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      • Characterization of the interaction between the yeast HAC1 transcription factor and the MCK1 protein kinase

        이경호 Rutgers, State University of New Jersey 1999 해외박사

        RANK : 169743

        HAC1 encodes a transcription factor mediating the unfolded protein response (UPR) in Saccharomyces cerevisiae. I identified Hac 1 p in a two-hybrid screen for factors interacting with Mcklp (Meiosis and Centromere regulatory Kinase).Characterization of SK1 hac lΔ mutants revealed a novel function for HAC1 in ploidy control. hac 1Δ spore clones contain a diploid DNA content as determined by FACS and genetic analyses, Autodiploidization of hacl spore clones occurs post-germination: hacl spores are born haploid but efficiently generate diploid progeny during subsequent mitotic division. Once the hacl mutant has acquired a diploid DNA content no further ploidy increase is observed. Interestingly, the increase in genome content following meiosis is not a general property associated with hacl spore clones; rather, it is restricted to an inability to tolerate the haploid state. A role for HACl in ploidy control is supported by the observation that HACl overexpression suppresses the autodiploidization seen in strains deficient in Scp 160p, an ER-nuclear membrane associated protein required for the maintenance of the haploid state. Reciprocal genetic background-dependent mutant phenotypes were conferred by the hacl and scp160 alleles: no ploidy increase was observed in W303 hacl or SK1 scp160 mutants. Genetic analyses involving the UPR target gene KAR2 and the UPR regulator IRE1 revealed that autodiploidization associated with SK1 hacl mutants is a consequence of its role in the UPR pathway. Inhibition of the pathway results in autodiploidization and overexpression of target genes suppresses this phenomenon. The Mcklp kinase regulates meiotic progression, centromere activity and pyruvate kinase activity. Interaction of Haclp and Mcklp in the two-hybrid assay suggests a functional relationship. I found that Haclp can be phosphorylated by Mcklp in vitro. Expression of Haclp fused to the Ga14p transactivation domain can suppress the meiotic induction defect associated with mckl mutations, supporting the notion that Haclp functions downstream of Mcklp. Furthermore, there is a functional relationship between MCKI and HACI in vivo: mckl mutations confer mild defects in the UPR and hacl mutants display sporulation defects reminiscent of an mckl deficiency. Thus, I have uncovered new roles for both Mck lp and Hac lp in yeast.

      • Conversational Artificial Intelligence and Patient Generated Health Data: Transitional Patient Applications to Improve Outcomes in the 30 Day Post-discharge Window

        Mazza, Kathleen Rutgers The State University of New Jersey, Rutger 2020 해외박사(DDOD)

        RANK : 169503

        Readmission within 30 days of hospital discharge and avoidable emergency room visits have been shown to result in substantial costs and increased risk to patients. Evolving payment models under the ACA are focused on reducing unnecessary costs and decreasing short-term readmissions and will eliminate or reduce payment for 30-day readmissions after treatment for specified conditions and procedures. Evolving communications technology can help providers and patients to exchange critical patient data in the vulnerable post-discharge period and can encourage a shift to shared responsibility and collaboration between patients and providers. However, many providers are not prepared to collect, analyze, or respond to PGHD in their existing workflows, to make it actionable at the point of care, and to establish best practices for the use of PGHD. This study considers the patient’s outcomes of readmission and/or emergency department use in relation to the use of conversational artificial intelligence in the form of chatbots to gather structured PGHD which is integrated directly into the patient’s EHR and into usual provider workflow, making it available in real time for the provider for use in treatment decisions. Additionally, the study describes characteristics of patients elect or decline to participate in the use of chatbots and their preferences for how they receive and send messages. This study may provide valuable insight into developing optimal models of chatbot use for PGHD sharing and for the establishment of best practices for future implementations of this emerging technology.

      • Investigation of a Novel Decision Support Metric for Head and Neck Adaptive Radiation Therapy (ART) Using a Real-Time in-vivo Portal Dosimetry System

        Lim, Seng Boh Rutgers The State University of New Jersey, Rutger 2020 해외박사(DDOD)

        RANK : 169503

        In adaptive radiation therapy (ART) of head and neck cancer, any significant anatomical changes observed are used to adapt the treatment plan to maintain target coverage without elevating the xerostomia risk. However, the additional resources required for ART pose a challenge for broad-based implementation. It is hypothesized that the transit fluence change is associated with volumetric change in the vicinity of the target and therefore can be used as a decision support metric (DMS) for ART. This was evaluated by comparing the fluence with volumetric changes in twenty-four patients. Transit fluence was measured by an in-vivo portal dosimetry system (RTPD). Weekly cone beam computed-tomography (CBCT) was used to determine volume change in the rectangular region of interest (ROI) from condyloid process to C6. The integrated fluence through the ROI and the salivary glands (SG) on the day of the CBCT scan was calculated with the first treatment as the baseline. The correlation between fluence and volume changes was determined. Logistic regression was also used to associate the 5% ROI volume reduction replanning trigger-point and the fluence change. The model was assessed by a chi-squared test. The area (AUC) under the receiver operating characteristic curve (ROC) was also determined. The xerostomia risk was assessed by the scores change of the patients’ MD Anderson Dysphagia Inventory (MDADI). The association of the MDADI with age, gender, mean dose to SG, weight, volumetric and fluence changes were assessed using Spearman rank-correlation. A total of 108 pairs of CBCT and RTPD measurements were obtained. The correlation between fluence and volumetric changes were found to be -0.837 (p-value<0.001). The AUC of the ROC was found to be 0.91. The correlation between SG-specific fluence and volumetric changes was found to be -0.62 (p-value<0.001). Twenty-one patients responded to the MDADI. Fluence and volumetric changes were found to have association with the physical, functional and total MDADI changes. No significant association with age, gender, and weight change were found. A transit fluence based DSM is not only a viable alternative to serial CBCT in assisting clinicians in the patient selection, but also lowers the resource barrier of ART implementation.

