A geometry-based suite of molecular docking processes

We have developed a geometry-based suite of processes for molecular docking. The suite consists of a molecular surface representation, a docking algorithm, and a surface inter-penetration and contact filter. The surface representation is composed of a sparse set of critical points (with their associated normals) positioned at the face centers of the molecular surface, providing a concise yet representative set. The docking algorithm is based on the Geometric Hashing technique, which indexes the critical points with their normals in a transformation invariant fashion preserving the multi-element geometric constraints. The inter-penetration and surface contact filter features a three-layer scoring system, through which docked models with high contact area and low clashes are funneled. This suite of processes enables a pipelined operation of molecular docking with high efficacy. Accurate and fast docking has been achieved with a rich collection of complexes and unbound molecules, including protein-protein and protein-small molecule associations. An energy evaluation routine assesses the intermolecular interactions of the funneled models obtained from the docking of the bound molecules by pairwise van der Waals and Coulombic potentials. Applications of this routine demonstrate the goodness of the high scoring, geometrically docked conformations of the bound crystal complexes.     

Molecular shape comparisons in searches for active sites and functional similarity

Here we examine the reliability of surface comparisons in searches for active sites in proteins. Detection of a patch of surface on one protein which is similar to an active site in another, may suggest similarities in enzymatic mechanisms, in enzyme functions and implicate a potential target for ligand/inhibitor design. Specifically, we compare the efficacy of molecular surface comparisons with comparisons of surface atoms and of C(alpha) backbone atoms. We further investigate comparisons of specific atoms, belonging to a predefined pattern of catalytic residues versus comparisons of molecular surfaces and, separately, of surface atoms. This aspect is particularly relevant, as catalytic residues may be (partially) buried. We also explore active site comparisons versus comparisons in which the entire molecular surfaces are scanned. While here we focus on the geometrical aspect of the problem, we also investigate the effect of adding residue labels in these comparisons. Our extensive studies cover the serine proteases, containing the highly conserved triad motif, and the chorismate mutases. Since such active site comparisons entail comparisons between unconnected points in 3D space, an order-independent comparison technique is necessary. The geometric hashing algorithm is ideally suited to handling such a task. It can perform both global shape matching for the whole surfaces of large protein molecules and searching for local shape similarities for small surface motifs. Our results show that molecular surface comparisons work best when the similarity is high. As the similarity deteriorates, the number of potential solutions increases rapidly, making their ranking difficult, particularly when scanning entire molecular surfaces. Utilizing atomic coordinates directly appears more adequate under such circumstances.     

Adolescent responses to the MacAndrew Alcoholism Scale.

Compared the MacAndrew Alcoholism Scale (MAC) scores of 306 13–28 yr olds from 4 groups: (1) 76 female and 59 male high school students, (2) 43 female and 47 male inpatient psychiatry patients, (3) 43 female and 38 male outpatient psychiatry and psychology clinic patients, and (4) 50 female and 50 male randomly selected clients at a residential center for drug abuse. Results show differences in mean male and female MAC scores and similarities between mean scores of females in Groups 1–3. Females in Group 4 scored significantly higher. Results further show significant differences in mean scores between males in Groups 1 and 3 and males in Group 4. It is suggested that the cutting score for females should be equal to or greater than 24, while for males it should be equal to or greater than 26. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Minimization of communication cost through caching in mobileenvironments

Users of mobile computers will soon have online access to a large number of databases via wireless networks. Because of limited bandwidth, wireless communication is more expensive than wire communication. In this paper, we present and analyze various static and dynamic data allocation methods. The objective is to optimize the communication cost between a mobile computer and the stationary computer that stores the online database. Analysis is performed in two cost models. One is connection (or time) based, as in cellular telephones, where the user is charged per minute of connection. The other is message based, as in packet radio networks, where the user is charged per message. Our analysis addresses both the average case and the worst case for determining the best allocation method     

Competitive analysis of caching in distributed databases

This paper makes two contributions. First, we introduce a model for evaluating the performance of data allocation and replication algorithms in distributed databases. The model is comprehensive in the sense that it accounts for I/O cost, for communication cost, and, because of reliability considerations, for limits on the minimum number of copies of the object. The model captures existing replica-management algorithms, such as read-one-write-all, quorum-consensus, etc. These algorithms are static in the sense that, in the absence of failures, the copies of each object are allocated to a fixed set of processors. In modern distributed databases, particularly in mobile computing environments, processors will dynamically store objects in their local database and will relinquish them. Therefore, as a second contribution of this paper, we introduce an algorithm for automatic dynamic allocation of replicas to processors. Then, using the new model, we compare the performance of the traditional read-one-write-all static allocation algorithm to the performance of the dynamic allocation algorithm. As a result, we obtain the relationship between the communication cost and I/O cost for which static allocation is superior to dynamic allocation, and the relationships for which dynamic allocation is superior     

