bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of glycosylated haemoglobin level and diabetes mellitus duration with the severity of coronary artery disease
Authors: Saleem Tahir , Mohammad Kazim Hameedullah , Abdel-Fattah Moataz M , Abbasi Abdul Hafeez
Published: September 2008

Diabetes mellitus (DM) is known to cause microvascular and possibly macrovascular complications. This study was performed to find the association between glycosylated haemoglobin (HbA1C) level and the severity of coronary artery disease. One hundred and ten consecutive patients admitted to hospital with acute myocardial infarction were studied. Seventy-eight patients (70.9%) had DM, 73 (93.58%) had HbA1C > 7%, 52 (47.3%) were hypertensive, 19 (17.3%) had a history of smoking and 37 (33.6%) had raised cholesterol. Coronary angiography was carried out in 87 (79.1%) patients and the severity of disease was assessed using the Gensini score. The mean Gensini score was 53.36±36.94 and the mean HbA1C was 8.4±2.39%. There was a significant association between Gensini score and DM (p=0.003) and between Gensini score and hypertension (p=0.018). HbA1C (r=0.427, p=0.001) and duration of DM (r=0.362, p=0.004) had a positive linear correlation with the Gensini score. Multiple regression analysis showed HbA1C to be an independent factor that influenced the Gensini score (p=0.021).
Dominance of cytokine- over FasL-induced impairment of the mitochondrial transmembrane potential (ΔΨm) in the pancreatic β-cell line NIT-1
Authors: Augstein Petra , Heinke Peter , Salzsieder Eckhard , Grimm Rita , Giebel Jürgen , Salzsieder Christel , Harrison Leonard C
Published: September 2008

Mitochondria of pancreatic β-cells are potential targets of intrinsic and extrinsic apoptotic pathways in the autoimmune pathogenesis of type 1 diabetes. We aimed to investigate whether cytokine- and FasLigand (FasL)-induced apoptosis is associated with impaired mitochondrial transmembrane potential (ΔΨm) in the pancreatic β-cell line NIT-1. NIT-1 cells were exposed to the interleukin-1 β/interferon-γ (IL-1 β/IFN-γ) cytokine combination to induce apoptosis in vitro. Low concentrations of cytokines resulted in ΔΨm impairment, and increasing concentrations had only a minor additional effect. Treatment with the inducible nitric oxide synthase (iNOS) inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) prevented cytokine-mediated ΔΨm impairment, implying that cytokines affect ΔΨm via nitric oxide. The broad-spectrum caspase inhibitor Z-VAD(Ome)-FMK (ZVAD) revealed dichotomic actions. In the presence of ZVAD, cytokine-induced nitrite generation was increased but cell death and ΔΨm impairment were reduced. ΔΨm impairment was also reduced by inhibitors of caspases 1, 6 and 8. Induction of Fas by IL-1 β/IFN-γ coupled with activation by Super-FasL augmented cytokine-induced cell death. We observed a clear dominance of cytokine- over FasL-induced effects on ΔΨm.

Our findings show that IL-1 β/IFN-γ cytokines have a strong effect to impair ΔΨm and prime β-cells for apoptosis via the intrinsic pathway mediated by iNOS and caspases. Furthermore, at least in NIT-1 cells, the extrinsic FasL/Fas pathway has only a minor additive effect on cytokine-induced ΔΨm impairment.
The application of proteomics technology to thrombosis research: the identification of potential therapeutic targets in cardiovascular disease
Authors: Howes Joanna-Marie , Keen Jeff N , Findlay John BC , Carter Angela M
Published: September 2008

Thrombus formation underpins the development of cardiovascular diseases, including acute coronary syndromes and ischaemic stroke. A number of wellcharacterised cardiovascular risk factors which contribute to the development of the majority of cardiovascular events have been identified, including dyslipidaemia, hypertension and diabetes. Individuals with type 2 diabetes mellitus (T2DM) have a 3- to 5-fold increased risk for development of cardiovascular disease (CVD). They may have a cluster of haemostatic abnormalities, including elevated levels of plasminogen activator inhibitor-1 (PAI-1) and fibrinogen, which contribute to acute thrombotic events. It is clear that additional unidentified risk factors contribute to the pathogenesis of cardiovascular events, and so the search for novel biomarkers and effectors, particularly in individuals with T2DM, remains a major challenge of cardiovascular medicine.

Plasma and cellular proteins which contribute to thrombus formation have the potential to confer a prothrombotic state and represent a link between genotype, environment and disease phenotype. The comprehensive analysis of these proteins is now increasingly facilitated through the continued development of proteomic technologies which provide multifaceted approaches to the identification of novel biomarkers and/or effectors of thrombus formation and on which future anticoagulant and thrombolytic therapies may be based.

