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Cancer Drug Resistance 2022年第3期5卷 560-576页

作者： Alex j.Eustace Min jie Lee Grace Colley jack Roban tim Downing Paul j.Buchanan DCU Cancer Research Dublin City UniversityDublin D9Ireland National Institute Cellular Biotechnology Dublin City UniversityDublin D9Ireland School of Biotechnology Dublin City UniversityDublin D9Ireland School of Nursing Psychotherapyand Community HealthDublin City UniversityDublin D9Ireland

Triple-negative breast cancer(TNBC)is characterized as an aggressive form of breast cancer(BC)associated with poor patient *** the majority of patients,there is a lack of approved targeted ***,chemotherapy remains a key treatment option for these patients,but significant issues around acquired resistance limit its ***,TNBC has an unmet need for new targeted personalized medicine ***(Ca^(2+))is a ubiquitous second messenger that is known to control a range of key cellular processes by mediating signalling transduction and gene *** in Ca^(2+)through altered calcium channel expression or activity are known to promote tumorigenesis and treatment resistance in a range of cancers including *** evidence shows that this is mediated by Ca^(2+)modulation,supporting the function of tumour suppressor genes(TSGs)and *** review provides insight into the underlying alterations in calcium signalling and how itplays a key role in promoting disease progression and therapy resistance in TNBC which harbours mutations intumour protein p53(TP53)and the PI3K/AKT pathway.

关键词： Triple-negative breast cancer TP53 PI3K/AKT pathway calcium

High-resolution peat records for Holocene monsoon history in the eastern Tibetan Plateau

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Science China Earth Sciences 2006年第6期49卷 615-621页

作者： Lars G. Franzen A.j.tim jull Department of Earth Sciences Goteborg University P.O. Box 460 SE-405 30 Goteborg Sweden NSF-AMS Facility University of Arizona Arizona AZ85721 USA

The variations of summer and winter monsoons during the Holocene in the eastern Ti-betan Plateau are shown to follow two basic models based on the reliable dating and high-resolution monsoon proxies determinations, one being a synchronous model in that both summer and winter monsoons are strengthening or decreasing, and the other to form a complementary pattern. These two different patterns evenly interact with each other on different time scales and together compose a complicated monsoon climatic model in this region. The climatic condition integrated by winter and summer monsoons is synchronous to the global pattern, which also shows the instability of the Holocene climate on centennial-millennial timescale. The abrupt monsoon event in about 6.2 ka cal. BP is much more severe than that in ca. 8.0 ka cal. BP, which indicates the regional character of the Asian monsoon and that the Asian monsoon climate is indeed a window on the global climate system.

关键词： eastern Tibetan Plateau, Holocene, winter and summer monsoons, asynchronous, peat, climate instability.

A discussion of‘optimal reinsurance designs based on risk measures:a review’

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Statistical Theory and Related Fields 2020年第1期4卷 14-15页

作者： tim j.Boonen Amsterdam School of Economics University of AmsterdamAmsterdamThe Netherlands

I congratulate the authors on their review article(Cai and Chi,2020).Their paper reviews the academic literature on optimal reinsurance problems with risk *** optimal reinsurance,an insurer seeks to share the exogenou... 详细信息

关键词： academic insurance optimal

SARS-CoV-2 inhibition and specific targeting of infected cells by VSV particles carrying the ACE2 receptor

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2463-2466页

作者： Fabian Zech Stefanie Weber Hanna Dietenberger Linyun Zhang Sabrina Noettger Meta Volcic tim Bergner Clarissa Read Konstantin M.j.Sparrer Thomas F.E.Barth Frank Kirchhoff Institute of Molecular Virology Ulm University Medical CenterUlmGermany Institute of Pathology Ulm UniversityUlmGermany Central Facility for Electron Microscopy Ulm UniversityUlmGermany

Dear Editor Effective vaccines and some antiviral agents against SARS-CoV-2,the causative agent of coronavirus disease 2019(COVID-19),have been ***,additional therapeutics are needed since emerging SARS-CoV-2 variants evade immunity induced by vaccination or previous infection and are resistant to therapeutic antibodies and fusion inhibitors.^(1)In addition,many patients experience prolonged post-acute sequelae of SARS-CoV-2.

关键词： ACE2 immunity acute

Impact of smoking cannabidiol (CBD)-rich marijuana on driving ability

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Forensic Sciences Research 2021年第4期6卷 195-207页

作者： tim j.Gelmi Wolfgang Weinmann Matthias Pfäffli Department of Forensic Toxicology and chemistry institute of Forensic MedicineUniversity of BernBernswitzerland Graduate school for cellular and Biomedical sciences(GcB) University of BernBernswitzerland Department of Traffic sciences institute of Forensic MedicineUniversity of BernBernswitzerland

