129 research outputs found
Tailored graph ensembles as proxies or null models for real networks I: tools for quantifying structure
We study the tailoring of structured random graph ensembles to real networks,
with the objective of generating precise and practical mathematical tools for
quantifying and comparing network topologies macroscopically, beyond the level
of degree statistics. Our family of ensembles can produce graphs with any
prescribed degree distribution and any degree-degree correlation function, its
control parameters can be calculated fully analytically, and as a result we can
calculate (asymptotically) formulae for entropies and complexities, and for
information-theoretic distances between networks, expressed directly and
explicitly in terms of their measured degree distribution and degree
correlations.Comment: 25 pages, 3 figure
Resolution of Linear Algebra for the Discrete Logarithm Problem Using GPU and Multi-core Architectures
In cryptanalysis, solving the discrete logarithm problem (DLP) is key to
assessing the security of many public-key cryptosystems. The index-calculus
methods, that attack the DLP in multiplicative subgroups of finite fields,
require solving large sparse systems of linear equations modulo large primes.
This article deals with how we can run this computation on GPU- and
multi-core-based clusters, featuring InfiniBand networking. More specifically,
we present the sparse linear algebra algorithms that are proposed in the
literature, in particular the block Wiedemann algorithm. We discuss the
parallelization of the central matrix--vector product operation from both
algorithmic and practical points of view, and illustrate how our approach has
contributed to the recent record-sized DLP computation in GF().Comment: Euro-Par 2014 Parallel Processing, Aug 2014, Porto, Portugal.
\<http://europar2014.dcc.fc.up.pt/\>
Differential binding studies applying functional protein microarrays and surface plasmon resonance
A variety of different in vivo and in vitro technologies provide comprehensive insights in protein-protein interaction networks. Here we demonstrate a novel approach to analyze, verify and quantify putative interactions between two members of the S100 protein family and 80 recombinant proteins derived from a proteome-wide protein expression library. Surface plasmon resonance (SPR) using Biacore technology and functional protein microarrays were used as two independent methods to study protein-protein interactions. With this combined approach we were able to detect nine calcium-dependent interactions between Arg-Gly-Ser-(RGS)-His6 tagged proteins derived from the library and GST-tagged S100B and S100A6, respectively. For the protein microarray affinity-purified proteins from the expression library were spotted onto modified glass slides and probed with the S100 proteins. SPR experiments were performed in the same setup and in a vice-versa approach reversing analytes and ligands to determine distinct association and dissociation patterns of each positive interaction. Besides already known interaction partners, several novel binders were found independently with both detection methods, albeit analogous immobilization strategies had to be applied in both assays
Towards Forward Secure Internet Traffic
Forward Secrecy (FS) is a security property in key-exchange algorithms which
guarantees that a compromise in the secrecy of a long-term private-key does not
compromise the secrecy of past session keys. With a growing awareness of
long-term mass surveillance programs by governments and others, FS has become
widely regarded as a highly desirable property. This is particularly true in
the TLS protocol, which is used to secure Internet communication. In this
paper, we investigate FS in pre-TLS 1.3 protocols, which do not mandate FS, but
still widely used today. We conduct an empirical analysis of over 10 million
TLS servers from three different datasets using a novel heuristic approach.
Using a modern TLS client handshake algorithms, our results show 5.37% of top
domains, 7.51% of random domains, and 26.16% of random IPs do not select FS
key-exchange algorithms. Surprisingly, 39.20% of the top domains, 24.40% of the
random domains, and 14.46% of the random IPs that do not select FS, do support
FS. In light of this analysis, we discuss possible paths toward forward secure
Internet traffic. As an improvement of the current state, we propose a new
client-side mechanism that we call "Best Effort Forward Secrecy" (BEFS), and an
extension of it that we call "Best Effort Forward Secrecy and Authenticated
Encryption" (BESAFE), which aims to guide (force) misconfigured servers to FS
using a best effort approach. Finally, within our analysis, we introduce a
novel adversarial model that we call "discriminatory" adversary, which is
applicable to the TLS protocol
A kilobit hidden SNFS discrete logarithm computation
We perform a special number field sieve discrete logarithm computation in a
1024-bit prime field. To our knowledge, this is the first kilobit-sized
discrete logarithm computation ever reported for prime fields. This computation
took a little over two months of calendar time on an academic cluster using the
open-source CADO-NFS software. Our chosen prime looks random, and
has a 160-bit prime factor, in line with recommended parameters for the Digital
Signature Algorithm. However, our p has been trapdoored in such a way that the
special number field sieve can be used to compute discrete logarithms in
, yet detecting that p has this trapdoor seems out of reach.
