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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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Therapies for Tau-associated neurodegenerative disorders:targeting molecules,synapses,and cells

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Neural Regeneration Research 2023年第12期18卷 2633-2637页

作者： miranda Robbins MRC Laboratory of Molecular Biology Cambridge Biomedical CampusFrancis Crick AveTrumpingtonCambridgeUKUniversity of CambridgeDepartment of ZoologyCambridgeUK

Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders(Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating(1) the broad class of chemicals termed “small molecules”;(2) adaptive immunity through both passive and active antibody treatments;(3) innate immunity with an emphasis on microglial modulation;(4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.

关键词： Alzheimer's disease antibody frontotemporal dementia immunotherapy small molecules synapses tau therapeutics

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A single session of strength training changed plasma levels of resistin,but not leptin in overweight and obese men

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Sports Medicine and Health Science 2024年第4期6卷 324-330页

作者： Yago Martins Fortes Antonio Felipe Souza-Gomes Alessandro Roberto Silveira Moreira Leo Nogueira Campos Samara Silva de Moura Lucelia Scarabeli Silva Barroso Marcelo Henrique Salviano de Faria Heliana de Barros Fernandes Aline Silva de miranda Hugo Cesar Martins-Costa Ana Cristina Simoes e Silva Janaina Matos Moreira Albena Nunes-Silva Laboratory of Inflammation and Exercise Immunology Department of Physical EducationSchool of Physical EducationFederal University of Ouro PretoOuro PretoMGBrazil Postgraduate Program in Health and Nutrition Nutrition SchoolFederal University of Ouro PretoOuro PretoMGBrazil Interdisciplinary Medical Research Laboratory Faculty of MedicineFederal University of Minas GeraisBelo HorizonteMGBrazil Neurobiology Laboratory Institute of Biological SciencesFederal University of Minas GeraisBelo HorizonteMGBrazil Department of Physical Education Pontifical Catholic University of Minas GeraisBrazil Department of Pediatrics Faculty of MedicineFederal University of Minas Gerais(UFMG)Belo HorizonteMGBrazil

Obesity has a complex multifactorial etiology and is characterized by excessive accumulation of adipose *** adipose tissue has deleterious effects on health because it secretes large amounts of inflammatory *** calorie restriction associated with strength training may be useful in managing chronic systemic *** study aimed to evaluate the acute effect of a single strength-training session on plasma adipokine levels in sedentary,overweight,and obese young *** study included twelve men(Age:[34.95±9.77]years;Height:[174.16±3.66]centimeter[cm];Weight:[97.83±12.87]kilogram(kg);body mass index[BMI]:[32.30±4.51]kg/m2),who performed a single strength training *** strength training protocol consisted of 4 sets of 12 repetitions in the following six exercises,45°leg press,bench press,leg extension,machine row,leg curl,and shoulder *** samples were collected before,immediately after,and 1-h subsequent after strength *** plasma levels of resistin and leptin were measured.A significant decrease in resistin levels were found 1 h after the strength training session if compared to levels before the training session(pre-[before][2390±1199]picograms per milliliter[pg/mL]vs post-1 h[1-h subsequent][1523±798],6 pg/mL,p=0.0028).The plasma leptin levels did not differ at any time *** conclusion,a very well controlled single session of strength training significantly decreased the plasma levels of resistin without altering the concentration of leptin in overweight and obese *** effect,at least in part,supports the benefits of exercise by reducing the low grade inflammation and insulin resistance in obesity.

关键词： Strength training Adipose tissue Obesity Chronicinflammation Resistin Leptin

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Fiber Laser Sensor Based on a Phase-Shifted Chirped Grating for Acoustic Sensing of Partial Discharges

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Photonic Sensors 2013年第1期3卷 44-51页

作者： Sanderson E. U. LIMA Rubem G FARIAS Francisco M. ARAUJO Luis A. FERREIRA José L. SANTOS vl.dimiro miranda1 Orlando FRAZAO INESC Porto Rua do Campo Alegre 687 Porto 4169-007 Portugal Faeuldade de Engenharia da Computacāo Universidade Federal do Pará Belém Brasil Faculdade de Ciēncias da Universidade do Porto Rua do Campo Alegre 687 Porto 4169-007 Portugal Faculdade de Engenharia da Universidade do Porto Rua Dr. Roberto Frias s/n Porto 4200-465Portugal

Acoustic emission monitoring is often used in the diagnosis of electrical and mechanical incipient faults in the high voltage apparatus. Partial discharges are a major source of insulation failure in electric power transformers, and the differentiation from other sources of acoustic emission is of the utmost importance. This paper reports the development of a new sensor concept - a fiber laser sensor based on a phase-shifted chirped fiber grating - for the acoustic emission detection of incipient faults in oil-filled power transformers. These sensors can be placed in the inner surface of the transformer tank wall, not affecting the insulation integrity of the structure and improving fault detection and location. The performance of the sensing head is characterized and compared for different surrounding media： air, water, and oil. The results obtained indicate the feasibility of this sensing approach for the industrial development of practical solutions.

