bluuebunny/crossref_metadata_2025 huggingface dataset:
LC‐APCI mass spectrometric method development and validation for the determination of atovaquone in human plasma
Authors: Gurule Sanjay , Goswami Dipanjan , Khuroo Arshad H. , Monif Tausif
Published: August 2009

A newly developed LC—APCI mass spectrometric method is described for human plasma determination of atovaquone using lapachol internal standard. A single‐step protein precipitation technique for plasma extraction of atovaquone achieving mean recovery of 94.17% (CV 8%) without compromising sensitivity (limit of quantitation 50.3 ng/mL) or linearity (50.3 ng/mL—23924.6 ng/mL) is delineated in this paper. Heated nebulizer in negative multiple reaction monitoring mode was employed with transitions m/z 365.2 → m/z 337.1 and m/z 240.9 → m/z 185.7 for atovaquone and lapachol respectively in this liquid chromatographic–tandem mass spectrometric method. Excellent chromatographic separation on a Synergi 4 μ Polar‐RP 80A (150 × 2.0 mm) column, using 100 μL of plasma extraction volume along with 10 μL of injection load, completing analysis run‐time within 2.5 min, highlights this simple yet unique bioanalytical method. The developed method can be successfully applied to pharmacokinetic studies on atovaquone suspension administered in healthy volunteers or HIV‐infected patients. Moreover full method validation results not published before are presented and discussed in detail for the first time in this article. Copyright © 2009 John Wiley & Sons, Ltd.
The effects of source likeability and need for cognition on advertising effectiveness under explicit persuasion
Authors: Reinhard Marc‐André , Messner Matthias
Published: August 2009

While there is evidence that an endorser's likeability plays a determining role in the advertising effectiveness of explicit persuasive appeals, this paper examines the impact of the need for cognition (NFC) as a moderator of this relationship. We find that this effect holds, as predicted, for individuals with lower NFC, but not for those with higher NFC. Furthermore, the effects of explicit persuasion and the endorser's likeability on evaluations of products or services by lower‐NFC consumers were found to be mediated by the attribution of self‐interest. In contrast, advertising effectiveness for higher‐NFC consumers was predictable only by the valence of their cognitive responses to the product.

Copyright © 2009 John Wiley & Sons, Ltd.
Insiders, regulars and tourists: exploring selves and music consumption in adolescence
Authors: Nuttall Pete
Published: August 2009

Adolescents, with respect to consumption and the symbolic self, are in a crucial period of identity formation. Music is significant in this respect as it has been described as a catalyst for individuals seeking to construct the ‘self’ and can play a central role in forming an identity. This paper seeks to explore the ways in which adolescent music use and consumption facilitates a greater understanding of identity formation and psychological or peer group practices. Twenty four in‐depth interviews were conducted with 12 adolescents over a 6–12 month period. All adolescents were interviewed twice with a view to observing changes in music consumption practices. The author adopts the terms of insiders, regulars and tourists to illustrate the different characteristics of adolescent music consumers in the context of their varying levels of investment and commitment. Initial findings demonstrate that music is used to build social capital, to create boundaries and to enhance social inclusion and exclusion.

Copyright © 2009 John Wiley & Sons, Ltd.
A Novel Approach for Chemical Vapor Synthesis of ZnO Nanocrystals: Optimization of Yield, Crystallinity
Authors: Ali Moazzam , Friedenberger Nina , Spasova Marina , Winterer Markus
Published: August 2009

The experimental yield of ZnO nanocrystals decreases drastically with increasing reactor temperature in a typical chemical vapor synthesis (CVS) of ZnO nanocrystals from diethylzinc. A novel CVS set‐up – a microwave plasma combined with a hot‐wall zone – is described to minimize the loss of particles at higher reactor temperatures. The powder samples have been characterized by transmission electron microscopy (TEM) and X‐ray diffraction (XRD). It is observed that the synthesis set‐up and reaction temperature have substantial influence not only on yield but also on crystallite size and crystallinity of the pure wurtzite‐type ZnO nanocrystals. The lattice constants of ZnO nanocrystals increase with decreasing crystallite size. Defect densities (twin and stacking faults), as well as microstrain, decrease with increasing reactor temperature, whereas crystallinity increases.
The Effect of the H2 Flow Rate on the Deposition of TiO2 Film Produced by Inductively Coupled Plasma‐Assisted CVD
Authors: Jang Dong‐Su , Kwon Soon‐Ho , Lee Hee‐Yong , Yang Won‐Kyun , Lee Jung‐Joong
Published: August 2009

Titanium dioxide (TiO2) films are produced by inductively coupled plasma‐assisted (ICP) CVD at various H2 flow rates. Anatase and rutile TiO2 films are obtained without any external heating. The surface morphologies, structures, and deposition rates of the TiO2 films are strongly affected by the H2 flow rate. By plasma diagnostics, using a single Langmuir probe (SLP) and optical emission spectroscopy (OES), it is found that the amount of H2 plays a dominant role in determining the deposition rate of the TiO2 films, while the substrate temperature or plasma density do not appreciably affect the deposition rate.
New Insights into the Chemistry of the Antineoplastic Lanthanum Complex Tris(1,10‐phenanthroline)tris(thiocyanato‐κN)lanthanum(III) (KP772) and Its Interaction with Biomolecules
Authors: Biba Florian , Groessl Michael , Egger Alexander , Roller Alexander , Hartinger Christian G. , Keppler Bernhard K.
Published: August 2009

The lanthanide complex tris(1,10‐phenanthroline)tris(thiocyanato‐κN)lanthanum(III) [La(phen)3(NCS)3] (KP772) is a promising anticancer drug candidate, capable of overcoming resistance of tumors to established chemotherapeutics. The compound was characterized by elemental analysis, IR, 1H NMR spectroscopy, TG/DTA measurements, mass spectrometry and X‐ray diffraction analysis. The results indicate that KP772 is a neutral, nine‐coordinate complex. In addition the behavior in water, important for the application as a chemotherapeutic drug, and the binding to biomolecules was investigated by capillary electrophoresis and ICP‐MS.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Preparation of Hollow Carbon and Silicon Carbide Fibers with Different Cross‐Sections by using Electrospun Fibers as Templates
Authors: Cheng Yongliang , Zhang Jiangfeng , Zhang Yanfei , Chen Xiaolong , Wang Ying , Ma Hongmei , Cao Xueqiang
Published: August 2009

Hollow carbon nanofibers with circular and rectangular opening were prepared by using electrospun silica fibers as templates. Silica fibers were synthesized by electrospinning, and they were coated with a carbon layer formed by thermal decomposition and carbonization of polystyrene under a nitrogen atmosphere. Hollow carbon nanofibers with circular and rectangular openings were then obtained after the silica core was etched by hydrofluoric acid. The carbon nanofibers with different morphologies also could be used as templates to fabricate silicon carbide fibers. The silicon carbide fibers with circular and rectangular openings could be obtained by using hollow carbon nanofibers and carbon belts as templates, respectively. The hollow carbon nanofibers and silicon carbide fibers were characterized by scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, and Raman spectroscopy, and the formation mechanism was also discussed(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Electron Paramagnetic Resonance Investigation of Some 11‐Tungstoruthenate(III) Polyoxoanions
Authors: Rong Charles C. , So Hyunsoo , Pope Michael T.
Published: August 2009

EPR spectra of three Keggin structure polyoxotungstates containing ruthenium(III), [PW11O39Ru(L)]4– (L = H2O, pyridine, dimethyl sulfoxide), have been recorded at 77 K and yield details of the symmetry and ligand field parameters of the embedded low‐spin d5 ruthenium cation. The magnitudes of the g tensors and 99,101Ru hyperfine coupling constants of the dmso derivative show that the unpaired electron occupies a dxy‐type orbital as a result of the axial component of the ligand field with Δ(dxy – dxz,dyz) ≈ 6200 cm–1. A weak broad absorption in the electronic spectrum at ca. 5600 cm–1 is consistent with this interpretation. A smaller rhombic component imposed by the polytungstate ligand further splits the dxz and dyz orbitals (< 2000 cm–1). The orbital reduction factor k of the dmso complex (0.69) is significantly smaller than those for the aqua and pyridine derivatives (0.80, 0.83), and this implies that, as previously found for the RuII analog, the dmso ligand is S‐bonded in the RuIII complex.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Nature of some insoluble materials recovered from biodiesel samples
Authors: Bondioli Paolo
Published: August 2009

This paper summarises the work carried out over the last few years on the identification of the insoluble material that may affect quality and performance of biodiesel. The correct isolation and purification procedure is important for sediment identification. The main objective is FTIR analysis of the purified materials. In the present report the FTIR technique was used to provide some preliminary information about the nature of the isolated solid product. In every case, starting from this information, several other tests (carried out by TLC, GC, GC/MS and HPLC) were used to identify the real structure of contaminants. Interesting case studies, such as the recovery and identification of waxes, lysophosphatides, filter aids, citric acid salts, steryl glucosides and other contaminating molecules are presented and discussed. For each case, the logical path for the solution of problem is presented, starting from the purification step, through the FTIR spectrum until specific chemical tests.
Jatropha curcas, a promising crop for the generation of biodiesel and value‐added coproducts
Authors: Makkar Harinder P. S. , Becker Klaus
Published: August 2009

The review highlights the specific features of the Jatropha curcas plant and its potential for the production of biofuel, protein concentrates as livestock feed and value‐added products that could enhance the economic viability of Jatropha seed oil‐based biodiesel production. The roles of the plant in carbon capture, enhancing socio‐economic conditions, food production in the tropical regions, and influencing micro‐climate, vegetation and soil quality are discussed. The paper also gives a comparative account of the toxic and non‐toxic genotypes of J. curcas from the point of view of their physical and chemical properties and their potential for biodiesel and livestock feed production. Future areas of research are also presented.
Implications of biodiesel production and utilisation on global climate – A literature review
Authors: Majer Stefan , Mueller‐Langer Franziska , Zeller Vanessa , Kaltschmitt Martin
Published: August 2009

Over the last few years, the favourable political environment has led to an increasing use of biofuels in the worldwide transportation sector. This development is mainly driven by concerns about the security of energy supplies and the intention to mitigate anthropogenic greenhouse gases (GHG). However, recently, the sustainability of a broad biofuel production and use has, in particular, been strongly questioned. Against this background, in this study a literature review on available and recently published life cycle assessment (LCA) studies for biodiesel has been carried out and the potential GHG emission savings from biodiesel production and use compared to fossil diesel have been analysed. The results of the reviewed studies underline the significant influence of the effects of land use change and the importance of avoiding the conversion of natural land into agricultural areas. If no land use change takes place, the results show moderate to good GHG savings for biodiesel (depending on the type of converted raw materials as well as on the chosen biomass conversion technology). In particular, the biodiesel feedstock production and the source of energy for the production process strongly influence the overall result of the GHG balance of biodiesel.
Higher Aggregation of β‐Peptide Networks Controlled by Nucleobase Pairing
Authors: Srivastava Ratika , Kumar Ray Anmol , Diederichsen Ulf
Published: August 2009

