Universal radiation tolerant semiconductor.

Radiation tolerance is determined as the ability of crystalline materials to withstand the accumulation of the radiation induced disorder. Nevertheless, for sufficiently high fluences, in all by far known semiconductors it ends up with either very high disorder levels or amorphization. Here we show that gamma/beta (γ/ß) double polymorph Ga2O3 structures exhibit remarkably high radiation tolerance. Specifically, for room temperature experiments, they tolerate a disorder equivalent to hundreds of displacements per atom, without severe degradations of crystallinity; in comparison with, e.g., Si amorphizable already with the lattice atoms displaced just once. We explain this behavior by an interesting combination of the Ga- and O- sublattice properties in γ-Ga2O3. In particular, O-sublattice exhibits a strong recrystallization trend to recover the face-centered-cubic stacking despite the stronger displacement of O atoms compared to Ga during the active periods of cascades. Notably, we also explained the origin of the ß-to-γ Ga2O3 transformation, as a function of the increased disorder in ß-Ga2O3 and studied the phenomena as a function of the chemical nature of the implanted atoms. As a result, we conclude that γ/ß double polymorph Ga2O3 structures, in terms of their radiation tolerance properties, benchmark a class of universal radiation tolerant semiconductors.

Special Issue "ALD Technique for Functional Coatings of Nanostructured Materials".

Atomic layer deposition (ALD) is a vapor-phase technique that consists of the alternation of separated self-limiting surface reactions, which enable film thickness to be accurately controlled at the angstrom level, based on the former atomic layer epitaxy method [...].

Hypertrophic cardiomyopathy surgery: Perioperative anesthetic management with two different and combined techniques.

Hypertrophic cardiomyopathy (HOCM) is the most common genetic heart disorder and the most common cause of sudden cardiac death among young population and a major cause of disability for patients of any age. An extended transaortic septal myectomy is the definitive treatment. It is very important to have a good knowledge of the characteristic pathophysiology of the disease in order to optimize intraoperative treatment of these patients. We present a case of a 68-year old woman who underwent hypertrophic elective cardiomyopathy surgery. Anesthetic management is crucial to guarantee maximum safety, since HOCM has the capacity to produce hemodynamic events of such severity that put patient's life at risk. The use and combination of intraoperative transesophageal echocardiography (TEE) and direct measurement of the left ventricular outflow tract gradient provides vital information to ensure successful surgical outcome in patients with HOCM.

Respiratory and Hemodynamic Effects of Prophylactic Alveolar Recruitment During Liver Transplant: A Randomized Controlled Trial.

OBJECTIVES: Prolonged surgical retraction may cause atelectasis. We aimed to recruit collapsed alveoli, stepwise, monitored by lung dynamic compliance and observe effects on arterial oxygenation and systemic and graft hemodynamics. Secondarily, we observed alveolar recruitment effects on postoperative mechanical ventilation, international normalized ratio, and pulmonary complications. MATERIALS AND METHODS: For 58 recipients (1 excluded), randomized with optimal positive end-expiratory pressure (n = 28) versus control (fixed positive end-expiratory pressure, 5 cm H2O; n = 29), alveolar recruitment was initiated (pressure-controlled ventilation guided by lung dynamic compliance) to identify optimal conditions. Ventilation shifted to volume-control mode with 0.4 fraction of inspired oxygen, 6 mL/kg tidal volume, and 1:2 inspiratory-to-expiratory ratio. Alveolar recruitment was repeated postretraction and at intensive care unit admission. Primary endpoints were changes in lung dynamic compliance, arterial oxygenation, and hemodynamics (cardiac output, invasive arterial and central venous pressures, graft portal and hepatic vein flows). Secondary endpoints were mechanical ventilation period and postoperative international normalized ratio, aspartate/alanine aminotransferases, lactate, and pulmonary complications. RESULTS: Alveolar recruitment increased positive end-expiratory pressure, lung dynamic compliance, and arterial oxygenation (P < .01) and central venous pressure (P = .004), without effects on corrected flow time (P = .7). Cardiac output and invasive arterial pressure were stable with (P = .11) and without alveolar recruitment (P = .1), as were portal (P = .27) and hepatic vein flow (P = .30). Alveolar recruitment reduced postoperative pulmonary complications (n = 0/28 vs 8/29; P = .001), without reduction in postoperative mechanical ventilation period (P = .08). International normalization ratio, aspartate/alanine aminotransferases, and lactate were not different from control (P > .05). CONCLUSIONS: Stepwise alveolar recruitment identified the optimal positive end-expiratory pressure to improve lung mechanics and oxygenation with minimal hemodynamic changes, without liver graft congestion/dysfunction, and was associated with significant reduction in postoperative pulmonary complications.

