1,262 research outputs found
Consumption Taxes: An Examination
The current in orne tax system fails to achieve several of these goals. This paper will examine three alternatives to the income tax: a national sales tax, a value added tax, and a personal expen iture tax. The three taxes create the same tax on an item of consumption through different methods. These options will be discussed in comparison to the current income tax on the basis of administrative efficiency, equity, economic consequences, and transitional difficulties
Building and maintaining trust in clinical decision support: Recommendations from the Patient‐Centered CDS Learning Network
Knowledge artifacts in digital repositories for clinical decision support (CDS) can promote the use of CDS in clinical practice. However, stakeholders will benefit from knowing which they can trust before adopting artifacts from knowledge repositories. We discuss our investigation into trust for knowledge artifacts and repositories by the Patient‐Centered CDS Learning Network’s Trust Framework Working Group (TFWG). The TFWG identified 12 actors (eg, vendors, clinicians, and policy makers) within a CDS ecosystem who each may play a meaningful role in prioritizing, authoring, implementing, or evaluating CDS and developed 33 recommendations distributed across nine “trust attributes.” The trust attributes and recommendations represent a range of considerations such as the “Competency” of knowledge artifact engineers and the “Organizational Capacity” of institutions that develop and implement CDS. The TFWG findings highlight an initial effort to make trust explicit and embedded within CDS knowledge artifacts and repositories and thus more broadly accepted and used.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154962/1/lrh210208.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154962/2/lrh210208_am.pd
An immortalised mesenchymal stem cell line maintains mechano-responsive behaviour and can be used as a reporter of substrate stiffness
The mechanical environment can influence cell behaviour, including changes to transcriptional and proteomic regulation, morphology and, in the case of stem cells, commitment to lineage. However, current tools for characterizing substrates’ mechanical properties, such as atomic force microscopy (AFM), often do not fully recapitulate the length and time scales over which cells ‘feel’ substrates. Here, we show that an immortalised, clonal line of human mesenchymal stem cells (MSCs) maintains the responsiveness to substrate mechanics observed in primary cells, and can be used as a reporter of stiffness. MSCs were cultured on soft and stiff polyacrylamide hydrogels. In both primary and immortalised MSCs, stiffer substrates promoted increased cell spreading, expression of lamin-A/C and translocation of mechano-sensitive proteins YAP1 and MKL1 to the nucleus. Stiffness was also found to regulate transcriptional markers of lineage. A GFP-YAP/RFP-H2B reporter construct was designed and virally delivered to the immortalised MSCs for in situ detection of substrate stiffness. MSCs with stable expression of the reporter showed GFP-YAP to be colocalised with nuclear RFP-H2B on stiff substrates, enabling development of a cellular reporter of substrate stiffness. This will facilitate mechanical characterisation of new materials developed for applications in tissue engineering and regenerative medicine
Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus.
HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans
Teacher Salaries in the Mountain West, 2019 - 2021
This fact sheet examines state-level data of teacher salary benchmarks from the National Education Association, a labor union representing public school teachers and other education faculty in the U.S. Data are presented on average teacher salaries, average teacher starting salaries, and teacher pay penalties in the Mountain West (Arizona, Colorado, Nevada, New Mexico, and Utah)
Self-healing, stretchable and robust interpenetrating network hydrogels
A self-healable stretchable hydrogel system that can be readily synthesized while also possessing robust compressive strength has immense potential for regenerative medicine. Herein, we have explored the addition of commercially available unfunctionalized polysaccharides as a route to synthesize self-healing, stretchable poly(ethylene glycol) (PEG) interpenetrating networks (IPNs) as extracellular matrix (ECM) mimics. The introduction of self-healing and stretchable properties has been achieved while maintaining the robust mechanical strength of the orginal, single network PEG-only hydrogels (ultimate compressive stress up to 2.4 MPa). This has been accomplished without the need for complicated and expensive functionalization of the natural polymers, enhancing the translational applicability of these new biomaterials.Postprint (published version
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