Distinctiveness in Christian Business Education: A Call for Faculty Educational Entrepreneurship

How do Christian business departments foster distinctive business education? Using the literature in interpretive planning and distinctiveness, it is suggested that one important way is through faculty educational entrepreneurship. By calling for faculty entrepreneurship, out of the core values and competencies of each institution/department/faculty member, there is great potential to foster distinctive education that models being “salt and light” to students. Unleashing the creative energy among the faculty at each institution can lead to distinctive business education on the campus and great diversity among the business departments/schools of the CCCU

First Determination of the Weak Charge of the Proton

The Q(weak) experiment has measured the parity-violating asymmetry in (e) over right arrowp elastic scattering at Q(2) = 0.025 (GeV/c)(2), employing 145 mu A of 89% longitudinally polarized electrons on a 34.4 cm long liquid hydrogen target at Jefferson Lab. The results of the experiment\u27s commissioning run, constituting approximately 4% of the data collected in the experiment, are reported here. From these initial results, the measured asymmetry is A(ep) = -279 +/- 35 (stat) +/- 31 (syst) ppb, which is the smallest and most precise asymmetry ever measured in (e) over right arrowp scattering. The small Q(2) of this experiment has made possible the first determination of the weak charge of the proton Q(W)(p) by incorporating earlier parity-violating electron scattering (PVES) data at higher Q(2) to constrain hadronic corrections. The value of Q(W)(p) obtained in this way is Q(W)(p) (PVES) = 0.064 +/- 0.012, which is in good agreement with the standard model prediction of Q(W)(p) (SM) = 0.0710 +/- 0.0007. When this result is further combined with the Cs atomic parity violation (APV) measurement, significant constraints on the weak charges of the up and down quarks can also be extracted. That PVES + APV analysis reveals the neutron\u27s weak charge to be Q(W)(n) (PVES + APV) = -0.975 +/- 0.010

Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response

A major barrier to successful antitumor vaccination is tolerance of high-avidity T cells specific to tumor antigens. In keeping with this notion, HER-2/neu (neu)-targeted vaccines, which raise strong CD8+ T cell responses to a dominant peptide (RNEU420-429) in WT FVB/N mice and protect them from a neu-expressing tumor challenge, fail to do so in MMTV-neu (neu-N) transgenic mice. However, treatment of neu-N mice with vaccine and cyclophosphamide-containing chemotherapy resulted in tumor protection in a proportion of mice. This effect was specifically abrogated by the transfer of neu-N–derived CD4+CD25+ T cells. RNEU420-429-specific CD8+ T cells were identified only in neu-N mice given vaccine and cyclophosphamide chemotherapy which rejected tumor challenge. Tetramer-binding studies demonstrated that cyclophosphamide pretreatment allowed the activation of high-avidity RNEU420-429-specific CD8+ T cells comparable to those generated from vaccinated FVB/N mice. Cyclophosphamide seemed to inhibit regulatory T (T reg) cells by selectively depleting the cycling population of CD4+CD25+ T cells in neu-N mice. These findings demonstrate that neu-N mice possess latent pools of high-avidity neu-specific CD8+ T cells that can be recruited to produce an effective antitumor response if T reg cells are blocked or removed by using approaches such as administration of cyclophosphamide before vaccination

Trafficking of High Avidity HER-2/neu-Specific T Cells into HER-2/neu-Expressing Tumors after Depletion of Effector/Memory-Like Regulatory T Cells

Cancer vaccines are designed to activate and enhance cancer-antigen-targeted T cells that are suppressed through multiple mechanisms of immune tolerance in cancer-bearing hosts. T regulatory cell (Treg) suppression of tumor-specific T cells is one barrier to effective immunization. A second mechanism is the deletion of high avidity tumor-specific T cells, which leaves a less effective low avidity tumor specific T cell repertoire available for activation by vaccines. Treg depleting agents including low dose cyclophosphamide (Cy) and antibodies that deplete CD25-expressing Tregs have been used with limited success to enhance the potency of tumor-specific vaccines. In addition, few studies have evaluated mechanisms that activate low avidity cancer antigen-specific T cells. Therefore, we developed high and low avidity HER-2/neu-specific TCR transgenic mouse colonies specific for the same HER-2/neu epitope to define the tolerance mechanisms that specifically affect high versus low avidity tumor-specific T cells.High and low avidity CD8(+) T cell receptor (TCR) transgenic mice specific for the breast cancer antigen HER-2/neu (neu) were developed to provide a purified source of naïve, tumor-specific T cells that can be used to study tolerance mechanisms. Adoptive transfer studies into tolerant FVB/N-derived HER-2/neu transgenic (neu-N) mice demonstrated that high avidity, but not low avidity, neu-specific T cells are inhibited by Tregs as the dominant tolerizing mechanism. High avidity T cells persisted, produced IFNγ, trafficked into tumors, and lysed tumors after adoptive transfer into mice treated with a neu-specific vaccine and low dose Cy to deplete Tregs. Analysis of Treg subsets revealed a Cy-sensitive CD4(+)Foxp3(+)CD25(low) tumor-seeking migratory phenotype, characteristic of effector/memory Tregs, and capable of high avidity T cell suppression.Depletion of CD25(low) Tregs allows activation of tumor-clearing high avidity T cells. Thus, the development of agents that specifically deplete Treg subsets should translate into more effective immunotherapies while avoiding autoimmunity

Mesothelin-specific CD8+ T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients

Tumor-specific CD8+ T cells can potentially be activated by two distinct mechanisms of major histocompatibility complex class I–restricted antigen presentation as follows: direct presentation by tumor cells themselves or indirect presentation by professional antigen-presenting cells (APCs). However, controversy still exists as to whether indirect presentation (the cross-priming mechanism) can contribute to effective in vivo priming of tumor-specific CD8+ T cells that are capable of eradicating cancer in patients. A clinical trial of vaccination with granulocyte macrophage–colony stimulating factor–transduced pancreatic cancer lines was designed to test whether cross-presentation by locally recruited APCs can activate pancreatic tumor-specific CD8+ T cells. Previously, we reported postvaccination delayed-type hypersensitivity (DTH) responses to autologous tumor in 3 out of 14 treated patients. Mesothelin is an antigen demonstrated previously by gene expression profiling to be up-regulated in most pancreatic cancers. We report here the consistent induction of CD8+ T cell responses to multiple HLA-A2, A3, and A24-restricted mesothelin epitopes exclusively in the three patients with vaccine-induced DTH responses. Importantly, neither of the vaccinating pancreatic cancer cell lines expressed HLA-A2, A3, or A24. These results provide the first direct evidence that CD8 T cell responses can be generated via cross-presentation by an immunotherapy approach designed to recruit APCs to the vaccination site

Effect of scavenger receptor BI antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation

Hepatitis C virus (HCV) entry inhibitors have been hypothesized to prevent infection of the liver after transplantation. ITX5061 is a Scavenger Receptor B-I (SR-BI) antagonist that blocks HCV entry and infection in vitro. We assessed the safety and efficacy of ITX5061 to limit HCV infection of the graft. The study included 23 HCV infected patients undergoing liver transplantation. The first 13 "control" patients did not receive drug. The subsequent 10 patients received ITX5061 150 mg immediately pre- and post-transplant, and daily for 1 week thereafter. ITX5061 pharmacokinetics and plasma HCV RNA were quantified. Viral genetic diversity was measured by ultradeep pyrosequencing. ITX5061 was well tolerated with measurable plasma concentrations during therapy. Whilst the median HCV RNA reduction was greater in ITX treated patients at all time points in the first week after transplantation there was no difference in the overall change in the area over the HCV RNA curve in the 7-day treatment period. However, in genotype 1 infected patients treatment was associated with a sustained reduction in HCV RNA levels compared to the control group (area over the HCV RNA curve analysis, p=0.004). Ultradeep pyrosequencing revealed a complex and evolving pattern of HCV variants infecting the graft during the first week. ITX5061 significantly limited viral evolution where the median divergence between day 0 and day 7 was 3.5% in the control group compared to 0.1% in the treated group.CONCLUSIONS: ITX5061 reduces plasma HCV RNA post transplant notably in genotype 1 infected patients and slows viral evolution. Following liver transplantation the likely contribution of extrahepatic reservoirs of HCV necessitates combining entry inhibitors such as ITX5061 with inhibitors of replication in future studies. Clinicaltrials.gov NCT01292824. This article is protected by copyright. All rights reserved.</p

Q(weak): First Direct Measurement of the Proton\u27s Weak Charge

The Q(weak) experiment, which took data at Jefferson Lab in the period 2010 - 2012, will precisely determine the weak charge of the proton by measuring the parity-violating asymmetry in elastic e-p scattering at 1.1 GeV using a longitudinally polarized electron beam and a liquid hydrogen target at a low momentum transfer of Q(2) = 0.025 ( GeV/c)(2). The weak charge of the proton is predicted by the Standard Model and any significant deviation would indicate physics beyond the Standard Model. The technical challenges and experimental apparatus for measuring the weak charge of the proton will be discussed, as well as the method of extracting the weak charge of the proton. The results from a small subset of the data, that has been published, will also be presented. Furthermore an update will be given of the current status of the data analysis

Exhumation of the central Wasatch Mountains, Utah: 2. Thermokinematic model of exhumation, erosion, and thermochronometer interpretation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95279/1/jgrb13381.pd

ASASSN-14ko is a Periodic Nuclear Transient in ESO 253-G003

We present the discovery that ASASSN-14ko is a periodically flaring AGN at the center of the galaxy ESO 253-G003. At the time of its discovery by the All-Sky Automated Survey for Supernovae (ASAS-SN), it was classified as a supernova close to the nucleus. The subsequent six years of V- and g-band ASAS-SN observations reveal that ASASSN-14ko has nuclear flares occurring at regular intervals. The seventeen observed outbursts show evidence of a decreasing period over time, with a mean period of $P_0 = 114.2 \pm 0.4$ days and a period derivative of $\dot{P} = -0.0017\pm0.0003$. The most recent outburst in May 2020, which took place as predicted, exhibited spectroscopic changes during the rise and a had a UV bright, blackbody spectral energy distribution similar to tidal disruption events (TDEs). The X-ray flux decreased by a factor of 4 at the beginning of the outburst and then returned to its quiescent flux after ~8 days. TESS observed an outburst during Sectors 4-6, revealing a rise time of $5.60 \pm 0.05$ days in the optical and a decline that is best fit with an exponential model. We discuss several possible scenarios to explain ASASSN-14ko's periodic outbursts, but currently favor a repeated partial TDE. The next outbursts should peak in the optical on UT 2020-09-7.4$\pm$1.1 and UT 2020-12-26.5$\pm$1.4.Comment: 26 pages, 15 figures, 7 tables. Will be submitted to ApJ. The latest flare is currently ongoing, as we predicte