A simulated reality scenario compared with the computerized Wisconsin card sorting test: an analysis of preliminary results.

Neuropsychologists and other clinicians often comment on the minimal relationship that frequently exists between formal assessments of executive functions, analysis of findings, recommendations, and the person's real-life functioning. The authors' believe that current assessments of executive functions do not transfer easily to real-world behavior. There are limitations in the current examinations and in the settings in which they are given. The tests are artificial and the test settings lack the usual stresses, distractions, and multiple demands common to real life. The interactions are unlike what they experience in everyday life. The examiner often, but unintentionally orients the participant to relevant information that in turn can help the person compensate for the difficulties with executive control processes and bias the findings. We believe that virtual reality (VR) more closely approximates real life settings, the distractions, and the common interchanges (VR) provides a "life-like," three-dimensional (3-D) highly interactive environment, and safety from potential dangers that could arise in actual situations. VR can increase motivation because of its gaming, interactive, and immersive qualities and features are easily modified and allow for multiple applications. Our goal is to develop VR assessments that can be administered under controlled and safe conditions, but which are more sensitive to difficulties with executive control processes critical to safe, independent living. This initial study compares several functions assessed by the Wisconsin Card Sorting Test (WCST) with our three-dimensional, stereographic scenario, Look for a Match (LFAM) Study participants completed questionnaires, alternately began with either the WCST or LFAM, and then took the second test. All participants completed motion sickness and follow-up questionnaires. The results demonstrated that the study participants found LFAM to be more enjoyable and interesting, but found the WCST to be easier. While there is an effect of order with participants doing relatively better on the assessment tool administered second, overall the LFAM performance was inferior to that on the WCST. However, even considering the order effect, LFAM seemed to be more difficult than the WCST.

Detection of DNA hybridization using the TISPR-1 surface plasmon resonance biosensor.

Biotinylated oligonucleotide probes were immobilized to the gold sensor surface of the TISPR-1 miniature integrated surface plasmon resonance liquid sensor system for the purpose of detecting specific DNA hybridization. The immobilization of the oligonucleotide capture probes was carried out through streptavidin-biotin binding technology. The sensor detected the immobilization of unlabeled DNA through shifts in index of refraction as the molecules entered and remained selectively bound to the surface in the vicinity of the exponentially decaying surface plasmon resonance wave. The surface immobilization chemistry was proven to be stable for long periods of time, reproducible, and practical for detecting DNA hybridization with the TISPR-1. DNA hybridization was detected as a slow, positive, and small (when compared to protein-protein or antibody-antigen binding experiments) increase in the measured index of refraction under passive hybridization conditions by the TISPR-1 sensor. The DNA hybridization signal was significant (index of refraction change of 0.001) when large fragment PCR-amplified DNA products were hybridized to the oligonucleotide probes (S/N = 6-10). The DNA hybridization techniques were demonstrated using DNA sequences from the HIV genome which encode the Tat and Rev genes.

Construction of biosensors using a gold-binding polypeptide and a miniature integrated surface plasmon resonance sensor.

Surface plasmon resonance (SPR) biosensors were constructed on miniature integrated sensors. Recognition elements were attached to the sensor surface using a gold-binding repeating polypeptide. Biosensors with fluorescyl groups attached to their surfaces were functional for at least 1 month of daily use with little decrease in response to the binding of an anti-fluorescyl monoclonal antibody. The coupling of protein A to the gold-binding polypeptide on the sensor surface enabled the biosensor to detect the binding of antibodies to the protein A and provided a sensor with convertible specificity. The system described herein provides a simple and rapid approach for the fabrication of highly specific, durable, portable and low cost SPR-based biosensors.

Computer-based compensation of adult reading disabilities.

We studied the use of computer readers, and especially their speech synthesis component, as a compensatory tool for adults with dyslexia. We first explored the enhancement of reading skills in a group of college students and working adults. Their unaided reading was very slow, and most participants in the study could sustain reading for only short periods. Although their timed comprehension was poor, their untimed comprehension was above average. The computer reader enhanced the reading rate and comprehension of most participants and enabled them to sustain reading longer. The difference between aided and unaided reading rate was inversely proportional to the unaided rate. Slower readers experienced greater enhancement than faster ones. The enhancement of comprehension was also inversely proportional to unaided scores, and good predictions of the enhancement were obtained from multiple regression models that included scores from specific standard tests of auditory and visual cognitive abilities. We also explored the use of computer readers in the workplace and show through case studies that their use can have important positive effects on individual careers and self-confidence when specific conditions exist. Finally, we investigated the use of computer readers to supplement an adult remediation program. The readers allowed and motivated the students to read more and, as a result, to progress more rapidly.

Using computer-based readers to improve reading comprehension of students with dyslexia.

Twenty-eight middle school students, diagnosed as dyslexic and attending a school using the Slingerland approach to remediation of dyslexia, used a computer-based reading system for reading literature for about one-half hour a day for a semester. The system proved to be a strong compensatory aid, enabling 70 percent of the students to read with greater comprehension, approximately one grade level or more improvement, as measured by the Gray Oral Reading Test. For 40 percent of the students, the gains were large, from two to as much as five grade levels. However, not all students benefited. Fourteen percent showed lower comprehension scores when using the system, and there is some indication that this degradation is associated with kinesthetic-motor weakness. Some students reported gains in reading speed and exhibited increased span of attention for and endurance in reading when using the system. We did not find evidence that the computer-reader technology provided a positive remediation benefit incremental to that obtained from the school's intensive Slingerland remediation program. Our results indicate that computer-readers are important compensatory aids that can enable many people with dyslexia to perform more effectively in reading-related tasks associated with school and work.

The incidence of disabilities in the United States.

Data from the Census Bureau and other sources are reviewed, reconciled, and extrapolated to 1990 to provide a consistent view of the incidence of disabilities in the United States. Four major categories of disabilities are considered: sensory, motor, cognitive, and illiteracy. About a third of the population is affected to some extent by handicaps of these types. Severe impairments from sensory, motor, and cognitive disabilities affect about 15% of the population; severely limited literacy affects another 7%. With the number of disabled people so large and the human and economic impact so great, considerable national attention has been focused on the problem of increasing employment of the disabled. The human factors community can and should make a major contribution to this effort.

Effects of charge, volume, and surface on binding of inhibitor and substrate moieties to acetylcholinesterase.

Reversible inhibitors for acetylcholinesterase, AcChE, have been studied. Sterically similar alcohols with tetra-substituted uncharged beta groups, (CH3)3SiCH2CH2OH (I), (CH3)3CCH2CH2OH (IA), and CH3S(O2)CH2CH2OH (VII), bind similarly, KI = 3-9 mM, and each binds similarly to its acetate substrate; cationic analogues, (CH3)3N+CH2CH2OH (IB) and (CH3)2S+CH2CH2OH (II), bind similarly to each other, KI = 0.4 mM, similar to Km values of their acetate substrates, and more strongly than the uncharged alcohols by approximately 1.5 kcal/mol. In comparisons of VII with CH3SO2CH3, II with (CH3)3S+, and IB with (CH3)4N+, hydroxyethyl leads to more favorable binding than methyl by approximately 0.8 kcal/mol, despite lower hydrophobicity. Two hydrophobic methyl groups, in comparison of IA with butanol, and two hydrophilic sulfone O atoms, in comparison of VII with 2-(methylthio)ethanol, increase binding similarly, by 1.0 kcal/mol. Conversion of (CH3)3S+ to (CH3)3S+O also improves binding. However, (CH3)3N+O- does not bind to AcChE, and conversion of 1-(dimethylammonio)-4-pentanone and 2-(dimethylammonio)ethyl acetate to their N-oxides, changes of identical to N+H to identical to N+--O-, decreases binding by 1.5 kcal/mol. Although the -COCH3 group in esters with well-binding beta substituents makes essentially no contribution to binding over that of the alcohols, in esters with weakly bound beta substituents, (CH3)2N+(O-), CH3N+H2, CH3S(O), CH3CH2, and CH3S binding is dominated by the ester -COCH3 group, with values of Km approximately 16 mM.