The aggregation and 3D organization of peptide helices are key elements in biology but might also be relevant in nanostructure formation. β‐Peptide helices were used as conformationally stable surrogates of α‐peptides to be organized by covalently attached nucleobases as recognition units. Because the β‐peptide 14‐helix conformation allows addressing individual sides of the helix, the aggregation of helices functionalized on two helix flanks was investigated. Nine helices varying in sequence and nucleobase composition were prepared by solid‐phase peptide synthesis and analyzed by temperature‐dependent UV and CD spectroscopy and FT‐ICR mass spectrometry. Already, sequences of three nucleobases on both sides of the helix provided stable aggregates. Aggregate formation was sequence dependent and led to one complex being stable in water at least up to 80 °C.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
New Thiazoline–Oxazoline Ligands and Their Application in the Asymmetric Friedel–Crafts Reaction
Authors: McKeon Seán C. , Müller‐Bunz Helge , Guiry Patrick J.
Published: August 2009

Six members of a novel non‐C2‐symmetric ligand class incorporating an oxazoline and thiazoline unit have been prepared in a four‐step, high‐yielding and convergent synthesis, in which the key step is a microwave‐assisted palladium‐catalyzed aryl amination. The new ligands induced enantiomeric excesses of up to 76 % in the asymmetric Friedel–Crafts reaction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Lectin‐based glycoproteomics to explore and analyze hepatocellular carcinoma‐related glycoprotein markers
Authors: Dai Zhi , Zhou Jian , Qiu Shuang‐Jian , Liu Yin‐Kun , Fan Jia
Published: August 2009

More and more new diagnostic biomarkers of hepatocellular carcinoma (HCC) have been found in association with advances in the standardization of 2‐DE coupled with MS analysis. However, the diagnosis of HCC is still detected in the late stages of the disease, when treatment options are limited and prognosis is poor. The glycosylation of proteins is known to change in tumor cells during the development of HCC as the result of alterations in the levels of glycosyltransferases, such as increased fucosylation of Golgi Protein 73 and α‐fetoprotein. These structural changes can influence the function or physiochemical properties of a protein, resulting in abnormal cancer cell behavior. Therefore, identification of HCC‐related glycoprotein markers and analysis of glycan structural alterations might assist in the early detection of HCC. Here, we summarize lectin‐based glycoproteomic strategies for the discovery of relevant biomarkers of HCC. The carbohydrate‐binding specificities of different lectins offer a biological affinity approach that complements existing MS capabilities. These strategies involve the enrichment of glycoproteins or glycopeptides by lectins, followed by releasing carbohydrates with peptide‐N‐glycosidase F or reductive β‐elimination. The obtained glycopeptides are then identified by automated MS/MS and structural analysis of glycans is performed through modern methods such as quadrupole IT‐TOF, MALDI‐TOF/TOF and lectin microarray. These strategies will lead to faster and more clinically adaptable tests with greater sensitivity and specificity.
Development of sensitive metalloporphyrin probes for chemiluminescent imaging detection of serum proteins
Authors: Liu Xia , Huang Lingyun , Baeyens Willy R. G. , Ouyang Jin , He Dacheng , Wan Genping , Zhang Li
Published: August 2009

The development of metalloporphyrin‐ (ferric protoporphyrin IX chloride (FePP), cobalt (III) protoporphyrin IX chloride, copper (II) protoporphyrin IX) enhanced chemiluminescent (CL) imaging detection of serum proteins after PAGE is described in this article. The detection is based on the catalytic activity of metalloporphyrins, especially FePP, in the CL reaction of the luminol–H2O2 system. Some relatively low abundant proteins such as hemopexin (Hpx) and complement C4 are sensitively detected by FePP‐enhanced CL imaging. Other proteins such as haptoglobin, apolipoprotein A‐1, complement C3, and α‐1‐antitrypsin are also detected and identified by MS and MS/MS techniques. Detection limit of Hpx is as low as 20 ng, without the need of expensive antibodies or tedious immunoassay procedures. The mechanism of the proposed method is discussed employing standard proteins. The application to the analysis of different protein patterns in healthy people and in Thalassemia patients is being investigated.
A rat‐to‐human search for proteomic alterations reveals transgelin as a biomarker relevant to colorectal carcinogenesis and liver metastasis
Authors: Peng Jiayuan , Zhang Qingfu , Ma Yanlei , Wang Yu , Huang Long , Zhang Peng , Chen Jie , Qin Huanlong
Published: August 2009

In this study, a modified rat model similar to the classic human evolution of colorectal cancer (CRC) was established. As such, the altered profiles of proteins involved in these processes were further verified in human specimens, so as to determine the potential biomarkers relevant to human CRC development. Protein samples of four specific stages involved in CRC progression ((i) normal mucosa, (ii) adenoma, (iii) carcinoma, and (iv) liver metastasis)) were investigated by 2‐DE. One protein spot displayed sequential suppression in the course of colorectal malignant transformation and was identified as transgelin by mass spectrometry. A decrease in its expression in both the epithelium and lamina propria was further confirmed by Western blot and immunohistochemistry analyses. Clinical and pathological parameter analysis revealed that downregulation of transgelin was associated with poor differentiation, and subsequent Dukes Stage and lower survival rate. Paradoxically, its sera level was significantly higher in CRC patients than in healthy donors, and the rise became dramatic, particularly in later Dukes Stages. These results indicate that downregulation of transgelin, in both the epithelium and lamina propria and accompanied with colorectal carcinogenesis, is correlated with worse prognosis. Its elevated serum levels might be the result of pathological hyperplasia of myofibroblasts and smooth muscle cells together with deeper tumor invasion into muscle layers. This altered expression represents interactions between cancer epithelium and stroma, such that transgelin might be a potential marker for CRC genesis and progression.
Reliability modelling of uninterruptible power supply systems using fault tree analysis method
Authors: Rahmat Mohd Khairil , Jovanovic Slobodan
Published: August 2009

