Conjunctival melanoma is a rare but potentially deadly tumor of the eye. Despite effective local therapies, recurrence and metastasis remain frequent. Once the tumor has metastasized, treatment ...options are limited and the prognosis is poor. To date, little is known of the genetic alterations in conjunctival melanomas.
We conducted genetic analysis of 78 conjunctival melanomas, to our knowledge the largest cohort reported to date. An oncogene hotspot array was run on 38 samples, screening for a panel of known cancer-relevant mutations. Thirty tumors were analyzed for genome-wide copy number alterations (CNA) using array-based comparative genomic hybridization. Sanger sequencing of selected target mutations was conducted in all samples.
BRAF mutations were identified in 23 of 78 (29%) tumors. NRAS mutations, previously not recognized as relevant in conjunctival melanoma, were detected in 14 of 78 (18%) tumors. We found CNAs affecting various chromosomes distributed across the genome in a pattern reminiscent of cutaneous and mucosal melanoma but differing markedly from uveal melanoma.
The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of CNAs argue for conjunctival melanoma being closely related to cutaneous and mucosal melanoma but entirely distinct from uveal melanoma. Patients with metastatic conjunctival melanoma should be considered for therapeutic modalities available for metastatic cutaneous and mucosal melanoma including clinical trials of novel agents.
Nitrone cycloaddition on a dearomatized bicyclic phenol enabled the facile construction of the correctly configured phenanthrene skeleton of codeine. Further steps yielded allopseudocodeine in a ...completely diastereoselective manner and finally (±)‐codeine by allylic transposition through the hydrolysis of chlorocodides.
In the design and realization of modern neutron scattering instrumentation, particularly when designing beamline concepts from the ground up, it is desirable to fully benchmark against realistically ...simulated data. This is especially true for total scattering beamlines, where the future deliverable data is to be analysed in both reciprocal‐ and real‐space representations, and needs must be carefully balanced to ensure sufficient range, resolution and flux of the instrument. An approach to optimize the design of neutron scattering instrumentation via a workflow including ray‐tracing simulations, event‐based data reduction, heuristic analysis and fitting against realistically simulated spectra is demonstrated here. The case of the DISCOVER beamline concept at the Spallation Neutron Source is used as an example. The results of the calculations are benchmarked through simulation of existing instrumentation and subsequent direct comparison with measured data. On the basis of the validated models, the ability to explore design characteristics for future beamline concepts or future instrument improvements is demonstrated through the examples of detector tube size and detector layout.
A method of simulating and benchmarking neutron time‐of‐flight instrumentation from inception of events at the moderator surface to fully reduced and fitted data is presented. The case of the DISCOVER beamline concept and its future place within the Spallation Neutron Source's time‐of‐flight diffraction suite is used as an example.
Within the project “LandCover4Wind”, we investigate the potential for improving 24 h mesoscale wind speed forecasts at altitudes of interest for wind energy applications by using different ...high-resolution satellite-based land cover maps such as the Global Land Cover Characterization (GLCC) from the US Geological Survey (USGS), MODIS collection 5 dataset (MODIS LCC), and the European CORINE Land Cover (CLC). The Advanced Weather Research and Forecasting (WRF) model version 3.9 was run at three different grid resolutions covering a wide range of weather conditions during July and November 2015. We evaluate results by tower measurements at 10, 40 and 98 m altitude for the rural station Falkenberg in the eastern part of Germany characterized by flat and open terrain. We test different configurations for model domain horizontal resolution, land cover classification (LCC) data, and land surface and boundary layer physics. We discuss the need of transforming native LCC spatial resolution to lower WRF domain grid resolutions and transforming different thematic resolutions in LCC datasets into the less-resolving WRF classes. In general, comparisons show better forecast performance for the stormy November period compared to hot-summer July conditions. Especially, correlations are significantly higher in November. All experiments show a positive wind speed bias which changes with altitude, time of day and model configuration. With respect to LCC, CLC shows the smallest wind speed errors while GLCC performs worst. Two different land surface models NOAH LSM and 5-layer thermal diffusion scheme (5LD) are tested in combination with Mellor-Yamada-Janjic (MYJ) and Yonsei University (YSU) boundary layer modules. In general NOAH–MYJ performs best with CLC for November conditions, while it gives worst results with MODIS LCC for July conditions. For any given LCC, results depend significantly on the WRF land surface and boundary layer physics configuration and the performance on a daily base varies considerably depending on the test metric and model configuration. Results show only a weak dependency on domain resolution with increasing biases with increasing resolution. In summary, using a high resolution LCC dataset as the CLC proves to be valuable for wind speed forecasts.
Lipidic cubic phases (LCPs) have emerged as successful matrixes for the crystallization of membrane proteins. Moreover, the viscous LCP also provides a highly effective delivery medium for serial ...femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs). Here, the adaptation of this technology to perform serial millisecond crystallography (SMX) at more widely available synchrotron microfocus beamlines is described. Compared with conventional microcrystallography, LCP-SMX eliminates the need for difficult handling of individual crystals and allows for data collection at room temperature. The technology is demonstrated by solving a structure of the light-driven proton-pump bacteriorhodopsin (bR) at a resolution of 2.4 Å. The room-temperature structure of bR is very similar to previous cryogenic structures but shows small yet distinct differences in the retinal ligand and proton-transfer pathway.
A set of low-sulfur diesel fuels from the Western Pacific region were found to be unstable during storage although they passed all standard specification tests. This sample set was found to have high ...nitrogen content. Initially, liquid–liquid extractions with a mild aqueous acid were performed to separate basic and nonbasic nitrogen groups in an attempt to determine if these organonitrogen classes were responsible for the poor stability. The findings of this study indicate that there may be a correlation between the acid-extractable nitrogen compounds in these fuels and the formation of high levels of particulates in storage. To develop a more comprehensive understanding of the classes and distributions of organonitrogen compounds in fuels, a novel analytical method was developed using two-dimensional gas chromatography with nitrogen chemiluminescence detection (GCxGC-NCD). The GCxGC-NCD analyses revealed the presence of three distinct groups of nitrogen compounds. One group corresponded to the acid-extractable basic nitrogen compounds, one with the nonbasic nitrogen compounds, and a third early-eluting lighter polar organonitrogen fraction that had previously not been observed. This light organonitrogen fraction was unique to these particularly unstable fuels. If this is found to be universally applicable, this light polar nitrogen fraction may serve as an indicator of potentially unstable diesel fuels. Overall, the GCxGC-NCD method has been shown to be a valuable tool to enhance our understanding of the chemistry of organonitrogen species and their impact on fuel stability.
SESAM mode-locked red praseodymium laser Gaponenko, Maxim; Metz, Philip Werner; Härkönen, Antti ...
Optics letters,
2014-Dec-15, Letnik:
39, Številka:
24
Journal Article
Recenzirano
We present the first semiconductor saturable absorber mirror (SESAM) mode-locked praseodymium solid-state laser. The laser is based on a Pr(3+):LiYF(4) crystal as gain medium and a GaInP-quantum ...well-based SESAM. Self-starting continuous-wave mode-locked laser operation with an average output power of 16 mW is achieved at a center wavelength of 639.5 nm. The laser operates at a repetition rate of ∼85.55 MHz and emits pulses with a duration of ∼18 ps.
Human settlements are the cause and consequence of most environmental and societal changes on Earth; however, their location and extent is still under debate. We provide here a new 10 m resolution ...(0.32 arc sec) global map of human settlements on Earth for the year 2015, namely the World Settlement Footprint 2015 (WSF2015). The raster dataset has been generated by means of an advanced classification system which, for the first time, jointly exploits open-and-free optical and radar satellite imagery. The WSF2015 has been validated against 900,000 samples labelled by crowdsourcing photointerpretation of very high resolution Google Earth imagery and outperforms all other similar existing layers; in particular, it considerably improves the detection of very small settlements in rural regions and better outlines scattered suburban areas. The dataset can be used at any scale of observation in support to all applications requiring detailed and accurate information on human presence (e.g., socioeconomic development, population distribution, risks assessment, etc.).
The DESIR (decay, excitation and storage of radioactive ions) facility at GANIL-SPIRAL2 will receive a large variety of exotic nuclei at low energy (up to 60keV) with high intensities. However, the ...production methods of radioactive beams are non selective, limiting the purity of the beams of interest. Moreover, the high precision needed for nuclear structure and astrophysics studies using beta decay spectroscopy, laser spectroscopy and trap-based experiments at DESIR requires highly pure samples of exotic nuclei. The aim of the double-Pennig-trap mass separator PIPERADE is to deliver large and very pure samples of exotic nuclei to the different experiments in DESIR. New excitation schemes and a large inner diameter of the first trap will mitigate space charge effects to attempt trapping of up to 105 ions per pulse. The purification cycle will be performed in a few milliseconds so that short-lived nuclei can be purified. To extract the nuclides of interest from the large amount of isobaric contaminants, a resolving power of 105 is mandatory. Afterwards the ions of interest will be accumulated in the second trap until they constitute a sufficiently pure sample for the measurements. The status of the project is presented.
Tracer techniques to assess very-low-density lipoprotein (VLDL) secretion in humans are expensive, are time consuming, and require mathematical models to estimate VLDL kinetics. Here, we describe an ...alternative, time- and cost-efficient protocol to directly determine VLDL1 secretion with an intravenous (i.v.) lipid emulsion test that does not require tracers and compartmental modeling. We describe steps for intralipid infusion, blood sampling, and removal of intralipid from plasma samples, followed by density gradient ultracentrifugation to isolate VLDL1 fraction and measure the secretion rate.
For complete details on the use and execution of this protocol, please refer to Bjorkegren et al. (1996),1 Al-Shayji et al. (2007),2 and Metz et al. (2022).3
Display omitted
•Assess VLDL secretion in vivo without tracers using an IV lipid emulsion•Isolation of VLDL1 particles with density gradient ultracentrifugation•Time- and cost-efficient technique that does not require compartmental modeling
Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Tracer techniques to assess very-low-density lipoprotein (VLDL) secretion in humans are expensive, are time consuming, and require mathematical models to estimate VLDL kinetics. Here, we describe an alternative, time- and cost-efficient protocol to directly determine VLDL1 secretion with an intravenous (i.v.) lipid emulsion test that does not require tracers and compartmental modeling. We describe steps for intralipid infusion, blood sampling, and removal of intralipid from plasma samples, followed by density gradient ultracentrifugation to isolate VLDL1 fraction and measure the secretion rate.
PDF
