bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of magnetic resonance imaging–based knee cartilage T2 measurements and focal knee lesions with body mass index: Thirty‐six–month followup data from a longitudinal, observational multicenter study
Authors: Baum Thomas , Joseph Gabby B. , Nardo Lorenzo , Virayavanich Warapat , Arulanandan Ahilan , Alizai Hamza , Carballido‐Gamio Julio , Nevitt Michael C. , Lynch John , McCulloch Charles E. , Link Thomas M.
Published: May 2012

Objective

To compare magnetic resonance imaging (MRI)–based knee cartilage T2 measurements and focal knee lesions and 36‐month changes in these parameters among knees of normal controls and knees of normal weight, overweight, and obese subjects with risk factors for knee osteoarthritis (OA).

Methods

A total of 267 subjects ages 45–55 years from the Osteoarthritis Initiative database were analyzed in this study. Two hundred thirty‐one subjects had risk factors for knee OA, but no radiographic OA (Kellgren/Lawrence score ≤1) at baseline. Thirty‐six subjects were normal controls. Subjects with OA risk factors were stratified in 3 groups: normal weight (n = 78), overweight (n = 84), and obese (n = 69). All subjects underwent 3T MRI of the right knee at baseline and after 36 months. Focal knee lesions were assessed and cartilage T2 measurements (mean T2 and T2 texture analysis) were performed.

Results

The baseline prevalence and severity of meniscal and cartilage lesions were highest in obese subjects and lowest in normal controls (P < 0.05). Obese subjects had the highest mean T2 values and the most heterogeneous cartilage (as assessed by T2 texture analysis), while normal controls had the lowest mean T2 values and the most homogeneous cartilage at baseline (P < 0.05). Increased body mass index (BMI) was significantly (P < 0.05) associated with greater progression of cartilage lesions and constantly elevated cartilage T2 entropy over 36 months.

Conclusion

In preclinical OA, increased BMI is associated with more severe cartilage degeneration as assessed by both morphologic and quantitative MRI measurements.
Diffuse idiopathic skeletal hyperostosis prevalence in subjects with severe atherosclerotic cardiovascular diseases
Authors: Zincarelli Carmela , Iervolino Salvatore , Di Minno Matteo Nicola Dario , Miniero Enzo , Rengo Carlo , Di Gioia Luisa , Vitale Dino , Nicolino Antonio , Furgi Giuseppe , Pappone Nicola
Published: May 2012

Objective

Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by ossification of different entheseal sites. Several metabolic factors have been suggested to be involved in DISH development. We assessed the prevalence of DISH and its relationship to traditional vascular risk factors in a cohort of patients diagnosed with cardiovascular diseases.

Methods

Among the 521 consecutive patients admitted to the heart diseases rehabilitation program in our Rehabilitative Cardiology Unit, only those (n = 436) with recent coronary artery bypass grafting (CABG), a heart valve replacement (HVR), or congestive heart failure (CHF) were enrolled (45 CHF, 338 CABG, and 53 HVR). All patients underwent a rheumatologic examination, blood sample collections, and chest radiographs. Body mass index (BMI), blood pressure, and information about sex, age, smoking habit, and other vascular risk factors were recorded. DISH was established according to the Resnick and Niwayama criteria.

Results

In the setting (77.1% men), the mean ± SD age was 65.44 ± 9.66 years and the overall prevalence of DISH was 30.3%. A logistic regression analysis showed that both age (odds ratio [OR] 1.076, 95% confidence interval [95% CI] 1.044–1.109; P < 0.001) and obesity (OR 2.28, 95% CI 1.33–3.89; P = 0.003) were significant predictors of the presence of DISH. An increasing OR for the presence of DISH was found for increasing tertiles of age and BMI. No difference resulted according to other traditional vascular risk factors. BMI and age directly correlated with C‐reactive protein levels.

Conclusion

The overall prevalence of DISH was 30.3%. This is expected because of the study population. Obese and older individuals exhibit a higher risk of DISH development.
Lithography‐Based Additive Manufacturing of Cellular Ceramic Structures
Authors: Felzmann Ruth , Gruber Simon , Mitteramskogler Gerald , Tesavibul Passakorn , Boccaccini Aldo R. , Liska Robert , Stampfl Jürgen
Published: May 2012

Lithography‐based additive manufacturing technology is a layered manufacturing approach where liquid photopolymerizable resins are solidified with ultraviolet, visible, or infrared light. Using a system based on digital mirror devices, photopolymers can be exposed selectively in order to build parts with defined geometries. By modifying the system with a rotating building platform, suspensions with a high solid loading of ceramic powders can be processed, despite the high viscosity of these resins. Depending on the field of application, various formulations were developed for fabricating customized ceramic parts made of alumina, tricalcium phosphate, or bioactive glasses, respectively. On the one hand the influence of the ceramic filler on the mechanical properties is characterized, on the other hand the good precision and the high surface quality of the process system is discussed. For alumina filled resins a solid loading of 50 vol% was used to obtain fully dense parts (>99% of theoretical density) with high fracture strength (biaxial strength of 516 MPa).
NiMn‐Based Alloys and Composites for Magnetically Controlled Dampers and Actuators
Authors: Liu Jian , Scheerbaum Nils , Kauffmann‐Weiss Sandra , Gutfleisch Oliver
Published: May 2012

