1,382 research outputs found

    Pre and post processing using the IBM 3277 display station graphics attachment (RPQ7H0284)

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    A graphical interactive procedure operating under TSO and utilizing two CRT display terminals is shown to be an effective means of accomplishing mesh generation, establishing boundary conditions, and reviewing graphic output for finite element analysis activity

    A novel superfamily containing the β-grasp fold involved in binding diverse soluble ligands

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    BACKGROUND: Domains containing the β-grasp fold are utilized in a great diversity of physiological functions but their role, if any, in soluble or small molecule ligand recognition is poorly studied. RESULTS: Using sensitive sequence and structure similarity searches we identify a novel superfamily containing the β-grasp fold. They are found in a diverse set of proteins that include the animal vitamin B12 uptake proteins transcobalamin and intrinsic factor, the bacterial polysaccharide export proteins, the competence DNA receptor ComEA, the cob(I)alamin generating enzyme PduS and the Nqo1 subunit of the respiratory electron transport chain. We present evidence that members of this superfamily are likely to bind a range of soluble ligands, including B12. There are two major clades within this superfamily, namely the transcobalamin-like clade and the Nqo1-like clade. The former clade is typified by an insert of a β-hairpin after the helix of the β-grasp fold, whereas the latter clade is characterized by an insert between strands 4 and 5 of the core fold. CONCLUSION: Members of both clades within this superfamily are predicted to interact with ligands in a similar spatial location, with their specific inserts playing a role in the process. Both clades are widely represented in bacteria suggesting that this superfamily was derived early in bacterial evolution. The animal lineage appears to have acquired the transcobalamin-like proteins from low GC Gram-positive bacteria, and this might be correlated with the emergence of the ability to utilize B12 produced by gut bacteria. REVIEWERS: This article was reviewed by Andrei Osterman, Igor Zhulin, and Arcady Mushegian

    Small but versatile: the extraordinary functional and structural diversity of the β-grasp fold

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    <p>Abstract</p> <p>Background</p> <p>The β-grasp fold (β-GF), prototyped by ubiquitin (UB), has been recruited for a strikingly diverse range of biochemical functions. These functions include providing a scaffold for different enzymatic active sites (e.g. NUDIX phosphohydrolases) and iron-sulfur clusters, RNA-soluble-ligand and co-factor-binding, sulfur transfer, adaptor functions in signaling, assembly of macromolecular complexes and post-translational protein modification. To understand the basis for the functional versatility of this small fold we undertook a comprehensive sequence-structure analysis of the fold and developed a natural classification for its members.</p> <p>Results</p> <p>As a result we were able to define the core distinguishing features of the fold and numerous elaborations, including several previously unrecognized variants. Systematic analysis of all known interactions of the fold showed that its manifold functional abilities arise primarily from the prominent β-sheet, which provides an exposed surface for diverse interactions or additionally, by forming open barrel-like structures. We show that in the β-GF both enzymatic activities and the binding of diverse co-factors (e.g. molybdopterin) have independently evolved on at least three occasions each, and iron-sulfur-cluster-binding on at least two independent occasions. Our analysis identified multiple previously unknown large monophyletic assemblages within the β-GF, including one which unifies versions found in the fasciclin-1 superfamily, the ribosomal protein L25, the phosphoribosyl AMP cyclohydrolase (HisI) and glutamine synthetase. We also uncovered several new groups of β-GF domains including a domain found in bacterial flagellar and fimbrial assembly components, and 5 new UB-like domains in the eukaryotes.</p> <p>Conclusion</p> <p>Evolutionary reconstruction indicates that the β-GF had differentiated into at least 7 distinct lineages by the time of the last universal common ancestor of all extant organisms, encompassing much of the structural diversity observed in extant versions of the fold. The earliest β-GF members were probably involved in RNA metabolism and subsequently radiated into various functional niches. Most of the structural diversification occurred in the prokaryotes, whereas the eukaryotic phase was mainly marked by a specific expansion of the ubiquitin-like β-GF members. The eukaryotic UB superfamily diversified into at least 67 distinct families, of which at least 19–20 families were already present in the eukaryotic common ancestor, including several protein and one lipid conjugated forms. Another key aspect of the eukaryotic phase of evolution of the β-GF was the dramatic increase in domain architectural complexity of proteins related to the expansion of UB-like domains in numerous adaptor roles.</p> <p>Reviewers</p> <p>This article was reviewed by Igor Zhulin, Arcady Mushegian and Frank Eisenhaber.</p

