bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving therapeutic engagement with adolescent sexual offenders
Authors: Smallbone Stephen , Crissman Belinda , Rayment‐McHugh Susan 
Published: November 2009

AbstractThis article reports a test of multisystemic predictors of therapeutic engagement (TE) with adolescent sexual offenders (ASOs), and an evaluation of clinical efforts to improve TE with this client group. First, clinicians rated their TE with 105 Australian court‐referred male ASOs (M = 15.53 years; SD = 1.30 years), who participated in treatment between 2001 and 2005. For this cohort, correlation analysis showed impulsivity/antisociality, negative peer relationships, and indigenous race to be associated with poorer TE. Multiple regression analysis identified impulsivity/antisociality and indigenous race as significant unique predictors. Clinical efforts subsequently focused on improving TE, particularly with higher‐antisocial youth and with indigenous youth and their families. Clinicians then rated TE with a second, independent cohort of 54 court‐referred male ASOs (M = 15.44 years; SD = 1.22 years), who participated in the modified treatment between 2006 and 2009. A two‐way ANCOVA, controlling for impulsivity/antisociality, indicated significant improvements in TE for both indigenous and non‐indigenous ASOs. Despite these general improvements, indigenous ASOs remained comparatively less engaged than their non‐indigenous counterparts. Copyright © 2009 John Wiley & Sons, Ltd.
Stimulation of glucose oxidase with white linearly polarized light
Authors: Konieczna‐Molenda Anna , Fiedorowicz Maciej , Tomasik Przemysław J. 
Published: November 2009

AbstractGlucose oxidase (GOD) was illuminated with white linearly polarized light (WLPL). The enzyme was illuminated at room temperature in separate vessels then admixed to a reactor filled with D‐glucose. The illumination of the enzyme for 60 min at 25–30°C and pH 6.5–7.0 provided its superior stimulation as proven in the oxidation of β‐D‐glucose. Lyophilization of the illuminated enzyme reduced its activity by, approximately, 30%. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
A noninvasive technique for the measurement of the energetic state of free‐suspension mammalian cells
Authors: Ben‐Tchavtchavadze M. , Chen J. , Perrier Michel , Jolicoeur Mario 
Published: November 2009

AbstractA perfusion small‐scale bioreactor allowing on‐line monitoring of the cell energetic state was developed for free‐suspension mammalian cells. The bioreactor was designed to perform in vivo nuclear magnetic resonance (NMR) spectroscopy, which is a noninvasive and nondestructive method that permits the monitoring of intracellular nutrient concentrations, metabolic precursors and intermediates, as well as metabolites and energy shuttles, such as ATP, ADP, and NADPH. The bioreactor was made of a 10‐mm NMR tube following a fluidized bed design. Perfusion flow rate allowing for adequate oxygen supply was found to be above 0.79 mL min−1for high‐density cell suspensions (108cells). Chinese hamster ovary (CHO) cells were studied here as model system. Hydrodynamic studies using coloration/decoloration and residence time distribution measurements were realized to perfect bioreactor design as well as to determine operating conditions bestowing adequate homogeneous mixing and cell retention in the NMR reading zone. In vivo31P NMR was performed and demonstrated the small‐scale bioreactor platform ability to monitor the cell physiological behavior for 30‐min experiments. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
National identity and international giving: Irish adults' accounts of charitable behaviour
Authors: Stevenson Clifford , Manning Rachel 
Published: November 2009

AbstractResearch on helping behaviour has emphasized the importance of the group and particularly the nation in establishing the norms and boundaries of emergency helping. Less attention has been paid to the role of the national group in longer‐term routine helping such as charitable giving. This is particularly important given recent research on intergroup helping which points to the impact of power relations on willingness of national groups to give and receive aid. The present research examines people's accounts of charitable giving in their day‐to‐day lives in Ireland, a country which has recently undergone a transformation in economic development and international relations. Discursive analysis of five focus groups with 14 Irish university students illustrates how participants proactively invoke national identity to account for giving or withholding charity. Our findings demonstrate how Irish national identity can be strategically and flexibly used to manage participants' local moral identity in the light of Ireland's changing international relations and in particular how participants display concerns to be seen to intend ‘autonomous’ rather than ‘dependency’‐oriented helping. The findings suggest that both national identity and international relations provide resources for individuals negotiating the complex demands and concerns surrounding charitable giving. Copyright © 2009 John Wiley & Sons, Ltd.
Sea bass from Texas: notes from the material poetics project at the San Francisco waste dump
Authors: Wijland Roel 
Published: November 2009

