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Cryo-EM structure of the plant 26S proteasome

Plant Communications 2022年第3期3卷 116-126页

作者： Susanne Kandolf Irina grishkovskaya Katarina Belacic Derek L.Bolhuis Sascha Amann Brent Foster Richard Imre Karl Mechtler Alexander Schleiffer Hemant D.Tagare Ellen D.Zhong Anton Meinhart nicholas g.brown David Haselbach Research Institute of Molecular Pathology(IMP) Vienna BioCenter(VBC)Campus-Vienna-BioCenter 11030 ViennaAustria Department of Radiology and Biomedical Imaging Yale UniversityNew HavenCT 06510USA Department of Pharmacology and Lineberger Comprehensive Cancer Center University of North Carolina School of MedicineChapel HillNC 27599USA Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of TechnologyCambridgeMA 02139USA Vienna BioCenter PhD Program Doctoral School of the University at Vienna and Medical University of ViennaVienna BioCenter(VBC)ViennaAustria Institute of Physical Chemistry University of FreiburgAlbertstraße 21Freiburg 79104Germany CIBSS Centre for Integrative Biological Signalling Studies University of FreiburgFreiburgGermany

Targeted proteolysis is a hallmark of *** is especially important in long-lived cells that can be found in higher eukaryotes,like *** task is mainly fulfilled by the ubiquitin–proteasome ***,proteolysis by the 26S proteasome is vital to development,immunity,and cell *** the yeast and animal proteasomes are well characterized,there is only limited information on the plant *** determined the first plant 26S proteasome structure from Spinacia oleracea by single-particle electron cryogenic microscopy at an overall resolution of 3.3 A°.We found an almost identical overall architecture of the spinach proteasome compared with the known structures from mammals and ***,we noticed a structural difference in the proteolytic active b1 ***,we uncovered an unseen compression state by characterizing the proteasome’s conformational *** suspect that this new conformation of the 20S core protease,in correlation with a partial opening of the unoccupied gate,may contribute to peptide release after *** data provide a structural basis for the plant proteasome,which is crucial for further studies.

关键词： 26S proteasome spinach UPS cryo-EM conformational landscape

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Digital re-analysis of lost architecture and the particular case of Lutyens＇ Liverpool Metropolitan Cathedral

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Frontiers of Architectural Research 2016年第2期5卷 265-275页

作者： nicholas Webb Andre brown School of Architecture University of Liverpool Liverpool L69 7ZN United Kingdom

Research and critique of unbuilt or destroyed works of architecture is traditionally carried out through the examination of surviving information such as drawings, models, photographs, biographies and monographs. The case study presented here demonstrates that this approach cannot always give a fuU-picture of the architect or designer＇s intentions, and may miss inconsistencies in the design and links to other precedents or antecedents in such schemes. Here, we employ strategic contemporary digital representation techniques to re-present and re-analyse the evidence available for a particular architectural project. We describe a systematic methodology, which shows that these techniques can challenge or enhance current understanding. The focus therefore is on the digital re-analysis process that has been devised. Sir Edwin Lutyens＇ unbuilt Liverpool Metropolitan Cathedral design, that would have delivered one of the largest cathedrals in the world, is used as a case study. The findings reveal new information about the cathedral by following structured lines of enquiry generated from the study of primary and secondary source data, as well as serendipitous results that occur as a potential by-product of the methodological process.

关键词： Unbuitt architecture Digitalcritique Forensic anatysis Digitat modetting

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PROJECT MANAgEMENT:RECENT DEVELOPMENTS AND RESEARCH OPPORTUNITIES

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Journal of Systems Science and Systems Engineering 2012年第2期21卷 129-143页

作者： nicholas g.HALL Department of Management Sciences Fisher College of Business The Ohio State UniversityUSA

This paper studies the business process known as project management. This process has exhibited a remarkable growth in business interest over the last 15 years, as demonstrated by a 1000% increase in membership in the Project Management Institute since 1996. This growth is largely attributable to the emergence of many new diverse business applications that can be successfully managed as projects. The new applications for project management include IT implementations, research and development, new product and service development, corporate change management, and software development. The characteristics of modem projects are typically very different from those of traditional projects such as construction and engineering, which necessitates the development of new project management techniques. We discuss these recent practical developments. The history of project management methodology is reviewed, from CPM and PERT to the influential modem directions of critical chain project management and agile methods. We identify one important application area for future methodological change as new product and service development. A list of specific research topics within project management is discussed. The conclusions suggest the existence of significant research opportunities within project management.

关键词： Project management overview recent practical developments opportunities for research

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Plasticity in the antipredator behavior of the orange-footed sea cucumber under shifting hydrodynamic forces

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Current Zoology 2019年第6期65卷 685-695页

作者： nicholas A.W.brown David R.WILSON Patrick gAgNON Department of Ocean Sciences Memorial University of NewfoundlandSt.John'sNewfoundlandA1C 5S7Canada Department of Psychology Memorial University of NewfoundlandSt.John'sNewfoundlandA1B 3X9Canada

Marine invertebrates that move too slowly to evade unfavorable environmental change may instead exhibit phenotypic plasticity,allowing them to adjust to varying *** orange-footed sea cucumber Cucumaria frondosa is a slow-moving suspension feeder that is preyed on by the purple sunstar Solaster *** sea cucumber's antipredator behavior involves changing shape and detaching from the substratum,which might increase its probability of being displaced by water motion into an unsuitable *** hypothesized that sea cucumbers'antipredator responses would be diminished under stronger hydrodynamic forces,and that behavioral strategies would be flexible so that individuals could adjust to frequent changes in water *** a natural orange-footed sea cucumber habitat,individuals lived along a pronounced hydrodynamic gradient,allowing us to measure antipredator behavior under different water flow *** placed purple sunstars in physical contact with sea cucumbers living at various points along the gradient to elicit antipredator *** then repeated this procedure in a laboratory mesocosm that generated weak and strong hydrodynamic forces similar to those observed at the field *** in the mesocosm experiment were tested in both wave conditions to determine if their antipredator behavior would change in response to sudden environmental change,as would be experienced under deteriorating sea *** responses did not covary with hydrodynamic forces in the ***,antipredator responses in the mesocosm experiment increased when individuals were transplanted from strong to weak forces and decreased when transplanted from weak to strong ***,our results indicate environmentally induced plasticity in the antipredator behavior of the orange-footed sea cucumber.

关键词： behavioral plasticity benthic invertebrate predator-prey interaction reciprocal transplant experiment Solaster endeca.wave environment

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Purines:From Diagnostic Biomarkers to Therapeutic Agents in Brain Injury

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Neuroscience Bulletin 2020年第11期36卷 1315-1326页

作者： Bruno g.Frenguelli nicholas Dale School of Life Sciences The University WarwickCoventry CV47ALUK

The purines constitute a family of inter-related compounds that serve a broad range of important intracellular and extracellular biological *** particular,adenosine triphosphate(ATP)and its metabolite and precursor,adenosine,regulate a wide variety of cellular and systems-level physiological processes extending from ATP acting as the cellular energy currency,to the adenosine arising from the depletion of cellular ATP and responding to reduce energy demand and hence to preserve ATP during times of metabolic *** inter-relationship provides opportunities for both the diagnosis of energy depletion during conditions such as stroke,and the replenishment of ATP after such *** this review we address these opportunities and the broad potential of purines as diagnostics and restorative agents.

关键词： Purines Adenosine ATP Biomarker Stroke Cerebral ischemia Traumatic brain injury Adenine D-ribose

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Testing for temperature acclimation of plant carbon exchange:a comment on‘global patterns of the responses of leaf-level photosynthesis and respiration in terrestrial plants to experimental warming’by liang et al.

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Journal of Plant Ecology 2015年第3期8卷 333-334页

作者： nicholas g.Smith Department of Biological Sciences Purdue University915 West State StreetWest LafayetteIN 47907USA

In a recent issue of Journal of Plant Ecology,Liang et al.(2013)use meta-analytical techniques to analyze the leaf carbon exchanges responses to experimental warming and,in part,observe that leaf dark respiration,but not photosynthesis,acclimates to the warming *** authors should be commended for putting together and analyzing such a large data *** of the results provide fine syntheses for understanding leaf carbon exchange responses to ***,the acclimation analyses are,in my opinion,flawed and are not appropriate for supporting their results.

关键词： exchange carbon supporting

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Cooperation and Contract Design in Project Management with Outsourcing

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Journal of Systems Science and Systems Engineering 2023年第1期32卷 34-70页

作者： Xiaoqiang Cai nicholas g.Hall Siyi Wang Feng Zhang School of Data Science The Chinese University of Hong KongShenzhen518172China Shenzhen Research Institute of Big Data Shenzhen518172China Department of Operations&Business Analytics Fisher College of BusinessOhio State UniversityColumbusOhioUSA School of Science and Engineering The Chinese University of Hong KongShenzhen518172China Suning Bank Nanjing210019China

We study a project management problem where the prime contractor needs to outsource tasks to subcontractors with the required *** execution of the project requires proper coordination among the subcontractors,as well as contract design by the prime contractor to incentivize the *** modeling the subcontractors’coordination problem as a cooperative game,we develop a profit sharing scheme to facilitate the subcontractors’*** consider two contract designs for the prime contractor:a uniform contract across all subcontractors,and a nonuniform one that customizes incentives for each *** propose efficient algorithms to solve the implicit optimization problems for optimal contract *** experiments show that the pooling effect of subcontractors’cooperation mitigates the negative impact of poor estimates about the crashing cost and resource *** observe three unexpected results through the randomized computation experiments:(i)the subcontractors’profits may decrease if they provide false information;(ii)it is safer for the prime contractor to overestimate subcontractors’crashing costs than underestimate them;and(iii)uniform contracts deliver more project profit for the subcontractors in the coalitions.

