729 research outputs found

    On Advanced Mobility Concepts for Intelligent Planetary Surface Exploration

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    Surface exploration by wheeled rovers on Earth's Moon (the two Lunokhods) and Mars (Nasa's Sojourner and the two MERs) have been followed since many years already very suc-cessfully, specifically concerning operations over long time. However, despite of this success, the explored surface area was very small, having in mind a total driving distance of about 8 km (Spirit) and 21 km (Opportunity) over 6 years of operation. Moreover, ESA will send its ExoMars rover in 2018 to Mars, and NASA its MSL rover probably this year. However, all these rovers are lacking sufficient on-board intelligence in order to overcome longer dis-tances, driving much faster and deciding autonomously on path planning for the best trajec-tory to follow. In order to increase the scientific output of a rover mission it seems very nec-essary to explore much larger surface areas reliably in much less time. This is the main driver for a robotics institute to combine mechatronics functionalities to develop an intelligent mo-bile wheeled rover with four or six wheels, and having specific kinematics and locomotion suspension depending on the operational terrain of the rover to operate. DLR's Robotics and Mechatronics Center has a long tradition in developing advanced components in the field of light-weight motion actuation, intelligent and soft manipulation and skilled hands and tools, perception and cognition, and in increasing the autonomy of any kind of mechatronic systems. The whole design is supported and is based upon detailed modeling, optimization, and simula-tion tasks. We have developed efficient software tools to simulate the rover driveability per-formance on various terrain characteristics such as soft sandy and hard rocky terrains as well as on inclined planes, where wheel and grouser geometry plays a dominant role. Moreover, rover optimization is performed to support the best engineering intuitions, that will optimize structural and geometric parameters, compare various kinematics suspension concepts, and make use of realistic cost functions like mass and consumed energy minimization, static sta-bility, and more. For self-localization and safe navigation through unknown terrain we make use of fast 3D stereo algorithms that were successfully used e.g. in unmanned air vehicle ap-plications and on terrestrial mobile systems. The advanced rover design approach is applica-ble for lunar as well as Martian surface exploration purposes. A first mobility concept ap-proach for a lunar vehicle will be presented

    The albino perinatal lethal mutation

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    Just-for-Me: An Adaptive Personalization System for Location-Aware Social Music Recommendation

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    The fast growth of online communities and increasing pop-ularity of internet-accessing smart devices have significantly changed the way people consume and share music. As an emerging technology to facilitate effective music retrieval on the move, intelligent recommendation has been recently re-ceived great attentions in recent years. While a large amount of efforts have been invested in the field, the technology is still in its infancy. One of the major reasons for this stagna-tion is due to inability of the existing approaches to compre-hensively take multiple kinds of contextual information into account. In the paper, we present a novel recommender sys-tem called Just-for-Me to facilitate effective social music rec-ommendation by considering users ’ location related contexts as well as global music popularity trends. We also develop an unified recommendation model to integrate the contex-tual factors as well as music contents simultaneously. Fur-thermore, pseudo-observations are proposed to overcome the cold-start and sparsity problems. An extensive experimental study based on different test collections demonstrates that Just-for-Me system can significantly improve the recommen-dation performance at various geo-locations

    Sperm Status Regulates Sexual Attraction in Caenorhabditis elegans

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    Mating behavior of animals is regulated by the sensory stimuli provided by the other sex. Sexually receptive females emit mating signals that can be inhibited by male ejaculate. The genetic mechanisms controlling the release of mating signals and encoding behavioral responses remain enigmatic. Here we present evidence of a Caenorhabditis elegans hermaphrodite-derived cue that stimulates male mating-response behavior and is dynamically regulated by her reproductive status. Wild-type males preferentially mated with older hermaphrodites. Increased sex appeal of older hermaphrodites was potent enough to stimulate robust response from mating-deficient pkd-2 and lov-1 polycystin mutant males. This enhanced response of pkd-2 males toward older hermaphrodites was independent of short-chain ascaroside pheromones, but was contingent on the absence of active sperm in the hermaphrodites. The improved pkd-2 male response toward spermless hermaphrodites was blocked by prior insemination or by genetic ablation of the ceh-18-dependent sperm-sensing pathway of the hermaphrodite somatic gonad. Our work suggests an interaction between sperm and the soma that has a negative but reversible effect on a hermaphrodite-derived mating cue that regulates male mating response, a phenomenon to date attributed to gonochoristic species only

    Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease

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    Cerebral ischemic small vessel disease (SVD) is the leading cause of vascular dementia and a major contributor to stroke in humans. Dominant mutations in NOTCH3 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic archetype of cerebral ischemic SVD. Progress toward understanding the pathogenesis of this disease and developing effective therapies has been hampered by the lack of a good animal model. Here, we report the development of a mouse model for CADASIL via the introduction of a CADASIL-causing Notch3 point mutation into a large P1-derived artificial chromosome (PAC). In vivo expression of the mutated PAC transgene in the mouse reproduced the endogenous Notch3 expression pattern and main pathological features of CADASIL, including Notch3 extracellular domain aggregates and granular osmiophilic material (GOM) deposits in brain vessels, progressive white matter damage, and reduced cerebral blood flow. Mutant mice displayed attenuated myogenic responses and reduced caliber of brain arteries as well as impaired cerebrovascular autoregulation and functional hyperemia. Further, we identified a substantial reduction of white matter capillary density. These neuropathological changes occurred in the absence of either histologically detectable alterations in cerebral artery structure or blood-brain barrier breakdown. These studies provide in vivo evidence for cerebrovascular dysfunction and microcirculatory failure as key contributors to hypoperfusion and white matter damage in this genetic model of ischemic SVD

    Theoretical analysis of the role of chromatin interactions in long-range action of enhancers and insulators

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    Long-distance regulatory interactions between enhancers and their target genes are commonplace in higher eukaryotes. Interposed boundaries or insulators are able to block these long distance regulatory interactions. The mechanistic basis for insulator activity and how it relates to enhancer action-at-a-distance remains unclear. Here we explore the idea that topological loops could simultaneously account for regulatory interactions of distal enhancers and the insulating activity of boundary elements. We show that while loop formation is not in itself sufficient to explain action at a distance, incorporating transient non-specific and moderate attractive interactions between the chromatin fibers strongly enhances long-distance regulatory interactions and is sufficient to generate a euchromatin-like state. Under these same conditions, the subdivision of the loop into two topologically independent loops by insulators inhibits inter-domain interactions. The underlying cause of this effect is a suppression of crossings in the contact map at intermediate distances. Thus our model simultaneously accounts for regulatory interactions at a distance and the insulator activity of boundary elements. This unified model of the regulatory roles of chromatin loops makes several testable predictions that could be confronted with \emph{in vitro} experiments, as well as genomic chromatin conformation capture and fluorescent microscopic approaches.Comment: 10 pages, originally submitted to an (undisclosed) journal in May 201

    Discovery of anthelmintic drug targets and drugs using chokepoints in nematode metabolic pathways

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    Parasitic roundworm infections plague more than 2 billion people (1/3 of humanity) and cause drastic losses in crops and livestock. New anthelmintic drugs are urgently needed as new drug resistance and environmental concerns arise. A "chokepoint reaction" is defined as a reaction that either consumes a unique substrate or produces a unique product. A chokepoint analysis provides a systematic method of identifying novel potential drug targets. Chokepoint enzymes were identified in the genomes of 10 nematode species, and the intersection and union of all chokepoint enzymes were found. By studying and experimentally testing available compounds known to target proteins orthologous to nematode chokepoint proteins in public databases, this study uncovers features of chokepoints that make them successful drug targets. Chemogenomic screening was performed on drug-like compounds from public drug databases to find existing compounds that target homologs of nematode chokepoints. The compounds were prioritized based on chemical properties frequently found in successful drugs and were experimentally tested using Caenorhabditis elegans. Several drugs that are already known anthelmintic drugs and novel candidate targets were identified. Seven of the compounds were tested in Caenorhabditis elegans and three yielded a detrimental phenotype. One of these three drug-like compounds, Perhexiline, also yielded a deleterious effect in Haemonchus contortus and Onchocerca lienalis, two nematodes with divergent forms of parasitism. Perhexiline, known to affect the fatty acid oxidation pathway in mammals, caused a reduction in oxygen consumption rates in C. elegans and genome-wide gene expression profiles provided an additional confirmation of its mode of action. Computational modeling of Perhexiline and its target provided structural insights regarding its binding mode and specificity. Our lists of prioritized drug targets and drug-like compounds have potential to expedite the discovery of new anthelmintic drugs with broad-spectrum efficacy

    Innexin function dictates the spatial relationship between distal somatic cells in the Caenorhabditis elegans gonad without impacting the germline stem cell pool

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    Gap-junctional signaling mediates myriad cellular interactions in metazoans. Yet, how gap junctions control the positioning of cells in organs is not well understood. Innexins compose gap junctions in invertebrates and affect organ architecture. Here, we investigate the roles of gap-junctions in controlling distal somatic gonad architecture and its relationship to underlying germline stem cells i

    Selection and maintenance of sexual identity in the Drosophila germline.

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    Unlike sex determination in the soma, which is an autonomous process, sex determination in the germline of Drosophila has both inductive and autonomous components. In this paper, we examined how sexual identity is selected and maintained in the Drosophila germline. We show that female-specific expression of genes in the germline is dependent on a somatic signaling pathway. This signaling pathway requires the sex-non-specific transformer 2 gene but, surprisingly, does not appear to require the sex-specific genes, transformer and doublesex. Moreover, in contrast to the soma where pathway initiation and maintenance are independent processes, the somatic signaling pathway appears to function continuously from embryogenesis to the larval stages to select and sustain female germline identity. We also show that the primary target for the somatic signaling pathway in germ cells can not be the Sex-lethal gene
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