30 results on '"Dar WA"'
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2. FREQUENCY OF SUBCLINICAL HYPO AND HYPERTHYROIDISM IN PATIENTS PRESENTING WITH CONGESTIVE HEART FAILURE
- Author
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ANUM, H, primary, QURESHI, AE, additional, ULLAH, N, additional, SAJJAD, M, additional, FAROOQ, U, additional, and DAR, WA, additional
- Published
- 2023
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3. FREQUENCY OF SIGNIFICANT CORONARY ARTERY DISEASE IN CASES WITH ST SEGMENT DEPRESSION DURING RECOVERY PHASE OF EXERCISE
- Author
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FAROOQ, U, primary, ULLAH, N, additional, QURESHI, AE, additional, SAJJAD, M, additional, ANUM, H, additional, and DAR, WA, additional
- Published
- 2023
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4. The investor-state arbitration legitimacy crisis: Could AI be its future savior (or resurrector)?
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Dar Wasiq and Praštalo Boris
- Subjects
artificial intelligence ,arbitration ,decision making ,investor-state dispute settlement ,investor-state arbitration ,Law - Abstract
The world of arbitration has not escaped the all-pervading impact of AI. Stakeholders are not only assessing the current impact of AI on the practice of arbitration but also speculating on its future role. The possibility of AI replacing human arbitrators has also figured in the discussions. This paper focuses on the use of AI in the context of investor-State arbitration, which of late, has been facing fierce backlash for its purported deficiencies. The paper explores whether AI could be used to remedy some of the burning issues in the investor-state dispute settlement system, which have culminated in its "existential crisis". The paper assesses the extent to which human arbitrators and other relevant factors have contributed to the crisis, and then examines the suitability of AI to act as an arbitrator. The paper lays a road map for the potential role of AI in ISA and attempts to answer the central question-could AI prove to be a resurrector or a disruptor of the ISA system.
- Published
- 2023
5. PENERAPAN BRANDING PADA UKM MAKANAN RINGAN DI KABUPATEN JEPARA
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Hari Susanta Nugraha, Fitrie Ariyanti, and Dar wanto
- Subjects
branding, marketing attractiveness, competition ,Business ,HF5001-6182 - Abstract
The implementation of branding to SME’s products can help the consumers to choose products from the competitors. The emergence of branding on SME’s products cause by the needed of identity for product’s of SME’s for entering in the national market, thus increasing penetration. In fact, many SMEs are not yet aware of the importance of branding for competitiveness. The SME’s are more focused on aspects of product sales. The purpose of the study is that known the business conditions and application of branding of SME’s snacks in Jepara District. The research used qualitative approach to disclusore the emergence of branding. The implementation of branding to SME’s focus on desgn of packaging and labeling. Packaging with attractive designs and informative labels can determine the consumer's interest in purchasing the product. The more familiar a product, the easier it will be for market to choose.
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- 2017
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6. Correction: Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission.
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Sugi KS, Sandra AP, Nonappa, Ghosh D, Mohanty JS, Kannan MP, Sooraj BS, Srikrishnarka P, Roy J, Dar WA, and Pradeep T
- Abstract
Correction for 'Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission' by Korath Shivan Sugi, et al. , Nanoscale , 2023, https://doi.org/10.1039/d3nr02561f.
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- 2023
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7. Secondary ligand-induced orthogonal self-assembly of silver nanoclusters into superstructures with enhanced NIR emission.
- Author
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Sugi KS, Sandra AP, Nonappa, Ghosh D, Mohanty JS, Paulthangam Kannan M, Sooraj BS, Srikrishnarka P, Roy J, Dar WA, and Pradeep T
- Abstract
Orthogonal self-assembly is one of the crucial strategies for forming complex and hierarchical structures in biological systems. However, creating such ordered complex structures using synthetic nanoparticles is a challenging task and requires a high degree of control over structure and multiple non-covalent interactions. In this context, nanoarchitectonics serves as an emerging tool to fabricate complex functional materials. Here, we present a secondary ligand-induced orthogonal self-assembly of atomically precise silver nanoclusters into complex superstructures. Specifically, we use Ag
14 NCs protected with naphthalene thiol and 1,6-bis(diphenylphosphino)hexane ligands. Controlled addition of 1,6-bis(diphenylphosphino)hexane, the secondary ligand resulted in a self-assembled supracolloidal structure including helical fibers, spheres, and nanosheets. The self-assembly process is tunable by controlling the molar ratio of the ligand. The resulting superstructures exhibit enhanced NIR emission due to restricted intramolecular motion. This demonstrates that by tuning supramolecular interactions, hierarchical nanostructures with desired properties similar to biomolecules can be obtained from atomically precise building blocks.- Published
- 2023
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8. Carborane-thiol protected copper nanoclusters: stimuli-responsive materials with tunable phosphorescence.
