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SummaryWith the recent rapid advancements in sequencing technology, the analysis of omics data has become increasingly important for biomedical research. However, many laboratories lack the time or expertise to thoroughly analyze such data. Among omics assays, ATAC-Seq (Assay for transposase-accessiblechromatin usingsequencing) and mRNA-Seq (messengerRNA sequencing) are easy and cost-effective methods that are commonly used to define chromatin accessibility and gene expression levels, respectively. Here we introduce Cactus (Chromatinaccessibility and transcriptomicsunifyingsoftware), a pipeline that streamlines the individual or integrated analysis of ATAC-Seq and mRNA-Seq data. The pipeline is written in Nextflow for efficient scaling, caching, and parallelization, and all tools are packaged in Singularity/Docker containers or conda/Mamba virtual environments for simple installation and high reproducibility. Cactus conducts preprocessing on raw sequencing reads, followed by differential analysis between conditions. Results are split into Differential Analysis Subsets (DASs) based on significance threshold, direction of change, annotated genomic regions, and experiment type. Then, Cactus computes enrichments of entries from internal (i.e., DASs) and external (i.e., ontologies, pathways, DNA binding motifs, ChIP-Seq (Chromatin immunoprecipitationsequencing) binding sites, and chromatin states) databases in DASs and presents results in barplots and customizable heatmaps. The visualization of the results is simplified by the generation of merged PDFs, merged tables, and formatted Excel tables. In conclusion, Cactus can assist researchers in gaining comprehensive insights from chromatin accessibility and gene expression data in a quick, easy, and reproducible manner.Availability and implementationCactus can be installed via Nextflow pull jsalignon/cactus. Source code and documentation are available online (https://github.com/jsalignon/cactus).Contactjerome.salignon@ki.seorchristian.riedel@ki.se

5-Fluorouracil (5-FU) is an anticancer drug extensively used for different cancers. Intracellular metabolic activation leads to several nucleoside and nucleotide metabolites essential to exert its cytotoxic activity on multiple cellular targets such as enzymes, DNA and RNA. In this paper, we describe the development of a method based on liquid chromatography coupled with high resolution mass spectrometry suitable for the simultaneous determination of the ten anabolic metabolites (nucleoside, nucleotide and sugar nucleotide) of 5-FU. The chromatographic separation was optimized on a porous graphitic carbon column allowing the analysis of the metabolites of 5-FU as well as endogenous nucleotides. The detection was performed on an Orbitrap® tandem mass spectrometer. Linearity of the method was verified in intracellular content and in RNA extracts. The limit of detection was equal to 12 pg injected on column for nucleoside metabolites of 5-FU and 150 pg injected on column for mono- and tri-phosphate nucleotide metabolites. Matrix effect was evaluated in cellular contents, DNA and RNA extracts for nucleoside and nucleotides metabolites. The method was successfully applied to i) measure the proportion of each anabolic metabolite of 5-FU in cellular contents, ii) follow the consequence of inhibition of enzymes on the endogenous nucleotide pools, iii) study the incorporation of metabolites of 5-FU into RNA and DNA, and iv) to determine the incorporation rate of 5-FUrd into 18 S and 28 S sub-units of rRNA., Graphical abstract Image 1, Highlights • The LC-MS-HRMS method allows the analysis of the ten anabolic metabolites of 5-FU. • The present method is useful to study the incorporation of 5-FU into RNA and DNA. • Method to determine the incorporation rate of 5-FU into subunit of rRNA is innovative.

Acoustic allometry occurs when features of animal vocalisations can be predicted from body size measurements. Despite this being considered the norm, allometry sometimes breaks, resulting in species sounding smaller or larger than expected for their size. A recent hypothesis suggests that allometry-breaking mammals cluster into two groups: those with anatomical adaptations to their vocal tracts and those capable of learning new sounds (vocal learners). Here, we tested which mechanism is used to escape from acoustic allometry by probing vocal tract allometry in a proven mammalian vocal learner, the harbour seal (Phoca vitulina). We tested whether vocal tract structures and body size scale allometrically in 68 young individuals. We found that both body length and body mass accurately predict vocal tract length and one tracheal dimension. Independently, body length predicts vocal fold length while body mass predicts a second tracheal dimension. All vocal tract measures are larger in weaners than in pups and some structures are sexually dimorphic within age classes. We conclude that harbour seals do comply with anatomical allometric constraints. However, allometry between body size and vocal fold length seems to emerge after puppyhood, suggesting that ontogeny may modulate the anatomy–learning distinction previously hypothesised as clear cut. We suggest that seals, and perhaps other species producing signals that deviate from those expected from their vocal tract dimensions, may break allometry without morphological adaptations. In seals, and potentially other vocal learning mammals, advanced neural control over vocal organs may be the main mechanism for breaking acoustic allometry.