This review provides an overview of current proteomic technologies. It focuses on the recent studies in which these technologies have been applied in the search for novel proteins that may confer increased risk of acute cardiovascular diseases and therefore that may influence disease progression and therapy.
Comparing measures of cognitive bias relating to eating behaviour
Authors: Pothos Emmanuel M. , Calitri Raff , Tapper Katy , Brunstrom Jeffrey M. , Rogers Peter J.
Published: September 2008

Consumption of and/or abstinence from substances with a high reward value (e.g. heroin, marijuana, alcohol, nicotine, certain foods) are associated with cognitive biases for information related to the substance. Such cognitive biases are important since they may contribute to difficulties in controlling intake of the substance. We examine cognitive biases for stimuli related to food. For the first time, we concurrently employ and compare five conceptually distinct measures of cognitive bias (dot probe, emotional Stroop, recognition, EAST, explicit attitudes). Contrary to expectations from current theory, the relation between the cognitive measures was weak and evident only in certain subsets of the population sample, as defined by gender and emotional‐, restrained‐ and external‐eating characteristics of our participants. We discuss some methodological implications of our findings. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of mugshot commitment on lineup performance in young and older adults
Authors: Goodsell Charles A. , Neuschatz Jeffrey S. , Gronlund Scott D.
Published: September 2008

Two experiments assessed the effects of mugshot commitment on the ability to make a subsequent lineup identification. Young (17–37 years) and older (55–87 years) participants viewed a crime video featuring a younger (20 years) or older (64 years) culprit. Some participants viewed a 50‐photograph culprit‐absent mugbook. Following a 1‐week delay, participants returned to view a culprit present lineup. In Experiment 1, mugbook choosers tended to select their prior selection in the lineup and mugbook nonchoosers tended to reject the lineup. In Experiment 2, mugshot choosers rejected a lineup that did not contain their prior selection. Commitment to a prior selection and commitment to a selection strategy were the cause of the majority of lineup errors. As previously reported, mugshot exposure harms subsequent lineup identification, and this appears to be primarily the result of commitment effects. Copyright © 2008 John Wiley & Sons, Ltd.
Illustrating computational solvent screening: Prediction of standard Gibbs energies of reaction in solution
Authors: Peters Martina , Greiner Lasse , Leonhard Kai
Published: September 2008

Prediction of thermodynamic properties of new compounds or mixtures is industrially important, especially when processes are established or alternatives for existing processes are evaluated. Of particular importance is the equilibrium constant, derived from the standard Gibbs energy of reaction in solution. Up to date, experimental determination is challenging, mirrored by a lack of data available. A straightforward computational way for the prediction using quantum mechanics and statistical thermodynamics is presented. The use of three standard quantum chemical methods for the determination of the ground state energies enables a comparison in terms of accuracy and computational cost. The results show that the two most laborious methods coupled cluster with single and double excitations and perturbative triple excitations and MP2 lead to comparable accuracy, whereas the fastest method density functional theory leads to considerable deviations. Hence, the method of choice for the prediction of standard Gibbs energies of reaction in solution with good accuracy at medium computational cost is MP2 combined with conductor‐like screening model for real solvents COSMO‐RS. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Ferrocenylimidazoline palladacycles as efficient catalysts for the aza‐Claisen rearrangement reaction of allylic imidates
Authors: Cui Xiuling , Ma Ji , Yang Dejian , Wu Junliang , Song Maoping , Wu Yangjie
Published: September 2008

Chloride‐bridged palladacycle dimers 1 have been evaluated as catalysts for the aza‐Claisen rearrangement of allylic imidates 2 to the corresponding allyl amides 3. Cyclopalladated complexes 1b–e bearing electron‐donating substituents on imidazoline ring were identified as being superior catalysts because excellent yields were obtained without using silver salts for activation. In addition, a correlation between substituents on the imidazoline ring and catalytic activity of palladacycles was established. The electron‐deficient ligands and good solubility of catalysts in the reaction solution increase the catalytic activity. Copyright © 2008 John Wiley & Sons, Ltd.
Styrene polymerization with nickel complexes/methylaluminoxane catalytic system
Authors: Li Yongfei , Gao Meili , Wu Qing
Published: September 2008

Polymerization of styrene using β‐diketiminate nickel (II) bromide complexes CH{C(R)NAr}2NiBr (R = CH3, Ar = 2,6‐iPr2C6H3, 1; R = CH3, Ar = 2,6‐Me2C6H3, 2; R = CF3, Ar = 2,6‐iPr2C6H3, 3; R = CF3, Ar = 2,6‐Me2C6H3, 4) in the presence of methylaluminoxane was studied. Compound 3 is the most active styrene polymerization catalyst of all the nickel complexes tested. The activity of these catalysts increases with increases in steric bulk of the substituents on the aryl rings. The electronic nature of the ligand backbone also affects the activity. Weight‐average molecular weight of the prepared polystyrene ranges from 21 000 to 72 000, with polydispersity indexes of 1.95–2.78. The microstructure of the obtained products is atactic polystyrenes from NMR analyses. Copyright © 2008 John Wiley & Sons, Ltd.
Dodo birds, doctors and the evidence of evidence
Authors: Freddi Jason
Published: September 2008

This paper asks what is evidence‐based psychology and looks at the ways in which psychoanalysts have sought to engage with the challenges posed by this method of deciding best science. The paper examines the evidence for the evidence‐based method and looks at how psychoanalysts have attempted to shift the scientific debate from evidence‐based models to practice‐based, outcome driven models and, ultimately, to a patient‐therapy approach that seeks to marry best practice with a spirit of open‐minded assessment of alternatives. Copyright © 2008 John Wiley & Sons, Ltd.
Sexual boundary violations in residential drug‐free therapeutic community treatment
Authors: Gottdiener William H.
Published: September 2008

The purpose of this study was to investigate the phenomenon of sexual boundary violations in residential therapeutic community (TC) programs for substance abusers using secondary data analysis methods. One hundred and ninety‐seven participants who had been treated in TCs in New York City were interviewed 30 days post‐discharge. Sexual boundary violations were reported by approximately one‐quarter of the sample. Possible psychodynamic causes (e.g. enactments, group dynamics) of sexual boundary violations are discussed. Implications for research, theory, and for prevention of sexual boundary violations in TC programs are addressed. Copyright © 2008 John Wiley & Sons, Ltd.
On the use of archetypes as benchmarks
Authors: Porzio Giovanni C. , Ragozini Giancarlo , Vistocco Domenico
Published: September 2008

Benchmarking plays a relevant role in performance analysis, and statistical methods can be fruitfully exploited for its aims. While clustering, regression, and frontier analysis may serve some benchmarking purposes, we propose to consider archetypal analysis as a suitable technique. Archetypes are extreme points that synthesize data and that, in our opinion, can be profitably used as benchmarks. That is, they may be viewed as key reference performers in the comparison process. We suggest a three‐step data driven benchmarking procedure, which enables users: (i) to identify some reference performers, (ii) to analyze their features, (iii) to compare observed performers with them. An exploratory point of view is preferred, and graphical devices are adopted throughout the procedure. Finally, our approach is presented by means of an illustrative example based onThe Timesleague table of the world top 200 universities. Copyright © 2008 John Wiley & Sons, Ltd.
Interleukin‐18 and gestosis: correlation with Helicobacter pylori seropositivity
Authors: Pugliese Agostino , Beltramo Tiziana , Todros Tullia , Cardaropoli Simona , Ponzetto Antonio
Published: September 2008

The aim of this brief communication was to determine the correlation between pre‐eclampsia (PE), Helicobacter pylori pathogenic strains seropositivity, and interleukin‐18 (IL‐18) levels. To this purpose 25 pre‐eclamptic women and 25 healthy parturient women of similar age were evaluated for:

IL‐18 levels, by ELISA

H. pylori seropositivity, by anti‐IgG ELISA

Anti‐Cag‐A antibodies using a commercial immunoblot assay.

We report similar values of IL‐18 in our pre‐eclamptic patients and in healthy parturient women (respectively 350 ± 150 vs. 399 ± 132 pg ml−1; p = 0.23). However the seropositivity for H. pylori was 84 and 32% (p < 0.001), and anti‐Cag‐A antibodies were present respectively in 80 and 28% of the two populations. On the basis of our data we hypothesize that H. pylori infection from Cag‐A strains can be involved in some cases of PE and that the microorganism could modulate IL‐18 release. In fact, differences on IL‐18 production have been described by different authors between pre‐eclamptic and healthy pregnant women, independently from infective pathology. Copyright © 2008 John Wiley & Sons, Ltd.
Improved inter‐modality image registration using normalized mutual information with coarse‐binned histograms
Authors: Nam Haewon , Renaut Rosemary A. , Chen Kewei , Guo Hongbin , Farin Gerald E.
Published: September 2008

In this paper we extend the method of inter‐modality image registration using the maximization of normalized mutual information (NMI) for the registration of [18F]‐2‐fluoro‐deoxy‐D‐glucose (FDG)‐positron emission tomography (PET) with T1‐weighted magnetic resonance (MR) volumes. We investigate the impact on the NMI maximization with respect to using coarse‐to‐fine grained B‐spline bases and to the number of bins required for the voxel intensity histograms of each volume. Our results demonstrate that the efficiency and accuracy of elastic, as well as rigid body, registration is improved both through the use of a reduced number of bins in the PET and MR histograms, and of a limited coarse‐to‐fine grain interpolation of the volume data. To determine the appropriate number of bins prior to registration, we consider the NMI between the two volumes, the mutual information content of the two volumes, as a function of the binning of each volume. Simulated data sets are used for validation and the registration improves that obtained with a standard approach based on the Statistical Parametric Mapping software. Copyright © 2008 John Wiley & Sons, Ltd.
Development and evaluation of a stabilized whole‐blood preparation as a process control material for screening of paroxysmal nocturnal hemoglobinuria by flow cytometry
Authors: Richards Stephen J. , Whitby Liam , Cullen Matthew J. , Dickinson Anita J. , Granger Viv , Reilly John T. , Hillmen Peter , Barnett David
Published: September 2008

Background:

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder in which correct diagnosis is essential for effective patient management. Demonstration of deficiency of glycosylphosphatidylinositol (GPI)‐linked antigens from red cells and/or granulocytes by flow cytometry represents a highly specific diagnostic test for PNH. Currently, no external quality assessment (EQA) programme or reference material is available for whole‐blood PNH testing (red cells and leucocytes) by flow cytometry.

Methods:

In order to address this issue, we report the development of a stabilized whole‐blood PNH sample. We present the results of a detailed time course study by flow cytometry that demonstrates the stability of GPI‐linked antigen expression on granulocytes and red cells in a stabilized PNH peripheral blood sample, using a previously described method.

Results:

The PNH cells, as well as the coexisting normal red cell and granulocyte populations, remained stable for up to 120 days, both in terms of immunophenotypic and light scatter characteristics. Subsequent samples were used for a PNH EQA programme and issued to 92 laboratories worldwide.

Conclusions:

This study has highlighted that PNH testing by flow cytometry has significant problems with regard to false‐positive and ‐negative results. In addition, the variation in GPI‐linked antigen detection methods has highlighted the urgent need for standardized protocols. © 2008 Clinical Cytometry Society
Experience‐dependent refinement of the inhibitory axons projecting to the medial superior olive
Authors: Werthat Florian , Alexandrova Olga , Grothe Benedikt , Koch Ursula
Published: September 2008

Neurons in the medial superior olive (MSO) analyze interaural time differences (ITDs) by comparing the arrival times of the two excitatory inputs from each ear using a coincidence detection mechanism. They also receive a prominent inhibitory, glycinergic projection from the ipsilateral medial nucleus of the trapezoid body (MNTB), which contributes to the fine‐tuning of ITD analysis. Here, we investigated developmental changes of the axonal arborisation pattern of single Microruby‐labeled MNTB neurons projecting to the MSO region. During the first 2 weeks after hearing onset, the axonal arborisation of MNTB neurons was significantly refined resulting in a narrowed projection area across the tonotopic axis of the MSO and a redistribution of the axonal endsegments to a mostly somatic location. Rearing the animals in omnidirectional noise prevented the structural changes of single MNTB projections. These results indicate that the functional elimination of inhibitory inputs on MSO neurons after hearing onset, as described previously, is paralleled by a structural, site‐specific refinement of the inputs and is dependent on the normal acoustic experience of the animal. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Extrinsic embryonic sensory stimulation alters multimodal behavior and cellular activation
Authors: Markham Rebecca G. , Shimizu Toru , Lickliter Robert
Published: September 2008

Embryonic vision is generated and maintained by spontaneous neuronal activation patterns, yet extrinsic stimulation also sculpts sensory development. Because the sensory and motor systems are interconnected in embryogenesis, how extrinsic sensory activation guides multimodal differentiation is an important topic. Further, it is unknown whether extrinsic stimulation experienced near sensory sensitivity onset contributes to persistent brain changes, ultimately affecting postnatal behavior. To determine the effects of extrinsic stimulation on multimodal development, we delivered auditory stimulation to bobwhite quail groups during early, middle, or late embryogenesis, and then tested postnatal behavioral responsiveness to auditory or visual cues. Auditory preference tendencies were more consistently toward the conspecific stimulus for animals stimulated during late embryogenesis. Groups stimulated during middle or late embryogenesis showed altered postnatal species‐typical visual responsiveness, demonstrating a persistent multimodal effect. We also examined whether auditory‐related brain regions are receptive to extrinsic input during middle embryogenesis by measuring postnatal cellular activation. Stimulated birds showed a greater number of ZENK‐immunopositive cells per unit volume of brain tissue in deep optic tectum, a midbrain region strongly implicated in multimodal function. We observed similar results in the medial and caudomedial nidopallia in the telencephalon. There were no ZENK differences between groups in inferior colliculus or in caudolateral nidopallium, avian analog to prefrontal cortex. To our knowledge, these are the first results linking extrinsic stimulation delivered so early in embryogenesis to changes in postnatal multimodal behavior and cellular activation. The potential role of competitive interactions between the sensory and motor systems is discussed. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Synthesis and Enzymatic Incorporation of Modified Deoxyadenosine Triphosphates
Authors: Lam Curtis , Hipolito Christopher , Perrin David M.
Published: September 2008

Several deoxyadenosine triphosphates containing modifications at the 8‐position have been synthesized. Suitably protected 8‐bromodeoxyadenosines were coupled with five imidazole‐containing moieties by nucleophilic aromatic substitution or Sonagashira coupling to give modified nucleosides that were then triphosphorylated. Incorporation assays were performed for these modified residues with many commercially available DNA polymerases, and it was found that two of the modified dATPs could be effectively taken up as substrates by Sequenase V2.0. These two residues are candidates for substrates in combinatorial selections in the search for improved catalysis from DNAzymes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis of New Allocolchicinoids with Seven‐ and Eight‐Membered B‐Rings by Enyne Ring‐Closing Metathesis
Authors: Boyer François‐Didier , Hanna Issam
Published: September 2008

Total syntheses of allocolchicines 4 and 5, with the ester functionality in the C‐ring at the C10 or C11 positions, is reported. An asymmetric synthesis of (7S)‐allocolchicine 5 is also described. The main features included the elaboration of a common intermediate, the AB bicyclic ring system, in which the construction of the seven‐membered ring was achieved by an enyne ring‐closing metathesis (RCM) reaction. A subsequent Diels–Alder/aromatization sequence afforded the set of functionalized ring‐C allocolchicinoids with high regioselectivity. This strategy was also applied for the synthesis of allocolchicine 6, containing an eight‐membered B‐ring.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Forecasting volatility with outliers in GARCH models
Authors: Charles Amélie
Published: September 2008

