The formation of a Sn monolayer on Ge(1 0 0) studied at the atomic scale

The growth of multi-layer germanium-tin (GeSn) quantum wells offers an intriguing pathway towards the integration of lasers in a CMOS platform. An important step in growing high quality quantum well interfaces is the formation of an initial wetting layer. However, key atomic-scale details of this process have not previously been discussed. We use scanning tunneling microscopy combined with density functional theory to study the deposition of Sn on Ge(1 0 0) at room temperature over a coverage range of 0.01 to 1.24 monolayers. We demonstrate the formation of a sub-2% Ge content GeSn wetting layer from three atomic-scale characteristic ad-dimer structural components, and show that small quantities of Sn incorporate into the Ge surface forming two atomic configurations. The ratio of the ad-dimer structures changes with increasing Sn coverage, indicating a change in growth kinetics. At sub-monolayer coverage, the least densely packing ad-dimer structure is most abundant. As the layer closes, forming a two-dimensional wetting layer, the more densely packing ad-dimer structure become dominant. These results demonstrate the capability to form an atomically smooth wetting layer at room temperature, and provide critical atomic-scale insights for the optimization of growth processes of GeSn multi-quantum-wells to meet the quality requirements of optical GeSn-based devices

Modelling radiation-induced cell cycle delays

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and Environmental Biophysic

A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for {beta} subunit interaction

A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel {alpha} subunit. The mutation decreased modulation of the {alpha} subunit by {beta}1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of {beta}1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type{alpha} subunit with the {beta}1or {beta}3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for {beta} subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the {alpha} and {beta}1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility

Adjunctive brivaracetam and sustained seizure frequency reduction in very active focal epilepsy

Objective: This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add-On First Italian Network Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5–20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6. Results: A total of 994 participants were included. During the 1-year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5–20, and >20 seizures per month (p <.001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p <.001). SSR was reached by 51.2% and 26.5% participants with a history of 1–5 and ≥6 ASMs (p <.001); the corresponding rates of SSF were 24.7% and 4.5% (p <.001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p <.001), and in participants with history of ≥6 prior ASMs compared to those with history of 1–5 ASMs (19.6% vs. 12.2%, p =.002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs. Significance: The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy

Thermodynamic driving force in the formation of hexagonal-diamond Si and Ge nanowires

The metastable hexagonal-diamond phase of Si and Ge (and of SiGe alloys) displays superior optical properties with respect to the cubic-diamond one. Based on first-principle calculations we show that the surface energy of the typical facets exposed in Si and Ge nanowires is lower in the hexagonal-diamond phase than in the cubic one. By exploiting a synergic approach based also on a recent state-of-the-art interatomic potential and on a simple geometrical model, we investigate the relative stability of nanowires in the two phases up to few tens of nm in radius, highlighting the surface-related driving force and discussing its relevance in recent experiments. We also explore the stability of Si and Ge core-shell nanowires with hexagonal cores (made of GaP for Si nanowires, of GaAs for Ge nanowires). In this case, the stability of the hexagonal shell over the cubic one is also favored by the energy cost associated with the interface linking the two phases. Interestingly, our calculations indicate a critical radius of the hexagonal shell much lower than the one reported in recent experiments, indicating the presence of a large kinetic barrier allowing for the enlargement of the wire in a metastable phase

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure\u2010freedom, seizure response ( 65 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45 years (33\u201356) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for 65 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017). Conclusion: The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations

Domain wall dynamics and Barkhausen effect in metallic ferromagnetic materials. I. Theory

The Barkhausen effect (BE) in metallic ferromagnetic systems is theoretically investigated by a Langevin description of the stochastic motion of a domain wall in a randomly perturbed medium. BE statistical properties are calculated from approximate analytical solutions of the Fokker-Planck equation associated with the Langevin model, and from computer simulations of domain‐wall motion. It is predicted that the amplitude probability distribution P0(Φ) of the B flux rate Φ should obey the equation P0(Φ)∝Φ−1 exp(−Φ/〈Φ〉), with >0. This result implies scaling properties in the intermittent behavior of BE at low magnetization rates, which are described in terms of a fractal structure of fractal dimension D<1. Analytical expressions for the B power spectrum are also derived. Finally, the extension of the theory to the case where many domain walls participate in the magnetization process is discussed