To investigate effects of smoking cannabidiol(CBD)-rich marijuana on driving ability and determine free CBD andΔ9-tetrahydrocannabinol(THC)concentrations in capillary blood samples,a randomised,double-blind,placebo-controlled,two-way crossover pilot study was conducted with 33 *** smoked a joint containing 500 mg of tobacco and either 500 mg of CBD-rich marijuana(16.6%total CBD;0.9%total THC)or 500 mg of a placebo substance,then performed three different dimensions of the Vienna Test System TRAFFIC examining reaction time,behaviour under stress,and concentration *** further assessment of participants’fitness to drive,three tests of balance and coordination were evaluated and vital signs(blood pressure and pulse)were *** blood spot samples of capillary blood were taken after smoking and after completion of the tests to determine the cannabinoid concentrations(CBD,THC and THC-metabolites).The results revealed no significant differences between the effects of smoking CBD-rich marijuana and placebo on reaction time,motor time,behaviour under stress,or concentration *** free CBD and THC concentrations in capillary blood were detected shortly after smoking,ranging between 2.6-440.0 ng/mL and 6.7-102.0 ng/mL,*** 45 min,capillary blood concentrations had already declined and were in the range of 1.9-135.0 ng/mL(free CBD)and 0.9-38.0 ng/mL(free THC).Although the observed levels of free THC concentrations have been reported to cause symptoms of impairment in previous studies in which THC-rich marijuana was smoked,no signs of impairment were found in the current *** finding suggests that higher CBD concentrations cause a negative allosteric effect in the endocannabinoid system,preventing the formation of such ***,it is recommended that consumers refrain from driving for several hours after smoking CBD-rich marijuana,as legal THC concentration limits may be exceeded.

关键词： Forensic sciences forensic toxicology cannabidiol driving while impaired road safety driving assessment

Hemolysis results in impaired intestinal microcirculation and intestinal epithelial cell injury

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World journal of Gastroenterology 2011年第2期17卷 213-218页

作者： Sebastiaan j Hanssen tim Lubbers Caroline M Hodin Frits W Prinzen Wim A Buurman Michael j jacobs Department of Surgery Maastricht University Medical Center Cardiovascular Research Institute Maastricht Maastricht University Medical Center European Vascular Center Aachen-Maastricht Department of Vascular SurgeryUniversity Hospital Aachen Nutrition and Toxicology Research Institute Maastricht Maastricht University Medical Center Department of Physiology Maastricht University Medical Center

AIM:To study the effect of circulating cell-free oxy-hemoglobin(FHb) on intestinal microcirculation and intestinal epithelial injury in a rat model. METHODS:To induce elevated intravascular circulating FHb,male Sprague-Dawley rats received water or FHb *** changes in jejunum,ileum and colon were evaluated using fluorescent *** injury was quantified as plasmatic release of ileal lipid binding protein(iLBP) and verified by histological analysis of the ileum. RESULTS:Water and FHb infusions resulted,when compared with saline infusion,in reduced intestinal microcirculation(after 30 min Pjejunum and colon) .Circulating FHb levels correlated significantly with release of iLBP(Spearman r=0.72,P=0.0011) .Epithelial cell injury of the villi was histologically observed after water and FHb infusions. CONCLUSION:This study shows that circulating FHb leads to a reduction in intestinal microcirculatory blood flow with marked injury to intestinal epithelial cells. These data support the hypothesis that circulating FHb contributes to the development of intestinal injury.

关键词：肠上皮细胞肠道损伤细胞损伤环和组织学观察生理盐水溶血卫生局

Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling

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Cellular & Molecular Immunology 2023年第1期20卷 26-37页

作者： Kelly A.Dingess Max Hoek Danique M.Hvan Rijswijk Sem Tamara Maurits Aden Boer tim Veth Mirjam j.A.Damen Arjan Barendregt Michelle Romijn Hannah G.juncker Britt jvan Keulen Gestur Vidarsson johannes Bvan Goudoever Albert Bondt Albert j.R.Heck Biomolecular Mass Spectrometry and Proteomics Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical SciencesUniversity of UtrechtPadualaan 8Utrecht 3584 CHThe Netherlands Netherlands Proteomics Center Padualaan 8Utrecht 3584 CHThe Netherlands Amsterdam UMC Vrije UniversiteitUniversity of AmsterdamEmma Children’s HospitalAmsterdam Reproduction&Development Research InstituteDepartment of PediatricsAmsterdamthe Netherlands Department of Experimental Immunohematology Sanquin Research and Landsteiner LaboratoryAmsterdam UMCUniversity of AmsterdamAmsterdamNetherlands

The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (j-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a j-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and j-chain coupled dimeric IgA1. The serum dimeric j-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins;one of these produces dimeric j-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum.

