bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of several kinds of polyethylene gel estimated by small‐angle light scattering under cross polarization
Authors: Luo Yanling , Kayakabe Seiko , Xi Ying , Bin Yuezhen , Xu Chunye , Matsuo Masaru 
Published: October 2010

AbstractUnusual phenomenon was confirmed in the gelation of polymer solution when branched low molecular weight polyethylene (B‐LMWPE) and ultrahigh molecular weight polyethylene (UHMWPE) solutions were quenched at their gelation temperature. That is, polarized light scattering (Hv scattering) from B‐LMWPE gels containing 95% solvent yielded a four‐leaf clover type as like the scattering from a perfect spherulite under Hv scattering but the corresponding polarized optical microscopy (POM) showed dark image showing no spherulite with Maltese cross color indicating considerable orientation fluctuation between the optical axes with respect to the radial axis of the spherulite. Hv scattering from pristine UHMWPE gels containing more than 99% solvent had an X‐type pattern, which became clearer with time. The corresponding POM images change from being dark, indicating no superstructure, to being slightly brighter, indicating the presence of indistinct superstructures. To analyze this unusual phenomenon of Hv scattering from B‐LMWPE and UHMWPE gels, new models were proposed using a statistical approach and optically anisotropic elements in three‐dimensional space. The theoretical patterns were in agreement with observation. Thus, it came to a conclusion that Hv scattering from the gels is attributed to strong distance correlation between polar and rotational angles of two optically anisotropic elements in the polymer‐rich phase. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2010
Proteomic profiling of blood‐dialyzer interactome reveals involvement of lectin complement pathway in hemodialysis‐induced inflammatory response
Authors: Mares Jan , Richtrova Pavlina , Hricinova Alena , Tuma Zdenek , Moravec Jiri , Lysak Daniel , Matejovic Martin 
Published: October 2010

AbstractPurpose: Dialysis‐induced inflammatory response including leukocyte and complement activation is considered a significant cofactor of chronic morbidity in long‐term hemodialysis (HD) patients. The aim of this study was to provide better insight into its molecular background.Experimental design: In 16 patients, basic biocompatibility markers, i.e. leukocyte counts and C5a levels, were monitored during HD on a polysulfone membrane. Proteins adsorbed to dialyzers were eluted and separated by 2‐DE. Selected proteins were identified by MS; ficolin‐2 plasma levels were assessed. Data are given as medians (quartile ranges).Results: In total, 7.2 (34.7) mg proteins were retrieved from dialyzer eluates and were resolved into 217 protein spots. The proteins most enriched in eluates (and hence selectively adsorbed) were those involved in complement activation (C3c, ficolin‐2, mannan‐binding lectin serine proteases, properdin) and cell adhesion (actin, caldesmon, tropomyosin, vitronectin, vinculin). A significant decrease of plasma ficolin‐2 (41% [4.7], p<0.001) was evidenced during one HD session, associated with leukopenia (r=0.73, p=0.001) and C5a production (r=−0.62, p=0.01) at 15 min.Conclusions and clinical relevance: Ficolin‐2 adsorption to polysulfone dialyzer initiates the lectin pathway of complement activation, mediates dialysis‐induced leukopenia, and results in a significant depletion of ficolin‐2, an essential component of innate immunity.
The absolute quantification of eight inter‐α‐trypsin inhibitor heavy chain 4 (ITIH4)‐derived peptides in serum from breast cancer patients
Authors: van den Broek Irene , Sparidans Rolf W. , van Winden Annemieke W. J. , Gast Marie‐Christine W. , van Dulken Eric J. , Schellens Jan H. M. , Beijnen Jos H. 
Published: October 2010

AbstractPurpose: Various studies exploring the potential of the low‐molecular‐weight serum peptidome have identified proteolytic cleavage products of inter‐α‐trypsin inhibitor heavy chain‐4 (ITIH4) as potential markers for different types of cancer, presumably generated by tumor‐associated exoproteases. However, further elucidation of the discriminative properties of such peptides requires specific quantitative analytical methods.Experimental design: Using a recently developed and fully validated liquid chromatography–tandem mass spectrometric method, we have compared absolute serum concentrations of eight peptides derived from ITIH4 [658–687] to [667–687] (ITIH4‐30 to −21) between breast cancer patients (n=45) and controls (n=78). Furthermore, serum samples obtained before and after surgical removal of the tumor were analyzed (n=30).Results: The inter‐individual variability in measured serum concentrations was high. Nevertheless, most peptides showed a tendency toward elevated levels in the presence of the breast cancer tumor. Significantly increased serum concentrations were observed in the breast cancer group for ITIH4‐25 (p=0.036) and −29 (p=0.015). Intra‐individual comparisons of serum obtained before and after surgery showed significantly decreased serum levels after surgery for seven of the ITIH4‐derived peptides (p<0.02).Conclusions and clinical relevance: The obtained results particularly suggest potential for these ITIH4‐derived peptides in the follow‐up of breast cancer after surgery.
Long‐term serum proteomes are quite similar under high‐ and low‐flux hemodialysis treatment
Authors: Hallbauer Julia , Kreusch Stefan , Klemm Andree , Wolf Gunter , Rhode Heidrun 
Published: October 2010

AbstractPurpose: Aim of the study was to identify long‐term differences of middle and high‐molecular‐weight serum constituents under high‐ and low‐flux hemodialysis treatments. Thus, the entire predialytic serum proteomes had to be analyzed using identical hemodialysis membrane material but with different cut‐off values.Methods and results: A cross‐over study and a global native chromatographic proteomic approach were used to analyze serum compositions of 16 patients suffering from end‐stage renal disease.Results: No significant or reproducible differences were found between predialytic serum samples from high‐ and low‐flux dialysis treatments using UV‐absorbance and fluorescence spectrometry, PMF, or sequence tags. In contrast, there are characteristic differences in the predialytic serum composition of the patients considered and two control sets, which include samples obtained post‐dialytically from patients and samples from healthy controls. Only a fraction of β2‐microglobulin, an example of so‐called middle molecules, exhibits the expected molecular weight. A small fraction was found with high molecular weight unaffected by any dialysis treatment. Moreover, immunoreactivity of fragments of β2‐microglobulin, surprisingly, was also not affected by the cut‐off of dialysis membranes.Conclusions and clinical relevance: Thus, simply increasing the pore size of a hemodialysis membrane may not have any long‐term effect on serum composition.
CE‐MS in biomarker discovery, validation, and clinical application
Authors: Mischak Harald , Schanstra Joost P. 
Published: October 2010

AbstractCE coupled MS (CE‐MS) has become an increasingly employed technology in proteome analysis with focus on the identification of biomarker peptides in clinical proteomics. In this review, we will cover technical aspects of CE‐MS coupling and highlight the improvements made in the last few years. We examine CE‐MS from an application point of view, and evaluate its merits and vices for biomarker discovery and clinical applications. We discus the principal theoretical and practical obstacles encountered when employing CE‐MS (and most other proteomic technologies) for the analysis of body fluids for biomarker discovery. We will present several examples of a successful application of CE‐MS for biomarker discovery, implications for disease diagnosis, prognosis, and therapy evaluation, and will discuss current challenges and possible future improvements.
Planning a Bayesian early‐phase phase I/II study for human vaccines in HER2 carcinomas
Authors: Zohar Sarah , Baldi Ileana , Forni Guido , Merletti Franco , Masucci Giuseppe , Gregori Dario 
Published: October 2010

AbstractRecent innovative statistical approaches for phase I/II clinical trials allow one to jointly model the toxicity and efficacy of a new treatment, taking into account the information gathered during the trial. Prior probabilities are then updated with interim data and thus predictive probabilities become more accurate as the trial progresses. In this study, prior distribution elicited from a physician's opinion on the available dose levels planned for a vaccination dose‐finding trial, with human DNA in patients with HER2‐positive tumours in terms of toxicity and therapeutic response is presented and discussed. A simulation study was conducted in order to quantify the impact of the choice of prior on study results, i.e. the recommended dose level at the end of the trial. Copyright © 2010 John Wiley & Sons, Ltd.
Issues for stratified randomization based on a factor derived from a continuous baseline variable
Authors: Qu Yongming 
Published: October 2010

