HIV-1 RT-dependent DNAzyme expression inhibits HIV-1 replication without the emergence of escape viruses

DNAzymes are easier to prepare and less sensitive to chemical and enzymatic degradation than ribozymes; however, a DNA enzyme expression system has not yet been developed. In this study, we exploited the mechanism of HIV-1 reverse transcription (RT) in a DNA enzyme expression system. We constructed HIV-1 RT-dependent lentiviral DNAzyme expression vectors including the HIV-1 primer binding site, the DNA enzyme, and either a native tRNA (Lys-3), tRMDtRL, or one of two truncated tRNAs (Lys-3), tRMDΔARMtRL or tRMD3′-endtRL. Lentiviral vector-mediated DNAzyme expression showed high levels of inhibition of HIV-1 replication in SupT1 cells. We also demonstrated the usefulness of this approach in a long-term assay, in which we found that the DNAzymes prevented escape from inhibition of HIV. These results suggest that HIV-1 RT-dependent lentiviral vector-derived DNAzymes prevent the emergence of escape mutations

Ninety-Degree Chevron Osteotomy for Correction of Hallux Valgus Deformity: Clinical Data and Finite Element Analysis

Hallux valgus is a very common foot disorder, with its prevalence estimated at 33% in adult shoe-wearing populations. Conservative management is the initial treatment of choice for this condition, but surgery is sometimes needed. The 600 angle Chevron osteotomy is an accepted method for correction of mild to moderate hallux valgus in adults less than 60 years old. A modified 900 angle Chevron osteotomy has also been described; this modified technique can confer some advantages compared to the 600 angle method, and reported results are good. In the current work we present clinical data from a cohort of fifty-one female patients who had surgery for sixty-two hallux valgus deformities. In addition, in order to get a better physical insight and study the mechanical stresses along the two osteotomies, Finite Element Analysis (FEA) was also conducted. FEA indicated enhanced mechanical bonding with the modified 900 Chevron osteotomy, because the compressive stresses that keep the two bone parts together are stronger, and the shearing stresses that tend to slide the two bone parts apart are weaker, compared to the typical 600 technique. Follow-up data on our patient cohort show good or excellent long-term clinical results with the modified 900 angle technique. These results are consistent with the FEA-based hypothesis that a 900 Chevron osteotomy confers certain mechanical advantages compared to the typical 600 procedure

Testing the proficiency to distinguish locations with elevated plantar pressure within and between professional groups of foot therapists

BACKGROUND: Identification of locations with elevated plantar pressures is important in daily foot care for patients with rheumatoid arthritis, metatarsalgia and diabetes. The purpose of the present study was to evaluate the proficiency of podiatrists, pedorthists and orthotists, to distinguish locations with elevated plantar pressure in patients with metatarsalgia. METHODS: Ten podiatrists, ten pedorthists and ten orthotists working in The Netherlands were asked to identify locations with excessively high plantar pressure in three patients with forefoot complaints. Therapists were instructed to examine the patients according to the methods used in their everyday clinical practice. Regions could be marked through hatching an illustration of a plantar aspect. A pressure sensitive platform was used to quantify the dynamic bare foot plantar pressures and was considered as 'Gold Standard' (GS). A pressure higher than 700 kPa was used as cut-off criterion for categorizing peak pressure into elevated or non-elevated pressure. This was done for both patient's feet and six separate forefoot regions: big toe and metatarsal one to five. Data were analysed by a mixed-model ANOVA and Generalizability Theory. RESULTS: The proportions elevated/non-elevated pressure regions, based on clinical ratings of the therapists, show important discrepancies with the criterion values obtained through quantitative plantar pressure measurement. In general, plantar pressures in the big toe region were underrated and those in the metatarsal regions were overrated. The estimated method agreement on clinical judgement of plantar pressures with the GS was below an acceptable level: i.e. all intraclass correlation coefficient's equal or smaller than .60. The inter-observer agreement for each discipline demonstrated worrisome results: all below .18. The estimated mutual agreements showed that there was virtually no mutual agreement between the professional groups studied. CONCLUSION: Identification of elevated plantar pressure through clinical evaluation is difficult, insufficient and may be potentially harmful. The process of clinical plantar pressure screening has to be re-evaluated. The results of this study point towards the merit of quantitative plantar pressure measurement for clinical practice

