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Inhibition of FLT3:A Prototype for Molecular Targeted Therapy in Acute Myeloid Leukemia

Engineering 2021年第10期7卷 1354-1368页

作者： Meira Yisraeli salman jacob M.Rowe Nir Weigert Department of Hematology Shaare Zedek Medical CenterJerusalem 9103102Israel Department of Hematology and Bone Marrow Transplantation Rambam Medical CenterHaifa 3109601Israel Technion—Israel Institute of Technology Haifa 3200003Israel

Modern therapy of acute myeloid leukemia(AML)began in 1973 with the first report of the successful combination of daunorubicin and cytarabine,which led to complete remission in approximately 45%of *** AML diagnosis was dependent on morphology,aided initially only by *** acute lymphoblastic leukemia(ALL),immunophenotyping offered little in the diagnosis of AML,at least during the 1970s and *** advent of reliable cytogenetics changed the entire prognostic outlook of *** karyotypic analysis,different groups of AML could be classified and stratified for various *** mutational profiling was a major advance in further categorizing AML patients,aided by the immunophenotypic identification of antigenic markers on the *** these advances were occurring as the understanding of the importance of the tumor burden—known as minimal residual disease(MRD)—became crucial for the management of AML *** efficacy of MRD has rapidly progressed in the past decade,from a specificity of 103 with immunophenotyping to 104 with polymerase chain reaction(PCR),which is only appropriate for some patients with AML,and finally to 105 or even 106 cells with the extraordinary sensitivity of next-generation sequencing(NGs).All of these advances have promoted the concept of personalized medicine,which has led to the advent of targeted agents that can accurately be used for specific diagnostic *** can be predicted and measured *** targeted agents have now become a cornerstone in the management of AML,increasing effi-cacy and dramatically reducing *** focus of this review is on one of the most well-studied targeted agents in AML:the FMs-like tyrosine kinase 3(FLT3)inhibitors,which have impacted the prognostication and therapeutics of *** review selectively discusses the FLT3 inhibitors in detail,as a model for the other burgeoning targeted agents that have already been approved,as well as tho

关键词： AML Targeted therapy FLT3 inhibitors Midostaurin Gilteritinib Quizartinib sorafenib

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Intraspecific genetic variability,differentiation and evolutionary relationships revealed through microsatellite loci in seven economically important Calamus species

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Journal of Forestry Research 2020年第5期31卷 1899-1911页

作者： Binoy Kurian A.s.Hemanthakumar Joemon jacob Wickneswari Ratnam C.Y.Choong Prabalee sarmah s.shefeek Vishnu V.Nair s.V.sajithkumar K.K.sabu Jawaharlal Nehru Tropical Botanic Garden and Research Institute(JNTBGRI) PalodeThiruvananthapuramKerala 695562India Universiti Kebangsaan Malaysia 43600 BangiSelangorMalaysia Assam Agricultural University JorhatAssam 785013India

Population density,species richness and critical population parameters are crucial in determining the levels of gene diversity in dioecious species of the genus *** extent of intraspecific and intrageneric genetic variability in Calamus from the southern Western Ghats of India was studied using 26 microsatellite markers by sampling 227 individuals belonging to seven economically important *** heterozygosity of microsatellite loci ranged from zero to *** gene diversity within species was 0.13;in all species it was 0.18 and amongst species was *** shannon Information Index was the lowest for Calamus metzianus(0.11),whereas it ranged from 0.16 to 0.26 for other *** expected heterozygosity varied from 0.08 to *** hookerianus and Calamu travancoricus showed the highest genetic differentiation(44%)revealed through Fst values,whereas the lowest(22%)was observed between Calamus gamblei and Calamu *** structuring and phylogenetic analysis differentiated the seven *** to overexploitation and loss of rare alleles,small populations could lead to fertilization between closely related individuals,resulting in inbreeding and increasing the risk of *** could be important for species such as *** where allelic polymorphism was 23%,whereas for all other species it was 38%to 46%.Genetic diversity“micro-hotspots”were identified from the protected area network of the southern and central Western Ghats with highest observed *** microhotspots from the Agasthyamalai Biosphere Reserve and the Pushpagiri Wildlife sanctuary may be possible for long-term conservation *** findings of this study lay a strong foundation for strengthening protected area networks,especially areas with intermediate levels of disturbance.

