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.

Investigating the Nature of Late-Time High-Energy GRB Emission Through Joint Fermi /Swift Observations.

We use joint observations by the Neil Gehrels Swift X-ray Telescope (XRT) and the Fermi Large Area Telescope (LAT) of gamma-ray burst (GRB) afterglows to investigate the nature of the long-lived high-energy emission observed by Fermi LAT. Joint broadband spectral modeling of XRT and LAT data reveal that LAT non-detections of bright X-ray afterglows are consistent with a cooling break in the inferred electron synchrotron spectrum below the LAT and/or XRT energy ranges. Such a break is sufficient to suppress the high-energy emission so as to be below the LAT detection threshold. By contrast, LAT-detected bursts are best fit by a synchrotron spectrum with a cooling break that lies either between or above the XRT and LAT energy ranges. We speculate that the primary difference between GRBs with LAT afterglow detections and the non-detected population may be in the type of circumstellar environment in which these bursts occur, with late-time LAT detections preferentially selecting GRBs that occur in low wind-like circumburst density profiles. Furthermore, we find no evidence of high-energy emission in the LAT-detected population significantly in excess of the flux expected from the electron synchrotron spectrum fit to the observed X-ray emission. The lack of excess emission at high energies could be due to a shocked external medium in which the energy density in the magnetic field is stronger than or comparable to that of the relativistic electrons behind the shock, precluding the production of a dominant synchrotron self-Compton (SSC) component in the LAT energy range. Alternatively, the peak of the SSC emission could be beyond the 0.1-100 GeV energy range considered for this analysis.

Search for Cosmic-Ray Electron and Positron Anisotropies with Seven Years of Fermi Large Area Telescope Data.

The Large Area Telescope on board the Fermi Gamma-ray Space Telescope has collected the largest ever sample of high-energy cosmic-ray electron and positron events since the beginning of its operation. Potential anisotropies in the arrival directions of cosmic-ray electrons or positrons could be a signature of the presence of nearby sources. We use almost seven years of data with energies above 42 GeV processed with the Pass 8 reconstruction. The present data sample can probe dipole anisotropies down to a level of 10^{-3}. We take into account systematic effects that could mimic true anisotropies at this level. We present a detailed study of the event selection optimization of the cosmic-ray electrons and positrons to be used for anisotropy searches. Since no significant anisotropies have been detected on any angular scale, we present upper limits on the dipole anisotropy. The present constraints are among the strongest to date probing the presence of nearby young and middle-aged sources.

Methods for immunoblot detection and electron microscopic localization of septin subunits in mammalian nervous systems.

The minimal functional units of the mammalian septin system are diverse heterooligomers of SEPT1-14 subunits, which are most abundantly and differentially expressed in postmitotic neurons and glia. The subunit compositions of such heterooligomers are thought to differentiate their affinity for other proteins and lipids, and subcellular localization. Thus, high-precision quantification and mapping of each subunit is necessary to understand their subcellular functions and physiological roles. However, systematic information on the localization of individual septin subunits in the mammalian nervous system is limited. Here, we present our experimental workflows for the study of septin expression and localization in the rodent brain by immunoblot and serial section immunoelectron microscopy. Our protocols, based on standard methods, have been rigorously optimized and simplified for universality and reproducibility to aid non-experts in the field.

Search for Spectral Irregularities due to Photon-Axionlike-Particle Oscillations with the Fermi Large Area Telescope.

We report on the search for spectral irregularities induced by oscillations between photons and axionlike-particles (ALPs) in the γ-ray spectrum of NGC 1275, the central galaxy of the Perseus cluster. Using 6 years of Fermi Large Area Telescope data, we find no evidence for ALPs and exclude couplings above 5×10^{-12} GeV^{-1} for ALP masses 0.5≲m_{a}≲5 neV at 95% confidence. The limits are competitive with the sensitivity of planned laboratory experiments, and, together with other bounds, strongly constrain the possibility that ALPs can reduce the γ-ray opacity of the Universe.

