Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Development of the multi-scale analysis model to simulate strain localization occurring during material processing

Abstract A detailed description of possibilities given by the developed Cellular Automata&mdash;Finite Element (CAFE) multi scale model for prediction of the initiation and propagation of micro shear bands and shear bands in metallic materials subjected to plastic deformation is presented in the work. Particular emphasis in defining the criterion for initiation of micro shear and shear bands, as well as in defining the transition rules for the cellular automata, is put on accounting for the physical aspects of these phenomena occurring in two different scales in the material. The proposed approach led to the creation of the real multi scale model of strain localization phenomena. This model predicts material behavior in various thermo-mechanical processes. Selected examples of applications of the developed model to simulations of metal forming processes, which involve strain localization, are presented in the work. An approach based on the Smoothed Particle Hydrodynamic, which allows to overcome difficulties with remeshing in the traditional CAFE method, is a subject of this work as well. In the developed model remeshing becomes possible and difficulties limiting application of the CAFE method to simple deformation processes are solved. Obtained results of numerical simulaA detailed description of possibilities given by the developed Cellular Automata&mdash;Finite Element (CAFE) multi scale model for prediction of the initiation and propagation of micro shear bands and shear bands in metallic materials subjected to plastic deformation is presented in the work. Particular emphasis in defining the criterion for initiation of micro shear and shear bands, as well as in defining the transition rules for the cellular automata, is put on accounting for the physical aspects of these phenomena occurring in two different scales in the material. The proposed approach led to the creation of the real multi scale model of strain localization phenomena. This model predicts material behavior in various thermo-mechanical processes. Selected examples of applications of the developed model to simulations of metal forming processes, which involve strain localization, are presented in the work. An approach based on the Smoothed Particle Hydrodynamic, which allows to overcome difficulties with remeshing in the traditional CAFE method, is a subject of this work as well. In the developed model remeshing becomes possible and difficulties limiting application of the CAFE method to simple deformation processes are solved. Obtained results of numerical simulations are compared with the experimental results of cold rolling process to show good predicative capabilities of the developed model.tions are compared with the experimental results of cold rolling process to show good predicative capabilities of the developed model.<br /

Bimetallic nanoparticles for biomedical applications: a review

Bimetallic nanoparticles, or BMNPs, are nanosized structures that are of growing interest in biomedical applications. Although their production shares aspects with physicochemical approaches for the synthesis of their monometallic counterparts, they can show a large variety of new properties and applications as a consequence of the synergetic effect between the two components. These applications can be as diverse as antibacterial treatments or anticancer or biological imaging approaches, as well as drug delivery. Nevertheless, utilization of BMNPs in such fields has received limited attention because of the severe lack of knowledge and concerns regarding the use of other nanomaterials, such as stability and biodegradability over time, tendency to form clusters, chemical reactivity, and biocompatibility. In this review, a close look at bimetallic systems is presented, focusing on their biomedical applications as antibacterial, anticancer, drug delivery, and imaging agents, showing significant enhancement of their features compared to their monometallic counterparts and other current used nanomaterials for biomedical applications.Peer reviewe

ALICE: Physics Performance Report, Volume II

ALICE is a general-purpose heavy-ion experiment designed to study the physics of strongly interacting matter and the quark\u2013gluon plasma in nucleus\u2013nucleus collisions at the LHC. It currently involves more than 900 physicists and senior engineers, from both the nuclear and high-energy physics sectors, from over 90 institutions in about 30 countries. The ALICE detector is designed to cope with the highest particle multiplicities above those anticipated for Pb\u2013Pb collisions (dNch/dy up to 8000) and it will be operational at the start-up of the LHC. In addition to heavy systems, the ALICE Collaboration will study collisions of lower-mass ions, which are a means of varying the energy density, and protons (both pp and pA), which primarily provide reference data for the nucleus\u2013nucleus collisions. In addition, the pp data will allow for a number of genuine pp physics studies. The detailed design of the different detector systems has been laid down in a number of Technical Design Reports issued between mid-1998 and the end of 2004. The experiment is currently under construction and will be ready for data taking with both proton and heavy-ion beams at the start-up of the LHC. Since the comprehensive information on detector and physics performance was last published in the ALICE Technical Proposal in 1996, the detector, as well as simulation, reconstruction and analysis software have undergone significant development. The Physics Performance Report (PPR) provides an updated and comprehensive summary of the performance of the various ALICE subsystems, including updates to the Technical Design Reports, as appropriate. The PPR is divided into two volumes. Volume I, published in 2004 (CERN/LHCC 2003-049, ALICE Collaboration 2004 J. Phys. G: Nucl. Part. Phys. 30 1517\u20131763), contains in four chapters a short theoretical overview and an extensive reference list concerning the physics topics of interest to ALICE, the experimental conditions at the LHC, a short summary and update of the subsystem designs, and a description of the offline framework and Monte Carlo event generators. The present volume, Volume II, contains the majority of the information relevant to the physics performance in proton\u2013proton, proton\u2013nucleus, and nucleus\u2013nucleus collisions. Following an introductory overview, Chapter 5 describes the combined detector performance and the event reconstruction procedures, based on detailed simulations of the individual subsystems. Chapter 6 describes the analysis and physics reach for a representative sample of physics observables, from global event characteristics to hard processes