication platform. Methods: All consecutive patients undergoing an Ivor-Lewis HO or Ivor-Lewis CMIO for cancer between 2016 and 2018 in three UK tertiary centres were included. The primary study outcome was 30-day overall complications, evaluated by the ECCG complication subgroups. Secondary outcomes included survival outcomes and perioperative parameters between the two approaches. Results: Of the 382 patients included, 228 (59.7%) patients had HOs and 154 (40.3%) patients had CMIOs with no inter-group baseline differences. Patients undergoing CMIO experienced less 30-day postoperative complications compared to those under undergoing HO (43.5% vs 57.0%, p= 0.010). ECCG defined pulmonary and infective complications were less frequent in the CMIO group. Anastomotic leak rates and oncological outcomes were similar between the two groups. Independent predictors of 30-day postoperative complications include surgical approach with HO and high ASA grade on multivariable analysis. Conclusions: Ivor-Lewis CMIO demonstrates superior short-term surgical outcomes when compared to Ivor-Lewis HO with no compromise in oncological feasibility. Anastomotic leak rates were equivalent between both groups. A robust randomised controlled trial is required to validate the findings of this study. more...
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- 2022
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7. Multi-Omic Analysis of Esophageal Adenocarcinoma Uncovers Candidate Therapeutic Targets and Cancer-Selective Posttranscriptional Regulation
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O'Neill, J. Robert, Yébenes Mayordomo, Marcos, Mitulović, Goran, Al Shboul, Sofian, Bedran, Georges, Faktor, Jakub, Hernychova, Lenka, Uhrik, Lukas, Gómez-Herranz, Maria, Kocikowski, Mikołaj, Save, Vicki, Vojtěšek, Bořivoj, Arends, Mark J., Fitzgerald, Rebecca C., Edwards, Paul A.W., Grehan, Nicola, Nutzinger, Barbara, Loreno, Christine, Redmond, Aisling M., Abbas, Sujath, Freeman, Adam, Smyth, Elizabeth C., O'Donovan, Maria, Miremadi, Ahmad, Malhotra, Shalini, Tripathi, Monika, Cheah, Calvin, Coles, Hannah, Millington, Curtis, Devonshire, Ginny, Eldridge, Matthew, Secrier, Maria, Jammula, Sriganesh, Davies, Jim, Crichton, Charles, Carroll, Nick, Hardwick, Richard H., Safranek, Peter, Hindmarsh, Andrew, Sujendran, Vijayendran, Hayes, Stephen J., Ang, Yeng, Sharrocks, Andrew, Preston, Shaun R., Bagwan, Izhar, Save, Vicki, Skipworth, Richard J.E., Hupp, Ted R., O'Neill, J Robert, Tucker, Olga, Beggs, Andrew, Taniere, Philippe, Puig, Sonia, Contino, Gianmarco, Underwood, Timothy J., Walker, Robert C., Grace, Ben L., Lagergren, Jesper, Gossage, James, Davies, Andrew, Chang, Fuju, Mahadeva, Ula, Goh, Vicky, Ciccarelli, Francesca D., Sanders, Grant, Berrisford, Richard, Chan, David, Cheong, Ed, Kumar, Bhaskar, Sreedharan, L., Parsons, Simon L., Soomro, Irshad, Kaye, Philip, Saunders, John, Lovat, Laurence, Haidry, Rehan, Scott, Michael, Sothi, Sharmila, Lishman, Suzy, Hanna, George B., Peters, Christopher J., Moorthy, Krishna, Grabowska, Anna, Turkington, Richard, McManus, Damian, Coleman, Helen, Petty, Russell D., Bartlet, Freddie, Hupp, Ted, and Alfaro, Javier Antonio more...
- Abstract
Efforts to address the poor prognosis associated with esophageal adenocarcinoma (EAC) have been hampered by a lack of biomarkers to identify early disease and therapeutic targets. Despite extensive efforts to understand the somatic mutations associated with EAC over the past decade, a gap remains in understanding how the atlas of genomic aberrations in this cancer impacts the proteome and which somatic variants are of importance for the disease phenotype. We performed a quantitative proteomic analysis of 23 EACs and matched adjacent normal esophageal and gastric tissues. We explored the correlation of transcript and protein abundance using tissue-matched RNA-seq and proteomic data from seven patients and further integrated these data with a cohort of EAC RNA-seq data (n = 264 patients), EAC whole-genome sequencing (n = 454 patients), and external published datasets. We quantified protein expression from 5879 genes in EAC and patient-matched normal tissues. Several biomarker candidates with EAC-selective expression were identified, including the transmembrane protein GPA33. We further verified the EAC-enriched expression of GPA33 in an external cohort of 115 patients and confirm this as an attractive diagnostic and therapeutic target. To further extend the insights gained from our proteomic data, an integrated analysis of protein and RNA expression in EAC and normal tissues revealed several genes with poorly correlated protein and RNA abundance, suggesting posttranscriptional regulation of protein expression. These outlier genes, including SLC25A30, TAOK2, and AGMAT, only rarely demonstrated somatic mutation, suggesting post-transcriptional drivers for this EAC-specific phenotype. AGMAT was demonstrated to be overexpressed at the protein level in EAC compared to adjacent normal tissues with an EAC-selective, post-transcriptional mechanism of regulation of protein abundance proposed. Integrated analysis of proteome, transcriptome, and genome in EAC has revealed several genes with tumor-selective, posttranscriptional regulation of protein expression, which may be an exploitable vulnerability. more...
