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Sökning: WFRF:(Gulati S.)

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1.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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2.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • 2021
  • swepub:Mat__t
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4.
  • Joffrin, E., et al. (författare)
  • Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
  • Forskningsöversikt (refereegranskat)abstract
    • For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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5.
  • Rathore, P. S., et al. (författare)
  • Comparative studies on tribocorrosion behaviour of plasma-sprayed and detonation gun coatings of Al2O3-13% TiO2 on biomedical alloy Ti-13Nb-13Zr and Gum metal
  • 2013
  • Ingår i: ASTM Special Technical Publication. ; , s. 88-104
  • Konferensbidrag (refereegranskat)abstract
    • The tribocorrosion behavior of titanium-based alloys is of significant interest as bio-implant materials. Bare alloys may not offer enough resistance to tribocorrosion, so coatings could be used to improve their performance. An important biomedical alloy, Ti-13Nb-13Zr, and a newly developed β titanium alloy called "Gum metal" (Ti-23%Ni-0.7%Ta-2%Zr-1 %O2) were used as substrates in the current work. Both were coated with conventional and nano-ceramic materials of Al2O3-TiO2. Bilayered coatings of ZrO2+Al2O3-13%TiO2 were also applied to the Ti-13Nb-13Zr using plasma spray. The coatings on Ti-13Nb-13Zr were applied using plasma spray, whereas that on the Gum metal was applied by a detonation gun (D-Gun). Surface morphology was characterized using a scanning electron microscope (SEM). Tribocorrosion experiments were performed in salt water using a linear reciprocating ball-on-plate tribometer with an aluminum ball as the slider. The nano particles are embedded in the fully melted splats and offered better crack propagation resistance. The high velocity of the D-Gun process resulted in a higher volume fraction of the embedded nano particles and produced substantial improvement in wear resistance relative to the air-plasma-sprayed coating. The conventional coating, with its higher porosity, exhibited a high corrosion rate compared to nano coating. The D-Gun coating, with its lower porosity, had a higher corrosion resistance than the plasma-sprayed coating, but bilayered plasma-sprayed coating showed even higher corrosion resistance, owing to its dense microstructure. Open-circuit potential measurements before and during tribocorrosion showed that the bilayered plasma-sprayed coating had better tribocorrosion resistance than the other coatings. Electrochemical impedance spectroscopy indicated stable impedance values for the bilayered plasma-sprayed coating before and after tribocorrosion. Copyright © 2013 by ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959.
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6.
  • Carlsten, C., et al. (författare)
  • COVID-19 as an occupational disease
  • 2021
  • Ingår i: American Journal of Industrial Medicine. - : Wiley. - 0271-3586 .- 1097-0274. ; 64:4, s. 227-237
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 permeates all aspects of society worldwide. Initial medical reports and media coverage have increased awareness of the risk imposed on healthcare workers in particular, during this pandemic. However, the health implications of COVID-19 for the global workforce are multifaceted and complex, warranting careful reflection and consideration to mitigate the adverse effects on workers worldwide. Accordingly, our review offers a framework for considering this topic, highlighting key issues, with the aim to prompt and inform action, including research, to minimize the occupational hazards imposed by this ongoing challenge. We address respiratory disease as a primary concern, while recognizing the multisystem spectrum of COVID-19-related disease and how clinical aspects are interwoven with broader socioeconomic forces.
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  • Currie, Michael J., et al. (författare)
  • Structural and biophysical analysis of a Haemophilus influenzae tripartite ATP-independent periplasmic (TRAP) transporter
  • 2024
  • Ingår i: ELIFE. - 2050-084X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the Haemophilus influenzae N-acetylneuraminate TRAP transporter (HiSiaQM) at 2.99 & Aring; resolution (extending to 2.2 & Aring; at the core), revealing new features. The improved resolution (the previous HiSiaQM structure is 4.7 & Aring; resolution) permits accurate assignment of two Na+ sites and the architecture of the substrate-binding site, consistent with mutagenic and functional data. Moreover, rather than a monomer, the HiSiaQM structure is a homodimer. We observe lipids at the dimer interface, as well as a lipid trapped within the fusion that links the SiaQ and SiaM subunits. We show that the affinity (K-D) for the complex between the soluble HiSiaP protein and HiSiaQM is in the micromolar range and that a related SiaP can bind HiSiaQM. This work provides key data that enhances our understanding of the 'elevator-with-an-operator' mechanism of TRAP transporters.
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8.
  • Davies, James S., et al. (författare)
  • Structure and mechanism of a tripartite ATP-independent periplasmic TRAP transporter
  • 2023
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In bacteria and archaea, tripartite ATP-independent periplasmic (TRAP) transporters uptake essential nutrients. TRAP transporters receive their substrates via a secreted soluble substrate-binding protein. How a sodium ion-driven secondary active transporter is strictly coupled to a substrate-binding protein is poorly understood. Here we report the cryo-EM structure of the sialic acid TRAP transporter SiaQM from Photobacterium profundum at 2.97 Å resolution. SiaM comprises a “transport” domain and a “scaffold” domain, with the transport domain consisting of helical hairpins as seen in the sodium ion-coupled elevator transporter VcINDY. The SiaQ protein forms intimate contacts with SiaM to extend the size of the scaffold domain, suggesting that TRAP transporters may operate as monomers, rather than the typically observed oligomers for elevator-type transporters. We identify the Na+ and sialic acid binding sites in SiaM and demonstrate a strict dependence on the substrate-binding protein SiaP for uptake. We report the SiaP crystal structure that, together with docking studies, suggest the molecular basis for how sialic acid is delivered to the SiaQM transporter complex. We thus propose a model for substrate transport by TRAP proteins, which we describe herein as an ‘elevator-with-an-operator’ mechanism.
