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microphysiological systems for solid tumor immunotherapy:opportunities and challenges

microsystems & Nanoengineering 2023年第6期9卷 77-106页

作者： Sara Abizanda-Campo maría Virumbrales-muñoz mouhita Humayun Ines marmol David J.Beebe Ignacio Ochoa Sara Oliván jose m.ayuso Department of Dermatology University of Wisconsin-MadisonMadisonWIUSA University of Wisconsin Carbone Cancer Center MadisonWIUSA Department of Biomedical Engineering University of WisconsinMadisonWIUSA Tissue microenvironment Lab(TmE lab) Aragón Institute of Engineering Research(I3A)University of ZaragozaZaragozaSpain Instituto de Investigación Sanitaria Aragón(IISA) ZaragozaSpain Centro Investigación Biomédica en Red.Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)ZaragozaSpain Department of Obstetrics and Gynecology University of Wisconsin-MadisonMadisonWIUSA Department of Biological Engineering Massachusetts Institute of Technology CambridgeCambridgeMAUSA Department of Pathology&Laboratory medicine University of WisconsinMadisonWIUSA

Immunotherapy remains more effective for hematologic tumors than for solid *** of the main challenges to immunotherapy of solid tumors is the immunosuppressive microenvironment these tumors generate,which limits the cytotoxic capabilities of immune effector cells(e.g.,cytotoxic T and natural killer cells).This microenvironment is characterized by hypoxia,nutrient starvation,accumulated waste products,and acidic ***-hijacked cells,such as fibroblasts,macrophages,and T regulatory cells,also contribute to this inhospitable microenvironment for immune cells by secreting immunosuppressive cytokines that suppress the antitumor immune response and lead to immune ***,there is a strong interest in developing new drugs and cell formulations that modulate the tumor microenvironment and reduce tumor cell immune *** systems(mPSs)are versatile tools that may accelerate the development and evaluation of these therapies,although specific examples showcasing the potential of mPSs remain *** in microtechnologies have led to the development of sophisticated microfluidic devices used to recapitulate tumor *** resulting models,also known as microphysiological systems(mPSs),are versatile tools with which to decipher the molecular mechanisms driving immune cell antitumor cytotoxicity,immune cell exhaustion,and immune cell exclusion and to evaluate new targeted ***,we review existing microphysiological platforms to study immuno-oncological applications and discuss challenges and opportunities in the field.

关键词： immunotherapy versatile solid

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Unveiling the brain’s symphony:exploring the necessity and sufficiency of neural networks in behavior control

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Neural Regeneration Research 2025年第1期20卷 186-187页

作者： Fernando jose Bustos Instituto de Ciencias Biomedicas Facultad de Medicina y Facultad de Ciencias de la VidaUniversidad Andres BelloSantiagoChile millennium Nucleus of Neuroepigenetics and Plasticity(EpiNeuro) SantiagoChile

Since the pioneering work by Broca and Wernicke in the 19th century,who examined individuals with brain lesions to associate them with specific behaviors,it was evident that behaviors are complex and cannot be fully attributable to specific brain areas ***,they involve connectivity among brain areas,whether close or *** that time,this approach was considered the optimal way to dissect brain circuitry and *** pioneering efforts opened the field to explore the necessity or sufficiency of brain areas in controlling behavior and hence dissecting brain ***,the connectivity of the brain and the mechanisms through which various brain regions regulate specific behaviors,either individually or collaboratively,remain largely *** animal models,researchers have endeavored to unravel the necessity or sufficiency of specific brain areas in influencing behavior;however,no clear associations have been firmly established.

关键词： behavior connectivity neural

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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer m.Colón-mercado Aranza I.Torrado-Tapias Iris K.Salgado jose m.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge D.miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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Analyzing the multilevel structure of the European airport network

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Chinese Journal of Aeronautics 2017年第2期30卷 554-560页

作者： Oriol Lordan jose m.Sallan Department of management Universitat Politecnica de Catalunya-BarcelonaTech Terrassa 08222 Spain

The multilayered structure of the European airport network（EAN）,composed of connections and flights between European cities,is analyzed through the k-core decomposition of the connections *** decomposition allows to identify the core,bridge and periphery layers of the *** core layer includes the best-connected cities,which include important business air traffic *** periphery layer includes cities with lesser connections,which serve low populated areas where air travel is an economic *** remaining cities form the bridge of the EAN,including important leisure travel origins and *** multilayered structure of the EAN affects network robustness,as the EAN is more robust to isolation of nodes of the core,than to the isolation of a combination of core and bridge nodes.

