1,292 research outputs found

    Delivering manufacturing technology and workshop appreciation to engineering undergraduates using the flipped classroom approach

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    Delivery of manufacturing technology and practical workshop-based work, on undergraduate engineering courses that engage the learners, is challenging. The paper presents an experimental method of workshop delivery using the flipped learning approach, a pedagogical model in which the typical lecture and homework elements of a course are reversed. Video lectures are viewed by students prior to class. In-class time can be devoted to exercises, projects, or discussions as in this case. Learners were asked to observe three audiovisual clips in preparation for class. The objective was to determine whether the flipped classroom approach can enhance the learning experience, through better engagement with the students, compared to conventional classroom-based learning. The level of student participation and level of success have been established by means of feedback questionnaires from more than 100 participants and peer observation. The results are encouraging and demonstrate that this approach is favoured by the students

    From Nonstandard Analysis to various flavours of Computability Theory

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    As suggested by the title, it has recently become clear that theorems of Nonstandard Analysis (NSA) give rise to theorems in computability theory (no longer involving NSA). Now, the aforementioned discipline divides into classical and higher-order computability theory, where the former (resp. the latter) sub-discipline deals with objects of type zero and one (resp. of all types). The aforementioned results regarding NSA deal exclusively with the higher-order case; we show in this paper that theorems of NSA also give rise to theorems in classical computability theory by considering so-called textbook proofs.Comment: To appear in the proceedings of TAMC2017 (http://tamc2017.unibe.ch/

    Induction of humoral immune response to multiple recombinant Rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

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    BACKGROUND: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiological agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect feeding success and possibly reduce tick-borne transmission of T. parva. Here we report the evaluation of a multivalent vaccine cocktail of tick antigens for their ability to reduce R. appendiculatus feeding success and possibly reduce tick-transmission of T. parva in a natural host-tick-parasite challenge model. METHODS: Cattle were inoculated with a multivalent antigen cocktail containing recombinant tick protective antigen subolesin as well as two additional R. appendiculatus saliva antigens: the cement protein TRP64, and three different histamine binding proteins. The cocktail also contained the T. parva sporozoite antigen p67C. The effect of vaccination on the feeding success of nymphal and adult R. appendiculatus ticks was evaluated together with the effect on transmission of T. parva using a tick challenge model. RESULTS: To our knowledge, this is the first evaluation of the anti-tick effects of these antigens in the natural host-tick-parasite combination. In spite of evidence of strong immune responses to all of the antigens in the cocktail, vaccination with this combination of tick and parasite antigens did not appear to effect tick feeding success or reduce transmission of T. parva. CONCLUSION: The results of this study highlight the importance of early evaluation of anti-tick vaccine candidates in biologically relevant challenge systems using the natural tick-host-parasite combination

    Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

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    Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans

    Identification of Streptococcus pneumoniae by a real-time PCR assay targeting SP2020.

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    Real-time PCR targeting lytA (the major autolysin gene) and piaB (permease gene of the pia ABC transporter) are currently used as the gold-standard culture-independent assays for Streptococcus pneumoniae identification. We evaluated the performance of a new real-time PCR assay - targeting SP2020 (putative transcriptional regulator gene) - and compared its performance with the assays previously described. A collection of 150 pneumococci, 433 non-pneumococci and 240 polymicrobial samples (obtained from nasopharynx, oropharynx, and saliva; 80 from each site) was tested. SP2020 and lytA-CDC assays had the best performance (sensitivity of 100% for each compared to 95.3% for piaB). The specificity for lytA and piaB was 99.5% and for SP2020 was 99.8%. Misidentifications occurred for the three genes: lytA, piaB and SP2020 were found in non-pneumococcal strains; piaB was absent in some pneumococci including a serotype 6B strain. Combining lytA and SP2020 assays resulted in no misidentifications. Most polymicrobial samples (88.8%) yielded concordant results for the three molecular targets. The remaining samples seemed to contain non-typeable pneumococci (0.8%), and non-pneumococci positive for lytA (1.7%) or SP2020 (8.7%). We propose that combined detection of both lytA-CDC and SP2020 is a powerful strategy for the identification of pneumococcus either in pure cultures or in polymicrobial samples

    Application of two machine learning algorithms to genetic association studies in the presence of covariates

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    BACKGROUND: Population-based investigations aimed at uncovering genotype-trait associations often involve high-dimensional genetic polymorphism data as well as information on multiple environmental and clinical parameters. Machine learning (ML) algorithms offer a straightforward analytic approach for selecting subsets of these inputs that are most predictive of a pre-defined trait. The performance of these algorithms, however, in the presence of covariates is not well characterized. METHODS AND RESULTS: In this manuscript, we investigate two approaches: Random Forests (RFs) and Multivariate Adaptive Regression Splines (MARS). Through multiple simulation studies, the performance under several underlying models is evaluated. An application to a cohort of HIV-1 infected individuals receiving anti-retroviral therapies is also provided. CONCLUSION: Consistent with more traditional regression modeling theory, our findings highlight the importance of considering the nature of underlying gene-covariate-trait relationships before applying ML algorithms, particularly when there is potential confounding or effect mediation

