bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rendering Conventional Molecular Fingerprints for Virtual Screening Independent of Molecular Complexity and Size Effects
Authors: Nisius Britta , Bajorath Jürgen 
Published: April 2010

AbstractMolecular complexity and size effects represent a known complication of fingerprint similarity searching and virtual screening that often leads to an increase in false‐positive rates and a decrease in hit rates. In standard fingerprints, differences in the complexity of reference and database molecules lead to different fingerprint bit densities, which negatively affects similarity search calculations, in particular, when fingerprints of reference molecules have higher bit density than corresponding fingerprints of database compounds. In pharmaceutical research, this is the case in many practical virtual screening applications when chemically optimized reference molecules are used. Herein we introduce an intuitive computational method to make standard fingerprints such as structural keys or pharmacophore feature fingerprints independent of molecular complexity and size effects. This is achieved by applying the concept of 'balanced codes' originating in computer science. Following this approach, binary fingerprints are transformed by incorporating the complement of their bit patterns. This straightforward transformation produces fingerprint representations with characteristic bit patterns that have exactly half of their bit positions set on, corresponding to a constant bit density of 50 % for all test compounds, regardless of their complexity and size. In similarity search calculations in the presence of complexity effects of increasing magnitude, transformed structural key and pharmacophore fingerprints display consistently better performance than their unmodified counterparts and recover active compounds in cases where the original fingerprints fail.
SPECT/CT hybrid imaging; with which CT?
Authors: Bach‐Gansmo Tore , Schwarzlmüller Thomas , Jøraholmen Vivi , Salbu Jan , Biermann Martin , Naum Alexandru , Kleven‐Madsen Nina 
Published: April 2010

AbstractAimThe aim of this study is to show the practical use of, and to discuss the rationale for, high‐end computed tomography (CT) integrated with intrinsic low‐resolution single‐photon emission tomography (SPECT).Materials and methodsAll examinations performed on three new SPECT/CT systems with diagnostic CT capabilities were recorded retrospectively. The use of CT was classified as low‐dose, using the CT with restraint as to the tube current and radiation dose, or diagnostic, with an optimum use of the CT, using CT protocols as used in ordinary radiological practice. The number of low‐dose CT was compared with the number of diagnostic CT examinations. The report is based on 436 patient examinations from three hospitals in Norway with recently installed SPECT/CT systems, the time of use varying from 6 months to 2 years. The examinations performed were myocardial perfusion (45%), various tumors (thyroid, parathyroid, neuroendocrine 37%), malignant skeletal disease (12%), brain perfusion (4%), sentinel nodes in breast cancer (1%) and gastrointestinal bleeding (1%).ResultsOf the 436 patients, 431 had a low‐dose CT for attenuation correction, anatomic localisation and, also for diagnosis, whereas five patients had a diagnostic CT. In these series, as was found in recent literature, the diagnostic potential of the CT was seldom used to its capacity and always in predetermined diagnostic situations.ConclusionThere is a low degree of utilization of the diagnostic capabilities of the CT in the SPECT/CT context, for a number of reasons. This raises questions about the cost–benefit of investing in high‐end CT for SPECT/CT applications. Copyright © 2010 John Wiley & Sons, Ltd.
Assessment of tumor angiogenesis: dynamic contrast‐enhanced MRI with paramagnetic nanoparticles compared with Gd‐DTPA in a rabbit Vx‐2 tumor model
Authors: Kassner Andrea , Thornhill Rebecca E. , Liu Fang , Winter Patrick M. , Caruthers Shelton D. , Wickline Samuel A. , Lanza Gregory M. 
Published: April 2010

AbstractThe purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd‐DTPA) using dynamic contrast‐enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12–14 days after Vx‐2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd‐DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (Ki) maps were calculated using a two‐compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The Ki values estimated using PNs were significantly lower than those obtained for Gd‐DTPA (p = 0.018). When PNs and Gd‐DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd‐DTPA data (p = 0.34). The mean Ki for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd‐DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd‐DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis. Copyright © 2010 John Wiley & Sons, Ltd.
The mediation effect of experiential avoidance between coping and psychopathology in chronic pain
Authors: Costa Joana , Pinto‐Gouveia José 
Published: April 2010

