School reform and tax reform: a successful marriage?

Education ; Property tax ; Michigan

Targeting deforestation rates in climate change policy: a "Preservation Pathway" approach

We present a new methodological approach to incorporating deforestation within the international climate change negotiating regime. The approach, called "Preservation Pathway" combines the desire for forest preservation with the need to reduce emissions associated with forest loss by focusing on the relative rate of change of forest cover as the criteria by which countries gain access to trading preserved forest carbon stocks. This approach avoids the technically challenging task of quantifying historical or future deforestation emission baselines. Rather, it places emphasis on improving quantification of contemporary stocks and the relative decline in deforestation rates necessary to preserve those stocks. This approach places emphasis on the complete emissions trajectory necessary to attain an agreed-upon preserved forest and as such, meets both forest conservation and climate goals simultaneously

Gamma-ray spectroscopy at TRIUMF-ISAC: The new frontier of radioactive ion beam research

High-resolution gamma-ray spectroscopy is essential to fully exploit the unique scientific opportunities at the next generation radioactive ion beam facilities such as the TRTUMF Isotope Separator and Accelerator (TSAC). At IS AC the 871 spectrometer and its associated auxiliary detectors is optimize for p-decay studies while TIGRESS an array of segmented clover HPGe detectors has been designed for studies with accelerated beams. This paper gives a brief overview of these facilities and also presents recent examples of the diverse experimental program carried out at the STI spectrometer. © 2009 American Institute of Physics

Rapid, High Throughput, Automated Detection of SARS-CoV-2 Neutralizing Antibodies Against Wuhan-Wt, Delta and Omicron BA1, BA2 Spike Trimers

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of human angiotensin converting enzyme 2 (hACE-2) binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using Wuhan-WT (vaccine strain), delta (B.1.167.2), omicron BA1 and BA2 variant viral strains showed strong correlation with cell-based pseudovirus neutralization activity (PNA) and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta and omicron variant resistance to neutralization in samples with paired vaccine strain and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. Importantly, this completely automated assay can be performed in 4 h to measure neutralizing antibody titers for 16 samples over 8 serial dilutions or, 128 samples at a single dilution with replicates. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels

Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray

Metastatic colorectal carcinomas (CRC) resistant to chemotherapy may benefit from targeting monoclonal therapy cetuximab when they express the epidermal growth factor receptor (EGFR). Because of its clinical implications, we studied EGFR expression by immunohistochemistry on tissue sections of primary CRC (n=32) and their related metastases (n=53). A tissue microarray (TMA) was generated from the same paraffin blocks to determine whether this technique could be used for EGFR screening in CRC. On tissue sections, 84% of the primary CRC and 94% of the metastases were EGFR-positive. When matched, they showed a concordant EGFR-positive status in 78% of the cases. Moreover, staining intensity and extent of EGFR-positive cells in the primary CRC correlated with those observed in the synchronous metastases. On TMA, 65% of the primary CRC, 66% of the metastases, and 43% of the matched primary CRC metastases were EGFR-positive. There was no concordant EGFR status between the primary and the metastatic sites. A strong discrepancy of EGFR status was noted between TMA and tissue sections. In conclusion, EGFR expression measured in tissue sections from primary CRC and their related metastases was found to be similar and frequent, but it was significantly underestimated by the TMA technique

Gamma-ray spectroscopy at TRIUMF-ISAC

The 8π spectrometer at TRIUMF-ISAC consists of 20 Compton-suppressed germanium detectors and various auxiliary devices. The Ge array, once used for studies of nuclei at high angular momentum, has been transformed into the world\u27s most powerful device dedicated to radioactive-decay studies. Many improvements in the spectrometer have been made, including a high-throughput data acquisition system, installation of a moving tape collector, incorporation of an array of 20 plastic scintillators for β-particle tagging, 5 Si(Li) detectors for conversion electrons, and 10 BaF2 detectors for fast-lifetime measurements. Experiments can be performed where data from all detectors are collected simultaneously, resulting in a very detailed view of the nucleus through radioactive decay. A number of experimental programmes have been launched that take advantage of the versatility of the spectrometer, and the intense beams available at TRIUMF-ISAC. © 2006 American Institute of Physics

Resveratrol regulates the PTEN/AKT pathway through androgen receptor-dependent and -independent mechanisms in prostate cancer cell lines

The tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome 10) and the androgen receptor (AR) play important roles in tumor development and progression in prostate carcinogenesis. Among many functions, PTEN negatively regulates the cytoplasmic phosphatidylinositol-3-kinase/AKT anti-apoptotic pathway; and nuclear PTEN affects the cell cycle by also negatively regulating the MAPK pathway via cyclin D. Decreased PTEN expression is correlated with prostate cancer progression. Over-expression of AR and upregulation of AR transcriptional activity are often observed in the later stages of prostate cancer. Recent studies indicate that PTEN regulates AR activity and stability. However, the mechanism of how AR regulates PTEN has never been studied. Furthermore, resveratrol, a phytoalexin enriched in red grapes, strawberries and peanuts, has been shown to inhibit AR transcriptional activity in prostate cancer cells. In this study, we use prostate cancer cell lines to test the hypothesis that resveratrol inhibits cellular proliferation in both AR-dependent and -independent mechanisms. We show that resveratrol inhibits AR transcriptional activity in both androgen-dependent and -independent prostate cancer cells. Additionally, resveratrol stimulates PTEN expression through AR inhibition. In contrast, resveratrol directly binds epidermal growth factor receptor (EGFR) rapidly inhibiting EGFR phosphorylation, resulting in decreased AKT phosphorylation, in an AR-independent manner. Thus, resveratrol may act as potential adjunctive treatment for late-stage hormone refractory prostate cancer. More importantly, for the first time, our study demonstrates the mechanism by which AR regulates PTEN expression at the transcription level, indicating the direct link between a nuclear receptor and the PI3K/AKT pathway

A proteomic approach for the identification of novel lysine methyltransferase substrates

<p>Abstract</p> <p>Background</p> <p>Signaling via protein lysine methylation has been proposed to play a central role in the regulation of many physiologic and pathologic programs. In contrast to other post-translational modifications such as phosphorylation, proteome-wide approaches to investigate lysine methylation networks do not exist.</p> <p>Results</p> <p>In the current study, we used the ProtoArray^®platform, containing over 9,500 human proteins, and developed and optimized a system for proteome-wide identification of novel methylation events catalyzed by the protein lysine methyltransferase (PKMT) SETD6. This enzyme had previously been shown to methylate the transcription factor RelA, but it was not known whether SETD6 had other substrates. By using two independent detection approaches, we identified novel candidate substrates for SETD6, and verified that all targets tested <it>in vitro </it>and in cells were genuine substrates.</p> <p>Conclusions</p> <p>We describe a novel proteome-wide methodology for the identification of new PKMT substrates. This technological advance may lead to a better understanding of the enzymatic activity and substrate specificity of the large number (more than 50) PKMTs present in the human proteome, most of which are uncharacterized.</p