Antiproliferative activity of yatein isolated from Austrocedrus chilensis against murine myeloma cells: Cytological studies and chemical investigations

Context: Fitzroya cupressoides (Molina) I. M. Johnst. and Austrocedrus chilensis (D. Don) Pic.Serm. & Bizzarri are two Chilean Cupressaceae that are naturally resistant to biodegradation. Secondary metabolites from these species display a variety of biological activities. Objective: To evaluate the antiproliferative activity of two lignans, a diterpene and a flavonol isolated from A. chilensis and F. cupressoides, to elucidate their cytological effects on P3X murine myeloma cells. Materials and methods: The antiproliferative activity of yatein, isotaxiresinol, ferruginol, and isorhamnetin was evaluated in vitro using the MTT assay. The effect of yatein at the cellular level, due to its high antiproliferative activity was evaluated. P3X cells treated for 24 h with 12.5 and 25 \u3bcg/mL of yatein were also examined at the cytological level using immunofluorescence and scanning and transmission electron microscopy. Results: Yatein, a lignan isolated from A. chilensis, potentially inhibited P3X murine myeloma cell proliferation, resulting in approximately 75% cell death in response to a 25 \u3bcg/mL treatment with the lignan. P3X cells lost membrane integrity at the nuclear and cytoplasmic levels, including organelles, in response to yatein treatment (12.5 \u3bcg/mL), and we observed changes in the cytoplasmic organization and distribution of microtubules. The other compounds tested had low activity. Discussion and conclusions: Yatein is a lignan precursor of podophyllotoxin, a key agent in anticancer drugs. Due to its structural similarities to podophyllotoxin, yatein could have similar cytoplasmic target(s), such as the microtubular apparatus. These findings suggest that yatein may be of potential pharmacological interest and warrants further investigation in human cell lines

The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR

Aberrant crossed corticospinal facilitation in muscles distant from a spinal cord injury.

Crossed facilitatory interactions in the corticospinal pathway are impaired in humans with chronic incomplete spinal cord injury (SCI). The extent to which crossed facilitation is affected in muscles above and below the injury remains unknown. To address this question we tested 51 patients with neurological injuries between C2-T12 and 17 age-matched healthy controls. Using transcranial magnetic stimulation we elicited motor evoked potentials (MEPs) in the resting first dorsal interosseous, biceps brachii, and tibialis anterior muscles when the contralateral side remained at rest or performed 70% of maximal voluntary contraction (MVC) into index finger abduction, elbow flexion, and ankle dorsiflexion, respectively. By testing MEPs in muscles with motoneurons located at different spinal cord segments we were able to relate the neurological level of injury to be above, at, or below the location of the motoneurons of the muscle tested. We demonstrate that in patients the size of MEPs was increased to a similar extent as in controls in muscles above the injury during 70% of MVC compared to rest. MEPs remained unchanged in muscles at and within 5 segments below the injury during 70% of MVC compared to rest. However, in muscles beyond 5 segments below the injury the size of MEPs increased similar to controls and was aberrantly high, 2-fold above controls, in muscles distant (>15 segments) from the injury. These aberrantly large MEPs were accompanied by larger F-wave amplitudes compared to controls. Thus, our findings support the view that corticospinal degeneration does not spread rostral to the lesion, and highlights the potential of caudal regions distant from an injury to facilitate residual corticospinal output after SCI

MAGIC Upper Limits for two Milagro-detected, Bright Fermi Sources in the Region of SNR G65.1+0.6

We report on the observation of the region around supernova remnant G65.1+0.6 with the stand-alone MAGIC-I telescope. This region hosts the two bright GeV gamma-ray sources 1FGL J1954.3+2836 and 1FGL J1958.6+2845. They are identified as GeV pulsars and both have a possible counterpart detected at about 35 TeV by the Milagro observatory. MAGIC collected 25.5 hours of good quality data, and found no significant emission in the range around 1 TeV. We therefore report differential flux upper limits, assuming the emission to be point-like (<0.1 deg) or within a radius of 0.3 deg. In the point-like scenario, the flux limits around 1 TeV are at the level of 3 % and 2 % of the Crab Nebula flux, for the two sources respectively. This implies that the Milagro emission is either extended over a much larger area than our point spread function, or it must be peaked at energies beyond 1 TeV, resulting in a photon index harder than 2.2 in the TeV band.Comment: 8 pages, 3 figures, 1 tabl

Simultaneous multi-frequency observation of the unknown redshift blazar PG 1553+113 in March-April 2008

The blazar PG 1553+113 is a well known TeV gamma-ray emitter. In this paper, we determine its spectral energy distribution using simultaneous multi-frequency data in order to study its emission processes. An extensive campaign was carried out between March and April 2008, where optical, X-ray, high-energy (HE) gamma-ray, and very-high-energy (VHE) gamma-ray data were obtained with the KVA, Abastumani, REM, RossiXTE/ASM, AGILE and MAGIC telescopes, respectively. This is the first simultaneous broad-band (i.e., HE+VHE) gamma-ray observation, though AGILE did not detect the source. We combine data to derive source's spectral energy distribution and interpret its double peaked shape within the framework of a synchrotron self compton modelComment: 5 pages, 2 figures, publishe

A search for spectral hysteresis and energy-dependent time lags from X-ray and TeV gamma-ray observations of Mrk 421

Blazars are variable emitters across all wavelengths over a wide range of timescales, from months down to minutes. It is therefore essential to observe blazars simultaneously at different wavelengths, especially in the X-ray and gamma-ray bands, where the broadband spectral energy distributions usually peak. In this work, we report on three "target-of-opportunity" (ToO) observations of Mrk 421, one of the brightest TeV blazars, triggered by a strong flaring event at TeV energies in 2014. These observations feature long, continuous, and simultaneous exposures with XMM-Newton (covering X-ray and optical/ultraviolet bands) and VERITAS (covering TeV gamma-ray band), along with contemporaneous observations from other gamma-ray facilities (MAGIC and Fermi-LAT) and a number of radio and optical facilities. Although neither rapid flares nor significant X-ray/TeV correlation are detected, these observations reveal subtle changes in the X-ray spectrum of the source over the course of a few days. We search the simultaneous X-ray and TeV data for spectral hysteresis patterns and time delays, which could provide insight into the emission mechanisms and the source properties (e.g. the radius of the emitting region, the strength of the magnetic field, and related timescales). The observed broadband spectra are consistent with a one-zone synchrotron self-Compton model. We find that the power spectral density distribution at $\gtrsim 4\times 10^{-4}$ Hz from the X-ray data can be described by a power-law model with an index value between 1.2 and 1.8, and do not find evidence for a steepening of the power spectral index (often associated with a characteristic length scale) compared to the previously reported values at lower frequencies.Comment: 45 pages, 15 figure

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum