Double Cysteine Mutations in Staphylococcal Nuclease: The effect of Artificially Introduced Disulfide Bonds on Protein Structure and Stability

Since a protein\u27s function depends on its structure, basic research in protein structure facilitates the solution of many practical problems, such as the synthesis of more effective medicines. With this larger goal in sight, the purpose of this research project is to understand better the chemical principles that underlie protein structure and stability. Disulfide bonds are a potentially stabilizing feature of many proteins. They may form between cysteine residues in close proximity to one another if the orientation is favorable. Often found in proteins produced by organisms that grow at high temperatures, disulfide bonds may anchor side chains together, making a protein resistant to thermal or chemical denaturation. In order to provide a better understanding of the stabilizing effects of disulfide bonds, disulfides are artificially introduced into the protein staphylococcal nuclease to create mutant versions of the protein. Wild-type S. nuclease has no cysteine residues, so disulfide bonds must be engineered by substituting cysteines for pairs of amino acid residues in the wild-type protein. To synthesize these double mutants, successive rounds of site-directed mutagenesis are performed on bacteriophage DNA using the Kunkel method. After transformation with the modified DNA, E. coli bacteria are used to synthesize the mutant proteins for analysis. Biophysical techniques such as solvent and thermal denaturation provide essential thermodynamic data for characterizing the stabilities of the mutants. On the basis of the data obtained from the S. nuclease mutants, generalized predictions about protein structure and stability can be established

Medicine and Health Care in Later Medieval Europe: Hospitals, Public Health,, and Minority Medical Practitioners in English and German Cities, 1250-1450

Hospitals and individual caregivers helped meet the physical and psychological needs of medieval people, just as they do today. My overall objective is to explain social and individual responses to disease within the context of Christian theology and the urban community, focusing on England and Germany in the period between 1250 and 1450. First I investigate social responses to disease, including hospitals and public health ordinances. Christianity mandated the care of the afflicted, yet physical and mental illness was associated with sin and divine punishment. Urban authorities often attempted to deal with plague outbreaks by imposing quarantines and strict regulations on minorities and outsiders. In addition to these more immediate concerns, the experience of plague permeated every aspect of medieval European culture, from the philosophy of health care to artistic representation. Next I discuss individual encounters with disease, focusing on the ambivalent positions that female and Jewish physicians occupied within the medical profession. Women were perceived as nurturers with natural healing abilities. In spite of restrictions on formal university education, many women trained privately under male physicians. Jewish physicians exerted a considerable influence on the medical profession, even though religious and racial discourse pervaded popular perceptions of their work in the medieval urban community. Yet municipal authorities occasionally engaged the services of Jewish physicians, and Jewish doctors often treated Christian patients. The roles of minority medical practitioners illustrate tolerance as well as prejudice, one aspect of the ambiguity that characterizes medieval views of health care and disease

A proposed music education curriculum for the small college based on a survey of curriculums in selected colleges

Thesis (Ph.D.)--Boston UniversityThe purposes of the study were (1) to analyze and evaluate present practices in the education of school music teachers; {2) to discover any differences that might exist between large and small colleges; (3) to determine any advantages that might characterize the small college; (4) to propose a music education curriculum~ in the light of data derived from a questionnaire and other sources~ for a small college with enrollment up to 2,000 students. Of the five hundred and twenty-five distributed questionnaires, two hundred and eight served as the source of primary data for this study. The responding institutions were classified as conservatories, liberal arts colleges, universities, and teachers colleges, located in forty-two states under both private and public control, and limited to enrollment of 2,000 students. Supplementary data were supplied through examination of one hundred catalogues; through conferences with thirty-five music educators and supervisors of public school music; and an informal inquiry sheet as to musical readiness in five hundred high school seniors. The data from the questionnaire analyzed and evaluated in terms of the National Music Association, the American Association of Teachers Colleges, Music Educators National Conference, and Music Teachers National Association, were tabulated according to the main headings of the questionnaire . Appropriate tabulation and outline presentation were made of the supplementary data. The proposed curriculum, including as an innovation, a special course in musical experiences and incorporating pertinent suggestions from all aforementioned sources and from the literature reviewed, was presented in outline form with explanatory tabulations. [TRUNCATED

