Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.     

Personal hypothesis testing: The role of consistency and self-schema.

We report the results of two experiments that examined the way individuals test hypotheses about themselves. Both experiments were based on the work of Snyder (e.g., Snyder, 1981; Snyder & Skrypnek, 1981), which suggests that individuals have a confirmatory bias when testing hypotheses about others and about themselves. In Experiment 1, we examined the extent to which this bias toward confirmation persists when a negative (e.g., depression) or nonconsistent (not consistent with the individual's evaluation of him- or herself) personal hypothesis is tested. Results suggest that the negative or positive nature of a personal hypothesis does not directly influence the way individuals test their hypothesis. However, the way individuals tested personal hypotheses was influenced by hypothesis consistency. In Experiment 2, we examined the relation of a cognitive schematic variable (i.e., vulnerability for depression) and hypothesis testing. Results suggest that vulnerability is related to the way individuals test a personal hypothesis about depression. Vulnerable, low-depression participants were confirmatory when testing a depression hypothesis, whereas nonvulnerable, low-depression participants were disconfirmatory. We discuss implications for counseling and future directions for research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Successful treatment of a heterotopic pregnancy by sonographically guided instillation of hyperosmolar glucose

A potassium channel toxin (AeK) was isolated from the sea anemone Actinia equina by gel filtration on Sephadex G-50 and reverse-phase HPLC on TSKgel ODS-120T. AeK and alpha-dendrotoxin inhibited the binding of 125I-alpha-dendrotoxin to rat synaptosomal membranes with IC50 of 22 and 0.34 nM, respectively, indicating that AeK is about sixty-five times less toxic than alpha-dendrotoxin. The complete amino acid sequence of AeK was elucidated; it is composed of 36 amino acid residues including six half-Cys residues. The determined sequence showed that AeK is analogous to the three potassium channel toxins from sea anemones (BgK from Bunodosoma granulifera, ShK from Stichodactyla helianthus and AsKS from Anemonia sulcata), with an especially high sequence homology (86%) with AsKS.     

Attitudes toward disabled persons as a function of social context and specific disability.

191 nondisabled 18–64 yr olds completed the Disability Social Relationship Scale, which includes social situation subscales of Work, Dating, and Marriage, and disability subscales of Amputee, Epilepsy, Cerebral Palsy, and Blind. Results reveal significant differences across social situations and among specific disabilities, as well as a significant interaction between social situation and disability. Thus, situational context affects attitudes toward disabled persons. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Counselor hypothesis-testing strategies.

Conducted 2 experiments relevant to the questioning strategies counselors use in testing their hypotheses about clients. In Exp I, 60 undergraduates were asked to select 12 questions from a list of 38 that would be most helpful in getting to know someone. Ss were asked to test a hypothesis that the other person was an extravert or introvert. The questions were categorized by the experimenters as extraverted, introverted, unbiased, or irrelevant. Most Ss selected a strategy that favored unbiased questions over biased ones. In Exp II, 40 Ss played the roles of clients, and 40 advanced doctoral students in counseling or clinical psychology played the roles of counselors. Counselors were advised that they would soon meet with their client to test a hypothesis that the client possessed or lacked self-control. Counselors were instructed to compose 10 questions to ask the client. The actual interviews were then recorded. The frequency with which counselors developed questions that were confirmatory, disconfirmatory, irrelevant, or unbiased in regard to the hypothesis was not influenced by the specific hypothesis. Results of both experiments do not confirm the hypothesis that counselors preferentially seek information to confirm hypotheses about clients. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Optimal OFDM design for time-frequency dispersive channels

Transmission over wireless channels is subject to time dispersion due to multipath propagation and to frequency dispersion due to the Doppler effect. Standard orthogonal frequency-division multiplexing (OFDM) systems, using a guard-time interval or cyclic prefix, combat intersymbol interference (ISI), but provide no protection against interchannel interference (ICI). This drawback has led to the introduction of pulse-shaping OFDM systems. We first present a general framework for pulse shape design. Our analysis shows that certain pulse shapes proposed in the literature are, in fact, optimal in a well-defined sense. Furthermore, our approach provides a simple way to adapt the pulse shape to varying channel conditions. We then show that (pulse-shaping) OFDM systems based on rectangular time-frequency lattices are not optimal for time- and frequency-dispersive wireless channels. This motivates the introduction of lattice-OFDM (LOFDM) systems which are based on general time-frequency lattices. Using results from sphere packing theory, we show how to design LOFDM systems (lattice and pulse shape) optimally for timeand frequency-dispersive channels in order to minimize the joint ISI/ICI. Our theoretical analysis is confirmed by numerical simulations, showing that LOFDM systems outperform traditional pulse-shaping OFDM systems with respect to robustness against ISI/ICI.     

A preliminary investigation of the role of differential complexity and response style in measuring attitudes toward people with disabilities.

Investigated the potentially complex relationship between cognitive complexity and attitudes towards people with disabilities in a 3-part study using 2 undergraduate student samples. In Exp 1 (n ?=?126), Ss' responses to the Attitudes Toward Disabled Persons Scale-Form O (ATDP-O) were not significantly correlated with the Repertory Grid Test (RGT). This finding suggests no relationship between attitudes and a measure of cognitive complexity. In Exp 2 (n ?=?57), Ss' responses to the ATDP-O were positively correlated with a disability specific repertory grid technique. This finding suggests an inverse relationship between domain-specific cognitive complexity and positive attitudes. In Exp 3, the findings from Exp 1 were reanalyzed and significant correlations were found between the tendency of Ss to respond redundantly and both positive attitudes and to lower cognitive complexity as measured by the ATDP-O and the RGT, respectively. These findings suggest that a large group of individuals who process information by focusing on differences, rather than similarities, may be inappropriately assessed by the ATDP, or other instruments that use a similar format in assessing attitudes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correction to Strohmer and Newman.

Reports an error in the original article by Douglas C. Strohmer and Lisa J. Newman (Journal of Counseling Psychology, 1983, Vol. 30, No. 4, pp. 557-565; see record 1984-04824-001). The concluding sentence of the discussion was incorrect. The correct version is presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

That's not my dog: A reply to Patton and Wampold.

Responds to the comments of M. J. Patton and B. E. Wampold (see record 1983-11132-001) concerning the present authors' article (see record 1983-11141-001). Issues addressed are (1) the use of a clinical model of prediction and elements of judgment considered, (2) questions relating to the statistical analysis, and (3) issues concerning modeling the counselor judgment process and directions for research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)