Analysis of radiation-induced bystander effects using high content screening

When cells are exposed to (ionising) radiation there is a rapid phosphorylation of a minor nucleosomal histone protein, H2AX, at the sites where double stranded breaks (DSB) occur. This phosphorylation is one of the earliest events in the repair cascade and extends over several mega base pairs surrounding the break. Nowadays it is generally accepted that the formation of γH2AX functions as a signal enhancer. Using immuno histochemistry we can visualise this phosphorylation as foci in the nucleus, where each foci represents a DSB [1]. For our research we use normal human primary fibroblasts (NHDF’s) to study the so called radiation-induced bystander effects which refer to the responses induced in non-irradiated cells, when neighbouring cells are irradiated. Although the exact pathways of transmission are yet to be determined, studies have shown that gap junction-mediated transport and secretion of soluble extracellular factors play an important role [2]. To exclude variation we first tried synchronisation of the fibroblasts using nocodazole or aphidicolin. Our attempts did not produce the desired synchronisation level. In addition, recent reports doubt the effectiveness of these products in cell synchronisation [3]. To resolve this problem, we used high content screening of cells together with specific cell cycle markers. One of these markers is 5-bromo-2-deoxyuridine (BrdU). BrdU, a synthetic nucleoside, is an analogue of thymidine that can be incorporated in replicating cells and specifically label S-phases [4]. Cells are cultured on membrane inserts, with a pore size of 0,4µm allowing soluble factors to pass but preventing the cells to interchange. These cells are irradiated with different doses and subsequently placed together with NHDF that are grown on cover glasses (see figure 1). Depending on the objectives BrdU is added 20-40 minutes before fixation. We found a differential pattern for γH2AX that we could specifically link to the cell cycle. During the S phase γH2AX is significantly more induced than during other phases of the cell cycle (see figure 2). This is probably due to the increased vulnerability caused by the unwinding of DNA during replication. 1. ¬¬S.H.Macphail, J.P.Banath, T.Y.Yu, E.H.Chu, H.Lambur, P.L.Olive, Int.J.Radiat.Biol. 79 (2003) P. 351-358. 2. H.Yang, N.Asaad, K.D.Held, Oncogene 24 (2005) p. 2096-2103. 3. S.Cooper, G.Iyer, M.Tarquini, P.Bissett, Cell Tissue Res. 324 (2006) p.237-242. 4. R.T.O'Keefe, S.C.Henderson, D.L.Spector, J.Cell Biol. 116 (1992) p.1095-1110

Father-Daughter Incest: Data from an Anonymous Computerized Survey

Retrospective data were entered anonymously by 1,521 adult women using computer-assisted self-interview. Nineteen were classified as victims of father–daughter incest, and 241 were classified as victims of sexual abuse by an adult other than their father before reaching 18 years of age. The remaining 1,261 served as controls. Incest victims were more likely than controls to endorse feeling damaged, psychologically injured, estranged from one or both parents, and shamed by others when they tried to open up about their experience. They had been eroticized early on by the incest experience, and it interfered with their adult sexuality. Incest victims experienced coitus earlier than controls and after reaching age 18 had more sex partners and were more likely to have casual sex outside their primary relationship and engage in sex for money than controls. They also had worse scores on scales measuring depression, sexual satisfaction, and communication about sex than controls

Cohesion, Instructional Time and Reading Performance at MUGC Summer Enrichment Program

As schools attempt to improve the services to struggling readers, teacher are encouraged to work collaboratively to enhance instruction. Studies are needed to examine the effects of teaming on student performance. The purpose of this study was to determine if team cohesion or instructional time at Marshall University Graduate College Summer Enrichment Program (MUGCSEP) would be correlated with measures of reading performance for students who attended the program. Statistical analyses yielded a statistically significant correlation between cohesion, instructional time and reading performance during the 2006 program. While in 2007, instructional time was not significantly correlated, cohesion results yielded a mildly inverse statistically significant correlation with reading performance. Due to differences in assessment procedures between the years, this finding supports the possibility that team cohesion may be an important factor in the assessment of children\u27s reading performance

Improving Prolog Programs: Refactoring for Prolog

Refactoring is an established technique from the OO-community to restructure code: it aims at improving software readability, maintainability and extensibility. Although refactoring is not tied to the OO-paradigm in particular, its ideas have not been applied to Logic Programming until now. This paper applies the ideas of refactoring to Prolog programs. A catalogue is presented listing refactorings classified according to scope. Some of the refactorings have been adapted from the OO-paradigm, while others have been specifically designed for Prolog. Also the discrepancy between intended and operational semantics in Prolog is addressed by some of the refactorings. In addition, ViPReSS, a semi-automatic refactoring browser, is discussed and the experience with applying \vipress to a large Prolog legacy system is reported. Our main conclusion is that refactoring is not only a viable technique in Prolog but also a rather desirable one.Comment: To appear in ICLP 200

