A Consideration of the Cobalt Complexes

This 13 page thesis examines structural problems and preparation methods of complex cobalt compounds

'Encore' Red Raspberry

'Encore' is a new red raspberry developed by Cornell University at the New York State Agricultural Experiment Station in Geneva, New York. 'Encore' is outstanding for its consistent performance over many years of testing. 'Encore' is a late season red raspberry cultivar developed for growers interested in increasing their late season production. Specifically, it has excellent winter hardiness in zone 5, very good plant production and vigor, and commercial yields of large size fruit that peak in production late in the harvest season. 'Encore' is adapted to upick, retail, and wholesale markets. Its firm fruit withstand handling and packing to produce an attractive pack for resale. 'Encore' has potential to become a leading red raspberry cultivar in the East Coast and Great Lakes regions

PuF, An Antimetastatic and Developmental Signaling Protein, Interacts with the Alzheimer’s Amyloid-β Precursor Protein via a Tissue-Specific Proximal Regulatory Element (PRE)

Background: Alzheimer’s disease (AD) is intimately tied to amyloid-β (Aβ) peptide. Extraneuronal brain plaques consisting primarily of Aβ aggregates are a hallmark of AD. Intraneuronal Aβ subunits are strongly implicated in disease progression. Protein sequence mutations of the Aβ precursor protein (APP) account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP) may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or “proximal regulatory element” (PRE), at −76/−47, from the +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay (EMSA) and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. Results: EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 (AP2), nm23 nucleoside diphosphate kinase/metastatic inhibitory protein (PuF), and specificity protein 1 (SP1). These sites crossed a known single nucleotide polymorphism (SNP). EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. Conclusions: We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also interacts with the integrins. These proteins are connected to vital cellular and neurological functions. In addition, the transcription factor PuF is a known inhibitor of metastasis and regulates cell growth during development. Given that APP is a known cell adhesion protein and ferroxidase, this suggests biochemical links among cell signaling, the cell cycle, iron metabolism in cancer, and AD in the context of overall aging

Novel upregulation of amyloid-β precursor protein (APP) by microRNA-346 via targeting of APP mRNA 5′-untranslated region: Implications in Alzheimer’s disease

In addition to the devastating symptoms of dementia, Alzheimer’s disease (AD) is characterized by accumulation of the processing products of the amyloid-β (Aβ) peptide precursor protein (APP). APP’s non-pathogenic functions include regulating intracellular iron (Fe) homeostasis. MicroRNAs are small (~ 20 nucleotides) RNA species that instill specificity to the RNA-induced silencing complex (RISC). In most cases, RISC inhibits mRNA translation through the 3′-untranslated region (UTR) sequence. By contrast, we report a novel activity of miR-346: specifically, that it targets the APP mRNA 5′-UTR to upregulate APP translation and Aβ production. This upregulation is reduced but not eliminated by knockdown of argonaute 2. The target site for miR-346 overlaps with active sites for an iron-responsive element (IRE) and an interleukin-1 (IL-1) acute box element. IREs interact with iron response protein1 (IRP1), an iron-dependent translational repressor. In primary human brain cultures, miR-346 activity required chelation of Fe. In addition, miR-346 levels are altered in late-Braak stage AD. Thus, miR-346 plays a role in upregulation of APP in the CNS and participates in maintaining APP regulation of Fe, which is disrupted in late stages of AD. Further work will be necessary to integrate other metals, and IL-1 into the Fe-miR-346 activity network. We, thus, propose a “FeAR” (Fe, APP, RNA) nexus in the APP 5′-UTR that includes an overlapping miR-346-binding site and the APP IRE. When a “healthy FeAR” exists, activities of miR-346 and IRP/Fe interact to maintain APP homeostasis. Disruption of an element that targets the FeAR nexus would lead to pathogenic disruption of APP translation and protein production

School Choice in Suburbia: Test Scores, Race, and Housing Markets

Home buyers exercise school choice when shopping for a private residence due to its location in a public school district or attendance area. In this quantitative study of one Connecticut suburban district, we measure the effect of elementary school test scores and racial composition on home buyers’ willingness to purchase single-family homes over a 10-year period, controlling for house and neighbor- hood characteristics. Overall, while both test scores and race explain home prices, we found that the influence of tests declined while race became nearly seven times more influential over our decade-long period of study. Our interpretation of the results draws on the shifting context of school accountability, the Internet, and racial dynamics in this suburb over time

