University of Essex at the TAC 2011 Multilingual Summarisation Pilot

We present the results of our Arabic and English runs at the TAC 2011 Multilingual summarisation (MultiLing) task. We partic- ipated with centroid-based clustering for multi- document summarisation. The automatically generated Arabic and English summaries were evaluated by human participants and by two automatic evaluation metrics, ROUGE and Au- toSummENG. The results are compared with the other systems that participated in the same track on both Arabic and English languages. Our Arabic summariser performed particularly well in the human evaluation

Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity that affects 30%-40% of patients undergoing cancer treatment. Although multiple mechanisms of chemotherapy-induced neurotoxicity have been described in preclinical models, these have not been translated into widely effective strategies for the prevention or treatment of CIPN. Predictive biomarkers to inform therapeutic approaches are also lacking. Recent studies have examined genetic risk factors associated with CIPN susceptibility. This review provides an overview of the clinical and pathologic features of CIPN and summarizes efforts to identify target pathways through genetic and functional studies. Structurally and mechanistically diverse chemotherapeutics are associated with CIPN; however, the current review is focused on microtubule-targeting agents since these are the focus of most pharmacogenetic association and functional studies of CIPN. Genome-wide pharmacogenetic association studies are useful tools to identify not only causative genes and genetic variants but also genetic networks implicated in drug response or toxicity and have been increasingly applied to investigations of CIPN. Induced pluripotent stem cell-derived models of human sensory neurons are especially useful to understand the mechanistic significance of genomic findings. Combined genetic and functional genomic efforts to understand CIPN hold great promise for developing therapeutic approaches for its prevention and treatment.Fil: Chua, Katherina C.. University of California; Estados UnidosFil: El Haj, Nura. University of California; Estados UnidosFil: Priotti, Josefina. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Kroetz, Deanna L.. University of California; Estados Unido

Immobilized WNT proteins act as a stem cell niche for tissue engineering

The timing, location, and level of WNT signaling are highly regulated during embryonic development and for the maintenance of adult tissues. Consequently the ability to provide a defined and directed source of WNT proteins is crucial to fully understand its role in tissue development and to mimic its activity in vitro. Here we describe a one-step immobilization technique to covalently bind WNT3A proteins as a basal surface with easy storage and long-lasting activity. We show that this platform is able to maintain adult and embryonic stem cells while also being adaptable for 3D systems. Therefore, this platform could be used for recapitulating specific stem cell niches with the goal of improving tissue engineering

Development and validation of broad-spectrum magnetic particle labelling processes for cell therapy manufacturing

Background Stem cells are increasingly seen as a solution for many health challenges for an ageing population. However, their potential benefits in the clinic are currently curtailed by technical challenges such as high cell dose requirements and point of care delivery, which pose sourcing and logistics challenges. Cell manufacturing solutions are currently in development to address the supply issue, and ancillary technologies such as nanoparticle-based labelling are being developed to improve stem cell delivery and enable post-treatment follow-up. Methods The application of magnetic particle (MP) labelling to potentially scalable cell manufacturing processes was investigated in a range of therapeutically relevant cells, including mesenchymal stromal cells (MSC), cardiomyocytes (CMC) and neural progenitor cells (ReN). The efficiency and the biological effect of particle labelling were analysed using fluorescent imaging and cellular assays. Results Flow cytometry and fluorescent microscopy confirmed efficient labelling of monolayer cultures. Viability was shown to be retained post labelling for all three cell types. MSC and CMC demonstrated higher tolerance to MP doses up to 100× the standard concentration. This approach was also successful for MP labelling of suspension cultures, demonstrating efficient MP uptake within 3 h, while cell viability was unaffected by this suspension labelling process. Furthermore, a procedure to enable the storing of MP-labelled cell populations to facilitate cold chain transport to the site of clinical use was investigated. When MP-labelled cells were stored in hypothermic conditions using HypoThermosol solution for 24 h, cell viability and differentiation potential were retained post storage for ReN, MSC and beating CMC. Conclusions Our results show that a generic MP labelling strategy was successfully developed for a range of clinically relevant cell populations, in both monolayer and suspension cultures. MP-labelled cell populations were able to undergo transient low-temperature storage whilst maintaining functional capacity in vitro. These results suggest that this MP labelling approach can be integrated into cell manufacturing and cold chain transport processes required for future cell therapy approaches

Development and validation of broad-spectrum magnetic particle labelling processes for cell therapy manufacturing

BACKGROUND: Stem cells are increasingly seen as a solution for many health challenges for an ageing population. However, their potential benefits in the clinic are currently curtailed by technical challenges such as high cell dose requirements and point of care delivery, which pose sourcing and logistics challenges. Cell manufacturing solutions are currently in development to address the supply issue, and ancillary technologies such as nanoparticle-based labelling are being developed to improve stem cell delivery and enable post-treatment follow-up. METHODS: The application of magnetic particle (MP) labelling to potentially scalable cell manufacturing processes was investigated in a range of therapeutically relevant cells, including mesenchymal stromal cells (MSC), cardiomyocytes (CMC) and neural progenitor cells (ReN). The efficiency and the biological effect of particle labelling were analysed using fluorescent imaging and cellular assays. RESULTS: Flow cytometry and fluorescent microscopy confirmed efficient labelling of monolayer cultures. Viability was shown to be retained post labelling for all three cell types. MSC and CMC demonstrated higher tolerance to MP doses up to 100× the standard concentration. This approach was also successful for MP labelling of suspension cultures, demonstrating efficient MP uptake within 3 h, while cell viability was unaffected by this suspension labelling process. Furthermore, a procedure to enable the storing of MP-labelled cell populations to facilitate cold chain transport to the site of clinical use was investigated. When MP-labelled cells were stored in hypothermic conditions using HypoThermosol solution for 24 h, cell viability and differentiation potential were retained post storage for ReN, MSC and beating CMC. CONCLUSIONS: Our results show that a generic MP labelling strategy was successfully developed for a range of clinically relevant cell populations, in both monolayer and suspension cultures. MP-labelled cell populations were able to undergo transient low-temperature storage whilst maintaining functional capacity in vitro. These results suggest that this MP labelling approach can be integrated into cell manufacturing and cold chain transport processes required for future cell therapy approaches

Short-Term Evaluation of Cellular Fate in an Ovine Bone Formation Model.