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Jana A, Jash M, Dar WA, Roy J, Chakraborty P, Paramasivam G, Lebedkin S, Kirakci K, Manna S, Antharjanam S, Machacek J, Kucerakova M, Ghosh S, Lang K, Kappes MM, Base T, and Pradeep T
- Abstract
Atomically precise nanomaterials with tunable solid-state luminescence attract global interest. In this work, we present a new class of thermally stable isostructural tetranuclear copper nanoclusters (NCs), shortly Cu
4 @oCBT, Cu4 @mCBT and Cu4 @ICBT, protected by nearly isomeric carborane thiols: ortho -carborane-9-thiol, meta -carborane-9-thiol and ortho -carborane 12-iodo 9-thiol, respectively. They have a square planar Cu4 core and a butterfly-shaped Cu4 S4 staple, which is appended with four respective carboranes. For Cu4 @ICBT, strain generated by the bulky iodine substituents on the carboranes makes the Cu4 S4 staple flatter in comparison to other clusters. High-resolution electrospray ionization mass spectrometry (HR ESI-MS) and collision energy-dependent fragmentation, along with other spectroscopic and microscopic studies, confirm their molecular structure. Although none of these clusters show any visible luminescence in solution, bright μs-long phosphorescence is observed in their crystalline forms. The Cu4 @oCBT and Cu4 @mCBT NCs are green emitting with quantum yields ( Φ ) of 81 and 59%, respectively, whereas Cu4 @ICBT is orange emitting with a Φ of 18%. Density functional theory (DFT) calculations reveal the nature of their respective electronic transitions. The green luminescence of Cu4 @oCBT and Cu4 @mCBT clusters gets shifted to yellow after mechanical grinding, but it is regenerated after exposure to solvent vapour, whereas the orange emission of Cu4 @ICBT is not affected by mechanical grinding. Structurally flattened Cu4 @ICBT didn't show mechanoresponsive luminescence in contrast to other clusters, having bent Cu4 S4 structures. Cu4 @oCBT and Cu4 @mCBT are thermally stable up to 400 °C. Cu4 @oCBT retained green emission even upon heating to 200 °C under ambient conditions, while Cu4 @mCBT changed from green to yellow in the same window. This is the first report on structurally flexible carborane thiol appended Cu4 NCs having stimuli-responsive tunable solid-state phosphorescence., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)- Published
- 2022
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9. Delineating meta-quantitative trait loci for anthracnose resistance in common bean ( Phaseolus vulgaris L.).
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Shafi S, Saini DK, Khan MA, Bawa V, Choudhary N, Dar WA, Pandey AK, Varshney RK, and Mir RR
- Abstract
Anthracnose, caused by the fungus Colletotrichum lindemuthianum , is one of the devastating disease affecting common bean production and productivity worldwide. Several quantitative trait loci (QTLs) for anthracnose resistance have been identified. In order to make use of these QTLs in common bean breeding programs, a detailed meta-QTL (MQTL) analysis has been conducted. For the MQTL analysis, 92 QTLs related to anthracnose disease reported in 18 different earlier studies involving 16 mapping populations were compiled and projected on to the consensus map. This meta-analysis led to the identification of 11 MQTLs (each involving QTLs from at least two different studies) on 06 bean chromosomes and 10 QTL hotspots each involving multiple QTLs from an individual study on 07 chromosomes. The confidence interval (CI) of the identified MQTLs was found 3.51 times lower than the CI of initial QTLs. Marker-trait associations (MTAs) reported in published genome-wide association studies (GWAS) were used to validate nine of the 11 identified MQTLs, with MQTL4.1 overlapping with as many as 40 MTAs. Functional annotation of the 11 MQTL regions revealed 1,251 genes including several R genes (such as those encoding for NBS-LRR domain-containing proteins, protein kinases, etc.) and other defense related genes. The MQTLs, QTL hotspots and the potential candidate genes identified during the present study will prove useful in common bean marker-assisted breeding programs and in basic studies involving fine mapping and cloning of genomic regions associated with anthracnose resistance in common beans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shafi, Saini, Khan, Bawa, Choudhary, Dar, Pandey, Varshney and Mir.)
- Published
- 2022
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10. The Impact of Health Literacy on Kidney Transplant Listing.
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Chen G, Siahaan J, Leon Novelo L, Rizvi I, De Golovine A, Edwards A, Pai A, and Dar WA
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- Adult, Humans, Renal Dialysis, Retrospective Studies, Waiting Lists, Health Literacy, Kidney Transplantation
- Abstract
Introduction: Limited health literacy has been associated with poor health outcomes in the general population, but there have been few studies investigating the association between functional health literacy and kidney transplant listing. The primary objective of this study was to determine if functional health literacy was associated with kidney transplant listing after controlling for demographic, psychosocial, and medical variables, which were secondarily examined for correlation with transplant listing. Design: We retrospectively reviewed 423 kidney transplant candidates who were prospectively administered the Test of Functional Health Literacy in Adults during their transplant evaluation. Results: The functional health literacy scores were found to correlate with transplant listing (P = 0.013). Unexpectedly, a subset of patients (n = 14 out of 36) who had scores < 59 was still able to obtain approval for listing. The probability of approval decreased when functional health literacy scores ranged from 0 to 59 and increased when functional health literacy scores varied between 60 to 100. Multivariable analysis found transplant listing to also be associated with substance use (OR = 0.15, P < 0.001), ESKD etiology other than diabetes or hypertension (OR = 2.62, P < 0.001), time on dialysis (P = 0.012), and pace of transplant evaluation (P < 0.001). Conclusion: Functional health literacy was associated with kidney transplant listing. Programmatic interventions that can help overcome the impact of functional health literacy and improve access to transplantation should be explored.
- Published
- 2022
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11. Cocrystals of Atomically Precise Noble Metal Nanoclusters.
