Physicochemical properties of the nucleoside prodrug R1626 leading to high oral bioavailability

The nucleoside analog R1479 is a potent and highly selective inhibitor of NS5b-directed hepatitis C virus (HCV) RNA polymerase in vitro. Because of its limited permeability, lipophilic prodrugs of R1479 were screened. Selection of the prodrug involved optimization of solubility, permeability, and stability parameters. R1626 has dissociation constant, intrinsic solubility, log partition coefficient (n-octanol water), and Caco-2 permeability of 3.62, 0.19 mg/mL, 2.45, and 14.95 x 10(-6) cm/s, respectively. The hydrolysis of the prodrug is significantly faster in the Caco-2 experiments than in hydrolytic experiments, suggesting that the hydrolysis is catalyzed by enzymes in the cellular membrane. Using GastroPlus, the physical properties of R1626 successfully predict the dose dependence of the pharmacokinetics in humans previously studied. The program predicts that if the particle size of R1626 is less than 25 microm, it will be well absorbed. Prodrugs with a solubility of greater than 100 microg/mL and permeability in the Caco-2 assay greater than 3 x 10(-6) cm/s are expected to achieve a high fraction absorbed.     

On modifying recognition memory tests for detection of malingering.

Considers symptom validity testing as a means of evaluating malingering. It is argued that G. J. Larrabee's (see record 1991-27876-001) cutting scores for significantly worse-than-chance performance on yes–no recognition memory tests are incorrect. Modification of these scores is discussed, with new values specified. Additional issues pertinent to assessment of malingering are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

TV News Test: A new measure of everday memory for prose.

In independent samples of 364 normal volunteers (mean age 56.58 yrs) and 30 individuals from a drug study (mean age 62.10 yrs), previous performance on the TV News Test (TVNT), a computerized measure of everyday verbal memory, was significantly correlated with the Logical Memory subtest of the Wechsler Memory Scale (WMS). Both test performances reflected significant associations with the Wechsler Adult Intelligence Scale (WAIS) Vocabulary subtest. The TVNT alone was significantly correlated with Ss' age. The TVNT and the Logical Memory subtest both had significant associations with self-reported memory functions. Logical Memory was significantly related to a third measure of verbal memory, WMS Paired Associate Learning. The cognitive demands of the TVNT and the Logical Memory task may differ. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Theory and application of a nondestructive photovoltaic technique for the measurement of resistivity variations in circular semiconductor slices

A nondestructive photovoltaic technique for measuring resistivity variations in high-resistivity semiconductor slices is described. The underlying theory of this measurement is reviewed, and the necessary expressions for its implementation are derived for a case of a small light spot scanned over a diameter of a large circular slice. The reduction of these theoretical results to practice is discussed and their validity demonstrated by comparing the results obtained with the photovoltaic technique to resistivity profiles of the same slice diameter measured by four-probe techniques.     

Gambit: A Prototyping Approach to Video Game Design

Video game designers don't have to be assembly language programmers. Their creative talents can be expressed in a prototyping language.     

Gigabit age microelectronics and their manufacture

The benefits of gigabit chips, which will enter production around the year 2000, are discussed. These chips will be enablers for smart and brilliant systems. The systems will be ultralow power. The design and software productivity enhancements needed are described. The numerous manufacturing challenges that lie ahead in the 1990s represent opportunities to implement advanced concepts currently under development in the industry. It is predicted that software-driven concepts such as flexible manufacturing and distributed computer integrated manufacturing will evolve. Processing concepts using cluster tools, real-time process control, all-dry processing, and wafer microenvironments should be ready for manufacturing in the gigabit age. The costs of electronics should continue to decrease, concomitant with extraordinary increases in functionality and performance     

Structure of everyday memory in adults with age-associated memory impairment.

Everyday memory was tested in a group of adults manifesting Age-Associated Memory Impairment; a computerized battery of tests was constructed to simulate memory tasks of daily life. Confirmatory and other structural equation models were estimated for the entire sample of 273 Ss and for 3 age groups. A 4-factor model was found to fit the data well and was invariant across age and gender. After education had been controlled, only the General Recall factor was found to be consistently related to age in both men and women; the other 3 factors—Narrative Memory, Digit Recall, and Visual Memory—were related to age only in men. Confirmatory factor analyses of the everyday memory tests combined with several psychometric memory tests suggested that some of the latter (the Benton Visual Retention Test and Wechsler Memory Scale Hard Paired Associates) load on more than 1 factor of everyday memory, suggesting complex relationships between the 2 types of tests. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A misleading review of response bias: Comment on McGrath, Mitchell, Kim, and Hough (2010).

In the May 2010 issue of Psychological Bulletin, R. E. McGrath, M. Mitchell, B. H. Kim, and L. Hough published an article entitled “Evidence for Response Bias as a Source of Error Variance in Applied Assessment” (pp. 450–470). They argued that response bias indicators used in a variety of settings typically have insufficient data to support such use in everyday clinical practice. Furthermore, they claimed that despite 100 years of research into the use of response bias indicators, “a sufficient justification for [their] use… in applied settings remains elusive” (p. 450). We disagree with McGrath et al.'s conclusions. In fact, we assert that the relevant and voluminous literature that has addressed the issues of response bias substantiates validity of these indicators. In addition, we believe that response bias measures should be used in clinical and research settings on a regular basis. Finally, the empirical evidence for the use of response bias measures is strongest in clinical neuropsychology. We argue that McGrath et al.'s erroneous perspective on response bias measures is a result of 3 errors in their research methodology: (a) inclusion criteria for relevant studies that are too narrow; (b) errors in interpreting results of the empirical research they did include; (c) evidence of a confirmatory bias in selectively citing the literature, as evidence of moderation appears to have been overlooked. Finally, their acknowledging experts in the field who might have highlighted these errors prior to publication may have prevented critiques during the review process. (PsycINFO Database Record (c) 2011 APA, all rights reserved)