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These findings provide the first evidence of alterations in long-distance phase connectivity and microstate indices at rest, and represent progress towards the understanding of the pathophysiology of fibromyalgia and the identification of novel biomarkers for its diagnosis.Despite the crucial role of the hypothalamus in the regulation of the human body, neuroimaging studies of this structure and its nuclei are scarce. Such scarcity partially stems from the lack of automated segmentation tools, since manual delineation suffers from scalability and reproducibility issues. Due to the small size of the hypothalamus and the lack of image contrast in its vicinity, automated segmentation is difficult and has been long neglected by widespread neuroimaging packages like FreeSurfer or FSL. Nonetheless, recent advances in deep machine learning are enabling us to tackle difficult segmentation problems with high accuracy. In this paper we present a fully automated tool based on a deep convolutional neural network, for the segmentation of the whole hypothalamus and its subregions from T1-weighted MRI scans. We use aggressive data augmentation in order to make the model robust to T1-weighted MR scans from a wide array of different sources, without any need for preprocessing. We rigorously assess the performance of the presented tool through extensive analyses, including inter- and intra-rater variability experiments between human observers; comparison of our tool with manual segmentation; comparison with an automated method based on multi-atlas segmentation; assessment of robustness by quality control analysis of a larger, heterogeneous dataset (ADNI); and indirect evaluation with a volumetric study performed on ADNI. The presented model outperforms multi-atlas segmentation scores as well as inter-rater accuracy level, and approaches intra-rater precision. Our method does not require any preprocessing and runs in less than a second on a GPU, and approximately 10 seconds on a CPU. The source code as well as the trained model are publicly available at https//github.com/BBillot/hypothalamus_seg, and will also be distributed with FreeSurfer.Functional MRI (fMRI) is extremely challenging to perform in subjects who move because subject motion disrupts blood oxygenation level dependent (BOLD) signal measurement. It has become common to use retrospective framewise motion detection and censoring in fMRI studies to eliminate artifacts arising from motion. Data censoring results in significant loss of data and statistical power unless the data acquisition is extended to acquire more data not corrupted by motion. Acquiring more data than is necessary leads to longer than necessary scan duration, which is more expensive and may lead to additional subject non-compliance. Therefore, it is well established that real-time prospective motion monitoring is crucial to ensure data quality and reduce imaging costs. In addition, real-time monitoring of motion allows for feedback to the operator and the subject during the acquisition, to enable intervention to reduce the subject motion. The most widely used form of motion monitoring for fMRI is based on volume-to-vated MRI Monitoring (SLIMM), provides more accurate motion measurements than a VVR based approach. Therefore, SLIMM offers improved online motion monitoring which is particularly important in fMRI for challenging patient populations. Real-time motion monitoring is crucial for online data quality control and assurance, for enabling feedback to the subject and the operator to act to mitigate motion, and in adaptive acquisition strategies that aim to ensure enough data of sufficient quality is acquired without acquiring excess data.Arterial Spin Labeling (ASL) is a non-invasive, non-contrast, perfusion imaging technique which is inherently SNR limited. It is, therefore, important to carefully design scan protocols to ensure accurate measurements. Many pseudo-continuous ASL (PCASL) protocol designs have been proposed for measuring cerebral blood flow (CBF), but it has not yet been demonstrated which design offers the most accurate and repeatable CBF measurements. In this study, a wide range of literature PCASL protocols were first optimized for CBF accuracy and then compared using Monte Carlo simulations and in vivo experiments. The protocols included single-delay, sequential and time-encoded multi-timepoint protocols, and several novel protocol designs, which are hybrids of time-encoded and sequential multi-timepoint protocols. It was found that several multi-timepoint protocols produced more confident, accurate, and repeatable CBF estimates than the single-delay protocol, while also generating maps of arterial transit time. Of the literature protocols, the time-encoded protocol with T1-adjusted label durations gave the most confident and accurate CBF estimates in vivo (16% and 40% better than single-delay), while the sequential multi-timepoint protocol was the most repeatable (20% more repeatable than single-delay). One of the novel hybrid protocols, HybridT1-adj, was found to produce the most confident, accurate and repeatable CBF estimates out of all the protocols tested in both simulations and in vivo (24%, 47%, and 28% more confident, accurate, and repeatable than single-delay in vivo). The HybridT1-adj protocol makes use of the best aspects of both time-encoded and sequential multi-timepoint protocols and should be a useful tool for accurately and efficiently measuring CBF.This study investigated the role of calcium2+/calmodulin-dependent protein kinase II (CaMKII), a protein in the second messenger pathway of NMDA receptors, in the ventral tegmental area (VTA) in the acquisition and performance of conditioned approach learning. Male Long-Evans rats (N = 79) were exposed to 3 (to test acquisition) or 7 (to test performance) conditioning sessions in which they received 30 paired presentations of a light stimulus (CS) and a food pellet (US) on a random time schedule. These conditioning sessions were then followed by one 30-min session without the CS or US and lastly by a CS-only test session, where only the light stimulus was presented (without food) according to the same