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Mathematical Methods in Physics: Partial Differential Equations, Fourier Series, and Special Functions 1st

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Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date

2009年

作者： Victor Henner Tatyana Belozerova kyle Forinash

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World Journal of Clinical Cases 2015年第8期3卷 694-704页

作者： kyle Crassini Stephen P Mulligan O Giles Best Northern Blood Research Centre and CLL Australian Research Consortium Kolling Institute of Medical Research Royal North Shore Hospital

Chronic lymphocytic leukemia(CLL) is the most common leukemia in the western world. Despite significantadvances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor(BCR) and cytokine receptors. A better understanding of the pathogenesis of the disease, the underlying biology of the CLL-cell and the roles of the tumour microenvironment has provided the rationale for trials of a range of novel, more targeted therapeutic agents. In particular, clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR signaling pathway respectively, have shown extremely promising results. Here we review the current literature on the key signaling pathways and interactions of CLL cells that mediate the survival and proliferation of the leukemic cells. For each we describe the results of the recent clinical trials and in vitro studies of novel therapeutic agents.

关键词： Chronic lymphocytic leukemia Therapy Microenvironment Leukemia Novel

Cdc2-like kinases:structure,biological function,and therapeutic targets for diseases

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2088-2112页

作者： Mengqiu Song Luping Pang Mengmeng Zhang Yingzi Qu kyle Vaughn Laster Zigang Dong Department of Pathophysiology School of Basic Medical SciencesCollege of MedicineZhengzhou UniversityZhengzhouHenan450001China China-US(Henan)Hormel Cancer Institute No.127Dongming RoadJinshui DistrictZhengzhouHenan450008China State Key Laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou UniversityZhengzhouHenanChina Academy of Medical Sciences College of MedicineZhengzhou UniversityZhengzhouHenan450001China Research Center of Basic Medicine Academy of Medical SciencesCollege of MedicineZhengzhou UniversityZhengzhouHenan450001China

The CLKs(Cdc2-like kinases)belong to the dual-specificity protein kinase family and play crucial roles in regulating transcript splicing via the phosphorylation of SR proteins(SRSF1–12),catalyzing spliceosome molecular machinery,and modulating the activities or expression of non-splicing *** dysregulation of these processes is linked with various diseases,including neurodegenerative diseases,Duchenne muscular dystrophy,inflammatory diseases,viral replication,and ***,CLKs have been considered as potential therapeutic targets,and significant efforts have been exerted to discover potent CLKs *** particular,clinical trials aiming to assess the activities of the small molecules Lorecivivint on knee Osteoarthritis patients,and Cirtuvivint and Silmitasertib in different advanced tumors have been investigated for therapeutic *** this review,we comprehensively documented the structure and biological functions of CLKs in various human diseases and summarized the significance of related inhibitors in *** discussion highlights the most recent CLKs research,paving the way for the clinical treatment of various human diseases.

关键词： diseases therapeutic specificity

Phototropism in land plants： Molecules and mechanism from light perception to response

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Frontiers in Biology 2018年第5期13卷 342-357页

作者： Johanna Morrow kyle T. Willenburg Emmanuel Liscum C.S. Bond Life Sciences Center University of Missouri Columbia MO USA Division of Biological Sciences University of Missouri Columbia MO USA

BACKGROUND： Phototropism is the response a plant exhibits when it is faced with a directional blue light stimulus. Though a seemingly simple differential cell elongation response within a responding tissue that results in organ curvature, phototropism is regulated through a complex set of signal perception and transduction events that move from the plasma membrane to the nucleus. In nature phototropism is one of several plant responses that have evolved to optimize photosynthesis and growth. OBJECTIVE： In the present work we will review the state of the field with respect to the molecules and mechanisms associated with phototropism in land plants. METHODS： A systematic literature search was done to identify relevant advances in the field. Though we tried to focus on literature within the past decade （1998-present）, we have discussed and cited older literature where appropriate because of context or its significant impact to the present field. Several previous review articles are also cited where appropriate and readers should seek those out. RESULTS： A total of 199 articles are cited that fulfill the criteria listed above. CONCLUSIONS： Though important numerous and significant advances have been made in our understanding of the molecular, biochemical, cell biological and physiologic mechanisms underlying phototropism in land plants over the past decade, there are many remaining unanswered questions. The future is indeed bright for researchers in the field and we look forward to the next decade worth of discoveries.

