Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.

Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients

Ultra-heavy cosmic-ray science--Are r-process nuclei in the cosmic rays produced in supernovae or binary neutron star mergers?

The recent detection of 60Fe in the cosmic rays provides conclusive evidence that there is a recently synthesized component (few MY) in the GCRs (Binns et al. 2016). In addition, these nuclei must have been synthesized and accelerated in supernovae near the solar system, probably in the Sco-Cen OB association subgroups, which are about 100 pc distant from the Sun. Recent theoretical work on the production of r-process nuclei appears to indicate that it is difficult for SNe to produce the solar system abundances relative to iron of r-process elements with high atomic number (Z), including the actinides (Th, U, Np, Pu, and Cm). Instead, it is believed by many that the heaviest r-process nuclei, or perhaps even all r-process nuclei, are produced in binary neutron star mergers. Since we now know that there is at least a component of the GCRs that has been recently synthesized and accelerated, models of r-process production by SNe and BNSM can be tested by measuring the relative abundances of these ultra-heavy r-process nuclei, and especially the actinides, since they are radioactive and provide clocks that give the time interval from nucleosynthesis to detection at Earth. Since BNSM are believed to be much less frequent in our galaxy than SNe (roughly 1000 times less frequent, the ratios of the actinides, each with their own half-life, will enable a clear determination of whether the heaviest r-process nuclei are synthesized in SNe or in BNSM. In addition, the r-process nuclei for the charge range from 34 to 82 can be used to constrain models of r-process production in BNSM and SNe. Thus, GCRs become a multi-messenger component in the study of BNSM and SNe.Comment: Astro2020 Science White Pape

Two dimensional Sen connections in general relativity

The two dimensional version of the Sen connection for spinors and tensors on spacelike 2-surfaces is constructed. A complex metric $\gamma_{AB}$ on the spin spaces is found which characterizes both the algebraic and extrinsic geometrical properties of the 2-surface $\$$. The curvature of the two dimensional Sen operator $\Delta_e$ is the pull back to $\$$ of the anti-self-dual part of the spacetime curvature while its `torsion' is a boost gauge invariant expression of the extrinsic curvatures of $\$$. The difference of the 2 dimensional Sen and the induced spin connections is the anti-self-dual part of the `torsion'. The irreducible parts of $\Delta_e$ are shown to be the familiar 2-surface twistor and the Weyl--Sen--Witten operators. Two Sen--Witten type identities are derived, the first is an identity between the 2 dimensional twistor and the Weyl--Sen--Witten operators and the integrand of Penrose's charge integral, while the second contains the `torsion' as well. For spinor fields satisfying the 2-surface twistor equation the first reduces to Tod's formula for the kinematical twistor.Comment: 14 pages, Plain Tex, no report numbe

XMM-Newton observations of the ultra-compact binary RX J1914+24

We present XMM-Newton observations of the 569 sec period system RX J1914+24 (V407 Vul). This period is believed to represent the binary orbital period making it an ultra-compact binary system. By comparing the phase of the rise to maximum X-ray flux at various epochs (this includes observations made using ROSAT, ASCA and Chandra) we find that the system is spinning up at a rate of 3.17+/-0.07x10^{-12} s/s. We find that the spectra softens as the X-ray flux declines towards the off-phase of the 569 sec period. Further, the spectra are best fitted by an absorbed blackbody component together with a broad emission feature around 0.59keV. This emission feature is most prominent at the peak of the on-phase. We speculate on its origin.Comment: Accepted by MNRA

UVES/VLT high resolution spectroscopy of GRB 050730 afterglow: probing the features of the GRB environment

We analyze high resolution spectroscopic observations of the optical afterglow of GRB050730, obtained with UVES@VLT about hours after the GRB trigger. The spectrum shows that the ISM of the GRB host galaxy at z = 3.967 is complex, with at least five components contributing to the main absorption system. We detect strong CII*, SiII*, OI* and FeII* fine structure absorption lines associated to the second and third component. For the first three components we derive information on the relative distance from the site of the GRB explosion. Component 1, which has the highest redshift, does not present any fine structure nor low ionization lines; it only shows very high ionization features, such as CIV and OVI, suggesting that this component is very close to the GRB site. From the analysis of low and high ionization lines and fine structure lines, we find evidences that the distance of component 2 from the site of the GRB explosion is 10-100 times smaller than that of component 3. We evaluated the mean metallicity of the z=3.967 system obtaining values about 0.01 of the solar metallicity or less. However, this should not be taken as representative of the circumburst medium, since the main contribution to the hydrogen column density comes from the outer regions of the galaxy while that of the other elements presumably comes from the ISM closer to the GRB site. Furthermore, difficulties in evaluating dust depletion correction can modify significantly these values. The mean [C/Fe] ratio agrees well with that expected by single star-formation event models. Interestingly the [C/Fe] of component 2 is smaller than that of component 3, in agreement with GRB dust destruction scenarios, if component 2 is closer than component 3 to the GRB site.Comment: 11 pages, 15 postscript figures, accepted for pubblication in A&

High-resolution mapping of the physical conditions in two nearby active galaxies based on 12CO(1-0), (2-1) and (3-2) lines

