bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic antitumor effects of FGFR2 inhibitor with 5‐fluorouracil on scirrhous gastric carcinoma
Authors: Yashiro Masakazu , Shinto Osamu , Nakamura Kazunori , Tendo Masashige , Matsuoka Tasuku , Matsuzaki Taro , Kaizaki Ryoji , Miwa Atsushi , Hirakawa Kosei
Published: July 2009

Scirrhous gastric carcinoma (SGC) carries the highest mortality because of a frequent metastasis to lymph node (LN). S1, a 5‐fluorouracil (5‐FU) analog, is clinically available for gastric cancer at an advanced stage. Fibroblast growth factor receptor 2 (FGFR2) is required for the proliferation of SGC. The objective of this study is to clarify the benefit of a combination of S1 and kinase inhibitors including FGFR2 inhibitor Ki23057 in gastric cancer. OCUM‐2MLN and KATO‐III were derived from SGC. MKN‐7 and MKN‐74 were derived from non‐SGC. MTT assay was used to examine the growth‐inhibitory activity of 5 small‐synthetic molecules including Ki23057, Sunitinib, Glivec, Lapatinib or SU11274, in cells cultured with 5‐FU. Combination effects of 5‐FU with Ki23057 on proliferation, apoptosis and mRNA expression were examined. S1 and/or Ki23057 were administered to murine models of SGC created by the orthotopic inoculation of OCUM‐2MLN cells. Ki23057 at 100 nM significantly (p < 0.01) inhibited the proliferation and decreased the phosphorylation of FGFR2 in SGC cells, but not in non‐SGC. Ki23057 showed synergistic antitumor effects for SGC cells in combination with 5‐FU using CalcuSyn analysis, but Sunitinib, Glivec, Lapatinib and SU11274 did not. The combination of Ki23057 and 5‐FU decreased DPD expression and increased apoptosis rates and p21 expression level of SGC cells. The combined administration of S1 and Ki23057 significantly (p < 0.05) decreased orthotopic tumors as well as LN metastasis more effectively than S1 alone. These findings suggested that the combined treatment with 5‐FU and Ki23057 produced synergistic antitumor effects and is therapeutically promising for SGC treatment.
Methods and limitations of ‘clumped’ CO2 isotope (Δ47) analysis by gas‐source isotope ratio mass spectrometry
Authors: Huntington K. W. , Eiler J. M. , Affek H. P. , Guo W. , Bonifacie M. , Yeung L. Y. , Thiagarajan N. , Passey B. , Tripati A. , Daëron M. , Came R.
Published: July 2009

The geochemistry of multiply substituted isotopologues (‘clumped‐isotope’ geochemistry) examines the abundances in natural materials of molecules, formula units or moieties that contain more than one rare isotope (e.g. 13C18O16O, 18O18O, 15N2, 13C18O16O22−). Such species form the basis of carbonate clumped‐isotope thermometry and undergo distinctive fractionations during a variety of natural processes, but initial reports have provided few details of their analysis. In this study, we present detailed data and arguments regarding the theoretical and practical limits of precision, methods of standardization, instrument linearity and related issues for clumped‐isotope analysis by dual‐inlet gas‐source isotope ratio mass spectrometry (IRMS). We demonstrate long‐term stability and subtenth per mil precision in 47/44 ratios for counting systems consisting of a Faraday cup registered through a 1012 Ω resistor on three Thermo‐Finnigan 253 IRMS systems. Based on the analyses of heated CO2 gases, which have a stochastic distribution of isotopes among possible isotopologues, we document and correct for (1) isotopic exchange among analyte CO2 molecules and (2) subtle nonlinearity in the relationship between actual and measured 47/44 ratios. External precisions of ∼0.01‰ are routinely achieved for measurements of the mass‐47 anomaly (a measure mostly of the abundance anomaly of 13C‐18O bonds) and follow counting statistics. The present technical limit to precision intrinsic to our methods and instrumentation is ∼5 parts per million (ppm), whereas precisions of measurements of heterogeneous natural materials are more typically ∼10 ppm (both 1 s.e.). These correspond to errors in carbonate clumped‐isotope thermometry of ±1.2 °C and ±2.4 °C, respectively. Copyright © 2009 John Wiley & Sons, Ltd.
Surface‐enhanced Raman scattering studies of carbon nanotubes using Ag‐core Au‐shell nanoparticles
Authors: Kumar G. V. Pavan
Published: July 2009

Surface‐enhanced Raman scattering from carbon nanotube bundles adsorbed with plasmon‐tunable Ag‐core Au‐shell nanoparticles (Ag@Au nps) was carried out for the first time. By utilizing nanoparticles whose plasmon resonance peak (541, 642 nm) closely matches the commonly used Raman excitation sources (532, 632.81 nm), we can observe a large enhancement in the Raman signatures of carbon nanotubes. We obtain greater enhancement in the Raman signal for the above case when compared to nanotubes adsorbed with conventional Ag, Au or other ‘off resonant’ Ag@Au nps. The power‐dependent SERS experiment on single‐walled nanotubes (SWNTs) with resonant Ag@Au nps reveals a linear behavior between the G‐band intensity and the photon flux density, which is in agreement with the vibrational pumping model of SERS. The observed enhancement by resonance matching is pronounced for carbon nanotubes and may lead to insights into understanding nanotube–nanoparticle interaction. Copyright © 2009 John Wiley & Sons, Ltd.
Thrombotic events in neonates receiving recombinant factor VIIa or fresh frozen plasma
Authors: Puetz John , Darling Ginger , Brabec Petr , Blatny Jan , Mathew Prasad
Published: July 2009

Background

Numerous recent reports have described the use of recombinant factor VIIa (rFVIIa) in non‐hemophilia bleeding situations for achievement of hemostasis. However, its use in clinical situations other than hemophilia patients with inhibitors has been complicated by some reports of thrombotic events. rFVIIa has been used successfully to treat coagulopathic and/or bleeding neonates. The prevalence of thrombotic events in these neonates is completely unknown. This study was initiated to determine the risk of thrombotic events associated with rFVIIa use in neonates.

