Deformation-Induced Chemical Inhomogeneity and Short-Circuit Diffusion in Shear Bands of a Bulk Metallic Glass.

The compositional changes in shear bands of a Cu_{50}Zr_{50} metallic glass after plastic deformation at room temperature have been monitored by atom probe tomography. Across the width of the shear bands an asymmetry of the enriched and depleted zones of the constituent elements is observed, while no change of the composition within the surrounding matrix occurs. The diffusion coefficients determined from the concentration profiles are orders of magnitude larger than the values of bulk diffusion at room temperature. The asymmetric concentration profiles of the constituent elements (Cu and Zr) remain stable during annealing at a temperature of 543 K, even though fast and preferential diffusion of a Ni tracer has been found along the shear band at the same temperature. The results indicate that the atomic structure and stress distribution within the shear bands is altered from that of the surrounding amorphous matrix. The fact that the shear band structure is unaltered at elevated temperatures and that fast diffusion occurs preferentially within the shear bands leads to the conclusion that they are structurally stable.

Versatile Control of

We demonstrate quantum control of ^{9}Be^{+} ions directly implemented by an optical frequency comb. Based on numerical simulations of the relevant processes in ^{9}Be^{+} for different magnetic field regimes, we demonstrate a wide applicability when controlling the comb's spectral properties. We introduce a novel technique for the selective and efficient generation of a spectrally tailored narrow-bandwidth optical frequency comb near 313 nm. We experimentally demonstrate internal state control and internal-motional state coupling of ^{9}Be^{+} ions implemented by stimulated-Raman manipulation using a spectrally optimized optical frequency comb. Our pulsed laser approach is a key enabling step for the implementation of quantum logic and quantum information experiments in Penning traps.

Robust and Resource-Efficient Microwave Near-Field Entangling

Microwave trapped-ion quantum logic gates avoid spontaneous emission as a fundamental source of decoherence. However, microwave two-qubit gates are still slower than laser-induced gates and hence more sensitive to fluctuations and noise of the motional mode frequency. We propose and implement amplitude-shaped gate drives to obtain resilience to such frequency changes without increasing the pulse energy per gate operation. We demonstrate the resilience by noise injection during a two-qubit entangling gate with ^{9}Be^{+} ion qubits. In the absence of injected noise, amplitude modulation gives an operation infidelity in the 10^{-3} range.

Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma: the oncogenic role of the ligands.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made. RESULTS: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported. CONCLUSIONS: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers.

Cervical cord and ventricle affection in neuromyelitis optica.

OBJECTIVES: Cervical cord involvement is common in neuromyelitis optica (NMO) and multiple sclerosis (MS), but its impact on disability in NMO has rarely been studied. Recent publications on NMO examined the periventricular system, areas of high aquaporin-4 expression, but not yet by using ventricle volumetry. PURPOSE: To compare cervical cord atrophy, ventricular widening, and supra- and infratentorial brain measures between NMO and MS, and study their impact on clinical disability. METHODS: Magnet resonance imaging-based volumetry of upper cervical cord, third and fourth lateral ventricles, grey matter, white matter, brainstem, cerebellum and clinical status of 18 NMO and 20 MS patients, was compared between the groups and with 26 healthy controls. Patterns of ventricular widening relative to healthy controls were inspected by voxel-based morphometry of the cerebrospinal fluid. RESULTS: Cervical cord atrophy was similar in NMO and MS (75.2 ± 10.0 mm2 , respectively, 76.5 ± 9.5 mm2 vs 84.1 ± 8.6 mm2 in controls).Third ventricle increase in both groups, and specific fourth ventricle widening in MS were detected. Patient groups differed in third to fourth ventricle ratio (P = 0.002). In NMO, white matter correlated inversely with the affected cord segments (P = 0.001) and with cervical cord area (P = 0.043). The disability status was explained by cervical cord area and third ventricle volume (R2 =0.524) in NMO, and by grey matter and fourth ventricle volume (R2 =0.565) in MS. CONCLUSION: Cervical cord atrophy and third ventricular enlargement are both clinically relevant in NMO. Third and fourth ventricle volumetry shows differences between NMO and MS regarding the involvement of periventricular structures.