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Bodiuzzaman M, Dar WA, and Pradeep T
- Abstract
Cocrystallization is a phenomenon involving the assembly of two or more different chemical entities in a lattice, occurring typically through supramolecular interactions. In this concept, recent advancements in the cocrystallization of atomically precise noble metal clusters and their potential future directions are presented. Different strategies to create coassemblies of thiolate-protected noble metal nanoclusters are presented first. An approach is the simultaneous synthesis, and cocrystallization of two clusters having similar structures. A unique pair of clusters found recently, namely Ag
40 and Ag46 with same core but different shell are taken to illustrate this. In another category, the case of the same core is presented, namely Ag116 with different shells, as in a mixture of Ag210 and Ag211 . Next, an intercluster reaction is presented to create cocrystals through selective crystallization of the reaction products. The coexistence of competing effects, magic sizes, and magic electron shells in a coassembly of alloy nanoclusters is discussed next. Finally, an assembly strategy for nanoclusters using electrostatic interactions is described. This concept is concluded with a future perspective on the emerging possibilities of such solids. Advancements in this field will certainly help the development of novel materials with exciting properties., (© 2020 Wiley-VCH GmbH.)- Published
- 2021
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12. Hypoxia-inducible factor-1α-dependent induction of miR122 enhances hepatic ischemia tolerance.
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Ju C, Wang M, Tak E, Kim B, Emontzpohl C, Yang Y, Yuan X, Kutay H, Liang Y, Hall DR, Dar WA, Bynon JS, Carmeliet P, Ghoshal K, and Eltzschig HK
- Subjects
- Animals, Female, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Ischemia genetics, Ischemia metabolism, Liver blood supply, Liver Diseases genetics, Male, Mice, Mice, Transgenic, MicroRNAs genetics, Reperfusion Injury genetics, Hepatocytes metabolism, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Liver metabolism, Liver Diseases metabolism, MicroRNAs metabolism, Reperfusion Injury metabolism
- Abstract
Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor-1α (HIF1α) in the induction of miR122 and identified the oxygen-sensing prolyl hydroxylase domain 1 (PHD1) as a miR122 target. Further studies indicated that HIF1α-dependent induction of miR122 participated in a feed-forward pathway for liver protection via the enhancement of hepatic HIF responses through PHD1 repression. Moreover, pharmacologic studies utilizing nanoparticle-mediated miR122 overexpression demonstrated attenuated liver injury. Finally, proof-of-principle studies in patients undergoing orthotopic liver transplantation showed elevated miR122 levels in conjunction with the repression of PHD1 in post-ischemic liver biopsies. Taken together, the present findings provide molecular insight into the functional role of miR122 in enhancing hepatic ischemia tolerance and suggest the potential utility of pharmacologic interventions targeting miR122 to dampen hepatic injury during liver transplantation.
- Published
- 2021
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13. Dual emitting Ag 35 nanocluster protected by 2-pyrene imine thiol.
- Author
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Jana A, Chakraborty P, Dar WA, Chandra S, Khatun E, Kannan MP, Ras RHA, and Pradeep T
- Abstract
In this communication, we present the synthesis of 2-pyrene imine thiol (2-PIT)-protected Ag
35 nanoclusters using a ligand exchange-induced structural transformation reaction. The formation of the nanocluster and its composition were confirmed through several spectroscopic and electron microscopic studies. The UV-vis absorption spectrum showed a set of characteristic features of the nanocluster. This nanocluster showed blue emission under UV light due to pyrene to metal core charge-transfer, and NIR emission due to charge-transfer within the metal core. This is the first report on dual emitting pyrene protected atomically precise silver nanoclusters.- Published
- 2020
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14. Quantitative assessment of liver fibrosis by digital image analysis reveals correlation with qualitative clinical fibrosis staging in liver transplant patients.
- Author
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Jiang K, Mohammad MK, Dar WA, Kong J, and Farris AB
- Subjects
- Adult, Aged, Biopsy, Disease Progression, Female, Follow-Up Studies, Hepacivirus, Hepatitis C, Chronic surgery, Hepatitis C, Chronic virology, Humans, Liver Cirrhosis pathology, Male, Middle Aged, Retrospective Studies, Image Processing, Computer-Assisted methods, Liver Cirrhosis diagnostic imaging, Liver Transplantation, Severity of Illness Index
- Abstract
Technologies for digitizing tissues provide important quantitative data for liver histopathology investigation. We aimed to assess liver fibrosis degree with quantitative morphometric measurements of histopathological sections utilizing digital image analysis (DIA) and to further investigate if a correlation with histopathologic scoring (Scheuer staging) exists. A retrospective study of patients with at least two post-liver transplant biopsies having a Scheuer stage of ≤ 2 at baseline were gathered. Portal tract fibrotic percentage (%) and size (μm2) were measured by DIA, while clinical fibrosis score was measured by the Scheuer system. Correlations between DIA measurements and Scheuer scores were computed by Spearman correlation analysis. Differences between mean levels of fibrosis (score, size, and percentage) at baseline versus second visit were computed by Student's t-test. P values < 0.05 were considered significant. Of 22 patients who met the study criteria, 54 biopsies were included for analysis. Average levels ±standard error [S.E.] of portal tract fibrotic percentage (%) and size (μm2) progressed from 46.5 ± 3.6% at baseline to 61.8 ± 3.8% at the second visit (P = 0.005 by Student's t-test), and from 28,075 ± 3,232 μm2 at base line to 67,146 ± 10,639 μm2 at the second visit (P = 0.002 by Student's t-test), respectively. Average levels of Scheuer fibrosis scores progressed from 0.55±0.19 at baseline to 1.14±0.26 at the second visit (P = 0.02 by Student's t-test). Portal tract fibrotic percentage (%) and portal tract fibrotic size were directly correlated with clinical Scheuer fibrosis stage, with Spearman correlation coefficient and P value computed as r = 0.70, P < 0.0001 and r = 0.41, P = 0.002, respectively. Digital quantitative assessment of portal triad size and fibrosis percentage demonstrates a strong correlation with visually assessed histologic stage of liver fibrosis and complements the standard assessment for allograft monitoring, suggesting the utility of future WSI analysis., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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15. Mst1/2 kinases restrain transformation in a novel transgenic model of Ras driven non-small cell lung cancer.
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Singh K, Pruski MA, Polireddy K, Jones NC, Chen Q, Yao J, Dar WA, McAllister F, Ju C, Eltzschig HK, Younes M, Moran C, Karmouty-Quintana H, Ying H, and Bailey JM
- Subjects
- Animals, Carcinoma, Non-Small-Cell Lung genetics, Carrier Proteins metabolism, Cell Line, Tumor, Gene Deletion, Hepatocyte Nuclear Factor 1-beta genetics, Intracellular Signaling Peptides and Proteins, Lung metabolism, Lung pathology, Lung Neoplasms genetics, Membrane Proteins metabolism, Mice, Mice, Transgenic, Protein Serine-Threonine Kinases deficiency, Protein Serine-Threonine Kinases genetics, Serine-Threonine Kinase 3, Thyroid Hormones metabolism, Thyroid Hormone-Binding Proteins, Carcinoma, Non-Small-Cell Lung pathology, Cell Transformation, Neoplastic, Disease Models, Animal, Lung Neoplasms pathology, Protein Serine-Threonine Kinases metabolism, ras Proteins genetics
- Abstract
Non-small cell lung cancer remains a highly lethal malignancy. Using the tamoxifen inducible Hnf1b:CreER
T2 (H) transgenic mouse crossed to the LsL-KrasG12D (K) transgenic mouse, we recently discovered that an Hnf1b positive cell type in the lung is sensitive to adenoma formation when expressing a mutant KrasG12D allele. In these mice, we observe adenoma formation over a time frame of three to six months. To study specificity of the inducible Hnf1b:CreERT2 in the lung, we employed lineage tracing using an mTmG (G) reporter allele. This technique revealed recombined, GFP+ cells were predominantly SPC+. We further employed this technique in HKG mice to determine Hnf1b+ cells give rise to adenomas that express SPC and TTF1. Review of murine lung tissue confirmed a diagnosis of adenoma and early adenocarcinoma, a pathologic subtype of non-small cell lung cancer. Our expanded mouse model revealed loss of Mst1/2 promotes aggressive lung adenocarcinoma and large-scale proteomic analysis revealed upregulation of PKM2 in the lungs of mice with genetic deletion of Mst1/2. PKM2 is a known metabolic regulator in proliferating cells and cancer. Using a human lung adenocarcinoma cell line, we show pharmacologic inhibition of Mst1/2 increases the abundance of PKM2, indicating genetic loss or pharmacologic inhibition of Mst1/2 directly modulates the abundance of PKM2. In conclusion, here we report a novel model of non-small cell lung cancer driven by a mutation in Kras and deletion of Mst1/2 kinases. Tumor development is restricted to a subset of alveolar type II cells expressing Hnf1b. Our data show loss of Mst1/2 regulates levels of a potent metabolic regulator, PKM2.- Published
- 2020
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16. Interparticle Reactions between Silver Nanoclusters Leading to Product Cocrystals by Selective Cocrystallization.
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Dar WA, Bodiuzzaman M, Ghosh D, Paramasivam G, Khatun E, Sugi KS, and Pradeep T
- Abstract
We present an example of an interparticle reaction between atomically precise nanoclusters (NCs) of the same metal, resulting in entirely different clusters. In detail, the clusters [Ag
12 (TBT)8 (TFA)5 (CH3 CN)]+ (TBT = tert -butylthiolate, TFA = trifluoroacetate, CH3 CN = acetonitrile) and [Ag18 (TPP)10 H16 ]2+ (TPP = triphenylphosphine) abbreviated as Ag12 and Ag18 , respectively, react leading to [Ag16 (TBT)8 (TFA)7 (CH3 CN)3 Cl]+ and [Ag17 (TBT)8 (TFA)7 (CH3 CN)3 Cl]+ , abbreviated as Ag16 and Ag17 , respectively. The two product NCs crystallize together as both possess the same metal chalcogenolate shell, composed of Ag16 S8 , making them indistinguishable. The occupancies of Ag16 and Ag17 are 66.66 and 33.33%, respectively, in a single crystal. Electrospray ionization mass spectrometry (ESI MS) of the reaction product and a dissolved crystal show the population of Ag16 and Ag17 NCs to be in a 1:1 and 2:1 ratio, respectively. This suggests selective crystallization in the cocrystal. Time-dependent ESI MS was employed to understand the formation of product clusters by monitoring the reaction intermediates formed in the course of the reaction. We present an unprecedented growth mechanism for the formation of silver NCs mediated by silver thiolate intermediates.- Published
- 2019
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17. Exploration of the Stanford Integrated Psychosocial Assessment for Transplantation With Psychosocial and Medical Outcomes in Kidney and Kidney-Pancreas Transplant Recipients.
