Enhanced Huff Model for Estimating Park and Ride (PnR) Catchment Areas in Perth, WA

A train station catchment area delineates the spatial territory from which the users of a train station are drawn. The size and shape of this catchment can be influenced by a variety of factors, such as the transport network, the location of stations and the service quality they offer, as well as the land use density and diversity in the transport corridor. Although numerous studies have been conducted to understand the size of catchment areas, limited research has focused on determining the spatial boundary (shape) of train station catchments. This paper develops a framework for deriving a spatial boundary of a Park and Ride (PnR) catchment area by incorporating the Huff model and Geographic Information Systems (GIS) technologies. The approach is staged, firstly determining the PnR station choice as a function of the attractiveness of a train station and the cost of access between the origin (such as a suburb) and the destination of a trip (such as the Perth CBD). Linear referencing method is then applied to re-define the origins to train stations based on the derived station choice probability. Finally, the spatial boundary of a catchment area is determined according to the adjusted origins, using GIS technologies. The model outputs were evaluated against licence plate survey of station users, where the Kappa coefficient (0.74) and overall accuracy (0.88) statistic suggested that the model's results are robust. The paper then shows how catchment area data can be used to better manage travel demand and plan design solutions aimed at increased accessibility to train stations

Inherently Fluorescent Peanut-Shaped Polymersomes for Active Cargo Transportation

Nanomotors have been extensively explored for various applications in nanomedicine, especially in cargo transportation. Motile properties enable them to deliver pharmaceutical ingredients more efficiently to the targeted site. However, it still remains a challenge to design motor systems that are therapeutically active and can also be effectively traced when taken up by cells. Here, we designed a nanomotor with integrated fluorescence and therapeutic potential based on biodegradable polymersomes equipped with aggregation-induced emission (AIE) agents. The AIE segments provided the polymersomes with autofluorescence, facilitating the visualization of cell uptake. Furthermore, the membrane structure enabled the reshaping of the AIE polymersomes into asymmetric, peanut-shaped polymersomes. Upon laser irradiation, these peanut polymersomes not only displayed fluorescence, but also produced reactive oxygen species (ROS). Because of their specific shape, the ROS gradient induced motility in these particles. As ROS is also used for cancer cell treatment, the peanut polymersomes not only acted as delivery vehicles but also as therapeutic agents. As an integrated platform, these peanut polymersomes therefore represent an interesting delivery system with biomedical potential.</p

SARS-CoV-2: The Monster Causes COVID-19

Coronaviruses are viruses whose particles look like crowns. SARS-CoV-2 is the seventh member of the human coronavirus family to cause COVID-19 which is regarded as a once-in-a-century pandemic worldwide. It holds has the characteristics of a pandemic, which has broy -55ught many serious negative impacts to human beings. It may take time for humans to fight the pandemic. In addition to humans, SARS-CoV-2 also infects animals such as cats. This review introduces the origins, structures, pathogenic mechanisms, characteristics of transmission, detection and diagnosis, evolution and variation of SARS-CoV-2. We summarized the clinical characteristics, the strategies for treatment and prevention of COVID-19, and analyzed the problems and challenges we face

Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivation

Cytotoxic CD8+ T cells play a critical role in controlling herpes simplex virus (HSV) infection and reactivation. However, little is known about the spatiotemporal dynamics of CD8+ T cells during HSV lesion evolution or about their involvement in immune surveillance after lesion resolution. Using quantum dot–conjugated peptide–major histocompatibility complex multimers, we investigated the in vivo localization of HSV-2–specific CD8+ T cells in sequential biopsies of human genital skin during acute, resolving, and healed stages of HSV-2 reactivation. Our studies revealed that functionally active CD8+ T cells selectively infiltrated to the site of viral reactivation. After lesion healing in concert with complete reepithelialization and loss of HSV DNA from skin biopsies, HSV-2–specific CD8+ T cells persisted for more than two months at the dermal–epidermal junction, adjacent to peripheral nerve endings. In two out of the six sequentially studied individuals, HSV-2 DNA reappeared in clinically and histologically normal–appearing skin. Detection of viral DNA was accompanied by increased numbers of both HSV-specific and total CD8+ T cells in the dermis. These findings indicate that the frequency and clinical course of HSV-2 reactivation in humans is influenced by virus-specific CD8+ T cells that persist in peripheral mucosa and genital skin after resolution of herpes lesions

In situ detection of Gag-specific CD8+ cells in the GI tract of SIV infected Rhesus macaques

