Numerical Simulation of a Passive Control of the Flow Around an Aerofoil Using a Flexible, Self Adaptive Flaplet

© 2018 The Author(s) Self-activated feathers are used by almost all birds to adapt their wing characteristics to delay stall or to moderate its adverse effects (e.g., during landing or sudden increase in angle of attack due to gusts). Some of the feathers are believed to pop up as a consequence of flow separation and to interact with the flow and produce beneficial modifications of the unsteady vorticity field. The use of self adaptive flaplets in aircrafts, inspired by birds feathers, requires the understanding of the physical mechanisms leading to the mentioned aerodynamic benefits and the determination of the characteristics of optimal flaps including their size, positioning and ideal fabrication material. In this framework, this numerical study is divided in two parts. Firstly, in a simplified scenario, we determine the main characteristics that render a flap mounted on an aerofoil at high angle of attack able to deliver increased lift and improved aerodynamic efficiency, by varying its length, position and its natural frequency. Later on, a detailed direct numerical simulation analysis is used to understand the origin of the aerodynamic benefits introduced by the flaplet movement induced by the interaction with the flow field. The parametric study that has been carried out, reveals that an optimal flap can deliver a mean lift increase of about 20% on a NACA0020 aerofoil at an incidence of 20 o degrees. The results obtained from the direct numerical simulation of the flow field around the aerofoil equipped with the optimal flap at a chord Reynolds number of 2 × 10 4 shows that the flaplet movement is mainly induced by a cyclic passage of a large recirculation bubble on the aerofoil suction side. In turns, when the flap is pushed downward, the induced plane jet displaces the trailing edge vortices further downstream, away from the wing, moderating the downforce generated by those vortices and regularising the shedding cycle that appears to be much more organised when the optimal flaplet configuration is selected

Deactylase inhibition in myeloproliferative neoplasms

Myeloproliferative neoplasms (MPN) are clonal haemopoietic progenitor cell disorders characterized by the proliferation of one or more of the haemopoietic lineages (myeloid, erythroid and/or megakaryocytic). The MPNs include eight haematological disorders: chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), systemic mastocytosis (SM), chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), chronic neutrophilic leukemia (CNL), and unclassifiable MPN (MPN, U). Therapeutic interventions for MPNs include the use of tyrosine kinase inhibitors (TKIs) for BCR-ABL1+ CML and JAK2 inhibitors for PV, ET and PMF. Histone deacetylase inhibitors (HDACi) are a novel class of drugs capable of altering the acetylation status of both histone and non-histone proteins, thereby affecting a repertoire of cellular functions in neoplastic cells including proliferation, differentiation, immune responses, angiogenesis and survival. Preliminary studies indicate that HDACi when used in combination with tyrosine kinase or JAK2 inhibitors may overcome resistance to the latter agents and enhance the pro-apoptotic effects on MPN cells. This review provides a review of pre-clinical and clinical studies that have explored the use of HDACi as potential therapeutics for MPNs

Epigenetic abnormalities in myeloproliferative neoplasms: a target for novel therapeutic strategies

The myeloproliferative neoplasms (MPNs) are a group of clonal hematological malignancies characterized by a hypercellular bone marrow and a tendency to develop thrombotic complications and to evolve to myelofibrosis and acute leukemia. Unlike chronic myelogenous leukemia, where a single disease-initiating genetic event has been identified, a more complicated series of genetic mutations appear to be responsible for the BCR-ABL1-negative MPNs which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Recent studies have revealed a number of epigenetic alterations that also likely contribute to disease pathogenesis and determine clinical outcome. Increasing evidence indicates that alterations in DNA methylation, histone modification, and microRNA expression patterns can collectively influence gene expression and potentially contribute to MPN pathogenesis. Examples include mutations in genes encoding proteins that modify chromatin structure (EZH2, ASXL1, IDH1/2, JAK2V617F, and IKZF1) as well as epigenetic modification of genes critical for cell proliferation and survival (suppressors of cytokine signaling, polycythemia rubra vera-1, CXC chemokine receptor 4, and histone deacetylase (HDAC)). These epigenetic lesions serve as novel targets for experimental therapeutic interventions. Clinical trials are currently underway evaluating HDAC inhibitors and DNA methyltransferase inhibitors for the treatment of patients with MPNs

Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib

We explored the impact of early molecular response (EMR; BCR-ABL 10%) on imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all arms, EMR failure was associated with lower rates of molecular response, an increased risk of progression, and lower overall survival compared with EMR achievement. We also analyzed patient and treatment characteristics associated with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm. High Sokal risk score was associated with a high rate of EMR failure on imatinib, but not on nilotinib. In contrast, reduced dose intensity and dose interruptions were strongly associated with EMR failure in nilotinib-treated, but not imatinib-treated, patients. This study is registered at www.clinicaltrials.gov as #NCT00471497.123913531360Novartis Pharmaceuticals Corporatio

Functional and genetic aberrations of in vitro cultured marrow-derived mesenchymal stromal cells of patients with classical Philedelphia-negative myeloproliferative neoplasms

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Reduced hematopoietic reserves in DNA interstrand crosslink repair-deficient Ercc1(−/−) mice

The ERCC1-XPF heterodimer is a structure-specific endonuclease involved in both nucleotide excision repair and interstrand crosslink repair. Mice carrying a genetic defect in Ercc1 display symptoms suggestive of a progressive, segmental progeria, indicating that disruption of one or both of these DNA damage repair pathways accelerates aging. In the hematopoietic system, there are defined age-associated changes for which the cause is unknown. To determine if DNA repair is critical to prolonged hematopoietic function, hematopoiesis in Ercc1(−/−) mice was compared to that in young and old wild-type mice. Ercc1(−/−) mice (3-week-old) exhibited multilineage cytopenia and fatty replacement of bone marrow, similar to old wild-type mice. In addition, the proliferative reserves of hematopoietic progenitors and stress erythropoiesis were significantly reduced in Ercc1(−/−) mice compared to age-matched controls. These features were not seen in nucleotide excision repair-deficient Xpa(−/−) mice, but are characteristic of Fanconi anemia, a human cancer syndrome caused by defects in interstrand crosslink repair. These data support the hypothesis that spontaneous interstrand crosslink damage contributes to the functional decline of the hematopoietic system associated with aging