Why do Particle Clouds Generate Electric Charges?

Grains in desert sandstorms spontaneously generate strong electrical charges; likewise volcanic dust plumes produce spectacular lightning displays. Charged particle clouds also cause devastating explosions in food, drug and coal processing industries. Despite the wide-ranging importance of granular charging in both nature and industry, even the simplest aspects of its causes remain elusive, because it is difficult to understand how inert grains in contact with little more than other inert grains can generate the large charges observed. Here, we present a simple yet predictive explanation for the charging of granular materials in collisional flows. We argue from very basic considerations that charge transfer can be expected in collisions of identical dielectric grains in the presence of an electric field, and we confirm the model's predictions using discrete-element simulations and a tabletop granular experiment

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.To investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.Residual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.There was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.The immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA

Product and process innovation in manufacturing firms: a 30-year bibliometric analysis

Built upon a thirty-year dataset collected from the Web of Science database, the present research aims to offer a comprehensive overview of papers, authors, streams of research, and the most influential journals that discuss product and process innovation in the manufacturing environment. The dataset is composed of 418 papers from more than 150 journals from the period between 1985 and 2015. Homogeneity analysis by means of alternating least squares (HOMALS) and Social Network Analysis (SNA) are used to accomplish the objectives listed above through the keywords given by authors. Initially, the paper highlights and discusses the similarity between the topics debated by the main journals in this field. Subsequently, a wide-range map of topics is presented highlighting five main areas of interests; namely, performance, patent, small firm, product development, and organization. A SNA is also performed in order to validate the results that emerged from HOMALS. Finally, several insights about future research avenues in the manufacturing field are provided

Global Analysis of Genes Essential for Francisella tularensis Schu S4 Growth In Vitro and for Fitness during Competitive Infection of Fischer 344 Rats

This is the final version. Available from American Society for Microbiology via the DOI in this record The highly virulent intracellular pathogen Francisella tularensis is a Gram-negative bacterium that has a wide host range, including humans, and is the causative agent of tularemia. To identify new therapeutic drug targets and vaccine candidates and investigate the genetic basis of Francisella virulence in the Fischer 344 rat, we have constructed an F. tularensis Schu S4 transposon library. This library consists of more than 300,000 unique transposon mutants and represents a transposon insertion for every 6 bp of the genome. A transposon-directed insertion site sequencing (TraDIS) approach was used to identify 453 genes essential for growth in vitro Many of these essential genes were mapped to key metabolic pathways, including glycolysis/gluconeogenesis, peptidoglycan synthesis, fatty acid biosynthesis, and the tricarboxylic acid (TCA) cycle. Additionally, 163 genes were identified as required for fitness during colonization of the Fischer 344 rat spleen. This in vivo selection screen was validated through the generation of marked deletion mutants that were individually assessed within a competitive index study against the wild-type F. tularensis Schu S4 strain.IMPORTANCE The intracellular bacterial pathogen Francisella tularensis causes a disease in humans characterized by the rapid onset of nonspecific symptoms such as swollen lymph glands, fever, and headaches. F. tularensis is one of the most infectious bacteria known and following pulmonary exposure can have a mortality rate exceeding 50% if left untreated. The low infectious dose of this organism and concerns surrounding its potential as a biological weapon have heightened the need for effective and safe therapies. To expand the repertoire of targets for therapeutic development, we initiated a genome-wide analysis. This study has identified genes that are important for F. tularensis under in vitro and in vivo conditions, providing candidates that can be evaluated for vaccine or antibacterial development.Biotechnology & Biological Sciences Research Council (BBSRC)Defence Science and Technology Laboratory (DSTL

An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions

This is the final version. Available from BMC via the DOI in this recordAvailability of data and materials: The datasets supporting the conclusions of this article are available at the NCBI GEO website https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100226.BACKGROUND: The World Health Organization has categorized plague as a re-emerging disease and the potential for Yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. Environmental temperature is a key signal which regulates virulence of the bacterium. The bacterium normally grows outside the human host at 28 °C. Therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °C is central to the development of vaccines or drugs for the prevention or treatment of human disease. RESULTS: Using a library of over 1 million Y. pestis CO92 random mutants and transposon-directed insertion site sequencing, we identified 530 essential genes when the bacteria were cultured at 28 °C. When the library of mutants was subsequently cultured at 37 °C we identified 19 genes that were essential at 37 °C but not at 28 °C, including genes which encode proteins that play a role in enabling functioning of the type III secretion and in DNA replication and maintenance. Using genome-scale metabolic network reconstruction we showed that growth conditions profoundly influence the physiology of the bacterium, and by combining computational and experimental approaches we were able to identify 54 genes that are essential under a broad range of conditions. CONCLUSIONS: Using an integrated computational-experimental approach we identify genes which are required for growth at 37 °C and under a broad range of environments may be the best targets for the development of new interventions to prevent or treat plague in humans.This work was funded by the Defence Science and Technology Laboratory, award DSTLX-1000060221 (WP1)

Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>P53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma.</p> <p>Methods</p> <p>Serum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted.</p> <p>Results</p> <p>Twenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT.</p> <p>Conclusions</p> <p>Anti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.</p

