Optical Imaging and Spectroscopic Observation of the Galactic Supernova Remnant G85.9-0.6

Optical CCD imaging with H$\alpha$ and [SII] filters and spectroscopic observations of the galactic supernova remnant G85.9-0.6 have been performed for the first time. The CCD image data are taken with the 1.5m Russian-Turkish Telescope (RTT150) at TUBITAK National Observatory (TUG) and spectral data are taken with the Bok 2.3 m telescope on Kitt Peak, AZ. The images are taken with narrow-band interference filters H$\alpha$, [SII] and their continuum. [SII]/H$\alpha$ ratio image is performed. The ratio obtained from [SII]/H$\alpha$ is found to be $\sim$0.42, indicating that the remnant interacts with HII regions. G85.9-0.6 shows diffuse-shell morphology. [SII]$\lambda\lambda 6716/6731$ average flux ratio is calculated from the spectra, and the electron density $N_{e}$ is obtained to be 395 $cm^{-3}$. From [OIII]/H$\beta$ ratio, shock velocity has been estimated, pre-shock density of $n_{c}=14$ $cm^{-3}$, explosion energy of $E=9.2\times10^{50}$ ergs, interstellar extinction of $E(B-V)=0.28$, and neutral hydrogen column density of $N(HI)=1.53\times10^{21}$ $cm^{-2}$ are reported.Comment: 20 pages, 4 tables, 4 figures. Accepted for publication in Astrophysics & Space Scienc

RXTE Studies of Long-Term X-ray Spectral Variations in 4U 1820-30

We present the results of detailed spectral studies of the ultra-compact low mass X-ray binary (LMXB) 4U 1820-30 carried out with the Rossi X-ray Timing Explorer (RXTE) during 1996-7. 4U 1820-30 is an ``atoll'' source X-ray burster (XRB) located in the globular cluster NGC 6624. It is known to have an 11 minute binary period and a ~176 day modulation in its 2--12 keV flux. Observations were made with the PCA and HEXTE instruments on RXTE at roughly one-month intervals to sample this long-term period and study flux-related spectral changes. There are clear correlations between our fitted spectral parameters and both the broad-band (2--50 keV) flux and the position in the color-color diagram, as described by the parameter S_a introduced by Mendez et al. (1999). In addition, we find a strong correlation between the position in the color-color diagram and the frequencies of the kilohertz quasi-periodic oscillations (kHz QPOs) reported by Zhang et al. (1998). This lends further support to the notion that evidence for the last stable orbit in the accretion disk of 4U 1820-30 has been observed. For a model consisting of Comptonization of cool photons by hot electrons plus an additional blackbody component, we report an abrupt change in the spectral parameters at the same accretion rate at which the kHz QPOs disappear. For a model consisting of a multicolor disk blackbody plus a cut-off power law, we find that the inner disk radius reaches a minimum at the same accretion rate at which the kHz QPO frequency saturates, as expected if the disk reaches the last stable orbit. Both models face theoretical and observational problems when interpreted physically for this system.Comment: 39 pages, 11 figures, accepted to the Astrophysical Journa

Possible evolution of dim radio quiet neutron star 1E 1207.4-5209 based on a B-decay model

Dim radio-quiet neutron star (DRQNS) 1E 1207.4-5209 is one of the most heavily examined isolated neutron stars. Wide absorption lines were observed in its spectrum obtained by both XMM-Newton and Chandra X-ray satellites. These absorption lines can be interpreted as a principal frequency centered at 0.7 keV and its harmonics at 1.4, 2.1 and possibly 2.8 keV. The principal line can be formed by resonant proton cyclotron scattering leading to a magnetic field which is two orders of magnitude larger than the perpendicular component of the surface dipole magnetic field (B) found from the rotation period (P) and the time rate of change in the rotation period (\.{P}) of 1E 1207.4-5209. Besides, age of the supernova remnant (SNR) G296.5+10.0 which is physically connected to 1E 1207.4-5209 is two orders of magnitude smaller than the characteristic age ($\tau$=P/2\.{P}) of the neutron star. These huge differences between the magnetic field values and the ages can be explained based on a B-decay model. If the decay is assumed to be exponential, the characteristic decay time turns out to be several thousand years which is three orders of magnitude smaller than the characteristic decay time of radio pulsars represented in an earlier work. The lack of detection of radio emission from DRQNSs and the lack of point sources and pulsar wind nebulae in most of the observed SNRs can also be partly explained by such a very rapid exponential decay. The large difference between the characteristic decay times of DRQNSs and radio pulsars must be related to the differences in the magnetic fields, equation of states and masses of these isolated neutron stars.Comment: 13 pages, 1 figur

MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome).