The truth about the 1st cycle Coulombic efficiency of LiNi1/3Co1/3Mn1/3O2 (NCM) cathodes.

The 1st cycle Coulombic efficiency (CE) of LiNi1/3Co1/3Mn1/3O2 (NCM) at 4.6 V vs. Li/Li(+) has been extensively investigated in NCM/Li half cells. It could be proven that the major part of the observed overall specific capacity loss (in total 36.3 mA h g(-1)) is reversible and induced by kinetic limitations, namely an impeded lithiation reaction during discharge. A measure facilitating the lithiation reaction, i.e. a constant potential (CP) step at the discharge cut-off potential, results in an increase in specific discharge capacity of 22.1 mA h g(-1). This capacity increase during the CP step could be proven as a relithiation process by Li(+) content determination in NCM via an ICP-OES measurement. In addition, a specific capacity loss of approx. 4.2 mA h g(-1) could be determined as an intrinsic reaction to the NCM cathode material at room temperature (RT). In total, less than 10.0 mA h g(-1) (=28% of the overall capacity loss) can be attributed to irreversible reactions, mainly to irreversible structural changes of NCM. Thus, the impact of parasitic reactions, such as oxidative electrolyte decomposition, on the irreversible capacity is negligible and could also be proven by on-line MS. As a consequence, the determination of the amount of extracted Li(+) ("Li(+) extraction ratio") so far has been incorrect and must be calculated by the charge capacity (=delithiation amount) divided by the theoretical capacity. In a NCM/graphite full cell the relithiation amount during the constant voltage (CV) step is smaller than in the half cell, due to irreversible Li(+) loss at graphite.

Normal values for transbulbar sonography and magnetic resonance imaging of the optic nerve sheath diameter (ONSD) in children and adolescents.

PURPOSE: To establish normal values of the optic nerve sheath diameter (ONSD) in children and adolescents for transbulbar sonography and magnetic resonance imaging. MATERIALS AND METHODS: In 99 children and adolescents (age: 5.6 - 18.6 years, mean: 12 years) without neurologic or ophthalmologic disease, measurements of the ONSD with transbulbar sonography were performed. For comparison 59 children and adolescents (age: 5.1 - 17.4 years, mean 12.3 years) with a normal MR examination of the brain had measurements of the ONSD on a T2-weighted thin section sequence of the orbit. Besides establishing modality-related normal values, age dependency, accuracy and reproducibility of measurements were assessed. RESULTS: Overall the mean ONSD was 5.75 ± 0.52 mm for transbulbar sonography and 5.69 ± 0.31 mm for MRI. There was no statistical significance between the 95 % percentiles and age for both transbulbar sonography (p = 0.332) and MRI (p = 0.336). As a parameter for the reproducibility of measurements, the repeatability coefficient (RC) was between 0.34 mm and 0.46 mm. The concordance correlation coefficient (CCC) values revealed a high agreement between readers both for transbulbar sonography (0.868) and MRI (0.796). CONCLUSION: Normal values for ONSD in children and adolescents found in this study are significantly higher than assumed. The values found for transbulbar sonography are confirmed by comparable results for MR measurements. A precise sonographic measurement technique and the consideration of normal values found hereby are essential for correct interpretation of ONSD measurements in children and adolescents.

Atomic structure and structural stability of Sc75Fe25 nanoglasses.