Effects of volume and surface property in hydrolysis by acetylcholinesterase. The trimethyl site.

beta-Substituted ethyl acetates, XCH2CH2OCOCH3, have been prepared, and their hydrolysis by acetylcholinesterase has been studied. Log of enzymic reactivity, normalized for intrinsic reactivity in hydrolysis by hydroxide, log (kcat/Km)n, rises linearly with increasing refraction volume, MR (or RD25), for substrates with beta-X = H, Cl, Br, CH3CH2, (CH3)2CH, (CH3)2S+, (CH3)3N+, and (CH3)3C. Larger substituents may be accommodated, (CH3)3Si and (CH3CH2)3N+, with no further increase in rate. Substrates with beta-substituents CH3S, CH3S(O), (CH3)3N+(OH), and CH3S(O2) are less reactive than consistent with the relation with MR by factors of 5-40, indicating that hydrophobic surface and desolvation of the substrate--enzyme interface may be necessary for maximum reactivity correlated with MR. Values of log (kcat/Km)n for substrates with beta-substituents X = CH3S, Cl, Br, CH3CH2, (CH3)2CH, (CH3)3C, and (CH3)3Si rise linearly with increasing hydrophobicity, pi, but reactivity of substrates with X = (CH3)3N+ and (CH3)2S+ are more reactive than consistent with a relation to pi by factors of 300 and 40 and with X = CH3S(O2), CH3S(O), and (CH3)2N+(OH), by factors of 7-100. Reactivity appears related to (i) volume of the beta-substituent and its fit in its subsite, which is trimethyl rather than anionic, and (ii) the hydrophobicity of its surface.

Cationic and uncharged substrates and reversible inhibitors in hydrolysis by acetylcholinesterase (EC 3.1.1.7). The trimethyl subsite.

Structurally related cationic and uncharged compounds have been studied as inhibitors of hydrolysis by acetylcholinesterase of acetylcholine and its uncharged carbon analog, 3,3-dimethylbutyl acetate. Similar effects of the inhibitors on hydrolysis of the two substrates indicate that the quaternary ammonium group of acetylcholine and the neopentyl group of 3,3-dimethylbutyl acetate bind at the same subsite. Comparison of (CH3)3+NCH2CH2CH2COCH3 (Compound I), Ki = 0.02 mM, and its tertiary homologue, (CH3)2-+NHCH2CH2CH2COCH3 (Compound V), Ki = 0.75 mM, with a secondary isomer of Compound I, 3-oxo-(N-tert-butyl)-butanaminium, (CH3)3C+NH2CH2CH2COCH3 (Compound II), Ki = 0.15 mM, and its lower homologue, (CH3)2CH+NH2CH2CH2COCH3 (Compound IX), Ki = 2 mM, attests to the importance of the branched trimethyl structure and the smaller effect of hydrophobicity of the quaternary ammonium structure. This is supported by competitive inhibition by tert-butyl ammonium, (CH3)3C+NH3 (Compound IV), Ki = 0.45 mM, compared with mixed inhibition by its quarternary isomer, (CH3)4+N (Compound VII), Ki = 1.5 mM, and choline (Compound VI), Ki = 1.0 mM. Uncharged analogues of Compound II, 4-tert-butylthio-2-butanone, (CH3)3CSCH2CH2COCH3 (Compound III), Ki = 0.4 mM, and 4-tert-butoxy-2-butanone, (CH3)3COCH2CH2COCH3 (Compound VIII), Ki = 1.6 mM, and of Compound VI, 3,3-dimethylbutanol (Compound XI), Ki = 7.5 mM, indicate that positive charge contributes factors of 3 to 10 to binding. This may be attributed to peripheral negative charges, present at pH 7-8 in the enzyme of isoelectric point approximately 5, indicating that the binding subsite may be explored more specifically by tert-butyl than by charged reagents.