| 1. |
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| 2. |
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- 2017
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Journal article (peer-reviewed)
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| 3. |
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| 4. |
- Mishra, A., et al.
(author)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Journal article (peer-reviewed)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 5. |
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| 6. |
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| 7. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 8. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 9. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 10. |
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| 11. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 12. |
- Dutta, Tanmoy, 1998, et al.
(author)
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Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial Defect (PED)
- 2023
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In: Pathogens. - : MDPI AG. - 2076-0817. ; 12:2
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Journal article (peer-reviewed)abstract
- Purpose: Failure of rapid re-epithelialization within 10-14 days after corneal injury, even with standard supportive treatment, is referred to as persistent corneal epithelial (CE) defect (PED). Though an array of genes regulates reepithelization, their mechanisms are poorly understood. We sought to understand the network of genes driving the re-epithelialization in PED. Method: After obtaining informed consent, patients underwent an ophthalmic examination. Epithelial scrapes and tears samples of six PED patients and six individuals (control) undergoing photorefractive keratectomy (PRK) were collected. RNA isolation and quantification were performed using either the epithelial scrape taken from PED patients or from HCLE cells treated with control tears or tears of PED patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of a few important genes in CE homeostasis, inflammation, and cell-cell communication, viz., Kruppel-like factor 4 (KLF4), GPX4, IL6, TNF alpha, STING, IL8, desmoglein, and E-cadherin, among others. Their expressions were normalized with their respective housekeeping genes and fold changes were recorded. KLF4 localization and MMPs activity was carried out via immunofluorescence and zymography, respectively. Results: KLF4, a transcription factor important for CE homeostasis, was upregulated in tears-treated HCLE cells and downregulated in PED patients compared to the healthy PRK group. Cell-cell communication genes were also upregulated in tears-treated cells, whereas they were downregulated in the PED tissue group. Genes involved in proinflammation (IL6, 282-fold; TNF alpha, 43-fold; IL8, 4.2-fold) were highly upregulated in both conditions. MMP9 activity increased upon tears treatment. Conclusions: This study suggests that tears create an acute proinflammatory milieu driving the PED disease pathology, whereas the PED patients scrapes are an indicator of the chronic stage of the disease. Interferons, pro-inflammatory genes, and their pathways are involved in PED, which can be a potential target for inducing epithelialization of the cornea.
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| 13. |
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| 14. |
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| 15. |
- Ray, A. K., et al.
(author)
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Damage resistance of a thermal barrier coated superalloy used in aero turbine blade under accelerated creep condition
- 2009
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In: High Temperature Materials and Processes. - 0334-6455 .- 2191-0324. ; 28:1-2, s. 35-53
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Journal article (peer-reviewed)abstract
- This paper highlights the hot tensile and accelerated creep properties of a thermal barrier coated (TBC) AE 437A alloy used as a candidate blade material in aero engines. Acoustic emission technique has been utilised to characterise the ductile-brittle transition temperature of the bond coat. Results revealed that the DBTT (ductile to brittle transition temperature) of this bond coat is around 923 K, which is in close proximity to the value reported for NiCoCrAlY type of bond coat. Finite element technique used for analysing the equivalent stresses in the bond coat well within the elastic limit, revealed highest order of equivalent stress at 1073 K as the bond coat is ductile above 923 K. The lifetime of the TBC coated superai loy was superior to that of the bare substrate and that oxidation is likely the cause of the reduced life of the bare substrate as compared to the coated substrate while stress rupture or accelerated creep experiments are carried out in an oxidizing environment.. Delamination of the bond coat and that of the TBC at high stresses during accelerated creep was evident. During accelerated creep, the mode of fracture in the substrate at very high stresses was transgranular whereas that at low stresses was intergranular.
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| 16. |
- Bisht, D. S., et al.
(author)
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Tethered balloon-born and ground-based measurements. of black carbon and particulate profiles within the lower troposphere during the foggy period in Delhi, India
- 2016
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 573, s. 894-905
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Journal article (peer-reviewed)abstract
- The ground and vertical profiles of particulate matter (PM) were mapped as part of a pilot study using a Tethered balloon within the lower troposphere (1000 m) during the foggy episodes in the winter season of 2015-16 in New Delhi, India. Measurements of black carbon (BC) aerosol and PM <2.5 and 10 mu m (PM2.5 &PM-10 respectively) concentrations and their associated particulate optical properties along with meteorological parameters were made. The mean concentrations of PM2.5, PM10, BC370 (nm), and BC880 nm were observed to be 146.8 +/- 42.1, 245.4 +/- 65.4, 30.3 +/- 122, and 24.1 +/- 103 mu g m(-3), respectively. The mean value of PM2.5 was similar to 12 times higher than the annual US-EPA air quality standard. The fraction of BC in PM2.5 that contributed to absorption in the shorter visible wavelengths (BC370 nm) was-21%. Compared to clear days, the ground level mass concentrations of PM2.5 and BC370 nm particles were substantially increased (59% and 24%, respectively) during the foggy episode. The aerosol light extinction coefficient (sigma(ext)) value was much higher (mean: 610 Mm(-1)) during the lower visibility (foggy) condition. Higher concentrations of PM2.5 (89 mu g m(-3)) and longer visible wavelength absorbing BC880 am (25.7 mu g m(-3)) particles were observed up to 200 m. The BC880 nm and PM2.5 aerosol concentrations near boundary layer (1 km) were significantly higher (similar to 1.9 and 12 mu g m(-3)), respectively. The BC (i.e BCtot) aerosol direct radiative forcing (DRF) values were estimated at the top of the atmosphere (TOA), surface (SFC), and atmosphere (ATM) and its resultant forcing were- 75.5 Wm(-2) at SFC indicating the cooling effect at the surface. A positive value (20.9 Wm(-2)) of BC aerosol DRF at TOA indicated the warming effect at the top of the atmosphere over the study region. The net DRF value due to BC aerosol was positive (96.4 Wm(-2)) indicating a net warming effect in the atmosphere. The contribution of fossil and biomass fuels to the observed BC aerosol DRF values was -78% and-22%, respectively. The higher mean atmospheric heating rate (2.71 K clay(-1)) by BC aerosol in the winter season would probably strengthen the temperature inversion leading to poor dispersion and affecting the formation of clouds. Serious detrimental impacts on regional climate due to the high concentrations of BC and PM (especially PM2.5) aerosol are likely based on this study and suggest the need for immediate, stringent measures to improve the regional air quality in the northern India.
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| 17. |
- Cole, J. W., et al.
(author)
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The copy number variation and stroke (CaNVAS) risk and outcome study
- 2021
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
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Journal article (peer-reviewed)abstract
- Background and purpose The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. Methods Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data. Results The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism. Conclusion The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum. Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Imani, Roghayeh, et al.
(author)
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Band edge engineering of TiO2@DNA nanohybrids and implications for capacitive energy storage devices.
- 2015
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In: Nanoscale. - : RSC Publishing. - 2040-3364 .- 2040-3372. ; 7:23, s. 10438-10448
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Journal article (peer-reviewed)abstract
- Novel mesoporous TiO2@DNA nanohybrid electrodes, combining covalently encoded DNA with mesoporous TiO2 microbeads using dopamine as linker, were prepared and characterised for application in supercapacitors. Detailed information about donor density, charge transfer resistance and chemical capacitance, which have important role in the performance of an electrochemical device, were studied by electrochemical methods. The results indicated the improvement of electrochemical performance of TiO2 nanohybrid electrode by DNA surface functionalisation. A supercapacitor was constructed from TiO2@DNA nanohybrids with PBS as electrolyte. From the supercapacitor experiment, it was found that the addition of DNA played an important role in improving the specific capacitance (Cs) of the TiO2 supercapacitor. The highest Cs value of 8 F/g was observed for TiO2@DNA nanohybrids. The nanohybrid electrodes were shown to be stable over long-term cycling, retaining 95% of their initial specific capacitance after 1500 cycles.
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| 22. |
- Imani, Roghayeh, et al.