Procedure

All published literature in non‐hemophilic, non‐congenital factor VII deficient neonates receiving rFVIIa was reviewed. In addition, all data submitted to the SeveN Bleep Registry, a web‐based registry of rFVIIa uses in non‐hemophilic children was analyzed. As the baseline risk of thrombotic events in bleeding and/or coagulopathic neonates is not known, we also reviewed the records of 100 consecutive neonates from a single institution who received fresh frozen plasma (FFP) alone to treat their coagulopathy and/or bleeding episode.

Results

A total of 134 neonates received rFVIIa. Of these, 10 (7.5%) had a thrombotic event. The baseline risk of thrombotic events in neonates receiving FFP was 7%.

Conclusions

Overall the prevalence of thrombotic events in bleeding and/or coagulopathic neonates appears to be around 7%, whether or not they receive rFVIIa. Pediatr Blood Cancer 2009;53:1074–1078. © 2009 Wiley‐Liss, Inc.
A general strategy for the bacterial expression of amyloidogenic peptides using BCL‐XL‐1/2 fusions
Authors: Yonemoto Isaac T. , Wood Malcolm R. , Balch William E. , Kelly Jeffery W.
Published: July 2009

Biophysical studies on amyloidogenic and aggregation‐prone peptides often require large quantities of material. However, solid‐phase synthesis, handling, and purification of peptides often present challenges on these scales. Recombinant expression is an attractive alternative because of its low cost, the ability to isotopically label the peptides, and access to sequences exceeding ∼50 residues. However, expression systems that seek to solubilize amyloidogenic peptides suffer from low yields, difficult optimizations, and isolation challenges. We present a general strategy for expressing and isolating amyloidogenic peptides in Escherichia coli by fusion to a polypeptide that drives the expression of attached peptides into bacterial inclusion bodies. This scheme minimizes toxicity during bacterial growth and enables the processing and handling of the peptides in denaturing solutions. Immobilized metal affinity chromatography, reverse phase HPLC, and cyanogen bromide cleavage are used to isolate the peptide, followed by further reverse phase HPLC, which yields milligram quantities of the purified peptide. We demonstrate that driving the peptides into inclusion bodies using fusion to BCL‐XL‐1/2 is a general strategy for their expression and isolation, as exemplified by the production of 11 peptides species.
Flux compactifications of string theory on twisted tori
Authors: Hull C.M. , Reid‐Edwards R.A.
Published: July 2009

Global aspects of Scherk‐Schwarz dimensional reduction are discussed and it is shown that it can usually be viewed as arising from a compactification on the compact space obtained by identifying a (possibly non‐compact) group manifold 𝒢 under a discrete subgroup Γ, followed by a truncation. This allows a generalisation of Scherk‐Schwarz reductions to string theory or M‐theory as compactifications on 𝒢/Γ, but only in those cases in which there is a suitable discrete subgroup of 𝒢. We analyse such compactifications with flux and investigate the gauge symmetry and its spontaneous breaking. We discuss the covariance under O(d,d), where d is the dimension of the group 𝒢, and the relation to reductions with duality twists. The compactified theories promote a subgroup of the O(d,d) that would arise from a toroidal reduction to a gauge symmetry, and we discuss the interplay between the gauge symmetry and the O(d,d,ℤ T‐duality group, suggesting the role that T‐duality should play in such compactifications.
On the modelling of over‐ocean hurricane surface winds and their uncertainty
Authors: Khare S. P. , Bonazzi A. , West N. , Bellone E. , Jewson S.
Published: July 2009

This paper investigates the modelling of over‐ocean hurricane surface wind fields and their associated uncertainty. The wind models tested include parameterized balance models, a two‐dimensional numerical planetary boundary‐layer model and a three‐dimensional (3D) linear analytical boundary‐layer model. Using a set of archived over‐ocean surface wind field reconstructions for validation, a series of cross‐validation experiments has been performed for a range of norms. For norms that quantify predictability of vector fields, a particular configuration of the 3D analytical model was found to be superior to the other models tested. Using residual fields derived from fitting the wind models to the validation data, the issue of how to model the uncertainty (in the form of a covariance) in the speed field has also been examined. Covariance models based on truncated empirical orthogonal function representations were found to be optimal. Copyright © 2009 Royal Meteorological Society
An Influence of the Aromatic Side Chains Conformations in Positions 2 and 3 of Vasopressin Analogs on Interactions with Vasopressin and Oxytocin Receptors
Authors: Ślusarz Rafał , Ślusarz Magdalena J.
Published: July 2009