Nanoglasses are solids consisting of nanometer-sized glassy regions connected by interfaces having a reduced density. We studied the structure of Sc(75)Fe(25) nanoglasses by electron microscopy, positron annihilation spectroscopy, and small-/wide-angle X-ray scattering. The positron annihilation spectroscopy measurements showed that the as-prepared nanoglasses consisted of 65 vol% glassy and 35 vol% interfacial regions. By applying temperature annealing to the nanoglasses and measuring in situ small-angle X-ray scattering, we observed that the width of the interfacial regions increased exponentially as a function of the annealing temperature. A quantitative fit to the small-angle X-ray scattering data using a Debye-Bueche random phase model gave a correlation length that is related to the sizes of the interfacial regions in the nanoglass. The correlation length was found to increase exponentially from 1.3 to 1.7 nm when the sample temperature was increased from 25 to 230 °C. Using simple approximations, we correlate this to an increase in the width of interfacial regions from 0.8 to 1.2 nm, while the volume fraction of interfacial regions increased from 31 to 44%. Using micro-compression measurements, we investigated the deformation behavior of ribbon glass and the corresponding nanoglass. While the nanoglass exhibited a remarkable plasticity even in the annealed state owing to the glass-glass interfaces, the corresponding ribbon glass was brittle. As this difference seems not limited to Sc(75)Fe(25) glasses, the reported result suggest that nanoglasses open the way to glasses with high ductility resulting from the nanometer sized microstructure.

Endothelial apoptosis in Braf-deficient mice.

Tyrosine kinase growth factor receptors and Ras/Raf/MEK/MAPK signalling have been implicated in the suppression as well as augmentation of programmed cell death. In addition, a Ras-independent role for Raf as a suppressor of programmed cell death has been suggested by the recent finding that Craf1 interacts with members of the Bcl-2 family at mitochondrial membranes. However, genetic studies of C. elegans and Drosophila, as well as the targeted mutagenesis of the murine Araf gene, have failed to support such a role. Here we show that mice with a targeted disruption in the Braf gene die of vascular defects during mid-gestation. Braf -/- embryos, unlike Araf -/- or Craf1 -/- embryos (L.W. et al., unpublished), show an increased number of endothelial precursor cells, dramatically enlarged blood vessels and apoptotic death of differentiated endothelial cells. These results establish Braf as a critical signalling factor in the formation of the vascular system and provide the first genetic evidence for an essential role of Raf gene in the regulation of programmed cell death.

Simulation of vertical dispersion and pollution impact of artificial light at night in urban environment.

The use of artificial light at night (ALAN) enables social and commercial activities for urban living. However, the excessive usage of lighting causes nuisance and waste of energy. Light is provided to illuminate target areas on the street level where activities take place, yet light can also cause trespass to residents at the floors above. While regulations are beginning to cover light design, simulation tools for the outdoor environment have also become more popular for assessing the design condition. Simulation tools allow visualisation of the impact of the selected light sources on those who are affected. However, this cause-and-effect relationship is not easy to determine in the complex urban environment. The current work offers a simple methodology that takes site survey results and correlates them with the simulation model to determine lighting impact on the investigated area in 3D. Four buildings in two mixed commercial and residential streets in Hong Kong were studied. Data collection from each residential building requires lengthy work and permission from each household. Therefore, a valid lighting simulation model could help determine the light pollution impact in the area. A light model using DIALux is developed and calibrated by correlating the simulated data with the actual measured data. The correlation value R2 achieved ranged from 0.95 to 0.99, verifying the accuracy of this model and matched from 340 lx to 46 lx for the lower to higher floors of one building and 10 lx to 4 lx for floors of another building. This model can also be applied to human health research, by providing light-level data on residential windows in an area or determining the environmental impact of a development project.

A comparison of serum inflammatory cytokines according to phenotype in patients with psoriasis.