Appropriateness of antibiotic prescribing in the Emergency Department

Background Antibiotics are some of the most commonly prescribed drugs in the Emergency Department (ED) and yet data describing the overall appropriateness of antibiotic prescribing in the ED is scarce. Objectives To describe the appropriateness of antibiotic prescribing in the ED. Methods A retrospective, observational study of current practice. All patients who presented to the ED during the study period and were prescribed at least one antibiotic were included. Specialists from Infectious Disease, Microbiology and Emergency Medicine and a Senior Pharmacist assessed antibiotic appropriateness against evidence-based guidelines. Results A total of 1019 (13.6%) of patient presentations involved the prescription of at least one antibiotic. Of these, 640 (62.8%) antibiotic prescriptions were assessed as appropriate, 333 (32.7%) were assessed as inappropriate and 46 (4.5%) were deemed to be not assessable. Adults were more likely to receive an inappropriate antibiotic prescription than children (36.9% versus 22.9%; difference 14.1%, 95% CI 7.2%–21.0%). Patients who met quick Sepsis-related Organ Failure Assessment (qSOFA) criteria were more likely to be prescribed inappropriate antibiotics (56.7% versus 36.1%; difference 20.5%, 95% CI, 2.4%–38.7%). There was no difference in the incidence of appropriate antibiotic prescribing based on patient gender, disposition (admitted/discharged), reason for antibiotic administration (treatment/prophylaxis) or time of shift (day/night). Conclusions Inappropriate administration of antibiotics can lead to unnecessary adverse events, treatment failure and antimicrobial resistance. With over one in three antibiotic prescriptions in the ED being assessed as inappropriate, there is a pressing need to develop initiatives to improve antibiotic prescribing to prevent antibiotic-associated patient and community harms.No Full Tex

Excavations at the site of Vasino, Lautem District, Timor-Leste

This chapter explores the archaeology and ethnohistory of one of the distinctive fortified settlements in the eastern part of Timor-Leste. In 2009, a team from The Australian National University (ANU), together with local people, partially excavated the site of Vasino, located close to the north coast of Timor-Leste, above the modern village of Moro-Parlamento (Figure 4.1). The site had been fortified with large stone walls and the aim was to provide more data on when, how and why these fortifications were used in the region. Two related questions guided the research. First, when was the main period of fort construction initiated? Secondly, what were the prevailing environmental and social conditions of those times

POLOCAM: a millimeter wavelength cryogenic polarimeter prototype for MUSIC-POL

As a proof-of-concept, we have constructed and tested a cryogenic polarimeter in the laboratory as a prototype for the MUSIC instrument (Multiwavelength Sub/millimeter Kinetic Inductance Camera). The POLOCAM instrument consists of a rotating cryogenic polarization modulator (sapphire half-waveplate) and polarization analyzer (lithographed copper polarizers deposited on a thin film) placed into the optical path at the Lyot stop (4K cold pupil stop) in a cryogenic dewar. We present an overview of the project, design and performance results of the POLOCAM instrument (including polarization efficiencies and instrumental polarization), as well as future application to the MUSIC-POL instrument

The site of Leki Wakik, Manatuto District, Timor‑Leste

Leki Wakik is a large hilltop site with several large stone walls and circular stone arrangements located within the Manatuto district in the central region of Timor-Leste. It is similar to other hilltop sites in the area whose function and occupation time frame have been subject to debate (e.g. Lape and Chao 2008; O’Connor et al. 2012). In August 2011, a team from The Australian National University (ANU) supported by Timorese workers mapped the site and excavated five test pits intended to assess site use and occupation time frame. A substantial artefact assemblage was recovered that includes lithics, earthenware pottery, ceramics and faunal remains, which provides evidence of the use of the site and the surrounding landscape and, particularly, whether unusual circular stone arrangements demarcate special activity or occupation areas. A series of radiocarbon dates from an unusual area surrounded on three sides by large stone walls provide chronological context for the site

Non-linear sigma models with anti-de Sitter target spaces

We present evidence that there is a non-trivial fixed point for the AdS_{D+1} non-linear sigma model in two dimensions, without any matter fields or additional couplings beyond the standard quadratic action subject to a quadratic constraint. A zero of the beta function, both in the bosonic and supersymmetric cases, appears to arise from competition between one-loop and higher loop effects. A string vacuum based on such a fixed point would have string scale curvature. The evidence presented is based on fixed-order calculations carried to four loops (corresponding to O(\alpha'^3) in the spacetime effective action) and on large D calculations carried to O(D^{-2}) (but to all orders in \alpha'). We discuss ways in which the evidence might be misleading, and we discuss some features of the putative fixed point, including the central charge and an operator of negative dimension. We speculate that an approximately AdS_5 version of this construction may provide a holographic dual for pure Yang-Mills theory, and that quotients of an AdS_3 version might stand in for Calabi-Yau manifolds in compactifications to four dimensions.Comment: 44 pages, 4 figures. v2: references adde