In this work, the receptor‐bound conformation of nine vasopressin (CYFQNCPRG‐NH2, AVP) analogs substituted in positions 2 or 3 with 2‐aminoindane‐2‐carboxylic acid have been investigated using molecular modeling methods. The synthesis and functional assays of the analogs have been recently described. For comparison, the molecular dynamics of the selected analogs has been conducted. We have observed the relationship between the value of valence angle between the aromatic rings in positions 2 and 3 and the biological activity of the analogs. Both, in restricted space of the receptor cavities and unlimited continuous water environment, the same valence angles prevail, thus seem to be energetically more favorable for the particular peptides. Moreover, the residues responsible for analogs binding to the receptors have been identified.
OpenIGTLink: an open network protocol for image‐guided therapy environment
Authors: Tokuda Junichi , Fischer Gregory S. , Papademetris Xenophon , Yaniv Ziv , Ibanez Luis , Cheng Patrick , Liu Haiying , Blevins Jack , Arata Jumpei , Golby Alexandra J. , Kapur Tina , Pieper Steve , Burdette Everette C. , Fichtinger Gabor , Tempany Clare M. , Hata Nobuhiko
Published: July 2009

Background

With increasing research on system integration for image‐guided therapy (IGT), there has been a strong demand for standardized communication among devices and software to share data such as target positions, images and device status.

Method

We propose a new, open, simple and extensible network communication protocol for IGT, named OpenIGTLink, to transfer transform, image and status messages. We conducted performance tests and use‐case evaluations in five clinical and engineering scenarios.

Results

The protocol was able to transfer position data with submillisecond latency up to 1024 fps and images with latency of <10 ms at 32 fps. The use‐case tests demonstrated that the protocol is feasible for integrating devices and software.

Conclusion

The protocol proved capable of handling data required in the IGT setting with sufficient time resolution and latency. The protocol not only improves the interoperability of devices and software but also promotes transitions of research prototypes to clinical applications. Copyright © 2009 John Wiley & Sons, Ltd.
Bactericidal performance of photocatalytic titanium dioxide particle mixture under ultraviolet and fluorescent light: an in vitro study
Authors: Koseki Hironobu , Shiraishi Koutaro , Tsurumoto Toshiyuki , Asahara Tomohiko , Baba Koumei , Taoda Hiroshi , Terasaki Nao , Shindo Hiroyuki
Published: July 2009

When ultraviolet (UV) light comes into contact with titanium dioxide (TiO2), a variety of free radicals are released to provide a potent oxidizing power. Few reports are available, however, evaluating the bactericidal effects of TiO2 particle under UV light and fluorescent light (FL) in the same line of research for clinical applications. In the present study, we set out to evaluate the in vitro photocatalytic bactericidal effects on Staphylococcus aureus, which is one of the most common pathogens of infectious disease, in an aqueous system of TiO2 particles irradiated by UV and FL. A TiO2 particle mixture containing 0.019 mg/ml of TiO2 was prepared. A bacterial solution was added dropwise to the mixture, and the resulting product was irradiated by UV or FL light. The colony‐forming units were counted and the bacterial survival rate was calculated. Control samples maintained a relatively high bacterial survival rate. In the TiO2 mixture group, however, the bacterial survival rate decreased steadily, reaching 9.4% after 60 min of exposure to UV light and 10.9% after 60 min of FL irradiation. Distributing the TiO2 particles in a water mixture produces highly efficient light absorption and enables greater and more frequent adhesion with bacteria, allowing a high degree of photocatalytic antibacterial action. Although the quantity was inferior to UV, our TiO2 particles were able to show effective bactericidal activity even under FL. The TiO2 particle mixture is expected to prove effective in preventing postoperative infection. Copyright © 2009 John Wiley & Sons, Ltd.
Formaldehyde‐assisted isolation of regulatory elements
Authors: Nagy Peter L. , Price David H.
Published: July 2009

Formaldehyde‐Assisted Isolation of Regulatory Elements (FAIRE) is based on locus‐specific variations in the ability of protein components of chromatin to trap genomic DNA following formaldehyde treatment. This variation is mostly due to uneven nucleosome distribution since histones are the most abundant and highly crosslinkable components of chromatin. The method can identify and enrich for physically accessible DNA segments of the eukaryotic genome corresponding to known regulatory regions and regions that might have thus far unidentified structural role in the nuclear organization of chromatin. The enrichment patterns are cell type specific and thus might provide information about how transcriptional systems are organized and regulated in various tissues and how they might be disrupted in disease states. Analysis of a 268 kb region of chromosome 19 in human fibroblasts shown here demonstrates that while most DNA fragments detected by FAIRE correspond to sites of DNaseI hypersensitivity in active regions of chromatin, some are found in otherwise repressed chromatin domains and at other sites that are not found with other methods used to probe chromatin structure. Further exploration of FAIRE is warrented due to the simplicity of the protocol and recent advancements in massively parallel sequencing. Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Laboratory Methods and Technologies > Genetic/Genomic Methods
The mammalian phenotype ontology: enabling robust annotation and comparative analysis
Authors: Smith Cynthia L. , Eppig Janan T.
Published: July 2009