BACKGROUND: Plaque-type psoriasis manifests with various morphological phenotypes and different clinical activity over time in the same individual or from one patient to another. Circulating cytokines, especially T-helper (Th) 1- and Th17-related, have been suggested to reflect the inflammatory nature of psoriasis. However, studies regarding cytokine profile according to morphological phenotypes are quite scarce. OBJECTIVES: We sought to analyse the circulating Th1 and Th17 cytokines according to clinical phenotype and investigated the correlation between disease severity [Psoriasis Area and Severity Index (PASI)] and the serum level of inflammatory cytokines. METHODS: Seventy-one patients with psoriasis were divided into two groups according to clinical phenotype: chronic stable (CS) and eruptive inflammatory (EI). Th1- and Th17-derived cytokines were measured using multiplex cytokine assay. RESULTS: It was noted that interleukin (IL)-1 receptor antagonist and IL-17A were elevated in the EI group compared with the CS group. We also noticed that the PASI is relatively well correlated with serum cytokine level in the CS state but not as well in the EI counterpart. CONCLUSIONS: The level of serum inflammatory cytokines differs according to morphological phenotype. Also, the PASI does not seem to be a suitable tool to assess disease severity in patients with psoriasis with EI characteristics.

Fourier transform infrared imaging analysis in discrimination studies of squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) of the oral cavity and oropharynx represents more than 95% of all malignant neoplasms in the oral cavity. Histomorphological evaluation of this cancer type is invasive and remains a time consuming and subjective technique. Therefore, novel approaches for histological recognition are necessary to identify malignancy at an early stage. Fourier transform infrared (FTIR) imaging has become an essential tool for the detection and characterization of the molecular components of biological processes, such as those responsible for the dynamic properties of tumor progression. FTIR imaging is a modern analytical technique enabling molecular imaging of a complex biological sample and is based on the absorption of IR radiation by vibrational transitions in covalent bonds. One major advantage of this technique is the acquisition of local molecular expression profiles, while maintaining the topographic integrity of the tissue and avoiding time-consuming extraction, purification, and separation steps. With this imaging technique, it is possible to obtain unique images of the spatial distribution of proteins, lipids, carbohydrates, cholesterols, nucleic acids, phospholipids, and small molecules with high spatial resolution. Analysis and visualization of FTIR imaging datasets are challenging and the use of chemometric tools is crucial in order to take advantage of the full measurement. Therefore, methodologies for this task based on the novel developed algorithm for multivariate image analysis (MIA) are often necessary. In the present study, FTIR imaging and data analysis methods were combined to optimize the tissue measurement mode after deparaffinization and subsequent data evaluation (univariate analysis and MIAs). We demonstrate that it is possible to collect excellent IR spectra from formalin-fixed paraffin-embedded (FFPE) tissue microarrays (TMAs) of OSCC tissue sections employing an optimised analytical protocol. The correlation of FTIR imaging to the morphological tissue features obtained by histological staining of the sections demonstrated that many histomorphological tissue patterns can be visualized in the colour images. The different algorithms used for MIAs of FTIR imaging data dramatically increased the information content of the IR images from squamous cell tissue sections. These findings indicate that intra-operative and surgical specimens of squamous cell carcinoma tissue can be characterized by FTIR imaging.

Morphological and tissue characterization of the medicinal fungus Hericium coralloides by a structural and molecular imaging platform.

In this study the potential of new imaging techniques such as Magnetic Resonance Imaging (MRI), Matrix-Assisted Laser Desorption/Ionization (MALDI) profiling mass spectrometry ("MALDI Profiling") and Fourier Transform Infrared (FTIR) spectroscopic imaging was evaluated to study morphological and molecular patterns of the potential medicinal fungus Hericium coralloides. For interpretation, the MALDI profiling, FTIR imaging and MRI results were correlated with histological information gained from Scanning Electron Microscopy (SEM) and Light Microscopy (LM). Additionally we tested several evaluation processes and optimized the methodology for use of complex FTIR images to monitor molecular patterns. It is demonstrated that the combination of these spectroscopic methods enables to gain a more distinct picture concerning morphology and distribution of active ingredients. We were able to obtain high quality FTIR imaging and MALDI-profiling results and to distinguish different tissue types with their chemical ingredients. Beside this, we have created a 3-D reconstruction of a mature Hericium basidioma, based on the MRI dataset: analyses allowed, for the first time, a realistic approximation of the "evolutionary effectiveness" of this bizarrely formed basidioma type, concerning the investment of sterile tissue and its reproductive output (production of basidiospores).

