Transient Crystal Size Distribution in DTB and FC Crystallizers

This work deals with the transient analysis of crystal size distribution (CSD) for imperfectly mixed draft tube baffled (DTB) and forced circulation (FC) crystallizers. The DTB and FC crystallizers are described by the Compartmental and Mixed models respectively. Monte Carlo (MC) scheme has been employed for simulation purposes. The simulation results have been compared with the available experimental data of BENNETT and VAN BUREN for continuous urea crystallizers.

Benzylguanidines and Other Galegine Analogues Inducing Weight Loss in Mice

Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing properties when evaluated in BALB/c mice. However, retention of the guanidine and replacement of the dimethylallyl group by a series of functionalized benzyl substituents was shown to exhibit, and in some cases significantly improve, the weight reducing properties of these molecules in BALB/c, ob/ob, and diet induced obesity (DIO) mice models. The lead compound identified, across all models, was 1-(4-chlorobenzyl)guanidine hemisulfate, which gave an average daily weight difference (% from time-matched controls; +/- SEM) of -19.7 +/- 1.0, -11.0 +/- 0.7, and -7.3 +/- 0.8 in BALB/c, ob/ob, and DIO models, respectively.

Langerin(+) Dermal Dendritic Cells Are Critical for CD8(+) T Cell Activation and IgH gamma-1 Class Switching in Response to Gene Gun Vaccines

The C-type lectin langerin/CD207 was originally discovered as a specific marker for epidermal Langerhans cells (LC). Recently, additional and distinct subsets of langerin(+) dendritic cells (DC) have been identified in lymph nodes and peripheral tissues of mice. Although the role of LC for immune activation or modulation is now being discussed controversially, other langerin(+) DC appear crucial for protective immunity in a growing set of infection and vaccination models. In knock-in mice that express the human diphtheria toxin receptor under control of the langerin promoter, injection of diphtheria toxin ablates LC for several weeks whereas other langerin(+) DC subsets are replenished within just a few days. Thus, by careful timing of diphtheria toxin injections selective states of deficiency in either LC only or all langerin(+) cells can be established. Taking advantage of this system, we found that, unlike selective LC deficiency, ablation of all langerin(+) DC abrogated the activation of IFN-gamma producing and cytolytic CD8(+) T cells after gene gun vaccination. Moreover, we identified migratory langerin(+) dermal DC as the subset that directly activated CD8(+) T cells in lymph nodes. Langerin(+) DC were also critical for IgG1 but not IgG2a Ab induction, suggesting differential polarization of CD4(+) T helper cells by langerin(+) or langerin-negative DC, respectively. In contrast, protein vaccines administered with various adjuvants induced IgG1 independently of langerin(+) DC. Taken together, these findings reflect a highly specialized division of labor between different DC subsets both with respect to Ag encounter as well as downstream processes of immune activation. The Journal of Immunology, 2011, 186: 1377-1383.

Unfunded pension liabilities and sponsoring firm credit risk: an international analysis of corporate bond spreads

This paper tests empirically whether pension information derived by corporate pension accounting disclosures is priced in corporate bond spreads. The model represents a hybrid of more traditional accounting ratio-based models of credit risk and structural models of bond spreads initiated by Merton (1974). The model is fitted to 5 years of data from 2002 to 2006 featuring companies from the US and Europe. The paper finds that while unfunded pension liabilities are priced in the overall sample, they are not priced as aggressively as traditional leverage. Furthermore, an extended model shows that the pension–credit risk relation is most evident in the US and Germany, where unfunded pension liabilities are priced more aggressively than traditional forms of leverage. No pension–credit risk relation is found in the other countries sampled, notably the UK, Netherlands and France.

Residential consumption of gas and electricity in the U.S.: The role of prices and income

We study the residential demand for electricity and gas, working with nationwide household-level data that cover recent years, namely 1997-2007. Our dataset is a mixed panel/multi-year cross-sections of dwellings/households in the 50 largest metropolitan areas in the United States as of 2008. We estimate static and dynamic models of electricity and gas demand. We find strong household response to energy prices, both in the short and long term. From the static models, we get estimates of the own price elasticity of electricity demand in the -0.860 to -0.667 range, while the own price elasticity of gas demand is -0.693 to -0.566. These results are robust to a variety of checks. Contrary to earlier literature (Metcalf and Hassett, 1999; Reiss and White, 2005), we find no evidence of significantly different elasticities across households with electric and gas heat. The price elasticity of electricity demand declines with income, but the magnitude of this effect is small. These results are in sharp contrast to much of the literature on residential energy consumption in the United States, and with the figures used in current government agency practice. Our results suggest that there might be greater potential for policies which affect energy price than may have been previously appreciated. (C) 2011 Elsevier B.V. All rights reserved.

Seen but never heard: rethinking approaches to researching racism and young children

This paper is concerned with the methodology underlying attempts to understand the nature and impact of racism among young children. In drawing upon data gathered from a year-long ethnographic study of five- and six-year-old children in an English multi-ethnic, inner-city primary school, the paper provides a critique of traditional approaches to the study of racial attitudes among young children. It is argued that such research has been conceived through the articulation of two, inter-related discourses on children and on 'race'; the former couched in traditional socialisation and developmental models of childhood with their tendency to neglect the agency and social competency of young children and the latter being embedded within essentialist notions of 'race' and ethnicity that tend to deny the contingent and context-specific nature of racialised identities. The paper argues that the result of this has been that while children have often been the objects of research they have rarely been the subjects; in other words they are often seen but never heard. The paper argues for the need to move beyond the methodological confines set by these discourses and rethink alternative approaches that begin with the assumption that young children are socially competent. One such approach, drawing upon ethnographic methods and fore-grounding the importance of largely unstructured small group interviews with young children, is illustrated. Through the use of a number of examples, it is shown how this approach can help to emphasise the ability of children as young as five and six to respond to and negotiate their social worlds and more specifically within this the competency with which they are able to appropriate, rework and reproduce a number of discourses on 'race' to make sense of their own social experiences. In doing this the paper also illustrates the way in which it provides a methodology able to draw out and highlight the contradictions, contingency and complexity of racialised identities among young children. Ultimately, it is an approach concerned with placing the children themselves central within the research processes and foregrounding their voices and experiences.

Down with MNE-centric theories! Market entry and expansion as the bundling of MNE and local assets

Both Anderson and Gatignon and the Uppsala internationalization model see the initial mode of foreign market entry and subsequent modes of operation as unilaterally determined by multinational enterprises (MNEs) arbitraging control and risk and increasing their commitment as they gain experience in the target market. OLI and internalization models do recognize that foreign market entry requires the bundling of MNE and complementary local assets, which they call location or country-specific advantages, but implicitly assume that those assets are freely accessible to MNEs. In contrast to both of these MNE-centric views, I explicitly consider the transactional characteristics of complementary local assets and model foreign market entry as the optimal assignment of equity between their owners and MNEs. By looking at the relative efficiency of the different markets in which MNE and complementary local assets are traded, and at how these two categories of assets match, I am able to predict whether equity will be held by MNEs or by local firms, or shared between them, and whether MNEs will enter through greenfields, brownfields, or acquisitions. The bundling model I propose has interesting implications for the evolution of the MNE footprint in host countries, and for the reasons behind the emergence of Dragon MNEs.

Abeta oligomer toxicity inhibitor protects memory in models of synaptic toxicity

BACKGROUND AND PURPOSE:

Amyloid-ß (Aß) aggregation into synaptotoxic, prefibrillar oligomers is a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The pharmacological and neuroprotective properties of a novel Aß aggregation inhibitor, SEN1269, were investigated on aggregation and cell viability and in test systems relevant to synaptic function and memory, using both synthetic Aß(1-42) and cell-derived Aß oligomers.
EXPERIMENTAL APPROACH:

Surface plasmon resonance studies measured binding of SEN1269 to Aß(1-42) . Thioflavin-T fluorescence and MTT assays were used to measure its ability to block Aß(1-42) -induced aggregation and reduction in cell viability. In vitro and in vivo long-term potentiation (LTP) experiments measured the effect of SEN1269 on deficits induced by synthetic Aß(1-42) and cell-derived Aß oligomers. Following i.c.v. administration of the latter, a complex (alternating-lever cyclic ratio) schedule of operant responding measured effects on memory in freely moving rats.
KEY RESULTS:

SEN1269 demonstrated direct binding to monomeric Aß(1-42) , produced a concentration-related blockade of Aß(1-42) aggregation and protected neuronal cell lines exposed to Aß(1-42) . In vitro, SEN1269 alleviated deficits in hippocampal LTP induced by Aß(1-42) and cell-derived Aß oligomers. In vivo, SEN1269 reduced the deficits in LTP and memory induced by i.c.v. administration of cell-derived Aß oligomers.
CONCLUSIONS AND IMPLICATIONS:

SEN1269 protected cells exposed to Aß(1-42) , displayed central activity with respect to reducing Aß-induced neurotoxicity and was neuroprotective in electrophysiological and behavioural models of memory relevant to Aß-induced neurodegeneration. It represents a promising lead for designing inhibitors of Aß-mediated synaptic toxicity as potential neuroprotective agents for treating AD.

