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Dual Effects of IL-1 Overactivity on the Immune System in a mouse model of Arthritis due to Deficiency of IL-1 Receptor Antagonist

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Journal of Genetics and Genomics 2013年第2期40卷 83-91页

作者： Jian Yan Yan Jiao Hong Chen Feng Jiao Karen A.Hasty john m.stuart Weikuan Gu Department of medicine University of Tennessee Health Science Center Department of Orthopedic Surgery and BmE University of Tennessee Health Science Center mudanjiang medical College The First Hospital of Qiqihaer City Department of Veterans Affairs medical Center

Previous studies have revealed the significance of cytokine interleukin 1 （IL-1） in the onset and progression of rheumatoid arthritis （RA）. The precise molecular mechanisms related to IL-1 underlying RA is still elusive. We conducted a whole genome-wide tran- scriptomal comparison of wild-type （WT） and arthritis-prone IL-1 receptor antagonist （IL-lrn） deficient BALB/c mice to address this issue. To refine our search efforts, gene expression profiling was also performed on paired wild-type and arthritis-resistant IL-lrn deficient DBA/1 mice as internal controls when identifying causative arthritis candidate genes. Two hundred and fifteen transcripts were found to be dysregulated greater than or equal to 2-fold in the diseased mice. The altered transcriptome in BALB/c mice revealed increased myeloid cell activities and impaired lymphocyte functionality, suggesting dual regulatory effects of IL-1 hyperactivity on immunological changes associated with arthritis development. Phase-specific gene expression changes were identified, such as early increase and late decrease of heat shock protein coding genes. moreover, common gene expression changes were also observed, especially the upregulation of paired Ig-like receptor A （Pira） in both early and late phases of arthritis. Real-time PCR was performed to validate the expression of Pira and an intervention experiment with a major histocompatibility complex （mHC） class I inhibitor （brefeldin A） was carded out to investigate the role of suppressing Pira activity. We conclude that global pattern changes of common and distinct gene expressions may represent novel opportunities for better control of RA through early diagnosis and development of alternative therapeutic strategies.

关键词： Arthritis Gene expression mouse Transcriptome

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The influence of resistance exercise training prescription variables on skeletal muscle mass,strength,and physical function in healthy adults:An umbrella review

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Journal of Sport and Health Science 2024年第1期13卷 47-60页

作者： Jonathan C.mcleod Brad S.Currier Caroline V.Lowisz stuart m.Phillips Department of Kinesiology Faculty of ScienceMcMaster UniversityHamilton L8S4L8Canada

Purpose:The aim of this umbrella review was to determine the impact of resistance training(RT)and individual RT prescription variables on muscle mass,strength,and physical function in healthy ***:Following Preferred Reporting Items for Systematic Reviews and meta-Analyses(PRISmA)guidelines,we systematically searched and screened eligible systematic reviews reporting the effects of differing RT prescription variables on muscle mass(or its proxies),strength,and/or physical function in healthy adults aged>18 ***:We identified 44 systematic reviews that met our inclusion *** methodological quality of these reviews was assessed using A measurement Tool to Assess Systematic Reviews;standardized effectiveness statements were *** found that RT was consistently a potent stimulus for increasing skeletal muscle mass(4/4 reviews provide some or sufficient evidence),strength(4/6 reviews provided some or sufficient evidence),and physical function(1/1 review provided some evidence).RT load(6/8 reviews provided some or sufficient evidence),weekly frequency(2/4 reviews provided some or sufficient evidence),volume(3/7 reviews provided some or sufficient evidence),and exercise order(1/1 review provided some evidence)impacted RT-induced increases in muscular *** discovered that 2/3 reviews provided some or sufficient evidence that RT volume and contraction velocity influenced skeletal muscle mass,while 4/7 reviews provided insufficient evidence in favor of RT load impacting skeletal muscle *** was insufficient evidence to conclude that time of day,periodization,inter-set rest,set configuration,set end point,contraction velocity/time under tension,or exercise order(only pertaining to hypertrophy)influenced skeletal muscle adaptations.A paucity of data limited insights into the impact of RT prescription variables on physical ***:Overall,RT increased muscle mass,strength,and physical function compared to no ***

关键词： Hypertrophy Resistance training Resistance training prescription variables Strength Umbrella review

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Nonuniform Dependence on the Initial Data for Solutions of Conservation Laws

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Communications on Applied mathematics and Computation 2024年第1期6卷 489-500页

作者： john m.Holmes Barbara Lee Keyfitz Department of mathematics The Ohio State UniversityColumbusOH43210USA

In this paper,we study systems of conservation laws in one space *** prove that for classical solutions in Sobolev spaces H^(s),with s>3/2,the data-to-solution map is not uniformly *** results apply to all nonlinear s... 详细信息

关键词： Conservation laws Data-to-solution map Nonuniform dependence

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Ergodicity and Accuracy of Optimal Particle Filters for Bayesian Data Assimilation

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Chinese Annals of mathematics,Series B 2019年第5期40卷 811-842页

作者： David KELLY Andrew m.stuart Courant Institute of mathematical Sciences New York UniversityNew YorkUSAThe Voleon Group2150 Dwight WayBerkeleyCA94704USA Department of Computing and mathematical Sciences California Institute of TechnologyPasadenaCA91125USA.

