The construction and evaluation of four series of lessons to stimulate the flow of ideas in the creative writing of fourth, fifth, and sixth grade pupils.

Thesis (Ed.M.)--Boston Universit

Identifying KIF Subtype that Mediates Axonal Targeting of Kv7 Channels

Early-onset Benign Familial Neonatal Epilepsy (BFNE) and Epileptic Encephalopathy (EE), are associated with mutations in neuronal KCNQ/Kv7 channel subunits Kv7.2 and Kv7.3. Kv7 channels are voltage-dependent potassium channels. Enriched at the axonal plasma membrane, they pump potassium ions out of the neurons and inhibit repetitive or burst firing of action potentials. A single neuronal Kv7 channel is a heterotetramer composed of two Kv7.2 and two Kv7.3 subunits. BFNE and EE mutations in Kv7.2 and Kv7.3 lead to decreased surface expression along the axon, which means less potassium ions are moved across the axonal membrane where action potentials are generated and propagated. This prevents the neuron from returning to its resting potential and allows repetitive action potentials indicative of a seizure. The purpose of this project is to uncover the molecular mechanism by which Kv7 channels are targeted to the axonal surface and enriched at the axonal initial segment (AIS). Since epilepsy mutations in Kv7 channels reduce this axonal targeting, understanding the mechanism underlying axonal targeting could provide therapeutic targets to treat epilepsy. Two motor proteins KIF3A and KIF5B are shown to target other potassium channels such as Kv1 to the axon. Here, we are investigating to test if overexpression of KIF3A and KIF5B proteins will lead to increased surface expression of neuronal Kv7 channels in the axon of hippocampal neurons

Social Support for Changing Multiple Behaviors: Factors Associated With Seeking Support and the Impact of Offered Support

Introduction. Social support is important for behavior change, and it may be particularly important for the complexities of changing multiple risk behaviors (MRB). Research is needed to determine if participants in an MRB intervention can be encouraged to activate their social network to aid their change efforts. Methods. Healthy Directions 2, a cluster-randomized controlled trial of an intervention conducted in two urban health centers, targeted five behaviors (physical activity, fruit and vegetable intake, red meat consumption, multivitamin use, and smoking). The self-guided intervention emphasized changing MRB simultaneously, focused on self-monitoring and action planning, and encouraged participants to seek support from social network members. An MRB score was calculated for each participant, with one point being assigned for each behavioral recommendation that was not met. Analyses were conducted to identify demographic and social contextual factors (e.g., interpersonal, neighborhood, and organizational resources) associated with seeking support and to determine if type and frequency of offered support were associated with changes in MRB score. Results. Half (49.6%) of participants identified a support person. Interpersonal resources were the only contextual factor that predicted engagement of a support person. Compared to individuals who did not seek support, those who identified one support person had 61% greater reduction in MRB score, and participants identifying multiple support persons had 100% greater reduction. Conclusion. Engagement of one’s social network leads to significantly greater change across multiple risk behaviors. Future research should explore strategies to address support need for individuals with limited interpersonal resources

Concomitant Tumor Immunity to a Poorly Immunogenic Melanoma Is Prevented by Regulatory T Cells

Concomitant tumor immunity describes immune responses in a host with a progressive tumor that rejects the same tumor at a remote site. In this work, concomitant tumor immunity was investigated in mice bearing poorly immunogenic B16 melanoma. Progression of B16 tumors did not spontaneously elicit concomitant immunity. However, depletion of CD4+ T cells in tumor-bearing mice resulted in CD8+ T cell–mediated rejection of challenge tumors given on day 6. Concomitant immunity was also elicited by treatment with cyclophosphamide or DTA-1 monoclonal antibody against the glucocorticoid-induced tumor necrosis factor receptor. Immunity elicited by B16 melanoma cross-reacted with a distinct syngeneic melanoma, but not with nonmelanoma tumors. Furthermore, CD8+ T cells from mice with concomitant immunity specifically responded to major histocompatibility complex class I–restricted epitopes of two melanocyte differentiation antigens. RAG1−/− mice adoptively transferred with CD8+ and CD4+ T cells lacking the CD4+CD25+ compartment mounted robust concomitant immunity, which was suppressed by readdition of CD4+CD25+ cells. Naturally occurring CD4+CD25+ T cells efficiently suppressed concomitant immunity mediated by previously activated CD8+ T cells, demonstrating that precursor regulatory T cells in naive hosts give rise to effective suppressors. These results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor

The Grizzly, February 18, 1983

Rally at Bomberger: Students Protest Criticism • Rushes, Administration Meet Before Pledging • Editorial: Staff Members Defend Grizzly • USGA Notes • Letters to the Editor: Letter to the Editor Receives Support; Constructive Criticism Appreciated; Student Interest Sparked; Irresponsible Groups Cause Anger • Is Reaganomics a Reality? • Admissions Standards at Ursinus • President\u27s Corner • Happy Birthday to U • Talent Show Tonight • Occupational Hazards • Fighting Ursini Head to MACs Optimistically • Inconsistency Still Haunting Women\u27s Basketball • Gymnastics Ranked 13th • Badminton Team Tops Rosemont and Moravian • Lady Swimmers Boast 9-1 Record • Werley\u27s Record Speaks for Itselfhttps://digitalcommons.ursinus.edu/grizzlynews/1094/thumbnail.jp

Development of a prototype Lateral Flow Immunoassay (LFI) for the rapid diagnosis of melioidosis

Burkholderia pseudomallei is a soil-dwelling bacterium and the causative agent of melioidosis. Isolation of B. pseudomallei from clinical samples is the “gold standard” for the diagnosis of melioidosis; results can take 3–7 days to produce. Alternatively, antibody-based tests have low specificity due to a high percentage of seropositive individuals in endemic areas. There is a clear need to develop a rapid point-of-care antigen detection assay for the diagnosis of melioidosis. Previously, we employed In vivo Microbial Antigen Discovery (InMAD) to identify potential B. pseudomallei diagnostic biomarkers. The B. pseudomallei capsular polysaccharide (CPS) and numerous protein antigens were identified as potential candidates. Here, we describe the development of a diagnostic immunoassay based on the detection of CPS. Following production of a CPS-specific monoclonal antibody (mAb), an antigen-capture immunoassay was developed to determine the concentration of CPS within a panel of melioidosis patient serum and urine samples. The same mAb was used to produce a prototype Active Melioidosis Detect Lateral Flow Immunoassay (AMD LFI); the limit of detection of the LFI for CPS is comparable to the antigen-capture immunoassay (~0.2 ng/ml). The analytical reactivity (inclusivity) of the AMD LFI was 98.7% (76/77) when tested against a large panel of B. pseudomallei isolates. Analytical specificity (cross-reactivity) testing determined that 97.2% of B. pseudomallei near neighbor species (35/36) were not reactive. The non-reactive B. pseudomallei strain and the reactive near neighbor strain can be explained through genetic sequence analysis. Importantly, we show the AMD LFI is capable of detecting CPS in a variety of patient samples. The LFI is currently being evaluated in Thailand and Australia; the focus is to optimize and validate testing procedures on melioidosis patient samples prior to initiation of a large, multisite pre-clinical evaluation

A combined wear-fatigue design methodology for fretting in the pressure armour layer of flexible marine risers

This paper presents a combined experimental and computational methodology for fretting wear-fatigue prediction of pressure armour wire in flexible marine risers. Fretting wear, friction and fatigue parameters of pressure armour material have been characterised experimentally. A combined fretting wear-fatigue finite element model has been developed using an adaptive meshing technique and the effect of bending-induced tangential slip has been characterised. It has been shown that a surface damage parameter combined with a multiaxial fatigue parameter can accurately predict the beneficial effect of fretting wear on fatigue predictions. This provides a computationally efficient design tool for fretting in the pressure armour layer of flexible marine risers