schedule as the conditioning sessions. Bilateral intra-VTA injections of KN93 (vehicle, 3.0, 4.5 or 6.0 μg/0.5 μL), a CaMKII inhibitor, were administered prior to each conditioning session to test effects on the acquisition of conditioned approach or prior to the CS-only test session to test effects on the performance of conditioned approach. KN93, when given prior to conditioning sessions, significantly reduced the number of conditioned approach responses emitted during CS presentations in the CS-only test. When KN93 was given prior to the CS-only test it had no effect. These results suggest that CaMKII activation in the VTA is necessary for the acquisition, but not the performance, of reward-related learning.Molluscs are a highly successful group of invertebrates characterised by a specialised feeding organ called the radula. The diversity of this structure is associated with distinct feeding strategies and ecological niches. However, the precise function of the radula (each tooth type and their arrangement) remains poorly understood. Here for the first time, we use a quantitative approach, Finite-Element-Analysis (FEA), to test hypotheses regarding the function of particular taenioglossan tooth types. Taenioglossan radulae are of special interest, because they are comprised of multiple teeth that are regionally distinct in their morphology. For this study we choose the freshwater gastropod species Spekia zonata, endemic to Lake Tanganyika, inhabiting and feeding on algae attached to rocks. As a member of the African paludomid species flock, the enigmatic origin and evolutionary relationships of this species has received much attention. Its chitinous radula comprises several tooth types with distinctly different shapes. We characterise the tooth’s position, material properties and attachment to the radular membrane and use this data to evaluate 18 possible FEA scenarios differing in the above parameters. Our estimations of stress and strain indicate different functional loads for different teeth. We posit that the central and lateral teeth are best suitable for scratching substrate loosening ingesta, whereas the marginals are best suited for gathering food particles. Our successful approach and workflow are readily applicable to other mollusc species.Development of non-viral gene vectors which can efficiently and safely transfect plasmid DNA and siRNA into cells is of great importance for gene therapy. Despite lots of efforts spent, it is still imperative to develop suitable gene vectors with better transfection efficiency and low cytotoxicity. To this end, we successfully designed, synthesized and screened a library of 120 polymers (via nucleophilic substitution reaction between dihalides and amines). With cell-based transfection screening assays, 120 polymers were tested to evaluate their transfection efficiency of transporting DNA and siRNA into cells. Our results indicated that hydrophobic modification could greatly enhance cationic polymers’ transfection efficiency, and polymers with long linkers usually showed better transfection performance, especially for polymers with the linker of 1, 12-dibromododecane (L3 linker). Besides, polyalkylamines exhibited better transfection efficiency with the polymer particle size around 200 nm and the zeta potential in the range of + 40 mV to +50 mV. Interestingly, polymer particles made from N15HL3 not only exhibited better DNA transfection efficiency in HEK 293T cells but also showed higher siRNA transfection efficiency in U87 Luc-GFP cells together with low cell toxicity than Lipofectamine 2000 (one of commercial transfection reagents). Therefore, it is hoped that our study here not only provides promising gene vector candidates for further evaluation in gene therapy, but also provides valuable insights for better understanding of the relationship between the chemical structures and gene transfection efficiency to rationally design better non-viral gene vectors for gene therapy in the future.The active and passive mechanical behavior of a cosmetic tightening product for skin anti-aging is investigated based on a wide range of in vivo and in vitro measurements. The experimental data are used to inform a numerical model of the attained cosmetic effect, which is then implemented in a commercial finite-element framework and used to analyze the mechanisms that regulate the biomechanical interaction between the native tissue and the tightening film. selleck inhibitor Such a film reduces wrinkles and enhances skin consistency by increasing its stiffness by 48-107% and reducing inelastic, non-recoverable deformations (-47%). The substrate deformability influences both the extent of tightening and the reduction of wrinkle amplitude. The present findings allow, for the first time, to rationalize the mechanisms of action of cosmetic products with a tightening action and provide quantitative evidence for further optimization of this fascinating class of biomaterials.Partially due to the unavailability of ideal bone substitutes, the treatment of large bony defects remains one of the most important challenges of orthopedic surgery. Additively manufactured (AM) biodegradable porous metals that have emerged since 2018 provide unprecedented opportunities for fulfilling the requirements of an ideal bone implant. First, the multi-scale geometry of these implants can be customized to mimic the human bone in terms of both micro-architecture and mechanical properties. Second, a porous structure with interconnected pores possesses a large surface area, which is favorable for the adhesion and proliferation of cells and, thus, bony ingrowth. Finally, the freeform geometrical design of such biomaterials could be exploited to adjust their biodegradation behavior so as to maintain the structural integrity of the implant during the healing process while ensuring that the implant disappears afterwards, paving the way for full bone regeneration. While the AM biodegradable porous metals that have been studied so far have shown many unique properties as compared to their solid counterparts, the unprecedented degree of flexibility in their geometrical design has not yet been fully exploited to optimize their properties and performance.