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Discovery of the inhibitor of DNA binding 1 as a novel marker for radioresistance in pancreatic cancer using genome-wide rNA-seq

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Cancer Drug resistance 2022年第4期5卷 926-938页

作者： scar Zuniga Stephanie Byrum adam r.wolfe Department of radiation Oncology University of Arkansas for Medical SciencesLittle RockAR 72205USA Department of Biochemistry and Molecular Biology University of Arkansas for Medical SciencesLittle RockAR 72205USA

Purpose/Objective(s): Discovery of genetic drivers of radioresistance is critical for developing novel therapeuticstrategies to combine with radiotherapy of radioresistant PDAC. In this study, we used genome-wide rNA-seq toidentify genes upregulated in generated radioresistant PDAC cell lines and discovered the Inhibitor of DNA Binding1 (ID1) gene as a potential regulator of radioresistance in ***/Methods: radioresistant clones of the PDAC cell lines MIA PaCa-2 and PANC-1 were generated bydelivering daily ionizing irradiation (Ir) (2 Gy/day) in vitro over two weeks (total 20 Gy) followed by standardclonogenic assays following one week from the end of Ir. The generated rr and parental cell lines were submittedfor rNA-seq analysis to identify differentially expressed genes. The Limma r package was used to calculatedifferential expression among genes. Log2 fold change values were calculated for each sample compared to thecontrol. Genes with an absolute fold change > 1 were considered significant. rNA sequencing expression data fromthe Cancer Genome Atlas (TCGA) database was analyzed through the online databases GEPIA, cBioPortal, and theHuman Protein ***: Following exposure to two weeks of 2 Gy daily Ir in vitro, the two PDAC cell lines showed significantlygreater clonogenic cell survival than their parental cell lines, indicating enhanced rr in these cells. rNA-seqanalysis comparing parental and rr cell lines found upregulated seven genes (TNS4, ZDHHC8P1, APLNr, AQP3,SPP1, ID1, ID2) and seven genes downregulated (PTX3, ITGB2, EPS8L1, ALDH1L2, KCNT2, ArHGAP9, IFI16) in bothrr cell lines. Western blotting confirmed increased expression of the ID1 protein in the rr cell lines compared totheir parental cell lines. We found that ID1 mrNA was significantly higher in PDAC tumors compared to matchednormal and high ID1 expression correlated with significantly worse disease-free survival (DFS) in PDAC patients(Hr = 2.2, log rank P = 0.009). ID1 mrNA express

关键词： Pancreatic cancer radiation resistance ID1 rNA-seq

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural regeneration research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy

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Asian Journal of Urology 2024年第2期11卷 316-323页

作者： ryan A.Dornbier Chirag P.Doshi Shalin C.Desai Petar Bajic Michelle Van Kuiken Mark Khemmani Ahmer V.Farooq Larissa Bresler Thomas M.T.Turk Alan J.wolfe Kristin G.Baldea Loyola University Medical Center Department of UrologyMaywoodILUSA Loyola University Chicago Department of Microbiology and ImmunologyMaywoodILUSA

Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains *** evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis ***:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without *** sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal rNA gene ***:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS *** controls had uric acid stone *** EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to *** validate our EQUC results,we performed 16 S ribosomal rNA gene *** 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced *** were detected in both“infectious”and“non-infectious”stone ***:Bacteria are more common and more abundant in MetS stones than control *** findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

关键词： Nephrolithiasis Urolithiasis Metabolic syndrome Urinary microbiome Percutaneous nephrolithotomy

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不对称光纤非互易相移的全光纤磁-光隔离器

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光纤与电缆及其应用技术 1996年第2期 42-44,53页

作者： r.wolfe 鲍赛红美

据我们所知,本文第一个提出并观察到光纤中存在新的磁-光效应.以前人们在平面波导的TM模中发现过垂直磁场内存在非互易相移,最近我们在可传输类TM模的不对称纤芯的光纤(如纤芯一侧掺钬的特殊光纤)中也发现这种现象.提出了单偏振和偏振... 详细信息

据我们所知,本文第一个提出并观察到光纤中存在新的磁-光效应.以前人们在平面波导的TM模中发现过垂直磁场内存在非互易相移,最近我们在可传输类TM模的不对称纤芯的光纤(如纤芯一侧掺钬的特殊光纤)中也发现这种现象.提出了单偏振和偏振无关的新颖的全光纤隔离器,这种隔离器是基于在马赫-曾德干涉仪中采用这些特殊光纤.该效应还可用于环行器和萨格奈克效应光纤陀螺仪.

