High Throughput Screens Against Heat Shock Protein 70 (Hsp 70)

The molecular chaperone Hsp70 plays important roles in protein quality control. Moreover, Hsp70 has been linked to diseases of protein misfolding, such as neurodegenerative disorders, suggesting that it could be a promising new drug target. However, the molecular mechanisms that link Hsp70 to these diseases remain unclear. We hypothesized that one way to better understand the roles of Hsp70 would be to develop chemical probes that disrupt its specific functions. In this thesis, we developed the first high throughput screens for the ATPase activity of Hsp70. Using this platform, we explored the idea of “gray-box” screening, in which multiple components of the Hsp70 chaperone system are reconstituted in vitro to better approximate the biochemical properties of the physiological complexes. We wanted to understand whether this approach would provide a compromise between “black box” cell-based screens and assays that rely on individual purified proteins. Accordingly, we screened over 50,000 compounds and natural product extracts and reported a number of new Hsp70 inhibitors, including myricetin. Interestingly, we found that many of these inhibitors blocked the protein-protein interactions between the Hsp70, DnaK, and its important co-chaperone, DnaJ. Thus, we expect these compounds to be powerful probes for exploring the biological roles of the DnaK-DnaJ complex. Finally, we explored whether other Hsp70 chaperone functions, such as substrate binding or refolding, might also be useful targets for high throughput screening. Towards that goal, we generated point mutants in DnaK and human Hsc70 and studied how their different in vitro biochemical activities correlated with cellular functions. We found that luciferase refolding activity, not ATPase rate, was more predictive of certain cellular chaperone activities, such as heat shock rescue and effects on tau stability. These results suggest the need for multiple primary and secondary assays in searching for Hsp70 inhibitors. Together, these studies have provided important insights into the Hsp70 chaperone system and they have discovered molecules that could be used to further validate Hsp70 as a drug target.Ph.D.Chemical BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/86340/1/taiwlyra_1.pd

The Effect of Empowerment Program on Health Education Teachers with Health Insurance Education

Taiwan has been promoting its national health insurance (NHI), which provides people with appropriate medical resources; however, health insurance education is missing from schools, and teachers lack relevant teaching abilities. This study describes the development of the health insurance education empowerment program (HIEEP) to promote effective teaching on educators. A two-group parallel-controlled trial was conducted with health education teachers, in which participants learned to discuss its importance through demonstration and practice. The questionnaire measured their teaching effectiveness in HIEEP using a baseline measurement and a one-week follow-up measurement. Of 196 people that started the trial, 186 completed it. The intervention effects were evaluated using the Johnson-Neyman method. The results showed that in the experimental group, the program raised all teachers’ variable scores, which evaluated health insurance meaning, teaching competence, self-determination, and impact. The empowerment program can provide teachers will allow for more effective health insurance education

COMPARISON OF KINESIO TAPING AND SPORTS TAPING IN FUNCTIONAL ACTIVITIES FOR COLLEGIATE BASKETBALL PLAYERS: A PILOT STUDY

The purpose of this study was to identify the effects of kinesio taping and sports taping for collegiate basketball players in functional activities. Seventeen collegiate basketball players were recruited in particapitate this study and divided into three groups(Kinesio taping group, sports taping group and control group) in random. The ankle range of motion, plantarflexor muscle strength and endurance, vertical jump, and dynamic balance were measured before and after taping applied. The results was showed significantly increasing in ankle plantar-flexion range for Kinesio taping group(p=.03). There were no remarkable difference in the other measurements. In conclusion, the Kinesio Taping would not restriction the ankle plantar-flexion range. In future, we may recruited more subjects to identify the effect of Kinesio taping in functional activities for collegiate bsketball players

Efficacy of Sanfujiu to Treat Allergies: Patient Outcomes at 1 Year after Treatment

Sanfujiu is a treatment method of applying herbal paste onto the acupoints Fengmen and Feishu during the three hottest days of summer to treat patients with allergies. The objectives of this study were to determine the treatment efficacy at 1 year after the Sanfujiu treatment, and examine variations in the perceived efficacy of Sanfujiu among different subgroups, based on the patients' ages, diagnoses and number of reactive symptoms immediately after the treatment. We enrolled 105 patients who completed Sanfujiu treatment at a medical university hospital in Taipei as the subjects. One year after treatment, trained interviewers conducted telephone interviews with the patients. Approximately 60% of them perceived the treatment as being effective at 1 year later, which was higher than that at 1 week after treatment (45.7%). Younger subjects (<19 years of age) and patients with asthma were more likely to report the treatment as being effective. Patients who had more reactive symptoms after the third Sanfujiu treatment were more likely to report the treatment as being effective. The results demonstrated that Sanfujiu was moderately effective, as perceived by patients in Taiwan, in treating their allergic symptoms

An Empirical Evaluation Of User Satisfaction With A School Nursing Information System

The adoption of a school nursing information system is considered one of the most efficient ways in which to document health records as well as monitor health conditions electronically. However, despite the importance of computerized health records in school nursing practice, few studies have examined user satisfaction of a school nursing information system. The aim of this study is to investigate the critical factors effecting school nurses’ satisfaction with a school nursing information system Utilizing a survey approach, questionnaires are distributed to nurses working in a primary or high school which introduces a new school nursing information system. The findings show several factors, including perceived usefulness, perceived of ease of use, training and workload are significant with user satisfaction. These results suggest that school nursing information system designers should comprehensively understand users’ demands and perceptions about the system, which will further facilitate user satisfaction, decrease their workload, and ultimately enhance job performance

