462 research outputs found

    Human Amniocytes Are Receptive to Chemically Induced Reprogramming to Pluripotency

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    Restoring pluripotency using chemical compounds alone would be a major step forward in developing clinical-grade pluripotent stem cells, but this has not yet been reported in human cells. We previously demonstrated that VPA_ AFS cells, human amniocytes cultivated with valproic acid (VPA) acquired functional pluripotency while remaining distinct from human embryonic stem cells (hESCs), questioning the relationship between the modulation of cell fate and molecular regulation of the pluripotency network. Here, we used single-cell analysis and functional assays to reveal that VPA treatment resulted in a homogeneous population of self-renewing non-transformed cells that fulfill the hallmarks of pluripotency, i.e., a short G1 phase, a dependence on glycolytic metabolism, expression of epigenetic modifications on histones 3 and 4, and reactivation of endogenous OCT4 and downstream targets at a lower level than that observed in hESCs. Mechanistic insights into the process of VPA-induced reprogramming revealed that it was dependent on OCT4 promoter activation, which was achieved independently of the PI3K (phosphatidylinositol 3-kinase)/ AKT/ mTOR (mammalian target of rapamycin) pathway or GSK3 beta inhibition but was concomitant with the presence of acetylated histones H3K9 and H3K56, which promote pluripotency. Our data identify, for the first time, the pluripotent transcriptional and molecular signature and metabolic status of human chemically induced pluripotent stem cells

    PSR J1907+0602: A Radio-Faint Gamma-Ray Pulsar Powering a Bright TeV Pulsar Wind Nebula

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    We present multiwavelength studies of the 106.6 ms gamma-ray pulsar PSR J1907+06 near the TeV source MGRO J1908+06. Timing observations with Fermi result in a precise position determination for the pulsar of R.A. = 19h07m547(2), decl. = +06:02:16(2) placing the pulsar firmly within the TeV source extent, suggesting the TeV source is the pulsar wind nebula of PSR J1907+0602. Pulsed gamma-ray emission is clearly visible at energies from 100 MeV to above 10 GeV. The phase-averaged power-law index in the energy range E > 0.1 GeV is = 1.76 \pm 0.05 with an exponential cutoff energy E_{c} = 3.6 \pm 0.5 GeV. We present the energy-dependent gamma-ray pulsed light curve as well as limits on off-pulse emission associated with the TeV source. We also report the detection of very faint (flux density of ~3.4 microJy) radio pulsations with the Arecibo telescope at 1.5 GHz having a dispersion measure DM = 82.1 \pm 1.1 cm^{-3}pc. This indicates a distance of 3.2 \pm 0.6 kpc and a pseudo-luminosity of L_{1400} ~ 0.035 mJy kpc^2. A Chandra ACIS observation revealed an absorbed, possibly extended, compact <(4 arcsec) X-ray source with significant non-thermal emission at R.A. = 19h07m54.76, decl. = +06:02:14.6 with a flux of 2.3^{+0.6}_{-1.4} X 10^{-14} erg cm^{-2} s^{-1}. From archival ASCA observations, we place upper limits on any arcminute scale 2--10 keV X-ray emission of ~ 1 X 10^{-13} erg cm^{-2} s^{-1}. The implied distance to the pulsar is compatible with that of the supernova remnant G40.5-0.5, located on the far side of the TeV nebula from PSR J1907+0602, and the S74 molecular cloud on the nearer side which we discuss as potential birth sites

    HEALTHCARE PROCESS OF THE PATIENT WITH ACUTE PANCREATITIS

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    Akutni pankreatitis je nagla upala gušterače koja se može javiti u blagom ili teškom obliku. Ova nagla upala se u gotovo 80% prijema u bolnicu pripisuje postojanju žučnih kamenaca ili konzumaciji alkohola. Žučni kamenci kao uzrok budu 1,5 puta češći kod žena, dok se alkohol kao uzrok u muškaraca pojavljuje šest puta više nego kod žena. Žučni kamenci najčešće začepe otvor pankreatičnog voda ili se na neko vrijeme zaustave u Oddijevu sfinkteru uzrokujući time upalu dok svakodnevna konzumacija alkohola također može dovesti do začepljenja malih vodova. Jaki bolovi se javljaju najčešće naglo nakon konzumacije prekomjerne količine obroka ili alkohola u gornjem srednjem dijelu abdomena. Osim što je bol nagla, pacijenti je opisuju kao probadajuću bol koja se širi u leđa. Može se javiti mučnina kao i nagon na povraćanje, u većini slučajeva popratnu uz temperaturu. Bolesnik se javlja u hitni trakt radi jakih bolova koji se ne smanjuju te se podvrgava daljnjoj dijagnostici. Laboratorijskim pretragama ne može se potvrditi dijagnoza akutnog pankreatitisa ali povišenom razinom enzima gušterače tu dijagnozu možemo potkrijepiti. Daljnjim radiološkim pretragama (rendgen abdomena, kompjutorizirana tomografija) dokazuje se mogućnost postojanja žučnih kamenaca kao i promjene u veličini i strukturi gušterače. Sa utvrđenom dijagnozom akutnog pankreatitisa, osoba se zaprima na odjel gdje se prekida daljnji unos hrane i pića kako bi se smanjila daljnja proizvodnja enzima u gušterači. Svu potrebnu tekućinu i ostale hranjive tvari nadoknađuju se intravenskim putem. U cijelom procesu liječenja ključna je i medicinska sestra koja najprije može uočiti eventualne promjene koje se mogu javiti kod pacijenta, kao što su primjerice smanjeno mokrenje, otežano disanje te stagniranje ili pogoršavanje intenziteta boli unatoč primijenjenoj analgetskoj terapiji.Acute pancreatitis is a sudden pancreatic inflammation occurring in mild or severe form. This sudden inflammation in almost 80% of admission to the hospital is attributed to the existence of gallstones or drinking alcohol. The gallstones as a cause of Acute pancreatitis are 1.5 times more common in women, while alcohol as a cause is present men appears six times more than in women. Gallstones usually close the pancreatic opening or stop for a while in Oddies sphincter causing it to inflate ,while daily alcohol consumption also leads to clogging of small lines. Strong pain usually are occurring suddnely after eating excessive meals or presence of alcohol in the upper mid-section of the abdomen. Apart pain is acute, patients are describeing as a stabbing kind of pain that is spreading in their back. There can be nausea and vomiting, in most cases accompanied by temperature. The patient is coming to an emergency with severe pain that does not diminish and undergoes further diagnosis. Laboratory examinations can not confirm the diagnosis of acute pancreatitis but elevated pancreatic enzyme levels can be supported by this diagnosis. Further radiological examinations (X-ray abdomena, computerized tomography) are proveing the possibility of gallstones as well as changes in the size and structure of the pancreas. With established diagnosis of acute pancreatitis, a person is hospitalized in intensice care where further food and drink intake is discontinued in order to reduce further enzyme production in the pancreas. All the necessary fluid and other nutrients are compensated by the intravenous. Throughout the process of treatment, role of nurse is also crucial to notice possible changes that may occur in the patient, such as decreased urination, difficulty breathing and stagnation or aggravation of pain intensity despite analgesic therapy

    Fermi Large Area Telescope Observations of the Crab Pulsar and Nebula

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    We report on gamma-ray observations of the Crab Pulsar and Nebula using 8 months of survey data with the Fermi Large Area Telescope (LAT). The high quality light curve obtained using the ephemeris provided by the Nancay and Jodrell Bank radio telescopes shows two main peaks stable in phase with energy. The first gamma-ray peak leads the radio main pulse by (281 \pm 12 \pm 21) mus, giving new constraints on the production site of non-thermal emission in pulsar magnetospheres. The improved sensitivity and the unprecedented statistics afforded by the LAT enable precise measurement of the Crab Pulsar spectral parameters: cut-off energy at E_c = (5.8 \pm 0.5 \pm 1.2) GeV, spectral index of Gamma = (1.97 \pm 0.02 \pm 0.06) and integral photon flux above 100 MeV of (2.09 \pm 0.03 \pm 0.18) x 10^{-6} cm^{-2} s^{-1}. The first errors represent the statistical error on the fit parameters, while the second ones are the systematic uncertainties. Pulsed gamma-ray photons are observed up to ~ 20 GeV which precludes emission near the stellar surface, below altitudes of around 4 to 5 stellar radii in phase intervals encompassing the two main peaks. The spectrum of the nebula in the energy range 100 MeV - 300 GeV is well described by the sum of two power-laws of indices Gamma_{sync} = (3.99 \pm 0.12 \pm 0.08) and Gamma_{IC} = (1.64 \pm 0.05 \pm 0.07), corresponding to the falling edge of the synchrotron and the rising edge of the inverse Compton components, respectively. This latter, which links up naturally with the spectral data points of Cherenkov experiments, is well reproduced via inverse Compton scattering from standard Magnetohydrodynamics (MHD) nebula models, and does not require any additional radiation mechanism.Comment: 17 pages, 9 figures, Accepted for publications in Astrophysical Journa

    Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory

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    The azimuthal asymmetry in the risetime of signals in Auger surface detector stations is a source of information on shower development. The azimuthal asymmetry is due to a combination of the longitudinal evolution of the shower and geometrical effects related to the angles of incidence of the particles into the detectors. The magnitude of the effect depends upon the zenith angle and state of development of the shower and thus provides a novel observable, (secθ)max(\sec \theta)_\mathrm{max}, sensitive to the mass composition of cosmic rays above 3×10183 \times 10^{18} eV. By comparing measurements with predictions from shower simulations, we find for both of our adopted models of hadronic physics (QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass increases slowly with energy, as has been inferred from other studies. However, the mass estimates are dependent on the shower model and on the range of distance from the shower core selected. Thus the method has uncovered further deficiencies in our understanding of shower modelling that must be resolved before the mass composition can be inferred from (secθ)max(\sec \theta)_\mathrm{max}.Comment: Replaced with published version. Added journal reference and DO

    Calibration of the Logarithmic-Periodic Dipole Antenna (LPDA) Radio Stations at the Pierre Auger Observatory using an Octocopter

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    An in-situ calibration of a logarithmic periodic dipole antenna with a frequency coverage of 30 MHz to 80 MHz is performed. Such antennas are part of a radio station system used for detection of cosmic ray induced air showers at the Engineering Radio Array of the Pierre Auger Observatory, the so-called Auger Engineering Radio Array (AERA). The directional and frequency characteristics of the broadband antenna are investigated using a remotely piloted aircraft (RPA) carrying a small transmitting antenna. The antenna sensitivity is described by the vector effective length relating the measured voltage with the electric-field components perpendicular to the incoming signal direction. The horizontal and meridional components are determined with an overall uncertainty of 7.4^{+0.9}_{-0.3} % and 10.3^{+2.8}_{-1.7} % respectively. The measurement is used to correct a simulated response of the frequency and directional response of the antenna. In addition, the influence of the ground conductivity and permittivity on the antenna response is simulated. Both have a negligible influence given the ground conditions measured at the detector site. The overall uncertainties of the vector effective length components result in an uncertainty of 8.8^{+2.1}_{-1.3} % in the square root of the energy fluence for incoming signal directions with zenith angles smaller than 60{\deg}.Comment: Published version. Updated online abstract only. Manuscript is unchanged with respect to v2. 39 pages, 15 figures, 2 table

    Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory

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    We report a multi-resolution search for anisotropies in the arrival directions of cosmic rays detected at the Pierre Auger Observatory with local zenith angles up to 8080^\circ and energies in excess of 4 EeV (4×10184 \times 10^{18} eV). This search is conducted by measuring the angular power spectrum and performing a needlet wavelet analysis in two independent energy ranges. Both analyses are complementary since the angular power spectrum achieves a better performance in identifying large-scale patterns while the needlet wavelet analysis, considering the parameters used in this work, presents a higher efficiency in detecting smaller-scale anisotropies, potentially providing directional information on any observed anisotropies. No deviation from isotropy is observed on any angular scale in the energy range between 4 and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no other deviation from isotropy is observed for moments beyond the dipole one. The corresponding pp-values obtained after accounting for searches blindly performed at several angular scales, are 1.3×1051.3 \times 10^{-5} in the case of the angular power spectrum, and 2.5×1032.5 \times 10^{-3} in the case of the needlet analysis. While these results are consistent with previous reports making use of the same data set, they provide extensions of the previous works through the thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report Numbe

    Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory

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    On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within ±500\pm 500 s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.Comment: Published version. Added journal reference and DOI. Added Report Numbe
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