In this paper, we detect and correct abnormal returns in 17 French stocks returns and the French index CAC40 from additive‐outlier detection method in GARCH models developed by Franses and Ghijsels (1999) and extended to innovative outliers by Charles and Darné (2005). We study the effects of outlying observations on several popular econometric tests. Moreover, we show that the parameters of the equation governing the volatility dynamics are biased when we do not take into account additive and innovative outliers. Finally, we show that the volatility forecast is better when the data are cleaned of outliers for several step‐ahead forecasts (short, medium‐ and long‐term) even if we consider a GARCH‐t process. Copyright © 2008 John Wiley & Sons, Ltd.
Expectations, use and judgmental adjustment of external financial and economic forecasts: an empirical investigation
Authors: Gönül Sinan , Önkal Dilek , Goodwin Paul
Published: September 2008

A survey of 124 users of externally produced financial and economic forecasts in Turkey investigated their expectations and perceptions of forecast quality and their reasons for judgmentally adjusting forecasts. Expectations and quality perceptions mainly related to the timeliness of forecasts, the provision of a clear justifiable rationale and accuracy. Cost was less important. Forecasts were frequently adjusted when they lacked a justifiable explanation, when the user felt they could integrate their knowledge into the forecast, or where the user perceived a need to take responsibility for the forecast. Forecasts were less frequently adjusted when they came from a well‐known source and were based on sound explanations and assumptions. The presence of feedback on accuracy reduced the influence of these factors. The seniority and experience of users had little effect on their attitudes or propensity to make adjustments. Copyright © 2008 John Wiley & Sons, Ltd.
Sports forecasting: a comparison of the forecast accuracy of prediction markets, betting odds and tipsters
Authors: Spann Martin , Skiera Bernd
Published: September 2008

This article compares the forecast accuracy of different methods, namely prediction markets, tipsters and betting odds, and assesses the ability of prediction markets and tipsters to generate profits systematically in a betting market. We present the results of an empirical study that uses data from 678–837 games of three seasons of the German premier soccer league. Prediction markets and betting odds perform equally well in terms of forecasting accuracy, but both methods strongly outperform tipsters. A weighting‐based combination of the forecasts of these methods leads to a slightly higher forecast accuracy, whereas a rule‐based combination improves forecast accuracy substantially. However, none of the forecasts leads to systematic monetary gains in betting markets because of the high fees (25%) charged by the state‐owned bookmaker in Germany. Lower fees (e.g., approximately 12% or 0%) would provide systematic profits if punters exploited the information from prediction markets and bet only on a selected number of games. Copyright © 2008 John Wiley & Sons, Ltd.
Parsimonious modeling and forecasting of corporate yield curve
Authors: Yu Wei‐Choun , Salyards Donald M.
Published: September 2008

This paper investigates the sensitivity of out‐of‐sample forecasting performance over a span of different parameters of l in the dynamic Nelson–Siegel three‐factor AR(1) model. First, we find that the ad hoc selection of l is not optimal. Second, we find a substantial difference in factor dynamics between investment‐grade and speculative‐grade corporate bonds from 1994:12 to 2006: 4. Third, we suggest that the three‐factor model is sufficient to explain the main variations of corporate yield changes. Finally, the parsimonious Nelson–Siegel three‐factor AR(1) model remains competitive in the out‐of‐sample forecasting of corporate yields. Copyright © 2008 John Wiley & Sons, Ltd.
Discriminating accuracy of medial temporal lobe volumetry and fMRI in mild cognitive impairment
Authors: Jauhiainen Anne M. , Pihlajamäki Maija , Tervo Susanna , Niskanen Eini , Tanila Heikki , Hänninen Tuomo , Vanninen Ritva L. , Soininen Hilkka
Published: September 2008

We investigated structural and functional changes in the medial temporal lobe (MTL) using magnetic resonance imaging (MRI) and compared the discriminative power of these measures with neuropsychological testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Functional MRI (fMRI) was performed in 21 elderly controls, 14 MCI subjects, and 15 mild AD patients during encoding and cued retrieval of word‐picture pairs. A region‐of‐interest‐based approach in SPM2 was used to extract the extent of hippocampal activation. The volumes of the hippocampus and entorhinal cortex (EC) were manually outlined from anatomical MR images. Discriminant analyses were conducted to assess the ability of hippocampal fMRI, MTL volumetry, and neuropsychological measures to classify subjects into clinical groups. Entorhinal but not hippocampal volumes differed significantly between the control and MCI subjects. Both entorhinal and hippocampal volumes differed between MCI and AD patients. There were no significant differences in the extent of hippocampal fMRI activation during encoding or retrieval between the groups. Entorhinal volume was the best discriminator with a discriminating accuracy of 85.7% between controls and MCI, 86.2% between MCI and AD, and 97.2% between controls and AD. Delayed recall of a wordlist classified the subjects, second best, with a discriminating accuracy of 81.8% between controls and MCI, 75% between MCI and AD and 93.5% between controls and AD. The accuracy of hippocampal volumetry ranged from 42.9 to 69.4%, and hippocampal fMRI activation during encoding and retrieval had a classification accuracy of only 41.4–57.7% between the groups. Our results suggest that evaluation of entorhinal atrophy, in addition to the prevailing diagnostic criteria, seems promising in the identification of prodromal AD. Future technical improvements may improve the utilization of hippocampal fMRI for early diagnostic purposes. © 2008 Wiley‐Liss, Inc.
Stromal myofibroblasts are drivers of invasive cancer growth
Authors: De Wever Olivier , Demetter Pieter , Mareel Marc , Bracke Marc
Published: September 2008

Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer‐associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow‐derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor‐associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth‐promoting factors, through direct cell–cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis. © 2008 Wiley‐Liss, Inc.
A new method for creating maps of artificially drained areas in large river basins based on aerial photographs and geodata
Authors: Tetzlaff Björn , Kuhr Petra , Wendland Frank
Published: September 2008

With regard to the creation of river basin plans and programmes of measures according to the EU Water Framework Directive, the importance of model‐supported analyses of nutrient inputs into aquatic systems and the localization of source areas is increasing. Especially in lowland regions artificial drainage installations play a major role, but little information exists concerning their location within larger river basins. Therefore, artificially drained lands were identified by interpreting aerial photographs and typical site conditions of the drained plots were derived. A GIS‐based approach was then developed, which allows the delineation of artificially drained lands by combining various site conditions like soil properties and land use type. After checking the validity of a derived map for the River Ems basin (12 940 km2) with small‐scale drainage installation maps, the approach was applied to northwestern Germany (98 000 km2). This was followed by a discussion of results and uncertainties. Copyright © 2008 John Wiley & Sons, Ltd.
Residual total protein and total organic carbon levels on reprocessed gastrointestinal (GI) biopsy forceps
Authors: Lappalainen Sharon K. , Gomatam Shanti V. , Hitchins Victoria M.
Published: September 2008

Many single‐use (disposable) devices are reprocessed between patient uses. In the past, a visual determination was considered the endpoint of “clean” for cleaned reusable devices. In this report, we measured quantitative endpoints by measuring residual total protein and residual total organic carbon before and after cleaning with commercially available cleaners for medical devices on 15 single‐use gastrointestinal biopsy forceps inoculated with a three‐protein test soil before and after cleaning. Each device was extracted separately and tested using Bradford's reagent for total protein and a direct digestion method for total organic carbon. Data for pre‐ and post‐cleaned devices were generated for all five cleaning cycles. The highest amounts of residual total protein and total organic carbon found on precleaned devices were 61.8 μg/cm2 and 39.1 μg/cm2, respectively, on the outer surfaces. The highest amounts of residual total protein and total organic carbon on postcleaned device extracts were 4.0 μg/cm2 and 2.2 μg/cm2, respectively, on the outer surfaces. All postcleaned devices were visually clean. Our results provide quantitative total protein and total organic carbon levels for cleaned single‐use biopsy forceps. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Surfactant effects on the kinetics of Michael‐type addition reaction in reverse emulsion polymeric systems
Authors: McLemore Ryan , Lee Bae Hoon , Vernon Brent
Published: September 2008

To ensure patients' safety during vascular surgery involving polymer injection, it is important to ensure a high degree of control over the gelation rate of the materials to prevent the formation of uncontrolled emboli from shear or dispersion. Through manipulation of factors affecting the kinetics of in situ forming polymeric systems, patients' safety can be maximized. The rate of Michael‐Type Addition is known to be affected by the pH of the accompanying solution, as thiols will become nucleophilic thiolates in an aqueous environment. This work evaluates the effect of the addition of 2 and 4 wt % of several common surfactants on the gelation rate of reverse emulsion polymeric systems as a method for augmenting control of in vivo Michael‐type addition kinetics. This work shows that both Tween‐20 (HLB 16.7) and Pluronic type surfactants (HLB ∽ 6.7) stabilize our emulsion, with gelation rates being significantly different in the presence of Pluronic type surfactants (p < 0.05). This work has demonstrated the ability of surfactants to promote faster gelation at lower pH by maximizing emulsion stability and reducing cohesion of smaller bubbles, thereby maximizing surface area between the initiator and the bulk phases. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Experimental optimization of an in situ forming hydrogel for hemorrhage control
Authors: Peng Henry T. , Blostein Mark D. , Shek Pang N.
Published: September 2008

