189 research outputs found

    Edge Chipping Resistance and Flexural Strength of Polymer Infiltrated Ceramic Network and Resin Nanoceramic Restorative Materials

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    Statement of problem Two novel restorative materials, a polymer infiltrated ceramic network (PICN) and a resin nanoceramic (RNC), for computer-assisted design and computer-assisted manufacturing (CAD-CAM) applications have recently become commercially available. Little independent evidence regarding their mechanical properties exists to facilitate material selection. Purpose The purpose of this in vitro study was to measure the edge chipping resistance and flexural strength of the PICN and RNC materials and compare them with 2 commonly used feldspathic ceramic (FC) and leucite reinforced glass-ceramic (LRGC) CAD-CAM materials that share the same clinical indications. Material and methods PICN, RNC, FC, and LRGC material specimens were obtained by sectioning commercially available CAD-CAM blocks. Edge chipping test specimens (n=20/material) were adhesively attached to a resin substrate before testing. Edge chips were produced using a 120-degree, sharp, conical diamond indenter mounted on a universal testing machine and positioned 0.1 to 0.7 mm horizontally from the specimen’s edge. The chipping force was plotted against distance to the edge, and the data were fitted to linear and quadratic equations. One-way ANOVA determined intergroup differences (α=.05) in edge chipping toughness. Beam specimens (n=22/material) were tested for determining flexural strength using a 3-point bend test. Weibull statistics determined intergroup differences (α=.05). Flexural modulus and work of fracture were also calculated, and 1-way ANOVA determined intergroup differences (α=.05) Results Significant (PLRGC=FC\u3ePICN; flexural strength: RNC=LRGC\u3ePICN\u3eFC; flexural modulus: RNCLRGC=PICN\u3eFC. Conclusions The RNC material demonstrated superior performance for the mechanical properties tested compared with the other 3 materials

    Partial wave treatment of Supersymmetric Dark Matter in the presence of CP - violation

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    We present an improved partial wave analysis of the dominant LSP annihilation channel to a fermion-antifermion pair which avoids the non-relativistic expansion being therefore applicable near thresholds and poles. The method we develop allows of contributions of any partial wave in the total angular momentum J in contrast to partial wave analyses in terms of the orbital angular momentum L of the initial state, which is usually truncated to p-waves, and yields very accurate results. The method is formulated in such a way as to allow easy handling of CP-violating phases residing in supersymmetric parameters. We apply this refined partial wave technique in order to calculate the neutralino relic density in the constrained MSSM (CMSSM) in the presence of CP-violating terms occurring in the Higgs - mixing parameter \mu and trilinear A coupling for large tanb. The inclusion of CP-violating phases in mu and A does not upset significantly the picture and the annihilation of the LSP's to a b b_bar, through Higgs exchange, is still the dominant mechanism in obtaining cosmologically acceptable neutralino relic densities in regions far from the stau-coannihilation and the `focus point'. Significant changes can occur if we allow for phases in the gaugino masses and in particular the gluino mass.Comment: 23 pages LaTeX, 10 eps figures, version to appear in PR

    PocketMatch: A new algorithm to compare binding sites in protein structures

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    Background: Recognizing similarities and deriving relationships among protein molecules is a fundamental
requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of
the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.

Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant
manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless
combined with chemical nature of amino acids.

Conclusions: A new algorithm has been developed to compare binding sites in accurate, efficient and
high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along
with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented

    Effects of seagrasses and algae of the Caulerpa family on hydrodynamics and particle-trapping rates

