bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitors of human indoleamine 2,3‐dioxygenase identified with a target‐based screen in yeast
Authors: Vottero Eduardo , Balgi Aruna , Woods Kate , Tugendreich Stuart , Melese Teri , Andersen Raymond J. , Mauk A. Grant , Roberge Michel 
Published: February 2006

AbstractIndoleamine 2,3‐dioxygenase (IDO) is a tryptophan degradation enzyme that is emerging as an important drug target. IDO is expressed by many human tumors to help them escape immune detection, and it has been implicated in depression and in the formation of senile nuclear cataracts. There is a need for potent and selective IDO inhibitors for use in research and as lead compounds for drug development. We show that expression of human IDO in a Saccharomyces cerevisiae tryptophan auxotroph restricts yeast growth in the presence of low tryptophan concentrations and that inhibition of IDO activity can restore growth. We use this assay to screen for IDO inhibitors in collections of pure chemicals and crude natural extracts. We identify NSC 401366 (imidodicarbonimidic diamide, N‐methyl‐N"‐9‐phenanthrenyl‐, monohydrochloride) as a potent nonindolic IDO inhibitor (Ki=1.5 ± 0.2 μM) that is competitive with respect to tryptophan. We also use this assay to identify the active compound caulerpin from a crude algal extract. The yeast growth restoration assay is simple and inexpensive. It combines desirable attributes of cell‐ and target‐based screens and is an attractive tool for chemical biology and drug screening.
Ligand‐Template Directed Assembly: An Efficient Approach for the Supramolecular Encapsulation of Transition‐Metal Catalysts
Authors: Kleij Arjan W. , Reek Joost N. H. 
Published: February 2006

AbstractSupramolecular encapsulation of small guest molecules inside well‐defined cavities of molecular capsules has witnessed broad attention because of the unusual behaviour of these systems. The molecular capsules generally consist of rigid complementary building blocks that are held together by multiple, complementary non‐covalent interactions. Interestingly, it has been shown that chemical transformations can take place inside these capsules and in some examples the reaction is accelerated, while in other cases otherwise instable intermediates could be isolated in the capsulated form. Many reactions of interest require a transition‐metal (TM) catalyst, and the creation of new capsules in which such catalysts are implemented within the structure is thus required for the development of resourceful type of catalyst systems for these processes. In this concept article we will discuss new strategies to arrive at such systems, with a focus on a ligand‐templated approach. In this approach, multifunctional ligands are used as templates for the encapsulation process by supramolecular building blocks and concomitantly for the formation of TM complexes that are active in catalytic processes. The obtained encapsulated transition‐metal catalysts show unusual reactivity and selectivity behaviour that will be discussed in detail.
Slater‐Like Model for Carbon 1s Core Ionization Energies of Halomethanes
Authors: Cao Chenzhong 
Published: February 2006

AbstractBased on the atomic electron affinity EA, the average energy of the valence‐shell electrons EI and the polarizability α, the charge effect and the relaxation effect were evaluated for the carbon 1s core ionization energies of halomethanes CHnY4−n−mZm (Y, Z=F, Cl, Br, I). The charge effect was scaled by the electronegativity discrepancy (the discrepancy of EA and the discrepancy of EI between the C and H or halogen atom in the CH or Chalogen chemical bond). The relaxation effect (induced dipole) was scaled by the charge on the carbon atom together with the polarizability of the H and halogen atoms. Further, the electrostatic relaxation shielding ΔSi of the carbon 1s electron in the halomethane was expressed by the charge effect together with the relaxation effect. By introducing ΔSi into the Slater model, a Slater‐like model was obtained for calculating the carbon 1s core ionization energy E1,C of halomethane, whose correlation coefficient r is 0.99985 and the average absolute error is only 0.041 eV between the calculated and the experimental carbon 1s core ionization energies for 27 halomethanes. Also the cross‐correlation was tested by the leave‐one‐out (LOO) cross‐validation method, and the obtained model has good predictive ability and stability (the correlation coefficient rcv is 0.99976, the average absolute error between the predicted and the experimental values is only 0.052 eV). The proposed model perhaps lays a good foundation for computing the core ionization energies of various atoms in more complex molecules.
Novel Insights into the Mechanism of the Ortho/Para Spin Conversion of Hydrogen Pairs: Implications for Catalysis and Interstellar Water
Authors: Limbach Hans‐Heinrich , Buntkowsky Gerd , Matthes Jochen , Gründemann Stefan , Pery Tal , Walaszek Bernadeta , Chaudret Bruno 
Published: February 2006

AbstractThe phenomenon of exchange coupling is taken into account in the description of the magnetic nuclear spin conversion between bound ortho‐ and para‐dihydrogen. This conversion occurs without bond breaking, in contrast to the chemical spin conversion. It is shown that the exchange coupling needs to be reduced so that the corresponding exchange barrier can increase and the given magnetic interaction can effectively induce a spin conversion. The implications for related molecules such as water are discussed. For ice, a dipolar magnetic conversion and for liquid water a chemical conversion are predicted to occur within the millisecond timescale. It follows that a separation of water into its spin isomers, as proposed by Tikhonov and Volkov (Science 2002, 296, 2363), is not feasible. Nuclear spin temperatures of water vapor in comets, which are smaller than the gas‐phase equilibrium temperatures, are proposed to be diagnostic for the temperature of the ice or the dust surface from which the water was released.
Nine fluorescence parameter analysis on a four‐color fluorescence activated flow cytometer
Authors: Frischmann Ursula , Müller Werner 
Published: February 2006

AbstractBackgroundIn many cases a frequent monitoring of blood is important, e.g. during an infection. Often the availability of blood is the limiting factor.Methods50 μl blood were stained and analyzed using a standard four‐color cytometer. Percentages of leukocytes were calculated by FlowJo software.ResultsOur protocol allows the differentiation of B cells, T cells, NK cells, neutrophils, and monocytes/macrophages in small volumes of blood.ConclusionsUsing nine fluorochrome‐labeled antibodies and a specific gating strategy we were able to differentiate the main immune cells in minute amounts using one staining step. © 2006 International Society for Analytical Cytology
Analysis and visualization of cell movement in the developing zebrafish brain
Authors: Langenberg Tobias , Dracz Tadeusz , Oates Andrew C. , Heisenberg Carl‐Philip , Brand Michael 
Published: February 2006

AbstractDetailed reconstruction of the spatiotemporal history of embryonic cells is key to understanding tissue formation processes but is often complicated by the large number of cells involved, particularly so in vertebrates. Through a combination of high‐resolution time‐lapse lineage tracing and antibody staining, we have analyzed the movement of mesencephalic and metencephalic cell populations in the early zebrafish embryo. To facilitate the analysis of our cell tracking data, we have created TracePilot, a software tool that allows interactive manipulation and visualization of tracking data. We demonstrate its utility by showing novel visualizations of cell movement in the developing zebrafish brain. TracePilot (http://www.mpi‐cbg.de/tracepilot) is Java‐based, available free of charge, and has a program structure that allows the incorporation of additional analysis tools. Developmental Dynamics 235:928–933, 2006. © 2006 Wiley‐Liss, Inc.
Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio
Authors: Reugels Alexander M. , Boggetti Barbara , Scheer Nico , Campos‐Ortega José A. 
Published: February 2006

AbstractIn the neural plate and tube of the zebrafish embryo, cells divide with their mitotic spindles oriented parallel to the plane of the neuroepithelium, whilst in the neural keel and rod, the spindle is oriented perpendicular to it. This change is achieved by a 90° rotation of the mitotic spindle. We cloned zebrafish homologues of the gene for the Drosophila cell fate determinant Numb, and analyzed the localization of EGFP fusion proteins in vivo in dividing neuroepithelial cells during neurulation. Whereas Numb isoform 3 and the related protein Numblike are localized in the cytoplasm, Numb isoform 1 is localized to the cell membrane. Time‐lapse analyses showed that Numb 1 is distributed uniformly around the cell cortex in dividing cells during plate and keel stages, but becomes localized at the basolateral membrane of some dividing cells during the transition from neural rod to tube. Using in vitro mutagenesis and Numb:EGFP deletion constructs, we showed that the first 196 amino acids of Numb are sufficient for this localization. Furthermore, we found that an 11–amino acid insertion in the PTB domain is essential for localization to the cortex, whereas amino acids 2–12 mediate the basolateral localization in the neural tube stage. Developmental Dynamics 235:934–948, 2006. © 2006 Wiley‐Liss, Inc.
Vertebrate rel proteins exhibit dorsal‐like activities in early Drosophila embryogenesis
Authors: Prothmann Christian , Armstrong Neil J. , Roth Siegfried , Rupp Ralph A.W. 
Published: February 2006

