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Cancer immunotherapy with envelopedself-amplifying mRNA CARG-2020 thatmodulates IL-12,IL-17 and PD-L1 pathways toprevent tumor recurrence

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Acta Pharmaceutica Sinica B 2024年第1期14卷 335-349页

作者： Ju Chen Bhaskara Reddy Madina Elham Ahmadi Timur Olegovich Yarovinsky marie marthe krady Eileen Victoria Meehan Isabella China Wang Xiaoyang Ye Elise Pitmon Xian-Yong Ma Bijan Almassian Valerian Nakaar Kepeng Wang Department of Immunology School of MedicineUniversity of Connecticut Health CenterFarmingtonCT 06030USA CaroGen Corporation FarmingtonCT 06030USA The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine Foshan Hospital of Traditional Chinese MedicineFoshan 528000China The Loomis Chaffee School WindsorCT 06095USA

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for ***,we describe the application of virus-like vesicles(VLV)for delivery of three immunomodulators alone and in combination,as a promising approach for cancer *** vectors were designed to deliver single chain interleukin(IL)-12,shorthairpin RNA(shRNA)targeting programmed death ligand 1(PD-L1),and a dominant-negative form of IL-17 receptor A(dn-IL17RA)as a single payload or as a combination *** delivery of the VLV vector expressing IL-12 alone,as well as the trivalent vector(designated CARG-2020)eradicated large established ***,only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice,indicating a benefit of the combined *** abscopal effects of CARG-2020 on the non-injected contralateral tumors,as well as protection from the tumor cell re-challenge,suggest immune-mediated mechanism of protection and establishment of immunological ***,CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting *** ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

关键词： Virus-like vesicles Oncolytic virus IL-12 IL-17 PD-L1 T cell exhaustion Combination therapy Cancer immunotherapy

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Digital Twin-Assisted Semi-Federated Learning Framework for Industrial Edge Intelligence

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China Communications 2024年第5期21卷 314-329页

作者： Wu Xiongyue Tang Jianhua marie Siew Shien-Ming Wu School of Intelligent Engineering South China University of TechnologyGuangzhou 511442China Electrical and Computer Engineering Department Carnegie Mellon UniversityPittsburghPA 15213United States

The rapid development of emerging technologies,such as edge intelligence and digital twins,have added momentum towards the development of the Industrial Internet of Things(IIo T).However,the massive amount of data generated by the IIo T,coupled with heterogeneous computation capacity across IIo T devices,and users’data privacy concerns,have posed challenges towards achieving industrial edge intelligence(IEI).To achieve IEI,in this paper,we propose a semi-federated learning framework where a portion of the data with higher privacy is kept locally and a portion of the less private data can be potentially uploaded to the edge *** addition,we leverage digital twins to overcome the problem of computation capacity heterogeneity of IIo T devices through the mapping of physical *** formulate a synchronization latency minimization problem which jointly optimizes edge association and the proportion of uploaded nonprivate *** the joint problem is NP-hard and combinatorial and taking into account the reality of largescale device training,we develop a multi-agent hybrid action deep reinforcement learning(DRL)algorithm to find the optimal *** results show that our proposed DRL algorithm can reduce latency and have a better convergence performance for semi-federated learning compared to benchmark algorithms.

关键词： digital twin edge association industrial edge intelligence(IEI) semi-federated learning

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Photovoltaic waste management in sub-Saharan Africa:current practices in Burkina Faso

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Waste Disposal and Sustainable Energy 2024年第2期6卷 271-282页

作者： Kodami Badza Yrebegnan Moussa Soro marie Sawadogo Laboratoire Energies Renouvelables et EfficacitéEnergétique Institut International d'Ingenierie de I'Eau et de I'Environnement(2iE)01 BP 594 OuagadougouBurkina Faso

Sub-Saharan Africa is witnessing a proliferation of photovoltaic(PV)waste due to the increasing number of solar PV power *** waste(panels,batteries,electrical cables,mounting structures,and inverters)consists of elements such as mercury,cadmium,chromium,lead,copper,aluminum,fluorinated compounds,and plastics that are toxic to human health and the environment if a proper management system is not *** many studies worldwide have focused on PV waste management,very few have been conducted in sub-Saharan *** study aims to investigate the current PV waste management system in Burkina Faso,determine stakeholder profiles,and propose strategies to enhance the existing *** research,interviews,questionnaires,and field visits were used in the *** survey showed that young people,mainly under 30 years of age and with a primary education,dominate(70%)in terms of PV waste collection and repair activities,while the more technical recycling and export activities are carried out mainly(88%)by stakeholders older than 40 years and with a secondary education(60%).Among the older stakeholders,100%are aware of the hazardous nature of PV waste,whereas 36%are young *** an environmental perspective,the main source of contamination observed is the release of lead-rich sulfuric acids into water and soil during the collection and repair *** the recycling of batteries and electrical cables,toxic fumes are emitted into the air,and recycling residues rich in toxic substances are *** reduce risks to human health and the environment when managing PV waste,the introduction of legislation,the multiplication of collection points and appropriate infrastructures,the training and awareness-raising of stakeholders,and the extended responsibility of manufacturers are *** on the economic feasibility of setting up formal management structures are needed to complete this work.

