bluuebunny/crossref_metadata_2025 huggingface dataset:
Turning working papers into journal articles: An exercise in microbibliometrics
Authors: Frandsen Tove Faber , Wouters Paul
Published: January 2009

This article focuses on the process of scientific and scholarly communication. Data on open access publications on the Internet not only provides a supplement to the traditional citation indexes but also enables analysis of the microprocesses and daily practices that constitute scientific communication. This article focuses on a stage in the life cycle of scientific and scholarly information that precedes the publication of formal research articles in the scientific and scholarly literature. Binomial logistic regression models are used to analyse precise mechanisms at work in the transformation of a working paper (WP) into a journal article (JA) in the field of economics. The study unveils a fine‐grained process of adapting WPs to their new context as JAs by deleting and adding literature references, which perhaps can be best captured by the term sculpting.
Integrating multiple windows and document features for expert finding
Authors: Zhu Jianhan , Song Dawei , Rüger Stefan
Published: January 2009

Expert finding is a key task in enterprise search and has recently attracted lots of attention from both research and industry communities. Given a search topic, a prominent existing approach is to apply some information retrieval (IR) system to retrieve top ranking documents, which will then be used to derive associations between experts and the search topic based on cooccurrences. However, we argue that expert finding is more sensitive to multiple levels of associations and document features that current expert finding systems insufficiently address, including (a) multiple levels of associations between experts and search topics, (b) document internal structure, and (c) document authority. We propose a novel approach that integrates the above‐mentioned three aspects as well as a query expansion technique in a two‐stage model for expert finding. A systematic evaluation is conducted on TREC collections to test the performance of our approach as well as the effects of multiple windows, document features, and query expansion. These experimental results show that query expansion can dramatically improve expert finding performance with statistical significance. For three well‐known IR models with or without query expansion, document internal structures help improve a single window‐based approach but without statistical significance, while our novel multiple window‐based approach can significantly improve the performance of a single window‐based approach both with and without document internal structures.
Scaling rules in the science system: Influence of field‐specific citation characteristics on the impact of individual researchers
Authors: Costas Rodrigo , Bordons Maria , van Leeuwen Thed N. , van Raan Anthony F.J.
Published: January 2009

The representation of science as a citation density landscape and the study of scaling rules with the field‐specific citation density as a main topological property was previously analyzed at the level of research groups. Here, the focus is on the individual researcher. In this new analysis, the size dependence of several main bibliometric indicators for a large set of individual researchers is explored. Similar results as those previously observed for research groups are described for individual researchers. The total number of citations received by scientists increases in a cumulatively advantageous way as a function of size (in terms of number of publications) for researchers in three areas: Natural Resources, Biology & Biomedicine, and Materials Science. This effect is stronger for researchers in low citation density fields. Differences found among thematic areas with different citation densities are discussed.
Preattentive auditory information processing under exposure to the 902 MHz GSM mobile phone electromagnetic field: A mismatch negativity (MMN) study
Authors: Kwon Myoung Soo , Kujala Teija , Huotilainen Minna , Shestakova Anna , Näätänen Risto , Hämäläinen Heikki
Published: January 2009

Previous studies on the effects of the mobile phone electromagnetic field (EMF) on various event‐related potential (ERP) components have yielded inconsistent and even contradictory results, and often failed in replication. The mismatch negativity (MMN) is an auditory ERP component elicited by infrequent (deviant) stimuli differing in some physical features from the repetitive frequent (standard) stimuli in a sound sequence. The MMN provides a sensitive measure for cortical auditory stimulus feature discrimination, regardless of attention and other contaminating factors. In this study, MMN responses to duration, intensity, frequency, and gap changes were recorded in healthy young adults (n = 17), using a multifeature paradigm including several types of auditory change in the same stimulus sequence, while a GSM mobile phone was placed on either ear with the EMF (902 MHz pulsed at 217 Hz; SAR1g = 1.14 W/kg, SAR10g = 0.82 W/kg, peak value = 1.21 W/kg, measured with an SAM phantom) on or off. An MMN was elicited by all deviant types, while its amplitude and latency showed no significant differences due to EMF exposure for any deviant types. In the present study, we found no conclusive evidence that acute exposure to GSM mobile phone EMF affects cortical auditory change detection processing reflected by the MMN. Bioelectromagnetics 30:241–248, 2009. © 2009 Wiley‐Liss, Inc.
Teratological evaluation of mouse fetuses exposed to a 20 kHz EMF
Authors: Lee Hae‐June , Pack Jeong‐Ki , Gimm Youn‐Myoung , Choi Hyung‐Do , Kim Nam , Kim Sung‐Ho , Lee Yun‐Sil
Published: January 2009

As a continuation of our previous study, we performed a teratological evaluation of the importance of gestational age with regards to the exposure of 20 kHz intermediate frequency magnetic field (IF) on pregnant ICR mice. The pregnant mice were exposed to a 20 kHz IF magnetic field for 8 h/day in a carousel irradiator at 30 µT which is the limit standard for occupational population in Korea. The animals were sacrificed on the 18th day of gestation and the fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. We concluded that exposure to 30 µT with 20 kHz IF did not cause any observable adverse effects on mouse fetuses. Bioelectromagnetics 30:330–333. © 2009 Wiley‐Liss, Inc.
Befestigungen über Eck unter Zug‐ und Querlast
Authors: Mallée Rainer
Published: January 2009