As a new class of magnetically driven active materials, magnetic shape memory (MSM) alloys show large strains of up to 10% in Ni2MnGa single crystal with a modulated martensitic structure. The magnetic field induced twin boundary motion can be exploited for actuators, sensors, and as it is an energy dissipating process, also for vibration damping devices. However, single crystals of Ni2MnGa are difficult to prepare and are inherently very brittle. One solution is the use of aligned MSM particles suspended in a stiffness‐matched polymer matrix. In this review, we focus on the preparation and characterization of textured NiMn‐based MSM composite. Essential issues, e.g., the criterion of polymer selection and the interface of MSM particles and polymer are discussed. Second aspect of the paper is to review recent developments in metamagnetic shape memory NiMn‐(In,Sn,Sb) systems which exhibit field‐driven multifunctional properties such as magnetocaloric effect, magnetoresistant change, magnetoelectricity, and thermoelectricity.
Flammability of Mg–X Binary Alloys
Authors: Prasad Arvind , Shi Zhiming , Atrens Andrej
Published: May 2012

Flammability of Mg–X alloys was studied for X = Al, Ca, Si, Sn, Sr, La, Mn, Zn, Zr, Ce, Gd, and Nd. One end of a horizontal cylindrical specimen was subjected to a free diffusion liquid petroleum gas (LPG) flame. There was no burning without some melting of the specimen tip. Mg5%Gd, Mg3%Ca, and Mg5%Ca had considerable resistance to burning. Otherwise, on sufficient LPG flame exposure, there was melting and ignition of the specimen tip; any hot detached blob continued to burn until consumed, except for Mg1%Ca, Mg3%La, Mg3%Ce, and Mg5%Nd; and the burning specimen tip extinguished upon withdrawal of the applied LPG flame.
Genetic heterogeneity according to age at onset in bipolar disorder: A combined positional cloning and candidate gene approach
Authors: Dizier Marie‐Hélène , Etain Bruno , Lajnef Mohamed , Lathrop Mark , Grozeva Detelina , Craddock Nick , Henry Chantal , Gard Sébastien , Jamain Stéphane , Leboyer Marion , Bellivier Frank , Mathieu Flavie
Published: May 2012

This study is the first that formally tests for genetic heterogeneity of bipolar disorder (BD) according to age at onset (AAO) sub‐groups by combining positional cloning and candidate gene approaches. Our previous genome‐wide linkage‐scan identified five genomic regions linked to early‐onset form of BD. The present study uses association analysis to test genetic heterogeneity of candidate genes located in these five regions in a sample of 443 unrelated bipolar patients and 1,731 controls. The study involved the following steps: (1) test of heterogeneity by comparing early‐onset BD patients versus later‐onset BD patients; and (2) for significant results in step 1, comparison of early‐onset BD patients and later‐onset BD patients separately to controls. Two types of analyses were used: the single SNP test and the gene‐based association test. We provide evidence for genetic heterogeneity within the ADRB2 (beta‐2adrenoreceptor) gene region that is specifically associated with the early onset form of BD with an OR of 1.8. Unfortunately, the genotyping coverage of ADRB2 in the Wellcome Trust Case Control Consortium sample meant undermined our efforts to undertake a replication. However, as the ADRB2 gene product directly interacts with the CACNA1C gene product, and is known to be implicated in BD susceptibility, we conclude that further exploration of the relationships between ADRB2 and BD needs to be undertaken. © 2012 Wiley Periodicals, Inc.
Amidoxime copolymer beads containing Cu/Cu2O microparticles as a biocidal material for water disinfection
Authors: Gangadharan D. , Dixit Dhara , Popat Kiritkumar Mangaldas , Anand Pritpal Singh
Published: May 2012

Macroporous crosslinked acrylonitrile‐divinylbenzene copolymer beads were synthesized by suspension polymerization technique. The beads were chemically modified to have amidoxime functional group, which was used as a solid support for anchoring copper microparticles. The copper ions loaded on the copolymer beads were reduced using strong reducing agent to have copper microparticles on the amidoxime copolymer beads. The size of copper particles formed depends upon the amount of copper ions loaded on the beads. The formation of copper microparticles on the copolymer was confirmed by instrumental analysis. The copper containing amidoxime copolymer beads were investigated for the biocidal activity. The size and the distribution of copper particles on the amidoxime copolymer beads influenced their biocidal activity. The biocidal activity was tested against two Gram‐positive bacteria, Bacillus subtilis and Staphylococcus aureus, and against two Gram‐negative bacteria, Pseudomonas aeruginosa and Escherichia coli. The beads containing copper particles showed better biocidal activity against the Gram‐negative bacteria when compared with the Gram‐positive organisms. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Gold deposition on Fe3O4/(co)Poly(N‐octadecyl methacrylate) hybrid particles to obtain nanocomposites With ternary intrinsic features
Authors: Yang Yuzhen , Mahdavian Ali Reza , Daniels Eric S. , Klein Andrew , El‐Aasser Mohamed S.
Published: May 2012

