5,078 research outputs found
Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo
AbstractSpecific inhibitors for cathepsin L and cathepsin S have been developed with the help of computer-graphic modeling based on the stereo-structure. The common fragment, N-(L-trans-carbamoyloxyrane-2-carbonyl)-phenylalanine-dimethylamide, is required for specific inhibition of cathepsin L. Seven novel inhibitors of the cathepsin L inhibitor Katunuma (CLIK) specifically inhibited cathepsin L at a concentration of 10−7 M in vitro, while almost no inhibition of cathepsins B, C, S and K was observed. Four of the CLIKs are stable, and showed highly selective inhibition for hepatic cathepsin L in vivo. One of the CLIK inhibitors contains an aldehyde group, and specifically inhibits cathepsin S at 10−7 M in vitro
Second order analysis of geometric functionals of Boolean models
This paper presents asymptotic covariance formulae and central limit theorems
for geometric functionals, including volume, surface area, and all Minkowski
functionals and translation invariant Minkowski tensors as prominent examples,
of stationary Boolean models. Special focus is put on the anisotropic case. In
the (anisotropic) example of aligned rectangles, we provide explicit analytic
formulae and compare them with simulation results. We discuss which information
about the grain distribution second moments add to the mean values.Comment: Chapter of the forthcoming book "Tensor Valuations and their
Applications in Stochastic Geometry and Imaging" in Lecture Notes in
Mathematics edited by Markus Kiderlen and Eva B. Vedel Jensen. (The second
version mainly resolves minor LaTeX problems.
Structure-based development of specific inhibitors for individual cathepsins and their medical applications
Specific inhibitors for individual cathepsins have been developed based on their tertiary structures of X-ray crystallography. Cathepsin B-specific inhibitors, CA-074 and CA-030, and cathepsin L specific inhibitors, CLIK-148 and CLIK-195, were designed as the epoxysuccinate derivatives. Cathepsin S inhibitor, CLIK-060, and cathepsin K inhibitor, CLIK-166, were synthesized. These inhibitors can use in vitro and also in vivo, and show no toxicity for experimental animals by the amounts used as the cathepsin inhibitor
A Family of Maximum Margin Criterion for Adaptive Learning
In recent years, pattern analysis plays an important role in data mining and
recognition, and many variants have been proposed to handle complicated
scenarios. In the literature, it has been quite familiar with high
dimensionality of data samples, but either such characteristics or large data
have become usual sense in real-world applications. In this work, an improved
maximum margin criterion (MMC) method is introduced firstly. With the new
definition of MMC, several variants of MMC, including random MMC, layered MMC,
2D^2 MMC, are designed to make adaptive learning applicable. Particularly, the
MMC network is developed to learn deep features of images in light of simple
deep networks. Experimental results on a diversity of data sets demonstrate the
discriminant ability of proposed MMC methods are compenent to be adopted in
complicated application scenarios.Comment: 14 page
Minkowski Tensors of Anisotropic Spatial Structure
This article describes the theoretical foundation of and explicit algorithms
for a novel approach to morphology and anisotropy analysis of complex spatial
structure using tensor-valued Minkowski functionals, the so-called Minkowski
tensors. Minkowski tensors are generalisations of the well-known scalar
Minkowski functionals and are explicitly sensitive to anisotropic aspects of
morphology, relevant for example for elastic moduli or permeability of
microstructured materials. Here we derive explicit linear-time algorithms to
compute these tensorial measures for three-dimensional shapes. These apply to
representations of any object that can be represented by a triangulation of its
bounding surface; their application is illustrated for the polyhedral Voronoi
cellular complexes of jammed sphere configurations, and for triangulations of a
biopolymer fibre network obtained by confocal microscopy. The article further
bridges the substantial notational and conceptual gap between the different but
equivalent approaches to scalar or tensorial Minkowski functionals in
mathematics and in physics, hence making the mathematical measure theoretic
method more readily accessible for future application in the physical sciences
Sensing the danger in mosquito spit
Factors contained within mosquito saliva enhance transmission of mosquito-borne viruses to the mammalian host. In this issue, Wang et al (2024) identify AaNRP as a crucial pro-viral factor in Aedes aegypti mosquito saliva that promotes recruitment of Zika and dengue virus-susceptible myeloid cells
A bank of unscented Kalman filters for multimodal human perception with mobile service robots
A new generation of mobile service robots could be ready soon to operate in human environments if they can robustly estimate position and identity of surrounding people. Researchers in this field face a number of challenging problems, among which sensor uncertainties and real-time constraints.
