529 research outputs found
PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis
The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al
Characterization of complex networks: A survey of measurements
Each complex network (or class of networks) presents specific topological
features which characterize its connectivity and highly influence the dynamics
of processes executed on the network. The analysis, discrimination, and
synthesis of complex networks therefore rely on the use of measurements capable
of expressing the most relevant topological features. This article presents a
survey of such measurements. It includes general considerations about complex
network characterization, a brief review of the principal models, and the
presentation of the main existing measurements. Important related issues
covered in this work comprise the representation of the evolution of complex
networks in terms of trajectories in several measurement spaces, the analysis
of the correlations between some of the most traditional measurements,
perturbation analysis, as well as the use of multivariate statistics for
feature selection and network classification. Depending on the network and the
analysis task one has in mind, a specific set of features may be chosen. It is
hoped that the present survey will help the proper application and
interpretation of measurements.Comment: A working manuscript with 78 pages, 32 figures. Suggestions of
measurements for inclusion are welcomed by the author
Continuous and transparent multimodal authentication: reviewing the state of the art
Individuals, businesses and governments undertake an ever-growing range of activities online and via various Internet-enabled digital devices. Unfortunately, these activities, services, information and devices are the targets of cybercrimes. Verifying the user legitimacy to use/access a digital device or service has become of the utmost importance. Authentication is the frontline countermeasure of ensuring only the authorized user is granted access; however, it has historically suffered from a range of issues related to the security and usability of the approaches. They are also still mostly functioning at the point of entry and those performing sort of re-authentication executing it in an intrusive manner. Thus, it is apparent that a more innovative, convenient and secure user authentication solution is vital. This paper reviews the authentication methods along with the current use of authentication technologies, aiming at developing a current state-of-the-art and identifying the open problems to be tackled and available solutions to be adopted. It also investigates whether these authentication technologies have the capability to fill the gap between high security and user satisfaction. This is followed by a literature review of the existing research on continuous and transparent multimodal authentication. It concludes that providing users with adequate protection and convenience requires innovative robust authentication mechanisms to be utilized in a universal level. Ultimately, a potential federated biometric authentication solution is presented; however it needs to be developed and extensively evaluated, thus operating in a transparent, continuous and user-friendly manner
Stringent response of Escherichia coli: revisiting the bibliome using literature mining
Understanding the mechanisms responsible for cellular responses depends on the systematic collection and analysis of information on the main biological concepts involved. Indeed, the identification of biologically relevant concepts in free text, namely genes, tRNAs, mRNAs, gene products and small molecules, is crucial to capture the structure and functioning of different responses.
Results
In this work, we review literature reports on the study of the stringent response in Escherichia coli. Rather than undertaking the development of a highly specialised literature mining approach, we investigate the suitability of concept recognition and statistical analysis of concept occurrence as means to highlight the concepts that are most likely to be biologically engaged during this response. The co-occurrence analysis of core concepts in this stringent response, i.e. the (p)ppGpp nucleotides with gene products was also inspected and suggest that besides the enzymes RelA and SpoT that control the basal levels of (p)ppGpp nucleotides, many other proteins have a key role in this response. Functional enrichment analysis revealed that basic cellular processes such as metabolism, transcriptional and translational regulation are central, but other stress-associated responses might be elicited during the stringent response. In addition, the identification of less annotated concepts revealed that some (p)ppGpp-induced functional activities are still overlooked in most reviews.
Conclusions
In this paper we applied a literature mining approach that offers a more comprehensive analysis of the stringent response in E. coli. The compilation of relevant biological entities to this stress response and the assessment of their functional roles provided a more systematic understanding of this cellular response. Overlooked regulatory entities, such as transcriptional regulators, were found to play a role in this stress response. Moreover, the involvement of other stress-associated concepts demonstrates the complexity of this cellular response
Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy
A search for new physics is performed in events with two same-sign isolated
leptons, hadronic jets, and missing transverse energy in the final state. The
analysis is based on a data sample corresponding to an integrated luminosity of
4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of
7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of
140 increase in integrated luminosity over previously published results. The
observed yields agree with the standard model predictions and thus no evidence
for new physics is found. The observations are used to set upper limits on
possible new physics contributions and to constrain supersymmetric models. To
facilitate the interpretation of the data in a broader range of new physics
scenarios, information on the event selection, detector response, and
efficiencies is provided.Comment: Published in Physical Review Letter
Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV
The azimuthal anisotropy of charged particles in PbPb collisions at
nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS
detector at the LHC over an extended transverse momentum (pt) range up to
approximately 60 GeV. The data cover both the low-pt region associated with
hydrodynamic flow phenomena and the high-pt region where the anisotropies may
reflect the path-length dependence of parton energy loss in the created medium.
The anisotropy parameter (v2) of the particles is extracted by correlating
charged tracks with respect to the event-plane reconstructed by using the
energy deposited in forward-angle calorimeters. For the six bins of collision
centrality studied, spanning the range of 0-60% most-central events, the
observed v2 values are found to first increase with pt, reaching a maximum
around pt = 3 GeV, and then to gradually decrease to almost zero, with the
decline persisting up to at least pt = 40 GeV over the full centrality range
measured.Comment: Replaced with published version. Added journal reference and DO
Compressed representation of a partially defined integer function over multiple arguments
In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one
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