AbstractThis study explores experiential avoidance as a mediator in the relationship between coping (rational coping, avoidant coping and detached/ emotional coping) and psychopathology (depression, anxiety and stress). A battery of self‐report questionnaires was used to assess coping, experiential avoidance and depression, anxiety and stress in 70 participants with a chronic pain from Portuguese primary health care units.Regression analyses were performed and showed preliminary evidence supporting the mediation role of experiential avoidance in a Portuguese sample with chronic pain. Results show that experiential avoidance partially or fully mediate the effects of rational coping and detached/emotional coping on depression and stress. Implications for clinical practice were discussed and suggest that psychopathology is not necessary direct product of coping and other processes, such as experiential avoidance, are likely involved. Copyright © 2010 John Wiley & Sons, Ltd.Key Practitioner Message:• Low use of adaptive coping was associated with more psychopathology via differences in psychological (in)flexibility as a general characteristic.• Findings suggest that psychopathology is not necessary direct product of coping and other processes, such as experiential avoidance, are likely involved.• Patients with chronic pain may achieve better psychosocial outcomes they reduce their avoidance and other attempts to control pain, accept it, and direct their efforts toward valued goal.
Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry
Authors: Borowitz Michael J. , Craig Fiona E. , DiGiuseppe Joseph A. , Illingworth Andrea J. , Rosse Wendell , Sutherland D. Robert , Wittwer Carl T. , Richards Stephen J. 
Published: April 2010

AbstractBackground:Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disorder characterized by a somatic mutation in the PIGA gene, leading to a deficiency of proteins linked to the cell membrane via glycophosphatidylinositol (GPI) anchors. While flow cytometry is the method of choice for identifying cells deficient in GPI‐linked proteins and is, therefore, necessary for the diagnosis of PNH, to date there has not been an attempt to standardize the methodology used to identify these cells.Methods:In this document, we present a consensus effort that describes flow cytometric procedures for detecting PNH cells.Results:We discuss clinical indications and offer recommendations on data interpretation and reporting but mostly focus on analytical procedures important for analysis. We distinguish between routine analysis (defined as identifying an abnormal population of 1% or more) and high‐sensitivity analysis (in which as few as 0.01% PNH cells are detected). Antibody panels and gating strategies necessary for both procedures are presented in detail. We discuss methods for assessing PNH populations in both white blood cells and red blood cells and the relative advantages of measuring each. We present steps needed to validate the more elaborate high‐sensitivity techniques, including the need for careful titration of reagents and determination of background rates in normal populations, and discuss technical pitfalls that might affect interpretation.Conclusions:This document should both enable laboratories interested in beginning PNH testing to establish a valid procedure and allow experienced laboratories to improve their techniques. © 2010 Clinical Cytometry Society
Characterization of indoor time reversal UWB communication systems: Spatial, temporal and frequency properties
Authors: Abbasi‐Moghadam Dariush , Vakili Vahid Tabataba 
Published: April 2010

AbstractIn this paper, an indoor UWB communications system that applies time reversal (TR) for transmitting the desired signal is proposed. First we define equivalent channel model of TR‐UWB, which is the convolution of channel impulse response and its complex conjugate time‐reversed version. Then spatial, temporal and frequency characteristics of equivalent channel are analyzed and the analytical or semi‐analytical results are validated by comparing measurements with simulation. (Semi) analytical expression of equivalent channel transfer function, TR UWB power delay profile (PDP), focusing gain, spatial correlation and power azimuth spectrum (PAS) is performed. Also probability density function (PDF) of TR‐UWB amplitude and path‐gain is derived.Analysis and simulation results of different distributions, such as uniform, Laplacian and Gaussian for PAS, are considered and presented. It is shown that uniform and truncated Laplacian distributions are appropriate fits to the measurement results for power azimuth spectrum of TR‐UWB. It is seen that for distances greater than λ/2 from the authorized receiver, received signal decreases 10 dB, where λ is the wavelength of the central frequency. Finally, PDF of TR‐UWB path‐gain is described. Measurement results show that for small time windows, the densities of the path‐gain are highly non‐Gaussian. But for starting time of 10Tw or more, and window size of 2Tw or more the densities are nearly Gaussian, where Tw is the transmitted pulse duration. Copyright © 2010 John Wiley & Sons, Ltd.
CD137 ligand signaling induces human monocyte to dendritic cell differentiation
Authors: Kwajah M. M. Shaqireen , Schwarz Herbert 
Published: April 2010