Werden Dübel in zwei senkrecht zueinander stehenden Ebenen verankert (z. B. in Gebäude‐ oder Stützenecken) und gleichzeitig belastet, dann können sie sich bei kleinen Randabständen gegenseitig in ihrem Tragverhalten beeinflussen. Zur Klärung des Tragverhaltens wurden Versuche durchgeführt. Auf Basis der Versuchsergebnisse wird ein Bemessungsvorschlag abgeleitet.
Tragverhalten von Stahlbetonbalken bei geneigter Querkraft
Authors: Birtel Veit , Stangenberg Friedhelm , Mark Peter
Published: January 2009

Das Querkrafttragverhalten schubbewehrter Stahlbetonbalken ist nach wie vor Gegenstand intensiver Diskussionen und aktueller Forschungen. Dabei konzentrieren sich die Untersuchungen stets auf einachsige Belastungen, die parallel zu den Querschnittshauptachsen verlaufen. Erst in den letzten Jahren wurde eine mögliche Querkraftneigung erstmals theoretisch berücksichtigt und in Tragmodelle integriert. Experimentelle Untersuchungen hierzu liegen nur sehr begrenzt vor. Im vorliegenden Beitrag wird daher eine umfangreiche Versuchsreihe mit geneigten Querkraftwirkungen vorgestellt und analysiert. Der Vergleich experimenteller und rechnerischer Bruchlasten zeigt die Notwendigkeit einer mechanisch konsistenten Berücksichtigung der Querkraftneigung in allen Widerstandsanteilen von Zug‐ wie Druckstreben. Ein weiterentwickeltes Bemessungsmodell, das wirtschaftlichere Bemessungen ermöglicht, wird vorgestellt und zur praktischen Anwendung weiterentwickelt.
Zur Qualitätssicherung bei der Ausführung von Elementwänden für wasserundurchlässige Betonkonstruktionen
Authors: Mähner Dietmar , Weber Jochen
Published: January 2009

Dieser Beitrag befasst sich mit der Qualitätssicherung bei der Herstellung von Elementwänden als wasserundurchlässige Betonkonstruktionen nach der WU‐Richtlinie des DAfStb. Dazu wurde im Rahmen von diversen Untersuchungen an der FH Münster während der Bauausführung vor allem solchen Aspekten nachgegangen, die besonders häufig bei dieser Bauweise als Schadensursache identifiziert worden waren oder bei denen die WU‐Richtlinie ein vergleichsweise hohes Qualitätsniveau erwartet. Auf der Grundlage der Untersuchungsergebnisse werden abschließend Empfehlungen zum Umgang mit Elementwänden gegeben.
Optimierungen im Zuge der Ausführungsplanung – Hochhaus Süddeutscher Verlag München
Authors: Dietz Jörg , Roth Eckard , Meyer Julian
Published: January 2009

In der kurzen Zeitspanne zwischen Mai 2006 und April 2007 wurde der Rohbau des Neubaus Süddeutscher Verlag in München errichtet. Das Bauwerk besteht aus drei Untergeschossen, einem Hochhaus mit 28 Geschossen und einem fünfgeschossigen Flachbau mit überdachtem Atrium. Die technische Bearbeitung der Ausführungsplanung erfolgte auf Grundlage der vom Bauherrn beigestellten Genehmigungsstatik. Trotz des sehr kurzen zeitlichen Vorlaufs der Planung wurden diverse Optimierungen der Rohbauplanung durchgeführt, die im folgenden Beitrag näher erläutert werden.
Dauerhaftigkeit vom Spritzbeton mit erhöhtem Sulfatgehalt beim Einsatz alkalifreier Erstarrungsbeschleuniger
Authors: Brux Gunther
Published: January 2009

Mit dem Einsatz von alkalifreien Erstarrungsbeschleunigern für Spritzbeton im konstruktiven Ingenieurbau (Tunnelbau und Hangsicherungen) können mehrere bisher aufgetretene Probleme, wie Auslaugbarkeit und verringerte Festigkeiten, gelöst werden. Durch diese Betonzusatzmittel erhöht sich jedoch der Sulfatgehalt des Spritzbetons. Ob dadurch seine Dauerhaftigkeit beeinträchtigt wird, wurde vor kurzem in einem Forschungsvorhaben untersucht. Darauf wird näher eingegangen.
Betonbau hat Zukunft – Visionen werden Realität
Authors: Bergmeister Konrad
Published: January 2009

Aktives Erhaltungsmanagement von Infrastrukturbauwerken ist ein Problem des einundzwanzigsten Jahrhunderts, da sich der Erhaltungszustand und in Folge die Zuverlässigkeit bestehender Strukturen zunehmend verschlechtern. Diese Problematik fordert nach Fähigkeiten, Methoden und neuen Technologien, welche in bereits bestehende Ansätze und die Interaktion zwischen verschiedenen Interessenspartner, wie Wissenschaftler, Planer, öffentliche Einrichtungen und Benutzer einfließen sollten. Obwohl bereits großer Fortschritt im Bereich Strukturmanagement, Konstruktion und Lebenszyklus‐Betrachtungen erzielt wurde, ist für jedes dieser Teilgebiete nach wie vor ein enormer Forschungsbedarf gegeben.
Characterization of nucleic acid higher order structure by gas‐phase H/D exchange in a quadrupole‐FT‐ICR mass spectrometer
Authors: Mo Jingjie , Todd Gabrielle C. , Håkansson Kristina
Published: January 2009