关键词： phototropism phototropin phytochrome crytochrome auxin auxin response factor phosphorylation ubiquitination transcriptional control cell elongation growth non-phototropic hypocotyl 3 NPH3/RPT2-1ike protein kinase calcium

The Association Between Subjective Wellness Symptoms and Blood Biomarker Data in English Premier League Footballers

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Journal of Science in Sport and Exercise 2023年第4期5卷 340-347页

作者： Marc Cleary Fearghal McHugh kyle F.Paradis Galway-May Institute of Technology GalwayIreland Ulster University BelfastNorthern Ireland

The present study investigates the association between subjective wellness symptoms,and categorical point-of-care(POC)blood biomarkers of the free oxygen radical test(FORT),and systemic inflammation through high sensitivity C-reactive protein(Hs-CRP),in English Premier League *** from 38 male professional elite athletes(Mean Age=25.8,SD=4.4)from the English Premier League were included in the study,with a total of 674 individual testing records collected over an entire Premier League season.A player wellness questionnaire,along with fasted and rested point-of-care blood biomarker testing were collected weekly across the *** wellness questionnaire collected subjective symptoms of illness and fatigue,while FORT and Hs-CRP were assessed through point-of-care analysis to highlight periods of excessive hydroperoxide production and systemic *** a chi square goodness of fit model,results showed that there was a significant association between the frequency of symptoms logged and categorical POC blood biomarker data of FORT and HsCRP(P<0.01).Of the records demonstrating normal levels of Hs-CRP and FORT concentrations,27%logged symptoms with an average of 1.5 symptoms reported per answered ***,excessive biomarker values demonstrated 55%of records having symptoms logged,averaging 2.4 symptoms reported per record.

关键词： athlete wellness blood biomarkers premier league football elite athletes high performance sport

Guest editorial-special issue on ground control in mining in 2019

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International Journal of Mining Science and Technology 2020年第1期30卷 1-2页

作者： Michael M.Murphy Ted Klemetti Heather Lawson Brijes Mishra kyle Perry Pittsburgh Mining Research Division NIOSHPittsburghPA 15228USA Spokane Mining Research Division NIOSHSpokaneWA 99207USA Mining Engineering West Virginia UniversityMorgantownWV 26506USA Mining&Nuclear Engineering Missouri S&TRollaMO 65409USA

Ground control is the science of studying and controlling the behavior of rock strata in response to mining ***-control-related research has seen significant advancements over the last 39 years,and these accomplishments are well documented in the proceedings of the annual International Conference on Ground Control in Mining(ICGCM)[1].The ICGCM is a forum to promote closer communication among researchers,consultants,regulators,manufacturers,and mine operators to expedite solutions to ground control problems in mining[2–7].Fundamental research and advancements in ground control science define the central core of the conference *** information to mine operators is a priority,as the conference goal is to offer solutions-oriented *** addition,the conference has included innovative technologies and ideas in miningrelated fields such as exploration,geology,and surface and underground mining in all *** new ground control technologies and design standards adopted by the mining industry were first discussed at ***,this conference is recognized as the best international forum for introducing new groundcontrol-related research and products.

关键词： operators closer accomplishment

Clinical Factors Associated with Hepatocellular Iron Deposition in End-stage Liver Disease

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Journal of Clinical and Translational Hepatology 2020年第3期8卷 231-239页

作者： Amelia Fierro-Fine Leana Guerin Hasan Hicsasmaz kyle E.Brown Department of Pathology University of Iowa Roy J.and Lucille A.Carver College of MedicineIowa CityIAUSA ObjectRelational LLP Iowa CityIAUSA Division of Gastroenterology-Hepatology University of Iowa Roy J.and Lucille A.Carver College of MedicineIowa CityIAUSA Program in Free Radical and Radiation Biology University of Iowa Roy J.and Lucille A.Carver College of MedicineIowa CityIAUSA Iowa City Veterans Administration Medical Center Iowa CityIAUSA

