Showing papers by "University of Perugia published in 2009"

The Large Area Telescope on the Fermi Gamma-ray Space Telescope Mission

Abstract: (Abridged) The Large Area Telescope (Fermi/LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV. This paper describes the LAT, its pre-flight expected performance, and summarizes the key science objectives that will be addressed. On-orbit performance will be presented in detail in a subsequent paper. The LAT is a pair-conversion telescope with a precision tracker and calorimeter, each consisting of a 4x4 array of 16 modules, a segmented anticoincidence detector that covers the tracker array, and a programmable trigger and data acquisition system. Each tracker module has a vertical stack of 18 x,y tracking planes, including two layers (x and y) of single-sided silicon strip detectors and high-Z converter material (tungsten) per tray. Every calorimeter module has 96 CsI(Tl) crystals, arranged in an 8 layer hodoscopic configuration with a total depth of 8.6 radiation lengths. The aspect ratio of the tracker (height/width) is 0.4 allowing a large field-of-view (2.4 sr). Data obtained with the LAT are intended to (i) permit rapid notification of high-energy gamma-ray bursts (GRBs) and transients and facilitate monitoring of variable sources, (ii) yield an extensive catalog of several thousand high-energy sources obtained from an all-sky survey, (iii) measure spectra from 20 MeV to more than 50 GeV for several hundred sources, (iv) localize point sources to 0.3 - 2 arc minutes, (v) map and obtain spectra of extended sources such as SNRs, molecular clouds, and nearby galaxies, (vi) measure the diffuse isotropic gamma-ray background up to TeV energies, and (vii) explore the discovery space for dark matter.

Nonlinear energy harvesting.

Abstract: Ambient energy harvesting has been in recent years the recurring object of a number of research efforts aimed at providing an autonomous solution to the powering of small-scale electronic mobile devices. Among the different solutions, vibration energy harvesting has played a major role due to the almost universal presence of mechanical vibrations. Here we propose a new method based on the exploitation of the dynamical features of stochastic nonlinear oscillators. Such a method is shown to outperform standard linear oscillators and to overcome some of the most severe limitations of present approaches. We demonstrate the superior performances of this method by applying it to piezoelectric energy harvesting from ambient vibration.

Measurement of the Cosmic Ray e+ + e- spectrum from 20 GeV to 1 TeV with the Fermi Large Area Telescope.

Abstract: Designed as a high-sensitivity gamma-ray observatory, the Fermi Large Area Telescope is also an electron detector with a large acceptance exceeding 2 m2 sr at 300 GeV. Building on the gamma-ray analysis, we have developed an efficient electron detection strategy which provides sufficient background rejection for measurement of the steeply falling electron spectrum up to 1 TeV. Our high precision data show that the electron spectrum falls with energy as E-3.0 and does not exhibit prominent spectral features. Interpretations in terms of a conventional diffusive model as well as a potential local extra component are briefly discussed.

Surface hydrophobin prevents immune recognition of airborne fungal spores

Abstract: The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10(9) per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus. Although these conidia contain many antigens and allergens, it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (DeltarodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.

Fermi Observations of High-Energy Gamma-Ray Emission from GRB 080916C

Abstract: Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gamma-ray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.

A limit on the variation of the speed of light arising from quantum gravity effects

Abstract: A cornerstone of Einstein's special relativity is Lorentz invariance-the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, l(Planck) approximate to 1.62 x 10(-33) cm or E(Planck) = M(Planck)c(2) approximate to 1.22 x 10(19) GeV), at which quantum effects are expected to strongly affect the nature of space-time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy(1-7). Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in gamma-ray burst (GRB) light-curves(2). Here we report the detection of emission up to similar to 31GeV from the distant and short GRB090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of l(Planck)/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories(3,6,7) in which the quantum nature of space-time on a very small scale linearly alters the speed of light.

Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study

Abstract: Summary Background Clinical trials are needed to assess the clinical benefit of antithrombotic prophylaxis in patients with cancer who are receiving chemotherapy, since these patients are at an increased risk of developing a thromboembolism. We did a trial to assess the clinical benefit of the low-molecular-weight heparin nadroparin for the prophylaxis of thromboembolic events in ambulatory patients receiving chemotherapy for metastatic or locally advanced solid cancer. Methods Between October, 2003, and May, 2007, ambulatory patients with lung, gastrointestinal, pancreatic, breast, ovarian, or head and neck cancer were randomly assigned in a double-blind manner to receive subcutaneous injections of nadroparin (3800 IU anti-Xa once a day, n=779) or placebo (n=387), in a 2:1 ratio. Study treatment was given for the duration of chemotherapy up to a maximum of 4 months. The primary study outcome was the composite of symptomatic venous or arterial thromboembolic events, as assessed by an independent adjudication committee. All randomised patients who received at least one dose of study treatment were included in the efficacy and safety analyses (modified intention-to-treat population). The study is registered with ClinicalTrials.gov, NCT 00951574. Findings 1150 patients were included in the primary efficacy and safety analyses: 769 patients in the nadroparin group and 381 patients in the placebo group. 15 (2·0%) of 769 patients treated with nadroparin and 15 (3·9%) of 381 patients treated with placebo had a thromboembolic event (single-sided p=0·02). Five (0·7%) of 769 patients in the nadroparin group and no patients in the placebo group had a major bleeding event (two-sided p=0·18). The incidences of minor bleeding were 7·4% (57 of 769) with nadroparin and 7·9% (30 of 381) with placebo. There were 121 (15·7%) serious adverse events in the nadroparin goup and 67 (17·6%) serious adverse events in the placebo group. Interpretation Nadroparin reduces the incidence of thromboembolic events in ambulatory patients with metastatic or locally advanced cancer who are receiving chemotherapy. Future studies should focus on patients who are at a high risk for thromboembolic events. Funding Italfarmaco SpA, Milan, Italy.

Bright Active Galactic Nuclei Source List from the First Three Months of the Fermi Large Area Telescope All-Sky Survey

Abstract: The first three months of sky-survey operation with the Fermi Gamma Ray Space Telescope (Fermi) Large Area Telescope (LAT) reveals 132 bright sources at |b|>10 deg with test statistic greater than 100 (corresponding to about 10 sigma). Two methods, based on the CGRaBS, CRATES and BZCat catalogs, indicate high-confidence associations of 106 of these sources with known AGNs. This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely Centaurus A and NGC 1275, and 104 blazars consisting of 57 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 5 blazars with uncertain classification. Four new blazars were discovered on the basis of the LAT detections. Remarkably, the LBAS includes 10 high-energy peaked BL Lacs (HBLs), sources which were so far hard to detect in the GeV range. Another 10 lower-confidence associations are found. Only thirty three of the sources, plus two at |b|>10 deg, were previously detected with EGRET, probably due to the variable nature of these sources. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. No significant correlation between radio and peak gamma-ray fluxes is observed. Blazar log N - log S and luminosity functions are constructed to investigate the evolution of the different blazar classes, with positive evolution indicated for FSRQs but none for BLLacs. The contribution of LAT-blazars to the total extragalactic gamma-ray intensity is estimated.

The Bile Acid Receptor FXR Is a Modulator of Intestinal Innate Immunity

Abstract: The farnesoid X receptor (FXR) is a bile acid-regulated nuclear receptor expressed in enterohepatic tissues. In this study we investigated whether FXR is expressed by cells of innate immunity and regulates inflammation in animal models of colitis. Acute (7 days) and chronic (8 wk) colitis were induced in wild-type and FXR−/− mice by intrarectal administration of trinitrobenzensulfonic acid or by 7-day administration of 5% dextran sulfate in drinking water. The results of this experiment demonstrate that FXR is expressed by and exerts counterregulatory effects on cells of innate immunity. Exposure of LPS-activated macrophages to 6-ethyl chenodeoxycholic acid (6E-CDCA; INT-747) a synthetic FXR ligand, results in a reciprocal regulation of NF-κB dependent-genes (TNF-α, IL-1β, IL-6, COX-1, COX-2, and iNOS) and induction of SHP, a FXR-regulated gene. FXR activation stabilizes the nuclear corepressor NCoR on the NF-κB responsive element on the IL-1β promoter. Colon inflammation in Crohn’s disease patients and in rodent models of colitis is associated with a reduced expression of FXR mRNA. Using two rodent models of colon inflammation, we show that progression of these immune-mediated disorders is exacerbated in FXR−/− mice (p < 0.01). In vivo treatment with INT-747 attenuates organ injury and immune cell activation. FXR activation increased the colon expression of I-BABP, FXR, and SHP while reducing IL-1β, IL-2, IL-6, TNF-α, and IFN-γ mRNA expression and attenuating disease severity. In aggregate, these findings provide evidence that FXR is an essential component of a network of nuclear receptors that regulate intestinal innate immunity and homeostasis.

Fermi/Large Area Telescope bright gamma-ray source list

Abstract: Following its launch in June 2008, the Fermi Gamma-ray Space Telescope (Fermi) began a sky survey in August. The Large Area Telescope (LAT) on Fermi in 3 months produced a deeper and better-resolved map of the gamma-ray sky than any previous space mission. We present here initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than 10-sigma) gamma-ray sources in these data. These are the best-characterized and best-localized gamma-ray sources in the early-mission data.

Fermi Observations of GRB 090902B: A Distinct Spectral Component in the Prompt and Delayed Emission

Abstract: We report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. ...