AbstractStratified randomization based on the baseline value of the primary analysis variable is common in clinical trial design. We illustrate from a theoretical viewpoint the advantage of such a stratified randomization to achieve balance of the baseline covariate. We also conclude that the estimator for the treatment effect is consistent when including both the continuous baseline covariate and the stratification factor derived from the baseline covariate. In addition, the analysis of covariance model including both the continuous covariate and the stratification factor is asymptotically no less efficient than including either only the continuous baseline value or only the stratification factor. We recommend that the continuous baseline covariate should generally be included in the analysis model. The corresponding stratification factor may also be included in the analysis model if one is not confident that the relationship between the baseline covariate and the response variable is linear. In spite of the above recommendation, one should always carefully examine relevant historical data to pre‐specify the most appropriate analysis model for a perspective study. Copyright © 2010 John Wiley & Sons, Ltd.
Reduction of lipid accumulation in HepG2 Cells by luteolin is associated with activation of AMPK and Mitigation of oxidative stress
Authors: Liu Jin‐Feng , Ma Ying , Wang Ying , Du Zhi‐Yan , Shen Jing‐Kang , Peng Hong‐Li 
Published: October 2010

AbstractThe present study was carried out to investigate the lipid‐lowering effect of luteolin by using a cell model of steatosis induced by palmitate. Incubation of HepG2 cells with palmitate markedly increased lipid accumulation (Oil Red O staining), the genes involved in lipogenesis, including fatty acid synthase (FAS) and its upstream regulator sterol regulatory element binding protein 1c (SREBP‐1c), and reactive oxygen species (ROS) production. Luteolin enhanced the phosphorylation of AMP‐activated protein kinase α (AMPKα) and its primary downstream targeting enzyme, acetyl‐CoA carboxylase (ACC), up‐regulated gene expression of carnitine palmitoyl transferase 1 (CPT‐1), which is the rate‐limiting enzyme in mitochondrial fatty acid β‐oxidation, and down‐regulated SREBP‐1c and FAS mRNA levels in the absence and presence of palmitate. In addition, luteolin significantly decreased ROS production and ameliorated lipid accumulation in HepG2 cells caused by palmitate. Furthermore, intracellular triglyceride (TG) measurement indicated that the luteolin‐mediated reduction of enhanced TG caused by palmitate was blocked by pretreatment with the AMPK inhibitor, compound C. The results suggested that the lipid‐lowering effect of luteolin might be partially mediated by the up‐regulation of CPT‐1 and down‐regulation of SREBP‐1c and FAS gene expression, possibly by activation of the AMPK signaling pathway, and partially might be through its antioxidative actions. Copyright © 2010 John Wiley & Sons, Ltd.
Bile Acid‐binding Ability of Kaki‐tannin from Young Fruits of Persimmon (Diospyros kaki) In Vitro and In Vivo
Authors: Matsumoto Kenji , Kadowaki Akio , Ozaki Natsumi , Takenaka Makiko , Ono Hiroshi , Yokoyama Shin‐ichiro , Gato Nobuki 
Published: October 2010

AbstractThe bile acid‐binding ability of a highly polymerized tannin (kaki‐tannin) extracted from dried‐young fruits of persimmon (Diospyros kaki) was examined. The kaki‐tannin was composed mainly of epicatechin, epigallocatechin, epicatechin‐3‐O‐gallate and epigallocatechin‐3‐O‐gallate. Bile acid‐binding ability of kaki‐tannin was examined against cholic acid, glycocholic acid, taurocholic acid and deoxycholic acid in vitro, and its effect on fecal bile acid excretion in mice was also examined. Although the bile acid‐binding ability of kaki‐tannin was weaker than that of cholestyramine, kaki‐tannin adsorbed all the bile acids tested and significantly promoted fecal bile acid excretion in mice when supplied at 1% (w/w) in the diet. Copyright © 2010 John Wiley & Sons, Ltd.
Liposome and Lipid Bilayer Arrays Towards Biosensing Applications
Authors: Bally Marta , Bailey Kelly , Sugihara Kaori , Grieshaber Dorothee , Vörös Janos , Städler Brigitte 
Published: October 2010

