bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon regulatory factor 3 deficiency leads to interleukin-17-mediated liver ischemia-reperfusion injury
Authors: Loi Patrizia , Yuan Qing , Torres David , Delbauve Sandrine , Laute Marie-Aline , Lalmand Marie-Claude , Pétein Michel , Goriely Stanislas , Goldman Michel , Flamand Véronique
Published: August 2012

Interferon regulatory factor 3 (IRF3) is an important transcription factor in Toll-like receptor 4 (TLR4) signaling, a pathway that is known to play a critical role in liver ischemia-reperfusion injury. In order to decipher the involvement of IRF3 in this setting, we first compared the intensity of hepatic lesions in IRF3-deficient versus wildtype mice. We found increased levels of blood transaminases, enhanced liver necrosis, and more pronounced neutrophil infiltrates in IRF3-deficient mice. Neutrophil depletion by administration of anti-Ly6G monoclonal antibody indicated that neutrophils play a dominant role in the development of severe liver necrosis in IRF3-deficient mice. Quantification of cytokine genes expression revealed increased liver expression of interleukin (IL)-12/IL-23p40, IL-23p19 messenger RNA (mRNA), and IL-17A mRNA in IRF3-deficient versus wildtype (WT) mice, whereas IL-27p28 mRNA expression was diminished in the absence of IRF3. The increased IL-17 production in IRF3-deficient mice was functionally relevant, as IL-17 neutralization prevented the enhanced hepatocellular damages and liver inflammation in these animals. Evidence for enhanced production of IL-23 and decreased accumulation of IL-27 cytokine in M1 type macrophage from IRF3-deficient mice was also observed after treatment with lipopolysaccharide, a setting in which liver gamma-delta T cells and invariant natural killer T cells were found to be involved in IL-17A hyperproduction. Conclusion: IRF3-dependent events downstream of TLR4 control the IL-23/IL-17 axis in the liver and this regulatory role of IRF3 is relevant to liver ischemia-reperfusion injury. (Hepatology 2013)
In Vivo Hyperpolarized Carbon-13 Magnetic Resonance Spectroscopy Reveals Increased Pyruvate Carboxylase Flux in an Insulin-Resistant Mouse Model
Authors: Lee Philip , Leong Waifook , Tan Trish , Lim Miangkee , Han Weiping , Radda George K.
Published: August 2012

The pathogenesis of type 2 diabetes is characterized by impaired insulin action and increased hepatic glucose production (HGP). Despite the importance of hepatic metabolic aberrations in diabetes development, there is currently no molecular probe that allows measurement of hepatic gluconeogenic pathways

in vivo

and in a noninvasive manner. In this study, we used hyperpolarized carbon 13 (13C)-labeled pyruvate magnetic resonance spectroscopy (MRS) to determine changes in hepatic gluconeogenesis in a high-fat diet (HFD)-induced mouse model of type 2 diabetes. Compared with mice on chow diet, HFD-fed mice displayed higher levels of oxaloacetate, aspartate, and malate, along with increased 13C label exchange rates between hyperpolarized [1-13C]pyruvate and its downstream metabolites, [1-13C]malate and [1-13C]aspartate. Biochemical assays using liver extract revealed up-regulated malate dehydrogenase activity, but not aspartate transaminase activity, in HFD-fed mice. Moreover, the 13C label exchange rate between [1-13C]pyruvate and [1-13C]aspartate (kpyr->asp) exhibited apparent correlation with gluconeogenic pyruvate carboxylase (PC) activity in hepatocytes. Finally, up-regulated HGP by glucagon stimulation was detected by an increase in aspartate signal and

k

pyr

->

asp

, whereas HFD mice treated with metformin for 2 weeks displayed lower production of aspartate and malate, as well as reduced

k

pyr

->

asp

and 13C-label exchange rate between pyruvate and malate, consistent with down-regulated gluconeogenesis.

Conclusion:

Taken together, we demonstrate that increased PC flux is an important pathway responsible for increased HGP in diabetes development, and that pharmacologically induced metabolic changes specific to the liver can be detected

in vivo

with a hyperpolarized 13C-biomolecular probe. Hyperpolarized 13C MRS and the determination of metabolite exchange rates may allow longitudinal monitoring of liver function in disease development.
An autonomous mathematical reconstruction to effectively measure volume loss on retrieved polyethylene tibial inserts
Authors: Knowlton Christopher B. , Wimmer Markus A.
Published: August 2012

Wear of the polyethylene tibial component is a major factor in the success of total knee replacements. However, sampling resolution and the challenges of estimating original surfaces with relatively complex articulating geometries have limited the accuracy of volumetric measurements of wear on surgically retrieved inserts. A mathematical model analyzed volume error due to sampling resolution and found that 100 × 100 μm2 point spacing reduced error below 1 mm3. Small volumes of material were progressively removed from the topside of three unworn tibial inserts, after which each component was weighed and digitized with a laser coordinate measuring machine. Six inserts worn in knee simulator tests and nine surgically retrieved inserts visually scored for damage were also digitized. For these tests, the original surface of an insert was mathematically reconstructed from unworn regions of the same component, and volume loss and its spatial distribution were calculated. Volume loss estimated by autonomous reconstruction correlated strongly to mass removed manually (R2 = 0.954, slope = 1.02 ± 0.04), mass lost during simulator testing (R2 = 0.935, slope = 1.01 ± 0.07) and visual damage scores separated by size (R2large = 0.9824, R2small = 0.9728). These results suggest that an autonomous mathematical reconstruction can be used to effectively measure volume loss in retrieved tibial inserts. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 449–457, 2013.
Enhanced attachment, proliferation, and differentiation of human gingival fibroblasts on titanium surface modified with biomolecules
Authors: Jin Can , Ren Ling‐fei , Ding Hua‐zhu , Shi Geng‐sheng , Lin Hai‐sheng , Zhang Feng
Published: August 2012

