bluuebunny/crossref_metadata_2025 huggingface dataset:
Harnessing the diversity of the human T‐cell repertoire: A monitoring tool for transplantation tolerance?
Authors: Naesens Maarten , Sarwal Minnie M.
Published: October 2010

There is significant diversity in the TCR repertoire in heterologous and allogeneic immunity. A paper in this issue of the European Journal of Immunology shows that changes in the TCR repertoire can be correlated with outcomes of renal transplantation. This indicates that the diversity of the TCR repertoire could be utilized to monitor clinical phenotypes, such as chronic humoral rejection and operational tolerance in organ transplantation. However, prior to the clinical use of monitoring changes in the TCR repertoire as a biomarker to monitor clinical status after organ transplantation, many questions regarding time dependency, triggering factors and specificity need to be addressed. A causative role for TCR repertoire disruption in organ transplantation will need to be proven by interventional trials that can demonstrate that the TCR repertoire is modifiable and predictive of graft outcome. In this Commentary, we discuss the strengths and opportunities of TCR repertoire monitoring, and point towards yet unanswered questions that will become important if the Vβ CDR3‐length distribution assay will be clinically applied.
Synthesis, Structures, and Heterogeneous Catalytic Applications of {Co3+–Eu3+} and {Co3+–Tb3+} Heterodimetallic Coordination Polymers
Authors: Kumar Girijesh , Singh Amit Pratap , Gupta Rajeev
Published: October 2010

Two {Co3+–Eu3+} and {Co3+–Tb3+} heterodimetallic coordination polymers have been synthesized by using a Co3+‐based coordination complex as the building block. Structural studies show that the lanthanide atoms are coordinated to the cobalt complex through Oamide groups. This results in the generation of a one‐dimensional zigzag coordination polymer. These coordination polymers have been shown to catalyze the ring‐opening reactions of the epoxides with anilines and alcohols under heterogeneous and solvent‐free conditions. Interestingly, a perfect regioselectivity was observed in the aminolysis and alcoholysis reaction of styrene oxide.
Enantioselective Organocatalytic Michael Additions of Oxyacetaldehydes to Nitroolefins
Authors: Huťka Martin , Poláčková Viera , Marák Jozef , Kaniansky Dušan , Šebesta Radovan , Toma Štefan
Published: October 2010

Alkyl and aryloxyacetaldehydes add enantioselectively to various nitroalkenes. Addition products were isolated in good yield and high enantiomeric purity (up to 96 % ee) but only mediocre syn/anti ratios were achieved. The course of the reaction was investigated by mass spectrometry and by DFT calculations.
Analysis of trace degradation products (decarboxylated diastereoisomers) of S‐adenosylmethionine by electrophoresis in capillaries with cationic coatings (N‐methylpolyvinylpyridinium or divalent barium)
Authors: Sebastiano Roberto , Knob Radim , Citterio Attilio , Righetti Pier Giorgio
Published: October 2010

Commercial preparations of S‐adenosylmethionine (SAM) when analyzed in uncoated capillaries show a minute impurity believed to be decarboxylated (dc) SAM. By using two types of cationic coatings, thus reducing the electro‐endo‐osmotic flow (EOF), it was possible to separate this impurity into two diastereoisomers of dcSAM. The coatings evaluated for this purpose were: (i) N‐methylpolyvinylpyridinium, used under reversed EOF at acidic conditions (pH 4.0) and (ii) deposition of divalent barium at alkaline pH values (pH 9.4), providing reduced EOF. Under these conditions, it was possible to separate this impurity into two diastereoisomers, which by chemical synthesis were indeed proven to be dcSAM. It was further demonstrated that, in the alkylation of 5′‐methylthioadenosine by 3‐bromopropylamine in bromidric acid to dcSAM, another minute impurity was present, proven, via mass spectrometry, to consist of S‐(5′‐adenosyl)‐3‐thiopropylamine (decarboxylated and demethylated (dc‐SAH)). The LOD for the two dcSAM diastereoisomers was assessed as 17.5 μg/mL and their LOQ as 25.5 μg/mL. By the barium‐based protocol it was possible to quantify the dcSAM, present in a commercial sample of SAM, as a 0.1% impurity.
Identification of methylated regions with peak search based on Poisson model from massively parallel methylated DNA immunoprecipitation‐sequencing data
Authors: Yang Yao , Wang Wei , Li Yanqiang , Tu Jing , Bai Yunfei , Xiao Pengfeng , Zhang Dingdong , Lu Zuhong
Published: October 2010