Stiffness of the human foot and evolution of the transverse arch

The stiff human foot enables an efficient push-off when walking or running, and was critical for the evolution of bipedalism(1-6). The uniquely arched morphology of the human midfoot is thought to stiffen it(5-9), whereas other primates have flat feet that bend severely in the midfoot(7,10,11). However, the relationship between midfoot geometry and stiffness remains debated in foot biomechanics(12,13), podiatry(14,15) and palaeontology(4-6). These debates centre on the medial longitudinal arch(5,6) and have not considered whether stiffness is affected by the second, transverse tarsal arch of the human foot(16). Here we show that the transverse tarsal arch, acting through the inter-metatarsal tissues, is responsible for more than 40% of the longitudinal stiffness of the foot. The underlying principle resembles a floppy currency note that stiffens considerably when it curls transversally. We derive a dimensionless curvature parameter that governs the stiffness contribution of the transverse tarsal arch, demonstrate its predictive power using mechanical models of the foot and find its skeletal correlate in hominin feet. In the foot, the material properties of the inter-metatarsal tissues and the mobility of the metatarsals may additionally influence the longitudinal stiffness of the foot and thus the curvature-stiffness relationship of the transverse tarsal arch. By analysing fossils, we track the evolution of the curvature parameter among extinct hominins and show that a human-like transverse arch was a key step in the evolution of human bipedalism that predates the genus Homo by at least 1.5 million years. This renewed understanding of the foot may improve the clinical treatment of flatfoot disorders, the design of robotic feet and the study of foot function in locomotion

Astrid project, from conceptual to basic design progress status

International audienceSince the beginning of this year, after 6 years of conceptual design phase, the French 600 eMW ASTRID project has started a 4 years basic design phase. The ASTRID project is funding for basic design phase (2016-2019) through France Future Investments Program. All the Industrials partners involved in the project during the last phase have decided to pursue in the ASTRID project, and the strategic partnership with Japan is going to be reinforced. This very efficient industrial network with CEA as contracting authority is an original and effective project management. Very high level and up-to-date project management methods are performed, including technical control with engineering System tools and 3D mock-up consolidation. On the technical point of view, the first ten months have been kept for a reopening options phase called P2C (Configuration Confirmation Phase) concluded by a configuration review in October. According to conclusions of conceptual design phases, several items had been checked and challenged through three main drivers safety, cost killing and operability. Global consistency was also watched over.It has been also decided for the next two years, to investigate and integrate Gas Power Conversion System in the basic design configuration. The objective for the ASTRID project is to raise Gas PCS integration studies at the same level that was achieved for Water/steam PCS at the end of 2015. A go-no go decision for Gas PCS integration will be organized at the end of 2017.In the same time an ongoing effort started two years ago is underway to map all the qualification needs and define all joined processes consistent with safety regulator requirement. A more realistic planning has been prepared, adding a four years consolidation phase between basic design and detailed design, in order to increase the level of confidence and progress on the technology feasibility including experimental validations of the ASTRID's main innovative options

Status of the astrid sodium fast reactor project from conceptualdesign to basic design phase

International audienceThe ASTRID project is pursuing its progress and has reached at the end of 2015 the Conceptual Design phasefollowed by the starting of the Basic Design phase from 2016 to 2019.The transition from the Conceptual Design phase (2010-2015) to the Basic Design phase (2016-2019) was validated by theproduction of the Conceptual Design files. According to the production of this report, at the end of the Conceptual Designphase (December 2015), the French ministries representatives agreed to launch the Basic Design Phase due to the goodprogression of the program all the milestones have been met during the Conceptual Design phase, and relevant innovationshave been proposed in order to propose a technological demonstration reactor that could fulfilled Generation IV objectives.For the Basic Design phase, the ASTRID project has consolidated its industrial partnership with fourteen industrial partnersespecially strengthened with JAEA / MHI MFBR.The Basic Design phase started with a particular step named Confirmation Configuration Phase (P2C) where during the firstnine months of the 2016 year, the project - with all partners has- re-analyzed several structural options regarding three main drivers safety, operability and cost killing,- implemented the Gas (Nitrogen) Energy Conversion system within the plant design,- and built a coherent reactor layout shared by all partners as a starting point of a new ASTRID configuration forthe Basic Design phase.Therefore, this papers aims at presenting the recent progress of the ASTRID project either in terms of project managementand organization, than in terms of technological progress in reactor design and support studies

ASTRID, The SFR GENIV Technology Demonstrator Project Where Are We, Where Do We Stand For?

International audienceThe Preconceptual Design phase (AVP1) of the ASTRID Project ended late 2012, the main goal was to evaluate innovative options. It is now followed by the AVP2 phase planned until the end of 2015 whose objectives are both to focus the design in order to finalize a coherent reactor outline and to finalize by December 2015 the Safety Option Report.The CEA acts as the industrial architect of the project. In 2014, twelve industrial partners were involved in the project. Japan which participates now in the design studies and also in RandD in support of the ASTRID Project and VELAN of the French Pole Nucleaire de Bourgogne, are the latest partners to join the Project.The Option Selection Process (RCO) is continuing during the AVP2 phase although structuring decisions remain to be made (the choice of the Energy Conversion System between Rankine cycle and Gas Brayton cycle). Other important option selections, which could nevertheless be reconsidered before starting the core of the Basic Design phase are: the choice of an internal fuelstorage and a gas fuel handling chain, a rectangular reactor building with a single wall containment, the steam generator size the vertical handling of components. In addition, BOP studies considering the MARCOULE site as a possible one are going on.The next important milestone is at the end of 2015 with the release by the Project team of a convincing and coherent Conceptual Design file