Vortex nozzle interaction in solid rocket motors: A scaling law for upstream acoustic response

In solid rocket motors, vortex nozzle interactions can be a source of large-amplitude pressure pulsations. Using a two-dimensional frictionless flow model, a scaling law is deduced, which describes the magnitude of a pressure pulsation as being proportional to the product of the dynamic pressure of the upstream main flow and of vortex circu- lation. The scaling law was found to be valid for both an integrated noz- zle with surrounding cavity and a nozzle geometry without surrounding cavity that forms a right angle with the combustion chamber side wall. Deviations from the scaling law only occur when unrealistically strong circulations are considered

Sights and insights: Vocational outdoor students’ learning

Outdoor leader and adventure sport education in the United Kingdom has been characterized by an over-emphasis on technical skills at the expense of equally important, but often marginalized intra- and inter-personal skills necessary for contemporary outdoor employment. This study examined the lived experience of vocational outdoor students in order, firstly, to identify what was learned about the workplace through using reflective practice and, secondly, what was learned about reflective practice through this experience. The study used a purposive sample of students (n=15) who were invited to maintain reflective journals during summer work experience, and this was followed up with semi-structured interviews. Manual Interpretative Phenomenological Analysis (IPA) revealed that in the workplace setting students used reflective practice to understand and develop technical proficiency, support awareness of the value of theory, and acted as a platform to express emergent concepts of ‘professionalism’. Lessons about reflective practice emphasized its value in social settings, acknowledging different ways of reflection, and understanding and managing professional life beyond graduation

Trocar-guided total tension-free vaginal mesh repair of post-hysterectomy vaginal vault prolapse

Contains fulltext : 81076.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The objective of this study was to report 1 year anatomical and functional outcomes of trocar-guided total tension-free vaginal mesh (Prolift) repair for post-hysterectomy vaginal vault prolapse with one continuous piece of polypropylene mesh. METHODS: We conducted a prospective observational cohort study of 46 patients. A minimum sample size of 35 patients was needed to detect a recurrence rate of less than 20% at 12 months. Instruments of measurement used were pelvic organ prolapse quantification and validated questionnaires. RESULTS: Overall anatomical success was 91% (95% confidence interval 83-99), with significant improvement in experienced bother and quality of life. Mesh exposure occurred in seven patients (15%). No adverse effects on sexual function could be detected. CONCLUSIONS: Trocar-guided total tension-free vaginal mesh (Prolift) repair with one continuous piece of mesh for post-hysterectomy vaginal vault prolapse is well tolerated and anatomically and functionally highly effective. Results of controlled trials will determine its position in the operative armamentarium

Perrault Aux Prises Avec la Fontaine: Imitation, Compétition et Correction Dans Les Fables de Faërne (1699)

Known especially for his fairy tales, Charles Perrault is also the author of the Fables de Faërne (1699). In this French translation of the Neo-Latin volume Fabulae Centum (1564), written by the Italian humanist Gabriel Faerno, Perrault had to position himself against his renowned predecessor Jean de La Fontaine, who had been dominating fable literature for decades. Perrault could either imitate his famous example, or evade it, due to anxiety of influence. To illustrate this inner struggle, we systematically compare both authors’ fables, concentrating our analysis on versification (metre and rhyme), vocabulary and apostrophe. In our comparison, we constantly verify whether any of the resemblances could be attributable to other French, versified fable books read by both Perrault and La Fontaine. Occasionally, this seems to be the case for the anonymous collection L’Esbatement moral des animaux (1578).Vakpublicati

Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling

Despite substantial efforts to understand the interactions between nanoparticles and cells, the cellular processes that determine the efficiency of intracellular drug delivery remain largely unclear. Here we examined cellular uptake of siRNA delivered in lipid nanoparticles (LNPs) using cellular trafficking probes in combination with automated high-throughput confocal microscopy as well as defined perturbations of cellular pathways paired with systems biology approaches to uncover protein-protein and protein-small molecule interactions. We show that multiple cell signaling effectors are required for initial cellular entry of LNPs through macropinocytosis, including proton pumps, mTOR, and cathepsins. SiRNA delivery is substantially reduced as ≅70% of the internalized siRNA undergoes exocytosis through egress of LNPs from late endosomes/lysosomes. Niemann Pick type C1 (NPC1) is shown to be an important regulator of the major recycling pathways of LNP-delivered siRNAs. NPC1-deficient cells show enhanced cellular retention of LNPs inside late endosomes/lysosomes and increased gene silencing of the target gene. Our data suggests that siRNA delivery efficiency might be improved by designing delivery vehicles that can escape the recycling pathways

Proteomic Analysis of the Dysferlin Protein Complex Unveils Its Importance for Sarcolemmal Maintenance and Integrity

Dysferlin is critical for repair of muscle membranes after damage. Mutations in dysferlin lead to a progressive muscular dystrophy. Recent studies suggest additional roles for dysferlin. We set out to study dysferlin's protein-protein interactions to obtain comprehensive knowledge of dysferlin functionalities in a myogenic context. We developed a robust and reproducible method to isolate dysferlin protein complexes from cells and tissue. We analyzed the composition of these complexes in cultured myoblasts, myotubes and skeletal muscle tissue by mass spectrometry and subsequently inferred potential protein functions through bioinformatics analyses. Our data confirm previously reported interactions and support a function for dysferlin as a vesicle trafficking protein. In addition novel potential functionalities were uncovered, including phagocytosis and focal adhesion. Our data reveal that the dysferlin protein complex has a dynamic composition as a function of myogenic differentiation. We provide additional experimental evidence and show dysferlin localization to, and interaction with the focal adhesion protein vinculin at the sarcolemma. Finally, our studies reveal evidence for cross-talk between dysferlin and its protein family member myoferlin. Together our analyses show that dysferlin is not only a membrane repair protein but also important for muscle membrane maintenance and integrity

Apical and basal matrix remodeling control epithelial morphogenesis

Epithelial tissues can elongate in two dimensions by polarized cell intercalation, oriented cell division, or cell shape change, owing to local or global actomyosin contractile forces acting in the plane of the tissue. In addition, epithelia can undergo morphogenetic change in three dimensions. We show that elongation of the wings and legs of Drosophila involves a columnar-to-cuboidal cell shape change that reduces cell height and expands cell width. Remodeling of the apical extracellular matrix by the Stubble protease and basal matrix by MMP1/2 proteases induces wing and leg elongation. Matrix remodeling does not occur in the haltere, a limb that fails to elongate. Limb elongation is made anisotropic by planar polarized Myosin-II, which drives convergent extension along the proximal-distal axis. Subsequently, Myosin-II relocalizes to lateral membranes to accelerate columnar-to-cuboidal transition and isotropic tissue expansion. Thus, matrix remodeling induces dynamic changes in actomyosin contractility to drive epithelial morphogenesis in three dimensions

Peripheral Nervous System Genes Expressed in Central Neurons Induce Growth on Inhibitory Substrates

Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS’s enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons