Investigating the medium range order in amorphous Ta₂O₅ coatings

Ion-beam sputtered amorphous heavy metal oxides, such as Ta2O5, are widely used as the high refractive index layer of highly reflective dielectric coatings. Such coatings are used in the ground based Laser Interferometer Gravitational-wave Observatory (LIGO), in which mechanical loss, directly related to Brownian thermal noise, from the coatings forms an important limit to the sensitivity of the LIGO detector. It has previously been shown that heat-treatment and TiO2 doping of amorphous Ta2O5 coatings causes significant changes to the levels of mechanical loss measured and is thought to result from changes in the atomic structure. This work aims to find ways to reduce the levels of mechanical loss in the coatings by understanding the atomic structure properties that are responsible for it, and thus helping to increase the LIGO detector sensitivity. Using a combination of Reduced Density Functions (RDFs) from electron diffraction and Fluctuation Electron Microscopy (FEM), we probe the medium range order (in the 2-3 nm range) of these amorphous coatings

Optical absorption of ion-beam sputtered amorphous silicon coatings

Low mechanical loss at low temperatures and a high index of refraction should make silicon optimally suited for thermal noise reduction in highly reflective mirror coatings for gravitational wave detectors. However, due to high optical absorption, amorphous silicon (aSi) is unsuitable for being used as a direct high-index coating material to replace tantala. A possible solution is a multimaterial design, which enables exploitation of the excellent mechanical properties of aSi in the lower coating layers. The possible number of aSi layers increases with absorption reduction. In this work, the optimum heat treatment temperature of aSi deposited via ion-beam sputtering was investigated and found to be 450 °C. For this temperature, the absorption after deposition of a single layer of aSi at 1064 nm and 1550 nm was reduced by more than 80%

Correlations between the mechanical loss and atomic structure of amorphous TiO2-doped Ta2O5 coatings

<p>Highly reflective dielectric mirror coatings are critical components in a range of precision optics applications including frequency combs, optical atomic clocks, precision interferometry and ring laser gyroscopes. A key limitation to the performance in these applications is thermal noise, arising from the mechanical loss of the coatings. The origins of the mechanical loss from these coatings is not well understood.</p> <p>Recent work suggests that the mechanical loss of amorphous Ta2O5 coatings can drop by as much as 40% when it is doped with TiO2. We use a combination of electron diffraction data and atomic modelling using molecular dynamics to probe the atomic structure of these coatings, and examine the correlations between changes in the atomic structure and changes in the mechanical loss of these coatings. Our results show the first correlation between changes in the mechanical loss and experimentally measured changes in the atomic structure resulting from variations in the level of TiO2 doping in TiO2-doped Ta2O5 coatings, in that increased homogeneity at the nearest-neighbour level appears to correlate with reduced mechanical loss. It is demonstrated that subtle but measurable changes in the nearest-neighbour homogeneity in an amorphous material can correlate with significant changes in macroscopic properties.</p&gt

Translational development of difluoromethylornithine (DFMO) for the treatment of neuroblastoma

Neuroblastoma is a childhood tumor in which MYC oncogenes are commonly activated to drive tumor progression. Survival for children with high-risk neuroblastoma remains poor despite treatment that incorporates high-dose chemotherapy, stem cell support, surgery, radiation therapy and immunotherapy. More effective and less toxic treatments are sought and one approach under clinical development involves re-purposing the anti-protozoan drug difluoromethylornithine (DFMO; Eflornithine) as a neuroblastoma therapeutic. DFMO is an irreversible inhibitor of ornithine decarboxylase (Odc), a MYC target gene, bona fide oncogene, and the rate-limiting enzyme in polyamine synthesis. DFMO is approved for the treatment of Trypanosoma brucei gambiense encephalitis (“African sleeping sickness”) since polyamines are essential for the proliferation of these protozoa. However, polyamines are also critical for mammalian cell proliferation and the finding that MYC coordinately regulates all aspects of polyamine metabolism suggests polyamines may be required to support cancer promotion by MYC. Pre-emptive blockade of polyamine synthesis is sufficient to block tumor initiation in an otherwise fully penetrant transgenic mouse model of neuroblastoma driven by MYCN, underscoring the necessity of polyamines in this process. Moreover, polyamine depletion regimens exert potent anti-tumor activity in pre-clinical models of established neuroblastoma as well, in combination with numerous chemotherapeutic agents and even in tumors with unfavorable genetic features such as MYCN, ALK or TP53 mutation. This has led to the testing of DFMO in clinical trials for children with neuroblastoma. Current trial designs include testing lower dose DFMO alone (2,000 mg/m2/day) starting at the completion of standard therapy, or higher doses combined with chemotherapy (up to 9,000 mg/m2/day) for patients with relapsed disease that has progressed. In this review we will discuss important considerations for the future design of DFMO-based clinical trials for neuroblastoma, focusing on the need to better define the principal mechanisms of anti-tumor activity for polyamine depletion regimens. Putative DFMO activities that are both cancer cell intrinsic (targeting the principal oncogenic driver, MYC) and cancer cell extrinsic (altering the tumor microenvironment to support anti-tumor immunity) will be discussed. Understanding the mechanisms of DFMO activity are critical in determining how it might be best leveraged in upcoming clinical trials. This mechanistic approach also provides a platform by which iterative pre-clinical testing using translational tumor models may complement our clinical approaches

Cryogenic mechanical loss of a single-crystalline GaP coating layer for precision measurement applications

The first direct observations of gravitational waves have been made by the Advanced LIGO detectors. However, the quest to improve the sensitivities of these detectors remains, and epitaxially grown single-crystal coatings show considerable promise as alternatives to the ion-beam sputtered amorphous mirror coatings typically used in these detectors and other such precision optical measurements. The mechanical loss of a 1 μm thick single-crystalline gallium phosphide (GaP) coating, incorporating a buffer layer region necessary for the growth of high quality epitaxial coatings, has been investigated over a broad range of frequencies and with fine temperature resolution. It is shown that at 20 K the mechanical loss of GaP is a factor of 40 less than an undoped tantala film heat-treated to 600 °C and is comparable to the loss of a multilayer GaP/AlGaP coating. This is shown to translate into possible reductions in coating thermal noise of a factor of 2 at 120 K and 5 at 20 K over the current best IBS coatings (alternating stacks of silica and titania-doped tantala). There is also evidence of a thermally activated dissipation process between 50 and 70 K

Coronary graft patency after perioperative myocardial infarction: a study with multislice computed tomography‏

A total of 55 consecutive patients who experienced perioperative myocardial infarction (MI) after coronary artery bypass grafting were studied using multislice computed tomography (MSCT) angiography to evaluate for graft patency. The MSCT detected acute graft occlusion in 23% grafts. Of the 55 patients, 40% patients had occluded grafts and perioperative MI in the area of the grafted vessels; remaining 60% had patent grafts with infarction in the area of the grafted vessels. Compared with the patients with patent grafts, those with occluded grafts had a higher blood sugar level. In addition, graft occlusion was higher in grafts with severe distal disease. Among the patients with patent grafts, luminal stenosis of the native vessels supplying the infarcted myocardium was higher than that in the native vessels supplying the non-infarcted myocardium. In conclusion, MSCT is feasible for the assessment of graft patency in the setting of perioperative MI. Graft occlusion is detected in less than half of the cases and usually occurs in the grafts with severe distal involvement and the patients with uncontrolled hyperglycemia. In patients with patent grafts, the severity of luminal stenosis of the native grafted vessel is the main predisposing factor for perioperative MI

Theory of the propagation of coupled waves in arbitrarily-inhomogeneous stratified media

We generalize the invariant imbedding theory of the wave propagation and derive new invariant imbedding equations for the propagation of arbitrary number of coupled waves of any kind in arbitrarily-inhomogeneous stratified media, where the wave equations are effectively one-dimensional. By doing this, we transform the original boundary value problem of coupled second-order differential equations to an initial value problem of coupled first-order differential equations, which makes the numerical solution of the coupled wave equations much easier. Using the invariant imbedding equations, we are able to calculate the matrix reflection and transmission coefficients and the wave amplitudes inside the inhomogeneous media exactly and efficiently. We establish the validity and the usefulness of our results by applying them to the propagation of circularly-polarized electromagnetic waves in one-dimensional photonic crystals made of isotropic chiral media. We find that there are three kinds of bandgaps in these structures and clarify the nature of these bandgaps by exact calculations.Comment: 7 pages, 1 figure, to appear in Europhys. Let

Order within disorder: the atomic structure of ion-beam sputtered amorphous tantala (a-Ta2O5)

Amorphous tantala (a-Ta2O5) is a technologically important material often used in high-performance coatings. Understanding this material at the atomic level provides a way to further improve performance. This work details extended X-ray absorption fine structure measurements of a-Ta2O5 coatings, where high-quality experimental data and theoretical fits have allowed a detailed interpretation of the nearest-neighbor distributions. It was found that the tantalum atom is surrounded by four shells of atoms in sequence; oxygen, tantalum, oxygen, and tantalum. A discussion is also included on how these models can be interpreted within the context of published crystalline Ta 2O5 and other a-T2O5 studies

Constitutive activation of the EGFR-STAT1 axis increases proliferation of meningioma tumor cells.

Background: Meningiomas are the most frequent primary brain tumors of the central nervous system. The standard of treatment is surgery and radiotherapy, but effective pharmacological options are not available yet. The well-characterized genetic background stratifies these tumors in several subgroups, thus increasing diversification. We identified epidermal growth factor receptor-signal transducer and activator of transcription 1 (EGFR-STAT1) overexpression and activation as a common identifier of these tumors. Methods: We analyzed STAT1 overexpression and phosphorylation in 131 meningiomas of different grades and locations by utilizing several techniques, including Western blots, qPCR, and immunocytochemistry. We also silenced and overexpressed wild-type and mutant forms of the gene to assess its biological function and its network. Results were further validated by drug testing. Results: STAT1 was found widely overexpressed in meningioma but not in the corresponding healthy controls. The protein showed constitutive phosphorylation not dependent on the JAK-STAT pathway. STAT1 knockdown resulted in a significant reduction of cellular proliferation and deactivation of AKT and ERK1/2. STAT1 is known to be activated by EGFR, so we investigated the tyrosine kinase and found that EGFR was also constitutively phosphorylated in meningioma and was responsible for the aberrant phosphorylation of STAT1. The pharmaceutical inhibition of EGFR caused a significant reduction in cellular proliferation and of overall levels of cyclin D1, pAKT, and pERK1/2. Conclusions: STAT1-EGFR-dependent constitutive phosphorylation is responsible for a positive feedback loop that causes its own overexpression and consequently an increased proliferation of the tumor cells. These findings provide the rationale for further studies aiming to identify effective therapeutic options in meningioma