Asia-Europe: the third link

The report provides a comprehensive analysis of Europe-East Asia interdependences (in terms of relative economic weights, trade and financial integration, trade and financial flows, exchange rate and wealth transfers). The prime motivation of the paper is that linkages between Europe and East Asia remain frequently underestimated. While the “third link†between them is in many respects as important as the linkages between the two regions and North America, it is too often regarded only as of secondary importance.Regional integration, Financial integration, Trade integration, East Asia, European Monetary Union, Pisani-Ferry , Cohen-Setton

O-020 Modifying Flow in the ICA Bifurcation: Pipeline Deployment from the supraclinoid ICA Extending into the M1 Segment: Clinical and Anatomical Results

BACKGROUND: Utility of the pipeline embolization device (PED) extending to the M1 segment as well as its clinical and flow consequences at the ICA bifurcation, has not clearly described. We describe clinical and anatomical flow modifications results at the ICA bifurcation. METHODS: In this retrospective analysis of patients treated for distal supraclinoid carotid aneurysms, a single PED was deployed from the proximal M1 segment to the distal supraclinoid carotid. Flow assessment prior to the procedure, to predict the competence of the ACA/AcomA complex, was achieved by formal DSA angiography and occasional manual cross compression. In all cases a single PED was deployed over the ostium of the A1, while treating a single or multiple aneurysms. Anatomical vessels diameters and ratios between the size of the proximal segments of the A1 and M1 as well as the distal ICA were assessed. Relationships between the PED nominal diameter and the diameters of the vessels at the landing zones were obtained. All measurements were evaluated in respect to flow modifications and size regression of the A1 in the immediate postoperative images, at 3 month MRI/MRA and at 6-9 month formal DSA angiography. Immediate and mid-term clinical results were assessed. RESULTS: We treated seven patients using this technique. Median age was 62. Four patients were treated for multiple aneurysms. The following aneurysms were treated: 3 posterior communicating artery aneurysms, 3 anterior choroidal artery aneurysms, 4 ICA bifurcation aneurysms and one A1 segment aneurysm. 6/7 patients demonstrated no change of flow in ACA/AComA complex at the immediate post embolization angiography. One patient demonstrated immediate antegrade flow retardation in the ipsilateral A1 segment. Five patients underwent 3-4 month MRA follow up. All demonstrated size regression of the ipsilateral A1 segment and occlusion of the neurysms. Five patients underwent mid-term follow-up angiography (5.5-12 month). Complete reversal of flow in the ipsilateral A1, was noted in 4/5 patients (Figure 1). One patient did not demonstrate any flow modification. This patient had a dominant ipsilateral A1 segment. Interestingly, ratios of the vessels participating in this bifurcation demonstrated a unique configuration of a higher A1/M1, A1/ICA ratios and a lower M1/ICA ratio, possibly in favor of maintaining patency of the ipsilateral A1. In this specific patient, a minimal length (0.97 mm) of PED was deployed in the M1 segment. This was the most oversized PED in respect to the M1 segment. All patients were stable in the post-procedural period and with no new neurological deficits. There were no clinical nor radiographic signs of ischemia. One patient experienced asymptomatic angiographic in-stent stenosis at the M1 segment. CONCLUSIONS: We found that the deployment of PED from the distal supraclinoid carotid to the M1 segment may result in reversal of flow in the ACA/AcomA complex as well as regression of the ipsilateral A1 segment. Preoperative anatomical disposition and sizing of the PED may predict the flow modification results. This modification of flow is safe and effective, based on pre-embolization flow assessments, and may be useful in treating distal ICA aneurysm by a flow diverter. DISCLOSURES: E. Nossek: None. D. Chalif: None. S. Chakraborty: None. A. Setton: None

The role of extracellular matrix elasticity and composition in regulating the nucleus pulposus cell phenotype in the intervertebral disc: a narrative review.

Intervertebral disc (IVD) disorders are a major contributor to disability and societal health care costs. Nucleus pulposus (NP) cells of the IVD exhibit changes in both phenotype and morphology with aging-related IVD degeneration that may impact the onset and progression of IVD pathology. Studies have demonstrated that immature NP cell interactions with their extracellular matrix (ECM) may be key regulators of cellular phenotype, metabolism and morphology. The objective of this article is to review our recent experience with studies of NP cell-ECM interactions that reveal how ECM cues can be manipulated to promote an immature NP cell phenotype and morphology. Findings demonstrate the importance of a soft (<700 Pa), laminin-containing ECM in regulating healthy, immature NP cells. Knowledge of NP cell-ECM interactions can be used for development of tissue engineering or cell delivery strategies to treat IVD-related disorders

Differentiation of mouse induced pluripotent stem cells (iPSCs) into nucleus pulposus-like cells in vitro.

