Domain flexibility in retroviral proteases: structural implications for drug resistant mutations

Rigid body rotation of five domains and movements within their interfacial joints provide a rational context for understanding why HIV protease mutations that arise in drug resistant strains are often spatially removed from the drug or substrate binding sites. Domain motions associated with substrate binding in the retroviral HIV-1 and SIV proteases are identified and characterized. These motions are in addition to closure of the flaps and result from rotations of approximately 6-7 degrees at primarily hydrophobic interfaces. A crystal structure of unliganded SIV protease (incorporating the point mutation Ser 4 His to stabilize the protease against autolysis) was determined to 2.0 A resolution in a new space group, P3221. The structure is in the most "open" conformation of any retroviral protease so far examined, with six residues of the flaps disordered. Comparison of this and unliganded HIV structures, with their respective liganded structures by difference distance matrixes identifies five domains of the protease dimer that move as rigid bodies against one another: one terminal domain encompassing the N- and C-terminal beta sheet of the dimer, two core domains containing the catalytic aspartic acids, and two flap domains. The two core domains rotate toward each other on substrate binding, reshaping the binding pocket. We therefore show that, for enzymes, mutations at interdomain interfaces that favor the unliganded form of the target active site will increase the off-rate of the inhibitor, allowing the substrate greater access for catalysis. This offers a mechanism of resistance to competitive inhibitors, especially when the forward enzymatic reaction rate exceeds the rate of substrate dissociation.     

Laser-speckle angular-displacement sensor: theoretical and experimental study

A novel, to our knowledge, method for the measurement of angular displacement for arbitrarily shaped objects is presented in which the angular displacement is perpendicular to the optical axis. The method is based on Fourier-transforming the scattered field from a single laser beam that illuminates the target. The angular distribution of the light field at the target is linearly mapped on a linear image sensor placed in the Fourier plane. Measuring this displacement facilitates the determination of the angular displacement of the target. It is demonstrated both theoretically and experimentally that the angular-displacement sensor is insensitive to object shape and target distance if the linear image sensor is placed in the Fourier plane. A straightforward procedure for positioning the image sensor in the Fourier plane is presented. Any transverse or longitudinal movement of the target will give rise to partial speckle decorrelation, but it will not affect the angular measurement. Furthermore, any change in the illuminating wavelength will not affect the angular measurements. Theoretically and experimentally it is shown that the method has a resolution of 0.3 mdeg ( approximately 5 murad) for small angular displacements, and methods for further improvement in resolution is discussed. No special surface treatment is required for surfaces giving rise to fully developed speckle. The effect of partially developed speckle is considered both theoretically and experimentally.     

Minimizing the average cost of paging and registration: A timer-based method

Methods of balancing call registration and paging are developed in this paper. Given that the probability distribution on the user location as a function of time is either known or can be calculated, previous work shows the existence of lower bounds on the average cost of paging. Here these bounds are used in conjunction with a Poisson incoming-call arrival model to formulate the paging/registration optimization problem in terms oftimeout parameters, _m ; the maximum amount of time to wait before registering given the last known location wasm. Timer-based methods, as opposed to location-based methods, do not require the user to record and process location information during the time between location updates. This feature might be desirable for minimizing mobile transceiver use during idle periods. We then consider uniform motion processes where a spatial translation of starting location produces an identical spatial translation of the associated time-varying probability distribution. This leads to a universal timeout parameter which may be readily calculated. We study and the minimum cost of paging/registration for a simple model of user motion and compare our results to an earlier method of location-based paging/registration cost minimization.     

Development of categorical representations for above and below spatial relations in 3- to 7-month-old infants.

A series of experiments examined the abilities of infants to form categorical representations for the spatial relations above and below. Exp 1 provided evidence that 3–4 mo olds can form categorical representations for above and below when a diamond shape was presented above or below a horizontal bar. Exps 2 and 3 showed that 3- and 4-mo olds did not form categorical representations for above and below when a number of discriminably different shapes (e.g., a diamond, a triangle, a dot) appeared above or below the bar. These more abstract categorical representations for above and below were formed by 6- to 7-mo olds (Exp 4). The findings suggest an experientially or maturationally based trend, from concrete to abstract, in the categorical representation of common spatial relations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intelligent backtracking in CLP(ℜ)

CLP() is a constraint logic programming language in which constraints can be expressed in the domain of real numbers. Computation in this specialized domain gives access to information useful in intelligent backtracking. In this paper, we present an efficient constraint satisfaction algorithm for linear constraints in the real number domain and show that our algorithm directly generates minimal sets of conflicting constraints when failures occur. We demonstrate how information gleaned during constraint satisfaction can be integrated with unification failure analysis. The resulting intelligent backtracking method works in the context of a two-sorted domain, where variables can be bound to either structured terms or real number expressions. We discuss the implementation of backtracking and show examples where the benefit of pruning the search tree outweights the overhead of failure analysis.     