AbstractThe ligand for CD137 (4‐1BB) is expressed on peripheral human monocytes and delivers a potent activating signal via reverse signaling. Here we show that treatment of monocytes with a recombinant CD137 protein that induces reverse signaling through CD137 ligand reduces typical macrophage characteristics such as phagocytosis, oxidative burst and CD14 expression; however, typical DC characteristics including endocytosis, costimulatory molecule expression and the ability to stimulate proliferation of naïve T cells are induced. CD137‐generated DC do not express DC‐SIGN, CD1a or IL‐12 and secrete less IL‐10 than classical DC. CD137‐generated DC are mature, and addition of LPS+IFN‐γ does not enhance their T‐cell‐stimulatory capacity. This indicates that CD137 as a sole factor is sufficient to induce development to mature DC, making stimulation of CD137 ligand the most simple protocol to generate mature DC. CD137‐generated DC are more potent in inducing T‐cell proliferation than classical DC. They inhibit development of Treg cells but induce T‐cell expression of perforin, IFN‐γ, IL‐13 and IL‐17. These data demonstrate that CD137 as a single factor is sufficient to induce differentiation of peripheral monocytes to mature inflammatory DC that have a more potent T‐cell‐stimulatory capacity than classical DC.
Epidermis‐to‐dermis migration of immature Langerhans cells upon topical irritant exposure is dependent on CCL2 and CCL5
Authors: Ouwehand Krista , Scheper Rik J. , de Gruijl Tanja D. , Gibbs Susan 
Published: April 2010

AbstractSkin irritation is generally not considered to be an immunological event; however, alterations in the density of Langerhans cells (LC) in the epidermis do occur, which is indicative of LC migration. In this study, we investigated the migration of LC out of the epidermis after skin exposure to contact irritants and identified the chemokines involved. With the aid of ex vivo‐intact human skin and epidermal sheets we show that dermal fibroblasts play a role in mediating LC migration towards the dermis. Exposure of ex vivo‐intact human skin to a panel of seven irritants (SDS, salicylic acid, phenol, isopropanol, DMSO, TritonX, or benzalkonium chloride) resulted in decreased numbers of CD1a+ cells in the epidermis and the accumulation of CD1a+ cells in the dermis. In contrast to allergen exposure, neutralizing antibodies to either CXCL12 or CCL19/CCL21 did not inhibit LC migration out of the epidermis. Exposure of epidermal sheets to the prototypical irritant SDS resulted in a TNF‐α‐dependent LC migration towards dermal fibroblasts. This was a result of CCL2/MCP‐1 and CCL5/RANTES chemokine secretion by fibroblasts: injection of CCL2‐ and CCL5‐neutralizing antibodies into intact human skin totally inhibited LC migration into the dermis. We have thus identified a novel role for TNF‐α‐inducible dermis‐derived CCL2 and CCL5 in initiating migration of irritant‐exposed human LC out of the epidermis.
Ligand dimensions are important in controlling NK‐cell responses
Authors: Brzostek Joanna , Chai Jian‐Guo , Gebhardt Friedemann , Busch Dirk H. , Zhao Rui , van der Merwe P. Anton , Gould Keith G. 
Published: April 2010

