Main Hub Research Articles

Gut-liver axis: Potential mechanisms of action of food-derived extracellular vesicles.

Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.

Intermodal Transportation Challenges in Eastern Europe: Case Study of Romania

Abstract The purpose of this paper is to analyze data from the Romanian intermodal transportation sector and provide an overview of its main terminals (sea, river, road and rail) and the operational challenges faced by its most important logistics service providers. Intermodal transportation (by rail) is encouraged at EU level as a sustainable alternative to current predominant truck haulage. Most research articles outline issues with connectivity, terminal handling infrastructure and cost efficiency as factors hindering large scale adoption. Other authors tend to emphasize the more reliable delivery schedules, reduced road congestion and emissions as drivers of cost competitiveness on medium term. Relevant cargo volume traffic (tons, TEU and ITU) is analyzed at Romania’s main intermodal hubs in the last 10 years (2014-2023) using quantitative and qualitative data to provide a comprehensive overview of its overall competitiveness in this sector. Most Eastern European countries are faced with the same challenge in terms of intermodal transportation: the shortcomings of their supporting network due to insufficient public investment, highlighted by the results from Romania (case study method). Main results show Constanta Port had record cargo traffic in 2023, but its throughput is hindered by constant congestion issues, similar to the highly competitive road sector where intense truck traffic creates bottlenecks on the major roads leading to Western Europe. Cargo is also shipped via the Danube and freight trains, but to a limited extent due to low average speeds and inconsistent reliability along most sectors. The paper highlights the importance of a country’s strategic hubs and their connectivity (sea and/or river ports, main railway lines and road sectors) as a source of future growth and development perspectives, for terminal operators as well as neighboring regions (EU and EEA) through increased business activity.

Study on pedestrian accessibility from urban transportation hubs to tourist destinations: A case of Shanghai Yuyuan station to Yuyuan garden

Public transportation is a crucial means for tourists to visit urban attractions. This study aims to explore pedestrian accessibility from tourist destinations to urban transportation hubs, using the renowned Yuyuan Garden in Shanghai as a case study and employing spatial syntax methodology. By investigating spatial relationships and accessibility levels from the perspectives of depth and choice. The research finds that the main transportation hubs around the Yuyuan Garden area have a limited capacity to attract visitors, and visitors have limited choices when it comes to using public transportation. Additionally, there are barriers from transportation hubs to the entrance of the tourist area, and some segments of accessibility overlap, posing challenges for the operation of the tourist area, especially during specific festivals. The study emphasizes the significance of the straightforward data acquisition method of spatial syntax for further research on transportation network accessibility, as well as the layout of commercial areas, tourist attractions, and historic districts. However, it also highlights the limitations of spatial syntax, including its abstraction, disregard for temporal attributes, and insufficient qualitative analysis. It acknowledges the subjectivity inherent in pedestrian accessibility and model creation.

FORMATION OF THE STRUCTURE OF TRANSPORT AND TRANSFER NODES OF THE HIGH-SPEED RAILWAY NETWORK

On the basis of a systematic approach, the prospects for forming the structure of high-quality rubber in Ukraine are analyzed. The structure is examined on three hierarchical levels: regional, local, object. The regional structure to improve living standards and economic efficiency is proposed to be formed in three stages. With the help of variable design and analogues, promising routes and lines of program implementation are identified. At the local level, the main regional transport hubs of Ukraine were analyzed and the structures of the high-grade liquids in them were included. On the objective level, the functional skeleton of two types of transport nodes has been identified. Possible ways to improve comfort have been analyzed. The fragmented structure can become a butt for accomplishing similar tasks within other world regions.

Studies on the PII-PipX-NtcA Regulatory Axis of Cyanobacteria Provide Novel Insights into the Advantages and Limitations of Two-Hybrid Systems for Protein Interactions.