BACKGROUND: Putative nucleotidyltransferase MAB21L1 is a member of an evolutionarily well-conserved family of the male abnormal 21 (MAB21)-like proteins. Little is known about the biochemical function of the protein; however, prior studies have shown essential roles for several aspects of embryonic development including the eye, midbrain, neural tube and reproductive organs. OBJECTIVE: A homozygous truncating variant in MAB21L1 has recently been described in a male affected by intellectual disability, scrotal agenesis, ophthalmological anomalies, cerebellar hypoplasia and facial dysmorphism. We employed a combination of exome sequencing and homozygosity mapping to identify the underlying genetic cause in subjects with similar phenotypic features descending from five unrelated consanguineous families. RESULTS: We identified four homozygous MAB21L1 loss of function variants (p.Glu281fs*20, p.Arg287Glufs*14 p.Tyr280* and p.Ser93Serfs*48) and one missense variant (p.Gln233Pro) in 10 affected individuals from 5 consanguineous families with a distinctive autosomal recessive neurodevelopmental syndrome. Cardinal features of this syndrome include a characteristic facial gestalt, corneal dystrophy, hairy nipples, underdeveloped labioscrotal folds and scrotum/scrotal agenesis as well as cerebellar hypoplasia with ataxia and variable microcephaly. CONCLUSION: This report defines an ultrarare but clinically recognisable Cerebello-Oculo-Facio-Genital syndrome associated with recessive MAB21L1 variants. Additionally, our findings further support the critical role of MAB21L1 in cerebellum, lens, genitalia and as craniofacial morphogenesis

Nuclear Inelastic X-Ray Scattering of FeO to 48 GPa

The partial density of vibrational states has been measured for Fe in compressed FeO (w\"ustite) using nuclear resonant inelastic x-ray scattering. Substantial changes have been observed in the overall shape of the density of states close to the magnetic transiton around 20 GPa from the paramagnetic (low pressure) to the antiferromagnetic (high pressure) state. Our data indicate a substantial softening of the aggregate sound velocities far below the transition, starting between 5 and 10 GPa. This is consistent with recent radial x-ray diffraction measurements of the elastic constants in FeO. The results indicate that strong magnetoelastic coupling in FeO is the driving force behind the changes in the phonon spectrum of FeO.Comment: 4 pages, 4 figure

Measuring velocity of sound with nuclear resonant inelastic x-ray scattering

Nuclear resonant inelastic x-ray scattering is used to measure the projected partial phonon density of states of materials. A relationship is derived between the low-energy part of this frequency distribution function and the sound velocity of materials. Our derivation is valid for harmonic solids with Debye-like low-frequency dynamics. This method of sound velocity determination is applied to elemental, composite, and impurity samples which are representative of a wide variety of both crystalline and noncrystalline materials. Advantages and limitations of this method are elucidated

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Mechanism of selective benzene hydroxylation catalyzed by iron-containing zeolites

A direct, catalytic conversion of benzene to phenol would have wide-reaching economic impacts. Fe zeolites exhibit a remarkable combination of high activity and selectivity in this conversion, leading to their past implementation at the pilot plant level. There were, however, issues related to catalyst deactivation for this process. Mechanistic insight could resolve these issues, and also provide a blueprint for achieving high performance in selective oxidation catalysis. Recently, we demonstrated that the active site of selective hydrocarbon oxidation in Fe zeolites, named α-O, is an unusually reactive Fe(IV)=O species. Here, we apply advanced spectroscopic techniques to determine that the reaction of this Fe(IV)=O intermediate with benzene in fact regenerates the reduced Fe(II) active site, enabling catalytic turnover. At the same time, a small fraction of Fe(III)-phenolate poisoned active sites form, defining a mechanism for catalyst deactivation. Density-functional theory calculations provide further insight into the experimentally defined mechanism. The extreme reactivity of α-O significantly tunes down (eliminates) the rate-limiting barrier for aromatic hydroxylation, leading to a diffusion-limited reaction coordinate. This favors hydroxylation of the rapidly diffusing benzene substrate over the slowly diffusing (but more reactive) oxygenated product, thereby enhancing selectivity. This defines a mechanism to simultaneously attain high activity (conversion) and selectivity, enabling the efficient oxidative upgrading of inert hydrocarbon substrates

Rare deleterious mutations of the gene EFR3A in autism spectrum disorders

Background: Whole-exome sequencing studies in autism spectrum disorder (ASD) have identified de novo mutations in novel candidate genes, including the synaptic gene Eighty-five Requiring 3A (EFR3A). EFR3A is a critical component of a protein complex required for the synthesis of the phosphoinositide PtdIns4P, which has a variety of functions at the neural synapse. We hypothesized that deleterious mutations in EFR3A would be significantly associated with ASD. Methods: We conducted a large case/control association study by deep resequencing and analysis of whole-exome data for coding and splice site variants in EFR3A. We determined the potential impact of these variants on protein structure and function by a variety of conservation measures and analysis of the Saccharomyces cerevisiae Efr3 crystal structure. We also analyzed the expression pattern of EFR3A in human brain tissue. Results: Rare nonsynonymous mutations in EFR3A were more common among cases (16 / 2,196 = 0.73%) than matched controls (12 / 3,389 = 0.35%) and were statistically more common at conserved nucleotides based on an experiment-wide significance threshold (P = 0.0077, permutation test). Crystal structure analysis revealed that mutations likely to be deleterious were also statistically more common in cases than controls (P = 0.017, Fisher exact test). Furthermore, EFR3A is expressed in cortical neurons, including pyramidal neurons, during human fetal brain development in a pattern consistent with ASD-related genes, and it is strongly co-expressed (P < 2.2 × 10−16, Wilcoxon test) with a module of genes significantly associated with ASD. Conclusions: Rare deleterious mutations in EFR3A were found to be associated with ASD using an experiment-wide significance threshold. Synaptic phosphoinositide metabolism has been strongly implicated in syndromic forms of ASD. These data for EFR3A strengthen the evidence for the involvement of this pathway in idiopathic autism