关键词：隔离器磁光效应光纤元件

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resilience, the 6th Vital Sign: Conceptualizing, Contextualizing, and Operationalizing All Six Vital Signs

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Health 2024年第7期16卷 657-673页

作者： rose E. Constantino Betty J. Braxter Chi Ching Vivian Hui Larissa C. Allen Lillian J. wolfe Katherine H. Endres Jezyl Cempron Cutamora Laurence L. Garcia Daisy r. Palompon Kathleen Thimsen Brayden N. Kameg Margarete L. Zalon Department of Health and Community Systems School of Nursing University of Pittsburgh Pittsburgh PA USA Undergraduate Affairs School of Nursing University of Pittsburgh Pittsburgh PA USA The Hong Kong Polytechnic University Hong Kong China School of Nursing Adjunct Faculty at the University of Pittsburgh Pittsburgh PA USA School of Nursing University of Pittsburgh Pittsburgh PA USA Department of Health Promotion and Development School of Nursing University of Pittsburgh Pittsburgh PA USA College of Nursing Cebu Normal University Cebu City Philippines School of Nursing University of Nevada Las Vegas USA Department of Health and Community Systems University of Pittsburgh PA USA Department of Nursing University of Scranton Scranton PA USA

There are five vital signs that healthcare providers assess: temperature, pulse, respiration, blood pressure, and pain. Normal levels for the five vital signs are published by the American Heart Association, and other specialty organizations, however, the sixth vital sign (resilience) which adopts the measure of immune resilience is suggested in this paper. resilience is the ability of the immune system to respond to attacks and defend effectively against infections and inflammatory stressors, and psychological resilience is the capacity to resist, adapt, recover, thrive, and grow from a challenge or a stressor. Individuals with better optimal immune resilience had better health outcomes than those with minimal immune resilience. The purpose of this paper is to conceptualize, contextualize, and operationalize all six vital signs. We suggest measuring resilience subjectively and objectively. Subjectively, use a 5-item guided interview revised from the Connor-Davidson resilience Scale (CDrC), a scale of 10 items. The revised CDrC scale is a 5-item scale. The scale is rated on a 5-point Likert scale from 0 (not true) to 4 (true all the time). The total score ranges from 0 to 20, with higher total scores indicating greater resilience. The scale demonstrated good construct validity and internal consistency (α = 0.85) during the development of the scale. The CD-rISC had a good Cronbach’s alpha level of 0.85. The revised CD-rISC can be completed in 2 - 4 minutes. To measure resilience objectively, we suggest using Immune resilience (Ir) levels, the level of resilience to preserve and/or rapidly restore immune resilience functions that promote disease resistance and control inflammation and other inflammatory stress. Ir levels are gauged with two peripheral blood metrics that quantify the balance between CD8 and CD4 T-cell levels and gene expression signatures tracking longevity-associated immunocompetence and mortality- or entropy-associated inflammation. Ir deregulation i

关键词： Conceptualization Contextualization Operationalization Body Temperature Pulse respiration Blood Pressure Pain resilience

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reforming the World Trade Organization: Practitioner Perspectives from China, the EU, and the US

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China & World Economy 2021年第4期29卷 1-34页

作者： Bernard Hoekman robert wolfe European University Institute and the Centre for Economic Policy research Italy Queen's University Canada

China,the European Union,and the United States are the world s largest *** have a big stake in a multilateral system of rules to manage the inevitable frictions among interdependent economies organized on different *** paper discusses elements of the WTO reform agenda through the lens of positions taken by these three WTO members,identifying the extent of alignment on key subjects,including transparency,dispute settlement,and plurilateral *** draw on findings of a recent research project on WTO reform and use responses to an expert survey to assess the prospects for actions that all three trade powers might *** premise is that reforming WTO is a necessary condition for the organization to be a more salient forum for the three large economies to address trade tensions,and that agreement among these three trade powers^in turn,is necessary to resolve the problems of the WTO.

关键词： China plurilateral cooperation trade agreements trade conflict WTO

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Effects of aqueous extracts of Irvingia gabonensis seeds on the hormonal parameters of male guinea pigs

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Asian Pacific Journal of Tropical Medicine 2010年第3期3卷 200-204页

作者： Obianime Acubowyedia wolfe Uche Fidelia Ijeoma Department of Pharmacology University of Port Harcourt Nigeria Department of Pharmacognosy and Phytotherapy University of Port Harcourt Nigeria