In this paper, we propose a novel and efficient solution for simultaneous tracking and recognition of people within the observation range of a mobile robot. Multisensor techniques for legs and face detection are fused in a robust probabilistic framework to height, clothes and face recognition algorithms. The system is based on an efficient bank of Unscented Kalman Filters that keeps a multi-hypothesis estimate of the person being tracked, including the case where the latter is unknown to the robot.
Several experiments with real mobile robots are presented to validate the proposed approach. They show that our solutions can improve the robot's perception and recognition of humans, providing a useful contribution for the future application of service robotics
Security and Efficiency Analysis of the Hamming Distance Computation Protocol Based on Oblivious Transfer
open access articleBringer et al. proposed two cryptographic protocols for the computation of Hamming distance. Their first scheme uses Oblivious Transfer and provides security in the semi-honest model. The other scheme uses Committed Oblivious Transfer and is claimed to provide full security in the malicious case. The proposed protocols have direct implications to biometric authentication schemes between a prover and a verifier where the verifier has biometric data of the users in plain form.
In this paper, we show that their protocol is not actually fully secure against malicious adversaries. More precisely, our attack breaks the soundness property of their protocol where a malicious user can compute a Hamming distance which is different from the actual value. For biometric authentication systems, this attack allows a malicious adversary to pass the authentication without knowledge of the honest user's input with at most complexity instead of , where is the input length. We propose an enhanced version of their protocol where this attack is eliminated. The security of our modified protocol is proven using the simulation-based paradigm. Furthermore, as for efficiency concerns, the modified protocol utilizes Verifiable Oblivious Transfer which does not require the commitments to outputs which improves its efficiency significantly
Identification of specificity determining residues in peptide recognition domains using an information theoretic approach applied to large-scale binding maps
<p>Abstract</p> <p>Background</p> <p>Peptide Recognition Domains (PRDs) are commonly found in signaling proteins. They mediate protein-protein interactions by recognizing and binding short motifs in their ligands. Although a great deal is known about PRDs and their interactions, prediction of PRD specificities remains largely an unsolved problem.</p> <p>Results</p> <p>We present a novel approach to identifying these Specificity Determining Residues (SDRs). Our algorithm generalizes earlier information theoretic approaches to coevolution analysis, to become applicable to this problem. It leverages the growing wealth of binding data between PRDs and large numbers of random peptides, and searches for PRD residues that exhibit strong evolutionary covariation with some positions of the statistical profiles of bound peptides. The calculations involve only information from sequences, and thus can be applied to PRDs without crystal structures. We applied the approach to PDZ, SH3 and kinase domains, and evaluated the results using both residue proximity in co-crystal structures and verified binding specificity maps from mutagenesis studies.</p> <p>Discussion</p> <p>Our predictions were found to be strongly correlated with the physical proximity of residues, demonstrating the ability of our approach to detect physical interactions of the binding partners. Some high-scoring pairs were further confirmed to affect binding specificity using previous experimental results. Combining the covariation results also allowed us to predict binding profiles with higher reliability than two other methods that do not explicitly take residue covariation into account.</p> <p>Conclusions</p> <p>The general applicability of our approach to the three different domain families demonstrated in this paper suggests its potential in predicting binding targets and assisting the exploration of binding mechanisms.</p
Recognising facial expressions in video sequences
We introduce a system that processes a sequence of images of a front-facing human face and recognises a set of facial expressions. We use an efficient appearance-based face tracker to locate the face in the image sequence and estimate the deformation of its non-rigid components. The tracker works in real-time. It is robust to strong illumination changes and factors out changes in appearance caused by illumination from changes due to face deformation. We adopt a model-based approach for facial expression recognition. In our model, an image of a face is represented by a point in a deformation space. The variability of the classes of images associated to facial expressions are represented by a set of samples which model a low-dimensional manifold in the space of deformations. We introduce a probabilistic procedure based on a nearest-neighbour approach to combine the information provided by the incoming image sequence with the prior information stored in the expression manifold in order to compute a posterior probability associated to a facial expression. In the experiments conducted we show that this system is able to work in an unconstrained environment with strong changes in illumination and face location. It achieves an 89\% recognition rate in a set of 333 sequences from the Cohn-Kanade data base
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