Hepatocyte growth factor receptor (Met) plays an important role in the progression of multiple cancer types. The overexpression of Met in DLD-1 colon carcinoma cells with kirsten rat sarcoma oncogene ...homolog (KRAS) oncogene activation resulted in enhanced subcutaneous and orthotopic tumor growth rate and increased metastatic potential. To elucidate the mechanism of this effect, we stably expressed kinase-inactive MetK1110A, Src homology 2 (SH2)-binding domain-inactive MetY1349/1356F, growth factor receptor-bound protein 2 (Grb2) non-binding MetN1358H and mutant receptors with ability to selectively recruit signaling proteins Grb2, src homology domain c-terminal adaptor homolog (Shc), phospholipase c-gamma (PLCγ) and p85 phosphatidyl inositol 3 kinase. As subcutaneous implants, DLD-1 cells that expressed the majority of these receptor constructs failed to recapitulate the tumor growth-enhancing effect of the wild-type Met receptor. The Grb2- and Shc-recruiting Met mutants demonstrated slight but consistent tumor-suppressive activity, whereas the expression of N1358H mutant stimulated tumor growth rate comparable with the wild-type receptor. This suggests that direct Grb2/Shc binding does not contribute to the tumor progression activity of Met receptor. The tumors expressing Grb2- and Shc-recruiting Met receptors demonstrated a marked loss in Grb2-associated adaptor protein 1 (Gab1) protein levels, which was not observed in the cell lines, consistent with a post-translationally regulated process. Moreover, a moderate level of Gab1 overexpression stimulated tumor growth. The findings suggest a delicate balance for intact Y1349/1356 SH2-binding domain to mediate the tumor progression activity of the coactivated Met–rat sarcoma oncogene homolog (RAS) pathways. Selectivity for specific adaptor protein involvement may be the key that determines the tissue- and cell-type specificity of Met-mediated tumorigenicity in human cancers.
Chinese Herbal Medicine has been mainstream practice for hundreds of generations, however the merits of herbal therapeutics have been debated in the era of modern medicine. With a shift towards ...scientific analysis and rigorous testing of conventional pharmaceuticals in the past century, critics have questioned the proclaimed effects of herbal concoctions. Nonetheless, herbal medicines are still used frequently and have spawned clinical studies meant to determine their therapeutic efficacy. This paper aims to evaluate many aspects of Chinese Herbal Medicine applications that have already been analyzed in other papers, then propose a study which explores the effects of the herbal concoction Ban Xia Bai Zhu Tian Ma Pian in lowering blood pressure. Hypertension was chosen as the focus of the study due to its extensive presence in the population and the impact a significant outcome can provide given its prevalence. The ultimate goal is to find a balance between both eastern and western practices of medicine, thus preserving Chinese medical traditions that are concurrently buttressed by scientific research.
The development of functional flexible electronics is essential to enable applications such as conformal medical imagers, wearable health monitoring systems, and flexible light-weight displays. ...Intensive research on thin-film transistors (TFTs) is being conducted with the goal of producing high-performance devices for improved backplane electronics. However, there are many challenges regarding the performance of devices fabricated at low temperatures that are compatible with flexible plastic substrates. Prior work has reported on the change in TFT characteristics due to mechanical strain, with especially extensive data on the effect of strain on field-effect mobility. This thesis investigates the effect of gate-bias stress and elastic strain on the long-term stability of flexible low-temperature hydrogenated amorphous silicon (a-Si:H) TFTs, as the topic has yet to be explored systematically.
An emphasis was placed on bias-stress measurements over time in order to obtain information on the physical mechanisms of instability. Drain current was measured over various intervals of time to track the degradation of devices due to metastability, and results were then compared across devices of various sizes under tensile, compressive, and zero strain. Transfer characteristics of the TFTs were also measured under the different conditions, to allow for extraction of parameters that would provide insight into the instability mechanisms. In addition to parameter extraction, the degradation and recovery of TFT output current was quantitatively compared for various bias-stress times across the different levels of strain. Finally, the instability mechanisms are modelled with a Markov system to further examine the effect of strain on long-term TFT operation.
From the analysis of results, it was found that shallow charge trapping in the dielectric is the main mechanism of instability for short bias stress times, and did not seem to be greatly affected by strain. For longer bias stress times of over 10000 seconds, defect creation in the a-Si:H becomes a more significant contributor to instability. Both tension and compression increased defect creation compared to TFTs with zero applied strain. Compression appeared to cause the greatest increase in the rate of defect formation, likely by weakening Si-Si bonds in the a-Si:H. Tension appeared to cause a less significant increase, possibly due to a strengthening of some proportion of the Si-Si bonds caused by the slight elongation of bond length or because the applied tension relieves intrinsic compressive stress in a-Si:H film. A longer conduction path and greater dielectric area appears to increase the bias-stress and strain-related effects. Therefore reducing device size should increase the reliability of flexible TFTs.
