Active oculography as a method of diagnosing the psychophysiologic condition of a man

The effect of stress factors on the oculomotor reactions of electric train drivers with various degrees of fatigue was studied in a modelled accidental situation. The spatio-temporal parameters of oculomotor reactions were shown to characterize not always correctly the state of a driver. More informative were found to be the values of asymmetry of saccades obtained by separate recordings of the right and left eye movements. A comparison between the character of the phase saccade disturbances of tired operators and that of patients with a deficiency in cerebral blood supply showed that the latter may be used as a model.     

Discrimination strategies of humans and rhesus monkeys for complex visual displays

By learning to discriminate among visual stimuli, human observers can become experts at specific visual tasks. The same is true for Rhesus monkeys, the major animal model of human visual perception. Here, we systematically compare how humans and monkeys solve a simple visual task. We trained humans and monkeys to discriminate between the members of small natural-image sets. We employed the "Bubbles" procedure to determine the stimulus features used by the observers. On average, monkeys used image features drawn from a diagnostic region covering about 7% +/- 2% of the images. Humans were able to use image features drawn from a much larger diagnostic region covering on average 51% +/- 4% of the images. Similarly for the two species, however, about 2% of the image needed to be visible within the diagnostic region on any individual trial for correct performance. We characterize the low-level image properties of the diagnostic regions and discuss individual differences among the monkeys. Our results reveal that monkeys base their behavior on confined image patches and essentially ignore a large fraction of the visual input, whereas humans are able to gather visual information with greater flexibility from large image regions.     

The use of hierarchic classification in the image analysis of a complex cell population. Experience with the sediment of voided urine

Microscopic analysis of cells in the sediment of voided urine is the principal noninvasive method of diagnosing and detecting cancer of the lower urinary tract, mainly the bladder. The sediments contain several populations of cells of unequal diagnostic value. By applying a system of hierarchic classification to the computer analysis of digitized cell images, we were able to eliminate from diagnostic consideration cells that are difficult to classify, such as degenerated cells, multinucleated cells, cell clusters, renal tubular cells and cells infected by the human polyomavirus. When this method of triage was applied to the images of sequentially encountered epithelial cells and clusters, the cell images accepted for final analysis by the computer were sufficient in number and quality to automatically construct cytologic profiles of documented diagnostic value in 15 patients with bladder cancer. The method proved to be applicable to smears and quantitative cytocentrifuge preparations processed by methods developed in our laboratory. This work clearly documents the feasibility of automated analysis of cells in voided urine for the purpose of diagnosing bladder cancer. It also confirms prior observations suggesting that a relatively small sample of sequential images of epithelial cells (200 to 300) is sufficient to establish a diagnostic profile of clinical value on patients with high-grade cancer of the urinary bladder.     

Genomic data reveal a complex making of humans

In the last few years, two paradigms underlying human evolution have crumbled. Modern humans have not totally replaced previous hominins without any admixture, and the expected signatures of adaptations to new environments are surprisingly lacking at the genomic level. Here we review current evidence about archaic admixture and lack of strong selective sweeps in humans. We underline the need to properly model differential admixture in various populations to correctly reconstruct past demography. We also stress the importance of taking into account the spatial dimension of human evolution, which proceeded by a series of range expansions that could have promoted both the introgression of archaic genes and background selection.     

Experience in the operation of an x-ray diagnostic complex with a remote-controlled stand

Functional potentialities of serial stands of the RUM-20 radiodiagnostic units were critically analyzed. The clinical use of remote-controlled stands of Rentgen-100T type was shown to hold promise.     

Solid state 15N NMR evidence for a complex Schiff base counterion in the visual G-protein-coupled receptor rhodopsin.