Vocal production learning (VPL) is the experience-driven ability to produce novel vocal signals through imitation or modification of existing vocalizations. A parallel strand of research investigates acoustic allometry, namely how information about body size is conveyed by acoustic signals. Recently, we proposed that deviation from acoustic allometry principles as a result of sexual selection may have been an intermediate step towards the evolution of vocal learning abilities in mammals. Adopting a more hypothesis-neutral stance, here we perform phylogenetic regressions and other analyses further testing a potential link between VPL and being an allometric outlier. We find that multiple species belonging to VPL clades deviate from allometric scaling but in the opposite direction to that expected from size exaggeration mechanisms. In other words, our correlational approach finds an association between VPL and being an allometric outlier. However, the direction of this association, contra our original hypothesis, may indicate that VPL did not necessarily emerge via sexual selection for size exaggeration: VPL clades show higher vocalization frequencies than expected. In addition, our approach allows us to identify species with potential for VPL abilities: we hypothesize that those outliers from acoustic allometry lying above the regression line may be VPL species. Our results may help better understand the cross-species diversity, variability and aetiology of VPL, which among other things is a key underpinning of speech in our species. This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part II)’.

Vocal production learning (VPL) is the experience-driven ability to produce novel vocal signals through imitation or modification of existing vocalizations. A parallel strand of research investigates acoustic allometry, namely how information about body size is conveyed by acoustic signals. Recently, we proposed that deviation from acoustic allometry principles as a result of sexual selection may have been an intermediate step towards the evolution of vocal learning abilities in mammals. Adopting a more hypothesis-neutral stance, here we perform phylogenetic regressions and other analyses further testing a potential link between VPL and being an allometric outlier. We find that multiple species belonging to VPL clades deviate from allometric scaling but in the opposite direction to that expected from size exaggeration mechanisms. In other words, our correlational approach finds an association between VPL and being an allometric outlier. However, the direction of this association, contra our original hypothesis, may indicate that VPL did not necessarily emerge via sexual selection for size exaggeration: VPL clades show higher vocalization frequencies than expected. In addition, our approach allows us to identify species with potential for VPL abilities: we hypothesize that those outliers from acoustic allometry lying above the regression line may be VPL species. Our results may help better understand the cross-species diversity, variability and aetiology of VPL, which among other things is a key underpinning of speech in our species. This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part II)’.

Acoustic allometry occurs when features of animal vocalisations can be predicted from body size measurements. Despite this being considered the norm, allometry sometimes breaks, resulting in species sounding smaller or larger than expected for their size. A recent hypothesis suggests that allometry-breaking mammals cluster into two groups: those with anatomical adaptations to their vocal tracts and those capable of learning new sounds (vocal learners). Here we test which mechanism is used to escape from acoustic allometry by probing vocal tract allometry in a proven mammalian vocal learner, the harbour seal (Phoca vitulina). We test whether vocal tract structures and body size scale allometrically in 68 young individuals. We find that both body length and body mass accurately predict vocal tract length and one tracheal dimension. Independently, body length predicts vocal fold length while body mass predicts a second tracheal dimension. All vocal tract measures are larger in weaners than in pups and some structures are sexually dimorphic within age classes. We conclude that harbour seals do comply with anatomical allometric constraints. However, allometry between body size and vocal fold length seems to emerge after puppyhood, suggesting that ontogeny may modulate the anatomy-learning distinction previously hypothesised as clear-cut. We suggest that seals, like other species producing signals that deviate from those expected from their vocal tract dimensions, may break allometry without morphological adaptations. In seals, and potentially other vocal learning mammals, advanced neural control over vocal organs may be the main mechanism for breaking acoustic allometry.

