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Harnessing naturally occurring mutations for T-cell therapy:a potential new avenue to enhance treatment efficacy

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signal Transduction and Targeted Therapy 2024年第5期9卷 1799-1801页

作者： michael Hiltensperger j.rgen Ruland Kilian schober Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und HygieneFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany Institute of Clinical Chemistry and Pathobiochemistry School of MedicineTechnical University of MunichMunichGermany TranslaTUM Center for Translational Cancer ResearchTechnical University of MunichMunichGermany German Cancer Consortium(DKTK) HeidelbergGermany German Center for Infection Research(DZIF) partner site MunichMunichGermany FAU Profile Center Immunomedicine Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Garcia et al.use a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rej.ction and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.

关键词： al. cancer potential

Evaluating Methods of Visual Assistance for Workers to Improve Quality and Usability in Individualized Kitchen Cabinet Assembly

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j.urnal of Computer and Communications 2024年第2期12卷 156-172页

作者： Albert Eff michael s. j. Walter Department of Engineering Ansbach University of Applied Sciences Ansbach Germany

In times of digitalisation, visual assistance systems in assembly are increasingly important. The design of these assembly systems needs to be highly complex to meet the requirements. Due to the increasing number of variants in production processes, as well as shorter innovation and product life cycles, assistance systems should improve quality and reduce complexity of assembly processes. However, many large kitchen manufacturers still assemble kitchen cabinets manually, due to the high variety of components, such as rails and fittings. This paper focuses on the analysis and evaluation of virtual assistance systems to improve quality and usability in individualised kitchen cabinet assembly processes at a large German manufacturer. A solution is identified and detailed.

关键词： Digitalisation Assembly Process Visual Assistance Usability Human-Centred Assembly Design

Universal Hyperthermal Model for Mass Extinctions

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j.urnal of Earth science 2024年第2期35卷 704-707页

作者： michael j.Benton Paleobiology Research Group School of Earth SciencesUniversity of BristolLife Sciences BuildingTyndall AvenueBristolBS81TQUK

INTRODUCTION Earth scientists have long sought universal features of past extinction crises.It can be argued that each past extinction event was a singularity,caused by combinations of circumstances that are unique in each case,and therefore that the search for common causes is futile.However,a key feature of the uniformitarian approach to geology is that past processes are the same as modern-day processes and,with that in mind,earth scientists are keen to use their knowledge to contribute some understanding to the study of the present and future climate crisis.

关键词： extinction singularity Extinction

Editorial for the special Issue on Emerging Technology and Advanced Application of Nondestructive Detection for Power Equipment

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Chinese j.urnal of Electrical Engineering 2024年第1期10卷 1-2页

作者： Li j. Mei H. Li s. Tianj.n University China Tsinghua shenzhen International Graduate school China Lanzhou j.aotong University China

The rapid development of clean and renewable energy technologies represented by wind and solar energy,as well as the continuous growth of load demand,have put forward higher requirements for the safe operation of the power equipment.The performance of power equipment based on traditional dielectric materials is often limited by various defects generated during molding,transportation,assembly,and operation,which cannot meet the reliability requirements of power systems in the new situation.Nondestructive detection is an essential technical method in industrial development,which can detect and evaluate the defect and damage status of in-service equipment,key components,and materials without damaging the obj.ct.

关键词： service Application operation

Dietary fibre effects and the interplay with exogenous carbohydrases in poultry nutrition

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Animal Nutrition 2024年第1期16卷 231-240页

作者： michael R.Bedford Birger svihus Aaron j.Cowieson AB Vista Feed Ingredients Ltd Norwegian University of Life sciences DsM Nutritional Products