The aim of this paper is to investigate the reliability parameters estimation method for the uninterruptible power supply (UPS) systems using the Fault Tree Analysis (FTA) technique. FTA is a top–down approach to identify all potential causes leading to system failure. The computation of the system's failure probability is the main goal of this analysis, as this value can be used to calculate other important system reliability parameters such as failure rates, mean time between failures and reliability. In this paper, the FTA method was applied to five different UPS topologies and the results obtained were compared and discussed in detail. By comparing the critical fault path of the system, it was found that the inverter failures contributed most significantly to the system failure. It was also found that the probability of failure of a UPS system can be reduced by the inclusion of bypass supply, given that the failure rate of the events that causing the failure of the bypass supply should be lower compared to the ones for the main utility supply. Finally, to validate the results obtained from this method, comparisons were made to the results from other methods such as the Reliability Block Diagram, Boolean Truth Table, Probability Tree, Monte‐Carlo Simulation and Field Data reliability estimation methods. Copyright © 2008 John Wiley & Sons, Ltd.
A fast corrective load shedding control scheme to prevent AC/DC systems voltage collapse
Authors: Cai Guanglin , Zhang Yongjun , Chen Rouyi , Cai Zexiang
Published: August 2009

This paper proposes a corrective load shedding algorithm to restore power flow solvability of AC/DC systems after severe contingencies. Firstly, contingency parameterization power flow is constructed to describe a set of multiple contingencies, including generators, HVDC links, ac lines and transformers. The post‐contingency critical point is quickly determined through optimal multiplier power flow and a simple optimization‐based outage parameter updating procedure. The updating strategy is better improved by the analysis of stability surface. At the nose point, the sensitivity analysis is performed to select the most effective control measure. Then, the corrective load shedding sensitivity‐based linear programming model is constructed to improve the stability margin. The numerical simulations on a practical 1621 bus system testify that the proposed method can prevent system from voltage collapse effectively and efficiently. Copyright © 2008 John Wiley & Sons, Ltd.
Power flow algorithm and practical contingency analysis for distribution systems with distributed generation
Authors: Liu Bo , Zhang Yan
Published: August 2009

Distributed generation (DG) is playing an important role in enhancing the social sustainability. Because DGs connected to distribution network will impact power flow, it is necessary to develop a new approach of power flow analysis. In this paper, the interfaces between DGs and distribution network are introduced, the operating principles and control schemes of typical DGs, including asynchronous generators and solar batteries, are studied. A DC–AC sequential iteration approach is applied for calculating power flow with DGs. In addition, a practical sensitivity based contingency analysis approach is proposed in this paper. A 15‐bus distribution network with wind power generation and solar energy is analyzed to exhibit the effectiveness of the proposed approaches. Copyright © 2008 John Wiley & Sons, Ltd.
Treatment of subsyndromal depressive symptoms in middle‐aged and older adults with schizophrenia: effect on functioning
Authors: Kasckow John , Lanouette Nicole , Patterson Thomas , Fellows Ian , Golshan Shahrokh , Solorzano Ellen , Zisook Sidney
Published: August 2009

Background

Subsyndromal symptoms of depression (SSD) in patients with schizophrenia are common and clinically important. SSRI's appear to be helpful in alleviating depressive symptoms in patients with schizophrenia who have SSD in patients age 40 and greater. It is not known whether SSRI's help improve functioning in this population. We hypothesized that treating this population with the SSRI citalopram would lead to improvements in social, mental and physical functioning as well as improvements in medication management and quality of life.

Methods

Participants were 198 adults ⩾ 40 years old with schizophrenia or schizoaffective disorder who met study criteria for subsyndromal depression based on having two or more of the nine DSM‐IV symptoms of a major depressive episode, for at least 2 weeks, and a Hamilton depression rating scale (HAM‐D 17) score ⩾ 8. Patients were randomly assigned to flexible‐dose treatment with citalopram or placebo augmentation of their current antipsychotic medication(s) which was stable for 1 month. Subjects were assessed with the following functional scales at baseline and at the end of the 12‐week trial: (1) social skills performance assessment (SSPA), (2) medication management ability assessment (MMAA), (3) mental and physical components of the medical outcomes study SF‐12 Scale, and (4) the Heinrichs quality of life scale (QOLS). Analysis of covariance (ANCOVA) was used to compare differences between endpoint scores of the citalopram and placebo treated groups, controlling for site and baseline scores. ANCOVAs were also used to compare differences in the above endpoint scores in responders versus non‐responders (responders = those with > 50% reduction in depressive symptoms).

Results

Overall, the citalopram group had significantly higher SSPA, mental functioning SF‐12, and quality of life scale (QOLS) scores compared to the placebo group. There was no effect on MMAA or physical functioning SF‐12 scores. Responders had significantly better endpoint mental SF‐12 and QOLS scores compared to non‐responders. Response to citalopram in terms of depressive symptoms mediated the effect of citalopram on mental functioning, but not on the quality of life.

