X-ray Emission from the Radio Jet in 3C 120

We report the discovery of X-ray emission from a radio knot at a projected distance of 25" from the nucleus of the Seyfert galaxy, 3C 120. The data were obtained with the ROSAT High Resolution Imager (HRI). Optical upper limits for the knot preclude a simple power law extension of the radio spectrum and we calculate some of the physical parameters for thermal bremsstrahlung and synchrotron self-Compton models. We conclude that no simple model is consistent with the data but if the knot contains small regions with flat spectra, these could produce the observed X-rays (via synchrotron emission) without being detected at other wavebands.Comment: 6 pages latex plus 3 ps/eps figures. Uses 10pt.sty and emulateapj.sty. Accepted for publication in the ApJ (6 Jan 99

Results from the Blazar Monitoring Campaign at the Whipple 10m Gamma-ray Telescope

In September 2005, the observing program of the Whipple 10 m gamma-ray telescope was redefined to be dedicated almost exclusively to AGN monitoring. Since then the five Northern Hemisphere blazars that had already been detected at Whipple are monitored routinely each night that they are visible. Thanks to the efforts of a large number of multiwavelength collaborators, the first year of this program has been very successful. We report here on the analysis of Markarian 421 observations taken from November, 2005 to May, 2006 in the gamma-ray, X-ray, optical and radio bands.Comment: 4 pages; contribution to the 30th International Cosmic Ray Conference, Merida, Mexico, July 200

Topological Phases near a Triple Degeneracy

We study the pattern of three state topological phases that appear in systems with real Hamiltonians and wave functions. We give a simple geometric construction for representing these phases. We then apply our results to understand previous work on three state phases. We point out that the ``mirror symmetry'' of wave functions noticed in microwave experiments can be simply understood in our framework.Comment: 4 pages, 1 figure, to appear in Phys. Rev. Let

The geometry of entanglement: metrics, connections and the geometric phase

Using the natural connection equivalent to the SU(2) Yang-Mills instanton on the quaternionic Hopf fibration of $S^7$ over the quaternionic projective space ${\bf HP}^1\simeq S^4$ with an $SU(2)\simeq S^3$ fiber the geometry of entanglement for two qubits is investigated. The relationship between base and fiber i.e. the twisting of the bundle corresponds to the entanglement of the qubits. The measure of entanglement can be related to the length of the shortest geodesic with respect to the Mannoury-Fubini-Study metric on ${\bf HP}^1$ between an arbitrary entangled state, and the separable state nearest to it. Using this result an interpretation of the standard Schmidt decomposition in geometric terms is given. Schmidt states are the nearest and furthest separable ones lying on, or the ones obtained by parallel transport along the geodesic passing through the entangled state. Some examples showing the correspondence between the anolonomy of the connection and entanglement via the geometric phase is shown. Connections with important notions like the Bures-metric, Uhlmann's connection, the hyperbolic structure for density matrices and anholonomic quantum computation are also pointed out.Comment: 42 page

Another look at the BL Lacertae flux and spectral variability

The GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT) monitored BL Lacertae in 2008-2009 at radio, near-IR, and optical frequencies. During this period, high-energy observations were performed by XMM-Newton, Swift, and Fermi. We analyse these data with particular attention to the calibration of Swift UV data, and apply a helical jet model to interpret the source broad-band variability. The GASP-WEBT observations show an optical flare in 2008 February-March, and oscillations of several tenths of mag on a few-day time scale afterwards. The radio flux is only mildly variable. The UV data from both XMM-Newton and Swift seem to confirm a UV excess that is likely caused by thermal emission from the accretion disc. The X-ray data from XMM-Newton indicate a strongly concave spectrum, as well as moderate flux variability on an hour time scale. The Swift X-ray data reveal fast (interday) flux changes, not correlated with those observed at lower energies. We compare the spectral energy distribution (SED) corresponding to the 2008 low-brightness state, which was characterised by a synchrotron dominance, to the 1997 outburst state, where the inverse-Compton emission was prevailing. A fit with an inhomogeneous helical jet model suggests that two synchrotron components are at work with their self inverse-Compton emission. Most likely, they represent the radiation from two distinct emitting regions in the jet. We show that the difference between the source SEDs in 2008 and 1997 can be explained in terms of pure geometrical variations. The outburst state occurred when the jet-emitting regions were better aligned with the line of sight, producing an increase of the Doppler beaming factor. Our analysis demonstrates that the jet geometry can play an extremely important role in the BL Lacertae flux and spectral variability.Comment: 12 pages, 10 figures, accepted for publication in A&

Secondary post-geniculate involvement in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B\u200a=\u200a0.002; P<0.05) and lack of recovery of visual acuity (B\u200a=\u200a0.060; P<0.01). Post-mortem investigation detected atrophy (41.9\% decrease of neuron soma size in the magnocellular layers and 44.7\% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5\% decrease of neuron density in the magnocellular layers and 28.7\% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99\%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons

Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study

BACKGROUND: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials. METHODS: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G&gt;A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a period of up to 52 months after onset of vision loss. A locally estimated scatterplot smoothing regression model was used to analyze changes in BCVA over time. Vision-related quality of life was reported using the visual function questionnaire-25 (VFQ-25). RESULTS: The population of MT-ND4 subjects enrolled in RESTORE was representative of the combined cohorts of RESCUE and REVERSE for mean age (35.1 years) and gender distribution (79% males). There was a progressive and sustained improvement of BCVA up to 52 months after the onset of vision loss. The final mean BCVA was 1.26 logarithm of the minimal angle of resolution 48 months after the onset of vision loss. The mean VFQ-25 composite score increased by 7 points compared with baseline. CONCLUSION: The treatment effect of lenadogene nolparvovec on BCVA and vision-related quality of life observed 96 weeks (2 years) after treatment in RESCUE and REVERSE was sustained at 3 years in RESTORE, with a maximum follow-up of 52 months (4.3 years) after the onset of vision loss

Multifrequency Photo-polarimetric WEBT Observation Campaign on the Blazar S5 0716+714: Source Microvariability and Search for Characteristic Timescales

Here we report on the results of the WEBT photo-polarimetric campaign targeting the blazar S5~0716+71, organized in March 2014 to monitor the source simultaneously in BVRI and near IR filters. The campaign resulted in an unprecedented dataset spanning $\sim 110$\,h of nearly continuous, multi-band observations, including two sets of densely sampled polarimetric data mainly in R filter. During the campaign, the source displayed pronounced variability with peak-to-peak variations of about $30\%$ and "bluer-when-brighter" spectral evolution, consisting of a day-timescale modulation with superimposed hourlong microflares characterized by $\sim 0.1$\,mag flux changes. We performed an in-depth search for quasi-periodicities in the source light curve; hints for the presence of oscillations on timescales of $\sim 3$\,h and $\sim 5$\,h do not represent highly significant departures from a pure red-noise power spectrum. We observed that, at a certain configuration of the optical polarization angle relative to the positional angle of the innermost radio jet in the source, changes in the polarization degree led the total flux variability by about 2\,h; meanwhile, when the relative configuration of the polarization and jet angles altered, no such lag could be noted. The microflaring events, when analyzed as separate pulse emission components, were found to be characterized by a very high polarization degree ($> 30\%$) and polarization angles which differed substantially from the polarization angle of the underlying background component, or from the radio jet positional angle. We discuss the results in the general context of blazar emission and energy dissipation models.Comment: 16 pages, 17 Figures; ApJ accepte

Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison

Objective: This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies. Design: A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2-ND4 vs. 11 pooled NH studies used as an external control. Subjects: The LHON subjects carried the m.11778G&gt;A ND4 mutation and were aged ≥15 years at onset of vision loss. Methods: A total of 76 subjects received a single intravitreal rAAV2/2-ND4 injection in one eye and sham injection in the fellow eye within 1 year after vision loss in REVERSE and RESCUE. Both eyes were considered as treated due to the rAAV2/2-ND4 treatment efficacy observed in the contralateral eyes. Best corrected visual acuity (BCVA) from REVERSE, RESCUE, and CLIN06 up to 4.3 years after vision loss was compared to the visual acuity of 208 NH subjects matched for age and ND4 genotype. The NH subjects were from a LHON registry (REALITY) and from 10 NH studies. A locally estimated scatterplot smoothing (LOESS), non-parametric, local regression model was used to modelize visual acuity curves over time, and linear mixed model was used for statistical inferences. Main Outcome Measures: The main outcome measure was evolution of visual acuity from 12 months after vision loss, when REVERSE and RESCUE patients had been treated with rAAV2/2-ND4. Results: The LOESS curves showed that the BCVA of the treated patients progressively improved from month 12 to 52 after vision loss. At month 48, there was a statistically and clinically relevant difference in visual acuity of −0.33 logarithm of the minimal angle of resolution (LogMAR) (16.5 ETDRS letters equivalent) in favor of treated eyes vs. NH eyes (p &lt; 0.01). Most treated eyes (88.7%) were on-chart at month 48 as compared to 48.1% of the NH eyes (p &lt; 0.01). The treatment effect at last observation remained statistically and clinically significant when adjusted for age and duration of follow-up (−0.32 LogMAR, p &lt; 0.0001). Conclusions: The m.11778G&gt;A LHON patients treated with rAAV2/2-ND4 exhibited an improvement of visual acuity over more than 4 years after vision loss to a degree not demonstrated in NH studies. Clinical Trial Registration: NCT02652767, NCT02652780, NCT03406104, and NCT03295071