The fabrication of a novel in situ forming hydrogel composed of a multifunctional poly(ethylene glycol) (PEG) N‐hydroxysuccinimide ester (NHS) and poly(allylamine hydrochloride) (PAA) was investigated. FTIR confirmed that PAA formed the hydrogel matrix (i.e., the formation of a PAA‐like hydrogel). A factorial experiment was conducted to identify the key parameters that controlled gelation time, gel content, and swelling properties. The type of PEG (e.g., 4‐ and 6‐arm) appeared to play a major role in determining all three performance parameters, with the greatest effect on gelation time. Other influencing factors include (a) the PEG concentration, which contributes to the gelation time and gel content; (b) pH of the buffer used for dissolving each polymer, which can affect the gelation time; and (c) PAA molecular weights, which contribute to the gel content and swelling. The concentration of PAA solution had no significant effects on hydrogel formation and properties within the investigated range, presumably due to negligible changes in the crosslinking density of the hydrogels. The PAA buffer pH influenced the gel content as well. Finally, thromboelastography was used to examine the effects of each polymer and their in situ gelation on blood coagulation in vitro. All individual polymers tested reduced clot strength, while the gelation of the polymers enhanced overall procoagulant effects. These results suggest that the biomaterial can be optimized to provide a combination of rapid gelation and swelling properties suitable for hemorrhage control and thus warrant further studies in animal bleeding models. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Drak2 overexpression results in increased β‐cell apoptosis after free fatty acid stimulation
Authors: Mao Jianning , Luo Hongyu , Wu Jiangping
Published: September 2008

Drak2 is a serine threonine kinase in the death‐associated protein family. In this study, we investigated its role in free fatty acid (FFA)‐induced islet apoptosis. Drak2 mRNA and protein were rapidly induced in islet β‐cells after FFA stimulation. Such Drak2 upregulation was accompanied by increased β‐cell apoptosis, which was inhibited by Drak2 knockdown using siRNA. Conversely, transgenic (Tg) Drak2 overexpression led to aggravated β‐cell apoptosis triggered by FFA. Drak2 overexpression in islets compromised the increase of anti‐apoptotic factors, such as Bcl‐2, Bcl‐xL and Flip, upon FFA assault. Further in vivo experiments demonstrated that Drak2 Tg mice presented compromised glucose tolerance in a diet‐induced obesity model. Our data show that Drak2 is detrimental to islet survival in the presence of excessive lipid. J. Cell. Biochem. 105: 1073–1080, 2008. © 2008 Wiley‐Liss, Inc.
Microsatellite DNA markers applied to detection of multiple paternity in Caiman latirostris in Santa Fe, Argentina
Authors: Amavet Patricia , Rosso Esteban , Markariani Rosa , Piña Carlos Ignacio
Published: September 2008

Detecting multiple paternity in wild populations of the broad‐snouted caiman (Caiman latirostris) has important implications for conservation efforts. We have applied microsatellite markers to examine genetic variation in C. latirostris and also have provided the first data concerning detection of multiple paternity in wild populations of this species. Blood samples from four nest‐guarding C. latirostris females and their hatchlings were obtained from Santa Fe Province, Argentina. Amplified products were analyzed by electrophoresis on 10% polyacrylamide gels and visualized with silver staining. Four out of the eight markers tested reliably amplified and yielded useful data. Using polyacrylamide gels with silver staining provides high enough resolution to obtain individual genotypes. In order to assess the presence or absence of more than two parents in each nest, we used the single locus Minimum Method, and applied Cervus 3.0 and Gerud 2.0 software in parentage analyses. Our results indicate more than one father in at least two families. This behavior could be the consequence of high habitat variability in the area where our population was sampled. The ability to understand mating systems is important for maintaining viable populations of exploited taxa like C. latirostris. J. Exp. Zool. 309A:637–642, 2008. © 2008 Wiley‐Liss, Inc.
Homologous and heterologous recombination between adenovirus vector DNA and chromosomal DNA
Authors: Stephen Sam Laurel , Sivanandam Vijayshankar Ganesh , Kochanek Stefan
Published: September 2008

Background

Adenovirus vector DNA is perceived to remain as episome following gene transfer. We quantitatively and qualitatively analysed recombination between high capacity adenoviral vector (HC‐AdV) and chromosomal DNA following gene transfer in vitro.

Methods

We studied homologous and heterologous recombination with a single HC‐AdV carrying (i) a large genomic HPRT fragment with the HPRT CHICAGO mutation causing translational stop upon homologous recombination with the HPRT locus and (ii) a selection marker to allow for clonal selection in the event of heterologous recombination. We analysed the sequences at the junctions between vector and chromosomal DNA.

Results

In primary cells and in cell lines, the frequency of homologous recombination ranged from 2 × 10−5 to 1.6 × 10−6. Heterologous recombination occurred at rates between 5.5 × 10−3 and 1.1 × 10−4. HC‐AdV DNA integrated via the termini mostly as intact molecules. Analysis of the junction sequences indicated vector integration in a relatively random manner without an obvious preference for particular chromosomal regions, but with a preference for integration into genes. Integration into protooncogenes or tumor suppressor genes was not observed. Patchy homologies between vector termini and chromosomal DNA were found at the site of integration. Although the majority of integrations had occurred without causing mutations in the chromosomal DNA, cases of nucleotide substitutions and insertions were observed. In several cases, deletions of even relative large chromosomal regions were likely.

