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

Recent structural evolution of forni glacier tongue (Ortles-Cevedale Group, Central Italian Alps)

Structural glaciology yields important details about the evolution of glacier dynamics in response to climate change. The maps provided here document the occurrence and evolution of brittle and ductile structures on the tongue of Forni Glacier, Ortles-Cevedale Group, Central Italian Alps, between 2003 and 2014. Through the remote sensing-based analysis of structures, we found evidence of brittle fractures such as crevasses, faults and ring faults, and ductile structures such as ogives at the base of the icefall in the eastern glacier tongue. Although each of the three glacier tongues have evolved differently, a reduction in flow-related dynamics and an increase in the number of collapse structures occurred over the study period. Analysis of the glacier structural evolution based on the numbers and the locations of different structures, suggest a slowdown of glacier flow on the eastern tongue. The recent evolution of the glacier also suggests that the occurrence of a disintegration scenario is likely to worsen over the next decades

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+)

Climate change effects on landscape and environment in glacierized Alpine areas: retreating glaciers and enlarging forelands in the Bernina group (Italy) in the period 1954&#8211;2007

We analysed the recent involution of glaciers in the Bernina group (Italy), which are shrinking thus permitting a rapid enlargement of the forelands. We delimited glacier outlines upon aerial photographs (1954 and 1981 stereo pairs analysed through an optical system) and orthophotos (2003 and 2007 digital imagines directly managed via GIS software). All the obtained data were overlapped and compared. The estimated glacier area change during 1954\u20132007 was 1236.5 \ub1 2.4% ( 1216.2 \ub1 0.4 km2). The changes sped up more recently; in fact, during 1981\u20131954 (27 years) the variation was 120.206 km2/y, against 120.387 km2/y during 1981\u20132003 (22 years), and 120.535 km2/y during 2007\u20132003 (4 years). In the 1954\u20132007 period, the forelands experienced a continuous increase (+14.7 km2). Moreover, the analysis of the colour orthophotos allowed observations of: (i) changes a\ufb00ecting shape and geometry of glaciers (growing rock outcrops, tongue separations, increasing supraglacial debris and collapse structures) and (ii) main features of glacier forelands (bare rock exposures, debris and sediments and, in the latter case, occurrence of vegetation colonizing such pristine areas). Glacier forelands resulted also subjected to the action of melting water, debris transport, and periglacial processes, with consequences on landscape and geoheritage

Long-Term Treatment with Aqueous Garlic and/or Tomato Suspensions Decreases Ehrlich Ascites Tumors

We evaluated the preventive and therapeutic effects of aqueous suspensions of garlic, tomato, and garlic + tomato in the development of experimental Ehrlich tumors in mice. The aqueous suspensions (2%) were administered over a short term for 30 days before tumor inoculation and 12 days afterward, and suspensions at 6% were administered for 180 days before inoculation and for 12 days afterward. The volume, number, and characteristics of the tumor cells and AgNOR counts were determined to compare the different treatments. Aqueous 6% suspensions of garlic, tomato, and garlic + tomato given over the long term significantly reduced tumor growth but when given over the short term, they did not alter tumor growth

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

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

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