Characterizations of diverse residue clusters in protein three-dimensional structures.

We present new methods for identifying and analyzing statistically significant residue clusters that occur in three-dimensional (3D) protein structures. Residue clusters of different kinds occur in many contexts. They often feature the active site (e.g., in substrate binding), the interface between polypeptide units of protein complexes, regions of protein-protein and protein-nucleic acid interactions, or regions of metal ion coordination. The methods are illustrated with 3D clusters centering on four themes. (i) Acidic or histidine-acidic clusters associated with metal ions. (ii) Cysteine clusters including coordination of metals such as zinc or iron-sulfur structures, cysteine knots prominent in growth factors, multiple sets of buried disulfide pairings that putatively nucleate the hydrophobic core, or cysteine clusters of mostly exposed disulfide bridges. (iii) Iron-sulfur proteins and charge clusters. (iv) 3D environments of multiple histidine residues. Study of diverse 3D residue clusters offers a new perspective on protein structure and function. The algorithms can aid in rapid identification of distinctive sites, suggest correlations among protein structures, and serve as a tool in the analysis of new structures.

How are close residues of protein structures distributed in primary sequence?

Structurally neighboring residues are categorized according to their separation in the primary sequence as proximal (1-4 positions apart) and otherwise distal, which in turn is divided into near (5-20 positions), far (21-50 positions), very far ( > 50 positions), and interchain (from different chains of the same structure). These categories describe the linear distance histogram (LDH) for three-dimensional neighboring residue types. Among the main results are the following: (i) nearest-neighbor hydrophobic residues tend to be increasingly distally separated in the linear sequence, thus most often connecting distinct secondary structure units. (ii) The LDHs of oppositely charged nearest-neighbors emphasize proximal positions with a subsidiary maximum for very far positions. (iii) Cysteine-cysteine structural interactions rarely involve proximal positions. (iv) The greatest numbers of interchain specific nearest-neighbors in protein structures are composed of oppositely charged residues. (v) The largest fraction of side-chain neighboring residues from beta-strands involves near positions, emphasizing associations between consecutive strands. (vi) Exposed residue pairs are predominantly located in proximal linear positions, while buried residue pairs principally correspond to far or very far distal positions. The results are principally invariant to protein sizes, amino acid usages, linear distance normalizations, and over- and underrepresentations among nearest-neighbor types. Interpretations and hypotheses concerning the LDHs, particularly those of hydrophobic and charged pairings, are discussed with respect to protein stability and functionality. The pronounced occurrence of oppositely charged interchain contacts is consistent with many observations on protein complexes where multichain stabilization is facilitated by electrostatic interactions.

Partial rescue of retinal function in chronically hypoglycemic mice

Purpose. Mice rendered hypoglycemic by a null mutation in the glucagon receptor gene Gcgr display late-onset retinal degeneration and loss of retinal sensitivity. Acute hyperglycemia induced by dextrose ingestion does not restore their retinal function, which is consistent with irreversible loss of vision. The goal of this study was to establish whether long-term administration of high dietary glucose rescues retinal function and circuit connectivity in aged Gcgr−/− mice. Methods. Gcgr−/− mice were administered a carbohydrate-rich diet starting at 12 months of age. After 1 month of treatment, retinal function and structure were evaluated using electroretinographic (ERG) recordings and immunohistochemistry. Results. Treatment with a carbohydrate-rich diet raised blood glucose levels and improved retinal function in Gcgr−/− mice. Blood glucose increased from moderate hypoglycemia to euglycemic levels, whereas ERG b-wave sensitivity improved approximately 10-fold. Because the b-wave reflects the electrical activity of second-order cells, we examined for changes in rod-to-bipolar cell synapses. Gcgr−/− retinas have 20% fewer synaptic pairings than Gcgr+/− retinas. Remarkably, most of the lost synapses were located farthest from the bipolar cell body, near the distal boundary of the outer plexiform layer (OPL), suggesting that apical synapses are most vulnerable to chronic hypoglycemia. Although treatment with the carbohydrate-rich diet restored retinal function, it did not restore these synaptic contacts. Conclusions. Prolonged exposure to diet-induced euglycemia improves retinal function but does not reestablish synaptic contacts lost by chronic hypoglycemia. These results suggest that retinal neurons have a homeostatic mechanism that integrates energetic status over prolonged periods of time and allows them to recover functionality despite synaptic loss.

Familias de curvas elípticas adecuadas para Criptografía Basada en la Identidad

La Criptografía Basada en la Identidad hace uso de curvas elípticas que satisfacen ciertas condiciones (pairingfriendly curves), en particular, el grado de inmersión de dichas curvas debe ser pequeño. En este trabajo se obtienen familias explicitas de curvas elípticas idóneas para este escenario. Dicha criptografía está basada en el cálculo de emparejamientos sobre curvas, cálculo factible gracias al algoritmo de Miller. Proponemos una versión más eficiente que la clásica de este algoritmo usando la representación de un número en forma no adyacente (NAF).

