Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Purα

JC virus is activated to replicate in glial cells of many AIDS patients with neurological disorders. In human glial cells, the human immunodeficiency virus 1 (HIV-1) Tat protein activates the major late promoter of JC virus through a Tat-responsive DNA element, termed upTAR, which is a recognition site for cellular Purα, a sequence-specific single-stranded DNA binding protein implicated in cell cycle control of DNA replication and transcription. Tat interacts with two leucine-rich repeats in Purα to form a complex that can be immunoprecipitated from cell extracts. Tat enhances the ability of purified glutathione S-transferase-Purα (GST-Purα) to bind the upTAR element. Tat acts synergistically with Purα, in a cell-cycle-dependent manner, to activate transcription at an upTAR element placed upstream of a heterologous promoter. Since Purα is ubiquitously expressed in human cells and since PUR elements are located near many promoters and origins of replication, the Tat-Purα interaction may be implicated in effects of HIV-1 throughout the full range of HIV-1-infected cells.

Effect of deletion of 5'HS3 or 5'HS2 of the human beta-globin locus control region on the developmental regulation of globin gene expression in beta-globin locus yeast artificial chromosome transgenic mice.

To analyze the function of the 5' DNase I hypersensitive sites (HSs) of the locus control region (LCR) on beta-like globin gene expression, a 2.3-kb deletion of 5'HS3 or a 1.9-kb deletion of 5'HS2 was recombined into a beta-globin locus yeast artificial chromosome, and transgenic mice were produced. Deletion of 5'HS3 resulted in a significant decrease of epsilon-globin gene expression and an increase of gamma-globin gene expression in embryonic cells. Deletion of 5'HS2 resulted in only a small decrease in expression of epsilon-, gamma-, and beta-globin mRNA at all stages of development. Neither deletion affected the temporal pattern of globin gene switching. These results suggest that the LCR contains functionally redundant elements and that LCR complex formation does not require the presence of all DNase I hypersensitive sites. The phenotype of the 5'HS3 deletion suggests that individual HSs may influence the interaction of the LCR with specific globin gene promoters during the course of ontogeny.

Nonlinear control of heart rate variability in human infants.

Nonlinear analyses of infant heart rhythms reveal a marked rise in the complexity of the electrocardiogram with maturation. We find that normal mature infants (gestation greater than or equal to 35 weeks) have complex and distinctly nonlinear heart rhythms (consistent with recent reports for healthy adults) but that such nonlinearity is lacking in preterm infants (gestation > or = to 27 weeks) where parasympathetic-sympathetic interaction and function are presumed to be less well developed. Our study further shows that infants with clinical brain death and those treated with atropine exhibit a similar lack of nonlinear feedback control. These three lines of evidence support the hypothesis championed by Goldberger et al. [Goldberger, A.L., Rigney, D.R. & West, B.J. (1990) Sci. Am. 262, 43-49] that autonomic nervous system control underlies the nonlinearity and possible chaos of normal heart rhythms. This report demonstrates the acquisition of nonlinear heart rate dynamics and possible chaos in developing human infants and its loss in brain death and with the administration of atropine. It parallels earlier work documenting changes in the variability of heart rhythms in each of these cases and suggests that nonlinearity may provide additional power in characterizing physiological states.

A human RNase E-like activity that cleaves RNA sequences involved in mRNA stability control.

We have detected an endoribonucleolytic activity in human cell extracts that processes the Escherichia coli 9S RNA and outer membrane protein A (ompA) mRNA with the same specificity as RNase E from E. coli. The human enzyme was partially purified by ion-exchange chromatography, and the active fractions contained a protein that was detected with antibodies shown to recognize E. coli RNase E. RNA containing four repeats of the destabilizing motif AUUUA and RNA from the 3' untranslated region of human c-myc mRNA were also found to be cleaved by E. coli RNase E and its human counterpart in a fashion that may suggest a role of this activity in mammalian mRNA decay. It was also found that RNA containing more than one AUUUA motif was cleaved more efficiently than RNA with only one or a mutated motif. This finding of a eukaryotic endoribonucleolytic activity corresponding to RNase E indicates an evolutionary conservation of the components of mRNA degradation systems.

System for robot control inspired by the functionality and organisation of the human nervous system

This paper presents a model of a control system for robot systems inspired by the functionality and organisation of human neuroregulatory system. Our model was specified using software agents within a formal framework and implemented through Web Services. This approach allows the implementation of the control logic of a robot system with relative ease, in an incremental way, using the addition of new control centres to the system as its behaviour is observed or needs to be detailed with greater precision, without the need to modify existing functionality. The tests performed verify that the proposed model has the general characteristics of biological systems together with the desirable features of software, such as robustness, flexibility, reuse and decoupling.