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.

Searching for Dark Matter Annihilation from Milky Way Dwarf Spheroidal Galaxies with Six Years of Fermi Large Area Telescope Data.

The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on γ-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new Pass8 event-level analysis. None of the dSphs are significantly detected in γ rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass ≲100 GeV annihilating via quark and τ-lepton channels.

Inferred cosmic-ray spectrum from Fermi large area telescope γ-ray observations of Earth's limb.

Recent accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. We use the Fermi Large Area Telescope observations of the γ-ray emission from Earth's limb for an indirect measurement of the local spectrum of CR protons in the energy range ∼90 GeV-6 TeV (derived from a photon energy range 15 GeV-1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68±0.04 and 2.61±0.08 above ∼200 GeV, respectively.

Fermi LARGE AREA TELESCOPE OBSERVATIONS OF BLAZAR 3C 279 OCCULTATIONS BY THE SUN.

Observations of occultations of bright γ-ray sources by the Sun may reveal predicted pair halos around blazars and/or new physics, such as, e.g., hypothetical light dark matter particles-axions. We use Fermi Gamma-Ray Space Telescope (Fermi) data to analyze four occultations of blazar 3C 279 by the Sun on October 8 each year from 2008 to 2011. A combined analysis of the observations of these occultations allows a point-like source at the position of 3C 279 to be detected with significance of ≈3σ, but does not reveal any significant excess over the flux expected from the quiescent Sun. The likelihood ratio test rules out complete transparency of the Sun to the blazar γ-ray emission at a 3σ confidence level.

Binary millisecond pulsar discovery via gamma-ray pulsations.

Millisecond pulsars, old neutron stars spun up by accreting matter from a companion star, can reach high rotation rates of hundreds of revolutions per second. Until now, all such "recycled" rotation-powered pulsars have been detected by their spin-modulated radio emission. In a computing-intensive blind search of gamma-ray data from the Fermi Large Area Telescope (with partial constraints from optical data), we detected a 2.5-millisecond pulsar, PSR J1311-3430. This unambiguously explains a formerly unidentified gamma-ray source that had been a decade-long enigma, confirming previous conjectures. The pulsar is in a circular orbit with an orbital period of only 93 minutes, the shortest of any spin-powered pulsar binary ever found.

The imprint of the extragalactic background light in the gamma-ray spectra of blazars.

The light emitted by stars and accreting compact objects through the history of the universe is encoded in the intensity of the extragalactic background light (EBL). Knowledge of the EBL is important to understand the nature of star formation and galaxy evolution, but direct measurements of the EBL are limited by galactic and other foreground emissions. Here, we report an absorption feature seen in the combined spectra of a sample of gamma-ray blazars out to a redshift of z ∼ 1.6. This feature is caused by attenuation of gamma rays by the EBL at optical to ultraviolet frequencies and allowed us to measure the EBL flux density in this frequency band.

CC-chemokine ligand 4/macrophage inflammatory protein-1ß participates in the induction of neuropathic pain after peripheral nerve injury.