Abstract

Every poem is an abstract. Three famous market makers reincarnate as fish from a bone dry country and are brutally hijacked for an excursion through a vengeful landscape of disposal. As they are returned to their wasted natural origins, they contemplate their mythical journey.

This poem was written as a scratch and sniff version of research into the rotting materiality of consumer culture at the occasion of the Heretical Consumer Research Performance in October 2008. The purpose of HCR is to create a small scale experiential quests that aspire to produce epiphanies. The annual performances are collaborative events performed with a sense of radical urgency. In that respect the HCR‐days are reminiscent of past innovative disruptions in consumer research that cherish the ‘revelatory incident’ and that perpetuate the heretical disconnect from academic pursuits that prioritize the social re‐production of research paradigms. More paradoxical evocations of affluence and superfluousness created for the Material Poetics Project may be viewed at www.hcr2008.com. Everything that happened to the Lehman Brothers and Sea Bass from Texas is real, or so the poet thinks.

Copyright © 2009 John Wiley & Sons, Ltd.
Measurement and Prediction of Oral Absorption
Authors: Keldenich Joerg 
Published: November 2009

AbstractAfter defining oral absorption, this review article summarizes the influence of different physiological and physicochemical parameters on oral absorption explained according to the situation at BayerScheringPharma. Along the optimization process in industries, prediction of oral absorption is exemplified.In silico prediction of oral absorption in early stages of research is highlighted with three examples, i.e., a classification algorithm, a single parameter prediction, and a linear free‐energy relationship.In vitro prediction of permeation using Caco‐2 cell layers and physicochemical modeling is exemplified. The influence of solubility is shown by a concrete example, in particular, using physiologically based pharmacokinetic (PBPK) modeling and physicochemical parameters.For later stages, optimization examples of in vivo animal models stress the importance of excellent in vivo data and in vivo/in vivo correlations for the prediction of human oral absorption from animal experiments.
Stability Challenges in Drug Discovery
Authors: Di Li , Kerns Edward H. 
Published: November 2009

AbstractStability is one of the most important properties of drug candidates. Instable compounds can lead to false positive high‐throughput screening (HTS) hits, incorrect bioassay results, erroneous structure–activity relationships (SAR), low oral bioavailability, drug withdrawal, toxic reactions from degradation products, and difficult formulation development. Screening of stability has been implemented early in drug discovery to identify labile chemotypes and guide structural modification. The most commonly applied stability studies in drug discovery are stability–pH profile, stability in gastrointestinal fluids, stability in bioassay media, excipient compatibility, and prodrug screening. The strategy enhances the quality of drug development candidates and reduces the risks.
Ionization‐Specific QSAR Models of Blood–Brain Penetration of Drugs
Authors: Lanevskij Kiril , Japertas Pranas , Didziapetris Remigijus , Petrauskas Alanas 
Published: November 2009

AbstractThis study presents a mechanistic QSAR (quantitative structure–activity relationship) analysis of blood–brain barrier (BBB) penetration of drugs and drug‐like compounds governed by passive diffusion in rats and mice. The analyzed data included a previously compiled set of almost 200 experimental BBB permeation rates (expressed as log PS values) as well as steady‐state brain/plasma distribution ratios for ca. 500 compounds (represented as log BB constants) that were considered free of carrier‐mediated transport and other unwanted effects. These data were modeled in terms of nonlinear lipophilicity and ionization dependences. The necessity to separate the influence of drug binding to plasma and brain constituents on the distribution ratio is discussed. Preliminary results demonstrate that, if both the rate and extent of BBB penetration are considered, it is possible to estimate whether a given compound may exhibit central nervous system (CNS) penetration.
Computational Oral Absorption Simulation for Low‐Solubility Compounds
Authors: Sugano Kiyohiko 
Published: November 2009