DNA methylation is one of the most important epigenetic modification types, which plays a critical role in gene expression. High efficient surveying of whole genome DNA methylation has been aims of many researchers for long. Recently, the rapidly developed massively parallel DNA‐sequencing technologies open the floodgates to vast volumes of sequence data, enabling a paradigm shift in profiling the whole genome methylation. Here, we describe a strategy, combining methylated DNA immunoprecipitation sequencing with peak search to identify methylated regions on a whole‐genome scale. Massively parallel methylated DNA immunoprecipitation sequencing combined with methylation DNA immunoprecipitation was adopted to obtain methylated DNA sequence data from human leukemia cell line K562, and the methylated regions were identified by peak search based on Poison model. From our result, 140 958 non‐overlapping methylated regions have been identified in the whole genome. Also, the credibility of result has been proved by its strong correlation with bisulfite‐sequencing data (Pearson R2=0.92). It suggests that this method provides a reliable and high‐throughput strategy for whole genome methylation identification.
Genomic N6‐methyladenine determination by MEKC with LIF
Authors: Krais Annette M. , Cornelius Michael G. , Schmeiser Heinz H.
Published: October 2010

2′‐Deoxy‐N6‐methyladenosine (N6mdA) is frequently found in prokaryotic and unicellular eukaryotic genomes. Although methylated bases represent only a minor fraction of the genome, they, however, exhibit strong biological effects. Here, we report a fast and sensitive method for the quantification of global adenine methylation in DNA. The method is based on a recently developed procedure consisting of fluorescence labeling of deoxyribonucleotides with BODIPY FL EDA and analysis by CE with LIF. An oligodeoxyribonucleotide site specifically modified with N6mdA was used for peak assignment, to establish separation conditions and to determine the LOD. The method yielded a LOD for N6mdA of 280 pM (1.4 amol), which is equivalent to ∼1 N6mdA per 104 normal nucleotides (0.01%) using 1 μg of DNA as the matrix. After calibration with completely dam methylated λ DNA, the assay was applied to the analysis of various DNAs.
Im Zeichen der Nachhaltigkeit
Authors: Finetti Marco
Published: October 2010

Vom Humboldt‐Jubiläum über die Wiedervereinigung zum Erkenntnistransfer: Die diesjährige Festversammlung der DFG füllte einen viel gebrauchten Begriff mit Leben.
Coastal wetlands and the Neanderthal settlement of Portuguese Estremadura
Authors: Haws Jonathan A. , Benedetti Michael M. , Funk Caroline L. , Bicho Nuno F. , Daniels J. Michael , Hesp Patrick A. , Minckley Thomas A. , Forman Steven L. , Jeraj Marjeta , Gibaja Juan F. , Hockett Bryan S.
Published: October 2010

Coastal wetlands are ecotone settings that offer diverse sets of resources for human exploitation, yet evidence for Pleistocene occupation rarely preserves due to recent postglacial sea‐level rise. During an ongoing geoarchaeological survey of Portuguese Estremadura we identified uplifted Pleistocene sediments that record coastal features including raised beaches, tidal channels, muds, peat, and coastal dunes. Stratified concentrations of Middle Paleolithic artifacts were found at Mira Nascente and Praia Rei Cortiço, two new sites in coastal wetland settings. The Mira Nascente locality yielded a chert‐dominated lithic assemblage in a tidal flat setting dated to MIS 3. The raw material economy differs markedly from sites found in other landscape settings. Praia Rei Cortiço is located near a thick peat deposit that formed in a freshwater coastal swamp and marsh likely dated to the Last Interglacial. These two sites represent a novel expression of Neanderthal land use strategies in Portugal. © 2010 Wiley Periodicals, Inc.

The riparian origin of mankind is most probable whether by the side of fresh or salt water.

