Spike-forming model of the neural membrane: computer simulation of some perfused axon experiments.
(49/3102)
This paper is an attempt to account for the action potential spikes observed when the normal axoplasm of a squid giant neuron is replaced by a postassium-free, sodium-rich fluid, and the axon is immersed in a potassiumand sodium-free, calcium-rich bath. For this purpose a recently described model of the neural membrane [Wooldridge, D. E. (1975) Proc. Nat. Acad. Sci. USA 72, 3468-3471] is extended. Allowances are made for the flow of Ca++, Cl-, and Na+ ions through some of the membrane pore configurations, as well as for some electron conductance, all of amounts too small to be significant in the normal neuron. It is also postulated that the nature of the perfusing fluid affects the rates of some of the reactions that change the convertible gates from one configuration to another, as well as the ionic permeabilities of the resulting configurations. The result of the modifications is a single membrane model that accounts for the 3-sec, 15 muA/cm2 action potential spikes of the perfused axon as well as for the 0.5-msec, 1 mA/cm2 spikes of the normal neuron. (+info)
Spike-forming model of neural membrane: computer simulation of additional perfused axon experiments.
(50/3102)
In this paper a physical model of the neural membrane that I developed is tested for its ability to account for the details of the action potential spikes observed in squid giant axons, when perfused with sodium- and potassium-free fluids and surrounded by a calcium chloride solution. The near-zero resting potential of these perfused axons is accounted for by the model. The sizes, shapes, and conductances of the spikes observed with a number of different perfusates are also accounted for, when suitable values are assigned to the so-far unmeasured membrane constants that control the model properties. The three papers comprising the series are summarized at the end of this paper. (+info)
Attempts to locate residues in complementarity-determining regions of antibody combining sites that make contact with antigen.
(51/3102)
From collected data on variable region sequences of heavy chains of immunoglobulins, the probability of random associations of any two amino-acid residues in the complementarity-determining segments was computed, and pairs of residues occurring significantly more frequently than expected were selected by computer. Significant associations between Phe 32 and Tyr 33, Phe 32 and Glu 35, and Tyr 33 and Glu 35 were found in six proteins, all of which were mouse myeloma proteins which bound phosphorylcholine (= phosphocholine). From the x-ray structure of McPC603, Tyr 33 and Glu 35 are contacting residues; a seventh phosphorylcholine-binding mouse myeloma protein also contained Phe 32 and Tyr 33 but position 35 had only been determined as Glx and thus this position had not been selected. Met 34 occurred in all seven phosphorylcholine-binding myeoma proteins but was also present at this position in 29 other proteins and thus was not selected; it is seen in the x-ray structure not to be a contacting residue. The role of Phe 32 is not obvious but it could have some conformational influence. A human phosphorylcholine-binding myeloma protien also had Phe, Tyr, and Met at positions 32, 33, and 34, but had Asp instead of Glu at position 35 and showed a lower binding constant. The ability to use sequence data to locate residues in complementarity-determing segments making contact with antigenic determinants and those playing essentially a structural role would contribute substantially to the understanding of antibody specificity. (+info)
Knowledge-based analysis of microarray gene expression data by using support vector machines.
(52/3102)
We introduce a method of functionally classifying genes by using gene expression data from DNA microarray hybridization experiments. The method is based on the theory of support vector machines (SVMs). SVMs are considered a supervised computer learning method because they exploit prior knowledge of gene function to identify unknown genes of similar function from expression data. SVMs avoid several problems associated with unsupervised clustering methods, such as hierarchical clustering and self-organizing maps. SVMs have many mathematical features that make them attractive for gene expression analysis, including their flexibility in choosing a similarity function, sparseness of solution when dealing with large data sets, the ability to handle large feature spaces, and the ability to identify outliers. We test several SVMs that use different similarity metrics, as well as some other supervised learning methods, and find that the SVMs best identify sets of genes with a common function using expression data. Finally, we use SVMs to predict functional roles for uncharacterized yeast ORFs based on their expression data. (+info)
Explaining the moon illusion.
(53/3102)
An old explanation of the moon illusion holds that various cues place the horizon moon at an effectively greater distance than the elevated moon. Although both moons have the same angular size, the horizon moon must be perceived as larger. More recent explanations hold that differences in accommodation or other factors cause the elevated moon to appear smaller. As a result of this illusory difference in size, the elevated moon appears to be more distant than the horizon moon. These two explanations, both based on the geometry of stereopsis, lead to two diametrically opposed hypotheses. That is, a depth interval at a long distance is associated with a smaller binocular disparity, whereas an equal depth interval at a smaller distance is associated with a larger disparity. We conducted experiments involving artificial moons and confirmed the hypothesis that the horizon moon is at a greater perceptual distance. Moreover, when a moon of constant angular size was moved closer it was also perceived as growing smaller, which is consistent with the older explanation. Although Emmert's law does not predict the size-distance relationship over long distances, we conclude that the horizon moon is perceived as larger because the perceptual system treats it as though it is much farther away. Finally, we observe that recent explanations substitute perceived size for angular size as a cue to distance. Thus, they imply that perceptions cause perceptions. (+info)
Randomised controlled trial comparing effectiveness of touch screen system with leaflet for providing women with information on prenatal tests.
(54/3102)
OBJECTIVE: To compare the effectiveness of touch screen system with information leaflet for providing women with information on prenatal tests. DESIGN: Randomised controlled trial; participants allocated to intervention group (given access to touch screen and leaflet information) or control group (leaflet information only). SETTING: Antenatal clinic in university teaching hospital. SUBJECTS: 875 women booking antenatal care. INTERVENTIONS: All participants received a leaflet providing information on prenatal tests. Women in the intervention arm also had access to touch screen information system in antenatal clinic. MAIN OUTCOME MEASURES: Women's informed decision making on prenatal testing as measured by their uptake of and understanding of the purpose of specific tests; their satisfaction with information provided; and their levels of anxiety. RESULTS: All women in the trial had a good baseline knowledge of prenatal tests. Women in the intervention group did not show any greater understanding of the purpose of the tests than control women. However, uptake of detailed anomaly scans was significantly higher in intervention group than the control group (94% (351/375) v 87% (310/358), P=0.0014). Levels of anxiety among nulliparous women in intervention group declined significantly over time (P<0.001). CONCLUSIONS: The touch screen seemed to convey no benefit over well prepared leaflets in improving understanding of prenatal tests among the pregnant women. It did, however, seem to reduce levels of anxiety and may be most effective for providing information to selected women who have a relevant adverse history or abnormal results from tests in their current pregnancy. (+info)
Conformational flexibility and protein folding: rigid structural fragments connected by flexible joints in subtilisin BPN.
(55/3102)
Conformational energy calculations are used to analyze the interactions of structural substructures in subtilisin BPN. These substructures are kept fixed or "rigid" so that the only variables in the calculations are the backbone segments that separate them. The flexible segments are assumed to be free turns. Using this representation of the protein it is possible to predict both a likely order of events along a folding pathway and preferred modes of conformational changes of the native protein. Moreover, when the native structure has been perturbed by moving the substructures apart, it is possible to assess the range of interactions that return the protein, upon energy minimization, to its original conformation. These results suggest an approach to the folding problem based on the piecemeal formation of tertiary structure from smaller prefolded fragments. (+info)
Organization of DNA in chromatin.
(56/3102)
Conformational changes in DNA that accompany drug intercalation have led us to ask if DNA first bends or "kinks" to accept an intercalative drug or dye. Kinking is made possible by altering the normal C2' endo deoxyribose sugar ring puckering in B DNA to a mixed sugar puckering pattern of the type C3' and partially unstacking base-pairs. A kinking scheme such as this would require minimal stereochemical rearrangement and would also involve small energies. This has prompted us to ask more generally if a conformational change such as this could be used by proteins in their interactions with nucleic acids. In this papter we describe an interesting superhelical DNA structure formed by kinking DNA every 10 base-pairs. The structure may be used in the organization of DNA in chromatin. (+info)