bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Photovoltaic Properties of a Thienylenevinylene and Diketopyrrolopyrrole Copolymer with High Mobility
Authors: Lim Bogyu , Yeo Jun‐Seok , Khim Dongyoon , Kim Dong‐Yu
Published: July 2011

A novel donor–acceptor‐type polymer with a low band‐gap that alternates electron‐rich thienylenevinylene groups with electron‐deficient diketopyrrolopyrrole (DPP) units (PETVTDPP) has been synthesized by Pd‐catalyzed Stille cross‐coupling polymerization. The polymer shows a broad absorption band of wavelengths that range from 330 to 900 nm, and a low band‐gap value of 1.43 eV. The field‐effect mobility of an organic thin‐film transistor based on this polymer is 0.05 cm2 · Vs−1. Bulk‐heterojunction solar cells using a mixture of PETVTDPP and PC[71]BM for the active layer show a power conversion efficiency (PCE) of 1.94% under simulated AM 1.5 G solar irradiation at 100 mW · cm−2.

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Reversible Photoinduced Switching of Permeability in a Cast Non‐Porous Film Comprising Azobenzene Liquid Crystalline Polymer
Authors: Liu Jian , Wang Mingle , Dong Mingling , Gao Liude , Tian Jingjing
Published: July 2011

Permeation characteristics of an azobenzene‐containing liquid crystalline (LC) non‐porous film are investigated using a metallic corrosion method. Thin films (300 nm) are fabricated by the solution casting of an azobenzene side‐chain LC polymer on freshly polished carbon steel coupons. Coated coupons are treated under the following conditions: a) gradual annealing at a cooling rate lower than 1 °C · min−1 from 150 °C (above its Tg) to room temperature, and b) irradiation at 465 nm (20 mW · cm−2) with either circularly polarized light (CPL) or non‐polarized light (NPL). The morphology of these films is characterized using X‐ray diffraction, polarized optical microscopy, and transmission measurements. The results suggest that the annealing treatment resulted in the formation of a polydomain structure consisting of locally ordered small smectic domains that lack mutual orientation. Ordered micro domains are surrounded by disordered phases. CPL and NPL irradiation generates a monodomain orientated structure and an isotropic liquid crystal glass, respectively. The permeability of these non‐porous films treated by CPL, NPL, and annealing are found to be 6.14 × 10−4, 1.92 × 10−2, and 1.56 × 10−3 cm3 · m−2 · d−1. An orientation‐dependent structure model is constructed to explain the permeation phenomenon, considering the ordered phase is impermeable, only the disordered phase is accessible to penetrating molecules. Fast switching of gas permeation is demonstrated by alternative irradiation of the film with CPL and NPL, which results in an approximately 30‐fold difference in the permeability of the non‐porous film.

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Simulations of Blood Flow in Plain Cylindrical and Constricted Vessels with Single Cell Resolution
Authors: Janoschek Florian , Toschi Federico , Harting Jens
Published: July 2011

Understanding the physics of blood is challenging due to its nature as a suspension of soft particles and the fact that typical problems involve different scales. This is valid also for numerical investigations. In fact, many computational studies either neglect the existence of discrete cells or resolve relatively few cells very accurately. The authors recently developed a simple and highly efficient yet still particulate model with the aim to bridge the gap between currently applied methods. The present work focuses on its applicability to confined flows in vessels of diameters up to ≈100 µm. For hematocrit values below 30%, a dependence of the apparent viscosity on the vessel diameter in agreement with experimental literature data is found.

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Characteristic Times of Polymer Tumbling Under Shear Flow
Authors: Usabiaga Florencio Balboa , Delgado‐Buscalioni Rafael
Published: July 2011

The tumbling dynamics of flexible chains in shear flow, analysed by Brownian Dynamics simulations, are found to be ruled by three characteristic times τtumb, τdif and τlag. The average tumbling time τtumb scales with the shear rate with a robust exponent against excluded volume (EV) or hydrodynamic interactions, $\tau _{{\rm tumb}} \approx {\dot {\gamma }}^{{-} 2/3} $. The chain extensions in the flow plane decorrelate in a time τdif determined by the diffusion of the chain configuration in gradient direction, $\tau _{{\rm dif}} \approx Y^{2} /D$. The chain keeps memory of its configuration over a number of tumblings events given by the ratio τdif/τtumb. While for ideal chains $\tau _{{\rm dif}} /\tau _{{\rm tumb}} \approx O(1)$, for expanded (EV) chains we find $\tau _{{\rm dif}} /\tau _{{\rm tumb}} \approx {\dot {\gamma }}^{0.2} $. Hence, EV chains tumble in a more deterministic way as ${\dot {\gamma }}$ is increased. As a consequence, contrary to previous assumptions, the exponential tail of the tumbling time distribution $P(\tau )\approx {\exp} ({-} \nu \tau )$ presents a non‐Poissonian exponent. This exponent ν is found to be determined by a new characteristic time τlag measuring how fast the chain in‐flow elongation X responses to the drag force induced by chain fluctuations in gradient direction Y. PSCS numbers.