关键词： Air transport networks Complex networks k-core decomposition Network multilevel structure Robustness

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Twists and Gromov Hyperbolicity of Riemann Surfaces

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Acta mathematica Sinica,English Series 2011年第1期27卷 29-44页

作者： Katsuhiko mATSUZAKI jose m. RODRIGUEZ Department of mathematics School of Education Waseda University Shinjuku Tokyo 169-8050 Japan Departamento de matemdticas Universidad Carlos IH de Madrid Avenida de la Universidad 30 28911 Legangs Madrid Spain

The main aim of this paper is to study whether the Gromov hyperbolicity is preserved under some transformations on Riemann surfaces （with their Poincare metrics）. We prove that quasiconformal maps between Riemann surfaces preserve hyperbolicity; however, we also show that arbitrary twists along simple closed geodesics do not preserve it, in general.

关键词： Quasiconformal maps Riemann surfaces Gromov hyperbolicity

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Cellular senescence: is the problem a solution for muscle repair?

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Cellular & molecular Immunology 2023年第5期20卷 429-431页

作者： jose m.Izquierdo Centro de Biologia molecular Severo Ochoa Consejo Superior de Investigaciones CientificasUniversidad Autonoma de Madrid(CSIC/UAM)C/Nicolas Cabrera 1Campus de Cantoblanco28049 MadridSpain

In their recent article in Nature,moiseeva et *** that senescent cells are integral components of the skeletal muscle regenerative niche,showing that they repress regeneration in response to different types of injuries in young mice and that this regeneration is even more profound in aged *** observations point to selective links between the conservation of cell identity traits and two universal senescence hallmarks(i.e.,inflammation and matrix remodeling/fibrosis)across cell types,regeneration times,and aging statuses.

关键词： showing injuries regeneration

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A versatile microfluidic device for multiple ex vivo/ in vitro tissue assays unrestrained from tissue topography

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microsystems & Nanoengineering 2020年第1期6卷 806-819页

作者： jose m.de Hoyos-Vega Alan m.Gonzalez-Suarez jose L.Garcia-Cordero Unidad monterrey Centro de Investigacion y de Estudios Avanzados del IPNVia del conocimiento 201Parque PIITApodacaNL 66628Mexico

Precision-cut tissue slices are an important in vitro system to study organ function because they preserve most of the native cellular microenvironments of organs,including complex intercellular ***,during sample manipulation or slicing,some of the natural surface topology and structure of these tissues is lost or ***,we introduce a microfluidic platform to perform multiple assays on the surface of a tissue section,unhindered by surface *** device consists of a valve on one side and eight open microchannels located on the opposite side,with the tissue section sandwiched between these two *** the valve is actuated,eight independent microfluidic channels are formed over a tissue *** strategy prevents cross-contamination when performing assays and enables *** irregular tissues such as an aorta,we conducted multiple in vitro and ex vivo assays on tissue sections,including short-term culturing,a drug toxicity assay,a fluorescence immunohistochemistry staining assay,and an immune cell assay,in which we observed the interaction of neutrophils with lipopolysaccharide(LPS)-stimulated *** microfluidic platform can be employed in other disciplines,such as tissue physiology and pathophysiology,morphogenesis,drug toxicity and efficiency,metabolism studies,and diagnostics,enabling the conduction of several assays with a single biopsy sample.

关键词： metabolism topography versatile

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Implicit Continuous User Authentication for mobile Devices based on Deep Reinforcement Learning

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Computer Systems Science & Engineering 2023年第2期44卷 1357-1372页

作者： Christy James jose m.S.Rajasree Government Engineering College Idukki685603India APJ Abdul Kalam Technological University Thiruvananthapuram695016India

The predominant method for smart phone accessing is conﬁned to methods directing the authentication by means of Point-of-Entry that heavily depend on physiological biometrics like,ﬁngerprint or *** continuous authentication initiating to be loftier to conventional authentication mechanisms by continuously conﬁrming users’identities on continuing basis and mark the instant at which an illegitimate hacker grasps dominance of the ***,divergent issues remain *** research aims to investigate the power of Deep Reinforcement Learning technique to implicit continuous authentication for mobile devices using a method called,Gaussian Weighted Cauchy Kriging-based Continuous Czekanowski’s(GWCK-CC).First,a Gaussian Weighted Non-local mean Filter Preprocessing model is applied for reducing the noise pre-sent in the raw input face *** Kriging Regression function is employed to reduce the ***,Continuous Czekanowski’s Clas-siﬁcation is utilized for proﬁcient classiﬁcation between the genuine user and *** this way,the proposed GWCK-CC method achieves accurate authen-tication with minimum error rate and *** assessment of the pro-posed GWCK-CC method and existing methods are carried out with different factors by using UmDAA-02 Face *** results conﬁrm that the proposed GWCK-CC method enhances authentication accuracy,by 9%,reduces the authen-tication time,and error rate by 44%,and 43%as compared to the existing methods.

关键词： Deep reinforcement learning gaussian weighted non-local meanﬁlter cauchy kriging regression continuous czekanowski’s implicit continuous authentication mobile devices

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morphodynamics of sandy beaches under the influence of storm sequences:Current research status and future needs

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Water Science and Engineering 2019年第3期12卷 221-234页

作者： Sonja Eichentopf Harshinie Karunarathna jose m.Alsina Department of Civil and Environmental Engineering Imperial College London South Kensington Campus London SW7 2AZ UK College of Engineering Swansea University Bay Campus Swansea SA1 8EN UK Laboratori d'Enginyeria marítima Universitat Politecnica de Catalunya Barcelona 08034 Spain

This paper reviews and discusses the current research status, trends, and future needs in the field of beach morphodynamics under the influence of storm *** paper reviews how the three main research methods, field investigations, numerical modelling, and physical modelling, have been used to study beach morphodynamics during storm *** quantitative definitions of storm sequences at different sites are presented and *** is shown that the definition of storm sequences is site-specific and requires knowledge of the storm climate, beach characteristics, and the temporal scale of beach ***, the paper brings together currently available approaches aimed at describing the effect of storm sequences on beach erosion in a general *** importance of storm chronology and the effects of an extreme storm within a sequence of storms are *** that, the more poorly studied aspect of beach recovery in between storms within a sequence is *** indicators for defining beach recovery, namely the shoreline location, sediment volumes, and the beach state, are identified and ***, important research needs, including the need for detailed physical modelling, are identified.

关键词： Storm sequences Beach morphodynamics Beach erosion Extreme storms Return period Beach recovery

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On a Classical Theorem on the Diameter and minimum Degree of a Graph

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Acta mathematica Sinica,English Series 2017年第11期33卷 1477-1503页

作者： Veronica HERNANDEZ Domingo PESTANA jose m. RODRIGUEZ Universidad CarlosⅢde madrid Avenida de la Universidad3028911 LeganesSpain

In this work, we obtain good upper bounds for the diameter of any graph in terms of its minimum degree and its order, improving a classical theorem due to Erdos, Pach, Pollack and Tuza. We use these bounds in order to study hyperbolic graphs （in the Gromov sense）. To compute the hyperbolicity constant is an almost intractable problem, thus it is natural to try to bound it in terms of some parameters of the graph. Let H（n, δ0） be the set of graphs G with n vertices and minimum degree 50, and J（n, Δ） be the set of graphs G with n vertices and maximum degree A. We study the four following extremal problems on graphs： a（n,δ0） = min{δ（G）｜ G ∈H（n, δ0）}, b（n, δ0） =- max{δ（G）｜ e ∈H（n, δ0）}, α（n, Δ） = min{δ（G） [ G ∈ J（n, Δ）} and β（n,Δ） = max{δ（G） ] G∈Π（n,Δ）}. In particular, we obtain bounds for b（n, δ0） and we compute the precise value of a（n, δ0）, α（n, Δ） and w（n, Δ） for all values of n, r0 and A, respectively.

关键词： Extremal problems on graphs diameter minimum degree maximum degree Gromov hyperbolicity hyperbolicity constant finite graphs

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