Quantum Monte Carlo Calculations of Pion Scattering from Li

We show that the neutron and proton transition densities predicted by recent quantum Monte Carlo calculations for A=6,7 nuclei are consistent with pion scattering from 6Li and 7Li at energies near the Delta resonance. This has provided a microscopic understanding of the enhancement factors for quadrople excitations, which were needed to describe pion inelastic scattering within the nuclear shell model of Cohen and Kurath.Comment: 10 pages, REVTeX, 3 postscript figures; added calculation of elastic and inelastic pion scattering from 6Li at multiple energie

Atomic Parity Nonconservation: Electroweak Parameters and Nuclear Structure

There have been suggestions to measure atomic parity nonconservation (PNC) along an isotopic chain, by taking ratios of observables in order to cancel complicated atomic structure effects. Precise atomic PNC measurements could make a significant contribution to tests of the Standard Model at the level of one loop radiative corrections. However, the results also depend upon certain features of nuclear structure, such as the spatial distribution of neutrons in the nucleus. To examine the sensitivity to nuclear structure, we consider the case of Pb isotopes using various recent relativistic and non-relativistic nuclear model calculations. Contributions from nucleon internal weak structure are included, but found to be fairly negligible. The spread among present models in predicted sizes of nuclear structure effects may preclude using Pb isotope ratios to test the Standard Model at better than a one percent level, unless there are adequate independent tests of the nuclear models by various alternative strong and electroweak nuclear probes. On the other hand, sufficiently accurate atomic PNC experiments would provide a unique method to measure neutron distributions in heavy nuclei.Comment: 44 pages, INT Preprint DOE/ER/40561-050-INT92-00-1

Parity Violating Measurements of Neutron Densities

Parity violating electron nucleus scattering is a clean and powerful tool for measuring the spatial distributions of neutrons in nuclei with unprecedented accuracy. Parity violation arises from the interference of electromagnetic and weak neutral amplitudes, and the $Z^0$ of the Standard Model couples primarily to neutrons at low $Q^2$. The data can be interpreted with as much confidence as electromagnetic scattering. After briefly reviewing the present theoretical and experimental knowledge of neutron densities, we discuss possible parity violation measurements, their theoretical interpretation, and applications. The experiments are feasible at existing facilities. We show that theoretical corrections are either small or well understood, which makes the interpretation clean. The quantitative relationship to atomic parity nonconservation observables is examined, and we show that the electron scattering asymmetries can be directly applied to atomic PNC because the observables have approximately the same dependence on nuclear shape.Comment: 38 pages, 7 ps figures, very minor changes, submitted to Phys. Rev.

Microscopic calculations of medium effects for 200-MeV (p,p') reactions

We examine the quality of a G-matrix calculation of the effective nucleon-nucleon (NN) interaction for the prediction of the cross section and analyzing power for 200-MeV (p,p') reactions that populate natural parity states in $^{16}$O, $^{28}$Si, and $^{40}$Ca. This calculation is based on a one-boson-exchange model of the free NN force that reproduces NN observables well. The G-matrix includes the effects of Pauli blocking, nuclear binding, and strong relativistic mean-field potentials. The implications of adjustments to the effective mass ansatz to improve the quality of the approximation at momenta above the Fermi level will be discussed, along with the general quality of agreement to a variety of (p,p') transitions.Comment: 36 pages, TeX, 18 figure

Application of the New Classification on Patients with a Disorder of Sex Development in Indonesia

Disorder of sex development (DSD) patients in Indonesia most often do not receive a proper diagnostic evaluation and treatment. This study intended to categorize 88 Indonesian patients in accordance with the new consensus DSD algorithm. Diagnostic evaluation including clinical, hormonal, genetic, imaging, surgical, and histological parameters was performed. Fifty-three patients were raised as males, and 34 as females. Of 22 patients with 46, XX DSD, 15 had congenital adrenal hyperplasia, while in one patient, an ovarian Leydig cell tumor was found. In all 58 46, XY DSD patients, 29 were suspected of a disorder of androgen action (12 with an androgen receptor mutation), and in 9, gonadal dysgenesis was found and, in 20, severe hypospadias e.c.i. Implementation of the current consensus statement in a resource-poor environment is very difficult. The aim of the diagnostic workup in developing countries should be to end up with an evidence-based diagnosis. This is essential to improve treatment and thereby to improve the patients' quality of life

Congenital deficiency reveals critical role of ISG15 in skin homeostasis

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15(-/-) dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. ISG15(-/-) fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15(-/-) fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15(-/-) 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-beta 1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets

High-Throughput Screening for Modulators of CFTR Activity Based on Genetically Engineered Cystic Fibrosis Disease-Specific iPSCs