Decomposition of human behavior using model of competencies: application to robotic control system

For many years, humans and machines have shared the same physical space. To facilitate their interaction with humans, their social integration and for more rational behavior has been sought that the robots demonstrate human-like behavior. For this it is necessary to understand how human behavior is generated, discuss what tasks are performed and how relate to themselves, for subsequent implementation in robots. In this paper, we propose a model of competencies based on human neuroregulator system for analysis and decomposition of behavior into functional modules. Using this model allow separate and locate the tasks to be implemented in a robot that displays human-like behavior. As an example, we show the application of model to the autonomous movement behavior on unfamiliar environments and its implementation in various simulated and real robots with different physical configurations and physical devices of different nature. The main result of this work has been to build a model of competencies that is being used to build robotic systems capable of displaying behaviors similar to humans and consider the specific characteristics of robots.

Model of Competencies for Decomposition of Human Behavior: Application to Control System of Robots

Humans and machines have shared the same physical space for many years. To share the same space, we want the robots to behave like human beings. This will facilitate their social integration, their interaction with humans and create an intelligent behavior. To achieve this goal, we need to understand how human behavior is generated, analyze tasks running our nerves and how they relate to them. Then and only then can we implement these mechanisms in robotic beings. In this study, we propose a model of competencies based on human neuroregulator system for analysis and decomposition of behavior into functional modules. Using this model allow separate and locate the tasks to be implemented in a robot that displays human-like behavior. As an example, we show the application of model to the autonomous movement behavior on unfamiliar environments and its implementation in various simulated and real robots with different physical configurations and physical devices of different nature. The main result of this study has been to build a model of competencies that is being used to build robotic systems capable of displaying behaviors similar to humans and consider the specific characteristics of robots.

President's Private Sector Survey on Cost Control : report on Department of Health and Human Services, Public Health Service/Health Care Financing Administration.

Mode of access: Internet.

Human factors aspects of the transfer of control from the automated highway system to the driver /

"July 1995."

Medicaid prescription drug diversion : a major problem, but state approaches offer some promise : statement of Janet L. Shikles, Director, Health Financing and Policy Issues, Human Resources Division, before the Select Committee on Narcotics Abuse and Control, House of Representatives /

"July 29, 1992."

Postural and respiratory activation of the trunk muscles changes with mode and speed of locomotion

Despite the importance of the deep intrinsic spinal muscles for trunk control, few studies have investigated their activity during human locomotion or how this may change with speed and mode of locomotion. Furthermore, it has not been determined whether the postural and respiratory functions, of which these muscles take part, can be coordinated when locomotor demands are increased. EMG recordings of abdominal and paraspinal muscles were made in seven healthy subjects using fine-wire and surface electrodes. Measurements were also made of respiration and gait parameters. Recordings were made for 10s as subjects walked on a treadmill at 1 and 2 ms(-1) and ran at 2, 3, 4 and 5 ms(-1). Unlike the superficial muscles, transversus abdominis was active tonically throughout the gait cycle with all tasks, except running at speeds of 3 ms(-1) and greater. All other muscles were recruited in a phasic manner. The relative duration of these bursts of activity was influenced by speed and/or mode of locomotion. Activity of all abdominal muscles, except rectus abdominis (RA), was modulated both for respiration and locomotor-related functions but this activity was affected by the speed and mode of locomotion. This study provides evidence that the deep abdominal muscles are controlled independently of the other trunk muscles. Furthermore, the pattern of recruitment of the trunk muscles and their respiratory and postural coordination is dependent on the speed and mode of locomotion. (C) 2003 Published by Elsevier B.V.

Deceleration affects anticipatory and reactive components of triggered postural responses

Understanding the physiological and psychological factors that contribute to healthy and pathological balance control in man has been made difficult by the confounding effects of the perturbations used to test balance reactions. The present study examined how postural responses were influenced by the acceleration-deceleration interval of an unexpected horizontal translation. Twelve adult males maintained balance during unexpected forward and backward surface translations with two different acceleration-deceleration intervals and presentation orders (serial or random). SHORT perturbations consisted of an initial acceleration (peak acceleration 1.3 m s(-2); duration 300 ms) followed 100 ms later by a deceleration. LONG perturbations had the same acceleration as SHORT perturbations, followed by a 2-s interval of constant velocity before deceleration. Surface and intra-muscular electromyography (EMG) from the leg, trunk, and shoulder muscles were recorded along with motion and force plate data. LONG perturbations induced larger trunk displacements compared to SHORT perturbations when presented randomly and larger EMG responses in proximal and distal muscles during later (500-800 ms) response intervals. During SHORT perturbations, activity in some antagonist muscles was found to be associated with deceleration and not the initial acceleration of the support surface. When predictable, SHORT perturbations facilitated the use of anticipatory mechanisms to attenuate early (100-400 ms) EMG response amplitudes, ankle torque change and trunk displacement. In contrast, LONG perturbations, without an early deceleration effect, did not facilitate anticipatory changes when presented in a predictable order. Therefore, perturbations with a short acceleration-deceleration interval can influence triggered postural responses through reactive effects and, when predictable with repeated exposure, through anticipatory mechanisms.