—Carl O. Sauer (1962: 47)
Team collectivist culture: A remedy for creating team effectiveness
Authors: McAtavey Jean , Nikolovska Irena
Published: October 2010

This article provides a review of literature on collective orientation and effective teams by theoretically elucidating the relationship between these two constructs. The relationship between these two constructs is found by identifying the elements that go into creating an effective team, which are also found in a collectivist orientation. As those elements are identified, a model encompassing “team collectivist” corporate culture is proposed. The model depicts the development of team collectivist corporate culture, including members' attitudes, behaviors, and characteristics that reflect collectivist orientation that would aid in the development of effective teams, thus increasing performance and productivity within the organization. The model seeks to provide the Human Resource Development (HRD) professional with a tool that will (a) enable them to predict whether or not certain individuals have the potential to be an effective team player, (b) enable the organization to be proactive in building effective teams, and (c) allow team managers to diagnose and provide solutions to dysfunctional teams.
Development and exploratory validation of an organizational efficacy scale
Authors: Bohn James G.
Published: October 2010

Although many instruments have been developed to measure organizational constructs such as citizenship, climate, and organization‐based esteem, to date no scale has been designed specifically to measure efficacy at the organizational level. Tools to measure organizational efficacy in a business context have been recommended for over two decades. This research developed an instrument to assess organizational efficacy, an extension of the theory of self‐efficacy and group‐level efficacy in two studies. The first study included employees of seven organizations to test divergent and convergent validity of the Organizational Efficacy Scale with existing instruments. The second study combined 22 organizations (n = 886) to validate the instrument statistically. The scale demonstrated appropriate levels of convergent and discriminant validity with existing instruments. The final 17 items displayed high reliability and supported a three‐factor solution predicted by efficacy theory around the factors of collaboration, sense of mission, and sense of resilience. Additional psychometric properties for goodness of fit were acceptable.
Differentiation of mesenchymal stem cells in chitosan scaffolds with double micro and macroporosity
Authors: García Cruz Dunia M. , Gomes M. , Reis Rui. L. , Moratal David , Salmerón‐Sánchez Manuel , Gómez Ribelles Jose L. , Mano Joao F.
Published: October 2010

Bone Marrow mesenchymal stem cells can be induced to differentiate into osteoblasts to regenerate damaged bone tissue using tissue engineering techniques. In this study, we examine the use of chitosan scaffolds with double pore structure prepared by an innovative method that combines freeze gelation (that produces micropores) and particle leaching out technique (that produces interconnected spherical macropores) seeking to enhance the osteogenic differentiation of goat bone marrow stromal cells (GBMSCs). The double pore architecture of the scaffold was characterized by scanning electron microscopy (SEM), microcomputed tomography and confocal laser scanning microscopy. The obtained hierarchical pore structure allowed very efficient seeding of GBMSCs that are able to occupy the whole volume of the scaffold, showing good adhesion and proliferation. GBMSCs were differentiated into osteoblasts as indicated by alkaline phosphatase activity and osteocalcin expression. The results of this study demonstrate that chitosan scaffold may be promising biomaterial for bone regeneration. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
The effect of various denier capillary channel polymer fibers on the alignment of NHDF cells and type I collagen
Authors: Sinclair Kristofer D. , Webb Ken , Brown Philip J.
Published: October 2010

If tissue engineers are to successfully repair and regenerate native tendons and ligaments, it will be essential to implement contact guidance to induce cellular and type I collagen alignment to replicate the native structure. Capillary channel polymer (CC‐P) fibers fabricated by melt‐extrusion have aligned micrometer scale surface channels that may serve the goal of achieving biomimetic, physical templates for ligament growth and regeneration. Previous work characterizing the behavior of normal human dermal fibroblasts (NHDF), on the 19 denier per filament (dpf) CC‐P fibers, demonstrated a need for improved cellular and type I collagen alignment. Therefore, 5 and 9 dpf CC‐P fibers were manufactured to determine whether their channel dimensions would achieve greater alignment. A 29 dpf CC‐P fiber was also examined to determine whether cellular guidance could still be achieved within the larger dimensions of the fiber's channels. The 9 dpf CC‐P fiber appeared to approach the topographical constraints necessary to induce the cellular and type I collagen architecture that most closely mirrored that of native ACL tissue. This work demonstrated that the novel cross‐section of the CC‐P fiber geometry could approach the necessary surface topography to align NHDF cells along the longitudinal axis of each fiber. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Rapid estimation of activation enthalpies for cytochrome‐P450‐mediated hydroxylations
Authors: Mayeno Arthur N. , Robinson Jonathan L. , Reisfeld Brad
Published: October 2010

