The XPF-ERCC1 endonuclease and homologous recombination contribute to the repair of minor groove DNA interstrand crosslinks inmammalian cells produced by the pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136

SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3' sequence in the DNA minor groove. SJG-136 crosslinks form rapidly and persist compared to those produced by conventional crosslinking agents such as nitrogen mustard, melphalan or cisplatin which bind in the DNA major groove. A panel of Chinese hamster ovary (CHO) cells with defined defects in specific DNA repair pathways were exposed to the bi-functional agents SJG-136 and melphalan, and to their mono-functional analogues mmy-SJG and mono-functional melphalan. SJG-136 was >100 times more cytotoxic than melphalan, and the bi-functional agents were much more cytotoxic than their respective mono-functional analogues. Cellular sensitivity of both SJG-136 and melphalan was dependent on the XPF-ERCC1 heterodimer, and homologous recombination repair factors XRCC2 and XRCC3. The relative level of sensitivity of these repair mutant cell lines to SJG-136 was, however, significantly less than with major groove crosslinking agents. In contrast to melphalan, there was no clear correlation between sensitivity to SJG-136 and crosslink unhooking capacity measured using a modified comet assay. Furthermore, repair of SJG-136 crosslinks did not involve the formation of DNA double-strand breaks. SJG-136 cytotoxicity is likely to result from the poor recognition of DNA damage by repair proteins resulting in the slow repair of both mono-adducts and more importantly crosslinks in the minor groove

Certification of a class of industrial predictive controllers without terminal conditions

Three decades have passed encompassing a flurry of research and commercial activities in model predictive control (MPC). However, the massive strides made by the academic community in guaranteeing stability through a state- space framework have not always been directly applicable in an industrial setting. This paper is concerned with a priori and/or a posteriori certification of persistent feasibility, boundedness of industrial MPC controllers (i) based on input-output formu- lation (ii) using shorter control than prediction horizon (iii) and without terminal conditions.This work has been supported by FDOC, UGent

Reverse-engineering of architectural buildings based on an hybrid modeling approach

We thank MENSI and REALVIZ companies for their helpful comments and the following people for providing us images from their works: Francesca De Domenico (Fig. 1), Kyung-Tae Kim (Fig. 9). The CMN (French national center of patrimony buildings) is also acknowledged for the opportunity given to demonstrate our approach on the Hotel de Sully in Paris. We thank Tudor Driscu for his help on the English translation.This article presents a set of theoretical reflections and technical demonstrations that constitute a new methodological base for the architectural surveying and representation using computer graphics techniques. The problem we treated relates to three distinct concerns: the surveying of architectural objects, the construction and the semantic enrichment of their geometrical models, and their handling for the extraction of dimensional information. A hybrid approach to 3D reconstruction is described. This new approach combines range-based modeling and image-based modeling techniques; it integrates the concept of architectural feature-based modeling. To develop this concept set up a first process of extraction and formalization of architectural knowledge based on the analysis of architectural treaties is carried on. Then, the identified features are used to produce a template shape library. Finally the problem of the overall model structure and organization is addressed

Responsible innovation and political accountability: genetically modified mosquitoes in Brazil

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.In this paper, we analyse the introduction of genetically modified (GM) mosquitoes in Brazil and use this case to probe the notion of Responsible Innovation and its applicability to the development of new public health biotechnologies in the global South. OX513A, a strain of GM Aedes aegypti mosquitoes developed by the British firm Oxitec, has been used experimentally in Brazil since 2009, when it was imported into the country as a promising new tool in the fight against dengue. We discuss the regulatory history of OX513A in Brazil, as well as the forms of ‘community engagement’ that have accompanied the release of transgenic mosquitoes. We argue that the conduct of a scientific research project is only part of a broader effort to localise insect biotechnology in Brazil, an effort that has enjoyed very visible support from political authorities across the country. We conclude by arguing that if the framework of Responsible Innovation is to have purchase on this sort of transnational and multifaceted innovation trajectory, it has to include at its centre a strong notion of political accountability.Research by Javier Lezaun was supported by the European Research Council (ERC) under the European Community’s Seventh Framework Programme [grant number 263447: BioProperty]. Research by Sarah Hartley was supported by the Leverhulme Trust ‘Making Science Public’ programme [grant number RP2011-SP-013]

The Acute Calcific Prevertebral Tendinitis: Report of Two Cases

Acute calcific prevertebral tendinitis, which is also known as retropharyngeal calcific tendinitis and longus colli tendinitis, is an under-recognized cause of acute cervical pain produced by an inflammation of the longus colli muscle. The typical characteristics of this entity are calcifications at the superior insertion of the longus colli tendons at the C1-C2 level and fluid collection in the retropharyngeal space. The differential diagnosis includes a retropharyngeal abscess, infectious spondylitis or traumatic injury. Knowledge of the clinical and imaging findings can prevent a misdiagnosis and inappropriate attempts at surgical drainage