Organotypic culture systems from disease-specific induced pluripotent stem cells (iPSCs) exhibit obvious advantages compared with immortalized cell lines and primary cell cultures, but implementation of iPSC-based high-throughput (HT) assays is still technically challenging. Here, we demonstrate the development and conduction of an organotypic HT Cl/I exchange assay using cystic fibrosis (CF) disease-specific iPSCs. The introduction of a halide-sensitive YFP variant enabled automated quantitative measurement of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function in iPSC-derived intestinal epithelia. CFTR function was partially rescued by treatment with VX-770 and VX-809, and seamless gene correction of the p.Phe508del mutation resulted in full restoration of CFTR function. The identification of a series of validated primary hits that improve the function of p.Phe508del CFTR from a library of 42,500 chemical compounds demonstrates that the advantages of complex iPSC-derived culture systems for disease modeling can also be utilized for drug screening in a true HT format

Scale-invariance of galaxy clustering

Some years ago we proposed a new approach to the analysis of galaxy and cluster correlations based on the concepts and methods of modern statistical Physics. This led to the surprising result that galaxy correlations are fractal and not homogeneous up to the limits of the available catalogs. The usual statistical methods, which are based on the assumption of homogeneity, are therefore inconsistent for all the length scales probed so far, and a new, more general, conceptual framework is necessary to identifythe real physical properties of these structures. In the last few years the 3-d catalogs have been significatively improved and we have extended our methods to the analysis of number counts and angular catalogs. This has led to a complete analysis of all the available data that we present in this review. The result is that galaxy structures are highly irregular and self-similar: all the available data are consistent with each other and show fractal correlations (with dimension $D \simeq 2$) up to the deepest scales probed so far (1000 \hmp) and even more as indicated from the new interpretation of the number counts. The evidence for scale-invariance of galaxy clustering is very strong up to 150 \hmp due to the statistical robustness of the data but becomes progressively weaker (statistically) at larger distances due to the limited data. In These facts lead to fascinating conceptual implications about our knowledge of the universe and to a new scenario for the theoretical challenge in this field.Comment: Latex file 165 pages, 106 postscript figures. This paper is also available at http://www.phys.uniroma1.it/DOCS/PIL/pil.html To appear in Physics Report (Dec. 1997

SARS-CoV-2 variant Alpha has a spike-dependent replication advantage over the ancestral B.1 strain in human cells with low ACE2 expression

Epidemiological data demonstrate that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) Alpha and Delta are more transmissible, infectious, and pathogenic than previous variants. Phenotypic properties of VOC remain understudied. Here, we provide an extensive functional study of VOC Alpha replication and cell entry phenotypes assisted by reverse genetics, mutational mapping of spike in lentiviral pseudotypes, viral and cellular gene expression studies, and infectivity stability assays in an enhanced range of cell and epithelial culture models. In almost all models, VOC Alpha spread less or equally efficiently as ancestral (B.1) SARS-CoV-2. B.1. and VOC Alpha shared similar susceptibility to serum neutralization. Despite increased relative abundance of specific sgRNAs in the context of VOC Alpha infection, immune gene expression in infected cells did not differ between VOC Alpha and B.1. However, inferior spreading and entry efficiencies of VOC Alpha corresponded to lower abundance of proteolytically cleaved spike products presumably linked to the T716I mutation. In addition, we identified a bronchial cell line, NCI-H1299, which supported 24-fold increased growth of VOC Alpha and is to our knowledge the only cell line to recapitulate the fitness advantage of VOC Alpha compared to B.1. Interestingly, also VOC Delta showed a strong (595-fold) fitness advantage over B.1 in these cells. Comparative analysis of chimeric viruses expressing VOC Alpha spike in the backbone of B.1, and vice versa, showed that the specific replication phenotype of VOC Alpha in NCI-H1299 cells is largely determined by its spike protein. Despite undetectable ACE2 protein expression in NCI-H1299 cells, CRISPR/Cas9 knock-out and antibody-mediated blocking experiments revealed that multicycle spread of B.1 and VOC Alpha required ACE2 expression. Interestingly, entry of VOC Alpha, as opposed to B.1 virions, was largely unaffected by treatment with exogenous trypsin or saliva prior to infection, suggesting enhanced resistance of VOC Alpha spike to premature proteolytic cleavage in the extracellular environment of the human respiratory tract. This property may result in delayed degradation of VOC Alpha particle infectivity in conditions typical of mucosal fluids of the upper respiratory tract that may be recapitulated in NCI-H1299 cells closer than in highly ACE2-expressing cell lines and models. Our study highlights the importance of cell model evaluation and comparison for in-depth characterization of virus variant-specific phenotypes and uncovers a fine-tuned interrelationship between VOC Alpha- and host cell-specific determinants that may underlie the increased and prolonged virus shedding detected in patients infected with VOC Alpha