We present a detailed analysis of high resolution observations of the three lowest CO transitions in two nearby active galaxies, NGC4569 and NGC4826. The CO(1-0) and (2-1) lines were observed with the Plateau de Bure Interferometer and the CO(3-2) line with the Submillimeter Array. Combining these data allows us to compare the emission in the three lines and to map the line ratios, R21=I_{CO(2-1)}/I_{CO(1-0)} and R32=I_{CO(3-2)}/I_{CO(1-0)} at a resolution of ~2", i.e., a linear resolution of 160 pc for NGC4569 and 40 pc for NGC4826. In both galaxies the emission in the three lines is similarly distributed spatially and in velocity, and CO is less excited (R32<0.6) than in the Galactic Center or the centers of other active galaxies studied so far. According to a pseudo-LTE model the molecular gas in NGC4569 is cold and mainly optically thick in the CO(1-0) and (2-1) lines; less than 50% of the gas is optically thin in the CO(3-2) line. LVG modeling suggests the presence of an elongated ring of cold and dense gas coinciding with the ILR of the stellar bar. More excited gas is resolved in the circumnuclear disk of NGC4826. According to our pseudo-LTE model this corresponds to warmer gas with a ~50% of the CO(3-2) emission being optically thin. LVG modeling indicates the presence of a semicircular arc of dense and cold gas centered on the dynamical center and ~70 pc in radius. The gas temperature increases and its density decreases toward the center. A near side/far side asymmetry noticeable in the CO, R32 and Pa-alpha maps suggests that opacity effects play a role. Examining published CO maps of nearby active galaxies we find similar asymmetries suggesting that this could be a common phenomenon in active galaxies. These mainly qualitative results open new perspectives for the study of active galaxies with the future Atacama Large Millimeter/submillimeter Array.Comment: accepted for publication in A&

GRB 050904 at redshift 6.3: observations of the oldest cosmic explosion after the Big Bang

We present optical and near-infrared observations of the afterglow of the gamma-ray burst GRB 050904. We derive a photometric redshift z = 6.3, estimated from the presence of the Lyman break falling between the I and J filters. This is by far the most distant GRB known to date. Its isotropic-equivalent energy is 3.4x10^53 erg in the rest-frame 110-1100 keV energy band. Despite the high redshift, both the prompt and the afterglow emission are not peculiar with respect to other GRBs. We find a break in the J-band light curve at t_b = 2.6 +- 1.0 d (observer frame). If we assume this is the jet break, we derive a beaming-corrected energy E_gamma = (4-12)x10^51 erg. This limit shows that GRB 050904 is consistent with the Amati and Ghirlanda relations. This detection is consistent with the expected number of GRBs at z > 6 and shows that GRBs are a powerful tool to study the star formation history up to very high redshift.Comment: 3 figures, 5 pages, accepted for publication in A&A Letters. One figure added, minor modifications. Full author list in the pape

Gemini Imaging of Mid-IR Emission from the Nuclear Region of Centaurus A

We present high spatial resolution mid-IR images of the nuclear region of NGC 5128 (Centaurus A). Images were obtained at 8.8 micron, N-band (10.4 micron), and 18.3 micron using the mid-IR imager/spectrometer T-ReCS on Gemini South. These images show a bright unresolved core surrounded by low-level extended emission. We place an upper limit to the size of the unresolved nucleus of 3.2 pc (0.19") at 8.8 micron and 3.5 pc (0.21") at 18.3 micron at the level of the FWHM. The most likely source of nuclear mid-IR emission is from a dusty torus and possibly dusty narrow line region with some contribution from synchrotron emission associated with the jet as well as relatively minor starburst activity. Clumpy tori models are presented which predict the mid-IR size of this torus to be no larger than 0.05" (0.85pc). Surrounding the nucleus is extensive low-level mid-IR emission. Previously observed by ISO and Spitzer, this paper presents to date the highest spatial resolution mid-IR images of this extended near nuclear structure. Much of the emission is coincident with Pa-alpha sources seen by HST implying emission from star forming areas, however evidence for jet induced star formation, synchrotron emission from the jet, a nuclear bar/ring, and an extended dusty narrow emission line region is also discussed.Comment: 22 pages, 6 figures, accepted by Ap

Resolved photometry of extragalactic young massive star clusters

We present colour-magnitude diagrams (CMDs) for a sample of seven young massive clusters in the galaxies NGC 1313, NGC 1569, NGC 1705, NGC 5236 and NGC 7793. The clusters have ages in the range 5-50 million years and masses of 10^5 -10^6 Msun. Although crowding prevents us from obtaining photometry in the central regions of the clusters, we are still able to measure up to 30-100 supergiant stars in each of the richest clusters, along with the brighter main sequence stars. The resulting CMDs and luminosity functions are compared with photometry of artificially generated clusters, designed to reproduce the photometric errors and completeness as realistically as possible. In agreement with previous studies, our CMDs show no clear gap between the H-burning main sequence and the He-burning supergiant stars, contrary to predictions by common stellar isochrones. In general, the isochrones also fail to match the observed number ratios of red-to-blue supergiant stars, although the difficulty of separating blue supergiants from the main sequence complicates this comparison. In several cases we observe a large spread (1-2 mag) in the luminosities of the supergiant stars that cannot be accounted for by observational errors. This spread can be reproduced by including an age spread of 10-30 million years in the models. However, age spreads cannot fully account for the observed morphology of the CMDs and other processes, such as the evolution of interacting binary stars, may also play a role.Comment: 15 pages, 12 figures, accepted for publication in A&