Evaluation of sampling method effects in 3D non-rigid registration

Since the beginning of 3D computer vision problems, the use of techniques to reduce the data to make it treatable preserving the important aspects of the scene has been necessary. Currently, with the new low-cost RGB-D sensors, which provide a stream of color and 3D data of approximately 30 frames per second, this is getting more relevance. Many applications make use of these sensors and need a preprocessing to downsample the data in order to either reduce the processing time or improve the data (e.g., reducing noise or enhancing the important features). In this paper, we present a comparison of different downsampling techniques which are based on different principles. Concretely, five different downsampling methods are included: a bilinear-based method, a normal-based, a color-based, a combination of the normal and color-based samplings, and a growing neural gas (GNG)-based approach. For the comparison, two different models have been used acquired with the Blensor software. Moreover, to evaluate the effect of the downsampling in a real application, a 3D non-rigid registration is performed with the data sampled. From the experimentation we can conclude that depending on the purpose of the application some kernels of the sampling methods can improve drastically the results. Bilinear- and GNG-based methods provide homogeneous point clouds, but color-based and normal-based provide datasets with higher density of points in areas with specific features. In the non-rigid application, if a color-based sampled point cloud is used, it is possible to properly register two datasets for cases where intensity data are relevant in the model and outperform the results if only a homogeneous sampling is used.

Molecular dynamics simulations of the hydrophobin SC3 at a hydrophobic/hydrophilic interface

Hydrophobins are small (similar to 100 aa) proteins that have an important role in the growth and development of mycelial fungi. They are surface active and, after secretion by the fungi, self-assemble into amphipathic membranes at hydrophobic/hydrophilic interfaces, reversing the hydrophobicity of the surface. In this study, molecular dynamics simulation techniques have been used to model the process by which a specific class I hydrophobin, SC3, binds to a range of hydrophobic/ hydrophilic interfaces. The structure of SC3 used in this investigation was modeled based on the crystal structure of the class II hydrophobin HFBII using the assumption that the disulfide pairings of the eight conserved cysteine residues are maintained. The proposed model for SC3 in aqueous solution is compact and globular containing primarily P-strand and coil structures. The behavior of this model of SC3 was investigated at an air/water, an oil/water, and a hydrophobic solid/water interface. It was found that SC3 preferentially binds to the interfaces via the loop region between the third and fourth cysteine residues and that binding is associated with an increase in a-helix formation in qualitative agreement with experiment. Based on a combination of the available experiment data and the current simulation studies, we propose a possible model for SC3 self-assembly on a hydrophobic solid/water interface.

Sponsorship-linked marketing: The role of articulation in memory

Corporate sponsorship of events contributes significantly to marketing aims, including brand awareness as measured by recall and recognition of sponsor-event pairings. Unfortunately, resultant advantages accrue disproportionately to brands having a natural or congruent fit with the available sponsorship properties. In three cued-recall experiments, the effect of articulation of sponsorship fit on memory for sponsor-event pairings is examined. While congruent sponsors have a natural memory advantage, results demonstrate that memory improvements via articulation are possible for incongruent sponsor-event pairings. These improvements are, however, affected by the presence of competitor brands and the way in which memory is accessed.

Analysis of computer communication systems by use of digital signal processing methods

Queueing theory is an effective tool in the analysis of canputer camrunication systems. Many results in queueing analysis have teen derived in the form of Laplace and z-transform expressions. Accurate inversion of these transforms is very important in the study of computer systems, but the inversion is very often difficult. In this thesis, methods for solving some of these queueing problems, by use of digital signal processing techniques, are presented. The z-transform of the queue length distribution for the Mj GY jl system is derived. Two numerical methods for the inversion of the transfom, together with the standard numerical technique for solving transforms with multiple queue-state dependence, are presented. Bilinear and Poisson transform sequences are presented as useful ways of representing continuous-time functions in numerical computations.

The attenuation surface for contrast sensitivity has the form of a witch’s hat within the central visual field

Over the full visual field, contrast sensitivity is fairly well described by a linear decline in log sensitivity as a function of eccentricity (expressed in grating cycles). However, many psychophysical studies of spatial visual function concentrate on the central ±4.5 deg (or so) of the visual field. As the details of the variation in sensitivity have not been well documented in this region we did so for small patches of target contrast at several spatial frequencies (0.7–4 c/deg), meridians (horizontal, vertical, and oblique), orientations (horizontal, vertical, and oblique), and eccentricities (0–18 cycles). To reduce the potential effects of stimulus uncertainty, circular markers surrounded the targets. Our analysis shows that the decline in binocular log sensitivity within the central visual field is bilinear: The initial decline is steep, whereas the later decline is shallow and much closer to the classical results. The bilinear decline was approximately symmetrical in the horizontal meridian and declined most steeply in the superior visual field. Further analyses showed our results to be scale-invariant and that this property could not be predicted from cone densities. We used the results from the cardinal meridians to radially interpolate an attenuation surface with the shape of a witch's hat that provided good predictions for the results from the oblique meridians. The witch's hat provides a convenient starting point from which to build models of contrast sensitivity, including those designed to investigate signal summation and neuronal convergence of the image contrast signal. Finally, we provide Matlab code for constructing the witch's hat.

