A reflective characterisation of occasional user

This work revisits established user classifications and aims to characterise a historically unspecified user category, the Occasional User (OU). Three user categories, novice, intermediate and expert, have dominated the work of user interface (UI) designers, researchers and educators for decades. These categories were created to conceptualise user's needs, strategies and goals around the 80s. Since then, UI paradigm shifts, such as direct manipulation and touch, along with other advances in technology, gave new access to people with little computer knowledge. This fact produced a diversification of the existing user categories not observed in the literature review of traditional classification of users. The findings of this work include a new characterisation of the occasional user, distinguished by user's uncertainty of repetitive use of an interface and little knowledge about its functioning. In addition, the specification of the OU, together with principles and recommendations will help UI community to informatively design for users without requiring a prospective use and previous knowledge of the UI. The OU is an essential type of user to apply user-centred design approach to understand the interaction with technology as universal, accessible and transparent for the user, independently of accumulated experience and technological era that users live in

Hepatocellular carcinoma: updates in pathogenesis, detection and treatment

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the second most common cause of cancer mortality worldwide [1]. The prognosis of HCC patients is very poor. The rates of HCC incidence and mortality are almost equivalent [2] and have increased across most countries over the past three decades [3]. HCC development is closely associated with the presence of chronic liver disease and cirrhosis, albeit the risk factors underlying this condition vary geographically. Hepatitis B virus (HBV) infection and aflatoxin B1 exposure are predominant risk factors in Asia and Africa, while hepatitis C virus (HCV) infection and alcohol consumption are the main risk factors in Europe, the USA and Japan [3,4,5]. Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease worldwide, and approximately 60% of biopsied NAFLD patients have non-alcoholic steatohepatitis (NASH) [3]. Importantly, patients with NASH are at high risk of developing HCC even without presenting established cirrhosis [6]. With widespread HBV vaccination and the advent of direct-acting antiviral drugs for HCV infection, NAFLD and associated conditions such as diabetes and obesity are emerging as major global risk factors for HCC. In view of the dismal prognosis of HCC patients, implementing preventive strategies would be an ideal approach to quell the incidence of the disease. Obvious interventions include advocating HBV vaccination in endemic regions, achieving HCV eradication with direct-acting antivirals, promoting healthy nutrition and weight reduction, improving diabetes control, and avoiding excessive alcohol consumption. Still, the implementation of these measures is not always feasible

Overview of neutrino-nucleus quasielastic scattering

A review of quasielastic neutrino-nucleus scattering will be presented, with emphasis on bringing together the knowledge (and language) of neutrino physics, electron scattering, and nuclear structure communities. Assumptions commonly made which simplify the theoretical calculations will be examined. Finally, an attempt will be made to identify places where improvement from either theoretical or experimental sides would be more significant.Dirección General de Investigación (DGI). España FPA2007-62216, FIS2008-04189 y FPA2006-13807-C02-01Spanish Consolider-Ingenio programme CPAN CSD2007-0004

Analysis of genetic variability and mapping of point mutations in influenza virus by the RNase A mismatch cleavage method

We have applied the RNase A mismatch cleavage method to analyze genetic variability in RNA viruses by using influenza virus as a model system. Uniformly labeled RNA probes synthesized from a cloned hemagglutinin gene of a given viral strain were hybridized to RNA isolated from other strains of characterized or uncharacterized genetic composition. The RNA.RNA heteroduplexes containing a variable number of base mismatches were digested with RNase A, and the resistant products were analyzed by denaturing polyacrylamide gel electrophoresis. We show that many of these single base mismatches are cleaved by RNase A, generating unique and characteristic patterns of resistant RNA fragments specific for each of the different viral strains. Comparative analysis of the cleavage patterns allows a qualitative estimation of the genetic relatedness and evolution of field strains. We also show that cleavage by RNase A at single base mismatches can readily detect and localize point mutations present in monoclonal antibody-resistant variants. This method should have wide applications in the study of RNA viruses, not only for epidemiological analysis but also in some diagnostic problems, such as characterization of phenotypic mutants.This work was supported by National Institutes of Health Grant CA33021 awarded by the Nationa l Cancer Institute to M.P. and by grants from the Comision Asesora de Investigacion Cientificay Tecnica (Grant 608/438) and Fondo de Investigaciones Sanitarias to J.O. and J.A.M.C.L.-G. was a recipient of a NATO short-term post doctoral fellow-ship while on leave from the Centro Nacional de Microbiologia, Majadahonda, Madri

Matrix metalloproteinase-10 is upregulated by thrombin in endothelial cells and increased in patients with enhanced thrombin generation

OBJECTIVE: Thrombin is a multifunctional serine protease that promotes vascular proinflammatory responses whose effect on endothelial MMP-10 expression has not previously been evaluated. METHODS AND RESULTS: Thrombin induced endothelial MMP-10 mRNA and protein levels, through a protease-activated receptor-1 (PAR-1)-dependent mechanism, in a dose- and time-dependent manner. This effect was mimicked by a PAR-1 agonist peptide (TRAP-1) and antagonized by an anti-PAR-1 blocking antibody. MMP-10 induction was dependent on extracellular regulated kinase1/2 (ERK1/2) and c-jun N-terminal kinase (JNK) pathways. By serial deletion analysis, site-directed mutagenesis and electrophoretic mobility shift assay an AP-1 site in the proximal region of MMP-10 promoter was found to be critical for thrombin-induced MMP-10 transcriptional activity. Thrombin and TRAP-1 upregulated MMP-10 in murine endothelial cells in culture and in vivo in mouse aorta. This effect of thrombin was not observed in PAR-1-deficient mice. Interestingly, circulating MMP-10 levels (P<0.01) were augmented in patients with endothelial activation associated with high (disseminated intravascular coagulation) and moderate (previous acute myocardial infarction) systemic thrombin generation. CONCLUSIONS: Thrombin induces MMP-10 through a PAR-1-dependent mechanism mediated by ERK1/2, JNK, and AP-1 activation. Endothelial MMP-10 upregulation could be regarded as a new proinflammatory effect of thrombin whose pathological consequences in thrombin-related disorders and plaque stability deserve further investigation

The Escherichia coli RutR transcription factor binds at targets within genes as well as intergenic regions.

The Escherichia coli RutR protein is the master regulator of genes involved in pyrimidine catabolism. Here we have used chromatin immunoprecipitation in combination with DNA microarrays to measure the binding of RutR across the chromosome of exponentially growing E. coli cells. Twenty RutR-binding targets were identified and analysis of these targets generated a DNA consensus logo for RutR binding. Complementary in vitro binding assays showed high-affinity RutR binding to 16 of the 20 targets, with the four low-affinity RutR targets lacking predicted key binding determinants. Surprisingly, most of the DNA targets for RutR are located within coding segments of the genome and appear to have little or no effect on transcript levels in the conditions tested. This contrasts sharply with other E. coli transcription factors whose binding sites are primarily located in intergenic regions. We suggest that either RutR has yet undiscovered function or that evolution has been slow to eliminate non-functional DNA sites for RutR because they do not have an adverse effect on cell fitness