      • Evaluating the Impact of Dietary Macronutrient Ratios on Cardiovascular Blood Biomarkers

        Nickless, Peter G Rutgers The State University of New Jersey, Rutger 2020 해외박사(DDOD)

        RANK : 169503

        Background: Cardiovascular disease is the number one killer in the United States leading to 647,000 deaths in 2017 alone. Not restricted to the United States, cardiovascular disease is also the number one cause of death worldwide accounting for 9 million annual deaths. The prevention of cardiovascular disease presents not only an opportunity to save lives, but also billions of dollars in healthcare costs. Lifestyle modification through diet presents an effective means of reducing the incidence of cardiovascular morbidity and mortality. Dietary approaches aimed at reducing cardiovascular risk have focused on the reduction of saturated fat limiting its potential for negatively impacting cardiovascular risk blood parameters. Recent evidence suggests, however, that while reducing saturated fat may be of benefit, the replacement nutrient selected is an equally important consideration. Dietary approaches aimed at replacing saturated fat with mono and polyunsaturated fat have shown promise as a means of improving cardiovascular biomarkers and possibly reducing the mortality and morbidity of cardiovascular disease.Objective: The objective of this study is to determine the associations between macronutrient ratios and cardiovascular lipid biomarkers and try to determine the appropriate recommendations for beneficial biomarker outcomes.Methods: This retrospective correlational analysis used data obtained from the 2005–2016 NHANES dataset. Data included nutritional variables, patient demographic information, and patient laboratory examinations. After cleaning and processing correlational analysis, simple and multivariate regression analysis, and ANOVA testing were performed between the independent nutritional variables and the dependent laboratory variables.Results: There were a total of 20,007 cases to be considered from the data set. 3089 samples met the inclusion criteria for further consideration. Statistically significant correlations were noted between the percent of the polyunsaturated to saturated fat ratio and total cholesterol (r = −.055), LDL cholesterol (r = −.038), HDL cholesterol (r = .043), triglycerides (r = −.08), apolipoprotein B (r = −.065), and the total cholesterol to HDL ratio (r = −.08). Statistically significant correlations were noted between the percent of carbohydrate consumption and total cholesterol (r = −.045), HDL cholesterol (r = −.10), and the total cholesterol to HDL ratio (r = .04). Statistically significant correlations were noted between the percent of sugar consumption and HDL cholesterol (r = −.11), and the total cholesterol to HDL ratio (r = .074). Statistically significant correlations were noted between the percent of fiber consumption and HDL cholesterol (r = .061), and the total cholesterol to HDL ratio (r = −.059). Statistically significant correlations were noted between the carbohydrate to total fat consumption and HDL cholesterol (r = −.070), triglycerides (r = .041), and the total cholesterol to HDL ratio (r = .044). ANOVA analysis showed a statistically significant impact of differing ratios of polyunsaturated to saturated fatty acids and total cholesterol (p = .0076), triglycerides (p = .0002), apolipoprotein B (p = .0042), and the total cholesterol to HDL ratio (p = .0005). Statistically significance was seen between the impact of differing ratios of monounsaturated to saturated fatty acids and triglycerides (p = .0015). Significant impact of differing ratios of carbohydrate to total fat and HDL cholesterol (p = .0035). Statistically significant impact of differing dietary fat concentrations HDL cholesterol (p < .0001).Conclusions: Some, but not all, of the ratios suggested by this study were consistent with the expectations following the review of literature. No significant relationship exists between saturated fat and cardiovascular biomarker data. The ratio of polyunsaturated to saturated fat showed a relationship with positive cardiovascular biomarker outcomes. Diets should follow a > 1.0 polyunsaturated to saturated fat ratio. There is a small inverse relationship between the ratio of monounsaturated fat to saturated fat and diet should be kept to a < 2.0 ratio. The ratio of carbohydrate consumption to saturated fat shows a small positive correlation. The ratio of carbohydrate to total fat shows a strong association between higher ratios and negative biomarker data. A diet should be less than a 1.5 ratio of carbohydrate to total fat and contain 45% or less of its calories from carbohydrates. Differences between biomarker outcome data and individual fatty acids suggest that food choice needs to consider specific fatty acid makeup.