关键词： Genetic diversity Differentiation Population structure Conservation Microsatellites Calamus spp

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Navigated laser in diabetic macular edema: the impact of reduced injection burden on patients and physicians-who wins and who loses?

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International Journal of Ophthalmology(English edition) 2019年第2期12卷 342-345页

作者： jacob Menzler Aljoscha Neubauer Focke Ziemssen Institute for Health and Pharmacoeconomics Private Practice Ophthalmology Center for Ophthalmology Eberhard-Karls University

We inquired the impact of reduced therapy discontinuation in diabetic macular edema(DME) on physician's revenue considering anti-vascular endothelial growth factor(VEGF) monotherapy and its combination with Navilas treatment. Data were collected on injection frequency, treatment discontinuation and reimbursement fees for DME treatment with anti-VEGF compared to anti-VEGF in combination with navigated laser. Based on these data an economic model was built to compare physicians revenue over a 5y period using either therapy for 4 European countries and the UsA. Due to patients' higher therapy adherence, physicians using navigated laser therapy with anti-VEGF generate similar or higher revenues compared to VEGF monotherapy in all analyzed countries. The use of Navilas decreases the patient's injection burden at the same clinical outcome, while the physician's revenue remained stable or increased. Therewith, therapy discontinuation in DME can be reduced using the combination therapy with Navilas.

关键词： diabetic macular edema laser therapy Navilas cost-effectiveness injection burden adherence

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Effect of a 26-month floorball training on male elderly's cardiovascular fitness, glucose control, body composition, and functional capacity

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Journal of sport and Health science 2018年第2期7卷 149-158页

作者： Mogens Theisen Pedersen jacob Vorup Jens Bangsbo Copenhagen Centre of Team sport and Health Department of NutritionExercise and SportsSection of Integrated PhysiologyUniversity of Copenhagen Health science Research Center University College Lillebaelt

Background: Floorball training offers a motivating and socially stimulating team activity for older adults, and 12 weeks of floorball training twice a week among men aged 65—76 years have been shown to have positive effects on a number of physiological parameters important for health. However, the effect of long-term participation in floorball training among male elderly has not been investigated. The aim of the present study was to examine the effect of 26-month self-organized regular participation in floorball training on cardiovascular fitness, body composition, blood lipids, glucose control, and physical function among recreationally active men aged 66—78 ***: After completing a 12-week randomized and controlled intervention with floorball and petanque training in the autumn 2014 or spring2015, 15 subjects chose to participate in floorball training(floorball group, FG), whereas 16 subjects resumed their usual lifestyle(control group,CG). FG took part in self-organized floorball training 1.7 sessions of 40 min/week, and CG continued their normal recreationally active lifestyle during a 26-month follow-up period. At baseline and after the follow-up period subjects were tested for cardiovascular fitness, glucose control(resting blood samples), body composition dual-energy X-ray absorptiometry(DXA-scanning), and functional ***: In FG, the decline in maximal oxygen uptake(VO_(2max)) during the follow-up period was lower(242 ± 379 mL/min, p = 0.01), blood glycosylated hemoglobin(HbA1c) increased less(—1.6 ± 2.9 mmol/L, p = 0.02), and leg bone mineral density increased more(0.03 ± 0.05 g/cm^2,p = 0.02) than those in CG. The effects on body mass, total lean body mass, fat mass, blood lipids, and physical function were similar in FG and ***: Approximately twice weekly floorball sessions with 40 min/session over 26-month appear to reduce age-related decline in cardiovascular fitness and glucose control and improve leg bone mineral density,

关键词： Bone mineral density Elderly Floorball Glucose control VO2max

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VOLUME sEGMENTATION BY POsT-PROCEssING DATA FROM sIMULATION OF sOLIDIFICATION IN THE METAL CAsTING PROCEss

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International Journal of Modeling, simulation, and scientific Computing 2013年第S01期4卷 128-141页

作者： ELIZABETH jacob M.MANOJ ROsCHEN sAsIKUMAR Computational Modeling and simulation Unit National Institute for Interdisciplinary science and Technology Council of scientific and Industrial Research Trivandrum–695019 India