Cytochrome P450 (CYP) enzymes play a critical role in detoxication and bioactivation of xenobiotics; thus, the ability to predict the biotransformation rates and regioselectivity of CYP enzymes toward substrates is an important goal in toxicology and pharmacology. Here, we present the use of the semiempirical quantum chemistry method SAM1 to rapidly estimate relative activation enthalpies (ΔH‡) for the hydroxylation of aliphatic carbon centers of various substrates. The ΔH‡ were determined via a reaction path calculation, in the reverse direction (RRP), using the iron‐hydroxo‐porphine intermediate and the substrate radical. The SAM1 ΔH‡ were calculated via unrestricted Hartree‐Fock (UHF) and configuration interaction (CI) formalisms for both the doublet and quartet spin states. The SAM1 RRP ΔH‡, after subtracting a correction factor, were compared with density functional theory (DFT) B3LYP activation energies for two sets of substrates and showed R2 ranging from 0.69 to 0.89, and mean absolute differences ranging from 1.2 ± 1.0 to 1.7 ± 1.5 kcal/mol. SAM1 UHF and CI RRP calculation times were, on average, more than 200 times faster than those for the corresponding forward reaction path DFT calculations. Certain key transition‐state (TS) geometry measurements, such as the forming O···H bond length, showed good correlation with the DFT values. These results suggest that the SAM1 RRP approach can be used to rapidly estimate the DFT activation energy and some key TS geometry measurements and can potentially be applied to estimate substrate hydroxylation rates and regioselectivity by CYP enzymes. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
Transport properties of graphene nanoribbon‐based molecular devices
Authors: Ding Zongling , Jiang Jun , Xing Huaizhong , Shu Haibo , Dong Ruibin , Chen Xiaoshuang , Lu Wei
Published: October 2010

The electronic and transport properties of an edge‐modified prototype graphene nanoribbon (GNR) slice are investigated using density functional theory and Green's function theory. Two decorating functional group pairs are considered, such as hydrogen‐hydrogen and NH2‐NO2 with NO2 and NH2 serving as a donor and an acceptor, respectively. The molecular junctions consist of carbon‐based GNR slices sandwiched between Au electrodes. Nonlinear I‐V curves and quantum conductance have been found in all the junctions. With increasing the source‐drain bias, the enhancement of conductance is quantized. Several key factors determining the transport properties such as the electron transmission probabilities, the density of states, and the component of Frontier molecular orbitals have been discussed in detail. It has been shown that the transport properties are sensitive to the edge type of carbon atoms. We have also found that the accepter‐donor functional pairs can cause orders of magnitude changes of the conductance in the junctions. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
Multipole electrostatics in hydration free energy calculations
Authors: Shi Yue , Wu Chuanjie , Ponder Jay W. , Ren Pengyu
Published: October 2010

Hydration free energy (HFE) is generally used for evaluating molecular solubility, which is an important property for pharmaceutical and chemical engineering processes. Accurately predicting HFE is also recognized as one fundamental capability of molecular mechanics force field. Here, we present a systematic investigation on HFE calculations with AMOEBA polarizable force field at various parameterization and simulation conditions. The HFEs of seven small organic molecules have been obtained alchemically using the Bennett Acceptance Ratio method. We have compared two approaches to derive the atomic multipoles from quantum mechanical calculations: one directly from the new distributed multipole analysis and the other involving fitting to the electrostatic potential around the molecules. Wave functions solved at the MP2 level with four basis sets (6‐311G*, 6‐311++G(2d,2p), cc‐pVTZ, and aug‐cc‐pVTZ) are used to derive the atomic multipoles. HFEs from all four basis sets show a reasonable agreement with experimental data (root mean square error 0.63 kcal/mol for aug‐cc‐pVTZ). We conclude that aug‐cc‐pVTZ gives the best performance when used with AMOEBA, and 6‐311++G(2d,2p) is comparable but more efficient for larger systems. The results suggest that the inclusion of diffuse basis functions is important for capturing intermolecular interactions. The effect of long‐range correction to van der Waals interaction on the hydration free energies is about 0.1 kcal/mol when the cutoff is 12Å, and increases linearly with the number of atoms in the solute/ligand. In addition, we also discussed the results from a hybrid approach that combines polarizable solute with fixed‐charge water in the HFE calculation. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
Predicting posttraumatic stress symptoms in children following Hurricane Katrina: A prospective analysis of the effect of parental distress and parenting practices
Authors: Kelley Mary Lou , Self‐Brown Shannon , Le Brenda , Bosson Julia Vigna , Hernandez Brittany C. , Gordon Arlene T.
Published: October 2010