      • Modal structure in sixteen instrumental works from Giovanni Gabrieli's Sacrae Symphoniae (1597)

        변혜련 Rutgers, State University of New Jersey 1994 해외박사

        RANK : 169487

        이 논문은 1960-70년대 한국의 고도성장 과정에서 임금의 불평등의 성격을 밝히고 , 그 변동을 분석하는것이 주요내용이다. 임금불평등의 세가지 측면 -임금결정, 임금 분배, 임금구조-의 분석이 중심이 되고 있다. 사용된 자료는 주로 노동부의 「직종별 임금실태 조사 보고서」이고, 특히 1971년도분은 컴퓨터 테이프가 이용되었다. 임금 결정의 분석에서는 민간자본 모델이 원용되었는데, 교육및 경력연수에서 다소 유용한 구분을 시도하였다. 그리하여 상이한 경력이 남녀간에 상이한 효과를 갖고 있음이 발견되었다. 남녀간 임금차별의 문제도 분석되고 있다. 임금분배의 불평등을 몇가지 불평등지표를 써서 분석한 결과 임금의 분산은 축소하고있는 것으로 나타났다. 그러 나 외국과의 비교에 의하면 한국의 임금 불평등을 여전히 매우 큰것으로보인다. 임 금구조는 역니 宇를 보이는 것으로 나타났으나 역시 국제비교에 의하면 한국의 임금 격차는 상당히 높은 것이라고 결론내릴 수 있다.

      • Molecular genetics of flat revertants of ras-EJ oncogene transformed NIT3T3 mouse fibroblast cells

        이진선 Rutgers, State University of New Jersey 1986 해외박사

        RANK : 169487

        인체 ras-EJ 발암유전자를 NIH3T3 마우스 섬유아세포에 주입시키면 형태적으로 변형된 세포를 얻을 수 있다. ras-EJ 발암유전자에 의한 세포의 형태변형에 관여하는 조절현상을 이해하기 위하여, 에틸메탄설포네이트를 이용, 돌연변이를 유도한 후 플루오르디옥시우리딘을 통한 선별, 혹은 모집단에서 직접 선별하는 두가지 기술을 이용하여 형태변형 모세포주로부터 10개의 서로 다른 형태복귀변이주를 선발하였다. 이들은 모두 발암유전자가 주입된 모세포와 달리 편평한 모양을 하며 배양용기에 부착되어 자라는 배양적 특성을 지니고 있었다. Southern blot hybridization 분석을 실시한 결과, 그중 6개의 세포주에서는 ras-EJ 발암유전자가 들어있는 6.6 Kb의 BamHI DNA 절편을 발견할 수 있었으나, 나머지 4개에서는 해당 DNA 절편이 잔존하지 않음이 확인되었다. 상기 6개의 형태복귀변이주내 DNA 절편을 정밀 분석한 결과, exon I 내의 35번째 뉴클레오타이드가 비발암성 코드로 복귀되지는 않았으며, exon의 우측 끝에 반복염기서열 (tandemly repeated sequence)의 길이에 변동이 있지는 않은 것으로 판명되었다. 또한 6개의 세포주중 하나는 4.5 Kb BamHI DNA를 하나 더 가지고 있는 것으로 나타났다. 본인의 컴퓨터 검색에 의하면 반복염기서열은 대부분 단순반복염기서열이나 대칭성염기서열에 인접하고 있는 것으로 보이며, 이 때문에 증식과정중 재조합에 의해 4.5Kb DNA 절편이 발생한 것이 아닌가 추측된다. MspI과 Hpall로 DNA를 절단하여 분석한 결과 6개의 형태복귀변이주는 메틸레이션 형태가 형태변형 모세포주와 다르게 나타났으며, 모노클론 항체를 사용한 항체침전분석결과 이 6개의 형태복귀변이주는 여전히 ras-EJ 발암유전자의 단백질을 생산하고 있었다. 이 마우스 형태복귀변이주를 편평한 랫트 세포주와 융합시켰을 경우, 형태변형이 재현됨을 볼 수 있었다. 이 결과는 형태복귀변이주가 기능적으로 이상이 없는 ras-EJ 발암유전자를 가지고 있으나, ras-EJ 단백질로 하여금 궁극적으로 세포형태변형에 기여하도록 하는 다음 단계의 유전자에 결함을 가지고 있을 가능성을 시사하고 있다. 이와 같이 형태복귀변이주내의 고장난 마우스 유전자를 대신할 수 있는 인체 DNA 절편을 찾아내기 위하여 형태복귀변이주에 인체 EJ 방광암 세포주로부터 얻은 DNA를 주입시킨 후, 배양용기에 부착하지 않고 생장하는 변이주를 분리하였다. 이 중 2개의 형태재변형 세포주는 ras-EJ DNA 절편외에 다른 새로운 인체 DNA를 가지고 있었다. 이 DNA 절편은 ras 유전자에 의해 촉발되는 형태변형에 필요한 유전자를 포함할 것으로 추측되며, 해당유전자를 분리하는데 본 형태재변형 변이세포주가 유용하게 쓰일 것으로 사료된다.

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