bluuebunny/crossref_metadata_2025 huggingface dataset:
The dynamics of primary source and electronic resource: The digital renaissance and the post‐reformation digital library
Authors: Ballor Jordan J.
Published: April 2012

Editor's Summary

The transition from mechanical printing to electronic information dissemination amounts to a digital renaissance, enabling primary source documents to be reborn as electronic resources. For history scholars, this presents opportunities and challenges for preserving centuries‐old original texts in a digital environment, supporting downloading and digital access and presenting original research. The Post‐Reformation Digital Library (PRDL) serves as a case study, capturing a select set of resources on theology and philosophy of the 15th to 18th centuries from a variety of physical locations and digital libraries. Through digitization, digital access and systematic cataloging, the PRDL – along with the database, social networking and dedicated website it has prompted – are helping to overcome barriers to access. Though a modest initiative, the progress of the PRDL demonstrates possibilities for rediscovering historical materials and making them available for modern scholarly studies.
The ISO 25964 data model for the structure of an information retrieval thesaurus
Authors: Will Leonard
Published: April 2012

Editor's Summary

The international standard for thesaurus structure, ISO 259641:2011 – Thesauri for Information Retrieval, published August 2011, presents an extensive data model more advanced than previous versions. The standard facilitates presenting a knowledge organization system in machine compatible SKOS (simple knowledge organization system) format. The model lays out the concepts and terminology applicable to single thesauri, establishing the important difference between concepts and terms. It provides strategies to go beyond simple hierarchical relationships and related concepts, clarifying the nature of relationships between concepts. The new standard addresses several details in thesaurus construction and use for information retrieval, including compound equivalence and node labels. The updated standard supports concept groups or microthesauri and provides for term notes and file versions. Mapping concepts between thesauri will be covered in Part 2 of the standard.
Changing strategies of the retrograde approach for chronic total occlusion during the past 7 years
Authors: Muramatsu Toshiya , Tsukahara Reiko , Ito Yoshiaki , Ishimori Hiroshi , Park Seung‐Jung , de Winter Robert , Shokry Khaled , Wang Lefeng , Chen Jiyan , Wang Haichang
Published: April 2012

Objective

We reviewed the technical changes and results achieved with the retrograde approach since we introduced it 7 years ago.

Subjects and Methods

The subjects were 1,268 patients who were treated for CTO between January 2004 and December 2010. They were investigated with respect to the success rate, the frequency of employing the retrograde approach and its outcome, and other factors.

Results

The retrograde approach was employed in ∼30% of chronic total occlusion (CTO) patients (n = 281) and the retrograde guidewire success rate was 81.1%. The kissing wire technique was substituted for the retrograde approach in 126 of the 281 patients, with antegrade crossing of a guidewire being successful in 88 of them (70%). The retrograde approach was combined with the CART and reverse controlled antegrade retrograde tracking (CART) techniques in 22 and 21 patients, respectively. Among 83 patients treated with Corsair catheters, crossing of the CTO was achieved in 63. The overall procedural success rate was 79.7% (224 patients). Complications of the retrograde approach included collateral channel dissection (2.1%), channel perforation (1.7%), CTO perforation (1.7%), and donor artery occlusion (1.1%).

Conclusion

The success rate and safety of the retrograde approach are both satisfactory if the appropriate devices and techniques are selected. © 2012 Wiley Periodicals, Inc.
Early clearance of peripheral blood blasts predicts response to induction chemotherapy in acute myeloid leukemia
Authors: Arellano Martha , Pakkala Suchita , Langston Amelia , Tighiouart Mourad , Pan Lin , Chen Zhengjia , Heffner Leonard T. , Lonial Sagar , Winton Elliott , Khoury H. Jean
Published: April 2012

BACKGROUND:

Early marrow blast clearance 14 days after induction chemotherapy is an independent prognostic indicator of outcomes in acute myeloid leukemia (AML).

METHODS:

We evaluated the relationship between time to peripheral blood blast clearance after induction and disease status as assessed by day 14 and day 30 marrow biopsies in 162 patients with AML. Day 6 after induction was the optimal cutoff point determined by a receiver operating characteristic analysis and was selected to divide patients into early blast clearance (EBC; ≤6 days; n = 119) and delayed blast clearance (DBC; >6 days; n = 43) groups.

RESULTS:

DBC patients were older, but otherwise the 2 groups were comparable. Marrow blast clearance on day 14 after induction chemotherapy was observed in 84% of patients in the EBC group and 60% in the DBC group. With a median follow‐up of 1538 days, both relapse‐free survival (RFS) (442 vs 202 days, P = .0017) and overall survival (OS) (930 vs 429 days, P < .0001) were longer in the EBC group, and a multivariable analysis showed that EBC independently predicted clearance of marrow blasts at day 14 (P = .0018), remission (P = .0179), RFS (P = .0171), and OS (P = .0122).

CONCLUSIONS:

Early clearance of peripheral blood blasts after induction chemotherapy predicts for early marrow blast clearance, complete remission, RFS, and OS. Cancer 2012. © 2012 American Cancer Society.
A safety run‐in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306)
Authors: Nabors L. Burt , Mikkelsen Thomas , Hegi Monika E. , Ye Xiaubu , Batchelor Tracy , Lesser Glenn , Peereboom David , Rosenfeld Myrna R. , Olsen Jeff , Brem Steve , Fisher Joy D. , Grossman Stuart A. ,   for the New Approaches to Brain Tumor Therapy (NABTT) Central Nervous System Consortium
Published: April 2012

BACKGROUND:

Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose for comparative clinical testing.

