Policy Analysis: Minimum Wage in the Portland Metropolitan Area

Oregon’s current minimum wage of $9.25 per hour is unsustainable as it does not provide adequate nutritional resources or housing for full time employees. Additionally, employers of minimum wage workers often rely on social safety net benefits for their workers which effectively subsidize wages. This creates an unnecessary burden on the taxpayer. Oregon Senate Bill 1532 increases the minimum wage incrementally within Portland’s Metropolitan Area to$14.75 in 2022. This wage provides full time minimum wage workers enough income for adequate nutrition and reasonable housing while reducing reliance on social safety net programs

Seconds-scale coherence in a tweezer-array optical clock

Optical clocks based on atoms and ions achieve exceptional precision and accuracy, with applications to relativistic geodesy, tests of relativity, and searches for dark matter. Achieving such performance requires balancing competing desirable features, including a high particle number, isolation of atoms from collisions, insensitivity to motional effects, and high duty-cycle operation. Here we demonstrate a new platform based on arrays of ultracold strontium atoms confined within optical tweezers that realizes a novel combination of these features by providing a scalable platform for isolated atoms that can be interrogated multiple times. With this tweezer-array clock, we achieve greater than 3 second coherence times and record duty cycles up to 96%, as well as stability commensurate with leading platforms. By using optical tweezer arrays --- a proven platform for the controlled creation of entanglement through microscopic control --- this work further promises a new path toward combining entanglement enhanced sensitivities with the most precise optical clock transitions

Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases.

We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA) (pU6.g1) or in vitro transcribed gRNA (gR.1). Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34+ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34+ cells had the capacity to engraft in NOD-PrkdcSCID-IL2Rγnull mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34+ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs), highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs

The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.

Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of these vectors may be limited by transgene silencing due to the genomic environment surrounding the integration site. Barrier insulators can be used to give more consistent expression and resist silencing even with lower vector copies. Here, the barrier activity of an insulator element from the human ankyrin-1 gene was analyzed in a lentiviral vector carrying an antisickling human β-globin gene. Inclusion of a single copy of the Ankyrin insulator did not affect viral titer, and improved the consistency of expression from the vector in murine erythroleukemia cells. The presence of the Ankyrin insulator element did not change transgene expression in human hematopoietic cells in short-term erythroid culture or in vivo in primary murine transplants. However, analysis in secondary recipients showed that the lentiviral vector with the Ankyrin element preserved transgene expression, whereas expression from the vector lacking the Ankyrin insulator decreased in secondary recipients. These studies demonstrate that the Ankyrin insulator may improve long-term β-globin expression in hematopoietic stem cells for gene therapy of hemoglobinopathies

Educational Demo Hyperboloid Hole in the Wall

ME450 Capstone Design and Manufacturing Experience: Fall 2015A hyperboloid of revolution demonstrates that a straight rod rotating about a central axis follows a curved path in three-dimensional space, forming a hyperboloid. This project aims to scale up a typical, tabletop hyperboloid of revolution demonstration to be life-size. The new demonstration, now six feet tall, will allow a child up to eight years of age to replace the rod. The mission of this project on a broader scale is to provide more mathematical background than traditionally available, with the hopes of getting younger generations interested in the STEM fields. As this demonstration would like to be used in classrooms and museums, the entire display will need to be easily assembled and transported.http://deepblue.lib.umich.edu/bitstream/2027.42/117344/1/ME450-F15-Project27-FinalReport.pd

Preclinical Demonstration of Lentiviral Vector-mediated Correction of Immunological and Metabolic Abnormalities in Models of Adenosine Deaminase Deficiency

Gene transfer into autologous hematopoietic stem cells by γ-retroviral vectors (gRV) is an effective treatment for adenosine deaminase (ADA)–deficient severe combined immunodeficiency (SCID). However, current gRV have significant potential for insertional mutagenesis as reported in clinical trials for other primary immunodeficiencies. To improve the efficacy and safety of ADA-SCID gene therapy (GT), we generated a self-inactivating lentiviral vector (LV) with a codon-optimized human cADA gene under the control of the short form elongation factor-1α promoter (LV EFS ADA). In ADA−/− mice, LV EFS ADA displayed high-efficiency gene transfer and sufficient ADA expression to rescue ADA−/− mice from their lethal phenotype with good thymic and peripheral T- and B-cell reconstitution. Human ADA-deficient CD34+ cells transduced with 1–5 × 107 TU/ml had 1–3 vector copies/cell and expressed 1–2x of normal endogenous levels of ADA, as assayed in vitro and by transplantation into immune-deficient mice. Importantly, in vitro immortalization assays demonstrated that LV EFS ADA had significantly less transformation potential compared to gRV vectors, and vector integration-site analysis by nrLAM-PCR of transduced human cells grown in immune-deficient mice showed no evidence of clonal skewing. These data demonstrated that the LV EFS ADA vector can effectively transfer the human ADA cDNA and promote immune and metabolic recovery, while reducing the potential for vector-mediated insertional mutagenesis

Leveraging text data for causal inference using electronic health records

Text is a ubiquitous component of medical data, containing valuable information about patient characteristics and care that are often missing from structured chart data. Despite this richness, it is rarely used in clinical research, owing partly to its complexity. Using a large database of patient records and treatment histories accompanied by extensive notes by attendant physicians and nurses, we show how text data can be used to support causal inference with electronic health data in all stages, from conception and design to analysis and interpretation, with minimal additional effort. We focus on studies using matching for causal inference. We augment a classic matching analysis by incorporating text in three ways: by using text to supplement a multiple imputation procedure, we improve the fidelity of imputed values to handle missing data; by incorporating text in the matching stage, we strengthen the plausibility of the matching procedure; and by conditioning on text, we can estimate easily interpretable text-based heterogeneous treatment effects that may be stronger than those found across categories of structured covariates. Using these techniques, we hope to expand the scope of secondary analysis of clinical data to domains where quantitative data is of poor quality or nonexistent, but where text is available, such as in developing countries

Controlling Catalyst–Semiconductor Contacts: Interfacial Charge Separation in p‑InP Photocathodes

Charge-carrier-selective interfaces between electrocatalyst particles and semiconductor light absorbers are critical for solar photochemistry, but controlling their properties is challenging. Using thin films and nanoparticle arrays of Pt hydrogen-evolution catalysts on p-InP (a high-performance photocathode material), along with macroscopic and nanoscopic electrical and chemical analysis, we show how hydrogen alloying, the pinch-off effect for nanoscale contacts, and the formation of a native surface oxides all play different roles in creating charge-carrier-selective junctions. The new insights can be broadly applied to photocathodes, photoanodes, and overall water-splitting systems to control charge-carrier selectivity and improve performance