Membrane depolarization is an effective neurotrophic stimulus, with its trophic effect on spiral ganglion neurons (SGNs) even surpassing that of neurotrophins. Thus, SGN cultures are a favorable system to investigate pro-survival signal transduction downstream of depolarization. Depolarization promotes SGN survival by recruiting three distinct kinase pathways: cyclic AMP-dependent protein kinase (PKA), Ca2+/calmodulin-dependent protein kinase II (CaMKII) and CaMKIV. CaMKIV mediates the pro-survival effect of depolarization by activating CREB in nucleus. However, the mechanisms by which PKA and CaMKII promote survival are still not clear. By targeting constitutively active PKA or a PKA inhibitor (PKI) to the outer mitochondrial membrane (OMM), we showed that PKA activity at the OMM is sufficient to support SGN survival in the absence of other trophic factors and necessary for cAMP-dependent SGN survival. It has been suggested that PKA can promote survival by inactivating pro-apoptotic protein Bad. By cotransfection of SGNs with OMM-PKA and wild-type Bad, we showed that this was the case. We further showed that Ser112 and Ser136 in Bad, but not Ser155, a hypothetical PKA target, were necessary for functional inactivation of Bad by PKA. CaMKII mediates the third depolarization-dependent pro-survival pathway. A specific pro-survival target for CaMKII was identified through a separate investigation of the pro-apoptotic JNK-Jun signaling pathway, which we had identified as active in apoptotic SGNs in vivo. By measuring anti-phosphoJun immunofluorescence, we could quantify JNK-Jun activation in SGNs under different conditions. We showed that JNK inhibition or genetic deletion of JNK3 reduces SGN death after neurotrophic factor withdrawal. Neurotrophins have been shown to suppress JNK activation via their receptor protein tyrosine kinases (PTKs). By expressing constitutively active and dominant negative forms of candidate protein kinases, we identified a novel signaling pathway linking depolarization to JNK: Ca2+ entry - CaMKII - FAK/Pyk2 - PI-3-OH Kinase - Protein Kinase B - inhibition of MLKs (upstream activators of JNK). Thus, depolarization also recruits PTKs - the nonreceptor PTKs FAK and Pyk2 - to suppress JNK activation, implying a conserved PTK-PI3K-PKB pathway for suppression of pro-apoptotic JNK activation by neurotrophic stimuli.

Typically, dormant seedlings are transplanted when revegetating nonirrigated disturbed lands in order to prevent transplant shock triggered by water stress. Since dormant seedlings have to be used, this limits the duration of the transplant season. It may be possible to increase this limited season by inducing acclimation responses that would increase drought tolerance. Preconditioning actively growing seedlings to water stress prior to transplanting could induce acclimation responses such as solute accumulation and/or stomatal modulation. Under greenhouse conditions, A. cana and A. intermedium seedlings were subjected to three water stress preconditioning treatments: a well watered control, one dry-down cycle, and three dry-down cycles. After conditioning, seedlings were either allowed to dry-down in their containers until leaf senescence, or were transplanted to disturbed land sites. Plant water potential components, relative water content, and leaf mortality were measured. Immediately following treatments, water relations parameters of preconditioned seedlings were not markedly different from controls in either species. At the end of the final dry-down, water stress preconditioning had not induced active or passive solute accumulation, prolonged leaf survival when exposed to lethal drought conditions, or resulted in differences in transplant survival rates under the experimental conditions of this study.

Alzheimer's disease (AD) has multiple factors that contribute to the disease process. Among these is a state of chronic inflammation that is endured by the brain during the aging process. The use of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the amount of neuroinflammation sustained by the brain, and greater levels of NSAID use have been demonstrated to be associated with decreased probability of developing AD. This study looked at whether greater rates of NSAID use were also associated with decreased rates of cognitive and funtional decline and survival in a population-based sample of persons with AD.

Twenty-nine Rhizobium leguminosarum biovar trifolii strains were tested for acidity tolerance in acidified liquid medium. Only 41\ of the strains grew at pH 4.1. One acid-tolerant strain, USDA 2160, and one acid-sensitive strain, 162-X-103 from Nitragin Co., were inoculated on seeds of 'Nungarin', 'Seaton Park' and 'Clare' subclover cultivars. The inoculated and pelleted seeds were sown in potted Cluff soil with pH 5. 7. Three desiccation levels were imposed by delaying watering for 0, 15 or 30 days. Four gravimetric soil water contents (6.0, 6.6, 10.5 and 12.5\) were maintained under a greenhouse line-source sprinkler system for 7 weeks. The desiccation treatments were more detrimental to the survival of the acid-tolerant Rhizobium strain (USDA 2160) than they were for the acid sensitive strain (162-X-103). Symbiotic effectiveness, measured as shoot dry weight, was higher with strain 162-X- 103 than with strain USDA 2160 and was comparable to the Nfertilized control at the highest water level (12.5 %). At the lower water levels (6.0, 6.6 %) symbiotic N2-fixation was more affected than N-uptake. The Rhizobium strains were able to survive and grow even at the lowest soil water level. The number of rhizobia in the soil and nodulation of the subclover plants had a correlation of 0.56.

Though a new player in town, Amy isn't afraid to get her hands dirty. When she discovers a ruthless sadist named Angel is operating in her new home, Amy makes it her goal to stop Angel. Though Amy quickly finds her sense of justice is putting her at odds with her own survival when Angel takes her own interest in Amy.

How a single party and personal dictatorship survive has been a question of much debate among scholars. Geddes (1999, 2003) creates a model to determine which survives the longest. Within her model, she finds that a single party dictatorship – one with a party apparatus – survives longer than a personal dictatorship – one where a single person has sole policymaking ability. She argues that the fundamental difference between the two is how each treats the opposition. The party apparatus allows a single party dictatorship the means to silence the opposition by coopting it into the party structure whereas a personal dictatorship must rely on the wealthy and military to keep any opposition at bay. With a single party dictatorship being able to coalesce the opposition, this dictatorship is more stable and survives longer. I agree with Geddes’ reasoning and seek to clarify how this situation works in Sub-Saharan Africa. I argue that a single party dictatorship can silence and use religious leaders in the opposition to gain support from the religious leaders’ followers. This additional support from the religious leaders and the followers makes single party dictatorships survive longer than personal dictatorships in Sub-Saharan Africa. In this research, I explain the importance of religion as a variable for dictatorship survival research in Sub-Saharan Africa. I show that religious leaders have a certain level of control over followers and if coopted by a dictatorship, religious leaders’ control garners support among followers. I further explain how religious leaders are in the opposition and therefore can only be coopted by a single party dictatorship. I conclude by showing that religious leaders increase a single party dictatorship’s survival likelihood.

Small business owners play a leading role in the United States economy by creating jobs. However, small businesses have a high failure rate, with approximately 50% going out of business during the first 5 years. The purpose of this multiple case study was to explore the competitive advantage strategies that owners of small businesses used to sustain their businesses longer than the first 5 years. A sample of 6 small service industry business owners in Houston, TX that have been in business for 5 years or more participated in semistructured interviews. Additional data were collected from company documents and the review of artifacts related to small business success and longevity. Entrepreneurship theory provided the conceptual framework for the study. Member checking enhanced the credibility of the interpretations of the participant responses. Data were analyzed using Yin's 5 stages of coding: compiling, disassembling, reassembling, interpreting, and concluding the data. From the data analysis, 3 themes were revealed: financial capital, marketing and competitive advantages, and great customer service. Findings of this study might help owners of small businesses to ensure business growth, increase revenues, and stimulate job creation.

Acute lymphoblastic leukemia (ALL) predominates in children ages 0-14 years and has an excellent prognosis for cure with 5-year survival exceeding 90% in the United States. However, not all children experience such positive outcomes. The purpose of this quantitative, retrospective cohort study was to evaluate differences in survival of ALL among children who reside in the 32-county Texas-Mexico border region. While factors such as poverty and health insurance have been strongly associated with poorer cancer outcomes, additional factors such as geographic isolation and treatment disparities are not as well-documented in children. This study examined the association between use of Texas Children's Oncology Group (COG) pediatric research facilities and survival among children in Texas diagnosed with ALL. This study used cancer incidence data 1995-2009 from the Texas Cancer Registry. Differences in survival and use of COG facilities were investigated between children who reside within the 32-county Texas-Mexico border region and the combined remaining 222 Texas counties. Chi-square was used to analyze area of residence, gender, race/ethnicity, and poverty status between COG and non-COG reported cases. Logistic regression was used to examine ALL survival differences between COG and non-COG facilities controlling for multiple variables. COG affiliation alone was not a significant predictor of survival. An interaction between race/ethnicity, region, poverty status, and COG facility affiliation was observed as a significant predictor of poorer survival. The results of this study have the potential to promote positive social change by implementing interventions addressing access to equivalent pediatric cancer care in the 32-county Texas-Mexico border area.

Serine/threonine phosphatase 2A (PP2A) consists of an AC core dimer composed of catalytic (C), structural (A) subunits complexed to a variable regulatory subunit derived from three gene families (B, B', B"). My dissertation work characterized the structure and function of a neuron-specific splice variant of the Bbeta regulatory gene termed Bbeta2. I found that the divergent N-terminus of Bbeta2 does not affect phosphatase activity or holoenzyme association but encodes a mitochondrial targeting signal. Moreover, transient and stable expression of wild-type Bbeta2 but not Bbeta1, Bbeta2 mutants defective in mitochondrial targeting or a monomeric mutant unable to associate with the holoenzyme, promotes apoptosis in neurons while knock-down of endogenous Bbeta2 is neuroprotective. Furthermore, I identified the mechanisms by which Bbeta2 incorporates the PP2A holoenzyme. By performing charge reversal mutagenesis in Bgamma as a model for B family regulatory subunits, I found that holoenzyme association requires multiple electrostatic charges clustered in WD repeats 3 and 4 of the beta-propeller. To identify residues in Bbeta2 important for mitochondrial association, I performed mutagenesis of the divergent N-terminus of Bbeta2 and identified basic and hydrophobic residues that are critical for mitochondrial association. The variable N-terminal tail of Bbeta2 is a cryptic mitochondrial import sequence that promotes import of GFP, but not full-length Bbeta2, because its beta-propeller domain resists the partial unfolding step necessary for translocation. Lastly, I addressed the mechanism by which Bbeta2 promotes apoptosis in neurons. I found that overexpressing Bbeta2 fragments mitochondria while RNAi of the endogenous protein promotes mitochondrial fusion in neurons. Conversely, targeting PKA, a well characterized prosurvival kinase, to the OMM by overexpressing A kinase anchoring protein 121 (AKAP121) opposes the effects of the phosphatase by elongating mitochondria. Furthermore, downregulating the endogenous AKAP121 by RNAi, or inhibiting PKA at the OMM by overexpressing an inhibitor of PKA (OMM-PKI) fragments mitochondria. The effects of OMM-targeted PP2A or PKA on survival require remodeling of mitochondria, since blocking mitochondrial fission reversed the proapoptotic effects of Bbeta2 and OMM-PKI. My dissertation provides a novel mechanism by which kinase/phosphatase signaling determines neuronal survival.

Infectious diseases, including influenza, measles, and sexually transmitted diseases, spread from person to person. Different attempts have been made to modify or extend traditional epidemic models to relax homogeneity assumptions, so as to handle more complex and realistic situations. We propose a network-based approach to the modeling and prediction of infectious disease outbreaks. Our focus is on heterogeneous populations where there is variation in individual susceptibility, infectivity, and person-to-person contact patterns. To address the complexity of disease propagation over a contact network, we develop a Bayesian survival model that maps the network onto a latent space and uses latent positions to predict disease transmission. We present an R package (`epinet') implementation of our methods and an application to a high school contact network. The package uses C code to implement an MCMC algorithm to efficiently estimate parameters and predict disease outcomes. Our application involves contact data collected by mobile sensors distributed to individuals, and provides estimates of disease transmission in line with the network structure. In it, we address issues that are of direct interest to public health professionals, such as prediction of future outbreaks of diseases. Questions such as whether quarantine will help mitigate an outbreak can also be explored using our proposed model.