Transfer-Expanded Graphs for On-Demand Multimodal Transit Systems

This paper considers a generalization of the network design problem for On-Demand Multimodal Transit Systems (ODMTS). An ODMTS consists of a selection of hubs served by high frequency buses, and passengers are connected to the hubs by on-demand shuttles which serve the first and last miles. This paper generalizes prior work by including three additional elements that are critical in practice. First, different frequencies are allowed throughout the network. Second, additional modes of transit (e.g., rail) are included. Third, a limit on the number of transfers per passenger is introduced. Adding a constraint to limit the number of transfers has a significant negative impact on existing Benders decomposition approaches as it introduces non-convexity in the subproblem. Instead, this paper enforces the limit through transfer-expanded graphs, i.e., layered graphs in which each layer corresponds to a certain number of transfers. A real-world case study is presented for which the generalized ODMTS design problem is solved for the city of Atlanta. The results demonstrate that exploiting the problem structure through transfer-expanded graphs results in significant computational improvements.Comment: 9 pages, 4 figure

Bilevel Optimization for On-Demand Multimodal Transit Systems

This study explores the design of an On-Demand Multimodal Transit System (ODMTS) that includes segmented mode switching models that decide whether potential riders adopt the new ODMTS or stay with their personal vehicles. It is motivated by the desire of transit agencies to design their network by taking into account both existing and latent demand, as quality of service improves. The paper presents a bilevel optimization where the leader problem designs the network and each rider has a follower problem to decide her best route through the ODMTS. The bilevel model is solved by a decomposition algorithm that combines traditional Benders cuts with combinatorial cuts to ensure the consistency of mode choices by the leader and follower problems. The approach is evaluated on a case study using historical data from Ann Arbor, Michigan, and a user choice model based on the income levels of the potential transit riders

Fatty acid profile in peri-prostatic adipose tissue and prostate cancer aggressiveness in African-Caribbean and Caucasian patients

BACKGROUND: Genetic and nutritional factors have been linked to the risk of aggressive prostate cancer (PCa). The fatty acid (FA) composition of peri-prostatic adipose tissue (PPAT), which reflects the past FA intake, is potentially involved in PCa progression. We analysed the FA composition of PPAT, in correlation with the ethno-geographical origin of the patients and markers of tumour aggressiveness. METHODS: From a cohort of 1000 men treated for PCa by radical prostatectomy, FA composition of PPAT was analysed in 156 patients (106 Caucasians and 50 African-Caribbeans), 78 with an indolent tumour (ISUP group 1 + pT2 + PSA <10 ng/mL) and 78 with an aggressive tumour (ISUP group 4-5 + pT3). The effect of FA extracted from PPAT on in-vitro migration of PCa cells DU145 was studied in 72 patients, 36 Caucasians, and 36 African-Caribbeans. RESULTS: FA composition differed according to the ethno-geographical origin. Linoleic acid, an essential n-6 FA, was 2-fold higher in African-Caribbeans compared with Caucasian patients, regardless of disease aggressiveness. In African-Caribbeans, the FA profile associated with PCa aggressiveness was characterised by low level of linoleic acid along with high levels of saturates. In Caucasians, a weak and negative association was observed between eicosapentaenoic acid level (an n-3 FA) and disease aggressiveness. In-vitro migration of PCa cells using PPAT from African-Caribbean patients was associated with lower content of linoleic acid. CONCLUSION: These results highlight an important ethno-geographical variation of PPAT, in both their FA content and association with tumour aggressiveness

α,β-D-Constrained Nucleic Acids Are Strong Terminators of Thermostable DNA Polymerases in Polymerase Chain Reaction

(SC5′, RP) α,β-D- Constrained Nucleic Acids (CNA) are dinucleotide building blocks that can feature either B-type torsional angle values or non-canonical values, depending on their 5′C and P absolute stereochemistry. These CNA are modified neither on the nucleobase nor on the sugar structure and therefore represent a new class of nucleotide with specific chemical and structural characteristics. They promote marked bending in a single stranded DNA so as to preorganize it into a loop-like structure, and they have been shown to induce rigidity within oligonucleotides. Following their synthesis, studies performed on CNA have only focused on the constraints that this family of nucleotides introduced into DNA. On the assumption that bending in a DNA template may produce a terminator structure, we investigated whether CNA could be used as a new strong terminator of polymerization in PCR. We therefore assessed the efficiency of CNA as a terminator in PCR, using triethylene glycol phosphate units as a control. Analyses were performed by denaturing gel electrophoresis and several PCR products were further analysed by sequencing. The results showed that the incorporation of only one CNA was always skipped by the polymerases tested. On the other hand, two CNA units always stopped proofreading polymerases, such as Pfu DNA polymerase, as expected for a strong replication terminator. Non-proofreading enzymes, e.g. Taq DNA polymerase, did not recognize this modification as a strong terminator although it was predominantly stopped by this structure. In conclusion, this first functional use of CNA units shows that these modified nucleotides can be used as novel polymerization terminators of proofreading polymerases. Furthermore, our results lead us to propose that CNA and their derivatives could be useful tools for investigating the behaviour of different classes of polymerases

Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation

Impact of shipbuilding steel plates with an initial tensile stress

The present investigation is concerned with the impact of thin steel plates used in shipbuilding. The problem is studied numerically with the commercial code LS-DYNA and experimentally with an apparatus propelling a 200g projectile up to 30m/s with a crossbow. The clamped sample of sheet metal is rectangular (250 mm wide; 20 mm width and 4 mm thick), in common shipbuilding material with a 360MPa elastic limit. Impact takes place at the center of the sample. Moreover, an initial tensile stress can be applied to the plate, up to 300 MPa. The aim of this study is first to illustrate the influences of the boundary conditions and the initial tensile stress value on the deflection of the central point of the plate. The second part is concerned with wave propagation. The objective is to explain analytically the dispersive form of the measured strains at different locations and to establish the relationship between the flexural waves and the observed losses of contact

Syn-kinematic emplacement of the Pangong metamorphic and magmatic complex along the Karakorum Fault (N Ladakh)

International audienceThis paper investigates the age, P–T conditions and kinematics of Karakorum Fault (KF) zone rocks in the NW part of the Himalaya–Karakorum belt. Granulite to greenschist facies assemblages were developed within the KF zone during strike-slip shearing. The granulites were formed at high temperature (800 °C, 5.5 kbar), were subsequently retromorphosed into the amphibolite facies (700–750 °C, 4–5 kbar) and the greenschist facies (350–400 °C, 3–4 kbar). The Tangtse granite emplaced syn-kinematically at the contact between a LT and the HT granulite facies. Intrusion occurred during the juxtaposition of the two units under amphibolite conditions. Microstructures observed within the Tangtse granite exhibit a syn-magmatic dextral S–C fabric. Compiled U–Pb and Ar–Ar data show that in the central KF segment, granulite facies metamorphism occurred at a minimum age of 32 Ma, subsequent amphibolite facies metamorphism at 20–18 Ma. Further shearing under amphibolite facies (650–500 °C) was recorded at 13.6 ± 0.9 Ma, and greenschist-facies mica growth at 11 Ma. These data give further constrains to the age of initiation and depth of the Karakorum Fault. The granulite-facies conditions suggest that the KF, accommodating the lateral extrusion of Tibet, could be at least a crustal or even a Lithosphere-scale shear zone comparable to other peri-Himalayan faults