关键词： Antigen binding fragment Immunoglobulin A1 Clonal repertoires human milk Serum

Characterizing Human Collective Behaviors During COVID-19 — Hong Kong SAR, China, 2020

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China CDC weekly 2023年第4期5卷 71-75,I0001-I0003页

作者： Zhanwei Du Xiao Zhang Lin Wang Sidan Yao Yuan Bai Qi Tan Xiaoke Xu Sen Pei jingyi Xiao tim K.Tsang Qiuyan Liao Eric H.YLau Peng Wu Chao Gao Benjamin j.Cowling WHO Collaborating Centre for Infectious Disease Epidemiology and Control School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Laboratory of Data Discovery for Health Hong Kong Science and Technology ParkNew TerritoriesHong Kong Special Administrative RegionChina Department of Genetics University of CambridgeCambridgeCB23EHUK Institute of High Performance Computing(IHPC) Agency for ScienceTechnology and Research(A*STAR)Singapore College of Information and Communication Engineering Dalian Minzu UniversityDalian CityLiaoning ProvinceChina Department of Environmental Health Sciences Mailman School of Public HealthColumbia UniversityNew York CityNYUSA School of Artificial Intelligence Opticsand Electronics(iOpen)Northwestern Polytechnical UniversityXi’an CityShaanxi ProvinceChina

Summary What is already known about this topic?People are likely to engage in collective behaviors online during extreme events,such as the coronavirus disease 2019(COVID-19)crisis,to express awareness,take action,and... 详细信息

关键词： collective likely extreme

An investigation into intermittent electrification strategies and an analysis of resulting CO_(2) emissions using a high-fidelity train model

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Railway Engineering Science 2021年第3期29卷 314-326页

作者： Bilal M.Abdurahman tim Harrison Christopher P.Ward William j.B.Midgley Wolfson School of Mechanical Electrical and Manufacturing EngineeringLoughborough UniversityLoughborough LE113TUUK

A near-term strategy to reduce emissions from rail vehicles,as a path to full electrification for maximal decarbonisation,is to partially electrify a route,with the remainder of the route requiring an additional self-powered traction *** rail vehicles are usually powered by a diesel engine when not operating on electrified track and are referred to as bi-mode *** paper analyses the benefits of discontinuous electrification compared to continuous electrification using the CO_(2)estimates from a validated high-fidelity bi-mode(diesel-electric)rail vehicle *** analysis shows that 50%discontinuous electrification provides a maximum of 54%reduction in operational CO_(2)emissions when compared to the same length of continuously electrified *** highest emissions savings occurred when leaving train stations where vehicles must accelerate quickly to line *** results were used to develop a linear regression model for fast estimation of CO_(2)emissions from diesel running and electrification *** model was able to estimate the CO_(2)emissions from a route to within 10%of that given by the high-fidelity ***,additional considerations such as cost and the embodied CO_(2)in electrification infrastructure were analysed to provide a comparison between continuous and discontinuous *** electrification can cost up to 56%less per reduction in lifetime emissions than continuous electrification and can save up to 2.3 times more lifetime CO_(2)per distance electrified.

关键词： Railway electrification CO_(2)reduction Discontinuous electrification Bi-mode rail vehicle

Multi-scale drivers of soil resistance predict vulnerability of seasonally wet meadows to trampling by pack stock animals in the Sierra Nevada,USA

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Ecological Processes 2020年第1期9卷 364-377页

作者： joy S.Baccei Mitchel P.McClaran tim j.Kuhn Stephen C.Hart Environmental Systems Graduate Group University of CaliforniaMercedCA 95343USA UC Merced Vernal Pools and Grassland Reserve UC Merced Natural Reserve SystemMercedCA 95343USA School of Natural Resources and the Environment University of ArizonaTucsonAZ 85721USA Resources Management and Science Yosemite National ParkEl PortalCA 95318USA Department of Life&Environmental Sciences and Sierra Nevada Research Institute University of CaliforniaMercedCA 95343USA.

Background:Meadow ecosystems have important ecological functions and support socioeconomic services,yet are subject to multiple stressors that can lead to rapid *** the Sierra Nevada of the western USA,recreational pack stock(horses and mules)use in seasonally wet mountain meadows may lead to soil trampling and meadow degradation,especially when soil water content is high and vegetation is ***:In order to improve the ability to predict meadow vulnerability to soil disturbance from pack stock use,we measured soil resistance(SR),which is an index of vulnerability to trampling disturbance,at two spatial scales using a stratified-random sampling *** then compared SR to several soil and vegetation explanatory variables that were also measured at the two spatial scales:plant community type(local scale)and topographic gradient class(meadow scale).Results:We found that local-scale differences in drivers of SR were contingent on the meadow scale,which is important because multiple spatial scale evaluation of ecological metrics provides a broader understanding of the potential controls on ecological processes than assessments conducted at a single spatial *** also found two contrasting explanatory models for drivers of SR at the local scale:(1)soil gravimetric water content effects on soil disaggregation and(2)soil bulk density and root mass influence on soil *** resistance was insufficient to sustain pack stock use without incurring soil deformation in wet plant communities,even when plant cover was maximal during a major ***:Our study provides new information on seasonally wet meadow vulnerability to trampling by pack stock animals using multi-scale drivers of SR,including the contrasting roles of soil disaggregation,friction,and *** work aims to inform meadow management efforts in the Sierra Nevada and herbaceous ecosystems in similar regions that are subject to seasonal soil saturation and livestock u

关键词： Hydrogeomorphic classification Hydrologic regime Pack stock Plant communities Soil properties Soil strength