Transforming growth factor beta peptide antagonists and their conversion to partial agonists

Transforming growth factor beta (TGF-beta) has been implicated in the pathogenesis of various human diseases. Synthetic TGF-beta antagonists therefore could have therapeutic utility. Here we show the development of such compounds. Three synthetic pentacosapeptides designated beta125-(41-65), beta225-(41-65), and beta325-(41-65), whose amino acid sequences correspond to the 41st to 65th amino acid residues of TGF-beta1, TGF-beta2, and TGF-beta3, respectively, inhibit the binding of 125I-labeled TGF-beta isoforms to TGF-beta receptors in mink lung epithelial cells with IC50 of approximately 0.06-2 microM. beta125-(41-65) blocks TGF-beta1-induced growth inhibition and TGF-beta1-induced plasminogen activator inhibitor-1 expression in these cells. The variants designated beta125-(41-65)W52A/D55A and beta325-(41-65)R52A/D55A, in which both Trp52/Arg52 and Asp55 are replaced by alanine residues, do not have TGF-beta antagonist activity. Multiple conjugation of beta125-(41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as measured by DNA synthesis inhibition. These results suggest that the (W/R)XXD motif is important for the activities of these TGF-beta peptide antagonists and that this motif may be the active site sequence of TGF-beta.     

The influence of some non-starch polysaccharides on the metabolic response to sucrose-based and fructose-based chocolates in non-insulin-dependent diabetics

Non-insulin-dependent diabetic patients were given test meals (75 g) of conventional (sucrose-based) milk chocolate or diabetic (fructose-based), either free of non-starch polysaccharide (NSP) or supplemented with pectin (5 g (100 g)^?1), or a combination of pectin and oat fibre. The presence of pectin in the conventional formulation led to a reduction in the area under the post-prandial blood-glucose curve (P < 0.05). However, the effect was small in comparison to the reduction obtained by substituting fructose for sucrose, and the pectin-supplemented chocolate had a very viscous mouthfeel. The substitution of an insoluble form of NSP derived from oat husk for a proportion of the pectin abolished the hypoglycaemic effect of the NSP. Inclusion of NSP in fructose-based chocolate was associated with a small reduction in post-prandial fructosaemia but had no effect on the glycaemic response to this chocolate. It was concluded that viscous NSP slows the absorption of carbohydrate from chocolate. However, the necessary viscosity had an adverse effect on the palatability of the product.     

Prospective study of human herpesvirus 6, human herpesvirus 7, and cytomegalovirus infections in human immunodeficiency virus-positive patients

Blood samples from human immunodeficiency virus (HIV)-positive patients were monitored for cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and HHV-7 by PCR. We detected CMV in 17% of the patients, HHV-6 in 6%, and HHV-7 in 3%. The viral loads of CMV were significantly higher than those of HHV-6 (P = 0.007) or HHV-7 (P = 0.01). Detection of CMV and HHV-6 was associated with low and high CD4 counts, respectively.     

Rethinking neural efficiency: Effects of controlling for strategy use.

A sentence verification task (SVT) was used to test whether differences in neural activation patterns that have been attributed to IQ may actually depend on differential strategy use between IQ groups. Electroencephalograms were recorded from 14 low (89     

Structural change detection in a disturbed conifer forest using a geometric optical reflectance model in multiple-forward mode

Geometric optical reflectance models provide a physical linkage between image data and forest structure. We developed a "multiple-forward-mode" pseudoinversion modeling approach to produce structural lookup tables for Landsat Thematic Mapper images before and after 1993 partial harvests in New Brunswick, Canada. Modeling results validated for stand density, crown radius, and stem counts enabled simple forest structural change detection.     

Toward an expert system for expressive musical performance

The development and implementation of an expert system that determines the tempo and articulations of Bach fugues are described. The rules in the knowledge base are based on the expertise of two professional performers. The system's input is a numeric representation of the fugue. The system processes the input using a transition graph, a data structure consisting of nodes where data is stored and edges that connect the nodes. The transition graph recognizes rhythmic patterns in the input. Once the system identifies a pattern, it applies a specific rule or performs a procedure. System output consists of a listing of tempo and articulation instructions. To validate the expert system, its output was compared with versions of fugues edited by one of the two experts used in developing the system. In tests with six fugues, the expert system generated the same editing instructions 85 to 90% of the time     

Sex differences in the consequences that children anticipate for aggression.

Hypothesized that the outcomes that children expect for aggression vary with child sex, degree of provocation, and target sex. Ss (M age?=?10.6 years) rated their confidence that specified outcomes would ensure for performing acts of provoked and unprovoked aggression toward male and female peers. Boys expected less guilt and less parental disapproval for aggression (especially for provoked aggression toward a boy) than girls. When provoked, children expected more tangible rewards, less guilt, and less parental disapproval than when not provoked. When aggressing toward boys, children expected less tangible rewards, more guilt, less suffering by the target, less parental disapproval, more disapproval from male peers, and less disapproval from female peers than when aggressing toward girls. Implications for a cognitive social learning perspective on sex differences in aggression were discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A computer management system for patient simulations

A series of interactive videodisc patient simulations is being used to teach clinical problem-solving skills, including diagnosis and management, to dental students. This series is called Oral Disease Simulations for Diagnosis and Management (ODSDM). A computer management system has been developed in response to the following needs. First, the sequence in which students perform simulations is critical. Second, maintaining records of completed simulations and student performance on each simulation is a time-consuming task for faculty. Third, the simulations require ongoing evaluation to ensure high quality instruction. The primary objective of the management system is to ensure that each student masters diagnosis. Mastery must be obtained at a specific level before advancing to the next level. The management system does this by individualizing the sequence of the simulations to adapt to the needs of each student. The management system generates reports which provide information about students or the simulations. Student reports contain demographic and performance information. System reports include information about individual patient simulations and act as a quality control mechanism for the simulations.