Fault zone fabric and fault weakness

Abstract: Geological and geophysical evidence suggests that some crustal faults are weak compared to laboratory measurements of frictional strength. Explanations for fault weakness include the presence of weak minerals, high fluid pressures within the fault core and dynamic processes such as normal stress reduction, acoustic fluidization or extreme weakening at high slip velocity. Dynamic weakening mechanisms can explain some observations; however, creep and aseismic slip are thought to occur on weak faults, and quasi-static weakening mechanisms are required to initiate frictional slip on mis-oriented faults, at high angles to the tectonic stress field. Moreover, the maintenance of high fluid pressures requires specialized conditions and weak mineral phases are not present in sufficient abundance to satisfy weak fault models, so weak faults remain largely unexplained. Here we provide laboratory evidence for a brittle, frictional weakening mechanism based on common fault zone fabrics. We report on the frictional strength of intact fault rocks sheared in their in situ geometry. Samples with well-developed foliation are extremely weak compared to their powdered equivalents. Micro- and nano-structural studies show that frictional sliding occurs along very fine-grained foliations composed of phyllosilicates (talc and smectite). When the same rocks are powdered, frictional strength is high, consistent with cataclastic processes. Our data show that fault weakness can occur in cases where weak mineral phases constitute only a small percentage of the total fault rock and that low friction results from slip on a network of weak phyllosilicate-rich surfaces that define the rock fabric. The widespread documentation of foliated fault rocks along mature faults in different tectonic settings and from many different protoliths suggests that this mechanism could be a viable explanation for fault weakening in the brittle crust.

Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

Abstract: Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p=5.95610 246 ). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p=6.78610 29 ) and eicosapentanoic acid (EPA; p=1.07610 214 ). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher lowdensity lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; p=1.1610 26 ). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids.

The Borexino detector at the Laboratori Nazionali del Gran Sasso

Abstract: Borexino, a large volume detector for low energy neutrino spectroscopy, is currently running underground at the Laboratori Nazionali del Gran Sasso, Italy. The main goal of the experiment is the real-time measurement of sub-MeV solar neutrinos, and particularly of the monoenergetic (862 keV) 7 Be electron capture neutrinos, via neutrino–electron scattering in an ultra-pure liquid scintillator. This paper is mostly devoted to the description of the detector structure, the photomultipliers, the electronics, and the trigger and calibration systems. The real performance of the detector, which always meets, and sometimes exceeds, design expectations, is also shown. Some important aspects of the Borexino project, i.e. the fluid handling plants, the purification techniques and the filling procedures, are not covered in this paper and are, or will be, published elsewhere (see Introduction and Bibliography).

Detection of 16 Gamma-Ray Pulsars Through Blind Frequency Searches Using the Fermi LAT

Abstract: Pulsars are rapidly rotating, highly magnetized neutron stars emitting radiation across the electromagnetic spectrum. Although there are more than 1800 known radio pulsars, until recently only seven were observed to pulse in gamma rays, and these were all discovered at other wavelengths. The Fermi Large Area Telescope (LAT) makes it possible to pinpoint neutron stars through their gamma-ray pulsations. We report the detection of 16 gamma-ray pulsars in blind frequency searches using the LAT. Most of these pulsars are coincident with previously unidentified gamma-ray sources, and many are associated with supernova remnants. Direct detection of gamma-ray pulsars enables studies of emission mechanisms, population statistics, and the energetics of pulsar wind nebulae and supernova remnants.

Phenolic compounds in olive oil: antioxidant, health and organoleptic activities according to their chemical structure.

Abstract: Hydrophilic phenols are the most abundant natural antioxidants of virgin olive oil (VOO), in which, however, tocopherols and carotenes are also present. The prevalent classes of hydrophilic phenols found in VOO are phenolic alcohols and acids, flavonoids, lignans and secoiridoids. Among these substances the last two classes include the most concentrate phenols of VOO. Secoiridoids, like aglycone derivatives of oleuropein, demethyloleuropein and ligstroside, are present in olive fruit as most abundant VOO phenolic antioxidants. Several important biological properties (antioxidant, anti-inflammatory, chemopreventive and anti-cancer) and the characteristic pungent and bitter tasty properties have been attributed to VOO phenols. Relationships between polyphenols activities and their chemical structures are discussed in this paper.

Radio-Loud Narrow-Line Seyfert 1 as a New Class of Gamma-Ray Active Galactic Nuclei

Abstract: We report the discovery with Fermi/LAT of gamma-ray emission from three radio-loud narrow-line Seyfert 1 galaxies: PKS 1502+036 (z=0.409), 1H 0323+342 (z=0.061) and PKS 2004-447 (z=0.24). In addition to PMN J0948+0022 (z=0.585), the first source of this type to be detected in gamma rays, they may form an emerging new class of gamma-ray active galactic nuclei (AGN). These findings can have strong implications on our knowledge about relativistic jets and the unified model of AGN.

NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo

Abstract: NK cells use a variety of receptors to detect abnormal cells, including tumors and their metastases. However, in the case of melanoma, it remains to be determined what specific molecular interactions are involved and whether NK cells control metastatic progression and/or the route of dissemination. Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1), two emerging NK cell receptors key for cancer cell recognition, but not NK group 2 member D (NKG2D). Compared with cell lines derived from metastases taken from other anatomical sites, LN metastases were more susceptible to NK cell lysis and preferentially targeted by adoptively transferred NK cells in a xenogeneic model of cell therapy. In mice, DNAM-1 and NCR ligands were also found on spontaneous melanomas and melanoma cell lines. Interference with DNAM-1 and NCRs by antibody blockade or genetic disruption reduced killing of melanoma cells. Taken together, these results show that DNAM-1 and NCRs are critical for NK cell-mediated innate immunity to melanoma cells and provide a background to design NK cell-based immunotherapeutic strategies against melanoma and possibly other tumors.

EML4-ALK Rearrangement in Non-Small Cell Lung Cancer and Non-Tumor Lung Tissues

Abstract: A fusion gene, echinoderm microtubule associated protein like 4 – anaplastic lymphoma kinase (EML4-ALK), with transforming activity has recently been identified in a subset of non-small cell lung cancer (NSCLC), but its pathogenetic, diagnostic, and therapeutic roles remain unclear. Both frequency and type of EML4-ALK transcripts were investigated by reverse transcription PCR in 120 frozen NSCLC specimens from Italy and Spain; non-neoplastic lung tissues taken far from the tumor were used as controls. In cases carrying the fusion transcript, we determined EML4-ALK gene and protein levels using fluorescence in situ hybridization, Western blotting, and immunoprecipitation. We also analyzed ALK protein levels in paraffin samples from 662 NSCLC specimens, including the 120 cases investigated in the molecular studies. EML4-ALK transcripts (variants 1 and 3) were detected in 9 of 120 NSCLC samples but were not specific for NSCLC since they were also found in non-cancerous lung tissues taken far from the tumor. Notably, no transcripts were detected in matching tumor samples from these patients. Fluorescence in situ hybridization analysis of cases expressing EML4-ALK transcripts showed that only a minority of cells harbored the EML4-ALK gene. None of these cases was found to express the EML4-ALK protein as examined by immunohistochemistry, Western blotting, and immunoprecipitation. The EML4-ALK transcript cannot be regarded as a specific diagnostic tool for NSCLC. Our results show therefore that the causal role and value of EML4-ALK as a therapeutic target remain to be defined.

Glucocorticoid-induced leucine zipper (GILZ): a new important mediator of glucocorticoid action

Abstract: Glucocorticoids (GCs) represent the mainstay of current anti-inflammatory and immunosuppressive strategies, mediating effects that mostly result in transcriptional regulation of glucocorticoid receptor target genes. A variety of actions are tied together in the response to GC treatment. Dissecting the beneficial from the detrimental actions in GC therapy is a major challenge in basic research, raising the critical issue of whether a single target gene or gene family might eventually be linked to a specific GC function. Glucocorticoid-induced leucine zipper (GILZ) was originally discovered in studies aimed at characterizing genes targeted by dexamethasone. The first suggestion that GILZ plays an important role in GC immunomodulation came from observations of GILZ up-regulation by GCs, mainly in lymphoid organs, and inhibition of anti-CD3-induced activation and apoptosis. The identification of GILZ interaction with and inhibition of NF-kappaB provided a first molecular mechanistic basis for explaining GILZ effects on T cells. Subsequently, other GILZ targets have been identified, including AP-1, Raf-1, and Ras, all involved in GC effects. The finding that GILZ silencing abrogates the antiproliferative activity of dexamethasone and reduces GC inhibition of cytokine-induced COX-2 expression clearly gained GILZ a distinguished reputation within the critical mediators of GC effects. The multiple functions of GILZ and their potential biological relevance are here reviewed.

Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells

Abstract: Rare cells with the properties of stem cells are integral to the development and perpetuation of leukaemias. A defining characteristic of stem cells is their capacity to self-renew, which is markedly extended in leukaemia stem cells. The underlying molecular mechanisms, however, are largely unknown. Here we demonstrate that expression of the cell-cycle inhibitor p21 is indispensable for maintaining self-renewal of leukaemia stem cells. Expression of leukaemia-associated oncogenes in mouse haematopoietic stem cells (HSCs) induces DNA damage and activates a p21-dependent cellular response, which leads to reversible cell-cycle arrest and DNA repair. Activated p21 is critical in preventing excess DNA-damage accumulation and functional exhaustion of leukaemic stem cells. These data unravel the oncogenic potential of p21 and suggest that inhibition of DNA repair mechanisms might function as potent strategy for the eradication of the slowly proliferating leukaemia stem cells.