Yeast two-hybrid approaches, which are based on fusion proteins that must co-localise to the nucleus to reconstitute the transcriptional activity of GAL4, have greatly contributed to our understanding of the nitrogen interaction network of cyanobacteria, the main hubs of which are the trimeric PII and the monomeric PipX regulators. The bacterial two-hybrid system, based on the reconstitution in the E. coli cytoplasm of the adenylate cyclase of Bordetella pertussis, should provide a relatively faster and presumably more physiological assay for cyanobacterial proteins than the yeast system. Here, we used the bacterial two-hybrid system to gain additional insights into the cyanobacterial PipX interaction network while simultaneously assessing the advantages and limitations of the two most popular two-hybrid systems. A comprehensive mutational analysis of PipX and bacterial two-hybrid assays were performed to compare the outcomes between yeast and bacterial systems. We detected interactions that were previously recorded in the yeast two-hybrid system as negative, as well as a "false positive", the self-interaction of PipX, which is rather an indirect interaction that is dependent on PII homologues from the E. coli host, a result confirmed by Western blot analysis with relevant PipX variants. This is, to our knowledge, the first report of the molecular basis of a false positive in the bacterial two-hybrid system.

Crafting resilience: persistence and adaptation of the ceramic manufacture at Roca Vecchia from the Middle to the Final Bronze Age phases

Through the second millennium BC, Bronze Age communities of Southern Italy have shown a remarkable degree of resilience in coping with changes in both macro-trends of cultural interaction and the landscape. In this paper, we will examine long-term processes of adaptation to shifting historical and environmental conditions from the vantage point of the impasto ware production at the site of Roca Vecchia (Melendugno-Lecce, IT), one of the main hubs of interaction for the Bronze Age of the Central Mediterranean. Sixty-eight ceramic individuals coming from the Middle to the Final Bronze Age levels and seven soil deposits from the site surroundings were analysed by petrography and fifteen were selected for SEM–EDX examination. We explore how changes in the complex history of the settlement and the surrounding landscape are matched in technological choices operated by the community of practice responsible for producing impasto pottery at Roca, in a moment when the long-range connection with the Aegean world was at its historical peak.

Proteomics Study of Benzene Metabolite Hydroquinone Induced Hematotoxicity in K562 Cells

ObjectiveHydroquinone (HQ), one of the phenolic metabolites of benzene, is widely recognized as an important participant in benzene-induced hematotoxicity. However, there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn't been fully understood yet. MethodsIn this study, we treated K562 cells with 40 μmol/L HQ for 72 h, examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring (PRM), and performed bioinformatics analysis to identify interaction networks. ResultsOne hundred and eighty-seven upregulated differentially expressed proteins (DEPs) and 279 downregulated DEPs were identified in HQ-exposed K562 cells, which were involved in neutrophil-mediated immunity, blood microparticle, and other GO terms, as well as the lysosome, metabolic, cell cycle, and cellular senescence-related pathways. Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways, we constructed the network of protein interactions and determined 6 DEPs (STAT1, STAT3, CASP3, KIT, STAT5B, and VEGFA) as main hub proteins with the most interactions, among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity. ConclusionOur work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.

Effectiveness of Billion Trees Tsunami Afforestation Projects in restoration of forests in Pakistan

AbstractThe history of forest cover dynamics in Pakistan reveals an unsatisfactory environmental situation. In the past 5 decades, particularly during the period between 1990 and 2010, the country lost an average of 41,100 hectares of green cover with a deforestation rate of 1.6% per year. The factors behind that this high deforestation rate is numerous including socio-economic transformation after the major political change during the 1970s in the mountainous areas of Pakistan, demographic changes, accessibility improvements, and land use changes. Several social forestry campaigns have been launched over time to cope with this socioecological and environmental issue. However, most of them have not been very effective due to certain shortcomings. This study aims to evaluate the effectiveness of the most recent and history’s biggest forest restoration program initiated by the government of the Khyber Pakhtunkhwa Province called the Billion Trees Tsunami Afforestation Project (BTTAP). This project was announced in 2013 when a new political party, Pakistan Tehreek-e-Insaf, came into power. The study is focused on one of the main forest hubs of the country in the Hindukush Mountains spanning five districts. Forest cover in this study area decreased from 20 to 2% between 1990 and 2010. After the launch of the BTTAP, the forest cover increased considerably from 2 to 35% by the year 2021. This growth was achieved through planting new trees, banning forest cutting, practicing surveillance, and enhancing community participation. If the project continues and the protection measures are not suspended, it can play a historical role in forest restoration.