In the process of interpreting simulation results,new post-processing techniques are *** work presents a post-processing method that analyzes the solidification pattern formed by simulation of the solidification process of molten metal in a mold to produce shaped *** generally involve numerical solutions of differential equations which are discretized by dividing the three-dimensional computational domain into small finite volume elements using a 3D *** locations of the grid points and values of the solidification time at these locations are used to divide the spatial data into 3D sections such that starting from a hotspot location within the section that has high solidification time,there is a gradient outwards with lower values of solidification *** section is assumed to be fed by one or more feeders that must freeze only after the section has solidified *** volume of a feeder can be determined from the volume of the section it is supposed to *** volume and surface area of sections are determined approximately to calculate feeder size and *** post-processing algorithm is a simulation-based quantitative approach to feeder design which in conventional foundry practice has been more of an art than *** is also general enough for use in other 3D segmentation applications.

关键词： Metal casting simulation solidification pattern volume segmentation feeder design.

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On the mechanistic origins of maximum strength in nanocrystalline metals

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npj Computational Materials 2020年第1期6卷 393-404页

作者： Ankit Gupta jacob Gruber satish s.Rajaram Gregory B.Thompson David L.McDowell Garritt J.Tucker Colorado school of Mines Mechanical EngineeringGoldenCO 80401USA Department of Mechanical Engineering Drexel UniversityPhiladelphiaPA 19104USA Department of Metallurgical and Materials Engineering University of AlabamaTuscaloosaAL 35487USA Department of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA

The maximum strength of polycrystalline metals/alloys has been suggested to occur at nanoscale grain sizes where the governing deformation mechanism transitions from dislocation plasticity to grain boundary mediated *** tremendous progress recently uncovering links between transitions in nanoscale mechanisms and peak strength,the scientific literature is mostly devoid of any quantitative support,owing to the difficulty in measuring the resolved contribution of individual mechanisms to microstructural strain *** this study,the contribution of individual nanoscale mechanisms to the overall deformation of nanocrystalline Ni is calculated from atomistic simulations leveraging continuum-based kinematic metrics to compute mechanistic contributions to microstructural strain.

关键词： strength deformation grain

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spectroscopic studies of gel-grown lanthanum malonate crystals

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Journal of Rare Earths 2012年第3期30卷 245-249页

作者： Varghese Mathew sabu jacob Lizymol Xavier K.E.Abraham Department of Physics St.Aloysius'CollegeEdathua-689573India Department of Physics S.B.CollegeChanganacherry-686101India

Lanthanum malonate crystals were grown by single tube ionic diffusion through silica gel. The crystallinity of the grown crystals was analyzed by powder X-ray diffraction studies. Fourier transform infrared spectroscopy （FTIR） and fourier transform （FT） Raman studies confirmed the presence of functional groups in the title compound. The optical band gap energy of the material was extracted from diffuse reflectance spectrum.

关键词： lanthanum malonate crystal growth X-ray diffraction analysis DRs studies FTIR and FT Raman studies rare earths

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Minor fibrillar collagens,variable regions alternative splicing,intrinsic disorder,and tyrosine sulfation

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Protein & Cell 2012年第6期3卷 419-433页

作者： Ming Fang Reed jacob Owen McDougal Julia Thom Oxford Department of Biological sciences Boise State UniversityBoiseID 83725USA Department of Chemistry and Biochemistry Boise State UniversityBoiseID 83725USA Biomolecular Research Center Boise State UniversityBoiseID 83725USA

Minor fibrillar collagen types V and XI,are those less abundant than the fibrillar collagen types I,II and *** alpha chains share a high degree of similarity with respect to protein sequence in all domains except the variable *** variation and,in some cases,extensive alternative splicing contribute to the unique sequence characteristics of the variable *** unique expression patterns in tissues exist,the functions and biological relevance of the variable regions have not been *** this review,we summarize the existing knowledge about expression patterns and biological functions of the collagen types V and XI alpha *** of biochemical similarities among the peptides encoded by each exon of the variable region suggests the potential for a shared *** alternative splicing,conservation of biochemical characteristics in light of low sequence conservation,and evidence for intrinsic disorder,suggest modulation of binding events between the surface of collagen fibrils and surrounding extracellular molecules as a shared function.

