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Specific CD8^+ T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis

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World Journal of Gastroenterology 2016年第28期22卷 6469-6483页

作者： Elia Moreno-Cubero Juan-ramón Larrubia Translational Hepatology Unit Guadalajara University Hospital University of Alcalá Department of Biology of Systems University of Alcalá Department of Medicine and Medical Specialties University of Alcalá

Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8+ T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8+ T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.

关键词： Hepatocellular carcinoma CD8+ T cells Immune checkpoint modulation Chronic viral hepatitis Cytotoxic T-lymphocyte antigen-4 Programmed cell death protein-1

Stochastic Models to Mitigate Sparse Sensor Attacks in Continuous-Time non-Linear Cyber-Physical Systems

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Computers, Materials & Continua 2023年第9期76卷 3189-3218页

作者： Borja Bordel Sánchez ramón Alcarria Tomás Robles Information Technologies Department Universidad Politécnica de MadridMadrid28031Spain Geospatial Information Department Universidad Politécnica de MadridMadrid28031Spain

Cyber-Physical Systems are very vulnerable to sparse sensor *** current protection mechanisms employ linear and deterministic models which cannot detect attacks ***,in this paper,we propose a new non-linear generalized model to describe Cyber-Physical *** model includes unknown multivariable discrete and continuous-time functions and different multiplicative noises to represent the evolution of physical processes and randomeffects in the physical and ***,the digitalization stage in hardware devices is represented *** and most critical sparse sensor attacks are described through a stochastic *** reconstruction and protectionmechanisms are based on aweighted *** probability in data samples is estimated through different indicators commonly employed in non-linear dynamics(such as the Fourier transform,first-return maps,or the probability density function).A decision algorithm calculates the final reconstructed value considering the previous error *** experimental validation based on simulation tools and real deployments is also carried ***,the new technology performance and scalability are *** prove that the proposed solution protects Cyber-Physical Systems against up to 92%of attacks and perturbations,with a computational delay below 2.5 *** proposed model shows a linear complexity,as recursive or iterative structures are not employed,just algebraic and probabilistic *** conclusion,the new model and reconstructionmechanism can protect successfully Cyber-Physical Systems against sparse sensor attacks,even in dense or pervasive deployments and scenarios.

关键词： Cyber-physical systems sparse sensor attack non-linear models stochastic models security

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

A Probabilistic Trust Model and Control Algorithm to Protect 6G networks against Malicious Data Injection Attacks in Edge Computing Environments

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Computer Modeling in Engineering & Sciences 2024年第10期141卷 631-654页

作者： Borja Bordel Sánchez ramón Alcarria Tomás Robles Department of Computer Systems Universidad Politécnica de MadridMadrid28031Spain Department of Geospatial Engineering Universidad Politécnica de MadridMadrid28031Spain

Future 6G communications are envisioned to enable a large catalogue of pioneering *** will range from networked Cyber-Physical Systems to edge computing devices,establishing real-time feedback control loops critical for managing Industry 5.0 deployments,digital agriculture systems,and essential *** provision of extensive machine-type communications through 6G will render many of these innovative systems autonomous and *** full automation will enhance industrial efficiency significantly,it concurrently introduces new cyber risks and *** particular,unattended systems are highly susceptible to trust issues:malicious nodes and false information can be easily introduced into control ***,Denialof-Service attacks can be executed by inundating the network with valueless *** anomaly detection schemes require the entire transformation of the control software to integrate new steps and can only mitigate anomalies that conform to predefined mathematical *** based on an exhaustive data collection to detect anomalies are precise but extremely *** models,with their limited understanding of mobile networks,can achieve precision rates no higher than 75%.Therefore,more general and transversal protection mechanisms are needed to detect malicious behaviors *** paper introduces a probabilistic trust model and control algorithm designed to address this *** model determines the probability of any node to be *** channels are pruned for those nodes whose probability is below a given *** trust control algorithmcomprises three primary phases,which feed themodel with three different probabilities,which are weighted and ***,anomalous nodes are identified using Gaussian mixture models and clustering ***,traffic patterns are studied using digital Bessel functions and the functional scalar ***,the in

关键词： 6G networks noise injection attacks Gaussian mixture model Bessel function traffic filter Volterra filter

Geostatistical seismic inversion and 3D modelling of metric flow units,porosity and permeability in Brazilian presalt reservoir

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Petroleum Science 2024年第3期21卷 1699-1718页

作者： Rodrigo Penna Wagner moreira Lupinacci Exploratory Interpretation and Reservoir Characterization Group(GIECAR) Department of Geology and GeophysicsUniversidade Federal FluminenseNiteroiRJ24210-346Brazil Petrobras Rio de JaneiroRJ20031-912Brazil