AbstractSize‐dependent protein segregation at the cell–cell contact interface has been suggested to be critical for regulation of lymphocyte function. We investigated the role of ligand dimensions in regulation of mouse NK‐cell activation and inhibition. Elongated forms of H60a, a mouse NKG2D ligand, were generated and expressed stably in the RMA cell line. RMA cells expressing the normal size H60a were lysed efficiently by both freshly isolated and IL‐2 stimulated C57BL/6 mouse‐derived NK cells; however the level of lysis decreased as the H60a ligand size increased. Importantly, H60a elongation did not affect NKG2D binding, as determined by soluble NKG2D tetramer staining, and by examining NK‐cell target cell conjugate formation. CHO cells are efficient at activating NK cells from C57BL/6 mice, and expression of a single chain form of H‐2Kb, a ligand for the mouse inhibitory receptor Ly49C, strongly inhibited such activation of Ly49C/I positive NK cells. Elongation of H‐2Kb resulted in decreased inhibition of both lysis and IFN‐γ production by NK cells. These results establish that small ligand dimensions are important for both NK‐cell activation and inhibition, and suggest that there are shared features between the mechanisms of receptor triggering on different types of lymphocytes.
The Role of C–H···H–B Interactions in Establishing Rotamer Configurations in Metallabis(dicarbollide) Systems
Authors: Juárez‐Pérez Emilio José , Núñez Rosario , Viñas Clara , Sillanpää Reijo , Teixidor Francesc 
Published: April 2010

AbstractThe aim of this work is to explore the self‐interaction capability of the anion [3,3′‐Co(1,2‐C2B9H11)2]–throughCcluster–H···H–B (Cc–H···H–B) dihydrogen bonds. A set of theoretical and empirical data aiming to establish the main rules that account for the binding mode between the negatively charged borane framework made by [3,3′‐Co(1,2‐C2B9H11)2]–and the [NMe4]+ions have been compiled. The interaction between cation and anion is mainly electrostatic but the covalent contribution is also proven and quantified. The existing intermolecular H···H short contacts have been studied and are compared with available data from the Cambridge Structural Database. The results show that the electronic configuration of the transition metal atom in the sandwich complex is not enough to define the preferred rotamer due to the influence of the anion environment and the H···H interactions present in the solid state. We present a methodology with widely used theoretical tools to study cation···cobaltabisdicarbollide interactions in the solid state.
Facile Synthesis of Lanthanidocenes by the “Borohydride/Alkyl Route” and Their Application in Isoprene Polymerization
Authors: Visseaux Marc , Terrier Michael , Mortreux André , Roussel Pascal 
Published: April 2010

AbstractSeveral borohydridolanthanidocenes were synthesized by means of a straightforward approach starting from equimolar amounts of Ln(BH4)3(thf)3 (Ln = Nd, Sm) and n‐butylethylmagnesium (BEM) in the presence of 2 equiv. of a cyclopentadiene derivative. Depending on the nature of the cyclopentadiene, monometallic Cp*2Nd(BH4)(thf) (Cp* = C5Me5) (1), heterodimetallic [Cp2Nd(BH4)(μ‐BH4)]2Mg(thf)4 (Cp = C5H5) (2), [(CMe2C5H4)2Ln(BH4)(μ‐BH4)]2Mg(thf)3 (Ln = Nd, 3a; Ln = Sm, 3b), and monometallic anilidocyclopentadienyl compounds (C5Me4CH2SiMe2NPh)Ln(BH4)(thf)2 (Ln = Nd, 4a; Ln = Sm, 4b) were isolated. The complexes were characterized by 1H NMR spectroscopy, elemental analysis, and X‐ray structural analysis. Mg(BH4)2(thf)3 (5) was isolated as a byproduct and structurally characterized, revealing an unprecedented structural arrangement. In combination with BEM, complexes 2a, 3a, and 4a were found to be efficient in isoprene polymerization to afford highly stereoregular trans‐polyisoprene. Similar results were obtained by an “all in situ” approach starting from Nd(BH4)3(thf)3/BEM mixtures in the presence of 2 equiv. of cyclopentadiene derivative.
Electron‐Withdrawing, Biphenyl‐2,2′‐diol‐Based Compounds for Asymmetric Catalysis
Authors: Gutierrez Elisa G. , Moorhead Eric J. , Smith Eva H. , Lin Vivian , Ackerman Laura K. G. , Knezevic Claire E. , Sun Victoria , Grant Sharday , Wenzel Anna G. 
Published: April 2010

