[Visual requirements of work on data display terminals].
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Computers↗
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Sister Susie. Susie: terminal care specialist.
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Computers↗
Computer-aided discrimination between active and inactive mutants of the N-terminal domain of the bacteriophage lambda repressor.
Binding of the N-terminal domain of the lambda repressor to DNA is coupled to dimerization. Hydrophobic interactions between helix-5 and helix-5' drive the packing at the dimer interface. We have carried out computations of the conformational energy of packing of the fifth helices (and of the helix-4-loop-helix-5 portions) of variants of the lambda repressor operator binding domain, using an ECEPP/3-based packing algorithm. Here, we report the results for 26 mutants chosen among those that hve been characterized experimentally. We find that the relative orientation of the fifth helices for active mutants is very similar to the wild-type. The fifth helices of the inactive mutants have a significantly different relative orientation. This result illustrates that a unique specific orientation pattern of helix-5 relative to helix-5' is required for dimerization-coupled DNA binding activity. This finding is further supported by computational studies of the whole N-terminal domain of ten variants that showed that the active mutants, including the wild-type protein, have similar values of the number of contacts between the two monomers in the dimer, involving two amino acid residues of the fifth helices (positions 84 and 87 in each monomer). A decrease in the number of such contacts abolishes DNA-binding activity. Furthermore, all active mutants have their "DNA-recognition helices", numbers 3 and 3' positioned so that they can fit in the DNA operator like those of the wild-type protein, while some inactive mutants exhibit a substantial change in the relative orientation of their recognition helices.
Algorithms↗
[Usefulness of the newly developed transtelephonic electrocardiogram and computer-supported response system].
The "Cardiophone System" is a system designed to expand the relationship between patients and medical services using a transtelephonic electrocardiogram and computer-assisted answering system. The transtelephonic electrocardiogram, or so-called "Cardiophone", developed by Nihon Kohden, Inc., allows the patients to carry a "Cardiophone" to record electrocardiograms during paroxysmal occurrences of palpitation, chest pain, and other symptoms. The Cardiophone may function as a terminal of the host computer at the hospital, which stores the electrocardiogram and print it as soon as the computer receives the electrocardiogram over the phone. Cardiologists can examine the electrocardiogram immediately after it is printed. Cardiologists and operators are on duty 24 hours a day. Judgments based on the electrocardiogram are made by the cardiologist on duty, and stored in the computer by the operator. The patients may listen to the judgment over the phone within 30 min of sending the electrocardiogram. In the case of potentially lethal findings on the electrocardiogram, the cardiologist on duty calls the patient directly to give a medical advice. We studied 184 outpatients who were enrolled in the Cardiophone System of our hospital. The average number of transtelephonic electrocardiograms was 10 per day. Abnormal electrocardiographic changes were observed in 42 patients, and the diagnoses were as follows: paroxysmal supraventricular tachycardia in 18 patients, paroxysmal atrial fibrillation in 17, ventricular tachycardia in 3, and angina in 7. Among seven patients in whom ST changes were documented by Cardiophone, six were diagnosed as variant angina. In several patients with diagnoses already made by Holter monitoring, the Cardiophone was used to monitor the drug effects and the correlations between symptoms and arrhythmic events. We conclude that the Cardiophone System is useful for diagnosing the causes of paroxysmal cardiac symptoms in some patients and for improving home medical services.
Adolescent↗
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated by calmodulin with two bound calciums.
Changes in synaptic strength that underlie memory formation in the CNS are initiated by pulses of Ca2+ flowing through NMDA-type glutamate receptors into postsynaptic spines. Differences in the duration and size of the pulses determine whether a synapse is potentiated or depressed after repetitive synaptic activity. Calmodulin (CaM) is a major Ca2+ effector protein that binds up to four Ca2+ ions. CaM with bound Ca2+ can activate at least six signaling enzymes in the spine. In fluctuating cytosolic Ca2+, a large fraction of free CaM is bound to fewer than four Ca2+ ions. Binding to targets increases the affinity of CaM's remaining Ca2+-binding sites. Thus, initial binding of CaM to a target may depend on the target's affinity for CaM with only one or two bound Ca2+ ions. To study CaM-dependent signaling in the spine, we designed mutant CaMs that bind Ca2+ only at the two N-terminal or two C-terminal sites by using computationally designed mutations to stabilize the inactivated Ca2+-binding domains in the "closed" Ca2+-free conformation. We have measured their interactions with CaMKII, a major Ca2+/CaM target that mediates initiation of long-term potentiation. We show that CaM with two Ca2+ ions bound in its C-terminal lobe not only binds to CaMKII with low micromolar affinity but also partially activates kinase activity. Our results support the idea that competition for binding of CaM with two bound Ca2+ ions may influence significantly the outcome of local Ca2+ signaling in spines and, perhaps, in other signaling pathways.
Calcium↗
Computation of action potential propagation and presynaptic bouton activation in terminal arborizations of different geometries.
Action potential propagation in axons with bifurcations involving short collaterals with synaptic boutons has been simulated using SPICE, a general purpose electrical circuit simulation program. The large electrical load of the boutons may lead to propagation failure at otherwise uncritical geometric ratios. Because the action potential gradually fails while approaching the branch point, the electrotonic spread of the failing action potential cannot depolarize the terminal boutons above an assumed threshold of 20 mV (Vrest = 0 mV) for the presynaptic calcium inflow, and therefore fails to evoke transmitter release even for boutons attached at short collaterals. For even shorter collaterals the terminal boutons can again be activated by the spread of passive current reflected at the sealed end of the bouton which increases the membrane potential above firing threshold. The action potential is then propagated in anterograde fashion into the main axon and may activate the terminal bouton on the other collateral. Differential activation of the synaptic boutons can be observed without repetitive activation of the main axon and with the assumption of uniform membrane properties. Axon enlargements above a critical size at branch points can increase the safety factor for propagation significantly and may serve a double function: they can act both as presynaptic boutons and as boosters, facilitating invasion of the action potential into the terminal arborizations. The architecture of the terminal arborizations has a profound effect on the activation pattern of synapses, suggesting that terminal arborizations not only distribute neural information to postsynaptic cells but may also be able to process neural information presynaptically.
Action Potentials↗
Temporal dynamics of motion integration for the initiation of tracking eye movements at ultra-short latencies.
The perceived direction of a grating moving behind an elongated aperture is biased towards the aperture's long axis. This "barber pole" illusion is a consequence of integrating one-dimensional (1D) or grating and two-dimensional (2D) or terminator motion signals. In humans, we recorded the ocular following responses to this stimulus. Tracking was always initiated at ultra-short latencies (approximately 85 ms) in the direction of grating motion. With elongated apertures, a later component was initiated 15-20 ms later in the direction of the terminator motion signals along the aperture's long axis. Amplitude of the later component was dependent upon the aperture's aspect ratio. Mean tracking direction at the end of the trial (135-175 ms after stimulus onset) was between the directions of the vector sum computed by integrating either terminator motion signals only or both grating and terminator motion signals. Introducing an elongated mask at the center of the "barber pole" did not affect the latency difference between early and later components, indicating that this latency shift was not due to foveal versus peripheral locations of 1D and 2D motion signals. Increasing the size of the foveal mask up to 90% of the stimulus area selectively reduced the strength of the grating motion signals and, consequently, the amplitude of the early component. Conversely, reducing the contrast of, or indenting the aperture's edges, selectively reduced the strength of terminator motion signals and, consequently, the amplitude of the later component. Latencies were never affected by these manipulations. These results tease apart an early component of tracking responses, driven by the grating motion signals and a later component, driven by the line-endings moving at the intersection between grating and aperture's borders. These results support the hypothesis of a parallel processing of 1D and 2D motion signals with different temporal dynamics.
Eye Movements↗
Hand-held computers.
Changes in healthcare delivery, such as patient-focused, point-of-service care, demand that data be entered and accessed at the site where the patient is located (bedside, ER, home, ambulance). But this is not possible without some type of portable information system. The first step to bring information to the patient's side was through the use of bedside computers, but this delivery method has received limited acceptance. At present, some hospitals have begun to use hand-held computers that follow the healthcare clinician, not the patient. Why? Fewer terminals are needed. Handhelds have become easier to use with intuitive graphical user interfaces. As the size of computers has decreased, so has the cost. Personal-sized assistants come in many formats, using proprietary or off the shelf software, or bar code attachments, and with various ports for card or cable access. Most people are becoming computer literate, adapting to downloading, recharging, inserting, and pen/keystroking.
