Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence.

Fungal infections represent a serious threat, particularly in immunocompromised patients. Interleukin-1beta (IL-1beta) is a key pro-inflammatory factor in innate antifungal immunity. The mechanism by which the mammalian immune system regulates IL-1beta production after fungal recognition is unclear. Two signals are generally required for IL-1beta production: an NF-kappaB-dependent signal that induces the synthesis of pro-IL-1beta (p35), and a second signal that triggers proteolytic pro-IL-1beta processing to produce bioactive IL-1beta (p17) via Caspase-1-containing multiprotein complexes called inflammasomes. Here we demonstrate that the tyrosine kinase Syk, operating downstream of several immunoreceptor tyrosine-based activation motif (ITAM)-coupled fungal pattern recognition receptors, controls both pro-IL-1beta synthesis and inflammasome activation after cell stimulation with Candida albicans. Whereas Syk signalling for pro-IL-1beta synthesis selectively uses the Card9 pathway, inflammasome activation by the fungus involves reactive oxygen species production and potassium efflux. Genetic deletion or pharmalogical inhibition of Syk selectively abrogated inflammasome activation by C. albicans but not by inflammasome activators such as Salmonella typhimurium or the bacterial toxin nigericin. Nlrp3 (also known as NALP3) was identified as the critical NOD-like receptor family member that transduces the fungal recognition signal to the inflammasome adaptor Asc (Pycard) for Caspase-1 (Casp1) activation and pro-IL-1beta processing. Consistent with an essential role for Nlrp3 inflammasomes in antifungal immunity, we show that Nlrp3-deficient mice are hypersusceptible to Candida albicans infection. Thus, our results demonstrate the molecular basis for IL-1beta production after fungal infection and identify a crucial function for the Nlrp3 inflammasome in mammalian host defence in vivo.

Biodiesel Fuel Revolving Fund Expenditures Report Fiscal Year 2005 Report, January 2006

Report of expenditures from the biodiesel fuel revolving fund for biodiesel fuel used in Iowa Department of Transportation vehicles.

Role of CD44H carbohydrate structure in neuroblastoma adhesive properties.

BACKGROUND: CD44 represents a heterogeneous group of surface glycoproteins involved in cell-cell and cell-matrix interactions. CD44H is the major receptor for hyaluronate, and most if not all CD44H known functions are attributed to its ability to recognize hyaluronate. We have previously demonstrated a lack of CD44 expression in high stages and NMYC-amplified tumors and further have shown that NMYC-amplified cell lines either did not express CD44 at all or expressed a nonfunctional receptor. On the other hand, nonamplified cells constitutively expressed an active receptor, suggesting that absence of CD44-mediated hy aluronate binding could be related to increased malignancy in human neuroblastoma. PROCEDURE: In the present study we have compared the glycosylated structure of CD44 expressed by NMYC amplified vs. nonamplified cell lines in relation to their adhesive properties for hyaluronate. These adhesive properties were measured after modifications of the carbohydrate structure with enzymes and inhibitors of N- or O-linked glycosylation. RESULTS AND CONCLUSIONS: Our results indicate that increased sialylation, defective N-linked glycosylation, and substitution of the CD44 glycoprotein with keratan sulfate glycosaminoglycan might include modifications observed on neuroblastoma cells that could account for the inability of the receptor to bind hyaluronate.

IOWA Principles and Practices for Charitable Nonprofit Excellence, 2006

Task Force members formulated these principles and practices as a way to promote good management practices, ethical conduct, and public accountability. By compiling the information in this guide, we hope to provide a valuable tool for organizations and individuals as they go about the work of building better Iowa communities.

Age over 40 years increases the failure rate of non-operative management of blunt splenic injuries

Objective: Non-operative management (NOM) of blunt splenic injuries (BSI) is nowadays considered the standard treatment. The study aimed to determine the criteria applied for NOM and to identify risk factors for its failure. Methods: Review of all adult patients with BSI treated at the University Hospital Bern, Switzerland, between 2000 and 2008. Results: There were 206 patients (146 men, 70·9%) with a mean age of 38·2 ± 19·1 years and an Injury Severity Score of 30·9 ± 11·6. The American Association for the Surgery of Trauma classification of the splenic injury was: grade I, n=43 (20·9%); grade II, n=52 (25·2%); grade III, n=60 (29·1%); grade IV, n=42 (20·4%) and grade V, n=9 (4·4%). 47 patients (22·8%) required immediate surgery. Five or more units of red cell transfusions (P<0·001), Glasgow Coma Scale<11 (P=0·009) and age ≥55 years (P=0·038) were associated with primary operative management (OM). 159 patients (77·2%) qualified for NOM, which was successful in 89·9% (143/159). The overall splenic salvage rate was 69·4% (143/206). Multivariate analysis found age ≥40 years to be the only factor independently related to the failure of NOM (P=0·001). Conclusion: Advanced age is associated with an increased failure rate ofNOM in patients with BSI.

Savoir s'assurer : économie politique internationale des normes de services et mondialisation du marché de la (ré)assurance

The significance of the insurance industry in the functioning of the world economy is often underestimated, with premiums reaching 7.5 % of world gross domestic product (GDP), three times as much as worldwide military expenses. Insurance services mutualise risks in such a way as they provide a form of private governance that complements or makes up for guarantees otherwise supplied by the State. This case study of international standards developed for the insurance market provides evidence that deviates from conventional accounts considering service standards as heavily dependent of national environments and industry specificities. The chapter examines the relationship between tertiarisation, internationalisation and standardisation of contemporary economies by highlighting the complementarity between institutionalist approaches of the French regulation school and international political economy scholarship shedding light on the polarisation in the possible use of standards, notwithstanding thesectoraland institutional specificities of the activities concerned.