METHODS:

In total, 112 patients were accrued. Eighteen patients received standard radiation and temozolomide with cilengitide in a safety run‐in phase followed by a randomized phase 2 trial with 94 patients assigned to either a 500 mg dose group or 2000 mg dose group. The trial was designed to estimate overall survival benefit compared with a New Approaches to Brain Tumor Therapy (NABTT) Consortium internal historic control and data from the published European Organization for Research and Treatment of Cancer (EORTC) trial EORTC 26981.

RESULTS:

Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for the patients in the 500 mg dose group, 20.8 months for patients in the 2000 mg dose group, 30 months for patients who had methylated O6‐methylguanine‐DNA methyltransferase (MGMT) status, and 17.4 months for patients who had unmethylated MGMT status. For patients aged ≤70 years, the median survival and survival at 24 months was superior to what was observed in the EORTC trial (20.7 months vs 14.6 months and 41% vs 27%, respectively; P = .008).

CONCLUSIONS:

Cilengitide was well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with glioblastoma multiforme regardless of MGMT methylation status. The authors concluded that, from an efficacy and safety standpoint, future trials of this agent in this population should use the 2000 mg dose. Cancer 2012. © 2012 American Cancer Society.
Dynamics of charge‐pump phase‐locked loops
Authors: Curran Paul F. , Bi Chuang , Feely Orla
Published: April 2012

Certain problems in the existing treatment of the stability of charge‐pump phase‐locked loops are identified and addressed in this work. New results concerning the instability, stability, and asymptotic stability of charge‐pump phase‐locked loops are obtained by means of Lyapunov's direct and indirect methods. Closer consideration of the local dynamics provides further insight into the system's patterns of behavior. In particular, the influence of circuit parameters on the nature of the steady‐state orbits is investigated. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of municipal solid waste in Istanbul, Turkey
Authors: Yildiz Senol , Yaman Cevat , Demir Goksel , Ozcan H. Kurtulus , Coban Asli , Okten Hatice Eser , Sezer Kadir , Goren Sami
Published: April 2012

Solid waste management was one of the most significant environmental issues encountered in developing countries. Quantity of produced waste as well as its composition was known to vary by general consumption patterns that were affected by socio‐economic status, household size, or even by seasons. Due to the dynamic nature of waste quantity and composition, the handling and disposal of waste in an economically and environmentally feasible way presented itself as a challenge. Therefore, in order to conduct a successful decision‐making process to determine the feasible and sustainable processes in the disposal of waste, priority should be given to the statement of the problem at hand. The aim of this study is to achieve a characterization of municipal solid waste of Istanbul, Turkey. Waste samples were collected from the transfer stations servicing certain zones of the city and consequently substance group, moisture content and calorific value analyses were performed over these samples. Results indicated that approximately 54% of the municipal solid waste composition was of organic nature. The paper/cardboard group was coming next in ranking with a proportion of 15.57%. Average moisture content of samples was calculated to be 62.41% and 1435 kcal kg−1 was calculated to represent the average calorific value. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 734–739, 2013
Regulatory economics: “It's simple economics”
Authors: Barclay Richard A.
Published: April 2012

In his State of the Union speech, the president again called for a Clean Energy Standard. Senator Jeff Bingaman (D‐NM) introduced S. 2146. Compliance is phased in, with 8 percent of the largest utilities needing 24 percent clean energy by 2015 and all utilities needing 84 percent clean energy by 2035. There are no energy source mandates that let “the market… determine the best paths forward.”1 “Clean energy” includes renewables, nuclear, clean coal, and efficient natural gas.
Late Holocene Sea Level Reconstructions Based on Observations of Roman Fish Tanks, Tyrrhenian Coast of Italy
Authors: Evelpidou N. , Pirazzoli P. , Vassilopoulos A. , Spada G. , Ruggieri G. , Tomasin A.
Published: April 2012

We present estimates for late Holocene relative sea level change along the Tyrrhenian coast of Italy based on morphological characteristics of eight submerged Roman fish tanks (piscinae) constructed between the 1st century B.C. and the 2nd century A.D. Underwater geomorphological features and archaeological remains related to past sea level have been measured and corrected using recorded tidal values. We conclude that local sea level during the Roman period did not exceed 58 ± 5 cm below the present sea level. These results broadly agree with previous observations in the region but contrast with recent analysis that suggests a significantly larger sea level rise during the last 2000 years. Using a glacial isostatic adjustment model, we explain how regional sea level change departs from the eustatic component. Our calculation of relative sea level during the Roman period provides a reference for isolating the long‐wavelength contribution to sea level change from secular sea level rise. Precise determination of sea level rise in the study area improves our understanding of secular, instrumentally observed, variations across the Mediterranean. © 2012 Wiley Periodicals, Inc.
Stratification‐Score Matching Improves Correction for Confounding by Population Stratification in Case‐Control Association Studies
Authors: Epstein Michael P. , Duncan Richard , Broadaway K. Alaine , He Min , Allen Andrew S. , Satten Glen A.
Published: April 2012

Proper control of confounding due to population stratification is crucial for valid analysis of case‐control association studies. Fine matching of cases and controls based on genetic ancestry is an increasingly popular strategy to correct for such confounding, both in genome‐wide association studies (GWASs) as well as studies that employ next‐generation sequencing, where matching can be used when selecting a subset of participants from a GWAS for rare‐variant analysis. Existing matching methods match on measures of genetic ancestry that combine multiple components of ancestry into a scalar quantity. However, we show that including nonconfounding ancestry components in a matching criterion can lead to inaccurate matches, and hence to an improper control of confounding. To resolve this issue, we propose a novel method that assigns cases and controls to matched strata based on the stratification score (Epstein et al. [2007] Am J Hum Genet 80:921–930), which is the probability of disease given genomic variables. Matching on the stratification score leads to more accurate matches because case participants are matched to control participants who have a similar risk of disease given ancestry information. We illustrate our matching method using the African‐American arm of the GAIN GWAS of schizophrenia. In this study, we observe that confounding due to stratification can be resolved by our matching approach but not by other existing matching procedures. We also use simulated data to show our novel matching approach can provide a more appropriate correction for population stratification than existing matching approaches.
PSEA: Phenotype Set Enrichment Analysis—A New Method for Analysis of Multiple Phenotypes
Authors: Ried Janina S. , Döring Angela , Oexle Konrad , Meisinger Christa , Winkelmann Juliane , Klopp Norman , Meitinger Thomas , Peters Annette , Suhre Karsten , Wichmann H.‐Erich , Gieger Christian
Published: April 2012

Most genome‐wide association studies (GWAS) are restricted to one phenotype, even if multiple related or unrelated phenotypes are available. However, an integrated analysis of multiple phenotypes can provide insight into their shared genetic basis and may improve the power of association studies. We present a new method, called “phenotype set enrichment analysis” (PSEA), which uses ideas of gene set enrichment analysis for the investigation of phenotype sets. PSEA combines statistics of univariate phenotype analyses and tests by permutation. It does not only allow analyzing predefined phenotype sets, but also to identify new phenotype sets. Apart from the application to situations where phenotypes and genotypes are available for each person, the method was adjusted to the analysis of GWAS summary statistics. PSEA was applied to data from the population‐based cohort KORA F4 (N = 1,814) using iron‐related and blood count traits. By confirming associations previously found in large meta‐analyses on these traits, PSEA was shown to be a reliable tool. Many of these associations were not detectable by GWAS on single phenotypes in KORA F4. Therefore, the results suggest that PSEA can be more powerful than a single phenotype GWAS for the identification of association with multiple phenotypes. PSEA is a valuable method for analysis of multiple phenotypes, which can help to understand phenotype networks. Its flexible design enables both the use of prior knowledge and the generation of new knowledge on connection of multiple phenotypes. A software program for PSEA based on GWAS results is available upon request.
Antagonistic modulation of gliomagenesis by Pax6 and Olig2 in PDGF‐induced oligodendroglioma
Authors: Appolloni Irene , Calzolari Filippo , Barilari Manuela , Terrile Marta , Daga Antonio , Malatesta Paolo
Published: April 2012

Gliomas are aggressive tumors of the central nervous system originating from proliferating neural cells. Regulators of neural stem or progenitor cells biology may thus influence aspects of brain tumorigenesis, such as the maintenance of tumor‐propagating potential. We investigated the role of Pax6, a neurogenic transcription factor already suggested as a positive prognostic marker for human gliomas, in a well‐characterized in vivo model of PDGF‐B‐driven oligodendroglioma. In this system, the expression of Pax6 severely impairs tumor propagation by inducing a reduction of cell proliferation and the acquisition of differentiation traits in tumor‐initiating cells. The overexpression of Pax6 correlates with a downregulation of Olig2, a bHLH transcription factor that normally antagonizes Pax6 in adult neurogenic niches and that plays a key role in the maintenance of neural stem and progenitor cells. Furthermore, we found that Olig2 is strictly required to maintain the malignancy of oligodendroglioma cells, since its silencing by interfering RNA abrogates tumor propagation. We finally show evidence that this function depends, at least in part, on the silencing of ID4, a dominant negative bHLH protein, whose upregulation follows Olig2 loss. In our model, the upregulation of ID4 mimics the loss of Olig2 in impairing the tumor‐propagating potential of glioma cells. Our data, therefore, establish the relevance of physiological regulators of neural stem cell biology in regulating glial tumor malignancy and provide support for their functional interactions in this context.
Long‐term mechanical durability of dental nanocomposites containing amorphous calcium phosphate nanoparticles
Authors: Moreau Jennifer L. , Weir Michael D. , Giuseppetti Anthony A. , Chow Laurence C. , Antonucci Joseph M. , Xu Hockin H. K.
Published: April 2012

