Hormone replacement therapy and estrogen replacement therapy have shown the ability to reduce risk of colon cancer development in clinical and animal studies, but in vitro research has been unable to reproduce an estradiol (E2) induced response in colon cancer cell lines. We demonstrated that young adult mouse colonocytes (YAMC, non-malignant colonocytes) exhibit an anti-proliferative response to E2 treatment. These cells demonstrate reduced cell culture growth and increased apoptosis in response to E2. YAMC cells containing an activated Ras mutation are considered to be malignantly transformed, and lose the ability to respond to E2 treatment. Fulvestrant (ICI) was used as an estrogen receptor antagonist to determine that these results were estrogen receptor mediated. Furthermore, this effect was demonstrated to require the presence of ER? through the use of a transgenic ERbeta knockout mouse. In these mice, the presence of E2 significantly reduced the formation of azoxymethane induced premalignant lesions. Since YAMC cells exhibit an anti-proliferative response to E2 treatment, we utilized isogenic YAMC cell lines with and without a dominant negative p53 mutation to demonstrate that this E2 induced action involves p53 activity. E2 treatment results in increased p53 transcriptional activity and a pro-apoptotic change in expression of p53 downstream targets. Presence of the dominant negative p53 mutant nullifies these effects of E2 treatment. The involvement of p53 in the previously described protection against AOM induced premalignant lesions, was investigated using wild type and heterozygous p53 knockout (Het p53KO) mice. The reduction in p53 protein corresponded to reduced effectiveness of E2 treatment on the prevention of premalignant lesion formation in Het p53KO mice. In summary, our data indicate that E2 treatment induces anti-proliferative responses in non-malignant colonocytes and protects against the formation of carcinogen-induced premalignant lesions. These effects require the presence of functional ER? and p53. Further studies are required to more thoroughly elucidate the specific interactions and downstream effects of ER? and p53 in response to E2 stimulation.

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No description available.

No description available.

Organizational commitment has been recognized as a multiple foci phenomenon with two of the more important foci being the work team and the organization as a whole. That organizational and team commitment can vary differentially has been established. However, research has not attempted to determine the antecedents that may cause them to do so. At the same time, a number of constructs that have been explored as antecedents of organizational commitment have also been recognized as having particular salience in a self-directed work team environment. The purpose of this research is to test a model in which it has been hypothesized that certain antecedents will have differential effects on organizational commitment and team commitment. The model was developed employing constructs that are antecedents of commitment in the workplace and are of particular importance in a self-directed work team environment. All but one of the hypotheses were supported indicating that factors that are important in a self-directed work team environment have differential effects on organizational and team commitment. The results are discussed in terms of both theory and praxis. Implications for practicing managers and future research are presented along with the limitations of the study. / Ph. D.

Milk fat globule membrane surrounds the fat droplets of milk. It is a biopolymer containing primarily membrane glycoproteins and polar lipids which contribute to its properties as a possible neutraceutical. The aims of the studies were to determine if dietary milk fat globule membrane: (1) confers protection against colon carcinogenesis; and (2) promotes gut mucosal integrity while decreasing inflammation compared to diets containing corn oil or anhydrous milk fat. Aim 1. Three dietary treatments differing only in the fat source were formulated: (1) AIN-76A, corn oil; (2) AIN-76A, anhydrous milk fat; and (3) AIN-76A, 50% milk fat globule membrane, 50% anhydrous milk fat. Each diet was formulated to contain 50 g/kg diet of fat and to be identical in macro and micro nutrient content. To assess protection against colon carcinogenesis, male, weanling Fischer-344 rats were randomly assigned to one of the three dietary treatments. Animals were injected with 1,2-dimethylhydrazine once per week at weeks 3 and 4. After 13 weeks animals were sacrificed, colons were removed, and aberrant crypt foci were counted by microscopy. Rats fed the milk fat globule membrane diet (n = 16) had significantly fewer aberrant crypt foci (20.9 ± 5.7) compared to rats fed corn oil (n = 17) or anhydrous milk fat (n = 16) diets (31.3 ± 9.5 and 29.8 ± 11.4 respectively; P < 0.05). Aim 2. Male BALB/c mice were randomly assigned to one of two diets: AIN- 76A, corn oil or AIN-76A, 50% milk fat globule membrane, 50% anhydrous milk fat. After 5 weeks mice were injected with saline vehicle control or lipopolysaccharide and gavaged with dextran-FITC. To assess gut mucosal integrity and inflammation, serum samples were assayed for dextran-FITC 24 and 48 hours after gavage, and a panel of 16 cytokine concentrations was analyzed. Serum concentrations of IL-6, IL-10, IL-17, MCP-1, IFNγ, and TNFα decreased and gut permeability decreased 45% in lipopolysaccharide challenged mice fed milk fat globule membrane diet compared to control diet at 24 hours (P < 0.05). Overall, the results of these aims suggest that diets containing milk fat globule membrane are protective against colon carcinogenesis, inhibit the inflammatory response, and protect against gastrointestinal stress.