    Deficient prefrontal attentional control in late-life generalized anxiety disorder: an fMRI investigation

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    Younger adults with anxiety disorders are known to show an attentional bias toward negative information. Little is known regarding the role of biased attention in anxious older adults, and even less is known about the neural substrates of any such bias. Functional magnetic resonance imaging (fMRI) was used to assess the mechanisms of attentional bias in late life by contrasting predictions of a top-down model emphasizing deficient prefrontal cortex (PFC) control and a bottom-up model emphasizing amygdalar hyperreactivity. In all, 16 older generalized anxiety disorder (GAD) patients (mean age=66 years) and 12 non-anxious controls (NACs; mean age=67 years) completed the emotional Stroop task to assess selective attention to negative words. Task-related fMRI data were concurrently acquired. Consistent with hypotheses, GAD participants were slower to identify the color of negative words relative to neutral, whereas NACs showed the opposite bias, responding more quickly to negative words. During negative words (in comparison with neutral), the NAC group showed PFC activations, coupled with deactivation of task-irrelevant emotional processing regions such as the amygdala and hippocampus. By contrast, GAD participants showed PFC decreases during negative words and no differences in amygdalar activity across word types. Across all participants, greater attentional bias toward negative words was correlated with decreased PFC recruitment. A significant positive correlation between attentional bias and amygdala activation was also present, but this relationship was mediated by PFC activity. These results are consistent with reduced prefrontal attentional control in late-life GAD. Strategies to enhance top-down attentional control may be particularly relevant in late-life GAD treatment

    Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

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    The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the hostÂŽs cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, JesĂșs SebastiĂĄn. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas MĂ©dicas. Instituto de HistologĂ­a y EmbriologĂ­a de Mendoza Dr. Mario H. Burgos; Argentin

    Control of MRSA infection and colonisation in an intensive care unit by GeneOhm MRSA assay and culture methods

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    Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major nosocomial pathogens. Due to the diffusion of MRSA strains in both hospital and community settings, prevention and control strategies are receiving increased attention. Approximately 25% to 30% of the population is colonised with S. aureus and 0.2% to 7% with MRSA. The BD GeneOhm MRSA real-time PCR assay offers quicker identification of MRSA-colonised patients than do culture methods. Ninety-five patients admitted to the Intensive Care Unit of IRCCS Policlinico San Matteo of Pavia (Italy) for a period > 24 h were screened for MRSA colonisation with both the culture method and the GeneOhm assay. Of the 246 nasal swabs collected from 95 patients, 36 samples were found to be positive by both methods (true-positive). 30% of colonised patients had developed the MRSA infection. Our results show that the GeneOhm MRSA assay is a valuable diagnostic tool for detecting MRSA quickly in nasal swabs. This study confirms that colonisation represents a high risk factor for MRSA infection, and that good MRSA surveillance in an Intensive Care Unit is therefore an excellent way to prevent MRSA infectio

    Psychometric Properties and factor structure of the spanish version of the HC-PAIRS questionnaire

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    Objective To develop a Spanish version of the Health Care Providers" Pain and Impairment Relationship Scale (HC-PAIRS) and to test its psychometric properties. Methods A forward and backward translation methodology was used to translate the questionnaire, which was then applied to 206 participants (174physiotherapy students and 32 family physicians). The intraclass correlation coefficient was calculated to assess testretest reliability. Internal consistency was evaluated using Cronbach"s alpha and item analysis. Construct validity was measured using Pearson correlation coefficients between HC-PAIRS and FABQ, FABQ-Phys, FABQ-Work and the responses given by participants to three clinical case scenarios. An exploratory factor analysis was carried out following the Kaiser normalization criteria and principal axis factoring with an oblique rotation (quartimax). Sensitivity to change was assessed after a teaching module. Results Testretest reliability was ICC 0.50 (p\0.01)and Cronbach"s alpha was 0.825. The HC-PAIRS scores correlated significantly with the scores of the FABQ and also with the recommendations for work and activity given by the participants in the three clinical case scenarios. Sensitivity to change test showed an effect size of 1.5, which is considered a large change. Factor analysis suggests that the Spanish version of HC-PAIRS measures a unidimensional construct. Conclusion The Spanish version of the HC-PAIRS has proven to be a reliable, valid and sensitive instrument to assess health care providers" attitudes and beliefs about LBP. It can be used in evaluating clinical practice and in undergraduate acquisition of skills and knowledge
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