Preventing Ventilator Associated Pneumonia

Ventilator Associated Pneumonia is a serious infection in the lungs that affects individuals who are being mechanically ventilated. These patients, who are already critically ill, have decreased defense mechanisms that allow pathogens such as bacteria to invade the sterile respiratory tract (Cooper, 2021). Many of the risk factors for the development of VAP may be preventable, and it is up to the ICU nurses, who care for these mechanically ventilated patients, to play a role in the implementation of certain guidelines and/or bundles that may help with the prevention of ventilator associated pneumonia ( Aysegul et al., 2020). Although ventilator associated pneumonia may never be 100% prevented, the existing prevention guidelines are the best available resources to improve outcomes for ventilated patients. In our presentation, we elaborated on the most common prevention guidelines used in practice today

Equivalency and Reciprocity of Qualifications for LIS Professionals in a Web 2.0 Environment

In the age of Web 2.0 and globalization of information, the challenge of information professionals included the determination of equivalent educational experiences as professionals move more freely in the international information environment. Reciprocity of degrees among recognized LIS education program is one possible solution, but the establishment of an international program of reciprocity has been difficult up to this time. The authors discuss the background of efforts over a 30 year period to develop acceptable guidelines for international equivalency and reciprocity of qualifications for LIS professionals by IFLA and other library interests. The challenges of the latest IFLA effort our detailed and options provided in a 2.0 web environment are explored. The possibility that applying the principles of interactivity of the web in the 21st Century to provide a solution to the equivalency and reciprocity problem are analyzed and specific proposal are presented for discussion. The results of surveys of library education professionals are presented and specific proposal for the future are outlined

Are methodological quality and completeness of reporting associated with citation-based measures of publication impact? A secondary analysis of a systematic review of dementia biomarker studies

Objective: To determine whether methodological and reporting quality are associated with surrogate measures of publication impact in the field of dementia biomarker studies. Methods: We assessed dementia biomarker studies included in a previous systematic review in terms of methodological and reporting quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) and Standards for Reporting of Diagnostic Accuracy (STARD), respectively. We extracted additional study and journal-related data from each publication to account for factors shown to be associated with impact in previous research. We explored associations between potential determinants and measures of publication impact in univariable and stepwise multivariable linear regression analyses. Outcome measures: We aimed to collect data on four measures of publication impact: two traditional measures—average number of citations per year and 5-year impact factor of the publishing journal and two alternative measures—the Altmetric Attention Score and counts of electronic downloads. Results: The systematic review included 142 studies. Due to limited data, Altmetric Attention Scores and electronic downloads were excluded from the analysis, leaving traditional metrics as the only analysed outcome measures. We found no relationship between QUADAS and traditional metrics. Citation rates were independently associated with 5-year journal impact factor (β=0.42; p<0.001), journal subject area (β=0.39; p<0.001), number of years since publication (β=-0.29; p<0.001) and STARD (β=0.13; p<0.05). Independent determinants of 5-year journal impact factor were citation rates (β=0.45; p<0.001), statement on conflict of interest (β=0.22; p<0.01) and baseline sample size (β=0.15; p<0.05). Conclusions: Citation rates and 5-year journal impact factor appear to measure different dimensions of impact. Citation rates were weakly associated with completeness of reporting, while neither traditional metric was related to methodological rigour. Our results suggest that high publication usage and journal outlet is not a guarantee of quality and readers should critically appraise all papers regardless of presumed impact