Partial response to chemotherapy leads to disease resurgence. Upon treatment, a subpopulation of cancer cells, called drug-tolerant persistent cells, display a transitory drug tolerance that lead to treatment resistance 1,2. Though drug-tolerance mechanisms remain poorly known, they have been linked to non-genomic processes, including epigenetics, stemness and dormancy 2–4. 5-fluorouracil (5-FU), the most widely used chemotherapy in cancer treatment, is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways 5–9. Here, we show that 5-FU treatment leads to the unexpected production of fluorinated ribosomes, exhibiting altered mRNA translation. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts and human tumours. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs according to the nature of their 5’-untranslated region. As a result, we found that sustained translation of IGF-1R mRNA, which codes for one of the most potent cell survival effectors, promoted the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that “man-made” fluorinated ribosomes favour the drug-tolerant cellular phenotype by promoting translation of survival genes. This could be exploited for developing novel combined therapies. By unraveling translation regulation as a novel gene expression mechanism helping cells to survive a drug-challenge, our study extends the spectrum of molecular mechanisms driving drug-tolerance.

Introduction: Immune checkpoint inhibitors (ICIs) are a major breakthrough in cancer treatment. Their increasingly frequent use leads to an uprising incidence of immune-related adverse events (irAEs). Among those, myocarditis is the most reported fatal cardiovascular irAE, frequently associated with ICI-related myositis. Case series: Here, we report three cases of ICI-induced myocarditis/myositis with an extremely severe myasthenia gravis-like (MG-like) presentation, highlighting the main challenges in irAEs management. These patients were over 60 years old and presented an ongoing melanoma, either locally advanced or metastatic, treated with ICI combinations. Shortly after the first or second ICI infusion, they were admitted in an intensive care unit (ICU) for grade 3 ICI-induced MG-like symptoms leading to acute respiratory failure (ARF) requiring invasive mechanical ventilation (IMV). The initial misdiagnosis was later corrected to severe ICI-induced seronegative myocarditis/myositis upon biological results and histopathology from muscular/endomyocardial biopsies. All of them received urgent high-dose corticosteroids pulses. The oldest patient died prematurely, but the two others received targeted therapies leading to complete recovery for one of them. Discussion: These cases highlight the four main challenges of irAEs, encompassing the lack of knowledge among physicians, the risk of misdiagnosis due to numerous and non-specific symptoms, the frequent overlapping forms of irAEs, and the extremely rare MG-like misleading presentation of myocarditis/myositis. The exact pathophysiology of irAEs remains unclear, although a major involvement of the lymphoid compartment (specifically T lymphocytes) was evidenced. Therapeutic management is based on urgent high-dose corticosteroids. For the severest forms of irAEs, case-by-case targeted immunosuppressive therapies should be urgently administered upon multidisciplinary meetings. Conclusion: These cases highlight the lack of knowledge of irAEs among physicians, aggravated by misleading overlapping forms, requiring specific management in trained units and multidisciplinary care. Severe MG-like presentation of irAEs constitutes an absolute therapeutic emergency with high-dose corticosteroids and targeted immunosuppressive therapy.

ORAL; International audience; This work aims to understand the origin of propagation losses in GaN-on-Si devices at microwave frequencies thanks to original AFM's electrical modes such as scanning capacitance microscopy (SCM) and scanning spreading resistance microscopy (SSRM). AlN films on Si substrate were grown using Metalorganic Vapor Phase Epitaxy (MOVPE) technique. SCM and SSRM measurements evidence a p-type conductive channel as well as a pn-junction beneath the AlN/Si interface. The diffusion depths of Al and Ga atoms obtained by Secondary Ion Mass Spectroscopy (SIMS) are in good agreement with those deduced from SCM and SSRM. Sample grown at lower temperature (1000°C) exhibits a conductive channel and a junction over a shallow depth explaining its lower propagation losses in comparison with those synthesized at higher temperature (1150°C). Thus, monitoring the dopant diffusion beneath the AlN/Si interface is crucial to achieve efficient GaN-on-Si microwave power devices.

The broadening utilisation of ancient DNA to address archaeological, palaeontological, and biological questions is resulting in a rising diversity in the size of laboratories and scale of analyses being performed. In the context of this heterogeneous landscape, we present nf-core/eager, an advanced and entirely redesigned and extended version of the EAGER pipeline for the analysis of ancient genomic data. This Nextflow pipeline aims to address three main themes: accessibility and adaptability to different computing configurations, reproducibility to ensure robust analytical standards, and updating the pipeline to the latest routine ancient genomic practises. This new version of EAGER has been developed within the nf-core initiative to ensure high-quality software development and maintenance support; contributing to a long-term lifecycle for the pipeline. nf-core/eager will assist in ensuring that ancient DNA sequencing data can be used by a diverse range of research groups and fields.Competing Interest StatementThe authors have declared no competing interest. Introduction Materials and methods - Updated Workflow - Usage - Benchmarking -- Functionality demonstration -- Run-time comparison Results - Functionality demonstration - Run-time comparison Discussion Conclusion

