Optimizing fares and transfer discounts for a bus-subway corridor

This paper aims to optimize fares and transfer discounts for public transit service along a bus-subway corridor with the consideration of effects of uncertainty in travel times and difference in stop spacing between bus and subway services on passenger behavior. The former factor is captured by the reserved time in travel cost and the latter one produces some passenger Origin–Destination (O–D) pairs along the corridor that can not be served by one mode only. This problem is formulated as a bi-level program, of which the upper level maximizes the social welfare and the lower-level capturing traveler choice behavior is a variable-demand Stochastic User Equilibrium (SUE) assignment model. A Genetic Algorithm (GA) is applied to solve the bi-level program while the Method of Successive Averages (MSA) is adopted to solve the lower-level model. A series of numerical experiments are carried out to illustrate the performance of the model and solution method. Numerical results indicate that the implementation of transfer discounts may be of great benefit to the social welfare and that the uncertainty in travel time and the difference in stop spacing play an important role in determining optimal fares and transfer discounts for the service along a bus-subway corridor

Observation of tunable topological polaritons in a cavity waveguide

Topological polaritons characterized by light-matter interactions have become a pivotal platform in exploring new topological phases of matter. Recent theoretical advances unveiled a novel mechanism for tuning topological phases of polaritons by modifying the surrounding photonic environment (light-matter interactions) without altering the lattice structure. Here, by embedding a dimerized chain of microwave helical resonators (electric dipole emitters) in a metallic cavity waveguide, we report the pioneering observation of tunable topological phases of polaritons by varying the cavity width which governs the surrounding photonic environment and the strength of light-matter interactions. Moreover, we experimentally identified a new type of topological phase transition which includes three non-coincident critical points in the parameter space: the closure of the polaritonic bandgap, the transition of the Zak phase, and the hybridization of the topological edge states with the bulk states. These results reveal some remarkable and uncharted properties of topological matter when strongly coupled to light and provide an innovative design principle for tunable topological photonic devices.Comment: 6 pages, 4 figure

Acoustic Three-dimensional Chern Insulators with Arbitrary Chern Vectors

The Chern vector is a vectorial generalization of the scalar Chern number, being able to characterize the topological phase of three-dimensional (3D) Chern insulators. Such a vectorial generalization extends the applicability of Chern-type bulk-boundary correspondence from one-dimensional (1D) edge states to two-dimensional (2D) surface states, whose unique features, such as forming nontrivial torus knots or links in the surface Brillouin zone, have been demonstrated recently in 3D photonic crystals. However, since it is still unclear how to achieve an arbitrary Chern vector, so far the surface-state torus knots or links can emerge, not on the surface of a single crystal as in other 3D topological phases, but only along an internal domain wall between two crystals with perpendicular Chern vectors. Here, we extend the 3D Chern insulator phase to acoustic crystals for sound waves, and propose a scheme to construct an arbitrary Chern vector that allows the emergence of surface-state torus knots or links on the surface of a single crystal. These results provide a complete picture of bulk-boundary correspondence for Chern vectors, and may find use in novel applications in topological acoustics

Observation of Dirac hierarchy in three-dimensional acoustic topological insulators

Dirac cones (DCs) play a pivotal role in various unique phenomena ranging from massless electrons in graphene to robust surface states in topological insulators (TIs). Recent studies have theoretically revealed a full Dirac hierarchy comprising an eightfold bulk DC, a fourfold surface DC, and a twofold hinge DC, associated with a hierarchy of topological phases including first-order to third-order three-dimensional (3D) topological insulators, using the same 3D base lattice. Here, we report the first experimental observation of the Dirac hierarchy in 3D acoustic TIs. Using acoustic measurements, we unambiguously reveal that lifting of multifold DCs in each hierarchy can induce two-dimensional (2D) topological surface states with a fourfold DC in a first-order 3D TI, one-dimensional (1D) topological hinge states with a twofold DC in a second-order 3D TI, and zero-dimensional (0D) topological corner states in a third-order 3D TI. Our work not only expands the fundamental research scope of Dirac physics, but also opens up a new route for multidimensional robust wave manipulation

High-throughput Screening and Sensitized Bacteria Identify an M. tuberculosis Dihydrofolate Reductase Inhibitor with Whole Cell Activity

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a bacterial pathogen that claims roughly 1.4 million lives every year. Current drug regimens are inefficient at clearing infection, requiring at least 6 months of chemotherapy, and resistance to existing agents is rising. There is an urgent need for new drugs that are more effective and faster acting. The folate pathway has been successfully targeted in other pathogens and diseases, but has not yielded a lead drug against tuberculosis. We developed a high-throughput screening assay against Mtb dihydrofolate reductase (DHFR), a critical enzyme in the folate pathway, and screened a library consisting of 32,000 synthetic and natural product-derived compounds. One potent inhibitor containing a quinazoline ring was identified. This compound was active against the wild-type laboratory strain H37Rv (MIC99 = 207 µM). In addition, an Mtb strain with artificially lowered DHFR levels showed increased sensitivity to this compound (MIC99 = 70.7 µM), supporting that the inhibition was target-specific. Our results demonstrate the potential to identify Mtb DHFR inhibitors with activity against whole cells, and indicate the power of using a recombinant strain of Mtb expressing lower levels of DHFR to facilitate the discovery of antimycobacterial agents. With these new tools, we highlight the folate pathway as a potential target for new drugs to combat the tuberculosis epidemic

Curcumin Inhibits Growth of Human NCI-H292 Lung Squamous Cell Carcinoma Cells by Increasing FOXA2 Expression

Lung squamous cell carcinoma (LSCC) is a common histological lung cancer subtype, but unlike lung adenocarcinoma, limited therapeutic options are available for treatment. Curcumin, a natural compound, may have anticancer effects in various cancer cells, but how it may be used to treat LSCC has not been well studied. Here, we applied curcumin to a human NCI-H292 LSCC cell line to test anticancer effects and explored underlying potential mechanisms of action. Curcumin treatment inhibited NCI-H292 cell growth and increased FOXA2 expression in a time-dependent manner. FOXA2 expression was decreased in LSCC tissues compared with adjacent normal tissues and knockdown of FOXA2 increased NCI-H292 cells proliferation. Inhibition of cell proliferation by curcumin was attenuated by FOXA2 knockdown. Moreover inhibition of STAT3 pathways by curcumin increased FOXA2 expression in NCI-H292 cells whereas a STAT3 activator (IL-6) significantly inhibited curcumin-induced FOXA2 expression. Also, SOCS1 and SOCS3, negative regulators of STAT3 activity, were upregulated by curcumin treatment. Thus, curcumin inhibited human NCI-H292 cells growth by increasing FOXA2 expression via regulation of STAT3 signaling pathways

Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma

Background/Aims: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL)-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. Methods: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR), immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level. Results: We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells. Conclusion: Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma

Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population

Background The genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis ( RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations

Association of ERAP1, but not IL23R, with ankylosing spondylitis in a Han Chinese population

Objective The results of a recent genome-wide association study have shown that ERAP1 and IL23R are associated with ankylosing spondylitis (AS) in Caucasian populations from North America and the UK. Based on these findings, we undertook the current study to investigate whether single-nucleotide polymorphisms (SNPs) covering the genes ERAP1 and IL23R are associated with AS in a Han Chinese population. Methods A case-control study was performed in Han Chinese patients with AS (n = 527) and controls (n = 945) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The Sequenom iPlex platform was used to genotype cases and controls for 21 tag SNPs covering IL23R and 38 tag SNPs covering ERAP1. Statistical analysis was performed using the Cochran-Armitage test for trend. Results Multiple SNPs in ERAP1 were significantly associated with AS (for rs27980, P = 0.0048; for rs7711564, P = 0.0081). However, no association was observed between IL23R and AS (for all SNPs, P > 0.1). The nonsynonymous SNP in IL23R, rs11209026, widely thought to be the primary AS-associated SNP in IL23R in Europeans, was found not to be polymorphic in Chinese. Conclusion Our results demonstrate that genetic polymorphisms in ERAP1 are associated with AS in Han Chinese, suggesting a common pathogenic mechanism for the disease in Chinese and Caucasian populations, and that IL23R is not associated with AS in Chinese, indicating a difference in the mechanism of disease pathogenesis between Chinese and Caucasian populations. This may result from the fact that rs11209026, the nonsynonymous SNP in IL23R, is not polymorphic in Chinese patients, providing further evidence that rs11209026 is the key polymorphism associated with AS (and likely inflammatory bowel disease and psoriasis) in this gene