An imaging agent to detect androgen receptor and its active splice variants in prostate cancer.

Constitutively active splice variants of androgen receptor (AR-Vs) lacking ligand-binding domain (LBD) are a mechanism of resistance to androgen receptor LBD-targeted (AR LBD-targeted) therapies for metastatic castration-resistant prostate cancer (CRPC). There is a strong unmet clinical need to identify prostate cancer patients with AR-V-positive lesions to determine whether they will benefit from further AR LBD-targeting therapies or should receive taxanes or investigational drugs like EPI-506 or galeterone. Both EPI-506 (NCT02606123) and galeterone (NCT02438007) are in clinical trials and are proposed to have efficacy against lesions that are positive for AR-Vs. AR activation function-1 (AF-1) is common to the N-terminal domains of full-length AR and AR-Vs. Here, we provide proof of concept for developing imaging compounds that directly bind AR AF-1 to detect both AR-Vs and full-length AR. 123I-EPI-002 had specific binding to AR AF-1, which enabled direct visualization of CRPC xenografts that express full-length AR and AR-Vs. Our findings highlight the potential of 123I-EPI-002 as an imaging agent for the detection of full-length AR and AR-Vs in CRPC.

An androgen receptor N-terminal domain antagonist for treating prostate cancer.

Hormone therapies for advanced prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD), but these ultimately fail and the disease progresses to lethal castration-resistant prostate cancer (CRPC). The mechanisms that drive CRPC are incompletely understood, but may involve constitutively active AR splice variants that lack the LBD. The AR N-terminal domain (NTD) is essential for AR activity, but targeting this domain with small-molecule inhibitors is complicated by its intrinsic disorder. Here we investigated EPI-001, a small-molecule antagonist of AR NTD that inhibits protein-protein interactions necessary for AR transcriptional activity. We found that EPI analogs covalently bound the NTD to block transcriptional activity of AR and its splice variants and reduced the growth of CRPC xenografts. These findings suggest that the development of small-molecule inhibitors that bind covalently to intrinsically disordered proteins is a promising strategy for development of specific and effective anticancer agents.

Niphatenones, glycerol ethers from the sponge Niphates digitalis block androgen receptor transcriptional activity in prostate cancer cells: structure elucidation, synthesis, and biological activity.

Extracts of the marine sponge Niphates digitalis collected in Dominica showed strong activity in a cell-based assay designed to detect antagonists of the androgen receptor (AR) that could act as lead compounds for the development of a new class of drugs to treat castration recurrent prostate cancer (CRPC). Assay-guided fractionation showed that niphatenones A (3) and B (4), two new glycerol ether lipids, were the active components of the extracts. The structures of 3 and 4 were elucidated by analysis of NMR and MS data and confimed via total synthesis. Biological evaluation of synthetic analogues of the niphatenones has shown that the enantiomers 7 and 8 are more potent than the natural products in the screening assay and defined preliminary SAR for the new AR antagonist pharmacophore, including the finding that the Michael acceptor enone functionality is not required for activity. Niphatenone B (4) and its enantiomer 8 blocked androgen-induced proliferation of LNCaP prostate cancer cells but had no effect on the proliferation of PC3 prostate cancer cells that do not express functional AR, consistent with activity as AR antagonists. Use of the propargyl ether 44 and Click chemistry showed that niphatenone B binds covalently to the activation function-1 (AF1) region of the AR N-terminus domain (NTD).

Molecular and phenotypic divergence in the bluethroat (Luscinia svecica) subspecies complex.

Subspecies complexes may provide valuable insights into the early stages of the speciation process. The bluethroat (Luscinia svecica) consists of many morphologically distinct subspecies that differ most strikingly in the ornamental colour pattern of the male throat. We investigated the genetic and phenotypic differentiation in this subspecies complex, using (i) microsatellite genotyping (11 loci) of a sample of 364 individuals from bluethroat populations in Europe and Asia, and (ii) spectrometric and morphological measurements of a sample of 131 museum skin specimens. Population genetic analyses, based on microsatellite allele frequency variation, revealed a slight but significant overall population differentiation (F(ST) = 0.042). There was a well-differentiated southern group of subspecies with white or no throat spots and a less-differentiated northern group of chestnut-spotted populations. Phylogenetic analyses indicated that the southern all-blue and white-spotted forms are ancestral to the chestnut-spotted subspecies. In addition to the qualitative variation in throat plumage pattern already described in the literature, we found significant quantitative variation among subspecies in hue, chroma and brightness of the ultraviolet (UV)/blue throat coloration, and this variation seemed to be unrelated to the phylogenetic distance between subspecies.