Integrated proteomic, transcriptomic, and metabolomic profiling reveals that the gibberellin-abscisic acid hub runs flower development in the Chinese orchid Cymbidium sinense.

The seasonal flowering Chinese Cymbidium produce an axillary floral meristem and require a dormancy period during cold conditions for flower development. However, the bud activation mechanism remains elusive. This study evaluates the multi-omics across six stages of flower development, along with functional analysis of core genes to decipher the innate mechanism of floral bud initiation and outgrowth in the Chinese orchid Cymbidium sinense. Transcriptome and proteome analyses identified 10 modules with essential roles in floral bud dormancy and activation. Gene clusters in the early stages of flower development were mainly related to flowering time regulation and meristem determination, while the late stages were correlated with hormone signaling pathways. The metabolome identified 69 potential hormones in which gibberellin (GA) and abscisic acid (ABA) were the main regulatory hubs, and GA4 and GA53 exhibited a reciprocal loop. Extraneous GA application caused rapid elongation of flower buds and promoted the expression of flower development genes. Contrarily, exogenous ABA application extended the dormancy process and ABA inhibitors induced dormancy release. Moreover, CsAPETALA1 (CsAP1) was identified as the potential target of ABA for floral bud activation. Transformation of CsAP1 in Arabidopsis and its transient overexpression in C. sinense protoplasts not only affected flowering time and floral organ morphogenesis in Arabidopsis but also orchestrated the expression of flowering and hormone regulatory genes. The presence of ABA response elements in the CsAP1 promoter, rapid downregulation of CsAP1 after exogenous ABA application, and the activation of the floral bud after ABA inhibitor treatment suggest that ABA can control bud outgrowth through CsAP1.

Heavy Metals in Common Fishes Consumed in Dhaka, a Megacity of Asia: A Probabilistic Carcinogenic and Non-Carcinogenic Health Hazard.

Heavy metal contamination of fish is a serious public health concern worldwide, including in Bangladesh. In this study, six commonly consumed fish species namely Hilsha (Tenualosa ilisha), Kachki (Corica soborna), Punti (Puntitus ticto), Taki (Channa punctatus), Meni (Nandus nandus), and Tengra (Mystus tengara) were analyzed for arsenic (As), cadmium (Cd), lead (Pb), zinc (Zn), copper (Cu), chromium (Cr), manganese (Mn), and nickel (Ni), by inductively coupled plasma mass spectrometry. The fish samples were collected from wholesale markets in Dhaka city, the main business hub of Bangladesh where the fishes converged from countrywide and are redistributed to the whole city. The metal concentration varied among the studied fish species. Hilsha, the national fish of Bangladesh, contained the highest As among the other fishes of this study, whereas Zn, Cd, Cu, Mn, and Ni were the highest in Kachki, and Pb and Cr were the highest in Tengra. The probable source of metal accumulation in the fish species may be the river or marine water that can be contaminated by industrial waste, pesticide, and/or fertilizer use in agriculture and/or commercial fish feeds. All analyzed fish species showed serious heavy metal pollution, having high average pollution load index (APLI) values (> 1). The estimated daily intake (EDI) values for the metals were lower than the maximum tolerable daily intake (MTDI). The hazard index (HI) for all the fish species was above 1 for adults, showing non-carcinogenic health risks. The targetcarcinogenic risk (TCR) values were below the acceptable limit (10-4) for most of the metals, indicating safe for consumption with respect to the risk of cancer.

Diagnosis of the main forest hubs in Paraná to mitigate climate change

In order to fulfill Brazil’s climate change mitigation goals and uphold its environmental commitments, it is crucial to have knowledge of volume, biomass, and carbon stocks of its native forests. This study aimed to evaluate the potential of the forest hubs from the state of Paraná, Brazil, towards climate change mitigation efforts. The Guarapuava hub possesses the largest area of native forests and the largest stored stock of volume, biomass, carbon, and carbon dioxide equivalent, while Sengés has the smallest area and the lowest stocks. Apart from Telêmaco Borba, which has only 12% of its native forests within Conservation Units, all the other hubs have more than 35% of their native area inside these locations. This emphasizes the significance of establishing and maintaining these Units. The total wood volume found was 276,136,486 m³, the total biomass 367,233,059 Mg, the total carbon 173,652,842 Mg, and the carbon dioxide equivalent 636,727,087 Mg. These values indicate that native forests can help mitigate climate change by sequestering carbon dioxide from the atmosphere.

Illegal wildlife trade: An analysis of carnivore products found in markets in Benin and Niger

West Africa is home to one of the largest protected area systems in Africa, the W-Arly- Pendjari (WAP) Complex, which provides a last refuge for many threatened carnivore species extirpated from most other protected areas in the region. However, rising global demand for wildlife products has increased concerns about the impacts of Illegal Wildlife Trade (IWT) on these species. To assess the extent of IWT, covert market surveys were conducted in Benin and Niger to identify wildlife products and derivatives coming from carnivore species (African civet, serval, caracal, lion, cheetah, leopard, and spotted hyena) suspected to be targeted by IWT. When possible, information about product origin was gathered to understand trading routes. Data were analysed to determine if products were available in markets due to their proximity to source populations or due to accessibility to trade and transport hubs. A variety of products from several threatened species, including multiple lion skins, were found in Benin and Niger. Products were found more frequently in markets near the WAP Complex and main trade and transport hubs. Sellers reported that a large majority of products originated from international trade, but some could also have been sourced from the WAP Complex. There was little evidence indicating that product availability was more affected by the distance to the WAP Complex than by the distance to international transport hubs, suggesting that trade was widespread across both countries. The study provides an evidence base and monitoring baselines to identify and assess interventions to address IWT and ultimately reduce illegal trafficking of wildlife.

Analysis of the risks of investing in the regional transport industry using the example of the Moscow region

This paper examines the significance of the development of the regional transport industry using the example of the Moscow region, which is currently the main transport hub between Moscow and the regions. An analysis of the general risks of the regional transport industry was carried out, which included the following groups: macroeconomic, geopolitical, environmental and technological, operational, tariff, etc. It was established that when implementing projects in the transport sector, not all financial responsibility should lie exclusively with the public sector. It is necessary to attract private investors interested in using transport services to participate in such projects. In this connection, an investment mechanism for the development of the regional transport industry arises in the form of public-private partnership. The relevance of this conclusion for the object of study is confirmed by statistical data on the location of the Moscow region in first place in the ranking of regions in terms of the level of development of these projects. The paper provides a classification of the risks of investing in the regional transport industry according to risk manageability criteria, according to participants in the investment mechanism, as well as a possible risk management mechanism. It has been established that regional management must draw up a risk map and develop methods and mechanisms for managing investment risks in order to minimize adverse consequences and achieve the objectives of sustainable development of the region’s transport industry. Reducing risks and threats to Russia's economic security within the transport industry makes it possible to solve internal problems and obtain a synergistic effect, ultimately increasing the competitiveness of the national economy and contributing to its stable growth.

Analysis of Road Infrastructure Problems in Urban City, Karachi

Road infrastructure is a significant part of the economic development of countries. Better performance of road communication system is significant part of all over the world. Developed countries make a significant effort for designing a well-managed traffic arrangement for the individuals. Furthermore, an efficient transport system is the key element for improving the country's economic conditions. Sustainable and efficient traffic management system is the backbone for humanizing the economic growth of developing countries. In case of Pakistan, Karachi is the main industrial hub for whole country's economy and accommodates enormous number of migrants. Due to this reason the population of city is increasing day by day. This paper presents the current situation of road infrastructure troubles in Karachi. The urban city is facing several numbers of issues that were already documented by researchers such as traffic congestion and road safety problems. On an urgent basis an efficient mass transit system is required to reduce the traffic jam conditions. The transport system of Karachi requires instant proper management rules and designed transport facilities. The aim of the paper is to identify the main traffic problems of the large urban city, Karachi, which is faced by the people in their daily life and to suggest recommendations for reducing the current situation related to traffic management strategies. The research methodology for this paper will be based on qualitative analysis of the road infrastructure troubles that are identified by the individuals through interviews and detailed group meetings.

