Junior Recital, Scot Mitchell, trumpet

The presentation of this junior recital will fulfill in part the requirements for the Bachelor of Music degree in Music Education. Scot Mitchell studies trumpet with Dr. Rex Richardson

Genome editing of HBG1 and HBG2 to induce fetal hemoglobin

Induction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic repeats/Cas9-mediated disruption of DNA regulatory elements that repress gamma-globin gene (HBG1 and HBG2) expression is a promising therapeutic strategy for sickle cell disease (SCD) and beta-thalassemia, although the optimal technical approaches and limiting toxicities are not yet fully defined. We disrupted an HBG1/HBG2 gene promoter motif that is bound by the transcriptional repressor BCL11A. Electroporation of Cas9 single guide RNA ribonucleoprotein complex into normal and SCD donor CD34+ hematopoietic stem and progenitor cells resulted in high frequencies of on-target mutations and the induction of HbF to potentially therapeutic levels in erythroid progeny generated in vitro and in vivo after transplantation of hematopoietic stem and progenitor cells into nonobese diabetic/severe combined immunodeficiency/Il2rgamma-/-/KitW41/W41 immunodeficient mice. On-target editing did not impair CD34+ cell regeneration or differentiation into erythroid, T, B, or myeloid cell lineages at 16 to 17 weeks after xenotransplantation. No off-target mutations were detected by targeted sequencing of candidate sites identified by circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq), an in vitro genome-scale method for detecting Cas9 activity. Engineered Cas9 containing 3 nuclear localization sequences edited human hematopoietic stem and progenitor cells more efficiently and consistently than conventional Cas9 with 2 nuclear localization sequences. Our studies provide novel and essential preclinical evidence supporting the safety, feasibility, and efficacy of a mechanism-based approach to induce HbF for treating hemoglobinopathies

Junior Recital, Aaron Bottoms, trumpet

The presentation of this junior recital will fulfill in part the requirements for the Bachelor of Music degree in Performance. Aaron Bottoms studies trumpet with Kevin Maloney

Methane storms as a driver of Titan's dune orientation

Titan's equatorial regions are covered by eastward propagating linear dunes. This direction is opposite to mean surface winds simulated by Global Climate Models (GCMs), which are oriented westward at these latitudes, similar to trade winds on Earth. Different hypotheses have been proposed to address this apparent contradiction, involving Saturn's gravitational tides, large scale topography or wind statistics, but none of them can explain a global eastward dune propagation in the equatorial band. Here we analyse the impact of equinoctial tropical methane storms developing in the superrotating atmosphere (i.e. the eastward winds at high altitude) on Titan's dune orientation. Using mesoscale simulations of convective methane clouds with a GCM wind profile featuring superrotation, we show that Titan's storms should produce fast eastward gust fronts above the surface. Such gusts dominate the aeolian transport, allowing dunes to extend eastward. This analysis therefore suggests a coupling between superrotation, tropical methane storms and dune formation on Titan. Furthermore, together with GCM predictions and analogies to some terrestrial dune fields, this work provides a general framework explaining several major features of Titan's dunes: linear shape, eastward propagation and poleward divergence, and implies an equatorial origin of Titan's dune sand.Comment: Published online on Nature Geoscience on 13 April 201

eXtreme Adaptive Optics Planet Imager: overview and status

As adaptive optics (AO) matures, it becomes possible to envision AO systems oriented towards specific important scientific goals rather than general-purpose systems. One such goal for the next decade is the direct imaging detection of extrasolar planets. An "extreme" adaptive optics (ExAO) system optimized for extrasolar planet detection will have very high actuator counts and rapid update rates - designed for observations of bright stars - and will require exquisite internal calibration at the nanometer level. In addition to extrasolar planet detection, such a system will be capable of characterizing dust disks around young or mature stars, outflows from evolved stars, and high Strehl ratio imaging even at visible wavelengths. The NSF Center for Adaptive Optics has carried out a detailed conceptual design study for such an instrument, dubbed the eXtreme Adaptive Optics Planet Imager or XAOPI. XAOPI is a 4096-actuator AO system, notionally for the Keck telescope, capable of achieving contrast ratios >10^7 at angular separations of 0.2-1". ExAO system performance analysis is quite different than conventional AO systems - the spatial and temporal frequency content of wavefront error sources is as critical as their magnitude. We present here an overview of the XAOPI project, and an error budget highlighting the key areas determining achievable contrast. The most challenging requirement is for residual static errors to be less than 2 nm over the controlled range of spatial frequencies. If this can be achieved, direct imaging of extrasolar planets will be feasible within this decade