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A Simulation Model of Biofilms with Autonomous Cells, 2 ‐ Explicit Representation of the Extracellular Polymeric Substance
Authors: Tao Yu‐Guo , Slater Gary W.
Published: July 2011

Biofilms are complex colonies of bacteria that grow in contact with a wall, often in the presence of a water flow. In the current work, biofilm colony growth is investigated using a two‐dimensional lattice Monte–Carlo algorithm based on the bond‐fluctuation algorithm (BFA). One of the distinguishing characteristics of biofilms, the synthesis and physical properties of the extracellular polymeric substance (EPS) in which the cells are embedded, is explicitly taken into account. Cells are modeled as autonomous closed loops with well‐defined mechanical and biological properties, while the EPS is modeled as flexible polymeric chain synthesized by the cells during their growth. By tuning the structural, energy, biological, and morphologic parameters of the model, the cell shapes as well as the growth and maturation of various types of biofilm colonies (including colonies with multiple species) can be controlled.

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Polymerization Reactor Modeling in Industry
Authors: Mueller Philipp A. , Richards John R. , Congalidis John P.
Published: July 2011

This paper provides an industrial perspective for the development of polymer reaction engineering models and their application to create new materials, products, and improved or novel processes. The challenges specific to polymer reactor modeling are discussed in the context of articles and books that the authors have found useful. Four components of a polymer reactor model (kinetics, thermodynamics, transport effects, and particle dynamics) are discussed with illustrative examples. Finally typical outputs of polymer reactor models are shown to demonstrate that a first principles model supported and validated by experiments can be a very powerful tool for fundamental understanding of polymer reactors and is a recommended alternative to empirical methods and experimentation alone.

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Accurate noninvasive measurement of cell size and compartment shape anisotropy in yeast cells using double‐pulsed field gradient MR
Authors: Shemesh Noam , Özarslan Evren , Basser Peter J. , Cohen Yoram
Published: July 2011

The accurate characterization of pore morphology is of great interest in a wide range of scientific disciplines. Conventional single‐pulsed field gradient (s‐PFG) diffusion MR can yield compartmental size and shape only when compartments are coherently ordered using q‐space approaches that necessitate strong gradients. However, double‐PFG (d‐PFG) methodology can provide novel microstructural information even when specimens are characterized by polydispersity in size and shape, and even when anisotropic compartments are randomly oriented. In this study, for the first time, we show that angular d‐PFG experiments can be used to accurately measure cellular size and shape anisotropy of fixed yeast cells employing relatively weak gradients. The cell size, as measured by light microscopy, was found to be 5.32 ± 0.83 µm, whereas the results from noninvasive angular d‐PFG experiments yielded a cell size of 5.46 ± 0.45 µm. Moreover, the low compartment shape anisotropy of the cells could be inferred from experiments conducted at long mixing times. Finally, similar experiments were conducted in a phantom comprising anisotropic compartments that were randomly oriented, showing that angular d‐PFG MR provides novel information on compartment eccentricity that could not be accessed using conventional methods. Angular d‐PFG methodology seems to be promising for the accurate estimation of compartment size and compartment shape anisotropy in heterogeneous systems in general, and biological cells and tissues in particular. Copyright © 2011 John Wiley & Sons, Ltd.
Comparative effectiveness of individual angiotensin receptor blockers on risk of mortality in patients with chronic heart failure
Authors: Desai Rishi J. , Ashton Carol M. , Deswal Anita , Morgan Robert O. , Mehta Hemalkumar B. , Chen Hua , Aparasu Rajender R. , Johnson Michael L.
Published: July 2011

Objective

There is little evidence on comparative effectiveness of individual angiotensin receptor blockers (ARBs) in patients with chronic heart failure (CHF). This study compared four ARBs in reducing risk of mortality in clinical practice.

Methods

A retrospective analysis was conducted on a national sample of patients diagnosed with CHF from 1 October 1996 to 30 September 2002 identified from Veterans Affairs electronic medical records, with supplemental clinical data obtained from chart review. After excluding patients with exposure to ARBs within the previous 6 months, four treatment groups were defined based on initial use of candesartan, valsartan, losartan, and irbesartan between the index date (1 October 2000) and the study end date (30 September 2002). Time to death was measured concurrently during that period. A marginal structural model controlled for sociodemographic factors, comorbidities, comedications, disease severity (left ventricular ejection fraction), and potential time‐varying confounding affected by previous treatment (hospitalization). Propensity scores derived from a multinomial logistic regression were used as inverse probability of treatment weights in a generalized estimating equation to estimate causal effects.

Results

Among the 1536 patients identified on ARB therapy, irbesartan was most frequently used (55.21%), followed by losartan (21.74%), candesartan (15.23%), and valsartan (7.81%). When compared with losartan, after adjusting for time‐varying hospitalization in marginal structural model, candesartan (OR = 0.79, 95%CI = 0.42–1.50), irbesartan (OR = 1.17, 95%CI = 0.72–1.90), and valsartan (OR = 0.98, 95%CI = 0.45–2.14) were found to have similar effectiveness in reducing mortality in CHF patients.

Conclusion

Effectiveness of ARBs in reducing mortality is similar in patients with CHF in everyday clinical practice. Copyright © 2011 John Wiley & Sons, Ltd.
Development of gallium gradients in three‐stage Cu(In,Ga)Se2 co‐evaporation processes
Authors: Schleussner Sebastian Michael , Törndahl Tobias , Linnarsson Margareta , Zimmermann Uwe , Wätjen Timo , Edoff Marika
Published: July 2011

We use secondary‐ion mass spectrometry, X‐ray diffraction and scanning electron microscopy to investigate the development over time of compositional gradients in Cu(In,Ga)Se2 thin films grown in three‐stage co‐evaporation processes and suggest a comprehensive model for the formation of the well‐known ‘notch’ structure. The model takes into account the need for compensating Cu diffusion by movement of group‐III ions in order to remain on the quasi‐binary tie line and indicates that the mobilities of In and Ga ions differ. Cu diffuses towards the back in the second stage and towards the front in the third, and this is the driving force for the movement of In and Ga. The [Ga]/[In + Ga] ratio then increases in the direction of the respective Cu movement because In has a higher mobility at process conditions than has Ga. Interdiffusion of In and Ga can be considerable in the (In,Ga)2Se3 film of the first stage, but seems largely to cease in Cu(In,Ga)Se2 and shows no signs of being boosted by the presence of a Cu2Se layer. Copyright © 2011 John Wiley & Sons, Ltd.
Use of support vector regression and numerically predicted cloudiness to forecast power output of a photovoltaic power plant in Kitakyushu, Japan
Authors: da Silva Fonseca Joao Gari , Oozeki Takashi , Takashima Takumi , Koshimizu Gentarou , Uchida Yoshihisa , Ogimoto Kazuhiko
Published: July 2011

The development of a methodology to forecast accurately the power produced by photovoltaic systems can be an important tool for the dissemination and integration of such systems on the public electricity grids. Thus, the objective of this study was to forecast the power production of a 1‐MW photovoltaic power plant in Kitakyushu, Japan, using a new methodology based on support vector machines and on the use of several numerically predicted weather variables, including cloudiness. Hourly forecasts of the power produced for 1 year were carried out. Moreover, the effect of the use of numerically predicted cloudiness on the quality of the forecasts was also investigated. The forecasts of power production obtained with the proposed methodology had a root mean square error of 0.0948 MW h and a mean absolute error of 0.058 MW h. It was also found that the forecast and measured values of power production had a good level of correlation varying from 0.8 to 0.88 according to the season of the year. Finally, the use of numerically predicted cloudiness had an important role in the accuracy of the forecasts, and when cloudiness was not used, the root mean square error of the forecasts increased more than 32%, and the mean absolute error increased more than 42%. Copyright © 2011 John Wiley & Sons, Ltd.
Evaluation of two‐dimensional electrical properties of photovoltaic modules using bias‐dependent electroluminescence
Authors: Li Biao , Stokes Adam , Doble Dan M. J.
Published: July 2011

An approach to deriving two‐dimensional maps of cell and module electrical properties from electroluminescence imaging is presented. The technique involves quantitative comparison of the intensity differences in the electroluminescence images at different bias currents, enabling the derivation of junction voltages of individual pixels. These data were then fitted to a distributed electrical model that allows the derivation of a two‐dimensional dark I–V curve for each point across the module. Interpretation of the dark I–V curve enabled the evaluation of series resistance, shunt resistance, ideality factor, and reverse saturation current for each pixel. These parameters were then used to enable the prediction of module performance under illumination. Copyright © 2011 John Wiley & Sons, Ltd.
Exploration of Atmospheric Pressure Plasma Nanofilm Technology for Straightforward Bio‐Active Coating Deposition: Enzymes, Plasmas and Polymers, an Elegant Synergy
Authors: Heyse Pieter , Van Hoeck Arne , Roeffaers Maarten B. J. , Raffin Jean‐Paul , Steinbüchel Alexander , Stöveken Tim , Lammertyn Jeroen , Verboven Pieter , Jacobs Pierre A. , Hofkens Johan , Paulussen Sabine , Sels Bert F.
Published: July 2011

While protein or enzyme immobilization methodologies are readily applicable in a majority of industrial processes, some lacunas still remain. For example, the multi‐step, wet‐chemical nature of current immobilization reactions limits straightforward bio‐film fabrication in continuous production units. As such, a fast and preferably single step immobilization technique, minimizing solvent use and decoupling deposition substrate from used method is awaited. In this research, an atmospheric pressure plasma reaction environment is chosen for its flexibility in terms of reactivity and the ease of coating depositions on a wide variety of substrates. Organic coating precursors such as acetylene or pyrrole are injected simultaneously with an atomized enzyme solution directly in the discharge. By atomizing the enzyme solution, the enzyme molecules are surrounded by a watery shell. It is envisioned that such droplet act as “shuttles”, delivering the enzymes to the discharge while protecting them from the harsh plasma conditions. In the discharge, polymerization of the added organic coating precursor takes place and consequently, the enzyme molecules become trapped in the growing polymer network. In addition, atomization of the protein solution favors the spatial distribution of the proteins in the coating. Several enzymes are evaluated and enhanced temperature and solvent stability is observed. Moreover, single molecule fluorescence, enzyme activity and bio‐recognition experiments demonstrate protein integrity after plasma assisted immobilization.

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Frailty models: Applications to biomedical and genetic studies
Authors: Govindarajulu Usha S. , Lin Haiqun , Lunetta Kathryn L. , D'Agostino R.B.
Published: July 2011

In survival analysis, frailty models are potential choices for modeling unexplained heterogeneity in a population. This tutorial presents an overview and general framework of frailty modeling and estimation for multiplicative hazards models in the context of biomedical and genetic studies. Other topics in frailty models, such as diagnostic methods for model adequacy and inference in frailty models, are also discussed. Examples of analyses using multivariate frailty models in a non‐parametric hazards setting on biomedical datasets are provided, and the implications of choosing to use frailty and relevance to genetic applications are discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Characterizing global statistical significance of spatiotemporal hot spots in magnetoencephalography/ electroencephalography source space via excursion algorithms
Authors: Xu Yang , Sudre Gustavo P. , Wang Wei , Weber Douglas J. , Kass Robert E.
Published: July 2011

Identifying brain regions with high differential response under multiple experimental conditions is a fundamental goal of functional imaging. In many studies, regions of interest (ROIs) are not determined a priori but are instead discovered from the data, a process that requires care because of the great potential for false discovery. An additional challenge is that magnetoencephalography/electroencephalography sensor signals are very noisy, and brain source images are usually produced by averaging sensor signals across trials. As a consequence, for a given subject, there is only one source data vector for each condition, making it impossible to apply testing methods such as analysis of variance. We solve these problems in several steps. (1) To obtain within‐condition uncertainty, we apply the bootstrap across trials, producing many bootstrap source images. To discover ‘hot spots’ in space and time that could become ROIs, (2) we find source locations where likelihood ratio statistics take unusually large values. We are not interested in isolated brain locations where a test statistic might happen to be large. Instead, (3) we apply a clustering algorithm to identify sources that are contiguous in space and time where the test statistic takes an ‘excursion’ above some threshold. Having identified possible spatiotemporal ROIs, (4) we evaluate global statistical significance of ROIs by using a permutation test. After these steps, we check performance via simulation, and then illustrate their application in a magnetoencephalography study of four‐direction center‐out wrist movement, showing that this approach identifies statistically significant spatiotemporal ROIs in the motor and visual cortices of individual subjects. Copyright © 2011 John Wiley & Sons, Ltd.
Optimization of an Analytical Procedure for Extraction of Lipids from Microalgae
Authors: Ryckebosch Eline , Muylaert Koenraad , Foubert Imogen
Published: July 2011

An optimized procedure for extraction of total and non‐polar lipids from microalgae is proposed. The effects of solvent, pretreatment (lyophilization, inactivation of lipases, and addition of antioxidants) and cell‐disruption (liquid nitrogen, sonication, and bead beating) on total lipid content, lipid class, and fatty acid composition were examined. Chloroform–methanol 1:1 was shown to be the best solvent mixture for extraction of total lipids from microalgae. When performing this extraction, lyophilized algae can be used, no pretreatment with isopropanol to inactivate the lipases is needed and addition of antioxidants is not necessary. Furthermore, cell‐disruption is not essential, although in that case two extractions must be performed in series to ensure that, irrespective of the microalgal species, all lipids are extracted. Determination of non‐polar lipid content should be performed by separation of the total lipid extract on an SPE column. Extraction using petroleum ether is only appropriate when a bead beater is used for pretreatment.
Cabazitaxel: Evidence and Clinical Experience
Authors: Malik Zafar Iqbal
Published: July 2011

Cabazitaxel, a novel taxane that lacks susceptibility to the drug-resistance mechanism seen with previous drugs in the same class, has demonstrated a survival benefit in metastatic castrate-resistant prostate cancer (mCRPC), plus a manageable toxicity profile. It is the first active treatment to receive a European licence for the second-line treatment of mCRPC post-docetaxel. Novel non-chemotherapeutic treatments for this indication are at various stages of development and regulatory status. These new and emerging treatments bring a potential opportunity to extend the lives of patients with mCRPC, and improve quality of life in this setting, but they also raise pertinent questions about the optimal timing and sequencing of their use. Based on my clinical experience with cabazitaxel, first as a phase III trialist, and then as a participant in an expanded-access programme, I believe that the chemotherapeutic option should be offered before non-chemotherapeutic agents, where the patient's performance status allows, so that there is an opportunity to gain the potential benefits of this treatment within the likely therapeutic window. Other second-line/third-line treatments, notably the hormonal agent abiraterone, are likely to remain useful even after a decline in the patient's performance status.
Ghrelin levels are reduced in Rett syndrome patients with eating difficulties
Authors: Hara Munetsugu , Nishi Yoshihiro , Yamashita Yushiro , Yoh Junko , Takahashi Satoru , Nagamitsu Shin‐ichiro , Kakuma Tatsuyuki , Hosoda Hiroshi , Kangawa Kenji , Kojima Masayasu , Matsuishi Toyojiro
Published: July 2011

Most patients with Rett syndrome (RTT) have both gastrointestinal problems and somatic growth failure, including microcephaly. Ghrelin is a peptide hormone involved in growth hormone secretion, interdigestive motility, and feeding behavior. Plasma ghrelin assays have previously been described for other neurodevelopmental disorders. To examine the pathophysiology of RTT, we measured plasma levels of ghrelin in patients with RTT. A case–control study examining plasma levels of ghrelin, serum growth hormone, and insulin‐like growth factor‐1 (IGF‐1) was performed on 27 patients with RTT and 53 controls. Plasma levels of total (T)‐ and octanoyl (O)‐ghrelin were significantly lower in patients with RTT than in controls. Plasma levels of T‐ghrelin correlated significantly with serum IGF‐1 levels and head circumference. Significantly lower levels of plasma T‐ghrelin and O‐ghrelin were observed in RTT patients with eating difficulties, while lower levels of plasma T‐ghrelin were observed in RTT patients with constipation, in comparison to patients without either of these symptoms. Alterations in plasma ghrelin levels may reflect various clinical symptoms and signs in RTT patients, including growth failure, acquired microcephalus, autonomic nerve dysfunction, and feeding difficulties. We describe the role of ghrelin in RTT and suggest this peptide as a novel biological marker in patients with RTT.
Design and Construction of a First-Generation High-Throughput Integrated Robotic Molecular Biology Platform for Bioenergy Applications
Authors: Hughes Stephen R. , Butt Tauseef R. , Bartolett Scott , Riedmuller Steven B. , Farrelly Philip
Published: July 2011

