We present high angular resolution (∼80 mas) ALMA continuum images of the SN 1987A system, together with CO J = 2 1, J = 6 5, and SiO J = 5 4 to J = 7 6 images, which clearly resolve the ejecta (dust ...continuum and molecules) and ring (synchrotron continuum) components. Dust in the ejecta is asymmetric and clumpy, and overall the dust fills the spatial void seen in H images, filling that region with material from heavier elements. The dust clumps generally fill the space where CO J = 6 5 is fainter, tentatively indicating that these dust clumps and CO are locationally and chemically linked. In these regions, carbonaceous dust grains might have formed after dissociation of CO. The dust grains would have cooled by radiation, and subsequent collisions of grains with gas would also cool the gas, suppressing the CO J = 6 5 intensity. The data show a dust peak spatially coincident with the molecular hole seen in previous ALMA CO J = 2 1 and SiO J = 5 4 images. That dust peak, combined with CO and SiO line spectra, suggests that the dust and gas could be at higher temperatures than the surrounding material, though higher density cannot be totally excluded. One of the possibilities is that a compact source provides additional heat at that location. Fits to the far-infrared-millimeter spectral energy distribution give ejecta dust temperatures of 18-23 K. We revise the ejecta dust mass to Mdust = 0.2-0.4 for carbon or silicate grains, or a maximum of <0.7 for a mixture of grain species, using the predicted nucleosynthesis yields as an upper limit.
Using techniques to target the liver, enhance gene expression, and avoid eliciting an immune response, the authors administered an adenovirus-associated virus containing the gene for factor IX (FIX) ...in six patients with hemophilia B. The result was either reduction or elimination of the need for FIX prophylaxis.
Hemophilia B is an X-linked bleeding disorder that results from a defect in the gene encoding coagulation factor IX (FIX), a serine protease that is critical for blood clotting. Persons with severe hemophilia B have functional FIX levels that are less than 1% of normal values and have frequent bleeding episodes, which are associated with crippling arthropathy and early death.
1
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Current treatment involves frequent intravenous injections of FIX protein concentrate (i.e., two to three times a week). However, this treatment is prophylactic rather than curative, is extremely expensive, and is associated with inhibitor formation. Somatic gene therapy for hemophilia . . .
We use a combined 1.2 Ms of NuSTAR observations of M31 to search for x-ray lines from sterile neutrino dark matter decay. For the first time in a NuSTAR analysis, we consistently take into account ...the signal contribution from both the focused and unfocused fields of view. We also reduce the modeling systematic uncertainty by performing spectral fits to each observation individually and statistically combining the results, instead of stacking the spectra. We find no evidence of unknown lines, and thus derive limits on the sterile neutrino parameters. Our results place stringent constraints for dark matter masses ≳12 keV, which reduces the available parameter space for sterile neutrino dark matter produced via neutrino mixing (e.g., in the νMSM) by approximately one-third. Additional NuSTAR observations, together with improved low-energy background modeling, could probe the remaining parameter space in the future. Lastly, we also report model-independent limits on generic dark matter decay rates and annihilation cross sections.
GEMINGA'S PUZZLING PULSAR WIND NEBULA Posselt, B.; Pavlov, G. G.; Slane, P. O. ...
The Astrophysical journal,
01/2017, Letnik:
835, Številka:
1
Journal Article
Recenzirano
Odprti dostop
ABSTRACT We report on six new Chandra observations of the Geminga pulsar wind nebula (PWN). The PWN consists of three distinct elongated structures-two 0.2 d 250 pc long lateral tails and a segmented ...axial tail of 0.05 d 250 pc length, where d 250 = d / ( 250 pc ) . The photon indices of the power-law spectra of the lateral tails, Γ 1 , are significantly harder than those of the pulsar ( Γ 1.5 ) and the axial tail ( Γ 1.6 ). There is no significant diffuse X-ray emission between the lateral tails-the ratio of the X-ray surface brightness between the south tail and this sky area is at least 12. The lateral tails apparently connect directly to the pulsar and show indications of moving footpoints. The axial tail comprises time-variable emission blobs. However, there is no evidence for constant or decelerated outward motion of these blobs. Different physical models are consistent with the observed morphology and spectra of the Geminga PWN. In one scenario, the lateral tails could represent an azimuthally asymmetric shell whose hard emission is caused by the Fermi acceleration mechanism of colliding winds. In another scenario, the lateral tails could be luminous, bent polar outflows, while the blobs in the axial tail could represent a crushed torus. In a resemblance to planetary magnetotails, the blobs of the axial tail might also represent short-lived plasmoids, which are formed by magnetic field reconnection in the relativistic plasma of the pulsar wind tail.
Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations ...have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
Background & Aims The epidemiology of Helicobacter pylori infection has changed with improvements in sanitation and methods of eradication. We performed a systematic review and meta-analysis to ...evaluate changes in the global prevalence of H pylori infection. Methods We performed a systematic search of the MEDLINE and EMBASE databases for studies of the prevalence of H pylori infection published from January 1, 1970 through January 1, 2016. We analyzed data based on United Nations geoscheme regions and individual countries. We used a random effects model to calculate pooled prevalence estimates with 95% confidence intervals (CIs), weighted by study size. We extrapolated 2015 prevalence estimates to obtain the estimated number of individuals with H pylori infection. Results Among 14,006 reports screened, we identified 263 full-text articles on the prevalence of H pylori infection; 184 were included in the final analysis, comprising data from 62 countries. Africa had the highest pooled prevalence of H pylori infection (70.1%; 95% CI, 62.6−77.7), whereas Oceania had the lowest prevalence (24.4%; 95% CI, 18.5−30.4). Among individual countries, the prevalence of H pylori infection varied from as low as 18.9% in Switzerland (95% CI, 13.1−24.7) to 87.7% in Nigeria (95% CI, 83.1−92.2). Based on regional prevalence estimates, there were approximately 4.4 billion individuals with H pylori infection worldwide in 2015. Conclusions In a systematic review and meta-analysis to assess the prevalence of H pylori infection worldwide, we observed large amounts of variation among regions—more than half the world’s population is infected. These data can be used in development of customized strategies for the global eradication.
The Falls Risk for Older People in the Community assessment (FROP-Com) was originally developed using 13 risk factors to identify the fall risks of community-dwelling older people. To suit the ...practical use in busy clinical settings, a brief version adopting 3 most fall predictive risk factors from the original FROP-Com, including the number of falls in the past 12 months, assistance required to perform domestic activities of daily living and observation of balance, was developed for screening purpose (FROP-Com screen). The objectives of this study were to investigate the inter-rater and test-retest reliability, concurrent and convergent validity, and minimum detectable change of the FROP-Com screen in community-dwelling people with stroke.
Community-dwelling people with stroke (n = 48) were recruited from a local self-help group, and community-dwelling older people (n = 40) were recruited as control subjects.
The FROP-Com screen exhibited moderate inter-rater (Intraclass correlation coefficient ICC2,1 = 0.79, 95% confidence interval CI: 0.65-0.87) and test-retest reliability (ICC3,1 = 0.70, 95% CI: 0.46-0.83) and weak associations with two balance measures, the Berg Balance Scale (BBS) (rho = -0.38, p = 0.008) and the Timed "Up & Go" (TUG) test (rho = 0.35, p = 0.016). The screen also exhibited a moderate association with the Chinese version of the Activities-specific Balance Confidence Scale (ABC-C) (ABC-C; rho = -0.65, p<0.001), a measure of subjective balance confidence.
The FROP-Com screen is a reliable clinical tool with convergent validity paralleled with subjective balance confidence measure that can be used in fall risk screening of community-dwelling people with stroke. However, one individual item, the observation of balance, will require additional refinement to improve the potential measurement error.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most massive stars end their lives in core-collapse supernova explosions and enrich the interstellar medium with explosively nucleosynthesized elements. Following core collapse, the explosion is ...subject to instabilities as the shock propagates outward through the progenitor star. Observations of the composition and structure of the innermost regions of a core-collapse supernova provide a direct probe of the instabilities and nucleosynthetic products. SN 1987A in the Large Magellanic Cloud is one of very few supernovae for which the inner ejecta can be spatially resolved but are not yet strongly affected by interaction with the surroundings. Our observations of SN 1987A with the Atacama Large Millimeter/submillimeter Array are of the highest resolution to date and reveal the detailed morphology of cold molecular gas in the innermost regions of the remnant. The 3D distributions of carbon and silicon monoxide (CO and SiO) emission differ, but both have a central deficit, or torus-like distribution, possibly a result of radioactive heating during the first weeks ("nickel heating"). The size scales of the clumpy distribution are compared quantitatively to models, demonstrating how progenitor and explosion physics can be constrained.
We analyze two dedicated NuSTAR observations with exposure ∼ 190 ks located ∼ 1 0 ° from the Galactic plane, one above and the other below, to search for x-ray lines from the radiative decay of ...sterile-neutrino dark matter. These fields were chosen to minimize astrophysical x-ray backgrounds while remaining near the densest region of the dark matter halo. We find no evidence of anomalous x-ray lines in the energy range 5–20 keV, corresponding to sterile neutrino masses 10–40 keV. Interpreted in the context of sterile neutrinos produced via neutrino mixing, these observations provide the leading constraints in the mass range 10–12 keV, improving upon previous constraints in this range by a factor ∼ 2 . We also compare our results to Monte Carlo simulations, showing that the fluctuations in our derived limit are not dominated by systematic effects. An updated model of the instrumental background, which is currently under development, will improve NuSTAR's sensitivity to anomalous x-ray lines, particularly for energies 3–5 keV.
Background and Aims
Mutations in the disheveled, Egl‐10 and pleckstrin domain‐containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. ...However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized.
Materials and Methods
We studied a kindred of familial focal epilepsy with variable foci using whole‐exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing.
Results
We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the
DEPDC5 gene.
Discussion and Conclusions
Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.
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