Conclusions

These results extend previous information on the integration patterns of adenovirus vector DNA and contribute to a risk–benefit assessment of adenovirus‐mediated gene transfer. Copyright © 2008 John Wiley & Sons, Ltd.
A comparative analysis of constitutive and cell‐specific promoters in the adult mouse hippocampus using lentivirus vector‐mediated gene transfer
Authors: Kuroda Hitoshi , Kutner Robert H. , Bazan Nicolas G. , Reiser Jakob
Published: September 2008

Background

Viral vectors provide powerful tools for transgene delivery to the mammalian brain to assess the effects of therapeutic proteins, antisense RNAs or small interfering RNAs. A key advantage of such approaches is that specific brain regions implicated in a particular disease can be independently targeted.

Methods

To optimize transgene expression in sub‐regions of the mouse hippocampus and with a view towards devising gene therapy strategies for Alzheimer's disease, we designed lentivirus‐based reporter vectors bearing various promoters, including constitutive and cell‐specific promoters. Furthermore, we devised methods allowing a side‐by‐side comparison of transgene expression levels in neural cells both in vitro and in vivo.

Results

Following stereotaxic injection into the adult mouse hippocampus, titer‐adjusted lentiviral vectors bearing constitutive promoters resulted in robust and sub‐region‐specific transgene expression. Our results show that the human CMV‐IE promoter resulted in efficient transgene expression in the entire hippocampus whereas transgene expression mediated by the hybrid hEF1α/HTLV promoter was limited mainly in the dentate gyrus and the CA2/3 region. Finally, the neuron‐specific human synapsin I promoter was particularly effective in the dentate gyrus.

Conclusions

These findings indicate that subregion‐specific transgene expression in the hippocampus can be achieved following lentivirus vector‐mediated gene transfer. Copyright © 2008 John Wiley & Sons, Ltd.
Skeletal indicators of locomotor adaptations in living and extinct rodents
Authors: Samuels Joshua X. , Van Valkenburgh Blaire
Published: September 2008

Living rodents show great diversity in their locomotor habits, including semiaquatic, arboreal, fossorial, ricochetal, and gliding species from multiple families. To assess the association between limb morphology and locomotor habits, the appendicular skeletons of 65 rodent genera from 16 families were measured. Ecomorphological analyses of various locomotor types revealed consistent differences in postcranial skeletal morphology that relate to functionally important traits. Behaviorally similar taxa showed convergent morphological characters, despite distinct evolutionary histories. Semiaquatic rodents displayed relatively robust bones, enlarged muscular attachments, short femora, and elongate hind feet. Arboreal rodents had relatively elongate humeri and digits, short olecranon processes of the ulnae, and equally proportioned fore and hind limbs. Fossorial rodents showed relatively robust bones, enlarged muscular attachments, short antebrachii and digits, elongate manual claws, and reduced hind limb elements. Ricochetal rodents displayed relatively proximal insertion of muscles, disproportionate limbs, elongate tibiae, and elongate hind feet. Gliding rodents had relatively elongate and gracile bones, short olecranon processes of the ulnae, and equally proportioned fore and hind limbs. The morphological differences observed here can readily be used to discriminate extant rodents with different locomotor strategies. This suggests that the method could be applied to extinct rodents, regardless of ancestry, to accurately infer their locomotor ecologies. When applied to an extinct group of rodents, we found two distinct ecomorphs represented in the beaver family (Castoridae), semiaquatic and semifossorial. There was also a progressive trend toward increased body size and increased aquatic specialization in the giant beaver lineage (Castoroidinae). J. Morphol., 2008. © 2008 Wiley‐Liss, Inc.
Accumulation of yolk in a caecilian (Gegeneophis ramaswamii) oocyte: A light and transmission electron microscopic study
Authors: Beyo Reston S. , Divya Lekha , Oommen Oommen V. , Akbarsha Mohammad A.
Published: September 2008

There is a paucity of information on the female reproductive biology of the caecilian amphibians when compared with the other vertebrate groups. Hence, the accumulation of nutrient reserves in the form of yolk and formation of yolk platelets were studied in Gegeneophis ramaswamii, adopting light microscopic histological and transmission electron microscopy analysis. Previtellogenic as well as vitellogenic follicles were observed in appropriate preparations. On the basis of the source and the routes of entry, we identified four types of yolk precursor materials, precursors 1 to 4. The earliest material appearing in the oocyte consists of abundant lipid vesicles during the previtellogenic phase, i.e., much before the follicular epithelium is fully established. This is a contribution from the oocyte mitochondria, which we identified as yolk precursor material 1, and it is autosynthetic. Once the follicle cell‐oocyte interface is fully established, there is an accumulation of the principal component of the heterosynthetic yolk by sequestration from the blood through the intercellular spaces between follicle cells in a pinocytic process. This we identified as yolk precursor material 2. There was also an indication of a lipidic yolk material synthesis in the follicle cells sequestered from maternal blood through the follicle cells in an endocytic process in which the macrovilli of follicle cells and the microvilli of the oocyte play a role. This we identified as yolk precursor material 3. Contribution to the yolk of peptidic, glycosidic, and/or lipidic material synthesized in the vitellogenic oocyte was also indicated. This we identified as yolk precursor material 4. The sequential development of intercellular associations and indications of synthesis/sequestration of the yolk have been traced. Thus, we report the mechanistic details of synthesis/sequestration of the yolk materials in a caecilian. J. Morphol., 2008. © 2008 Wiley‐Liss, Inc.