Measurement of the Optic Nerve Sheath Diameter in Children: Comparison Between Transbulbar Sonography and Magnetic Resonance Imaging.

PURPOSE: To evaluate the accuracy of measurements of the optic nerve sheath diameter (ONSD) in children by comparing transbulbar sonography with magnetic resonance imaging (MRI). MATERIALS AND METHODS: 65 children (age: 3 mo- 17y; mean age: 11.3y) underwent MR imaging of the brain including a heavily T 2-w sequence of the orbit and transbulbar sonography using a 17 MHz linear array transducer. Measurements of the ONSD were performed retrospectively by two experienced readers and all images were evaluated regarding the image quality. Bland-Altman Plots were produced to assess the accuracy of measurements. The correlation between readers and between MR imaging and transbulbar sonography was calculated by the concordance correlation coefficient (CCC). RESULTS: Overall the mean values of the ONSD for MRI (5.86 ±â€Š0.66 mm) and transbulbar sonography (5.86 ±â€Š0.71 mm) were identical. There was a high correlation between readers for measurements of the ONSD both for transbulbar sonography (CCC = 0.93) as well as for MRI (CCC = 0.9). Comparing the measurement values between transbulbar sonography and MRI, the correlation of ONSD values was good to moderate with a high dependency on image quality (CCC [0.31, 0.68]). CONCLUSION: We were able to demonstrate that the ONSD values of transbulbar sonography in children correlate well with MRI if the relevant anatomic structures are depicted and the measuring points are set correctly. Based on the findings of our study, it seems necessary to define normal and cut-off values for the ONSD in children again to finally assess the clinical relevance of the ONSD as a noninvasive parameter for the evaluation of intracranial pressure.

The relationship between borderline personality symptoms and body mass index in a consecutive sample of cardiac stress test patients.

Borderline personality disorder (BPD) is characterized by inherent difficulties with self-regulation. While a number of studies have examined the relationship between BPD and body mass index (BMI)/overweight/obesity, findings have been mixed. In this cross-sectional study of a consecutive sample of 238 participants presenting for cardiac stress testing, we investigated the relationship between borderline personality symptoms, according to two self-report measures, and BMI. Compared to participants who were negative on both measures of borderline personality symptoms, participants who were positive on either measure of borderline personality symptoms demonstrated no differences in current BMI or highest BMI in adulthood. These results in a unique study population mirror the findings of other studies in medical and community populations.

Surface plasmon polariton absorption modulator.

An electrically controlled ultra-compact surface plasmon polariton absorption modulator (SPPAM) is proposed. The device can be as small as a few micrometers depending on the required extinction ratio and the acceptable loss. The device allows for operation far beyond 100 Gbit/s, being only limited by RC time constants. The absorption modulator comprises a stack of metal/insulator/metal-oxide/metal layers, which support a strongly confined asymmetric surface plasmon polariton (SPP) in the 1.55 µm telecommunication wavelength window. Absorption modulation is achieved by electrically modulating the free carrier density in the intermediate metal-oxide layer. The concept is supported by proof-of-principle experiments.

Immediate pigment darkening and persistent pigment darkening as means of measuring the ultraviolet A protection factor in vivo: a comparative study.

BACKGROUND: Persistent pigment darkening (PPD) is a widely used in vivo method for measurement of ultraviolet (UV) A protection factor (UVAPF). However, with increased emphasis on UVA protection and sunscreen products with higher UVAPF gaining popularity, the immediate pigment darkening (IPD) method is drawing attention again. Furthermore, only about a quarter of the recommended quantity of sunscreen is used during daily activities. However, there is as yet no clearly defined relationship between the UVAPF and the amount of sunscreen applied. OBJECTIVES: To analyse the differences between the IPD and PPD methods, and to establish a relationship between the quantity of sunscreen application and the UVAPF. METHODS: Different doses of sunscreen were applied on the back of 15 healthy volunteers, and the UVAPF was measured using both the IPD and the PPD methods. RESULTS: Both methods proved to be effective for measuring the UVAPF. However, all the UVAPF values determined by the PPD method were lower than those determined by the IPD method. Additionally, an exponential relationship between the amount of sunscreen applied and the UVAPF was observed. CONCLUSIONS: The IPD method can also be used as an appropriate endpoint in the determination of UVA protection. It is time saving, and thus considerably lowers the risk of UV exposure, particularly when testing sunscreen products with higher UVAPF. We further state that in order to achieve the desired protective effect of the sunscreen, the quantity of application is also very important.

Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome.

Gorlin (or nevoid basal cell carcinoma) syndrome is characterized by a variety of clinical problems including generalized overgrowth of the body, cysts, developmental abnormalities of the skeleton and a predisposition to benign and malignant tumors. The syndrome results from germline mutations of the human homolog of the drosophila segment polarity gene patched (ptc). Here we report that mice heterozygous for ptc develop many of the features characteristic of Gorlin syndrome and that they exhibit a high incidence of rhabdomyosarcomas (RMS), the most common soft-tissue sarcoma in children. The downstream signalling partner of ptc, gli1, was overexpressed in all RMSs analyzed, indicating that abnormal signalling of the ptc-gli1 pathway may be common for the various tumors associated with the syndrome. igf2, implicated in the formation of RMSs, was also overexpressed, suggesting cross-talk between the ptc and igf2 pathways in tumorigenesis. Developmental defects in Gorlin syndrome resemble those induced by ionizing radiation. We show that ptc heterozygous mice exhibit increased incidence of radiation-induced teratogenesis. This suggests a role for ptc in the response to ionizing radiation and provides a model for both the systemic (developmental) and stochastic (cancer) abnormalities observed in Gorlin syndrome.

High resolution ultrasound and magnetic resonance imaging of the optic nerve and the optic nerve sheath: anatomic correlation and clinical importance.

PURPOSE: We performed a cadaver study to evaluate the accuracy of measurements of the optic nerve and the optic nerve sheath for high resolution US (HRUS) and magnetic resonance imaging (MRI). MATERIALS AND METHODS: Five Thiel-fixated cadaver specimens of the optic nerve were examined with HRUS and MRI. Measurements of the optic nerve and the ONSD were performed before and after the filling of the optic nerve sheath with saline solution. Statistical analysis included the calculation of the agreement of measurements and the evaluation of the intraobserver and interobserver variation. RESULTS: Overall a good correlation of measurement values between HRUS and MRI can be found (mean difference: 0.02-0.97 mm). The repeatability coefficient (RC) and concordance correlation coefficient (CCC) values were good to excellent for most acquisitions (RC 0.2-1.11 mm; CCC 0.684-0.949). The highest variation of measurement values was found for transbulbar sonography (RC 0.58-1.83 mm; CCC 0.615/0.608). CONCLUSION: If decisive anatomic structures are clearly depicted and the measuring points are set correctly, there is a good correlation between HRUS and MRI measurements of the optic nerve and the ONSD even on transbulbar sonography. As most of the standard and cut-off values that have been published for ultrasound are significantly lower than the results obtained with MRI, a reevaluation of sonographic ONSD measurement with correlation to MRI is necessary.

Ultra-low-vibration closed-cycle cryogenic surface-electrode ion trap apparatus.

We describe the design, commissioning, and operation of an ultra-low-vibration closed-cycle cryogenic ion trap apparatus. One hundred lines for low-frequency signals and eight microwave/radio frequency coaxial feed-lines offer the possibility of implementing a small-scale ion-trap quantum processor or simulator. With all supply cables attached, more than 1.3 W of cooling power at 5 K is still available for absorbing energy from electrical pulses introduced to control ions. The trap itself is isolated from vibrations induced by the cold head using a helium exchange gas interface. The performance of the vibration isolation system has been characterized using a Michelson interferometer, finding residual vibration amplitudes on the order of 10 nm rms. Trapping of 9Be+ ions has been demonstrated using a combination of laser ablation and photoionization.