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Randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes

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Translational Neurodegeneration 2014年第1期3卷 89-97页

作者： justin B Miller Sarah j Banks Gabriel C Léger jeffrey L cummings Cleveland Clinic Lou Ruvo Center for Brain Health888 W.Bonneville AveLas VegasNevada 89106USA

progress has been made in understanding the genetics and molecular biology of frontotemporal dementia(FTD).Targets for intervention have been identified,therapies are being developed,and clinical trials are advancing.A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous *** neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction,language impairments and behavioral *** variant FTD is characterized by an initial presentation of changes in personality,behavior and/or emotion,which are often difficult to objectively capture using traditional neuropsychological *** two principal language variants of FTD are progressive Nonfluent Aphasia(pNFA)with predominant agrammatic/non-fluent impairments and Semantic Dementia(SD)with semantic impairments and visual *** of appropriate endpoints for clinical trials is critical to ensure that the measures are adequately sensitive to detect change,yet specific enough to isolate signal from noise,and acceptable to regulatory *** the anticipated potential for small effect sizes,measures must be able to identify small incremental changes over *** is also imperative that the measures provide adequate coverage of the constructs or behaviors of *** outcome measures should be suitable for repeat administration,yet relatively robust to practice effects to ensure that observed changes reflect true signal variance and not residual effects due to repeated measurement or poor *** facilitate widespread adoption as an endpoint,measures should be readily *** provide several examples of potential global,composite,and individual cognitive measures,as well as behavioral measures promising for FTD *** and application of appropriate trial outcomes is critically important to success in advancing new treatments for FTD patients.

关键词： Frontotemporal dementia primary endpoints Secondary endpoints Randomized controlled trial Methods

Reinterpretation of histology of proximal colon polyps called hyperplastic in 2001

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World journal of Gastroenterology 2009年第30期15卷 3767-3770页

作者： omer Khalid Sofyan Radaideh oscar W cummings Michael j o'Brien john R Goldblum Douglas K Rex Department of Medicine Indiana University Medical CenterIndianapolisIN 46202United States Department of pathology Indiana University Medical CenterIndianapolisIN 46202United States Department of Anatomic pathology Boston University Medical CenterBostonMA 02118United States Department of Anatomic pathology Cleveland ClinicClevelandOH 44195United States Division of Gastroenterology/Hepatology Indiana University Medical CenterIndianapolisIN 46202United States

AIM: To evaluate how proximal colon polyps interpreted as hyperplastic polyps in 2001 would be interpreted by expert pathologists in 2007. METHoDS: Forty consecutive proximal colon polyps ≥ 5 mm in size, removed in 2001, and originally interpreted as hyperplastic polyps by general pathologists at Indiana University, were reviewed in 2007 by 3 GI pathologists. RESULTS: The gastrointestinal (GI) pathologists interpreted 85%, 43% and 30% of the polyps as sessile serrated polyps (sessile serrated adenomas). The overall Kappa was 0.16. When diagnoses were compared in pairs, Kappa values were 0.38 and 0.25 (fair agreement) and 0.14 (slight agreement). CoNCLUSIoN: Many polyps interpreted as hyperplastic in 2001 were considered sessile serrated lesions by GI pathologists in 2007, but there is substantial inter-observer variation amongst GI pathologists.

关键词：增生性结肠组织学肉解读病理学印第安纳胃肠

Management information systems for the information age / 5th ed.

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Management information systems: ed.

2005年

作者： Stephen Haag Maeve cummings Donald j. McCubbrey.

Includes bibliographical references and index.

ISBN: (数字)0072935863

ISBN: (纸本)0073023884

Includes bibliographical references and index.

关键词： Management information systems.

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Testing for selection on color and pattern in a mimetic radiation

2002年

作者： Stephen Haag Maeve cummings Donald j. McCubbrey.

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Current Zoology 2012年第4期58卷 668-676页

作者： justin YEAger jason L. BRoWN Victor MoRALES Molly cummings Kyle SUMMERS Department of Biology East Carolina University Greenville NC 27858 Department of Ecology and Evolutionary Biology Tulane University New Orleans LA 70118 Department of Biology Duke University Durham NC 27708 Universidad de Ricardo palma Lima Peru Department of Integrative Biology University of Texas Austin Texas 78712

In this paper, we analyze variation in spectral reflectance and color pattern among populations to demonstrate dramatic divergence between four distinct morphs of the mimic poison frogRanitomeya imitator. We also analyze genetic divergence in d-loop mtDNA sequences between populations. We then use coalescent-based simulations to demonstrate that the high levels of observed phenotypic divergence are not consistent with levels of genetic divergence expected under neutral drift among populations, implying an important role for selection in driving divergence between these populations.

关键词：彩色图案辐射测试模仿颜色遗传分化光谱反射率成膜助剂种群

A Class of Quasi-exact Solutions of Rabi Hamiltonian

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Communications in Theoretical physics 2007年第7期48卷 53-56页

作者： j.p.Draayer Department of physics and Astronomy Louisiana State UniversityBaton RougeLA 70803-4001USA

A class of quasi-exact solutions of the Rabi Hamiltonian,which describes a two-level atom interacting witha single-mode radiation field via a dipole interaction without the rotating-wave approximation,are obtained by using awavefunction *** solutions for part of the spectrum are obtained when the atom-field coupling strength and thefield frequency satisfy certain *** an example,the lowest exact energy level and the corresponding atom-fieldentanglement at the quasi-exactly solvable point are calculated and compared to results from the jaynes-cummings andcounter-rotating cases of the Rabi Hamiltonian.

关键词： Rabi Hamiltonian quasi-exact solutions energy spectrum atom-field entanglement

plasma Edge Kinetic-MHD Modeling in Tokamaks Using Kepler Workflow for Code Coupling,Data Management and Visualization

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Communications in Computational physics 2008年第8期4卷 675-702页

作者： j.cummings A.pankin N.podhorszki G.park S.Ku R.Barreto S.Klasky C.S.Chang H.Strauss L.Sugiyama p.Snyder D.pearlstein B.Ludascher G.Bateman A.Kritz the CpES Team California Institute of Technology PasadenaCA 91125 Lehigh University BethlehemPA 18015 University of California at Davis DavisCA 95616 Courant Institute of Mathematical Sciences New York UniversityNY 10012 oak Ridge National Laboratory Oak RidgeTN 37830 Massachusetts Institute of Technology CambridgeMA 02139 General Atomics San DiegoCA 92186 Lawrence Livermore National Laboratory LivermoreCA 94550 SciDAC FSp Center for plasma Edge Simulation

A new predictive computer simulation tool targeting the development of the H-mode pedestal at the plasma edge in tokamaks and the triggering and dynamics of edge localizedmodes(ELMs)is presented in this *** tool brings together,in a coordinated and effective manner,several first-principles physics simulation codes,stability analysis packages,and data processing and visualization tools.A Kepler workflow is used in order to carry out an edge plasma simulation that loosely couples the kinetic code,XGC0,with an ideal MHD linear stability analysis code,ELITE,and an extended MHD initial value code such as M3D or ***0 includes the neoclassical ion-electron-neutral dynamics needed to simulate pedestal growth near the *** Kepler workflow processes the XGC0 simulation results into simple images that can be selected and displayed via the Dashboard,a monitoring tool implemented in AjAX allowing the scientist to track computational resources,examine running and archived jobs,and view key physics data,all within a standard Web *** XGC0 simulation is monitored for the conditions needed to trigger an ELM crash by periodically assessing the edge plasma pressure and current density profiles using the ELITE *** an ELM crash is triggered,the Kepler workflow launches the M3D code on a moderate-size opteron cluster to simulate the nonlinear ELM crash and to compute the relaxation of plasma profiles after the *** process is monitored through periodic outputs of plasma fluid quantities that are automatically visualized with AVS/Express and may be displayed on the ***,the Kepler workflow archives all data outputs and processed images using HpSS,as well as provenance information about the software and hardware used to create the *** complete process of preparing,executing and monitoring a coupled-code simulation of the edge pressure pedestal buildup and the ELM cycle using the Kepler scientific workflow system is described

关键词： plasma simulation magnetohydrodynamic and fluid equation gyrofluid and gyrokinetic simulations hybrid methods

Insights into A Novel Molecular Based Recognition of 6’-sulfo sLex

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Insights into A Novel Molecular Based Recognition of 6’-sul...

Regulation of Mucin-type o-Glycan Biosynthesis Through the Cosmc and T-synthase—Implications in Human Diseases

2019中国化学会第十五届全国计算（机）化学学术会议

作者：王晓聪 Melinda Hanes Richard cummings Robert j.Woods 华中农业大学 Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School Complex Carbohydrate Research Center University of Georgia

The binding of sialylated glycans to selectins and siglecs mediates inflammatory responses. While the selectins prefer to bind to sialyl Lewis X（sLex）, the siglec ligands show a wider diversity in glycan motifs. Many siglecs either do not tolerate the presence of fucose in sLex or prefer to have a 6-o-sulfate moiety in the epitope. In contrast, fucose is essential for selectin binding, while the presence of 6-o-sulfation abrogates binding. Elucidating the molecular mechanisms for their binding specificities is crucial for understanding their biological functions and specificities. Here we used molecular modeling to design a double mutant of E-selectin（E92 A＆E107 A） that when expressed showed binding preference for 6’-sulfo s Lex that were indistinguishable from that displayed by siglec-8. The result confirmed the theoretical prediction that the aversion of endogenous E-selectin for 6’-sulfo sLex arises from strong electrostatic repulsions between the conserved acidic residues in the binding site and the sulfate group at the galactose 6-o position. Structural analyses of the E-selectin/siglec-8 – 6’-sulfo sLex complexes indicated that the glycan ligand maintains the same conformation in each, but forms completely unique set of protein-glycan interactions in each system. Therefore, a new binding scheme for 6’-sulfo sLex was discovered in E-selectin, which is different from that in siglec-8. The results indicate that identical specificities may be displayed through completely different binding motifs, and indicate a role for computational studies in the design of high-specificity carbohydrate-binding proteins.

关键词： E-selectin 6’-sulfo sLex recognition mechanism siglec carbohydrate-binding protein design

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Regulation of Mucin-type O-Glycan Biosynthesis Through the C...