Objective:To investigate the effects of the aqueous extracts of Irvingia gabonensis(Irvingaceae) seeds on the hormonal parameters of male guinea ***:The hormonal effects of Irvingia gabonensis on hormonal parameters of male guinea pigs were investigated and compared with that of proviron using enzyme immuno assay method,which was done by reaction of antibody with serum testosterone and testosterone label,magnetic solid phase separation and colour development *** phytochemical screening of Irvingia gabonensis seeds was also carried out using standard ***:The aqueous extract of the Irvingia gabonensis seeds(50-400 mg/kg) caused a statistically significance increase(Prone in male guinea pigs,from (2.70±0.26) ng/mL to(3.10±0.42) ng/mL on the 7th day and to(3.30±0.48) ng/mL on the 28th day of the administration of the *** highest increase was(3.30±0.48) ng/mL,being obtained after 28 days of *** effects were similar to that of proviron,which was (2.80±0.28) ng/mL and(3.00±0.41) ng/mL on the 7th and 28th day of treatment respectively. The phytochemical screening of Irvingia gabonensis seeds revealed the presence of flavonoids. tannin,alkaloids,carbohydrate,volatile oils,terpenoids,saponins and cardiac glycosides. Conclusions:This study supports the claims on the use of the seeds of Irvingia gabonensis by traditional medicine practitioners as a fertility ***,further studies need to be done to isolate and characterize the active principle(s) responsible for this activity in this plant.

关键词： Irvingia gabonensis Hormonal parameters Male guinea pigs

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region Analysis Approach for Constructing Solutions of Nonlinear Operator Equations(Dedicated to Professor You Zhaoyong for his 60th brithday)

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工程数学学报 1991年第2期8卷 31-45页

作者： M.A.wolfe University of St.Andrews

Based on a variety of geometric observations for location of solutions, a general and unified region analysis framework for developing constructive solvability of nonlinear operator equations are proposed. Within this framework, the methods including interval, ball and ellipsoid methods can be studied in a unified way. The ball algorithm, as a typical example, is in particular analysed.

关键词： Geometric estimator ball algorithm region contraction algorithm computable test for existence of solution special types of nonlinear operators

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Does urbanization influence the diet of a large snake？

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Current Zoology 2018年第3期64卷 311-318页

作者： Ashleigh K. wolfe Philip W. BATEMAN Patricia A. FLEMING Department of Environment and Agriculture Curtin University Perth Bentley WA 6102 Australia School of Veterinary and Life Sciences Murdoch University Perth Murdoch WA 6150 Australia

Urbanization facilitates synanthropic species such as rodents, which benefit the diets of many predators in cities. We investigated how urbanization affects the feeding ecology of dugites Pseudonaja affi- nis, a common elapid snake in south-west Western Australia. We predicted that urban snakes： 1） more frequently contain prey and eat larger meals, 2） eat proportionally more non-native prey, 3） eat a lower diversity of prey species, and 4） are relatively heavier, than non-urban dugites. We analyzed the diet of 453 specimens obtained from the Western Australian Museum and opportunistic road-kill collections. Correcting for size, sex, season, and temporal biases, we tested whether location influenced diet for our 4 predictions. Body size was a strong predictor of diet （larger snakes had larger prey present, a greater number of prey items, and a greater diversity of prey）. We identified potential collection biases： urban dugites were relatively smaller （snout-vent length） than non-urban specimens, and females were relatively lighter than males. Accounting for these effects, urban snakes were less likely to have prey present in their stomachs and were relatively lighter than non-urban snakes. Other urban-adapted carnivores appear to benefit from urbanization through increased food supplementation, but we found the opposite of this： urban dugites were less likely to contain a meal, and their meals were smaller, indicating they did not make greater use of synanthropic species than was evident for non-urban snakes. In contrast to other carnivores, snakes do not appear to fit a consistent directional pattern for size differences between urban and non-urban populations.

关键词： adaptation dissection feeding ecology reptile.

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The future environmental and health impacts of coal

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Energy Geoscience 2021年第2期2卷 99-112页

作者： robert B.Finkelman Amy wolfe Michael S.Hendryx University of Texas at Dallas RichardsonTX75080USA University of Kentucky Kentucky Geological SurveyLexingtonKY40506USA Indiana University Bloomington BloomingtonIN47405USA

In the United States,coal consumption in the last 12 years has declined from 1,045,140 million short tons in 2007 to 539,420 million short tons in 2019,a decrease of almost 50%.During that period the number of electric power coal generators has declined from 1,470 to 738 accounting for 21%of *** even more dramatic decrease in coal use has occurred in Western *** significant reduction in coal use and the concomitant closure of coal mines and coal-burning power plants will result in substantially cleaner air,reductions in respiratory problems such as asthma,less heart disease,fewer hospitalizations,and other health benefits,as well as a reduction in occupational health problems such as silicosis and Coal Workers’Pneumoconiosis(Black Lung Disease).However,in China,India,russia and in several other Asian countries some projections indicate an increase in coal production and *** some situations,the coal is burned in old,highly polluting power *** these regions the health impacts of coal use could *** addition,millions of people in these regions still burn coal in their homes resulting in maximal exposure to the pollutants such as arsenic,selenium,fluorine,and mercury released from coal combustion.

关键词： Coal Combustion Pollutants Human health Environment

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