Expression of Fas (APO-1/CD95) and Fas ligand (FasL) in human neuroblastoma.

BACKGROUND AND PROCEDURE: To determine the possible role of Fas/FasL system in the particularly heterogeneous behaviour of neuroblastoma (NB), we have measured the functional expression of Fas and its ligand, FasL, in primary neuroblastoma samples and cell lines by immunohistochemistry and flow cytometry. RESULTS: Our results reveal that while Fas expression is associated with low stage and more mature tumors, heterogeneous FasL expression was mostly detected in high stage tumors, with our apparent correlation to MYCN amplification. Flow cytometric analysis of cell lines demonstrated a high expression of Fas in epithelial-type, HLA class I positive cell lines, which was lost upon activation with phorbol esters. In contrast, Fas ligand was detected in only a small subset of cell lines. CONCLUSIONS: In some cell lines, cytotoxic assays revealed the ability of NB-associated Fas receptor to transduce an apoptotic signal upon triggering. The pattern of functional Fas/FasL expression in tumours and cell lines suggests that this system may be involved in the evasion of highly malignant neuroblastoma cells to host immune response.

The Impact of Trade on Technology and Skill Upgrading Evidence from Argentina

In the last 20 years, wage inequality has increased in many developing countries. Most research on this topic focuses on two alternative causes: trade or skill-biased technical change. Several empirical studies in both developed and developing countries document increases in skill intensity within all sectors, favoring the technological change explanation over trade. Instead, I present and test a model where bilateral trade liberalization increases exporting revenues inducing more firms to enter the export market and to adopt skilled-biased new technologies. I find that the increase in the relative demand of skilled labor does not come from labor reallocation across sectors or firms but from skill upgrading within firms. Firms that upgrade technology faster also upgrade skill faster. Finally, firms entering the export market after liberalization become more skill and technology-intensive than non exporters.

Government Spending and Re-election

Does additional government spending improve the electoral chances of incumbent political parties? This paper provides the first quasi-experimental evidence on this question. Our research design exploits discontinuities in federal funding to local governments in Brazil around several population cutoffs over the period 1982-1985. We find that extra fiscal transfers resulted in a 20% increase in local government spending per capita, and an increase of about 10 percentage points in the re-election probability of local incumbent parties. We also find positive effects of the government spending on education outcomes and earnings, which we interpret as indirect evidence of public service improvements. Together, our results provide evidence that electoral rewards encourage incumbents to spend part of additional revenues on public services valued by voters, a finding in line with agency models of electoral accountability.

Intraclass reliability of the Alberta Infant Motor Scale in the Brazilian version

This study had as its objective to analyze the intraclass reliability of the Alberta Infant Motor Scale (AIMS), in the Brazilian version, in preterm and term infants. It was a methodological study, conducted from November 2009 to April 2010, with 50 children receiving care in two public institutions in Fortaleza, Ceará, Brazil. Children were grouped according to gestational age as preterm and term, and evaluated by three evaluators in the communication laboratory of a public institution or at home. The intraclass correlation indices for the categories prone, supine, sitting and standing ranged from 0.553 to 0.952; most remained above 0.800, except for the standing category of the third evaluator, in which the index was 0.553. As for the total score and percentile, rates ranged from 0.843 to 0.954. The scale proved to be a reliable instrument for assessing gross motor performance of Brazilian children, particularly in Ceará, regardless of gestational age at birth.

Markups, Gaps, and the Welfare Costs of Business Fluctuations

In this paper we present a simple theory-based measure of the variations in aggregate economic efficiency: the gap between the marginal product of labor and the household s consumption/leisure tradeoff. We show that this indicator corresponds to the inverse of the markup of price over social marginal cost, and give some evidence in support of this interpretation. We then show that, with some auxilliary assumptions our gap variable may be used to measure the efficiency costs of business fluctuations. We find that the latter costs are modest on average. However, to the extent the flexible price equilibrium is distorted, the gross efficiency losses from recessions and gains from booms may be large. Indeed, we find that the major recessions involved large efficiency losses. These results hold for reasonable parameterizations of the Frisch elasticity of labor supply, the coefficient of relative risk aversion, and steady state distortions.

Financial Crises and International Portfolio Dynamics

This paper analyzes the behavior of international capital flows by foreigners and domestic agents, especially during financial crises. We show that gross capital flows by foreigners and domestic agents are very large and volatile, especially relative to net capital flows. This is because when foreigners invest in a country domestic agents tend to invest abroad and vice versa. Gross capital flows are also pro-cyclical. During expansions, foreigners tend to bring in more capital and domestic agents tend to invest more abroad. During crises, there is retrenchment, i.e. a reduction in capital inflows by foreigners and an increase in capital inflows by domestic agents. This is especially true during severe crises and during systemic crises. The evidence can shed light on the nature of shocks driving international capital flows. It seems to favor shocks that affect foreigners and domestic agents asymmetrically -e.g. sovereign risk and asymmetric information- over productivity shocks.

Biodiesel Fuel Revolving Fund Expenditures Report, FY 06

Report of expenditures from the biodiesel fuel revolving fund for biodiesel fuel used in Iowa Department of Transportation vehicles.

Study of Iowa's Current Road Use Tax Funds (RUTF) and Future Road Maintenance and Construction Needs, 2006

The 81st General Assembly of the Iowa Legislature, in Section 85 of House File 868, required the Iowa Department of Transportation (DOT) to conduct a study of current Road Use Tax Fund (RUTF)revenues, and projected roadway construction and maintenance needs.