ARMS2 Increases the Risk of Early and Late Age-Related Macular Degeneration in the European Eye Study

OBJECTIVE:
To study associations between severity stages of early and late age-related macular degeneration (AMD) and genetic variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and to investigate potential interactions between smoking and ARMS2.
DESIGN:
Population-based, cross-sectional European Eye Study in 7 countries in Europe.
PARTICIPANTS:
Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling.
METHODS:
Participants were classified on the basis of the more severely affected eye into 5 mutually exclusive AMD severity stages ranging from no AMD, 3 categories of early AMD, and late AMD. History of cigarette smoking was available and allowed classification into never, former, and current smokers, with the latter 2 groups combined into a single category of ever smokers for analysis. Genotyping was performed for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170 in CFH. Associations were analyzed by logistic regression.
MAIN OUTCOME MEASURES:
Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status.
RESULTS:
Early AMD was present in 36.4% and late AMD was present in 3.3% of participants. Data on both genotype and AMD were available for 4276 people. The ORs for associations between AMD stage and ARMS2 increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase in risk of late AMD (P<3 × 10(-20)). The ORs for associations with CFH were similar for stage 3 early AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted and adjusted models (P = 0.001). The highest risk was observed in those doubly homozygous for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16-242), with P values for trend ranging from 0.03 (early AMD, stage 1) to 1 × 10(-26) (late AMD).
CONCLUSIONS:
A strong association was demonstrated between all stages of AMD and genetic variation in ARMS2, and a significant gene-environment interaction with cigarette smoking was confirmed.

Wild-type Measles Virus Infection Upregulates Poliovirus Receptor-Related 4 and Causes Apoptosis in Brain Endothelial Cells by Induction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

Small numbers of brain endothelial cells (BECs) are infected in children with neurologic complications of measles virus (MV) infection. This may provide a mechanism for virus entry into the central nervous system, but the mechanisms are unclear. Both in vitro culture systems and animal models are required to elucidate events in the endothelium. We compared the ability of wild-type (WT), vaccine, and rodent-adapted MV strains to infect, replicate, and induce apoptosis in human and murine brain endothelial cells (HBECs and MBECs, respectively). Mice also were infected intracerebrally. All MV stains productively infected HBECs and induced the MV receptor PVRL4. Efficient WT MV production also occurred in MBECs. Extensive monolayer destruction associated with activated caspase 3 staining was observed in HBECs and MBECs, most markedly with WT MV. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), but not Fas ligand, was induced by MV infection. Treatment of MBECs with supernatants from MV-infected MBEC cultures with an anti-TRAIL antibody blocked caspase 3 expression and monolayer destruction. TRAIL was also expressed in the endothelium and other cell types in infected murine brains. This is the first demonstration that infection of low numbers of BECs with WT MV allows efficient virus production, induction of TRAIL, and subsequent widespread apoptosis.

Patterns of Holocene relative sea level change in the North of Britain and Ireland

Temporal and spatial patterns of relative sea level (RSL) change in the North of Britain and Ireland during the Holocene are examined. Four episodes, each defined by marked changes in the RSL trend, are identified. Each episode is marked by a rise to a culminating shoreline followed by a fall. Episode HRSL-1 dates from the Younger Dryas to early in the Holocene; HRSL-2 to HRSL-4 occurred later in the Holocene. There is extensive evidence for each episode, and on this basis the spatial distribution of the altitude data for three culminating shorelines and a shoreline formed at the time of the Holocene Storegga Slide tsunami (ca 8110 ± 100 cal. BP) is analysed. Ordinary Kriging is used to determine the general pattern, following which Gaussian Trend Surface Analysis is employed. Recognising that empirical measurements of RSL change can be unevenly distributed spatially, a new approach is introduced which enables the developing pattern to be identified. The patterns for the most widely occurring shorelines were analysed and found to be similar and common centre and axis models were developed for all shorelines. The analyses described provide models of the spatial pattern of Holocene RSL change in the area between ca 8100 cal. BP and ca 1000 cal. BP based on 2262 high resolution shoreline altitude measurements. These models fit the data closely, no shoreline altitude measurement lying more than −1.70 m or +1.82 m from the predicted value. The models disclose a similar pattern to a recently published Glacial Isostatic Adjustment model for present RSL change across the area, indicating that the overall spatial pattern of RSL change may not have varied greatly during the last ca 8000 years.

