Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript ...quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular.
The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80.
In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.
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•Mn transforms from paramagnetic to ferromagnetic system.•The results suggest the possibility of growing θ-MnN epitaxially.•Double MnN layer exhibits an antiferromagnetic behavior, ...with the magnetic moments coupled parallel and alternating along c.•Exchange bias effect is manifested in the interface CrN/MnN.
Spin polarized first principles calculations have been performed to study the structural and electronic properties, and spin coupling of the MnN deposit on the CrN (001) surface. Results indicate that Mn may transform from a paramagnetic to a ferromagnetic system, when adsorbed on a surface. Also, the first CrN layer switches from antiferromagnetic to ferromagnetic alignment. Surface formation energies show that epitaxial growth of θ-MnN on the CrN (001)-(1x1) surface is favorable for N-rich conditions and intermediate conditions. The double MnN layer exhibits an antiferromagnetic behavior, with the magnetic moments coupled parallel and alternating along c. Moreover, the exchange bias effect is manifested in the first CrN layer. The calculated projected densities of states spectra show a half metallic character in the first CrN layer. The Mn magnetic moments are in the range of 2.8–3.3 μB. This work identifies an antiferromagnetic system for possible applications in spintronics.
The cost of data movement in big-data systems motivates careful examination of near-data processing (NDP) frameworks. The concept of NDP was actively researched in the 1990s, but gained little ...commercial traction. After a decade-long dormancy, interest in this topic has spiked. A workshop on NDP was organized at MICRO-46 and was well attended. Given the interest, the organizers and keynote speakers have attempted to capture the key insights from the workshop into an article that can be widely disseminated. This article describes the many reasons why NDP is compelling today and identifies key upcoming challenges in realizing the potential of NDP.
The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This ...mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ̃ confidence level, using a low-background, 14.6-kilogram CsINa scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.
Myxomycetes (plasmodial slime molds, Amoebozoa) are often perceived as widely distributed, confounding to the "everything is everywhere" hypothesis. To test if gene flow within these spore-dispersed ...protists is restricted by geographical barriers, we chose the widespread but morphologically unmistakable species Hemitrichia serpula for a phylogeographic study. Partial sequences from nuclear ribosomal RNA genes (SSU) revealed 40 ribotypes among 135 specimens, belonging to three major clades. Each clade is dominated by specimens from a certain region and by one of two morphological varieties which can be differentiated by SEM micrographs. Partial sequences of the protein elongation factor 1 alpha (EF1A) showed each clade to possess a unique combination of SSU and EF1A genotypes. This pattern is best explained assuming the existence of several putative biospecies dominating in a particular geographical region. However, occasional mismatches between molecular data and morphological characters, but as well heterogeneous SSU and heterozygous EF1A sequences, point to ongoing speciation. Environmental niche models suggest that the putative biospecies are rather restricted by geographical barriers than by macroecological conditions. Like other protists, myxomycetes seem to follow the moderate endemicity hypothesis and are in active speciation, which is most likely shaped by limited gene flow and reproductive isolation.
Gene mutations and gene copy number variants are associated with autism spectrum disorders (ASDs). Affected gene products are often part of signaling networks implicated in synapse formation and/or ...function leading to alterations in the excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)-expressing interneurons has gained particular attention in ASD, little is known on PV's putative role with respect to ASD. Genetic mouse models represent powerful translational tools for studying the role of genetic and neurobiological factors underlying ASD. Here, we report that PV knockout mice (PV(-/-)) display behavioral phenotypes with relevance to all three core symptoms present in human ASD patients: abnormal reciprocal social interactions, impairments in communication and repetitive and stereotyped patterns of behavior. PV-depleted mice also showed several signs of ASD-associated comorbidities, such as reduced pain sensitivity and startle responses yet increased seizure susceptibility, whereas no evidence for behavioral phenotypes with relevance to anxiety, depression and schizophrenia was obtained. Reduced social interactions and communication were also observed in heterozygous (PV(+/-)) mice characterized by lower PV expression levels, indicating that merely a decrease in PV levels might be sufficient to elicit core ASD-like deficits. Structural magnetic resonance imaging measurements in PV(-/-) and PV(+/-) mice further revealed ASD-associated developmental neuroanatomical changes, including transient cortical hypertrophy and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated that the E/I balance in these mice is altered by modification of both inhibitory and excitatory synaptic transmission. On the basis of the reported changes in PV expression patterns in several, mostly genetic rodent models of ASD, we propose that in these models downregulation of PV might represent one of the points of convergence, thus providing a common link between apparently unrelated ASD-associated synapse structure/function phenotypes.
