An initial implementation of multiagent simulation of travel behavior for a medium-sized city in China

Since the traditional four-step model is so simple that it cannot solve complex modern transportation problems, microsimulation is gradually applied for transportation planning and some researches indicate that it is more compatible and realistic. In this paper, a framework of agent-based simulation of travel behavior is proposed, which is realized by MATSim, a simulation tool developed for large-scale agent-based simulation. MATSim is currently developed and some of its models are under training, so a detailed introduction of simulation structure and preparation of input data will be presented. In practice, the preparation process differs from one to another in different simulation projects because the available data for simulation is various. Thus, a simulation of travel behavior under a condition of limited available survey data will be studied based on MATSim; furthermore, a medium-sized city in China will be taken as an example to check whether agent-based simulation of travel behavior can be successfully applied in China

Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials

The exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili

Effect of tRF-Pro-CGG on the biological behavior of mouse pancreatic cancer cells and its molecular mechanism

Background and purpose: tRNA-derived fragments (tRF) are a kind of short non-coding RNA (14-30 nt) that influences the course of cancer. This study aimed to investigate the molecular pathways that might underlie the effects of tRF-Pro-CGG on the biological behavior of mouse pancreatic cancer cells. Methods: Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to assess the expression of tRF-Pro-CGG in mouse pancreatic cancer cell lines pan02 and LTPA, human pancreatic cancer cell line Capan-2, and normal pancreatic cells HPDE6-C7. tRF-Pro-CGG overexpression in pan02 cells and LTPA cell suppression were achieved through lentiviral transfection, and RTFQ-PCR and Western blot were used to determine overexpression and knockdown effects. Cell counting kit-8 (CCK-8) was used to detect cell proliferation. Transwell assays were used to detect cell migration and invasion ability. The effect of tRF-Pro-CGG on the growth and metastasis of pancreatic cancer transplantation tumors in nude mice model was investigated. H-E staining was used to observe the histopathological structure of transplantation tumors. Western blot was used to detect the expression and phosphorylation of proliferation-related protein Ki-67 and metastasis-related proteins. Western blot was used to assess the expressions of cadherin, vimentin, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway protein and phosphorylation in transplanted tumor tissues. Results: tRF-Pro-CGG expression was lowest in the mouse pancreatic cancer cell line pan02. Both mRNA and protein expression levels of tRF-Pro-CGG were significantly increased (P <0.01) after transfection of tRF-Pro-CGG mimics in pan02 cells, and cell proliferation ability (P<0.01), cell migration (P<0.001) and invasion ability (P<0.001) were significantly reduced. A significant decrease in the volume (P<0.01) and weight (P<0.001) of transplanted tumors in nude mice was observed, and significant necrotic and apoptotic cells in transplanted tumor were identified. In transplanted tumor tissues of nude mice, the Ki-67 proliferatien index and expression of vimentin were significantly decreased (P<0.001), while E-cadherin was increased (P<0.001). The expressions of PI3K, P-PI3K, AKT and P-AKT were significantly decreased (P<0.001). There was no significant difference in the number of liver metastases from pancreatic cancer (P>0.05). The mouse pancreatic cancer cell line LTPA had the greatest level of tRF-Pro-CGG expression. The mRNA and protein expression levels of tRF-Pro-CGG were significantly reduced (P<0.01) after transfection of tRF-Pro-CGG inhibitor in LTPA cells. The proliferation ability of cells was significantly increased (P<0.01), the migration of cells (P<0.001) and invasive ability (P<0.001) were significantly increased. The volume (P<0.01) and weight (P<0.01) of transplanted tumors in nude mice were significantly increased, and a limited proportion of necrotic and apoptotic cells were seen in nude mice tumor tissues implanted. In the transplanted tumor tissues of nude mice, the Ki-67 proliferation index and expression of vimentin were significantly increased (P<0.001), while E-cadherin was decreased (P<0.001). The expressions of PI3K, P-PI3K, AKT, and P-AKT were significantly increased (P<0.001). There was no difference in the number of liver metastases from pancreatic cancer (P>0.05). Conclusion: Overexpression of tRF-Pro-CGG reduced pancreatic cancer cell proliferation, migration and invasion in mice, slowed the formation of pancreatic cancer transplanted tumors in nude mice, and decreased Ki-67 proliferation index and expression of vimentin and PI3K/AKT phosphorylation levels. The PI3K/AKT signaling pathway may be regulated by tRF-Pro-CGG, which may suppress the development of pancreatic cancer

Computational design of transmembrane pores.

Transmembrane channels and pores have key roles in fundamental biological processes1 and in biotechnological applications such as DNA nanopore sequencing2-4, resulting in considerable interest in the design of pore-containing proteins. Synthetic amphiphilic peptides have been found to form ion channels5,6, and there have been recent advances in de novo membrane protein design7,8 and in redesigning naturally occurring channel-containing proteins9,10. However, the de novo design of stable, well-defined transmembrane protein pores that are capable of conducting ions selectively or are large enough to enable the passage of small-molecule fluorophores remains an outstanding challenge11,12. Here we report the computational design of protein pores formed by two concentric rings of α-helices that are stable and monodisperse in both their water-soluble and their transmembrane forms. Crystal structures of the water-soluble forms of a 12-helical pore and a 16-helical pore closely match the computational design models. Patch-clamp electrophysiology experiments show that, when expressed in insect cells, the transmembrane form of the 12-helix pore enables the passage of ions across the membrane with high selectivity for potassium over sodium; ion passage is blocked by specific chemical modification at the pore entrance. When incorporated into liposomes using in vitro protein synthesis, the transmembrane form of the 16-helix pore-but not the 12-helix pore-enables the passage of biotinylated Alexa Fluor 488. A cryo-electron microscopy structure of the 16-helix transmembrane pore closely matches the design model. The ability to produce structurally and functionally well-defined transmembrane pores opens the door to the creation of designer channels and pores for a wide variety of applications

Residential Security Maps and Neighborhood Appraisals. The Homeowners\u27 Loan Corporation and the Case of Philadelphia

At the request of the Home Loan Bank Board, the Home Owners’ Loan Corporation (HOLC) created color-coded maps for cities across the country between 1935 and 1940 that indicated risk levels for long-term real estate investment. Involvement in this City Survey Program marked a departure from the original mission of HOLC to provide new mortgages on an emergency basis to homeowners at risk of losing their homes during the Depression. This article considers why HOLC made these maps, how HOLC created them, and what the basis was for the grades on the maps. Geographic information systems and spatial regression models are used to show that racial composition was a significant predictor of map grades, controlling for housing characteristics

Analysis and Prediction Model of Resident Travel Satisfaction

To promote the sustainable development of urban traffic and improve resident travel satisfaction, the significant factors affecting resident travel satisfaction are analyzed in this paper. An evaluation and prediction model for travel satisfaction based on support vector machine (SVM) is constructed. First, a multinomial logit (MNL) model is constructed to reveal the impact of individual attributes, family attributes and safety hazards on resident travel satisfaction and to clarify the significant factors. Then, a travel satisfaction evaluation model based on the SVM is constructed by taking significant factors as independent variables. Finally, travel optimization measures are proposed and the SVM model is used to predict the effect. Futian Street in Futian District of Shenzhen is taken as the object to carry out specific research. The results show that the following factors have a significant effect on resident travel satisfaction: age, job, level of education, number of car, income, residential area and potential safety hazards of people, vehicles, roads, environment, etc. The model fitting accuracy is 87.76%. The implementation of travel optimization measures may increase travel satisfaction rate by 14.07%

Herpes Simplex Virus 1 UL24 Abrogates the DNA Sensing Signal Pathway by Inhibiting NF-κB Activation.

International audienceCyclic GMP-AMP synthase (cGAS) is a newly identified DNA sensor that recognizes foreign DNA, including the genome of herpes simplex virus 1 (HSV-1). Upon binding of viral DNA, cGAS produces cyclic GMP-AMP, which interacts with and activates stimulator of interferon genes (STING) to trigger the transcription of antiviral genes such as type I interferons (IFNs), and the production of inflammatory cytokines. HSV-1 UL24 is widely conserved among members of the herpesviruses family and is essential for efficient viral replication. In this study, we found that ectopically expressed UL24 could inhibit cGAS-STING-mediated promoter activation of IFN-β and interleukin-6 (IL-6), and UL24 also inhibited interferon-stimulatory DNA-mediated IFN-β and IL-6 production during HSV-1 infection. Furthermore, UL24 selectively blocked nuclear factor κB (NF-κB) but not IFN-regulatory factor 3 promoter activation. Coimmunoprecipitation analysis demonstrated that UL24 bound to the endogenous NF-κB subunits p65 and p50 in HSV-1-infected cells, and UL24 was also found to bind the Rel homology domains (RHDs) of these subunits. Furthermore, UL24 reduced the tumor necrosis factor alpha (TNF-α)-mediated nuclear translocation of p65 and p50. Finally, mutational analysis revealed that the region spanning amino acids (aa) 74 to 134 of UL24 [UL24(74-134)] is responsible for inhibiting cGAS-STING-mediated NF-κB promoter activity. For the first time, UL24 was shown to play an important role in immune evasion during HSV-1 infection.IMPORTANCE NF-κB is a critical component of the innate immune response and is strongly induced downstream of most pattern recognition receptors (PRRs), leading to the production of IFN-β as well as a number of inflammatory chemokines and interleukins. To establish persistent infection, viruses have evolved various mechanisms to counteract the host NF-κB pathway. In the present study, for the first time, HSV-1 UL24 was demonstrated to inhibit the activation of NF-κB in the DNA sensing signal pathway via binding to the RHDs of the NF-κB subunits p65 and p50 and abolishing their nuclear translocation