A large percentage of the population may be expected to experience painful symptoms or disability associated with intervertebral disc (IVD) degeneration - a condition characterized by diminished integrity of tissue components. Great interest exists in the use of autologous or allogeneic cells delivered to the degenerated IVD to promote matrix regeneration. Induced pluripotent stem cells (iPSCs), derived from a patient's own somatic cells, have demonstrated their capacity to differentiate into various cell types although their potential to differentiate into an IVD cell has not yet been demonstrated. The overall objective of this study was to assess the possibility of generating iPSC-derived nucleus pulposus (NP) cells in a mouse model, a cell population that is entirely derived from notochord. This study employed magnetic activated cell sorting (MACS) to isolate a CD24(+) iPSC subpopulation. Notochordal cell-related gene expression was analyzed in this CD24(+) cell fraction via real time RT-PCR. CD24(+) iPSCs were then cultured in a laminin-rich culture system for up to 28 days, and the mouse NP phenotype was assessed by immunostaining. This study also focused on producing a more conducive environment for NP differentiation of mouse iPSCs with addition of low oxygen tension and notochordal cell conditioned medium (NCCM) to the culture platform. iPSCs were evaluated for an ability to adopt an NP-like phenotype through a combination of immunostaining and biochemical assays. Results demonstrated that a CD24(+) fraction of mouse iPSCs could be retrieved and differentiated into a population that could synthesize matrix components similar to that in native NP. Likewise, the addition of a hypoxic environment and NCCM induced a similar phenotypic result. In conclusion, this study suggests that mouse iPSCs have the potential to differentiate into NP-like cells and suggests the possibility that they may be used as a novel cell source for cellular therapy in the IVD

Photocrosslinkable laminin-functionalized polyethylene glycol hydrogel for intervertebral disc regeneration

Intervertebral disc (IVD) disorders and age-related degeneration are believed to contribute to lower back pain. There is significant interest in cell-based strategies for regenerating the nucleus pulposus (NP) region of the disc; however, few scaffolds have been evaluated for their ability to promote or maintain an immature NP cell phenotype. Previous studies have shown that NP cell-laminin interactions promote cell adhesion and biosynthesis, which suggests a laminin-functionalized biomaterial may be useful for promoting or maintaining the NP cell phenotype. Here, a photocrosslinkable poly(ethylene glycol)-laminin 111 (PEG-LM111) hydrogel was developed. The mechanical properties of PEG-LM111 hydrogel could be tuned within the range of dynamic shear moduli values previously reported for human NP. When primary immature porcine NP cells were seeded onto PEG-LM111 hydrogels of varying stiffnesses, LM111-presenting hydrogels were found to promote cell clustering and increased levels of sGAG production as compared to stiffer LM111-presenting and PEG-only gels. When cells were encapsulated in 3-D gels, hydrogel formulation was found to influence NP cell metabolism and expression of proposed NP phenotypic markers, with higher expression of N-cadherin and cytokeratin 8 observed for cells cultured in softer (<1 kPa) PEG-LM111 hydrogels. Overall, these findings suggest that soft, LM111-functionalized hydrogels may promote or maintain the expression of specific markers characteristic of an immature NP cell phenotype. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

The Large Magellanic Cloud's ∼30\sim30 Kiloparsec Bow Shock and its Impact on the Circumgalactic Medium

The interaction between the supersonic motion of the Large Magellanic Cloud (LMC) and the Circumgalactic Medium (CGM) is expected to result in a bow shock that leads the LMC's gaseous disk. In this letter, we use hydrodynamic simulations of the LMC's recent infall to predict the extent of this shock and its effect on the Milky Way's (MW) CGM. The simulations clearly predict the existence of an asymmetric shock with a present day stand-off radius of $\sim6.7$ kpc and a transverse diameter of $\sim30$ kpc. Over the past 500 Myr, $\sim8\%$ of the MW's CGM in the southern hemisphere should have interacted with the shock front. This interaction may have had the effect of smoothing over inhomogeneities and increasing mixing in the MW CGM. We find observational evidence of the existence of the bow shock in recent $H\alpha$ maps of the LMC, providing a potential explanation for the envelope of ionized gas surrounding the LMC. Furthermore, the interaction of the bow shock with the MW CGM may also explain observations of ionized gas surrounding the Magellanic Stream. Using recent orbital histories of MW satellites, we find that many satellites have likely interacted with the LMC shock. Additionally, the dwarf galaxy Ret2 is currently sitting inside the shock, which may impact the interpretation of reported gamma ray excess in Ret2. This work highlights bow shocks associated with infalling satellites are an under-explored, yet potentially very important dynamical mixing process in the circumgalactic and intracluster media.Comment: Submitted to ApJ Letters, 5 figures and 1 table. Comments welcome

A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.

Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold

Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.

The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics

Internal Maxillary Artery-Middle Cerebral Artery Bypass: Infratemporal Approach for Subcranial-Intracranial (SC-IC) Bypass

BACKGROUND:Internal maxillary artery (IMax)-middle cerebral artery (MCA) bypass has been recently described as an alternative to cervical extracranial-intracranial bypass. This technique uses a keyhole craniectomy in the temporal fossa that requires a technically challenging end-to-side anastomosis.OBJECTIVE:To describe a lateral subtemporal craniectomy of the middle cranial fossa floor to facilitate wide exposure of the IMax to facilitate bypass.METHODS:Orbitozygomatic osteotomy is used followed by frontotemporal craniotomy and subsequently laterotemporal fossa craniectomy, reaching its medial border at a virtual line connecting the foramen rotundum and foramen ovale. The IMax was identified by using established anatomic landmarks, neuronavigation, and micro Doppler probe (Mizuho Inc. Tokyo, Japan). Additionally, we studied the approach in a cadaveric specimen in preparation for microsurgical bypass.RESULTS:There were 4 cases in which the technique was used. One bypass was performed for flow augmentation in a hypoperfused hemisphere. The other 3 were performed as part of treatment paradigms for giant middle cerebral artery aneurysms. Vein grafts were used in all patients. The proximal anastomosis was performed in an end-to-side fashion in 1 patient and end-to-end in 3 patients. Intraoperative graft flow measured with the Transonic flow probe ranged from 20 to 60 mL/min. Postoperative angiography demonstrated good filling of the graft with robust distal flow in all cases. All patients tolerated the procedure well.CONCLUSION:IMax to middle cerebral artery subcranial-intracranial bypass is safe and efficacious. The laterotemporal fossa craniectomy technique resulted in reliable identification and wide exposure of the IMax, facilitating the proximal anastomosis

Por uma história transnacional da sociologia: entrevista com Gisèle Sapiro

Gisèle Sapiro is Director of Research at the CNRS (National Center for Scientific Research) and Director of Studies at the EHESS (European Center for Sociology and Political Science) since 2011, CNRS 2021 Silver Medal. She defended her thesis in 1994 under the guidance of Pierre Bourdieu, mobilizing the concept of field to understand the structural history of the field of literature. Her training and contact with Bourdieu himself and his work make Sapiro one of the successors of the Bourdieusian legacy in France. Sapiro’s works address themes such as the autonomy of fields, the political role of writers and intellectuals, and the circulation of knowledge in an international perspective, especially in relation to Bourdieu’s ideas and especially in the United States. The purpose of this interview with Gisèle Sapiro is to put into perspective the different ways of reading and interpreting Pierre Bourdieu’s work resulting from its translation and its appropriation in Brazil and in the world from the point of view of a specialist who, while bringing her own contributions to critic sociology, has greatly contributed to the dissemination of Bourdieusian ideas. Sapiro’s work deserves the attention of all those who share her intellectual enthusiasm and lay the foundations for a transnational history of sociology.Gisèle Sapiro é diretora de pesquisa e medalhista de prata no Centro Nacional de Pesquisa Científica (CNRS) e diretora de estudos no Centro Europeu de Sociologia e Ciência Política (EHESS) desde 2011. Defendeu sua tese em 1994 sob a orientação de Pierre Bourdieu, mobilizando o conceito de campo para compreender a história estrutural da literatura. Sua formação e contato com Bourdieu e com sua obra tornam Sapiro uma das sucessoras do legado bourdieusiano na França. Os trabalhos de Sapiro abordam temas como a autonomia dos campos, o papel político dos escritores e intelectuais e a circulação dos saberes em uma perspectiva internacional, sobretudo no que concerne às ideias de Bourdieu e notadamente nos Estados Unidos. O objetivo da entrevista com Gisèle Sapiro é colocar em perspectiva as diferentes maneiras de ler e interpretar a obra de Pierre Bourdieu, consequências das distinções de tradução e de apropriação no Brasil e no mundo, a partir do ponto de vista de uma especialista que, sem deixar de trazer suas próprias contribuições para a sociologia crítica, muito cooperou para a difusão das ideias bourdieusianas. O trabalho de Sapiro merece a atenção de todos aqueles que compartilham seu entusiasmo intelectual e estabelecem as bases para uma história transnacional da sociologia