Nucleic acid higher order structure is of intense interest in antisense and antigene strategies toward novel chemotherapeutic agents. Understanding how structural characteristics affect solution‐phase properties is essential for a rational approach to nucleic acid‐targeted drug design. The most dominant nucleic acid secondary structure is the hairpin, formed by intrastrand hydrogen bonding between complementary nucleobases. We have previously applied gas‐phase hydrogen/deuterium exchange (HDX) with mass spectrometry detection to show that anionic DNA duplexes have lower HDX rates than their constituent monomers, indicating that hydrogen bonding can shield hydrogens from exchanging with the bath gas D2S. The same HDX assay is applied here to investigate nucleic acid hairpin structure. Variations in hairpin solution‐phase stabilities are achieved by changing their loop size, stem length, and stem composition (ratio of G/C and A/T(U) base pairs in the stem). These differences can be carried into the gas phase because electrospray ionization is a gentle ionization method that is able to preserve noncovalent interactions. Observed gas‐phase HDX rates of these hairpins are consistent with their relative solution‐phase stabilities as predicted by MFold, i.e., less stable nucleic acid hairpins exchange faster than more stable hairpins. To our knowledge, the presented experiments demonstrate for the first time that gas‐phase HDX may be used to characterize nucleic acid higher order structure and the results suggest that the relative stabilities of nucleic acid hairpins in the gaseous phase are correlated with those in solution. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 256–264, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Synthesis and chemoselective intramolecular crosslinking of a HER2‐binding affibody
Authors: Ekblad Torun , Tolmachev Vladimir , Orlova Anna , Lendel Christofer , Abrahmsén Lars , Karlström Amelie Eriksson
Published: January 2009

The human epidermal growth factor receptor HER2 has emerged as an important target for molecular imaging of breast cancer. This article presents the design and synthesis of a HER2‐targeting affibody molecule with improved stability and tumor targeting capacity, and with potential use as an imaging agent. The 58 aa three‐helix bundle protein was assembled using solid‐phase peptide synthesis, and a chemoselective ligation strategy was used to establish an intramolecular thioether bond between the side chain thiol group of a cysteine residue, positioned in the loop between helices I and II, and a chloroacetyl group on the side chain amino group of the C‐terminal lysine residue. The tethered protein offered an increased thermal stability, with a melting temperature of 64°C, compared to 54°C for the linear control. The ligation did not have a major influence on the HER2 binding affinity, which was 320 and 380 pM for the crosslinked and linear molecules, respectively. Biodistribution studies were performed both in normal and tumor‐bearing mice to evaluate the impact of the crosslinking on the in vivo behavior and on the tumor targeting performance. The distribution pattern was characterized by a low uptake in all organs except kidney, and rapid clearance from blood and normal tissue. Crosslinking of the protein resulted in a significantly increased tumor accumulation, rendering the tethered HER2‐binding affibody molecule a valuable lead in the development of superior HER2 imaging agents. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 116–123, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Hairpin ribozyme catalysis: A surface‐enhanced Raman spectroscopy study
Authors: Percot Aline , Lecomte Sophie , Vergne Jacques , Maurel Marie‐Christine
Published: January 2009

The existence of an “RNA world” as an early step in the history of life increases the interest for the characterization of these biomolecules. The hairpin ribozyme studied here is a self‐cleaving/ligating motif found in the minus strand of the satellite RNA associated with Tobacco ringspot virus. Surface‐enhanced Raman spectroscopy (SERS) is a powerful tool to study trace amounts of RNA. In controlled conditions, a SERS signal is proportional to the amount of free residues adsorbed on the metal surface. On RNA cleavage, residues are unpaired and free to interact with metal. SERS procedures are used to monitor and quantify the catalysis of ribozyme cleavage at biological concentrations in real time; thus, they propose an interesting alternative to electrophoretic methods. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 384–390, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The Strengthening Families Programme (SFP) 10‐14 and substance misuse in Barnsley: the perspectives of facilitators and families
Authors: Coombes Lindsey , Allen Debby , Marsh Megan , Foxcroft David
Published: January 2009

The aim of this study was to evaluate the Strengthening Families Programme for young people aged ten to 14 and their parents (SFP 10‐14) in Barnsley, a northern English city, based on the experience of facilitators and families who had participated in the programme. A mixed methods design blending both quantitative and qualitative data was used in the study carried out in two phases over a nine‐month period in 2005. Quantitative data were collected through: the SFP 10‐14 Parent/Caregiver Survey Questionnaire, the SFP 10‐14 Young Persons' Survey Questionnaire and the Strengths and Difficulties Questionnaire. Questionnaire data were compared at the beginning of the SFP 10‐14 programmes (weeks 1–2) and at the end of the programmes (week 7). In addition, two focus group meetings were held with families who had undertaken the SFP 10‐14 programme; and three focus group meetings were conducted with facilitators of SFP 10‐14 programmes. Once quantitative and qualitative data had been analysed separately, a synthesis of the main findings from both approaches was then completed. Following the programmes, parents reported significant changes in communication limit setting, emotional management, prosocial behaviour and drugs/alcohol use. Total difficulties scores were also significantly different pre‐ and post SFP 10‐14 programmes. For the young people, communication, and emotional management were improved and their drugs/alcohol use was less. Their total difficulties scores were also significantly different. Qualitative evidence indicated that families who participated in the study found the SFP 10‐14 useful in preventing young people's alcohol and drug use in terms of: learning more about alcohol and drugs, using knowledge and skills to reduce behaviours that might lead to alcohol and drug use and, for young people, dealing with peer pressure that might lead to drug and alcohol use. Parents/caregivers and young people reported that the SFP 10‐14 had played a part in improving family functioning through strengthening the family unit. The findings from this exploratory study suggest that the SFP 10‐14 may be a useful primary prevention intervention in helping to prevent drug and alcohol misuse in young people. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis of a Potent G‐Quadruplex‐Binding Macrocyclic Heptaoxazole
Authors: Tera Masayuki , Iida Keisuke , Ishizuka Hiromichi , Takagi Motoki , Suganuma Masami , Doi Takayuki , Shin‐ya Kazuo , Nagasawa Kazuo
Published: January 2009

