A Biomimetic steering robot for Minimally invasive surgery application

International audienceMinimally Invasive Surgery represents the future of many types of medical inter- ventions such as keyhole neurosurgey or transluminal endoscopic surgery. These procedures involve insertion of surgical instruments such as needles and endoscopes into human body through small incision/ body cavity for biopsy and drug delivery. However, nearly all surgical instruments for these procedures are inserted manually and there is a long learning curve for surgeons to use them properly. Many research efforts have been made to design active instruments (endoscope, needles) to improve this procedure during last decades. New robot mechanisms have been designed and used to improve the dexterity of current endoscope. Usually these robots are flexible and can pass the constrained space for fine manipulations. In recent years, a con- tinuum robotic mechanism has been investigated and designed for medical surgery. Those robots are characterized by the fact that their mechanical components do not have rigid links and discrete joints in contrast with traditional robot manipula- tors. The design of these robots is inspired by movements of natural animals such as tongues, elephant trunks and tentacles. The unusual compliance and redundant degrees of freedom of these robots provide strong potential to achieve delicate tasks successfully even in cluttered and unstructured environments. This chapter will present a complete application of a continuum robot for Mini- mally Invasive Surgery of colonoscopy. This system is composed of a micro-robotic tip, a set of position sensors and a real-time control system for guiding the explo- ration of colon. Details will be described on the modeling of the used pneumatic actuators, the design of the mechanical component, the kinematic model analysis and the control strategy for automatically guiding the progression of the device inside the human colon. Experimental results will be presented to check the perfor- mances of the whole system within a transparent tube

The study of metaphor as part of Critical Discourse Analysis

This article discusses how the study of metaphoric and more generally, figurative language use contributes to critical discourse analysis (CDA). It shows how cognitive linguists’ recognition of metaphor as a fundamental means of concept- and argument-building can add to CDA's account of meaning constitution in the social context. It then discusses discrepancies between the early model of conceptual metaphor theory and empirical data and argues that discursive-pragmatic factors as well as sociolinguistic variation have to be taken into account in order to make cognitive analyses more empirically and socially relevant. In conclusion, we sketch a modified cognitive approach informed by Relevance Theory within CDA

Studies on an alkali-thermostable xylanase from Aspergillus fumigatus MA28

An alkalitolerant fungus, Aspergillus fumigatus strain MA28 produced significant amounts of cellulase-free xylanase when grown on a variety of agro-wastes. Wheat bran as the sole carbon source supported higher xylanase production (8,450 U/L) than xylan (7,500 U/L). Soybean meal was observed to be the best nitrogen source for xylanase production (9,000 U/L). Optimum medium pH for xylanase production was 8 (9,800 U/L), though, significant quantities of the enzyme was also produced at pH 7 (8,500 U/L), 9 (8,200 U/L) and 10 (4,600 U/L). The xylanase was purified by ammonium sulphate precipitation and carboxymethyl cellulose chromatography, and was found to have a molecular weight of 14.4 kDa with a Vmax of 980 μmol/min/mg of protein and a Km of approximately 4.9 mg/mL. The optimum temperature and pH for enzyme activity was 50 °C and pH 8, respectively. However, the enzyme also showed substantial residual activity at 60–70 °C (53–75%) and at alkaline pH 8–9 (56–88%)

The Aminopeptidase CD13 Induces Homotypic Aggregation in Neutrophils and Impairs Collagen Invasion.

Aminopeptidase N (CD13) is a widely expressed cell surface metallopeptidase involved in the migration of cancer and endothelial cells. Apart from our demonstration that CD13 modulates the efficacy of tumor necrosis factor-α-induced apoptosis in neutrophils, no other function for CD13 has been ascribed in this cell. We hypothesized that CD13 may be involved in neutrophil migration and/or homotypic aggregation. Using purified human blood neutrophils we confirmed the expression of CD13 on neutrophils and its up-regulation by pro-inflammatory agonists. However, using the anti-CD13 monoclonal antibody WM-15 and the aminopeptidase enzymatic inhibitor bestatin we were unable to demonstrate any direct involvement of CD13 in neutrophil polarisation or chemotaxis. In contrast, IL-8-mediated neutrophil migration in type I collagen gels was significantly impaired by the anti-CD13 monoclonal antibodies WM-15 and MY7. Notably, these antibodies also induced significant homotypic aggregation of neutrophils, which was dependent on CD13 cross-linking and was attenuated by phosphoinositide 3-kinase and extracellular signal-related kinase 1/2 inhibition. Live imaging demonstrated that in WM-15-treated neutrophils, where homotypic aggregation was evident, the number of cells entering IL-8 impregnated collagen I gels was significantly reduced. These data reveal a novel role for CD13 in inducing homotypic aggregation in neutrophils, which results in a transmigration deficiency; this mechanism may be relevant to neutrophil micro-aggregation in vivo.This work was funded by a Medical Research Council Research Training Fellowship to CAF (G0900329), Addenbrooke’s Charitable Trust (ACT), CUHNHSFT, Papworth Hospital NHS Foundation Trust and the NIHR Cambridge Biomedical Research Centre. CAF received a Raymond and Beverly Sackler Studentship.This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pone.016010