International audience; We present a novel temporally coherent stylized rendering technique working entirely at the compositing stage.We first generate a distribution of 3D anchor points using an implicit grid based on the local object positions stored in a G-buffer, hence following object motion. We then draw splats in screen space anchored to these points so as to be motion coherent.To increase the perceived flatness of the style, we adjust the anchor points density using a fractalization mechanism.Sudden changes are prevented by controlling the anchor points opacity and introducing a new order-independent blending function.We demonstrate the versatility of our method by showing a large variety of styles thanks to the freedom offered by the splats content and their attributes that can be controlled by any G-buffer.

AlN nucleation layers are the basement of GaN-on-Si structures grown for light-emitting diodes, high frequency telecommunication and power switching systems. In this context, our work aims to understand the origin of propagation losses in GaN-on-Si High Electron Mobility Transistors at microwaves frequencies, which are critical for efficient devices and circuits. AlN/Si structures are grown by Metalorganic Vapor Phase Epitaxy. Acceptor dopant in-diffusion (Al and Ga) into the Si substrate is studied by Secondary Ion Mass Spectroscopy and is mainly located in the first 200 nm beneath the interface. In this region, an acceptor concentration of a few 1018 cm-3 is estimated from Capacitance–Voltage (C–V) measurements while the volume hole concentration of several 1017 cm-3 is deduced from sheet resistance. Furthermore, the combination of scanning capacitance microscopy and scanning spreading resistance microscopy enables the 2D profiling of both the p-type conductive channel and the space charge region beneath the AlN/Si interface. We demonstrate that samples grown at lower temperature exhibit a p-doped conductive channel over a shallower depth which explains lower propagation losses in comparison with those synthesized at higher temperature. Our work highlights that this p-type channel can increase the propagation losses in the high-frequency devices but also that a memory effect associated with the previous sample growths with GaN can noticeably affect the physical properties in absence of proper reactor preparation. Hence, monitoring the acceptor dopant in-diffusion beneath the AlN/Si interface is crucial for achieving efficient GaN-on-Si microwave power devices.

International audience; In this paper, we conduct a study for recognizing motion qualities in hand gestures using virtual reality trackers attached to the hand. From this 6D signal, we extract Euclidean, equi-affine and moving frame features and compare their effectiveness in the task of recognizing Laban Effort qualities. Our experimental results reveal that equi-affine features are highly discriminant features for this task. We also compare two classification methods on this task. In the first method, we trained separate HMM models for the 6 Laban Effort qualities (light, strong, sudden, sustained, direct, indirect). In the second method, we trained separate HMM models for the 8 Laban motion verbs (dab, glide, float, flick, thrust, press, wring, slash) and combined them to recognize individual qualities. In our experiments, the second method gives improved results. Together, those findings suggest that low-dimensional signals from VR trackers can be used to predict motion qualities with reasonable precision.

International audience; Herein, the interest of cubic silicon carbide as a template for the growth of AlGaN/ GaN high electron mobility transistor (HEMT) heterostructures on silicon substrates for high-frequency operation is shown. On the one hand, 0.6-0.8 μm-thick 3C-SiC grown by chemical vapor deposition on intrinsic silicon substrate having initial resistivity superior to 5 kΩ cm enables the metalorganic vapor phase epitaxy of GaN buffer layers with propagation losses below 0.4 dB mm À1 at 40 GHz and 0.5 dB mm À1 at 67 GHz. On the other hand, an HEMT heterostructure is grown on 1.5 μm-thick 3C-SiC on 4 off-axis silicon substrate having an initial resistivity superior to 200 Ω cm that allows to keep a sufficiently resistive epilayer stack limiting the loss up to 0.78 dB mm À1 at 40 GHz. Device process developed on a piece of the 100 mm diameter wafer leads to the demonstration of DC transistor operation with low leakage currents. Compared with direct growth on silicon, these templates enable reduced radio frequency (RF) propagation losses that are very interesting for high-frequency transistors and circuits operation.

Mechanical constraints imposed by anatomical adaptations are a ubiquitous feature of animal sound production. They can give rise to ‘vocal predispositions’ (i.e., acoustic structures strictly determined by vocal anatomy). Such predispositions are crucial to the investigation of the cognitive and evolutionary processes underlying acoustic communication in vertebrates, including human speech.

Whole-genome sequencing (WGS) is a fundamental technology for research to advance precision medicine, but the limited availability of portable and user-friendly workflows for WGS analyses poses a major challenge for many research groups and hampers scientific progress. Here we present Sarek, an open-source workflow to detect germline variants and somatic mutations based on sequencing data from WGS, whole-exome sequencing (WES), or gene panels. Sarek features (i) easy installation, (ii) robust portability across different computer environments, (iii) comprehensive documentation, (iv) transparent and easy-to-read code, and (v) extensive quality metrics reporting. Sarek is implemented in the Nextflow workflow language and supports both Docker and Singularity containers as well as Conda environments, making it ideal for easy deployment on any POSIX-compatible computers and cloud compute environments. Sarek follows the GATK best-practice recommendations for read alignment and pre-processing, and includes a wide range of software for the identification and annotation of germline and somatic single-nucleotide variants, insertion and deletion variants, structural variants, tumour sample purity, and variations in ploidy and copy number. Sarek offers easy, efficient, and reproducible WGS analyses, and can readily be used both as a production workflow at sequencing facilities and as a powerful stand-alone tool for individual research groups. The Sarek source code, documentation and installation instructions are freely available at https://github.com/nf-core/sarek and at https://nf-co.re/sarek/.

Summary This study investigates the effect of the ventricular folds on fundamental frequency (fo) in the voice production of domestic pigs (Sus scrofa domesticus). The excised larynges of six subadult pigs were phonated in two preparation stages, with the ventricular folds present (PS1) and removed (PS2). Vocal fold resonances were tested with a laser vibrometer, and a four-mass computational model was created. Highly significant fo differences were found between PS1 and PS2 (means at 93.7 and 409.3 Hz, respectively). Two tissue resonances were found at 115 Hz and 250–290 Hz. The computational model had unique solutions for abducted and adducted ventricular folds at about 150 and 400 Hz, roughly matching the fo measured ex vivo for PS1 and PS2. The differing fo encountered across preparation stages PS1 and PS2 is explained by distinct activation of either a high or a low eigenfrequency mode, depending on the engagement of the ventricular folds. The inability of the investigated larynges to vibrate at frequencies below 250 Hz in PS2 suggests that in vivo low-frequency calls of domestic pigs (pre-eminently grunts) are likely produced with engaged ventricular folds. Allometric comparison suggests that the special, mechanically coupled “double oscillator” has evolved to prevent signaling disadvantages. Given these traits, the porcine larynx might – apart from special applications relating to the involvement of ventricular folds – not be an ideal candidate for emulating human voice production in excised larynx experimentation.

Introduction L’incidence de la syphilis augmente depuis plusieurs annees. Devant un tableau clinique evocateur de forme secondaire, le diagnostic repose habituellement sur la positivite de la serologie. Nous rapportons une observation de syphilis secondaire restant seronegative chez un patient traite par rituximab ou le diagnostic a ete porte par les donnees histologiques et un test PCR sur les lesions cutanees. Materiel et Methodes Un patient de 25 ans traite par rituximab depuis 6 ans pour un pemphigus vulgaire etait adresse pour une recidive atypique de son pemphigus. A l’examen, il avait une eruption maculopapuleuse diffuse non prurigineuse avec localisation palmaire, des lesions acneiformes du menton, et des erosions du gland. Le patient rapportait un rapport homosexuel non protege 3 mois avant le debut de l’eruption. Le tableau etait tres evocateur de syphilis secondaire mais la serologie syphillitique (test treponemique et test non treponemique) ainsi que la PCR treponeme dans les urines etaient negatives. Il y avait un effondrement total de la population lymphocytaire B (zero lymphocyte B) sur l’immunophenotypage sanguin, les autres elements biologiques etant normaux. Le diagnostic de syphilis secondaire [MR2] etait redresse grâce a la positivite des tests PCR treponeme preleves a partir des lesions cutaneomuqueuses. La biopsie cutanee d’une lesion papuleuse mettait egalement en evidence de multiples treponemes en immunohistochimie. Resultats La syphilis seronegative chez les sujets avec un deficit immunitaire humoral est un piege diagnostique. Devant un tableau clinique evocateur, le diagnostic peut etre redresse grâce aux tests PCR et a l’examen histologique. Discussion Le rituximab est un anticorps monoclonal chimerique dirige contre la molecule de surface CD20 present sur les lymphocytes B, entrainant ainsi leur depletion. Les lymphocytes B etant a l’origine de la production des anticorps, leur absence met en defaut une bonne interpretation serologique. Cette observation confirme l’interet des tests PCR sur les lesions cutanees et des examens histologiques en cas de suspicion clinique de syphillis non attestee sur le plan serologique. Il s’agit a notre connaissance du deuxieme cas rapporte dans un contexte de traitement par rituximab. Le premier concernait un patient traite pour une sclerose en plaque, et comme dans notre observation, le diagnostic etait redresse grâce aux PCR treponeme.