Here, nanocomposite particles with three domains including magnetite nanoparticles, poly(N‐octadecyl methacrylate) (PODMA) or poly(N‐octadecyl methacrylate‐co‐1‐vinylimidazole) (P(ODMA‐co‐VIMZ)), and gold nanoparticles were prepared. Fe3O4 nanoparticles with narrow particle size distribution were prepared through a synthetic route in an organic phase in order to achieve good control of the size and size distribution and prevent their aggregation during their preparation. These magnetite nanoparticles, ∼ 5 nm in size, were then encapsulated and well‐dispersed in PODMA and P(ODMA‐co‐VIMZ) matrices via a miniemulsion polymerization process to obtain the corresponding nanocomposite particles. The results revealed that Fe3O4 nanoparticles were encapsulated and did not migrate towards the monomer/water interface during polymerization. The resulting latex was used as a precursor for the adsorption of Au3+ ions on the surface of the polymeric particles and subsequent reduction to produce Fe3O4/P(ODMA‐co‐VIMZ)/Au nanocomposite particles. The morphology of the particles from each step was fully characterized by TEM and AFM, and the results of DLS analysis showed their size and size distribution. Measurement of magnetic properties illustrated the superparamagnetic characteristic of the products and it was observed that the encapsulation process and deposition of gold had no effect on the magnetic properties of the resulting particles. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Synthesis, properties and self‐assembly of intelligent core‐shell nanoparticles based on chitosan with different molecular weight and N‐isopropylacrylamide
Authors: Wang Yajing , Wang Jiu , Ge Liang , Liu Qi , Jiang Liqun , Zhu Jiabi , Zhou Jianping , Xiong Fei
Published: May 2012

In this study, a series of chitosan‐graft‐poly(N‐isopropylacrylamide) (CTS‐g‐PNIPAAm) copolymers based on different molecular weight (Mw) of CTS and NIPAAm were synthesized through the polymerization of NIPAAm in an acid aqueous solution. The structures were verified by Fourier transform infrared and nuclear magnetic resonance. The influence of the CTS Mw on the properties of the resulting copolymers and self‐assembled nanoparticles was fully examined. The grafting ratio and grafting efficiency of the copolymers increased with the CTS Mw. All the copolymers have a similar low critical solution temperature of 33.5°C, which was independent of the CTS Mw. Furthermore, the copolymers were less temperature sensitive, when CTS Mw increased to 200 kDa. Besides, once the CTS Mw increased to 700 kDa, the copolymers were less pH sensitive near the tumor site (from pH 7.4 to 6.8). The copolymers could form uniform nanoparticles once the temperature increased to 34°C, which was reversible. After crosslinking by N,N‐methylenebisacrylamide (MBA), structurally stable nanoparticles could be obtained. The results from Transmission electron microscope (TEM) and Atomic force microscopy (AFM) showed that the MBA crosslinked nanoparticles were uniformly spherical with a loose structure. Surface tension method indicated that the critical aggregate concentrations were 0.045, 0.042, 0.037, and 0.036 mg mL−1 prepared from CTS 50, 100, 200, and 700 kDa, respectively. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Synthesis and characterization of in situ polymerized poly(methyl methacrylate)–cerium molybdate nanocomposite for electroanalytical application
Authors: Khan Asif Ali , Paquiza Leena
Published: May 2012

In the present study, a new technique to synthesize composites of poly(methyl methacrylate) cerium molybdate (PMMA–CeMoO4) is reported. The study concerns the characterization of poly(methyl methacrylate; PMMA) and PMMA–CeMoO4 nanocomposites are also discussed. The physical properties of the material were described using TGA–DTA, FTIR, X‐ray, TEM, and SEM studies. The adsorption efficiency towards heavy metal ions was determined by distribution studies and material was found to be highly selective for lead, a heavy toxic metal ion, indicating the utility of the synthesized material for the removal of this ion from the waste stream. The material was used as electroactive component for the construction of an ion‐selective membrane electrode. The membrane electrode was mechanically stable, having wide dynamic range, with quick response time and could be operated for at least 5 months without any considerable divergence in the potential response characteristics. The electrode was successfully used as indicator electrode in complexation titrations. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Analysis of the dielectric spectroscopy of an epoxy‐ZnO nanocomposite using the universal relaxation law
Authors: Yang Wenhu , Yi Ran , Hui Sisi , Xu Yang , Cao Xiaolong
Published: May 2012

There is currently no unified theory that explains the role of nanofillers in polymeric insulation. Consequently, different methods such as dielectric spectroscopy analysis are used to understand this role. The existence of a strong interaction between nanoparticles and a polymer is widely accepted. However, the interaction between dipoles has been taken into consideration in Jonscher's Universal Relaxation Law (URL) but not in the Debye theory. Hence, the URL was used in this article as a method to analyze the spectra of epoxy‐ZnO nanocomposites and to try to determine the nanoeffect mechanism. At 160°C above Tg (116°C), the typical phenomenon of low‐frequency dispersion occurs in the epoxy‐ZnO nanocomposites, and with filler loading increased up to 5 wt %, the value of n (calculated from the εr″ spectrum of the nanocomposites) increases both at high and low frequencies. This result indicates that higher loadings correspond to lower dielectric losses changing per radian. Moreover, the decrease in quasi‐direction conduction indicates that the gross dielectric losses of the nanocomposites are also less than pure epoxy resin (EP) at low frequencies. This finding may be attributed to the strong bonding between the nanofillers and the EP, which limits the movement of some macromolecular chains. The URL provides an analytical method for determining the mechanism of the effect of nanofillers on polymers. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Thermal and flammability studies of poly(vinyl alcohol) composites filled with sodium hydroxide
Authors: Arora Sanjiv , Kumar Mahender , Kumar Mahesh
Published: May 2012

