A novel de novo HDAC8 missense mutation causing Cornelia de Lange syndrome

Background: Cornelia de Lange syndrome (CdLS) is a rare and clinically variable syndrome characterized by growth impairment, multi-organ anomalies, and a typical set of facial dysmorphisms. Here we describe a 2-year-old female child harboring a novel de novo missense variant in HDAC8, whose phenotypical score, according to the recent consensus on CdLS clinical diagnostic criteria, allowed the diagnosis of a non-classic CdLS. Methods: Clinical exome sequencing was performed on the trio, identifying a de novo heterozygous variant in HDAC8 (NM_018486; c. 356C>G p.Thr119Arg). Molecular modeling was performed to evaluate putative functional consequence of the HDAC8 protein. Results: The variant HDAC8 c.356C>G is classified as pathogenic following the ACMG (American College of Medical Genetics and Genomics)/AMP (Association for Molecular Pathology) guidelines. By molecular modeling, we confirmed the deleterious effect of this variant, since the amino acid change compromises the conformational flexibility of the HDAC8 loop required for optimal catalytic function. Conclusion: We described a novel Thr119Arg mutation in HDAC8 in a patient displaying the major phenotypic traits of the CdLS. Our results suggest that a modest change outside an active site is capable of triggering global structural changes that propagate through the protein scaffold to the catalytic site, creating de facto haploinsufficiency

Non-operatively managed small to medium-sized subscapularis tendon tears: MRI evaluation with a minimum of 5 years follow-up

Background Isolated or combined subscapularis (SSC) tendon tears are frequently found in patients with shoulder pain. The purpose of this study was to evaluate the structural changes associated with SSC tear in a consecutive series of patients with nonoperatively treated small size to midsize SSC tendon tears using magnetic resonance imaging (MRI). Methods In this retrospective case series, all patients with an isolated or combined SSC tendon tear treated nonoperatively between 1999 and 2019 were identified from our MRI and clinical databases. Twenty-one patients with a mean age of 52.6 years (range 26.6-64.8, standard deviation 9.3) with a second MRI scan at a minimum of 5 years of follow-up were enrolled. The mean follow-up was 8.6 years (range 5.6-12.6, standard deviation 1.8). Initial and last follow-up MRI scans were used to determine concomitant cuff lesions, size of the SSC tear, fatty infiltration of the SSC muscle, and biceps pathology. Results Five patients had an isolated SSC lesion; 7 patients had a concomitant tear of the supraspinatus, and 9 patients had a supraspinatus and anterior infraspinatus tendon tear. At diagnosis, 14 patients had a type 1 SSC lesion as classified by Lafosse et al, 4 patients had type 2, and 3 patients had type 3 lesions. Nineteen patients (90%) were found to have an SSC tear progression of at least one Lafosse grade (P < .001); however, no tear had progressed to an irreparable type lesion (defined as Lafosse type 5). In addition, the size of SSC tendon tears increased significantly from 75 mm2 to 228 mm2 (P < .001). At the final MRI scan, the grading of fatty infiltration increased by 1 grade in 4 cases and by 2 grades in 4 cases (P = .042). At the final follow-up, in eight patients, the condition of the long head of biceps tendon was unchanged from the initial MRI; in nine patients, there was a newly subluxated biceps tendon, and in 6 patients, there was a newly ruptured long head of biceps tendon (P < .001). Conclusion After a mean of 8.6 years, almost all nonoperatively treated SSC tendon tears had increased in size, but only one-third showed additional progression of muscle fatty degeneration on MRI scan. None of the SSC lesions became irreparable during the observation period

Configuration development study of the X-24C hypersonic research airplane

Bottom line results were made of a three-phase study to determine the feasibility of designing, building, and operating, and maintaining an air-launched high performance aircraft capable of cruising at speeds up to Mach 8 for short durations. The results show that Lockalloy heat-sink structure affords the capability for a 'work-horse' vehicle which can serve as an excellent platform for this research. It was further concluded that the performance of a blended wing body configuration surpassed that of a lifting body design for typical X-24C missions. The cost of a two vehicle program, less engines, B-52 modification and contractor support after delivery, can be kept within $70M (in Jan. 1976 dollars)

Model-based Aeroservoelastic Design and Load Alleviation of Large Wind Turbine Blades

This paper presents an aeroservoelastic modeling approach for dynamic load alleviation in large wind turbines with trailing-edge aerodynamic surfaces. The tower, potentially on a moving base, and the rotating blades are modeled using geometrically non-linear composite beams, which are linearized around reference conditions with arbitrarily-large structural displacements. Time-domain aerodynamics are given by a linearized 3-D unsteady vortexlattice method and the resulting dynamic aeroelastic model is written in a state-space formulation suitable for model reductions and control synthesis. A linear model of a single blade is used to design a Linear-Quadratic-Gaussian regulator on its root-bending moments, which is finally shown to provide load reductions of about 20% in closed-loop on the full wind turbine non-linear aeroelastic model

