Structural features of thyroid hormone response elements that increase susceptibility to inhibition by an RTH mutant thyroid hormone receptor

The chicken lysozyme silencer F2 (F2) thyroid hormone response element (TRE) contains an unusual everted palindromic arrangement, has a high affinity for thyroid hormone receptor (TR) homodimers, and is especially sensitive to dominant negative inhibition by, the T3 resistance (RTH) mutant TR beta P453H. We used various TREs and TR mutations to determine the mechanisms for this sensitivity. Changing the F2 orientation from an everted palindrome to a direct repeat with a 4-bp gap (DR+4) (F2-DR) decreased the sensitivity to inhibition at high T3 concentrations, while a loss of this sensitivity occurred with a palindromic arrangement of these same half-sites. F2 contains the dinucleotide TG 5' to each consensus half-site conforming to the optimal TR-binding octamer, YRRGGTCA. A T to A change in position 1 of both F2 half-sites markedly reduced T3-induction, yet only slightly reduced TR homodimer or TR-retinoid X receptor (RXR) heterodimer binding. The TR beta ninth heptad mutation, L428R, prevents TR heterodimerization with RXR and eliminates the inhibitory effect of the P453H mutant TR on the F2-DR, but not the F2 element. Structural features of a TRE that favor strong TR binding of both TR homodimers and TR-RXR heterodimers containing the mutant TR, such as the everted palindromic conformation or the optimal TR-binding consensus octamer, enhance the sensitivity of a TRE to inhibition by the mutant TR. Thus, both half-site orientation and sequence contribute to the sensitivity of a given TRE to dominant negative inhibition by a mutant TR.     

Change in working alliance, social support, and psychological symptoms in brief therapy.

Many interpersonal therapists use the working alliance as a vehicle for client change and as a corrective experience for clients to learn new relationship skills. 34 19–28-yr-old clients in brief therapy completed measures of social support and psychological symptoms at pretest and termination and a measure of working alliance after the third session and at termination. Path analysis suggested that improvement in the working alliance was significantly related to improvement in social support and that improvement in social support was significantly related to symptom reduction. The working alliance appears to have an important indirect connection to symptom reduction, through the mediating influence of increased support. After the effects of improved alliance were controlled, increased support was still related to decreased symptoms; however, after the effects of social support were controlled, the relation between change in alliance and symptoms was not significant. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of low-volatile additives on the structure and strength of cokes

Blends of medium-volatile or high-volatile coals have been carbonized in a 7 kg oven with low-volatile coals (6–16% VM, dmmf). A comparison is made of the strength and structural properties of these cokes with those of the cokes made under corresponding conditions from the medium or high-volatile coals alone. With increasing levels of addition of the low-volatile coals the tensile strength of the blend cokes generally attains a maximum and then decreases. These strength changes are related to changes in porosity, pore-wall thickness and pore dimensions. Coals which display some degree of plasticity and which are weakly caking improve coke quality by altering the pore-structure due to the combined effects of decreasing the pore diameter and slightly increasing the wall thickness. Those additives which are non-caking act primarily as wall thickeners.     

The primacy of affective judgment from a teleological perspective.

States that in overlooking the studies on affective judgment of J. F. Rychlak (1977), R. B. Zajonc (see record 1980-09733-001) has omitted an entire theoretical approach that should be seriously considered in discussions of the primacy of affect. This omission is corrected with a brief review of Rychlak's teleological theory and its contrast with Zajonc's approach. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial coherence of backscatter for the nonlinearly produced second harmonic for specific transmit apodizations

To be successful, correlation-based, phase-aberration correction requires a high correlation among backscattered signals. For harmonic imaging, the spatial coherence of backscatter for the second harmonic component is different than the spatial coherence of backscatter for the fundamental component. The purpose of this work was to determine the effect of changing the transmit apodization on the spatial coherence of backscatter for the nonlinearly generated second harmonic. Our approach was to determine the effective apodizations for the fundamental and second harmonic using both experimental measurements and simulations. Two-dimensional measurements of the transverse cross sections of the finite-amplitude ultrasonic fields generated by rectangular and circular apertures were acquired with a hydrophone. Three different one-dimensional transmit apodization functions were investigated: uniform, Riesz, and trapezoidal. An effective apodization was obtained for each transmit apodization by backpropagating the values measured from within the transmit focal zone using a linear angular spectrum approach. Predictions of the spatial coherence of backscatter were obtained using the pulse-echo Van Cittert-Zernike theorem. In all cases the effective apodization at 2f was narrower than the transmit apodization. We demonstrate that certain transmit apodizations result in a greater spatial coherence of backscatter at the second harmonic than at the fundamental.     