Poly(vinyl alcohol) (PVA) is a polymer of great value due to its wide spread applications. The present article describes the effect of sodium hydroxide on the flammability, thermal degradation, and tensile strength properties of PVA. The PVA/sodium hydroxide composite films at different loading levels of sodium hydroxide, i.e., 0.5, 1, 2, 3, and 4.5 wt % were prepared by solution casting technique. Dynamic thermogravimetry was used to study the thermal degradation behavior of samples at four different linear heating rates, i.e., 2.5, 5, 10, and 20 °C min−1under nitrogen atmosphere. The degradation activation energy values were calculated using reliable and preferred multiple‐heating rate methods. Limiting oxygen index (LOI) and UL 94 tests were carried out to check the flammability behavior of the samples. The presence of sodium hydroxide in PVA brought significant changes in the thermal and flammability performance. PVA/sodium hydroxide samples though showed lower initial decomposition temperature, but overall more thermal stability results as evidenced from the higher activation energy and char residue values. LOI and UL 94 tests indicate that sodium hydroxide greatly enhanced the flame retardancy of PVA/sodium hydroxide films. Based on the thermal and flammability level, the optimum concentration of sodium hydroxide is worked out. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Ring opening metathesis copolymerization of norbornene with norbornadiene from solutions with different mole fractions of the comonomers catalyzed by Ru‐amine complexes
Authors: Silva Sá José L. , Nascimento Eduardo S. P. , Fonseca Larissa R. , Lima‐Neto Benedito S.
Published: May 2012

Copolymers from norbornene (NBE) with norbornadiene (NBD) were synthesized via ring opening metathesis copolymerization varying the mole fractions of the comonomers (0.8 : 0.2; 0.6 : 0.4; 0.4 : 0.6; 0.2 : 0.8) for a total monomer quantity of 5000 equivalents/[Ru]. The batch reactions were performed with [RuCl2(PPh3)2(amine)] complex types as precatalysts, where amine is perhydroazepine (1) or piperidine (2), in CHCl3 (2 mL) in the presence of ethyl diazoacetate (5 μL) for different intervals of times (5, 30, 60, and 120 min) at 40°C. The copolymers were characterized by 13C NMR. Quantitative yields of isolated materials were obtained from solutions with NBD : NBE 0.8 : 0.2 mole fraction in the presence of 1, decreasing to 70% for NBD : NBE 0.2 : 0.8 solutions. Concerning 2, the yields were 70% at most. Polymeric materials obtained with 1 were less soluble in CHCl3 than those synthesized with 2. The dependence of the reaction yields and occurrence of crosslinking on the starting NBE : NBD proportion related to reactivity of the complexes 1 and 2 were discussed. A few differences in the amines such as ancillary ligands were sufficient to change the reactivity of the {RuCl2(PPh3)} moiety complex to provide copolymers with different compositions. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Ultrastructural and Spectrophotometric Study on the Effects of Putative Triggers on Aortic Valve Interstitial Cells in In Vitro Models Simulating Metastatic Calcification
Authors: Bonetti Antonella , Mora Alberto Della , Contin Magali , Tubaro Franco , Marchini Maurizio , Ortolani Fulvia
Published: May 2012

Metastatic calcification of cardiac valves is a common complication in patients affected by chronic renal failure. In this study, primary bovine aortic valve interstitial cells (AVICs) were subjected to pro‐calcific treatments consisting in cell stimulation with (i) elevated inorganic phosphate (Pi = 3 mM), to simulate hyperphosphatemic conditions; (ii) bacterial endotoxin lipopolysaccharide (LPS), simulating direct effects by microbial agents; and (iii) conditioned media (CM) derived from cultures of either LPS‐stimulated heterogenic macrophages (commercial murine RAW264.7 cells) or LPS‐stimulated fresh allogenic monocytes/macrophages (bCM), simulating consequent inflammatory responses, alone or combined. Compared to control cultures, spectrophotometric assays revealed shared treatment‐dependent higher values of both calcium amounts and alkaline phosphatase activity for cultures involving the presence of elevated Pi. Ultrastructurally, shared peculiar pro‐calcific degeneration patterns were exhibited by AVICs from these latter cultures irrespectively of the additional treatments. Disappearance of all cytomembranes and concurrent formation of material showing positivity to Cuprolinic Blue and co‐localizing with silver precipitation were followed by the outcropping of such a material, which transformed in layers outlining the dead cells. Subsequent budding of these layers resulted in the formation of bubbling bodies and concentrically laminated calcospherulae mirroring those in actual soft tissue calcification. In conclusion, the in vitro models employed appear to be reliable tools for simulating metastatic calcification and indicate that hyperphosphatemic‐like conditions could trigger valve calcification per se, with LPS and allogenic macrophage‐derived secretory products acting as possible calcific enhancers via inflammatory responses. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
Albumin 3′untranslated region facilitates increased recombinant protein production from Chinese hamster ovary cells
Authors: Pearson Mark J. , Khazaipoul Siavash , Optun Asta , Pryme Ian F. , Stern Beate , Hesketh John E.
Published: May 2012