关键词： Transformer insulation partial discharges acoustic detection fiber laser sensors

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Comparison between Care Strategies for Patients with Osteoarthritis of the Hands Based on the Use of Joint Protection, Assistive Technology and Exercises

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Open Journal of Orthopedics 2024年第7期14卷 295-311页

作者： Daniele dos Santos Scarcella Talita Dias da Silva Victoria Yanara Hernandes da Silva Maria Cândida de miranda Luzo Selma Lancman Marcia Uchoa de Rezende Carlos Bandeira de Mello Monteiro Instituto de Ortopedia e Traumatologia Hospital das Clnicas HCFMUSP Faculdade de Medicina Universidade de So Paulo So Paulo Brazil Programa de Ps-Graduao em Cincias da Reabilitao Faculdade de Medicina Universidade de So Paulo So Paulo Brazil Escola de Artes Cincias e Humanidades Universidade de So Paulo So Paulo Brazil

Background: Osteoarthritis (OA) is a disabling disease that can affect 6% to 12% of the adult population and more than a third of people over 65 years of age. Purpose: To assess whether a group of people with hand osteoarthritis (hOA) who received different types of treatment improved their function after two years of follow-up. Method: The entire sample (n = 97) underwent three follow-up assessments regarding anthropometric parameters of the upper limbs and ability to perform functional activities. Subsequently, the sample was divided into two groups for the intervention periods, called the First Period (n = 73) and the Second Period (n = 24);the First Period kept the same protocol with orientations, and the Second Period went to an intervention with orientation strength exercises and use of orthosis. Findings: In the separate analysis of the three questions of the DASH pain module, no differences were found between the assessment moments for groups of guidelines, treatment, or symptoms. Significant effects were observed for F(2, 162) = 3.5, p = 0.033, η2 = 0.04, and interaction for moments and intervention F(2, 162) = 4.3, p = 0.016, η2 = 0.05. Implications: It can be concluded that only guidance treatment does not benefit patients with hand osteoarthritis. In contrast, guidance, exercise, and orthosis treatment can significantly improve the disease.

关键词： Hand Osteoarthritis Hand Deformities Occupational Therapy

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On Building Practical Biocomputers for Real-world Applications： Receptacles for Culturing Slime Mould Memristors and Component Standardisation

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Journal of Bionic Engineering 2017年第1期14卷 151-162页

作者： Edward Braund Eduardo Reck miranda Interdisciplinary Centre for Computer Music Research (ICCMR) The House Plymouth University Drake Circus UK PL4 8AA

Our application of bionic engineering is novel： we are interested in developing hybrid hardware-wetware systems for music. This paper introduces receptacles for culturing Physarum polycephalum-based memristors that are highly accessible to the creative practitioner. The myxomycete Physarum polycephalum is an amorphous unicellular organism that has been found to exhibit memristive properties. Such a discovery has potential to allow us to move towards engineering electrical systems that encompass Physarum polycephalum components. To realise this potential, it is necessary to address some of the constraints associated with harnessing living biological entities in systems for real-time application. Within the paper, we present 3D printed receptacles designed to standardise both the production of components and memristive observations. Subsequent testing showed a significant decrease in growth time, increased lifespan, and superior similarity in component-to-component responses. The results indicate that our receptacle design may provide means of implementing hybrid electrical systems for music technology.

