1,140 research outputs found
ITSxpress: Software to rapidly trim internally transcribed spacer sequences with quality scores for marker gene analysis [version 1; referees: 2 approved]
The internally transcribed spacer (ITS) region between the small subunit ribosomal RNA gene and large subunit ribosomal RNA gene is a widely used phylogenetic marker for fungi and other taxa. The eukaryotic ITS contains the conserved 5.8S rRNA and is divided into the ITS1 and ITS2 hypervariable regions. These regions are variable in length and are amplified using primers complementary to the conserved regions of their flanking genes. Previous work has shown that removing the conserved regions results in more accurate taxonomic classification. An existing software program, ITSx, is capable of trimming FASTA sequences by matching hidden Markov model profiles to the ends of the conserved genes using the software suite HMMER. ITSxpress was developed to extend this technique from marker gene studies using Operational Taxonomic Units (OTU’s) to studies using exact sequence variants; a method used by the software packages Dada2, Deblur, QIIME 2, and Unoise. The sequence variant approach uses the quality scores of each read to identify sequences that are statistically likely to represent real sequences. ITSxpress enables this by processing FASTQ rather than FASTA files. The software also speeds up the trimming of reads by a factor of 14-23 times on a 4-core computer by temporarily clustering highly similar sequences that are common in amplicon data and utilizing optimized parameters for Hmmsearch. ITSxpress is available as a QIIME 2 plugin and a stand-alone application installable from the Python package index, Bioconda, and Github
Report on the Third Workshop on Sustainable Software for Science: Practice and Experiences (WSSSPE3)
This report records and discusses the Third Workshop on Sustainable Software
for Science: Practice and Experiences (WSSSPE3). The report includes a
description of the keynote presentation of the workshop, which served as an
overview of sustainable scientific software. It also summarizes a set of
lightning talks in which speakers highlighted to-the-point lessons and
challenges pertaining to sustaining scientific software. The final and main
contribution of the report is a summary of the discussions, future steps, and
future organization for a set of self-organized working groups on topics
including developing pathways to funding scientific software; constructing
useful common metrics for crediting software stakeholders; identifying
principles for sustainable software engineering design; reaching out to
research software organizations around the world; and building communities for
software sustainability. For each group, we include a point of contact and a
landing page that can be used by those who want to join that group's future
activities. The main challenge left by the workshop is to see if the groups
will execute these activities that they have scheduled, and how the WSSSPE
community can encourage this to happen
A Tabletop X-Ray Tomography Instrument for Nanometer-Scale Imaging: Integration of a Scanning Electron Microscope with a Transition-Edge Sensor Spectrometer
X-ray nanotomography is a powerful tool for the characterization of nanoscale
materials and structures, but is difficult to implement due to competing
requirements on X-ray flux and spot size. Due to this constraint,
state-of-the-art nanotomography is predominantly performed at large synchrotron
facilities. Compact X-ray nanotomography tools operated in standard analysis
laboratories exist, but are limited by X-ray optics and destructive sample
preparation techniques. We present a laboratory-scale nanotomography instrument
that achieves nanoscale spatial resolution while changing the limitations of
conventional tomography tools. The instrument combines the electron beam of a
scanning electron microscope (SEM) with the precise, broadband X-ray detection
of a superconducting transition-edge sensor (TES) microcalorimeter. The
electron beam generates a highly focused X-ray spot in a metal target, while
the TES spectrometer isolates target photons with high signal-to-noise. This
combination of a focused X-ray spot, energy-resolved X-ray detection, and
unique system geometry enable nanoscale, element-specific X-ray imaging in a
compact footprint. The proof-of-concept for this approach to X-ray
nanotomography is demonstrated by imaging 160 nm features in three dimensions
in a Cu-SiO2 integrated circuit, and a path towards finer resolution and
enhanced imaging capabilities is discussed.Comment: The following article has been submitted to Physical Review Applie
A tabletop x-ray tomography instrument for nanometer-scale imaging: demonstration of the 1,000-element transition-edge sensor subarray
We report on the 1,000-element transition-edge sensor (TES) x-ray
spectrometer implementation of the TOMographic Circuit Analysis Tool (TOMCAT).
TOMCAT combines a high spatial resolution scanning electron microscope (SEM)
with a highly efficient and pixelated TES spectrometer to reconstruct
three-dimensional maps of nanoscale integrated circuits (ICs). A 240-pixel
prototype spectrometer was recently used to reconstruct ICs at the 130 nm
technology node, but to increase imaging speed to more practical levels, the
detector efficiency needs to be improved. For this reason, we are building a
spectrometer that will eventually contain 3,000 TES microcalorimeters read out
with microwave superconducting quantum interference device (SQUID)
multiplexing, and we currently have commissioned a 1,000 TES subarray. This
still represents a significant improvement from the 240-pixel system and allows
us to begin characterizing the full spectrometer performance. Of the 992
maximimum available readout channels, we have yielded 818 devices, representing
the largest number of TES x-ray microcalorimeters simultaneously read out to
date. These microcalorimeters have been optimized for pulse speed rather than
purely energy resolution, and we measure a FWHM energy resolution of 14 eV at
the 8.0 keV Cu K line.Comment: 5 pages, 4 figures, submitted to IEEE Transactions on Applied
Superconductivit
The DAC system and associations with multiple myeloma
Despite the clear progress achieved in recent years in the treatment of MM, most patients eventually relapse and therefore novel therapeutic options are still necessary for these patients. In this regard, several drugs that target specific mechanisms of the tumor cells are currently being explored in the preclinical and clinical setting. This manuscripts offers a review of the rationale and current status of the antimyeloma activity of one of the most relevant examples of these targeted drugs: deacetylase inhibitors (DACi). Several studies have demonstrated the prooncogenic activity of deacetylases (DACs) through the targeting not only of histones but also of non histone proteins relevant to tumor progression, such as p53, E2F family members, Bcl-6, Hsp90, HIF-1α or Nur77. This fact together with the DACs overexpression present in several tumors, has prompted the development of some DACi with potential antitumor effect. This situation is also evident in the case of MM as two mechanisms of DACi, the inhibition of the epigenetic inactivation of p53 and the blockade of the unfolded protein response, through the inhibition of the aggressome formation (by targeting DAC6) and the inactivation of the chaperone system (by acetylating HSP-90), provides the rationale for the exploration of the potential antimyeloma activity of these compounds. Several DACi with different chemical structure and different selectivity for targeting the DAC families have been tested in MM. Their preclinical activity in monotherapy has been quite exciting and has been described to be mediated by various mechanisms: the induction of apoptosis and cell cycle arrest mainly by the upregulation of p21; the interferece with the interaction between plasma cells and the microenvironment, by reducing the expression and signalling of several cytokines or by inhibiting angiogenesis. Finally they also have a role in protecting murine models from myeloma bone disease. Neverteless, the clinical activity in monotherapy of these drugs in relapsed/refractory MM patients has been very modest. This has prompted the development of combinations such as the one with bortezomib or lenalidomide and dexamethasone, which have already been taken into the clinics with positive preliminary results
The state of the Martian climate
60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
Comparative analytical performance of multiple plasma Aβ42 and Aβ40 assays and their ability to predict positron emission tomography amyloid positivity
INTRODUCTION: This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (Aβ) peptides in plasma and the extent to which they improve the prediction of amyloid positivity. METHODS: Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma Aβ assays. Statistical tests were performed to determine whether the plasma Aβ measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype. RESULTS: The age and APOE genotype model predicted amyloid status with an area under the curve (AUC) of 0.75. Three assays improved AUCs to 0.81, 0.81, and 0.84 (P < .05, uncorrected for multiple comparisons). DISCUSSION: Measurement of Aβ in plasma contributes to addressing the amyloid component of the ATN (amyloid/tau/neurodegeneration) framework and could be a first step before or in place of a PET or cerebrospinal fluid screening study. HIGHLIGHTS: The Foundation of the National Institutes of Health Biomarkers Consortium evaluated six plasma amyloid beta (Aβ) assays using Alzheimer's Disease Neuroimaging Initiative samples. Three assays improved prediction of amyloid status over age and apolipoprotein E (APOE) genotype. Plasma Aβ42/40 predicted amyloid positron emission tomography status better than Aβ42 or Aβ40 alone
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