A comparison of microphone and speech recognition engine efficacy for mobile data entry

The research presented in this paper is part of an ongoing investigation into how best to incorporate speech-based input within mobile data collection applications. In our previous work [1], we evaluated the ability of a single speech recognition engine to support accurate, mobile, speech-based data input. Here, we build on our previous research to compare the achievable speaker-independent accuracy rates of a variety of speech recognition engines; we also consider the relative effectiveness of different speech recognition engine and microphone pairings in terms of their ability to support accurate text entry under realistic mobile conditions of use. Our intent is to provide some initial empirical data derived from mobile, user-based evaluations to support technological decisions faced by developers of mobile applications that would benefit from, or require, speech-based data entry facilities.

Paradoxical psychometric functions ("swan functions") are explained by dilution masking in four stimulus dimensions

The visual system dissects the retinal image into millions of local analyses along numerous visual dimensions. However, our perceptions of the world are not fragmentary, so further processes must be involved in stitching it all back together. Simply summing up the responses would not work because this would convey an increase in image contrast with an increase in the number of mechanisms stimulated. Here, we consider a generic model of signal combination and counter-suppression designed to address this problem. The model is derived and tested for simple stimulus pairings (e.g. A + B), but is readily extended over multiple analysers. The model can account for nonlinear contrast transduction, dilution masking, and signal combination at threshold and above. It also predicts nonmonotonic psychometric functions where sensitivity to signal A in the presence of pedestal B first declines with increasing signal strength (paradoxically dropping below 50% correct in two-interval forced choice), but then rises back up again, producing a contour that follows the wings and neck of a swan. We looked for and found these "swan" functions in four different stimulus dimensions (ocularity, space, orientation, and time), providing some support for our proposal.

Pattern integration in the normal and abnormal human visual system

The processing conducted by the visual system requires the combination of signals that are detected at different locations in the visual field. The processes by which these signals are combined are explored here using psychophysical experiments and computer modelling. Most of the work presented in this thesis is concerned with the summation of contrast over space at detection threshold. Previous investigations of this sort have been confounded by the inhomogeneity in contrast sensitivity across the visual field. Experiments performed in this thesis find that the decline in log contrast sensitivity with eccentricity is bilinear, with an initial steep fall-off followed by a shallower decline. This decline is scale-invariant for spatial frequencies of 0.7 to 4 c/deg. A detailed map of the inhomogeneity is developed, and applied to area summation experiments both by incorporating it into models of the visual system and by using it to compensate stimuli in order to factor out the effects of the inhomogeneity. The results of these area summation experiments show that the summation of contrast over area is spatially extensive (occurring over 33 stimulus carrier cycles), and that summation behaviour is the same in the fovea, parafovea, and periphery. Summation occurs according to a fourth-root summation rule, consistent with a “noisy energy” model. This work is extended to investigate the visual deficit in amblyopia, finding that area summation is normal in amblyopic observers. Finally, the methods used to study the summation of threshold contrast over area are adapted to investigate the integration of coherent orientation signals in a texture. The results of this study are described by a two-stage model, with a mandatory local combination stage followed by flexible global pooling of these local outputs. In each study, the results suggest a more extensive combination of signals in vision than has been previously understood.

A comparison of microphone and speech recognition engine efficacy for mobile data entry

The research presented in this paper is part of an ongoing investigation into how best to incorporate speech-based input within mobile data collection applications. In our previous work [1], we evaluated the ability of a single speech recognition engine to support accurate, mobile, speech-based data input. Here, we build on our previous research to compare the achievable speaker-independent accuracy rates of a variety of speech recognition engines; we also consider the relative effectiveness of different speech recognition engine and microphone pairings in terms of their ability to support accurate text entry under realistic mobile conditions of use. Our intent is to provide some initial empirical data derived from mobile, user-based evaluations to support technological decisions faced by developers of mobile applications that would benefit from, or require, speech-based data entry facilities.

On Finite Element Methods for 2nd order (semi–) periodic Eigenvalue Problems

We deal with a class of elliptic eigenvalue problems (EVPs) on a rectangle Ω ⊂ R^2 , with periodic or semi–periodic boundary conditions (BCs) on ∂Ω. First, for both types of EVPs, we pass to a proper variational formulation which is shown to fit into the general framework of abstract EVPs for symmetric, bounded, strongly coercive bilinear forms in Hilbert spaces, see, e.g., [13, §6.2]. Next, we consider finite element methods (FEMs) without and with numerical quadrature. The aim of the paper is to show that well–known error estimates, established for the finite element approximation of elliptic EVPs with classical BCs, hold for the present types of EVPs too. Some attention is also paid to the computational aspects of the resulting algebraic EVP. Finally, the analysis is illustrated by two non-trivial numerical examples, the exact eigenpairs of which can be determined.

Key Agreement Protocol Using Elliptic Curve Matrix Power Function

* Work is partially supported by the Lithuanian State Science and Studies Foundation.