PINK1 homozygous W437X mutation in a patient with apparent dominant transmission of parkinsonism.

We analyzed the PINK1 gene in 58 patients with early-onset Parkinsonism and detected the homozygous mutation W437X in 1 patient. The clinical phenotype was characterized by early onset (22 years of age), good re- sponse to levodopa, early fluctuations and dyskinesias, and psychiatric symptoms. The mother, heterozygote for W437X mutation, was affected by Parkinson’s disease and 3 further relatives were reported affected, according to an autosomal dominant transmission

Measuring the Three-Dimensional Structure of Galaxy Clusters. I. Application to a Sample of 25 Clusters

We discuss a method to constrain the intrinsic three-dimensionale shapes of galaxy clusters by combining X-Ray and Sunyaev-Zeldovich observations. The method is applied to a sample of 25 X-Ray selected clusters, with measured Sunyaev-Zeldovich temperature decrements. The sample turns out to be slightly biased, with strongly elongated clusters preferentially aligned along the line of sight. This result demonstrates that X-Ray selected cluster samples may be affected by morphological and orientation effects even if a relatively high threshold signal-to-noise ratio is used to select the sample. A large majority of the clusters in our sample exhibit a marked triaxial structure, with prolate-like shapes being slightly more likely than oblate-like ones; the spherical hypothesis is strongly rejected for most sample members. Cooling flow clusters do not show preferentially regular morphologies.Comment: 13 pages, 9 figures. Accepted by Ap

Influence of rotational force fields on the determination of the work done on a driven Brownian particle

For a Brownian system the evolution of thermodynamic quantities is a stochastic process. In particular, the work performed on a driven colloidal particle held in an optical trap changes for each realization of the experimental manipulation, even though the manipulation protocol remains unchanged. Nevertheless, the work distribution is governed by established laws. Here, we show how the measurement of the work distribution is influenced by the presence of rotational, i.e. nonconservative, radiation forces. Experiments on particles of different materials show that the rotational radiation forces, and therefore their effect on the work distributions, increase with the particle refractive index.Comment: 12 pages, 4 figure

Measuring the Three-Dimensional Structure of Galaxy Clusters. II. Are clusters of galaxies oblate or prolate?

The intrinsic shape of galaxy clusters can be obtained through a combination of X-ray and Sunyaev-Zeldovich effect observations once cosmological parameters are assumed to be known. In this paper we discuss the feasibility of modelling galaxy clusters as either prolate or oblate ellipsoids. We analyze the intra-cluster medium distribution for a sample of 25 X-ray selected clusters, with measured Sunyaev-Zeldovich temperature decrements. A mixed population of prolate and oblate ellipsoids of revolution fits the data well, with prolate shapes preferred on a 60-76% basis. We observe an excess of clusters nearly aligned along the line of sight, with respect to what is expected from a randomly oriented cluster population, which might imply the presence of a selection bias in our sample. We also find signs that a more general triaxial morphology might better describe the morphology of galaxy clusters. Additional constraints from gravitational lensing could disentangle the degeneracy between an ellipsoidal and a triaxial morphology, and could also allow an unbiased determination of the Hubble constant.Comment: 9 pages, 8 figures, accepted for publication in Astrophys.

Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis

We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line.All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits.64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5 months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). No difference was found in patients treated with sunitinib (P = 0.370).A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Deletions in exon 11 seemed to be correlated with worse outcome in patients receiving imatinib-based second line

Rashba spin precession in quantum Hall edge channels

Quasi--one dimensional edge channels are formed at the boundary of a two-dimensional electron system subject to a strong perpendicular magnetic field. We consider the effect of Rashba spin--orbit coupling, induced by structural inversion asymmetry, on their electronic and transport properties. Both our analytical and numerical results show that spin--split quantum--Hall edge channels exhibit properties analogous to that of Rashba--split quantum wires. Suppressed backscattering and a long spin life time render these edge channels an ideal system for observing voltage--controlled spin precession. Based on the latter, we propose a magnet--less spin--dependent electron interferometer.Comment: 7 pages, 6 figure

Dynamic correlations in symmetric electron-electron and electron-hole bilayers

The ground-state behavior of the symmetric electron-electron and electron-hole bilayers is studied by including dynamic correlation effects within the quantum version of Singwi, Tosi, Land, and Sjolander (qSTLS) theory. The static pair-correlation functions, the local-field correction factors, and the ground-state energy are calculated over a wide range of carrier density and layer spacing. The possibility of a phase transition into a density-modulated ground state is also investigated. Results for both the electron-electron and electron-hole bilayers are compared with those of recent diffusion Monte Carlo (DMC) simulation studies. We find that the qSTLS results differ markedly from those of the conventional STLS approach and compare in the overall more favorably with the DMC predictions. An important result is that the qSTLS theory signals a phase transition from the liquid to the coupled Wigner crystal ground state, in both the electron-electron and electron-hole bilayers, below a critical density and in the close proximity of layers (d <~ r_sa_0^*), in qualitative agreement with the findings of the DMC simulations.Comment: 13 pages, 11 figures, 2 table

Critical points of maximal D=8 gauged supergravities

We study the general deformations of maximal eight-dimensional supergravity by using the embedding tensor approach. The scalar potential induced by these gaugings is determined. Subsequently, by combining duality covariance arguments and algebraic geometry techniques, we find the complete set of critical points of the scalar potential. Remarkably, up to SO(2) X SO(3) rotations there turns out to be a unique theory admitting extrema. The gauge group of the theory is CSO(2,0,1).Comment: 14 pages. v2: minor changes - published versio

Moving forward through the in silico modeling of tuberculosis : a further step with UISS-TB

In 2018, about 10 million people were found infected by tuberculosis, with approximately 1.2 million deaths worldwide. Despite these numbers have been relatively stable in recent years, tuberculosis is still considered one of the top 10 deadliest diseases worldwide. Over the years, Mycobacterium tuberculosis has developed a form of resistance to first-line tuberculosis treatments, specifically to isoniazid, leading to multi-drug-resistant tuberculosis. In this context, the EU and Indian DBT funded project STriTuVaD-In Silico Trial for Tuberculosis Vaccine Development-is supporting the identification of new interventional strategies against tuberculosis thanks to the use of Universal Immune System Simulator (UISS), a computational framework capable of predicting the immunity induced by specific drugs such as therapeutic vaccines and antibiotics. Here, we present how UISS accurately simulates tuberculosis dynamics and its interaction within the immune system, and how it predicts the efficacy of the combined action of isoniazid and RUTI vaccine in a specific digital population cohort. Specifically, we simulated two groups of 100 digital patients. The first group was treated with isoniazid only, while the second one was treated with the combination of RUTI vaccine and isoniazid, according to the dosage strategy described in the clinical trial design. UISS-TB shows to be in good agreement with clinical trial results suggesting that RUTI vaccine may favor a partial recover of infected lung tissue. In silico trials innovations represent a powerful pipeline for the prediction of the effects of specific therapeutic strategies and related clinical outcomes. Here, we present a further step in UISS framework implementation. Specifically, we found that the simulated mechanism of action of RUTI and INH are in good alignment with the results coming from past clinical phase IIa trials