- Author
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Chen G, Bell CS, Loughhead P, Ibeche B, Bynon JS, Hall DR, De Golovine A, Edwards A, and Dar WA
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- Adult, Black or African American psychology, Black or African American statistics & numerical data, Age Factors, Educational Status, Ethnicity psychology, Female, Graft Survival, Hispanic or Latino psychology, Hispanic or Latino statistics & numerical data, Humans, Incidence, Infections epidemiology, Male, Middle Aged, Patient Compliance, Patient Readmission statistics & numerical data, Preoperative Period, Psychometrics, Retrospective Studies, Social Class, Social Support, Transplant Recipients psychology, White People psychology, White People statistics & numerical data, Diabetes Mellitus epidemiology, Ethnicity statistics & numerical data, Graft Rejection epidemiology, Kidney Transplantation, Mental Disorders epidemiology, Pancreas Transplantation, Substance-Related Disorders epidemiology, Transplant Recipients statistics & numerical data
- Abstract
Introduction: The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a psychometric instrument designed to assess patient risk for transplant. We investigated the association between SIPAT scores and demographic data with psychosocial and medical outcomes within a diverse kidney/kidney-pancreas transplant population., Design: The SIPAT was administered to all pretransplant candidates. A retrospective review of transplanted patients who had at least 6 months of follow-up was completed., Results: The sample included 136 patients: male (n = 77 [57%]) with a mean age of 47 years old. Thirty-eight percent were black (n = 51), 55% had less than a high school education (n = 74), and 65% had low socioeconomic status (n = 89). Statistical difference was found among SIPAT scores and substance use and support system instability ( P = .035, P = .012). Females ( P = .012) and patients with a history of psychopathology ( P = .002) developed or had a relapse of psychopathology following transplant. Patients with more than a high school education ( P = .025) and who were less than 30 years ( P = .026) had higher rejection incidence rates. Risk factors for rehospitalizations included Hispanic race, diabetes, and low socioeconomic status ( P = .036, P = .038, P = .014). African American/Black and male patients had higher incidence of infection events ( P = .032, P = .049). Mortality and treatment nonadherence were not significantly associated with SIPAT scores or demographic variables., Conclusion: The SIPAT was associated with posttransplant substance use and support system instability, while demographic variables were associated with the development and/or relapse of psychopathology, graft loss, rejection, infection events, and medical rehospitalizations. Revision of the SIPAT to include additional demographic components may lend to improved prediction of transplant outcomes.
- Published
- 2019
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18. Seroprevalence of Strongyloides stercoralis and Evaluation of Universal Screening in Kidney Transplant Candidates: A Single-Center Experience in Houston (2012-2017).
- Author
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Al-Obaidi M, Hasbun R, Vigil KJ, Edwards AR, Chavez V, Hall DR, Dar WA, De Golovine A, Ostrosky-Zeichner L, Bynon JS, and Nigo M
- Abstract
Background: Disseminated strongyloidiasis in solid organ transplant recipients is a rare but devastating infection. In our center, we implemented a universal screening of all candidates for kidney transplantation. We assessed the seroprevalence and utility of universal screening for strongyloidiasis in our center., Methods: Patients were identified from our transplant referral list (from July 2012 to June 2017). Demographics, pretransplant laboratory, and serological screenings were retrospectively collected. For Strongyloides-seropositive (SSp) patients, data on travel history, symptoms, treatment, and stool ova and parasite examinations were extracted. Logistic regression and multiple imputation for missing data were performed., Results: A total of 1689 patients underwent serological screening, of whom 168 (9.9%) were SSp. Univariate analysis revealed that SSp patients had higher rates of eosinophilia, diabetes mellitus, latent tuberculosis and were likely to be either Hispanic or Asian (P < .05). In multivariate analysis, eosinophilia (P = .01), diabetes mellitus (P = .02), and Asian race (P = .03) were associated with being SSp, but 45 (27%) of the SSp patients did not have any of these 3 factors, and 18 SSp patients (11%) had no epidemiological risk factors. All patients received ivermectin, and none developed disseminated strongyloidiasis. Of patients who underwent serological screening on multiple occasions, 6.8% seroconverted while waiting for kidney transplantation., Conclusions: We found a high rate of Strongyloides seropositivity among our kidney transplantation candidates. No epidemiological risk factors effectively predicted SSp status in our population, and universal screening identified a large number of patients without such factors. Serial screening should be considered when a long wait time is expected before transplantation., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2019
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19. Mutant p53 R175H promotes cancer initiation in the pancreas by stabilizing HSP70.
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Polireddy K, Singh K, Pruski M, Jones NC, Manisundaram NV, Ponnela P, Ouellette M, Van Buren G, Younes M, Bynon JS, Dar WA, and Bailey JM
- Subjects
- Carcinogenesis, Cell Line, Tumor, Cell Nucleus metabolism, Cell Survival physiology, HSP70 Heat-Shock Proteins biosynthesis, HSP70 Heat-Shock Proteins genetics, Humans, Mutation, Pancreatic Neoplasms pathology, Proteomics, HSP70 Heat-Shock Proteins metabolism, Pancreatic Neoplasms genetics, Pancreatic Neoplasms metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism
- Abstract
Pancreatic cancer remains a highly lethal malignancy. We have recently shown that simultaneous expression of Kras and mutant Tp53
R175H promotes invasive ductal adenocarcinoma from pancreatic ductal cells. We hypothesized specific mutations in TP53 have divergent mechanisms of transforming ductal cells. In order to understand the role of mutant TP53 in transforming pancreatic ductal cells, we used a lentiviral system to express mutant TP53R175H and TP53R273H , two of the most frequently mutated TP53 alleles in pancreatic cancer patients, in immortalized, but not transformed, pancreatic ductal epithelial cells carrying a KRAS mutation (HPNE:KRASG12D ). Mutant TP53 expression enhanced colony formation and an RPPA assay results revealed TP53R175H uniquely induced HSP70 expression in HPNE:KRASG12D cells. In the context of TP53R175H expression; we observed nuclear localization of HSP70. We performed immunoprecipitation experiments to show mutant p53R175H binds to HSP70. We also provide evidence mutant p53R175H is important for HSP70 stability and, more importantly, HSP70 is required for mutant p53 stability. These data are critical in the context of events leading to cellular transformation in the pancreas., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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20. Confining an Ag 10 Core in an Ag 12 Shell: A Four-Electron Superatom with Enhanced Photoluminescence upon Crystallization.
- Author
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Khatun E, Bodiuzzaman M, Sugi KS, Chakraborty P, Paramasivam G, Dar WA, Ahuja T, Antharjanam S, and Pradeep T
- Abstract
We introduce a cluster coprotected by thiol and diphosphine ligands, [Ag
22 (dppe)4 (2,5-DMBT)12 Cl4 ]2+ (dppe = 1,2-bis(diphenylphosphino)ethane; 2,5-DMBT= 2,5-dimethylbenzenethiol), which has an Ag10 core encapsulated by an Ag12 (dppe)4 (2,5-DMBT)12 Cl4 shell. The Ag10 core comprises two Ag5 distorted trigonal bipyramidal units and is uncommon in Au and Ag nanoclusters. The electrospray ionization mass spectrum reveals that the cluster is divalent and contains four free electrons. An uncommon crystallization-induced enhancement of emission is observed in the cluster. The emission is weak in the solution and amorphous states. However, it is enhanced 12 times in the crystalline state compared to the amorphous state. A detailed investigation of the crystal structure suggests that well-arranged C-H···π and π···π interactions between the ligands are the major factors for this enhanced emission. Further, in-depth structural elucidation and density functional theory calculations suggest that the cluster is a superatom with four magic electrons.- Published
- 2019
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21. Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms.
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Dar WA, Sullivan E, Bynon JS, Eltzschig H, and Ju C
- Subjects
- Animals, Endothelial Cells metabolism, Hepatocytes metabolism, Humans, Kupffer Cells metabolism, Liver pathology, Reactive Oxygen Species metabolism, Reperfusion Injury therapy, Signal Transduction, Tissue Donors, Toll-Like Receptors metabolism, Liver blood supply, Liver Transplantation adverse effects, Reperfusion Injury etiology, Reperfusion Injury metabolism
- Abstract
Liver disease causing end organ failure is a growing cause of mortality. In most cases, the only therapy is liver transplantation. However, liver transplantation is a complex undertaking and its success is dependent on a number of factors. In particular, liver transplantation is subject to the risks of ischaemia-reperfusion injury (IRI). Liver IRI has significant effects on the function of a liver after transplantation. The cellular and molecular mechanisms governing IRI in liver transplantation are numerous. They involve multiple cells types such as liver sinusoidal endothelial cells, hepatocytes, Kupffer cells, neutrophils and platelets acting via an interconnected network of molecular pathways such as activation of toll-like receptor signalling, alterations in micro-RNA expression, production of ROS, regulation of autophagy and activation of hypoxia-inducible factors. Interestingly, the cellular and molecular events in liver IRI can be correlated with clinical risk factors for IRI in liver transplantation such as donor organ steatosis, ischaemic times, donor age, and donor and recipient coagulopathy. Thus, understanding the relationship of the clinical risk factors for liver IRI to the cellular and molecular mechanisms that govern it is critical to higher levels of success after liver transplantation. This in turn will help in the discovery of therapeutics for IRI in liver transplantation - a process that will lead to improved outcomes for patients suffering from end-stage liver disease., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
22. Chitinase 3-like-1 promotes intrahepatic activation of coagulation through induction of tissue factor in mice.
- Author
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Shan Z, Liu X, Chen Y, Wang M, Gao YR, Xu L, Dar WA, Lee CG, Elias JA, Castillo PD, Di Paola J, and Ju C
- Subjects
- Animals, Cells, Cultured, Female, Male, Mice, Blood Coagulation physiology, Chitinase-3-Like Protein 1 physiology, Liver blood supply, Liver Diseases etiology, Thromboplastin physiology
- Abstract
Coagulation is a critical component in the progression of liver disease. Identification of key molecules involved in the intrahepatic activation of coagulation (IAOC) will be instrumental in the development of effective therapies against liver disease. Using a mouse model of concanavalin A (ConA)-induced hepatitis, in which IAOC plays an essential role in causing liver injury, we uncovered a procoagulant function of chitinase 3-like 1 (Chi3l1). Chi3l1 expression is dramatically elevated after ConA challenge, which is dependent on ConA-induced T cell activation and the resulting interferon γ and tumor necrosis factor α productions. Compared with wild-type mice, Chi3l1
-/- mice show less IAOC, reduced tissue factor (TF) expression, and attenuated liver injury. Reconstituting Chi3l1-/- mice with recombinant TF triggers IAOC and augments liver injury., Conclusion: Our data demonstrate that Chi3l1, through induction of TF via mitogen-activated protein kinase activation, promotes IAOC and tissue injury. (Hepatology 2018;67:2384-2396)., (© 2017 by the American Association for the Study of Liver Diseases.)- Published
- 2018
- Full Text
- View/download PDF
23. The New Kidney Donor Allocation System and Implications for Anesthesiologists.
- Author
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Sridhar S, Guzman-Reyes S, Gumbert SD, Ghebremichael SJ, Edwards AR, Hobeika MJ, Dar WA, and Pivalizza EG
- Subjects
- Anesthesia, Humans, Tissue Donors, Anesthesiologists, Kidney Transplantation adverse effects, Tissue and Organ Procurement
- Abstract
Given potential disparity and limited allocation of deceased donor kidneys for transplantation, a new federal kidney allocation system was implemented in 2014. Donor organ function and estimated recipient survival in this system has implications for perioperative management of kidney transplant recipients. Early analysis suggests that many of the anticipated goals are being attained. For anesthesiologists, implications of increased dialysis duration and burdens of end-stage renal disease include increased cardiopulmonary disease, challenging fluid, hemodynamic management, and central vein access. With no recent evidence to guide anesthesia care within this new system, we describe the kidney allocation system, summarize initial data, and briefly review organ systems of interest to anesthesiologists. As additional invasive and echocardiographic monitoring may be indicated, one consideration may be development of a dedicated anesthesiology team experienced in management and monitoring of complex patients, in a similar manner as has been done for liver transplant recipients.