Data assimilation refers to the methodology of combining dynamical models and observed data with the objective of improving state estimation. most data assimilation algorithms are viewed as approximations of the Bayesian posterior(filtering distribution)on the signal given the observations. Some of these approximations are controlled, such as particle filters which may be refined to produce the true filtering distribution in the large particle number limit, and some are uncontrolled, such as ensemble Kalman filter methods which do not recover the true filtering distribution in the large ensemble limit. Other data assimilation algorithms, such as cycled 3 DVAR methods, may be thought of as controlled estimators of the state, in the small observational noise scenario, but are also uncontrolled in general in relation to the true filtering distribution. For particle filters and ensemble Kalman filters it is of practical importance to understand how and why data assimilation methods can be effective when used with a fixed small number of particles, since for many large-scale applications it is not practical to deploy algorithms close to the large particle limit asymptotic. In this paper, the authors address this question for particle filters and,in particular, study their accuracy(in the small noise limit) and ergodicity(for noisy signal and observation) without appealing to the large particle number limit. The authors first overview the accuracy and minorization properties for the true filtering distribution,working in the setting of conditional Gaussianity for the dynamics-observation model. They then show that these properties are inherited by optimal particle filters for any fixed number of particles, and use the minorization to establish ergodicity of the filters. For completeness we also prove large particle number consistency results for the optimal particle filters, by writing the update equations for the underlying distributions as recursions. In addition to loo

关键词： Particle filters Data assimilation Ergodic theory

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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos m.Kanczler stuart Lanham Andrew Rawlings marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECm)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBmSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECm(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBmSCs viability upon *** composite of human bone-ECm-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAm)*** inclusion of bone morphogenetic protein-2(BmP-2)with the HBmSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECm)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

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Immunotherapy of gastric cancer:Present status and future perspectives

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World Journal of Gastroenterology 2024年第8期30卷 779-793页

作者： john K Triantafillidis manousos m Konstadoulakis Apostolos E Papalois Inflammatory Bowel Disease Unit “Metropolitan General”HospitalHolargos 15562AtticaGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece Second Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528AtticaGreece Unit of Surgical Research and Training Second Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528AtticaGreece

In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of *** focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 *** that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the *** then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant *** describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)*** attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with *** is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in ***,an attempt is made to draw some conclusions and to point out possible future directions.

关键词： Gastric cancer Chemotherapy Immunotherapy Immune checkpoint inhibitors Bibliometrics Scientometrics

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Aerodynamics of a Tandem-Bladed Axial Compressor Rotor under Circumferential Distortion at Different Rotational Speeds

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Journal of Thermal Science 2024年第4期33卷 1340-1356页

作者： Amit KUmAR Jerry T.john A.m.PRADEEP R.A.DAKKERmANS Dragan KOZULOVIC Department of Aerospace Engineering Indian Institute of Technology BombayMumbai400076India Department of Automotive and Aeronautical Engineering Hamburg University of Applied Sciences20099HamburgGermany Institute of Jet Propulsion Bundeswehr University Munich85577NeubibergGermany

For most aircraft engines,inflow distortion is *** distortion is known to degrade the aerodynamic performance and stable operating limits of a *** rotor configuration is an arrangement that effectively controls the growth of the boundary layer over the suction surface of the ***,a higher total pressure rise can be achieved through this unconventional design approach involving the splitting of the blade into forward and aft *** is expected that the effect of inlet flow distortion would be more severe for a tandem-rotor design due to the greater flow turning inherent in such ***,this aspect needs to be thoroughly *** present study discusses the effect of circumferential distortion on the tandem-rotor at different rotational ***-annulus RANS simulations using ANSYS CFX are used in the present *** performance of the rotor at a particular flow coefficient and different rotational speeds is *** total pressure and efficiency are observed to drop at lower mass flow rates under the influence of circumferential *** loss region in each blade passage is mainly associated with the blade wake,tip leakage vortex,secondary flow,and boundary ***,their contribution varies from passage to passage,particularly in the distorted *** the lower span,the wake width is found to be higher than that at a higher *** to the redistribution of the mass flow,the circumferential extent reduces at a higher *** the undistorted sector,the strength of the tip leakage vortex is significantly higher at the design rotational speed than at lower *** distortion near the tip region promotes an early vortex breakdown even at the design operating *** adversely affects the total pressure,efficiency,and stall *** clean flow conditions,this phenomenon is only observed near the stall *** the design operating condition,the breakdown of the forward rotor tip l