The Low-Potential Approach of Glucose Sensing

Study of glucose sensing using a smooth Pt electrode and cyclic voltammetry (CV) at low potentials revealed two well-defined, redox current peaks of adsorbed species. At 370 C a reduction peak occurs at ?0.80 V versus Ag/AgCl and an oxidation peak at ?0.72 V. Furthermore, the redox couple has been shown to be reversible, involving a simple, direct, electron-transfer process under diffusion control. The reaction is not complicated by secondary chemical (nonelectro-chemical) reactions. Based on this approach, a square wave voltammetry (SWV) technique has been adopted to obtain pure faradaic currents (noncapacitance current), fast response times, and enhanced sensitivity-for the designated reversible redox peaks. The SWV technique also permits the employment of much smaller-sized Pt wire electrodes (0.5 mm diameter) for glucose sensing. Plots of current versus glucose concentration in Krebs-Ringer solutions, for both redox peaks, are linear for glucose levels in the 70-350 mg/dl range. Studies of glucose concentration variations in the ultrafiltrate of human serum have also demonstrated a linear relationship between current and glucose level. Thus far, the linearity is limited to a narrow glucose range (80?180 mg/dl), but this is within the critical domain for diabetic control. The advantages of the low-potential approach using SWV is an improvement over CV and could be a promising method for implantable microelectrode glucose sensing.     

Electromyographic patterns associated with nonnutritive sucking in 11–13-day-old rat pups.

Three experiments used an EMG technique to measure the frequency, duration, and intensity of nonnutritive sucking (NNS) in 56 11–13 day old Wistar pups. Ss were separated from their mothers for 2–6 or 20–24 hrs and then allowed to suckle an anesthetized dam for up to 3 hrs without receiving any milk. Jaw-muscle EMG and nipple detachments were recorded. EMG patterns representing 2 discrete modes of sucking were reliably discerned, as were changes in overall intensity of EMG. 20–24 hr separated Ss engaged in more frequent NNS bouts and bouts of longer duration than 2–6 hr separated Ss. Ss separated by 20–24 hrs also engaged in a mode of NNS not seen in 2–6 hr separated Ss. Overall EMG intensity was higher and frequency of nipple detachments was lower in Ss separated for 20–24 hrs. In both groups, but particularly the 20–24 hr Ss, frequency of some NNS patterns decreased as the length of the "dry" suckling increased. EMG intensity also decreased over time in both groups, and frequency of nipple detachments increased in 2–6 hr separated Ss. Data indicate that some aspects of NNS are highly labile and respond to variations of both deprivation from the mother and nutritive deprivation. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estimating sleep patterns with activity monitoring in children and adolescents: how many nights are necessary for reliable measures?

STUDY OBJECTIVES: This study provides estimates of reliability for aggregated values from 1 to 7 recording nights for five commonly used actigraphic measures of sleep patterns, reliability as a function of night type (weeknight or weekend night), and stability of measures over several months. DESIGN AND SETTING: Data are from three studies that obtained 7 nights of actigraph data (using Mini Motionlogger actigraphs and associated validated algorithms [ASA]) on children and adolescents living at home on self-selected sleep-wake schedules. PARTICIPANTS: Participants were 169 children aged 12-60 months, and 55 adolescents aged 11-16 years. MEASUREMENTS AND RESULTS: Up to 28% of weekly recordings may be unacceptable for analysis in young participants because of illness, technical problems, and participant noncompliance; studies aiming to collect 5 nights of actigraph data should record for at least 1 full week. Reliability estimates for values aggregated over any 5 nights were adequate (> or = .70) for sleep start time, wake minutes, and sleep efficiency. Measures of sleep minutes and sleep period were less reliable and may require 7 or more nights for estimates of stable individual differences. Reliability for 1- or 2-night aggregates were poor for all measures. We found significant and high correlations between summer and fall session measures for all five variables when weekend nights were included. CONCLUSIONS: Five or more nights of usable recordings are required to obtain reliable actigraph measures of sleep for children and adolescents.