522 research outputs found

    Glauber theory of atomic hydrogen excitation by electron impact

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    Glauber approximation of differential and integrated atomic hydrogen excitation cross sections at electron impac

    Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

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    Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD

    Elastic and total reaction cross sections of oxygen isotopes in Glauber theory

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    We systematically calculate the total reaction cross sections of oxygen isotopes, 15−24^{15-24}O, on a 12^{12}C target at high energies using the Glauber theory. The oxygen isotopes are described with Slater determinants generated from a phenomenological mean-field potential. The agreement between theory and experiment is generally good, but a sharp increase of the reaction cross sections from ^{21}O to ^{23}O remains unresolved. To examine the sensitivity of the diffraction pattern of elastic scattering to the nuclear surface, we study the differential elastic-scattering cross sections of proton-^{20,21,23}O at the incident energy of 300 MeV by calculating the full Glauber amplitude.Comment: 9 pages, 8 figure

    MED12 regulates a transcriptional network of calcium-handling genes in the heart

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    The Mediator complex regulates gene transcription by linking basal transcriptional machinery with DNA-bound transcription factors. The activity of the Mediator complex is mainly controlled by a kinase submodule that is composed of 4 proteins, including MED12. Although ubiquitously expressed, Mediator subunits can differentially regulate gene expression in a tissue-specific manner. Here, we report that MED12 is required for normal cardiac function, such that mice with conditional cardiac-specific deletion of MED12 display progressive dilated cardiomyopathy. Loss of MED12 perturbs expression of calcium-handling genes in the heart, consequently altering calcium cycling in cardiomyocytes and disrupting cardiac electrical activity. We identified transcription factors that regulate expression of calcium-handling genes that are downregulated in the heart in the absence of MED12, and we found that MED12 localizes to transcription factor consensus sequences within calcium-handling genes. We showed that MED12 interacts with one such transcription factor, MEF2, in cardiomyocytes and that MED12 and MEF2 co-occupy promoters of calcium-handling genes. Furthermore, we demonstrated that MED12 enhances MEF2 transcriptional activity and that overexpression of both increases expression of calcium-handling genes in cardiomyocytes. Our data support a role for MED12 as a coordinator of transcription through MEF2 and other transcription factors. We conclude that MED12 is a regulator of a network of calcium-handling genes, consequently mediating contractility in the mammalian heart

    Final-state interactions in the response of nuclear matter

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    Final-state interactions in the response of a many-body system to an external probe delivering large momentum are normally described using the eikonal approximation, for the trajectory of the struck particle, and the frozen approximation, for the positions of the spectators. We propose a generalization of this scheme, in which the initial momentum of the struck particle is explicitly taken into account. Numerical calculations of the nuclear matter response at 1 <∣q∣<< |{\bf q}| < 2 GeV/c show that the inclusion of this momentum dependence leads to a sizable effect in the low energy tail. Possible implications for the analysis of existing electron-nucleus scattering data are discussed.Comment: 21 pages, 4 figure

    Diminished ovarian reserve in recurrent pregnancy loss : a systematic review and meta-analysis

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    Objective To evaluate the association between diminished ovarian reserve (DOR) in women at risk of recurrent pregnancy loss (RPL) using ovarian reserve tests. Design Systematic review and meta-analysis. Setting University medical schools. Patient(s) Women with a history of RPL. Intervention(s) Systematic reviews of major electronic databases (MEDLINE, EMBASE, Web of Science, and Scopus) for studies that evaluated the incidence of DOR in women with RPL. Main Outcome Measure(s) Association between RPL and DOR. Result(s) In studies up to May 2019 we assessed quality using the Newcastle-Ottawa Scale and meta-analyzed data using a random-effect model. We included 15 studies (n = 3,082 women) reporting on six ovarian reserve tests: antimĂŒllerian hormone [AMH], antral follicle count, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and FSH:LH ratio. More women with RPL seemed to have DOR compared with women who did not have RPL as measured by low AMH levels (odds ratio [OR] 2.77; 95% confidence interval [CI], 1.41–5.46) and AFC (OR 2.45; 95% CI, 1.16–5.19). Women with unexplained RPL also seemed to have a higher association with DOR compared with women whose RPL had a known etiology, as measured by low AMH levels (OR 3.23; 95% CI, 1.81–5.76). No statistically significant differences were found in the levels of any of the remaining ovarian reserve tests between those groups of women. Conclusion(s) There is an apparent association between DOR and RPL. Low AMH and AFC levels could predict higher odds for pregnancy loss, but more studies are needed to evaluate their prognostic value in the management of women with RPL

    Coherent QCD phenomena in the Coherent Pion-Nucleon and Pion-Nucleus Production of Two Jets at High Relative Momenta

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    We use QCD to compute the cross section for coherent production of a di-jet (treated as a qqˉq\bar q moving at high relative transverse momentum,Îșt\kappa_t ). In the target rest frame,the space-time evolution of this reaction is dominated by the process in which the high Îșt\kappa_t qqˉq\bar q component of the pion wave function is formed before reaching the target. It then interacts through two gluon exchange. In the approximation of keeping the leading order in powers of αs\alpha_s and all orders in αsln⁥(Îșt2/k02),\alpha_{s}\ln(\kappa_{t}^2/k_{0}^2), the amplitudes for other processes are shown to be smaller at least by a power of αs\alpha_{s}. The resulting dominant amplitude is proportional to z(1−z)Îșt−4z(1-z) \kappa_t^{-4} (zz is the fraction light-cone(+)momentum carried by the quark in the final state) times the skewed gluon distribution of the target. For the pion scattering by a nuclear target, this means that at fixed xN=2Îșt2/sx_{N}= 2\kappa_{t}^2/s (but Îșt2→∞\kappa_{t}^2\to \infty) the nuclear process in which there is only a single interaction is the most important one to contribute to the reaction. Thus in this limit color transparency phenomena should occur.These findings are in accord with E971 experiment at FNAL. We also re-examine a potentially important nuclear multiple scattering correction which is positive and ∝A1/3/Îșt4\propto A^{1/3}/\kappa_t^4. The meaning of the signal obtained from the experimental measurement of pion diffraction into two jets is also critically examined and significant corrections are identified.We show also that for values of Îșt\kappa_t achieved at fixed target energies, di-jet production by the e.m. field of the nucleus leads to an insignificant correction which gets more important as Îșt\kappa_t increases.Comment: 23 pages, 9 figure

    Macro optical projection tomography for large scale 3D imaging of plant structures and gene activity

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    Optical projection tomography (OPT) is a well-established method for visualising gene activity in plants and animals. However, a limitation of conventional OPT is that the specimen upper size limit precludes its application to larger structures. To address this problem we constructed a macro version called Macro OPT (M-OPT). We apply M-OPT to 3D live imaging of gene activity in growing whole plants and to visualise structural morphology in large optically cleared plant and insect specimens up to 60 mm tall and 45 mm deep. We also show how M-OPT can be used to image gene expression domains in 3D within fixed tissue and to visualise gene activity in 3D in clones of growing young whole Arabidopsis plants. A further application of M-OPT is to visualise plant-insect interactions. Thus M-OPT provides an effective 3D imaging platform that allows the study of gene activity, internal plant structures and plant-insect interactions at a macroscopic scale
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