Flow units(FU)rock typing is a common technique for characterizing reservoir flow behavior,producing reliable porosity and permeability estimation even in complex geological ***,the lateral extrapolation of FU away from the well into the whole reservoir grid is commonly a difficult task and using the seismic data as constraints is rarely a subject of *** paper proposes a workflow to generate numerous possible 3D volumes of flow units,porosity and permeability below the seismic resolution limit,respecting the available seismic data at larger *** methodology is used in the Mero Field,a Brazilian presalt carbonate reservoir located in the Santos Basin,who presents a complex and heterogenic geological setting with different sedimentological processes and diagenetic *** generated metric flow units using the conventional core analysis and transposed to the well log ***,given a Markov chain Monte Carlo algorithm,the seismic data and the well log statistics,we simulated acoustic impedance,decametric flow units(DFU),metric flow units(MFU),porosity and permeability volumes in the metric *** aim is to estimate a minimum amount of MFU able to calculate realistic scenarios porosity and permeability scenarios,without losing the seismic lateral *** other words,every porosity and permeability volume simulated produces a synthetic seismic that match the real seismic of the area,even in the metric *** achieved 3D results represent a high-resolution fluid flow reservoir modelling considering the lateral control of the seismic during the process and can be directly incorporated in the dynamic characterization workflow.

关键词： Flowunits Geostatistical inversion Presalt reservoir 3D reservoir modelling Petrophysical modelling

Metapopulation approach for landscape level management of western tarnished plant bug,Lygus hesperus,in Texas( Hemiptera,Miridae)

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植物保护学报 2014年第6期41卷 761-768页

作者： Parajulee Megha n Shrestha ram B Texas A & M University System AgriLife Research and Extension Center

Insect source-sink dynamics are vital to ecologically intensive pest management. Maintaining sink plant hosts,or "trap crops",and destroying alternate hosts or breeding places adjacent to the field crop are effective pest management strategies for some arthropods. However,determining whether a host acts as a source or a sink is challenging, especially when the pest species is highly mobile and polyphagous. The western tarnished plant bug,Lygus hesperus,is highly polyphagous,and can utilize >300 hosts. Its presence has been documented in 26 roadside weed hosts in the Texas High *** studies demonstrated that L. hesperus prefer alfalfa over cotton and several alternate weed hosts.A four-year project involved surveying and sampling for L. hesperus in the agricultural landscapes of several sub-regions of the southwestern United States,including the Texas High Plains. In Texas,geographic information of the landscape vegetation complex was compiled from a 150 km radius in the Texas High Plains. In one study,fifty irrigated cotton fields representing the crop diversity within this region were sampled via sweep-net for 10 weeks. This effort also included sampling of up to six noncotton insect habitats within a 3 km radius of each field. Seasonal average L. hesperus abundance data were regressed with 27 field characteristics( variables),including habitat-specific land cover,distance between focal cotton fields and non-cotton habitats,longitude,latitude,elevation,habitat heterogeneity index,and several environmental / ecological variables. Significant variables were selected using a stepwise regression at 15% probability rate. A 10-parameter linear model explained 93% of the variation in the data. Major parameters contributing significantly to variation in L. hesperus abundance in cotton were corn and sunflower acreages,focal cotton field distances from several non-cotton hosts,and habitat heterogeneity index. In addition,field marking-and-capture studies were cond

关键词： western tarnished plant bug cotton IPM ecological pest management alternate host management

neurocircuit regeneration by extracellular matrix reprogramming

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neural Regeneration Research 2025年第8期20卷 2300-2301页

作者： Shengzhang Su Ian n.Levasseur Kimberly M.Alonge Department of Medicinal Chemistry University of WashingtonSeattleWAUSA Department of Chemistry University of WashingtonSeattleWAUSA Department of Medicine University of Washington Medicine Diabetes InstituteSeattleWAUSA

The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

关键词： matrix programming

Vagus nerve stimulation in intracerebral hemorrhage:the need for further research

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neural Regeneration Research 2025年第11期20卷 3213-3214页

作者： Sheharyar S.Baig Ali n.Ali Arshad Majid Sheffield Institute for Translational neuroscience Division of NeuroscienceThe University of SheffieldSheffieldUK

Vagus nerve stimulation(VnS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical *** chronic ischemic stroke,invasive VnS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

关键词： stimulation acute

A question on partial CAP-subgroups of finite groups

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Science China Mathematics 2012年第5期55卷 961-966页

作者： BALLESTER-BOLInCHES Adolfo ESTEBAn-ROMERO ramón LI YangMing Departament d'Àlgebra Universitat de ValènciaBurjassot 46100ValènciaSpain Institut Universitari de Matemàtica Pura i Aplicada Universitat Politècnica de ValènciaValència 46022Spain Department of Mathematics Guangdong University of EducationGuangzhou 510310China

A subgroup H of a finite group G is a partial CAP-subgroup of G if there is a chief series of G such that H either covers or avoids every chief factor of the *** structural impact of the partial cover and avoidance property of some distinguished subgroups of a group has been studied by many ***,there are still some open questions which deserve an *** purpose of the present paper is to give a complete answer to one of these questions.

关键词： finite groups minimal subgroups partial cover and avoidance property saturated formations