BACKGROUND: Neuropathic pain is caused by neural damage or dysfunction and neuropathic pain-related symptoms are resistant to conventional analgesics. Neuroinflammation due to the cytokine-chemokine network may play a pivotal role in neuropathic pain. We demonstrate that macrophage inflammatory protein-1ß (MIP-1ß) participates in neuropathic pain. METHODS: Mice received partial sciatic nerve ligation (PSL), and tactile allodynia and thermal hyperalgesia were assessed by von Frey test and Hargreaves test, respectively. Agents were administered into the region surrounding the sciatic nerve (SCN). RESULTS: Using reverse transcription polymerase chain reaction, the mRNA expressions of MIP-1ß and its receptor (CC-chemokine receptor 5; CCR5) in the injured SCN were up-regulated after PSL. MIP-1ß immunoreactivity was localized in macrophages and Schwann cells and increased in the injured SCN on day 1. PSL-induced tactile allodynia on days 4 to 7 was prevented by the administration of MIP-1ß neutralizing antibody (anti-MIP-1ß; on days 0, 3 and 6). PSL-induced up-regulations of inflammatory cytokine-chemokine mRNAs in the injured SCN were suppressed with anti-MIP-1ß treatment on day 7. Administration of CCR5 antagonist, D-ala-peptide T-amide (on days 0, 3 and 6) prevented tactile allodynia and thermal hyperalgesia on days 4 to 14. Single administration of recombinant mouse MIP-1ß (rmMIP-1ß) elicited tactile allodynia. Moreover, rmMIP-1ß increased the mRNA expression of inflammatory mediators in the SCN on day 1 after administration. CONCLUSIONS: These results suggest that MIP-1ß is a novel key mediator, and the peripheral MIP-1ß-CCR5 axis contributes to neuropathic pain. Therefore, investigation of this cascade might be a validated approach for the elucidation of neuropathic pain mechanisms.

Inhibition of morphine tolerance is mediated by painful stimuli via central mechanisms.

Tolerance to morphine analgesia following repeated administration disturbs the continuation of opioid therapy for severe pain. Emerging evidence suggests that the development of morphine tolerance may be antagonized by painful stimuli. To clarify the detailed mechanisms of these phenomena, we examined the effects of several pain stimuli on morphine-induced tolerance. Subcutaneous (s.c.) injection of morphine (10 mg/kg) produced an analgesic effect, which was evaluated by tail-pinch test. Morphine-induced analgesia was diminished by repeated administration of morphine (10 mg/kg, s.c.) once a day for 5 days, demonstrating the development of tolerance. Morphine analgesic tolerance was suppressed by nerve injury-induced neuropathic pain and formalin- or carrageenan-induced inflammatory pain. Tolerance to serum corticosterone elevation by morphine (10 mg/kg), which was evaluated by fluorometric assay, was also suppressed by formalin-induced inflammatory pain. Moreover, morphine analgesia induced by intracerebroventricular (10 nmol) or intrathecal (5 nmol) injection was diminished by repeated administration of morphine s.c., and this was also suppressed by carrageenan-induced inflammatory pain. These results suggest that morphine tolerance is inhibited by several pain stimuli, including neuropathic and inflammatory pain, through central mechanisms.

Measurement of separate cosmic-ray electron and positron spectra with the fermi large area telescope.

We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting Earth's shadow, which is offset in opposite directions for opposite charges due to Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 and 200 GeV. We confirm that the fraction rises with energy in the 20-100 GeV range. The three new spectral points between 100 and 200 GeV are consistent with a fraction that is continuing to rise with energy.

A cocoon of freshly accelerated cosmic rays detected by Fermi in the Cygnus superbubble.

The origin of Galactic cosmic rays is a century-long puzzle. Indirect evidence points to their acceleration by supernova shockwaves, but we know little of their escape from the shock and their evolution through the turbulent medium surrounding massive stars. Gamma rays can probe their spreading through the ambient gas and radiation fields. The Fermi Large Area Telescope (LAT) has observed the star-forming region of Cygnus X. The 1- to 100-gigaelectronvolt images reveal a 50-parsec-wide cocoon of freshly accelerated cosmic rays that flood the cavities carved by the stellar winds and ionization fronts from young stellar clusters. It provides an example to study the youth of cosmic rays in a superbubble environment before they merge into the older Galactic population.

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.

Pioglitazone attenuates tactile allodynia and microglial activation in mice with peripheral nerve injury.

To test the possibility of a peroxisome proliferator activated receptor (PPAR) γ agonist to treat neuropathic pain, we examined the effects of pioglitazone, a PPARγ agonist, on tactile allodynia and expression of activated microglia in the dorsal horn of spinal cord using neuropathic pain model. The unilateral sciatic nerve was partially ligated (PSL) in male ICR mice. Pioglitazone (1-25 mg/kg p.o.) was administrated to mice once daily for five days immediately after PSL. We stimulated the footpad of the hind paw of mice using a von Frey filament to estimate tactile allodynia on day 5 of PSL. The activated microglia in the lumbar spinal cord was observed by immunohistochemistry with anti-Iba1 antibody, a marker for activated microglia. The number of Iba1-immunoreactive cells was counted in the dorsal horn spinal cord. On day 5, significant allodynia was developed in PSL mice. Pioglitazone significantly attenuated the tactile allodynia in a dose of 1-25 mg/kg. However, these doses of pioglitazone did not affect nociceptive responses in sham mice. Moreover, on day 6, the number of activated microglia was significantly increased in the ipsilateral dorsal horn of mice. The increase in the number of activated microglia induced by PSL was significantly suppressed by pioglitazone (1-25 mg/kg p.o.). Pioglitazone did not affect the number of activated microglia in sham mice. These results suggest that PPARγ activation inhibits the development of tactile allodynia and the expression of activated microglia in the dorsal horn of spinal cord in mice with PSLinduced peripheral nerve injury.

Multiple mechanisms are involved in apoptotic cell death in the mouse uterus and vagina after ovariectomy.

Withdrawal of sex hormones by gonadectomy results in rapid involution of mouse reproductive organs. To study the regression mechanism in the uterus and vagina after ovariectomy, histologic and biochemical changes were examined. Apoptotic cells were detected by in situ 3'-DNA nick end labeling method and electron microscopy, while the number of cells showing incorporation of bromo-deoxyuridine (BrdU) decreased in the uterus and vagina after ovariectomy. DNA fragmentation in the uterus was observed even at estrus and the degree of fragmentation increased after ovariectomy. DNA fragmentation in the vagina occurred 1-5 days after ovariectomy. Semi-quantitative RT-PCR revealed that expression of Fas-ligand and tumor necrosis factor-alpha (TNF-alpha) mRNA in the uterus and vagina was increased by ovariectomy. These results suggest that apoptotic cell death is induced by ovariectomy through the mediation of both Fas and TNF-alpha in the mouse uterus and vagina; however, uterine and vaginal cells in CBA lpr(cg)/lpr(cg) mice lacking functional Fas showed apoptosis, indicating that Fas is not the sole regulator of apoptosis in female reproductive organs in mice.

Effects of proteasome inhibitors on the synaptic localization of Vesl-1S/Homer-1a proteins.

The Vesl-1S/Homer-1a proteins are upregulated during seizure and long-term potentiation, but are rapidly degraded by ubiquitin-proteasome systems under normal conditions. We examined the distribution of Vesl-1S proteins in cultured hippocampal neurons. Application of proteasome inhibitors caused accumulation of Vesl-1S immunoreactivity in the neurons which showed a punctate distribution in the cortical regions of the cells, and these puncta were found to be juxtaposed with synaptophysin, a presynaptic, synapse-specific protein. These results suggest that Vesl-1S protein is synaptically targeted.

Regulated expression of an actin-associated protein, synaptopodin, during long-term potentiation.

We report NMDA receptor-dependent expression of synaptopodin mRNA in the dentate granule cells of the hippocampus following induction of long-term potentiation (LTP) in vivo. Synaptopodin did not belong to immediate-early genes, as de novo protein synthesis was required for the induction of synaptopodin gene transcription. An increased level of synaptopodin mRNA was observed at 75 min and 3.5 h after the onset of LTP. Importantly, there was correlation between the induction of mRNA expression and the persistence of LTP. Synaptopodin immunoreactivity was elevated specifically in synaptic layers, middle and outer molecular layers of dentate gyrus where LTP was induced. As synaptopodin is an actin-associated protein present in spine neck and implicated in the modulation of cell morphology, our results suggest that synaptopodin, by regulating the dynamics of the actin cytoskeleton, contributes to the morphological change in spine shape considered to be important for the maintenance of synaptic plasticity.