Optimization Study of Beam Position and Angular Jitter Independent Bunch Length Monitor for Awake Run 2

In this paper, a study using the Polarization Current Approach (PCA) model is performed to optimize the design of a short bunch length monitor using two dielectric radiators that produce coherent Cherenkov Diffraction Radiation (ChDR). The electromagnetic power emitted from each radiator is measuring a different part of the bunch spectrum using Schottky diodes. For various bunch lengths, the coherent ChDR spectrums are calculated to find the most suitable frequency bands for the detection system. ChDR intensities measured by each detector are estimated for different impact parameters to explore the dependence of bunch length monitor on beam position and angular jitter. It is found that, in the present configuration, the effects of beam position and angular jitter are negligibly small for bunch length measurement

Analytical and Numerical Characterization of Cherenkov Diffraction Radiation as a Longitudinal Electron Bunch Profile Monitor for AWAKE Run 2

In this paper, CST simulations of the coherent Cherenkov Diffraction Radiation with a range of parameters for different dielectric target materials and geometries are discussed and compared with the theoretical investigation of the Polarization Current Approach to design a prototype of a radiator for the bunch length/profile monitor for AWAKE Run 2. It was found that the result of PCA theory and CST simulation are consistent with each other regarding the shape of the emitted ChDR cone

Evaluation of CT vascularization patterns for survival prognosis in patients with hepatocellular carcinoma treated by conventional TACE

PURPOSE:Transarterial chemoembolization (TACE) is an established treatment for intermediate stage hepatocellular carcinoma (HCC). The aim of this retrospective study was to evaluate the power of lesion vascularization criteria based on computed tomography for prognosis of overall survival before initiation of treatment.METHODS:A total of 59 patients with intermediate stage HCC treated with TACE as first-line treatment were retrospectively evaluated. TACE procedures were performed using doxorubicin, cisplatin, and lipiodol. Response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) were used to determine the initial tumor response. Four vascularization patterns (VP) of the largest target lesion (homogeneous vascularization [VP1], homogeneous vascularization with additional arterial hypervascularization [VP2], heterogeneous vascularization with [VP3] and without zones of hypervascularization [VP4]) were assessed prior to the first TACE and correlated to survival.RESULTS:Kaplan-Meier analysis yielded a median overall survival of 608 days (standard error [SE], 120.5 days). Survival analysis showed significant differences depending on the vascularization patterns (P = 0.012; hazard ratio, 0.327): patients with homogeneously vascularized lesions (VP1, VP2) had a median overall survival of 1091 days (SE, 235.5 days). Patients with heterogeneous vascularization of the lesion (VP3 and VP4) showed a median overall survival of 508 days (SE, 113.9 days).CONCLUSION:The vascularization pattern of the largest HCC lesion is helpful for survival prognosis under TACE treatment and therefore has the potential to be used as an additional parameter for treatment stratification

Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene

<p>Abstract</p> <p>Background</p> <p>Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance.</p> <p>Methods</p> <p>Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the <it>EVC/EVC2 </it>locus. The results did not exclude linkage, so samples were sequenced for mutations.</p> <p>Results</p> <p>We identified a c.1868T>C mutation in <it>EVC</it>, which predicts p.L623P, and was homozygous in affected individuals.</p> <p>Conclusion</p> <p>We conclude that this <it>EVC </it>mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. <it>EVC </it>mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.</p

Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene

<p>Abstract</p> <p>Background</p> <p>Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance.</p> <p>Methods</p> <p>Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the <it>EVC/EVC2 </it>locus. The results did not exclude linkage, so samples were sequenced for mutations.</p> <p>Results</p> <p>We identified a c.1868T>C mutation in <it>EVC</it>, which predicts p.L623P, and was homozygous in affected individuals.</p> <p>Conclusion</p> <p>We conclude that this <it>EVC </it>mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. <it>EVC </it>mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.</p

Development of the self-modulation instability of a relativistic proton bunch in plasma