Research exhibits a robust relation between child hurricane exposure, parent distress, and child posttraumatic stress disorder (PTSD). This study explored parenting practices that could further explicate this association. Participants were 381 mothers and their children exposed to Hurricane Katrina. It was hypothesized that 3–7 months (T1) and 14–17 months (T2) post‐Katrina: (a) hurricane exposure would predict child PTSD symptoms after controlling for history of violence exposure and (b) hurricane exposure would predict parent distress and negative parenting practices, which, in turn, would predict increased child PTSD symptoms. Hypotheses were partially supported. Hurricane exposure directly predicted child PTSD at T1 and indirectly at T2. Additionally, several significant paths emerged from hurricane exposure to parent distress and parenting practices, which were predictive of child PTSD.
An magnetic resonance imaging T2*‐weighted sequence at short echo time to detect putaminal hypointensity in Parkinsonisms
Authors: Arabia Gennarina , Morelli Maurizio , Paglionico Sandra , Novellino Fabiana , Salsone Maria , Giofrè Laura , Torchia Giusi , Nicoletti Giuseppe , Messina Demetrio , Condino Francesca , Lanza Pierluigi , Gallo Olivier , Quattrone Aldo
Published: October 2010

At 1.5 T, T2*‐weighted gradient echo (GE) sequences are more sensitive in revealing mineral deposition in the basal ganglia than standard T2 weighted sequences. T2*‐weighted GE sequences, however, may detect putaminal hypointensities either in patients affected by parkinsonian syndromes or in healthy subjects. The aim of this study was to identify the magnetic resonance imaging (MRI) T2*‐weighted sequence which more specifically detected putaminal hypointensities differentiating atypical parkinsonian syndromes from Parkinson's disease (PD) and control subjects. In a sample of 38 healthy subjects, we performed three T2*‐weighted GE sequences at increasing time echo (TE; TE = 15 millisecond, TE = 25 millisecond, and echoplanar at TE = 40 millisecond; T2* sequences study). The sequence not showing any putaminal abnormality in the healthy subjects was then used to assess putaminal signal intensity in 189 patients with PD, 20 patients with multiple system atrophy (MSA), 41 patients with progressive supranuclear palsy (PSP), and in 150 age and sex‐matched control subjects. In the T2* sequences study, the T2*‐weighted TE = 15 (T2*/15) did not show any putaminal abnormalities in the healthy subjects. This sequence detected putaminal hypointensities in a significantly higher proportion of patients with MSA (35%, P < 0.05) and PSP (24.4%, P < 0.05) than in patients with PD (5.3%), but in none of the controls. The sensitivity of putaminal hypointensity in T2*/15 sequence was 25.4% for PD, 43.9% for PSP, and 55% for MSA versus controls whereas the specificity was 93.2% for all groups. Despite the suboptimal sensitivity, the high specificity of the T2*/15 sequence performed on routine MRI suggests its usefulness in clinical practice for identifying putaminal hypointensities associated with parkinsonian disorders. © 2010 Movement Disorder Society
A motor cortex excitability and gait analysis on Parkinsonian patients
Authors: Vacherot François , Attarian Shahram , Vaugoyeau Marianne , Azulay Jean‐Philippe
Published: October 2010

Transcranial magnetic stimulation (TMS) parameters were recorded in a lower limb muscle and correlated with the gait parameters of 25 patients with Parkinson's disease (PD) with and without dopamine substitution treatment (DST) and 10 control subjects. Single and paired‐pulse TMS were recorded in the tibialis anterior muscle (TA). Gait analysis was performed using a 3D motion analysis system. Parkinsonian patients (PP) did not differ from the control subjects (CS) in terms of relaxed motor threshold, active motor threshold (AMT), cortical silent period (CSP), motor‐evoked potential (MEP) amplitude and area, or paired‐pulse TMS with short interstimulus intervals (ISI). At longer ISIs, paired‐pulse TMS showed that the amplitudes of the conditioned MEPs were lower in untreated PP than in CS. DST partially compensated for this difference. Gait analysis showed that the gait of PP undergoing no treatment was slower and the stride length shorter than normal. Both of these parameters improved under DST, however. Analysis of data obtained on all the subjects combined showed that both of the latter parameters were correlated with the paired‐pulse MEP amplitude and area at longer ISIs. In PP, the cortical areas responsible for the lower limb movements seem to undergo intracortical facilitation (ICF) impairments, whereas the intracortical inhibition process is normal. The ICF level was found to be associated to the stride length and the velocity. The fact that only these two gait parameters were found to be dopa responsive indicates that dopaminergic treatment may improve gait disorders by restoring the ICF. © 2010 Movement Disorder Society
A mixture model of nuchal translucency thickness in screening for chromosomal defects: validation of a single operator dataset
Authors: Gasiorek‐Wiens A. , Kotsis S. , Staboulidou I. , Stumm M. , Wegner R. D. , Soergel P. , Schippert C. , von Kaisenberg C. S.
Published: October 2010