AbstractFacile synthetic routes to a chiral chloro‐substituted biphenyl‐2,2′‐diyl hydrogen phosphate and a chiral O,O‐biphenyl‐2,2′‐diyl phosphoramidothioate are described. The performance of these compounds as catalysts for the hydrophosphonylation of imines and the Friedel–Crafts alkylation of indole was investigated. In the latter reaction, the chloro‐substituted phosphoric acid derivative was found to rival the best Brønsted acid catalysts reported to date.
Acid‐Induced Rearrangement of Epoxygermacra‐8,12‐olides: Synthesis and Absolute Configuration of Guaiane and Eudesmane Derivatives from Artemisiifolin
Authors: Rosselli Sergio , Maggio Antonella , Raccuglia Rosa Angela , Bruno Maurizio 
Published: April 2010

AbstractA study on the acid‐induced rearrangement of 4,5‐epoxy‐ and 1,10‐epoxygermacra‐8,12‐olides was carried out. From a 4,5‐epoxy derivative, guaianes were obtained, whereas 1,10‐epoxy derivatives furnished, depending on the stereochemistry of the C‐1/C‐10 epoxy ring, trans‐5β,10α‐ or trans‐5α,10β‐eudesmanolides.
Time‐course of micronucleated erythrocytes in response to whole‐body gamma irradiation in a model mammalian species, the bank vole (Clethrionomys glareolus, Schreber)
Authors: Smolich Igor I. , Savina Natalya V. , Ryabokon Nadezhda I. 
Published: April 2010

AbstractThe time course of the formation of micronucleated polychromatic (MNPCEs) and normochromatic erythrocytes (MNNCEs) in the bone marrow of the bank vole (Clethrionomys glareolus, Schreber), a model mouse‐like species, was studied using the standard micronucleus test at 0, 6, 12, 18, 24, 30, 36 and 48 hr following whole‐body acute γ‐irradiation at a dose of 0.5 Gy. Based on the existing literature on laboratory mice, it was suggested that such a dose will not have significant effect on erythroid cell proliferation in the bank vole and hence on the time course of the rise of micronucleated cells. In total, ∼905,000 polychromatic (PCEs) and normochromatic erythrocytes (NCEs) from 82 adult bank voles were analyzed. Although the mean frequencies of MNNCEs were too low to allow for the correct assessment of their time course, an analysis of PCEs showed an increasing rate of MNPCE appearance at 6 hr that reached a maximum at 18–24 hr after irradiation and subsequently decreased. Because the kinetics of MNPCEs reflects the process of erythropoiesis, the current results regarding the time points of appearance of radiation‐induced MNPCEs provide the first information on the prolongation of one of the terminal stages of erythrocyte formation in bank vole specimens, namely the stage of maturation of PCEs from erythroblasts. Moreover, the observed time‐course data, as well as the low‐background frequencies of MNPCEs and characteristic level of PCEs response to radiation, showed similarities between the two model species: bank vole (this study) and laboratory mice (literature data). Environ. Mol. Mutagen. 52:50–57, 2011. © 2010 Wiley‐Liss, Inc.
Reflections on the origins and evolution of genetic toxicology and the environmental mutagen society
Authors: Wassom John S. , Malling Heinrich V. , Sankaranarayanan K. , Lu Po‐Yung 
Published: April 2010

AbstractThis article traces the development of the field of mutagenesis and its metamorphosis into the research area we now call genetic toxicology. In 1969, this transitional event led to the founding of the Environmental Mutagen Society (EMS). The charter of this new Society was to “encourage interest in and study of mutagens in the human environment, particularly as these may be of concern to public health.” As the mutagenesis field unfolded and expanded, new wording appeared to better describe this evolving area of research. The term “genetic toxicology” was coined and became an important subspecialty of the broad area of toxicology. Genetic toxicology is now set for a thorough reappraisal of its methods, goals, and priorities to meet the challenges of the 21st Century. To better understand these challenges, we have revisited the primary goal that the EMS founders had in mind for the Society's main mission and objective, namely, the quantitative assessment of genetic (hereditary) risks to human populations exposed to environmental agents. We also have reflected upon some of the seminal events over the last 40 years that have influenced the advancement of the genetic toxicology discipline and the extent to which the Society's major goal and allied objectives have been achieved. Additionally, we have provided suggestions on how EMS can further advance the science of genetic toxicology in the postgenome era. Any oversight or failure to make proper acknowledgment of individuals, events, or the citation of relevant references in this article is unintentional. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.