Symmetry classes for even-order tensors

The purpose of this article is to give a complete and general answer to the recurrent problem in continuum mechanics of the determination of the number and the type of symmetry classes of an even-order tensor space. This kind of investigation was initiated for the space of elasticity tensors. Since then, different authors solved this problem for other kinds of physics such as photoelectricity, piezoelectricity, flexoelectricity, and strain-gradient elasticity. All the aforementioned problems were treated by the same computational method. Although being effective, this method suffers the drawback not to provide general results. And, furthermore, its complexity increases with the tensorial order. In the present contribution, we provide general theorems that directly give the sought results for any even-order constitutive tensor. As an illustration of this method, and for the first time, the symmetry classes of all even-order tensors of Mindlin second strain-gradient elasticity are provided.Comment: Mathematics and Mechanics of Complex Systems (2013) (Accepted

Analytical continuum mechanics \`a la Hamilton-Piola: least action principle for second gradient continua and capillary fluids

In this paper a stationary action principle is proven to hold for capillary fluids, i.e. fluids for which the deformation energy has the form suggested, starting from molecular arguments, for instance by Cahn and Hilliard. Remark that these fluids are sometimes also called Korteweg-de Vries or Cahn-Allen. In general continua whose deformation energy depend on the second gradient of placement are called second gradient (or Piola-Toupin or Mindlin or Green-Rivlin or Germain or second gradient) continua. In the present paper, a material description for second gradient continua is formulated. A Lagrangian action is introduced in both material and spatial description and the corresponding Euler-Lagrange bulk and boundary conditions are found. These conditions are formulated in terms of an objective deformation energy volume density in two cases: when this energy is assumed to depend on either C and grad C or on C^-1 and grad C^-1 ; where C is the Cauchy-Green deformation tensor. When particularized to energies which characterize fluid materials, the capillary fluid evolution conditions (see e.g. Casal or Seppecher for an alternative deduction based on thermodynamic arguments) are recovered. A version of Bernoulli law valid for capillary fluids is found and, in the Appendix B, useful kinematic formulas for the present variational formulation are proposed. Historical comments about Gabrio Piola's contribution to continuum analytical mechanics are also presented. In this context the reader is also referred to Capecchi and Ruta.Comment: 52 page

Computational disease modeling – fact or fiction?

BACKGROUND: Biomedical research is changing due to the rapid accumulation of experimental data at an unprecedented scale, revealing increasing degrees of complexity of biological processes. Life Sciences are facing a transition from a descriptive to a mechanistic approach that reveals principles of cells, cellular networks, organs, and their interactions across several spatial and temporal scales. There are two conceptual traditions in biological computational-modeling. The bottom-up approach emphasizes complex intracellular molecular models and is well represented within the systems biology community. On the other hand, the physics-inspired top-down modeling strategy identifies and selects features of (presumably) essential relevance to the phenomena of interest and combines available data in models of modest complexity. RESULTS: The workshop, "ESF Exploratory Workshop on Computational disease Modeling", examined the challenges that computational modeling faces in contributing to the understanding and treatment of complex multi-factorial diseases. Participants at the meeting agreed on two general conclusions. First, we identified the critical importance of developing analytical tools for dealing with model and parameter uncertainty. Second, the development of predictive hierarchical models spanning several scales beyond intracellular molecular networks was identified as a major objective. This contrasts with the current focus within the systems biology community on complex molecular modeling. CONCLUSION: During the workshop it became obvious that diverse scientific modeling cultures (from computational neuroscience, theory, data-driven machine-learning approaches, agent-based modeling, network modeling and stochastic-molecular simulations) would benefit from intense cross-talk on shared theoretical issues in order to make progress on clinically relevant problems

Clinical trials in children: Equity, quality and relevance

This thesis investigates the equity, quality and relevance of clinical trials in children to inform better evidence-based child healthcare and outcomes worldwide. A comprehensive review of the literature revealed that despite current initiatives to encourage more trials in children, there is still a paucity of safety and efficacy data of many medicines prescribed in this population. An analysis of trials registered in children showed that disease burden was moderately correlated to trials and this scarcity was particularly prevalent in low-and middle-income countries. We explored the contributory factors to this inequity by conducting a systematic review of stakeholders’ views of trials in children in low-and middle-income countries. In the study evaluating the completeness of protocols of trials in children submitted to ethics committees, we found that protocols are generally comprehensive, but many key domains in trial design and conduct are not reported. Key-informant trial stakeholders who were interviewed proposed strategies to improve trials such as addressing the unique needs of children, embedding trials as part of routine clinical care and streamlining regulatory approvals. Increasing international collaboration, establishing sustainable centralised trials infrastructure, and aligning research to child health priorities were proposed to encourage more high-quality trials that address global child healthcare needs

A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED

RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement. RESULTS: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. CONCLUSION: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity

Systems biologists seek fuller integration of systems biology approaches in new cancer research programs

Systems biology takes an interdisciplinary approach to the systematic study of complex interactions in biological systems. This approach seeks to decipher the emergent behaviors of complex systems rather than focusing only on their constituent properties. As an increasing number of examples illustrate the value of systems biology approaches to understand the initiation, progression, and treatment of cancer, systems biologists from across Europe and the United States hope for changes in the way their field is currently perceived among cancer researchers. In a recent EU-US workshop, supported by the European Commission, the German Federal Ministry for Education and Research, and the National Cancer Institute of the NIH, the participants discussed the strengths, weaknesses, hurdles, and opportunities in cancer systems biology

Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered

Studies of the Response of the Prototype CMS Hadron Calorimeter, Including Magnetic Field Effects, to Pion, Electron, and Muon Beams

We report on the response of a prototype CMS hadron calorimeter module to charged particle beams of pions, muons, and electrons with momenta up to 375 GeV/c. The data were taken at the H2 and H4 beamlines at CERN in 1995 and 1996. The prototype sampling calorimeter used copper absorber plates and scintillator tiles with wavelength shifting fibers for readout. The effects of a magnetic field of up to 3 Tesla on the response of the calorimeter to muons, electrons, and pions are presented, and the effects of an upstream lead tungstate crystal electromagnetic calorimeter on the linearity and energy resolution of the combined calorimetric system to hadrons are evaluated. The results are compared with Monte Carlo simulations and are used to optimize the choice of total absorber depth, sampling frequency, and longitudinal readout segmentation.Comment: 89 pages, 41 figures, to be published in NIM, corresponding author: P de Barbaro, [email protected]

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing

Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2‐deficient mice (CCR2−/−) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2−/− and WT mice revealed a significant decrease in inflammatory, Ly6CHi recruited monocyte/macrophages in CCR2−/− wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2−/− wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2+/+ and CCR2−/− mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2+/+ and CCR2−/− mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2‐deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.Upon initial tissue injury, CCL2, one of the primary ligands for CCR2, is increased in the wound. This ligand binds the CCR2 receptors that are present on Ly6CHi monocytes, recruiting these cells to the wound, allowing initiation of the macrophage‐mediated inflammatory phase of wound healing.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145550/1/eji4256.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145550/2/eji4256_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145550/3/eji4256-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145550/4/eji4256-sup-0002-PRC.pd