This study examines how federal farm policies, specifically crop Insurance, have affected the farm economic structure of North Dakota's agriculture sector. The system of derived input demand ...equations is estimated to quantify the changes in North Dakota farmers' input use when they purchase crop insurance. Further, the cumulative rolling regression technique is applied to capture the varying effects of the farm policies over time. Empirical results from the system of input demand functions indicate that there is no moral hazard since North Dakota farmers will increase fertilizer and pesticide use in the presence of crop insurance. Results also indicate that farmers in this state will not increase the use of land.
The development of personal empowerment in nursing students is thought to be a critical element not only in the promotion of a positive personal and professional self-image among graduate nurses, but ...also in the advancement of the nursing profession. This study was designed to explore and describe the experiences of master's nursing students with the aim of adding to the knowledge and understanding of the development of personal empowerment in graduate level nursing education. The qualitative method of ethnography was used to conduct this study.
Data were collected through formal interviews, informal interviews, and observations of master's nursing students within the settings related to teaching/learning experiences. The majority of the data were collected through 27 semi-structured interviews that were conducted with 13 informants. Ten of these informants were full-time, currently-enrolled students, and three of the informants were full-time students who had graduated from the program with the past year. Data collection and analysis were conducted simultaneously. The process of data analysis gave rise to themes that were clarified and validated by the informants and gave direction to the construction of the informants' accounts of their experiences.
All of the students described themselves as having been personally empowered, to varying degrees, as a result of their experiences in the master's nursing program. They perceived that they had acquired knowledge and skills that would contribute to the achievement of their professional goals. Further, by being successful in the program, they had developed a positive self-concept that was associated with a sense of being able to take control under difficult circumstances and overcome adversity. However, most of the informant also perceived that the level to which they had been empowered was limited by the excessive pain of some of their experiences in the program. Often, these negative experiences tended to overshadow the more positive experiences and to color the students' perceptions of their experiences as master's nursing students in a negative way.
The data revealed that the development of personal empowerment is, ultimately, the result of a collaborative effort between and among master's nursing students and nursing faculty. First, students, themselves, have the capacity to promote their own sense of personal empowerment through constructive adaptive strategies directed toward acquiring knowledge and skills and toward coping with adversity. These strategies often necessitate reflection on personal beliefs, values, and assumptions; they often require a shift in students' perceptions of self in relation to the experience of being a master's nursing student. Second, supportive peer relationships, build on mutual trust and respect, are important in promoting both professional and personal growth. And third, the nursing faculty play a critical role instructuring learning experiences and fostering collegial, caring relationships that nurture the students' development of personal empowerment. The research findings have implications for nursing education and nursing research such that the development of personal empowerment in nursing education will be enhanced.
Part I. The synthesis of inoffensively labelled micellar and surfactant bilayer probes are described. The terminal acetylenic group is sensitive to its environment and experiences the high polarity ...of its surroundings. This was studied via NMR spectroscopy and lends additional support for the Menger porous-cluster model of a micelle. Part II. A proton transfer reaction effects an (alpha)-proton-deuterium exchange in endo-5-hydroxy- and endo-5-methoxybicyclo{2.2.1}heptan-2-one. The first compound demonstrates the possibility of intramolecularly induced base catalysis. Kinetic studies of the deuterium exchange were monitored via NMR spectroscopy and the results are discussed relative to the directionality of a proton transfer reaction.
To examine the influence of sexual activity on the composition and consistency of the vaginal microbiota over time, and distribution of Gardnerella vaginalis clades in young women.
Fifty-two ...participants from a university cohort were selected. Vaginal swabs were self-collected every 3-months for up to 12 months with 184 specimens analysed. The vaginal microbiota was characterised using Roche 454 V3/4 region 16S rRNA sequencing, and G.vaginalis clade typing by qPCR.
A Lactobacillus crispatus dominated vaginal microbiota was associated with Caucasian ethnicity (adjusted relative risk ratioARRR = 7.28, 95%CI:1.37,38.57,p = 0.020). An L.iners (ARRR = 17.51, 95%CI:2.18,140.33,p = 0.007) or G.vaginalis (ARRR = 14.03, 95%CI:1.22,160.69, p = 0.034) dominated microbiota was associated with engaging in penile-vaginal sex. Microbiota dominated by L.crispatus, L.iners or other lactobacilli exhibited greater longitudinal consistency of the bacterial communities present compared to ones dominated by heterogeneous non-lactobacilli (p<0.030); sexual activity did not influence consistency. Women who developed BV were more likely to have clade GV4 compared to those reporting no sex/practiced non-coital activities (OR = 11.82, 95%CI:1.87,74.82,p = 0.009). Specimens were more likely to contain multiple G.vaginalis clades rather than a single clade if women engaged in penile-vaginal sex (RRR = 9.55, 95%CI:1.33,68.38,p = 0.025) or were diagnosed with BV (RRR = 31.5, 95%CI:1.69,586.87,p = 0.021).
Sexual activity and ethnicity influenced the composition of the vaginal microbiota of these young, relatively sexually inexperienced women. Women had consistent vaginal microbiota over time if lactobacilli were the dominant spp. present. Penile-vaginal sex did not alter the consistency of microbial communities but increased G.vaginalis clade diversity in young women with and without BV, suggesting sexual transmission of commensal and potentially pathogenic clades.
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