Understanding European cross-border cooperation: a framework for analysis

European integration has had a dual impact on border regions. On the one hand, borders were physically dismantled across most of the EU’s internal territory. On the other hand, they have become a fertile ground for territorial co-operation and institutional innovation. The degree of cross-border co-operation and organization achieved varies considerably from one region to another depending on a combination of various facilitating factors for effective cross-border co-operation, more specifically, economic, political leadership, cultural/identity and state formation, and geographical factors. This article offers a conceptual framework to understand the growth and diversity of cross-border regionalism within the EU context by focusing on the levels of and drives for co-operation

Density and expansion effects on pion spectra in relativistic heavy-ion collisions

We compute the pion inclusive momentum distribution in heavy-ion collisions at AGS energies, assuming thermal equilibrium and accounting for density and expansion effects at the time of decoupling. We compare to data on mid rapidity charged pions produced in central Au + Au collisions and find a very good agreement. The shape of the distribution at low $m_t-m$ is explained in part as an effect arising from the high mean pion density achieved in these reactions. The difference between the positive and negative pion distributions in the same region is attributed in part to the different average yields of each kind of charged pions.Comment: Minor changes, typo in Fig. 2b corrected, version to appear in Phys. Rev.

X-ray diffraction measurements of plasticity in shock-compressed vanadium in the region of 10-70 GPa

We report experiments in which powder-diffraction data were recorded from polycrystalline vanadium foils, shock-compressed to pressures in the range of 10-70 GPa. Anisotropic strain in the compressed material is inferred from the asymmetry of Debye-Scherrer diffraction images and used to infer residual strain and yield strength (residual von Mises stress) of the vanadium sample material. We find residual anisotropic strain corresponding to yield strength in the range of 1.2 GPa-1.8 GPa for shock pressures below 30 GPa, but significantly less anisotropy of strain in the range of shock pressures above this. This is in contrast to our simulations of the experimental data using a multi-scale crystal plasticity strength model, where a significant yield strength persists up to the highest pressures we access in the experiment. Possible mechanisms that could contribute to the dynamic response of vanadium that we observe for shock pressures ≥30 GPa are discussed

SUSY Quivers, Intersecting Branes and the Modest Hierarchy Problem

We present a class of chiral non-supersymmetric D=4 field theories in which quadratic divergences appear only at two loops. They may be depicted as ``SUSY quivers'' in which the nodes represent a gauge group with extended e.g., N=4 SUSY whereas links represent bifundamental matter fields which transform as chiral multiplets with respect to different N=1 subgroups. One can obtain this type of field theories from simple D6-brane configurations on Type IIA string theory compactified on a six-torus. We discuss the conditions under which this kind of structure is obtained from D6-brane intersections. We also discuss some aspects of the effective low-energy field theory. In particular we compute gauge couplings and Fayet-Iliopoulos terms from the Born-Infeld action and show how they match the field theory results. This class of theories may be of phenomenological interest in order to understand the modest hierarchy problem i.e., the stability of the hierarchy between the weak scale and a fundamental scale of order 10-100 TeV which appears e.g. in low string scale models. Specific D-brane models with the spectrum of the SUSY Standard Model and three generations are presented.Comment: 36 pages, using JHEP3.cls, 8 figures. References update

A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome

ETV6/TEL is the first transcription factor identified that is specifically required for hematopoiesis within the bone marrow. This gene has been found to have multiple fusion partners of which 16 have been cloned. Fluorescence in situ hybridization (FISH) analysis in a patient with myelodysplastic syndrome (MDS) revealed a t(1;12)(p36;p13) involving ETV6, with the breakpoint in this gene between exon 2 and exon 3. We report here the cloning of a novel ETV6 partner located on 1p36.1, involved in the t(1;12). 3' RACE-PCR from RNA identified a novel sequence fused to exon 2 of ETV6. Database searches localized this sequence in a bacterial artificial chromosome (BAC) mapped to 1p36 by fingerprint analysis. This result was confirmed by FISH using this BAC as probe. 5' and 3' RACE experiments with primers from this novel sequence were carried out on RNA from a healthy donor and identified a novel full-length mRNA, which we named MDS2 (myelodysplastic syndrome 2). RT-PCR experiments were performed on a panel of human cDNAs to analyze the expression pattern of this gene and they revealed four splicing variants. RT-PCR analysis showed that ETV6-MDS2, but not the reciprocal MDS2-ETV6 fusion transcript, was expressed in the bone marrow of the patient. The product of the ETV6-MDS2 fusion transcript predicts a short ETV6 protein containing the first 54 amino acids of ETV6 plus four novel amino acids, lacking both the PTN and the DNA-binding domains. Possible mechanisms to account for the development of MDS in this patient are discussed

Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: implications for pre-mRNA processing

