4,846 research outputs found

    component of this work in other works. Area-Efficient Synthesis of Fault-Secure NoC Switches

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    Relationships between soil physicochemical properties and nitrogen fixing, nitrifying and denitrifying under varying land-use practices in the northwest region of Argentina

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    The aim of this study was to evaluate the response pattern of diazotrophic microbes, denitrifiers and nitrifiers to different types of land use management, such as soybean monoculture (M) during 5 and 24 years (M5 and M24) and soybean-maize rotation (R) during 4 and 15 years (R4 and R15) in two subsequent years at the time point of flowering. Soil samples from a site recently introduced into agriculture (RUA) and a pristine soil under native vegetation (NV) were used as controls. Abundances of different functional groups of microbes were assessed using the direct quantification of marker genes by quantitative real-time PCR using extracted DNA from rhizosphere samples. In addition, soil chemical and physical properties were analysed and correlated with the abundance data from the functional microbial groups under investigation. Overall, the results indicate that the abundance of nifH genes was higher under R treatments compared to M treatments. The abundance of ammonium monooxygenase genes amoA (AOA) was generally higher under rotation systems and decreased under M24. RUA evidenced a negative effect on the establishment and development of AOA communities. The influence of land use on nirS abundance was inconsistent. However, R treatments showed a high abundance of nirK genes compared to M treatments. In both growing seasons, the abundance of nosZ genes was higher under NV compared with the other treatments. Furthermore, M24 treatment was related to strongly changed chemical and physical soil properties compared with the other sites. As expected, soil samples from RUA showed the strong dynamics of measured parameters indicating the high sensitivity of soils under transition to environmental parameters. Our results also indicated that the long-term crop rotation modified the abundance of the investigated microbial groups compared to the monoculture and increased soil chemical and physical quality. Therefore, our results provide evidence for a stimulatory effect of the long-term crop rotation on the abundance of microbes involved in N transformation.Fil: Perez Brandan, Carolina Gabriela. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Meyer, Annabel. Helmholtz Center Munich German Research Center For Environmental Health; AlemaniaFil: Meriles, Jose Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Huidobro, Jorgelina. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Schloter, Michael. Helmholtz Center Munich German Research Center For Environmental Health; AlemaniaFil: Vargas Gil, Silvina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Toward a molecular understanding of yeast silent chromatin : roles for H4K16 acetylation and the Sir3 C-terminus

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    Discrete regions of the eukaryotic genome assume a heritable chromatin structure that is refractory to gene expression. In budding yeast, silent chromatin is characterized by the loading of the Silent Information Regulatory (Sir) proteins (Sir2, Sir3 and Sir4) onto unmodified nucleosomes. This requires the deacetylase activity of Sir2, extensive contacts between Sir3 and the nucleosome, as well as interactions between Sir proteins forming the Sir2-3-4 complex. During my PhD thesis I sought to advance our understanding of these phenomena from a molecular perspective. Previous studies of Sir-chromatin interactions made use of histone peptides and recombinant Sir protein fragments. This gave us an idea of possible interactions, but could not elucidate the role of histone modifications in the assembly of silent chromatin. This required that we examine nucleosomal arrays exposed to full length Sir proteins or the holo Sir complex. In Chapter 2, I made use of an in vitro reconstitution system, that allows the loading of Sir proteins (Sir3, Sir2-4 or Sir2-3-4) onto arrays of regularly spaced nucleosomes, to examine the impact of specific histone modifications (methylation of H3K79, acetylation of H3K56 and H4K16) on Sir protein binding and linker DNA accessibility. The “active” H4K16ac mark is thought to limit the loading of the Sir proteins to silent domain thus favoring the formation of silent regions indirectly by increasing Sir concentration locally. Strikingly, I found that the Sir2-4 subcomplex, unlike Sir3, has a slight higher affinity for H4K16ac-containing chromatin in vitro, consistent with H4K16ac being a substrate for Sir2. In addition the NAD-dependent deacetylation of H4K16ac promotes the binding of the holo Sir complex to chromatin beyond generating hypoacetylated histone tails. We conclude that the Sir2-dependent turnover of the “active” H4K16ac mark directly helps to seed repression. The tight association of the holo Sir complex within silent domains relies on the ability of Sir3 to bind unmodified nucleosomes. In addition, Sir3 dimerization is thought to reinforce and propagate silent domains. However, no Sir3 mutants that fail to dimerize were characterized to date. It was unclear which domain of Sir3 mediates dimerization in vivo. In Chapter 3, we present the X-ray crystal structure of the Sir3 extreme C-terminus (aa 840-978), which folds into a variant winged helix-turn-helix (Sir3 wH) and forms a stable homodimer through a large hydrophobic interface. Loss of wH homodimerization impairs holo Sir3 dimerization in vitro showing that the Sir3 wH module is key to Sir3-Sir3 interaction. Homodimerization mediated by the wH domain can be fully recapitulated by an unrelated bacterial homodimerization domain and is essential for stable association of the Sir2-3-4 complex with chromatin and the formation of silent chromatin in vivo

