The Railway Line Frequency and Size Setting Problem

[EN] The problem studied in this paper takes as input data a set of lines forming a railway network, and an origin¿destination (OD) matrix. The OD pairs may use either the railway network or an alternative transportation mode. The objective is to determine the frequency/headway of each line as well as its number of carriages, so that the net profit of the railway network is maximized. We propose a mixed integer non-linear programming formulation for this problem. Because of the computational intractability of this model, we develop four algorithms: a mixed integer linear programming (MIP) model, a MIP-based iterative algorithm, a shortest-path based algorithm, and a local search. These four algorithms are tested and compared over a set of randomly generated instances. An application over a case study shows that only the local search heuristic is capable of dealing with large instances.This research was partly funded by the Canadian Natural Sciences and Engineering Research Council under Grant 2015-06189, by the Ministerio de Economía y Competitividad (Spain)/FEDER under projects MTM2012-37048, MTM2015-67706-P and DPI2012-36243-C02-01, and by Junta de Andalucía (Spain)/FEDER under excellence project P10-FQM-5849. Part of this research was done while Federico Perea was enjoying a research visit to CIRRELT, funded by the Universitat Politècnica de València, under program PAID-00-15. This support is gratefully acknowledged. Thanks are due to the referees for their valuable comments.De-Los-Santos, A.; Laporte, G.; Mesa, JA.; Perea Rojas Marcos, F. (2017). The Railway Line Frequency and Size Setting Problem. Public Transport. 9(1-2):33-53. https://doi.org/10.1007/s12469-017-0154-2S335391-2Albrecht T (2009) Automated timetable design for demand-oriented service on suburban railways. Public Transport 1(1):5–20Caprara A, Kroon L, Monaci M, Peeters M, Toth P (2007) Passenger Railway optimization. In: Barnhart C, Laporte G (eds) Handbooks in operations research and management science, vol 14. Transportation, chapter 3. North-Holland, Amsterdam, pp 129–187De-Los-Santos A, Laporte G, Mesa J, Perea F (2014) Simultaneous frequency and capacity setting in uncapacitated metro lines in presence of a competing mode. Transp Res Proc 3:289–298Desaulniers G, Hickman M (2007) Public transport. In: Barnhart C, Laporte G (eds) Handbook in operations research and management science, vol 14, Transportation, chapter 2. North-Holland, Amsterdam, pp 69–127Gallo M, Montella B, D’Acierno L (2011) The transit network design problem with elastic demand and internalisation of external costs: An application to rail frequency optimisation. Transp Res Part C Emerg Technol 19(6):1276–1305Laporte G, Marín A, Mesa JA, Perea F (2011) Designing robust rapid transit networks with alternative routes. J Adv Transp 45(1):54–65Marín A, García-Ródenas R (2009) Location of infrastructure in urban railway networks. Comput Oper Res 36(5):1461–1477Michaelis M, Schöbel A (2009) Integrating line planning, timetable, and vehicle scheduling: a customer oriented heuristic. Public Transport 1(3):211–232Perea F, Mesa JA, Laporte G (2014) Adding a new station and a road link to a road-rail network in the presence of modal competition. Transp Res Part B Methodol 68:1–16Schmidt M, Schöbel A (2015) The complexity of integrating passenger routing decisions in public transportation models. Networks 65(3):228–243Schmidt ME (2014) Integrating routing decisions in public transportation problems. Springer, New YorkSchöbel A (2012) Line planning in public transportation. OR Spectrum 34:491–510van Oort N, van Nes R (2009) Regularity analysis for optimizing urban transit network design. Public Transport 1(2):155–168Vuchic VR (2005) Urban transit: operations, planning, and economics. Wiley, Hoboken, New Jerse

Genotype, environment and their interaction on olive

Resumen del trabajo presentado en la 6th International Conference on the Olive Tree and Olive Products, celebrada en Sevilla (España) del 15 al 19 de octubre de 2018.The wide olive genetic patrimony has revealed high variability for most of the agronomic and oil quality traits of interest in olive growing. Few studies, however, have addressed the interaction of this variability with the environment, a subject of particular interest considering the natural high instability of the Mediterranean climate and the challenge of the predicted climate change. The current work presents results on the interaction between genotype and environment from multi-environment trials of olive cultivars and breeding selections, planted in different edaphoclimatic conditions of Andalusia, Southern Peninsular Spain and Canary Islands. For most of the agronomic and oil quality characters evaluated (flowering phenology, flower quality, pattern of oil accumulation, fatty acid composition and phenol content and composition), significant genotype and environment effects have been observed. For example, olive cultivars grown in Tenerife under much milder winter temperatures than in the Iberian Peninsula showed substantially earlierflowering and oil accumulation. Only in the case of flowering phenology was no significant genotype effect found. Furthermore, a strong genotype x environment effect was highly consistent in all characters considered. Regarding resistance to disease, such as Verticillium wilt, the variability of results from both natural and artificial inoculations also tends to indicate a considerable environmental effect and the need for careful testing of disease evolution. All this information strongly suggests the necessity of comparative trials of olive cultivars for both adequate choice of cultivar and final selection in breeding programs