The mouse has long been an important model for the study of human genetic disease. Through the application of genetic engineering and mutagenesis techniques, the number of unique mutant mouse models and the amount of phenotypic data describing them are growing exponentially. Describing phenotypes of mutant mice in a computationally useful manner that will facilitate data mining is a major challenge for bioinformatics. Here we describe a tool, the Mammalian Phenotype (MP) ontology, for classifying and organizing phenotypic information related to the mouse and other mammalian species. The MP ontology has been applied to mouse phenotype descriptions in the Mouse Genome Informatics (MGI) Database (http://www.informatics.jax.org/), the Rat Genome Database (RGD, http://rgd.mcw.edu), the Online Mendelian Inheritance in Animals (OMIA, http://omia.angis.org.au/), and elsewhere. Use of this ontology allows comparisons of data from diverse sources, facilitates comparisons across mammalian species, assists in identifying appropriate experimental disease models, and aids in the discovery of candidate disease genes and molecular signaling pathways. Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Analytical and Computational Methods > Computational Methods
Comparison of prenatal care coverage in early adolescents, late adolescents, and adult pregnant women in the Peruvian Amazon
Authors: Ryan Julia A. , Casapía Martín , Aguilar Eder , Silva Hermánn , Joseph Serene A. , Gyorkos Theresa W.
Published: July 2009

Objective

To compare prenatal care coverage between adolescent (early and late) and adult pregnant women in Iquitos, Peru.

Methods

A random sample of 4467 birth records was collected. Multivariate analyses were performed to compare prenatal care coverage in all adolescent (10–14 years, 15–19 years) and adult (≥ 20 years) age groups and then for primiparous women only.

Results

The mean number of visits was 5.0 for adolescents aged 10–14 years, 6.1 for adolescents aged 15–19 years, and 6.2 for women aged 20 years or older. For primiparous women, the means were 5.1, 6.2, and 6.8, for the respective age groups. Both the proportion attending and the number of prenatal visits were significantly lower in primiparous adolescents aged 10–14 years than in primiparous women aged 20 years or older (aOR 0.25; 95% CI, 0.10–0.62 and aRR 0.83; 95% CI, 0.74–0.94, respectively).

Conclusion

All women attended prenatal care more frequently than the WHO's recommended 4 visits; however, early adolescents attended significantly less often than late adolescents or adult women. Further study of this inequality is warranted to adequately inform local health services.
Short‐period variability in the galactic cosmic ray intensity: High statistical resolution observations and interpretation around the time of a Forbush decrease in August 2006
Authors: Mulligan T. , Blake J. B. , Shaul D. , Quenby J. J. , Leske R. A. , Mewaldt R. A. , Galametz M.
Published: July 2009

On 20 August 2006 a Forbush decrease observed at Polar in the Earth's magnetosphere was also seen at the INTEGRAL spacecraft outside the magnetosphere during a very active time in the solar wind. High‐resolution energetic particle data from ACE SIS, the Polar high‐sensitivity telescope, and INTEGRAL's Ge detector saturation rate, which measures the galactic cosmic ray (GCR) background with a threshold of ∼200 MeV, show similar, short‐period GCR variations in and around the Forbush decrease. Focusing upon the GCR intensity within a 3‐day interval from 19 August 2006 to 21 August 2006 reveals many intensity variations in the GCR on a variety of time scales and amplitudes. These intensity variations are greater than the 3σ error in all the data sets used. The fine structures in the GCR intensities along with the Forbush decrease are propagated outward from ACE to the Earth with very little change. The solar wind speed stays relatively constant during these periods, indicating that parcels of solar wind are transporting the GCR population outward in the heliosphere. This solar wind convection of GCR fine structure is observed for both increases and decreases in GCR intensity, and the fine structure increases and decreases are bracketed by solar wind magnetic field discontinuities associated with interplanetary coronal mass ejection (ICME) magnetosheath regions, clearly seen as discontinuous rotations of the field components at ACE and at Wind. Interestingly, the electron heat flux shows different flux tube connectivity also associated with the different regions of the ICME and magnetosheath. Gosling et al. (2004) first discussed the idea that solar energetic particle intensities commonly undergo dispersionless modulation in direct association with discontinuous changes in the solar wind electron strahl. The observations show that the intensity levels in the GCR flux may undergo a similar partitioning, possibly because of the different magnetic field regions having differing magnetic topologies.
Ocean tidal cooling effect on summer sea fog over the Okhotsk Sea
Authors: Tokinaga Hiroki , Xie Shang‐Ping
Published: July 2009

Ocean tide is a periodic phenomenon of the rise and fall of the sea level that depends on the bathymetry and positions of the moon and sun relative to the earth. In the Okhotsk Sea, the ocean tide causes strong vertical mixing in the upper ocean, generating rich structures in summer SST with extraordinarily cold patches on Kashevarov Bank, along the Kuril Islands, northeast of the Terpeniya Peninsula, and inside Shelikhov Bay. The present study analyzes and synthesizes a suite of ship‐board and satellite observations, and numerical simulations to investigate the ocean tidal cooling effect on summer sea fog over the Okhotsk Sea. Over the tide‐induced cold patches, atmospheric stability increases, and surface wind weakens markedly possibly through suppressed atmospheric vertical mixing. Our analysis of ship‐board observations reveals frequent sea‐fog occurrence over the cold patches with a maximum exceeding 70% along the Kuril Islands in July–August. Numerical simulations with the Weather Research and Forecasting (WRF) model support that the cold patches cool air temperature, decelerate surface wind, and form a strong surface inversion layer up to 0.5 km high, creating favorable conditions for sea‐fog occurrence. The WRF simulation without the tidal cooling effect reduces sea‐fog occurrence by more than 20% over cold patches, illustrating the importance of SST products for climate models.
Solar trends and global warming
Authors: Benestad R. E. , Schmidt G. A.
Published: July 2009

We use a suite of global climate model simulations for the 20th century to assess the contribution of solar forcing to the past trends in the global mean temperature. In particular, we examine how robust different published methodologies are at detecting and attributing solar‐related climate change in the presence of intrinsic climate variability and multiple forcings. We demonstrate that naive application of linear analytical methods such as regression gives nonrobust results. We also demonstrate that the methodologies used by Scafetta and West (2005, 2006a, 2006b, 2007, 2008) are not robust to these same factors and that their error bars are significantly larger than reported. Our analysis shows that the most likely contribution from solar forcing a global warming is 7 ± 1% for the 20th century and is negligible for warming since 1980.
European cooperation in polar research
Authors: Showstack Randy
Published: July 2009

A new European Polar Framework agreement aims to increase research cooperation, streamline links between many European national research programs in the Arctic and Antarctic, and possibly create international research teams similar to the Integrated Ocean Drilling Program. The new framework includes commitments to collaborate on new multinational research initiatives and to have national polar programs converge where appropriate.
Seismic anisotropy of the Pacific slab and mantle wedge beneath the Japanese islands
Authors: Tono Yoko , Fukao Yoshio , Kunugi Takashi , Tsuboi Seiji
Published: July 2009

The mantle beneath the Japanese islands is complex because of subduction of the Pacific and Philippine Sea plates and the deformation associated with it. Detection of seismic anisotropy should be useful for understanding the processes occurring in such mantle. Here we resolve seismic anisotropy of the mantle wedge from that of the underlying subducted Pacific slab using a large number of measurements of shear wave splitting for a family of core‐reflected shear phases: ScS, sScS, ScS2, and sScS2. The anisotropy of the mantle wedge changes sharply across the volcanic front. On the Pacific side of the volcanic front a vertically propagating shear wave is polarized with the fast direction approximately parallel to the trench, whereas on the back‐arc side it is polarized with the fast direction approximately parallel to the plate convergence direction. The Pacific slab is uniformly anisotropic with the NNW fast direction, consistent with the paleospreading direction of the northwestern Pacific seafloor. The preferential alignment of anisotropic crystals frozen in the plate at the time of its formation appears to be preserved down to depths beyond 400 km within the slab.
Political Interference in the Philippine Civil Service
Authors: Hodder Rupert
Published: July 2009

When set against a more international and generic literature, the relative thinness of the debate on the Philippine civil service, and its comparatively limited engagement with that literature, is very marked, as is the need for more critical attention to be directed at the problems facing the service. In particular, the certainty and ease with which the service is presented as a mere appendage of a distorted polity, and its informal qualities are viewed rather negatively, seem to deserve closer scrutiny. But the relative paucity of substantial empirical material renders the development and application of models, and any reinterpretations which they might yield, problematic and less open to contradiction. Therefore, in this paper I focus on the accounts of civil servants and politicians as a means of enriching the empirical base. In doing so I draw out the dimensionality of political interference in the Philippine civil service; I challenge perspectives on bureaucracy to accommodate these dimensions within more unified theory; and I point the way to an approach which might be capable of accommodating those dimensions.
Patterns of Innovation in EU-25 Regions: A Typology and Policy Recommendations
Authors: Navarro Mikel , Gibaja Juan José , Bilbao-Osorio Beñat , Aguado Ricardo
Published: July 2009

With this paper we depict a typology of regions, capturing the diversity of regional innovation systems (RISs) across the EU-25. Following the RIS literature, we select twenty-one variables related to the ability of a region to generate and absorb knowledge, and its capacity to transform research and development into innovation and economic growth. On the basis of the results of principal components and cluster analyses, we identify seven types of RIS where the 186 regions group together according to their sectoral specialisation, technological and economic capacity, and performance. By allowing us to identify similar and more advanced regions, the paper facilitates comparisons and benchmarking between similar regions, thus enabling more accurate policy learning. For each group a number of policy recommendations are suggested, contingent on their local specific characteristics. In short, the contribution of this paper is twofold. Firstly, it provides the first RIS typology for the EU-25 regions completed using a large number of variables. Secondly, the conclusions obtained from the analysis may be used to lead policy makers' actions in the field of regional innovation policy in the EU.
Minimally Invasive Mitral Valve Replacement Using the Valve-in-valve Technique
Authors: Santana Orlando , Tarrazzi Francisco A. , Lamelas Joseph
Published: July 2009

A 90-year-old woman with two previous mitral valve replacements, presented with pulmonary edema due to mitral regurgitation from degeneration of her bioprosthetic mitral valve. A minimally invasive approach was used to replace the bioprosthetic mitral valve. During surgery, the bioprosthetic valve was noted to be too adherent to the endocardium of the left atrium, making removal of the prosthesis not only difficult, but also potentially harmful. The new bioprosthetic valve was instead placed using a valve-in-valve approach.
Thymopericardial Augmented Encasement for Coronary Artery Bypass Graft Surgery
Authors: Ohtsuka Toshiya , Ninomiya Mikio , Nonaka Takahiro
Published: July 2009

Objective

A pedicled prepericardial fat flap was created to augment the pericardial cavity and applied for patients undergoing coronary artery bypass grafting. The efficacy and durability of this method were investigated.