Pre-mRNA processing is an important mechanism for globally modifying cellular protein composition during tumorigenesis. To understand this process during lung cancer, expression of two key pre-mRNA alternative splicing factors was compared in a mouse model of early lung carcinogenesis and during regenerative growth following reversible lung injury. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and alternative splicing factor/splicing factor 2 (ASF/SF2) act antagonistically to modulate splice site selection. Both hnRNP A1 and ASF/SF2 contents rose in adenomas and during injury-induced hyperplasia compared to control lungs, as measured by immunoblotting. While both proteins increased similarly during compensatory hyperplasia, hnRNP A1 increased to a much greater extent than ASF/SF2 in tumors, resulting in a 6-fold increase of the hnRNP A1 to ASF/SF2 ratio. Immunohistochemical analysis showed that hnRNP A1 localized exclusively within tumor nuclei, while ASF/SF2 appeared in cytoplasm and/or nuclei, depending on the growth pattern of the tumor cells. We also demonstrated cancer-associated changes in the pre-mRNA alternative splicing of CD44, a membrane glycoprotein involved in cell-cell and cell-extracellular matrix interactions. hnRNP A1 and ASF/SF2 expression is thus differentially altered in neoplastic lung cells by mechanisms that do not strictly arise from increased cell division. These changes are influenced by tumor histology and may be associated with production of variant CD44 mRNA isoforms

A gene-alteration profile of human lung cancer cell lines

ABSTRACT: Aberrant proteins encoded from genes altered in tumors drive cancer development and may also be therapeutic targets. Here we derived a comprehensive gene-alteration profile of lung cancer cell lines. We tested 17 genes in a panel of 88 lung cancer cell lines and found the rates of alteration to be higher than previously thought. Nearly all cells feature inactivation at TP53 and CDKN2A or RB1, whereas BRAF, MET, ERBB2, and NRAS alterations were infrequent. A preferential accumulation of alterations among histopathological types and a mutually exclusive occurrence of alterations of CDKN2A and RB1 as well as of KRAS, epidermal growth factor receptor (EGFR), NRAS, and ERBB2 were seen. Moreover, in nonsmall- cell lung cancer (NSCLC), concomitant activation of signal transduction pathways known to converge in mammalian target of rapamycin (mTOR) was common. Cells with single activation of ERBB2, PTEN, or MET signaling showed greater sensitivity to cell-growth inhibition induced by erlotinib, LY294002, and PHA665752, respectively, than did cells featuring simultaneous activation of these pathways, underlining the need for combined therapeutic strategies in targeted cancer treatments. In conclusion, our gene-alteration landscape of lung cancer cell lines provides insights into how gene alterations accumulate and biological pathways interact in cancer. Hum Mutat 30, 1199–1206, 2009. & 2009Wiley-Liss, Inc

Falso aneurisma aórtico 30 años después de la corrección de una coartación: tratamiento quirúrgico bajo hipotermia profunda

We report a case of a large false aortic aneurysm that had developed in a 43-year-old man who had had coarctation repair 30 years previously. The coarctation repair had been done by inserting an end-to-end Dacron tubular graft which was sutured with silk. The re-operation was successfully performed under deep hypothermic arrest and it was noted that there was complete separation of the graft from both ends and no sutures were visualised. The deep hypothermic technique has considerably improved the ease and safety of this operation. We attribute this complication to the reabsorption of the silk sutures. Patients after coarctectomy with graft material should have regular chest X-rays for life in order to detect false aneurys

Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury

Traumatic brain injury (TBI) is a devastating event for which current therapies are limited. Stem cell transplantation may lead to recovery of function via different mechanisms, such as cell replacement through differentiation, stimulation of angiogenesis and support to the microenvironment. Adult hair follicle bulge-derived stem cells (HFBSCs) possess neuronal differentiation capacity, are easy to harvest and are relatively immune-privileged, which makes them potential candidates for autologous stem cell-based therapy. In this study, we apply in vivo multimodal, optical and magnetic resonance imaging techniques to investigate the behavior of mouse HFBSCs in a mouse model of TBI. HFBSCs expressed Luc2 and copGFP and were examined for their differentiation capacity in vitro. Subsequently, transduced HFBSCs, preloaded with ferumoxytol, were transplanted next to the TBI lesion (cortical region) in nude mice, 2 days after injury. Brains were fixed for immunohistochemistry 58 days after transplantation. Luc2- and copGFP-expressing, ferumoxytol-loaded HFBSCs showed adequate neuronal differentiation potential in vitro. Bioluminescence of the lesioned brain revealed survival of HFBSCs and magnetic resonance imaging identified their localization in the area of transplantation. Immunohistochemistry showed that transplanted cells stained for nestin and neurofilament protein (NF-Pan). Cells also expressed laminin and fibronectin but extracellular matrix masses were not detected. After 58 days, ferumoxytol could be detected in HFBSCs in brain tissue sections. These results show that HFBSCs are able to survive after brain transplantation and suggest that ce