Recent studies indicate that employees distinguish between commitments to interpersonal foci within the organization, such as supervisors and coworkers. Often, these commitments account for variance in outcomes incremental to organizational commitment (e.g., Becker, 1992). Unfortunately, research has tended to focus on affective forms of commitment to foci, while ignoring normative and continuance commitment. To address this gap, the current study proposed and tested models of commitment to foci which incorporate normative and continuance commitment in addition to affective commitment. Results showed some parallels with findings concerning organizational commitment. Much like organizational commitment, support from a focus relates to affective commitment to that focus, while expectations from a focus predict normative commitment to the focus. Additionally, both affective and normative commitment to supervisors and coworkers predicted favorable outcomes, but continuance commitment did not. In line with researchers recommendations (e.g., Johnson, Groff & Taing, in press), interactions among different bases and foci of commitment were also examined. Exploratory analyses suggested a three-way interaction between affective organizational, supervisor, and coworker commitment for predicting in-role performance.

Syftet med denna uppsats är att undersöka vad som händer med vänskap på Facebook. En utgångspunkt i undersökningen är presentation av relevanta teorier om vänskap som jämförs med resultat av intervjuer med fem personer som är Facebookanvändare. Semistrukturerade intervjuer används som en kvalitativ ansats för att genomföra undersökningen. Undersökningens teoriunderlag består bl.a. utav redogörelsen av teorier om vänskap, ”aktivitetsfokus”, mångfalden av vänskap, vänskapsmekanismer, samt nätverk, organisation och partiell organisation. Facebook är ett snabbt växande socialt medium med fler än 500 miljoner registrerade användare över hela världen. Det intressanta är om vänskapens innehåll och mening förblir samma som vi upplevde det innan Facebook. Präglar Facebook som en social nätgemenskap våra vänskapsrelationer idag? Det är svårt att definiera vänskap. Intervjuerna har visat att vi fortfarande tänker på våra bästa vänner som de som alltid finns där när man behöver dem. En vänskap är sann, äkta, verklig och riktig. Enligt intervjuresultat ser man att alla vänner på Facebookvänskapslistor inte kan kallas för vänner egentligen. De är uppdelade i följande grupper som bekanta, ”yttre bekanta”, kollegor, släkt och gamla klasskompisar t ex. Man kan få nya vänner på Facebook, men då handlar det om ett gemensamt intresse eller en aktivitet som är substansen till den nya vänskapsrelationen. Undersökningens resultat har visat att man ofta blir vän på Facebook även med t ex sina vänners vänner. Detta är ett beteende som avviker från vänskapsteorin. Enligt vänskapsteorin behöver vi inte vara vänner med våra vänners vänner. Undersökningens slutsats är att alla intervjupersonerna upplever att deras vänskapsrelationer på Facebook inte har förändrats eller har möjligtvis blivit bättre. Det är tydligt att man upplever att Facebook underlättar kommunikation med vänner. Man har känslan av att ha sina vänner nära hela tiden pga. Facebook. Men sina bästa vänner kontaktar man ofta på ett annat sätt, dvs. via telefon eller träffar.

Aberrant DNA synthesis and maintenance have been implicated in numerous human diseases. I describe here a novel strategy for systematically identifying budding yeast mutants with elevated levels of DNA damage foci, which represent hubs of DNA damage and repair. A previous study manually scored foci in single mutants but was limited in its ability to survey many conditions in large populations. I developed an automated and statistically robust method for identifying aberrant foci phenotypes by combining synthetic genetic array (SGA) and high-content screening (HCS) methodology. Using this approach, I scored thousands of essential and non-essential gene mutants subjected to environmental and genetic perturbations, including the DNA damaging agent, phleomycin, and deletions of DNA repair genes, SGS1 and YKU80. Collectively, I identified a functionally enriched set of 367 mutants that had increased frequencies of DNA damage foci and established SGA-HCS as a powerful tool for investigating the yeast DNA damage response.

Aberrant DNA synthesis and maintenance have been implicated in numerous human diseases. I describe here a novel strategy for systematically identifying budding yeast mutants with elevated levels of DNA damage foci, which represent hubs of DNA damage and repair. A previous study manually scored foci in single mutants but was limited in its ability to survey many conditions in large populations. I developed an automated and statistically robust method for identifying aberrant foci phenotypes by combining synthetic genetic array (SGA) and high-content screening (HCS) methodology. Using this approach, I scored thousands of essential and non-essential gene mutants subjected to environmental and genetic perturbations, including the DNA damaging agent, phleomycin, and deletions of DNA repair genes, SGS1 and YKU80. Collectively, I identified a functionally enriched set of 367 mutants that had increased frequencies of DNA damage foci and established SGA-HCS as a powerful tool for investigating the yeast DNA damage response.