AbstractBile micelles play an important role in oral absorption of low‐solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH–solubility profile in bile micelles, the Henderson–Hasselbalch equation should be modified to take bile‐micelle partition into account. For the dissolution rate, in the Nernst–Brunner equation, the effective diffusion coefficient in bile‐micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8‐ to 18‐fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral‐absorption data of low‐solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed.
In silico Prediction of Human Oral Absorption Based on QSAR Analyses of PAMPA Permeability
Authors: Akamatsu Miki , Fujikawa Masaaki , Nakao Kazuya , Shimizu Ryo 
Published: November 2009

AbstractThe parallel artificial membrane permeation assay (PAMPA) was developed as a model for the prediction of transcellular permeation in the process of drug absorption. Our research group has measured the PAMPA permeability of peptide‐related compounds, diverse drugs, and agrochemicals. This work led to a classical quantitative structure–activity relationship (QSAR) equation for PAMPA permeability coefficients of structurally diverse compounds based on simple physicochemical parameters such as lipophilicity at a particular pH (log Poct and |pKa−pH|), H‐bond acceptor ability (SAHA), and H‐bond donor ability (SAHD). Since the PAMPA permeability of lipophilic compounds decreased with their apparent lipophilicity due to the unstirred water layer (UWL) barrier on membrane surfaces and to membrane retention, a bilinear QSAR model was introduced to explain the permeability of a broader set of compounds using the same physicochemical parameters as those used for the linear model. We also compared PAMPA and Caco‐2 cell permeability coefficients of compounds transported by various absorption mechanisms. The compounds were classified according to their absorption pathway (passively transported compounds, actively transported compounds, and compounds excreted by efflux systems) in the plot of Caco‐2 vs. PAMPA permeability. Finally, based on the QSAR analyses of PAMPA permeability, an in silico prediction model of human oral absorption for possibly transported compounds was proposed, and the usefulness of the model was examined.
Small Chemicals, Bioactivation, and the Immune System – A Fragile Balance of i‐Tox and Benefits?
Authors: Esser Charlotte , Jux Bettina 
Published: November 2009

AbstractImmunotoxicology concerns actions of chemicals which lead to adverse immune reactions. Current research challenges are the prediction of the immunotoxicologic risk potential of a chemical and a deeper mechanistic understanding of chemical‐induced adverse immune reactions, to develop therapeutic or avoidance strategies. Small chemicals (SCs) can interfere with any cell type or function of the immune system. SCs are ubiquitous as food components, life‐style products, or environmental pollutants. Besides their possible unspecific toxicity, they might form protein adducts, become part of recognized antigens, or they could be disruptors of immune signalling pathways. The incidence of autoimmune and allergic diseases has been rising over the last years, and evidence increases that SCs are important in this. Also, immunopharmacologists actively search for immunomodulating chemicals as urgently needed drugs. The aryl hydrocarbon receptor (AhR) is a SC‐triggered transcription factor, and thus could link environmental signals to cellular responses. Recent research has shown a defined role for AhR in immunotoxicology. Here, we discuss concepts of SC immunotoxicity, and how AhR might be involved in adverse immune responses.
RNA‐Interference Approach to Study Functions of NADPH : Cytochrome P450 Oxidoreductase in Human Hepatocytes
Authors: Feidt Diana M. , Klein Kathrin , Nüssler Andreas , Zanger Ulrich M. 
Published: November 2009