Surface modification of dental implants with biomolecules is of particularly interest recently. To mimic the structure and function of native extracellular matrix (ECM), a derivative of hyaluronic acid (HA), HA–GRGDSP, was synthesized, Arg–Gly–Asp (RGD)‐containing collagen (Col)/HA multilayer polyelectrolyte films (MPFs) coating was fabricated on titanium (Ti) through alternate deposition of Col and HA–GRGDSP with 4.5 assembly cycles; moreover, bioactive molecule, basic fibroblast growth factor (bFGF), was also incorporated into such coating. This coating was then carefully characterized using scanning electronic microscope (SEM) and scanning force microscopy (SFM); bFGF release from the coating was also evaluated. (Col + bFGF)/HA–RGD coating was successfully deposited on Ti surface, and about 300 pg of bFGF could be slowly released from this coating for a week. This coating significantly promoted the initial cell attachment of human gingival fibroblasts (HGFs) compared with other groups (p < 0.05), and HGFs adhered and spread better on this coating than other groups (p < 0.05). Regarding cell proliferation and differentiation of HGFs, they were greatly stimulated when cultured on this coating (p < 0.05). These results indicated that surface modification of Ti using biomolecules might improve the sealing between the neck section of a dental implant and the soft tissue. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
VEGF‐incorporated biomimetic poly(lactide‐co‐glycolide) sintered microsphere scaffolds for bone tissue engineering
Authors: Jabbarzadeh Ehsan , Deng Meng , Lv Qing , Jiang Tao , Khan Yusuf M. , Nair Lakshmi S. , Laurencin Cato T.
Published: August 2012

Regenerative engineering approaches utilizing biomimetic synthetic scaffolds provide alternative strategies to repair and restore damaged bone. The efficacy of the scaffolds for functional bone regeneration critically depends on their ability to induce and support vascular infiltration. In the present study, three‐dimensional (3D) biomimetic poly(lactide‐co‐glycolide) (PLAGA) sintered microsphere scaffolds were developed by sintering together PLAGA microspheres followed by nucleation of minerals in a simulated body fluid. Further, the angiogenic potential of vascular endothelial growth factor (VEGF)‐incorporated mineralized PLAGA scaffolds were examined by monitoring the growth and phenotypic expression of endothelial cells on scaffolds. Scanning electron microscopy micrographs confirmed the growth of bone‐like mineral layers on the surface of microspheres. The mineralized PLAGA scaffolds possessed interconnectivity and a compressive modulus of 402 ± 61 MPa and compressive strength of 14.6 ± 2.9 MPa. Mineralized scaffolds supported the attachment and growth and normal phenotypic expression of endothelial cells. Further, precipitation of apatite layer on PLAGA scaffolds resulted in an enhanced VEGF adsorption and prolonged release compared to nonmineralized PLAGA and, thus, a significant increase in endothelial cell proliferation. Together, these results demonstrated the potential of VEGF‐incorporated biomimetic PLAGA sintered microsphere scaffolds for bone tissue engineering as they possess the combined effects of osteointegrativity and angiogenesis. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Variability and trends of heating degree‐days in Argentina
Authors: Castañeda M. Elizabeth , Claus Federico
Published: August 2012

This study analyses heating degree‐days (HDDs) in Argentina during the period 1900–2008. Gridded temperature data provided by the University of Delaware were analysed to calculate monthly and annual cumulative HDDs. Mean, maximum and minimum values as well as the average duration of the heating season are used to characterize the mean features of the region. Spatial variations are driven by latitude and altitude. The analysis of the temporal distribution of HDDs reveals that the centre of the mean heating season varies from mid‐June to mid‐July. The length of the cold season grows with increasing latitude and westward with increasing altitude. In the high Andes, the heating season extends all year round. S‐mode principal component analysis is used to identify sub‐groups of grid points with similar temporal variability. Negative trends in annual cumulative HDDs are detected in most of the country. Linear and nonlinear trends as well as temporal statistics are examined for inter‐ and intra‐annual variability of HDDs to discuss its potential incidence on residential use of natural gas. Seasonal increases in natural gas consumption in the country, including the effect of regional price benefits, could be now better explained not only by population growth but also by the spatial and temporal characterization of the HDD season.
Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice
Authors: Zhang Dawei , Jin Li , Reames Davis L. , Shen Francis H. , Shimer Adam L. , Li Xudong
Published: August 2012