Objective

(1) To validate the mixture model in a single operator dataset and (2) to compare the detection rates for fetal chromosomal defects obtained from the mixture model with those obtained from either the delta nuchal translucency (NT) or log multiple of the median (MoM) approach.

Methods

Database query, viable singletons [crown‐rump length (CRL) 45–84 mm corresponding to 11–13+6 weeks], December 1997 to November 2006, examined by Adam Gasiorek‐Wiens, the statistical mixture model was applied.

Results

Seventy‐four of 4171 were lost to follow‐up (1.8%), 4097 singleton pregnancies included trisomy 21 (n = 34, 0.8%), trisomy 18 (n = 20, 0.5%), trisomy 13 (n = 8, 0.2%), Turner syndrome (n = 9, 0.2%) and other chromosomal abnormalities (n = 14, 0.3%). The main findings are that (1) the log‐transformed NT measurements follow a mixture of two Gaussian distributions and (2) the criteria to apply either the delta‐NT or log MoM models are not met. In the normal group, the majority of NT measurements were dependent on the CRL, a small group showed a median independent of the CRL. In the abnormal group it was the opposite. For a 5% false‐positive rate (FPR), the trisomy 21 detection rate was 83%.

Conclusions

The use of the mixture model in a single operator dataset produces results compatible with the original study. The mixture model has thus been validated. Copyright © 2010 John Wiley & Sons, Ltd.
Epidemiologic study of aripiprazole use and the incidence of suicide events
Authors: Ulcickas Yood Marianne , DeLorenze Gerald , Quesenberry Charles P. , Tsai Ai‐Lin , Phillips Syd , Willey Vincent J. , Niemcryk Steve J. , Wells Karen , Skovron Mary Lou , Cziraky Mark J. , Carson William , Oliveria Susan A.
Published: October 2010

Purpose

Because second generation antipsychotics (SGA) might affect the risk of suicide, systematic assessment of suicide risk associated with SGA in the postmarketing setting is important and of interest to regulatory authorities. To fulfill a postmarketing request, our objective was to determine suicide event (attempted or completed) incidence in patients with schizophrenia or bipolar disorder, prescribed aripiprazole.

Methods

Using administrative data from three US sources, we assessed study endpoints of suicide attempts and death by suicide in patients aged ≥18 enrolled continuously for ≥3 months in their health plans before receiving their first ever antipsychotic (November 2002–December 2005).

Results

Among 20 489 antipsychotic users (8985 patient‐years), unadjusted suicide event rates (per 1000 patient‐years) were: 20.69 (aripiprazole); 23.99 (olanzapine); 32.33 (quetiapine); 19.69 (risperidone); 48.52 (ziprasidone). Compared with current users of other SGA combined, aripiprazole users did not have an increased risk of suicide events (crude hazard ratio (HR) = 0.79, 95%CI: 0.48–1.30; adjusted HR = 0.69, 95%CI: 0.42–1.14—(controlling for study site, age, sex, index prescription year, antipsychotic use history, other pharmacotherapy exposure, comorbidity presence, schizophrenia/bipolar disorder, suicide attempts, number inpatient/outpatient encounters).

Conclusions

In this large, multi‐site study, compared with other SGA combined, aripiprazole is not associated with an increased risk of suicide events in an inception cohort of patients with ICD‐9/ICD‐10 codes indicative of schizophrenia or bipolar disorder. Copyright © 2010 John Wiley & Sons, Ltd.
Characterization of copolyesteramides from reactive blending of PET and MXD6 in the molten state
Authors: Samperi Filippo , Montaudo Maurizio S. , Battiato Salvatore , Carbone Domenico , Puglisi Concetto
Published: October 2010