AbstractHuman NADPH : cytochrome P450 oxidoreductase (POR) is encoded by a single gene on chromosome 7q11.2. This flavoprotein donates electrons derived from NADPH to a variety of acceptor proteins, including squalene monooxygenase, heme oxygenase, cytochrome b5, and many microsomal cytochromes P450 (CYPs), which are involved in oxidative drug metabolism, steroidogenesis, and other functions. Numerous aspects related to cellular POR expression have not been systematically investigated. Interestingly, POR expression is lower compared to CYPs and may thus be limiting for monooxygenase activities, but conversely, POR knock‐out in mice resulted in compensatory upregulation of CYPs. POR may also influence intracellular cholesterol and lipid homeostasis. To systematically investigate such effects, we developed specific POR gene silencing in cell lines and primary human hepatocytes by RNA interference using small interfering RNAs (siRNAs). In HepG2 cells, POR mRNA could be reduced by 95% over 4 days accompanied by reduced protein content and activity. In primary human hepatocytes, POR mRNA knock‐down was less effective and more variable. Analysis of CYPs indicated induction of CYP3A4 but not CYP1A2 or CYP2D6. These results demonstrate that POR can be efficiently and almost completely silenced in HepG2 cells and, at least partially, in primary human hepatocytes. This will allow systematic studies of various consequences of POR variability in human cells.
A PAMPA Study of the Permeability‐Enhancing Effect of New Ceramide Analogues
Authors: Sinkó Bálint , Kökösi József , Avdeef Alex , Takács‐Novák Krisztina 
Published: November 2009

AbstractThere is a major need in drug discovery for quick, precise, and cost‐effective high‐throughput screening (HTS) systems in the early stages of drug research. The Parallel Artificial Membrane Permeability Assay (PAMPA) aims at predicting the passive membrane properties of drugs. Since 1998, model membranes have been developed to predict gastro‐intestinal absorption or transport through the blood–brain barrier. This paper presents recent results in a project aiming to improve the prediction of transdermal penetration. Using the PAMPA system, we investigated the effect of four newly synthetized ceramide analogues (certramides) on the permeability of three model compounds (ciprofloxacin, nifedipine, and verapamil). The certramides differ in the length of one alkyl chain, while the other alkyl chain and the head group remained the same. A relationship between the membrane concentration of certramides (from 0 to 100%) and the permeability of compounds was found, and the results of different certramides were compared. The strongest effect on permeability was caused by the ceramide analogue CTR(C12–C16). The reproducibility of the experiments and the impact of presence or absence of organic solvents (dodecane and CHCl3) in the membrane were also investigated.
In silico pKa Prediction and ADME Profiling
Authors: Cruciani Gabriele , Milletti Francesca , Storchi Loriano , Sforna Gianluca , Goracci Laura 
Published: November 2009

AbstractImproving the ADME profile of drug candidates is a critical step in lead optimization, and because pKa affects most ADME properties such as lipophilicity, solubility, and metabolism, it is extremely advantageous to predict pKa in order to guide the design of new compounds. However, accurately (<0.5 log units) predicting pKa by empirical methods can be challenging especially for novel series, because of lack of knowledge on determinants of pKa (steric effects, ring effects, H‐bonding, etc.), and because of limited experimental data on the effects of specific chemical groups on the ionization of an atom. To address these issues, we recently developed the computational package MoKa, which integrates graphical and command line tools designed for computational and medicinal chemists to predict the pKa values of organic compounds. Here, we present the major issues considered when we developed MoKa, such as the accurate selection of training data, the fundamentals of the methodology (which has also been extended to predict protein pKa), the treatment of multiprotic compounds, and the selection of the dominant tautomer for the calculation. Last, we illustrate some specific applications of MoKa to predict solubility, lipophilicity, and metabolism.
Transporters in Absorption, Distribution, and Elimination
Authors: Scherrmann Jean‐Michel 
Published: November 2009

AbstractDuring the past decades, pharmacokinetics has been defined as the study of drug absorption, distribution, metabolism, and excretion (ADME), when the drug is introduced into a biological system, such as the human body. Pharmacokinetics is now challenged by the growing importance of transporters, a relatively new and potentially major factor in drug ADME. The recent intrusion of drug transporters means that there is no single mechanism by which drugs permeate through membranes. The presence of transporters in membranes modulates the traditional theory of ‘diffusional pharmacokinetics’ towards ‘vectorial pharmacokinetics’ in which ADME processes are governed more deterministically. Drug transporters are also clinically important. They can modulate the pharmacological activity of drugs by affecting their intracellular concentrations and causing toxicity in specific organs due to intracellular drug accumulation. Finally, they are key players in drug–drug interactions, where they are as important as the drug metabolizing enzymes.
Oxidation of an Oligonucleotide‐Bound CeIII/Multiphosphonate Complex for Site‐Selective DNA Scission
Authors: Lönnberg Tuomas , Aiba Yuichiro , Hamano Yuya , Miyajima Yoshitaka , Sumaoka Jun , Komiyama Makoto 
Published: November 2009

