A fast branch-and-bound algorithm for non-convex quadratic integer optimization subject to linear constraints using ellipsoidal relaxations

We propose two exact approaches for non-convex quadratic integer minimization subject to linear constraints where lower bounds are computed by considering ellipsoidal relaxations of the feasible set. In the first approach, we intersect the ellipsoids with the feasible linear subspace. In the second approach we penalize exactly the linear constraints. We investigate the connection between both approaches theoretically. Experimental results show that the penalty approach significantly outperforms CPLEX on problems with small or medium size variable domains. © 2015 Elsevier B.V. All rights reserved

Direct Selling: a Marketing Strategy to Shorten Distances between Production and Consumption

Direct sales became in recent years a diversification strategy increasingly used by farms to answer the CAP reform, as well as to react to the continuous price squeeze. Direct sales is in fact a form of marketing that allow farmers to retain a higher share of the final value of products. Far from being a way back to tradition, short chains and direct sales can be seen as strategies to capture new segments of demand interested in local and fresh food, and in more direct contact between consumers and suppliers. The aim of this work is to study the recent evolution of direct selling in Italy and the determinants of the adoption of this marketing strategy. The first part of the paper analyses the evolution of Italian short supply chains and the development of the related institutional framework (national laws and financial incentives). In the second part of the paper the analysis is focused on the determinants of the adoption of direct selling. Specific attention will be devoted to empirically test if the probability of using of this marketing channel is influenced by the farm location in proximity to urban areas.farm diversification, direct selling, short supply chain, periurban agriculture, discrete choice models, Marketing,

Automatic and Intrinsic Auditory "What” and "Where” Processing in Humans Revealed by Electrical Neuroimaging

The auditory system includes 2 parallel functional pathways—one for treating sounds' identities and another for their spatial attributes (so-called "what” and "where” pathways). We examined the spatiotemporal mechanisms along auditory "what” and "where” pathways and whether they are automatically engaged in differentially processing spatial and pitch information of identical stimuli. Electrical neuroimaging of auditory evoked potentials (i.e., statistical analyses of waveforms, field strength, topographies, and source estimations) was applied to a passive "oddball” paradigm comprising 2 varieties of blocks of trials. On "what” blocks, band-pass-filtered noises varied in pitch, independently of perceived location. On "where” blocks, the identical stimuli varied in perceived location independently of pitch. Beginning 100 ms poststimulus, the electric field topography significantly differed between conditions, indicative of the automatic recruitment of distinct intracranial generators. A distributed linear inverse solution and statistical analysis thereof revealed activations within superior temporal cortex and prefrontal cortex bilaterally that were common for both conditions, as well as regions within the right temporoparietal cortices that were selective for the "where” condition. These findings support models of automatic and intrinsic parallel processing of auditory information, such that segregated processing of spatial and pitch features may be an organizing principle of auditory functio

FUS mutant human motoneurons display altered transcriptome and microRNA pathways with implications for ALS pathogenesis

The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to sporadic ALS and other neurological diseases. Several microRNAs (miRNAs) were also deregulated in FUS mutant motoneurons, including miR-375, involved in motoneuron survival. We report that relevant targets of miR-375, including the neural RNA-binding protein ELAVL4 and apoptotic factors, are aberrantly increased in FUS mutant motoneurons. Characterization of transcriptome changes in the cell type primarily affected by the disease contributes to the definition of the pathogenic mechanisms of FUS-linked ALS

Evolution of late Cenozoic Antarctic Ice on the Central Basin of the Ross Sea, Antarctica

第6回極域科学シンポジウム[OG] 地圏11月16日（月）　国立極地研究所３階セミナー

Marked efficacy of Rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced anti-ganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the efficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Marked efficacy of rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced antiganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the eficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Epigenetic control of EMT/MET dynamics: HNF4α impacts DNMT3s through miRs-29