Self-modulation is a beam–plasma instability that is useful to drive large-amplitude wakefields with bunches much longer than the plasma skin depth. We present experimental results showing that, when increasing the ratio between the initial transverse size of the bunch and the plasma skin depth, the instability occurs later along the bunch, or not at all, over a fixed plasma length because the amplitude of the initial wakefields decreases. We show cases for which self-modulation does not develop, and we introduce a simple model discussing the conditions for which it would not occur after any plasma length. Changing bunch size and plasma electron density also changes the growth rate of the instability. We discuss the impact of these results on the design of a particle accelerator based on the self-modulation instability seeded by a relativistic ionization front, such as the future upgrade of the Advanced WAKefield Experiment

Phenotypic expansion in DDX3X - a common cause of intellectual disability in females

De novo variants in DDX3X account for 1-3% of unexplained intellectual disability (ID) cases and are amongst the most common causes of ID especially in females. Forty-seven patients (44 females, 3 males) have been described. We identified 31 additional individuals carrying 29 unique DDX3X variants, including 30 postnatal individuals with complex clinical presentations of developmental delay or ID, and one fetus with abnormal ultrasound findings. Rare or novel phenotypes observed include respiratory problems, congenital heart disease, skeletal muscle mitochondrial DNA depletion, and late-onset neurologic decline. Our findings expand the spectrum of DNA variants and phenotypes associated with DDX3X disorders

Simulation and experimental study of proton bunch self-modulation in plasma with linear density gradients

We present numerical simulations and experimental results of the self-modulation of a long proton bunch in a plasma with linear density gradients along the beam path. Simulation results agree with the experimental results reported [F. Braunmller, T. Nechaeva et al. (AWAKE Collaboration), Phys. Rev. Lett. 125, 264801 (2020)PRLTAO0031-900710.1103/PhysRevLett.125.264801]: with negative gradients, the charge of the modulated bunch is lower than with positive gradients. In addition, the bunch modulation frequency varies with gradient. Simulation results show that dephasing of the wakefields with respect to the relativistic protons along the plasma is the main cause for the loss of charge. The study of the modulation frequency reveals details about the evolution of the self-modulation process along the plasma. In particular for negative gradients, the modulation frequency across time-resolved images of the bunch indicates the position along the plasma where protons leave the wakefields. Simulations and experimental results are in excellent agreement

Monoallelic Variation in DHX9, the Gene Encoding the Dexh-Box Helicase DHX9, Underlies Neurodevelopment Disorders and Charcot-Marie-Tooth Disease

DExD/H-box RNA helicases (DDX/DHX) are encoded by a large paralogous gene family; in a subset of these human helicase genes, pathogenic variation causes neurodevelopmental disorder (NDD) traits and cancer. DHX9 encodes a BRCA1-interacting nuclear helicase regulating transcription, R-loops, and homologous recombination and exhibits the highest mutational constraint of all DDX/DHX paralogs but remains unassociated with disease traits in OMIM. Using exome sequencing and family-based rare-variant analyses, we identified 20 individuals with de novo, ultra-rare, heterozygous missense or loss-of-function (LoF) DHX9 variant alleles. Phenotypes ranged from NDDs to the distal symmetric polyneuropathy axonal Charcot-Marie-Tooth disease (CMT2). Quantitative Human Phenotype Ontology (HPO) analysis demonstrated genotype-phenotype correlations with LoF variants causing mild NDD phenotypes and nuclear localization signal (NLS) missense variants causing severe NDD. We investigated DHX9 variant-associated cellular phenotypes in human cell lines. Whereas wild-type DHX9 was restricted to the nucleus, NLS missense variants abnormally accumulated in the cytoplasm. Fibroblasts from an individual with an NLS variant also showed abnormal cytoplasmic DHX9 accumulation. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress. Two NDD-associated variants, p.Gly411Glu and p.Arg761Gln, altered DHX9 ATPase activity. The severe NDD-associated variant p.Arg141Gln did not affect DHX9 localization but instead increased R-loop levels and double-stranded DNA breaks. Dhx

Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state, ultimately shortening the period of neurogenesis. This study provides a mechanism for DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families