Chinese hamster ovary (CHO) cells are used for recombinant protein production in the pharmaceutical industry but there is a need to improve expression levels. In the present work experiments were carried out to test the effectiveness of different 3′untranslated regions (3′UTRs) in promoting production of a naturally secreted luciferase. Seamless cloning was used to produce expression vectors in which Gaussia princeps luciferase coding sequences were linked to the human albumin, immunoglobulin or chymotrypsinogen 3′UTR. Stably transfected CHO cells expressing these constructs were selected. Luciferase activity in the culture medium was increased 2–3‐fold by replacing the endogenous 3′UTR with the albumin 3′UTR and decreased by replacement with immunoglobulin or chymotrypsinogen 3′UTR. Replacement of the native 3′UTR with the albumin 3′UTR led to a 10‐fold increase in luciferase mRNA levels. Deletion analysis of the albumin 3′UTR showed that loss of nucleotides 1–50, which removed an AU‐rich complex stem loop region, caused significant reductions in both luciferase protein expression and luciferase mRNA levels. The results suggest that recombinant protein expression and yield could be improved by the careful selection of appropriate 3′UTR sequences.
A revisited folding reporter for quantitative assay of protein misfolding and aggregation in mammalian cells
Authors: Gregoire Simpson , Kwon Inchan
Published: May 2012

Protein misfolding and aggregation play important roles in many physiological processes. These include pathological protein aggregation in neurodegenerative diseases and biopharmaceutical protein aggregation during production in mammalian cells. To develop a simple non‐invasive assay for protein misfolding and aggregation in mammalian cells, the folding reporter green fluorescent protein (GFP) system, originally developed for bacterial cells, was evaluated. As a folding reporter, GFP was fused to the C‐terminus of a panel of human copper/zinc superoxide dismutase (SOD1) mutants with varying misfolding/aggregation propensities. Flow cytometric analysis of transfected HEK293T and NSC‐34 cells revealed that the mean fluorescence intensities of the cells expressing GFP fusion of SOD1 variants exhibited an inverse correlation with the misfolding/aggregation propensities of the four SOD1 variants. Our results support the hypothesis that the extent of misfolding/aggregation of a target protein in mammalian cells can be quantitatively estimated by measuring the mean fluorescence intensity of the cells expressing GFP fusion. The assay method developed herein will facilitate the understanding of aggregation process of SOD1 variants and the identification of aggregation inhibitors. The method also has great promise for misfolding/aggregation studies of other proteins in mammalian cells.
Improving piezoelectric cell printing accuracy and reliability through neutral buoyancy of suspensions
Authors: Chahal Daljeet , Ahmadi Ali , Cheung Karen C.
Published: May 2012

The sedimentation and aggregation of cells within inkjet printing systems has been hypothesized to negatively impact printer performance. The purpose of this study was to investigate this influence through the use of neutral buoyancy. Ficoll PM400 was used to create neutrally buoyant MCF‐7 breast cancer cell suspensions, which were ejected using a piezoelectric drop‐on‐demand inkjet printing system. It was found that using a neutrally buoyant suspension greatly increased the reproducibility of consistent cell counts, and eliminated nozzle clogging. Moreover, the use of Ficoll PM400 was shown to not affect cellular viability. This is the first demonstration of such scale and accuracy achieved using a piezoelectric inkjet printing system for cellular dispensing. Biotechnol. Bioeng. 2012; 109: 2932–2940. © 2012 Wiley Periodicals, Inc.
Quantitative methods to characterize morphological properties of cell lines
Authors: Mancia Annalaura , Elliott John T. , Halter Michael , Bhadriraju Kiran , Tona Alessandro , Spurlin Tighe A. , Middlebrooks Bobby L. , Baatz John E. , Warr Gregory W. , Plant Anne L.
Published: May 2012

Descriptive terms are often used to characterize cells in culture, but the use of nonquantitative and poorly defined terms can lead to ambiguities when comparing data from different laboratories. Although recently there has been a good deal of interest in unambiguous identification of cell lines via their genetic markers, it is also critical to have definitive, quantitative metrics to describe cell phenotypic characteristics. Quantitative metrics of cell phenotype will aid the comparison of data from experiments performed at different times and in different laboratories where influences such as the age of the population and differences in culture conditions or protocols can potentially affect cellular metabolic state and gene expression in the absence of changes in the genetic profile. Here, we present examples of robust methodologies for quantitatively assessing characteristics of cell morphology and cell–cell interactions, and of growth rates of cells within the population. We performed these analyses with endothelial cell lines derived from dolphin, bovine and human, and with a mouse fibroblast cell line. These metrics quantify some characteristics of these cells lines that clearly distinguish them from one another, and provide quantitative information on phenotypic changes in one of the cell lines over large number of passages. Published 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 1069–1078, 2012
Purification of IgG and albumin from human plasma by aqueous two phase system fractionation
Authors: Vargas Mariángela , Segura Álvaro , Herrera María , Villalta Mauren , Angulo Yamileth , Gutiérrez José María , León Guillermo , Burnouf Thierry
Published: May 2012

The current shortages in human plasma products at global levels justify the development of new, cost effective plasma fractionation methods. We have developed a fractionation process to obtain immunoglobulin G (IgG) and albumin‐enriched fractions based on polymer‐salt aqueous two phase system (ATPS). A small‐scale (0.02 L) ATPS composed of polyethyleneglycol 3350 (PEG), potassium phosphate and sodium chloride, at pH 6.1, was evaluated and subjected to 50‐fold scale‐up (1 L). Further purification of the fractions was performed using caprylic acid precipitation and ion exchange chromatography. Similar yield and purity were obtained at both small and large scales. IgG precipitated in the PEG rich upper phase at 83% recovery and 2.75‐fold purification factor. An 81% pure albumin fraction was obtained in the salt rich bottom phase with a 91% yield. After polishing, IgG was obtained at a recovery of 70% and a purity of 92%. Corresponding values for albumin were 91% and 90%. This IgG and albumin fractionation technology deserves further evaluation as it may represent a potential alternative to conventional plasma fractionation methods. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 1005–1011, 2012
Quadratic PLS1 regression revisited
Authors: Verdun Stéphane , Hanafi Mohamed , Cariou Véronique , Qannari El Mostafa
Published: May 2012

Within the framework of nonlinear partial least squares (PLS), the quadratic PLS regression approach, involving both linear and quadratic terms in the criterion, is discussed. A new algorithm for the determination of the components is proposed, and its advantages over the original algorithm are outlined. The approach of analysis is illustrated on the basis of simulated and real data. Copyright © 2012 John Wiley & Sons, Ltd.
Structural Characterization and Computer‐Aided Optimization of a Small‐Molecule Inhibitor of the Arp2/3 Complex, a Key Regulator of the Actin Cytoskeleton
Authors: Baggett Andrew W. , Cournia Zoe , Han Min Suk , Patargias George , Glass Adam C. , Liu Shih‐Yuan , Nolen Brad J.
Published: May 2012

CK‐666 (1) is a recently discovered small‐molecule inhibitor of the actin‐related protein 2/3 (Arp2/3) complex, a key actin cytoskeleton regulator with roles in bacterial pathogenesis and cancer cell motility. Although 1 is commercially available, the crystal structure of Arp2/3 complex with 1 bound has not been reported, making its mechanism of action uncertain. Furthermore, its relatively low potency increases its potential for off‐target effects in vivo, complicating interpretation of its influence in cell biological studies and precluding its clinical use. Herein we report the crystal structure of 1 bound to Arp2/3 complex, which reveals that 1 binds between the Arp2 and Arp3 subunits to stabilize the inactive conformation of the complex. Based on the crystal structure, we used computational docking and free‐energy perturbation calculations of monosubstituted derivatives of 1 to guide optimization efforts. Biochemical assays of ten newly synthesized compounds led to the identification of compound 2, which exhibits a threefold increase in inhibitory activity in vitro relative to 1. In addition, our computational analyses unveiled a surface groove at the interface of the Arp2 and Arp3 subunits that can be exploited for additional structure‐based optimization.
Scandium‐Catalyzed Preparation of Cytotoxic 3‐Functionalized Quinolin‐2‐ones: Regioselective Ring Enlargement of Isatins or Imino Isatins
Authors: Alcaide Benito , Almendros Pedro , Aragoncillo Cristina , Gómez‐Campillos Gonzalo , Arnó Manuel , Domingo Luis R.
Published: May 2012

Trimethylsilyldiazomethane in the presence of catalytic amounts of Sc(OTf)3 smoothly promotes the ring expansion of isatins or imino isatins to efficiently afford 3‐functionalized quinolin‐2‐ones through controlled ring enlargement. Whereas the ring‐expansion reaction of azetidine‐2,3‐diones led to the adduct resulting from migration of the carbonyl group, the ring‐expansion reaction of oxindole derivatives gave the adduct resulting from migration of the aryl group. To rationalize the experimental observations, theoretical studies have been performed. Moreover, the biological activity of some of the synthesized heterocycles has been evaluated in four cancer cell lines.
6LoWPAN: a study on QoS security threats and countermeasures using intrusion detection system approach
Authors: Le Anhtuan , Loo Jonathan , Lasebae Aboubaker , Aiash Mahdi , Luo Yuan
Published: May 2012

Fuelled to bring the Internet of Things concept to real life, the Internet Engineering Task Force is working on 6LoWPAN, in which the standard allows a vast number of smart objects to be deployed in local wireless sensor networks (WSNs) using the huge address space of IPv6 for data and information harvesting through the Internet. From the security point of view, 6LoWPAN/WSN will be open to security threats from the local network itself and the Internet. Cryptography techniques applied as the front line of defence or deterrent can easily be broken because of the weak secure nature of LoWPAN devices and the wireless environment. Compromised nodes could lead to insider attacks without being detected by any cryptography checking. An intrusion detection system (IDS) is, primarily needed as a second line of defence to monitor the network operations and raise an alarm in case of any anomaly. This paper analyses potential security threats in 6LoWPAN and reviews the current countermeasures, in particular, the IDS‐based solutions for countering insider/internal threats. Additionally, it discovers three novel QoS‐related security threats, namely rank attack, local repair attack, and resource depleting attack, which are more seriously affecting the routing protocol for low‐power and lossy network, the routing protocol used to establish 6LoWPAN network topology. A new two‐layer IDS concept is introduced as a countermeasure method for securing the routing protocol for low‐power and lossy network‐built network topology from the internal QoS attacks. Potential research works are also presented to provide baseline reference to researchers in this field. Copyright © 2012 John Wiley & Sons, Ltd.
An educational experiment system for simulated CT devices with coherent light
Authors: Ogura Izumi , Nyui Yoshiyuki , Abe Shinji , Negishi Toru , Shinoda Yukitaka , Date Norihiko , Tsumuraya Mitsunori , Higo Takashi
Published: May 2012

