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An inexpensive and portable talking-tactile terminal for the visually handicapped.

The visually handicapped computer user or programmer is faced with a very difficult task in interfacing with computing hardware. The types of equipment currently available for this purpose fall into one of several general categories: expensive, nonportable, and domain-specific. In the current paper, we describe a new terminal device designed specifically for the visually handicapped that answers all of the problems mentioned above. The work is already under way, with a prototype model is currently in use by a visually handicapped programmer on the development team. In the remainder of this paper we will present a report on the current status of our project as well as plans and milestones for future work.

Algorithms↗

Carboxyl-terminal domain dimer interface mutant 434 repressors have altered dimerization and DNA binding specificities.

Strong dimerization of the repressor, mediated by the carboxyl (C)-terminal domain, is a prerequisite for forming a specific complex with DNA and cooperative DNA binding to form tetramers. We have generated a computer model of the C-terminal domain of the 434 repressor based on the crystal structure of the homologous UmuD' protein. This model predicts that residues in the primary sequence between 93 and 168 contribute to the dimer interface. We changed several amino acid residues located in this region. Gel filtration and crosslinking assays were used to characterize the strength and specificity of dimerization of the purified repressor C-terminal domain dimer interface mutants. These results indicate that amino acid residues K121, H139, D161 and N163 contribute to the strength and/or specificity of dimerization. The relative affinity of the bacteriophage 434 repressor for 434 operators is determined, in part, by the repressor's ability to detect sequence-dependent structural alterations in the non-contacted region at the center of an operator site. We find that the relative ability of C-terminal domain dimer interface mutant repressors to dimerize does not necessarily predict their relative abilities to bind DNA, and that these proteins are deficient in detecting non-contacted base-dependent differences in operator strength. Our results show that the structure of the DNA in complex with these mutant proteins differs from that found in wild-type repressor-operator complexes, even though the sites of these mutations lie in a separate domain from that which contacts the DNA. These observations demonstrate that the structural integrity of the C-terminal domain dimer interface is required to appropriately orient the DNA binding information contained within the DNA-contacting N-terminal domain.

Amino Acid Sequence↗

Development of optical process for accessing three-dimensional patient topology.

A commercial optical system developed by Solid Photography, Inc., has been used to generate precise paraffin--polyethylene tissue compensators. A program with the objective of constructing a medical facility has been undertaken to access patient topology for treatment planning, tissue-compensator fabrication, and patient positioning verification on the treatment table. Currently, patients are taken to a specially equipped studio where a series of microprocessor-controlled reticles are projected on the surface to be analyzed and photographs are taken automatically for computer processing. The topology data then drives a machine tool to sculpt the tissue compensators and may be transmitted via acoustic-coupled terminals to a treatment-planning computer at the Medical Center. The tissue compensators have been found to conform accurately to patient contours. At present, data bases can be generated to accommodate volumes of approximately 70,000 cm3.

Models, Structural↗

C-terminal nsP1a protein of human astrovirus colocalizes with the endoplasmic reticulum and viral RNA.

Computational and biological approaches were undertaken to characterize the role of the human astrovirus nonstructural protein nsP1a/4, located at the C-terminal fragment of nsP1a. Computer analysis reveals sequence similarities to other nonstructural viral proteins involved in RNA replication and/or transcription and allows the identification of a glutamine- and proline-rich region, the prediction of many phosphorylation and O-glycosylation sites, and the occurrence of a KKXX-like endoplasmic reticulum retention signal. Immunoprecipitation analysis with an antibody against a synthetic peptide of the nsP1a/4 sequence detected polyprotein precursors of 160, 75, and 38 to 40 kDa as well as five smaller proteins in the range of 21 to 27 kDa. Immunofluorescence labeling showed that the nsP1a/4 protein is accumulated at the perinuclear region, in association with the endoplasmic reticulum and the viral RNA. These results suggest the involvement of nsP1a/4 protein in the RNA replication process in endoplasmic reticulum-derived intracellular membranes.

Caco-2 Cells↗

NMR and computational evidence that high-affinity bradykinin receptor antagonists adopt C-terminal beta-turns.

