Selective prediction of interaction sites in protein structures with THEMATICS

<p>Abstract</p> <p>Background</p> <p>Methods are now available for the prediction of interaction sites in protein 3D structures. While many of these methods report high success rates for site prediction, often these predictions are not very selective and have low precision. Precision in site prediction is addressed using Theoretical Microscopic Titration Curves (THEMATICS), a simple computational method for the identification of active sites in enzymes. Recall and precision are measured and compared with other methods for the prediction of catalytic sites.</p> <p>Results</p> <p>Using a test set of 169 enzymes from the original Catalytic Residue Dataset (CatRes) it is shown that THEMATICS can deliver precise, localised site predictions. Furthermore, adjustment of the cut-off criteria can improve the recall rates for catalytic residues with only a small sacrifice in precision. Recall rates for CatRes/CSA annotated catalytic residues are 41.1%, 50.4%, and 54.2% for Z score cut-off values of 1.00, 0.99, and 0.98, respectively. The corresponding precision rates are 19.4%, 17.9%, and 16.4%. The success rate for catalytic sites is higher, with correct or partially correct predictions for 77.5%, 85.8%, and 88.2% of the enzymes in the test set, corresponding to the same respective Z score cut-offs, if only the CatRes annotations are used as the reference set. Incorporation of additional literature annotations into the reference set gives total success rates of 89.9%, 92.9%, and 94.1%, again for corresponding cut-off values of 1.00, 0.99, and 0.98. False positive rates for a 75-protein test set are 1.95%, 2.60%, and 3.12% for Z score cut-offs of 1.00, 0.99, and 0.98, respectively.</p> <p>Conclusion</p> <p>With a preferred cut-off value of 0.99, THEMATICS achieves a high success rate of interaction site prediction, about 86% correct or partially correct using CatRes/CSA annotations only and about 93% with an expanded reference set. Success rates for catalytic residue prediction are similar to those of other structure-based methods, but with substantially better precision and lower false positive rates. THEMATICS performs well across the spectrum of E.C. classes. The method requires only the structure of the query protein as input. THEMATICS predictions may be obtained via the web from structures in PDB format at: <url>http://pfweb.chem.neu.edu/thematics/submit.html</url></p

Integrating experiential learning into formal curriculum : the HKU experience

In September 2009, the Hong Kong SAR Government implemented the ‘New Academic Structure for Senior Secondary Education and Higher Education’. Under the new academic structure, local universities now offer 4-year undergraduate programmes instead of 3-year. In preparing for the 4-year undergraduate programmes, universities establish experiential learning as an important component for all undergraduate degrees. At The University of Hong Kong (HKU), the synergy between experiential learning and formal curriculum has been introduced long before government’s policy. The overview of HKU’s experience in experiential learning will be introduced with case studies of innovative design and course structure to illustrate students’ experiences and learning as well as, the development, implementation and evaluation of experiential learning projects. These case studies are drawn from experiential learning courses offered by Faculty of Architecture, Faculty of Business and Economics and Faculty of Engineering

Collaborative Teaching and Learning: A Model for Building Capacity and Partnerships to Address NTDs

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-05-06T13:25:49Z No. of bitstreams: 1 Wilson Mary Elizabeth Collaborative teaching....pdf: 431785 bytes, checksum: b48099b637f1357115235beafce0ceab (MD5)Made available in DSpace on 2014-05-06T13:25:49Z (GMT). No. of bitstreams: 1 Wilson Mary Elizabeth Collaborative teaching....pdf: 431785 bytes, checksum: b48099b637f1357115235beafce0ceab (MD5) Previous issue date: 2011Department of Global Health and Population. Harvard School of Public Health. Boston, Massachusetts, USAYale School of Public Health Epidemiology of Microbial Disease Division. New Haven, Connecticut, USAFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Faculdade de Medicina da Bahia. Federal University of Bahia. Salvador, BA, Brasi

Faculty Formation in the Jesuit and Mercy Traditions

Mentorship plays a major role in engaging faculty and supporting their development and growth within an academic institution. In order to support new faculty members’ success and belonging, the host institution piloted the Faculty Formation Program during the 2022-2023 academic year. The foundation of this mentorship program is based on Jesuit and Mercy values that align with the mission of the university. The program has engaged new and seasoned faculty in shared conversations about their roles as faculty members and their place in Jesuit and Mercy higher education. This paper articulates the foundation and characteristics of high-impact mentorship and describes how a mission-centered mentoring program was implemented at the host institution, along with lessons learned and future program enhancements. The paper also offers faculty members’ reflections on their relationship to Catholic higher education and how working in a Jesuit and Mercy institution informs their roles as faculty. The Faculty Formation Program can be adapted by other mission-focused institutions as a tool for faculty development and retention

Likelihood of Neoplasia for Diagnoses Modified by Probability Terms in Canine and Feline Lymph Node Cytology: How Probable Is Probable?