A comprehensive understanding of the role of dietary fibre in non-ruminant animal production is elusive. Equivocal and conflated definitions of fibre coupled with significant analytical complexity,interact with poorly defined host and microbiome relationships. Dietary fibre is known to influence gut development, feed intake and passage rate, nutrient absorption, microbiome taxonomy and function, gut p H, endogenous nutrient loss, environmental sustainability, animal welfare and more. Whilst significant gaps persist in our understanding of fibre in non-ruminant animal production, there is substantial interest in optimizing the fibre fraction of feed to induce high value phenotypes such as improved welfare,live performance and to reduce the environmental footprint of animal production systems. In order to achieve these aspirational goals, it is important to tackle dietary fibre with the same level of scrutiny as is currently done for other critical nutrient classes such as protein, minerals and vitamins. The chemical,mechanical and nutritional role of fibre must be explored at the level of monomeric sugars, oligosaccharides and polysaccharides of varying molecular weight and decoration, and this must be in parallel to standardisation of analytical tools and definitions for speciation. To further complicate subj.ct, exogenous carbohydrases recognise dietary fibre as a focal substrate and have varying capacity to generate lower molecular weight carbohydrates that interact differentially with the host and the enteric microbiome. This short review article will explore the interactive space between dietary fibre and exogenous carbohydrases and will include their nutritional and health effects with emphasis on functional development of the gut, microbiome modulation and host metabolism.

关键词： Fibre Carbohydrase Nutrition Microbiome Gastro-intestinal development Feed

Use of donepezil for neurocognitive recovery after brain inj.ry in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson j.michael Taylor University of Cincinnati College of Medicine CincinnatiOHUSA Department of Pediatrics University of CincinnatiCincinnatiOHUSA Department of Neurology and Rehabilitation Medicine University of CincinnatiCincinnatiOHUSA Division of Pediatric Rehabilitation Medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA Division of Neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain inj.ry in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain inj.ry,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a dj.vant treatment fo r neurocognitive decline in pediatric patients with traumatic brain inj.ry.Investigators queried PubMed to identify literature published from database inception thro ugh j.ne 2023 desc ribing the use of donepezil in young adult traumatic brain inj.ry and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the proj.ct.In adult traumatic brain inj.ry,we review results from 14 papers detailing 227 subj.cts where evidence suggests donepezil is well tole rated and shows both obj.ctive and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain inj.ry,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain inj.ry and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain inj.ry is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain inj.ry

Application of a simplified ADM1 for full-scale anaerobic co-digestion of cattle slurry and grass silage:assessment of input variability

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Frontiers of Environmental science & Engineering 2024年第4期18卷 125-139页

作者： sofia Tisocco sören Weinrich Gary Lyons michael Wills Xinmin Zhan Paul Crosson Civil Engineering College of Science and EngineeringUniversity of GalwayGalwayH91 TK33Ireland Teagasc Animal and Bioscience Research Department Animal and Grassland Research and Innovation CentreDunsanyC15 PW93Ireland Biochemical Conversion Department Deutsches Biomasseforschungszentrum gemeinnützige GmbHLeipzig 04347Germany Faculty of Energy·Building services·Environmental Engineering Münster University of Applied SciencesSteinfurt 48565Germany Agri-Food and Biosciences Institute HillsboroughBT266DRUK Ryan Institute University of GalwayGalwayH91 TK33Ireland MaREI Research Centre for Energy Climate and MarineRyan InstituteUniversity of GalwayGalwayH91 TK33Ireland

Mathematical modeling of anaerobic digestion is a powerful tool to predict gas yields and optimize the process.The Anaerobic Digestion Model No.1(ADM1)is a widely implemented model for this purpose.However,modeling full-scale biogas plants is challenging due to the extensive substrate and parameter characterization required.This study describes the modification of the ADM1 through a simplification of individual process phases,characteristic components and required parameters.Consequently,the ability of the simplified model to simulate the co-digestion of grass silage and cattle slurry was evaluated using data from a full-scale biogas plant.The impacts of substrate composition(crude carbohydrate,protein and lipid concentration)and variability of carbohydrate degradability on simulation results were assessed to identify the most influential parameters.Results indicated that the simplified version was able to depict biogas and biomethane production with average model efficiencies,according to the Nash-sutcliffe efficiency(NsE)coefficient,of 0.70 and 0.67,respectively,and was comparable to the original ADM1(average model efficiencies of 0.71 and 0.63,respectively).The variability of crude carbohydrate,protein and lipid concentration did not significantly impact biogas and biomethane output for the data sets explored.In contrast,carbohydrate degradability seemed to explain much more of the variability in the biogas and methane production.Thus,the application of simplified models provides a reliable basis for the process simulation and optimization of full-scale agricultural biogas plants.

关键词： ADM1 Agricultural feedstocks Biogas technology Input variability Parameter estimation

Buechel Pappas Resurfacing shoulder Replacement: Evolution and over 40 Years of Clinical Experience

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Open j.urnal of Orthopedics 2024年第5期14卷 218-228页

作者： Frederick F. Buechel michael j. Pappas Rutgers Nj.Medical school Newark NJ USA south Mountain Orthopaedic Associates South Orange NJ USA New j.rsey Institute of Technology Newark NJ USA

Background: Early exploration of the semi constrained “Floating-socket” total shoulder replacement (TsR) in 1974 led to a proliferation of various unconstrained designs that allowed resection or retention of the humeral head, depending upon the pathological process involved. Degenerative glenohumeral arthritis with mild to moderate involvement of subchondral bone allowed for a resurfacing option, while severe humeral head involvement required a partial or full humeral head replacement attached to an intramedullary stem for fixation. All components evolved from cemented to cementless application by 1982. The purpose of this paper is to describe the progression of Buechel-Pappas (B-P) shoulder replacement development from the early 1970’s in both cemented and cement less applications. Methods: Clinical evaluations of “Floating-socket” TsR, followed by B-P stem-type, resurfacing types, bipolar-type and revision components, all of which comprise the B-P shoulder Replacement system, were performed over a 49-year period. Results: “Floating-socket” implants improved the results of simple, constrained ball-in-socket designs, but generally failed by glenoid component loosening in both chimpanzee and human applications. Unconstrained resurfacing-type components, both anatomical humeral head and full proximal humeral components, were quite successful, with minimal failures observed in long-term studies. Bipolar salvage implants, used for severe proximal deficiencies, revisions and massive rotator cuff arthropathy, were also very successful;providing overhead range of motion in many patients. Conclusions: Resurfacing hemiarthroplasty, in patients with intact or repairable rotator cuff mechanisms, gave the most satisfactory results and were the least technically complicated to perform, requiring minimal instrumentation. Resurfacing of full proximal humeral deficiencies, using femoral resurfacing components, gave similar clinical results to more complex semi-constrained devices, also with less technical difficulties and simple

关键词： Total shoulder Replacement Resurfacing shoulder Replacement

The Global Energy and Water Exchanges(GEWEX)Proj.ct in Central Asia:The Case for a Regional Hydroclimate Proj.ct

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Advances in Atmospheric sciences 2024年第5期41卷 777-783页

作者： michael BRODY Maksim KULIKOV sagynbek ORUNBAEV Peter j.VAN OEVELEN International Agricultural University Tashkent 111200Uzbekistan George Mason University FairfaxVirginia 22030USA University of Central Asia Bishkek 720001Kyrgyz Republic American University of Central Asia Bishkek 720060Kyrgyz Republic International GEWEX proj.ct George Mason UniversityFairfaxVirginia 22030USA

Central Asia consists of the former soviet Republics,Kazakhstan,Kyrgyz Republic,Taj.kistan,Turkmenistan,and Uzbekistan.The region’s climate is continental,mostly semi-arid to arid.Agriculture is a significant part of the region’s economy.By its nature of intensive water use,agriculture is extremely vulnerable to climate change.Population growth and irrigation development have significantly increased the demand for water in the region.Maj.r climate change issues include melting glaciers and a shrinking snowpack,which are the foundation of the region’s water resources,and a changing precipitation regime.Most glaciers are located in Kyrgyzstan and Taj.kistan,leading to transboundary water resource issues.summer already has extremely high temperatures.Analyses indicate that Central Asia has been warming and precipitation might be increasing.The warming is expected to increase,but its spatial and temporal distribution depends upon specific global scenarios.Proj.ctions of future precipitation show significant uncertainties in type,amount,and distribution.Regional Hydroclimate Proj.cts(RHPs)are an approach to studying these issues.Initial steps to develop an RHP began in 2021 with a widely distributed online survey about these climate issues.It was followed up with an online workshop and then,in 2023,an in-person workshop,held in Tashkent,Uzbekistan.Priorities for the Global Energy and Water Exchanges(GEWEX)proj.ct for the region include both observations and modeling,as well as development of better and additional precipitation observations,all of which are topics for the next workshop.A well-designed RHP should lead to reductions in critical climate uncertainties in policy-relevant timeframes that can influence decisions on necessary investments in climate adaptation.

关键词： GEWEX Central Asia climate change agriculture