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Khoomei is a unique singing style originating from the Central Asian republic of Tuva. Singers produce two pitches simultaneously: a booming low-frequency rumble alongside a hovering high-pitched whistle-like tone. The biomechanics of this biphonation are not well-understood. Here, we use sound analysis, dynamic magnetic resonance imaging, and vocal tract modeling to demonstrate how biphonation is achieved by modulating vocal tract morphology. Tuvan singers show remarkable control in shaping their vocal tract to narrowly focus the harmonics (or overtones) emanating from their vocal cords. The biphonic sound is a combination of the fundamental pitch and a focused filter state, which is at the higher pitch (1-2 kHz) and formed by merging two formants, thereby greatly enhancing sound-production in a very narrow frequency range. Most importantly, we demonstrate that this biphonation is a phenomenon arising from linear filtering rather than a nonlinear source. Data is placed in four zipped files (compression done via Mac OS 10.12.4). The four files each contain a particular subset of the data: 1. Model.zip - Modeling software (Tube Talker) and several illustrative simulations 2. CroppedMRI_CB.zip - Both statis and dynamic MRI images (as .dcm files). Note that the DICOM files have been cropped (so to only show the relevant anatomical features) and metadata have been stripped. 3. SoundboothRecordings.zip - All soundbooth recordings, saved as .wav files (SR 96 kHz) 4. STL.zip - Reonstruction of the 3-D airspace, saved as a .stl file 5. MRIaudio.zip - Audio files collected during the MRI runs 6. MRImoviesC.zip - Movies of the dynamic data (with audio). Data is a combination of acoustical recordings, MRI data, and vocal tract modeling. Movie of the dynamic MRI data are also included. All details are included in the manuscript "Overtone focusing in biphonic Tuvan throat singing".

We introduce Sleep, a new Python open-source graphical user interface (GUI) dedicated to visualization, scoring and analyses of sleep data. Among its most prominent features are: (1) Dynamic display of polysomnographic data, spectrogram, hypnogram and topographic maps with several customizable parameters, (2) Implementation of several automatic detection of sleep features such as spindles, K-complexes, slow waves, and rapid eye movements (REM), (3) Implementation of practical signal processing tools such as re-referencing or filtering, and (4) Display of main descriptive statistics including publication-ready tables and figures. The software package supports loading and reading raw EEG data from standard file formats such as European Data Format, in addition to a range of commercial data formats. Most importantly, Sleep is built on top of the VisPy library, which provides GPU-based fast and high-level visualization. As a result, it is capable of efficiently handling and displaying large sleep datasets. Sleep is freely available (http://visbrain.org/sleep) and comes with sample datasets and an extensive documentation. Novel functionalities will continue to be added and open-science community efforts are expected to enhance the capacities of this module.

Objective: To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy. Methods: UX001-CL301 was a Phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE Myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6g/day or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by Upper Extremity Composite (UEC) score. Key secondary endpoints included change in Lower Extremity Composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results. Results: Eighty-nine patients were randomized (Ace-ER n = 45; Placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs Placebo -2.99 kg; LSM difference (confidence interval [CI]) 0.74 (-1.61, 3.09); p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83, 2.86); knee extension strength -0.40 (-2.38, 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01, 0.57). Gastrointestinal events were the most common AEs. Conclusions: Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy. Lochmuller et al UX001 CL301 MS supp materials protocol 13Dec2018Supplemental Material for Lochmuller et al Neurology: Table e-1. Change from Baseline to Week 48 in UEC and LEC Individual Muscle Groups with Hand-Held Dynamometry; Figure e-1. UX001-CL301 CONSORT Flow Diagram; UX001-CL301 Protocol

A central question in biology is how animals successfully behave under complex natural conditions. Although changes in locomotor behaviour, motor control and force production in relation to incline are commonly examined, a wide range of other factors, including a range of perch diameters, pervades arboreal habitats. Moving on different substrate diameters requires considerable alteration of body and limb posture, probably causing significant shifts in the lengths of the muscle–tendon units powering locomotion. Thus, how substrate shape impacts in vivo muscle function remains an important but neglected question in ecophysiology. Here, we used high-speed videography, electromyography, in situ contractile experiments and morphology to examine gastrocnemius muscle function during arboreal locomotion in the Cuban knight anole, Anolis equestris. The gastrocnemius contributes more to the propulsive effort on broad surfaces than on narrow surfaces. Surprisingly, substrate inclination affected the relationship between the maximum potential force and fibre recruitment; the trade-off that was present between these variables on horizontal surfaces became a positive relationship on inclined surfaces. Finally, the biarticular nature of the gastrocnemius allows it to generate force isometrically, regardless of substrate diameter and incline, despite the fact that the tendons are incapable of stretching during cyclical locomotion. Our results emphasize the importance of considering ecology and muscle function together, and the necessity of examining both mechanical and physiological properties of muscles to understand how animals move in their environment. Raw DataThis file contains the raw data used for generating all results for the manuscript. There are 6 sheets: Morphology contains the morphometric data for the hind limb and muscles for each individual; EMGdata contains all EMG variables used for analyses; HindlimbAngles contains all kinematic data of hind limb joint angles; HindlimbVelocities contains all kinematic data of hind limb joint angular velocities; ForceData contains values of potential force calculated for bursts and strides for each individual; and Force-LengthCurves contains the twitch force-length curves for the gastrocnemius muscles of each individual.dataForDryad.xlsx