关键词： Photovoltaic waste Sub-Saharan Africa Waste management Recycling Batteries Incineration

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Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

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Neural Regeneration Research 2024年第3期19卷 536-541页

作者： Georges Jourdi Samuel Fleury Imane Boukhatem marie Lordkipanidzé Research Center Montreal Heart InstituteMontrealQCCanada Faculty of Pharmacy Universitéde MontréalMontrealQCCanada UniversitéParis Cité INSERMInnovative Therapies in HaemostasisParisFrance Service d’Hématologie Biologique AP-HPHôpital LariboisièreParisFrance

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical *** p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and *** cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and *** is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic *** p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open *** this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative *** also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis biomarker dementia diabetic neuropathy nerve growth factor receptor(NGFR) neurodegeneration p75^(NTR) schizophrenia

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A Review on Sources,Extractions and Analysis Methods of a Sustainable Biomaterial:Tannins

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Journal of Renewable Materials 2024年第3期12卷 397-425页

作者： Antonio Pizzi marie-Pierre Laborie Zeki Candan LERMAB University of LorraineFaculty of SciencesBlvd des AiguillettesNancy54000France Chair of Forest Biomaterials Institute of Earth and Environmental SciencesUniversity of FreiburgFreiburgGermany Freiburg Materials Research Center Alberst Ludwig University of FreiburgFreiburg79104Germany Department of Forest Products Engineering Faculty of ForestryIstanbul UniversitySariyerIstanbul34473Turkey

Condensed and hydrolysable tannins are non-toxic natural polyphenols that are a commercial commodity industrialized for tanning hides to obtain leather and for a growing number of other industrial applications mainly to substitute petroleum-based *** are a definite class of sustainable materials of the forestry *** have been in operation for hundreds of years to manufacture leather and now for a growing number of applications in a variety of other industries,such as wood adhesives,metal coating,pharmaceutical/medical applications and several *** review presents the main sources,either already or potentially commercial of this forestry by-materials,their industrial and laboratory extraction systems,their systems of analysis with their advantages and drawbacks,be these methods so simple to even appear primitive but nonetheless of proven effectiveness,or very modern and *** constitutes a basic but essential summary of what is necessary to know of these sustainable *** doing so,the review highlights some of the main challenges that remain to be addressed to deliver the quality and economics of tannin supply necessary to fulfill the industrial production requirements for some materials-based uses.

关键词： Tannins flavonoids sources extraction methods analysis methods

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Development of PROTACS degrading KRAS and SOS1

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Oncology Research 2024年第8期32卷 1257-1264页

作者： GERHARD HAMILTON marie-THERESE EGGERSTORFER SANDRA STICKLER Institute of Pharmacology Medical University of ViennaVienna1090Austria

The Kirsten rat sarcoma virus—son of sevenless 1(KRAS-SOS1)axis drives tumor growth preferentially in pancreatic,colon,and lung ***,KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of ***,the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%,lasting for a mean period of 8 *** approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras(PROTACs),which degrade the proteins of interest and exhibit much higher antitumor activity through multiple cycles of ***,PROTACs have been developed based on KRAS-or SOS1-directed inhibitors coupled to either von Hippel-Lindau(VHL)or Cereblon(CRBN)ligands that invoke the proteasomal *** of these PROTACs show increased activity in vitro and in vivo compared to their cognate inhibitors but their toxicity in normal tissues is not *** CRBN PROTACs containing thalidomide derivatives cannot be tested in experimental *** to such PROTACS arises through downregulation or inactivation of CRBN or factors of the functional VHL E3 ubiquitin *** highly active KRAS and SOS1 PROTACs have been formulated their clinical application remains difficult.

关键词： Proteolysis-targeting chimeras(PROTACs) Kirsten rat sarcoma virus(KRAS) Son of sevenless 1(SOS1) Von Hippel-Lindau Cereblon

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SmartMicro Grid Energy System Management Based on Optimum Running Cost for Rural Communities in Rwanda

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Energy Engineering 2024年第7期121卷 1805-1821页

作者： Fabien Mukundufite Jean marie Vianney Bikorimana Alexander Kyaruzi Lugatona Electrical and Electronic Engineering Department University of RwandaKigaliRwanda Electrical Engineering Department University of Dar es SalaamDar es SalaamTanzania

The governmental electric utility and the private sector are joining hands to meet the target of electrifying all households by ***,the aforementioned goal is challenged by households that are scattered in remote *** far,Solar Home Systems(SHS)have mostly been applied to increase electricity access in rural *** have continuous constraints to meet electricity demands and cannot run income-generating *** current research presents the feasibility study of electrifying Remera village with the smart microgrid as a case *** renewable energy resources available in Remera are the key sources of electricity in that *** generation capacity is estimated based on the load *** microgrid configurations are simulated with HOMER,and the genetic algorithm is used to analyze the optimum *** analyzing the impact of operation and maintenance costs,the results show that the absence of subsidies increases the levelized cost of electricity(COE)five times greater than the electricity price from the public *** microgrid made up of PV,diesel generator,and batteries proved to be the most viable solution and ensured continuous power supply to *** considering the subsidies,COE reaches 0.186$/kWh,a competitive price with electricity from public utilities in Rwanda.