Half of all dental restorations fail within 10 years, with secondary caries and restoration fracture being the main reasons. Calcium phosphate (CaP) composites can release Ca and PO4 ions and remineralize tooth lesions. However, there has been no report on their long‐term mechanical durability. The objective of this study was to investigate the wear, thermal‐cycling, and water‐aging of composites containing amorphous calcium phosphate nanoparticles (NACP). NACP of 112‐nm and glass particles were used to fabricate four composites: (1) 0% NACP+75% glass; (2) 10% NACP+65% glass; (3) 15% NACP+60% glass; and (4) 20% NACP+50% glass. Flexural strength and elastic modulus of NACP nanocomposites were not degraded by thermal‐cycling. Wear depth increased with increasing NACP filler level. Wear depths of NACP nanocomposites after 4 × 105 cycles were within the range for commercial controls. Mechanical properties of all the tested materials decreased with water‐aging time. After 2 years, the strengths of NACP nanocomposites were moderately higher than the control composite, and much higher than the resin‐modified glass ionomers. The mechanism of strength loss for resin‐modified glass ionomer was identified as microcracking and air‐bubbles. NACP nanocomposites and control composite were generally free of microcracks and air‐bubbles. In conclusion, combining NACP nanoparticles with reinforcement glass particles resulted in novel nanocomposites with long‐term mechanical properties higher than those of commercial controls, and wear within the range of commercial controls. These strong long‐term properties, plus the Ca‐PO4 ion release and acid‐neutralization capability reported earlier, suggest that the new NACP nanocomposites may be promising for stress‐bearing and caries‐inhibiting restorations. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2012.
GPU accelerated numerical simulations of viscoelastic phase separation model
Authors: Yang Keda , Su Jiaye , Guo Hongxia
Published: April 2012

We introduce a complete implementation of viscoelastic model for numerical simulations of the phase separation kinetics in dynamic asymmetry systems such as polymer blends and polymer solutions on a graphics processing unit (GPU) by CUDA language and discuss algorithms and optimizations in details. From studies of a polymer solution, we show that the GPU‐based implementation can predict correctly the accepted results and provide about 190 times speedup over a single central processing unit (CPU). Further accuracy analysis demonstrates that both the single and the double precision calculations on the GPU are sufficient to produce high‐quality results in numerical simulations of viscoelastic model. Therefore, the GPU‐based viscoelastic model is very promising for studying many phase separation processes of experimental and theoretical interests that often take place on the large length and time scales and are not easily addressed by a conventional implementation running on a single CPU. © 2012 Wiley Periodicals, Inc.
Novel methods for the quantification of changes in actin organization in chondrocytes using fluorescent imaging and linear profiling
Authors: Qusous Ala , Parker Eleanor , Geewan Corinne , Kapasi Arva , Getting Stephen J. , Hucklebridge Frank , Keshavarz Tajalli , Kerrigan Mark J.P.
Published: April 2012

We present three novel reproducible methodologies for the quantification of changes in actin organization from microscope images. Striation and integrative analysis were devised for the investigation of trans‐cellular filaments and F‐actin localization, respectively, in response to physiological or mechanical actin‐modulatory conditions. Additionally, the Parker‐Qusous (PQ) formula was developed as a measure of total quantity of F‐actin, independent of cell volume changes, whereby fluorescence intensity was divided by the cube root of cell volume, squared. Values obtained were quantified in Mauricean Units (Mu; pixel/μm3). Upon isolation, there was a 49% decrease in total F‐actin fluorescence from 1.91 ± 0.16 pixel/μm3 (Mu) to 0.95 ± 0.55 Mu, whereas upon culture, an apparent increase in total fluorescence was deemed insignificant due to an increase in average cell volume, with a rise, however, in striation units (StU) from 1 ± 1 to 5 ± 1 StU/cell, and a decrease in percentage cortical fluorescence to 30.45% ± 1.52% (P = 7.8 × 10−5). Freshly isolated chondrocytes exhibited a decrease in total F‐actin fluorescence to 0.61 ± 0.05 Mu and 0.32 ± 0.02 Mu, 10 min posthypertonic and hypotonic challenges, respectively. Regulatory volume decrease was inhibited in the presence of REV5901 with maintenance of actin levels at 1.15 Mu. Following mechanical impact in situ, there was a reduction in total F‐actin fluorescence to 0.95 ± 0.08 Mu and 0.74 ± 0.06 Mu under isotonic and hypotonic conditions, respectively, but not under hypertonic conditions. We report simple methodologies for quantification of changes in actin organization, which will further our understanding of the role of actin in various cellular stress responses. These techniques can be applied to better quantify changes in localization of various proteins using fluorescent labeling. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Automated quantification of white matter disease extent at 3 T: Comparison with volumetric readings
Authors: Hulsey Keith M. , Gupta Mohit , King Kevin S. , Peshock Ronald M. , Whittemore Anthony R. , McColl Roderick W.
Published: April 2012

Purpose:

To develop and validate an algorithm to automatically quantify white matter hyperintensity (WMH) volume.

Materials and Methods:

Images acquired as part of the Dallas Heart Study, a multiethnic, population‐based study of cardiovascular health, were used to develop and validate the algorithm. 3D magnetization prepared rapid acquisition gradient echo (MP‐RAGE) and 2D fluid‐attenuated inversion recovery (FLAIR) images were acquired from 2082 participants. Images from 161 participants (7.7% of the cohort) were used to set an intensity threshold to maximize the agreement between the algorithm and a qualitative rating made by a radiologist. The resulting algorithm was run on the entire cohort and outlier analyses were used to refine the WMH volume measurement. The refined, automatic WMH burden estimate was then compared to manual quantitative measurements of WMH volume in 28 participants distributed across the range of volumes seen in the entire cohort.

Results:

The algorithm showed good agreement with the volumetric readings of a trained analyst: the Spearman's Rank Order Correlation coefficient was r = 0.87. Linear regression analysis showed a good correlation WMHml[automated] = 1.02 × WMHml[manual] − 0.48. Bland–Altman analysis showed a bias of 0.34 mL and a standard deviation of 2.8 mL over a range of 0.13 to 41 mL.

Conclusion:

We have developed an algorithm that automatically estimates the volume of WMH burden using an MP‐RAGE and a FLAIR image. This provides a tool for evaluating the WMH burden of large populations to investigate the relationship between WMH burden and other health factors. J. Magn. Reson. Imaging 2012;36:305–311. ©2012 Wiley Periodicals, Inc.
Reproducibility of total choline/water ratios in mouse U87MG xenograft tumors by 1H‐MRS
Authors: Zhu Mingming , Fischl Anthony S. , Trowbridge Melissa A. , Shannon Harlan E.
Published: April 2012

Purpose:

To evaluate the reproducibility of the measurement of the total choline‐to‐water ratio, and the effect of repositioning the subject between scans, using 1H‐magnetic resonance spectroscopy in a mouse U87MG xenograft model.

Materials and Methods:

In vivo single‐voxel MR spectra at 7T from xenograft tumors were obtained using both a water‐suppressed and a nonwater‐suppressed point‐resolved spectroscopy (PRESS) sequence. Reproducibility of the total choline/water ratio was evaluated under the conditions of immediate rescan with no change in position of the animal or voxel, immediate reposition, and reposition after 1 or 7 days.

Results:

Total choline‐to‐water ratios in U87MG tumor xenografts averaged ≈0.018 across all of the groups. The average percent difference between the two scans in each condition was always less than ≈3.0%, and the coefficient of variation was always less than ≈12%. Bias was unrelated to the testing condition and relatively negligible in magnitude (<3%). Due to heteroscedasticity in the ratios, the limits of agreement were calculated after log transformation of the data and ranged from ≈12% when animals were maintained in the same position and immediately rescanned to ≈52% when the two scans were 7 days apart.

Conclusion:

The total choline‐to‐water ratio provides a reproducible measure of choline‐containing metabolites in subcutaneous U87MG xenograft tumors in mice. J. Magn. Reson. Imaging 2012;36:459–467. ©2012 Wiley Periodicals, Inc.
Re‐establishment of cytoskeletal tensional homeostasis in lax tendons occurs through an actin‐mediated cellular contraction of the extracellular matrix
Authors: Gardner Keri , Lavagnino Michael , Egerbacher Monika , Arnoczky Steven P.
Published: April 2012

Cytoskeletal tensional homeostasis is known to be an important factor in controlling catabolic gene expression in tendon cells. Loss of cell tension in lax rat tail tendon fascicles (RTTfs) has been associated with an upregulation of MMP‐13 gene expression and protein synthesis. To determine the role of the actin cytoskeleton in re‐establishing tensional homeostasis in lax tendons, RTTfs were allowed to freely contract in vitro for 8 days. The cultured RTTfs contracted rapidly, reaching 50% of their initial length by 3 days. This contraction was associated with the presence of α‐smooth muscle actin positive cells within the tendon. Disruption of the actin network by cytochalasian D caused an immediate and significant elongation of the contracted RTTfs. Subsequent removal of the cytochalasian D re‐initiated the contraction process. When lax RTTfs were allowed to contract between fixed clamps in culture and become taut, they demonstrated a marked decrease in MMP‐13 staining intensity when compared to freely contracting RTTfs. The ability of native tendon cells to contract lax tendons and re‐establish their homeostatic “set point” with respect to collagenase production may be an important mechanism in the recovery of tendons elongated by injury, surgical positioning, or cyclic, viscoelastic creep secondary to repetitive exercise. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1695–1701, 2012
Hydrodynamic and Molecular Study of Poly{4‐[4‐(hexyloxy)phenyl]ethynylphenyl methacrylate} in Dilute Solutions and Conformational Peculiarities of Brush‐Like Macromolecules
Authors: Pavlov Georges M. , Breul Alexander M. , Hager Martin D. , Schubert Ulrich S.
Published: April 2012

Brush‐like poly{4‐[4‐(hexyloxy)phenyl]ethynylphenyl methacrylate}s are synthesized using RAFT polymerization, fractionated and studied by molecular hydrodynamic methods. The values of the velocity sedimentation coefficient, the frictional ratio, and the intrinsic viscosity are obtained in toluene. The conformational and structural parameters of the studied polymer chains are estimated by the use of theories that describe the hydrodynamic behavior of the wormlike cylinders without intra‐chain excluded volume effects and the hydrodynamic behavior of bending rods. The intrinsic viscosity data obtained for poly{4‐[4‐(hexyloxy)phenyl]ethynylphenyl methacrylate}s and for other brush‐like macromolecules are discussed in terms of a doubly‐normalized scaling plot.
Reduction of inflammatory bowel disease‐induced tumor development in IL‐10 knockout mice with soluble epoxide hydrolase gene deficiency
Authors: Zhang Wanying , Liao Jie , Li Haonan , Dong Hua , Bai Han , Yang Allison , Hammock Bruce D. , Yang Guang‐Yu
Published: April 2012