International audience; We present a method for easily drafting expressive character animation by playing with instrumented rigid objects. We parse the input 6D trajectories (position and orientation over time)-called spatial motion doodles-into sequences of actions and convert them into detailed character animations using a dataset of parameterized motion clips which are automatically fitted to the doodles in terms of global trajectory and timing. Moreover, we capture the expres-siveness of user-manipulation by analyzing Laban effort qualities in the input spatial motion doodles and transferring them to the synthetic motions we generate. We validate the ease of use of our system and the expressiveness of the resulting animations through a series of user studies, showing the interest of our approach for interactive digital storytelling applications dedicated to children and non-expert users, as well as for providing fast drafting tools for animators.

For technology nodes beyond 14nm silicon nitride spacer etching has become a major challenge. Conventional plasma etching techniques based on CHF3/O2 cannot achieve thorough nitride removal on horizontal surfaces without inducing either CD loss or Si/SiGe source/drain recess. This leads to either gate leakage increase or poor raised source/drain epitaxy. To overcome atomic scale control issues faced with continuous plasma processes, several techniques aiming at achieving atomic layer etching or thin layer etching were recently described [1]. An original etching approach has been reported which consists in modifying the silicon nitride through H2 ion implantation by plasma (ICP or CCP) and then selectively removing the modified fraction of the layer thanks to chemical etching [2]. Layer modification depth is controlled thanks to plasma parameters (bias voltage and process time). This unconventional technique was demonstrated on 14nm FDSOI logic device and showed less than 1nm spacer CD loss, less than 0.6nm SiGe recess which enabled defect-free source/drain epitaxy [2]. Mechanisms for silicon nitride modifications and selective removal are discussed in this article by comparing downstream plasma, liquid-phase HF and gas-phase HF as removal techniques.

Summary Objective Electroglottography (EGG) is a widely used noninvasive method that purports to measure changes in relative vocal fold contact area (VFCA) during phonation. Despite its broad application, the putative direct relation between the EGG waveform and VFCA has to date only been formally tested in a single study, suggesting an approximately linear relationship. However, in that study, flow-induced vocal fold (VF) vibration was not investigated. A rigorous empirical evaluation of EGG as a measure of VFCA under proper physiological conditions is therefore still needed. Methods/design Three red deer larynges were phonated in an excised hemilarynx preparation using a conducting glass plate. The time-varying contact between the VF and the glass plate was assessed by high-speed video recordings at 6000 fps, synchronized to the EGG signal. Results The average differences between the normalized [0, 1] VFCA and EGG waveforms for the three larynges were 0.180 (±0.156), 0.075 (±0.115), and 0.168 (±0.184) in the contacting phase and 0.159 (±0.112), −0.003 (±0.029), and 0.004 (±0.032) in the decontacting phase. Discussions and conclusions Overall, there was a better agreement between VFCA and the EGG waveform in the decontacting phase than in the contacting phase. Disagreements may be caused by nonuniform tissue conductance properties, electrode placement, and electroglottograph hardware circuitry. Pending further research, the EGG waveform may be a reasonable first approximation to change in medial contact area between the VFs during phonation. However, any quantitative and statistical data derived from EGG should be interpreted cautiously, allowing for potential deviations from true VFCA.

