Verifying big data topologies by-design: a semi-automated approach

Big data architectures have been gaining momentum in recent years. For instance, Twitter uses stream processing frameworks like Apache Storm to analyse billions of tweets per minute and learn the trending topics. However, architectures that process big data involve many different components interconnected via semantically different connectors. Such complex architectures make possible refactoring of the applications a difficult task for software architects, as applications might be very different with respect to the initial designs. As an aid to designers and developers, we developed OSTIA (Ordinary Static Topology Inference Analysis) that allows detecting the occurrence of common anti-patterns across big data architectures and exploiting software verification techniques on the elicited architectural models. This paper illustrates OSTIA and evaluates its uses and benefits on three industrial-scale case-studies

Effects of combined drug treatments on Plasmodium falciparum : in vitro assays with doxycycline, ivermectin and efflux pump inhibitors

There is great concern regarding the rapid emergence and spread of drug-resistance in Plasmodium falciparum, the parasite responsible for the most severe form of human malaria. Parasite populations resistant to some or all the currently available antimalarial treatments are present in different world regions. Considering the need for novel and integrated approaches to control malaria, combinations of drugs were tested on P. falciparum. The primary focus was on doxycycline, an antibiotic that specifically targets the apicoplast of the parasite. In combination with doxycycline, three different drugs known to inhibit efflux pumps (verapamil, elacridar and ivermectin) were tested, with the assumption that they could increase the intracellular concentration of the antibiotic and consequently its efficacy against P. falciparum. We emphasize that elacridar is a third-generation ABC transporters inhibitor, never tested before on malaria parasites. In vitro experiments were performed on asexual stages of two strains of P. falciparum, chloroquine-sensitive (D10) and chloroquineresistant (W2). Incubation times on asynchronous or synchronous cultures were 72h or 96h, respectively. The antiplasmodial effect (i.e. the IC50) was determined by measuring the activity of the parasite lactate dehydrogenase, while the interaction between drugs was determined through combination index (CI) analyses. Elacridar achieved an IC50 concentration comparable to that of ivermectin, approx. 10-fold lower than that of verapamil, the other tested ABC transporter inhibitor. CI results showed synergistic effect of verapamil plus doxycycline, which is coherent with the starting hypothesis, i.e. that ABC transporters represent potential targets, worth of further investigations, towards the development of companion molecules useful to enhance the efficacy of antimalarial drugs. At the same time, the observed antagonistic effect of doxycycline in combination with ivermectin or elacridar highlighted the importance of drug testing, to avoid the de-facto generation of a sub-dosage, a condition that facilitates the development of drug resistance

The interplay between hormone signaling and defense gene expression in grapevine genotypes carrying genetic resistance against Plasmopara viticola

The present study aimed to investigate plant defense related pathways during Plasmopara viticola infection in Vitis vinifera varieties. Plant material consisted of 'Chardonnay' (no Rpv), 'Regent' (Rpv3-1), 'Bronner' (Rpv3-3+Rpv10), 'Calardis Blanc' (Rpv3-1+Rpv3-2), and the breeding selection GF15 (Rpv1+Rpv3-1). Gene expression analysis was carried out for the varieties 'Regent', GF15, 'Bronner', and 'Chardonnay'. Hormonal quantification was performed for jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), indole-3-acetic acid (IAA), and trans-zeatin-ribose (tZR). The samples were collected from plants cultivated in vitro inoculated with Plasmopara viticola sporangia, and collected at 0, 1-, 3-, 5-, and 7-days post inoculation (DPI) for gene expression; and 0, 3, 5, and 7 DPI for hormonal quantification. The results showed an interaction between genotype and time post inoculation in gene expression and hormonal pathways linked with pathogen recognition. Both jasmonate and salicylic acids were involved in the resistance response. The role of stilbenes acting against the pathogen at different times was also confirmed. Changes in the expression of genes linked to cell defense were observed in all evaluated genotypes; however, genotypes with R-loci responded more quickly than the variety without R-loci, activating mechanisms of cell death, resulting in symptoms of hypersensitivity

Anthracnose susceptibility for grapevines with resistance loci to downy and powdery mildew in Southern Brazil