AbstractSensitive and selective biosensors for high‐throughput screening are having an increasing impact in modern medical care. The establishment of robust protein biosensing platforms however remains challenging, especially when membrane proteins are involved. Although this type of proteins is of enormous relevance since they are considered in >60% of the pharmaceutical drug targets, their fragile nature (i.e., the requirement to preserve their natural lipid environment to avoid denaturation and loss of function) puts strong additional prerequisites onto a successful biochip. In this review, the leading approaches to create lipid membrane‐based arrays towards the creation of membrane protein biosensing platforms are described. Liposomes assembled in micro‐ and nanoarrays and the successful set‐ups containing functional membrane proteins, as well as the use of liposomes in networks, are discussed in the first part. Then, the complementary approaches to create cell‐mimicking supported membrane patches on a substrate in an array format will be addressed. Finally, the progress in assembling free‐standing (functional) lipid bilayers over nanopore arrays for ion channel sensing will be reported. This review illustrates the rapid pace by which advances are being made towards the creation of a heterogeneous biochip for the high‐throughput screening of membrane proteins for diagnostics, drug screening, or drug discovery purposes.
An Intein‐Mediated Site‐Specific Click Conjugation Strategy for Improved Tumor Targeting of Nanoparticle Systems
Authors: Elias Drew R. , Cheng Zhiliang , Tsourkas Andrew 
Published: October 2010

AbstractThe ability to modify and directly target nanoparticulate carriers has greatly increased their applicability in diagnostic and therapeutic studies. Generally essential to the targeting of nanoparticles is the bioconjugation of targeting ligands to the agent's surface. While bioconjugation techniques have steadily improved in recent years, the field is still plagued with inefficient conjugations reactions and/or the lack of site‐specific coupling. To overcome these limitations, click chemistry and expressed protein ligation (EPL) are combined to produce a highly efficient, site‐specific reaction. This new EPL–click conjugation strategy is applied to create superparamagnetic iron oxide nanoparticles (SPIO) labeled with HER2/neu affibodies. These HER2‐SPIO nanoparticles prove to be highly potent and receptor‐specific in both in vitro cell studies and murine tumor models. Moreover, when EPL–click‐derived HER2‐SPIO are compared with SPIO that had been labeled with HER2 affibodies using other popular bioconjugation methods, they produce a statistically significant improvement in contrast enhancement upon cell binding. The EPL–click system is also successfully extended to other nanoparticle platforms (i.e., liposomes and dendrimers) highlighting the versatility of the approach.
Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China
Authors: Wang Fei , Han Lianshu , Yang Yanling , Gu Xuefan , Ye Jun , Qiu Wenjuan , Zhang Huiwen , Zhang Yafen , Gao XiaoLan , Wang Yu 
Published: October 2010

AbstractThe most common inborn error of cobalamin (cbl) metabolism in China is the cblC type characterized by combined methylmalonic acidemia and hyperhomocysteinemia. The clinical presentation is relatively nonspecific, such as feeding difficulty, recurrent vomiting, hypotonia, lethargy, seizures, progressive developmental delay, and mental retardation, together with anemia and metabolic acidosis. More specific biochemical findings include high levels of propionylcarnitine (C3), free carnitine (C3/C0), and acetylcarnitine (C3/C2) measured by tandem mass spectrometry (MS/MS), elevation of methylmalonic acid (MMA) measured by gas chromatography–mass spectrometry (GC‐MS), and increased total homocysteine with normal or decreased methionine. We report on 50 Chinese patients with combined methylmalonic acidemia and hyperhomocysteinemia. Forty‐six belonged to the cblC complementation group. Mutation analysis of the MMACHC gene was performed to characterize the mutational spectrum of cblC deficiency, and 17 different mutations were found. Most were clustered in exons 3 and 4, accounting for 91.3% of all mutant alleles. Two mutations were novel, namely, c.315 C>G (p.Y105X) and c.470 G>C(p.W157S). In terms of genotype–phenotype correlation, the c.609 G>A mutation was associated with early‐onset disease when homozygous. Unlike previous reports from other populations, c.609 G>A (p.W203X) was the most frequent cblC mutation detected in our study of Chinese patients #Affecting 51 of 92 MMACHC alleles (55.4%). The high prevalence of this nonsense mutation could have potential therapeutic significance for Chinese cblC patients. Besides traditional approaches consisting of hydroxocobalamin injections, carnitine, betaine, and protein restriction, novel drugs that target premature termination codons may have a role in the future.
Stratum Corneum Lipid Structure Investigated by EPR Spin‐Probe Method: Application of Terpenes
Authors: Nakagawa Kouichi , Anzai Kazunori 
Published: October 2010