Using CH3F/O2/He based chemistries in high density plasmas for silicon nitride spacer etching, loss of silicon in active source/drain regions of CMOS transistors can be observed. Minimizing the so-called silicon recess during nitride spacer etching is extremely difficult to achieve but mandatory since it directly impacts the device performance. In this work, the authors investigated the benefits of CH3F/O2/He/SiCl4 plasma to limit this recess. Using x-ray photoelectron spectroscopy, the mechanism for high Si3N4/Si selectivity is identified as the formation of a preferential thick SiOxFyClz passivation layer, generated at the silicon surface. The silicon damage is reduced by the growth of this thick layer, limiting the transfer of the reactive layer into the silicon film. These results have been confirmed on pattern structures for fully depleted silicon on insulator 14 nm technology showing the benefit of CH3F/O2/He/SiCl4 etch plasma compared to CH3F/O2/He plasma.

International audience; Spacer etching realization is considered today as one of the most critical processes for the fully depleted silicon on insulator devices realization. The challenge arises from the fact that low-k spacer needs to be introduced to improve device performances. In this paper, a new approach to etch the low-k SiCO film was investigated. This approach is based on the SiCO film modification by H-2 plasma followed by a removal step of this modified layer using hydrofluoric acid- (HF) based wet cleaning. It has been demonstrated that SiCO layer modification depth is controlled by plasma parameters like bias voltage. The SiCO film modification induced by H-2 plasma has been well understood by x-ray photoelectron spectroscopy, infrared spectroscopy analyses in transmission or in multi-internal reflection. It has been demonstrated that the H-2 plasma exposure converts the SiCO film in volume into an SiOxHy film, explaining the higher damaged film removal rate when dipped in liquid phase HF. Finally, the compatibility of the new etch approach with the SiCO low-k film has been demonstrated on pattern structures.

SummaryWhole-genome sequencing (WGS) is a cornerstone of precision medicine, but portable and reproducible open-source workflows for WGS analyses of germline and somatic variants are lacking. We present Sarek, a modular, comprehensive, and easy-to-install workflow, combining a range of software for the identification and annotation of single-nucleotide variants (SNVs), insertion and deletion variants (indels), structural variants, tumor sample heterogeneity, and karyotyping from germline or paired tumor/normal samples. Sarek is implemented in a bioinformatics workflow language (Nextflow) with Docker and Singularity compatible containers, ensuring easy deployment and full reproducibility at any Linux based compute cluster or cloud computing environment. Sarek supports the human reference genomes GRCh37 and GRCh38, and can readily be used both as a core production workflow at sequencing facilities and as a powerful stand-alone tool for individual research groups.AvailabilitySource code and instructions for local installation are available at GitHub (https://github.com/SciLifeLab/Sarek) under the MIT open-source license, and we invite the research community to contribute additional functionality as a collaborative open-source development project.

A fundamental issue in the evolution of communication is the degree to which signals convey accurate (“honest”) information about the signaler. In bioacoustics, the assumption that fundamental frequency (fo) should correlate with the body size of the caller is widespread, but this belief has been challenged by various studies, possibly because larynx size and body size can vary independently. In the present comparative study, we conducted excised larynx experiments to investigate this hypothesis rigorously and explore the determinants of fo. Using specimens from eleven primate species, we carried out an inter-specific investigation, examining correlations between the minimum fo produced by the sound source, body size and vocal fold length (VFL). We found that, across species, VFL predicted minimum fo much better than body size, clearly demonstrating the potential for decoupling between larynx size and body size in primates. These findings shed new light on the diversity of primate vocalizations and vocal morphology, highlighting the importance of vocal physiology in understanding the evolution of mammal vocal communication.

Summary Acoustic allometry consists of looking at how an organism’s body size scales with the characteristics of its vocalizations. A typical finding based on this framework is that across mammals body size is reflected in the fundamental frequency (fo) of vocalizations, whereby lower fo indicates larger body size [1] . This relationship holds owing to the fact that vocal fold length generally scales with body size [2] . Cross-species comparisons allow for the identification of interesting outliers from the body size–f0 regression [3] . Such cases are of particular relevance as they can provide insight into the selective forces potentially driving deviations from standard allometric principles [2] . In a recent study in Current Biology, Grawunder et al. [4] argue that selective pressure for higher f0 has led to the evolution of shorter vocal folds in bonobos than in chimpanzees. Thus, they claim, vocal fold length has evolved independently of body size in bonobos for the purposes of signal diminution (i.e., reducing the impression of body size that they advertise through their calls). However, considering both the existing literature and their own data, this conclusion does not appear to be supported for several reasons.

