Unresolved Gamma-Ray Sky through its Angular Power Spectrum.

The gamma-ray sky has been observed with unprecedented accuracy in the last decade by the Fermi -large area telescope (LAT), allowing us to resolve and understand the high-energy Universe. The nature of the remaining unresolved emission [unresolved gamma-ray background (UGRB)] below the LAT source detection threshold can be uncovered by characterizing the amplitude and angular scale of the UGRB fluctuation field. This Letter presents a measurement of the UGRB autocorrelation angular power spectrum based on eight years of Fermi-LAT Pass 8 data products. The analysis is designed to be robust against contamination from resolved sources and noise systematics. The sensitivity to subthreshold sources is greatly enhanced with respect to previous measurements. We find evidence (with ∼3.7σ significance) that the scenario in which two classes of sources contribute to the UGRB signal is favored over a single class. A double power law with exponential cutoff can explain the anisotropy energy spectrum well, with photon indices of the two populations being 2.55±0.23 and 1.86±0.15.

Resolving the Extragalactic γ-Ray Background above 50 GeV with the Fermi Large Area Telescope.

The Fermi Large Area Telescope (LAT) Collaboration has recently released a catalog of 360 sources detected above 50 GeV (2FHL). This catalog was obtained using 80 months of data re-processed with Pass 8, the newest event-level analysis, which significantly improves the acceptance and angular resolution of the instrument. Most of the 2FHL sources at high Galactic latitude are blazars. Using detailed Monte Carlo simulations, we measure, for the first time, the source count distribution, dN/dS, of extragalactic γ-ray sources at E>50 GeV and find that it is compatible with a Euclidean distribution down to the lowest measured source flux in the 2FHL (∼8×10^{-12} ph cm^{-2} s^{-1}). We employ a one-point photon fluctuation analysis to constrain the behavior of dN/dS below the source detection threshold. Overall, the source count distribution is constrained over three decades in flux and found compatible with a broken power law with a break flux, S_{b}, in the range [8×10^{-12},1.5×10^{-11}] ph cm^{-2} s^{-1} and power-law indices below and above the break of α_{2}∈[1.60,1.75] and α_{1}=2.49±0.12, respectively. Integration of dN/dS shows that point sources account for at least 86_{-14}^{+16}% of the total extragalactic γ-ray background. The simple form of the derived source count distribution is consistent with a single population (i.e., blazars) dominating the source counts to the minimum flux explored by this analysis. We estimate the density of sources detectable in blind surveys that will be performed in the coming years by the Cherenkov Telescope Array.

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

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) approximately 1.62 x 10(-33) cm or E(Planck) = M(Planck)c(2) approximately 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. 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. Here we report the detection of emission up to approximately 31 GeV from the distant and short GRB 090510. 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 in which the quantum nature of space-time on a very small scale linearly alters the speed of light.

Constraining dark matter models from a combined analysis of Milky Way satellites with the Fermi Large Area Telescope.

Satellite galaxies of the Milky Way are among the most promising targets for dark matter searches in gamma rays. We present a search for dark matter consisting of weakly interacting massive particles, applying a joint likelihood analysis to 10 satellite galaxies with 24 months of data of the Fermi Large Area Telescope. No dark matter signal is detected. Including the uncertainty in the dark matter distribution, robust upper limits are placed on dark matter annihilation cross sections. The 95% confidence level upper limits range from about 10(-26) cm3 s(-1) at 5 GeV to about 5×10(-23) cm3 s(-1) at 1 TeV, depending on the dark matter annihilation final state. For the first time, using gamma rays, we are able to rule out models with the most generic cross section (∼3×10(-26) cm3 s(-1) for a purely s-wave cross section), without assuming additional boost factors.

Inhibition of maturation of human precursor lymphocytes by coformycin, an inhibitor of the enzyme adenosine deaminase.