    In-Line-Test of Variability and Bit-Error-Rate of HfOx-Based Resistive Memory

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    Spatial and temporal variability of HfOx-based resistive random access memory (RRAM) are investigated for manufacturing and product designs. Manufacturing variability is characterized at different levels including lots, wafers, and chips. Bit-error-rate (BER) is proposed as a holistic parameter for the write cycle resistance statistics. Using the electrical in-line-test cycle data, a method is developed to derive BERs as functions of the design margin, to provide guidance for technology evaluation and product design. The proposed BER calculation can also be used in the off-line bench test and build-in-self-test (BIST) for adaptive error correction and for the other types of random access memories.Comment: 4 pages. Memory Workshop (IMW), 2015 IEEE Internationa

    On quantifying the climate of the nonautonomous lorenz-63 model

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    The Lorenz-63 model has been frequently used to inform our understanding of the Earth's climate and provide insight for numerical weather and climate prediction. Most studies have focused on the autonomous (time invariant) model behaviour in which the model's parameters are constants. Here we investigate the properties of the model under time-varying parameters, providing a closer parallel to the challenges of climate prediction, in which climate forcing varies with time. Initial condition (IC) ensembles are used to construct frequency distributions of model variables and we interpret these distributions as the time-dependent climate of the model. Results are presented that demonstrate the impact of ICs on the transient behaviour of the model climate. The location in state space from which an IC ensemble is initiated is shown to significantly impact the time it takes for ensembles to converge. The implication for climate prediction is that the climate may, in parallel with weather forecasting, have states from which its future behaviour is more, or less, predictable in distribution. Evidence of resonant behaviour and path dependence is found in model distributions under time varying parameters, demonstrating that prediction in nonautonomous nonlinear systems can be sensitive to the details of time-dependent forcing/parameter variations. Single model realisations are shown to be unable to reliably represent the model's climate; a result which has implications for how real-world climatic timeseries from observation are interpreted. The results have significant implications for the design and interpretation of Global Climate Model experiments. Over the past 50 years, insight from research exploring the behaviour of simple nonlinear systems has been fundamental in developing approaches to weather and climate prediction. The analysis herein utilises the much studied Lorenz-63 model to understand the potential behaviour of nonlinear systems, such as the 5 climate, when subject to time-varying external forcing, such as variations in atmospheric greenhouse gases or solar output. Our primary aim is to provide insight which can guide new approaches to climate model experimental design and thereby better address the uncertainties associated with climate change prediction. We use ensembles of simulations to generate distributions which 10 we refer to as the \climate" of the time-variant Lorenz-63 model. In these ensemble experiments a model parameter is varied in a number of ways which can be seen as paralleling both idealised and realistic variations in external forcing of the real climate system. Our results demonstrate that predictability of climate distributions under time varying forcing can be highly sensitive to 15 the specification of initial states in ensemble simulations. This is a result which at a superficial level is similar to the well-known initial condition sensitivity in weather forecasting, but with different origins and different implications for ensemble design. We also demonstrate the existence of resonant behaviour and a dependence on the details of the \forcing" trajectory, thereby highlighting 20 further aspects of nonlinear system behaviour with important implications for climate prediction. Taken together, our results imply that current approaches to climate modeling may be at risk of under-sampling key uncertainties likely to be significant in predicting future climate

    A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients

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    Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir ( 5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log(10) higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo

    Combinatorial Hopf algebras and Towers of Algebras

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    Bergeron and Li have introduced a set of axioms which guarantee that the Grothendieck groups of a tower of algebras n0An\bigoplus_{n\ge0}A_n can be endowed with the structure of graded dual Hopf algebras. Hivert and Nzeutzhap, and independently Lam and Shimozono constructed dual graded graphs from primitive elements in Hopf algebras. In this paper we apply the composition of these constructions to towers of algebras. We show that if a tower n0An\bigoplus_{n\ge0}A_n gives rise to graded dual Hopf algebras then we must have dim(An)=rnn!\dim(A_n)=r^nn! where r=dim(A1)r = \dim(A_1).Comment: 7 page

    q-Analogue of Am1An1Amn1A_{m-1}\oplus A_{n-1}\subset A_{mn-1}

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    A natural embedding Am1An1Amn1A_{m-1}\oplus A_{n-1}\subset A_{mn-1} for the corresponding quantum algebras is constructed through the appropriate comultiplication on the generators of each of the Am1A_{m-1} and An1A_{n-1} algebras. The above embedding is proved in their qq-boson realization by means of the isomorphism between the Aq\mathcal{A}_q^{-} (mn)nAq\sim {\otimes} ^n \mathcal{A}_q^{-}(m)mAq\sim {\otimes}^m\mathcal{A}_q^{-}(n) algebras.Comment: 11 pages, no figures. In memory of professor R. P. Rousse
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