(author)
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Band edge engineering of TiO2@DNA nanohybrids and implications for capacitive energy storage devices
- 2015
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:23, s. 10438-10448
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Journal article (peer-reviewed)abstract
- Novel mesoporous TiO2@DNA nanohybrid electrodes, combining covalently encoded DNA with mesoporous TiO2 microbeads using dopamine as a linker, were prepared and characterised for application in supercapacitors. Detailed information about donor density, charge transfer resistance and chemical capacitance, which have an important role in the performance of an electrochemical device, were studied by electrochemical methods. The results indicated the improvement of electrochemical performance of the TiO2 nanohybrid electrode by DNA surface functionalisation. A supercapacitor was constructed from TiO2@DNA nanohybrids with PBS as the electrolyte. From the supercapacitor experiment, it was found that the addition of DNA played an important role in improving the specific capacitance (C-s) of the TiO2 supercapacitor. The highest Cs value of 8 F g(-1) was observed for TiO2@DNA nanohybrids. The nanohybrid electrodes were shown to be stable over long-term cycling, retaining 95% of their initial specific capacitance after 1500 cycles.
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| 23. |
- Kandpal, M, et al.
(author)
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Dysbiosis of Gut Microbiota from the Perspective of the Gut-Brain Axis: Role in the Provocation of Neurological Disorders
- 2022
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In: Metabolites. - : MDPI AG. - 2218-1989. ; 12:11
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Journal article (peer-reviewed)abstract
- The gut–brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. The axis keeps track of gastrointestinal activities and integrates them to connect gut health to higher cognitive parts of the brain. Disruption in this connection may facilitate various neurological and gastrointestinal problems. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity and that aid in the collapse of cellular proteostasis are a defining characteristic of neurodegenerative proteinopathies. These disorders are not only caused by changes in the neural compartment but also due to other factors of non-neural origin. Mounting data reveal that the majority of gastrointestinal (GI) physiologies and mechanics are governed by the central nervous system (CNS). Furthermore, the gut microbiota plays a critical role in the regulation and physiological function of the brain, although the mechanism involved has not yet been fully interpreted. One of the emerging explanations of the start and progression of many neurodegenerative illnesses is dysbiosis of the gut microbial makeup. The present understanding of the literature surrounding the relationship between intestinal dysbiosis and the emergence of certain neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, is the main emphasis of this review. The potential entry pathway of the pathogen-associated secretions and toxins into the CNS compartment has been explored in this article at the outset of neuropathology. We have also included the possible mechanism of undelaying the synergistic effect of infections, their metabolites, and other interactions based on the current understanding.
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| 24. |
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| 25. |
- Kukkonen, J., et al.
(author)
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Towards a Comprehensive Evaluation of the Environmental and Health Impacts of Shipping Emissions
- 2022
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In: Springer Proceedings in Complexity. - Cham : Springer International Publishing. - 2213-8684 .- 2213-8692. ; , s. 329-336
-
Conference paper (peer-reviewed)abstract
- We present a new concept for marine research, applied in the EU-funded project EMERGE, “Evaluation, control and Mitigation of the EnviRonmental impacts of shippinG Emissions” (2020–2024; https://emerge-h2020.eu/ ). For the first time, both the various marine and atmospheric impacts of the shipping sector have been and will be comprehensively analyzed, using a concerted modelling and measurements framework. The experimental part of the project focuses on five European geographical case studies in different ecologically vulnerable regions, and a mobile onboard case study. The EMERGE consortium has also developed a harmonised and integrated modelling framework to assess the combined impacts of shipping emissions, both (i) on the marine ecosystems and (ii) the atmospheric environment. The first results include substantial refinements of a range of models to be applied, especially those for the STEAM and OpenDrift models. In particular, the STEAM (Ship Traffic Emission Assessment Model) model has been extended to allow for the effects of atmospheric and oceanographic factors on the fuel consumption and emissions of the ships. The OpenDrift model has been improved to take into account the partitioning, degradation, and volatilization of pollutants in water. The predicted emission and discharge values have been used as input for both regional scale atmospheric dispersion models, such as WRF-CMAQ (Weather Research and Forecasting—Community Multiscale Air Quality Model) and SILAM (System for Integrated modeLling of Atmospheric composition), and water quality and circulation models, such as OpenDrift (Open source model for the drifting of substances in the ocean) and Delft3D (oceanographic model). The case study regions are Eastern Mediterranean, Northern Adriatic Sea, the Lagoon of Aveiro, the Solent Strait and the Öresund Strait. We have also conducted a substantial part of the experimental campaigns scheduled in the project. The final assessment will include the benefits and costs of control and mitigation options affecting water quality, air pollution exposure, health impacts, climate forcing, and ecotoxicological effects and bioaccumulation of pollutants in marine biota.
