2,237 research outputs found

    The role of tool geometry in process damped milling

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    The complex interaction between machining structural systems and the cutting process results in machining instability, so called chatter. In some milling scenarios, process damping is a useful phenomenon that can be exploited to mitigate chatter and hence improve productivity. In the present study, experiments are performed to evaluate the performance of process damped milling considering different tool geometries (edge radius, rake and relief angles and variable helix/pitch). The results clearly indicate that variable helix/pitch angles most significantly increase process damping performance. Additionally, increased cutting edge radius moderately improves process damping performance, while rake and relief angles have a smaller and closely coupled effect

    Lumbar spinal stenosis treatment with aperius perclid interspinous system

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    The purpose of this study is to report clinical outcome and imaging changes of percutaneous Aperius stand-alone implant in patients with degenerative lumbar spinal stenosis and neurogenic intermittent claudication, which did not respond to conservative treatment.Between January 2008 and July 2010, 37 patients (20 males and 17 females) with mean age of 64.3 years underwent surgery for the onset of claudicatio spinalis with Aperius PercLID interspinous device (Medtronic). In all patients, the diagnosis was: foraminal stenosis, in one case (2.7 \%) it was associated to a degenerative anterior listhesis (I grade), in three cases (8.1 \%) it was associated to an intraforaminal disc herniation. The mean follow-up was of 18 months (range 2-35 months). The patients were evaluated through the Oswestry disability index, Zurich Claudication Questionnaire (ZCQ), VAS scales. In all cases were obtained preoperative and in postoperative radiographs and magnetic resonance imaging.The VAS score decreased significantly after surgery: the patients presented a mean VAS of seven preoperatively and two postoperatively (p < 0.001). The ZCQ score significantly decreased postoperatively, with an average reduction of 21.89 \% (p < 0.001). The ODI score as well showed a significant reduction postoperatively of an average 26.09 \% (p < 0.001).Despite of the brief follow up, the preliminary results are encouraging, showing a significantly decrease of the disability parameters, a marked improvement of the function with the vanishing of the claudicatio spinalis and the following increase of the free interval during the walk. Aperius PercLID system seems to offer an alternative to the traditional decompression surgery

    Analytic Markovian Rates for Generalized Protein Structure Evolution

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    A general understanding of the complex phenomenon of protein evolution requires the accurate description of the constraints that define the sub-space of proteins with mutations that do not appreciably reduce the fitness of the organism. Such constraints can have multiple origins, in this work we present a model for constrained evolutionary trajectories represented by a Markovian process throughout a set of protein-like structures artificially constructed to be topological intermediates between the structure of two natural occurring proteins. The number and type of intermediate steps defines how constrained the total evolutionary process is. By using a coarse-grained representation for the protein structures, we derive an analytic formulation of the transition rates between each of the intermediate structures. The results indicate that compact structures with a high number of hydrogen bonds are more probable and have a higher likelihood to arise during evolution. Knowledge of the transition rates allows for the study of complex evolutionary pathways represented by trajectories through a set of intermediate structures

    The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

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    We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

    Differentially expressed genes in a flock of Chinese local-breed chickens infected with a subgroup J avian leukosis virus using suppression subtractive hybridization

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    Avian leukosis virus subgroup J (ALV-J) is a new type of virus that mainly induces myeloid leukosis (ML) in chickens. To further elucidate the pathogenesis of ALV-J infection and tumor development, expression profiles from the bone marrow tissue of 15 infected and 18 non-infected birds from a local-breed poultry-farm under naturally infected conditions, were analyzed by suppression-subtractive hybridization. The birds were diagnosed as ML+ (or ML-) by specific ALV-J detection methods, involving serological tests for antigens and antibodies, and RT-PCR to detect viral RNA. A total of 59 partial gene sequences were revealed by differential screening of 496 forward and 384 reverse subtracted cDNA clones. Of these, 22 identified genes, including 8 up-regulated and 14 down-regulated, were related to immune functions, these genes being, MHC B-G antigen, translationally-controlled tumor protein (TPT1/TPTC), transferrin and ferritin, hemoglobin and Carbonic anhydrase. Four of the down-regulated genes were selected for further analysis, in view of their predicted roles in infection and immunity by real-time qRT-PCR, using RNA collected from the same birds as those used for SSH. The four genes were expressed at significantly lower levels (p < 0.001) in ALV-J infected birds than in non-infected ones