Soluble epoxide hydrolase (sEH) quickly inactivates anti‐inflammatory epoxyeicosatrienoic acids (EETs) by converting them to dihydroxyeicosatrienoic acids (DHETs). Inhibition of sEH has shown effects against inflammation, but little is studied about the role of sEH in inflammatory bowel disease (IBD) and its induced carcinogenesis. In the present study, the effect of sEH gene deficiency on the development of IBD‐induced tumor development was determined in IL‐10 knockout mice combined with sEH gene deficiency. Tumor development in the bowel was examined at the age of 25 wk for male mice and 35 wk for female mice. Compared to IL‐10(−/−) mice, sEH (−/−)/IL‐10(−/−) mice exhibited a significant decrease of tumor multiplicity (2 ± 0.9 tumors/mouse vs. 1 ± 0.3 tumors/mouse) and tumor size (344.55 ± 71.73 mm3 vs. 126.94 ± 23.18 mm3), as well as a marked decrease of precancerous dysplasia. The significantly lower inflammatory scores were further observed in the bowel in sEH(−/−)/IL‐10(−/−) mice as compared to IL‐10(−/−) mice, including parameters of inflammation‐involved area (0.70 ± 0.16 vs. 1.4 ± 0.18), inflammation cell infiltration (1.55 ± 0.35 vs. 2.15 ± 0.18), and epithelial hyperplasia (0.95 ± 0.21 vs. 1.45 ± 0.18), as well as larger ulcer formation. qPCR and Western blotting assays demonstrated a significant downregulation of cytokines/chemokines (TNF‐α, MCP‐1, and IL‐12, 17, and 23) and NF‐κB signals. Eicosanoid acid metabolic profiling revealed a significant increase of ratios of EETs to DHETs and EpOMEs to DiOMEs. These results indicate that sEH plays an important role in IBD and its‐induced carcinogenesis and could serve as a highly potential target of chemoprevention and treatment for IBD. © 2012 Wiley Periodicals, Inc.
Limit cycles in a Gause‐type predator–prey model with sigmoid functional response and weak Allee effect on prey
Authors: González‐Olivares Eduardo , Rojas‐Palma Alejandro
Published: April 2012

The goal of this work is to examine the global behavior of a Gause‐type predator–prey model in which two aspects have been taken into account: (i) the functional response is Holling type III; and (ii) the prey growth is affected by a weak Allee effect.

Here, it is proved that the origin of the system is a saddle point and the existence of two limit cycles surround a stable positive equilibrium point: the innermost unstable and the outermost stable, just like with the strong Allee effect.

Then, for determined parameter constraints, the trajectories can have different  ω − limit sets. The coexistence of a stable limit cycle and a stable positive equilibrium point is an important fact for ecologists to be aware of the kind of bistability shown here.

So, these models are undoubtedly rather sensitive to disturbances and require careful management in applied contexts of conservation and fisheries. Copyright © 2012 John Wiley & Sons, Ltd.
Removable isolated singularities of solutions to the weighted p‐Laplacian with singular convection
Authors: Song Huijuan , Yin Jingxue
Published: April 2012

This paper is concerned with the removability of isolated singularities for the weighted p‐Laplacian with singular convection. Critical singular exponents included in diffusion and convection are exactly determined. Copyright © 2012 John Wiley & Sons, Ltd.
Development of a Large‐Scale Stopped‐Flow System for Heterogeneous Olefin Polymerization Kinetics
Authors: Taniike Toshiaki , Sano Shinya , Ikeya Mitsuhiro , Thang Vu Quoc , Terano Minoru
Published: April 2012

Stopped‐flow (SF) polymerization is a powerful tool to investigate the nature of the active site of heterogeneous Ziegler‐Natta catalysts, but poor polymer yields due to short polymerization times limit detailed structural analyses of the obtained polymer. A new large‐scale SF polymerization system is described in which an arbitrary volume of slurry can be transferred to obtain a polymer yield sufficient for a variety of analytic purposes. The developed LSF system is proven to be highly scalable and stable, leading to reproducible polymerization in an expanded time range from 0.03 s to a few seconds. The accurate polymerization below 0.1 s is promising for future studies to evaluate accurate kinetics as well as dormant processes in Ziegler‐Natta olefin polymerization.

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Future directions of sickle cell disease research: The NIH perspective
Authors: Hoots W. Keith , Shurin Susan B.
Published: April 2012

Efforts to enhance therapy for children and adults with sickle cell disease (SCD) have proven more challenging than might have been predicted from the fact that an understanding of the underlying pathogenesis antedated that of many other diseases for which good treatments presently exist. The multi‐organ injury that occurs with SCD certainly contributes to this clinical reality. Research over decades indicates that the primary defect in hemoglobin that results in polymerization of the protein under low oxygen conditions and resultant cellular deformity of the red blood cell initiates a complex downstream pathogenesis associated with vascular injury and organ ischemia. Deciphering this in a manner that informs successful therapies that improve all target organs continues to challenge hematologists. The National Heart, Lung and Blood Institute (NHLBI) is dedicated to support research across the basic science, translational and clinical spectrum to achieve these clinical outcomes. The following provides a brief summary of the research strategies which NHLBI is presently supporting and will support in the future to enhance care and ultimately, to effect cure of this hemoglobin disease that causes such suffering to those who inherit this monogenic disease. Pediatr Blood Cancer 2012;59:353–357. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
High‐resolution crystal structure of FKBP12 from Aedes aegypti
Authors: Rajan Sreekanth , Saw Kai Qian , Nguyen Quoc Toan , Baek Kwanghee , Yoon Ho Sup
Published: April 2012

Dengue is one of the most infectious viral diseases prevalent mainly in tropical countries. The virus is transmitted by Aedes species of mosquito, primarily Aedes aegypti. Dengue remains a challenging drug target for years as the virus eludes the immune responses. Currently, no vaccines or antiviral drugs are available for dengue prevention. Previous studies suggested that the immunosuppressive drug FK506 shows antimalarial activity, and its molecular target, FK506‐binding protein (FKBP), was identified in the Plasmodium parasite. Likewise, a FKBP family protein has been identified in A. aegypti (AaFKBP12) in which AaFKBP12 is assumed to play a similar role in its life cycle. FKBPs belong to a highly conserved class of proteins and are considered as an attractive pharmacological target. Herein, we present a high‐resolution crystal structure of AaFKBP12 at 1.3 Å resolution and discuss its structural features throwing light in facilitating the design of potential antagonists against the dengue‐transmitting mosquito.
Choice of synonymous codons associated with protein folding
Authors: Huang Jitao T. , Xing Dajie J. , Huang Wei
Published: April 2012

Bioinformatical studies suggest that additional information provided by nucleic acids is necessary to construct protein three‐dimensional structures. We find underlying correlations between the contents of bases. All correlations occur at the third codon position of a gene sequence. Four inverse relationships are observed between u3 and c3, between a3 and g3, between u3 and g3, and between c3 and a3; and two positive relationships are apparent between u3 and a3, and between c3 and g3. Their correlation coefficients reach −0.92, −0.89, −0.83, −0.85, 0.83, and 0.66, respectively, for large proteins with multistate folding kinetics. The interconnection of bases can be ascribed to choice of synonymous codons associated with protein folding in vivo. In this study, the refolding rate constants of large proteins correlate with the contents of the third base, suggesting that there is underlying biochemical rationale of guiding protein folding in choosing synonymous codons. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Computational analysis predicts the Kaposi's sarcoma‐associated herpesvirus tegument protein ORF63 to be alpha helical
Authors: Boyle Joseph P. , Monie Tom P.
Published: April 2012

The innate immune response provides our first line of defence against infection. Over the course of evolution, pathogens have evolved numerous strategies to either avoid activating or to limit the effectiveness of the innate immune system. The Kaposi's sarcoma‐associated herpesvirus (KSHV) contains tegument proteins in the virion that contribute to immune evasion and aid the establishment of viral infection. For example, the KSHV tegument protein ORF63 modulates inflammasome activation to inhibit the innate immune response against the virus. Understanding the likely structure of proteins involved in immune evasion enables potential mechanisms of action to be proposed. To understand more fully how ORF63 modulates the innate immune system we have utilized widely available bioinformatics tools to analyze the primary protein sequence of ORF63 and to predict its secondary and tertiary structure. We found that ORF63 is predicted to be almost entirely alpha‐helical and may possess similarity to HEAT repeat containing proteins. Consequently, ORF63 is unlikely to be a viral homolog of the NLR protein family. ORF63 may inhibit the innate immune response by flexibly interacting with its target protein and inhibiting the recruitment of protein co‐factors and/or conformational changes required for immune signaling. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Study of Dependability Evaluation for Multi‐hierarchical Systems Based on Max–Min Composition
Authors: Tanasijević Miloš , Ivezić Dejan , Jovančić Predrag , Ćatić Dobrivoje , Zlatanović Dragan
Published: April 2012

This article presents the model for calculating the performance of dependability for complex technical systems. According to ISO‐IEC 300, dependability is an overall indicator for the quality of service and considers simultaneously reliability, maintainability, and maintenance support. For a proper understanding of the quality of service for any technical system, it is important to define dependability performance at the level of single component as well as at the upper levels—levels of subsystems and entire system. As dependability indicators (reliability, maintainability, and maintenance support) have been defined as linguistic variables, the fuzzy max–min composition has been used for the dependability determination and integration of its indicators. A procedure for the synthesis of single components dependability performance to upper levels in complex technical system is proposed. Max–min composition is again used as a tool for fuzzy synthesis because it enables obtaining the comprehensive and synergetic effect in a process of dependability evaluation. A practical engineering example (mechanical systems at bucket wheel excavator) has been used to demonstrate the proposed dependability synthesis model. Copyright © 2012 John Wiley & Sons, Ltd.
Effect of native and acetylated‐crosslinked waxy corn starch‐beeswax coatings on quality attributes of raspberries during storage
Authors: Pérez‐Gallardo Alfonso , Mattinson Scott D. , Lazcano‐Peralta Alma , Fellman John K. , Barbosa‐Cánovas Gustavo , García‐Almendárez Blanca , Regalado Carlos
Published: April 2012

