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Dagmara Baraniak Piotr Ruszkowski Daniel Baranowski Grzegorz Framski Jerzy Boryski 《Nucleosides, nucleotides & nucleic acids》2013,32(12):980-1005
AbstractTwo series of novel fluorinated nucleosides dimers with an unnatural 1,2,3-triazole linkage were synthesized. The obtained molecules were prepared using “click” chemistry approach based on copper(I) catalyzed Huisgen azide–alkyne cycloaddition. It was performed between 3′- and 5′-azido-nucleosides as the azide components, and the 3′-O- and 5′-O-propargyl-nucleosides as the alkyne components. Based on analysis of the 3JHH, 3JH1′C2 and 3JH1′C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. All described nucleosides dimers analogs were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7). 相似文献
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Lawrence Livermore National Laboratory (LLNL) uses a cost-effective sampling (CES) methodology to evaluate and review ground water contaminant data and optimize the site's ground water monitoring plan. The CES methodology is part of LLNL's regulatory approved compliance monitoring plan (Lamarre et al., 1996). It allows LLNL to adjust the ground water sampling plan every quarter in response to changing conditions at the site. Since the use of the CES methodology has been approved by the appropriate regulatory agencies, such adjustments do not need additional regulatory approval. This permits LLNL to respond more quickly to changing conditions. The CES methodology bases the sampling frequency for each location on trend, variability, and magnitude statistics describing the contaminants at that location, and on the input of the technical staff (hydrologists, chemists, statisticians, and project leaders). After initial setup is complete, each application of CES takes only a few days for as many as 400 wells. Effective use of the CES methodology requires sufficient data, an understanding of contaminant transport at the site, and an adequate number of monitoring wells downgradient of the contamination. The initial implementation of CES at LLNL in 1992 produced a 40% reduction in the required number of annual routine ground water samples at LLNL. This has saved LLNL $390,000 annually in sampling, analysis, and data management costs. 相似文献
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《Nucleosides, nucleotides & nucleic acids》2013,32(3):229-241
The Divakar-Reese procedure has been successfully applied for transforming 7-oxo-isothiazolo[4,5-d]pyrimidine C-nucleosides (4a,b, 5a,b, 6a) via 1,2,4-triazol-1-yl intermediates (7a,b, 8a,b) into various 7-substituted C-nucle- osides 15a,b, 16a,b, 17a, 18a, 19a,b, 20a,b; their subsequent deprotection provides novel types of unusual C-glycosides 22b, 23a, 24a,b, 25b, 26b. C-Nucleosides, possessing on its heterocyclic base other than naturally occuring oxo- or amino substituents, are important model compounds for biological or medicinal studies [2a], [2b], [2c], [2d], [2e], [2f], [2g], [2h], [2i] [3a], [3b], [3c], [3d], [3e], [3f], [3g], [3h]. We want to report on the synthesis of novel 7-substituted isothiazolo = [4,5-d]pyrimidine C-nucleosides. As we could show in previous papers [1], [4], there exists a simple approach to the protected C-glycosides 4–6. 相似文献
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Ilya V. Buynevich 《Ichnos》2013,20(4):189-191
Recognition and sampling of traces in unconsolidated sands present a major challenge for ichnologists. This can be partially remedied through the application of high-resolution geophysical techniques, such as ground-penetrating radar (GPR or georadar), which uses electromagnetic impulse for continuous imaging of shallow subsurface. It addition to geological applications, GPR imaging has been used in several studies focused on animal traces as related to conservation of endangered fossorial species (Kinlaw et al., 2007; Martin et al., 2011), slope and levee stability (Nichol et al., 2003; Di Prinzio et al., 2010), and mapping of fossil tracks (Matthews et al., 2006; Aucoin and Hasbargen, 2010) and tracking surfaces (Webb, 2007). Few efforts have been dedicated specifically to characterizing burrow and track characteristics (Stott, 1996; Sensors & Software Inc., 2010 [compilation on geophysical projects related to animal burrows]; Buynevich and Hasiotis, 2011; Buynevich et al., 2011; Martin et al., 2011) and most of the above studies are published in journals not routinely accessed by ichnologists. 相似文献
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Shraddha Thakkar Nisha Nanaware-Kharade Guillermo Gonzalez III Reha Celikel Eric Peterson 《Journal of biomolecular structure & dynamics》2013,31(1):112-113