Three tetrapeptides were prepared, each corresponding to the four C-terminal amino acid residues of highly potent, second-generation bradykinin receptor antagonists. The tetrapeptides are (IA) Ser-D-Phe-Oic-Arg, (IIA) Ser-D-Tic-Oic-Arg, and (IIIA) Ser-D-Hype(trans-propyl)-Oic-Arg. Solution conformations for each were determined by incorporating interproton distance restraints, determined by 2D NMR experiments performed in water at neutral pH, into a series of distance geometry/simulated annealing model building calculations. Similarly, systematic conformational analyses were performed for each using molecular mechanics calculations. Both the NMR-derived structures, as well as the calculated structures, are shown to adopt a beta-turn as the primary conformation. Excellent agreement between the predicted structures and the NMR-derived structures is demonstrated. Aside from being the first examples of linear tetrapeptides reported to be ordered in aqueous solvent, the results presented support the hypothesis that high-affinity bradykinin receptor antagonists must adopt C-terminal beta-turn conformations.

Amino Acid Sequence↗

[Polymicrobial sepsis and perityphlic abscess: case report and review of literature].

AIM: To evaluate the safety and efficacy of conservative therapy of polymicrobial anaerobic sepsis and appendiceal mass. CASE REPORT: We report on an 18-year-old patient admitted for fever (38.8 degrees C), abdominal pain and vomiting. Leukocytosis with left shift maturation, and diarrhea were noted during hospital stay. A Fusobacterium species and Bacteroides ovatus were isolated from blood culture specimens. Radiologic examination with barium enema showed normal ileocecal region, while colonoscopy indicated terminal ileitis. Abdominal ultrasound and computed tomography showed appendiceal mass sized 6.5x5.5 cm in the right lower quadrant. The patient was treated with intravenous antibiotic therapy consisting of amoxicillin + clavulanic acid and metronidazole for 21 days. He was discharged from the hospital when control ultrasound indicated disappearance of the appendiceal mass. DISCUSSION: Acute appendicitis is the most common cause of urgent surgery in children. Bacterial enteritis limited to the ileocecal region appears to be responsible for an appreciable number of unnecessary appendectomies. On the other hand, diagnostic errors in appendicitis may delay early appendectomy and result in the formation of appendiceal mass. The advent of high-resolution real-time scanners and graded compression sonography has enabled not only an accurate diagnosis of acute appendicitis but also a reliable diagnosis of other diseases of the ileocecal region. Acute terminal ileitis has similar clinical and laboratory manifestations as acute appendicitis, thus presenting a common diagnostic problem in daily practice. Perforation occurs in 20% to 30% of children with acute appendicitis. Perforation may be difficult to diagnose by sonography. The most common complications are peritonitis and intraperitoneal abscesses. The management of appendiceal mass remains controversial, such as interval appendectomy after nonoperative treatment. CONCLUSION: Successful conservative treatment for polymicrobial anaerobic sepsis and appendiceal mass in an 18-year-old patient is described. The case report is followed by review of the literature on the appendiceal mass management.

Abdominal Abscess↗

A microscopic view of helix propagation: N and C-terminal helix growth in alanine helices.

Molecular dynamics simulations with umbrella sampling are used to perform free energy simulations of C-terminal and N-terminal helix propagation in small helices of Ace-(Ala)n-NMe, with n= (4,5,10,15), in water. From the resulting free energy surfaces, computed as a function of the terminal psi dihedral angle, the roles of length and end effects in helix propagation are explored. An energetic analysis of the helices, both formed and partially formed, is used to develop a molecular rationalization for the observed trends in helix stability. We find that the microscopic helix propagation parameters vary significantly depending on the end and length of the helix in which the terminal hydrogen bond is forming. A model which considers propagation of the helices from either end as statistically independent yields Zimm-Bragg s parameters in the range of 0.5 to 1.5, depending on helical length. Analysis of the mechanism of helix propagation suggests that 3(10)-helix plays a role in helix formation but its population should be low in the helical state of these model peptides.

Computer Simulation↗

Epidemiological surveillance of suicides and attempted suicides in Aquitaine, south-west France, using an original computer network of sentinel general practitioners.

To improve the epidemiological study of suicide and attempted suicides in Aquitaine, France, we developed a comprehensive surveillance system based on the input of Sentinel General Practitioners (SGPs). From October 1986 to May 1988, for each case of suicide or attempted suicide, the SGPs reported epidemiological data to our system through a computer network of personal home terminals (Minitels). Data included age, sex, method and result of attempt and antecedents. In an analysis of the relationship between the suicidal method, antecedents and results of suicidal act, the principal findings were a high rate of antecedents of suicide attempts by drug overdoses, hangings and drownings; and no antecedents for attempts by the use of firearms. This may show that the increasing accessibility of firearms is making it more likely that impulsive suicide attempts will be lethal.

Adult↗

A technique for quantitating airway size from bronchial casts.