Using the baculovirus/Sf9 cell expression system, we have incorporated 99% 15N-enriched [alpha,epsilon-15N2]-L-lysine into the rod visual pigment rhodopsin. We have subsequently investigated the protonated Schiff base (pSB) linkage in the [alpha, epsilon-15N2]Lys-rhodopsin with cross-polarization magic angle spinning (CP/MAS) 15N NMR. The Schiff base (SB) 15N in [alpha, epsilon-15N2]Lys-rhodopsin resonates with an isotropic shift sigmaI of 155.9 ppm, relative to 5.6 M 15NH4Cl. This suggests that the SB in rhodopsin is protonated and stabilized by a complex counterion. The 15N shifts of retinal SBs correlate with the energy difference between the ground and excited states and the frequency of maximum visible absorbance, numax, associated with the pi-pi transition of the polyene chromophore. Experimental modeling of the relation between the numax and the size of the counterion with a set of pSBs provides strong evidence that the charged chromophore in rhodopsin is stabilized by a counterion with an estimated effective center-center distance (deff) between the counterion and the pSB of 0.43 +/- 0.01 nm. While selected prokaryotic proteins and complexes have been labeled before, this is the first time to our knowledge that a 15N-labeled eukaryotic membrane protein has been generated in sufficient amount for such NMR investigations.     

An extensometer for global measurement of bone strain suitable for use in vivo in humans

An axial extensometer able to measure global bone strain magnitudes and rates encountered during physiological activity, and suitable for use in vivo in human subjects, is described. The extensometer uses paired capacitive sensors mounted to intraosseus pins and allows measurement of strain due to bending in the plane of the extensometer as well as uniaxial compression or tension. Data are presented for validation of the device against a surface-mounted strain gage in an acrylic specimen under dynamic four-point bending, with square wave and sinusoidal loading inputs up to 1500 mu epsilon and 20 Hz, representative of physiological strain magnitudes and frequencies. Pearson's correlation coefficient (r) between extensometer and strain gage ranged from 0.960 to 0.999. Mean differences between extensometer and strain gage ranged up to 15.3 mu epsilon. Errors in the extensometer output were directly proportional to the degree of bending that occurs in the specimen, however, these errors were predictable and less than 1 mu epsilon for the loading regime studied. The device is capable of tracking strain rates in excess of 90,000 mu epsilon/s.     

Aging-related changes of EEG synchronization during a visual working memory task

Differences of EEG synchronization between normal old and young people during a working memory (WM) task were investigated. The synchronization likelihood (SL) is a novel method to assessed synchronization in multivariate time series for non-stationary systems. To evaluate this method to study the mechanisms of WM, we calculated the SL values in brain electrical activity for both resting state and task state. EEG signals were recorded from 14 young adults and 12 old adults during two different states, respectively. SL was used to measure EEG synchronization between 19 electrodes in delta, theta, alpha1, alpha2 and beta frequency bands. Bad task performance and significantly decreased EEG synchronization were found in old group compared to young group in alpha1, alpha2 and beta frequency bands during the WM task. Moreover, significantly decreased EEG synchronization in beta band in the elder was also detected during the resting state. The findings suggested that reduced EEG synchronization may be one of causes for WM capacity decline along with healthy aging.     

A novel spectroscopic titration method for determining the dissociation constant and stoichiometry of protein-ligand complex.

We offer a new titration protocol for determining the dissociation constant and binding stoichiometry of protein-ligand complex, detectable by spectroscopic methods. This approach neither is limited to the range of protein or ligand concentrations employed during titration experiment nor relies on precise determinations of the titration "endpoint," i.e., the maximal signal changes upon saturation of protein by ligand (or vice versa). In this procedure, a fixed concentration of protein (or ligand) is titrated by increasing volumes of a stock ligand (or protein) solution, and the changes in the spectroscopic signal are recorded after each addition of the titrant. The signal for interaction between protein and ligand first increases, reaches a maximum value, and then starts decreasing due to dilution effect. The volume of the titrant required to achieve the maximum signal changes is utilized to calculate the dissociation constant and the binding stoichiometry of the protein-ligand complex according to the theoretical relationships developed herein. This procedure has been tested for the interaction of avidin with a chromophoric biotin analogue, 2-(4'-hydroxyazobenzene)benzoic acid by following the absorption signal of their interaction at 500 nm. The widespread applicability of this procedure to protein-ligand complexes detected by other spectroscopic techniques and its advantages over conventional methods are discussed.     

