Showing papers by "University of Milan published in 2007"

Matching NLO QCD computations with Parton Shower simulations: the POWHEG method

Abstract: The aim of this work is to describe in detail the POWHEG method, first suggested by one of the authors, for interfacing parton-shower generators with NLO QCD computations. We describe the method in its full generality, and then specify its features in two subtraction frameworks for NLO calculations: the Catani-Seymour and the Frixione-Kunszt-Signer approach. Two examples are discussed in detail in both approaches: the production of hadrons in e+e− collisions, and the Drell-Yan vector-boson production in hadronic collisions.

CMS physics technical design report, volume II: Physics performance

Abstract: CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking--through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb−1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z' and supersymmetric particles, Bs production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb−1 to 30 fb−1. The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing ET, B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model

Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells.

Abstract: Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP(+) cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers only in differentiated myotubes, which they form spontaneously with high efficiency. When transplanted into severe combined immune deficient-X-linked, mouse muscular dystrophy (scid-mdx) mice, pericyte-derived cells colonize host muscle and generate numerous fibres expressing human dystrophin. Similar cells isolated from Duchenne patients, and engineered to express human mini-dystrophin, also give rise to many dystrophin-positive fibres in vivo. These data show that myogenic precursors, distinct from satellite cells, are associated with microvascular walls in the human skeletal muscle, may represent a correlate of embryonic 'mesoangioblasts' present after birth and may be a promising candidate for future cell-therapy protocols in patients.

CO2 balance of boreal, temperate, and tropical forests derived from a global database

Abstract: Terrestrial ecosystems sequester 2.1 Pg of atmospheric carbon annually. A large amount of the terrestrial sink is realized by forests. However, considerable uncertainties remain regarding the fate of this carbon over both short and long timescales. Relevant data to address these uncertainties are being collected at many sites around the world, but syntheses of these data are still sparse. To facilitate future synthesis activities, we have assembled a comprehensive global database for forest ecosystems, which includes carbon budget variables (fluxes and stocks), ecosystem traits (e.g. leaf area index, age), as well as ancillary site information such as management regime, climate, and soil characteristics. This publicly available database can be used to quantify global, regional or biome-specific carbon budgets; to re-examine established relationships; to test emerging hypotheses about ecosystem functioning [e.g. a constant net ecosystem production (NEP) to gross primary production (GPP) ratio]; and as benchmarks for model evaluations. In this paper, we present the first analysis of this database. We discuss the climatic influences on GPP, net primary production (NPP) and NEP and present the CO2 balances for boreal, temperate, and tropical forest biomes based on micrometeorological, ecophysiological, and biometric flux and inventory estimates. Globally, GPP of forests benefited from higher temperatures and precipitation whereas NPP saturated above either a threshold of 1500 mm precipitation or a mean annual temperature of 10 degrees C. The global pattern in NEP was insensitive to climate and is hypothesized to be mainly determined by nonclimatic conditions such as successional stage, management, site history, and site disturbance. In all biomes, closing the CO2 balance required the introduction of substantial biome-specific closure terms. Nonclosure was taken as an indication that respiratory processes, advection, and non-CO2 carbon fluxes are not presently being adequately accounted for.

Spectral Energy Distributions of Hard X-Ray Selected Active Galactic Nuclei in the XMM-Newton Medium Deep Survey

Abstract: We present the SEDs of a hard X-ray selected sample containing 136 sources with F_(2-10 keV) > 10^(-14) erg cm^(-2) s^(-1); 132 are AGNs. The sources are detected in a 1 deg^2 area of the XMM-Newton Medium Deep Survey where optical data from the VVDS and CFHTLS and infrared data from the SWIRE survey are available. Based on a SED fitting technique we derive photometric redshifts with σ(1 + z) = 0.11 and 6% of outliers and identify AGN signatures in 83% of the objects. This fraction is higher than derived when a spectroscopic classification is available. The remaining 17^(+9)_(-6)% of AGNs show star-forming galaxy SEDs (SF class). The sources with AGN signatures are divided in two classes, AGN1 (33^(+6)_(-1)%) and AGN2 (50^(+6)_(-11)%). The AGN1 and AGN2 classes include sources whose SEDs are fitted by type 1 and type 2 AGN templates, respectively. On average, AGN1s show soft X-ray spectra, consistent with being unabsorbed, while AGN2s and SFs show hard X-ray spectra, consistent with being absorbed. The analysis of the average SEDs as a function of X-ray luminosity shows a reddening of the infrared SEDs, consistent with a decreasing contribution from the host galaxy at higher luminosities. The AGNs in the SF classes are likely obscured in the mid-infrared, as suggested by their low L_(3-20 μm)/L^(corr)_(0.5-10 keV) ratios. We confirm the previously found correlation for AGNs between the radio luminosity and the X-ray and the mid-infrared luminosities. The X-ray-radio correlation can be used to identify heavily absorbed AGNs. However, the estimated radio fluxes for the missing AGN population responsible for the bulk of the background at E > 10 keV are too faint to be detected even in the deepest current radio surveys.

HISTALP—historical instrumental climatological surface time series of the Greater Alpine Region

Abstract: This paper describes the HISTALP database, consisting of monthly homogenised records of temperature, pressure, precipitation, sunshine and cloudiness for the ‘Greater Alpine Region’ (GAR, 4–19°E, 43–49°N, 0–3500m asl). The longest temperature and air pressure series extend back to 1760, precipitation to 1800, cloudiness to the 1840s and sunshine to the 1880s. A systematic QC procedure has been applied to the series and a high number of inhomogeneities (more than 2500) and outliers (more than 5000) have been detected and removed. The 557 HISTALP series are kept in different data modes: original and homogenised, gap-filled and outlier corrected station mode series, grid-1 series (anomaly fields at 1° × 1°, lat × long) and Coarse Resolution Subregional (CRS) mean series according to an EOF-based regionalisation. The leading climate variability features within the GAR are discussed through selected examples and a concluding linear trend analysis for 100, 50 and 25-year subperiods for the four horizontal and two altitudinal CRSs. Among the key findings of the trend analysis is the parallel centennial decrease/increase of both temperature and air pressure in the 19th/20th century. The 20th century increase (+1.2 °C/+ 1.1 hPa for annual GAR-means) evolved stepwise with a first peak near 1950 and the second increase (1.3 °C/0.6hPa per 25 years) starting in the 1970s. Centennial and decadal scale temperature trends were identical for all subregions. Air pressure, sunshine and cloudiness show significant differences between low versus high elevations. A long-term increase of the high-elevation series relative to the low-elevation series is given for sunshine and air pressure. Of special interest is the exceptional high correlation near 0.9 between the series on mean temperature and air pressure difference (high-minus low-elevation). This, further developed via some atmospheric statics and thermodynamics, allows the creation of ‘barometric temperature series’ without use of the measures of temperature. They support the measured temperature trends in the region. Precipitation shows the most significant regional and seasonal differences with, e.g., remarkable opposite 20th century evolution for NW (9% increase) versus SE (9% decrease). Other long- and short-term features are discussed and indicate the promising potential of the new database for further analyses and applications. Copyright © 2006 Royal Meteorological Society.

N-doped TiO2: Theory and experiment

Abstract: Nitrogen doped titanium dioxide is attracting a continuously increasing attention because of its potential as material for environmental photocatalysis In this paper we review experimental and theoretical work done on this system in our groups in recent years The analysis is largely based on electron paramagnetic resonance (EPR) spectra and on their interpretation based on high-level ab initio calculations N-doped anatase TiO2 contains thermally stable single N-atom impurities either as charged diamagnetic Nb- centers or as neutral paramagnetic Nb centers (b stays for bulk) The N-atoms can occupy both interstitial or substitutional positions in the solid, with some evidence for a preference for interstitial sites All types of Nb centers give rise to localized states in the band-gap of the oxide, thus accounting for the related reduction of absorption band edge The relative abundance of these species depends on the oxidation state of the solid In fact, upon reduction, oxygen vacancies form and transfer electrons from Ti3+ ions to the Nb with formation of Ti4+ and Nb- EPR spectra measured under irradiation show that the Nb centers are responsible for visible light absorption with promotion of electrons from the localized N-impurity states to the conduction band or to electron scavengers like O2 adsorbed on the surface These results provide an unambiguous characterization of the electronic states associated with N-impurities in TiO2 and a realistic picture of the processes occurring in the solid under irradiation with visible light

Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Abstract: Background At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. Methods We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case – control studies that included 10 244 head and neck cancer case subjects and 15 227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. Results Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose – response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. Conclusions Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology. J Natl Cancer Inst 2007;99: 777 – 89

Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease

Abstract: Objective. Transient elastography (TE) is gaining popularity as a non-invasive method for predicting liver fibrosis, but intra- and interobserver agreement and factors influencing TE reproducibility have not been adequately assessed. This study addresses these aspects. Setting. Tertiary referral Liver Unit. Patients. Over a four month period, 200 patients with chronic liver disease (CLD) of different etiologies, consecutively underwent TE and liver biopsy. Interventions. TE was performed twice by two different operators either concomitantly or within three days of the bioptic procedure (Metavir classification). Main outcome measures. Intra- and interobserver agreement was analyzed using the intraclass correlation coefficient (ICC) and correlated with different patient and liver disease-related covariates. Results. 800 TE examinations were performed with an indeterminate result rate of 2.4%. The overall inter-observer agreement ICC was 0.98(95% CI:0.977-0.987). Increased BMI(>28Kg/m2), steatosis, and low staging grades ( 7.9 for ≥F2, >10.3 for ≥F3 and >11.9 for F=4. TE values by the 2 raters fell within the same cut-off of fibrosis in 88% of the cases for F≥2, in 92% for F≥3 and 91% for F=4. Conclusions. TE is a highly reproducible and user-friendly technique for assessing liver fibrosis in patients with CLD. However, since TE reproducibility is significantly reduced in patients with steatosis, increased BMI and lower degrees of hepatic fibrosis, caution is warranted in the clinical use of TE as a surrogate for liver biopsy.

Correlation of the highest-energy cosmic rays with nearby extragalactic objects.

Abstract: Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrate that there is a correlation between the arrival directions of cosmic rays with energy above {approx} 6 x 10{sup 19} eV and the positions of active galactic nuclei (AGN) lying within {approx} 75 Mpc. We reject the hypothesis of an isotropic distribution of these cosmic rays at over 99% confidence level from a prescribed a priori test. The correlation we observe is compatible with the hypothesis that the highest energy particles originate from nearby extragalactic sources whose flux has not been significantly reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.

Functionally specialized junctions between endothelial cells of lymphatic vessels

Abstract: Recirculation of fluid and cells through lymphatic vessels plays a key role in normal tissue homeostasis, inflammatory diseases, and cancer. Despite recent advances in understanding lymphatic function (Alitalo, K., T. Tammela, and T.V. Petrova. 2005. Nature. 438:946–953), the cellular features responsible for entry of fluid and cells into lymphatics are incompletely understood. We report the presence of novel junctions between endothelial cells of initial lymphatics at likely sites of fluid entry. Overlapping flaps at borders of oak leaf–shaped endothelial cells of initial lymphatics lacked junctions at the tip but were anchored on the sides by discontinuous button-like junctions (buttons) that differed from conventional, continuous, zipper-like junctions (zippers) in collecting lymphatics and blood vessels. However, both buttons and zippers were composed of vascular endothelial cadherin (VE-cadherin) and tight junction–associated proteins, including occludin, claudin-5, zonula occludens–1, junctional adhesion molecule–A, and endothelial cell–selective adhesion molecule. In C57BL/6 mice, VE-cadherin was required for maintenance of junctional integrity, but platelet/endothelial cell adhesion molecule–1 was not. Growing tips of lymphatic sprouts had zippers, not buttons, suggesting that buttons are specialized junctions rather than immature ones. Our findings suggest that fluid enters throughout initial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics.

Affective Interactions Using Virtual Reality: The Link between Presence and Emotions

Abstract: Many studies showed the ability of movies and imagery techniques to elicit emotions. Nevertheless, it is less clear how to manipulate the content of interactive media to induce specific emotional responses. In particular, this is true for the emerging medium virtual reality (VR), whose main feature is the ability to induce a feeling of "presence" in the computer-generated world experienced by the user. The main goal of this study was to analyze the possible use of VR as an affective medium. Within this general goal, the study also analyzed the relationship between presence and emotions. The results confirmed the efficacy of VR as affective medium: the interaction with "anxious" and "relaxing" virtual environments produced anxiety and relaxation. The data also showed a circular interaction between presence and emotions: on one side, the feeling of presence was greater in the "emotional" environments; on the other side, the emotional state was influenced by the level of presence. The significance of these r...

An online repository of Swift/XRT light curves of Γ-ray bursts

Abstract: Context. Swift data are revolutionising our understanding of Gamma Ray Bursts. Since bursts fade rapidly, it is desirable to create and disseminate accurate light curves rapidly.Aims. To provide the community with an online repository of X-ray light curves obtained with Swift . The light curves should be of the quality expected of published data, but automatically created and updated so as to be self-consistent and rapidly available.Methods. We have produced a suite of programs which automatically generates Swift /XRT light curves of GRBs. Effects of the damage to the CCD, automatic readout-mode switching and pile-up are appropriately handled, and the data are binned with variable bin durations, as necessary for a fading source. Results. The light curve repository website (http://www.swift.ac.uk/xrt_curves) contains light curves, hardness ratios and deep images for every GRB which Swift 's XRT has observed. When new GRBs are detected, light curves are created and updated within minutes of the data arriving at the UK Swift Science Data Centre.

Adjuvant mitotane treatment for adrenocortical carcinoma.

Abstract: Background Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival. Methods We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery. Results Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group. Recurrence-free s...

Cyclopamine-mediated Hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma

Abstract: Brain tumors can arise following deregulation of signaling pathways normally activated during brain development and may derive from neural stem cells. Given the requirement for Hedgehog in non-neoplastic stem cells, we investigated whether Hedgehog blockade could target the stem-like population in glioblastoma multiforme (GBM). We found that Gli1, a key Hedgehog pathway target, was highly expressed in 5 of 19 primary GBM and in 4 of 7 GBM cell lines. Shh ligand was expressed in some primary tumors, and in GBM-derived neurospheres, suggesting a potential mechanism for pathway activation. Hedgehog pathway blockade by cyclopamine caused a 40%–60% reduction in growth of adherent glioma lines highly expressing Gli1 but not in those lacking evidence of pathway activity. When GBM-derived neurospheres were treated with cyclopamine and then dissociated and seeded in media lacking the inhibitor, no new neurospheres formed, suggesting that the clonogenic cancer stem cells had been depleted. Consistent with this hypothesis, the stem-like fraction in gliomas marked by both aldehyde dehydrogenase activity and Hoechst dye excretion (side population) was significantly reduced or eliminated by cyclopamine. In contrast, we found that radiation treatment of our GBM neurospheres increased the percentage of these stem-like cells, suggesting that this standard therapy preferentially targets better-differentiated neoplastic cells. Most importantly, viable GBM cells injected intracranially following Hedgehog blockade were no longer able to form tumors in athymic mice, indicating that a cancer stem cell population critical for ongoing growth had been removed.