Cardiovascular risk factors are known to be associated with intervertebral disc degeneration, but the underlying mechanism is still unclear. The ApoE knockout (KO) mouse is a well‐established model for atheroscelorosis. We hypothesized that ApoE is involved in maintaining disc health and that ApoE KO mice will develop early disc degeneration. Discs of ApoE KO and wild‐type (WT) mice were characterized with histological/immunological, biochemical, and real‐time RT‐PCR assays. A comparison of the extracellular matrix production was also performed in disc cells. We demonstrated that ApoE was highly expressed in the endplates of WT discs, and ectopic bone formed in the endplates of ApoE KO discs. Glycosaminoglycan content was decreased in both ApoE KO annulus fibrosus (AF) and nucleus pulposus (NP) cells. Collagen levels were increased in AF and decreased in NP cells. Matrix metalloproteinase‐3, ‐9, and ‐13 expressions were increased, which may partially explain the impaired matrix production. We also found collagen I, II, aggrecan, and biglycan mRNA expressions were increased in AF cells but decreased in NP cells. Apoptosis was increased in the ApoE KO NP tissue. These results suggest early disc degeneration changes in the ApoE KO mice. ApoE may play a critical role in disc integrity and function. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 210–217, 2013
Can rapidly accumulating Holocene peat profiles provide sub‐decadal resolution proxy climate data?
Authors: Amesbury Matthew J. , Barber Keith E. , Hughes Paul D. M.
Published: August 2012

To test the potential for developing sub‐decadal resolution records of ombrotrophic bog surface wetness (BSW), selected abrupt climate events were identified in cores from four sites in north‐west Europe and time‐slices over each event were investigated at 2–5‐mm resolution using peat humification, testate amoeba and plant macrofossil analyses. Age–depth models based on radiocarbon, spheroidal carbonaceous particle and tephra dates were applied and the error in these models was used to determine the effective temporal sampling resolution, which in most cases was sub‐decadal. Fine‐resolution results revealed some inconsistencies in the co‐variability of individual proxies and there was a lack of correspondence between some results from adjacent cores. However, we found evidence of abrupt shifts in BSW occurring over ca. 5–20 years, indicating a more rapid proxy response than identified in previous research. To maximize potential temporal resolution and produce reliable sub‐decadal BSW data in future research, we recommended that peat‐based studies should obtain the best possible chronological control, focus on sites with high species diversity and rapid accumulation rates and perform replicate coring, or use open peat sections where the stratigraphy can be clearly seen, to assess intra‐site differences in microtopography. Site‐specific factors should be a primary consideration in the selection of sites for future fine‐resolution research. Copyright © 2012 John Wiley & Sons, Ltd.
Fluctuations in the late Quaternary East Asian winter monsoon recorded in sediment records of surface water cooling in the northern Japan Sea
Authors: Ikehara Ken , Fujine Kazuho
Published: August 2012

The East Asian monsoon climate system involves interactions between land and ocean and is composed of summer and winter monsoons. Cooling of surface water by the East Asian winter monsoon (EAWM) promotes the formation of sea ice and deep water in the northern Japan Sea. Modern observations suggest close relationships between intensification of the EAWM and both sea ice formation and sea‐surface temperature (SST) decrease in the northeastern Japan Sea. Records of ice‐rafted debris (IRD) and alkenone‐based SST in the northeastern Japan Sea are examined to clarify the temporal variability of the EAWM and its controlling factors. Close relationships with oxygen isotope records of Chinese stalagmites and Northern Hemisphere summer insolation are observed in the records of IRD occurrence and SST during Marine Isotope Stages (MIS) 3–5. The co‐occurrence of maxima in the abundance of IRD and minima in SST in the northeastern Japan Sea indicates that the intensity of the EAWM was enhanced during periods of low summer insolation and high oxygen isotope ratios in Chinese stalagmites. Decoupling between the IRD and SST records during MIS 2 and MIS 6 might be the result of differences in surface water conditions caused by low sea levels and the resultant closure of the Tsushima Strait. During MIS 3 and 4, some small but clear maxima in IRD and minima in SST occurred at relatively low summer insolation periods. Some of these peaks co‐occur with North Atlantic Heinrich events, suggesting a possible climate linkage between the North Atlantic and the Asian monsoon. The presence of finer fluctuations in the occurrence of IRD than in summer insolation suggests finer millennial–centurial timescale fluctuations in the intensity of the EAWM. Furthermore, some IRD peaks occurred during periods of high insolation, such as 39, 86, 103, 128, 145, and 153 ka. Some of these IRD peaks correlate with minima in reconstructed SST and maxima in oxygen isotope ratios of Chinese stalagmites. This result suggests that extremely cold winters occur even during periods of enhanced East Asian summer monsoon intensity, and indicates that solar insolation is not the only factor that controls variations in the intensity of the EAWM at millennial–centurial timescales. Copyright © 2012 John Wiley & Sons, Ltd.
Strategic positioning and grand strategies for high‐technology SMEs
Authors: O'Regan Nicholas , Kling Gerhard , Ghobadian Abby , Perren Lew
Published: August 2012

Firm size is found to affect strategic decisions significantly, whereas technology and market stability stimulate product development and innovation.
Disrupting practices: New insights into innovation
Authors: Beckett Antony
Published: August 2012

Innovation occurs not only in the laboratory but everywhere and the task facing firms wanting to innovate is to remain open and sensitive to changes in the performance of practice, to new technologies, or new combinations of existing technologies.
An engineering systems approach to strategic change: The case of the European automotive industry
Authors: Parry Glenn C. , Roehrich Jens K.
Published: August 2012

The European automotive industry has developed a demand‐driven production method called build to order (BTO) to build cars to customer demand, but its strategic vision has yet to be widely diffused.
Interaction with an autostereoscopic touch screen: effect of occlusion on subjective experiences when pointing to targets in planes of different depths
Authors: Pölönen Monika , Järvenpää Toni , Salmimaa Marja
Published: August 2012

It is well known that the usability of a typical touch screen depends on several parameters, including interface design, device characteristics, and input operations. However, there is virtually no knowledge regarding how people evaluate interaction with 3D display‐integrated touch screen. Twenty‐one participants were asked to use standard touch screen to point to targets in planes of different planes on an autostereoscopic display and evaluate how natural and easy this action was. Clear differences in pointing experiences across depth levels and input operators were found. Pointing to targets in a back plane was reported to be more natural and easier than the same action with targets in a front plane. The use of finger input was less unnatural than the use of a stylus, but the use of stylus with icons in the front plane was more fun and entertaining.
Influence of the topology of an artificial neural network on the results for estimating the cyclic material properties
Authors: el Dsoki C. , Lohmann F. , Hanselka H. , Kaufmann H.
Published: August 2012

Zur Abschätzung der Lebensdauer von zyklisch belasteten Bauteilen anhand statischer Werkstoffkennwerte existieren zahlreiche Abschätzungsverfahren, die größtenteils auf empirischen Gleichungen beruhen. Mit zunehmender Anzahl der Eingabe‐ und Einflussparameter steigt auch der Aufwand zur Ableitung dieser Gleichungen und die Abschätzungsgenauigkeit sinkt. Daher wurde nach neuartigen Methoden gesucht, um die zyklischen Kennwerte zuverlässig abschätzen zu können. Ein vielversprechender Ansatz ist mit den künstlich neuronalen Netzen gefunden worden, welche den Zusammenhang zwischen Eingangsparametern und Ausgabeparametern selbst erschließen können. Als Eingangsparameter kommen die statischen Kennwerte der zu untersuchenden Werkstoffe zum Einsatz, da diese gegenüber den zyklischen schneller und kostengünstiger zu ermitteln sind. Als Ausgabegrößen werden die zyklischen Kennwerte der Ramberg‐Osgood‐ und der Manson‐Coffin‐Basquin‐Gleichung abgeschätzt. Die künstlich neuronalen Netze können dabei sehr unterschiedlich und beliebig komplex aufgebaut sein. In dieser Arbeit wird der Einfluss der Verknüpfungen der Neuronen untereinander, der sogenannten Topologie, auf die Abschätzungsgüte der künstlich neuronalen Netze untersucht. Ausgehend von einem Referenzfall wird gezeigt, dass komplexere Topologien demgegenüber nicht die gewünschten Verbesserungen bei der Abschätzung der zyklischen Kennwerte erzielen.
The influence of the surface finishing on the electrochemical behaviour of austenitic and superaustenitic steels
Authors: Alar V. , Baršić G. , Runje B. , Alar Ž.
Published: August 2012

The influence of surface roughness on the pitting potential and the corrosion potential of the DIN W.Nr. 1.4541 and DIN W.Nr 1.4465 stainless steels were examined using electrochemical techniques. Roughness and electrochemical tests were performed on samples with various surface finishing. Electrochemical studies were conducted in an electrochemical cell where steel electrodes were immersed in 0.1 M NaCl and 0.1 M NaCl + 0.1 M Na2SO4 aqueous solutions. We found for both materials when immersed in 0.1 M NaCl aqueous solution lower pitting potential than in 0.1 M NaCl + 0.1 M Na2SO4. The results showed that the electrochemical behaviour of the DIN W.Nr. 1.4465 is better than of DIN W.Nr. 1.4541.
Hyperhydrophilic rough surfaces and imaginary contact angles
Authors: Jennissen H. P.
Published: August 2012

The complete wetting of rough surfaces is only poorly understood, since the underlying phenomena can neither be described by the Cassie‐Baxter nor the Wenzel equation. An experimental accessiblility by the sessile drop method is also very limited. The term “superhydrophilicity” was an attempt to understand the wetting of rough surfaces, but a clear definition is still forthcoming, mainly because non‐superhydrophilic surfaces can also display a contact angle of zero. Since the Wilhelmy balance is based on force measurements, it offers a technology for obtaining signals during the whole wetting process. We have obtained evidence that additional forces occur during the complete wetting of rough surfaces and that mathematically contact angles for a hydrophilicity beyond the contact angle of zero can be defined by imaginary numbers. A hydrophilized TPS‐surface obtained by chemical wettability switching from a superhydrophobic surface has been previously characterized by dynamic imaginary contact angles of 20i°–21i° and near‐zero hysteresis. Here an extremely high wetting rate is demonstrated reaching a virtual imaginary contact angle of ΘV,Adv > 3.5i° in less than 210 ms. For a rough surface displaying imaginary contact angles and extremely high wetting rates we suggest the term hyperhydrophilicity. Although, as will be shown, the physical basis of imaginary contact angles is still unclear, they significantly expand our methodology, the range of wettability measurements and the tools for analyzing rough hydrophilic surfaces. They may also form the basis for a new generation of rationally constructed medicinal surfaces.
One component? Two components? Three? The effect of including a nonexchanging “free” water component in multicomponent driven equilibrium single pulse observation of T1 and T2
Authors: Deoni Sean C. L. , Matthews Lucy , Kolind Shannon H.
Published: August 2012

Quantitative myelin content imaging provides novel and pertinent information related to underlying pathogenetic mechanisms of myelin‐related disease or disorders arising from aberrant connectivity. Multicomponent driven equilibrium single pulse observation of T1 and T2 is a time‐efficient multicomponent relaxation analysis technique that provides estimates of the myelin water fraction, a surrogate measure of myelin volume. Unfortunately, multicomponent driven equilibrium single pulse observation of T1 and T2 relies on a two water‐pool model (myelin‐associated water and intra/extracellular water), which is inadequate within partial volume voxels, i.e., containing brain tissue and ventricle or meninges, resulting in myelin water fraction underestimation. To address this, a third, nonexchanging “free‐water” component was introduced to the multicomponent driven equilibrium single pulse observation of T1 and T2 model. Numerical simulations and experimental in vivo data show that the model to perform advantageously within partial volume regions while providing robust and reproducible results. It is concluded that this model is preferable for future studies and analysis. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Hospitalisation for infection prior to diagnosis of acute lymphoblastic leukaemia in children
Authors: Vestergaard Therese Risom , Rostgaard Klaus , Grau Katrine , Schmiegelow Kjeld , Hjalgrim Henrik
Published: August 2012

Background

It has been proposed that infections in infancy and early childhood are associated with a reduced risk of childhood acute lymphoblastic leukaemia (ALL). We tested this hypothesis in a register‐based study of hospitalisations for infectious diseases prior to diagnosis of childhood ALL.

Procedure

A nation‐wide cohort encompassing all Danish children aged 0–14 years and born between 1977 and 2008 (N = 1,778,129) was established and followed for hospitalisations for infectious diseases and risk of childhood ALL. The exposure was lagged 1 year to limit reverse causality. In the statistical analyses exposure was defined as (time dependent) number of early or late (before 2 or at/after 2 years of age) hospitalisations to further explore possible age‐dependent associations.

Results

A total of 815 children were diagnosed with ALL during follow‐up. Risk of ALL was associated neither with hospitalisations for infectious diseases before (incidence rate ratio = 0.92, 95% confidence interval 0.78–1.07) nor at/after 2 years of age (incidence rate ratio = 1.04, 95% confidence interval 0.81–1.32). This also applied to subsets of ALL supposedly initiated prenatally.

Conclusion

The absence of association between hospitalisation for infections and risk of childhood ALL directs future investigations of the role of infections in development of childhood ALL towards exploration of less severe infections. Pediatr Blood Cancer 2013; 60: 428–432. © 2012 Wiley Periodicals, Inc.
Management of migraine in children
Authors: Barnes Nick
Published: August 2012

In the first of a new series on managing neurological and psychiatric conditions in children and adolescents, Dr Nick Barnes discusses the presentation, diagnosis and treatment of paediatric migraine.
Super‐atom properties of 13 atom clusters of group 13 elements
Authors: Varns Rebecca , Strange Paul
Published: August 2012

We report first principles calculations of the geometry and electronic structure of 13 atom clusters of boron, aluminium, gallium and indium. These density functional theory calculations support the jellium model in the energy levels and molecular orbitals of the cluster and enable us to discuss the relevance of the superatom concept. We go on to examine a number of cluster symmetries in detail as a function of charge and comment on the successes and limitations of the jellium and superatom models in describing these clusters. In particular we find that the monovalent anionic cluster is the most stable and has the most symmetric structure. As charge changes the symmetry of the clusters decreases in a way that is dependent on symmetry and charge, but not atomic species.
Spin in density‐functional theory
Authors: Jacob Christoph R. , Reiher Markus
Published: August 2012

The accurate description of open‐shell molecules, in particular of transition metal complexes and clusters, is still an important challenge for quantum chemistry. Although density‐functional theory (DFT) is widely applied in this area, the sometimes severe limitations of its currently available approximate realizations often preclude its application as a predictive theory. Here, we review the foundations of DFT applied to open‐shell systems, both within the nonrelativistic and the relativistic framework. In particular, we provide an in‐depth discussion of the exact theory, with a focus on the role of the spin density and possibilities for targeting specific spin states. It turns out that different options exist for setting up Kohn–Sham DFT schemes for open‐shell systems, which imply different definitions of the exchange–correlation energy functional and lead to different exact conditions on this functional. Finally, we suggest possible directions for future developments. © 2012 Wiley Periodicals, Inc.
Simulation of FIB‐SEM Images for Analysis of Porous Microstructures
Authors: Prill Torben , Schladitz Katja
Published: August 2012