Quantum mechanics: Myths and facts

A common understanding of quantum mechanics (QM) among students and practical users is often plagued by a number of "myths", that is, widely accepted claims on which there is not really a general consensus among experts in foundations of QM. These myths include wave-particle duality, time-energy uncertainty relation, fundamental randomness, the absence of measurement-independent reality, locality of QM, nonlocality of QM, the existence of well-defined relativistic QM, the claims that quantum field theory (QFT) solves the problems of relativistic QM or that QFT is a theory of particles, as well as myths on black-hole entropy. The fact is that the existence of various theoretical and interpretational ambiguities underlying these myths does not yet allow us to accept them as proven facts. I review the main arguments and counterarguments lying behind these myths and conclude that QM is still a not-yet-completely-understood theory open to further fundamental research.Comment: 51 pages, pedagogic review, revised, new references, to appear in Found. Phy

Study of Leading Hadrons in Gluon and Quark Fragmentation

The study of quark jets in e+e- reactions at LEP has demonstrated that the hadronisation process is reproduced well by the Lund string model. However, our understanding of gluon fragmentation is less complete. In this study enriched quark and gluon jet samples of different purities are selected in three-jet events from hadronic decays of the Z collected by the DELPHI experiment in the LEP runs during 1994 and 1995. The leading systems of the two kinds of jets are defined by requiring a rapidity gap and their sum of charges is studied. An excess of leading systems with total charge zero is found for gluon jets in all cases, when compared to Monte Carlo Simulations with JETSET (with and without Bose-Einstein correlations included) and ARIADNE. The corresponding leading systems of quark jets do not exhibit such an excess. The influence of the gap size and of the gluon purity on the effect is studied and a concentration of the excess of neutral leading systems at low invariant masses (<~ 2 GeV/c^2) is observed, indicating that gluon jets might have an additional hitherto undetected fragmentation mode via a two-gluon system. This could be an indication of a possible production of gluonic states as predicted by QCD.Comment: 19 pages, 6 figures, Accepted by Phys. Lett.

Determination of the b quark mass at the M_Z scale with the DELPHI detector at LEP

An experimental study of the normalized three-jet rate of b quark events with respect to light quarks events (light= \ell \equiv u,d,s) has been performed using the CAMBRIDGE and DURHAM jet algorithms. The data used were collected by the DELPHI experiment at LEP on the Z peak from 1994 to 2000. The results are found to agree with theoretical predictions treating mass corrections at next-to-leading order. Measurements of the b quark mass have also been performed for both the b pole mass: M_b and the b running mass: m_b(M_Z). Data are found to be better described when using the running mass. The measurement yields: m_b(M_Z) = 2.85 +/- 0.18 (stat) +/- 0.13 (exp) +/- 0.19 (had) +/- 0.12 (theo) GeV/c^2 for the CAMBRIDGE algorithm. This result is the most precise measurement of the b mass derived from a high energy process. When compared to other b mass determinations by experiments at lower energy scales, this value agrees with the prediction of Quantum Chromodynamics for the energy evolution of the running mass. The mass measurement is equivalent to a test of the flavour independence of the strong coupling constant with an accuracy of 7 permil.Comment: 24 pages, 10 figures, Accepted by Eur. Phys. J.

Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance

This paper presents DELPHI measurements and interpretations of cross-sections, forward-backward asymmetries, and angular distributions, for the e+e- -> ffbar process for centre-of-mass energies above the Z resonance, from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are consistent with the predictions of the Standard Model and are used to study a variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering and several models which include physics beyond the Standard Model: the exchange of Z' bosons, contact interactions between fermions, the exchange of gravitons in large extra dimensions and the exchange of sneutrino in R-parity violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.

A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events

Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy and momentum constraint methods. The results are expressed as deviations from the nominal LEP centre-of-mass energy, measured using other techniques. The results are found to be compatible with the LEP Energy Working Group estimates for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.

Study of Inclusive J/psi Production in Two-Photon Collisions at LEP II with the DELPHI Detector

Inclusive J/psi production in photon-photon collisions has been observed at LEP II beam energies. A clear signal from the reaction gamma gamma -> J/psi+X is seen. The number of observed N(J/psi -> mu+mu-) events is 36 +/- 7 for an integrated luminosity of 617 pb^{-1}, yielding a cross-section of sigma(J/psi+X) = 45 +/- 9 (stat) +/- 17 (syst) pb. Based on a study of the event shapes of different types of gamma gamma processes in the PYTHIA program, we conclude that (74 +/- 22)% of the observed J/psi events are due to `resolved' photons, the dominant contribution of which is most probably due to the gluon content of the photon.Comment: 13 pages, 8 figures, Accepted by Phys. Lett.