Phenotypic integration patterns in the mammalian skull have long been a focus of intense interest as a result of their suspected influence on the trajectory of hominid evolution. Here we test the hypothesis that perturbation of cartilage growth, which directly affects only the chondrocranium during development, will produce coordinated shape changes in the adult calvarium and face regardless of mechanism. Using two murine models of cartilage undergrowth that target two very different mechanisms, we show that strong reduction in cartilage growth produces a short, wide, and more flexed cranial base. This in turn produces a short, wide face in both models. Cranial base and face are already correlated early in ontogeny, and the relationship between these modules gains structure through postnatal growth and development. These results provide further evidence that there exist physical interactions between developing parts of the phenotype that produce variation at a distance from the actual locus upon which a particular selective pressure is acting. Phenotypic changes observed over the course of evolution may not all require adaptationist explanations; rather, it is likely that a substantial portion of observed phenotypic variation over the history of a clade is not directly adaptive but rather a secondary consequence of some local response to selection. Adult Skull Landmark DataThis file contains raw landmark coordinates for adult mouse skulls.Adult.csvNeonatal Skull Landmark DataThis file contains raw landmark coordinates for neonatal mouse skulls.Neonatal.csv

Bluegill sunfish (Lepomis macrochirus) are one of the classic systems for studying male alternative reproductive tactics (ARTs) in teleost fishes. In this species, there are two distinct life histories: parental and cuckolder, encompassing three reproductive tactics, parental, satellite, and sneaker. The parental life history is fixed, whereas individuals who enter the cuckolder life history transition from sneaker to satellite tactic as they grow. For this study, we used RNAseq to characterize the brain transcriptome of the three male tactics and females during spawning to identify gene ontology (GO) categories and potential candidate genes associated with each tactic. We found that sneaker males had higher levels of gene expression differentiation compared to the other two male tactics. Sneaker males also had higher expression in ionotropic glutamate receptor genes, specifically AMPA receptors, compared to other males, which may be important for increased spatial working memory while attempting to cuckold parental males at their nests. Larger differences in gene expression also occurred among male tactics than between males and females. We found significant expression differences in several candidate genes that were previously identified in other species with ARTs and suggest a previously undescribed role for cAMP-responsive element modulator (crem) in influencing parental male behaviors during spawning. Fish sampling informationA text file detailing sampling information for fish used in this study. It includes the sex, tactic, total and standard length, sampling colony, sampling location, and RNA integrity numbers.Fish_sampling_info.txtTranscript CountsRaw transcripts counts produced from eXpress for all samplesMerged.results.xprsR scriptContains the R scripts used with edgeR for differential gene expression analysisRscript_DE_Analysis.txtAssembled transcriptomeAssembled bluegill transcriptome. Assembled de novo using Trinity.bluegill.final.fa