Focused ion beam nanotomography‐scanning electron microscopy tomography yields high‐quality three‐dimensional images of materials microstructures at the nanometer scale combining serial sectioning using a focused ion beam with SEM. However, FIB‐SEM tomography of highly porous media leads to shine‐through artifacts preventing automatic segmentation of the solid component. We simulate the SEM process in order to generate synthetic FIB‐SEM image data for developing and validating segmentation methods. Monte‐Carlo techniques yield accurate results, but are too slow for the simulation of FIB‐SEM tomography requiring hundreds of SEM images for one dataset alone. Nevertheless, a quasi‐analytic description of the specimen and various acceleration techniques, including a track compression algorithm and an acceleration for the simulation of secondary electrons, cut down the computing time by orders of magnitude, allowing for the first time to simulate FIB‐SEM tomography. SCANNING 35: 189‐195, 2013. © 2012 Wiley Periodicals, Inc.
Fast linear mixed model computations for genome‐wide association studies with longitudinal data
Authors: Sikorska Karolina , Rivadeneira Fernando , Groenen Patrick J.F. , Hofman Albert , Uitterlinden André G. , Eilers Paul H.C. , Lesaffre Emmanuel
Published: August 2012

Genome‐wide association studies are characterized by a huge number of statistical tests performed to discover new disease‐related genetic variants [in the form of single‐nucleotide polymorphisms (SNPs)] in human DNA. Many SNPs have been identified for cross‐sectionally measured phenotypes. However, there is a growing interest in genetic determinants of the evolution of traits over time. Dealing with correlated observations from the same individual, we need to apply advanced statistical techniques. The linear mixed model is popular but also much more computationally demanding than fitting a linear regression model to independent observations. We propose a conditional two‐step approach as an approximate method to explore the longitudinal relationship between the trait and the SNP. In a simulation study, we compare several fast methods with respect to their accuracy and speed. The conditional two‐step approach is applied to relate SNPs to longitudinal bone mineral density responses collected in the Rotterdam Study. Copyright © 2012 John Wiley & Sons, Ltd.
A method for analyzing clustered interval‐censored data based on Cox's model
Authors: Kor Chew‐Teng , Cheng Kuang‐Fu , Chen Yi‐Hau
Published: August 2012

Methods for analyzing interval‐censored data are well established. Unfortunately, these methods are inappropriate for the studies with correlated data. In this paper, we focus on developing a method for analyzing clustered interval‐censored data. Our method is based on Cox's proportional hazard model with piecewise‐constant baseline hazard function. The correlation structure of the data can be modeled by using Clayton's copula or independence model with proper adjustment in the covariance estimation. We establish estimating equations for the regression parameters and baseline hazards (and a parameter in copula) simultaneously. Simulation results confirm that the point estimators follow a multivariate normal distribution, and our proposed variance estimations are reliable. In particular, we found that the approach with independence model worked well even when the true correlation model was derived from Clayton's copula. We applied our method to a family‐based cohort study of pandemic H1N1 influenza in Taiwan during 2009–2010. Using the proposed method, we investigate the impact of vaccination and family contacts on the incidence of pH1N1 influenza. Copyright © 2012 John Wiley & Sons, Ltd.
Skill relatedness and firm diversification
Authors: Neffke Frank , Henning Martin
Published: August 2012

Because of the importance of human capital, a firm's choice of diversification targets will depend on whether these targets offer opportunities for leveraging existing human resources. We propose to quantify the similarity of different industries' human capital or skill requirements, that is, the industries' skill relatedness, by using information on cross‐industry labor flows. Labor flows among industries can be used to identify skill relatedness, because individuals changing jobs will likely remain in industries that value the skills associated with their previous work. Estimates show that firms are far more likely to diversify into industries that have ties to the firms' core activities in terms of our skill‐relatedness measure than into industries without such ties or into industries that are linked by value chain linkages or by classification‐based relatedness. Copyright © 2012 John Wiley & Sons, Ltd.
Three‐Dimensional Gold Nanoparticle Clusters with Tunable Cores Templated by a Viral Protein Scaffold
Authors: Li Feng , Chen Huiling , Zhang Yejun , Chen Zhong , Zhang Zhi‐Ping , Zhang Xian‐En , Wang Qiangbin
Published: August 2012

Assembling nanoparticles (NPs) into ordered architectures remains a challenge in the field of nanotechnology. Templated strategies have been widely utilized for NP assembly. As typical biological nanostructures, virus‐based NPs (VNPs) have shown great promise in templating NP assembly. Here it is illustrated that the VNP of simian virus 40 (SV40) is a powerful scaffold in directing the assembly of 3D hybrid nanoarchitectures with one NP encapsulated inside as a core and a cluster of gold NPs (AuNPs) on the outer surface of the SV40 VNP as a shell, in which the core NPs can be CdSe/ZnS quantum dots (QDs), Ag2S QDs, or AuNPs. The assembling of AuNPs onto the SV40 VNP surface is determined by the interactions between the AuNPs and the amine groups on the outer surface of SV40 VNPs. It is expected that the VNP guided 3D hybrid nanoarchitectures provide ideal models for NP interaction studies and open new opportunities for integrating various functionalities in NP assemblies.
A New Method of Rail Head Hardening of Standard‐Gauge Rails for Improved Wear and Damage Resistance
Authors: Kuziak Roman , Zygmunt Tomasz
Published: August 2012