关键词： minor fibrillar collagens variable regions alternative splicing fibrillogenesis heparan sulfate binding sites intrinsic disorder tyrosine sulfation

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China＇s Belt and Road Initiative：Perspectives from India

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China & World Economy 2017年第5期25卷 78-100页

作者： Jabin T. jacob Fellow Institute of Chinese Studies India

China ＂s Belt and Road Initiative （BRI） is often simplistically understood as beingopposed by lndia and supported by Pakistan. The reality on the ground is rather morecomplex. The emerging consensus in lndia appears to be that, far from being exclusivelyan economic and infrastructure development program, the BRI may be understood as along-term strategic initiative that seeks to convert China ＂s current economic might intodiplomatic influence. While attempts have been made by Beijing, the reflexive lndiansuspicion of Chinese international projection, including of China ＂s BRL has not yetbeen met by a coherent discourse designed to specifically address lndian concerns. Incontrast, in Pakistan, widespread acceptance of the importance and necessity of theChina-Pakistan Economic Corridor is increasingly coupled with concerns within sectorsof Pakistani society over the fairness, transparency and eventual economic outcomesof the project. Accordingly, this paper is divided into two parts： the first looks at howlndian analysts have viewed and responded to the Chinese discourse and arguments onthe BR1; the second considers the debate over the China-Pakistan Economic Corridorwithin Pakistan.

关键词： diplomacy, economic integration, infrastructure development, mutual mistrust, strategic competition

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Leisure-time physical activity,anthropometrics,and body composition as predictors of quality of life domains after spinal cord injury:an exploratory cross-sectional study

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Neural Regeneration Research 2022年第6期17卷 1369-1375页

作者： Melody N.Mickens Paul Perrin jacob A.Goldsmith Refka E.Khalil William E.Carter III Ashraf s.Gorgey Division of Physical Medicine and Rehabilitation University of Utah School of MedicineSalt Lake CityUTUSA Department of Psychology Virginia Commonwealth UniversityRichmondVAUSA spinal Cord Injury&Disorders Hunter Holmes McGuire VA Medical CenterRichmondVAUSA Department of Physical Medicine and Rehabilitation Virginia Commonwealth University School of MedicineRichmondVAUSA

The objective of the current work was to examine the relationships between quality of life(QOL)domains in persons with spinal cord injury(sCI)and their levels of weekly leisure-time physical activity(LTPA),anthropometric variables,and body composition *** exploratory cross-sectional study consisted of baseline data collected as part of a randomized clinical trial at a VA Medical Center and sCI center.A convenience sample of 36 community-dwelling persons with sCI participated in the current *** measures included the World Health Organization Quality of Life short Form(WHOQOL-BREF),Leisure-Time Physical Activity Questionnaire for People with spinal Cord Injury(LTPAQ-sCI),anthropomorphic measures(waist,hip,and abdominal circumference),and dual-energy x-ray absorptiometry(DXA)to quantify regional and total body *** regression models suggested that engagement in LTPA accounted for 35.7%of the variance in physical health QOL,33.5%in psychological QOL,14.2%in social relationships QOL,and 38.2%in environmental *** measures accounted for 11.3%,3.1%,12.0%,and 6.7%of the variance in these QOL indices,respectively,and DXA indices accounted for 18.7%,17.5%,27.4%,and 21.9%.Within these models,the number of minutes of heavy LTPA per day uniquely predicted physical health QOL,the number of mild LTPA days per week uniquely predicted psychological QOL,and the amount of mild LTPA per day uniquely predicted environmental *** analyses also suggested that android and trunk fat,as well as supine waist and abdominal circumferences,were positively associated with social relationships *** individuals with sCI to engage in LTPA may robustly enhance multiple aspects of QOL while reducing the risk for cardiovascular and metabolic morbidities associated with ***,this may lead to a further understanding of how QOL may impact longitudinal intervention *** study protocol and procedures were reviewed and appro

关键词： anthropometrics body composition dual-energy-x-ray absorptiometry exercise physical activity quality of life spinal cord injury

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