A novel G‐quadruplex binder, L1H1‐7OTD (shown in color by atom type), was developed. This macrocyclic heptaoxazole potently and selectively stabilizes telomeric DNA in an intramolecular antiparallel G‐quadruplex conformation. L1H1‐7OTD shows selective cytotoxicity toward HeLa cells, a telomerase‐positive cell line.

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Modeling multi‐way data with linearly dependent loadings
Authors: Bro Rasmus , Harshman Richard A. , Sidiropoulos Nicholas D. , Lundy Margaret E.
Published: January 2009

A generalization/specialization of the PARAFAC model is developed that improves its properties when applied to multi‐way problems involving linearly dependent factors. This model is called PARALIND (PARAllel profiles with LINear Dependences). Linear dependences can arise when the empirical sources of variation being modeled by factors are causally or logically linked during data generation, or circumstantially linked during data collection. For example, this can occur in a chemical context when end products are related to the precursor or in a psychological context when a single stimulus generates two incompatible feelings at once. For such cases, the most theoretically appropriate PARAFAC model has loading vectors that are linearly dependent in at least one mode, and when collinear, are nonunique in the others. However, standard PARAFAC analysis of fallible data will have neither of these features. Instead, latent linear dependences become high surface correlations and any latent nonuniqueness is replaced by a meaningless surface‐level ‘unique orientation’ that optimally fits the particular random noise in that sample. To avoid these problems, any set of components that in theory should be rank deficient are re‐expressed in PARALIND as a product of two matrices, one that explicitly represents their dependency relationships and another, with fewer columns, that captures their patterns of variation. To demonstrate the approach, we apply it first to fluorescence spectroscopy (excitation‐emission matrices, EEM) data in which concentration values for two analytes covary exactly, and then to flow injection analysis (FIA) data in which subsets of columns are logically constrained to sum to a constant, but differently in each of two modes. In the PARAFAC solutions of the EEM data, all factors are ‘unique’ but this is only meaningful for two of the factors that are also unique at the latent level. In contrast, the PARALIND solutions directly display the extent and nature of partial nonuniqueness present at the latent level by exhibiting a corresponding partial uniqueness in their recovered loadings. For the FIA data, PARALIND constraints restore latent uniqueness to the concentration estimates. Comparison of the solutions shows that PARALIND more accurately recovers latent structure, presumably because it uses fewer parameters and hence fits less error. Copyright © 2009 John Wiley & Sons, Ltd.
Re‐parameterization of five‐parameter logistic function
Authors: Liao Jason J. Z. , Liu Rong
Published: January 2009

Recently, the five‐parameter logistic (5PL) function has seen increased use as a model for bioassay dose‐response curves. The 5PL function takes curve asymmetry into consideration to overcome some drawbacks of the four‐parameter logistic (4PL) function. These drawbacks include biased estimates of important model parameters, poor characterization of pharmacological pathways and the mechanisms, and inaccurate inference of drug‐receptor interactions. However, currently used 5PL functional form does not have the same practical useful parameter interpretation as the 4PL function. In this paper, we re‐parameterize the 5PL function to preserve the practical useful parameter interpretation of the 4PL. Comparing to the currently used 5PL, the re‐parameterized 5PL function preserves practical useful parameter interpretation of 4PL and has better statistical properties in terms of bias and mean squared error (MSE). Copyright © 2009 John Wiley & Sons, Ltd.
Photoinduced Reactions of cis,trans,cis‐[PtIV(N3)2(OH)2(NH3)2] with 1‐Methylimidazole
Authors: Phillips Hazel I. A. , Ronconi Luca , Sadler Peter J.
Published: January 2009

Lighting up new platinum anticancer complexes: Photoactivation of a platinum(IV) diazido anticancer complex in the presence of a derivative of imidazole, an important constituent of biomolecules, gives surprising photoproducts, including a tetrakis imidazole platinum(II) adduct (see figure), together with free azide, dioxygen and ammonia.