- Published
- 2018
- Full Text
- View/download PDF
24. Retrograde Flushing of Living Donor Renal Allografts via the Renal Vein: A Simple, Effective Technique.
- Author
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Hobeika MJ, Dar WA, Hall DR, and Bynon JS
- Subjects
- Adenosine administration & dosage, Adenosine adverse effects, Adult, Aged, Allopurinol administration & dosage, Allopurinol adverse effects, Female, Glomerular Filtration Rate, Glutathione administration & dosage, Glutathione adverse effects, Humans, Infusions, Intravenous, Insulin administration & dosage, Insulin adverse effects, Kidney Transplantation adverse effects, Male, Middle Aged, Organ Preservation Solutions adverse effects, Raffinose administration & dosage, Raffinose adverse effects, Recovery of Function, Retrospective Studies, Therapeutic Irrigation adverse effects, Time Factors, Treatment Outcome, Kidney Transplantation methods, Living Donors, Nephrectomy, Organ Preservation Solutions administration & dosage, Renal Veins surgery, Therapeutic Irrigation methods
- Abstract
Background: Prograde flushing (PF) of living donor renal allografts with preservation solution via the renal artery or arteries is standard practice. PF may be difficult and potentially injurious to the donor kidney, especially in grafts with small or multiple arteries. In this report, we present our experience with retrograde flushing (RF) of 7 living donor kidneys via the renal vein., Methods: Retrospective review of 7 consecutive living donor renal transplants performed using the RF technique was performed. The 7 preceding living donor renal transplants performed using the standard arterial PF technique served as a control group., Results: All 7 recipients of RF kidneys experienced immediate graft function. At postoperative days 3 and 30, there was no difference in estimated glomerular filtration rate between the RF study group and PF controls., Conclusions: The RF technique is simple and safe, with results equivalent to the PF technique. The RF technique may be especially useful after recovering kidneys with small and/or multiple arteries.
- Published
- 2017
- Full Text
- View/download PDF
25. Phase controlled colour tuning of samarium and europium complexes and excellent photostability of their PVA encapsulated materials. Structural elucidation, photophysical parameters and the energy transfer mechanism in the Eu(3+) complex by Sparkle/PM3 calculations.
- Author
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Dar WA and Iftikhar K
- Abstract
Luminescent [Sm(acac)3(pyz)2] (1) and [Eu(acac)3(pyz)2] (2) complexes (acac is the anion of acetylacetone and pyz is pyrazine) have been synthesized and thoroughly characterized by microanalyses, TGA, DTA, IR, ESI-MS(+) and NMR spectroscopy. The photophysical properties of these complexes have been investigated. The Sparkle/PM3 model was utilized for predicting the ground-state geometry of (2). The Judd-Ofelt intensity parameters, radiative parameters, intramolecular energy transfer rates and quantum efficiency are calculated and discussed. The intramolecular energy transfer rates predict that the major energy transfer (96%) is from the ligand triplet state to the levels (5)D1 (74.53%) and (5)D0 (21.87%) of the Eu(3+) ion, in the complex. Complexes (1) and (2) were analysed for colour tuning properties and these show varying colours upon changing phases. This property would possibly allow the use of these complexes as 'colour indicators'. The photoluminescence and photostability of the thin hybrid films of both complexes (1) and (2) in polyvinyl alcohol (PVA) are investigated and discussed. The hybrid films of (1) and (2) are quite robust due to their higher photostability. An important feature of complex (2) is that the excitation window extends close to the visible range (393 nm). The lasing property of the Eu(3+) complex in various phases is also presented.
- Published
- 2016
- Full Text
- View/download PDF
26. Reply to Vanhove et al.
- Author
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Page EK, Dar WA, and Knechtle SJ
- Subjects
- Animals, Humans, Antibodies, Monoclonal chemistry, Biological Products therapeutic use, Organ Transplantation methods
- Published
- 2013
- Full Text
- View/download PDF
27. Tolerogenic therapies in transplantation.
- Author
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Page EK, Dar WA, and Knechtle SJ
- Abstract
Since the concept of immunologic tolerance was discovered in the 1940s, the pursuit of tolerance induction in human transplantation has led to a rapid development of pharmacologic and biologic agents. Short-term graft survival remains an all-time high, but successful withdrawal of immunosuppression to achieve operational tolerance rarely occurs outside of liver transplantation. Collaborative efforts through the NIH sponsored Immune Tolerance Network and the European Commission sponsored Reprogramming the Immune System for Establishment of Tolerance consortia have afforded researchers opportunity to evaluate the safety and efficacy of tolerogenic strategies, investigate mechanisms of tolerance, and identify molecular and genetic markers that distinguish the tolerance phenotype. In this article, we review traditional and novel approaches to inducing tolerance for organ transplantation, with an emphasis on their translation into clinical trials.