The molecular biological techniques for plasmid-based assembly and cloning of gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. High-throughput integrated robotic molecular biology platforms that have the capacity to rapidly clone and express heterologous gene open reading frames in bacteria and yeast and to screen large numbers of expressed proteins for optimized function are an important technology for improving microbial strains Published by Elsevier Inc. on behalf of the Society for Laboratory Automation and Screening for biofuel production. The process involves the production of full-length complementary DNA libraries as a source of plasmid-based clones to express the desired proteins in active form for determination of their functions. Proteins that were identified by high-throughput screening as having desired characteristics are overexpressed in microbes to enable them to perform functions that will allow more cost-effective and sustainable production of biofuels. Because the plasmid libraries are composed of several thousand unique genes, automation of the process is essential. This review describes the design and implementation of an automated integrated programmable robotic workcell capable of producing complementary DNA libraries, colony picking, isolating plasmid DNA, transforming yeast and bacteria, expressing protein, and performing appropriate functional assays. These operations will allow tailoring microbial strains to use renewable feedstocks for production of biofuels, bioderived chemicals, fertilizers, and other coproducts for profitable and sustainable biorefineries.
Self-recognition mechanism of MamA, a magnetosome-associated TPR-containing protein, promotes complex assembly
Authors: Zeytuni Natalie , Ozyamak Ertan , Ben-Harush Kfir , Davidov Geula , Levin Maxim , Gat Yair , Moyal Tal , Brik Ashraf , Komeili Arash , Zarivach Raz
Published: July 2011

The magnetosome, a biomineralizing organelle within magnetotactic bacteria, allows their navigation along geomagnetic fields. Magnetosomes are membrane-bound compartments containing magnetic nanoparticles and organized into a chain within the cell, the assembly and biomineralization of magnetosomes are controlled by magnetosome-associated proteins. Here, we describe the crystal structures of the magnetosome-associated protein, MamA, fromMagnetospirillum magneticumAMB-1 andMagnetospirillum gryphiswaldenseMSR-1. MamA folds as a sequential tetra-trico-peptide repeat (TPR) protein with a unique hook-like shape. Analysis of the MamA structures indicates two distinct domains that can undergo conformational changes. Furthermore, structural analysis of seven crystal forms verified that the core of MamA is not affected by crystallization conditions and identified three protein–protein interaction sites, namely a concave site, a convex site, and a putative TPR repeat. Additionally, relying ontransmission electron microscopyand size exclusion chromatography, we show that highly stable complexes form upon MamA homooligomerization. Disruption of the MamA putative TPR motif or N-terminal domain led to protein mislocalization in vivo and prevented MamA oligomerization in vitro. We, therefore, propose that MamA self-assembles through its putative TPR motif and its concave site to create a large homooligomeric scaffold which can interact with other magnetosome-associated proteins via the MamA convex site. We discuss the structural basis for TPR homooligomerization that allows the proper function of a prokaryotic organelle.
Combinatorial synthesis of chemically diverse core-shell nanoparticles for intracellular delivery
Authors: Siegwart Daniel J. , Whitehead Kathryn A. , Nuhn Lutz , Sahay Gaurav , Cheng Hao , Jiang Shan , Ma Minglin , Lytton-Jean Abigail , Vegas Arturo , Fenton Patrick , Levins Christopher G. , Love Kevin T. , Lee Haeshin , Cortez Christina , Collins Sean P. , Li Ying Fei , Jang Janice , Querbes William , Zurenko Christopher , Novobrantseva Tatiana , Langer Robert , Anderson Daniel G.
Published: July 2011

Analogous to an assembly line, we employed a modular design for the high-throughput study of 1,536 structurally distinct nanoparticles with cationic cores and variable shells. This enabled elucidation of complexation, internalization, and delivery trends that could only be learned through evaluation of a large library. Using robotic automation, epoxide-functionalized block polymers were combinatorially cross-linked with a diverse library of amines, followed by measurement of molecular weight, diameter, RNA complexation, cellular internalization, and in vitro siRNA and pDNA delivery. Analysis revealed structure-function relationships and beneficial design guidelines, including a higher reactive block weight fraction, stoichiometric equivalence between epoxides and amines, and thin hydrophilic shells. Cross-linkers optimally possessed tertiary dimethylamine or piperazine groups and potential buffering capacity. Covalent cholesterol attachment allowed for transfection in vivo to liver hepatocytes in mice. The ability to tune the chemical nature of the core and shell may afford utility of these materials in additional applications.
Constitutive cAMP response element binding protein (CREB) activation by Alzheimer's disease presenilin-driven inositol trisphosphate receptor (InsP
3
R) Ca
2+
signaling
Authors: Müller Marioly , Cárdenas César , Mei Lijuan , Cheung King-Ho , Foskett J. Kevin
Published: July 2011

Mutations in presenilins (PS) account for most early-onset familial Alzheimer's disease (FAD). Accumulating evidence suggests that disrupted Ca
2+
signaling may play a proximal role in FAD specifically, and Alzheimer's disease (AD) more generally, but its links to the pathogenesis of AD are obscure. Here we demonstrate that expression of FAD mutant PS constitutively activates the transcription factor cAMP response element binding protein (CREB) and CREB target gene expression in cultured neuronal cells and AD mouse models. Constitutive CREB activation was associated with and dependent on constitutive activation of Ca
2+
/CaM kinase kinase β and CaM kinase IV (CaMKIV). Depletion of endoplasmic reticulum Ca
2+
stores or plasma membrane phosphatidylinositol-bisphosphate and pharmacologic inhibition or knockdown of the expression of the inositol trisphosphate receptor (InsP
3
R) Ca
2+
release channel each abolished FAD PS-associated constitutive CaMKIV and CREB phosphorylation. CREB and CaMKIV phosphorylation and CREB target gene expression, including nitric oxide synthase and c-fos, were enhanced in brains of M146V-KI and 3xTg-AD mice expressing FAD mutant PS1 knocked into the mouse locus. FAD mutant PS-expressing cells demonstrated enhanced cell death and sensitivity to Aβ toxicity, which were normalized by interfering with the InsP
3
R–CAMKIV–CREB pathway. Thus, constitutive CREB phosphorylation by exaggerated InsP
3
R Ca
2+
signaling in FAD PS-expressing cells may represent a signaling pathway involved in the pathogenesis of AD.
The Cosmic Linear Anisotropy Solving System (CLASS).
Part II: Approximation schemes
Authors: Diego Blas  , Julien Lesgourgues  , Thomas Tram
Published: July 2011

Boltzmann codes are used extensively by several groups for
constraining cosmological parameters with Cosmic Microwave
Background and Large Scale Structure data. This activity is
computationally expensive, since a typical project requires from
104 to 105 Boltzmann code executions. The newly released code
CLASS (Cosmic Linear Anisotropy Solving System) incorporates
improved approximation schemes leading to a simultaneous gain in
speed and precision. We describe here the three approximations used
by CLASS for basic ΛCDM models, namely: a baryon-photon
tight-coupling approximation which can be set to first order, second
order or to a compromise between the two; an ultra-relativistic
fluid approximation which had not been implemented in public
distributions before; and finally a radiation streaming
approximation taking reionisation into account.
Identifying disease-associated SNP clusters via contiguous outlier detection
Authors: Yang Can , Zhou Xiaowei , Wan Xiang , Yang Qiang , Xue Hong , Yu Weichuan
Published: July 2011

Motivation: Although genome-wide association studies (GWAS) have identified many disease-susceptibility single-nucleotide polymorphisms (SNPs), these findings can only explain a small portion of genetic contributions to complex diseases, which is known as the missing heritability. A possible explanation is that genetic variants with small effects have not been detected. The chance is < 8 that a causal SNP will be directly genotyped. The effects of its neighboring SNPs may be too weak to be detected due to the effect decay caused by imperfect linkage disequilibrium. Moreover, it is still challenging to detect a causal SNP with a small effect even if it has been directly genotyped.

Results: In order to increase the statistical power when detecting disease-associated SNPs with relatively small effects, we propose a method using neighborhood information. Since the disease-associated SNPs account for only a small fraction of the entire SNP set, we formulate this problem as Contiguous Outlier DEtection (CODE), which is a discrete optimization problem. In our formulation, we cast the disease-associated SNPs as outliers and further impose a spatial continuity constraint for outlier detection. We show that this optimization can be solved exactly using graph cuts. We also employ the stability selection strategy to control the false positive results caused by imperfect parameter tuning. We demonstrate its advantage in simulations and real experiments. In particular, the newly identified SNP clusters are replicable in two independent datasets.

Availability: The software is available at: http://bioinformatics.ust.hk/CODE.zip.

Contact:  eeyu@ust.hk

Supplementary information:  Supplementary data are available at Bioinformatics online.
GenSSI: a software toolbox for structural identifiability analysis of biological models
Authors: Chiş Oana , Banga Julio R. , Balsa-Canto Eva
Published: July 2011

Summary: Mathematical modeling has a key role in systems biology. Model building is often regarded as an iterative loop involving several tasks, among which the estimation of unknown parameters of the model from a certain set of experimental data is of central importance. This problem of parameter estimation has many possible pitfalls, and modelers should be very careful to avoid them. Many of such difficulties arise from a fundamental (yet often overlooked) property: the so-called structural (or a priori) identifiability, which considers the uniqueness of the estimated parameters. Obviously, the structural identifiability of any tentative model should be checked at the beginning of the model building loop. However, checking this property for arbitrary non-linear dynamic models is not an easy task. Here we present a software toolbox, GenSSI (Generating Series for testing Structural Identifiability), which enables non-expert users to carry out such analysis. The toolbox runs under the popular MATLAB environment and is accompanied by detailed documentation and relevant examples.

Availability: The GenSSI toolbox and the related documentation are available at http://www.iim.csic.es/%7Egenssi.

Contact:  ebalsa@iim.csic.es
Structural analysis of the hot spots in the binding between H1N1 HA and the 2D1 antibody: do mutations of H1N1 from 1918 to 2009 affect much on this binding?
Authors: Liu Qian , Hoi Steven C. H. , Su Chinh T. T. , Li Zhenhua , Kwoh Chee-Keong , Wong Limsoon , Li Jinyan
Published: July 2011

Motivation: Worldwide and substantial mortality caused by the 2009 H1N1 influenza A has stimulated a new surge of research on H1N1 viruses. An epitope conservation has been learned in the HA1 protein that allows antibodies to cross-neutralize both 1918 and 2009 H1N1. However, few works have thoroughly studied the binding hot spots in those two antigen–antibody interfaces which are responsible for the antibody cross-neutralization.