    FiberBlender: A Realistic Computer Model of Nerve Bundles for Simulating and Validating the Acquisition of Diffusion Tensor Imaging

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    Diffusion Tensor Imaging (DTI) is a powerful medical imaging technique that provides a unique method to investigate the structure and connectivity of neural pathways. DTI is a special magnetic resonance imaging (MRI) modality that combines the principles of magnetic resonance with molecular diffusion to trace the motion of water molecules. In the central nervous system, where nerve fibers are packed in highly-directional bundles, these molecules diffuse along the orientation of the fibers. Hence, characterizing the motion of water with DTI delivers a non-invasive in vivo technique to capture the connectivity of nerves themselves. Despite its promises and successful clinical applications for nearly thirty years, problems with validation and interpretation of measurements still persist. Most validation studies attempt to generate ground-truth data from animal models, phantoms, and computer models. This dissertation proposes a novel validation system, FiberBlender, capable of reproducing three-dimensional fiber structures and simulating the diffusion of water molecules to generate ground-truth synthetic DTI data. In particular FiberBlender contributes to: (i) creating more biologically accurate representations of fiber bundles with the inclusion of myelin and glial cells, (ii) examining the effect of demyelination and gliosis on DTI measurements, (iii) optimizing acquisition sequences, and (iv) evaluating the performance of multi-tensor models for the study of crossing fibers. FiberBlender strays away from the “one size fits all” approach taken by previous studies and uses computer algorithms in conjunction with some limited manual operations to produce brain-like geometries that take into account the random spatial location of axons and correct distributions of axon diameters, myelin to axon radius, and myelin to glia ratio. In this way no two models are the same and the system is capable of generating structures that can potentially represent any region of the brain and encompass the heterogeneity between human subjects. This feature is essential for optimization as the performance of DTI acquisition sequences may vary among subjects and the type of scanner used. In addition to better accuracy, the system offers a high degree of flexibility as the geometry can be modified to simulate events that cause drastic changes to the fiber structure. Specially, this dissertation looks at demyelination (an extensive loss of myelin volume), gliosis (a proliferation of glial cells), and axon compaction (a condensation of axons due to a loss of total brain volume) to determine their effects on the observed DTI signal. Simulation results confirm that axon compaction and partial remyelination have similar characteristics. Results also show that some standard clinically used acquisition sequences are incapable of capturing the effects of demyelination, gliosis and compaction when performing longitudinal studies. A novel sequence optimization technique based on Shannon entropy and mutual information is proposed to better capture demyelination. Optimized sequences are tested on a number of non-identical models to confirm their validity and can be used to improve the quality of DTI diagnostics. Finally this work looks at crossing fibers for the validation of multi-tensor models in their ability to characterize crossing diffusion profiles. The performance of multi-tensor models from CHARMED, Q-ball and spherical deconvolution that are widely used in both research and clinical settings are evaluated against ground-truth data generated with FiberBlender. The study is performed on a number of different crossing geometries and preliminary results show that the CHARMED model is the most comprehensive approach

    kBF: A Bloom Filter for key-value storage with an application on approximate state machines