Conclusions

Citalopram augmentation of antipsychotic treatment in middle aged and older patients with schizophrenia and subsyndromal depression appears to improve social and mental health functioning as well as quality of life. Thus it is important for clinicians to monitor these aspects of functioning when treating this population of patients with schizophrenia with SSRI agents. Copyright © 2009 John Wiley & Sons, Ltd.
The relationship between changes in depression symptoms and changes in health risk behaviors in patients with diabetes
Authors: Katon Wayne J. , Russo Joan E. , Heckbert Susan R. , Lin Elizabeth H.B. , Ciechanowski Paul , Ludman Evette , Young Bessie , Von Korff Michael
Published: August 2009

Background

This longitudinal study of patients with diabetes examined the relationship between changes in depressive symptoms and changes in diabetes self‐care behaviors over 5 years.

Design, Patients and Measurements

A total of 2759 patients with diabetes enrolled in a large HMO were followed over a 5‐year period. Patients filled out a baseline mail survey and participated in a telephone interview 5 years later. Depression was measured with the Patient Health Questionnaire (PHQ‐9) and diabetes self‐care was measured with the Summary of Diabetes Self‐Care Activities (SDSCA) questionnaire. Baseline and longitudinal evidence of diabetes and medical disease severity and complications were measured using ICD‐9 and CPT codes and verified by chart review.

Results

At the 5‐year follow‐up, patients with diabetes with either persistent or worsening depressive symptoms compared to those in the no depression group had significantly fewer days per week of following a healthy diet or participating in ≥30 min of exercise. At 5‐year follow‐up, patients with clinical improvement in depression symptoms showed no differences compared to the no depression group on number of days per week of adherence to diet but showed deterioration in adherence to exercise on some, but not all, measures.

Conclusions

Patients with diabetes with persistent or worsening depressive symptoms over 5 years had significantly worse adherence to dietary and exercise regimens than patients in the no depression group. These results emphasize the need to further develop and test interventions to improve both quality of care for depression and self‐care in diabetes patients. Copyright © 2009 John Wiley & Sons, Ltd.
Assessment of the WATCLASS hydrological model result of the Mackenzie River basin using the GRACE satellite total water storage measurement
Authors: Yirdaw Sitotaw Z. , Snelgrove Kenneth R. , Seglenieks Frank R. , Agboma Clement O. , Soulis Eric D.
Published: August 2009

Earlier efforts have been geared towards modelling the hydrological water balance of the Mackenzie River basin and its sub‐basins using a coupled land surface–hydrological model for the Canadian cold region known as WATCLASS. The goal of this current study is to effectively inter‐compare the resulting total water storage anomalies estimated from the gravity recovery and climate experiment (GRACE) satellite analysis with those estimated from the atmospheric‐based water balance approach as well as the model output from WATCLASS over the 1 · 8 × 106 km2 Mackenzie River basin in Canada. Since the success of the parameter estimation stage of the coupled land surface–hydrological model, WATCLASS over this large catchment, was entirely based on a goodness of fit between the simulated and observed flows, it is often desirable to assess the reliability of the generated state variables prior to concluding on the overall efficiency of this model in reproducing the relevant hydrological processes over this region. A major challenge here lies in finding suitable dataset with which this comparison can be made to further assess the ability of the model in accurately reproducing other mass fluxes. The outcome of this inter‐comparison reveals the potential application of the GRACE‐based approach as a veritable tool required for the closure of the hydrological water balance of the Mackenzie River basin as well as serving as a dependable source of data for the calibration of traditional hydrological models. Copyright © 2009 John Wiley & Sons, Ltd.
Requirement of a dynein light chain in TGFβ/Smad3 signaling
Authors: Jin Qunyan , Gao Guofeng , Mulder Kathleen M.
Published: August 2009

We have previously reported that the dynein light chain (DLC) km23‐1 is required for Smad2‐dependent TGFβ signaling. Here we describe another member of the km23/DYNLRB/LC7/robl family of DLCs, termed km23‐2, which is also involved in TGFβ signaling. We show not only that TGFβ stimulates the interaction of km23‐2 (DYNLRB2) with TGFβ receptor II (TβRII) but also that TGFβ regulates the interaction between km23‐2 and endogenous TβRII in vivo. In addition, TGFβ treatment causes km23‐2 phosphorylation, whereas a kinase‐deficient form of TβRII prevents km23‐2 phosphorylation. In contrast to the km23‐1 isoform, blockade of km23‐2 expression using small interfering RNAs (siRNAs) decreased key TGFβ/Smad3‐specific responses, including the induction of both plasminogen activator inhibitor‐1 (PAI‐1) gene expression and p21 protein expression. Blockade of km23‐1 expression had no effect on these two major TGFβ/Smad3 responses under similar conditions. Further, km23‐2 was required for TGFβ stimulation of Smad3‐dependent Smad‐binding element (SBE)2‐Luc transcriptional activity, but not for TGFβ stimulation of Smad2‐dependent activin responsive element (ARE)‐Lux transcriptional activity. In order to assess the mechanisms underlying the preferential stimulation of Smad3‐ versus Smad2‐specific TGFβ responses, immunoprecipitation (IP)/blot analyses were performed, which demonstrate that TGFβ stimulated preferential complex formation of km23‐2 with Smad3, relative to Smad2. Collectively, our findings indicate that km23‐2 is required for Smad3‐dependent TGFβ signaling. More importantly, we demonstrate that km23‐2 has functions in TGFβ signaling that are distinct from those for km23‐1. This is the first report to describe a differential requirement for unique isoforms of a specific DLC family in Smad‐specific TGFβ signaling. J. Cell. Physiol. 221: 707–715, 2009. © 2009 Wiley‐Liss, Inc.
SQ—SQ experiment for determination of relative signs of small nJ(29Si,13C) couplings in a wide variety of silicon compounds
Authors: Blechta Vratislav , Schraml Jan
Published: August 2009

A modification of double quantum–zero quantum (DQ—ZQ) experiment termed single‐quantum–single‐quantum (SQ—SQ) experiment is proposed for the determination of relative signs and magnitudes of coupling constants. The modification replaces the multiple‐quantum evolution period by two synchronously incremented single‐quantum periods. Similarly to DQ—ZQ experiment, the sequence requires only two coupling constants that share one nucleus, the one to be measured and a reference one. This allows application to a larger variety of molecular fragments than traditional 2D sequences producing E.COSY or TROSY pattern. The SQ—SQ experiment eliminates the effects of some other couplings during t1, thereby simplifying the 2D pattern and increasing the signal intensity in comparison with DQ—ZQ experiment.