High concentrations of adenosine are known to be toxic to fibroblasts and lymphocytes under conditions of in vitro culture (1,2). Normally, accumulation of adenosine nucleotides in all mammalian cells is prevented by the presence of adenosine deaminase, an aminohydrolase which converts adenosine to inosine (3). A genetically determined deficiency of adenosine deaminase has been associated with the autosomal recessive form of severe combined immunodeficiency, a syndrome in which precursor lymphocytes fail to mature into T cells and B cells (4-7). Erythrocytes of affected infants convert exogenous adenosine to AMP and ATP at an abnormally increased rate as a consequence of the enzyme defect, and ATP at an abnormally increased rate as a consequence of the enzyme defect, and fail to form inosine from the exogenous adenosine (8). These metabolic disturbances can be mimicked in normal erythrocytes by coformycin (8), a potent competitive inhibitor of adenosine deaminase (9, 10). In this study, the effects of coformycin were examined on the in vitro function of normal lymphocytes.

Spectrum of the isotropic diffuse gamma-ray emission derived from first-year Fermi Large Area Telescope data.

We report on the first Fermi Large Area Telescope (LAT) measurements of the so-called "extragalactic" diffuse gamma-ray emission (EGB). This component of the diffuse gamma-ray emission is generally considered to have an isotropic or nearly isotropic distribution on the sky with diverse contributions discussed in the literature. The derivation of the EGB is based on detailed modeling of the bright foreground diffuse Galactic gamma-ray emission, the detected LAT sources, and the solar gamma-ray emission. We find the spectrum of the EGB is consistent with a power law with a differential spectral index gamma = 2.41 +/- 0.05 and intensity I(>100 MeV) = (1.03 +/- 0.17) x 10(-5) cm(-2) s(-1) sr(-1), where the error is systematics dominated. Our EGB spectrum is featureless, less intense, and softer than that derived from EGRET data.

Fermi large area telescope search for photon lines from 30 to 200 GeV and dark matter implications.

Dark matter (DM) particle annihilation or decay can produce monochromatic gamma rays readily distinguishable from astrophysical sources. gamma-ray line limits from 30 to 200 GeV obtained from 11 months of Fermi Large Area Space Telescope data from 20-300 GeV are presented using a selection based on requirements for a gamma-ray line analysis, and integrated over most of the sky. We obtain gamma-ray line flux upper limits in the range 0.6-4.5x10{-9} cm{-2} s{-1}, and give corresponding DM annihilation cross-section and decay lifetime limits. Theoretical implications are briefly discussed.

Evaluation of water treatment plant UV reactor efficiency against Cryptosporidium parvum oocyst infectivity in immunocompetent suckling mice.

AIM: To assess the efficiency of a medium-pressure UV reactor under full-scale water treatment plant (WTP) conditions on the infectivity of Cryptosporidium parvum oocysts in an Naval Medical Research Institute (NMRI) suckling mice infectivity model. METHODS AND RESULTS: Six/seven-day-old mice were administered orally 2-10x10(4)Cryptosporidium parvum oocysts. Compared with nonirradiated oocysts, 40 mJ cm(-2) UV irradiation of ingested oocysts resulted 7 days later in a 3.4-4.0 log10 reduction in the counts of small intestine oocysts, using a fluorescent flow cytometry assay. CONCLUSION: Present data extend to industrial conditions previous observations of the efficiency of UV irradiation against Cryptosporidium parvum oocyst in vivo development. SIGNIFICANCE AND IMPACT OF THE STUDY: Present results suggest that in WTP conditions, a medium-pressure UV reactor is efficient in reducing the infectivity of Cryptosporidium parvum oocysts, one of the most resistant micro-organisms present in environmental waters.

Fermi large area telescope measurements of the diffuse gamma-ray emission at intermediate galactic latitudes.

The diffuse galactic gamma-ray emission is produced by cosmic rays (CRs) interacting with the interstellar gas and radiation field. Measurements by the Energetic Gamma-Ray Experiment Telescope (EGRET) instrument on the Compton Gamma-Ray Observatory indicated excess gamma-ray emission greater, > or approximately equal to 1 GeV relative to diffuse galactic gamma-ray emission models consistent with directly measured CR spectra (the so-called "EGRET GeV excess"). The Large Area Telescope (LAT) instrument on the Fermi Gamma-Ray Space Telescope has measured the diffuse gamma-ray emission with improved sensitivity and resolution compared to EGRET. We report on LAT measurements for energies 100 MeV to 10 GeV and galactic latitudes 10 degrees < or = |b| < or = 20 degrees. The LAT spectrum for this region of the sky is well reproduced by a diffuse galactic gamma-ray emission model that is consistent with local CR spectra and inconsistent with the EGRET GeV excess.