Background and aims: Epithelial-to-mesenchymal transition (EMT) and the reverse mesenchymal-to-epithelial transition (MET) are manifestations of cellular plasticity that imply a dynamic and profound gene expression reprogramming. While a major epigenetic code controlling the coordinated regulation of a whole transcriptional profile is guaranteed by DNA methylation, DNA methyltransferase (DNMT) activities in EMT/MET dynamics are still largely unexplored. Here, we investigated the molecular mechanisms directly linking HNF4α, the master effector of MET, to the regulation of both de novo of DNMT 3A and 3B. Methods: Correlation among EMT/MET markers, microRNA29 and DNMT3s expression was evaluated by RT-qPCR, Western blotting and immunocytochemical analysis. Functional roles of microRNAs and DNMT3s were tested by anti-miRs, microRNA precursors and chemical inhibitors. ChIP was utilized for investigating HNF4α DNA binding activity. Results: HNF4α silencing was sufficient to induce positive modulation of DNMT3B, in in vitro differentiated hepatocytes as well as in vivo hepatocyte-specific Hnf4α knockout mice, and DNMT3A, in vitro, but not DNMT1. In exploring the molecular mechanisms underlying these observations, evidence have been gathered for (i) the inverse correlation between DNMT3 levels and the expression of their regulators miR-29a and miR- 29b and (ii) the role of HNF4α as a direct regulator of miR-29a-b transcription. Notably, during TGFβ-induced EMT, DNMT3s' pivotal function has been proved, thus suggesting the need for the repression of these DNMTs in the maintenance of a differentiated phenotype. Conclusions: HNF4α maintains hepatocyte identity by regulating miR-29a and -29b expression, which in turn control epigenetic modifications by limiting DNMT3A and DNMT3B levels

A Cross-Sectional Survey on Burnout Prevalence and Profile in the Sicilian Population of Ambulance Driver-Rescuers

Introduction: Burnout is present at a high rate in emergency medicine. The ambulance driver-rescuers, who furnish first aid to the victims, are the non-medical part of the Italian 118-service staff. There is a lack of research on burnout risk in Italian Emergency Medical Services and, particularly, for this category of workers. The two Italian studies, including a little group of ambulance driver-rescuers, reported inconsistent findings. Hypothesis: This survey investigated for the first time the prevalence and exact profile of burnout in a large sample of Italian driver-rescuers. As a secondary aim, the study described how the items of the Italian version of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) cluster in components in this sample. Methods: This cross-sectional census survey was conducted from June 2015 through May 2016 and involved all the driver-rescuers operating in Sicily, the biggest and most southern region of Italy. The subjects received a classification according to different profiles of burnout by using the Italian version of the MBI-HSS (burnout, engagement, disengagement, over-extension, and work-inefficacy). In order to explore the existence of independent factors, a Principal Component Analysis (PCA) was conducted on the survey to obtain eigenvalues >one for each component in the data. Results: The final sample comprised 2,361 responders (96.6% of the initial sample). Of them, 29.8% were in burnout (95% confidence interval [CI], 27.8% to 31.8%) and 1.7% presented a severe form (95% CI, 1.1% to 2.3%); 30.0% were engaged in their work (95% CI, 21.0% to 34.8%), 24.7% of responders were disengaged (95% CI, 22.9% to 26.5%), 1.2% presented an over-extension profile (95% CI, 0.8% to 1.7%), and 12.6% felt work-inefficacy (95% CI, 11.3% to 14.1%). The factors loaded into a five-factor solution at PCA, explaining 48.1% of the variance and partially replicating the three-factor structure. The Emotional Exhaustion (EE) component was confirmed. New dimensions from Personal Accomplishment (PA) and Depersonalization (DP) sub-scales described empathy and disengagement with patients, respectively, and were responsible for the increased risk of burnout. Conclusions: These results endorse the importance of screening and psychological interventions for this population of emergency workers, where burnout could manifest itself more insidiously. It is also possible to speculate that sub-optimal empathy skills could be related to the disengagement and work-inefficacy feelings registered

Influence of Development and Dietary Phospholipid Content and Composition on Intestinal Transcriptome of Atlantic Salmon (Salmo salar)

The inclusion of intact phospholipids in the diet is essential during larval development and can improve culture performance of many fish species. The effects of supplementation of dietary phospholipid from marine (krill) or plant (soy lecithin) sources were investigated in Atlantic salmon,Salmo salar. First feeding fry were fed diets containing either krill oil or soybean lecithin supplying phospholipid at 2.6%, 3.2%, 3.6% and 4.2% of diet. Fish were sampled at ~ 2.5 g (~1,990°day post fertilization, dpf) and ~10 g (2,850°dpf). By comparison of the intestinal transcriptome in specifically chosen contrasts, it was determined that by 2,850°dpf fish possessed a profile that resembled that of mature and differentiated intestinal cell types with a number of changes specific to glycerophospholipid metabolism. It was previously shown that intact phospholipids and particularly phosphatidylcholine are essential during larval development and that this requirement is associated with the inability of enterocytes in young fry to endogenously synthesize sufficient phospholipid for the efficient export of dietary lipid. In the immature phase (~1,990°dpf), the dietary phospholipid content as well as its class composition impacted on several biochemical and morphological parameters including growth, but these differences were not associated with differences in intestinal transcriptomes. The results of this study have made an important contribution to our understanding of the mechanisms associated with lipid transport and phospholipid biosynthesis in early life stages of fish