Evaluation of enamel surface after bracket debonding and polishing

INTRODUCTION: Preserving the dental enamel structure during removal of orthodontic accessories is a clinician's obligation. Hence the search for an evidence based debonding protocol. OBJECTIVE: to evaluate and compare, by means of scanning electron microscopy (SEM), the effects of four different protocols of bracket debonding and subsequent polishing on enamel surface, and to propose a protocol that minimizes damage to enamel surface. METHODS: Twelve bovine permanent incisors were divided into four groups according to the instrument used for debonding and removal of the adhesive remnant. In groups 1 and 2, brackets were debonded with a straight debonding plier (Ormco Corp., Glendora, California, USA), and in groups 3 and 4, debonding was performed with the instrument Lift-Off (3M Unitek, Monrovia, California, USA). In groups 1 and 3, the adhesive remnant was removed using a long adhesive removing plier (Ormco Corp., Glendora, California, USA) and in groups 2 and 4, residual adhesive was removed with a tungsten carbide bur (Beavers Dental) at high-speed. After each stage of debonding and polishing, enamel surfaces were replicated and electron micrographs were obtained with 50 and 200X magnification. RESULTS: All four protocols of debonding and polishing caused enamel irregularities. CONCLUSION: Debonding brackets with straight debonding plier, removal of adhesive remnant with a tungsten carbide bur and polishing with pumice and rubber cup was found to be the protocol that caused less damage to enamel surface, therefore this protocol is suggested for debonding brackets.INTRODUÇÃO: a preservação da estrutura de esmalte após a remoção dos acessórios ortodônticos é obrigação do clínico. Portanto, procura-se um protocolo de descolagem com bases científicas. OBJETIVO: objetivou-se avaliar por microscopia eletrônica de varredura (MEV) a influência de quatro protocolos de remoção de braquetes e polimento da superfície do esmalte e propor um protocolo que minimize os danosà superfície do esmalte. MÉTODOS: doze incisivos permanentes bovinos foram divididos em quatro grupos de acordo com os instrumentos utilizados para a descolagem dos braquetes e remoção do remanescente adesivo. Os braquetes foram descolados com o alicate de descolagem reto (Ormco Corp.) nos grupos 1 e 2, e com o instrumento de descolagem Lift-Off (3M Unitek) nos grupos 3 e 4. Os remanescentes adesivos dos grupos 1 e 3 foram removidos com o alicate removedor de resina longo (Ormco Corp.) e dos grupos 2 e 4 com broca de carboneto de tungstênio (Beavers Dental) em alta-rotação. As superfícies, após cada etapa da descolagem e polimento, foram avaliadas em réplicas de resina epóxica e foram obtidas eletromicrografias com aumento de 50 e 200X. RESULTADOS: os quatro protocolos de remoção de acessórios ortodônticos e polimento ocasionaram irregularidades no esmalte. Conclusão: a remoção do braquete com o alicate de descolagem reto, seguido da remoção do remanescente adesivo com broca de carboneto de tungstênio e polimento final com pasta de pedra-pomes foi o procedimento que ocasionou menores danos ao esmalte, sendo o protocolo sugerido para a remoção dos acessórios ortodônticos

Shh Signaling from the Nucleus Pulposus Is Required for the Postnatal Growth and Differentiation of the Mouse Intervertebral Disc

Intervertebral discs (IVD) are essential components of the vertebral column. They maintain separation, and provide shock absorbing buffers, between adjacent vertebrae, while also allowing movements between them. Each IVD consists of a central semi-liquid nucleus pulposus (NP) surrounded by a multi-layered fibrocartilagenous annulus fibrosus (AF). Although the IVDs grow and differentiate after birth along with the vertebral column, little is known about the mechanism of this. Understanding the signals that control normal IVD growth and differentiation would also provide potential therapies for degenerative disc disease, which is the major cause of lower back pain and affects a large proportion of the population. In this work, we show that during postnatal growth of the mouse, Sonic hedgehog (Shh) signaling from the NP cells controls many aspects of growth and differentiation of both the NP cells themselves and of the surrounding AF, and that it acts, at least partly, by regulating other signaling pathways in the NP and AF. Recent studies have shown that the NP cells arise from the embryonic notochord, which acts as a major signaling center in the embryo. This work shows that this notochord-derived tissue continues to carry out a major signaling function in the postnatal body and that the IVDs are signaling centers, in addition to their already known functions in the mechanics of vertebral column function

Entrepreneurial orientation and the business performance of SMEs: a quantitative study from the Netherlands

Entrepreneurial Orientation (EO) is often mentioned as an antecedent of growth, competitive advantage and superior performance, and prior empirical research has often shown a positive relationship between EO and performance appears to exist. However, an important question that remains unanswered is what effect EO might have on firm performance during periods of economic crisis, and the severe environmental turbulence that accompany such crises. This research is a first investigation towards the effects of EO on the performance of small and medium sized firms during the current global economic crisis. In this study we use the multidimensional model of EO and test a series of hypotheses pertaining to its performance effects using survey data gathered from 164 Dutch SMEs. The present research shows that proactive firm behavior positively contributes to SME performance during the economic crisis. We further show that innovative SMEs do perform better in turbulent environments, but those innovative SMEs should minimize the level of risk and should take action to avoid projects that are too risky

Intestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation

The idea that stem cells of adult tissues with high turnover are protected from DNA replication-induced mutations by maintaining the same 'immortal' template DNA strands together through successive divisions has been tested in several tissues. In the epithelium of the small intestine, the provided evidence was based on the assumption that stem cells are located above Paneth cells. The results of genetic lineage-tracing experiments point instead to crypt base columnar cells intercalated between Paneth cells as bona fide stem cells. Here we show that these cells segregate most, if not all, of their chromosomes randomly, both in the intact and in the regenerating epithelium. Therefore, the 'immortal' template DNA strand hypothesis does not apply to intestinal epithelial stem cells, which must rely on other strategies to avoid accumulating mutations