Low-glycemic-load diets: impact on obesity and chronic diseases

Historically, carbohydrates have been thought to play only a minor role in promoting weight gain and in predicting the risk of development of chronic disease. Most of the focus had been on reducing total dietary fat. During the last 20 years, fat intake decreased, while the number of individuals who were overweight or developed a chronic conditions have dramatically increased. Simultaneously, the calories coming from carbohydrate have also increased. Carbohydrates can be classified by their post-prandial glycemic effect, called the glycemic index or glycemic load. Carbohydrates with high glycemic indexes and high glycemic loads produce substantial increases in blood glucose and insulin levels after ingestion. Within a few hours after their consumption, blood sugar levels begin to decline rapidly due to an exaggerated increase in insulin secretion. A profound state of hunger is created. The continued intake of high-glycemic load meals is associated with an increased risk of chronic diseases such as obesity, cardiovascular disease, and diabetes. In this review, the terms glycemic index and glycemic load are defined, coupled with an overview of short- and long-term changes that occur from eating diets of different glycemic indexes and glycemic loads. Finally, practical strategies for how to design low-glycemic-load diets consisting primarily of low-glycemic carbohydrates are provided.     

Self-assembled nanoscale biosensors based on quantum dot FRET donors

The potential of luminescent semiconductor quantum dots (QDs) to enable development of hybrid inorganic-bioreceptor sensing materials has remained largely unrealized. We report the design, formation and testing of QD-protein assemblies that function as chemical sensors. In these assemblies, multiple copies of Escherichia coli maltose-binding protein (MBP) coordinate to each QD by a C-terminal oligohistidine segment and function as sugar receptors. Sensors are self-assembled in solution in a controllable manner. In one configuration, a beta-cyclodextrin-QSY9 dark quencher conjugate bound in the MBP saccharide binding site results in fluorescence resonance energy-transfer (FRET) quenching of QD photoluminescence. Added maltose displaces the beta-cyclodextrin-QSY9, and QD photoluminescence increases in a systematic manner. A second maltose sensor assembly consists of QDs coupled with Cy3-labelled MBP bound to beta-cyclodextrin-Cy3.5. In this case, the QD donor drives sensor function through a two-step FRET mechanism that overcomes inherent QD donor-acceptor distance limitations. Quantum dot-biomolecule assemblies constructed using these methods may facilitate development of new hybrid sensing materials.     

Model-based evaluation of clustering validation measures

A cluster operator takes a set of data points and partitions the points into clusters (subsets). As with any scientific model, the scientific content of a cluster operator lies in its ability to predict results. This ability is measured by its error rate relative to cluster formation. To estimate the error of a cluster operator, a sample of point sets is generated, the algorithm is applied to each point set and the clusters evaluated relative to the known partition according to the distributions, and then the errors are averaged over the point sets composing the sample. Many validity measures have been proposed for evaluating clustering results based on a single realization of the random-point-set process. In this paper we consider a number of proposed validity measures and we examine how well they correlate with error rates across a number of clustering algorithms and random-point-set models. Validity measures fall broadly into three classes: internal validation is based on calculating properties of the resulting clusters; relative validation is based on comparisons of partitions generated by the same algorithm with different parameters or different subsets of the data; and external validation compares the partition generated by the clustering algorithm and a given partition of the data. To quantify the degree of similarity between the validation indices and the clustering errors, we use Kendall's rank correlation between their values. Our results indicate that, overall, the performance of validity indices is highly variable. For complex models or when a clustering algorithm yields complex clusters, both the internal and relative indices fail to predict the error of the algorithm. Some external indices appear to perform well, whereas others do not. We conclude that one should not put much faith in a validity score unless there is evidence, either in terms of sufficient data for model estimation or prior model knowledge, that a validity measure is well-correlated to the error rate of the clustering algorithm.     

Determinants and validity of self-estimates of abilities and self-concept measures.

How accurate are self-estimates of cognitive abilities? An investigation of self-estimates of verbal, math, and spatial abilities is reported with a battery of parallel objective tests of abilities. Self-estimates were obtained prior to and after objective ability testing (without test feedback) in order to examine whether self-estimates change after direct objective testing experience. Self-estimates showed small to large effect-size correlations with objective tests--larger for math and smaller for verbal. The construct space of self-estimates of abilities was explored in the context of self-concept, self-esteem, self-efficacy, personality, interests, motivational traits, and trait complexes. Self-efficacy and self-esteem variables showed the highest correlations with self-estimates of abilities. In general, trait complexes showed the highest correlations with verbal ability self-estimates and the lowest correlations with math ability self-estimates. Results are discussed in relation to the principle of aggregation, the influences of self-evaluative judgments, and uses for self-estimates of abilities measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)