Report of the 2006 ICCAT workshop for bluefin tuna direct ageing

This report provides the presentations, discussions and conclusions from the ICCAT bluefin tuna workshop for direct ageing held in Santander, Spain, in April 2006. The report summarizes the ageing criteria used in the past and the agreements on future age determination based on otoliths, vertebrae and spines. Advantages and disadvantages of each calcified structure for ageing and border interpretation were discussed. It was considered that bluefin tuna age interpretation becomes very difficult from age ten onwards using the whole vertebra and the spine sections methods, but this last technique continues to be useful for older ages. Otolith sections can be used for the whole age range. Participants agreed that none of these three structures could be excluded from routine ageing because otoliths are not easily available. Age estimations within the same structure and between different structures of the same specimen were compared for several readers. Better precision was found between spine readers compared to vertebra and otolith readers. Good age agreement was also achieved between readers of spines and vertebrae from the same bluefin for ages less than 12 years. Preliminary results from radiocarbon assays on otoliths were presented at the workshop and gave promising outcomes for bluefin tuna age validation. Also, these suggested that bluefin tuna can live longer than had previously been established and that a review is needed of the currently used asymptotic size and growth rate for both stocks. Another important contribution of the workshop was a manual for age interpretation.Le présent rapport recueille les présentations, discussions et conclusions de l’Atelier de l’ICCAT chargé de la détermination directe de l’âge du thon rouge, tenu à Santander (Espagne) au mois d’avril 2006. Le rapport résume les critères employés par le passé pour interpréter l’âge et les accords pour la détermination future de l’âge à partir des otolithes, vertèbres et épines. L’Atelier a discuté des avantages et des inconvénients de chaque structure calcifiée pour déterminer l’âge et l’interprétation du type de bord. On a abordé la difficulté de l’interprétation de l’âge des thons de plus de 10 ans au moyen de la vertèbre entière et des sections des épines, bien que cette dernière méthode continue d’être utile pour les âges avancés. Les sections d’otolithes peuvent être employées pour toute la gamme d’âges. Les participants ont convenu qu’aucune de ces trois structures ne doit être exclue pour l’interprétation de l’âge parce qu’il n’est pas toujours possible d’obtenir des otolithes. On a comparé les lectures de l’âge à l’intérieur de la même structure et entre différentes structures du même exemplaire pour divers lecteurs. On a obtenu une plus grande précision parmi les lecteurs d’épines que parmi les lecteurs de vertèbres et d’otolithes. On a également obtenu un bon accord entre les lecteurs d’épines et de vertèbres originaires du même exemplaire pour les âges inférieurs à 12 ans. Les résultats préliminaires des essais de radiocarbone dans les otolithes ont été présentés à l’Atelier, offrant de bonnes perspectives pour son utilisation dans la validation de l’âge. Ces résultats indiquent aussi que le thon rouge a une plus grande longévité que ce qui avait été auparavant établi et qu’il est nécessaire de réviser la longueur asymptotique et le taux de croissance actuellement utilisés. L’élaboration d’un manuel aux fins de l’interprétation de l’âge a constitué une autre contribution importante de l’Atelier.Este informe recoge las presentaciones, discusiones y conclusiones del congreso de ICCAT para la determinación directa de la edad de atún rojo, celebrado en Santander, España, en abril de 2006. El informe resume los criterios empleados en el pasado para interpretar la edad y los acuerdos para la determinación futura de la edad a partir de otolitos, vértebras y espinas. Se discutieron las ventajas y los inconvenientes de cada estructura calcificada para determinar la edad y la interpretación del tipo borde. Se planteó la dificultad en la interpretación de la edad de atunes mayores de 10 años utilizando la vértebra entera y las secciones de espinas, no obstante este último método continúa siendo útil para edades mayores. Las secciones de otolitos pueden ser empleadas para todo el rango de edades. Los participantes acordaron que ninguna de estas tres estructuras deben excluirse para la interpretación de la edad porque no siempre es posible obtener los otolitos. Se compararon las lecturas de edad dentro de la misma estructura y entre diferentes estructuras del mismo ejemplar para varios lectores. Se obtuvo una mayor precisión entre lectores de espinas comparada con las obtenidas por los lectores de vértebras y otolitos. También se obtuvo un buen acuerdo entre lectores de espinas y vértebras procedentes del mismo ejemplar para edades menores de 12 años. Los resultados preliminares de las pruebas de radiocarbono en otolitos fueron presentados en el congreso, proporcionando buenas expectativas para su uso en la validación de la edad. Estos resultados también indican que el atún rojo es más longevo de lo que se consideraba y que es necesaria una revisión de la longitud asintótica y de la tasa de crecimiento empleadas actualmente. Otra importante contribución del congreso fue la elaboración de un manual para la interpretación de la edad