Résumé La segmentation des faisceaux de matière blanche à l'aide de la tractographie des fibres IRM de diffusion est devenue la méthode de choix pour identifier les voies des fibres de matière blanche in vivo dans le cerveau humain. Cependant, comme d'autres analyses de données complexes, il existe une variabilité considérable dans les protocoles et les techniques de segmentation. Cela peut entraîner différentes reconstructions des mêmes voies de la substance blanche, ce qui affecte directement les résultats, la quantification et l'interprétation de la tractographie. Dans cette étude, nous visons à évaluer et quantifier la variabilité qui découle de différents protocoles de segmentation des faisceaux. Grâce à un appel ouvert aux utilisateurs de la tractographie par fibres, y compris les anatomistes, les cliniciens et les développeurs d'algorithmes, 42 équipes indépendantes ont reçu des ensembles traités de lignes de rationalisation du cerveau entier humain et ont été invitées à segmenter 14 fascicules de substance blanche sur six sujets. Au total, nous avons reçu 57 protocoles de segmentation de faisceau différents, ce qui a permis des analyses détaillées basées sur le volume et sur la rationalisation des accords et des désaccords entre les protocoles pour chaque voie de fibre. Les résultats montrent que même lorsqu'on leur donne exactement les mêmes ensembles de lignes de flux sous-jacentes, la variabilité entre les protocoles pour la segmentation des faisceaux est plus grande que toutes les autres sources de variabilité dans le processus de dissection virtuelle, y compris la variabilité au sein des protocoles et la variabilité entre les sujets. Afin de favoriser l'utilisation de la dissection de faisceaux de tractographie dans les contextes cliniques de routine, et en tant qu'outil analytique fondamental, les efforts futurs doivent viser à résoudre et à réduire cette hétérogénéité. Bien qu'une validation externe soit nécessaire pour vérifier l'exactitude anatomique des dissections de faisceaux, la réduction de l'hétérogénéité est une étape vers une recherche reproductible et peut être obtenue par l'utilisation d'une nomenclature et de définitions standard des faisceaux de matière blanche et de contraintes et de décisions bien choisies dans le processus de dissection. Resumen La segmentación del haz de materia blanca mediante tractografía de fibra por resonancia magnética de difusión se ha convertido en el método de elección para identificar las vías de fibra de materia blanca in vivo en cerebros humanos. Sin embargo, al igual que otros análisis de datos complejos, existe una variabilidad considerable en los protocolos y técnicas de segmentación. Esto puede dar lugar a diferentes reconstrucciones de las mismas vías de materia blanca previstas, lo que afecta directamente a los resultados de la tractografía, la cuantificación y la interpretación. En este estudio, nuestro objetivo es evaluar y cuantificar la variabilidad que surge de diferentes protocolos para la segmentación de paquetes. A través de una convocatoria abierta a los usuarios de la tractografía de fibra, incluidos anatomistas, médicos y desarrolladores de algoritmos, 42 equipos independientes recibieron conjuntos procesados de líneas aerodinámicas de todo el cerebro humano y se les pidió que segmentaran 14 fascículos de materia blanca en seis sujetos. En total, recibimos 57 protocolos de segmentación de paquetes diferentes, lo que permitió análisis detallados basados en el volumen y en la simplificación de la concordancia y el desacuerdo entre los protocolos para cada vía de fibra. Los resultados muestran que incluso cuando se les dan exactamente los mismos conjuntos de líneas de flujo subyacentes, la variabilidad entre protocolos para la segmentación de paquetes es mayor que todas las demás fuentes de variabilidad en el proceso de disección virtual, incluida la variabilidad dentro de los protocolos y la variabilidad entre sujetos. Para fomentar el uso de la disección del haz de tractografía en entornos clínicos de rutina, y como una herramienta analítica fundamental, los esfuerzos futuros deben apuntar a resolver y reducir esta heterogeneidad. Aunque se necesita una validación externa para verificar la precisión anatómica de las disecciones de haces, la reducción de la heterogeneidad es un paso hacia la investigación reproducible y se puede lograr mediante el uso de nomenclatura estándar y definiciones de haces de materia blanca y restricciones y decisiones bien elegidas en el proceso de disección. Abstract White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process. أصبح تجزئة حزمة المادة البيضاء باستخدام التصوير المقطعي بألياف التصوير بالرنين المغناطيسي المنتشر الطريقة المفضلة لتحديد مسارات ألياف المادة البيضاء في الجسم الحي في أدمغة الإنسان. ومع ذلك، مثل التحليلات الأخرى للبيانات المعقدة، هناك تباين كبير في بروتوكولات وتقنيات التجزئة. يمكن أن يؤدي ذلك إلى عمليات إعادة بناء مختلفة لنفس مسارات المادة البيضاء المقصودة، مما يؤثر بشكل مباشر على نتائج التصوير الشعاعي والقياس الكمي والتفسير. في هذه الدراسة، نهدف إلى تقييم وقياس التباين الذي ينشأ عن بروتوكولات مختلفة لتجزئة الحزمة. من خلال دعوة مفتوحة لمستخدمي تصوير المسالك الليفية، بما في ذلك علماء التشريح والأطباء ومطوري الخوارزميات، تم إعطاء 42 فريقًا مستقلًا مجموعات معالجة من خطوط الدماغ الكاملة البشرية وطُلب منهم تقسيم 14 كراسة مادة بيضاء على ستة مواضيع. في المجموع، تلقينا 57 بروتوكولًا مختلفًا لتجزئة الحزم، مما مكن من إجراء تحليلات مفصلة قائمة على الحجم وقائمة على التبسيط للاتفاق والاختلاف بين البروتوكولات لكل مسار من مسارات الألياف. تظهر النتائج أنه حتى عند إعطاء نفس مجموعات التبسيط الأساسية بالضبط، فإن التباين عبر بروتوكولات تجزئة الحزمة أكبر من جميع مصادر التباين الأخرى في عملية التشريح الافتراضية، بما في ذلك التباين داخل البروتوكولات والتباين عبر الموضوعات. من أجل تعزيز استخدام تشريح حزمة تخطيط المسالك في البيئات السريرية الروتينية، وكأداة تحليلية أساسية، يجب أن تهدف المساعي المستقبلية إلى حل هذا التباين وتقليله. على الرغم من الحاجة إلى التحقق الخارجي للتحقق من الدقة التشريحية لتشريح الحزم، فإن الحد من عدم التجانس هو خطوة نحو البحث القابل للتكرار ويمكن تحقيقه من خلال استخدام التسميات القياسية وتعريفات حزم المادة البيضاء والقيود والقرارات المختارة جيدًا في عملية التشريح.

This resource defines the Brain Imaging Data Structure (BIDS) specification, including the core specification as well as many modality-specific extensions. To get started, check out the introduction. For an overview of the BIDS ecosystem, visit the BIDS homepage. The entire specification can also be browsed in an HTML version. See Appendix I for a list of the BIDS contributors who jointly created this specification.