Methods

Between July 2005 and November 2008, the present technique was applied for consecutive 245 patients (165 men and 80 women, aged 67 ± 8.3 years) undergoing isolated coronary artery bypass grafting in which 240 (98.0%) were off-pump cases. The left and/or right internal thoracic artery and the gastroepiploic artery were used in 244 and 160 patients, respectively, and the saphenous vein and the radial artery were used in 51 and 10 patients, respectively. Ninety-seven (40.0%) patients had been diabetic, 18 (7.3%) had had chronic renal failure, and three were redo cases. The prepericardial soft tissue, involving the pedicled thymic gland, was dissected en bloc and sewn with pericardiotomies to wrap the heart and the grafts. Angiography or three-dimensional computed tomography was used to assess the intrapericardial pathways of each graft and a long-term durability of the fat pad.

Results

Early angiography or three-dimensional computed tomography proved that the graft pathways were unaffected by the encasements. Resternotomies in two patients and sternal treatments for infectious dehiscence in two patients were safely achievable. Five-year postoperative computed tomography showed the intact fat pad in the retrosternal space.

Conclusions

The present technique can encase the heart not the least jeopardizing each pathway of the grafts, and the durable fat pad functions protectively when the sternotomy is either reopened or infected.
Evidence for mirror systems in emotions
Authors: Bastiaansen J. A. C. J. , Thioux M. , Keysers C.
Published: July 2009

Why do we feel tears well up when we see a loved one cry? Why do we wince when we see other people hurt themselves? This review addresses these questions from the perspective of embodied simulation: observing the actions and tactile sensations of others activates premotor, posterior parietal and somatosensory regions in the brain of the observer which are also active when performing similar movements and feeling similar sensations. We will show that seeing the emotions of others also recruits regions involved in experiencing similar emotions, although there does not seem to be a reliable mapping of particular emotions onto particular brain regions. Instead, emotion simulation seems to involve a mosaic of affective, motor and somatosensory components. The relative contributions of these components to a particular emotion and their interrelationship are largely unknown, although recent experimental evidence suggests that motor simulation may be a trigger for the simulation of associated feeling states. This mosaic of simulations may be necessary for generating the compelling insights we have into the feelings of others. Through their integration with, and modulation by, higher cognitive functions, they could be at the core of important social functions, including empathy, mind reading and social learning.
The evolution of imitation: what do the capacities of non-human animals tell us about the mechanisms of imitation?
Authors: Huber Ludwig , Range Friederike , Voelkl Bernhard , Szucsich Andrea , Virányi Zsófia , Miklosi Adam
Published: July 2009

In this paper, we review reports and present new empirical data from studies with marmosets and dogs that address the correspondence problem of imitation research. We focus on the question of how it is possible to transform visual information into matching motor acts. Here, the important issue is not the learning of a complex skill, but determining the copying fidelity of animals at different levels of behavioural organization. As a theoretical framework, we suggest a classification in terms of movement, action and result, which shows a positive relationship between the organizational level of imitation and matching degree. While the monkey studies have provided evidence of very precise copying of movements and, to a lesser degree, of behaviours, the dog studies have provided evidence of action copying and the reproduction of results. In a Do-as-I-do study, a dog attempted to reproduce the results of demonstrated object manipulations at the expense of movement details. Transitive actions were more easily replicated than intransitive ones, and familiarity of actions had a major influence. The discussion of these findings addresses the question of the neuronal mechanisms underlying imitation and whether a single mechanism is sufficient to explain the different levels of copying fidelity.
From monkey mirror neurons to primate behaviours: possible ‘direct’ and ‘indirect’ pathways
Authors: Ferrari P. F. , Bonini L. , Fogassi L.
Published: July 2009

The discovery of mirror neurons (MNs), deemed to be at the basis of action understanding, could constitute the potential solution to the ‘correspondence problem’ between one's own and others' action that is crucial for of imitative behaviours. However, it is still to be clarified whether, and how, several imitative phenomena, differing in terms of complexity and cognitive effort, could be explained within a unified framework based on MNs. Here we propose that MNs could differently contribute to distinct imitative behaviours by means of two anatomo-functional pathways, subjected to changes during development. A ‘direct mirror pathway’, directly influencing the descending motor output, would be responsible for neonatal and automatic imitation. This proposal is corroborated by some new behavioural evidences provided here. During development, the increased control of voluntary movements and the capacity to efficiently suppress automatic motor activation during action observation assign to the core MNs regions essentially perceptuo-cognitive functions. These functions would be exploited by an ‘indirect mirror pathway’ from the core regions of the MN system to prefrontal cortex. This latter would play a key role in parsing, storing and organizing motor representations, allowing the emergence of more efficient and complex imitative behaviours such as response facilitation and true imitation.
Neuropsychological perspectives on the mechanisms of imitation
Authors: Rumiati Raffaella I. , Carmo Joana C. , Corradi-Dell'Acqua Corrado
Published: July 2009

Cognitive neuroscientists have contributed to the understanding of imitation according to their expertise. Neuropsychologists first established over a century ago that lesions to the left hemisphere of right-handed individuals lead to a dramatic reduction of their ability to imitate gestures. In contrast, after frontal lobe damage, patients may experience severe difficulties in inhibiting their imitative tendency. These findings suggested that our tendency to imitate is mostly sustained by the left hemisphere and that we normally manage successfully to keep it under control. Neuropsychologists went on investigating other aspects of gesture imitation. These include the existence of putative mechanisms involved in imitating different types of gestures (e.g. meaningful and meaningless or transitive and intransitive), the strategic control over these mechanisms and whether there are differences in imitation depending on the action goal or the body part used. Based on neuropsychological findings, some cognitive models of gesture imitation have been forwarded, the most influential of which will be reviewed here. In particular, reference will be made to the dual route model and to accounts that associate the imitative deficit to putative degraded body representations.
The natural history and epidemiology of insect venom allergy: clinical implications
Authors: Bilò M. B. , Bonifazi F.
Published: July 2009

Hymenoptera stings can cause severe systemic allergic reactions and occasionally fatal anaphylaxis, which contribute significantly to morbidity and deterioration in health‐related quality of life. The latest epidemiological data confirm the importance of insect sting allergy as a cause of anaphylaxis. Despite the high prevalence of asymptomatic sensitization, the prevalence of sting‐induced systemic reactions (SRs) is low. However, to date, no parameter has been identified that can predict who will have a future reaction and whether it will be a large local reaction or anaphylactic. The combination of several concomitant factors, which include environmental, genetics and individual factors, may account for the occurrence of a system reaction in individual patients. Several not completely known factors may be associated with the severity of systemic re‐stings. As about 50% of subjects with fatal sting reactions had no documented history of a previous SR, greater insight of the natural history and risk factors is required, especially in asymptomatic sensitized subjects. For patients with SRs, prevention of future severe allergic reactions starts with referral to an emergency department, correct administration of epinephrine by medical staff, referral to an allergist and coaching for the self‐administration of epinephrine. However, most insect sting victims failed to seek medical advice and hospital attendance does not always correlate with the severity of the allergic reaction. Moreover, only about one‐third of patients received a prescription for self‐injectable epinephrine and were officially referred to an allergist after being discharged, causing the non‐ or delayed prescription of specific immunotherapy. Significantly, this means that at least half of the sting fatalities in patients with a positive history could have been avoided through the timely administration of specific immunotherapy. These findings indicate the urgent need to educate the general population and doctors on the management of venom‐allergic patients.
Increased immunoglobulin A in alcoholic liver cirrhosis: exploring the response of B cells to Toll-like receptor 9 activation
Authors: Massonnet B , Delwail A , Ayrault J-M , Chagneau-Derrode C , Lecron J-C , Silvain C
Published: July 2009

Alcoholic liver cirrhosis (ALC) is characterized by increased circulating levels of immunoglobulins (Igs). ALC patients undergo bacterial translocation evidenced by the presence of bacterial DNA in peripheral blood. Bacterial pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS), peptidoglycan (PGN) and unmethylated cytosine-guanine dinucleotide (CpG) DNA are ligands of Toll-like receptor (TLR)-4, TLR-2 and TLR-9, respectively. Although TLR activation results generally in the secretion of proinflammatory cytokines, activation of B cells through TLR-7 or TLR-9 is involved in their maturation and Ig synthesis. The aim of the present study was to assess Ig synthesis by ALC B cells under PAMP activation in order to evaluate the possible involvement of TLR pathways in the increased Ig levels, and especially the hyper-IgA observed in ALC. CpG, in combination with interleukin (IL)-10 or IL-21, enhanced IgA, IgG and IgM synthesis by healthy donor (HD) PBMCs, but had only a weak effect on ALC PBMCs. Relative CpG-induced IgA production by purified ALC B cells was less important when compared to HD B cells, in accordance with the lower TLR-9 expression on ALC B cells compared to HD B cells, but the absolute IgA production by CpG-activated B cells was enhanced significantly for ALC when compared to HD, in agreement with their intrinsic ability to produce spontaneously more IgA than HD. LPS and PGN had no direct activity on B cells, whereas R848 also enhanced Ig synthesis, as reported recently. Taken together, these results suggest that TLR priming of B cells could account for the hyperimmunoglobulinaemia observed in ALC patients.
Replisome progression complex links DNA replication to sister chromatid cohesion in Xenopus egg extracts
Authors: Tanaka Hiroshi , Kubota Yumiko , Tsujimura Tsuyoshi , Kumano Maya , Masai Hisao , Takisawa Haruhiko
Published: July 2009

Cohesin‐mediated sister chromatid cohesion is established during the S‐phase, and recent studies demonstrate that a cohesin protein ring concatenates sister DNA molecules. However, little is known about how DNA replication is linked to the establishment of sister chromatid cohesion. Here, we used Xenopus egg extracts to show that AND‐1 and Tim1–Tipin, homologues of Saccharomyces cerevisiae Ctf4 and Tof1–Csm3, respectively, are associated with the replisome and are required for proper establishment of the cohesion observed in the M‐phase extracts. Immunodepletion of both AND‐1 and Tim1–Tipin from the extracts leads to aberrant sister chromatid cohesion, which is similarly induced by the depletion of cohesin. These results demonstrate that AND‐1 and Tim1–Tipin are key factors linking DNA replication and establishment of sister chromatid cohesion. On the basis of the physical interactions between AND‐1 and DNA polymerases, we discuss a model to describe how replisome progression complex establishes sister chromatid cohesion.
Reproductive outcome of men with azoospermia due to cryptorchidism using assisted techniques
Authors: Haimov‐Kochman R. , Prus D. , Farchat M. , Bdolah Y. , Hurwitz A.
Published: July 2009