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The photodecomposition of cis,trans,cis‐[PtIV(N3)2(OH)2(NH3)2] in phosphate buffered saline (PBS), as well as in the presence of 1‐methylimidazole (1‐MeIm), induced by UVA light (centred at λ=365 nm) has been studied by multinuclear NMR spectroscopy. We show that photoreduction, photoisomerisation and trans‐labilisation pathways are involved. The photodecomposition pathway in PBS, which involves azide release, as detected by 14N NMR spectroscopy, appears to differ from that in acidic aqueous conditions, under which N2 is a product. A number of trans‐{N‐PtII‐NH3} species were also observed as photoproducts, as well as the release of free ammonia with a corresponding increase in pH. Oxygen was also detected as a product in solution. In the presence of 1‐methylimidazole, surprisingly the major photoproduct was the tetra‐substituted PtII complex [PtII(1‐MeIm‐N3)4]2+ (structure confirmed by crystallography), even at a Pt/1‐MeIm molar ratio of 1:1, together with cis‐ and trans‐[PtII(NH3)2(1‐MeIm‐N3)2]2+ as minor products. In these photoinduced 1‐MeIm reactions, free ammonia, azide and oxygen were also detected. The results from this study illustrate that photoinduced reactions of platinum complexes can lead to novel reaction pathways, and therefore to new cytotoxic mechanisms in cancer cells.
Multi‐Drug‐Resistance‐Reverting Agents: 2‐Aryloxazole and 2‐Arylthiazole Derivatives as Potent BCRP or MRP1 Inhibitors
Authors: Colabufo Nicola A. , Berardi Francesco , Perrone Maria Grazia , Cantore Mariangela , Contino Marialessandra , Inglese Carmela , Niso Mauro , Perrone Roberto
Published: January 2009

The 2‐aryloxazole and 2‐arylthiazole scaffolds were used for generating compounds that we characterized for their inhibitory activity toward ATP binding cassette transporters involved in multi‐drug resistance, such as BCRP and MRP1, by using tumor cell lines overexpressing each transporter. These SAR studies are a significant step toward improving the inhibitory potency against P‐glycoprotein, BCRP, and MRP1.

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2‐Aryloxazole and 2‐arylthiazole derivatives were evaluated for their inhibitory activity toward P‐glycoprotein (P‐gp) as well as their selectivity toward other ABC transporters involved in multi‐drug resistance such as BCRP and MRP1. These derivatives have 6,7‐dimethoxytetrahydroisoquinoline or cyclohexylpiperazine moieties, which are the same basic nuclei of the potent P‐gp inhibitors MC70 (EC50=0.05 μM) and PB28 (EC50=0.55 μM), respectively. The results demonstrate that 2‐aryloxazole and 2‐arylthiazole derivatives, planned as cycloisosteres of MC70, were found to be less potent than the reference compound in inhibiting P‐gp. These compounds were evaluated for their BCRP and MRP1 inhibitory activities. In particular, 6,7‐dimethoxytetrahydroisoquinoline derivatives, unsubstituted, 3‐Br, 3‐Cl, and 3‐OCH3 2‐aryloxalzole derivatives showed the best BCRP inhibitory activity (EC50 range: 0.24–0.46 μM). In contrast, all cyclohexylpiperazine derivatives except one (EC50=0.56 μM), showed decreased BCRP inhibitory activity. All compounds tested were unable to inhibit the MRP1 pump, with the exception of the 2‐OCH3 and 4‐OCH3 derivatives of the 6,7‐dimethoxytetrahydroisoquinoline series, which displayed high MRP1 inhibitory activity (EC50=0.84 and 0.90 μM, respectively).
A phase 2, randomized study of SB‐485232, rhIL‐18, in patients with previously untreated metastatic melanoma
Authors: Tarhini Ahmad A. , Millward Michael , Mainwaring Paul , Kefford Richard , Logan Ted , Pavlick Anna , Kathman Steven J. , Laubscher Kevin H. , Dar Mohammed M. , Kirkwood John M.
Published: January 2009

BACKGROUND:

Phase 1 studies demonstrated evidence of recombinant human IL‐18 (rhIL‐18)‐mediated immunomodulatory and clinical activity, and defined a biologically active dose range.

METHODS:

A phase 2 study of rhIL‐18 was conducted in untreated AJCC stage IV melanoma. Patients were randomized to 1 of 3 dose groups (0.01, 0.1, and 1.0 mg/kg/d) of rhIL‐18 administered as 5 daily intravenous infusions repeated every 28 days. A 2‐stage design with a stopping rule was used.

RESULTS:

A total of 64 patients (median age, 57.5 years) with metastatic melanoma (M1a/b (30), M1c (34)) were accrued to stage I, and randomized to 3 groups (21 [0.01 mg/kg/d], 21 [0.1 mg/kg/d], 22 [1.0 mg/kg/d]). Five patients experienced 10 grade 3 drug‐related adverse events (AEs): polyarthritis (1 subject: 0.01 mg/kg); deep vein thrombosis, pulmonary embolism (1:0.01 mg/kg); cognitive disorder (1:0.1 mg/kg); fatigue, dyspnea, pleural effusion, lymphopenia (1:1.0 mg/kg); fatigue, lymphopenia (1:1.0 mg/kg). One patient experienced a grade 4 AE of increased lipase (0.1 mg/kg) that led to permanent discontinuation from the study. Among 63 subjects evaluable for response, 1 (M1c; 0.01 mg/kg) achieved a partial response after 4 cycles. Four subjects (3 at 0.01 mg/kg and 1 at 1.0 mg/kg) had stable disease maintained for 6 months or longer. Due to the low apparent level of clinical efficacy using RECIST criteria, the study was terminated at the end of stage 1. The median progression free survival for the 3 groups was 7.5 (0.01), 7.4 (0.1), and 7.3 (1.0) weeks.