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    Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

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    Correction to Martin et al. available at: Genes & Development 30 (19): 2158 (http://genesdev.cshlp.org/content/31/9/953.full.pdf+html).Compaction of chromosomes is essential for accurate segregation of the genome duringmitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here,we report that biallelic mutations inNCAPD2,NCAPH, orNCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.This work was supported by funding from the Medical Research Council, the Lister Institute for Preventative Medicine, and the European Research Council (ERC; 281847 to A.P.J.); a Biotechnology and Biological Sciences Research Council grant (BB/ K017632/1 to P.V); a Sir Henry Dale Fellowship (grant 102560/ Z/13/Z to A.J.W.); Medical Research Scotland (to L.S.B.); the Potentials Foundation (to C.A.W.); and the Indian Council of Medical Research (BMS 54/2/2013 to S.R.P). The Deciphering Developmental Disorders Study presents independent research commissioned by the Health Innovation Challenge Fund (grant no. HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant no. WT098051). The views expressed here are those of the authors and not necessarily those of the Wellcome Trust or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83) granted by the Cambridge South Research Ethics Committee, and GEN/ 284/12 granted by the Republic of Ireland. We acknowledge the support of the National Institute for Health Research through the Comprehensive Clinical Research Network

    Cognición y representación interna de entornos dinámicos en el cerebro de los mamíferos

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    Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 07/05/2021El tiempo es una de las dimensiones fundamentales de la realidad. Paradójicamente, los fenómenos temporales del mundo natural contienen ingentes cantidades de información redundante, y a pesar de ello, codificar internamente el tiempo en el cerebro es imprescindible para anticiparse a peligros en ambientes dinámicos. No obstante, dedicar grandes cantidades de recursos cognitivos a procesar las características espacio-temporales de entornos complejos debería ser incompatible con la supervivencia, que requiere respuestas rápidas. Aun así, los animales son capaces de tomar decisiones en intervalos de tiempo muy estrechos. ¿Cómo consigue hacer esto el cerebro? Como respuesta al balance entre complejidad y velocidad, la hipótesis de la compactación del tiempo propone que el cerebro no codifica el tiempo explícitamente, sino que lo integra en el espacio. En teoría, la compactación del tiempo simplifica las representaciones internas del entorno, reduciendo significativamente la carga de trabajo dedicada a la planificación y la toma de decisiones. La compactación del tiempo proporciona un marco operativo que pretende explicar cómo las situaciones dinámicas, percibidas o producidas, se representan cognitivamente en forma de predicciones espaciales o representaciones internas compactas (CIR), que pueden almacenarse en la memoria y recuperarse más adelante para generar respuestas. Aunque la compactación del tiempo ya ha sido implementada en robots, hasta ahora no se había comprobado su existencia como mecanismo biológico y cognitivo en el cerebro...Time is one of the most prominent dimensions that organize reality. Paradoxically, there are loads of redundant information contained within the temporal features of the natural world, and yet internal coding of time in the brain seems to be crucial for anticipating time-changing, dynamic hazards. Allocating such significant brain resources to process spatiotemporal aspects of complex environments should apparently be incompatible with survival, which requires fast and accurate responses. Nonetheless, animals make decisions under pressure and in narrow time windows. How does the brain achieve this? An effort to resolve the complexity-velocity trade-off led to a hypothesis called time compaction, which states the brain does not encode time explicitly but embeds it into space. Theoretically, time compaction can significantly simplify internal representations of the environment and hence ease the brain workload devoted to planning and decision-making. Time compaction also provides an operational framework that aims to explain how perceived and produced dynamic situations are cognitively represented, in the form of spatial predictions or compact internal representations (CIRs) that can be stored in memory and be used later on to guide behaviour and generate action. Although successfully implemented in robots, time compaction still lacked assessment of its biological soundness as an actual cognitive mechanism in the brain...Fac. de Ciencias BiológicasTRUEunpu
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