The aetiology of cryptorchidism is still undiscernible in the majority of cases. It has long been argued that cryptorchidism reflects a primary testicular maldevelopment, where the contralateral scrotal testis also suffers from aspermatogenesis and low spermatogonia count. The aim of the study was to determine the reproductive outcome of ex‐cryptorchid men with azoospermia post‐orchidopexy after testicular sperm extraction (TESE) and intracytoplasmatic sperm injection (ICSI). In a retrospective analysis, we compared the sperm retrieval, fertilization, pregnancy and live birth rates after ICSI of consecutive ex‐cryptorchid azoospermic patients (n = 15) undergoing TESE between Jan 2000 and Dec 2007 vs. non‐cryptorchid azoospermic men (n = 142). Sperm retrieval rate of ex‐cryptorchid men by TESE (66%) was comparable with non‐cryptorchid men (47%) (p = 0.15) despite significantly higher FSH levels (30.7 ± 25.4 vs. 17.9 ± 14.8 respectively) (p = 0.018) and a more prevalent histopathology diagnosis of aspermatogenesis (75% vs. 40%, p = 0.046). Fertilization (43.3%), pregnancy (30%) and live birth (20%) rates after TESE–IVF–ICSI in the ex‐cryptorchid group were not different from the non‐cryptorchid group (48.7, 43 and 29%, p = 0.26, p = 0.21, p = 0.29 respectively). We conclude that the reproductive outcome of ex‐cryptorchid men with azoospermia post‐orchidopexy employing TESE–IVF–ICSI is comparable with non‐cryptorchid azoospermic men.
Calpain‐mediated breakdown of cytoskeletal proteins contributes to cholecystokinin‐induced damage of rat pancreatic acini
Authors: Weber Heike , Hühns Saskia , Lüthen Frank , Jonas Ludwig
Published: July 2009

The cytosolic cysteine protease calpain is implicated in a multitude of cellular functions but also plays a role in cell damage. Our previous results suggest that an activation of calpain accompanied by a decrease in its endogenous inhibitor calpastatin may contribute to pancreatic damage during cerulein‐induced acute pancreatitis. The present study aimed at the time course of secretagogue‐induced calpain activation and cellular substrates of the protease. Isolated rat pancreatic acini were incubated with a supramaximal concentration of cholecystokinin (0.1 μM CCK) for 30 min in the presence or absence of the calpain inhibitor Z‐Val‐Phe methyl ester (100 μM ZVP). The activation of calpain and the expression of calpastatin and the actin cytoskeleton‐associated proteins αII‐spectrin, E‐cadherin and vinculin were studied by immunoblotting. The cell damage was assessed by lactate dehydrogenase release and ultrastructural analysis including fluorescence‐labelled actin filaments. Immediately after administration, CCK led to activation of both calpain isoforms, μ‐ and m‐calpain. The protease activation was accompanied by a decrease in the E‐cadherin level and formation of calpain‐specific breakdown products of αII‐spectrin. A calpain‐specific cleavage product of vinculin appeared concomitantly with changes in the actin filament organization. No effect of CCK on calpastatin was found. Inhibition of calpain by ZVP reduced CCK‐induced damage of the actin‐associated proteins and the cellular ultrastructure including the actin cytoskeleton. The results suggest that CCK‐induced acinar cell damage requires activation of calpain and that the actin cytoskeleton belongs to the cellular targets of the protease.
A study of Turkish critical care nurses’ perspectives regarding family‐witnessed resuscitation
Authors: Güneş Ülkü Yapucu , Zaybak Ayten
Published: July 2009

Aim.  This paper reports a study to determine the experiences and attitudes of Turkish critical care nurses concerning family presence during cardiopulmonary resuscitation.

Background.  The debate surrounding family‐member presence in resuscitation areas has been evolving since the 1980s. The practice of performing resuscitation of adults in the presence of family members is controversial and has stimulated discussion and debate worldwide.

Design.  A descriptive survey.

Method.  The survey was carried out in 2007 with 135 critical care nurses from two university hospitals in İzmir. A structured questionnaire was used, which incorporated a series of attitude statements that were rated using a three‐point Likert scale. The attitudes of the nurses were explored in three areas: decision making, processes and outcomes of resuscitation.

Results.  Of the nurses, only 22·2% experienced a situation where family members were present during cardiopulmonary resuscitation. Most of these nurses (n = 20) had one or more negative experiences. The majority disagreed that family members should always be offered the opportunity to be with the patient during cardiopulmonary resuscitation. The most common concerns for not favouring family‐witnessed resuscitation were reported as performance anxiety, fear of causing psychological trauma to family members and increased risk of litigation.

Conclusions.  Many Turkish critical care nurses have no knowledge of family‐witnessed resuscitation and do not support the practice. We suggest that Turkish critical care nurses should be informed by the international literature on the concept of family‐witnessed resuscitation and the culturally appropriate policies concerning this subject should be changed in Turkish hospitals.

Relevance to clinical practice.  Most critical care nurses in Turkey are not supportive of family‐witnessed resuscitation. All critical care nurses should be informed by the international literature on the concept of family‐witnessed resuscitation.