CONCLUSIONS:

rIL‐18 as tested in this trial was well tolerated, but had limited activity as a single agent in patients with metastatic melanoma. Cancer 2009. © 2009 American Cancer Society.
High‐order three‐dimensional discontinuous deformation analysis (3‐D DDA)
Authors: Beyabanaki S. Amir Reza , Jafari Ahmad , Yeung M. Ronald
Published: January 2009

Three‐dimensional discontinuous deformation analysis (3‐D DDA) with high‐order displacement functions has been derived for the requirement of highly accurate stress and strain calculations. The high‐order displacement function allows nonlinear distributions of stresses and strains within a discrete block, which significantly enhances 3‐D DDA as an analysis technique. Formulations of stiffness and force matrices in second‐ and third‐order 3‐D DDA due to elastic stress, initial stress, body force, point load, fixed point, inertial force, normal and shear contact forces and friction force are presented. The VC++ codes for the second‐ and third‐order cases have been developed, and they have been applied to examples of 3‐D beams, bending under various loading conditions applied at the end and to an example of discontinuous problem. Results of modeling, are well in agreement with theoretical solutions. In contrast, the results calculated for the same model, using original first‐order 3‐D DDA are far from the theoretical solutions. Copyright © 2009 John Wiley & Sons, Ltd.
[99mTc]polyamine analogs as potential tumor imaging agent
Authors: Wan Wei‐xing , Yang Min , Pan Shang‐ren , Yu Chun‐jing , Wu Na‐jing
Published: January 2009

Polyamines are essential for the growth and survival of all cells with biosynthesis and transportation of polyamines being very active in tumors. With the aim of developing a new tumor imaging agent, three artificial synthetic polyamine analogs, diethylenetriamine (DETA), triethylenetetramine (TETA), and tetraethylenepentamine (TEPA), were labeled with 99mTc. The 99mTc‐labeled complexes were characterized by TLC and studied for stability. 99mTc‐DETA, 99mTc‐TETA, and 99mTc‐TEPA were formed in high yields and found to be stable. 99mTc‐DETA, 99mTc‐TETA, and 99mTc‐TEPA revealed high tumor uptakes of 0.65, 0.58, and 0.59% ID/g at 4 h pi, respectively, in HepA tumor‐bearing mice. The ratios of the tumor to the contralataral muscle (T/CM) were 13.68, 5.99, and 9.81, respectively. SPECT images revealed clear visualization of tumors. Excretion routes were mainly through urine and feces. The tumor‐to‐muscle count density ratios of 99mTc‐DETA, 99mTc‐TETA, and 99mTc‐TEPA were 2.47, 2.45, and 2.91, respectively. [99mTc]‐labeled polyamine analogs are promising agents for tumor imaging and warrant further evaluation. Drug Dev Res 69:520–525, 2008. © 2008 Wiley‐Liss, Inc.
Mapping the Mechanism of Nickel‐Ferrophite Catalysed Methylation of Baylis–Hillman‐Derived SN2′ Electrophiles
Authors: Novak Andrew , Calhorda Maria José , Costa Paulo Jorge , Woodward Simon
Published: January 2009

Enantioselective Ni‐catalysed methylation of Baylis–Hillman‐derived allylic electrophiles in the presence of ferrophite ligands has been investigated computationally and experimentally. The sense and degree of enantioselectivity attained is independent of both the leaving group and the isomeric structure of the initial allylic halide. DFT studies support the selective formation of a limited number of energetically favoured anti and syn π‐allyl intermediates. The observed regio‐ and enantioselectivity can be rationalised based on the energetics of these structures. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Chiral N‐Phosphonylimine Chemistry: Asymmetric Synthesis of N‐Phosphonyl β‐Amino Weinreb Amides
Authors: Kaur Parminder , Nguyen Thao , Li Guigen
Published: January 2009

Various chiral N‐phosphonyl β‐amino Weinreb amides were synthesized by treating chiral N‐phosphonyl imines with the lithium enolate of N‐methoxy‐N‐methylacetamide. The N,N‐protection groups on chiral N‐phosphonyl imines and the types of deprotonation bases for enolate generation were found to be crucial for the successful synthesis. Eleven Weinreb amides were obtained in excellent chemical yields (92 to 98 %) and good to excellent diastereoselectivities (up to dr = 99:1). The absolute structures were unambiguously determined by converting the products into authentic samples and by comparing their optical rotation values.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
A Magnetically Separable Heterogeneous Deallylation Catalyst: [CpRu(η3‐C3H5)(2‐pyridinecarboxylato)]PF6 Complex Supported on a Ferromagnetic Microsize Particle Fe3O4@SiO2
Authors: Hirakawa Takuya , Tanaka Shinji , Usuki Naoki , Kanzaki Hisao , Kishimoto Mikio , Kitamura Masato
Published: January 2009

The highly reactive and chemoselective homogeneousdeallylation catalyst CpRu(η3‐C3H5)(4‐substituted‐2‐pyridinecarboxylato) was immobilized on microsize spherical Fe3O4@SiO2 particles. The resultant heterogeneous catalyst displays high saturation magnetization, weak coercive forces and high levels of dispersibility. The catalyst has increased the utility of deallylation by allowing the reaction to be conducted without extra additives. The only co‐product of the reaction is a volatile allyl ether compound. Here, we demonstrate the efficient deallylation and separation of highly polar multifunctional compounds as well as multiple rounds of catalyst recycling without significant loss of reactivity. The usefulness of this catalyst has been confirmed by the synthesis of a triribonucleotide 3–5 U. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
An Asymmetric Approach towards (–)‐Aphanorphine and Its Analogues
Authors: Donets Pavel A. , Goeman Jan L. , Van der Eycken Johan , Robeyns Koen , Van Meervelt Luc , Van der Eycken Erik V.
Published: January 2009