- Published
- 2012
- Full Text
- View/download PDF
28. Biologics in organ transplantation.
- Author
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Page EK, Dar WA, and Knechtle SJ
- Subjects
- Animals, B-Cell Activating Factor metabolism, B-Lymphocytes cytology, CD28 Antigens metabolism, Calcineurin pharmacology, Complement System Proteins, Cytokines metabolism, Europe, Humans, Immunologic Factors pharmacology, Immunosuppressive Agents therapeutic use, Interleukin-2 Receptor alpha Subunit metabolism, Models, Biological, Steroids therapeutic use, United States, Antibodies, Monoclonal chemistry, Biological Products therapeutic use, Organ Transplantation methods
- Abstract
The last two decades have witnessed a pandemic in antibody development, with over 600 entering clinical studies and a total of 28 approved by the FDA and European Union. The incorporation of biologics in transplantation has made a significant impact on allograft survival. Herein, we review the armamentarium of clinical and preclinical biologics used for organ transplantation--with the exception of belatacept--from depleting and IL-2R targeting induction agents to costimulation blockade, B-cell therapeutics, BAFF and complement inhibition, anti-adhesion, and anti-cytokine approaches. While individual agents may be insufficient for tolerance induction, they provide possibilities for reduction of steroid or calcineurin inhibitor use, alternatives to rejection episodes refractory to conventional therapies, and specialized immunosuppression for highly sensitized patients., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)
- Published
- 2012
- Full Text
- View/download PDF
29. With respect to elderly patients: finding kidneys in the context of new allocation concepts.
- Author
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Tso PL, Dar WA, and Henry ML
- Subjects
- Aged, Humans, Decision Support Techniques, Health Care Rationing, Kidney Transplantation, Tissue and Organ Procurement
- Abstract
The elderly have benefited from increased access to renal transplantation in recent years. New allocation concepts would shift distribution of kidneys to younger recipients, making expanded criteria and living donor kidneys more relevant for seniors. Current issues impacting expanded criteria donor kidney availability and living donor transplant opportunities for the elderly are explored. It is hoped that the kidney donor profile index will improve risk assessment and utilization of marginal kidneys. The usefulness of procurement biopsy remains controversial. Dual kidney transplantation and machine perfusion appear to be effective mechanisms to increase organ availability. "Old-for-old" allocation systems, donation service area variation and regulatory and reimbursement issues highlight disparities and disincentives affecting expanded criteria donor organ utilization, and considerations for the way forward are discussed. Living donor transplantation, even with older donors, may provide the best option for elderly recipients, and careful expansion of the living donor pool appears appropriate. In light of new allocation concepts, it will be important to understand issues pertinent to seniors and develop effective strategies to maintain or improve their access to the benefits of transplantation., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2012
- Full Text
- View/download PDF
30. CXCR3-mediated T-cell chemotaxis involves ZAP-70 and is regulated by signalling through the T-cell receptor.
- Author
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Dar WA and Knechtle SJ
- Subjects
- Adaptor Proteins, Signal Transducing metabolism, Cells, Cultured, Chemotaxis, Leukocyte drug effects, Humans, Jurkat Cells, Ligands, Lymphocyte Activation immunology, Membrane Proteins metabolism, Phospholipase C gamma metabolism, Phosphorylation, Protein-Tyrosine Kinases metabolism, Receptors, CXCR3, Signal Transduction immunology, Stilbenes pharmacology, ZAP-70 Protein-Tyrosine Kinase metabolism, Chemotaxis, Leukocyte immunology, Receptors, Antigen, T-Cell immunology, Receptors, Chemokine immunology, ZAP-70 Protein-Tyrosine Kinase immunology
- Abstract
The chemokine receptor CXCR3 is critical for the function of activated T cells. We studied the molecular mechanisms of CXCR3 signalling. The addition of CXCR3 ligands to normal human T cells expressing CXCR3 led to the tyrosine phosphorylation of multiple proteins. Addition of the same ligands to Jurkat T cells engineered to express CXCR3 induced tyrosine phosphorylation of proteins with molecular weights similar to those in normal cells. Immunoblotting with phosphotyrosine-specific antibodies identified Zeta-associated protein of 70,000 molecular weight (ZAP-70), linker for the activation of T cells (LAT), and phospholipase-C-gamma1 (PLCgamma1) to be among the proteins that become phosphorylated upon CXCR3 activation. ZAP-70 was phosphorylated on tyrosine 319, LAT on tyrosines 171 and 191, and PLCgamma1 on tyrosine 783. The ZAP-70 inhibitor piceatannol reduced CXCR3-mediated tyrosine phosphorylation of ZAP-70, LAT, PLCgamma1 and mitogen-activated protein kinase Erk and it reduced CXCL10-mediated chemotaxis of both CXCR3-transfected Jurkat T cells and normal T cells expressing CXCR3. These results are consistent with the involvement of ZAP-70 in CXCR3-mediated protein tyrosine phosphorylation and CXCR3-induced T-cell chemotaxis. Studies with the Lck-deficient Jurkat T-cell line, JCAM1.6, demonstrated that phosphorylation of ZAP-70 after CXCR3 activation is a Lck-dependent process. Finally, stimulating CXCR3-expressing Jurkat T cells and normal T cells expressing CXCR3 through the T-cell receptor attenuated CXCR3-induced tyrosine phosphorylation and CXCR3-mediated T-cell migration, indicating the occurrence of cross-talk between T-cell receptor and CXCR3-signalling pathways. These results shed light on the mechanisms of CXCR3 signalling. Such information could be useful when designing therapeutic strategies to regulate T-cell function.
- Published
- 2007
- Full Text
- View/download PDF
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