AbstractElectron paramagnetic resonance (EPR) in conjunction with a slow‐tumbling simulation was utilized for defining stratum corneum (SC) lipid structure. SC from the back of hairless mouse (HOS:HR‐1) was stripped consecutively from one to three or four times using a glass plate coated with a cyanoacrylate resin. Aliphatic spin probes, 5‐doxylstearic acid (5‐DSA) and 3β‐doxyl‐5α‐cholestane (CHL), were used to evaluate the SC ordering. EPR spectrum of 5‐DSA incorporated in the SC demonstrated a characteristic peak for the first strip. A slow‐tumbling simulation for 5‐DSA showed clear differences in EPR intensities as well as ordering values (S0) of the SC for control and terpenes treated SC. The α‐terpineol enhanced the permeation of the single chain 5‐DSA about three times more than that of the control. However, EPR spectra of CHL in the SC did not show a clear difference for each strip, except for the signal intensity. The results imply that CHL permeates into SC lipid differently from 5‐DSA. The enhancement of the 5‐DSA is more significant than that of CHL. Therefore, the present results can be useful for various drug administrations via the skin.
Application of a conceptual framework to interpret variability in rangeland responses to atmospheric CO2enrichment
Authors: POLLEY H. W. , MORGAN J. A. , FAY P. A. 
Published: October 2010

SUMMARYPlant productivity and other ecosystem processes vary widely in their responses to experimental increases in atmospheric carbon dioxide (CO2) concentration. A conceptual framework first suggested by Chapinet al.(1996) was adapted to address the question of why CO2effects on primary productivity vary so greatly among rangelands and among years for a given ecosystem. The ‘interactive controls’ framework is based on the premise that the influence of elevated CO2on productivity is governed by a set of internal variables that interact dynamically with ecosystem processes. These interactive controls, which include regional climate, soil resource supply, major functional groups of organisms and disturbance regimes, both regulate CO2effects on ecosystems and respond to CO2effects. Changes in interactive controls resulting from CO2enrichment may feed back to dampen or amplify ecosystem responses to CO2. Most feedbacks from interactive controls will be negative and dampen CO2effects on ecosystems. Negative feedbacks promote homeostasis in ecosystem processes and reduce the response of plant productivity to CO2. Positive feedbacks on CO2responses are fewer, but can sustain or even increase benefits of CO2enrichment for productivity. Positive feedbacks on CO2responses occur most frequently through changes in plant species and functional group composition. Understanding positive and negative feedbacks on CO2responses could be one key to predicting consequences of CO2enrichment for rangeland productivity and other processes.
The Discovery of Vorapaxar (SCH 530348), a Thrombin Receptor (Protease Activated Receptor-1) Antagonist with Potent Antiplatelet Effects
Authors: Chackalamannil Samuel 
Published: October 2010

The coagulation and platelet activation mechanisms synergize in hemostasis and thrombosis. Thrombin plays a key dual role in these by generation of fibrin from fibrinogen and by activation of platelets via protease activated receptors (PARs). Human platelets contain the high affinity PAR-1, also know as the thrombin receptor, and the low affinity PAR-4. Among the various platelet activating mechanisms, PAR-1 stimulation is the most potent one, and as such, a PAR-1 antagonist is expected to confer potent antiplatelet effects. Additionally, a PAR-1 antagonist is expected to produce less bleeding side effect than currently available antithrombotic agents, since fibrin generation would be unaffected, and platelet activation by other mechanisms needed for normal hemostasis would be maintained.
SCH 530348 is a potent thrombin receptor antagonist that was discovered by optimization of a lead derived from the natural product himbacine. It is a competitive antagonist of PAR-1 with a Ki of 8.1 nM and it was highly potent in multiple functional assays. In a preclinical ex vivo platelet aggregation model in cynomolgus monkeys, SCH 530348 showed complete and sustained inhibition of platelet aggregation for greater than 24 hours after an oral administration of 0.1 mg/kg. In phase I clinical trials, SCH 53048 demonstrated excellent safety and tolerability, and exhibited potent pharmacodynamic effects in human plasma. In a phase II clinical trial (TRA-PCI) in patients who underwent non-emergent percutaneous coronary intervention, SCH 530348 was not associated with increased TIMI major plus minor bleeding when compared with placebo, and therefore met its primary end point. For the secondary outcome endpoint, SCH 530348 was associated with a numerical reduction in periprocedural myocardial infarction and an overall reduction in arterial thrombotic events. SCH 530348 is currently undergoing two large Phase III studies in patients with acute coronary syndrome (TRA*CER) and in patients who are at risk of atherothrombotic events (TRA*2P).