关键词： tandem rotor circumferential distortion loss tip leakage vortex vortex breakdown diffusion factor aerodynamics of compressor blade

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A holistic approach to improving safety for battery energy storage systems

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Journal of Energy Chemistry 2024年第5期92卷 422-439页

作者： James Close Jonathan E.Barnard Y.m.john Chew Semali Perera Department of Chemical Engineering Centre for DigitalManufacturing&DesignUniversity of BathBath BA27AYUK iomosaic International Limited 16-18 Queen SquareBath BA12HNUK

The integration of battery energy storage systems(BESS)throughout our energy chain poses concerns regarding safety,especially since batteries have high energy density and numerous BESS failure events have *** spread adoption will only increase the prevalence of these failure events unless there is a step change in the management and design of *** understand the causes of failure,the main challenges of BESS safety are *** consequences and failure events are discussed,including specific focus on the chain of events causing thermal runaway,and a case study of a BESS explosion in Surprise Arizona is *** on the technology and past events,a paradigm shift is required to improve BESS *** this review,a holistic approach is *** combines currently adopted approaches including battery cell testing,lumped cell mathematical modelling,and calorimetry,alongside additional measures taken to ensure BESS safety including the requirement for computational fluid dynamics and kinetic modelling,assessment of installation level testing of the full BESS system and not simply a single cell battery test,hazard and layers of protection analysis,gas chromatography,and composition *** holistic approach proposed in this study aims to address challenges of BESS safety and form the basis of a paradigm shift in the safety management and design of these systems.

关键词： Energy storagesystems Process safety Battery safety Thermal safety

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Additively manufactured Ti–Ta–Cu alloys for the next-generation load-bearing implants

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International Journal of Extreme manufacturing 2024年第1期6卷 353-374页

作者： Amit Bandyopadhyay Indranath mitra Sushant Ciliveri Jose D Avila William Dernell stuart B Goodman Susmita Bose W.m.Keck Biomedical materials Research Laboratory School of Mechanical and Materials EngineeringWashington State UniversityPullmanWA 99164United States of America Veterinary Clinical Sciences College of Veterinary MedicineWashington State UniversityPullmanWA 99164United States of America Department of Orthopedic Surgery Stanford University Medical CenterRedwood CityCA 94063United States of America

Bacterial colonization of orthopedic implants is one of the leading causes of failure and clinical complexities for load-bearing metallic implants. Topical or systemic administration of antibiotics may not offer the most efficient defense against colonization, especially in the case of secondary infection, leading to surgical removal of implants and in some cases even limbs. In this study, laser powder bed fusion was implemented to fabricate Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders. Ti-Tantalum(Ta)–Copper(Cu) alloys were further analyzed by the addition of Ta and Cu into the Ti3Al2V custom alloy. The biological,mechanical, and tribo-biocorrosion properties of Ti3Al2V alloy were evaluated. A 10 wt.% Ta(10Ta) and 3 wt.% Cu(3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance. Additively manufactured implants were investigated for resistance against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 h. A 3 wt.% Cu addition to Ti3Al2V displayed improved antibacterial efficacy, i.e.78%–86% with respect to CpTi. mechanical properties for Ti3Al2V–10Ta–3Cu alloy were evaluated, demonstrating excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics when compared to Ti6Al4V. In vivo studies using a rat distal femur model revealed improved early-stage osseointegration for alloys with10 wt.% Ta addition compared to CpTi and Ti6Al4V. The 3 wt.% Cu-added compositions displayed biocompatibility and no adverse infammatory response in vivo. Our results establish the Ti3Al2V–10Ta–3Cu alloy’s synergistic effect on improving both in vivo biocompatibility and microbial resistance for the next generation of load-bearing metallic implants.

关键词： Ti6Al4V load-bearing implants additive manufacturing 3D printing antibacterial performance

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Combination treatment of inflammatory bowel disease:Present status and future perspectives

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World Journal of Gastroenterology 2024年第15期30卷 2068-2080页

作者： john K Triantafillidis Constantinos G Zografos manousos m Konstadoulakis Apostolos E Papalois Inflammatory Bowel Disease Unit "Metropolitan General"HospitalHolargos 15562AtticaGreece Hellenic Society for Gastrointestinal Oncology 354 Iera OdosChaidari 12461AtticaGreece The 2^(nd)Department of Surgery University of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece Unit of Surgical Research and Training The 2^(nd)Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical *** seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the *** daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical *** combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment ***,a part of these patients are going to *** recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe *** our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very *** mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal *** appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research *** this

关键词： Biologics for immune-mediated conditions Dual-targeted treatment Combination treatment Inflammatory bowel disease Crohn’s

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