Photosynthetic pigments in soils from northern Victoria Land (continental Antarctica) as proxies for soil algal community structure and function

Although soil algae are among the main primary producers in most terrestrial ecosystems of continental Antarctica, there are very few quantitative studies on their relative proportion in the main algal groups and on how their distribution is affected by biotic and abiotic factors. Such knowledge is essential for understanding the functioning of Antarctic terrestrial ecosystems. We therefore analyzed biological soil crusts from northern Victoria Land to determine their pH, electrical conductivity (EC) water content (W), total and organic C (TC and TOC) and total N (TN) contents, and the presence and abundance of photosynthetic pigments. In particular, the latter were tested as proxies for biomass and coarse-resolution community structure. Soil samples were collected from five sites with known soil algal communities and the distribution of pigments was shown to reflect differences in the relative proportions of Chlorophyta, Cyanophyta and Bacillariophyta in these sites. Multivariate and univariate models strongly indicated that almost all soil variables (EC, W, TOC and TN) were important environmental correlates of pigment distribution. However, a significant amount of variation is independent of these soil variables and may be ascribed to local variability such as changes in microclimate at varying spatial and temporal scales. There are at least five possible sources of local variation: pigment preservation, temporal variations in water availability, temporal and spatial interactions among environmental and biological components, the local-scale patchiness of organism distribution, and biotic interactions. (C) 2009 Elsevier Ltd. All rights reserved.

Therapeutic effects of PPARα agonists on diabetic retinopathy in type 1 diabetes models

Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator-activated receptor a (PPARa) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diabetes have not been reported. This study evaluated the efficacy of fenofibrate on DR in type 1 diabetes models and determined if the effect is PPARa dependent. Oral administration of fenofibrate significantly ameliorated retinal vascular leakage and leukostasis in streptozotocin-induced diabetic rats and in Akita mice. Favorable effects on DR were also achieved by intravitreal injection of fenofibrate or another specific PPARa agonist. Fenofibrate also ameliorated retinal NV in the oxygen-induced retinopathy (OIR) model and inhibited tube formation and migration in cultured endothelial cells. Fenofibrate also attenuated overexpression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF) and blocked activation of hypoxia-inducible factor-1 and nuclear factor-?B in the retinas of OIR and diabetic models. Fenofibrate's beneficial effects were blocked by a specific PPARa antagonist. Furthermore, Ppara knockout abolished the fenofibrate-induced downregulation of VEGF and reduction of retinal vascular leakage in DR models. These results demonstrate therapeutic effects of fenofibrate on DR in type 1 diabetes and support the existence of the drug target in ocular tissues and via a PPARa-dependent mechanism.

Laser-ion accelerators: State-of-the-art and scaling laws

A significant amount of experimental work has been devoted over the last decade to the development and optimization of proton acceleration based on the so-called Target Normal Sheath acceleration mechanism. Several studies have been dedicated to the determination of scaling laws for the maximum energy of the protons as a function of the parameters of the irradiating pulses, studies based on experimental results and on models of the acceleration process. We briefly summarize the state of the art in this area, and review some of the scaling studies presented in the literature. We also discuss some recent results, and projected scalings, related to a different acceleration mechanism for ions, based on the Radiation Pressure of an ultraintense laser pulse.

Using Mesh-Geometry Relationships to Transfer Analysis Models between CAE Tools

Integrating analysis and design models is a complex task due to differences between the models and the architectures of the toolsets used to create them. This complexity is increased with the use of many different tools for specific tasks during an analysis process. In this work various design and analysis models are linked throughout the design lifecycle, allowing them to be moved between packages in a way not currently available. Three technologies named Cellular Modeling, Virtual Topology and Equivalencing are combined to demonstrate how different finite element meshes generated on abstract analysis geometries can be linked to their original geometry. Establishing the equivalence relationships between models enables analysts to utilize multiple packages for specialist tasks without worrying about compatibility issues or rework.