To develop a technique for quantitating the size of airways at various positions in the bronchial tree, we analyzed casts of formalin-fixed excised lungs of five mature male ferrets. The left lower lobe of each cast was dissected, the diameter and position of each terminal bronchiole were entered into a computer programmed to reconstruct the airway system, and the cross-sectional areas of 120 conducting airways were measured. The fraction of the lobe served by each measured airway was estimated by dividing the sum of the squared diameters of the terminal bronchioles subtended by that airway by the summed squared diameters of all terminal bronchioles in the lobe. In each cast the relationship between an airway's cross-sectional area (Y) and the fraction of the lobe it was estimated to subtend (X) was described (0.91 less than R2 less than 0.95) by the expression ln(Y) = A + B ln(X) + C [ln(X)]2. Linear regression of ln(Y) on ln(X) for 30-50 airways estimated to serve fractions of the lobe around each of three arbitrarily selected levels (airways serving 0.7, 2.2, and 9.5% of the lobe) was adequate to characterize the area of airways at each level in each of the five animals with 95% confidence intervals narrower than 8% of the estimated area. Variability of airway size at each level among the five casts was modest, suggesting that this technique identified analagous airways in the various animals. Interindividual variability did not increase when the data were reanalyzed with terminal units defined on the basis of airway diameters rather than on the morphological identification of terminal bronchioles.

Animals↗

A computer-based frozen blood inventory and information system.

A computer-based, time-sharing data processing system was developed to assist in maintaining information regarding units of red blood cells frozen for eventual transfusion. An automated system has been programmed to compile and retrieve data concerning stored units, prepare shipping documents as required, and maintain transfusion records in a retrievable manner for thawed or shipped units. Requests for frozen red blood cells are processed through this system. Units are selected by the computer to meet requirements specified by the operator of a keyboard terminal. These requirements include method of cryopreservation, specific antigenic characteristics required, and the number of units requested. The computer prints out on the keyboard terminal the units meeting the requirements and the keyboard operator then indicates to the computer the name of the requesting facility, if these units are to be shipped. This input initiates a programmed routine that generates a shipping invoice and a new file for these units in a permanent transfusion record which can by acessed by either donor number or the frozen blood cell code.

Blood Banks↗

Selective frontal, parietal, and temporal networks in generalized seizures.

Are "generalized" seizures truly generalized? Generalized tonic-clonic seizures are classified as either secondarily generalized with local onset or primarily generalized, without known focal onset. In both types of generalized seizures widespread regions of the nervous system engage in abnormally synchronous and high-frequency neuronal firing. However, emerging evidence suggests that all neurons are not homogeneously involved; specific nodes within the network may be crucial for the propagation and behavioral manifestations of generalized tonic-clonic seizures. Study of human tonic-clonic seizures has been limited by problems with patient movement and variable seizure types. To circumvent these problems, we imaged generalized tonic-clonic seizures during electroconvulsive therapy, in which seizure type and timing are well controlled. (99m)Tc-hexamethylpropylene amine oxime injections during seizures provide a "snapshot" of cerebral blood flow that can be imaged by single photon emission computed tomography (SPECT) after seizure termination. Here we show that focal regions of frontal and parietal association cortex show the greatest relative signal increases. Involvement of the higher-order association cortex may explain the profound impairment of consciousness seen in generalized seizures. In addition, focal involvement of the dominant temporal lobe was associated with impaired retrograde verbal memory. Similar focal increases were also seen in imaging of spontaneous secondarily generalized tonic-clonic seizures. Relative sparing of many brain regions during both spontaneous and induced seizures suggests that specific networks may be more important than others in so-called generalized seizures.

Adult↗

Visual performance on CRT screens and hard-copy displays.

Three experiments examined the effect of hard-copy print and CRT screens of different resolution/addressability ratios (RAR) on accommodation and visual search performance. Three different display modes were generated with an IBM personal computer and a Princeton Graphics Terminal: capital letters in high-RAR mode, capital letters in low-RAR mode, and capital letters in high-RAR mode programmed to simulate the low-RAR mode. Same-sized letters were also presented on hard-copy print. Experiment 1 demonstrated that accommodation to hardcopy print and high-RAR screens was more accurate than to low-RAR screens. In Experiment 2 the spatial frequency channels activated by each display were evaluated by measuring the effect of display adaptation on the contrast-sensitivity function. The results suggested that high-RAR screens and hard-copy print activated higher-frequency channels than did low-RAR screens. In Experiment 3 significantly better visual search performance was obtained for high-RAR screens and for hard-copy print than for low-RAR screens. It was concluded that screen RAR is an important variable to consider in the design of CRTs.

Accommodation, Ocular↗