348 research outputs found
Investigation of cyclicity of kinematic resolution methods for serial and parallel planar manipulators
Kinematic redundancy of manipulators is a well-understood topic, and various methods were developed for the redundancy resolution in order to solve the inverse kinematics problem, at least for serial manipulators. An important question, with high practical relevance, is whether the inverse kinematics solution is cyclic, i.e., whether the redundancy solution leads to a closed path in joint space as a solution of a closed path in task space. This paper investigates the cyclicity property of two widely used redundancy resolution methods, namely the projected gradient method (PGM) and the augmented Jacobian method (AJM), by means of examples. Both methods determine solutions that minimize an objective function, and from an application point of view, the sensitivity of the methods on the initial configuration is crucial. Numerical results are reported for redundant serial robotic arms and for redundant parallel kinematic manipulators. While the AJM is known to be cyclic, it turns out that also the PGM exhibits cyclicity. However, only the PGM converges to the local optimum of the objective function when starting from an initial configuration of the cyclic trajector
A nonparametric procedure to assess the accuracy of the normality assumption for annual rainfall totals, based on the marginal statistics of daily rainfall: an application to the NOAA/NCDC rainfall database
We develop a nonparametric procedure to assess the accuracy of the normality assumption for annual rainfall totals (ART), based on the marginal statistics of daily rainfall. The procedure is addressed to practitioners and hydrologists that operate in data-poor regions. To do so we use 1) goodness-of-fit metrics to conclude on the approximate convergence of the empirical distribution of annual rainfall totals to a normal shape and classify 3007 daily rainfall time series from the NOAA/NCDC Global Historical Climatology Network database, with at least 30 years of recordings, into Gaussian (G) and non-Gaussian (NG) groups; 2) logistic regression analysis to identify the statistics of daily rainfall that are most descriptive of the G/NG classification; and 3) a random-search algorithm to conclude on a set of constraints that allows classification of ART samples on the basis of the marginal statistics of daily rain rates. The analysis shows that the Anderson–Darling (AD) test statistic is the most conservative one in determining approximate Gaussianity of ART samples (followed by Cramer–Von Mises and Lilliefors’s version of Kolmogorov–Smirnov) and that daily rainfall time series with fraction of wet days fwd < 0.1 and daily skewness coefficient of positive rain rates skwd > 5.92 deviate significantly from the normal shape. In addition, we find that continental climate (type D) exhibits the highest fraction of Gaussian distributed ART samples (i.e., 74.45%; AD test at α = 5% significance level), followed by warm temperate (type C; 72.80%), equatorial (type A; 68.83%), polar (type E; 62.96%), and arid (type B; 60.29%) climates
Common Molecular Pathways Mediate Long-Term Potentiation of Synaptic Excitation and Slow Synaptic Inhibition
SummarySynaptic plasticity, the cellular correlate for learning and memory, involves signaling cascades in the dendritic spine. Extensive studies have shown that long-term potentiation (LTP) of the excitatory postsynaptic current (EPSC) through glutamate receptors is induced by activation of N-methyl-D-asparate receptor (NMDA-R)—the coincidence detector—and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Here we report that the same signaling pathway in the postsynaptic CA1 pyramidal neuron also causes LTP of the slow inhibitory postsynaptic current (sIPSC) mediated by metabotropic GABAB receptors (GABAB-Rs) and G protein-activated inwardly rectifying K+ (GIRK) channels, both residing in dendritic spines as well as shafts. Indicative of intriguing differences in the regulatory mechanisms for excitatory and inhibitory synaptic plasticity, LTP of sIPSC but not EPSC was abolished in mice lacking Nova-2, a neuronal-specific RNA binding protein that is an autoimmune target in paraneoplastic opsoclonus myoclonus ataxia (POMA) patients with latent cancer, reduced inhibitory control of movements, and dementia
Combined microwave ablation and osteosynthesis for long bone metastases
Background and Objectives: The purpose of this study was to evaluate the feasibility, safety and efficacy of microwave ablation (MWA) in combination with open surgery nail positioning for the treatment of fractures or impending fractures of long bone metastases. Material and Methods: Eleven patients (four men, seven women) with painful bone metastases of the humerus, femur or tibia with non-displaced fractures (one case) or impending fractures (10 cases) underwent open MWA in combination with osteosynthesis by locked nail positioning. Pain intensity was measured using a VAS score before and after treatment. CT or MRI were acquired at one month before and 1, 3, 6, 12 and 18 months after treatment. Results: All procedures were successfully completed without major complications. The level of pain was significantly reduced one month after treatment. For the patients with humerus metastases, the complete recovery of arm use took 8 weeks, while for the patients with femoral metastases the complete recovery of walking capacity took 11 weeks. The VAS score ranged from 7 (4–9) before treatment to 1.5 (0–2.5) after treatment. During a mid-term follow-up of 18 months (range 4–29 months), none of the patients showed tumor relapse or new fractures in the treated site. Two patients died due to tumor disease progression. Conclusion: Results of this preliminary study suggest that combined MWA and surgical osteosynthesis with locked nails is a safe and effective treatment for pathological fractures or malignant impending fractures of long bone metastases of the humerus, femur and tibia. Further analyses with larger cohorts are warranted to confirm these findings
NANOS3 function in human germ cell development
Human infertility is common and frequently linked to poor germ cell development. Yet, human germ cell development is poorly understood, at least in part due to the inaccessibility of germ cells to study especially during fetal development. Here, we explored the function of a highly conserved family of genes, the NANOS genes, in the differentiation of human germ cells from human embryonic stem cells. We observed that NANOS-1, -2 and -3 mRNAs and proteins were expressed in human gonads. We also noted that NANOS3 was expressed in germ cells throughout spermatogenesis and oogenesis and thus, focused further efforts on this family member. NANOS3 expression was highest in human germ cell nuclei where the protein co-localized with chromosomal DNA during mitosis/meiosis. Reduced expression of NANOS3 (via morpholinos or short hairpin RNA) resulted in a reduction in germ cell numbers and decreased expression of germ cell-intrinsic genes required for the maintenance of pluripotency and meiotic initiation and progression. These data provide the first direct experimental evidence that NANOS3 functions in human germ cell development; indeed, NANOS3 is now one of just two genes that has been directly shown to function in germ cell development across diverse species from flies, worms, frogs and mice to humans [the other is BOULE, a member of the Deleted in Azoospermia (DAZ) gene family]. Findings may contribute to our understanding of the basic biology of human germ cell development and may provide clinical insights regarding infertility
Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline
The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline
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NOVA2-mediated RNA regulation is required for axonal pathfinding during development.
The neuron specific RNA-binding proteins NOVA1 and NOVA2 are highly homologous alternative splicing regulators. NOVA proteins regulate at least 700 alternative splicing events in vivo, yet relatively little is known about the biologic consequences of NOVA action and in particular about functional differences between NOVA1 and NOVA2. Transcriptome-wide searches for isoform-specific functions, using NOVA1 and NOVA2 specific HITS-CLIP and RNA-seq data from mouse cortex lacking either NOVA isoform, reveals that NOVA2 uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development. Corresponding axonal pathfinding defects were specific to NOVA2 deficiency: Nova2-/- but not Nova1-/- mice had agenesis of the corpus callosum, and axonal outgrowth defects specific to ventral motoneuron axons and efferent innervation of the cochlea. Thus we have discovered that NOVA2 uniquely regulates alternative splicing of a coordinate set of transcripts encoding key components in cortical, brainstem and spinal axon guidance/outgrowth pathways during neural differentiation, with severe functional consequences in vivo
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