AbstractIn Drosophila, the Toll/Dorsal pathway triggers the nuclear entry of the Rel protein Dorsal, which controls dorsoventral patterning in early embryogenesis and plays an important role in innate immunity of the adult fly. In vertebrates, the homologous Toll/IL‐1 receptor signaling pathway directs the nuclear localization of Rel/NF‐κB complexes, which activate genes involved in proliferation, apoptosis, and immune response. Recently, first evidence has been reported for the activity of vertebrate Rel proteins and a Toll‐like signaling pathway in the dorsoventral patterning process of Xenopus laevis embryos. Given the evolutionary divergence of the fly and frog model organisms, these findings raise the question, to what extent the effector functions of this pathway have been conserved? Here, we report the ability of two Xenopus Rel proteins to partially substitute for several, but not all, functions of the Dorsal protein in Drosophila embryos. Our results suggest the interaction between Rel proteins and their cytoplasmic inhibitors as an important interface of evolutionary adaptation. Developmental Dynamics 235:949–957, 2006. © 2006 Wiley‐Liss, Inc.
Comparative ontogeny and phylogeny of the upper jaw skeleton in amniotes
Authors: Richman Joy M. , Buchtová Marcela , Boughner Julia C. 
Published: February 2006

AbstractThe morphology, position, and presence of the upper jaw bones vary greatly across amniote taxa. In this review, we compare the development and anatomy of upper jaw bones from the three living amniote groups: reptiles, birds, and mammals. The study of reptiles is particularly important as comparatively little is known about the embryogenesis of the jaw in this group. Our review covers the ontogeny and phylogeny of membranous bones in the face. The aim is to identify conserved embryonic processes that may exist among the three major amniote groups. Finally, we discuss how temporal and spatial regulation of preosseous condensations and ossification centers can lead to variation in the morphology of amniote upper jaw bones. Developmental Dynamics 235:1230–1243, 2006. © 2006 Wiley‐Liss, Inc.
Synthesis and Metallation of the Diphosphanylsilane iPr2Si(PHMe)2
Authors: von Hänisch Carsten , Rubner Oliver 
Published: February 2006

AbstractThe reaction of [LiAl(PHMe)4] with iPr2SiCl2 yields the dialkyldiphosphanylsilane iPr2Si(PHMe)2 (1). This compound is formed as a diastereomeric mixture and was identified by NMR spectroscopy and mass spectrometry. Silane 1 reacts with [Sn{N(SiMe3)2}2] and [Zn{N(SiMe3)2}2] to form the polycyclic compounds [Sn{SnN(SiMe3)2}2{iPr2Si(PMe)2}2] (2) and [{ZnN(SiMe3)2}3{iPr2Si(PMe)2}2H] (3), respectively. The tricyclic compound 2 possesses one Sn–Sn bond and contains tin atoms in the formal oxidation states +1, +2 and +3. The central structural motif of the zinc–phosphorus cluster 3 is a Zn3P4Si2 cage. The compounds [iPr2Si{P(Me)MEt2}2]2 (4: M = Al; 5: M = Ga), which feature an adamantane‐like cage formed by four metal, four phosphorus and two silicon atoms can be obtained by the reaction of 1 with MEt3 (M = Al, Ga). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis and Molecular Structure of [Cp*Ta(Ph)(P6Ph5)]: A Terminal Phosphinidene Complex of the (P6Ph5)3– Ligand (Cp* = C5Me5)
Authors: Wolf Robert , Hey‐Hawkins Evamarie 
Published: February 2006