Today, X‐ray computed tomography (CT) devices are used in a wide range of fields including medical and industrial applications. It is not easy for students in engineering fields including electrical and electronic engineering to understand the electrical and image analysis principles of X‐ray CT devices. Also, in teaching facilities that educate radiographic personnel who actually work with this equipment in medical fields, testing and training are usually performed using real X‐ray CT devices. Since these devices are large and have a complex internal structure, students are currently limited with regard to the types of testing and training that they are able to perform. This makes it difficult for medical students to gain a proper understanding of the principles behind X‐ray CT devices. There is consequently a need for a simple educational test system that enables engineering and medical students to understand how X‐ray CT devices work. We report the construction of an educational test system that simulates an X‐ray CT device based on optical heterodyne detection using laser light for simulation experiments, and the construction of a system that is capable of performing image reconstruction experiments using data obtained with this test system. We also report a test system that is capable of acquiring simulated X‐ray CT images. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(6): 32–40, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11367
Sample‐based collection and adjustment of rules for metadata extraction in business documents
Authors: Matsumoto Toshiko , Oba Mitsuharu , Onoyama Takashi , Akiyoshi Masanori
Published: May 2012

Toward facile introduction of metadata‐based document management systems, we propose an algorithm which uses sample documents and their manually specified metadata as training data, and generates metadata‐extraction rules. Our algorithm enumerates candidates of keywords and layout characteristics specific to the metadata on the basis of metadata occurrence in the training data. It then examines whether each candidate is specific to only one kind of metadata. In an experiment on Japanese business documents and weekly reports, automatically generated rules achieved metadata extraction as accurate as manually adjusted ones. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(6): 1–11, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11373
Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice
Authors: Yoh Keigyou , Morito Naoki , Ojima Masami , Shibuya Kazuko , Yamashita Yumi , Morishima Yuko , Ishii Yukio , Kusakabe Manabu , Nishikii Hidekazu , Fujita Akiko , Matsunaga Emi , Okamura Midori , Hamada Michito , Suto Akira , Nakajima Hiroshi , Shibuya Akira , Yamagata Kunihiro , Takahashi Satoru
Published: May 2012

Retinoic acid related orphan receptor gamma‐t (RORγt) is known to be a master regulator of Th17‐cell development. In this study, we generated RORγt‐overexpressing transgenic (RORγt Tg) mice in which transgene expression was driven by the CD2 promoter, and found that these mice developed polyclonal plasmacytosis and autoantibody production. RORγt Tg mice were generated on a C57BL/6 background, and also were intercrossed with BALB/c mice. BALB/c F1 (BALB/F1) RORγt Tg mice developed massive polyclonal plasma‐cytosis, and had shorter life spans. Splenomegaly and infiltration of plasma cells into the lung were observed. Hyperglobulinemia, anti‐double‐stranded DNA antibodies, anti‐erythrocyte antibodies, and anti‐platelet antibodies were detected in BALB/F1 RORγt Tg mice. In the present study, polyclonal plasmacytosis in BALB/F1 RORγt Tg mice appeared to be due to the induction of excessive IL‐6 production by IL‐17. We detected increased numbers of CD11b+ cells that produced IL‐6. We also generatedIL‐6‐deficient RORγt Tg BALB/F1 background mice, which displayed high levels of serum IL‐17, but did not develop severe hyperglobulinemia. Excessive IL‐6 production by several cell types, including macrophages, in BALB/F1 RORγt Tg mice, might effect the development of plasma‐cytosis. These results suggest that RORγt plays important roles in the development of plasmacytosis and autoantibody production.
SpectraBank: An open access tool for rapid microbial identification by MALDI‐TOF MS fingerprinting
Authors: Böhme Karola , Fernández‐No Inmaculada C. , Barros‐Velázquez Jorge , Gallardo Jose M. , Cañas Benito , Calo‐Mata Pilar
Published: May 2012

MALDI‐TOF MS has proved to be an accurate, rapid, and cost‐effective technique for microbial identification in which the spectral fingerprint of an unknown strain can be compared to a database of spectra from reference strains. Most of the existing databases are private and often costly to access, and little spectral information is shared among researchers. The objective of the present communication is to introduce the SpectraBank database (http://www.spectrabank.org), which provides open access MALDI‐TOF mass spectra from a variety of microorganisms. This work aims to familiarize readers with the SpectraBank database, from the sample preparation, data collection, and data analysis to how the spectral reference data can be used for microbial species identification. The database currently includes more than 200 MALDI‐TOF MS spectra from more than 70 bacterial species and links to the freely available web‐based application SPECLUST (http://bioinfo.thep.lu.se/speclust.html) to allow comparisons of the obtained peak mass lists and evaluate phyloproteomic relationships. The SpectraBank database is intended to be expanded by the addition of new spectra from microbial strains, obtained in our laboratory and by other researchers.
A replaceable dual‐enzyme capillary microreactor using magnetic beads and its application for simultaneous detection of acetaldehyde and pyruvate
Authors: Shi Jing , Zhao Wenwen , Chen Yuanfang , Guo Liping , Yang Li
Published: May 2012