California↗
Cashing in on the trend toward variable-term computer leases.
Lessors make a large part of their profit from customer-requested changes such as upgrades or early termination of fixed-term computer leases. As lessees recognize the financial penalty associated with these changes, they are increasingly negotiating for variable-term computer leases.
Commerce↗
Assessment of distributed arterial network models.
The aim of this study is to evaluate the relative importance of elastic non-linearities, viscoelasticity and resistance vessel modelling on arterial pressure and flow wave contours computed with distributed arterial network models. The computational results of a non-linear (time-domain) and a linear (frequency-domain) mode were compared using the same geometrical configuration and identical upstream and downstream boundary conditions and mechanical properties. pressures were computed at the ascending aorta, brachial and femoral artery. In spite of the identical problem definition, computational differences were found in input impedance modulus (max. 15-20%), systolic pressure (max. 5%) and pulse pressure (max. 10%). For the brachial artery, the ratio of pulse pressure to aortic pulse pressure was practically identical for both models (3%), whereas for the femoral artery higher values are found for the linear model (+10%). The aortic/brachial pressure transfer function indicates that pressure harmonic amplification is somewhat higher in the linear model for frequencies lower than 6 Hz while the opposite is true for higher frequencies. These computational disparities were attributed to conceptual model differences, such as the treatment of geometric tapering, rather than to elastic or convective non-linearities. Compared to the effect of viscoelasticity, the discrepancy between the linear and non-linear model is of the same importance. At peripheral locations, the correct representation of terminal impedance outweight the computational differences between the linear and non-linear models.
Aorta↗
Structure of the type I collagen molecule based on conformational energy computations: the triple-stranded helix and the N-terminal telopeptide.
Various studies have implicated a crucial role for the non-helical ends (telopeptides) of the collagen molecule during fibrillogenesis. In this paper, the first extensive conformational analysis of the type I collagen N-terminal telopeptide is reported. The commonly used "build-up" procedure for peptides and proteins has been used, with relevant modifications to take account of all the stereochemical constraints affecting the telopeptide. In particular, consideration was given not only to the interactions among the three chains that constitute the telopeptide, but also to the interactions between the telopeptide and the covalently linked triple helix. The computations led to a limited number of different structures within an energy range of 25 kcal/mol. Comparison of these models clearly shows that the portion of the telopeptide linked to the triple helix is rather rigid whereas its N terminus is more flexible. Furthermore, the lowest-energy structure has an energy that is markedly lower (by 7.75 kcal/mol) than that of other conformations with different structural features. The lowest-energy model of the N-terminal telopeptide, which differs from previous proposed models, has a contracted conformation compared to the triple helix region, in agreement with X-ray and neutron diffraction data on collagen fibers. Finally, the side-chains of the lysine residues of the telopeptide, involved in intermolecular cross-links in mature collagen fibers, are oriented to protrude to the exterior, in positions to interact with adjacent collagen molecules.
Amino Acid Sequence↗
Case report: abnormal perfusion of iodinated contrast material into the ventricular system in cerebral death.
Apparent abnormal perfusion of iodinated contrast material into the ventricular system has been observed by computed tomography in a terminally ill patient with acute hydrocephalus due to cerebellar hematoma.
Aged↗
Use of social and health services by elderly people during the terminal 18 months of life.
In a randomised and controlled intervention study elderly people aged 75 or more were visited regularly in their own homes over a period of three years. An age and sex matched control group was not contacted until the conclusion of the study period. In the present study, the use of social and health services during the terminal 18 months of life was computed for each individual member of the study group. The categories of services included the bed usage in hospitals, the stays in nursing homes, the provisions of home help and home nursing care as well as contacts with general practitioners. No differences in the use of social and health services were found between the visited elderly (n = 25) and the control group (n = 46). About 50% of the elderly had a considerable use of public services during the months prior to death, and only 14% received no public support, disregarding the terminal phase. Among those elderly people belonging to the study group, and who died within the study period, an increased use of the above mentioned services was seen during all 18 months. However, an increased use of hospital beds was only computed during the terminal 6 months of life. 58% of the bed days were used for patients who died during the next few months.