Changes in DNA Methylation Patterns in Subjects Exposed to Low-Dose Benzene

Abstract: Aberrant DNA methylation patterns, including global hypomethylation, gene-specific hypermethylation/hypomethylation, and loss of imprinting (LOI), are common in acute myelogenous leukemia (AML) and other cancer tissues We investigated for the first time whether such epigenetic changes are induced in healthy subjects by low-level exposure to benzene, a widespread pollutant associated with AML risk Blood DNA samples and exposure data were obtained from subjects with different levels of benzene exposure, including 78 gas station attendants, 77 traffic police officers, and 58 unexposed referents in Milan, Italy (personal airborne benzene range, 020) This is the first human study to link altered DNA methylation, reproducing the aberrant epigenetic patterns found in malignant cells, to low-level carcinogen exposure

Mirrors in the Brain: How Our Minds Share Actions and Emotions

Abstract: 1 The motor system 2 The acting brain 3 The space around us 4 Action understanding 5 Mirror neurons in humans 6 Imitation and language 7 Sharing emotions

Hardwiring the brain: endocannabinoids shape neuronal connectivity.

Abstract: The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB(1) cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB(1)R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.

The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps

Abstract: The long pentraxin (PTX) 3 is produced by macrophages and myeloid dendritic cells in response to Toll-like receptor agonists and represents a nonredundant component of humoral innate immunity against selected pathogens. We report that, unexpectedly, PTX3 is stored in specific granules and undergoes release in response to microbial recognition and inflammatory signals. Released PTX3 can partially localize in neutrophil extracellular traps formed by extruded DNA. Eosinophils and basophils do not contain preformed PTX3. PTX3-deficient neutrophils have defective microbial recognition and phagocytosis, and PTX3 is nonredundant for neutrophil-mediated resistance against Aspergillus fumigatus. Thus, neutrophils serve as a reservoir, ready for rapid release, of the long PTX3, a key component of humoral innate immunity with opsonic activity.

Distinctive patterns of microRNA expression in primary muscular disorders

Abstract: The primary muscle disorders are a diverse group of diseases caused by various defective structural proteins, abnormal signaling molecules, enzymes and proteins involved in posttranslational modifications, and other mechanisms. Although there is increasing clarification of the primary aberrant cellular processes responsible for these conditions, the decisive factors involved in the secondary pathogenic cascades are still mainly obscure. Given the emerging roles of microRNAs (miRNAs) in modulation of cellular phenotypes, we searched for miRNAs regulated during the degenerative process of muscle to gain insight into the specific regulation of genes that are disrupted in pathological muscle conditions. We describe 185 miRNAs that are up- or down-regulated in 10 major muscular disorders in humans [Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophies types 2A and 2B, Miyoshi myopathy, nemaline myopathy, polymyositis, dermatomyositis, and inclusion body myositis]. Although five miRNAs were found to be consistently regulated in almost all samples analyzed, pointing to possible involvement of a common regulatory mechanism, others were dysregulated only in one disease and not at all in the other disorders. Functional correlation between the predicted targets of these miRNAs and mRNA expression demonstrated tight posttranscriptional regulation at the mRNA level in DMD and Miyoshi myopathy. Together with direct mRNA-miRNA predicted interactions demonstrated in DMD, some of which are involved in known secondary response functions and others that are involved in muscle regeneration, these findings suggest an important role of miRNAs in specific physiological pathways underlying the disease pathology.

The role of junctional adhesion molecules in vascular inflammation.

Abstract: Junctional adhesion molecules (JAMs) of the immunoglobulin superfamily are important in the control of vascular permeability and leukocyte transmigration across endothelial-cell surfaces, by engaging in homophilic, heterophilic and lateral interactions. Through their localization on the endothelial-cell surface and expression by platelets, JAMs contribute to adhesive interactions with circulating leukocytes and platelets. Antibody-blocking studies and studies using genetically modified mice have implicated these functions of JAMs in the regulation of leukocyte recruitment to sites of inflammation and ischaemia-reperfusion injury, in growth-factor-mediated angiogenesis, atherogenesis and neointima formation. The comparison of different JAM-family members and animal models, however, shows that the picture remains rather complex. This Review summarizes recent progress and future directions in understanding the role of JAMs as 'gate keepers' in inflammation and vascular pathology.