In vitro efficacy of nitro- and halogeno-thiazolide/thiadiazolide derivatives against Sarcocystis neurona.

Sarcocystis neurona is an obligate intracellular parasite that causes equine protozoal myeloencephalitis (EPM). The aim of this work was to document inhibitory activities of nitazoxanide (NTZ, [2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide]) and new thiazolides/thiadiazolides on S. neurona in vitro development, and investigate their structure-activity relationships. S. neurona was grown in bovine turbinate cell cultures. At concentrations varying from 1.0 to 5.0mg/L, nitazoxanide and 21 of 32 second generation thiazolide/thiadiazolide agents exerted a > or =95% maximum inhibition on S. neurona development. Most active agents were either NO(2) or halogen substituted in position 5 of their thiazole moiety. In contrast, other 5-substitutions such as hydrogen, methyl, SO(2)CH(3), and CH(3) negatively impacted activity. Compared with derivatives with an acetylated benzene moiety, deacetylated compounds which most probably represent primary metabolites exhibited similar inhibitory activities. Present data provide the first evidence of in vitro inhibitory activities of nitazoxanide and new thiazolides/thiadiazolides on S. neurona development. Active halogeno-thiazolide/thiadiazolides may provide a valuable nitro-free alternative to nitazoxanide for EPM treatment depending on further evaluation of their in vivo activities.

Rayleigh-Taylor instability experiments on the LULI2000 laser in scaled conditions for young supernova remnants.

We describe a platform developed on the LULI2000 laser facility to investigate the evolution of Rayleigh-Taylor instability (RTI) in scaled conditions relevant to young supernova remnants (SNRs) up to 200 years. An RT unstable interface is imaged with a short-pulse laser-driven (PICO2000) x-ray source, providing an unprecedented simultaneous high spatial (24µm) and temporal (10 ps) resolution. This experiment provides relevant data to compare with astrophysical codes, as observational data on the development of RTI at the early stage of the SNR expansion are missing. A comparison is also performed with FLASH radiative magnetohydrodynamic simulations.

Specific inhibition of in vitro Candida-induced lymphocyte proliferation by polysaccharidic antigens present in the serum of patients with chronic mucocutaneous candidiasis.

A specific inhibitory activity of in vitro proliferative responses of normal human lymphocytes to Candida metabolic antigen was found in the serum of 6 out of 23 children with chronic mucocutaneous candidiasis. In each of the six patients, the presence of an inhibitory activity was associated with Candida-specific cellular defects, characterized by a negative-skin test and a lack of in vitro lymphocyte proliferation. The presence of a circulating inhibitor was detected during relapses of the disease and disappeared under antifungal therapy. This inhibitory effect was not associated with any toxicity on tested lymphocytes. The factor was shown to be nondialysable, thermostable, nonprecipitable with ammonium sulfate and absorbable on anti-Candida antibodies or concanavalin A-coupled agarose columns. Altogether, these results suggest that the inhibitory factor is not an immunoglobulin, but rather a polysaccharidic antigen of Candida albicans. An inhibition of Candida-induced proliferative response of normal human lymphocytes was also obtained by addition of polysacharide antigens or purified mannans from C. albicans to cultures. Candida polysaccharidic antigens appeared, therefore, to be involved in specific depression of cellular functions observed in chronic candidiasis.

Pilot-Scale Pulsed UV Light Irradiation of Experimentally Infected Raspberries Suppresses Cryptosporidium parvum Infectivity in Immunocompetent Suckling Mice.