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations

<b>Background</b><p></p> Various tools exist for initial assessment of possible dementia with no consensus on the optimal assessment method. Instruments that use collateral sources to assess change in cognitive function over time may have particular utility. The most commonly used informant dementia assessment is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).<p></p> A synthesis of the available data regarding IQCODE accuracy will help inform cognitive assessment strategies for clinical practice, research and policy.<p></p> <b>Objectives</b><p></p> Our primary objective was to determine the diagnostic accuracy of the informant based questionnaire IQCODE, for detection of all cause (undifferentiated) dementia in community-dwelling adults with no previous cognitive assessment. We sought to describe the accuracy of IQCODE (the index test) against a clinical diagnosis of dementia (the reference standard).<p></p> Our secondary objective was to describe the effect of heterogeneity on the summary estimates. We were particularly interested in the traditional 26-item scale versus the 16-item short form; and language of administration. We explored the effect of varying the threshold IQCODE score used to define 'test positivity'.<p></p> <b>Search methods</b><p></p> We searched the following sources on 28 January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science with Conference Proceedings (ISI Web of Knowledge), LILACS (BIREME). We also searched sources relevant or specific to diagnostic test accuracy: MEDION (Universities of Maastrict and Leuven); DARE (York University); ARIF (Birmingham University). We used sensitive search terms based on MeSH terms and other controlled vocabulary.<p></p> <b>Selection criteria</b><p></p> We selected those studies performed in community settings that used (not necessarily exclusively) the IQCODE to assess for presence of dementia and, where dementia diagnosis was confirmed, with clinical assessment. Our intention with limiting the search to a 'community' setting was to include those studies closest to population level assessment. Within our predefined community inclusion criteria, there were relevant papers that fulfilled our definition of community dwelling but represented a selected population, for example stroke survivors. We included these studies but performed sensitivity analyses to assess the effects of these less representative populations on the summary results.<p></p> <b>Data collection and analysis</b><p></p> We screened all titles generated by the electronic database searches and abstracts of all potentially relevant studies were reviewed. Full papers were assessed for eligibility and data extracted by two independent assessors. For quality assessment (risk of bias and applicability) we used the QUADAS 2 tool. We included test accuracy data on the IQCODE used at predefined diagnostic thresholds. Where data allowed, we performed meta-analyses to calculate summary values of sensitivity and specificity with corresponding 95% confidence intervals (CIs). We pre-specified analyses to describe the effect of IQCODE format (traditional or short form) and language of administration for the IQCODE.<p></p> <b>Main results</b><p></p> From 16,144 citations, 71 papers described IQCODE test accuracy. We included 10 papers (11 independent datasets) representing data from 2644 individuals (n = 379 (14%) with dementia). Using IQCODE cut-offs commonly employed in clinical practice (3.3, 3.4, 3.5, 3.6) the sensitivity and specificity of IQCODE for diagnosis of dementia across the studies were generally above 75%.<p></p> Taking an IQCODE threshold of 3.3 (or closest available) the sensitivity was 0.80 (95% CI 0.75 to 0.85); specificity was 0.84 (95% CI 0.78 to 0.90); positive likelihood ratio was 5.2 (95% CI 3.7 to 7.5) and the negative likelihood ratio was 0.23 (95% CI 0.19 to 0.29).<p></p> Comparative analysis suggested no significant difference in the test accuracy of the 16 and 26-item IQCODE tests and no significant difference in test accuracy by language of administration. There was little difference in sensitivity across our predefined diagnostic cut-points.<p></p> There was substantial heterogeneity in the included studies. Sensitivity analyses removing potentially unrepresentative populations in these studies made little difference to the pooled data estimates. The majority of included papers had potential for bias, particularly around participant selection and sampling. The quality of reporting was suboptimal particularly regarding timing of assessments and descriptors of reproducibility and inter-observer variability.<p></p> <b>Authors' conclusions</b><p></p> Published data suggest that if using the IQCODE for community dwelling older adults, the 16 item IQCODE may be preferable to the traditional scale due to lesser test burden and no obvious difference in accuracy. Although IQCODE test accuracy is in a range that many would consider 'reasonable', in the context of community or population settings the use of the IQCODE alone would result in substantial misdiagnosis and false reassurance. Across the included studies there were issues with heterogeneity, several potential biases and suboptimal reporting quality

Rectifiable paths with polynomial log-signature are straight lines

The signature of a rectifiable path is a tensor series in the tensor algebra whose coefficients are definite iterated integrals of the path. The signature characterises the path up to a generalised form of reparametrisation. It is a classical result of K. T. Chen that the log-signature (the logarithm of the signature) is a Lie series. A Lie series is polynomial if it has finite degree. We show that the log-signature is polynomial if and only if the path is a straight line up to reparametrisation. Consequently, the log-signature of a rectifiable path either has degree one or infinite support. Though our result pertains to rectifiable paths, the proof uses results from rough path theory, in particular that the signature characterises a rough path up to reparametrisation.Comment: 11 page