Background: Descriptive probability modifiers are used often to convey the uncertainty of a pathology diagnosis, but they also contribute to ambiguity in communication between pathologists and clinicians.Objectives: Our goal was to determine the frequency and use of probability modifiers in canine and feline lymph node cytology diagnoses, and to determine the actual likelihood of neoplasia for diagnoses with and without modifiers, based on the histologic outcome.Methods: Canine and feline lymph node cytology and histology reports over an 11-year period (2001–2011; n = 367) were evaluated retrospectively. Diagnoses were categorized as neoplastic/malignant (lymphoma, metastatic) or non-neoplastic/benign. The frequency and type of modifier, and the sensitivity, specificity, and predictive values for neoplasia were determined for modified and unmodified diagnoses using histology as the gold standard.Results: Ninety-one of 367 (24.8%) cytology diagnoses were modified by probability terms, including 25/204 (12.2%) diagnoses of non-neoplastic lesions and 66/163 (40.5%) diagnoses of neoplasia. In addition, 26 unmodified diagnoses of neoplasia were followed by a probability phrase indicating specific tumor type. Based on the histologic outcome, modified diagnoses had higher sensitivity (87.3%, confidence interval [CI] 75.5, 94.7%) but lower specificity (50.0%, CI 32.9, 67.1%) for neoplasia than did unmodified diagnoses (60.6 and 100%, respectively; P &lt; 0.0001, Chi square). Modified phrases indicating the probability of a specific tumor type were accurate in 22/26 (84.6%) cases. Positive predictive values for neoplasia were 100% (CI 96.2, 100%) for unmodified and 72.7% (CI 60.4, 83.0%) for modified diagnoses. Negative predictive values were 65.9% (CI 58.5, 72.8%) for unmodified and 72.0% (CI 60.4, 83.0%) for modified diagnoses. No significant difference was found in the likelihood of neoplasia for individual terms used to modify a cytologic diagnosis except for “cannot rule out” (P = 0.0368).Conclusions: Most modified diagnoses of cancer in canine and feline lymph node cytology have a 60–83% likelihood of neoplasia based on histologic outcome, compared with 96–100% for unmodified diagnoses. Non-neoplastic lesions, regardless of modifiers, have a 12–49% likelihood of neoplasia. A limited number of risk categories based on these likelihoods may be a more effective and accurate way to communicate the risk of malignancy in lymph node cytology

Resonances and superlattice pattern stabilization in two-frequency forced Faraday waves

We investigate the role weakly damped modes play in the selection of Faraday wave patterns forced with rationally-related frequency components m*omega and n*omega. We use symmetry considerations to argue for the special importance of the weakly damped modes oscillating with twice the frequency of the critical mode, and those oscillating primarily with the "difference frequency" |n-m|*omega and the "sum frequency" (n+m)*omega. We then perform a weakly nonlinear analysis using equations of Zhang and Vinals (1997, J. Fluid Mech. 336) which apply to small-amplitude waves on weakly inviscid, semi-infinite fluid layers. For weak damping and forcing and one-dimensional waves, we perform a perturbation expansion through fourth order which yields analytical expressions for onset parameters and the cubic bifurcation coefficient that determines wave amplitude as a function of forcing near onset. For stronger damping and forcing we numerically compute these same parameters, as well as the cubic cross-coupling coefficient for competing waves travelling at an angle theta relative to each other. The resonance effects predicted by symmetry are borne out in the perturbation results for one spatial dimension, and are supported by the numerical results in two dimensions. The difference frequency resonance plays a key role in stabilizing superlattice patterns of the SL-I type observed by Kudrolli, Pier and Gollub (1998, Physica D 123).Comment: 41 pages, 13 figures; corrected figure 1b and minor typos in tex

Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist

The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment

Nutritional support and brain tissue glucose metabolism in poor-grade SAH: a retrospective observational study

INTRODUCTION: We sought to determine the effect of nutritional support and insulin infusion therapy on serum and brain glucose levels and cerebral metabolic crisis after aneurysmal subarachnoid hemorrhage (SAH). METHODS: We used a retrospective observational cohort study of 50 mechanically ventilated poor-grade (Hunt-Hess 4 or 5) aneurysmal SAH patients who underwent brain microdialysis monitoring for an average of 109 hours. Enteral nutrition was started within 72 hours of admission whenever feasible. Intensive insulin therapy was used to maintain serum glucose levels between 5.5 and 7.8 mmol/l. Serum glucose, insulin and caloric intake from enteral tube feeds, dextrose and propofol were recorded hourly. Cerebral metabolic distress was defined as a lactate to pyruvate ratio (LPR) > 40. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE). RESULTS: Daily mean caloric intake received was 13.8 ± 6.9 cal/kg and mean serum glucose was 7.9 ± 1 mmol/l. A total of 32% of hourly recordings indicated a state of metabolic distress and < 1% indicated a state of critical brain hypoglycemia (< 0.2 mmol/l). Calories received from enteral tube feeds were associated with higher serum glucose concentrations (Wald = 6.07, P = 0.048), more insulin administered (Wald = 108, P < 0.001), higher body mass index (Wald = 213.47, P < 0.001), and lower body temperature (Wald = 4.1, P = 0.043). Enteral feeding (Wald = 1.743, P = 0.418) was not related to brain glucose concentrations after accounting for serum glucose concentrations (Wald = 67.41, P < 0.001). In the presence of metabolic distress, increased insulin administration was associated with a relative reduction of interstitial brain glucose concentrations (Wald = 8.26, P = 0.017), independent of serum glucose levels. CONCLUSIONS: In the presence of metabolic distress, insulin administration is associated with reductions in brain glucose concentration that are independent of serum glucose levels. Further study is needed to understand how nutritional support and insulin administration can be optimized to minimize secondary injury after subarachnoid hemorrhage