Cryptosporidium spp., a significant cause of foodborne infection, have been shown to be resistant to most chemical food disinfectant agents and infective for weeks in irrigation waters and stored fresh vegetal produce. Pulsed UV light (PL) has the potential to inactivate Cryptosporidium spp. on surfaces of raw or minimally processed foods or both. The present study aimed to evaluate the efficacy of PL on viability and in vivo infectivity of Cryptosporidium parvum oocysts present on raspberries, a known source of transmission to humans of oocyst-forming apicomplexan pathogens. The skin of each of 20 raspberries was experimentally inoculated with five 10-µl spots of an oocyst suspension containing 6 × 10(7) oocysts per ml (Nouzilly isolate). Raspberries were irradiated by PL flashes (4 J/cm(2) of total fluence). This dose did not affect colorimetric or organoleptic characteristics of fruits. After immunomagnetic separation from raspberries, oocysts were bleached and administered orally to neonatal suckling mice. Seven days after infection, mice were euthanized, and the number of oocysts in the entire small intestine was individually assessed by immunofluorescence flow cytometry. Three of 12 and 12 of 12 inoculated mice that received 10 and 100 oocysts isolated from nonirradiated raspberries, respectively, were found infected. Four of 12 and 2 of 12 inoculated mice that received 10(3) and 10(4) oocysts from irradiated raspberries, respectively, were found infected. Oocyst counts were lower in animals inoculated with 10(3) and 10(4) oocysts from irradiated raspberries (92 ± 144 and 38 ± 82, respectively) than in animals infected with 100 oocysts from nonirradiated raspberries (35,785 ± 66,221, P = 0.008). PL irradiation achieved oocyst reductions of 2 and 3 log for an inoculum of 10(3) and 10(4) oocysts, respectively. The present pilot-scale evaluation suggests that PL is an effective mode of decontamination for raspberries and prompts further applicability studies in industrial contexts.

Impaired T-lymphocyte-dependent immune responses to microbial antigens in patients with HIV-1-associated persistent generalized lymphadenopathy.

T-cell mediated and humoral responses directed to microbial antigens were investigated, at the time of the initial visit, in a group of 139 patients with HIV-1-related persistent generalized lymphadenopathy (PGL) enrolled in a longitudinal study. In vivo and in vitro cell-mediated responses to tuberculin were lower in patients than in controls. Differences were not significant for candidin and streptococcal antigen in vitro, whereas higher responses were observed in the patient group for cytomegalovirus antigen. Following immunization, a subgroup of patients did not have a significantly raised serum antitetanus antibody level, whereas in vitro lymphocyte proliferative responses to tetanus toxoid were lower than in controls. No association was found between these abnormalities and other immunological parameters, including the blood level of CD4+ lymphocytes. Lower responses to most microbial antigens were observed in patients with HIV-1-related symptoms in addition to lymphadenopathy, or the patients who progressed to AIDS in the 2 years following the study. Moreover, intravenous drug users showed higher responses than homosexual patients, possibly because of the influence of previous infections on immunological responses to microbial antigens.

Responses of T cells from sensitized donors to recombinant and synthetic peptides corresponding to sequences of the Plasmodium falciparum SERP antigen.

In the present work, we intend to determine the capacity of human lymphocytes to recognize subfragments of the serine-stretch protein SERP, a blood-stage antigen from Plasmodium falciparum. Individuals sensitized by a previous P. falciparum infection were studied. Some recombinant proteins (RP) including RP7 and RP10 (amino acids 631-684 and 631-892 of SERP, respectively), were recognized in proliferation assays by lymphocytes from 28 sensitized individuals and not by lymphocytes from control, non-sensitized, donors. Synthetic peptides covering predefined zones of particular interest were tested and appeared to induce proliferative responses of lymphocytes from sensitized donors, allowing identification of putative T cell epitopes.

Enzyme immunoassay detection of Cryptosporidium parvum inhibition by sinefungin in sporozoite infected HCT-8 enterocytic cells.

Complete parasite development was obtained in differentiated human enterocytic HCT-8 cells infected at confluence with Cryptosporidium parvum sporozoites, and evaluated in a quantitative enzyme immunoassay. Forty-eight hours after infection, a linear correlation was found between optical density values and the number of parasites determined in an immunofluorescent assay. Sinefungin exerted an inhibitory effect when added within 4 h after sporozoite addition to HCT-8 cultures (MIC50 = 38 mumol L-1), while the inhibitory effects of paromomycin and pentamidine dimethanesulfonate were also easily detected (MIC50 = 0.87 mumol L-1 and 0.27 mumol L-1, respectively). Except for high pentamidine dimethanesulfonate concentrations, no alteration in optical microscopy morphology or trypan blue exclusion of HCT-8 cells was observed in the presence of anticryptosporidial agents, which suggests that they were primarily active against developing parasites. Data suggest that EIA detection of C. parvum development in sporozoite-infected HCT-8 cells provides an accurate and convenient model for in vitro evaluation of parasite infectivity, growth and response to anticryptosporidial agents.