Methamphetamine (METH) abuse is a major threat in the USA and worldwide without any FDA approved medications. Anti-METH antibody antagonists block or slow the rate of METH entry into the brain and have shown efficacy in preclinical studies (Peterson, Laurenzana, Atchley, Hendrickson, & Owens, 2008).?A key determinant of the antibody’s efficacy is its affinity for METH and we attempted to enhance the efficacy by designing mutations to alter the shape or the electrostatic character of the binding pocket. Towards this goal, we developed a single chain anti-METH antibody fragment (scFv6H4) from a parent IgG (1). The crystal structure of scFv-6H4 in complex with METH was determined (Celikel, Peterson, Owens, & Varughese, 2009). Based on its elucidated binding interactions, we designed point mutations in the binding pocket to improve its affinity for METH and amphetamine (AMP), the active metabolite of METH. The mutants, scFv-S93T,-I37?M and -Y34?M were cloned, expressed in yeast and tested for affinity against METH and AMP. Two mutants showed enhanced binding affinity for METH: scFv-I37?M by 1.3-fold and scFv-S93T by 2.6-fold. Additionally, all the mutants showed increase in affinity for AMP: scFv-I37?M by 56-fold, scFv-S93T by 17-fold and scFvY34?M by 5-fold. Crystal structure for one of the high-affinity mutant, scFv-S93T, in complex with METH was determined (Figure 1). Binding pocket of the mutant is more hydrophobic in comparison with the wild type. ScFv-6H4 binds METH in a deep pocket containing two water molecules. The substitution of a serine residue by a threonine leads to the expulsion of a water molecule (Figure 2), relieving some unfavorable contacts between the hydrocarbon atoms of METH and the water molecule and increasing the affinity to sub-nanomolar range. Therefore, the present study shows that efficacy could be enhanced by altering the hydrophobicity or the shape of the binding pocket. 相似文献
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We investigated the morphology, morphogenesis and small subunit rRNA gene-based phylogeny of three marine urostylids, Uncinata gigantea Bullington, 1940, Holosticha heterofoissneri Hu & Song, 2001, and Holosticha cf. heterofoissneri. The dorsal morphogenesis of Uncinata gigantea shows de novo formation of two groups of anlagen near the marginal rows. Holosticha cf. heterofoissneri demonstrates fragmentation of the first dorsal kinety anlage as in Holosticha heterofoissneri. Our population of H. heterofoissneri corresponds well with previously described populations in terms of its general morphology and ciliary pattern. Uncinata gigantea can be recognized by its large and highly contractile body, yellowish to brownish cell colour, two types of cortical granules, and 20–30 transversely oriented and densely arranged cirri in the left marginal row, which often overlie the buccal vertex. Based on the new data, especially infraciliature, the genus Uncinata is here redefined. Both the morphology and phylogenetic analyses suggest that the genus Uncinata should be classified within the family Urostylidae. In addition, both morphological and morphogenetic data suggest that Holosticha bradburyae Gong et al., 2001 should be transferred to Uncinata as U. bradburyae (Gong et al., 2001) comb. nov., due to its possession of a characteristically prominent beak-like, leftwards curved projection and the developmental mode of the dorsal kineties. This assignment is supported by the phylogenetic analyses, which placed Uncinata gigantea in a clade with U. bradburyae (Gong et al., 2001) comb. nov., and revealed only 1.13% (19 bp) difference in their SSU-rDNA gene sequence. 相似文献
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Srinivas Gopu Vuradi Ravi kumar Kotha Laxma Reddy Putta Venkat Reddy 《Nucleosides, nucleotides & nucleic acids》2019,38(5):349-373
A novel ligand BOPIP (BOPIP?=?{2-(4-(benzyloxy)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline}) and its mononuclear Ru(II) polypyridyl complexes [Ru(phen)2 BOPIP]2+(1) (phen?=?1,10-Phenanthrolene), [Ru(bpy)2 BOPIP]2+(2) (bpy?=?2,2′ bipyridyl), [Ru(dmb)2 BOPIP]2+(3) (dmb?=?4, 4′ -dimethyl 2, 2′ -bipyridine), [Ru(Hdpa)2 BOPIP]2+(4) (Hdpa?=?2,2′dipyridylamine) have been synthesized successfully and characterized by elemental analysis, UV-vis, IR, 1H, 13C-NMR, and ESI-MS Spectroscopy. The interaction of these complexes with CT-DNA was studied using absorption, emission techniques, viscosity measurements and molecular docking studies. The docking study also supports the binding ability of complexes obtained through the absorption and emission techniques. These studies reveal that the Four Ru(II) polypyridyl complexes bind to DNA predominantly by intercalation. The Antimicrobial activity and cytotoxicity of these complexes are also reported. 相似文献