An annotated corpus for the analysis of VP ellipsis

Verb Phrase Ellipsis (VPE) has been studied in great depth in theoretical linguistics, but empirical studies of VPE are rare. We extend the few previous corpus studies with an annotated corpus of VPE in all 25 sections of the Wall Street Journal corpus (WSJ) distributed with the Penn Treebank. We annotated the raw files using a stand-off annotation scheme that codes the auxiliary verb triggering the elided verb phrase, the start and end of the antecedent, the syntactic type of antecedent (VP, TV, NP, PP or AP), and the type of syntactic pattern between the source and target clauses of the VPE and its antecedent. We found 487 instances of VPE (including predicative ellipsis, antecedent-contained deletion, comparative constructions, and pseudo-gapping) plus 67 cases of related phenomena such as do so anaphora. Inter-annotator agreement was high, with a 0.97 average F-score for three annotators for one section of the WSJ. Our annotation is theory neutral, and has better coverage than earlier efforts that relied on automatic methods, e.g. simply searching the parsed version of the Penn Treebank for empty VP’s achieves a high precision (0.95) but low recall (0.58) when compared with our manual annotation. The distribution of VPE source–target patterns deviates highly from the standard examples found in the theoretical linguistics literature on VPE, once more underlining the value of corpus studies. The resulting corpus will be useful for studying VPE phenomena as well as for evaluating natural language processing systems equipped with ellipsis resolution algorithms, and we propose evaluation measures for VPE detection and VPE antecedent selection. The stand-off annotation is freely available for research purposes.     

The impact of drywall handling tools on the low back

Carpenters and other construction workers who install drywall have high rates of strains and sprains to the low back and shoulder. Drywall is heavy and awkward to handle resulting in increased risk of injury. The purpose of this study was to evaluate several low-cost coupling tools that have the potential to reduce awkward postures in drywall installers. Five coupling tools were evaluated using the Lumbar Motion Monitor that measures trunk kinematics and predicts probability of low back disorder group membership risk (LBD risk). Workers answered surveys about their comfort while using each tool. The results indicate that use of the 2-person manual lift and the J-handle provide the best reduction in awkward postures, motions, low back sagittal moment, and LBD risk. The two-person manual lift appears to be the safest method of lifting and moving drywall, though using the two-person J-handle also significantly reduces injury risk. Given that carpenters are skeptical about using equipment that can get in the way or get lost, a practical recommendation is promotion of two-person manual lifting. For single-person lifts, the Old Man tool is a viable option to decrease risk of MSDs.     

A survey of problems,solution techniques,and future challenges in scheduling semiconductor manufacturing operations

In this paper, we discuss scheduling problems in semiconductor manufacturing. Starting from describing the manufacturing process, we identify typical scheduling problems found in semiconductor manufacturing systems. We describe batch scheduling problems, parallel machine scheduling problems, job shop scheduling problems, scheduling problems with auxiliary resources, multiple orders per job scheduling problems, and scheduling problems related to cluster tools. We also present important solution techniques that are used to solve these scheduling problems by means of specific examples, and report on known implementations. Finally, we summarize some of the challenges in scheduling semiconductor manufacturing operations.     

Sources and nature of secondary school teachers’ education in computer-related ergonomics

Teachers’ knowledge of computer-related ergonomics in education will have an effect on the learning process and the work practices of their students. However little is known about teacher education in this area. The study aimed to investigate the sources and nature of secondary school teachers’ education about computer-related ergonomics. It also investigated the use of computers by secondary school children. The study included all secondary schools in the Republic of Ireland. The findings suggest that computers are widely available and are used frequently by students and teachers. However, there is evidence that teachers are not receiving information on computer-related ergonomics. Teachers were generally dissatisfied with this and would welcome information on the subject. The study discusses the implications of the findings and makes recommendations to meet the needs of the teachers.     

ARMAX modelling of international tourism demand

Box–Jenkins (1970) models are often used to capture the autoregressive moving average of past observations of tourist arrivals from Japan to Taiwan and New Zealand. However, other explanatory variables, such as real income in the origin country, have also affected the demand for international travel. The purpose of this paper is to use the ARMAX model to investigate the dynamic relationship between tourism demand and real income of Japan, and to compare the findings with the single-equation model. Unit root tests and diagnostics are performed before estimating the income elasticity of travel demand by Japan for New Zealand and Taiwan based on seasonally unadjusted quarterly data for 1980(1) to 2004(2). The empirical results of the ARMAX model support the economic theory that the demand for international travel is positively related to income of the origin country.