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- 2024
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8. Management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction: the Neo-AEGIS trial
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Sivarajan, Sri, Gismondi, Martha, Pipalia, Nisarg, Tasigiannopoulos, Zacharias, and Kumar, Bhaskar
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- 2024
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9. Single Step Solution Processed GaAs Thin Films from GaMe3and tBuAsH2under Ambient Pressure
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Sathasivam, Sanjayan, Arnepalli, Ranga R., Bhachu, Davinder S., Lu, Yao, Buckeridge, John, Scanlon, David O., Kumar, Bhaskar, Singh, Kaushal K., Visser, Robert J., Blackman, Christopher S., and Carmalt, Claire J. more...
- Abstract
This article reports on the possibility of low-cost GaAs formed under ambient pressure via a single step solution processed route from only readily available precursors, tBuAsH2and GaMe3. The thin films of GaAs on glass substrates were found to have good crystallinity with crystallites as large as 150 nm and low contamination with experimental results matching well with theoretical density of states calculations. These results open up a route to efficient and cost-effective scale up of GaAs thin films with high material properties for widespread industrial use. Confirmation of film quality was determined using XRD, Raman, EDX mapping, SEM, HRTEM, XPS, and SIMS. more...
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- 2016
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10. A Case of Hepatic Abscess - the Penny Dropped!
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Manning, Charelle, Rafiee, Hameed, Kumar, Bhaskar, and Alam, Syed
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- 2021
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11. Metastatic Breast Carcinoma Presenting as a Sigmoid Stricture: Report of a Case and Review of the Literature
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Nikkar-Esfahani, Kumar, Bhaskar G., Aitken, Douglas, and Wilson, Robert G.
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AbstractMetastatic spread of breast carcinoma to the colon and rectum is rare. We report the case of a patient treated for lobular breast carcinoma presenting 17 years later with metastatic breast cancer of the colon. A 63-year-old lady with a past history of right-sided invasive lobular carcinoma of the breast presented with persistent diarrhoea. Colonoscopy with biopsies revealed a benign-looking stricture at the rectosigmoid junction. A CT scan of the abdomen and pelvis revealed a benign-looking stricture in keeping with a probable diverticular stricture. A Hartmann procedure was performed and histology revealed a metastatic lobular carcinoma with oestrogen and progesterone receptor-positive status. Treatment was commenced with letrozole and the patient remains well under clinical surveillance. In a patient with a history of breast carcinoma who presents with gastrointestinal symptoms the possibility of gastrointestinal tract spread should always be considered. Endoscopic diagnosis may be misleading with pathological diagnosis only being made following surgical resection. A history of breast carcinoma must be declared to the histopathologist following surgical resection so that an accurate diagnosis is made and appropriate treatment is commenced.Copyright © 2013 S. Karger AG, Basel more...
- Published
- 2013
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12. Flow past a rotating cylinder
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MITTAL, SANJAY and KUMAR, BHASKAR
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Flow past a spinning circular cylinder placed in a uniform stream is investigated via two-dimensional computations. A stabilized finite element method is utilized to solve the incompressible NavierStokes equations in the primitive variables formulation. The Reynolds number based on the cylinder diameter and free-stream speed of the flow is 200. The non-dimensional rotation rate, α (ratio of the surface speed and freestream speed), is varied between 0 and 5. The time integration of the flow equations is carried out for very large dimensionless time. Vortex shedding is observed for α < 1.91. For higher rotation rates the flow achieves a steady state except for 4.34 < α < 4:70 where the flow is unstable again. In the second region of instability, only one-sided vortex shedding takes place. To ascertain the instability of flow as a function of α a stabilized finite element formulation is proposed to carry out a global, non-parallel stability analysis of the two-dimensional steady-state flow for small disturbances. The formulation and its implementation are validated by predicting the Hopf bifurcation for flow past a non-rotating cylinder. The results from the stability analysis for the rotating cylinder are in very good agreement with those from direct numerical simulations. For large rotation rates, very large lift coefficients can be obtained via the Magnus effect. However, the power requirement for rotating the cylinder increases rapidly with rotation rate. more...
- Published
- 2003
13. TRPM3 Expression and Function in Vascular Smooth Muscle
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Naylor, Jacqueline, Li, Jing, Zeng, Fanning, Sukumar, Piruthivi, Majeed, Yasser, Milligan, Carol J., Kumar, Bhaskar, Porter, Karen E., and Beech, David J.
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- 2010
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