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    The widespread decline of seagrass beds within the Mediterranean often results in the replacement of seagrasses by opportunistic green algae of the Caulerpa family. Because Caulerpa beds have a different height, stiffness and density compared to seagrasses, these changes in habitat type modify the interaction of the seafloor with hydrodynamics, influencing key processes such as sediment resuspension and particle trapping. Here, we compare the effects on hydrodynamics and particle trapping of Caulerpa taxifolia, C. racemosa, and C. prolifera with the Mediterranean seagrasses Cymodocea nodosa and Posidonia oceanica. All macrophyte canopies reduced near-bed volumetric flow rates compared to bare sediment, vertical profiles of turbulent kinetic energy revealed peak values around the top of the canopies, and maximum values of Reynolds stress increased by a factor of between 1.4 (C. nodosa) and 324.1 (P. oceanica) when vegetation was present. All canopies enhanced particle retention rates compared to bare sediment. The experimental C. prolifera canopy was the most effective at particle retention (m2 habitat); however, C. racemosa had the largest particle retention capacity per structure surface area. Hence, in terms of enhancing particle trapping and reducing hydrodynamic forces at the sediment surface, Caulerpa beds provided a similar or enhanced function compared to P.oceanica and C. nodosa. However, strong seasonality in the leaf area index of C. racemosa and C. taxifolia within the Mediterranean, combined with a weak rhizome structure, suggests that sediments maybe unprotected during winter storms, when most erosion occurs. Hence, replacement of seagrass beds with Caulerpa is likely to have a major influence on annual sediment dynamics at ecosystem scales.This research was funded by the European Network of Excellence ‘‘Marine Biodiversity and Ecosystem Function’’ (MarBEF); FP6, EC contract no. 505446 and a grant from the Fundacio ´n BBVA. EPM was supported by a European Union Marie Curie host fellowship for transfer of knowledge, MTKD-CT-2004-509254, the Spanish national project EVAMARIA (CTM2005-00395/MAR) and the regional government of Andalusia project FUNDIV(P07-RNM-2516)

    A Geometric Approach to CP Violation: Applications to the MCPMFV SUSY Model

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    We analyze the constraints imposed by experimental upper limits on electric dipole moments (EDMs) within the Maximally CP- and Minimally Flavour-Violating (MCPMFV) version of the MSSM. Since the MCPMFV scenario has 6 non-standard CP-violating phases, in addition to the CP-odd QCD vacuum phase \theta_QCD, cancellations may occur among the CP-violating contributions to the three measured EDMs, those of the Thallium, neutron and Mercury, leaving open the possibility of relatively large values of the other CP-violating observables. We develop a novel geometric method that uses the small-phase approximation as a starting point, takes the existing EDM constraints into account, and enables us to find maximal values of other CP-violating observables, such as the EDMs of the Deuteron and muon, the CP-violating asymmetry in b --> s \gamma decay, and the B_s mixing phase. We apply this geometric method to provide upper limits on these observables within specific benchmark supersymmetric scenarios, including extensions that allow for a non-zero \theta_QCD.Comment: 34 pages, 16 eps figures, to appear in JHE

    Research for PECH Committee - Discard ban, landing obligation and MSY in the Western Mediterranean Sea - the Spanish case

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    The demersal fisheries in the Mediterranean Sea are heavily overfished but the landing obligation will not help to reach MSY because it will not decrease fishing mortality. The new proposal of the Commission introduces total allowable effort as a new way to regulate Western Mediterranean demersal fisheries by significantly reducing fishing time. However, this new management measure must be complemented with increased gear selectivity, implementation of closed areas and local co-management plans. Different approaches to reduce fishing mortality may have different socio-economic impact

    High-throughput Screening and Sensitized Bacteria Identify an M. tuberculosis Dihydrofolate Reductase Inhibitor with Whole Cell Activity

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    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a bacterial pathogen that claims roughly 1.4 million lives every year. Current drug regimens are inefficient at clearing infection, requiring at least 6 months of chemotherapy, and resistance to existing agents is rising. There is an urgent need for new drugs that are more effective and faster acting. The folate pathway has been successfully targeted in other pathogens and diseases, but has not yielded a lead drug against tuberculosis. We developed a high-throughput screening assay against Mtb dihydrofolate reductase (DHFR), a critical enzyme in the folate pathway, and screened a library consisting of 32,000 synthetic and natural product-derived compounds. One potent inhibitor containing a quinazoline ring was identified. This compound was active against the wild-type laboratory strain H37Rv (MIC99 = 207 µM). In addition, an Mtb strain with artificially lowered DHFR levels showed increased sensitivity to this compound (MIC99 = 70.7 µM), supporting that the inhibition was target-specific. Our results demonstrate the potential to identify Mtb DHFR inhibitors with activity against whole cells, and indicate the power of using a recombinant strain of Mtb expressing lower levels of DHFR to facilitate the discovery of antimycobacterial agents. With these new tools, we highlight the folate pathway as a potential target for new drugs to combat the tuberculosis epidemic