AbstractOligodeoxyribonucleotide conjugates of ethylenediamine‐N,N,N′,N′‐tetrakis(methylenephosphonic acid) (EDTP) have been used to place a CeIII/EDTP complex in close proximity to predetermined phosphodiester linkages of a complementary target oligonucleotide. In the presence of atmospheric oxygen, the CeIII is oxidized into CeIV which, in turn, efficiently cleaves the target phosphodiester linkage. No cleavage occurs at the other single‐stranded regions, which suggests that the catalytic Ce species is strictly localized next to the target phosphodiester linkage. No decrease in the reaction rate is observed upon introduction of scavengers for hydroxyl radicals (such as DMSO or MeOH) or singlet oxygen (such as NaN3) to the system; this indicates that the reaction proceeds via a hydrolytic pathway. Any significant contribution by an oxidative pathway is further ruled out by the observation that nucleosides remain intact after incubation with CeIV/EDTP complex for extended periods.
Bonding Trends in Molecular Compounds of Lanthanides: The Double‐Bonded Carbene Cations LnCH2+ (Ln=Sc, Y, La–Lu)
Authors: Roos Björn O. , Pyykkö Pekka 
Published: November 2009

AbstractQuasi‐relativistic Douglas–Kroll CASPT2 calculations are reported for the title molecules, mainly to provide primary data for a fit of double‐bond covalent radii. Indeed, a well‐developed σ2π2 double bond is identified in all cases. For Eu and Yb, however, it is an excited state. The main valence orbitals of all Ln ions are 6s and 5d. In the σ bonds, more 5d than 6s character is found at the Ln. The LnC bond lengths show a systematic lanthanide contraction of 13 pm from La to Lu. An agostic symmetry breaking is demonstrated for Ce but its effect on the LnC length is small.
Bioinspired interactions studied by vibrational circular dichroism
Authors: Urbanová Marie 
Published: November 2009

AbstractVibrational circular dichroism (VCD) spectra are reliable indicators of the spatial structure of chiral molecules. The specific and characteristic feature of vibrational spectroscopy, and therefore also of VCD, where the energy of some vibrational modes is predominantly focused to a specific part of the molecule, enables monitoring both the structure of the molecule dissolved in different solvents and under different physicochemical conditions and molecular interactions. This minireview deals with recent contributions covering structural information on the bioinspired interactions obtained by means of VCD, especially in the following areas: interaction of DNA with biomolecules and biogenic metals, guanine tetramers and quadruplexes, biointeractions of bile pigments, and polypeptide and protein interactions with other biomolecules. Chirality 21:E215–E230, 2009. © 2009 Wiley‐Liss, Inc.
The extended website stage model: a study of Canadian winery websites
Authors: Zhu Ying , Basil Debra Z. , Hunter M. Gordon 
Published: November 2009

AbstractRao, Metts, and Mora Monge (2003) proposed a stage model to reflect the progression small businesses follow in their use of Internet technology. We extend their work in two ways. We introduce marketing integration into this technology‐focused model and further differentiate the transactions stage of the framework. We then use the model to examine differences in the degree of sophistication of websites used by businesses in the Canadian winery sector. Data collection entailed a content analysis on a census of English language Canadian winery websites (N = 206). A supplementary survey was used to distinguish among those sites that were making use of relatively advanced technologies. A multinomial logit analysis was applied to examine a series of research questions based upon our integrated model. Implications of the findings for scholarship and practice are discussed. Copyright © 2009 ASAC. Published by John Wiley & Sons, Ltd.