A short enantioselective approach towards the alkaloid(–)‐aphanorphine and its substituted analogues is described. The enantiomerically pure starting material for the synthesis was obtained by asymmetric hydrogenation in the presence of the Rh–(S)‐PipPhos complex. Microwave‐assisted Heckcyclization selectively provided the seven‐membered 3‐benzazepine ring. Further, the assembly of the tricyclic core of the alkaloid was accomplished by intramolecular radical cyclization. The X‐ray structure confirming the absolute configuration of the obtained products is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Dimensioning of secondary and tertiary control reserve by probabilistic methods
Authors: Maurer Christoph , Krahl Simon , Weber Holger
Published: January 2009

Given the rising share of intermittent generation out of renewable energy sources on the one hand and the increased regulatory efforts to lower transmission costs and tariffs on the other hand, the optimal dimensioning of necessary control reserve has gained additional importance during the last years. Grid codes like the UCTE Operation Handbook do not provide definitive and unambiguous methods for dimensioning of secondary and tertiary control reserves. This paper therefore presents a method which calculates the necessary control reserve considering all important drivers for power imbalances like power plant outages, load variations and forecast error. For dimensioning, a probabilistic criterion, the accepted probability of insufficient control reserve, is used. Probability density functions of control area imbalances are calculated using a convolution algorithm. This paper provides analyses for a stylised example system to demonstrate the capabilities of the method. In a sensitivity analysis the impact of drivers like plant failures and forecast errors of load and generation is shown. The presented method is used by transmission system operators and regulatory authorities to determine and substantiate the necessary amount of control reserve. Copyright © 2009 John Wiley & Sons, Ltd.
Unbiased estimation of odds ratios: combining genomewide association scans with replication studies
Authors: Bowden Jack , Dudbridge Frank
Published: January 2009

Odds ratios or other effect sizes estimated from genome scans are upwardly biased, because only the top‐ranking associations are reported, and moreover only if they reach a defined level of significance. No unbiased estimate exists based on data selected in this fashion, but replication studies are routinely performed that allow unbiased estimation of the effect sizes. Estimation based on replication data alone is inefficient in the sense that the initial scan could, in principle, contribute information on the effect size. We propose an unbiased estimator combining information from both the initial scan and the replication study, which is more efficient than that based just on the replication. Specifically, we adjust the standard combined estimate to allow for selection by rank and significance in the initial scan. Our approach explicitly allows for multiple associations arising from a scan, and is robust to mis‐specification of a significance threshold. We require replication data to be available but argue that, in most applications, estimates of effect sizes are only useful when associations have been replicated. We illustrate our approach on some recently completed scans and explore its efficiency by simulation. Genet. Epidemiol. 33:406–418, 2009. © 2009 Wiley‐Liss, Inc.
Genetic background comparison using distance‐based regression, with applications in population stratification evaluation and adjustment
Authors: Li Qizhai , Wacholder Sholom , Hunter David J. , Hoover Robert N. , Chanock Stephen , Thomas Gilles , Yu Kai
Published: January 2009

Population stratification (PS) can lead to an inflated rate of false‐positive findings in genome‐wide association studies (GWAS). The commonly used approach of adjustment for a fixed number of principal components (PCs) could have a deleterious impact on power when selected PCs are equally distributed in cases and controls, or the adjustment of certain covariates, such as self‐identified ethnicity or recruitment center, already included in the association analyses, correctly maps to major axes of genetic heterogeneity. We propose a computationally efficient procedure, PC‐Finder, to identify a minimal set of PCs while permitting an effective correction for PS. A general pseudo F statistic, derived from a non‐parametric multivariate regression model, can be used to assess whether PS exists or has been adequately corrected by a set of selected PCs. Empirical data from two GWAS conducted as part of the Cancer Genetic Markers of Susceptibility (CGEMS) project demonstrate the application of the procedure. Furthermore, simulation studies show the power advantage of the proposed procedure in GWAS over currently used PS correction strategies, particularly when the PCs with substantial genetic variation are distributed similarly in cases and controls and therefore do not induce PS. Genet. Epidemiol. 33:432–441, 2009. © 2009 Wiley‐Liss, Inc.
Quantifying and correcting for the winner's curse in genetic association studies
Authors: Xiao Rui , Boehnke Michael
Published: January 2009

Genetic association studies are a powerful tool to detect genetic variants that predispose to human disease. Once an associated variant is identified, investigators are also interested in estimating the effect of the identified variant on disease risk. Estimates of the genetic effect based on new association findings tend to be upwardly biased due to a phenomenon known as the “winner's curse.” Overestimation of genetic effect size in initial studies may cause follow‐up studies to be underpowered and so to fail. In this paper, we quantify the impact of the winner's curse on the allele frequency difference and odds ratio estimators for one‐ and two‐stage case‐control association studies. We then propose an ascertainment‐corrected maximum likelihood method to reduce the bias of these estimators. We show that overestimation of the genetic effect by the uncorrected estimator decreases as the power of the association study increases and that the ascertainment‐corrected method reduces absolute bias and mean square error unless power to detect association is high. Genet. Epidemiol. 33:453–462, 2009. © 2009 Wiley‐Liss, Inc.
Neuropsychiatric symptoms in mild cognitive impairment: differences by subtype and progression to dementia
Authors: Edwards Emily R. , Spira Adam P. , Barnes Deborah E. , Yaffe Kristine
Published: January 2009

Background

Neuropsychiatric symptoms (NPS) are common in patients with mild cognitive impairment (MCI). Little is known, however, about how NPS vary by MCI subtype (i.e. amnestic, single domain non‐memory, and multiple domain). In addition, it is unclear whether NPS increase risk of progression to dementia. We investigated the distribution of NPS across MCI subtypes and determined whether NPS increase risk of progression to dementia.

