Enhanced heat shock protein 70 expression alters proteasomal degradation of IkappaB kinase in experimental acute respiratory distress syndrome.

OBJECTIVES: Acute respiratory distress syndrome is a common and highly lethal inflammatory lung syndrome. We previously have shown that an adenoviral vector expressing the heat shock protein (Hsp)70 (AdHSP) protects against experimental sepsis-induced acute respiratory distress syndrome in part by limiting neutrophil accumulation in the lung. Neutrophil accumulation and activation is modulated, in part, by the nuclear factor-kappaB (NF-kappaB) signal transduction pathway. NF-kappaB activation requires dissociation/degradation of a bound inhibitor, IkappaBalpha. IkappaBalpha degradation requires phosphorylation by IkappaB kinase, ubiquitination by the SCFbeta-TrCP (Skp1/Cullin1/Fbox beta-transducing repeat-containing protein) ubiquitin ligase, and degradation by the 26S proteasome. We tested the hypothesis that Hsp70 attenuates NF-kappaB activation at multiple points in the IkappaBalpha degradative pathway. DESIGN: Laboratory investigation. SETTING: University medical center research laboratory. SUBJECTS: Adolescent (200 g) Sprague-Dawley rats and murine lung epithelial-12 cells in culture. INTERVENTIONS: Lung injury was induced in rats via cecal ligation and double puncture. Thereafter, animals were treated with intratracheal injection of 1) phosphate buffer saline, 2) AdHSP, or 3) an adenovirus expressing green fluorescent protein. Murine lung epithelial-12 cells were stimulated with tumor necrosis factor-alpha and transfected. NF-kappaB was examined using molecular biological tools. MEASUREMENTS AND MAIN RESULTS: Intratracheal administration of AdHSP to rats with cecal ligation and double puncture limited nuclear translocation of NF-kappaB and attenuated phosphorylation of IkappaBalpha. AdHSP treatment reduced, but did not eliminate, phosphorylation of the beta-subunit of IkappaB kinase. In vitro kinase activity assays and gel filtration chromatography revealed that treatment of sepsis-induced lung injury with AdHSP induced fragmentation of the IkappaB kinase signalosome. This stabilized intermediary complexes containing IkappaB kinase components, IkappaBalpha, and NF-kappaB. Cellular studies indicate that although ubiquitination of IkappaBalpha was maintained, proteasomal degradation was impaired by an indirect mechanism. CONCLUSIONS: Treatment of sepsis-induced lung injury with AdHSP limits NF-kappaB activation. This results from stabilization of intermediary NF-kappaB/IkappaBalpha/IkappaB kinase complexes in a way that impairs proteasomal degradation of IkappaBalpha. This novel mechanism by which Hsp70 attenuates an intracellular process may be of therapeutic value.

Permanent demand excess as business strategy: an analysis of the Brazilian higher-education market

Many Higher Education Institutions (HEIs) establish tuition below the equilibrium price to generate permanent demand excess. This paper first adapts Becker’s (1991) theory to understand why the HEIs price in this way. The fact that students are both consumers and inputs on the education production process gives rise to a market equilibrium where some firms have excess demand and charge high prices, and others charge low prices and have empty seats.Second, the paper analyzes this equilibrium empirically. We estimated the demand for undergraduate courses in Business Administration in the State of São Paulo. The results show that tuition, quality of incoming students and percentage of lecturers holding doctorates degrees are the determining factors of students’ choice. Since the student quality determines the demand for a HEI, it is calculated what the value is for a HEI to get better students; that is the total revenue that each HEI gives up to guarantee excess demand. Regarding the “investment” in selectivity, 39 HEIs in São Paulo give up a combined R$ 5 million (or US$ 3.14 million) in revenue per year per freshman class, which means 7.6% of the revenue coming from a freshman class.

Do Financial Incentives Affect Firms' Demand For Disabled Workers?

A number of OECD countries aim to encourage work integration of disabled persons using quota policies. For instance, Austrian firms must provide at least one job to a disabled worker per 25 nondisabled workers and are subject to a tax if they do not. This "threshold design" provides causal estimates of the noncompliance tax on disabled employment if firms do not manipulate nondisabled employment; a lower and upper bound on the causal effect can be constructed if they do. Results indicate that firms with 25 nondisabled workers employ about 0.04 (or 12%) more disabled workers than without the tax; firms do manipulate employment of nondisabled workers but the lower bound on the employment effect of the quota remains positive; employment effects are stronger in low-wage firms than in high-wage firms; and firms subject to the quota of two disabled workers or more hire 0.08 more disabled workers per additional quota job. Moreover, increasing the noncompliance tax increases excess disabled employment, whereas paying a bonus to overcomplying firms slightly dampens the employment effects of the tax.

The Rapid Rise of China’s Dairy Sector: Factors Behind the Growth in Demand and Supply, May 2005

With the rapid growth in China’s dairy industry, a number of recent papers have addressed either the supply or the demand trends for dairy products in China. None, however, presents a systematic explanation for the recent growth in both the supply and demand for dairy products. The goal of this paper is to sketch a more comprehensive picture of China’s dairy sector and to assess the nature of the sector’s development in the coming decades. Drawing upon several empirical studies, we examine the trends in dairy product consumption to create a composite picture of the factors underlying the recent growth. We also empirically investigate the sources of production gains in milk supply and assess the relative importance of expanding herd size, changes in the nature of production, technological change, and improvements in efficiency to the overall growth of milk production.

Lithuania’s Food Demand During Economic Transition, January 2000

The linear approximate version of the AIDS model is estimated using data from the Lithuanian household budget survey covering the period from July 1992 to December 1994. Price and real expenditure elasticities for twelve food groups were estimated based on the estimated coefficients of the model. Very little or nothing is known about the demand parameters of Lithuania and other former socialist countries, so the results are of intrinsic interest. Estimated expenditure elasticities were positive and statistically significant for all food groups while all own-price elasticities were negative and statistically significant, except for that of eggs which was insignificant. Results suggest that Lithuanian household consumption did respond to price and real income changes during their transition to a market-oriented economy.

Managing Quality under Heterogeneous Consumer Demand and Product Quality, October 2005

Based on accepted advances in the marketing, economics, consumer behavior, and satisfaction literatures, we develop a micro-foundations model of a firm that needs to manage the quality of a product that is inherently heterogeneous in the presence of varying customer tastes or expectations for quality. Our model blends elements of the returns to quality, customer lifetime value, and service profit chain approaches to marketing. The model is then used to explain several empirical results pertaining to the marketing literature by explicitly articulating the trade-offs between customer satisfaction and costs (including opportunity costs) of quality. In this environment firms will find it optimal to allow some customers to go unsatisfied. We show that the relationship between the expected number of repeated purchases by an individual customer is endogenous to the choice of quality by the firm, indicating that the number of purchases cannot be chosen freely to estimate a customer’s lifetime value.

Consumers’ Demand for Pork Quality: Applying Semantic Network Analysis, May 2006

Abstract Consideration of consumers’ demand for food quality entails several aspects. Quality itself is a complex and dynamic concept, and constantly evolving technical progress may cause changes in consumers’ judgment of quality. To improve our understanding of the factors influencing the demand for quality, food quality must be defined and measured from the consumer’s perspective (Cardello, 1995). The present analysis addresses the issue of food quality, focusing on pork—the food that respondents were concerned about. To gain insight into consumers’ demand, we analyzed their perception and evaluation and focused on their cognitive structures concerning pork quality. In order to more fully account for consumers’ concerns about the origin of pork, in 2004 we conducted a consumer survey of private households. The qualitative approach of concept mapping was used to uncover the cognitive structures. Network analysis was applied to interpret the results. In order to make recommendations to enterprises, we needed to know what kind of demand emerges from the given food quality schema. By establishing the importance and relative positions of the attributes, we find that the country of origin and butcher may be the two factors that have the biggest influence on consumers’ decisions about the purchase of pork.

Work-related stress according to the demand-control model and minor psychic disorders in nursing workers

This was a cross-sectional study that aimed to assess the association between work-related stress according to the Demand-Control Model, and the occurrence of Minor Psychic Disorder (MPD) in nursing workers. The participants were 335 professionals, out of which 245 were nursing technicians, aged predominantly between 20 and 40 years. Data were collected using the Job Stress Scale and the Self-Reporting Questionnaire-20. The analysis was performed using descriptive and analytical statistics. The prevalence of suspected MPD was 20.6%. Workers classified in the quadrants active job and high strain of the Demand-Control Model presented higher potential for developing MPD compared with those classified in the quadrant low strain. In conclusion, stress affects the mental health of workers and the aspects related to high psychological demands and high control still require further insight in order to understand their influence on the disease processes of nursing workers.

Identification of a key lysine residue in heat shock protein 90 required for azole and echinocandin resistance in Aspergillus fumigatus.

Heat shock protein 90 (Hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for the treatment of invasive aspergillosis. We previously showed that genetic repression of Hsp90 reduced Aspergillus fumigatus virulence and potentiated the effect of the echinocandin caspofungin. In this study, we sought to identify sites of posttranslational modifications (phosphorylation or acetylation) that are important for Hsp90 function in A. fumigatus. Phosphopeptide enrichment and tandem mass spectrometry revealed phosphorylation of three residues in Hsp90 (S49, S288, and T681), but their mutation did not compromise Hsp90 function. Acetylation of lysine residues of Hsp90 was recovered after treatment with deacetylase inhibitors, and acetylation-mimetic mutations (K27A and K271A) resulted in reduced virulence in a murine model of invasive aspergillosis, supporting their role in Hsp90 function. A single deletion of lysine K27 or an acetylation-mimetic mutation (K27A) resulted in increased susceptibility to voriconazole and caspofungin. This effect was attenuated following a deacetylation-mimetic mutation (K27R), suggesting that this site is crucial and should be deacetylated for proper Hsp90 function in antifungal resistance pathways. In contrast to previous reports in Candida albicans, the lysine deacetylase inhibitor trichostatin A (TSA) was active alone against A. fumigatus and potentiated the effect of caspofungin against both the wild type and an echinocandin-resistant strain. Our results indicate that the Hsp90 K27 residue is required for azole and echinocandin resistance in A. fumigatus and that deacetylase inhibition may represent an adjunctive anti-Aspergillus strategy.

Evaporation from a shallow water table: Diurnal dynamics of measured and simulated water and heat regime at the vicinity of a drying sand surface

Accurate estimates of water losses by evaporation from shallow water tables are important for hydrological, agricultural, and climatic purposes. An experiment was conducted in a weighing lysimeter to characterize the diurnal dynamics of evaporation under natural conditions. Sampling revealed a completely dry surface sand layer after 5 days of evaporation. Its thickness was <1 cm early in the morning, increasing to reach 4?5 cm in the evening. This evidence points out fundamental limitations of the approaches that assume hydraulic connectivity from the water table up to the surface, as well as those that suppose monotonic drying when unsteady conditions prevail. The computed vapor phase diffusion rates from the apparent drying front based on Fick's law failed to reproduce the measured cumulative evaporation during the sampling day. We propose that two processes rule natural evaporation resulting from daily fluctuations of climatic variables: (i) evaporation of water, stored during nighttime due to redistribution and vapor condensation, directly into the atmosphere from the soil surface during the early morning hours, that could be simulated using a mass transfer approach and (ii) subsurface evaporation limited by Fickian diffusion, afterward. For the conditions prevailing during the sampling day, the amount of water stored at the vicinity of the soil surface was 0.3 mm and was depleted before 11:00. Combining evaporation from the surface before 11:00 and subsurface evaporation limited by Fickian diffusion after that time, the agreement between the estimated and measured cumulative evaporation was significantly improved.

An analisys of suply and Demand Conditions for Cape Verde´s Banana Industry

Michigan State University

Developing a Simple and Rapid Test for Monitoring the Heat Evolution of Concrete Mixtures for Both Laboratory and Field Applications, January 2006

Various test methods exist for measuring heat of cement hydration; however, most current methods require expensive equipment, complex testing procedures, and/or extensive time, thus not being suitable for field application. The objectives of this research are to identify, develop, and evaluate a standard test procedure for characterization and quality control of pavement concrete mixtures using a calorimetry technique. This research project has three phases. Phase I was designed to identify the user needs, including performance requirements and precision and bias limits, and to synthesize existing test methods for monitoring the heat of hydration, including device types, configurations, test procedures, measurements, advantages, disadvantages, applications, and accuracy. Phase II was designed to conduct experimental work to evaluate the calorimetry equipment recommended from the Phase I study and to develop a standard test procedure for using the equipment and interpreting the test results. Phase II also includes the development of models and computer programs for prediction of concrete pavement performance based on the characteristics of heat evolution curves. Phase III was designed to study for further development of a much simpler, inexpensive calorimeter for field concrete. In this report, the results from the Phase I study are presented, the plan for the Phase II study is described, and the recommendations for Phase III study are outlined. Phase I has been completed through three major activities: (1) collecting input and advice from the members of the project Technical Working Group (TWG), (2) conducting a literature survey, and (3) performing trials at the CP Tech Center’s research lab. The research results indicate that in addition to predicting maturity/strength, concrete heat evolution test results can also be used for (1) forecasting concrete setting time, (2) specifying curing period, (3) estimating risk of thermal cracking, (4) assessing pavement sawing/finishing time, (5) characterizing cement features, (6) identifying incompatibility of cementitious materials, (7) verifying concrete mix proportions, and (8) selecting materials and/or mix designs for given environmental conditions. Besides concrete materials and mix proportions, the configuration of the calorimeter device, sample size, mixing procedure, and testing environment (temperature) also have significant influences on features of concrete heat evolution process. The research team has found that although various calorimeter tests have been conducted for assorted purposes and the potential uses of calorimeter tests are clear, there is no consensus on how to utilize the heat evolution curves to characterize concrete materials and how to effectively relate the characteristics of heat evolution curves to concrete pavement performance. The goal of the Phase II study is to close these gaps.