AbstractThe terminal phosphanyl phosphinidene complex [Cp*Ta(Ph)(P6Ph5)] (2) has been isolated in 16 % yield from the reaction of [Cp*TaCl4] with 2 equiv. Na2(P4Ph4) and displays an η4‐bound (P6Ph5)3– ligand according to X‐ray crystallography and 31P NMR spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A power function model for the basic geometry of solution dolines: considerations from the classical karst of south‐central Slovenia
Authors: Šušteršič France 
Published: February 2006

AbstractSolution doline geometry is generally too complex to be expressed in terms of a few parameters. A methodology previously designed by the author, based on acquisition of specific field data and subsequent processing by various Fourier techniques, enabled doline geometry to be considered in its entirety. This paper sets out to investigate which simple rotational body (rotated power function) best fits the geometry of 38 dolines studied within the Classical Karst of Slovenia. It transpires that doline radius to depth ratio changes as a function of volume, whereas the mode of change remains stable regardless of the actual dimensions of individual dolines, and is basically the same at different locations. Doline volumes are very close of those of regular cones of the same dimensions, growing relatively deeper as the volume increases. Two poly‐segment models implied by the power function model and based on earlier work are discussed. It transpires that the studied dolines may be relict forms superimposed upon pre‐existing hidden shafts formed by epikarstic water. Copyright © 2006 John Wiley & Sons, Ltd.
Planform dynamics of the Lower Mississippi River
Authors: Harmar Oliver P. , Clifford Nicholas J. 
Published: February 2006

AbstractThis paper presents an analysis of the planform behaviour of the Lower Mississippi River (LMR) using a series of maps and hydrographic surveys covering the period 1765–1975. Data allow analysis at various time and space scales, using fixed and statistically defined reaches, both before and after extensive channel modification. Previous research has interpreted planform change in relation to geomorphological or engineering regime‐type analyses of channel length and width for the LMR as a ‘single system’. The analysis here is broadly consistent with these approaches, but highlights the importance of meander geometry, in the form of the radius of curvature:width ratio. This neglected factor helps resolve paradoxes relating to observed changes in sediment transport and channel stability. When viewed over smaller time and space scales, analysis of dynamics using fixed reach boundaries reveals a downstream trend in the pattern of planform behaviour, which is closely related to the distribution of valley floor deposits, and which also reflects neotectonic influences. Analysis of changes using statistically determined reach boundaries shows that, over shorter time scales, meander trains are continually formed and modified over a period of approximately 120 years. Zones of more‐or‐less dynamic behaviour thus move through the LMR. The research also provides a context for 20th century engineering interventions to the river. These have constrained the magnitude of planform adjustment, but also altered the kind of response that is now possible in relation to changes in discharge and sediment load, and as a consequence of internal feedbacks within the LMR system. Copyright © 2006 John Wiley & Sons, Ltd.
The impact of different gridding methods on catchment geomorphology and soil erosion over long timescales using a landscape evolution model
Authors: Hancock G. R. 
Published: February 2006

AbstractMany digital elevation models are gridded from irregularly spaced data. This study examines differences in catchment geomorphology and hydrology as a result of kriging and Delaunay triangulation gridding methods. Both methods have been widely used as tools for placing irregularly spaced data onto a regular grid. In the past, numerical modelling has been performed with little assessment of model input variability and the variability produced by different gridding methods has not been fully assessed. Given the importance of the impact of digital elevation model error and potential impact on model output, little work has been done to understand the impact of this type of potential error. Examination of the different catchment realizations demonstrates that when using kriging (point or block) or Delaunay triangulation there are subtle differences in catchment area and elevation as well as networking properties. Subtle differences also exist in hillslope profile. Nevertheless, when comparing catchment descriptors such as the hypsometric curve, area–slope relationship and cumulative area distribution there is little hydrological and geomorphological difference between these catchments. Further, when these digital elevation models are used as landscape input in a long‐term landscape evolution model (i.e. SIBERIA) there is little geomorphological difference or hydrological difference between the two digital elevation models after a 50 000 year modelled period. Consequently either method is appropriate for the study catchment. These findings provide confidence in the conversion of irregularly spaced data onto a regular grid using kriging or Delaunay triangulation and that either method can be used. Copyright © 2006 John Wiley & Sons, Ltd.
Improved association analyses of disease subtypes in case‐parent triads
Authors: Epstein Michael P. , Waldman Irwin D. , Satten Glen A. 
Published: February 2006

