A method to assess demand growth vulnerability of travel times on road network links

Many national governments around the world have turned their recent focus to monitoring the actual reliability of their road networks. In parallel there have been major research efforts aimed at developing modelling approaches for predicting the potential vulnerability of such networks, and in forecasting the future impact of any mitigating actions. In practice-whether monitoring the past or planning for the future-a confounding factor may arise, namely the potential for systematic growth in demand over a period of years. As this growth occurs the networks will operate in a regime closer to capacity, in which they are more sensitive to any variation in flow or capacity. Such growth will be partially an explanation for trends observed in historic data, and it will have an impact in forecasting too, where we can interpret this as implying that the networks are vulnerable to demand growth. This fact is not reflected in current vulnerability methods which focus almost exclusively on vulnerability to loss in capacity. In the paper, a simple, moment-based method is developed to separate out this effect of demand growth on the distribution of travel times on a network link, the aim being to develop a simple, tractable, analytic method for medium-term planning applications. Thus the impact of demand growth on the mean, variance and skewness in travel times may be isolated. For given critical changes in these summary measures, we are thus able to identify what (location-specific) level of demand growth would cause these critical values to be exceeded, and this level is referred to as Demand Growth Reliability Vulnerability (DGRV). Computing the DGRV index for each link of a network also allows the planner to identify the most vulnerable locations, in terms of their ability to accommodate growth in demand. Numerical examples are used to illustrate the principles and computation of the DGRV measure

Identification of Putative Cytoskeletal Protein Homologues in the Protozoan Host \u3cem\u3eHartmannella vermiformis\u3c/em\u3e as Substrates for Induced Tyrosine Phosphatase Activity Upon Attachment to the Legionnaires\u27 Disease Bacterium, \u3cem\u3eLegionella pneumophila\u3c/em\u3e

The Legionnaires\u27 disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen that invades and replicates within two evolutionarily distant hosts, free living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaires\u27 disease. We have recently reported the identification of a galactose/N-acetyl-d-galactosamine (Gal/GalNAc) lectin in the protozoan host Hartmannella vermiformis as a receptor for attachment and invasion by L. pneumophila (Venkataraman, C., B.J. Haack, S. Bondada, and Y.A. Kwaik. 1997. J. Exp. Med. 186:537–547). In this report, we extended our studies to the effects of bacterial attachment and invasion on the cytoskeletal proteins of H. vermiformis. We first identified the presence of many protozoan cytoskeletal proteins that were putative homologues to their mammalian counterparts, including actin, pp125FAK, paxillin, and vinculin, all of which were basally tyrosine phosphorylated in resting H. vermiformis. In addition to L. pneumophila–induced tyrosine dephosphorylation of the lectin, bacterial attachment and invasion was associated with tyrosine dephosphorylation of paxillin, pp125FAK, and vinculin, whereas actin was minimally affected. Inhibition of bacterial attachment to H. vermiformis by Gal or GalNAc monomers blocked bacteria-induced tyrosine dephosphorylation of detergent-insoluble proteins. In contrast, inhibition of bacterial invasion but not attachment failed to block bacteria-induced tyrosine dephosphorylation of H. vermiformis proteins. This was further supported by the observation that 10 mutants of L. pneumophila that were defective in invasion of H. vermiformis were capable of inducing tyrosine dephosphorylation of H. vermiformis proteins. Entry of L. pneumophila into H. vermiformis was predominantly mediated by noncoated receptor-mediated endocytosis (93%) but coiling phagocytosis was infrequently observed (7%). We conclude that attachment but not invasion by L. pneumophila into H. vermiformis was sufficient and essential to induce protein tyrosine dephosphorylation in H. vermiformis. These manipulations of host cell processes were associated with, or followed by, entry of the bacteria by a noncoated receptor-mediated endocytosis. A model for attachment and entry of L. pneumophila into H. vermiformis is proposed

Tight-binding parameters for charge transfer along DNA

We systematically examine all the tight-binding parameters pertinent to charge transfer along DNA. The $\pi$ molecular structure of the four DNA bases (adenine, thymine, cytosine, and guanine) is investigated by using the linear combination of atomic orbitals method with a recently introduced parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are discussed and then used for calculating the corresponding wavefunctions of the two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO and LUMO energies of the bases are in good agreement with available experimental values. Our results are then used for estimating the complete set of charge transfer parameters between neighboring bases and also between successive base-pairs, considering all possible combinations between them, for both electrons and holes. The calculated microscopic quantities can be used in mesoscopic theoretical models of electron or hole transfer along the DNA double helix, as they provide the necessary parameters for a tight-binding phenomenological description based on the $\pi$ molecular overlap. We find that usually the hopping parameters for holes are higher in magnitude compared to the ones for electrons, which probably indicates that hole transport along DNA is more favorable than electron transport. Our findings are also compared with existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial

Introduction There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. Methods and analysis This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14–40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. Ethics and dissemination The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia’s National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12620000890932)

Cost effectiveness of endovascular ultrasound renal denervation in patients with resistant hypertension

Background: Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90 mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system. Methods: Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP (‘control’ patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). Results: A mean reduction in office SBP of 8.5 mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463–£5739 [€6341–€6661]); modelling demonstrated > 99% probability that the ICER is below the £20,000–£30,000 (€23,214–€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks. Conclusions: Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication

Soil nutrients and beta diversity in the Bornean Dipterocarpaceae: evidence for niche partitioning by tropical rain forest trees

1   The relative importance of niche- and dispersal-mediated processes in structuring diverse tropical plant communities remains poorly understood. Here, we link mesoscale beta diversity to soil variation throughout a lowland Bornean watershed underlain by alluvium, sedimentary and granite parent materials ( c . 340 ha, 8–200 m a.s.l.). We test the hypothesis that species turnover across the habitat gradient reflects interspecific partitioning of soil resources. 2   Floristic inventories (≥ 1 cm d.b.h.) of the Dipterocarpaceae, the dominant Bornean canopy tree family, were combined with extensive soil analyses in 30 (0.16 ha) plots. Six samples per plot were analysed for total C, N, P, K, Ca and Mg, exchangeable K, Ca and Mg, extractable P, texture, and pH. 3   Extractable P, exchangeable K, and total C, N and P varied significantly among substrates and were highest on alluvium. Thirty-one dipterocarp species ( n  = 2634 individuals, five genera) were recorded. Dipterocarp density was similar across substrates, but richness and diversity were highest on nutrient-poor granite and lowest on nutrient-rich alluvium. 4   Eighteen of 22 species were positively or negatively associated with parent material. In 8 of 16 abundant species, tree distribution (≥ 10 cm d.b.h.) was more strongly non-random than juveniles (1–10 cm d.b.h.), suggesting higher juvenile mortality in unsuitable habitats. The dominant species Dipterocarpus sublamellatus (> 50% of stems) was indifferent to substrate, but nine of 11 ‘subdominant’ species (> 8 individuals ha −1 ) were substrate specialists. 5   Eighteen of 22 species were significantly associated with soil nutrients, especially P, Mg and Ca. Floristic variation was significantly correlated with edaphic and geographical distance for all stems ≥ 1 cm d.b.h. in Mantel analyses. However, juvenile variation (1–10 cm d.b.h.) was more strongly related to geographical distance than edaphic factors, while the converse held for established trees (≥ 10 cm d.b.h.), suggesting increased importance of niche processes with size class. 6   Pervasive dipterocarp associations with soil factors suggest that niche partitioning structures dipterocarp tree communities. Yet, much floristic variation unrelated to soil was correlated with geographical distance between plots, suggesting that dispersal and niche processes jointly determine mesoscale beta diversity in the Bornean Dipterocarpaceae. Journal of Ecology (2005) doi: 10.1111/j.1365-2745.2005.01077.xPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72822/1/j.1365-2745.2005.01077.x.pd

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Research is needed to inform environmental management of hydrothermally inactive and extinct polymetallic sulfide (PMS) deposits

Polymetallic sulfide (PMS) deposits produced at hydrothermal vents in the deep sea are of potential interest to miners. Hydrothermally active sulfide ecosystems are valued for the extraordinary chemosynthetic communities that they support. Many countries, including Canada, Portugal, and the United States, protect vent ecosystems in their Exclusive Economic Zones. When hydrothermal activity ceases temporarily (dormancy) or permanently (extinction), the habitat and associated ecosystem change dramatically. Until recently, so-called "inactive sulfide" habitats, either dormant or extinct, received little attention from biologists. However, the need for environmental management of deep-sea mining places new imperatives for building scientific understanding of the structure and function of inactive PMS deposits. This paper calls for actions of the scientific community and the emergent seabed mining industry to i) undertake fundamental ecological descriptions and study of ecosystem functions and services associated with hydrothermally inactive PMS deposits, ii) evaluate potential environmental risks to ecosystems of inactive PMS deposits through research, and iii) identify environmental management needs that may enable mining of inactive PMS deposits. Mining of some extinct PMS deposits may have reduced environmental risk compared to other seabed mining activities, but this must be validated through scientific research on a case-by-case basis.FCT: IF/00029/2014/CP1230/CT0002/ UID/05634/2020/ CEECIND005262017/ UID/MAR/00350/2019; Direcao-Geral de Politica do Mar (DGPM) Mining2/2017/005/ Mining2/2017/001info:eu-repo/semantics/publishedVersio