Biliary tract cryptosporidiosis immunosuppressed rat model.

Rats immunosuppressed by hydrocortisone acetate and a low protein diet were challenged with Cryptosporidium Parvum oocysts and studied on days 10, 35 and 70 post-infection. The biliary tract was found to be a major site of parasite infection. C. parvum was visible in the biliary papillary area in association with a proliferation of highly convoluted tubular glands. The papillary lumen was narrowed, and an upstream dilation with bacterial proliferation was seen. The liver was initially free of lesions, and subsequently exhibited late lesions of cholestasis. Parasites were not found in the pancreatic duct, although pancreatitis was frequently observed. Oocysts were consistently present in the distal portion of the ileum. Both challenged and unchallenged immunosuppressed rats, exhibited widespread focal hepatic infarcts and pyelonephritis. Other organs appeared free of lesions. In addition to the intestine, data identified the biliary tract as a major site of C. parvum infection and as a potential protected reservoir which may sustain a chronic infection.

Virus recovery from stools of patients undergoing bone marrow transplantation.

Diarrhea in marrow transplant recipients is a frequent complication attributable to non-infectious events such as acute GVHD or infectious events such as viral gastroenteritis. Rotavirus and enteric adenovirus are the most frequent viral pathogens. To determine the frequency of these infections, we prospectively examined the stool specimens of 94 patients who underwent autologous BMT (34 cases) or allogeneic BMT (60 cases). Stool specimens were examined from patients twice weekly. Nineteen of the 94 patients were infected with viral pathogens. This study showed: (1) an incidence of viral gastroenteritis identical in autologous and allogeneic BMT (20%), (2) a persistent risk despite treatment in laminar air flow rooms, (3) a significant association with severe acute GVHD, and (4) a significant risk of multiple viral infections in autologous BMT recipients. Rotavirus and adenovirus are a cause of enteritis involvement in patients undergoing BMT and they may be underdiagnosed and confused with GVHD. Screening of stool specimens after BMT should be directed to prevention and treatment of these viral infections to decrease the morbidity and mortality associated with BMT.

Hydrogen peroxide gas plasma sterilization is effective against Cryptosporidium parvum oocysts.

The aim of this work was to evaluate in an immunosuppressed rat cryptosporidiosis model a new method that combines vacuum and low-temperature hydrogen peroxide gas plasma for sterilization of endoscopic material contaminated by Cryptosporidium parvum. Rats were challenged with oocysts either air-dried or air-dried and treated with vacuum alone or associated with gas plasma. No rat was found infected after gas plasma exposure of oocysts, whereas vacuum or air-drying alone resulted only in a decreased infectivity.

In vitro evaluation of B-CLL cells apoptotic responses to irradiation.

Defective apoptosis is a mechanism which could possibly explain B chronic lymphocytic leukemia (B-CLL) cell accumulation. Differences in evolution and prognosis of B-CLL patients may be due to heterogeneity in apoptotic cell death. We studied the apoptotic response to in vitro gamma radiation of blood mononuclear cells from 18 untreated B-CLL patients. In cells irradiated with 2, 4 or 8 Gy and then cultured for 20 hours, the percentage of trypan blue excluding (viable) cells was not modified (>92%). An apoptotic response to irradiation was detected in the majority of the patients, but the individual percentage of apoptotic cells varied widely (8 to 81% after 8 Gy irradiation) in individual cases. The flow cytometric analysis of nick-end DNA labeling demonstrated a dose effect of irradiation, particularly in patients with an apoptotic response of over 20%. In the future, a valuable clue to the selection of irradiation regimens for B-CLL patients may be the investigation of correlations between in vitro radiation-induced apoptosis and the in vivo response to radiation therapy.