Poly(ethylene terephthalate)‐poly(m‐xylylene adipamide) PET‐MXD6 copolymers were prepared by reactive blending of equimolar PET/MXD6 blends at 285 °C for different times in presence of terephthalic acid (1 wt %). First, the partial hydrolysis of PET and MXD6 occurs, yielding oligomers terminated with the reactive aromatic carboxyl groups. These oligomers quickly react with ester and amide inner groups producing a PET‐MXD6 copolymer that may compatibilize the initial biphasic blend. In this homogeneous environment, the aliphatic carboxyl‐terminated MXD6 chains, inactive in the initial biphasic blend, may promote the exchange reactions determining the formation of a random copolymer at longer reaction time (120 min). The progress of exchange reactions, and the microstructure of the formed copolyesteramides, versus the reaction time was followed by 1H and 13C NMR analyses using a CDCl3/TFA‐d/(CF3CO)2O mixture as solvent and applying appropriate mathematical models. Dyads and triads sequences were thoroughly characterized by NMR. Semicrystalline block copolymers were obtained at reaction time lower than 45 min. All PET‐MXD6 copolymers show a single Tg that change as a function of the dyads molar composition in the copolymers. The measured Tg values match with those calculated by a proposed modified Fox equation that take into account the weight fraction of the four dyad components of the PET‐MXD6 copolymers. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010
Poly‐(ε‐caprolactone) (PCL) and poly(hydroxy‐butyrate) (PHB) blends containing seaweed fibers: Morphology and thermal‐mechanical properties
Authors: Barghini Arianna , Ivanova Vassilka I. , Imam Syed H. , Chiellini Emo
Published: October 2010

Massive quantities of marine seaweed, Ulva armoricana are washed onto shores of many European countries and accumulates as waste. Attempts were made to utilize this renewable resource in hybrid composites by blending the algal biomass with biodegradable polymers such as poly(hydroxy‐butyrate) and poly‐(ε‐caprolactone). Compression‐molded films were developed and examined for their morphological, thermal and mechanical property. The Ulva fibers were well dispersed throughout the continous matrix exhibiting considerable cohesion with both polymers. Occasionally, regions with exposed fibres or aggregates were visible. About 50% algal content seemed to be an ideal concentration, thereafter, thermal stability was impacted. A progressive decrease in melting heat (ΔHm) was observed with increased algal content as well as a decrease in the crystallinity of the polymer matrix due to the presence of the organic filler. The addition of algal fibres improved the Young modulus of the blends, creating a concomitant loss in percent elongation (El) and ultimate tensile strength. Fiber content above 40% impacted tensile property negatively and composites with over 70% fiber contents composites were too fragile. Data suggest that macro algae are compatible with both polymers and processable as fillers in hybrid blends. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010
Effects of different composition ratio on the dielectric relaxation and dynamic mechanical properties of poly(ω‐dodecalactam‐co‐ε‐caprolactam‐co‐propylene oxide) copolymers
Authors: Mateva R. , Zhilkova KR. , Zamfirova G. , Díaz‐Calleja R. , Garcia‐Bernabé A.
Published: October 2010

The molecular dynamics of new poly (ω‐dodecalactam‐co‐ε‐caprolactam‐co‐propylene oxide) copolymers (DL/CL/PAC) has been investigated by using dynamic mechanical thermal analysis (DMTA) and dielectric relaxation spectroscopy (DRS) measurements. The copolymers were synthesized via anionic polymerization of relevant lactams activated with carbamoyl derivatives of telechelic hydroxyl terminated polypropylene oxide with isophorone diisocyanate (PAC). The calorimetric, X‐ray diffraction, and DMTA measurements were performed to recognize the influence of the composition ratio and the type of PAC on the physical, thermal, and mechanical properties of the synthesized copolymers. The DRS was used to study the frequency dependence of the dielectric permittivity of some isotherms from −110 to 145 °C. Copolymerization of ε‐caprolactam with about 10 wt % ω‐dodecalactam results in a copolymer that has lower water absorption, a melting point close to that of polyamide 6 and has a high enough degree of crystallinity in respect to high storage modulus. Five dielectric relaxations have been observed in the dielectric spectra, three at lower temperature and two at higher temperature. The copolymers have two glass transition temperatures for polyamide segments and polyether blocks, indicating microphase separation in the copolymers. Other studies directed toward molecular dynamics of polyamide DL/CL/PAC copolymers have not been reported. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2010
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

Unusual 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

Purpose: 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

Purpose: 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

Purpose: 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

CE 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

Recent 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

Stratified 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

The 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

The 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

Sensitive 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.