Interocular suppression and contrast gain control in human vision

The human visual system combines contrast information from the two eyes to produce a single cyclopean representation of the external world. This task requires both summation of congruent images and inhibition of incongruent images across the eyes. These processes were explored psychophysically using narrowband sinusoidal grating stimuli. Initial experiments focussed on binocular interactions within a single detecting mechanism, using contrast discrimination and contrast matching tasks. Consistent with previous findings, dichoptic presentation produced greater masking than monocular or binocular presentation. Four computational models were compared, two of which performed well on all data sets. Suppression between mechanisms was then investigated, using orthogonal and oblique stimuli. Two distinct suppressive pathways were identified, corresponding to monocular and dichoptic presentation. Both pathways impact prior to binocular summation of signals, and differ in their strengths, tuning, and response to adaptation, consistent with recent single-cell findings in cat. Strikingly, the magnitude of dichoptic masking was found to be spatiotemporally scale invariant, whereas monocular masking was dependent on stimulus speed. Interocular suppression was further explored using a novel manipulation, whereby stimuli were presented in dichoptic antiphase. Consistent with the predictions of a computational model, this produced weaker masking than in-phase presentation. This allowed the bandwidths of suppression to be measured without the complicating factor of additive combination of mask and test. Finally, contrast vision in strabismic amblyopia was investigated. Although amblyopes are generally believed to have impaired binocular vision, binocular summation was shown to be intact when stimuli were normalized for interocular sensitivity differences. An alternative account of amblyopia was developed, in which signals in the affected eye are subject to attenuation and additive noise prior to binocular combination.

Suppression and summation in contrast gain control for human vision

Over the last ten years our understanding of early spatial vision has improved enormously. The long-standing model of probability summation amongst multiple independent mechanisms with static output nonlinearities responsible for masking is obsolete. It has been replaced by a much more complex network of additive, suppressive, and facilitatory interactions and nonlinearities across eyes, area, spatial frequency, and orientation that extend well beyond the classical recep-tive field (CRF). A review of a substantial body of psychophysical work performed by ourselves (20 papers), and others, leads us to the following tentative account of the processing path for signal contrast. The first suppression stage is monocular, isotropic, non-adaptable, accelerates with RMS contrast, most potent for low spatial and high temporal frequencies, and extends slightly beyond the CRF. Second and third stages of suppression are difficult to disentangle but are possibly pre- and post-binocular summation, and involve components that are scale invariant, isotropic, anisotropic, chromatic, achromatic, adaptable, interocular, substantially larger than the CRF, and saturated by contrast. The monocular excitatory pathways begin with half-wave rectification, followed by a preliminary stage of half-binocular summation, a square-law transducer, full binocular summation, pooling over phase, cross-mechanism facilitatory interactions, additive noise, linear summation over area, and a slightly uncertain decision-maker. The purpose of each of these interactions is far from clear, but the system benefits from area and binocular summation of weak contrast signals as well as area and ocularity invariances above threshold (a herd of zebras doesn't change its contrast when it increases in number or when you close one eye). One of many remaining challenges is to determine the stage or stages of spatial tuning in the excitatory pathway.

Optic flow in human vision: MEG reveals a foveo-fugal bias in V1, specialization for spiral space in hMSTs, and global motion sensitivity in the IPS

Abstract We recorded MEG responses from 17 participants viewing random-dot patterns simulating global optic flow components (expansion, contraction, rotation, deformation, and translation) and a random motion control condition. Theta-band (3–7 Hz), MEG signal power was greater for expansion than the other optic flow components in a region concentrated along the calcarine sulcus, indicating an ecologically valid, foveo-fugal bias for unidirectional motion sensors in V1. When the responses to the optic flow components were combined, a decrease in MEG beta-band (17–23 Hz) power was found in regions extending beyond the calcarine sulcus to the posterior parietal lobe (inferior to IPS), indicating the importance of structured motion in this region. However, only one cortical area, within or near the V5/hMT+ complex, responded to all three spiral-space components (expansion, contraction, and rotation) and showed no selectivity for global translation or deformation: we term this area hMSTs. This is the first demonstration of an exclusive region for spiral space in the human brain and suggests a functional role better suited to preliminary analysis of ego-motion than surface pose, which would involve deformation. We also observed that the rotation condition activated the cerebellum, suggesting its involvement in visually mediated control of postural adjustment.