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  • Ngampasutadol, J, et al. (författare)
  • Human CO-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection
  • 2005
  • Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:47, s. 17142-17147
  • Tidskriftsartikel (refereegranskat)abstract
    • Neisseria gonorrhoeae is the causative agent of gonorrhea, a disease that is restricted to humans. Complement forms a key arm of the innate immune system that combats gonococcal infections. N. gonorrhoeae uses its outer membrane porin (Por) molecules to bind the classical pathway of complement down-regulatory protein C4b-binding protein (C4bp) to evade killing by human complement. Strains of N. gonorrhoeae that resisted killing by human serum complement were killed by serum from rodent, lagomorph, and primate species, which cannot be readily infected experimentally with this organism and whose C4bp molecules did not bind to N. gonorrhoeae. In contrast, we found that Yersinia pestis, an organism that can infect virtually all mammals, bound species-specific C4bp and uniformly resisted serum complement-mediated killing by these species. Serum resistance of gonococci was restored in these sera by human C4bp. An exception was serotype Por1B-bearing gonococcal strains that previously had been used successfully in a chimpanzee model of gonorrhea that simulates human disease. Por1B gonococci bound chimpanzee C4bp and resisted killing by chimpanzee serum, providing insight into the host restriction of gonorrhea and addressing why Por1B strains, but not Por1A strains, have been successful in experimental chimpanzee infection. Our findings may lead to the development of better animal models for gonorrhea and may also have implications in the choice of complement sources to evaluate neisserial vaccine candidates.
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11.
  • Bakker, Elisabeth S., et al. (författare)
  • Restoring macrophyte diversity in shallow temperate lakes : biotic versus abiotic constraints
  • 2013
  • Ingår i: Hydrobiologia. - : Springer Science and Business Media LLC. - 0018-8158 .- 1573-5117. ; 710:1, s. 23-37
  • Tidskriftsartikel (refereegranskat)abstract
    • Although many lake restoration projects have led to decreased nutrient loads and increased water transparency, the establishment or expansion of macrophytes does not immediately follow the improved abiotic conditions and it is often unclear whether vegetation with high macrophyte diversity will return. We provide an overview of the potential bottlenecks for restoration of submerged macrophyte vegetation with a high biodiversity and focus on the biotic factors, including the availability of propagules, herbivory, plant competition and the role of remnant populations. We found that the potential for restoration in many lakes is large when clear water conditions are met, even though the macrophyte community composition of the early 1900s, the start of human-induced large-scale eutrophication in Northwestern Europe, could not be restored. However, emerging charophytes and species rich vegetation are often lost due to competition with eutrophic species. Disturbances such as herbivory can limit dominance by eutrophic species and improve macrophyte diversity. We conclude that it is imperative to study the role of propagule availability more closely as well as the biotic interactions including herbivory and plant competition. After abiotic conditions are met, these will further determine macrophyte diversity and define what exactly can be restored and what not.
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12.
  • Baltzell, Kimberly, et al. (författare)
  • Febrile illness management in children under five years of age: a qualitative pilot study on primary health care workers' practices in Zanzibar.
  • 2013
  • Ingår i: Malaria journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: BACKGROUND: In Zanzibar, malaria prevalence dropped substantially in the last decade and presently most febrile patients seen in primary health care facilities (PHCF) test negative for malaria. The availability of rapid diagnostic tests (RDTs) allows rural health workers to reliably rule out malaria in fever patients. However, additional diagnostic tools to identify alternative fever causes are scarce, often leaving RDT-negative patients without a clear diagnosis and management plan. This pilot study aimed to explore health workers' practices with febrile children and identify factors influencing their diagnostic and management decisions in non-malarial fever patients. METHODS: Semi-structured key informant interviews were conducted with 12 health workers in six PHCFs in North A district, Zanzibar, April to June 2011. Interviews were coded using Atlas.ti to identify emerging themes that play a role in the diagnosis and management of febrile children. RESULTS: The following themes were identified: 1) health workers use caregivers' history of illness and RDT results for initial diagnostic and management decisions, but suggest caregivers need more education to prevent late presentation and poor health outcomes; 2) there is uncertainty regarding viral versus bacterial illness and health workers feel additional point-of-care diagnostic tests would help with differential diagnoses; 3) stock-outs of medications and limited caregivers' resources are barriers to delivering good care; 4) training, short courses and participation in research as well as; 5) weather also influences diagnostic decision-making. CONCLUSIONS: This pilot study found that health workers in Zanzibar use caregiver history of fever and results of malaria RDTs to guide management of febrile children. However, since most febrile children test negative for malaria, health workers believe additional training and point-of-care tests would improve their ability to diagnose and manage non-malarial fevers. Educating caregivers on signs and symptoms of febrile illness, as well as the introduction of additional tests to differentiate between viral and bacterial illness, would be important steps to get children to PHCFs earlier and decrease unnecessary antibiotic prescribing without compromising patient safety. More research is needed to expand an understanding of what would improve fever management in other resource-limited settings with decreasing malaria.