Results: We apply predictive methods to identify binding hot spots at the epitope sites of the HA1 proteins and at the paratope sites of the 2D1 antibody. We find that the six mutations at the HA1's epitope from 1918 to 2009 should not harm its binding to 2D1. Instead, the change of binding free energy on the whole exhibits an increased tendency after these mutations, making the binding stronger. This is consistent with the observation that the 1918 H1N1 neutralizing antibody can cross-react with 2009 H1N1. We identified three distinguished hot spot residues, including Lys166, common between the two epitopes. These common hot spots again can explain why 2D1 cross-reacted. We believe that these hot spot residues are mutation candidates which may help H1N1 viruses to evade the immune system. We also identified eight residues at the paratope site of 2D1, five from its heavy chain and three from its light chain, that are predicted to be energetically important in the HA1 recognition. The identification of these hot spot residues and their structural analysis are potentially useful to fight against H1N1 viruses.

Contact:  jinyan.li@uts.edu.au

Availability:  Z-score is available at http://155.69.2.25/liuqian/indexz.py

Supplementary information:  Supplementary data are available at Bioinformatics online.
phyloMeta: a program for phylogenetic comparative analyses with meta-analysis
Authors: Lajeunesse Marc J.
Published: July 2011

Summary:  phyloMeta is an easy to use console program for integrating phylogenetic information into meta-analysis. It is designed to help ecologists, evolutionary biologists and conservation biologists analyze effect size data extracted from published studies in a comparative phylogenetic context. This software estimates phylogenetic versions of all the traditional meta-analytical statistics used for: pooling effect sizes with weighted regressions; evaluating the homogeneity of these effect sizes; performing moderator tests akin to ANOVA style analyses; and analyzing data with fixed- and random-effects models. phyloMeta is developed in C/C++ and can be used via command line in MS Windows environments.

Availability:  phyloMeta can be obtained freely as an executable on the web at http://lajeunesse.myweb.usf.edu/publications

Contact:  lajeunesse@usf.edu
Prevalence and Associated Factors of Functional Gastrointestinal Disorders and Bowel Habits in Chinese Adolescents
Authors: Zhou Huiqing , Yao Min , Cheng Guang‐Yu , Chen Yan‐Ping , Li Ding‐Guo
Published: July 2011

Objectives:

In the present study, we explored the prevalence rates and association factors of functional gastrointestinal disorders and the most common modes and frequencies of bowel habit among a cohort of Chinese adolescents.

Patients and Methods:

A stratified, randomized study based on cross‐sectional data was performed using cluster sampling, which recruited 3671 students in Shanghai, China. All of the students were requested to complete a questionnaire.

Results:

Overall, 88.05% ± 0.28% of students had a bowel movement frequency of between 1 of 2 times per day and once every 2 days. Female students were found to have a lower bowel frequency than boys (P < 0.01). The prevalence of irritable bowel syndrome (IBS), functional constipation, and functional diarrhea were 19.89%, 24.93%, and 5.42%, respectively. Certain factors adjusted for age and sex were significantly associated with IBS (P < 0.05), including gastrointestinal tract infection (odds ratio [OR] 2.26), abuse of analgesics (OR 1.25), air swallowing to terminate hiccups (OR 1.28), fatigue (OR 1.15), and depression (OR 1.36). Other factors that were adjusted for age and sex, such as fried food (OR 1.68), air swallowing to terminate hiccups (OR 1.21), anxiety (OR 1.12), and depression (OR 1.57), were significantly associated with the presence of functional constipation (P < 0.05).

Conclusions:

Our findings suggest that normal bowel frequency among Chinese urban adolescents may be defined as between 1 or 2 bowel movements per day and once every 2 days. IBS, functional constipation, and diarrhea are common disorders among this adolescent group.
ORS Containing Zinc Does Not Reduce Duration or Stool Volume of Acute Diarrhea in Hospitalized Children
Authors: Wadhwa Nitya , Natchu Uma Chandra Mouli , Sommerfelt Halvor , Strand Tor A. , Kapoor Vishal , Saini Savita , Kainth Udaypal S. , Bhatnagar Shinjini
Published: July 2011

Background and Aim:

The World Health Organization recommends oral zinc (tablets or syrups) as adjunct therapy with oral rehydration solution (ORS) for acute childhood diarrhea. Mixing zinc with ORS can be an attractive approach for simultaneous provision of these 2 effective interventions. This double‐masked randomized controlled trial evaluated the efficacy of ORS containing 40 mg/L elemental zinc per liter (zinc‐ORS) in reducing stool weight and duration of diarrhea.

Patients and Methods:

Five hundred northern Indian children ages 1 to 35 months with diarrhea <7 days’ duration were randomized to zinc‐ORS or ORS. The primary outcomes were total stool output and time to recovery.

Results:

The median total stool output was 2.12 g · kg−1 · h−1 (interquartile range [IQR] 0.9–3.76) in the zinc‐ORS group compared with 1.78 g · kg−1 · h−1 (IQR 0.83–3.45) in the ORS group. The time to recovery was also similar in the 2 groups (hazard ratio 1.06 [95% confidence interval 0.88–1.27]). In subjects who received zinc‐ORS, the median (IQR) zinc intakes were 27 (16–46) mg on day 1, 15 (6–27) mg on day 2, and negligible thereafter.

