SAE-Baja 4WD Redesign

In collaboration with the Baja SAE club, this senior design team is tasked with designing and fabricating a Baja vehicle with the goal of competing with competitive success in a 2021-22 Baja SAE Collegiate Design Series competition. The project will include all aspects of the vehicle, including but not limited to: roll cage, suspension, steering/control, and drivetrain. Also, a goal of the project is to design the vehicle with the future AWD/4WD Baja requirement in mind, while making every effort to meet that goal for this upcoming Baja competition. The team will also manage the ONU Baja SAE Club which includes but is not limited to creating a competition checklist to ensure reliable operation during competition, coordinating the work assignments for club members not on the senior design team, preparing all required documentation/presentations to SAE, and ensuring the team’s vehicle adheres to all rules outlined in the official Baja SAE Rules

Redrafting Ohio\u27s Advance Directive Laws

The Bioethics Network of Ohio (BENO) held its second annual conference on June 12, 1992 at Ohio Dominican College, Columbus, Ohio. Attendees recommended that a Task Force\u27 review Ohio\u27s Durable Power of Attorney for Health Care (DPAHC) and Modified Uniform Rights for the Terminally Ill (MURTIA) laws and suggest changes that would retain the basic structure of these provisions but also simplify and clarify their meaning. The Task Force completed a draft in six months and circulated it to approximately 450 individual and institutional BENO members. About one hundred members responded and this article incorporates most of their comments

Knowledge user survey and Delphi process to inform development of a new risk of bias tool to assess systematic reviews with network meta-analysis (RoB NMA tool)

Background: Network meta-analysis (NMA) is increasingly used in guideline development and other aspects of evidence-based decision-making. We aimed to develop a risk of bias (RoB) tool to assess NMAs (RoB NMA tool). An international steering committee recommended that the RoB NMA tool to be used in combination with the Risk of Bias in Systematic reviews (ROBIS) tool (i.e. because it was designed to assess biases only) or other similar quality appraisal tools (eg, A MeaSurement Tool to Assess systematic Reviews 2 [AMSTAR 2]) to assess quality of systematic reviews. The RoB NMA tool will assess NMA biases and limitations regarding how the analysis was planned, data were analysed and results were presented, including the way in which the evidence was assembled and interpreted. Objectives: Conduct (a) a Delphi process to determine expert opinion on an item's inclusion and (b) a knowledge user survey to widen its impact. Design: Cross-sectional survey and Delphi process. Methods: Delphi panellists were asked to rate whether items should be included. All agreed-upon item were included in a second round of the survey (defined as 70% agreement). We surveyed knowledge users' views and preferences about the importance, utility and willingness to use the RoB NMA tool to evaluate evidence in practice and in policymaking. We included 12 closed and 10 open-ended questions, and we followed a knowledge translation plan to disseminate the survey through social media and professional networks. Results: 22 items were entered into a Delphi survey of which 28 respondents completed round 1, and 22 completed round 2. Seven items did not reach consensus in round 2. A total of 298 knowledge users participated in the survey (14% respondent rate). 75% indicated that their organisation produced NMAs, and 78% showed high interest in the tool, especially if they had received adequate training (84%). Most knowledge users and Delphi panellists preferred a tool to assess both bias in individual NMA results and authors' conclusions. Response bias in our sample is a major limitation as knowledge users working in high-income countries were more represented. One of the limitations of the Delphi process is that it depends on the purposive selection of experts and their availability, thus limiting the variability in perspectives and scientific disciplines. Conclusions: This Delphi process and knowledge user survey informs the development of the RoB NMA tool

Structural characterization of the Hepatitis C Virus NS3 protease from genotype 3a: The basis of the genotype 1b vs. 3a inhibitor potency shift

AbstractThe first structural characterization of the genotype 3a Hepatitis C Virus NS3 protease is reported, providing insight into the differential susceptibility of 1b and 3a proteases to certain inhibitors. Interaction of the 3a NS3 protease with a P2–P4 macrocyclic and a linear phenethylamide inhibitor was investigated. In addition, the effect of the NS4A cofactor binding on the conformation of the protease was analyzed. Complexation of NS3 with the phenethylamide inhibitor significantly stabilizes the protease but binding does not involve residues 168 and 123, two key amino acids underlying the different inhibition of genotype 1b vs. 3a proteases by P2–P4 macrocycles. Therefore, we studied the dynamic behavior of these two residues in the phenethylamide complex, serving as a model of the situation in the apo 3a protein, in order to explore the structural basis of the inhibition potency shift between the proteases of the genotypes 1b and 3a

Incomplete homogenization of 18 S ribosomal DNA coding regions in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>As a result of concerted evolution, coding regions of ribosomal DNA sequences are highly conserved within species and variation is generally thought to be limited to a few nucleotides. However, rDNA sequence variation has not been systematically examined in plant genomes, including that of the model plant <it>Arabidopsis thaliana </it>whose genome was the first to be sequenced.</p> <p>Findings</p> <p>Both genomic and transcribed 18 S sequences were sampled and revealed that most deviation from the consensus sequence was limited to single nucleotide substitutions except for a variant with a 270 bp deletion from position 456 to 725 in <it>Arabidopsis </it>numbering. The deletion maps to the functionally important and highly conserved 530 loop or helix18 in the structure of <it>E. coli </it>16 S. The expression of the deletion variant is tightly controlled during developmental growth stages. Transcripts were not detectable in young seedlings but could be amplified from RNA extracts of mature leaves, stems, flowers and roots of <it>Arabidopsis thaliana </it>ecotype Columbia. We also show polymorphism for the deletion variant among four <it>Arabidopsis </it>ecotypes examined.</p> <p>Conclusion</p> <p>Despite a strong purifying selection that might be expected against functionally impaired rDNAs, the newly identified variant is maintained in the <it>Arabidopsis </it>genome. The expression of the variant and the polymorphism displayed by <it>Arabidopsis </it>ecotypes suggest a transition state in concerted evolution.</p