Anti-feminism as anti-establishment and emancipatory: the gendered metapolitics of Incel

ABSTRACT In recent years Incel 1 has become a regularly cited example of extreme contemporary misogyny and antifeminism. This paper develops existing understandings of the phenomenon and contextualises Incel as in important ways the product of a painful embrace of neoliberal ideas about market outcomes and social value, expressed through the practices and rhetoric associated with gender relations in this era, with an emphasis on its gendered metapolitical constitution and vision. This is achieved in two steps. Based on a close thematic analysis of textual data collected from the main hub of Incel discourse, other Incel texts, and elements of digital ethnography, I first draw attention to the Incel worldview’s interpretation of the neoliberal era as uniformly pro-feminist and note how in doing so collapses the distinction between women, feminists, and elite power. Second, I highlight how this interpretation informs the self-ascription of transgressive and emancipatory qualities, which serve as additional animating logics in Incel hatred of feminism, feminists, and women. I conclude by suggesting that this approach allows for a more productive understanding of the Incel phenomenon and the role of antifeminism and misogyny within it, which includes complicating Incel’s purported parallels with the far-right.

Mitochondria: the gatekeepers between metabolism and immunity.

Metabolism and immunity are crucial monitors of the whole-body homeodynamics. All cells require energy to perform their basic functions. One of the most important metabolic skills of the cell is the ability to optimally adapt metabolism according to demand or availability, known as metabolic flexibility. The immune cells, first line of host defense that circulate in the body and migrate between tissues, need to function also in environments in which nutrients are not always available. The resilience of immune cells consists precisely in their high adaptive capacity, a challenge that arises especially in the framework of sustained immune responses. Pubmed and Scopus databases were consulted to construct the extensive background explored in this review, from the Kennedy and Lehninger studies on mitochondrial biochemistry of the 1950s to the most recent findings on immunometabolism. In detail, we first focus on how metabolic reconfiguration influences the action steps of the immune system and modulates immune cell fate and function. Then, we highlighted the evidence for considering mitochondria, besides conventional cellular energy suppliers, as the powerhouses of immunometabolism. Finally, we explored the main immunometabolic hubs in the organism emphasizing in them the reciprocal impact between metabolic and immune components in both physiological and pathological conditions.

Global trends and developments in mindfulness interventions for diabetes: a bibliometric study

BackgroundDiabetes is a metabolic disorder posing a global threat to health. Many scholars are dedicated to developing non-pharmacological therapies, and mindfulness intervention is among the potentially effective approaches. Due to the rapid increase in relevant research in recent years, along with the diverse focus and interventions used in studies, it has become challenging for practitioners to quickly comprehend the key features of this field and the directions worth paying attention to. Bibliometric analysis, in response, can help scholars understand this field and identify points of interest.MethodsPublications related to mindfulness intervention in diabetes from the establishment of the Web of Science Core Collection (WOSCC) to September 2023 were searched. We employed four bibliometric techniques: General Analysis of Publications, Collaborative Network Analysis, Co-citation Analysis, and Keyword Analysis. The CiteSpace 6.1.R was used to analyze the literature with the strongest citation bursts, while VOSviewer 1.6.13 was used to provide visualizations of publicly available data by analyzing co-citations or co-authorship affiliations.ResultsWe found a total of 387 articles. The results indicate that research on this topic has been steadily increasing over time. The United States is the top producer of relevant publications, with Tilburg University being the institution that publishes the most articles. The journal “Mindfulness” has the highest publication count. In the collaborative network analysis, the United States emerged as the main hub for global cooperation in this research field, contributing 182 articles with a total of 5872 citations. The journal “Diabetes Care” was frequently cited and played a central role. The keyword analysis revealed that researchers have shown a strong interest in how mindfulness interventions affect the mental health of diabetic individuals. Additionally, there is a focus on studying elderly diabetic groups and exploring how mindfulness interventions impact metabolic diseases. These areas are currently the main research priorities.ConclusionOur findings demonstrate the current trend and hotspots in mindfulness intervention and offer some directions for future research.