AbstractThe sampling of case‐parent triads is an appealing strategy for conducting association analyses of complex diseases. In certain situations, one may have interest in using the triads to identify genetic variants that are associated with a specific subtype of disease, perhaps related to a characteristic cluster of symptoms. A straightforward strategy for conducting such a subtype analysis would be to analyze only those triads with the subtype of interest. While such a strategy is valid, we show that triadswithoutthe subtype of interest can provide additional genetic information that increases power to detect association with the subtype of interest. We incorporate this additional information using a likelihood‐based framework that permits flexible modeling and estimation of allelic effects on disease subtypes and also allows for missing parental data. Using simulated data under a variety of genetic models, we show that our proposed association test consistently outperforms association tests that only analyze triads with the subtype of interest. We also apply our method to a triad study of attention‐deficit hyperactivity disorder and identify a genetic variant in the dopamine transporter gene that is associated with a subtype characterized by extreme levels of both inattentive and hyperactive‐impulsive symptoms.Genet. Epidemiol.2006. © 2006 Wiley‐Liss, Inc.
Genetic association tests based on ranks (GATOR) for quantitative traits with and without censoring
Authors: Allen Andrew S. , Martin Eden R. , Qin Xuejun , Li Yi‐Ju 
Published: February 2006

AbstractLinkage disequilibrium mapping of quantitative traits is a powerful method for dissecting the genetic etiology of complex phenotypes. Quantitative traits, however, often exhibit characteristics that make their use problematic. For example, the distribution of the trait may be censored, highly skewed, or contaminated with outlying values. We propose here a rank‐based framework for deriving tests of gene and trait association that explicitly take censoring into account and are insensitive to skewness and outlying values. Standard methods for mapping quantitative traits do not take these characteristics into account, which leads to the discarding of valuable information or their improper application. We show how this framework can be applied in nuclear families and discuss its implementation in general pedigrees. The power and efficacy of the approach is illustrated through a series of simulation experiments in which the approach is compared to existing methods. Genet. Epidemiol. 2006. © 2006 Wiley‐Liss, Inc.
Estimation and testing of genotype and haplotype effects in case‐control studies: comparison of weighted regression and multiple imputation procedures
Authors: Cordell Heather J. 
Published: February 2006

AbstractA popular approach for testing and estimating genotype and haplotype effects associated with a disease outcome is to conduct a population‐based case/control study, in which haplotypes are not directly observed but may be inferred probabilistically from unphased genotype data. A variety of methods exist to analyse the resulting data while accounting for the uncertainty in haplotype assignment, but most focus on the issue of testing the global null hypothesis that no genotype or haplotype effects exist. A more interesting question, once a region of disease association has been identified, is to estimate the relevant genotypic or haplotypic effects and to perform tests of complex null hypotheses such as the hypothesis that some loci, but not others, are associated with disease. Here I examine the assumptions behind, and the performance of, two classes of methods for addressing this question. The first is a weighted regression approach in which posterior probabilities of haplotype assignments are used as weights in a logistic regression analysis, generating a test based on either a weighted pseudo‐likelihood, or a weighted log‐likelihood. The second is a multiple imputation approach using either an improper procedure in which the posterior probabilities are used to generate replicate imputed data sets, or a proper data augmentation procedure. I compare these approaches to a simple expectation substitution (haplotype trend regression) approach. In simulations, all methods gave unbiased parameter estimation but the weighted pseudo‐likelihood, expectation substitution and multiple imputation methods had superior confidence interval coverage. For the weighted pseudo‐likelihood and expectation substitution methods it was necessary to estimate posterior haplotype assignment probabilities using the combined case/control data, whereas for the multiple imputation approaches it was necessary to estimate these probabilities in the case and control groups separately. Overall, multiple imputation was easiest approach to implement in standard statistical software and to extend to more complex models such as those that include gene‐gene or gene‐environment interactions.Genet. Epidemiol.2006. © 2006 Wiley‐Liss, Inc.