BCL11A enhancer edited hematopoietic stem cells persist in rhesus monkeys without toxicity

Gene editing of the erythroid-specific BCL11A enhancer in hematopoietic stem and progenitor cells (HSPCs) from sickle cell disease (SCD) patients induces fetal hemoglobin (HbF) without detectable toxicity as assessed by mouse xenotransplant. Here, we evaluated autologous engraftment and HbF induction potential of erythroid-specific BCL11A enhancer edited HSPCs in four non-human primates. We utilized a single guide RNA (sgRNA) with identical human and rhesus target sequences to disrupt a GATA1 binding site at the BCL11A +58 erythroid enhancer. Cas9 protein and sgRNA ribonucleoprotein complex (RNP) was electroporated into rhesus HSPCs, followed by autologous infusion after myeloablation. We found that gene edits persisted in peripheral blood (PB) and bone marrow (BM) for up to 101 weeks similarly for BCL11A enhancer or control locus (AAVS1) targeted cells. Biallelic BCL11A enhancer editing resulted in robust gamma-globin induction, with the highest levels observed during stress erythropoiesis. Indels were evenly distributed across PB and BM lineages. Off-target edits were not observed. Non-homologous end-joining repair alleles were enriched in engrafting HSCs. In summary, we find that edited HSCs can persist for at least 101 weeks post-transplant, and biallelic edited HSCs provide substantial HbF levels in PB red blood cells, together supporting further clinical translation of this approach

Os saberes a ensinar e para ensinar matemática e suas relações com o ensino industrial brasileiro

Disponível em: http://revistas.upel.edu.ve/index.php/paradigma/article/view/6907/0Este trabalho é parte de uma pesquisa de doutorado que se preocupa em investigar o ensino de matemática no Liceu e na Escola Industrial de Florianópolis no período de 1937 a 1961. O objetivo é identificar os saberes a ensinar e para ensinar nos cursos do Liceu Industrial e da Escola Industrial de Florianópolis e quais as principais mudanças no ensino de Mat emática destas instituições de ensino industrial. Foram utilizados como referenciais teóricos Chervel (1990) sobre história das disciplinas escolares, Julia (2001) sobre cultura escolar , Hofstetter & Valente (2017) a respeito dos saberes a ensinar , Hofstet ter et al . (2017) na definição dos experts e Cellard (2008) para a análise documental . Percebeu - se que o ensino de Matemática era voltado para cálculos básicos, pois o enfoque era formar o aluno para a indústria, apesar de se intensificar o ensino de Álgeb ra e Trigonometria no início dos anos de 1940. Palavras - chave: Ensino Industrial. História da Educação Matemática. Experts . Saberes a ensinar. Saberes para ensinar

Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: Complement component C1q and Prnp polymorphisms

The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case–control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in southcentral Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n = 68) and CWD-negative (n = 91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p \u3c 0.05. After controlling for Prnp, we found weak support for an elevated risk of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility

eXtreme Adaptive Optics Planet Imager: overview and status

As adaptive optics (AO) matures, it becomes possible to envision AO systems oriented towards specific important scientific goals rather than general-purpose systems. One such goal for the next decade is the direct imaging detection of extrasolar planets. An "extreme" adaptive optics (ExAO) system optimized for extrasolar planet detection will have very high actuator counts and rapid update rates - designed for observations of bright stars - and will require exquisite internal calibration at the nanometer level. In addition to extrasolar planet detection, such a system will be capable of characterizing dust disks around young or mature stars, outflows from evolved stars, and high Strehl ratio imaging even at visible wavelengths. The NSF Center for Adaptive Optics has carried out a detailed conceptual design study for such an instrument, dubbed the eXtreme Adaptive Optics Planet Imager or XAOPI. XAOPI is a 4096-actuator AO system, notionally for the Keck telescope, capable of achieving contrast ratios >10^7 at angular separations of 0.2-1". ExAO system performance analysis is quite different than conventional AO systems - the spatial and temporal frequency content of wavefront error sources is as critical as their magnitude. We present here an overview of the XAOPI project, and an error budget highlighting the key areas determining achievable contrast. The most challenging requirement is for residual static errors to be less than 2 nm over the controlled range of spatial frequencies. If this can be achieved, direct imaging of extrasolar planets will be feasible within this decade