Ribosomal RNAs (rRNAs) are main effectors of messenger RNA (mRNA) decoding, peptide-bond formation, and ribosome dynamics during translation. Ribose 2′-O-methylation (2′-O-Me) is the most abundant rRNA chemical modification, and displays a complex pattern in rRNA. 2′-O-Me was shown to be essential for accurate and efficient protein synthesis in eukaryotic cells. However, whether rRNA 2′-O-Me is an adjustable feature of the human ribosome and a means of regulating ribosome function remains to be determined. Here we challenged rRNA 2′-O-Me globally by inhibiting the rRNA methyl-transferase fibrillarin in human cells. Using RiboMethSeq, a nonbiased quantitative mapping of 2′-O-Me, we identified a repertoire of 2′-O-Me sites subjected to variation and demonstrate that functional domains of ribosomes are targets of 2′-O-Me plasticity. Using the cricket paralysis virus internal ribosome entry site element, coupled to in vitro translation, we show that the intrinsic capability of ribosomes to translate mRNAs is modulated through a 2′-O-Me pattern and not by nonribosomal actors of the translational machinery. Our data establish rRNA 2′-O-Me plasticity as a mechanism providing functional specificity to human ribosomes.

The voice of humans and most non-human mammals is generated in the larynx through self-sustaining oscillation of the vocal folds. Direct visual documentation of vocal fold vibration is challenging, particularly in non-human mammals. As an alternative, excised larynx experiments provide the opportunity to investigate vocal fold vibration under controlled physiological and physical conditions. However, the use of a full larynx merely provides a top view of the vocal folds, excluding crucial portions of the oscillating structures from observation during their interaction with aerodynamic forces. This limitation can be overcome by utilizing a hemi-larynx setup where one half of the larynx is mid-sagittally removed, providing both a superior and a lateral view of the remaining vocal fold during self-sustained oscillation. Here, a step-by-step guide for the anatomical preparation of hemi-laryngeal structures and their mounting on the laboratory bench is given. Exemplary phonation of the hemi-larynx preparation is documented with high-speed video data captured by two synchronized cameras (superior and lateral views), showing three-dimensional vocal fold motion and corresponding time-varying contact area. The documentation of the hemi-larynx setup in this publication will facilitate application and reliable repeatability in experimental research, providing voice scientists with the potential to better understand the biomechanics of voice production.

While the call repertoire and its communicative function is relatively well explored in Japanese macaques (Macaca fuscata), little empirical data is available on the physics and the physiology of this species' vocal production mechanism. Here, a 6 year old female Japanese macaque was trained to phonate under an operant conditioning paradigm. The resulting “coo” calls, and spontaneously uttered “growl” and “chirp” calls, were recorded with sound pressure level (SPL) calibrated microphones and electroglottography (EGG), a non-invasive method for assessing the dynamics of phonation. A total of 448 calls were recorded, complemented by ex vivo recordings on an excised Japanese macaque larynx. In this novel multidimensional investigative paradigm, in vivo and ex vivo data were matched via comparable EGG waveforms. Subsequent analysis suggests that the vocal range (range of fundamental frequency and SPL) was comparable to that of a 7-10 year old human, with the exception of low-intensity chirps, whose production may be facilitated by the species' vocal membranes. In coo calls, redundant control of fundamental frequency in relation to SPL was also comparable to humans. EGG data revealed that growls, coos, and chirps were produced by distinct laryngeal vibratory mechanisms. EGG further suggested changes in the degree of vocal fold adduction in vivo, resulting in spectral variation within the emitted coo calls, ranging from “breathy” (including aerodynamic noise components) to “non-breathy”. This is again analogous to humans, corroborating the notion that phonation in humans and non-human primates is based on universal physical and physiological principles.

International audience; The study of sound production mechanisms is a crucial, yet understudied, aspect of vocal communication research in vertebrates. In excised larynx experimentation (ELE), phonation is simulated ex vivo by forcing air through a larynx specimen mounted on a laboratory bench. The method provides unique insights into vocal production and allows inference of in vivo conditions. Here, we provide a historical overview of how this technique has been implemented, from antiquity to current state-of-the-art setups. We review the advances made by applying ELE to human voice and biophysics research. We then highlight the promising research output resulting from ELE in animal bioacoustics, a research field that has largely overlooked the use of this method until very recently, but is now increasingly relying on this tool. We continue by discussing the limitations of ELE, depending on the focus of investigation. Finally, we suggest how this approach should be implemented and can be applied to various research questions. We conclude by underlining the value that ELE contributes to the comprehension of human voice as well as mammalian and avian vocal communication within an interdisciplinary approach.

International audience