The ovine critical-sized defect model provides a robust preclinical model for testing tissue-engineered constructs for use in the treatment of non-union bone fractures and severe trauma. A critical question in cell-based therapies is understanding the optimal therapeutic cell dose. Key to defining the dose and ensuring successful outcomes is understanding the fate of implanted cells, e.g., viability, bio-distribution and exogenous infiltration post-implantation. This study evaluates such parameters in an ovine critical-sized defect model 2 and 7 days post-implantation. The fate of cell dose and behaviour post-implantation when combined with nanomedicine approaches for multi-model tracking and remote control using external magnetic fields is also addressed. Autologous STRO-4 selected mesenchymal stromal cells (MSCs) were labelled with a fluorescent lipophilic dye (CM-Dil), functionalised magnetic nanoparticles (MNPs) and delivered to the site within a naturally derived bone extracellular matrix (ECM) gel. Encapsulated cells were implanted within a critical-sized defect in an ovine medial femoral condyle and exposed to dynamic gradients of external magnetic fields for 1 h per day. Sheep were sacrificed at 2 and 7 days post-initial surgery where ECM was harvested. STRO-4-positive (STRO-4+) stromal cells expressed osteocalcin and survived within the harvested gels at day 2 and day 7 with a 50% loss at day 2 and a further 45% loss at 7 days. CD45-positive leucocytes were also observed in addition to endogenous stromal cells. No elevation in serum C-reactive protein (CRP) or non-haem iron levels was observed following implantation in groups containing MNPs with or without magnetic field gradients. The current study demonstrates how numbers of therapeutic cells reduce substantially after implantation in the repair site. Cell death is accompanied by enhanced leucocyte invasion, but not by inflammatory blood marker levels. Crucially, a proportion of implanted STRO-4+ stromal cells expressed osteocalcin, which is indicative of osteogenic differentiation. Furthermore, MNP labelling did not alter cell number or result in a further deleterious impact on stromal cells following implantation

Dynamic studies of biomimetic coated polycaprolactone nanofiber meshes as bone extracellular matrix analogues

This work aimed at studying the effects of dynamic culture conditions and biomimetic coating on bone cells grown on nanofiber meshes. In our previous work, biomimetic calcium phosphate coated polycaprolactone nanofibre meshes (BCP-NM) proved to be more efficient for supporting cell attachment and proliferation under static conditions, when compared to polycaprolactone nanofibre meshe (PCL-NM). However, no studies on the influence of bioreactors on the behaviour of cells cultivated on these materials were developed so far. [...]info:eu-repo/semantics/publishedVersio

The effect of reverse current on the dark properties of photovoltaic solar modules

AbstractForward and reverse dark current-voltage (I-V) and capacitance-voltage (C-V) characteristics of commercial amorphous silicon solar modules, were measured in order to study their performance under the influence of induced reverse currents. Maximum module surface temperatures were directly related to each value of the induced reverse current and in to the amount of current leakage respectively. Microscopic changes as a result of hot spots defects and overheating of the solar module, linked to reverse current effects, were also documented and discussed. Experimental evidence showed that different levels of reverse currents are confirmed to be a major degrading factor affecting the performance, efficiency, and power of solar modules

Dynamic culture of osteogenic cells in biomimetically coated poly(caprolactone) nanofibre mesh constructs

In our previous work, biomimetic calcium phosphate-coated poly(caprolactone) nanofibre meshes (BCP-NMs) were demonstrated to be more effective for supporting cell attachment and proliferation under static conditions, when compared with poly(caprolactone) nanofibre meshes (PCL-NMs). In many applications, in vitro cultivation of constructs using bioreactors that support efficient nutrition of cells has appeared as an important step toward the development of functional grafts. This work aimed at studying the effects of dynamic culture conditions and biomimetic coating on bone cells grown on the nanofibre meshes. BCP-NM and PCL-NM were seeded with osteoblast-like cells (MG63--human osteosarcoma-derived cell line). The cell-seeded constructs were cultured within a rotating bioreactor that simulated microgravity, at a fixed rotating speed, for different time periods, and then characterized. Cell morphology, viability, and phenotype were assessed. PCL-NM constructs presented a higher number of dead cells than BCP-NM constructs. Under dynamic conditions, the production of proteins associated with the extracellular matrix of bone was higher on BCP-NM constructs than in the PCL-NM ones, which indicates that coated samples may provide cells with a better environment for tissue growth. It is suggested that improved mass transfer in the bioreactor in combination with the appropriate substrate were decisive factors for this highly positive outcome for generating bone.This work was developed under the scope of the EU Project Network of Excellence "Expertissues'' (NMP3-CT-2004-500283) and supported by Alea jacta est Marie Curie Actions (MEST-CT-2004-008104). M. Alves da Silva would like to acknowledge the Portuguese Foundation for Science and Technology for her grant (SFRH-BD-28708-2006). Jose V. Araujo is grateful to S. Rathbone, H. Sura, I. Wimpenny, I. Dublon, G. Jones, and E. D. Pinho for useful technical discussions