Learn global and optimize local:A data-driven methodology for last-mile routing

In last-mile routing, the task of finding a route is often framed as a Traveling Salesman Problem to minimize travel time and associated cost. However, solutions stemming from this approach do not match the realized paths as drivers deviate due to navigational considerations and preferences. To prescribe routes that incorporate this tacit knowledge, a data-driven model is proposed that aligns well with the hierarchical structure of delivery data wherein each stop belongs to a zone — a geographical area. First, on the global level, a zone sequence is established as a result of a minimization over a cost matrix which is a weighted combination of historical information and distances (travel times) between zones. Subsequently, within zones, sequences of stops are determined, such that, integrated with the predetermined zone sequence, a full solution is obtained. The methodology is particularly promising as it propels itself within the top-tier of submissions to the Last-Mile Routing Research Challenge while maintaining an elegant decomposition that ensures a feasible implementation into practice. The concurrence between prescribed and realized routes underpins the adequateness of a hierarchical breakdown of the problem, and the fact that drivers make a series of locally optimal decisions when navigating. Furthermore, experimenting with the balance between historical information and distance exposes that historic information is pivotal in deciding a starting zone of a route. The experiments also reveal that at the end of a route, historical information can best be discarded, making the time it takes to return to the station the primary concern.</p

Pharmacological characterization of a new Ca2+ sensitizer

The benzimidazole molecule was modified to synthesize a Ca(2+) sensitizer devoid of additional effects associated with Ca(2+) overload. Newly synthesized compounds, termed 1, 2, 3, 4, and 5, were evaluated in spontaneously beating and electrically driven atria from reserpine-treated guinea pigs. Compound 3 resulted as the most effective positive inotropic agent, and experiments were performed to study its mechanism of action. In spontaneously beating atria, the inotropic effect of 3 was concentration-dependent (3.0 microM-0.3 mM). Compound 3 was more potent and more active than the structurally related Ca(2+) sensitizers sulmazole and caffeine, but unlike them it did not increase the heart rate. In electrically driven atria, the inotropic activity of 3 was well preserved and it was not inhibited by propranolol, prazosin, ranitidine, pyrilamine, carbachol, adenosine deaminase, or ruthenium red. At high concentrations (0.1-1.0 mM) 3 inhibited phosphodiesterase-III, whereas it did not affect Na(+)/K(+)-ATPase, sarcolemmal Ca(2+)-ATPase, Na(+)/Ca(2+) exchange carrier, or sarcoplasmic reticulum Ca(2+) pump activities of guinea pig heart. In skinned fibers obtained from guinea pig papillary muscle and skeletal soleus muscle, compound 3 (0.1 mM, 1 mM) shifted the pCa/tension relation curve to the left, with no effect on maximal tension and no signs of toxicity. Compound 3 did not influence the basal or raised tone of guinea pig isolated aorta rings, whose cells do not contain the contractile protein troponin. The present results indicate that the inotropic effect of compound 3 seems to be primarily sustained by sensitization of the contractile proteins to Ca(2+)

ISG15 Modulates Development of the Erythroid Lineage

Activation of erythropoietin receptor allows erythroblasts to generate erythrocytes. In a search for genes that are up-regulated during this differentiation process, we have identified ISG15 as being induced during late erythroid differentiation. ISG15 belongs to the ubiquitin-like protein family and is covalently linked to target proteins by the enzymes of the ISGylation machinery. Using both in vivo and in vitro differentiating erythroblasts, we show that expression of ISG15 as well as the ISGylation process related enzymes Ube1L, UbcM8 and Herc6 are induced during erythroid differentiation. Loss of ISG15 in mice results in decreased number of BFU-E/CFU-E in bone marrow, concomitant with an increased number of these cells in the spleen of these animals. ISG15-/- bone marrow and spleen-derived erythroblasts show a less differentiated phenotype both in vivo and in vitro, and over-expression of ISG15 in erythroblasts is found to facilitate erythroid differentiation. Furthermore, we have shown that important players of erythroid development, such as STAT5, Globin, PLC γ and ERK2 are ISGylated in erythroid cells. This establishes a new role for ISG15, besides its well-characterized anti-viral functions, during erythroid differentiation

Develop a basin scale analysis/initial assessment strongly MSP oriented for the Western Mediterranean

This Report has been created thanks to the collaboration of all the Member States involved in the SIMWESTMED project (Figure 1) that have been invited to complete the Country Fiche (CF), a document that has leaded to the development of shared knowledge regarding the marine area considered in the project. Thus, the aim of this Report is to entail a collection of information across the European countries of the Western Mediterranean region and the Strait of Sicily, including Malta waters. The Initial Assessment (IA), in fact, provides an initial overview of the area’s characteristics and this report is the harmonized output of all available information including the description of marine environment, maritime activities, key sectoral and socio-economic trends and emerging pressures, legal and transboundary issues, and governance aspects. The assessment uses existing information by organizing them in a comparable way in order to carry out a previous analysis on the main driver and issues that need to be considered for future MSP processes. The IA is based mainly on desk-based reviews, in order to build a shared synthetic view on the Western Mediterranean region, identifying key issues (main activities and priority conservation issues) and data gaps that are synthesized in the following report.peer-reviewe

Case study #4 : Strait of Sicily - Malta : Western Mediterreanean

The definition of spatial limits for the Strait of Sicily - Malta Case Study have been elaborated considering needs and priorities emerged from the Initial Assessment, as well as existing knowledge on: (i) maritime uses and economic domains; (ii) ecological features; (iii) legal jurisdictions and borders and (iv) transboundary issues. The definition of the case study area’s spatial limits constitute boundaries for the purpose to foster a proper analysis on human uses, ecological processes, synergies and conflicts, governance continuity, and define recommendations to establish appropriated strategies and plans. The boundaries have been drawn according to the scope of the project (e.g. to support the implementation of Maritime Spatial Planning in EU Member States with a concrete cross-border initiative) and the activities to be developed therefore on one hand they are representative of local conditions and policies and, on the other, they take in account potential transboundary and cross-border issues of MSP. The SIMWESTMED case study for Malta is focused on the Malta-Sicily marine waters, bordering the south of Sicily and the north of the Maltese Islands and including part of the continental shelves of Italy and Malta.Grant Agreement: EASME/EMFF/2015/1.2.1.3/02/SI2.742101peer-reviewe

Saude mental na estrategia saude da familia : revisao da literatura brasileira = Mental health in the Family Health Strategy : a review of Brazilian literature

The Family Health Strategy establishes the principles of the Brazilian Primary Health Care and shares important goals with the Psychiatric Reform. The principles of territory-centered care and longitudinal care should enhance innovative actions of mental health promotion, prevention and rehabilitation. The aim of this review was to analyze the main themes approached by the Brazilian scientific literature concerning mental health in the Family Health Strategy. We read the titles of 267 articles published between 1999 and 2009. We followed specific criteria to select 38 articles for thematic analysis. The main themes were the demands in mental health, the perceptions and practices of health personnel and the role of the psychologist in Primary Care. The publications identified several problems: stereotypical views about mental disorders, the dominance of the hospitalization rationale, and the absence of clinical reports, strategies, qualified support to families and integrated health actions. The qualitative meta-analysis indicated questions that may strengthen the debate on the topic, the reflection on further research and on professional practice in the interface between Mental Health and Family Health