MODELING THE DEMAND FOR DURABLE INPUTS: DISTRIBUTED LAGS AND CAUSALITY

Vector-autoregressive-moving-average (VARMA) modeling was used to identify distributed lag relationships among farm tractor derived demand variables and to provide a basis for formally testing the hypothesis that the price of new tractor horsepower is exogeneous to its quantity demanded. Similar causality tests were used for a number of other explanatory variables, including the interest rate, price of diesel fuel, and price of used tractors. Results indicate that several lagged variables are significant causal factors and that the dynamic nature of the demand structure cannot be ignored when explaining tractor demand.Demand and Price Analysis,

Physiological and immunoblot analyses of a nitric oxide synthase (NOS)-like protein of pea (Pisum sativum L.)

Nitric oxide (NO) functions as a signal molecule in different biological processes in plants, including disease resistance. Its production is related to nitric oxide synthase (NOS). The application of chemicals that induce systemic resistance in plants did not induce NOS activity in pea, suggesting that NO functions upstream of salicylic acid (SA) in the signaling pathway of defense responses in plants. NOS activity was induced in both the incompatible and compatible interactions of pea with Ralstonia solanacearum and Pseudomonas syringae pv pisi, respectively, between 3 h to 6 h post-infiltration, indicating that NOS was involved in both resistance and disease development responses in pea. Antibodies raised against mammalian NOS did not have specificity in detecting a NOS-like protein in pea, suggesting that the pea NOS-like protein could be structurally different from mammalian NOS, and immunodetection of a plant NOS-like protein must be conducted with caution and verified with functional assays

Expression kinetics and innate immune response after electroporation and LNP-mediated delivery of a self-amplifying mRNA in the skin

In this work, we studied the expression kinetics and innate immune response of a self-amplifying mRNA (sa-RNA) after electroporation and lipid-nanoparticle (LNP)-mediated delivery in the skin of mice. Intradermal electroporation of the sa-RNA resulted in a plateau-shaped expression, with the plateau between day 3 and day 10. The overall protein expression of sa-RNA was significantly higher than that obtained after electroporation of plasmid DNA (pDNA) or non-replication mRNAs. Moreover, using IFN-beta reporter mice, we elucidated that intradermal electroporation of sa-RNA induced a short-lived moderate innate immune response, which did not affect the expression of the sa-RNA. A completely different expression profile and innate immune response were observed when LNPs were used. The expression peaked 24 h after intradermal injection of sa-RNA-LNPs and subsequently showed a sharp drop. This drop might be explained by a translational blockage caused by the strong innate immune response that we observed in IFN-beta reporter mice shortly (4 h) after intradermal injection of sa-RNA-LNPs. A final interesting observation was the capacity of sa-RNA-LNPs to transfect the draining lymph nodes after intradermal injection

Ion Mobility-Mass Spectrometry with a Radial Opposed Migration Ion and Aerosol Classifier (ROMIAC)

The first application of a novel differential mobility analyzer, the radial opposed migration ion and aerosol classifier (ROMIAC), is demonstrated. The ROMIAC uses antiparallel forces from an electric field and a cross-flow gas to both scan ion mobilities and continuously transmit target mobility ions with 100% duty cycle. In the ROMIAC, diffusive losses are minimized, and resolution of ions, with collisional cross-sections of 200–2000 Å^2, is achieved near the nondispersive resolution of ~20. Higher resolution is theoretically possible with greater cross-flow rates. The ROMIAC was coupled to a linear trap quadrupole mass spectrometer and used to classify electrosprayed C2–C12 tetra-alkyl ammonium ions, bradykinin, angiotensin I, angiotensin II, bovine ubiquitin, and two pairs of model peptide isomers. Instrument and mobility calibrations of the ROMIAC show that it exhibits linear responses to changes in electrode potential, making the ROMIAC suitable for mobility and cross-section measurements. The high resolution of the ROMIAC facilitates separation of isobaric isomeric peptides. Monitoring distinct dissociation pathways associated with peptide isomers fully resolves overlapping peaks in the ion mobility data. The ability of the ROMIAC to operate at atmospheric pressure and serve as a front-end analyzer to continuously transmit ions with a particular mobility facilitates extensive studies of target molecules using a variety of mass spectrometric methods

Osteoprotegerin mediates tumor-promoting effects of Interleukin-1beta in breast cancer cells