Conclusions:

The World Health Organization–recommended daily dose of zinc for diarrhea was not achieved in most children beyond the first day of treatment. This is the likely explanation for the lack of improvement in outcomes from zinc‐ORS when compared with ORS alone. Our findings do not support a change from using zinc syrup or dispersible tablets for treatment of acute diarrhea in children.
Serum Concentrations of VEGF and TGF‐β1 During Exclusive Enteral Nutrition in IBD
Authors: Wedrychowicz Andrzej , Kowalska‐Duplaga Kinga , Jedynak‐Wasowicz Urszula , Pieczarkowski Stanislaw , Sladek Malgorzata , Tomasik Przemyslaw , Fyderek Krzysztof
Published: July 2011

Background and Aim:

Exclusive enteral nutrition (EEN) is an effective method of treatment in achieving remission in inflammatory bowel disease (IBD); however, its mechanism of action is still poorly understood. The objective of our study was to assess the influence of EEN on serum vascular endothelial growth factor (VEGF) and transforming growth factor‐beta 1 (TGF‐β1) in children and adolescents with IBD.

Patients and Methods:

Thirty‐nine children and adolescents with IBD (24 with Crohn disease [CD] and 15 with ulcerative colitis [UC]) and 25 healthy controls were enrolled in the study. VEGF and TGF‐β1 were assessed at the baseline and after 2 and 4 weeks of EEN in CD and UC groups and once in controls using enzyme‐linked immunosorbent assay immunoassays.

Results:

At the baseline, we found increased serum VEGF in the CD versus UC group and controls (P < 0.05) and serum TGF‐β1 in the UC versus CD group and controls (P < 0.05). During EEN, VEGF decreased in the UC and CD groups, whereas TGF‐β1 increased in the CD group and decreased in the UC group. The CD group achieved disease remission faster than the UC group, and the weight gain of patients with CD during EEN was higher compared with patients with UC. Additionally, TGF‐β1 concentration correlated with protein and energies daily intake in the CD group (R = 0.95; P < 0.05).

Conclusions:

Different effectiveness of EEN in achieving remission in CD and UC may result from a modification of growth factor production. EEN stimulated TGF‐β1 production in CD but not in UC, which possibly resulted in higher effectiveness of EEN in this group of patients.
Tolerance, Safety, and Effect on the Faecal Microbiota of an Enteral Formula Supplemented With Pre‐ and Probiotics in Critically Ill Children
Authors: Simakachorn Nipat , Bibiloni Rodrigo , Yimyaem Phisek , Tongpenyai Yothi , Varavithaya Wandee , Grathwohl Dominik , Reuteler Gloria , Maire Jean‐Claude , Blum Stephanie , Steenhout Philippe , Benyacoub Jalil , Schiffrin Eduardo J.
Published: July 2011

Objectives:

The aim of this study was to demonstrate the tolerance and safety of an enteral formula containing prebiotics/probiotics, and its effect on the faecal microbiota in critically ill children.

Subjects and Methods:

Ninety‐four patients between 1 and 3 years old under mechanical ventilation requiring enteral feeding were randomised to receive either a test formula containing a synbiotic blend (composed of 2 probiotic strains [Lactobacillus paracasei NCC 2461 and Bifidobacterium longum NCC 3001], fructooligosaccharides [FOS], inulin, and Acacia gum), or a control formula. Patients remained in the intensive care unit for 7 days and were examined at day 14. Tolerance was assessed by overall caloric intake and time to reach caloric goal. Safety was assessed by abdominal distention, vomiting, and stool frequency. Microbiota was analysed by culture‐ and molecular‐based methods.

Results:

Overall caloric intake and time to reach caloric goal were similar between groups (noninferiority was shown). Abdominal distention, vomiting, and stool frequency were not affected by the supplementation with pre‐ and probiotics. Faecal bifidobacteria were higher in the test group at the end of the study. A similar trend was observed for total lactobacilli. L paracasei NCC 2461 and B longum NCC 3001 were detected in 80.4% and 17% of the test group patients, respectively. Enterobacteria levels remained unchanged during hospitalisation in the control group but diminished in the test group.

Conclusions:

The enteral formula supplemented with synbiotics was well tolerated by children in intensive care units; it was safe and produced an increase in faecal bacterial groups of previously reported beneficial effects.
Safety of Pediatric Percutaneous Liver Biopsy Performed by Interventional Radiologists
Authors: Potter Carol , Hogan Mark J. , Henry‐Kendjorsky Katherine , Balint Jane , Barnard John A.
Published: July 2011

Objective:

National data suggest that pediatric percutaneous liver biopsy is increasingly being performed by interventional radiologists rather than pediatric gastroenterologists. The objective of the present report is to describe the safety and effectiveness of percutaneous liver biopsy performed by interventional radiologists in a large cohort of children and to compare the results with the existing literature on biopsies performed by pediatric gastroenterologists.

Patients and Methods:

The medical records of 249 children undergoing ultrasound‐guided percutaneous liver biopsy by interventional radiologists were reviewed for adverse events and success of obtaining tissue. Two hundred ninety‐four biopsies were reviewed.

Results:

There were no deaths. There were 2 instances of a 2‐g or greater drop in hemoglobin following biopsy, neither of which was associated with clinical signs of hemorrhage. A small, asymptomatic pneumothorax quickly resolved without treatment. One patient developed Klebsiella sepsis 48 hours after biopsy. In all but 1 case, an adequate sample size was obtained. This low incidence of adverse events compares favorably with existing published reports of morbidity and mortality following percutaneous liver biopsy performed by pediatric gastroenterologists.

Conclusions:

Ultrasound‐guided percutaneous liver biopsy performed by experienced pediatric interventional radiologists in a children's hospital setting is as safe and effective as biopsy performed by pediatric gastroenterologists.