关键词： Project management with outsourcing subcontracting cooperative game contract design

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Junctional epithelium and hemidesmosomes:Tape and rivets for solving the“percutaneous device dilemma”in dental and other permanent implants

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Bioactive Materials 2022年第12期7卷 178-198页

作者： nicholas g.Fischer Conrado Aparicio MDRCBB-Minnesota Dental Research Center for Biomaterials and Biomechanics University of Minnesota16-212 Moos Tower515 Delaware St.SEMinneapolisMN55455USA Division of Basic Research Faculty of OdontologyUIC Barcelona-Universitat Internacional de CatalunyaC/.Josep Trueta s/n08195Sant Cugat del VallesBarcelonaSpain Institute for Bioengineering of Catalonia(IBEC) The Barcelona Institute of Science and Technology(BIST)C/.Baldiri Reixac 10-1208028BarcelonaSpain

The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the “device”/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth’s imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE). The hallmark feature of JE is formation of hemidesmosomes, cell/matrix adhesive structures that attach surrounding oral gingiva to the tooth’s enamel through a basement membrane. Here, the authors survey the multifaceted functions of the JE, emphasizing the role of the matrix, with a particular focus on hemidesmosomes and their five main components. The authors highlight the known (and unknown) effects dental implant - as a model percutaneous device - placement has on JE regeneration and synthesize this information for application to other percutaneous devices. The authors conclude with a summary of bioengineering strategies aimed at solving the percutaneous device dilemma and invigorating greater collaboration between clinicians, bioengineers, and matrix biologists.

关键词： Percutaneous device Percutaneous implant Hemidesmosome Junctional epithelium Bioinspired surfaces

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Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales

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World Journal of gastroenterology 2016年第37期22卷 8414-8434页

作者： Muhammed RS Siddiqui Jemma Bhoday nicholas J Battersby Manish Chand nicholas P West Al-Mutaz Abulafi Paris P Tekkis gina brown Department of Colorectal Surgery Croydon University Hospital Croydon London CR7 7YE United Kingdom Department of Radiology Royal Marsden Hospital Sutton SM2 5PT United Kingdom Pathology and Tumour Biology Leeds Institute of Cancer and Pathology St. James's University Hospital Leeds LS9 7TF United Kingdom Department of Surgery Royal Marsden Hospital Fulham Rd London SM2 5PT United Kingdom

AIM To define good and poor regression using pathology and magnetic resonance imaging(MRI) regression scales after neo-adjuvant chemotherapy for rectal *** A systematic review was performed on all studies up to December 2015, without language restriction, t h a t w e r e i d e n t i f i e d f r o m M E D L I N E, C o c h r a n e Controlled Trials Register(1960-2015), and EMBASE(1991-2015). Searches were performed of article bibliographies and conference abstracts. MeS H and text words used included "tumour regression", "mr TRg", "poor response" and "colorectal cancers". Clinical studies using either MRI or histopathological tumour regression grade(TRg) scales to define good and poor responders were included in relation to outcomes [local recurrence(LR), distant recurrence(DR), disease-free survival(DFS), and overall survival(OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome *** Quantitative data(prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data(LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemoradiotherapy(CRT) was 37.7%(95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale(mrT Rg). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. good pathological response 5-year outcomes were LR

关键词： Tumour regression mrT Rg Poor response Neo-adjuvant therapy Rectal cancer

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Putting PLX5622 into perspective:microglia in central nervous system viral infection

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Neural Regeneration Research 2023年第6期18卷 1269-1270页

作者： Alanna g.Spiteri nicholas J.C.King Viral Immunopathology Laboratory InfectionImmunity and Inflammation Research ThemeSchool of Medical SciencesFaculty of Medicine and HealthThe University of SydneySydneyNSWAustralia Sydney Cytometry The University of Sydney and Centenary InstituteSydneyNSWAustralia Ramaciotti Facility for Human Systems Biology The University of Sydney and Centenary InstituteSydneyNSWAustralia Charles Perkins Centre The University of SydneyAustralia The University of Sydney Institute for Infectious Diseases The University of SydneySydneyNSWAustralia The University of Sydney Nano Institute the University of SydneySydneyNSWAustralia

Elucidating the exact contribution of microglia to central nervous system(CNS)pathology has historically been extremely *** resident parenchymal myeloid cells are considered to have critical roles as frontline responders during pathogen invasion and CNS ***,understanding the precise temporal kinetics of microglial function is central to the evolution of novel therapeutics for disease intervention and/or resolution(Spiteri et al.,2022a).The development of PLX5622,a colony-stimulating factor 1 receptor(CSF-1R)inhibitor typically formulated into a rodent chow for simple oral administration has facilitated exploration of microglial functions in disease(Spangenberg et al.,2019).

关键词： invasion system precise

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