Boron carbide (B4C) is one of the few materials that is expected to be most resilient with respect to the extremely high brilliance of the photon beam generated by free electron lasers (FELs) and is ...thus of considerable interest for optical applications in this field. However, as in the case of many other optics operated at light source facilities, B4C-coated optics are subject to ubiquitous carbon contaminations. Carbon contaminations represent a serious issue for the operation of FEL beamlines due to severe reduction of photon flux, beam coherence, creation of destructive interference, and scattering losses. A variety of B4C cleaning technologies were developed at different laboratories with varying success. We present a study regarding the low-pressure RF plasma cleaning of carbon contaminated B4C test samples via inductively coupled O2/Ar, H2/Ar, and pure O2 RF plasma produced following previous studies using the same ibss GV10x downstream plasma source. Results regarding the chemistry, morphology as well as other aspects of the B4C optical coating before and after the plasma cleaning are reported. We conclude that among the above plasma processes only plasma based on pure O2 feedstock gas exhibits the required chemical selectivity for maintaining the integrity of the B4C optical coatings.
The influence of winding pattern on the mechanical response of filament wound glass/epoxy cylinders exposed to external pressure is studied by testing cylindrical specimens having stacked layers with ...coincident patterns in a hyperbaric testing chamber. Different analytical models are evaluated to predict buckling pressure and modes of thin wall cylinders (diameter to thickness ratio
d/
h of 25) and satisfactory predictions are obtained which are in the same order of magnitude that those obtained in experimental results. Test results show no evident pattern influence on either strength (implosion pressure) or buckling behavior (buckling modes) of thin wall or thick wall (
d/
h of 10) cylinders.
The majority of presently exploitable marine methane hydrate reservoirs are likely to host hydrate in disseminated form in coarse grain sediments. For hydrate concentrations below 25–40%, ...disseminated or pore‐filling hydrate does not increase elastic frame moduli, thus making impotent traditional seismic velocity‐based methods. Here, we present a theoretical model to calculate frequency‐dependent P and S wave velocity and attenuation of an effective porous medium composed of solid mineral grains, methane hydrate, methane gas, and water. The model considers elastic wave energy losses caused by local viscous flow both (i) between fluid inclusions in hydrate and pores and (ii) between different aspect ratio pores (created when hydrate grows); the inertial motion of the frame with respect to the pore fluid (Biot's type fluid flow); and gas bubble damping. The sole presence of pore‐filling hydrate in the sediment reduces the available porosity and intrinsic permeability of the sediment affecting Biot's type attenuation at high frequencies. Our model shows that attenuation maxima due to fluid inclusions in hydrate are possible over the entire frequency range of interest to exploration seismology (1–106 Hz), depending on the aspect ratio of the inclusions, whereas maxima due to different aspect ratio pores occur only at sonic to ultrasound frequencies (104–106 Hz). This frequency response imposes further constraints on possible hydrate saturations able to reproduce broadband elastic measurements of velocity and attenuation. Our results provide a physical basis for detecting the presence and amount of pore‐filling hydrate in seafloor sediments using conventional seismic surveys.
Key Points
Pore‐filling hydrate in sediments enhances elastic wave attenuation at 1–1E6 Hz due to increased fluid‐solid contacts and squirt flow
Hydrate‐formed pores of different aspect ratios enhance elastic wave attenuation at 1E4–1E6 Hz and fluid inclusions in hydrate at 1–1E6 Hz
Elastic wave attenuation due to fluid inclusions in hydrate may provide signal contrasts to detect pore‐filling hydrate in seismic surveys
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