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  • Bartek, J, et al. (författare)
  • Surgery for chronic subdural hematoma in nonagenarians: A Scandinavian population-based multicenter study.
  • 2017
  • Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 136:5, s. 516-520
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic subdural hematoma (cSDH) is a prevalent condition often seen in the elderly, with surgery being the treatment of choice when symptomatic. So far, few have explored the surgical outcomes in patients 90years or older. The aim of this study was to investigate outcome after cSDH surgery in nonagenarians (≥90 y/o group) compared to younger adult patients (<90 y/o group).In a Scandinavian population-based cohort we conducted a retrospective review of 1,254 patients undergoing primary burr-hole procedures for cSDH between January 1, 2005 and December 31, 2010 at three neurosurgical centers. In a comparative analysis, the primary end-point was difference in hematoma recurrence rates between the ≥90 y/o and <90 y/o groups. The secondary end-points were differences in perioperative morbidity and mortality between groups.75 patients were 90years or older. There was no significant difference in recurrences resulting in reoperation between the age groups (10.7% vs 13.6%, P=.47). There was also no significant difference in overall complication rate (4.1% vs 8.1%, P=.21) or severe complications (1.4% vs 2.0%, P=.68). There were three (4.0%) perioperative deaths within 30days in the ≥90 y/o group and 40 (3.4%) in the <90 y/o group (P=.78).Patients 90years or older had similar rates of recurrence, perioperative morbidity and perioperative mortality as compared to younger patients. Age alone should not be a contraindication for surgery in patients with cSDH.
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  • Gulati, Sunita, et al. (författare)
  • Utilizing CMP-Sialic Acid Analogs to Unravel Neisseria gonorrhoeae Lipooligosaccharide-Mediated Complement Resistance and Design Novel Therapeutics
  • 2015
  • Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Neisseria gonorrhoeae deploys a novel immune evasion strategy wherein the lacto-N-neotetraose (LNnT) structure of lipooligosaccharide (LOS) is capped by the bacterial sialyltransferase, using host cytidine-5'-monophosphate (CMP)-activated forms of the ninecarbon nonulosonate (NulO) sugar N-acetyl-neuraminic acid (Neu5Ac), a sialic acid (Sia) abundant in humans. This allows evasion of complement-mediated killing by recruiting factor H (FH), an inhibitor of the alternative complement pathway, and by limiting classical pathway activation ("serum-resistance"). We utilized CMP salts of six additional natural or synthetic NulOs, Neu5Gc, Neu5Gc8Me, Neu5Ac9Ac, Neu5Ac9Az, legionaminic acid (Leg5Ac7Ac) and pseudaminic acid (Pse5Ac7Ac), to define structural requirements of Sia-mediated serum-resistance. While all NulOs except Pse5Ac7Ac were incorporated into the LNnT-LOS, only Neu5Gc incorporation yielded high-level serum-resistance and FH binding that was comparable to Neu5Ac, whereas Neu5Ac9Az and Leg5Ac7Ac incorporation left bacteria fully serum-sensitive and did not enhance FH binding. Neu5Ac9Ac and Neu5Gc8Me rendered bacteria resistant only to low serum concentrations. While serum-resistance mediated by Neu5Ac was associated with classical pathway inhibition (decreased IgG binding and C4 deposition), Leg5Ac7Ac and Neu5Ac9Az incorporation did not inhibit the classical pathway. Remarkably, CMP-Neu5Ac9Az and CMP-Leg5Ac7Ac each prevented serum-resistance despite a 100-fold molar excess of CMP-Neu5Ac in growth media. The concomitant presence of Leg5Ac7Ac and Neu5Ac on LOS resulted in uninhibited classical pathway activation. Surprisingly, despite near-maximal FH binding in this instance, the alternative pathway was not regulated and factor Bb remained associated with bacteria. Intravaginal administration of CMP-Leg5Ac7Ac to BALB/c mice infected with gonorrhea (including a multidrug-resistant isolate) reduced clearance times and infection burden. Bacteria recovered from CMP-Leg5Ac7Ac-treated mice were sensitive to human complement ex vivo, simulating in vitro findings. These data reveal critical roles for the Sia exocyclic side-chain in gonococcal serum-resistance. Such CMP-NulO analogs may provide a novel therapeutic strategy against the global threat of multidrug-resistant gonorrhea.
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  • Lange, J., et al. (författare)
  • Impact of cancer screening on metastasis: A prostate cancer case study
  • 2021
  • Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 28:4, s. 480-487
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study. Methods Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases. Results Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC. Conclusion Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.
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