Twenty-five years ago, there was considerable controversy around the
possibility of back-doored parameters for DSA. Our computations show that
trapdoored primes are entirely feasible with current computing technology. We
also describe special number field sieve discrete log computations carried out
for multiple weak primes found in use in the wild. As can be expected from a
trapdoor mechanism which we say is hard to detect, our research did not reveal
any trapdoored prime in wide use. The only way for a user to defend against a
hypothetical trapdoor of this kind is to require verifiably random primes
Design of a placebo-controlled, randomized study of the efficacy of repetitive transcranial magnetic stimulation for the treatment of chronic tinnitus
Efficacy and safety of bilateral continuous theta burst stimulation (cTBS) for the treatment of chronic tinnitus: design of a three-armed randomized controlled trial
<p>Abstract</p> <p>Background</p> <p>Tinnitus, the perception of sound and noise in absence of an auditory stimulus, has been shown to be associated with maladaptive neuronal reorganization and increased activity of the temporoparietal cortex. Transient modulation of tinnitus by repetitive transcranial magnetic stimulation (rTMS) indicated that these areas are critically involved in the pathophysiology of tinnitus and suggested new treatment strategies. However, the therapeutic efficacy of rTMS in tinnitus is still unclear, individual response is variable, and the optimal stimulation area disputable. Recently, continuous theta burst stimulation (cTBS) has been put forward as an effective rTMS protocol for the reduction of pathologically enhanced cortical excitability.</p> <p>Methods</p> <p>48 patients with chronic subjective tinnitus will be included in this randomized, placebo controlled, three-arm trial. The treatment consists of two trains of cTBS applied bilaterally to the secondary auditory cortex, the temporoparietal associaction cortex, or to the lower occiput (sham condition) every working day for four weeks. Primary outcome measure is the change of tinnitus distress as quantified by the Tinnitus Questionnaire (TQ). Secondary outcome measures are tinnitus loudness and annoyance as well as tinnitus change during and after treatment. Audiologic and speech audiometric measurements will be performed to assess potential side effects. The aim of the present trail is to investigate effectiveness and safety of a four weeks cTBS treatment on chronic tinnitus and to compare two areas of stimulation. The results will contribute to clarify the therapeutic capacity of rTMS in tinnitus.</p> <p>Trial registration</p> <p>The trial was registered with the clinical trials register of <url>http://www.clinicaltrials.gov</url> (NCT00518024).</p
Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation
A significant proportion of the population suffers from tinnitus, a bothersome auditory phantom perception that can severely alter the quality of life. Numerous experimental studies suggests that a maladaptive plasticity of the auditory and limbic cortical areas may underlie tinnitus. Accordingly, repetitive transcranial magnetic stimulation (rTMS) has been repeatedly used with success to reduce tinnitus intensity. The potential of transcranial direct current stimulation (tDCS), another promising method of noninvasive brain stimulation, to relieve tinnitus has not been explored systematically. In a double-blind, placebo-controlled and balanced order design, 20 patients suffering from chronic untreatable tinnitus were submitted to 20 minutes of 1 mA anodal, cathodal and sham tDCS targeting the left temporoparietal area. The primary outcome measure was a change in tinnitus intensity or discomfort assessed with a Visual Analogic Scale (VAS) change-scale immediately after tDCS and 1 hour later. Compared to sham tDCS, anodal tDCS significantly reduced tinnitus intensity immediately after stimulation; whereas cathodal tDCS failed to do so. The variances of the tinnitus intensity and discomfort VAS change-scales increased dramatically after anodal and cathodal tDCS, whereas they remained virtually unchanged after sham tDCS. Moreover, several patients unexpectedly reported longer-lasting effects (at least several days) such as tinnitus improvement, worsening, or changes in tinnitus features, more frequently after real than sham tDCS. Anodal tDCS is a promising therapeutic tool for modulating tinnitus perception. Moreover, both anodal and cathodal tDCS seem able to alter tinnitus perception and could, thus, be used to trigger plastic changes
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Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset
Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics
Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles
The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society
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