A link is established between biomechanical and acoustic 3D models for the numerical simulation of vowel-vowel utterances. The former rely on the activation and contraction of relevant muscles for voice production, which displace and distort speech organs. However, biomechanical models do not provide a closed computational domain of the 3D vocal tract airway where to simulate sound wave propagation. An algorithm is thus proposed to extract the vocal tract boundary from the surrounding anatomical structures at each time step of the transition between vowels. The resulting 3D geometries are fed into a 3D finite element acoustic model that solves the mixed wave equation for the acoustic pressure and particle velocity. An arbitrary Lagrangian-Eulerian framework is considered to account for the evolving vocal tract. Examples include six static vowels and three dynamic vowel-vowel utterances. Plausible muscle activation patterns are first determined for the static vowel sounds following an inverse method. Dynamic utterances are then generated by linearly interpolating the muscle activation of the static vowels. Results exhibit nonlinear trajectory of the vocal tract geometry, similar to that observed in electromagnetic midsagittal articulography. Clear differences are appreciated when comparing the generated sound with that obtained from direct linear interpolation of the vocal tract geometry. That is, interpolation between the starting and ending vocal tract geometries of an utterance, without resorting to any biomechanical model.Quantification of tumor-specific variants (TSVs) in cell-free DNA is rapidly evolving as a prognostic and predictive tool in patients with cancer. Currently, both variant allele frequency (VAF) and number of mutant molecules per mL plasma are used as units of measurement to report those TSVs. However, it is unknown to what extent both units of measurement agree and what are the factors underlying an existing disagreement. To study the agreement between VAF and mutant molecules in current clinical studies, we analyzed 1116 TSVs from 338 patients identified with next-generation sequencing (NGS) or digital droplet PCR (ddPCR). On different study cohorts, a Deming regression analysis was performed and its 95% prediction interval was used as surrogate for the limits of agreement between VAF and number of mutant molecules per mL and to identify outliers. VAF and number of mutant molecules per mL plasma yielded greater agreement when using ddPCR than NGS. https://www.selleckchem.com/ In case of discordance between VAF and number of mutant molecules per mL, insufficient molecular coverage in NGS and high cell-free DNA concentration were the main responsible factors. We propose several optimization steps needed to bring monitoring of TSVs in cell-free DNA to its full potential.The increase of sequencing capacity provided by high-throughput platforms has made it possible to routinely obtain large sets of genomic and transcriptomic sequences from model and non-model organisms. Subsequent genomic analysis and gene discovery in next-generation sequencing experiments are, however, bottlenecked by functional annotation. One common way to perform functional annotation of sets of sequences obtained from next-generation sequencing experiments, is by searching for homologous sequences and accessing the related functional information deposited in genomic databases. Functional annotation is especially challenging for non-model organisms, like many plant species. In such cases, existing free and commercial general-purpose applications may not offer complete and accurate results. We present TOA (Taxonomy-oriented annotation), a Python-based user-friendly open source application designed to establish functional annotation pipelines geared towards non-model plant species that can run in Linux/Mac computers, HPCs and cloud servers. TOA performs homology searches against proteins stored in the PLAZA databases, NCBI RefSeq Plant, Nucleotide Database and Non-Redundant Protein Sequence Database, and outputs functional information from several ontology systems Gene Ontology, InterPro, EC, KEGG, Mapman and MetaCyc. The software performance was validated by comparing the runtimes, total number of annotated sequences and accuracy of the functional information obtained for several plant benchmark data sets with TOA and other functional annotation solutions. TOA outperformed the other software in terms of number of annotated sequences and accuracy of the annotation and constitutes a good alternative to improve functional annotation in plants. TOA is especially recommended for gymnosperms or for low quality sequence data sets of non-model plants.We report a 77-year-old human on renal dialysis for end-stage renal disease with heart failure and atrial fibrillation (AF) complicated by a high ventricular frequency. The underlying disease was thought as tachycardia-induced-cardiomyopathy. Intravenous infusion of amiodarone was initiated, and direct current cardioversion succeeded in converting AF to sinus rhythm. Then, excessive increases in the QT and Tpeak-Tend (Tp-e) intervals were seen and hypokalemia induced by hemodialysis led to the development of numerous episodes of torsades de pointes (TdP). Magnesium repletion was effective in preventing TdP, while Tp-e intervals returned to the previous values 2 days after the discontinuation of amiodarone.Cryptochrome 2 (Cry2) is a core clock gene important for circadian regulation. It has also been associated with anxiety and depressive-like behaviors in mice, but the previous findings have been conflicting in terms of the direction of the effect. To begin to elucidate the molecular mechanisms of this association, we carried out behavioral testing, PET imaging, and gene expression analysis of Cry2-/- and Cry2+/+ mice. Compared to Cry2+/+ mice, we found that Cry2-/- mice spent less time immobile in the forced swim test, suggesting reduced despair-like behavior. Moreover, Cry2-/- mice had lower saccharin preference, indicative of increased anhedonia. In contrast, we observed no group differences in anxiety-like behavior. The behavioral changes were accompanied by lower metabolic activity of the ventro-medial hypothalamus, suprachiasmatic nuclei, ventral tegmental area, anterior and medial striatum, substantia nigra, and habenula after cold stress as measured by PET imaging with a glucose analog. Although the expression of many depression-associated and metabolic genes was upregulated or downregulated by cold stress, we observed no differences between Cry2-/- and Cry2+/+ mice.