Method

Participants were 521 patients diagnosed with MCI at the Alzheimer's Research Centers of California between 1988 and 1999. At baseline, patients were classified into MCI subtypes and were assessed for NPS.

Results

The mean number of NPS was 2.3 (range 0–9.6; 74% had ≥1 NPS). Patients with ≥4 NPS had more medical comorbidities and greater functional impairment (p ≤ 0.0001 for both). Patients with ≥4 NPS were more likely than patients with 0–3 NPS to have amnestic MCI (81% vs 71%, respectively, p = 0.03), and patients with amnestic MCI were more likely than those with other subtypes to exhibit depressive symptoms. Patients with ≥4 NPS had nearly 2.5 times the odds of developing dementia at follow‐up than patients with 0–3 NPS (adjusted OR = 2.44, 95% CI 1.07, 5.55).

Conclusion

NPS are common in MCI patients. Those with an elevated number of NPS may be more likely to have the amnestic subtype of MCI, and depression may be more common in amnestic MCI than in other subtypes. An elevated number of NPS may increase risk of progression to dementia for patients with MCI. Copyright © 2009 John Wiley & Sons, Ltd.
Measurement of human sensation for developing sensible textiles
Authors: Lee Myungeun , Cho Gilsoo
Published: January 2009

Human perceptive faculties consist of 5 senses: visual, auditory, olfactory, taste, and tactile sense. Visual is the most powerful sense for human perception followed by the auditory sense. This article attempts to find the connection between the visual and the auditory senses. In particular, the aim is to convert sound to color based on human perception. Natural sounds were selected as stimuli and analyzed by sound color and psychoacoustic factors. In addition, subjective perception was evaluated, and electroencephalogram (EEG) was measured using psychophysiological methods in 20 participants. From the factor analysis results of subjective responses, 4 factors were determined: Emotion, Action, Atmosphere, and Strength. To convert sounds to colors, a multidimensional scale analysis was performed using the results of the EEG responses. Bird sound was converted to green, wave sound to red, and rain sound to red‐purple. The results were presented by textile designs. From these results, the ability of natural sounds to convert to colors was proven, so that the transformed colors can be used to help design textiles. © 2009 Wiley Periodicals, Inc.
Development of a usability evaluation framework with quality function deployment: From customer sensibility to product design
Authors: Jin Beom Suk , Ji Yong Gu , Choi Kyeyoun , Cho Gilsoo
Published: January 2009

The aim of this research was to develop a usability evaluation model based on customer sensation using quality function deployment (QFD), which evaluates the relationship between consumer sensation and usability among the physical design factors of dishwashers. Four aspects of the evaluation model were analyzed with QFD: overall sensation factors, detail sensation factors, usability evaluation factors, and physical design factors of products in 3 sequential processes. The sensation evaluation factors and the usability evaluation factors were created from the results of the sensation and usability tests. Moreover, experts and manufacturers were involved in selecting the physical design factors. With the evaluation model using these 4 aspects, physical design factors influencing user sensation were generated. These factors were Label Icon, Rack Size, Shape of Knob, and LCD size. In addition, the degree of influences was tested and design guidelines derived from the final physical design factors were generated. © 2009 Wiley Periodicals, Inc.
Running wild: Neurogenesis in the hippocampus across the lifespan in wild and laboratory‐bred Norway rats
Authors: Epp Jonathan Richard , Barker Jennifer Marie , Galea Liisa Ann Margaret
Published: January 2009

The dogmatic view that new neurons are not produced in the adult mammalian brain has been overturned in light of mounting evidence that neurogenesis continues to occur within two neurogenic niches, the subventricular zone and the hippocampus. In mammals, new neurons are incorporated into the hippocampus throughout life and are influenced by environmental and genetic factors. Most studies use captive‐bred animals, and no previous studies have examined neurogenesis in free‐living rats despite the common use of laboratory rats. In particular, exercise upregulates neurogenesis in the hippocampus and exercise levels would certainly differ between wild and captive populations. Therefore, it is unclear whether results from captive populations can be generalized to natural populations or reflect variations from an artificial and inappropriate “baseline” level. To address this, we compared levels of cell proliferation and the number of immature neurons (using the endogenous markers Ki67 and doublecortin, respectively) in captured wild juvenile and adult Norway rats to three captive strains (Sprague‐Dawley, Long‐Evans, and Brown Norway) of the same species. Here, we show that the level of cell proliferation and young immature neuron survival in the dentate gyrus of juvenile wild rats is significantly higher than in Sprague‐Dawley rats, but not Long‐Evans or Brown Norway rats. However, cell proliferation and the number of immature neurons in the hippocampus of adult wild rats are within the normal range of captive‐bred rats at all adult ages examined. This finding is surprising given the dissimilar environments, including stressors and opportunities for exercise, encountered by each population. © 2009 Wiley‐Liss, Inc.