Reducing the metabolic cost of walking with an ankle exoskeleton: interaction between actuation timing and power

Background Powered ankle-foot exoskeletons can reduce the metabolic cost of human walking to below normal levels, but optimal assistance properties remain unclear. The purpose of this study was to test the effects of different assistance timing and power characteristics in an experiment with a tethered ankle-foot exoskeleton. Methods Ten healthy female subjects walked on a treadmill with bilateral ankle-foot exoskeletons in 10 different assistance conditions. Artificial pneumatic muscles assisted plantarflexion during ankle push-off using one of four actuation onset timings (36, 42, 48 and 54% of the stride) and three power levels (average positive exoskeleton power over a stride, summed for both legs, of 0.2, 0.4 and 0.5 W∙kg−1). We compared metabolic rate, kinematics and electromyography (EMG) between conditions. Results Optimal assistance was achieved with an onset of 42% stride and average power of 0.4 W∙kg−1, leading to 21% reduction in metabolic cost compared to walking with the exoskeleton deactivated and 12% reduction compared to normal walking without the exoskeleton. With suboptimal timing or power, the exoskeleton still reduced metabolic cost, but substantially less so. The relationship between timing, power and metabolic rate was well-characterized by a two-dimensional quadratic function. The assistive mechanisms leading to these improvements included reducing muscular activity in the ankle plantarflexors and assisting leg swing initiation. Conclusions These results emphasize the importance of optimizing exoskeleton actuation properties when assisting or augmenting human locomotion. Our optimal assistance onset timing and average power levels could be used for other exoskeletons to improve assistance and resulting benefits

Exploring the use of strategic frameworks in dental practice

This paper explores the use of strategic frameworks in NHS and private dental practice. It reviews the policy context of dentistry and suggests the challenges in this context will require dental practices to prioritise understanding and engagement with a strategic approach. A strategic approach will be required in order to enhance and improve performance. Two specific strategic frameworks will be explored in terms of their relevance to NHS and private dental practic

The Tiered Radio Extragalactic Continuum (T-RECS) simulation II: HI emission and continuum-HI cross-correlation

In this paper we extend the Tiered Radio Extragalactic Continuum Simulation (T-RECS) to include HI emission. The HI T-RECS model is based on the most recent HI mass function estimates, combined with prescriptions to convert HI mass to total integrated HI flux. It further models source size, morphology and kinematics, including rotational velocity and HI line width. The continuum T-RECS model is updated to improve the agreement with deeper number counts available at 150\,MHz. The model for star-forming galaxies (SFGs) is also modified according to the most recent indications of a star formation rate (SFR)--radio luminosity relation, which depends primarily on stellar mass rather than redshift. We further introduce prescriptions to associate an HI mass to the T-RECS radio continuum SFG and Active Galactic Nuclei (AGN) populations. This gives us a way to meaningfully associate counterparts between HI and continuum catalogues, thus building HI $\times$ continuum simulated observations. Clustering properties of the sources in both HI and continuum are reproduced by associating the galaxies to dark matter haloes of a cosmological simulation. We deliver a set of mock catalogues, as well as the code to produce them, which can be used for simulating observations and predicting results from radio surveys with existing and forthcoming radio facilities, such as the Square Kilometre Array (SKA)Comment: 18 pages, 10 figures, accepted by MNRA

Supplier development practice: arising the problems of upstream delivery for a food distribution SME in the UK

The paper aims to emphasize on the impacts of the supplier development on reducing the defects in supplier quality for a food distribution small–medium sized enterprise (SME). An empirical study was conducted to measure the performance of the suppliers in three different key performance indicators of the outsourcing and supplier’s performance to arise the existing problems via information exchange, data collection and data analysis. It was found that supplier development through data and information exchange and better communication by any food distribution SME raises the problems more promptly. This can dramatically change the supplier’s behavior to improve the quality of the supplier’s service and products. It is suggested that more research is required to raise other key performance indicators and their related problems and to develop more improvement practices. Six sigma methodologies could be the potential good practices to be focused in future research studies. Supplier performance measurement, which encompasses data exchange and data collection, develops the systematic flow of information, which potentially improves the flow of goods and the whole food supply chain to address the final consumer satisfaction. The research took a novel approach in adopting some transport related key performance indicators of the food supply to the food distribution and retailing sector, which is almost a new approach in food industry