A drug targeting only p110α can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types

Genetic alterations in PI3K (phosphoinositide 3-kinase) signalling are common in cancer and include deletions in PTEN (phosphatase and tensin homologue deleted on chromosome 10), amplifications of PIK3CA and mutations in two distinct regions of the PIK3CA gene. This suggests drugs targeting PI3K, and p110α in particular, might be useful in treating cancers. Broad-spectrum inhibition of PI3K is effective in preventing growth factor signalling and tumour growth, but suitable inhibitors of p110α have not been available to study the effects of inhibiting this isoform alone. In the present study we characterize a novel small molecule, A66, showing the S-enantiomer to be a highly specific and selective p110α inhibitor. Using molecular modelling and biochemical studies, we explain the basis of this selectivity. Using a panel of isoform-selective inhibitors, we show that insulin signalling to Akt/PKB (protein kinase B) is attenuated by the additive effects of inhibiting p110α/p110β/p110δ in all cell lines tested. However, inhibition of p110α alone was sufficient to block insulin signalling to Akt/PKB in certain cell lines. The responsive cell lines all harboured H1047R mutations in PIK3CA and have high levels of p110α and class-Ia PI3K activity. This may explain the increased sensitivity of these cells to p110α inhibitors. We assessed the activation of Akt/PKB and tumour growth in xenograft models and found that tumours derived from two of the responsive cell lines were also responsive to A66 in vivo. These results show that inhibition of p110α alone has the potential to block growth factor signalling and reduce growth in a subset of tumours

An evidence base to optimise methods for involving patient and public contributors in clinical trials: a mixed-methods study

BACKGROUND: In comparison with other study designs, randomised trials are regarded as particularly likely to benefit from patient and public involvement (PPI). Using mixed-methods research we investigated PPI from the perspectives of researchers and PPI contributors. METHODS: Randomised trials in receipt of funding from the Health Technology Assessment (HTA) programme between 2006 and 2010 were identified. Funding applications and board and referee comments were obtained and data relevant to PPI extracted. Chief investigators (CIs), PPI contributors and UK Clinical Research Collaboration Registered Clinical Trials Units (RCTUs) were surveyed. Interviews were conducted with researchers and PPI contributors. RESULTS: A total of 111 trials were included. Text relevant to PPI was identified in half of the trials for which the first-stage applications were available, but only one-quarter described PPI within their development. In the second stage of the application, the majority provided some text relevant to PPI, with over half having PPI in their development. Fewer than half of referees commented on PPI, and funding boards rarely provided comments in relation to PPI. Seventy-three per cent (81 of 111) of CIs responded to the survey and 98% (79 of 81) included PPI at some stage in their trial. CIs considered high impact from PPI contributors to occur more frequently in trial setup, with low or no impact being more common during trial conduct, analysis and dissemination. Only one-third of CIs provided PPI contributor contact details but all contributors contacted completed the survey. The majority of contributors felt engaged and valued by the research team. Interviews were conducted with researchers and/or PPI contributors for 28 trials identifying two main influences on perception of PPI impact: whether or not CIs expressed personal goals and plans for PPI; and the quality of their relationship with the PPI contributors. The importance of early engagement was identified, with opportunity for input thereafter limited. Three PPI roles were identified: oversight, managerial and responsive. Oversight roles, as required by funders, were associated with low impact in comparison with responsive or managerial roles. Most researchers could see some value in PPI training for researchers, although those that had received such training themselves expressed concerns about its purpose and evidence base. Training for PPI contributors was considered unnecessary, with conversational approaches preferred, although this did not appear to provide an opportunity for role negotiation. The RCTU survey response rate was 85% (39 of 46). The majority (37 of 39) reported PPI within trials co-ordinated by their unit. Trial characteristics were used by half to determine the approach to PPI. Two-thirds reported recent developments or changes in implementing plans for PPI (21 of 33). Support to PPI contributors was commonly offered through members of staff at the unit. CONCLUSIONS: PPI is occurring in the majority of trials funded by the HTA programme, but uncertainty remains about how it is assessed and valued. Early involvement, building a relationship between researchers and contributors, responsive or managerial roles, and having defined goals for PPI were associated with impact. Efficiency could be gained by utilising the RCTU network to identify and tackle challenges, and develop a risk-based approach utilising trial characteristics. Recommendations are made to trial funders and the research community. Given the difficulties for some informants in recalling PPI contributions, future research using a prospective approach would be valuable. Ethnographic research that combines observation and multi-informant interviews is likely to be informative in identifying impact. The research community needs to give further consideration to processes for selecting PPI contributors and models of implementing PPI

Populist Mobilization: A New Theoretical Approach to Populism*

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112280/1/j.1467-9558.2011.01388.x.pd

Haptics in Education: Exploring an Untapped Sensory Modality

As human beings, we can interact with our environment through the sense of touch, which helps us to build an understanding of objects and events. The implications of touch for cognition are recognized by many educators who advocate the use of “hands-on ” instruction. But is it possible to know something more completely by touching it? Does touch promote the construction of more connected and meaningful understandings? Current technology makes the addition of touch to computer-generated environments possible, but the educational implications of this innovation are still largely unknown. This article is a baseline review that examines the role of touch in cognition and learning and explores the research investigating the efficacy of the haptic augmentation of instruction