Innovative research methods for studying treatments for rare diseases: methodological review

Objective: To examine methods for generating evidence on health outcomes in patients with rare diseases. Design: Methodological review of existing literature. Setting: PubMed, Embase, and Academic Search Premier searched for articles describing innovative approaches to randomized trial design and analysis methods and methods for conducting observational research in patients with rare diseases. Main outcome measures We assessed information related to the proposed methods, the specific rare disease being studied, and outcomes from the application of the methods. We summarize methods with respect to their advantages in studying health outcomes in rare diseases and provide examples of their application. Results: We identified 46 articles that proposed or described methods for studying patient health outcomes in rare diseases. Articles covered a wide range of rare diseases and most (72%) were published in 2008 or later. We identified 16 research strategies for studying rare disease. Innovative clinical trial methods minimize sample size requirements (n=4) and maximize the proportion of patients who receive active treatment (n=2), strategies crucial to studying small populations of patients with limited treatment choices. No studies describing unique methods for conducting observational studies in patients with rare diseases were identified. Conclusions: Though numerous studies apply unique clinical trial designs and considerations to assess patient health outcomes in rare diseases, less attention has been paid to innovative methods for studying rare diseases using observational data

Dynamical model of sequential spatial memory: winnerless competition of patterns

We introduce a new biologically-motivated model of sequential spatial memory which is based on the principle of winnerless competition (WLC). We implement this mechanism in a two-layer neural network structure and present the learning dynamics which leads to the formation of a WLC network. After learning, the system is capable of associative retrieval of pre-recorded sequences of spatial patterns.Comment: 4 pages, submitted to PR

Field-Based Experience in Light of Changing Demographics

Due to changing demographics of students admitted to the School Psychology Training Program at Marshall University Graduate College, it has become imperative to significantly expand field experiences beginning in the first semester to address the lack of educational background of most of the students entering the program. This organized sequence of field experiences continues throughout the program, parallel to classroom instruction, affording opportunities for students to put theory into practice and to interact with professionals in the field, while also allowing for exposure to the public school environment. The collaborative field experience sequence provides the students with early and continuous feedback on their personal fit with schools as organizations and culminates with the summer enrichment program

Cultural Wellbeing Index: A Dynamic Cultural Analytics Process for Measuring and Managing Organizational Inclusion as an Antecedent Condition of Employee Wellbeing and Innovation Capacity

The purpose of this study was to validate an inclusive, holistic, evidence-based index to measure the impact of organizational culture on employee wellbeing. This study utilized a new Cultural Wellbeing Index (CWI), a composite of other validated cultural metrics including inputs of hope, trust, and belonging. Internal validity of the index was measured using Cronbach’s alpha and Pearson correlation. Four logistic regression models were completed to test the correlative power of the CWI to employee health, retention, engagement, and job satisfaction. CWI shows strong internal validity and strong correlative and predictive power with employee wellbeing metrics among the population surveyed

Interactive Effects of Drought and Fire on Co-Existing Woody and Herbaceous Communities in a Temperate Mesic Grassland

Increased drought and woody encroachment are likely to have substantial and interactive effects on grassland carbon and water cycling in the future. However, we currently lack necessary information to accurately predict grassland responses to drought-by-fire interactions in areas experiencing woody encroachment. A more thorough understanding of these interactive effects on grass-shrub physiology would improve the effectiveness of demographic vegetation models and refine predictions of future changes in grassland ecosystem function. To this end, we constructed passive rainout shelters over mature Cornus drummondii shrubs and co-existing grasses in two fire treatments (1-year and 4-year burn frequency) at the Konza Prairie Biological Station (north-eastern Kansas, USA) that reduced precipitation by 50%. Plant responses to drought and fire were monitored at the leaf-level (gas exchange, predawn and midday water potential, turgor loss point) and the whole-plant level (aboveground biomass). Here, we report results from the 2020 growing season, after three years of treatment. Photosynthetic rates of C. drummondii and Andropogon gerardii, a dominant C4 grass, were lower in drought treatments at the end of the growing season. A. gerardii also exhibited higher photosynthetic rates in the 4-year burn watershed, but C. drummondii rates were not impacted by burn frequency. Predawn and midday leaf water potential for both species, as well as turgor loss point for C. drummondii, were lower in the 4-year burn treatment, indicating increased water stress. This trend was more pronounced in drought shelters for C. drummondii. These results indicate that three years of 50% precipitation reduction has resulted in modest impacts on water stress and gas exchange in both species. Long-term studies of co-existing grasses and shrubs are useful for informing management of woody encroachment during drought and help to identify whether multiple external pressures (drought and fire) are needed to reverse grassland-to-shrubland transitions in temperate mesic grasslands