A novel replaceable dual‐enzyme capillary microreactor was developed and evaluated using magnetic fields to immobilize the alcohol dehydrogenase (ADH)‐ and lactate dehydrogenase (LDH)‐coated magnetic beads at desired positions in the capillary. The dual‐enzyme assay was achieved by measuring the two consumption peaks of the coenzyme β‐nicotinamide adenine dinucleotide (NADH), which were related to the ADH reaction and LDH reaction. The dual‐enzyme capillary microreactor was constructed using magnetic beads without any modification of the inner surface of the capillary, and showed great stability and reproducibility. The electrophoretic resolution for different analytes can be easily controlled by altering the relative distance of different enzyme‐coated magnetic beads. The apparent Km values for acetaldehyde with ADH‐catalyzed reaction and for pyruvate with LDH‐catalyzed reaction were determined. The detection limits for acetaldehyde and pyruvate determination are 0.01 and 0.016 mM (S/N = 3), respectively. The proposed method was successfully applied to simultaneously determine the acetaldehyde and pyruvate contents in beer samples. The results indicated that combing magnetic beads with CE is of great value to perform replaceable and controllable multienzyme capillary microreactor for investigation of a series of enzyme reactions and determination of multisubstrates.
Improving traditional fermented beverages: How to evolve from spontaneous to directed fermentation
Authors: Navarrete‐Bolaños José Luis
Published: May 2012

Fermented foods and beverages are an intrinsic part of our diet. All over the world, regional quality products are produced by native microorganisms in their natural ecosystems, giving the basis for registering appellations of origin. For wines, premium quality products can be obtained by spontaneous fermentation; its success depends heavily on environmental conditions. Inoculated fermentations with selected pure cultures have been developed as alternative; however, the products obtained have a plain aromatic profile compared to those obtained by successful spontaneous fermentations. Several studies have shown that inoculums of native mixed cultures are able to exalt the peculiarities (aroma, structure, and color) of a wine, and preserve their authenticity and uniqueness; however, reliable methods for native microorganism selection are still limited. Currently, the strain selection criterion is based on their genetic endowment; but, the design of an efficient fermentation process requires also knowledge on physicochemical effectors to maximize the metabolic capacity of the selected strains. This article reviews the guidelines for strain selection, and discusses directions for exploring the use of these microorganisms specifying their operating conditions. The main goal of this work is to present the strategy of how to evolve a spontaneous fermentation to directed fermentation.
Development of probiotic products for nutritional requirements of specific human populations
Authors: Arboleya Silvia , González Sonia , Salazar Nuria , Ruas‐Madiedo Patricia , de los Reyes‐Gavilán Clara G. , Gueimonde Miguel
Published: May 2012

Probiotic products constitute one of the most successful segments of the functional foods market. Recent regulations developed in different countries require extensive documentation from human studies before a health claim can be approved for a food product. This gives a new direction to this research area and underlines the need for products with a high functional efficacy. Most of the current probiotic products target the general population, whilst those formulated for specific human groups are still lacking. Some individuals or patient groups present particular nutritional needs and require nutritionally adapted products, thus constituting an opportunity for the development of specifically formulated foods. In this context, it is critical to identify both the target populations that may benefit the most from such products, and the specific probiotic properties that fulfil the requirements of such populations. Human groups that can benefit from this joint development include groups of extreme age and patients suffering from diseases in which intestinal microbiota and/or immune modulation may have beneficial effects. The development of such target‐specific probiotic foods, by including strains rationally selected for a specific health benefit, tailor‐made for a certain target population, into nutritionally optimal products constitutes a challenge for the food industry.
Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome
Authors: Li Feng , Zhai Yong‐Ping , Tang Yu‐Mei , Wang Li‐Ping , Wan Pin‐Jun
Published: May 2012

The 8p11 myeloproliferative syndrome (EMS) is an aggressive neoplasm caused by the fusion of various partner genes to fibroblast growth factor receptor 1 (FGFR1). Various FGFR1 fusions are associated with subtly distinct disease phenotypes. Here, we report a new translocation at the FGFR1 locus in a patient who carried t(1;8)(q25;p11.2) and presented with myeloproliferative neoplasm‐like symptoms. The patient was characterized by myeloid hyperplasia of bone marrow, markedly elevated numbers of monocytes, and normal to mildly elevated eosinophils. Initial fluorescent in situ hybridization analysis confirmed that FGFR1 in this patient was disrupted. Subsequent analysis led to the identification of a novel translocation, in which exon 23 of the translocated promoter region (TPR) gene at chromosome band 1q25 was fused to exon 13 of FGFR1 (RefSeq NM_0231102.2). The TPR portion of the fusion protein contains putative functional motifs including an N‐terminal TprMet domain, nuclear pore complexes associating domain, and multiple coiled‐coil domains. It is likely that one or more of the motifs from TPR contribute to dimerization, resulting in constitutive activation of the FGFR1 kinase domain. Our results further support a critical role of FGFR1 in the pathogenesis of EMS and may lead to more accurate diagnosis and potential targeted therapy. © 2012 Wiley Periodicals, Inc.
CONSISTENT ESTIMATION OF ZERO‐INFLATED COUNT MODELS
Authors: Staub Kevin E. , Winkelmann Rainer
Published: May 2012

Applications of zero‐inflated count data models have proliferated in health economics. However, zero‐inflated Poisson or zero‐inflated negative binomial maximum likelihood estimators are not robust to misspecification. This article proposes Poisson quasi‐likelihood estimators as an alternative. These estimators are consistent in the presence of excess zeros without having to specify the full distribution. The advantages of the Poisson quasi‐likelihood approach are illustrated in a series of Monte Carlo simulations and in an application to the demand for health services. Copyright © 2012 John Wiley & Sons, Ltd.