Edible coatings (ECs) are a thin layer of a mixture of edible materials, applied in the liquid state and dried over the surface of a food product to maintain its quality during storage. This work was aimed to study the effect of ECs made from wx corn starch (WCS) or acetylated cross‐linked starch (ACLS) added with beeswax on fresh raspberry quality attributes during short‐term cold storage. Freshly harvested fruits were coated, dried, packed in plastic trays and stored up to 8 days at 4°C. During storage quality parameters such as firmness, respiration rate, anthocyanins content, total phenols, color changes, and weight loss were evaluated. A clear effect on control of respiration rate was observed in coated raspberries. Respiration rate of uncoated fruit was 4.5 ± 0.28 mmol/kg/h and decreased to 4.2 ± 0.27 for ACLS and to 4.1 ± 0.08 mmol/kg/h for WCS‐coated raspberries, after 56 h of storage at 15°C. Ethylene production followed a similar trend under these conditions decreasing from 0.043 ± 0.005 to 0.034 ± 0.004 mmol/kg/h for uncoated and ACLS coated fruits, respectively, indicating an effect on ripening control. Additionally, ACLS and WCS coatings permitted the preservation of color without affecting anthocyanins content. However, the presence of anaerobic metabolites and reduction of terpenes production in cold stored coated raspberries indicated hypoxic conditions, which can adversely affect shelf‐life quality attributes of raspberries such as firmness and weight loss.
Bridging the innovation divide: The Brazilian experience
Authors: Gouvea Raul , Kassicieh Suleiman
Published: April 2012

The purpose of this article is to discuss the Brazilian innovation environment. It addresses the challenges, promises, bottlenecks, and opportunities by examining the country's quest to bridge the innovation divide. In addition, it applies the main dimensions of the “innovation diamond model” to assess how the country is faring in its journey toward competitiveness. The article analyzes Brazil's main innovation policies and agencies. Its companies and policymakers have recently understood that, without a dynamic and rich innovation environment, it will not be able to design long‐term economic development strategies and engage in long‐term sustainable growth. © 2012 Wiley Periodicals, Inc.
Business innovations from emerging market countries into developed countries: Implications for multinationals from developed countries
Authors: Nonis Sarath A. , Relyea Clint
Published: April 2012

This article addresses innovation and emerging‐market countries. Both are important topics in the business world today. The focus of this article is on the importance of innovation and market development in emerging‐market countries by Western multinational companies typically based in North America and Western Europe. The authors of this article argue that as Western multinationals innovate and develop emerging markets, this will give multinationals the opportunity not only to compete effectively in emerging markets but also to protect their home markets in developed countries. Implications for Western multinationals are discussed. © 2012 Wiley Periodicals, Inc.
A study of the impact of Western HRM systems on firm performance in China
Authors: Lin Zhaohong
Published: April 2012

Based on a sample of 324 firms in China, the relationship between Western human resource management (HRM) systems and firm performance is examined. The results show that the degree of adoption of Western HRM practices made no statistically significant difference between Chinese and foreign firms and also generally supports the hypothesis that Western HRM systems are positively associated with firm performance in a Chinese context. In addition, the proposed “motivation and support” HRM system appeared to have stronger and more significant relationships than the “skill and development” HRM system. The underlying reasons were identified and some managerial implications for both Chinese and foreign firms were drawn. © 2012 Wiley Periodicals, Inc.
Knowledge acquisition strategies of small and medium‐sized enterprises during institutional transition: Evidence from Hungary and Ukraine
Authors: Danis Wade M. , Shipilov Andrew
Published: April 2012

Drawing on data from Hungary and Ukraine, this study explores how small‐ and medium‐sized enterprises (SMEs) in transition economies acquire the managerial, marketing, and technological knowledge they need to compete in increasingly competitive local and global markets. Although Hungary and Ukraine are at different stages of transition and levels of economic and institutional development, the patterns we observed were remarkably similar, suggesting that shared institutional legacies shape management practice in important ways. Managerial knowledge was perceived as the most difficult to acquire, with technological knowledge being the easiest. Both managerial and marketing knowledge were perceived as critically important for success, although the priority may differ depending on stage of SME development. © 2012 Wiley Periodicals, Inc.
The role of subsidiaries from emerging economies—A survey involving the largest Brazilian multinationals
Authors: de Miranda Oliveira Moacir , Mendes Borini Felipe
Published: April 2012

Several research projects have been devoted to the study of the internationalization of Brazilian firms; however there is a lack of research related to the strategy and management of subsidiaries of Brazilian multinational corporations in other countries. This article seeks to contribute to filling this gap. An academic research study was conducted involving 30 Brazilian multinational corporations. Of the 93 subsidiaries involved, 66 foreign subsidiaries answered the questionnaires. The main results concern the identification of three factors and the proposition of a typology of Brazilian subsidiaries of multinational corporations: implementing subsidiaries; market‐exploiting subsidiaries, and aspirants to strategically relevant subsidiaries. © 2012 Wiley Periodicals, Inc.