The presented sequence is particularly designed for the determination of silicon–carbon coupling constants across several bonds at natural abundance using silicon–hydrogen couplings as the sign reference. The signs of silicon–carbon couplings across two and three bonds in dimethyl(phenoxy)silane which cannot be detected by traditional methods and which have not yet been determined are established by the SQ—SQ method here: 2J(Si,C) = +2.2 Hz and 3J(Si,C) = −1.7 Hz. Copyright © 2009 John Wiley & Sons, Ltd.
Kinetics Approximation Considering Different Reactivities of the Structural Units Formed by the Anionic Copolymerization of 1,3‐Butadiene and Styrene Using Al/Li/Ba as Initiator
Authors: Tenorio López José. A. , Benvenuta Tapia Juan. J. , Cuevas Díaz María del Carmen
Published: August 2009

The copolymerization reaction of butadiene and styrene copolymers prepared by anionic living polymerization using an initiator composed of alkyl aluminum, n‐butyl lithium, and barium alkoxide is studied using a kinetic model that considers the reactivity of active sites to be different; this assumption is justified by the varying geometric configurations. With the first‐order Markov model, the expressions for the fraction of active sites and dyad distribution are obtained. The rate constants are determined by fitting to the conversion and Bernoulli dyad data using the nonlinear least squares method. The conversion and dyad sequence distribution are correctly predicted, and the experimental results indicate that the microstructure and sequence distribution do not change with the conversion and temperature.

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Time‐domain BEM for three‐dimensional site response analysis of topographic structures
Authors: Sohrabi‐Bidar A. , Kamalian M. , Jafari M. K.
Published: August 2009

This paper presents a formulation of a time‐domain three‐dimensional boundary element method for site response analysis of topographic structures. The boundary element algorithm that uses the presented time‐convoluted traction kernels is applied to site response analyses of topographic structures. The seismic responses of canyon and ridge subjected to incident P and S waves are analyzed to demonstrate the accuracy of the kernels and the applicability of the presented boundary element algorithm for site response analysis of topographic structures. Seismic response analyses of three‐dimensional Gaussian‐shaped ridges show that the three‐dimensional axisymmetric ridge has a more amplification potential compared with three‐dimensional non‐axisymmetric elongated and two‐dimensional ridges, if the ridge is impinged by incident waves with wavelength of about the ridge's width. Copyright© 2009 John Wiley & Sons, Ltd.
Von Ginkgo über GbL zu EGb – ein langer Weg zum rationalen Phytopharmakon. Die Arzneipflanze mit dem seltsamsten Namen
Authors: Caesar Wolfgang
Published: August 2009

Obwohl der Ginkgo in Ostasien beheimatet ist, begann seine steile Karriere als Arzneipflanze in den 1960er Jahren in Deutschland. Während die von Chinesen und Japanern als Leckerbissen geschätzten Ginkgosamen hierzulande keine Freunde fanden, weckte das Ginkgoblatt umso mehr Aufmerksamkeit: anfangs bei Ästheten wie dem Dichterfürsten Goethe, schließlich bei Medizinern und Arzneipflanzenforschern.
Chemie, Pharmakokinetik und Metabolismus von Ginkgo‐Extrakt. Eines der bestuntersuchten Phytopharmaka
Authors: Ude Christian , Paulke Alexander , Schubert‐Zsilavecz Manfred , Wurglics Mario
Published: August 2009

Zusammenfassend kann festgehalten werden, dass für Ginkgo biloba umfangreiches präklinisches Datenmaterial vorhanden ist. Daneben sind aber auch gerade im Vergleich zu anderen Phytopharmaka die pharmakokinetischen Parameter der Ginkgo‐Spezialextrakte am Beispiel von EGb761® charakterisiert worden. Für die Flavonoide sind die Metabolisierungswege ausführlich beschrieben, so dass dadurch eine gezielte Suche nach den Metaboliten in Plasma‐ und ZNS‐Gewebe ermöglicht wurde. Es konnte für diese Substanzen gezeigt werden, dass sowohl in Plasma als auch im ZNS eine Bioverfügbarkeit gegeben ist. Für Ginkgo‐Triterpenlaktone ist eine hohe Plasma‐Bioverfügbarkeit mit einer schnellen Anflutung und relativ kurzen Halbwertszeiten sowohl im Menschen als auch im Tier gezeigt worden. Ungeachtet dessen ist weiterhin die entscheidende Frage offen, ob die Terpenlaktone aus Ginkgo biloba die Blut‐Hirn‐Schranke überwinden können, um an den eigentlichen Wirkort, das ZNS, zu gelangen. Die Beantwortung dieser Frage ist aktuell Gegenstand wissenschaftlicher Untersuchungen.
Stellenwert von Ginkgo‐biloba‐Extrakt bei Demenzerkrankungen. Wirksamkeit und Sicherheit belegt
Authors: Kasper Siegfried , Winkler Dietmar , Kutzelnigg Alexandra E.
Published: August 2009