__Background:__ It is widely recognized that inflammation promotes breast cancer invasion and metastasis. Given the complex nature of the breast tumor inflammatory microenvironment, much remains to be understood of the molecular mechanisms that govern these effects. We have previously shown that osteoprotegerin knockdown in breast cancer cells resulted in reduced invasion and metastasis. Here we present novel insight into the role of osteoprotegerin in inflammation-driven tumor progression in breast cancer by investigating the link between osteoprotegerin, macrophages and the potent pro-inflammatory cytokine Interleukin-1beta. __Methods:__ We used human breast cancer cell lines to investigate the effects of Interleukin-1beta treatment on osteoprotegerin secretion as measured by ELISA. We analyzed public datasets containing human breast cancer genome-wide mRNA expression data to reveal a significant and positive correlation between osteoprotegerin mRNA expression and the mRNA expression of Interleukin-1beta and of monocyte chemoattractant protein CC-chemokine ligand 2. Osteoprotegerin, Interleukin-1beta and CC-chemokine ligand 2 mRNA levels were also examined by qPCR on cDNA from normal and cancerous human breast tissue. We determined the effect of Interleukin-1beta-producing macrophages on osteoprotegerin expression by co-culturing breast cancer cells and differentiated THP-1 macrophages. Immunohistochemistry was performed on human breast tumor tissue microarrays to assess macrophage infiltration and osteoprotegerin expression. To demonstrate that osteoprotegerin mediated functional effects of Interleukin-1beta we performed cell invasion studies with control and OPG siRNA knockdown on Interleukin-1beta-treated breast cancer cells. __Results:__ We report that Interleukin-1beta induces osteoprotegerin secretion, independent of breast cancer subtype and basal osteoprotegerin levels. Co-culture of breast cancer cells with Interleukin-1beta-secreting macrophages resulted in a similar increase in osteoprotegerin secretion in breast cancer cells as Interleukin-1beta treatment. Macrophage infiltration correlates with osteoprotegerin secretion in human breast tumor tissue samples. We show that osteoprotegerin secretion is regulated by Interleukin-1beta in a p38- and p42/44-dependent manner. We also demonstrate that osteoprotegerin knockdown represses Interleukin-1beta expression, Interleukin-1beta-mediated breast cancer cell invasion and MMP3 expression. __Conclusions:__ These data indicate a novel role for osteoprotegerin as a mediator of inflammation- promoted breast cancer progression

Comparing knowledge, accessibility, and use of evidence-based chronic disease prevention processes across four countries

<p>Background: Evidence-based chronic disease prevention (EBCDP) effectively reduces incidence rates of many chronic diseases, but contextual factors influence the implementation of EBCDP worldwide. This study aims to examine the following contextual factors across four countries: knowledge, access, and use of chronic disease prevention processes.</p><p>Methods: In this cross-sectional study, public health practitioners (N = 400) from Australia (n = 121), Brazil (n = 76), China (n = 102), and the United States (n = 101) completed a 26-question survey on EBCDP. One-way ANOVA and Pearson's Chi-Square tests were used to assess differences in contextual factors of interest by country.</p><p>Results: Practitioners in China reported less knowledge of EBCDP processes (p < 0.001) and less use of repositories of evidence-based interventions, than those from other countries (p < 0.001). Academic journals were the most frequently used method for accessing information about evidence-based interventions across countries. When selecting interventions, Brazilian and Chinese practitioners were more likely to consider implementation ease while the Australian and United States practitioners were more likely to consider effectiveness (p < 0.001).</p><p>Conclusions: These findings can help inform and improve within and across country strategies for implementing EBCDP interventions.</p

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Notorious places: image, reputation, stigma: the role of newspapers in area reputations for social housing estates

This paper reviews work in several disciplines to distinguish between image, reputation and stigma. It also shows that there has been little research on the process by which area reputations are established and sustained through transmission processes. This paper reports on research into the portrayal of two social housing estates in the printed media over an extended period of time (14 years). It was found that negative and mixed coverage of the estates dominated, with the amount of positive coverage being very small. By examining the way in which dominant themes were used by newspapers in respect of each estate, questions are raised about the mode of operation of the press and the communities' collective right to challenge this. By identifying the way regeneration stories are covered and the nature of the content of positive stories, lessons are drawn for programmes of area transformation. The need for social regeneration activities is identified as an important ingredient for changing deprived-area reputations

Sabotage in Contests: A Survey

A contest is a situation in which individuals expend irretrievable resources to win valuable prize(s). ‘Sabotage’ is a deliberate and costly act of damaging a rival’s' likelihood of winning the contest. Sabotage can be observed in, e.g., sports, war, promotion tournaments, political or marketing campaigns. In this article, we provide a model and various perspectives on such sabotage activities and review the economics literature analyzing the act of sabotage in contests. We discuss the theories and evidence highlighting the means of sabotage, why sabotage occurs, and the effects of sabotage on individual players and on overall welfare, along with possible mechanisms to reduce sabotage. We note that most sabotage activities are aimed at the ablest player, the possibility of sabotage reduces productive effort exerted by the players, and sabotage may lessen the effectiveness of public policies, such as affirmative action, or information revelation in contests. We discuss various policies that a designer may employ to counteract sabotage activities. We conclude by pointing out some areas of future research