A new method of cyclic‐accelerated cooling of the head of pearlitic rails to increase their performance in service was described in this paper. It is essentially based upon the head's immersion in aqueous polymer solution. However, as opposed to the methods developed so far, the head's immersion is performed cyclically by raising and lowering the level of the cooling solution, dividing the entire process into fast and slow cooling stages. When the intervals of the fast and slow cooling stages are properly defined, there is no necessity to control the time of the entire process to prevent the bainite/martensite formation. The most important effect of the cyclic cooling is that the entire time of the process can be adjusted to obtain fine pearlitic structure in the whole cross‐section of the head. Applying this technology, the head hardened rails were produced at Huta Królewska S.A. and tested successfully in track.
Risk of epithelial ovarian cancer in asymptomatic women with ultrasound‐detected ovarian masses: a prospective cohort study within the UK collaborative trial of ovarian cancer screening (UKCTOCS)
Authors: Sharma A. , Apostolidou S. , Burnell M. , Campbell S. , Habib M. , Gentry‐Maharaj A. , Amso N. , Seif M. W. , Fletcher G. , Singh N. , Benjamin E. , Brunell C. , Turner G. , Rangar R. , Godfrey K. , Oram D. , Herod J. , Williamson K. , Jenkins H. , Mould T. , Woolas R. , Murdoch J. , Dobbs S. , Leeson S. , Cruickshank D. , Fourkala E.‐O. , Ryan A. , Parmar M. , Jacobs I. , Menon U.
Published: August 2012

Objective

To estimate the risk of primary epithelial ovarian cancer (EOC) and slow growing borderline or Type I and aggressive Type II EOC in postmenopausal women with adnexal abnormalities on ultrasound.

Methods

This was a prospective cohort study in the ultrasound group of the UK Collaborative Trial of Ovarian Cancer Screening of postmenopausal women with ultrasound‐detected abnormal adnexal (unilocular, multilocular, unilocular solid and multilocular solid, solid) morphology on their first scan. Women were followed up through the national cancer registries and by postal questionnaires. Absolute risks of EOC and borderline, Type I and Type II EOC within 3 years of initial scan were calculated.

Results

Of 48 053 women who underwent ultrasound examination and had complete scan data, 4367 (9.1% (95% CI, 8.8–9.3%)) had abnormal adnexal morphology. Median follow‐up was 7.09 (25th–75th centiles, 6.03–7.92) years. Forty‐seven (32 borderline or Type I, 15 Type II) were diagnosed with EOC. The overall absolute risk of EOC associated with abnormal adnexal morphology was 1.08% (95% CI, 0.79–1.43%); for borderline and Type I it was 0.73% (95% CI, 0.5–1.03%); and for Type II it was 0.34% (95% CI, 0.33–0.79%). In the subgroup (n = 741) with solid elements (unilocular solid, multilocular solid and solid) overall absolute risk was 4.45% (95% CI, 3.08–6.20%), for borderline and Type I it was 3.1% (95% CI, 1.9–4.6%) and for Type II it was 1.3% (95% CI, 0.6–2.4%). 11 982 women had both ovaries visualized and normal annual scans throughout the 3‐year follow‐up period. In this group, no borderline or Type I and eight Type II cancers were diagnosed.

Conclusion

Asymptomatic postmenopausal women with ultrasound‐detected adnexal abnormalities with solid elements have a 1 in 22 risk for EOC. Despite the higher prevalence of Type II EOC, the risk of borderline or Type I cancer in women with ultrasound abnormalities seems to be higher than does the risk of Type II cancer. This has important immediate implications for patients with incidental adnexal findings as well as for any future ultrasound‐based screening. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Changes in cardiopulmonary function induced by nanoparticles
Authors: Mann Erin E. , Thompson Leslie C. , Shannahan Jonathan H. , Wingard Christopher J.
Published: August 2012

Nanoparticles (NP) are highly applicable in a variety of technological and biomedical fields because of their unique physicochemical properties. The increased development and utilization of NP has amplified human exposure and raised concerns regarding their potential to generate toxicity. The biological impacts of NP exposures have been shown to be dependent on aerodynamic size, chemical composition, and the route of exposure (oral, dermal, intravenous, and inhalation), while recent research has demonstrated the cardiovascular (CV) system as an important site of toxicity. Proposed mechanisms responsible for these effects include inflammation, oxidative stress, autonomic dysregulation, and direct interactions of NP with CV cells. Specifically, NP have been shown to impact vascular endothelial cell (EC) integrity, which may disrupt the dynamic endothelial regulation of vascular tone, possibly altering systemic vascular resistance and impairing the appropriate distribution of blood flow throughout the circulation. Cardiac consequences of NP‐induced toxicity include disruption of heart rate and electrical activity via catecholamine release, increased susceptibility to ischemia/reperfusion injury, and modified baroreceptor control of cardiac function. These and other CV outcomes likely contribute to adverse health effects promoting myocardial infarction, hypertension, cardiac arrhythmias, and thrombosis. This review will assess the current knowledge regarding the principle sites of CV toxicity following NP exposure. Furthermore, we will propose mechanisms contributing to altered CV function and hypothesize possible outcomes resulting in decrements in human health. WIREs Nanomed Nanobiotechnol 2012, 4:691–702. doi: 10.1002/wnan.1194