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| 26. |
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| 27. |
- Maziarz, RT, et al.
(author)
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Patient-reported long-term quality of life after tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma
- 2020
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In: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 4:4, s. 629-637
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Journal article (peer-reviewed)abstract
- The JULIET phase 2 trial evaluated a single infusion of tisagenlecleucel in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). The objective of the current analysis was to evaluate patient-reported health-related quality of life (HRQoL) with a median follow-up of 19.3 months among patients infused with a single dose of tisagenlecleucel. Patients enrolled were ≥18 years of age with r/r DLBCL after ≥2 lines of therapy and had either undergone a failed autologous stem cell transplant or were ineligible for the procedure. Two validated HRQoL instruments, Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and Short Form-36 (SF-36) Health Survey, were used to measure HRQoL at baseline and months 3, 6, 12, and 18. At data cutoff (21 May 2018), 115 patients had received tisagenlecleucel infusion. Among the 99 patients evaluated, overall response rate was 54%, and 40% of patients achieved complete response (CR). Initially, 108 patients completed the HRQoL assessments at baseline, including 57 patients who eventually achieved CR or partial response (PR). Further, 30 and 21 patients in clinical response who completed assessments at baseline also completed assessments at months 12 and 18, respectively. Patients who achieved CR or PR sustained HRQoL improvement in all FACT scores at all time points. SF-36 instruments showed improvement above the minimal clinically important differences on 5 of 8 subscales. Long-term follow-up in the phase 2 JULIET study demonstrated that patients with r/r DLBCL who respond to tisagenlecleucel therapy had sustained, clinically meaningful improvements in HRQoL. This trial was registered at www.clinicaltrials.gov as #NCT02445248.
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| 28. |
- Mishra, Prashant, et al.
(author)
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Electrocatalytic biofuel cell based on highly efficient metal-polymer nano-architectured bioelectrodes
- 2017
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In: Nano Energy. - : ELSEVIER SCIENCE BV. - 2211-2855 .- 2211-3282. ; 39, s. 601-607
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Journal article (peer-reviewed)abstract
- Bioenergy based devices are rapidly gaining significant research interest because of growing quest for future alternative energy resources, but most of the existing technologies suffer from poor electron transfer and slow mass transport, which hinder the fabrication of realistic high-power devices. Using a versatile strategy, here we have demonstrated the fabrication of nanoparticle-polymer framework based bioelectrocatalytic interfaces which facilitate a high mass-transport and thus offers the simple construction of advanced enzyme-based biofuel cells. It has been shown that a gold nanoparticle-structured polyaniline network can be effectively used as an electrical cabling interface providing efficient electron transfer for bio-anode and cathode. The resulting bioelectrodes are capable of excellent diffusional mass-transport and thus can easily facilitate the design of new and highly efficient membrane-less advanced bioenergy devices. The biofuel cell delivers a high-power density of about 2.5 times (i.e., 685 mu W cm(-2)) and open circuit voltage of 760 mV compared to conventional conducting polymer-based biofuel cells.
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| 29. |
- Shukla, S. K., et al.
(author)
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Fabrication of electro-chemical humidity sensor based on zinc oxide/polyaniline nanocomposite
- 2012
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In: Advanced Materials Letters. - : Vinova Bhave Research Institute. - 0976-3961 .- 0976-397X. ; 3:5, s. 421-425
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Journal article (peer-reviewed)abstract
- The present work reports the synthesis of nano size zinc oxide encapsulated polyanaline by wet-chemical method at ambient condition. The prepared composite was characterized by XRD, SEM, TGA and UV-Vis spectroscopy. The results revealed the formation of the crystalline homogenous ZnO centered composite with electrical conductance in the range of 10-2scm-1 andthermal stability up to 280 0C. Further, electrical resistance of a ZnO/PANi film of ~200 nm thickness was monitored against humidity to use as humidity sensitive element. The observed sensing parameters were response time, 32 sec; and recovery time,45 sec; sensor has exhibited better sensing characteristics than pure PANi and other reported humidity sensors.
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| 30. |
- Wedemeyer, S., et al.