Die Wirksamkeit des Ginkgo‐Spezialextraktes EGb 761® bei Demenzerkrankungen wurde in randomisierten, kontrollierten Doppelblindstudien nachgewiesen. Entsprechend den Empfehlungen der Zulassungsbehörden wurden Behandlungsvorteile für die kognitive Leistung sowie weitere Messgrößen auf globaler, funktioneller und psychopathologischer Beurteilungsebene gezeigt. Damit sind die Behandlungswirkungen objektiv und als klinisch relevant belegt. Die Ergebnisse neuerer Studien legen nahe, dass Demenzpatienten mit neuropsychiatrischen Symptomen, die die Mehrheit der Demenzpatienten darstellen, besonders von der Behandlung mit EGb 761® profitieren. Hinsichtlich der Verzögerung der Symptomprogression und der Numbers Needed to Treat ist EGb 761® mit den Cholinesterasehemmern vergleichbar. Eine exploratorische Studie ließ zwischen EGb 761® und Donepezil keine statistisch signifikanten oder klinisch relevanten Unterschiede erkennen. Damit hat EGb 761® zurecht seinen Platz in der Behandlung von Patienten mit Demenz.
Beratungskompetenz in der Apotheke. Was bei Ginkgo wichtig ist
Authors: Laven Anna
Published: August 2009

Als pharmazeutische Empfehlung für die Selbstmedikation weisen nur wenige Ginkgo‐Produkte die geforderten Eigenschaften auf. Sie sind leicht an dem enthaltenen, in klinischen Studien gesicherten Spezialextrakt zu erkennen. Die beratungsaktive Apotheke wird zahlreiche Maßnahmen durchführen, um ihren Kunden die notwendigen Informationen zu vermitteln.
Abschlussbericht des IQWiG zu Ginkgo biloba. Patienten profitieren von der Therapie
Authors: Winckler Thomas
Published: August 2009

Das IQWiG kommt nach der Analyse aller relevanten Studien zu dem Schluss, dass Patienten mit einer Alzheimer‐Demenz von einer Therapie mit Ginkgo‐Extrakt profitieren könnten, wenn der Extrakt in einer Dosierung von 240 mg eingenommen wird (Tab. 4). Das IQWiG sieht für das Therapieziel “Aktivitäten des täglichen Lebens” und den “klinischen Gesamteindruck” einen “Beleg für einen Nutzen”, was der höchsten Evidenz in einer fünfstufigen Bewertungsskala entspricht. Für die Endgrößen “kognitive Fähigkeiten”, “psychopathologischer Zustand” und “Lebensqualität der (betreuenden) Angehörigen” hat das IQWiG einen “Hinweis auf einen Nutzen” von Ginkgo‐Extrakten festgestellt1. Allgemein lässt die Heterogenität der ausgewerteten Studien hinsichtlich Alter, Geschlecht, Schweregrad der Erkrankung und der begleitenden psychopathologischen Störungen keine Aussage über die Größe des Nutzens einer Therapie mit Ginkgo‐Extrakten zu. Hinsichtlich unerwünschter Ereignisse gab es keine signifikanten Unterschiede zu Placebo, obwohl statistisch mehr Patienten die Therapie unter Ginkgo abbrachen als unter Placebo. Zu einem Nutzen der 120‐mg‐Dosierung konnte aufgrund der Heterogenität der Studien keine Aussage getroffen werden. Künftige Studien sollten nach Empfehlung des IQWiG nur mit einer Dosierung von 240 mg Ginkgo‐Extrakt durchgeführt werden. Auch legt der IQWiG‐Bericht nahe, dass Demenzpatienten zukünftig nur mit der hohen Extrakt‐Dosierung behandelt werden sollten. Ob Ginkgo‐Extrakte einen Nutzen im Vergleich mit anderen Wirkstoffen wie Cholinesterase‐Hemmern oder Memantin hätten, konnte nicht beantwortet werden, da nur eine auswertbare Studie zu einem Vergleich mit Donepezil vorlag.
Dualspezifische therapeutische Antikörper
Authors: Winckler Thomas
Published: August 2009

Monoklonale Antikörper haben einen festen Platz unter den Turmortherapeutika. Die erstmalige Entwicklung eines dualspezifischen Antikörpers könnte eine neue Strategie zur Kombinationstherapie bei Brustkrebs aufzeigen.
Bitte ein BiTE®!
Authors: Freitag Helma , Gress Gesine , Messer Kim , Sivaz Gülcan , Weinbender Olga , Zündorf Ilse , Dingermann Theo
Published: August 2009

Vor kurzem wurde mit Removab® (Catumaxomab) der erste bispezifische, trifunktionale komplette Ratte/Maus‐Hybrid‐Antikörper von der EMEA zur intraperitonealen Behandlung des malignen Aszites bei Patienten mit EpCAM‐positiven Karzinomen zugelassen. Ein ähnlicher Ansatz, aber mit sehr viel kleineren Molekülen wird von der Firma Micromet AG mit ihren BiTE®‐Antikörperfragmenten verfolgt.
Urine proteomics for profiling of human disease using high accuracy mass spectrometry
Authors: Kentsis Alex , Monigatti Flavio , Dorff Kevin , Campagne Fabien , Bachur Richard , Steen Hanno
Published: August 2009