    The essential mycobacterial genes, fabG1 and fabG4, encode 3-oxoacyl-thioester reductases that are functional in yeast mitochondrial fatty acid synthase type 2

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    Mycobacterium tuberculosis represents a severe threat to human health worldwide. Therefore, it is important to expand our knowledge of vital mycobacterial processes, such as that effected by fatty acid synthase type 2 (FASII), as well as to uncover novel ones. Mycobacterial FASII undertakes mycolic acid biosynthesis, which relies on a set of essential enzymes, including 3-oxoacyl-AcpM reductase FabG1/Rv1483. However, the M. tuberculosis genome encodes four additional FabG homologs, designated FabG2–FabG5, whose functions have hitherto not been characterized in detail. Of the four candidates, FabG4/Rv0242c was recently shown to be essential for the survival of M. bovis BCG. The present work was initiated by assessing the suitability of yeast oar1Δ mutant cells lacking mitochondrial 3-oxoacyl-ACP reductase activity to act as a surrogate system for expressing FabG1/MabA directed to the mitochondria. Mutant yeast cells producing this targeted FabG1 variant were essentially wild type for all of the chronicled phenotype characteristics, including respiratory growth on glycerol medium, cytochrome assembly and lipoid acid production. This indicated that within the framework of de novo fatty acid biosynthesis in yeast mitochondria, FabG1 was able to act on shorter (C4) acyl substrates than was previously proposed (C8–20) during mycolic acid biosynthesis in M. tuberculosis. Thereafter, FabG2–FabG5 were expressed as mitochondrial proteins in the oar1Δ strain, and FabG4 was found to complement the mutant phenotype and contain high levels of 3-oxoacyl-thioester reductase activity. Hence, like FabG1, FabG4 is also an essential, physiologically functional 3-oxoacyl-thioester reductase, albeit the latter’s involvement in mycobacterial FASII remains to be explored

    An Anaerobic-Type α-Ketoglutarate Ferredoxin Oxidoreductase Completes the Oxidative Tricarboxylic Acid Cycle of Mycobacterium tuberculosis

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    Aerobic organisms have a tricarboxylic acid (TCA) cycle that is functionally distinct from those found in anaerobic organisms. Previous reports indicate that the aerobic pathogen Mycobacterium tuberculosis lacks detectable α-ketoglutarate (KG) dehydrogenase activity and drives a variant TCA cycle in which succinyl-CoA is replaced by succinic semialdehyde. Here, we show that M. tuberculosis expresses a CoA-dependent KG dehydrogenase activity, albeit one that is typically found in anaerobic bacteria. Unlike most enzymes of this family, the M. tuberculosis KG: ferredoxin oxidoreductase (KOR) is extremely stable under aerobic conditions. This activity is absent in a mutant strain deleted for genes encoding a previously uncharacterized oxidoreductase, and this strain is impaired for aerobic growth in the absence of sufficient amounts of CO2. Interestingly, inhibition of the glyoxylate shunt or exclusion of exogenous fatty acids alleviates this growth defect, indicating the presence of an alternate pathway that operates in the absence of β-oxidation. Simultaneous disruption of KOR and the first enzyme of the succinic semialdehyde pathway (KG decarboxylase; KGD) results in strict dependence upon the glyoxylate shunt for growth, demonstrating that KG decarboxylase is also functional in M. tuberculosis intermediary metabolism. These observations demonstrate that unlike most organisms M. tuberculosis utilizes two distinct TCA pathways from KG, one that functions concurrently with β-oxidation (KOR-dependent), and one that functions in the absence of β-oxidation (KGD-dependent). As these pathways are regulated by metabolic cues, we predict that their differential utilization provides an advantage for growth in different environments within the host
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