Freight Service Design for the Italian Railways Company

In this paper, we present a mathematical model to design the service network, that is the set of origin-destination connections. The resulting model considers both full and empty freight car movements, and takes into account handling costs. More specifically, the model suggests the services to provide, as well as the number of trains and the number and type of cars traveling on each connection. Quality of service, which is measured as total travel time, is established by minimizing the waiting time of cars at intermediate stations. Our approach yields a multi-commodity network design problem with concave arc cost functions. To solve this problem, we implement a tabu search procedure which adopts ``perturbing\u27\u27 mechanisms to force the algorithm to explore a larger portion of the feasible region. Computational results on realistic instances show a significant improvement over current practice

Operations Research for Planning and Managing City Logistics Systems

The chapter presents the Operations Research models and methods to plan and manage City Logistics systems, in particular their supply components. It presents the main planning issues and challenges, and reviews the proposed methodologies. The chapter concludes with a discussion on perspectives for City Logistics and decision-support methodological developments

A Distinct Genetic Cluster in Cultivated Chickpea as Revealed by Genome-wide Marker Discovery and Genotyping

The accurate description of plant biodiversity is of utmost importance to efficiently address efforts in conservation genetics and breeding. Herein, we report the successful application of a genotyping-by-sequencing (GBS) approach in chickpea ( L.), resulting in the characterization of a cultivated germplasm collection with 3187 high-quality single nucleotide polymorphism (SNP) markers. Genetic structure inference, principal component analysis, and hierarchical clustering all indicated the identification of a genetic cluster corresponding to black-seeded genotypes traditionally cultivated in Southern Italy. Remarkably, this cluster was clearly distinct at both genetic and phenotypic levels from germplasm groups reflecting commercial chickpea classification into and seed types. Fixation index estimates for individual polymorphisms pointed out loci and genomic regions that might be of significance for the diversification of agronomic and commercial traits. Overall, our findings provide information on genetic relationships within cultivated chickpea and highlight a gene pool of great interest for the scientific community and chickpea breeding, which is limited by the low genetic diversity available in the primary gene pool

All-Optical tunability of metalenses infiltrated with liquid crystals

Metasurfaces have been extensively engineered to produce a wide range of optical phenomena, allowing unprecedented control over the propagation of light. However, they are generally designed as single-purpose devices without a modifiable post-fabrication optical response, which can be a limitation to real-world applications. In this work, we report a nanostructured planar fused silica metalens permeated with a nematic liquid crystal (NLC) and gold nanoparticle solution. The physical properties of embedded NLCs can be manipulated with the application of external stimuli, enabling reconfigurable optical metasurfaces. We report all-optical, dynamic control of the metalens optical response resulting from thermo-plasmonic induced changes of the NLC solution associated with the nematic-isotropic phase transition. A continuous and reversible tuning of the metalens focal length is experimentally demonstrated, with a variation of 80 um (0.16% of the 5 cm nominal focal length) along the optical axis. This is achieved without direct mechanical or electrical manipulation of the device. The reconfigurable properties are compared with corroborating numerical simulations of the focal length shift and exhibit close correspondence.Comment: Main tex

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial

Background and purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. Methods This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. Results Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. Conclusions The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Characterisation of CDKL5 Transcript Isoforms in Human and Mouse

Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brain isoform of CDKL5, a 9.7 kb transcript comprised of 18 exons with a large 6.6 kb 3’-untranslated region (UTR), which we name hCDKL5_1. In addition we describe new exonic regions and a range of novel splice and UTR isoforms. This has enabled the description of an updated gene model in both species and a standardised nomenclature system for CDKL5 transcripts. Profiling revealed tissue- and brain development stage-specific differences in expression between transcript isoforms. These findings provide an essential backdrop for the diagnosis of CDKL5-related disorders, for investigations into the basic biology of this gene and its protein products, and for the rational design of gene-based and molecular therapies for these disorders

Research and Development for Near Detector Systems Towards Long Term Evolution of Ultra-precise Long-baseline Neutrino Experiments

With the discovery of non-zero value of $\theta_{13}$ mixing angle, the next generation of long-baseline neutrino (LBN) experiments offers the possibility of obtaining statistically significant samples of muon and electron neutrinos and anti-neutrinos with large oscillation effects. In this document we intend to highlight the importance of Near Detector facilities in LBN experiments to both constrain the systematic uncertainties affecting oscillation analyses but also to perform, thanks to their close location, measurements of broad benefit for LBN physics goals. A strong European contribution to these efforts is possible