关键词： unconventional computing Physarum polycephalum computer music biological computing memristor

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Dynamic expression of ATF3 as a novel tool to study activation and migration of endogenous spinal stem cells and their role in neural repair

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Neural Regeneration Research 2015年第5期10卷 713-714页

作者： miranda Mladinic Andrea Nistri Department of Biotechnology University of Rijeka Neuroscience Department International School for Advanced Studies (SISSA)34136 TriesteItaly (Nistri 1)

One of the major problems of modern neurobiology is how to replace dead or damaged neurons in the human brain or spinal cord after injury or as a consequence of neurodegenerative dis- eases. In fact, because adult mammalian neurons are post-mi- totic cells that cannot divide to replace dead cells, loss due to lesion or disease is permanent. Furthermore, surviving neurons have modest capacity to regenerate their damaged axons and re-establish functional connections. Thus, a gradual neurode- generative scenario with certain similarities in stroke, brain or spinal cord injuries and neurological diseases like Alzheimer＇s disease is produced. These conditions represent the major disease burden of the modern world in terms of mortality, dis- ability, productivity loss and health-care costs （World Health Organization, 2008）. While much effort has been directed to understand the molecular and cellular mechanisms involved in the pathology of these diseases to set new effective treatments, many neuroprotective and regenerative approaches, although showing positive results in preclinical studies, have so far failed to provide strong benefit to patients.

关键词： stem cell ATF

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Successful Large-scale Renewables Integration in Portugal:Technology and Intelligent Tools

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CSEE Journal of Power and Energy Systems 2017年第1期3卷 7-16页

作者： vl.dimiro miranda Faculty of Engineering University of PortoPortugal

Portugal is seen worldwide as a case of success in the large-scale integration of renewables in its power system,especially for wind *** policies and sound management decisions are fundamental,but a sustainable process is not possible without the development of endogenous *** paper summarizes a set of models,both applied by the industry and representing actual technologic advancement,denoting the context of research and innovation in the country that helps to explain such *** arise in reliability assessment for systems with renewables,active and reactive power control,integration of wind farms,storage,electric vehicle integration,wind and solar power forecasting and distribution operation and state estimation taking advantage of smart grid *** all cases,one relevant trait is evident:the pervasive use of computational intelligence tools.

关键词： Autoencoders electric vehicles EPSO evolutionary particle swarm optimization forecasting voltage/var control large-scale integration reliability renewables smart grids solar power state estimation storage wind power

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Piezoelectric constant temperature dependence in strained [111]-oriented zinc-blende MQW-SOAs

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Chinese Optics Letters 2023年第9期21卷 107-112页

作者： Horacio Soto-Ortiz Gerson Torres-miranda Applied Physics Division Center for Scientific Research and Higher Education of Ensenada

Here,we present a study of the effective piezoelectric constant(e_(14_(e)))temperature dependence in strained[111]-oriented zinc-blende quantum wells(QWs)embedded within a semiconductor optical amplifier(SOA).We determined e_(14_(e)) using a method that was insensitive to the segregation phenomenon and to the temperature dependence of the bandgap energy,which required neither fitting parameters nor temperature-dependent expressions for energy and out-of-plane effective masses of electrons and heavy *** e_(14_(e))=−0.0534±0.0040 C·m^(−2) at 23°C was obtained for an SOA with 1.2 nm[111]-oriented strained In0.687Ga0.313As/In0.807Ga0.193As0.304P0.696 *** previously published research,where e_(14_(e)) magnitude increased as temperature rised,we extracted an e_(14_(e)) magnitude that decreased as temperature increased.

关键词： piezoelectric constant pyroelectric effect quantum-confined Stark effect excitons semiconductor optical amplifiers zinc-blende quantum wells

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Elucidating the pathological mechanisms of neurodegeneration in the lethal serpinopathy FENIB

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Neural Regeneration Research 2022年第8期17卷 1733-1734页

作者： Elena miranda Giovanna Galliciotti Department of Biology and Biotechnologies‘Charles Darwin’and Pasteur Institute-Cenci Bo-lognetti Foundation Sapienza University of RomeRomeItaly Institute of Neuropathology University Medical Center Hamburg-EppendorfHamburgGermany

The term serpinopathies was introduced to describe a family of diseases caused by point mutations in serine protease inhibitors,or *** inhibit their cognate protease by an irreversible suicide mechanism starting with the attack of the active site serine on the reactive center loop of the inhibitor,followed by formation of a covalent complex between both proteins,insertion of the reactive center loop of the serpin into its own beta-sheet A,and culminating in distortion of the active site of the serine protease and thus irreversible *** inhibitory mechanism,reminiscent of the movement of a mousetrap,requires a structural flexibility that proves to be unfavorable when the folding of the serpin is altered by mutations responsible for conformational rearrangements,allowing an intermolecular domain exchange characterized by the insertion of the C-terminal domain of a molecule into a second one,thus forming a *** of this insertion reaction leads to the formation of serpin polymers that accumulate within the endoplasmic reticulum(ER)of the cell and consequently reduces the secretion of the wild-type serpin(Greene et al.,2016).

关键词： insertion irreversible starting

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