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of motor neurons leading to paralysis and death between 3–5?years of diagnosis. Through whole genome association studies, several single nucleotide polymorphisms (SNPs) encoding missense mutations in angiogenin (ANG) protein have been identified as one of the primary factors causing ALS. Structural studies of ANG show that catalytic triad comprising His13, Lys40, and His114 residues imparts ribonucleolytic activity while nuclear localization signal residues 31RRR33 are responsible for nuclear translocation activity. Loss of either ribonucleolytic activity or nuclear translocation activity or both of these functions due to mutations cause ALS. However, the mechanisms of loss-of-functions of ANG mutants are not completely understood. Here, we present a cohesive and comprehensive picture of functional loss mechanisms of all known ALS-associated ANG mutants by extensive molecular dynamics (MD) simulations (Padhi, Kumar, Vasaikar, Jayaram, & Gomes, 2012; AK, 2013). Our studies show that conformational switching of catalytic residue His114 is responsible for the loss of ribonucleolytic activity while reduction in solvent-accessible surface area (SASA) of 31RRR33 as a result of local folding is responsible for the loss of nuclear translocation activity (Padhi et al., 2012; AK, 2013). Our prediction of loss-of-functions of 17 ANG mutants correlated positively with the reported experimental results. We have subsequently developed a fast molecular dynamics method based on certain global attributes / dynamic markers that can be used to determine whether a mutation is deleterious or benign. To make our method accessible to researchers and clinicians, we created a web server-based tool, ANGDelMut, freely available at http://bioschool.iitd.ernet.in/research.htm, where a user can submit new mutations to ascertain whether they cause ALS. We hope that our method will benefit the community at large and will pave the way for the development of a successful therapy for patients suffering from ALS. 相似文献
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Zlatko Janeba Noha Maklad Morris J. Robins 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1729-1743
Copper(I)-catalyzed 5-endo-dig cyclizations of 5-(alkyn-1-yl)uracil derivatives had given poor yields of substituted furo[2, 3]pyrimidin-2-ones unless the uracil ring was substituted at N1 with alkyl or glycosyl groups. This limited flexibility for the synthesis of analogues with varied substituents at N3 and/or C6 of the furo[2, 3]pyrimidin-2-one core has been overcome with 5-(3-hydroxyalkyn-1-yl)uracil compounds with no substituent at N1. Manipulation of the side-chain hydroxyl group gives access to additional furo[2,3-d]pyrimidin-2-one analogues. 相似文献
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《Biodemography and social biology》2013,59(1):42-66
Recent adaptationist accounts of human mental and physical health have reinvigorated the debate over the evolution of human intelligence. In the tradition of strong inference the current study was developed to determine whether either Miller's (1998, 2000a) Fitness Indicator Theory or Rushton's (1985, 2000) Differential-K Theory better accounts for general intelligence (“g”) in an undergraduate university population (N = 192). Owing to the lengthy administration time of the test materials, a newly developed 18-item short form of the Ravens Advanced Progressive Matrices (APM-18; Sefcek, Miller, and Figueredo 2007) was used. A significant, positive relationship between K and F (r = .31, p < .001) emerged. Contrary to predictions, no significant relationships were found between “g” and either K or F (r = –.09, p ≥ .05 and r = .11, p ≥ .05, respectively). Though generally contrary to both hypotheses, these results may be explained in relation to antagonistic pleiotropy and a potential failure to derive correct predictions for within-species comparisons directly from the results of between-species comparisons. 相似文献
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The natural remobilization of an initially static mixed dense non-aqueous phase liquid (DNAPL) pool due to dissolution was demonstrated by (Roy et al. 2002, 2004) using a compositional mathematical model and laboratory experiments with open pools over a porous medium. The purposes of this study were to: a) demonstrate natural remobilization for a pool within porous media (as opposed to an open pool); and b) analyze the capillary effects associated with residual formation, a changing saturation profile, hysteresis, and aging, as these processes may reduce the potential for natural remobilization of pools in porous media. DNAPL pools comprised of tetrachloroethene and benzene were created within a zone of larger glass beads overlying smaller glass beads, in a water-saturated 2-D flow cell. In one case, remobilization occurred in the form of a DNAPL finger, after 56 days of flushing. In another case, no remobilization had occurred after 64 days of flushing, though the density increased by 430 kg m ?3 and remobilization was predicted by the compositional model. Comparison of observations with model predictions suggest that contact angle hysteresis, related to an observed change in wettability, was the most significant contributing factor causing overprediction of the potential for natural remobilization. 相似文献