Knowledge of the biologically relevant components of human tissues has enabled the invention of numerous clinically useful diagnostic tests, as well as non‐invasive ways of monitoring disease and its response to treatment. Recent use of advanced MS‐based proteomics revealed that the composition of human urine is more complex than anticipated. Here, we extend the current characterization of the human urinary proteome by extensively fractionating urine using ultracentrifugation, gel electrophoresis, ion exchange and reverse‐phase chromatography, effectively reducing mixture complexity while minimizing loss of material. By using high‐accuracy mass measurements of the linear ion trap‐Orbitrap mass spectrometer and LC‐MS/MS of peptides generated from such extensively fractionated specimens, we identified 2362 proteins in routinely collected individual urine specimens, including more than 1000 proteins not described in previous studies. Many of these are biomedically significant molecules, including glomerularly filtered cytokines and shed cell surface molecules, as well as renally and urogenitally produced transporters and structural proteins. Annotation of the identified proteome reveals distinct patterns of enrichment, consistent with previously described specific physiologic mechanisms, including 336 proteins that appear to be expressed by a variety of distal organs and glomerularly filtered from serum. Comparison of the proteomes identified from 12 individual specimens revealed a subset of generally invariant proteins, as well as individually variable ones, suggesting that our approach may be used to study individual differences in age, physiologic state and clinical condition. Consistent with this, annotation of the identified proteome by using machine learning and text mining exposed possible associations with 27 common and more than 500 rare human diseases, establishing a widely useful resource for the study of human pathophysiology and biomarker discovery.
Analysis of the differential proteome of human erythroblasts during in vitro erythropoiesis by 2‐D DIGE
Authors: Richardson Ben M. , Heesom Kate J. , Parsons Steve F. , Anstee Dave J. , Frayne Jan
Published: August 2009

In the present study we have used an in vitro culture system that induces differentiation of human CD34+ cells down the erythroid lineage along with 2‐D DIGE to determine the differential proteome of erythroblasts at specific developmental stages during erythropoiesis. We initially distinguished 154 proteins differentially expressed between pro‐normoblasts and polychromatic/orthochromatic erythroblasts, of which 24 protein spots, representing 21 different proteins, were identified following MS/MS and verification in replicate experiments with cells from different individuals. These data were confirmed by analysis of the differential proteome of erythroblasts at more discrete stages of erythropoiesis using 2‐D DIGE and by mapping the expression of three identified proteins (Annexin I, Annexin II, Carbonic Anhydrase I) throughout erythropoiesis by Western blot with specific antisera. In addition, the differential expression of proteins due to biological variation, such as polymorphism, was determined by comparing erythroblasts at the same developmental stage from different individuals; none of the proteins thus identified were represented in the above data set. Finally, we discuss the problems associated with 2‐D DIGE gel‐based proteomic approaches such as ours and suggest a modified approach for decreased inter‐gel variation, improved protein resolution and increased protein concentration, which should significantly facilitate protein identification.
Proteomic characterization of thiazolidinedione regulation of obese adipose secretome in Zucker obese rats
Authors: Chen Xiaoli , Hunt Desmond , Cushman Samuel W. , Hess Sonja
Published: August 2009

Signaling molecules released by adipose tissue have been implicated in inflammation, adipocyte dysfunction and systemic insulin resistance. In this study, we used 2‐D LC‐MS/MS and quantitative proteomics approaches to characterize the obese adipose secretory proteins that are responsive to the thiazolidinediones class of PPAR‐γ agonizts. We first showed the differential secretion profiling between obese and lean adipose tissue; 87 proteins were detected from the conditioned medium of adipose tissue of Zucker obese rats compared with 31 from lean rats. A total of 57 proteins comprising immune factors, inflammatory molecules, collagens, proteases, and extracellular matrix proteins were detected from obese, but not lean adipose tissue. More importantly, a quantitative proteomics approach using 18O proteolytic labeling allowed quantification of the difference in the secretion levels of 77 proteins, and thiazolidinediones treatment suppressed the secretion of most of the obese adipose tissue secretome, thus resembling a lean tissue. We have demonstrated an application of identifying the obese adipose secretome and characterizing the regulation of adipose secretion in obesity and insulin resistance. Our data provide the first evidence of changes in adipose secretion in obesity at a global level and show that such changes are correlated with systemic insulin resistance.
Profiling of rat urinary proteomic patterns associated with drug‐induced nephrotoxicity using CE coupled with MS as a potential model for detection of drug‐induced adverse effects
Authors: Mischak Harald , Espandiari Parvaneh , Sadrieh Nakissa , Hanig Joseph
Published: August 2009

We have investigated urine obtained from Sprague Dawley rats before and after administration of cis‐Platin, aiming at the definition of biomarkers for drug‐induced cytotoxicity. Rats were treated with 3 or 6 mg/kg cis‐Platin (i.p., single injection) and urine samples were collected before and after drug or saline treatment. Analysis of the low molecular weight proteome (<20 kDa) using capillary‐electrophoresis coupled mass spectrometry allowed us to tentatively identify 34 urinary peptides that show significant differences between control and treated animals, and hence may serve as a potential biomarker for cis‐Platin‐induced nephrotoxicity. These biomarkers were confirmed in a blinded assessment of additional samples. The blinded data also revealed time‐dependency of induced changes. Some of the potential biomarkers could be sequenced. This information revealed great similarity between cis‐Platin‐induced changes and significant changes in the urinary proteome of patients suffering from tubular injury (Fanconi syndrome). Our study strongly suggests that (drug‐induced) nephrotoxicity can be detected with high accuracy in laboratory rodents using urinary proteome analysis. The effects observed are very similar to those seen in corresponding human diseases and similar approaches may be very helpful in evaluating drug‐induced organ damage in preclinical animal models. This study aiming at the definition of biomarkers for drug‐induced cytotoxicity may serve as a proof‐of‐principle for the use of urinary proteomics in assessment of drug‐induced nephrotoxicity.