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease

Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Lattice study of infrared behaviour in SU(3) gauge theory with twelve massless flavours
Authors: Lin C.-J. David , Ogawa Kenji , Ohki Hiroshi , Shintani Eigo
Published: August 2012

Abstract

We present details of a lattice study of infrared behaviour in SU(3) gauge theory with twelve massless fermions in the fundamental representation. Using the step-scaling method, we compute the coupling constant in this theory over a large range of scale. The renormalisation scheme in this work is defined by the ratio of Polyakov loop correlators in the directions with different boundary conditions. We closely examine systematic effects, and find that they are dominated by errors arising from the continuum extrapolation. Our investigation suggests that SU(3) gauge theory with twelve flavours contains an infrared fixed point.
CT and MRI lower extremity torsional profile studies: Measurement reproducibility
Authors: Muhamad Abd R. , Freitas Joana M. , Bomar James D. , Dwek Jerry , Hosalkar Harish S.
Published: August 2012

Background

Assessment of lower extremity (LE) torsional profile using computed tomography (CT) imaging is a well-recognized imaging method that supplements the clinical examination. Magnetic resonance imaging (MRI) is another advanced imaging modality that can be used as an alternative, since there are many growing concerns of radiation exposure with traditional CT studies, particularly in the skeletally immature population.

Methods

Sixty-two patients between the ages of 7 and 19 years were included. Thirty-four had CT and 28 had MRI for assessment of LE torsional profile. All patients had clinical evidence of torsional malalignment. CT and MR images were randomized and de-identified. Two observers measured femoral anteversion and tibial torsion based on previously published methodologies. This exercise was repeated 2 weeks later and the data were tabulated and statistical analysis was performed. Radiation exposure for the patients studied by CT was estimated.

Results

The mean age of the patients was 14.4 years (range 9.5–18.9 years) and 13.8 years (range 7.3–18.9 years) for the CT and MRI groups, respectively. Inter-observer reliability for both CT and MRI studies were excellent. The intra-class correlation coefficient (ICC) for femoral anteversion and tibial torsion studied by CT and MRI for both observers at both times were excellent. The radiation exposure for CT examination averaged 0.3–0.5 mSv, compared to none with the MRI method.

Conclusions

MRI provides a reproducible method for assessing the torsional profile in children and adolescents using similar anatomic landmarks for measurements as those used on CT torsional profile. In circumstances where MRI methods are readily available (and affordable), the CT torsional profile can be replaced with MRI methods, in the current era of growing concerns of radiation hazards and increasing awareness about radiation safety.

Level of evidence

Diagnostic Level III.
A reconfigurable component model with semantic type system for dynamic WSN applications
Authors: Thoelen Klaas , Hughes Danny , Matthys Nelson , Fang Lei , Dobson Simon , Qiang Yizhou , Bai Wei , Man Ka Lok , Guan Sheng-Uei , Preuveneers Davy , Michiels Sam , Huygens Christophe , Joosen Wouter
Published: August 2012

Runtime reconfigurable component models provide several attractions with regard to the management of wireless sensor network (WSN) applications operating in dynamic environments and under evolving application requirements. One such attraction is the runtime discovery of suitable components for reuse in changing application compositions. Syntactic interface typing, provided by contemporary component models, however only supports exact interface matching. This causes limited reuse of components and complicates management of WSN applications. We argue that more flexibility is required to efficiently manage the complex, large-scale and dynamic WSN deployments of the future. In this paper, we describe the addition of semantic service descriptions to component interfaces to support compatibility and subtype testing. This allows rich discovery and reuse of third-party functionality and reasoning at the level of equivalent service types. We report on the incorporation of these semantic interface definitions in the Loosely Coupled Component Infrastructure (LooCI). Evaluation thereof shows that the scheme imposes minimal computational and memory overhead, while significantly reducing the complexity and cost of reconfiguration.
A regulatory perspective on whether the system of radiation protection is fit for purpose
Authors: Boyd M.A.
Published: August 2012

The system of radiation protection has its origins in the early efforts to protect people from x rays and radium. It was at the Second International Congress of Radiology in Stockholm in 1928 where the first radiation protection recommendations were adopted. The system of protection steadily evolved as new sources of exposure arose and understanding of radiation-related health risks improved. Safeguarding against these risks has required regulators to set enforceable (i.e. measurable) standards. From erythema dose to tolerance dose, critical organ dose to effective dose equivalent, and now effective dose, the units used to set these limits have evolved along with the science underpinning them. Similarly, the definition of the person or group being protected has changed - from Standard Man to Reference Man to Reference Person, with age and gender differences now considered explicitly. As regulators look towards implementing the changes in the 2007 Recommendations of the International Commission on Radiological Protection (ICRP), there remain questions about how to translate an optimisation-based system of constraints and reference levels into the more familiar regime of enforceable limits. Nevertheless, as the new ICRP Recommendations are refinements of a system that did the job it was designed to do more than adequately, so too will the new system of radiation protection be fit for purpose.