Phenotypic divergence between broiler and layer chicken lines is regulated at the molecular level during development

BackgroundUnderstanding the molecular underpinnings of phenotypic variations is critical for enhancing poultry breeding programs. The Brazilian broiler (TT) and laying hen (CC) lines exhibit striking differences in body weight, growth potential, and muscle mass. Our work aimed to compare the global transcriptome of wing and pectoral tissues during the early development (days 2.5 to 3.5) of these chicken lines, unveiling disparities in gene expression and regulation.ResultsDifferent and bona-fide transcriptomic profiles were identified for the compared lines. A similar number of up- and downregulated differentially expressed genes (DEGs) were identified, considering the broiler line as a reference. Upregulated DEGs displayed an enrichment of protease-encoding genes, whereas downregulated DEGs exhibited a prevalence of receptors and ligands. Gene Ontology analysis revealed that upregulated DEGs were mainly associated with hormone response, mitotic cell cycle, and different metabolic and biosynthetic processes. In contrast, downregulated DEGs were primarily linked to communication, signal transduction, cell differentiation, and nervous system development. Regulatory networks were constructed for the mitotic cell cycle and cell differentiation biological processes, as their contrasting roles may impact the development of distinct postnatal traits. Within the mitotic cell cycle network, key upregulated DEGs included CCND1 and HSP90, with central regulators being NF-κB subunits (RELA and REL) and NFATC2. The cell differentiation network comprises numerous DEGs encoding transcription factors (e.g., HOX genes), receptors, ligands, and histones, while the main regulatory hubs are CREB, AR and epigenetic modifiers. Clustering analyses highlighted PIK3CD as a central player within the differentiation network.ConclusionsOur study revealed distinct developmental transcriptomes between Brazilian broiler and layer lines. The gene expression profile of broiler embryos seems to favour increased cell proliferation and delayed differentiation, which may contribute to the subsequent enlargement of pectoral tissues during foetal and postnatal development. Our findings pave the way for future functional studies and improvement of targeted traits of economic interest in poultry.

NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype

NOD/Scid IL2Rγnull (NSG) mice reconstituted with peripheral blood mononuclear cells (PBMC) donated by patients with ulcerative colitis or Crohn’s disease highly reflect the respective pathological phenotype. To determine if these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from AD and PV patients were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of AD and PV patients with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network.Following dermal application of DMSO, both NSG-AD and NSG-PV mice exhibited increased clinical, skin and histological scores. Immuno-histochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLPR-expressing monocytes, switched B cells and MCP-3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD and NSG-PV mice differ and partially reflect the respective human disease.

METS-R SIM: A simulator for Multi-modal Energy-optimal Trip Scheduling in Real-time with shared autonomous electric vehicles

We develop an agent-based simulator named METS-R SIM to support operational decisions for multi-modal shared autonomous vehicle (SAEV) services. Compared with existing traffic simulators, METS-R SIM offers several valuable features including: 1) A microscopic vehicle movement model for SAEV services, which allows us to explicitly model vehicular interactions and generate detailed speed and acceleration profiles for energy estimation. 2) An efficient implementation in which parallel computing is embedded in METS-R SIM which can update the state of different agents (e.g., vehicle locations in different links) simultaneously. 3) A modular and extensible framework as the simulator is built upon an agent-based modeling environment named Repast Simphony which is featured by its well-factored abstractions; in addition, a server-client structure is introduced to implement real-time operational algorithms such as energy-efficient routing and adaptive transit scheduling. 4) Open-source, reproducible with web-based visualization (METS-R SIM introduces these features to promote transparency). We validate METS-R SIM by matching the aggregated travel time and travel distance with the real observed ones obtained from New York City (NYC). We also compare the generated speed profiles qualitatively to the ones reported in published studies. We demonstrate the functionalities of our simulator by simulating SAEV services deployed to serve travel needs related to three main transportation hubs in NYC.