A theory of mode of action of azolylalkylquinolines as DNA binding agents using automated flexible ligand docking

Azolylalkylquinolines (AAQs) are a family of quinolines with varying degrees of cytotoxic activity (comparable or moderately superior to adriamycin in some cases) developed in the past decade in our group where their exact mode of action is still unclear. In this study the most probable DNA binding mode of AAQs was investigated employing a novel flexible ligand docking approach by using AutoDock 3.0. Forty-nine AAQs with known experimental inhibitory activity were docked onto d(CGCAAATTTGCG)(2), d(CGATCG)(2) and d(CGCG)(2) oligonucleotides retrieved from the Protein Data Bank (PDB IDs: 102D, 1D12 and 1D32, respectively) as the representatives of the three plausible models of interactions between chemotherapeutic agents and DNA (groove binding, groove binding plus intercalation and bisintercalation, respectively). Good correlation (r(2)=0.64) between calculated binding energies and experimental inhibitory activities was obtained using groove binding plus intercalation model for phenyl-azolylalkylquinoline (PAAQ) series. Our findings show that the most probable mode of action of PAAQs as DNA binding agents is via intercalation of quinolinic moiety between CG base pairs with linker chain and azole moiety binding to the minor groove.     

Selection of regression models for predicting strength and deformability properties of rocks using GA

Recently, many regression models have been presented for prediction of mechanical parameters of rocks regarding to rock index properties. Although statistical analysis is a common method for developing regression models, but still selection of suitable transformation of the independent variables in a regression model is difficult. In this paper, a genetic algorithm (GA) has been employed as a heuristic search method for selection of best transformation of the independent variables (some index properties of rocks) in regression models for prediction of uniaxial compressive strength (UCS) and modulus of elasticity (E). Firstly, multiple linear regression (MLR) analysis was performed on a data set to establish predictive models. Then, two GA models were developed in which root mean squared error (RMSE) was defined as fitness function. Results have shown that GA models are more precise than MLR models and are able to explain the relation between the intrinsic strength/elasticity properties and index properties of rocks by simple formulation and accepted accuracy.     

The smooth (tractor) operator: insights of knowledge engineering

The design of and training for complex systems requires in-depth understanding of task demands imposed on users. In this project, we used the knowledge engineering approach (Bowles et al., 2004) to assess the task of mowing in a citrus grove. Knowledge engineering is divided into four phases: (1) Establish goals. We defined specific goals based on the stakeholders involved. The main goal was to identify operator demands to support improvement of the system. (2) Create a working model of the system. We reviewed product literature, analyzed the system, and conducted expert interviews. (3) Extract knowledge. We interviewed tractor operators to understand their knowledge base. (4) Structure knowledge. We analyzed and organized operator knowledge to inform project goals. We categorized the information and developed diagrams to display the knowledge effectively. This project illustrates the benefits of knowledge engineering as a qualitative research method to inform technology design and training.     

Place Versus Response Learning Revisited: Tests of Blocking on the Radial Maze.

Neurobiological and behavioral research indicates that place learning and response learning occur simultaneously, in parallel. Such findings seem to conflict with theories of associative learning in which different cues compete for learning. The authors conducted place + response training on a radial maze and then tested place learning and response learning separately by reconfiguring the maze in various ways. Consistent with the effects of manipulating place and response systems in the brain (M. G. Packard & J. L. McGaugh, 1996), well-trained rats showed strong place learning and strong response learning. Three experiments using associative blocking paradigms indicated that prior response learning interferes with place learning. Blocking and related tests can be used to better understand how memory systems interact during learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Understanding sources of user variability in computer-based data entry performance

The pervasive use of computers in work settings implies that an increased number of workers, with varying levels of skills and abilities, will be performing computerbased tasks. This study investigated the impact of age, cognitive abilities, and computer experience on the performance of a real world data entry task. One hundred and ten subjects, ranging in age from 20 - 75 years, performed the task for nine hours following task training. The results indicated that abilities such as visuo-spatial skills, motor skills and processing speed had a significant impact on performance as did age and prior computer experience. With respect to age, the older participants completed less work than the younger and middle-aged subjects. Age differences in psychomotor skills and processing speed appeared to be important factors underlying age effects. In fact, the data indicated that after controlling for differences in these abilities age was no longer a significant predictor of work output. Further, after controlling for differences in work output the older people made fewer errors than the younger people. Overall the data suggest that older people will be at a disadvantage in the performance of computer-based data entry work to the extent to which speed of responding is emphasized. However, if speed of responding is not a critical element of performance they will be able to achieve comparable levels of performance to that of younger people.     

Physical Maltreatment Victim to Antisocial Child: Evidence of an Environmentally Mediated Process.

The well-documented finding that child physical maltreatment predicts later antisocial behavior has at least 2 explanations: (a) Physical maltreatment causes antisocial behavior, and (b) genetic factors transmitted from parents to children influence the likelihood that parents will be abusive and that children will engage in antisocial behavior. The authors tested these hypotheses in the representative Environmental-Risk cohort of 1,116 twin pairs and their families, who were assessed when the twins were 5 and 7 years old. Mothers reported on children's experience of physical maltreatment, and mothers and teachers reported on children's antisocial behavior. The findings support the hypothesis that physical maltreatment plays a causal role in the development of children's antisocial behavior and that preventing maltreatment can prevent its violent sequelae. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Effectiveness of Telephone-Based Continuing Care in the Clinical Management of Alcohol and Cocaine Use Disorders: 12-Month Outcomes.

This study of continuing care for substance dependent patients compared a telephone-based monitoring and brief counseling intervention (TEL) with 2 face-to-face interventions, relapse prevention (RP) and standard 12-step group counseling (STND). The participants were graduates of intensive outpatient programs who had current dependence on alcohol and/or cocaine. Self-report, collateral, and biological measures of alcohol and cocaine use were obtained over a 12-month follow-up. The treatment groups did not differ on abstinence-related outcomes in the complete sample (N = 359) or on cocaine use outcomes in participants with cocaine dependence (n = 268). However, in participants with alcohol dependence only (n = 91), TEL produced better alcohol use outcomes than STND on all measures examined and better outcomes than RP on some of the measures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human, rhesus macaque, and feline sequences highly similar to mouse mammary tumor virus sequences

Sequences highly similar (>95%) to the mouse mammary tumor virus (MMTV) env gene have been amplified from human DNA samples, including DNA samples from patients with breast cancer (BC) and persons who did not have BC. The sequences from human DNA were distinct from the MMTV sequences used as controls in these PCR reactions, indicating that these results are not simply due to contamination. In addition to both, mouse and human-related sequences were also amplified from some monkey and cat genomic DNA samples. These products were shown to be distinct from, but highly related to, the MMTV env gene, whereas, testing of other sources (lambda phage, snake, cockroach, sea urchin, chicken, or dog) demonstrated no specific amplification. A sequence 90% similar to the MMTV group antigen gene (gag) was amplified from cat DNA. These results indicate that DNA from vertebrate species other than rodents, including some but not all humans, monkeys, and cats, can contain sequences closely related to MMTV.