Sarcoma of the Larynx: Treatment Results and Literature Review

BackgroundSarcomas of the larynx are rare neoplasms that constitute less than 1% of laryngeal malignancies. A Medline search found no large series focusing on laryngeal sarcomas. We reviewed the cases of laryngeal sarcomas treated in our cancer center and compared our experiences and treatment results with those from other centers.MethodsA retrospective review of 10 patients with laryngeal sarcoma treated in our institute between 1980 and 2000 was done to identify tumor characteristics, therapeutic modalities, and treatment outcomes.ResultsThe patients showed a male predominance (9/10) and presented 8 types of pathology. Nine patients underwent surgery, including 2 total laryngectomy, 4 partial laryngectomy, and 3 endoscopic laser cordectomy. During a median follow-up of 92 months, the 5-year overall survival and disease-specific survival were 76% and 90%, respectively. Two patients developed recurrence, including 1 local recurrence and 1 distant metastasis.ConclusionSurgical intervention was the first choice in the treatment of laryngeal sarcomas. The prognosis is relatively good when compared with sarcoma originating from other anatomic sites

Comparison of the mismatch-specific endonuclease method and denaturing high-performance liquid chromatography for the identification of HBB gene mutations

<p>Abstract</p> <p>Background</p> <p>Beta-thalassemia is a common autosomal recessive hereditary disease in the Meditertanean, Asia and African areas. Over 600 mutations have been described in the beta-globin (<it>HBB</it>), of which more than 200 are associated with a beta-thalassemia phenotype.</p> <p>Results</p> <p>We used two highly-specific mutation screening methods, mismatch-specific endonuclease and denaturing high-performance liquid chromatography, to identify mutations in the <it>HBB </it>gene. The sensitivity and specificity of these two methods were compared. We successfully distinguished mutations in the <it>HBB </it>gene by the mismatch-specific endonuclease method without need for further assay. This technique had 100% sensitivity and specificity for the study sample.</p> <p>Conclusion</p> <p>Compared to the DHPLC approach, the mismatch-specific endonuclease method allows mutational screening of a large number of samples because of its speed, sensitivity and adaptability to semi-automated systems. These findings demonstrate the feasibility of using the mismatch-specific endonuclease method as a tool for mutation screening.</p

Identification of the genetic determinants of Salmonella enterica serotype Typhimurium that may regulate the expression of the type 1 fimbriae in response to solid agar and static broth culture conditions

<p>Abstract</p> <p>Background</p> <p>Type 1 fimbriae are the most commonly found fimbrial appendages on the outer membrane of <it>Salmonella enterica </it>serotype Typhimurium. Previous investigations indicate that static broth culture favours <it>S</it>. Typhimurium to produce type 1 fimbriae, while non-fimbriate bacteria are obtained by growth on solid agar media. The phenotypic expression of type 1 fimbriae in <it>S</it>. Typhimurium is the result of the interaction and cooperation of several genes in the <it>fim </it>gene cluster. Other gene products that may also participate in the regulation of type 1 fimbrial expression remain uncharacterized.</p> <p>Results</p> <p>In the present study, transposon insertion mutagenesis was performed on <it>S</it>. Typhimurium to generate a library to screen for those mutants that would exhibit different type 1 fimbrial phenotypes than the parental strain. Eight-two mutants were obtained from 7,239 clones screened using the yeast agglutination test. Forty-four mutants produced type 1 fimbriae on both solid agar and static broth media, while none of the other 38 mutants formed type 1 fimbriae in either culture condition. The flanking sequences of the transposons from 54 mutants were cloned and sequenced. These mutants can be classified according to the functions or putative functions of the open reading frames disrupted by the transposon. Our current results indicate that the genetic determinants such as those involved in the fimbrial biogenesis and regulation, global regulators, transporter proteins, prophage-derived proteins, and enzymes of different functions, to name a few, may play a role in the regulation of type 1 fimbrial expression in response to solid agar and static broth culture conditions. A complementation test revealed that transforming a recombinant plasmid possessing the coding sequence of a NAD(P)H-flavin reductase gene <it>ubiB </it>restored an <it>ubiB </it>mutant to exhibit the type 1 fimbrial phenotype as its parental strain.</p> <p>Conclusion</p> <p>Genetic determinants other than the <it>fim </it>genes may involve in the regulation of type 1 fimbrial expression in <it>S</it>. Typhimurium. How each gene product may influence type 1 fimbrial expression is an interesting research topic which warrants further investigation.</p

A User-Centered Mapping Design for Geomorphological Hazard Thematic Map

Numerous studies have concentrated on developing user-centered designs for hazard zone maps but rarely for hazard-oriented geomorphological maps, named as Geomorphological Hazard Thematic Maps (GHTMs) in this study, which provide more detailed information about natural hazards. This study developed a user-centered mapping design for GHTMs for nonexperts in geomorphology. We invited civil engineers and high school educators to evaluate a sample GHTM\u27s design in group and focus group panel interviews. The civil engineers preferred maps with more geomorphological features, whereas the educators preferred simple designs. Both groups indicated that the inclusion of essential facilities and road networks is essential. The map was also adjusted by adding hillshade layer and by changing the symbology for mass wasting, fault scarps, and fluvial features to increase clarity and simplicity. This case study is the first step toward developing user-centered mapping designs for hazard communication that will deepen their understanding of natural hazards