<p>Abstract</p> <p>Background</p> <p>SIV and HIV predominantly replicate in lymphoid tissue, but the study of virus specific CD8⁺T cells in intact lymphoid tissue is difficult, as traditional <it>in situ </it>tetramer staining requires fresh tissue.</p> <p>Results</p> <p>In this report, we demonstrate a novel technique using Qdot 655-conjugated peptide-MHC multimers to directly visualize SIV specific cells in cryopreserved tissue biopsies from chronically SIVmac239 infected Rhesus macaques. Qdot 655 multimers showed similar sensitivity and specificity to APC-conjugated tetramers by flow cytometry analysis, but yielded ten-fold higher signal intensity when imaged by fluorescence microscopy. Using this technique, we detected CD8⁺T cells which recognize an immunodominant epitope (Gag CM9) in the spleen, lymph nodes, ileum and colon. In all these tissues, the Gag CM9 positive cells were mainly located in the extra follicular T cell zone. In the ileum and colon, we found Gag CM9 positive cells concentrated in Peyer's patches and solitary lymphoid follicles, a pattern of localization not previously described.</p> <p>Conclusions</p> <p>The use of Qdot multimers provide an anatomic and quantitative evaluation of SIV specific CD8⁺T cell responses in SIV pathogenesis, and may prove useful to studies of SIV specific CD8⁺T cell responses elicited by vaccines and other immunotherapies in the non-human primate model.</p

N6-Methyladenosine and Viral Infection

N6-methyladenosine (m6A), as a dynamic posttranscriptional RNA modification, recently gave rise to the field of viral epitranscriptomics. The interaction between virus and host is affected by m6A. Multiple m6A-modified viral RNAs have been observed. The epitranscriptome of m6A in host cells are altered after viral infection. The expression of viral genes, the replication of virus and the generation of progeny virions are influenced by m6A modifications in viral RNAs during virus infection. Meanwhile, the decorations of m6A in host mRNAs can make viral infections more likely to happen or can enhance the resistance of host to virus infection. However, the mechanism of m6A regulation in viral infection and host immune response has not been thoroughly elucidated to date. With the development of sequencing-based biotechnologies, transcriptome-wide mapping of m6A in viruses has been achieved, laying the foundation for expanding its functions and corresponding mechanisms. In this report, we summarize the positive and negative effects of m6A in distinct viral infection. Given the increasingly important roles of m6A in diverse viruses, m6A represents a novel potential target for antiviral therapy

Myelin Activates FAK/Akt/NF-κB Pathways and Provokes CR3-Dependent Inflammatory Response in Murine System

Inflammatory response following central nervous system (CNS) injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI), i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3)-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-κB signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-κB activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin) and myelin basic protein (MBP, one of the major proteins of myelin) are not able to activate NF-κB signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI

In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites

<p>Abstract</p> <p>Background</p> <p>Foot-and-mouth disease virus (FMDV) uses a highly conserved Arg-Gly-Asp (RGD) triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05) and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD) or an Arg-Ser-Asp (RSD) triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals.</p> <p>Results</p> <p>Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that developed typical clinical disease and viremia.</p> <p>Conclusions</p> <p>FMDV quasispecies evolving in a different biological environment gained the capability of selecting different receptor recognition site. The RDD-containing FMD viral genome can accommodate substitutions in the receptor binding site without additional changes in the capsid. The viruses expressing non-RGD receptor binding sites can replicate stably in vitro and produce typical FMD clinical disease in susceptible animals.</p

A Comparative Study on the Psychological Health of Frontline Health Workers in Wuhan Under and After the Lockdown

Background: The coronavirus disease-2019 (COVID-19) outbreak and a 3-month lockdown of Wuhan may have had a long-term impact on the mental health of frontline healthcare workers (HWs). However, there is still a lack of comparative studies on the mental health of front-line HWs in the initial phase of the lockdown and 1 month after the lifting of the lockdown.Methods: We recruited 1717 HWs during the initial phase of the lockdown and 2214 HWs 1 month after the lifting of the lockdown, and their baseline characteristics and psychiatric health in these two phases were compared. Furthermore, Pearson's Chi-square test and multivariate logistic regression analysis were used to determine the possible risk factors associated with depressive symptoms in the front-line HWs.Results: Compared with the initial phase of the lockdown, the proportion of HWs with anxiety symptoms and stress decreased, while the proportion of HWs with depressive symptoms increased a month after the lifting of the lockdown. Male sex, exercise habit, comorbidities, and having family members or relatives with suspected or confirmed COVID-19 infection were significantly related to the increased incidence of depressive symptoms during the initial phase of the lockdown. Comorbidities, negative effect of media coverage, working &gt;4 days a week, lower annual household income, and deteriorating relationships with family members were associated with depressive symptoms a month after the lifting of the lockdown.Conclusion: The increased proportion of HWs with depressive symptoms 1 month after the lifting of the lockdown suggested that mental health of front-line HWs should be a top-priority issue, not only during, but also after the pandemic