The rubric as an element of evaluation: application and analysis in humanistic disciplines

El presente artículo describe el desarrollo de un Proyecto Docente sobre la difusión, implementación y evaluación de la herramienta de la rúbrica de evaluación en asignaturas humanísticas, así como el fomento de la comunicación entre alumnado y profesorado en relación con los procesos e instrumentos de evaluación y aprendizaje por tareas, en base a los objetivos de evaluación por competencias. Las acciones han ido dirigidas a 18 asignaturas, (todas de la rama de humanidades), y en la que han intervenido profesorado de 4 departamentos de la Facultad de Filosofía y Letras de la Universidad de Córdoba. La aplicación de la rúbrica de evaluación en las diversas asignaturas relacionadas con el proyecto afectó a más de 850 alumnos de 5 titulaciones diferentes. Tras un proceso de estudio, elaboración, revisión e implementación, se llegó a una actividad evaluación dirigida tanto a el alumnado como al profesorado, que se resume en un alto grado de satisfacción por ambas partes y en la continuada aplicación de esta herramienta en cursos posteriores.This article describes the development of a Teaching Project on the dissemination, implementation and evaluation of the tool of the rubric of evaluation in humanistic subjects, as well as the promotion of the communication between students and teachers in relation to the processes and instruments of evaluation and learning by tasks, based on the objectives of evaluation by competences. The actions have been directed to 18 subjects, (all of them from the branches of humanities), and in which teachers from 4 departments of the Faculty of Philosophy and Letters of the University of Córdoba have intervened. The application of the rubric of evaluation in the various subjects related to the project affected more than 850 students of 5 different degrees. After a process of study, elaboration, review and implementation, an evaluation activity was reached aimed at both students and teachers, which is summarized in a high degree of satisfaction by both parties and in the continued application of this tool in subsequent courses

GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands

GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Developmental expression of Drosophila Wiskott-Aldrich Syndrome family proteins

PMCID: PMC3288701[Background]: Wiskott-Aldrich Syndrome (WASP) family proteins participate in many cellular processes involving rearrangements of the actin cytoskeleton. To the date, four WASP subfamily members have been described in Drosophila: Wash, WASp, SCAR, and Whamy. Wash, WASp, and SCAR are essential during early Drosophila development where they function in orchestrating cytoplasmic events including membrane-cytoskeleton interactions. A mutant for Whamy has not yet been reported. [Results]: We generated monoclonal antibodies that are specific to Drosophila Wash, WASp, SCAR, and Whamy, and use these to describe their spatial and temporal localization patterns. Consistent with the importance of WASP family proteins in flies, we find that Wash, WASp, SCAR, and Whamy are dynamically expressed throughout oogenesis and embryogenesis. For example, we find that Wash accumulates at the oocyte cortex. WASp is highly expressed in the PNS, while SCAR is the most abundantly expressed in the CNS. Whamy exhibits an asymmetric subcellular localization that overlaps with mitochondria and is highly expressed in muscle. [Conclusions]: All four WASP family members show specific expression patterns, some of which reflect their previously known roles and others revealing new potential functions. The monoclonal antibodies developed offer valuable new tools to investigate how WASP family proteins regulate actin cytoskeleton dynamics.This work was supported by CSIC Mobility Fellowship PA1003163 to AERN and by NIH grant GM097083 to SMP. Grant Sponsor: NIH; Grant Number: GM097083; Grant Sponsor: CSIC; Grant Number: PA1003163.Peer Reviewe

HID-1, a New Component of the Peptidergic Signaling Pathway

hid-1 was originally identified as a Caenorhabditis elegans gene encoding a novel conserved protein that regulates the decision to enter into the enduring dauer larval stage. We isolated a novel allele of hid-1 in a forward genetic screen for mutants mislocalizing RBF-1 rabphilin, a RAB-27 effector. Here we demonstrate that HID-1 functions in the nervous system to regulate neuromuscular signaling and in the intestine to regulate the defecation motor program. We further show that a conserved N-terminal myristoylated motif of both invertebrate and vertebrate HID-1 is essential for its association with intracellular membranes in nematodes and PC12 cells. C. elegans neuronal HID-1 resides on intracellular membranes in neuronal cell somas; however, the kinesin UNC-104 also transports HID-1 to synaptic regions. HID-1 accumulates in the axons of unc-13 and unc-31 mutants, suggesting it is associated with neurosecretory vesicles. Consistent with this, genetic studies place HID-1 in a peptidergic signaling pathway. Finally, a hid-1 null mutation reduces the levels of endogenous neuropeptides and alters the secretion of fluorescent-tagged cargos derived from neuronal and intestinal dense core vesicles (DCVs). Taken together, our findings indicate that HID-1 is a novel component of a DCV-based neurosecretory pathway and that it regulates one or more aspects of the biogenesis, maturation, or trafficking of DCVs