Aged↗
Self-assembled monolayer organic field-effect transistors.
The use of individual molecules as functional electronic devices was proposed in 1974 (ref. 1). Since then, advances in the field of nanotechnology have led to the fabrication of various molecule devices and devices based on monolayer arrays of molecules. Single molecule devices are expected to have interesting electronic properties, but devices based on an array of molecules are easier to fabricate and could potentially be more reliable. However, most of the previous work on array-based devices focused on two-terminal structures: demonstrating, for example, negative differential resistance, rectifiers, and re-configurable switching. It has also been proposed that diode switches containing only a few two-terminal molecules could be used to implement simple molecular electronic computer logic circuits. However, three-terminal devices, that is, transistors, could offer several advantages for logic operations compared to two-terminal switches, the most important of which is 'gain'-the ability to modulate the conductance. Here, we demonstrate gain for electronic transport perpendicular to a single molecular layer ( approximately 10-20 A) by using a third gate electrode. Our experiments with field-effect transistors based on self-assembled monolayers demonstrate conductance modulation of more than five orders of magnitude. In addition, inverter circuits have been prepared that show a gain as high as six. The fabrication of monolayer transistors and inverters might represent an important step towards molecular-scale electronics.
Journal Article↗
Terminators of transcription with RNA polymerase from Escherichia coli: what they look like and how to find them.
We present here a compilation of prokaryotic transcription terminator sequences (ref. 1-152). The compilation includes 49 independent terminators, 52 speculated independent terminators, 27 sites shown to function in vivo, and some 20 proven or speculated rho-dependent terminators. In addition to the well-known features of independent terminators (dyad symmetry and T-run), two consensus are found: CGGG(C/G) upstream and TCTG downstream of the termination point. A subset of the collection of sequence has been used to construct a computer algorithm to locate independent terminators by sequence analysis.
Algorithms↗
Clathrin-mediated endocytosis near active zones in snake motor boutons.
We have used the activity-dependent probe FM1-43 with electron microscopy (EM) to examine endocytosis at the vertebrate nerve-muscle synapse. Preparations were fixed after very brief neural stimulation at reduced temperature, and internalized FM1-43 was photoconverted into an electron-dense reaction product. To locate the reaction product, we reconstructed computer renderings of individual terminal boutons from serial EM sections. Most of the reaction product was seen in 40-60 nm vesicles. All of the labeled vesicles were clathrin-coated, and 92% of them were located within 300 nm of the plasma membrane, suggesting that they had undergone little processing after retrieval from their endocytic sites. The vesicles (and by inference the sites) were not dispersed randomly near the plane of the membrane but instead were clustered significantly near active zones. Additional reaction product was found within putative macropinosomes; these appeared to form from deep membrane invaginations near active zones. Thus two mechanisms of endocytosis were evident after brief stimulation. Endocytosis near active zones is consistent with the existence of local exo/endocytic cycling pools. This mechanism also might serve to maintain alignment of active zones with postsynaptic folds during periods of activity when vesicular and plasma membranes are interchanged.
Animals↗
Presynaptic control of neurones in pattern-generating networks.
Recent studies have revealed presynaptic influences on neurones that participate in rhythmic motor patterns. Although there is still little direct information about the effects of these inputs at presynaptic terminals, their functional consequences are being unraveled. These presynaptic influences gate sensory input to pattern-generating networks and locally alter the synaptic strength and/or the activity pattern of network neurones.
Animals↗
Computer-optimization of vascular trees.
Arterial branchings closely fulfill several "bifurcation rules" which are deemed to optimize blood flow. The question is whether these local criteria in conjunction with a general optimization principle can explain the overall structure of an arterial tree. We present a model of an arterial vascular tree which is grown on the computer by successively adding terminal vessel segments. Each new terminal segment is connected to the optimum site within the preexisting tree, and the new bifurcation is optimized geometrically. After each step of adding and optimizing, the whole tree is rescaled to meet invariant boundary conditions of pressure and flow at each terminal site. Thus, local geometric optimization is used to induce simultaneously an optimized global structure. The comparison between the model and real coronary arterial trees shows good agreement regarding structural appearance, morphometric parameters, and pressure profiles.
Arteries↗