(author)
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Solar Science with the Atacama Large Millimeter/Submillimeter Array-A New View of Our Sun
- 2016
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 200:1-4, s. 1-73
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Research review (peer-reviewed)abstract
- The Atacama Large Millimeter/submillimeter Array (ALMA) is a new powerful tool for observing the Sun at high spatial, temporal, and spectral resolution. These capabilities can address a broad range of fundamental scientific questions in solar physics. The radiation observed by ALMA originates mostly from the chromosphere-a complex and dynamic region between the photosphere and corona, which plays a crucial role in the transport of energy and matter and, ultimately, the heating of the outer layers of the solar atmosphere. Based on first solar test observations, strategies for regular solar campaigns are currently being developed. State-of-the-art numerical simulations of the solar atmosphere and modeling of instrumental effects can help constrain and optimize future observing modes for ALMA. Here we present a short technical description of ALMA and an overview of past efforts and future possibilities for solar observations at submillimeter and millimeter wavelengths. In addition, selected numerical simulations and observations at other wavelengths demonstrate ALMA's scientific potential for studying the Sun for a large range of science cases.
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| 31. |
- Wedemeyer, S., et al.
(author)
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SSALMON - The Solar Simulations for the Atacama Large Millimeter Observatory Network
- 2015
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In: Advances in Space Research. - : Elsevier BV. - 1879-1948 .- 0273-1177. ; 56:12, s. 2679-2692
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Journal article (peer-reviewed)abstract
- The Solar Simulations for the Atacama Large Millimeter Observatory Network (SSALMON) was initiated in 2014 in connection with two ALMA development studies. The Atacama Large Millimeter/submillimeter Array (ALMA) is a powerful new tool, which can also observe the Sun at high spatial, temporal, and spectral resolution. The international SSALMONetwork aims at co-ordinating the further development of solar observing modes for ALMA and at promoting scientific opportunities for solar physics with particular focus on numerical simulations, which can provide important constraints for the observing modes and can aid the interpretation of future observations. The radiation detected by ALMA originates mostly in the solar chromosphere - a complex and dynamic layer between the photosphere and corona, which plays an important role in the transport of energy and matter and the heating of the outer layers of the solar atmosphere. Potential targets include active regions, prominences, quiet Sun regions, flares. Here, we give a brief overview over the network and potential science cases for future solar observations with ALMA.
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| 32. |
- Weinstock, Joshua S, et al.
(author)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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In: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Journal article (peer-reviewed)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 33. |
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| 34. |
- Xia, Guoqing, et al.
(author)
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Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus, type 1
- 2002
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In: Journal of Biological Chemistry. - 1083-351X. ; 277:40, s. 37912-37919
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Journal article (peer-reviewed)abstract
- Heparan sulfate 3-O-sulfotransferase transfers sulfate to the 3-OH position of a glucosamine residue of heparan sulfate (HS) to form 3-O-sulfated HS. The 3-O-sulfated glucosamine residue contributes to two important biological functions of HS: binding to antithrombin and thereby carrying anticoagulant activity, and binding to herpes simplex viral envelope glycoprotein D to serve as an entry receptor for herpes simplex virus 1. A total of five HS 3-O-sulfotransferase isoforms were reported previously. Here we report the isolation and characterization of a novel HS 3-O-sulfotransferase isoform, designated as HS 3-O-sulfotransferase isoform 5 (3-OST-5). 3-OST-5 cDNA was isolated from a human placenta cDNA library and expressed in COS-7 cells. The disaccharide analysis of 3-OST-5-modified HS revealed that 3-OST-5 generated at least three 3-O-sulfated disaccharides as follows: IdoUA2S-AnMan3S, GlcUA-AnMan3S6S, and IdoUA2S-AnMan3S6S. Transfection of the plasmid expressing 3-OST-5 rendered wild type Chinese hamster ovary cells susceptible to the infection by herpes simplex virus 1, suggesting that 3-OST-5-modified HS serves as an entry receptor for herpes simplex virus 1. In addition, 3-OST-5-modified HS bound to herpes simplex viral envelope protein glycoprotein D. Furthermore, we found that 3-OST-5-modified HS also bound to antithrombin, suggesting that 3-OST-5 also produces anticoagulant HS. In summary, our results indicate that a new member of 3-OST family generates both anticoagulant HS and an entry receptor for herpes simplex virus 1. These results provide a new insight regarding the mechanism for the biosynthesis of biologically active HS.
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| 36. |
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