Background and Aims: Hepatocellular iron accumulation in patients with chronic liver disease has been linked to adverse outcomes. The objective of this study was to identify clinical factors associated with hemosiderosis. Methods: A total of 103 consecutive liver transplant recipients were identified, in whom liver biopsy had been performed prior to transplantation. Laboratory and clinical data at biopsy and transplant were abstracted from the medical records and hepatocyte iron was graded in the biopsy and explant. The association of change in iron score from biopsy to transplant, with the time interval between these two events, was examined using linear mixed model analysis for repeated measures. Results: Most subjects had advanced fibrosis (F3-F4) at liver biopsy, which was performed on average about 2.5 years before transplant. Over 80% of patients had no or 1+ hepatocyte iron at biopsy;iron increased between biopsy and transplant in about 40%. The only demographic or clinical feature that correlated with increased iron was the presence of a transjugular intrahepatic portosystemic shunt. Increased iron at transplant was associated with higher serum iron and transferrin saturation at biopsy, and with lower hemoglobin level, greater mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, higher ferritin and model for end-stage liver disease score at ***: The development of hemosiderosis in end-stage liver disease is associated with lower hemoglobin levels and alterations in red blood cell indices that are suggestive of hemolysis. These observations suggest that extravascular hemolysis may play a role in the development of secondary iron overload.

关键词： Erythrocyte indices End-stage liver disease Hemolysis Hemosiderosis Humans Iron

Occurrence of bed load transport in the presence of stable clast

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International Journal of Sediment Research 2017年第2期32卷 195-209页

作者： Mohd Sofiyan Sulaiman Shanker Kumar Sinnakaudan Set Foong Ng kyle Strom I-Geo Disaster Research Center Faculty of Engineering & Technology Infrastructure(FETI)Infrastructure University Kuala Lumpur(IUKL) Water Resources Engineering & Management Research Center(WAREM) Universiti Teknologi MARA Faculty of Computer & Mathematical Sciences Universiti Teknologi MARA Department of Civil and Environmental Engineering Virginia Tech

It is well-versed that transport occurrence is vital for in stream rehabilitation,river restoration and installment of sediment sampler on river *** practice emulates the use of continuous prediction using reach-averaged ***,prediction of transport occurrence entails the use of binary model through the execution of logistic regression *** load and turbulence data were physically measured at mountainous region with divergent surface bedform in its *** parameterization and statistical approaches are treated in the similar fashion with multiple regression except for the test for model fit and model selection *** parameters on near-bed turbulence characteristics at the entrainment threshold were assigned as independent variables containing 15 *** 80 models were generated by selecting the best possible combination in accordance with the statistical precaution of alleviating multicollinearity *** is postulated that the model containing shields stress in the form of turbulent kinetic energy(IKE) at vertical direction and fractional time for second quadrant provides better estimation of potential location for greatest sediment-entrainment;hence a high possibility for transport occurrence.

关键词： Logistic regression analysis Transport occurrence Bed load Entrainment Local bed shear

Intriguing Origins of Protein Lysine Methylation:Influencing Cell Function Through Dynamic Methylation

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Genomics, Proteomics & Bioinformatics 2019年第6期17卷 551-557页

作者： Natalie Mezey William C.S.Cho kyle K.Biggar Institute of Biochemistry and Department of Biology Carleton UniversityOttawaON K1S 5B6Canada Department of Clinical Oncology Queen Elizabeth HospitalKowloonHong Kong Special Administrative RegionChina

Introduction“There is a kink(shoulder)on[the]Lys peak...”These words scribed in Richard ***’s laboratory notebook marked the discovery of protein methylation and a segue into a new field of scientific research[1].Initially,through ion-exchange chromatography and two-dimensional paper chromatography of the hydrolysate of Salmonella typhimurium flagellin,this“kink”was interpreted as a“new amino acid”,the e-Nmethyl-lysine(NML).This discovery,bolstered by a subsequent examination of purified NML,was the first glimpse of protein methylation in living cells[1].

关键词： Lys Intriguing Origins of Protein Lysine Methylation:Influencing Cell Function Through Dynamic Methylation