关键词： Load demand load profile optimum running cost power demand satisfaction smart meters and smart micro grid

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Foraging valor linked with aggression:selection against completely abandoning aggression in the high-elevation ant Tetramorium alpestre?

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Insect Science 2024年第3期31卷 953-970页

作者： marie-Luise Contala Patrick Krapf Florian M.Steiner Birgit C.Schlick-Steiner Molecular Ecology Group Department of EcologyUniversitat InnsbruckInnsbruckAustria rganismal&Evolutionary Biology Research Programme University of HelsinkiHelsinkiFinland

Aggression has multiple benefits and is often coupled with other behaviors("behavioral syndromes").The level of aggressiveness is influenced by an adaptive benefit-cost ratio suggesting that benefits should outweigh the costs of ***,we assess if several behaviors are coupled in two behaviorally different populations(aggressive,peaceful)of the high-elevation ant Tetramorium *** three weeks,we collected colony fragments and analyzed boldness,exploring,foraging,and risk-taking *** hypothesized that the aggressive population is bolder,more explorative and risk-prone,and forages more food than the peaceful *** test whether(a)the combination of experiments and parameters used yields a good setup,(b)populations differ behaviorally,and(c)populations display behavioral syndromes,we assessed(a)the frequency of repeatable behaviors of each experiment,(b)the behavioral means among populations,and(c)the behavioral repeatability,*** found that(a)boldness and exploring were most repeatable and represent a good experimental setup,(b)the aggressive population was bolder and more explorative and risk-prone than the peaceful population,(c)boldness and exploring behaviors were highly repeatable in both populations,thus corroborating our *** results suggest that boldness,exploring,and risk-taking but not foraging are presumably coupled with aggression and indicate the presence of behavioral syndromes in this *** specific ecological conditions,aggression may be coupled with other behaviors and important for finding *** is probably adaptive in ***,possibly indicating that selection favors aggression at least partially,which may counteract the complete loss of intraspecific aggression.

关键词： adaptive value behavioral syndromes boldness exploration repeatability trade-off

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Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

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World Journal of Hepatology 2024年第4期16卷 650-660页

作者： Dorothy Liu Mark M Youssef Josephine A Grace marie Sinclair Department of Gastroenterology Austin HealthMelbourne 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthMelbourne 3084VictoriaAustralia Department of Medicine University of MelbourneMelbourne 3084VictoriaAustralia

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant *** immunosuppression has been shown to contribute to post-transplant malignancy(PTM)*** is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of *** inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour *** transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this ***,there is limited clinical data on this subject in both LT and other solid organ transplant *** To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ *** A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August *** terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the *** lists of retrieved articles were also reviewed to identify any additional *** duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in ***-text articles were assessed for eligibility based on pre-specified inclusion and exclusion *** A total of 6 studies were included in this *** studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol us

关键词： Immunosuppression Solid organ transplantation Liver transplantation Carcinogenicity Tacrolimus Mycophenolate

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Defense and senescence interplay in legume nodules

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Plant Communications 2024年第4期5卷 112-126页

作者： Fathi Berrabah Farouk Benaceur Chaoyan Yin Dawei Xin Ke´vin Magne marie Garmier Veronique Gruber Pascal Ratet Faculty of Sciences University Amar Telidji03000 LaghouatAlgeria Research Unit of Medicinal Plants(RUMP) National Center of Biotechnology ResearchCRBt25000 ConstantineAlgeria Universite´Paris-Saclay CNRSINRAEUniversity of EvryInstitute of Plant Sciences Paris-Saclay(IPS2)91190 Gif-sur-YvetteFrance Universite´Paris Cite´ Institute of Plant Sciences Paris-Saclay(IPS2)91190 Gif-sur-YvetteFrance Key Laboratory of Soybean Biology in the Chinese Ministry of Education College of AgricultureNortheast Agricultural UniversityHarbin 150030China These authors contributed equally to this article.

Immunity and senescence play a crucial role in the functioning of the legume symbiotic *** miss-regulation of one of these processes compromises the symbiosis leading to death of the endosymbiont and the arrest of the nodule *** relationship between immunity and senescence has been exten-sively studied in plant organs where a synergistic response can be ***,the interplay be-tween immunity and senescence in the symbiotic organ is poorly discussed in the literature and these phe-nomena are often mixed *** studies revealed that the cooperation between immunity and senescence is not always observed in the nodule,suggesting complex interactions between these two pro-cesses within the symbiotic ***,we discuss recent results on the interplay between immunity and senescence in the nodule and the specificities of this relationship during legume-rhizobium symbiosis.

关键词： immunity senescence symbiosis nodules legumes rhizobia

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