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Sivajini Gilchrist Alexander Gates Evert Elzinga Matthew Gorring Zoltan Szabo 《Soil & Sediment Contamination》2011,20(1):54-74
The abandoned Phillips sulfide mine in the critical Highlands watershed in New York has been shown to produce strongly acidic mine drainage (AMD) with anomalous metal contaminants in first-order streams that exceeded local water standards by up to several orders of magnitude (Gilchrist et al., 2009). The metal-sulfide-rich tailings also produce contaminated soils with pH < 4, organic matter < 2.5% and trace metals sequestered in soil oxides. A geochemical transect to test worst-case soil contamination showed that Cr, Co and Ni correlated positively with Mn, (r = 0.72, r = 0.89, r = 0.80, respectively), suggesting Mn-oxide sequestration and that Cu and Pb correlated with Fe (r = 0.76, r = 0.83, respectively), suggesting sequestration in goethite. Ubiquitous, yellow coating on the mine wastes, including jarosite and goethite, is a carrier of the metals. Geochemical and μ-SXRF analyses determined Cu to be the major soil contaminant. μ-SXRF also demonstrated that the heterogeneous nature of the soil chemistry at the micro-meter scale is self-similar to those in the bulk soil samples. Generally metals decreased, with some fluctuations, rapidly downslope through suspension of fines and dissolution in AMD leaving the area of substantial contamination << 0.5 km from the source. 相似文献
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Cajus Diedrich 《Ichnos》2013,20(3-4):215-228
This article examines the high-resolution track horizon stratigraphy at the outcrop Obernkirchen. Massive sandstones, products of marine sand bar and fluviatile environments are present at the tracksite. Recently two track beds were examined in the outcrop. One new track slab of the lower track bed is described exposing well-preserved quadrupedal iguanodontid tracktypes of Iguanodontipus Sarjeant, Delair, and Lockley, 1998, and bipedal theropod tracks Megalosauropus Kaever and Lapparent, 1974. The ichnogenus Iguanodontipus is discussed and the diagnosis extended. The tracksite Obernkirchen belongs to a megatracksite of the ancient coastline of the marginal marine Hercynic Basin of the Lower Cretaceous of Europe, including the four well-known sites Obernkirchen, Bad Rehburg, Münchehagen, and Bückeburg of Northwest Germany. Three different tracktypes of huge sauropods, theropods, and ornithopods are abundant at basal Lower Cretaceous siliciclastic coastlines in different regions in Spain, Portugal, England, Germany, and Switzerland. Dinosaur tracks are also present in carbonate platform environments of northern Italy and Istria. 相似文献
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《Journal of biological dynamics》2013,7(2):117-130
We address several conjectures raised in Cantrell et al. [Evolution of dispersal and ideal free distribution, Math. Biosci. Eng. 7 (2010), pp. 17–36 [9]] concerning the dynamics of a diffusion–advection–competition model for two competing species. A conditional dispersal strategy, which results in the ideal free distribution of a single population at equilibrium, was found in Cantrell et al. [9]. It was shown in [9] that this special dispersal strategy is a local evolutionarily stable strategy (ESS) when the random diffusion rates of the two species are equal, and here we show that it is a global ESS for arbitrary random diffusion rates. The conditions in [9] for the coexistence of two species are substantially improved. Finally, we show that this special dispersal strategy is not globally convergent stable for certain resource functions, in contrast with the result from [9], which roughly says that this dispersal strategy is globally convergent stable for any monotone resource function. 相似文献
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An automated, iterative approach to finding the lowest energy, ionic diffusion paths through a periodic structure has been developed within our new code (written in FORTRAN 77 and named Bubble). The approach is quite general in that it can be applied to find, at a chosen temperature, the accessible (ergodic) regions of a hyper-surface, which is defined across a uniform grid [1]. We describe both our implementation within the Bubble code and its application to locating the approximate transition states for Mg interstitial diffusion in forsterite, which can then be refined using standard transition state searching [2]. 相似文献