Analysis of SNPs and Haplotypes in Vitamin D Pathway Genes and Renal Cancer Risk

In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR), most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology. RCC cases (N = 777) and controls (N = 1,035) were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P) tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP) sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02) and retinoid-X-receptor-alpha (RXRA) (p-value = 0.10) were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991) across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09–1.57) haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3′ of the coding sequence (rs748964, rs3118523), increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings

Experimental determination of the stress-crack opening relation in fibre cementitious composites with a crack-tip singularity

A J -based-fracture-testing method is presented for determining the bridging-stress-crackopening-displacement (σ-δ) relationship in fibre-reinforced composites where the crack-tip toughness is not negligible. The J -based technique originally proposed for concrete has been well-established for cementitious composites where the fracture process is primarily dominated by the formation of a fracture-process zone and the contribution of the crack-tip toughness is negligibly small. In this study, the J -based technique is further extended to cover materials for which the crack-tip stress singularity coexists with the fracture-process zone. This extended version of the J -based technique explicitly accounts for the crack-tip singularity while considering the fracture-process zone. This newly derived testing technique has been applied to a high-strength-mortar (HSM) reinforced with carbon and steel fibres where the fibrebridging toughness can be of the same order of magnitude as the crack-tip toughness. The validity of the σ-δ relationships deduced has been examined by comparing with results obtained from direct uniaxial tension tests. It is suggested that the J -based-fracture-testing technique can provide reasonable σ-δ relationships and fracture parameters in a fibrereinforced HSM.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44728/1/10853_2004_Article_BF00356823.pd

Coadministration of the Three Antigenic Leishmania infantum Poly (A) Binding Proteins as a DNA Vaccine Induces Protection against Leishmania major Infection in BALB/c Mice

Highly conserved intracellular proteins from Leishmania have been described as antigens in natural and experimental infected mammals. The present study aimed to evaluate the antigenicity and prophylactic properties of the Leishmania infantum Poly (A) binding proteins (LiPABPs). Three different members of the LiPABP family have been described. Recombinant tools based on these proteins were constructed: recombinant proteins and DNA vaccines. The three recombinant proteins were employed for coating ELISA plates. Sera from human and canine patients of visceral leishmaniasis and human patients of mucosal leishmaniasis recognized the three LiPABPs. In addition, the protective efficacy of a DNA vaccine based on the combination of the three Leishmania PABPs has been tested in a model of progressive murine leishmaniasis: BALB/c mice infected with Leishmania major. The induction of a Th1-like response against the LiPABP family by genetic vaccination was able to down-regulate the IL-10 predominant responses elicited by parasite LiPABPs after infection in this murine model. This modulation resulted in a partial protection against L. major infection. LiPABP vaccinated mice showed a reduction on the pathology that was accompanied by a decrease in parasite burdens, in antibody titers against Leishmania antigens and in the IL-4 and IL-10 parasite-specific mediated responses in comparison to control mice groups immunized with saline or with the non-recombinant plasmid. The results presented here demonstrate for the first time the prophylactic properties of a new family of Leishmania antigenic intracellular proteins, the LiPABPs. The redirection of the immune response elicited against the LiPABP family (from IL-10 towards IFN-γ mediated responses) by genetic vaccination was able to induce a partial protection against the development of the disease in a highly susceptible murine model of leishmaniasisThe study was supported in Spain by grants from Ministerio de Ciencia e Innovación FIS PI11/00095 and FISPI14/00366 from the Instituto de Salud Carlos III within the Network of TropicalDiseases Research (VI P I+D+I 2008-2011, ISCIII -Subdirección General de Redes y Centros de Investigación Cooperativa (RD12/0018/0009)). This work was also supported in Brazil by a grant from CNPq (Ciencia sem Fronteiras-PVE 300174/2014-4). A CBMSO institutional grant from Fundación Ramón Areces is also acknowledged. EAFC is a grant recipient of CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip