Ground-Based GPS for Validation of Climate Models: The Impact of Satellite Antenna Phase Center Variations

The amount of water vapor in the atmosphere is an important indicator for climate change. Using the Global Positioning System (GPS), it is possible to estimate the integrated water vapor (IWV) above the ground-based GPS receiver. In order to optimally determine the IWV, a correct model of the received signal phase is essential. We have studied the effect of the satellite antenna phase center variations (PCVs) on the IWV estimates by simulating the effect and by studying the estimates of the IWV based on the observed GPS signals. During a period of five years, from 2003 to 2008, a new satellite type was introduced, and it steadily grew in numbers. The antenna PCVs for these satellites deviate from the earlier satellite types and contribute to excess IWV estimates. We find that ignoring satellite antenna phase variations for this time period can lead to an additional IWV trend of about 0.15 kg/m2/year for regular GPS processing

Benefit of Apabetalone on Plasma Proteins in Renal Disease.

Introduction:Apabetalone, a small molecule inhibitor, targets epigenetic readers termed BET proteins that contribute to gene dysregulation in human disorders. Apabetalone has in vitro and in vivo anti-inflammatory and antiatherosclerotic properties. In phase 2 clinical trials, this drug reduced the incidence of major adverse cardiac events in patients with cardiovascular disease. Chronic kidney disease is associated with a progressive loss of renal function and a high risk of cardiovascular disease. We studied the impact of apabetalone on the plasma proteome in patients with impaired kidney function. Methods:Subjects with stage 4 or 5 chronic kidney disease and matched controls received a single dose of apabetalone. Plasma was collected for pharmacokinetic analysis and for proteomics profiling using the SOMAscan 1.3k platform. Proteomics data were analyzed with Ingenuity Pathway Analysis to identify dysregulated pathways in diseased patients, which were targeted by apabetalone. Results:At baseline, 169 plasma proteins (adjusted P value <0.05) were differentially enriched in renally impaired patients versus control subjects, including cystatin C and β2 microglobulin, which correlate with renal function. Bioinformatics analysis of the plasma proteome revealed a significant activation of 42 pathways that control immunity and inflammation, oxidative stress, endothelial dysfunction, vascular calcification, and coagulation. At 12 hours postdose, apabetalone countered the activation of pathways associated with renal disease and reduced the abundance of disease markers, including interleukin-6, plasminogen activator inhibitor-1, and osteopontin. Conclusion:These data demonstrated plasma proteome dysregulation in renally impaired patients and the beneficial impact of apabetalone on pathways linked to chronic kidney disease and its cardiovascular complications

Effect of the ABCA1 agonist CS-6253 on amyloid-beta and lipoprotein metabolism in cynomolgus monkeys

BACKGROUND: Inducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer's disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans. METHODS: CS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models. RESULTS: Following CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aβ42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aβ42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids. CONCLUSIONS: Treatment with the ABCA1 agonist CS-6253 appears to favor Aβ clearance from the brain

Particular concerns with regard to the Rotterdam Rules

Resumen: A medida que el proceso de fi rma de las Reglas de Rotterdam va tomando cuerpo, también cobran fuerza las voces discordantes. Este artículo o manifi esto recoge la opinión crítica colectiva de un grupo de nueve destacados especialistas en Derecho marítimo de distintas partes del mundo, pertenecientes a los sectores académico y profesional. El artículo analiza con brevedad y precisión los rasgos más destacados de las Reglas de Rotterdam, particularmente aquéllos que, a juicio de los firmantes, meritan mayor debate y crítica. La conclusión a la que llegan los miembros de este grupo de juristas es que las Reglas de Rotterdam no vienen sino a añadir más complejidad a la actual regulación internacional del transporte marítimo y multimodal. El artículo finaliza con una propuesta de alternativas que permitan aprovechar lo mejor de la regulación vigente y abrir las puertas a una actualización y complementación de dicha regulación. Palabras clave: Reglas, Rotterdam, Crítica, Alternativas. Abstract: As the Rotterdam Rules signature process gains momentum, strong dissenting opinions are also starting to be heard. This article or manifesto sums up the collective critical voice of nine worldwide leading shipping lawyers and professors. It provides a short and precise analysis of the Rotterdam Rules main features from the point of view of those issues which the authors fi nd unworthy of praise. And their conclusion is that the Rotterdam Rules simply just add up more complexity to the present shipping and multimodal international regulation. The article closes with a quest for alternatives aimed to get the best of what we already have and opens the gate to proposals based on the updating and complementation of the regulation in force today. Key words: Rules, Rotterdam, Critical, Alternatives

A Blue Print for a Worldwide Multimodal Regime

Resumen: En el nº 2 de 2010 de CDT se publicó un manifiesto del llamado “Grupo de los 9” titulado “Particular concerns with regard to the Rotterdam Rules” en el que estos destacados profesores y juristas expresaban sus dudas acerca de este nuevo instrumento internacional. Este Grupo ofrece ahora un nuevo manifiesto que supone un paso adelante en el que se indica que a pesar de la innegable necesidad de poner al día las Reglas de La Haya-Visby, y de las aportaciones efectuadas en tal sentido por las Reglas de Rótterdam, las perspectivas de éxito de estas últimas se ven ensombrecidas por su pretensión de extenderse más allá de lo que en puridad debía ser su objeto, el transporte marítimo, para convertirse en el texto de referencia para el transporte multimodal que cuente con una fase marítima. Lejos de contribuir a un verdadero y efectivo régimen unificado de la multimodalidad, plantea nuevas dudas a la hora de determinar qué régimen, de entro los existentes para cada tipo de transporte, debe ser de aplicación en cada caso. Mientras tanto, parece que para conseguir los objetivos referidos al transporte marítimo de las Reglas de Rótterdam habría bastado con la introducción de Protocolos a las Reglas de La Haya-Visby, dejando que lo concerniente al transporte multimodal continuara por la senda establecida a tal efecto por el CMR, cuyo sistema quizás debiera traspasar las fronteras europeas con el impulso de las diferentes instituciones internacionales. Palabras clave: Reglas de Rotterdam, transporte multimodal, transporte marítimo, Reglas de La Haya-Visby, CMR.  Abstract: In the issue n. 2 of 2010 of CDT it was published a manifesto of the so-called “Group of the 9” under the title of “Particular concerns with regard to the Rotterdam Rules” where these renowned scholars and attorneys expressed their doubts about this new international legal instrument. The Group offers now a new manifesto providing a step further whereby they indicate that notwithstanding the undeniable necessity to update the Hague-Visby Rules and the contributions carried out in this direction by the Rotterdam Rules, success expectations of the latter rules are hindered because of the aim to expand the scope of application beyond their object in strict sense, namely maritime transport, so as to become the text of reference as for every multimodal transport that includes a sea leg. Far from contributing to a real and effective multimodal unified regime, new doubts arise when determining which regime, of all those for each type of transport, shall apply in each case. In any event, it seems that in order to reach the objectives appointed to by the Rotterdam Rules, introducing Protocols to the Hague-Visby Rules would have been good enough, whereas all that related to multimodal transport continues by the CMR established paths, a system which should trespass European borders with the help of different international institutions. Key words: Rotterdam Rules, multimodal transport, maritime transport, Hague-Visby Rules, CMR

Prevalence of systemic immunoreactivity to Aggregatibacter actinomycetemcomitans leukotoxin in relation to the incidence of myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Chronic infections and associated inflammatory markers are suggested risk factors for cardiovascular disease (CVD). The proinflammatory cytokine, interleukin (IL)-1β, is suggested to play a role in the regulation of local inflammatory responses in both CVD and periodontitis. The leukotoxin from the periodontal pathogen <it>Aggregatibacter actinomycetemcomitans </it>has recently been shown to cause abundant secretion of IL-1β from macrophages. The aim of the present study was to compare the prevalence of systemic immunoreactivity to <it>A. actinomycetemcomitans </it>leukotoxin in myocardial infarction (MI) cases (n = 532) and matched controls (n = 1,000) in a population-based case and referents study in northern Sweden.</p> <p>Methods</p> <p>Capacity to neutralize <it>A. actinomycetemcomitans </it>leukotoxin was analyzed in a bioassay with leukocytes, purified leukotoxin, and plasma. Plasma samples that inhibited lactate-dehydrogenase release from leukotoxin-lysed cells by ≥50% were classified as positive.</p> <p>Results</p> <p>Neutralizing capacity against <it>A. actinomycetemcomitans </it>leukotoxin was detected in 53.3% of the plasma samples. The ability to neutralize leukotoxin was correlated to increasing age in men (n = 1,082) but not in women (n = 450). There was no correlation between presence of systemic leukotoxin-neutralization capacity and the incidence of MI, except for women (n = 146). Women with a low neutralizing capacity had a significantly higher incidence of MI than those who had a high neutralizing capacity.</p> <p>Conclusion</p> <p>Systemic immunoreactivity against <it>A. actinomycetemcomitans </it>leukotoxin was found at a high prevalence in the analyzed population of adults from northern Sweden. The results from the present study do not support the hypothesis that systemic leukotoxin-neutralizing capacity can decrease the risk for MI.</p

Block Rate Pricing of Water in Indonesia: An Analysis of Welfare Effects

Block rate pricing of piped water in Indonesian cities has a progressive structure: the marginal price paid increases with the volume of demand. This paper estimates household water demand in Salatiga city using the Burtless and Hausman model, and finds that its distribution is not unimodal—that data cluster around kinks. The main estimation results are a price elasticity of approximately –1.2 and an income elasticity of 0.05. These elasticities are mutually dependent. The estimated model is used to investigate the social welfare consequences of a shift to uniform pricing. The principal beneficiaries would be large households, which are not necessarily wealthy. While replacing the complex rate structure by a uniform marginal price would have positive effects on average welfare, the equity consequences would be small. To improve equity, water companies could reduce installation fees, giving low-income households access to water connections, or reinvest profits in network expansion to unserviced areas

More on Massive 3D Supergravity

Completing earlier work on three dimensional (3D) N=1 supergravity with curvature-squared terms, we construct the general supergravity extension of cosmological massive gravity theories. We expand about supersymmetric anti-de Sitter vacua, finding the conditions for bulk unitarity and the critical points in parameter space at which the spectrum changes. We discuss implications for the dual conformal field theory.Comment: v1 : 53 pages, 1 figure; v2 : significantly shortened, 42 p., version published in Class. Quant. Gra

Outbreaks of Tularemia in a Boreal Forest Region Depends on Mosquito Prevalence

Background. We aimed to evaluate the potential association of mosquito prevalence in a boreal forest area with transmission of the bacterial disease tularemia to humans, and model the annual variation of disease using local weather data