Anthracnose, downy and powdery mildew are the principal fungal diseases of grapes in tropical and subtropical regions. The pesticide active ingredients that control downy and powdery mildew diseases provide some protection against anthracnose attack. The release of varieties with resistance alleles to downy and powdery mildew results in less pesticide use that can increase anthracnose attack. Thus, the present work aimed to evaluate anthracnose susceptibility of genotypes with resistance loci to downy and powdery mildew under Southern Brazilian conditions. Genotype susceptibility was tested, as well as the influence of the environment (location and crop season) on increased susceptibility to anthracnose infection. To accomplish the objective, a trifactorial design was established that included 20 genotypes, two locations, and two crop seasons. Anthracnose incidence and severity were evaluated under natural infection in the field. Temperature around 16 °C and relative humidity at 84 % increased susceptibility to anthracnose infection compared to temperature around 20 °C and relative humidity at 75 %. All tested genotypes with resistance alleles to downy and powdery mildew presented symptoms of anthracnose. 'Baron', 'Cabernet Cortis' and 'Calardis Blanc' showed the least susceptibility to anthracnose, whereas 'Aromera', 'Felicia', 'Gf.2004-043-0004' and 'Gf.2004-043-0021' were the most susceptible and bore symptoms of anthracnose. Other genotypes showed variable susceptibility during the evaluation period, depending on environmental conditions. Overall, all interactions among the three tested factors were highly significant

Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response

Communicating climate knowledge proxies, processes, politics

This forum article is the product of interdisciplinary discussion at a conference on climate histories held inCambridge, United Kingdom, in early 2011, with the specific aim of building a network around the issue of communicating cultural knowledge of environmental change. The lead articles, by Kirsten Hastrup as an anthropologist and Simon Schaffer as a historian of science, highlight the role of agents and proxies. These are followed by five interdisciplinary commentaries, which engage with the lead articles through new ethnographic material, and a set of shorter commentaries by leading scholars of different disciplines. Finally, the lead authors respond to the discussion. In this debate, climate change does not emerge as a single preformed "problem." Rather, different climate knowledges appear as products of particular networks and agencies. Just as the identification of proxies creates agents (ice, mountains, informants) by inserting them into new networks, we hope that these cross-disciplinary exchanges will produce further conversations and new approaches to action. © 2012 by The Wenner-Gren Foundation for Anthropological Research

Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats.

Abstract Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3–L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3–L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS

Solitary waves in the Nonlinear Dirac Equation

In the present work, we consider the existence, stability, and dynamics of solitary waves in the nonlinear Dirac equation. We start by introducing the Soler model of self-interacting spinors, and discuss its localized waveforms in one, two, and three spatial dimensions and the equations they satisfy. We present the associated explicit solutions in one dimension and numerically obtain their analogues in higher dimensions. The stability is subsequently discussed from a theoretical perspective and then complemented with numerical computations. Finally, the dynamics of the solutions is explored and compared to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger equation. A few special topics are also explored, including the discrete variant of the nonlinear Dirac equation and its solitary wave properties, as well as the PT-symmetric variant of the model

Endocannabinoids and cardiovascular prevention: real progress?

The prevalence of obesity continues to increase and represents one of the principal causes of cardiovascular morbidity and mortality. After the discovery of a specific receptor of the psychoactive principle of marijuana, the cannabinoid receptors and their endogenous ligands, several studies have demonstrated the role of this system in the control of food intake and energy balance and its overactivity in obesity. Recent studies with the CB1 receptor antagonist rimonabant have demonstrated favorable effects such as a reduction in body weight and waist circumference and an improvement in metabolic factors (cholesterol, triglycerides, glycemia etc). Therefore, the antagonism of the endocannabinoid (EC) system, if recent data can be confirmed, could be a new treatment target for high risk overweight or obese patients. Obesity is a growing problem that has epidemic proportions worldwide and is associated with an increased risk of premature death (1–3). Individuals with a central deposition of fats have elevated cardiovascular morbidity and mortality (including stroke, heart failure and myocardial infarction) and, because of a growing prevalence not only in adults but also in adolescents, it was reclassified in AHA guidelines as a “major modifiable risk factor” for coronary heart disease (4, 5). Although first choice therapy in obesity is based on correcting lifestyle (diet and physical activity) in patients with abdominal obesity and high cardiovascular risk and diabetes, often it is necessary to use drugs which reduce the risks. The EC system represents a new target for weight control and the improvement of lipid and glycemic metabolism (6, 7)