    Process Drivers, Inter-Model Spread, and the Path Forward: A Review of Amplified Arctic Warming

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    This is the final version. Available on open access from Frontiers Media via the DOI in this recordArctic amplification (AA) is a coupled atmosphere-sea ice-ocean process. This understanding has evolved from the early concept of AA, as a consequence of snow-ice line progressions, through more than a century of research that has clarified the relevant processes and driving mechanisms of AA. The predictions made by early modeling studies, namely the fall/winter maximum, bottom-heavy structure, the prominence of surface albedo feedback, and the importance of stable stratification have withstood the scrutiny of multi-decadal observations and more complex models. Yet, the uncertainty in Arctic climate projections is larger than in any other region of the planet, making the assessment of high-impact, near-term regional changes difficult or impossible. Reducing this large spread in Arctic climate projections requires a quantitative process understanding. This manuscript aims to build such an understanding by synthesizing current knowledge of AA and to produce a set of recommendations to guide future research. It briefly reviews the history of AA science, summarizes observed Arctic changes, discusses modeling approaches and feedback diagnostics, and assesses the current understanding of the most relevant feedbacks to AA. These sections culminate in a conceptual model of the fundamental physical mechanisms causing AA and a collection of recommendations to accelerate progress towards reduced uncertainty in Arctic climate projections. Our conceptual model highlights the need to account for local feedback and remote process interactions within the context of the annual cycle to constrain projected AA. We recommend raising the priority of Arctic climate sensitivity research, improving the accuracy of Arctic surface energy budget observations, rethinking climate feedback definitions, coordinating new model experiments and intercomparisons, and further investigating the role of episodic variability in AA.NASANatural Sciences and Engineering Research Council of Canada (NSERC)US National Science foundationAlfred P. Sloan FoundationNatural Environment Research Council (NERC

    Exploring forest structural complexity by multi-scale segmentation of VHR imagery

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    Forests are complex ecological systems, characterised by multiple-scale structural and dynamical patterns which are not inferable from a system description that spans only a narrow window of resolution; this makes their investigation a difficult task using standard field sampling protocols. We segment a QuickBird image covering a beech forest in an initial stage of old-growthness – showing, accordingly, a good degree of structural complexity – into three segmentation levels. We apply field-based diversity indices of tree size, spacing, species assemblage to quantify structural heterogeneity amongst forest regions delineated by segmentation. The aim of the study is to evaluate, on a statistical basis, the relationships between spectrally delineated image segments and observed spatial heterogeneity in forest structure, including gaps in the outer canopy. Results show that: some 45% of the segments generated at the coarser segmentation scale (level 1) are surrounded by structurally different neighbours; level 2 segments distinguish spatial heterogeneity in forest structure in about 63% of level 1 segments; level 3 image segments detect better canopy gaps, rather than differences in the spatial pattern of the investigated structural indices. Results support also the idea of a mixture of macro and micro structural heterogeneity within the beech forest: large size populations of trees homogeneous for the examined structural indices at the coarser segmentation level, when analysed at a finer scale, are internally heterogeneous; and vice versa. Findings from this study demonstrate that multiresolution segmentation is able to delineate scale-dependent patterns of forest structural heterogeneity, even in an initial stage of old-growth structural differentiation. This tool has therefore a potential to improve the sampling design of field surveys aimed at characterizing forest structural complexity across multiple spatio-temporal scales.L'articolo è disponibile sul sito dell'editore www.sciencedirect.co

    Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

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    A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease
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