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Two new sites with mammalian footprints in the early Oligocene of southeastern France are described here. They represent one of the best preserved and more numerous record of tracks and trackways in the world with more than 320 ichnites. Many of those are arranged in trackways and sometimes show pes-manus impressions, a quite rare feature in mammalian ichnology. The ichnotaxonomic study indicates the presence of perissodactyls tracks referred to as Rhinoceripeda voconcense (Demathieu et al., 1984), artiodactyls footprints referred to as Megapecoripeda velox (Demathieu et al., 1984) and a carnivore footprint referred to as Bestiopeda sp. Vialov (1966). They can be attributed to early Rhinocerotids, Lophiomerycids and/or Entelodonts and Mustelid-like carnivore, respectively. This study also aims at homogenizing the ichnotaxonomy used for mammal tracks where several genera were erected without a full review of the literature. All this taken together reveals a rich mammalian ichnofauna at a time period when no other fossils of mammals are known in the area and represents a good opportunity to provide state-of-the-art concerning the worldwide known sites that yielded mammalian footprints. 相似文献
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This paper contains a taxonomic study of the Permian tetrapod ichnofauna from the Carapacha Basin. Tetrapod traces are analyzed in their environmental context and compared with similar faunas from Europe and North America. This ichnofauna is particularly relevant because of the scarcity of Permian tetrapod tracks from South America and also of Permian tetrapod fossils from Argentina. Ephemeral fluvial and shallow lacustrine deposits compose the sedimentary succession of the basin, which is represented by the Carapacha Formation. Most of the tracks have been collected from the upper member of the formation (Urre-Lauquen Member), mainly from freshwater ephemeral lake deposits as well as from playa-lake mudflats. The deposits of this member have been attributed to the early Late Permian on the basis of a Glossopteris fossil flora. Ichnotaxonomic designations of tetrapod traces are made on the basis of morphologic features that reflect the anatomy of the producer and special attention has been paid to extramorphologic deformations observed in the track assemblage. A total of four footprint ichnotaxa have been recognized, namely Batrachichnus salamandroides (Geinitz, 1861), Hyloidichnus bifurcatus Gilmore, 1927, cf. Amphisauropus isp. and cf. Varanopus isp. These track taxa are associated with two forms of vertebrate swimming traces (Characichnos isp. and type A swimming trace) and a possible fish trail. Invertebrate trace fossils include abundant arthropod locomotion traces and Scoyenia isp. The ichnofauna is composed of six tetrapod ichnocoenoses that are dominated by tiny amphibian tracks attributed to Temnospondyli (Batrachichnus and type A swimming trace) and Seymouriamorpha (Amphisauropus), and also contain the footprints of small reptiles, mostly Captorhinomorpha and possibly Pelycosauria (Hyloidichnus and Varanopus). Even if the ichnofauna of the Carapacha Basin is slightly younger than typical examples from the literature of the Early Permian “red bed ichnofacies” (Hunt et al., 1995b), a comparison is made. However, further detailed case studies are needed to formally define this “red bed ichnofacies” and its prospective subdivisions. 相似文献
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ABSTRACT One proven strategy to help students make sense of abstract concepts is to sequence instruction so students have exploratory opportunities to investigate science before being introduced to new science explanations (Abraham and Renner 1986; Renner, Abraham, and Birnie 1988). To help physical science teachers make sense of how to effectively sequence lessons, this article summarizes our experiences using an exploration–explanation sequence of instruction to teach Bernoulli's principle to prospective middle and secondary science teachers in a science methods course. We use demonstrations during our Bernoulli unit to help students go back and forth between their observations of phenomenon and what occurs on the microscopic level with what we have termed molecular talk. Students engage in guiding questions, consider their old and new understandings of science, and use evidence to construct new ideas during all stages of the lesson. 相似文献