Pull-Down of Metalloproteins in Their Native States by Using Desthiobiotin-Based Probes

One-third of all proteins are estimated to require metals for structural stability and/or catalytic activity. Desthiobiotin probes containing metal binding groups can be used to capture metalloproteins with exposed active-site metals under mild conditions so as to prevent changes in metallation state. The proof-of-concept was demonstrated with carbonic anhydrase (CA), an open active site, Zn²⁺-containing protein. CA was targeted by using sulfonamide derivatives. Linkers of various lengths and structures were screened to determine the optimal structure for capture of the native protein. The optimized probes could selectively pull down CA from red blood cell lysate and other protein mixtures. Pull-down of differently metallated CAs was also investigated.     

Revising deductive knowledge and stereotypical knowledge in a student model

A user/student model must be revised when new information about the user/student is obtained. But a sophisticated user/student model is a complex structure that contains different types of knowledge. Different techniques may be needed for revising different types of knowledge. This paper presents a student model maintenance system (SMMS) which deals with revision of two important types of knowledge in student models: deductive knowledge and stereotypical knowledge. In the SMMS, deductive knowledge is represented by justified beliefs. Its revision is accomplished by a combination of techniques involving reason maintenance and formal diagnosis. Stereotypical knowledge is represented in the Default Package Network (DPN). The DPN is a knowledge partitioning hierarchy in which each node contains concepts in a sub-domain. Revision of stereotypical knowledge is realized by propagating new information through the DPN to change default packages (stereotypes) of the nodes in the DPN. A revision of deductive knowledge may trigger a revision of stereotypical knowledge, which results in a desirable student model in which the two types of knowledge exist harmoniously.     

Determinants of genital human papillomavirus infection among cytologically normal women attending the University of New Mexico student health center

OBJECTIVES: To confirm the risk factors for genital human papillomavirus (HPV) infection. GOAL OF THIS STUDY: To investigate risk factors for HPV detection apart from the correlated risk factors for cervical neoplasia. STUDY DESIGN: Cervical human papillomavirus (HPV) DNA was assessed in 357 cytologically normal women attending the University of New Mexico student health center. Cervical swab samples were obtained for HPV DNA detection and typing using a PCR-based DNA amplification system. Possible determinants of cervical HPV were examined including age, ethnicity, history of sexually transmitted disease, oral contraceptive use, smoking, age at first intercourse, lifetime number of sex partners, marital status, and history of pregnancy. RESULTS: A 44.3% overall prevalence of cervical HPV was observed. On univariate analysis, factors associated with increasing HPV prevalence included higher lifetime number of sex partners and single marital status. After adjustment for potential confounding variables, we found that HPV prevalence increased with higher lifetime number of sexual partners. CONCLUSION: These findings, along with those from the companion reports in this issue of the journal, support the sexual route of transmission of the virus.     

Clozapine reduces rehospitalization among schizophrenia patients

Diabetes mellitus positive for antibodies to glutamate decarboxylase is heterogeneous as far as the degree of impairment of endogenous insulin release, though antibodies to glutamate decarboxylase are the most useful marker for future insulin deficiency. To investigate what determines the prognosis of diabetes mellitus positive for antibodies to glutamate decarboxylase, we measured HLA-DRB1 alleles in three groups: 77 cases of insulin-dependent diabetes mellitus (IDDM), 44 of non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure of oral hypoglycemic therapy, and 22 of NIDDM well controlled by diet and/or sulfonylurea agents. The proportion of susceptible and resistant alleles to IDDM determined the degree of insulin deficiency, and comparison of IDDM to NIDDM well controlled by diet and/or sulfonylurea agents revealed significant differences in DRB1*0405 (P < 0.05; RR = 2.82 and RR = 0.89, respectively) and DRB1*1502 (P < 0.001; RR = 0.02 and RR = 2.19, respectively). This study revealed that HLA-DRB1 alleles contribute to determining the prognosis of Japanese diabetes mellitus positive for antibodies to glutamate decarboxylase.     

Distinctiveness and Correlation in Conceptual Structure: Behavioral and Computational Studies.

Patients with category-specific deficits have motivated a range of hypotheses about the structure of the conceptual system. One class of models claims that apparent category dissociations emerge from the internal structure of concepts rather than fractionation of the system into separate substores. This account claims that distinctive properties of concepts in the living domain are vulnerable because of their weak correlation with other features. Given the assumption that mutual activation among correlated properties produces faster activation in the normal system, the authors predicted a disadvantage for the distinctive features of living things for unimpaired adults. Results of a speeded feature verification study supported this prediction, as did a computational simulation in which networks mapped from orthography to semantics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Boundary formulations for shape sensitivity of temperature dependent conductivity problems

Used in concert with the Kirchhoff transformation, implicit differentiation of the discretized boundary integral equations governing the conduction of heat in solids with temperature dependent thermal conductivity is shown to generate an accurate and economical approach for computation of shape sensitivities. For problems with specified temperature and heat flux boundary conditions, a linear problem results for both the analysis and sensitivity analysis. In problems with either convection or radiation boundary conditions, a non-linear problem is generated. Several iterative strategies are presented for the solution of the resulting sets of non-linear equations and the computational performances examined in detail. Multi-zone analysis and zone condensation strategies are demonstrated to provide substantive computational economies in this process for models with either localized non-iinear boundary conditions or regions of geometric insensitivity to design variables. A series of non-linear example problems is presented that have closed form solutions. Exact anaytical expressions tor the shape sensitivities associated with these problems are developed and these are compared with the sensitivities computed using the boundary element formulation.     

Surface crystallization of melt-spun Pd40Ni40P20 glass

The crystallization of Pd₄₀Ni₄₀P₂₀ glass, produced by melt-spinning in air, has been studied by optical metallography. Crystallization is predominantly from the surface and is more prevalent on the wheel-side. The non-uniformity is attributed to variation in quench rate during production. A three-stage anneal permits crystals which have nucleated at the surface to be identified and their size distribution to be analysed. The surface nucleation is heterogeneous and appears to be hindered by mild oxidation. The annealing atmosphere markedly affects the surface crystallization behaviour, as does removal of the original ribbon surface. When nucleation is sparse, partial crystallization causes the development of noticeable relief on the sample surfaces.