Selective visual processing across competition episodes: a theory of task-driven visual attention and working memory

The goal of this review is to introduce a theory of task-driven visual attention and working memory (TRAM). Based on a specific biased competition model, the ‘theory of visual attention’ (TVA) and its neural interpretation (NTVA), TRAM introduces the following assumption. First, selective visual processing over time is structured in competition episodes. Within an episode, that is, during its first two phases, a limited number of proto-objects are competitively encoded—modulated by the current task—in activation-based visual working memory (VWM). In processing phase 3, relevant VWM objects are transferred via a short-term consolidation into passive VWM. Second, each time attentional priorities change (e.g. after an eye movement), a new competition episode is initiated. Third, if a phase 3 VWM process (e.g. short-term consolidation) is not finished, whereas a new episode is called, a protective maintenance process allows its completion. After a VWM object change, its protective maintenance process is followed by an encapsulation of the VWM object causing attentional resource costs in trailing competition episodes. Viewed from this perspective, a new explanation of key findings of the attentional blink will be offered. Finally, a new suggestion will be made as to how VWM items might interact with visual search processes.     

Comparative simulations of the ground state and the M-intermediate state of the sensory rhodopsin II-transducer complex with a HAMP domain model

The complex of sensory rhodopsin II (SRII) and its cognate transducer HtrII (2:2 SRII-HtrII complex) consists of a photoreceptor and its signal transducer, respectively, associated with negative phototaxis in extreme halophiles. In this study to investigate how photoexcitation in SRII affects the structures of the complex, we conducted two series of molecular dynamics simulations of the complex of SRII and truncated HtrII (residues 1-136) of Natronomonas pharaonis linked with a modeled HAMP domain in the lipid bilayer using the two crystal structures of the ground state and the M-intermediate state as the starting structures. The simulation results showed significant enhancements of the structural differences observed between the two crystal structures. Helix F of SRII showed an outward motion, and the C-terminal end of transmembrane domain 2 (TM2) in HtrII rotated by ～10°. The most significant structural changes were observed in the overall orientations of the two SRII molecules, closed in the ground state and open in the M-state. This change was attributed to substantial differences in the structure of the four-helix bundle of the HtrII dimer causing the apparent rotation of TM2. These simulation results established the structural basis for the various experimental observations explaining the structural differences between the ground state and the M-intermediate state.     

Three-dimensional structure of the barley beta-D-glucan glucohydrolase in complex with a transition state mimic

Glucophenylimidazole (PheGlcIm), a tetrahydroimidazopyridine-type inhibitor and 4H3 conformer mimic of a glucoside, binds very tightly to a barley beta-d-glucan glucohydrolase, with a Ki constant of 2 x 10(-9) m and a DeltaG of 51 kJ mol(-1). PheGlcIm binds to the barley beta-d-glucan glucohydrolase approximately 2 x 10(5) times tighter than laminarin, which is the best non-synthetic ground-state substrate found so far for this enzyme, 10(6) times tighter than 4-nitrophenyl beta-d-glucopyranoside, and 2 x 10(7) tighter than glucose. The three-dimensional structure of the beta-d-glucan glucohydrolase with bound PheGlcIm indicates that the complex resembles a hypothetical transition state during the hydrolytic cycle, that the enzyme derives substrate binding energy from the "aglycone" portion of the ligand, and that it also reveals an anti-protonation trajectory for hydrolysis. Continuous electron densities at the 1.6 sigma level form between the three active site residues Asp95, His207, and Asp285, and the C6OH, C7OH, C8OH, and C9OH groups of PheGlcIm. These electron densities correspond to the most favorable interactions in the three-dimensional structure of the beta-d-glucan glucohydrolase-PheGlcIm complex and indicate atomic distances equal to or less than 2.55 A. The crystallographic data were corroborated with ab initio molecular orbital calculations. The data indicate that the 4E conformation of the glucose part of PheGlcIm is critical for tight binding and provide the first evidence for probable substrate distortion during catalysis by this enzyme.