Early Changes in Gene Expression Induced by Tobacco Smoke: Evidence for the Importance of Estrogen within Lung Tissue

Lung cancer is the leading cause of cancer deaths in the United States, surpassing breast cancer as the primary cause of cancer-related mortality in women. The goal of the present study was to identify early molecular changes in the lung induced by exposure to tobacco smoke and thus identify potential targets for chemoprevention. Female A/J mice were exposed to either tobacco smoke or HEPA-filtered air via a whole-body exposure chamber (6 h/d, 5 d/wk for 3, 8, and 20 weeks). Gene expression profiles of lung tissue from control and smoke-exposed animals were established using a 15K cDNA microarray. Cytochrome P450 1b1, a phase I enzyme involved in both the metabolism of xenobiotics and the 4-hydroxylation of 17 beta-estradiol (E(2)), was modulated to the greatest extent following smoke exposure. A panel of 10 genes were found to be differentially expressed in control and smoke-exposed lung tissues at 3, 8, and 20 weeks (P < 0.001). The interaction network of these differentially expressed genes revealed new pathways modulated by short-term smoke exposure, including estrogen metabolism. In addition, E(2) was detected within murine lung tissue by gas chromatography-coupled mass spectrometry and immunohistochemistry. Identification of the early molecular events that contribute to lung tumor formation is anticipated to lead to the development of promising targeted chemopreventive therapies. In conclusion, the presence of E2 within lung tissue when combined with the modulation of cytochrome P450 1b1 and other estrogen metabolism genes by tobacco smoke provides novel insight into a possible role for estrogens in lung cancer. Cancer Prev Res; 3(6); 707-17. (C) 2010 AACR.

Skipping of exon 30 in C5 gene results in complete human C5 deficiency and demonstrates the importance of C5d and CUB domains for stability

The deficiency of complement C5 is rare and frequently associated with severe and recurrent infections, especially caused by Neisseria spp. We observed the absence of component C5 in the serum of 3 siblings from a Brazilian family with history of consanguinity. The patients had suffered from recurrent episodes of meningitis and other less severe infections. Sera from these patients were unable to mediate hemolytic activity either by the classical or alternative pathways and presented extremely low levels of C5 protein (13, 0.9 and 1.0 mu g/ml-normal range: 45-190 mu g/ml). Hemolytic activity could be restored by the addition of purified C5 to deficient serum. Sequencing of sibling C5 cDNA revealed a homozygous 153 bp deletion that corresponds precisely to exon 30. The parents carried the same deletion but only in one allele. Sequencing of the corresponding region in the genomic DNA revealed a C to C substitution within intron 30 and, most significantly, the substitution of GAG(4028) for GAA(4028) at the 3` end of exon 30 which is most likely responsible for skipping of exon 30. The resulting in-frame deletion in the C5 mRNA codes for a mutant C5 protein lacking residues 1289-1339. These residues map to the CUB and C5d domains of the C5 alpha chain. This deletion is expected to produce a non-functional and unstable C5 protein which is more susceptible to degradation. (C) 2009 Published by Elsevier Ltd.

The importance of protoporphyrin IX efflux for ALA-PDT dosimetry

One of the major advances in PDT is the use of 5-aminolevulinic acid (ALA) to induce the production of an enclogenous photosensitizer inside the cells using intracellular enzymatic pathways. ALA is the first intermediate in heme biosynthesis and a precursor of the protoporphyrin IX (PpIX). When activated by light, this efficient photosensitizer accumulated in the target cells can produce cytotoxicity. The aim of this study was to find the best conditions for cell killing using ALA to temporarily increase the concentration of PpIX in two cell lines. It was shown that a considerable efflux of synthesized PpIX occurs. Since this efflux is time-dependent, it is essential to know the optimum time for irradiation after ALA administration. So, the efflux of PpIX from the cells is an important parameter to be considered for ALA-PDT dosimetry.

Do crude oil price changes affect economic growth of India, Pakistan and Bangladesh? : A multivariate time series analysis

This paper analyzes empirically the effect of crude oil price change on the economic growth of Indian-Subcontinent (India, Pakistan and Bangladesh). We use a multivariate Vector Autoregressive analysis followed by Wald Granger causality test and Impulse Response Function (IRF). Wald Granger causality test results show that only India’s economic growth is significantly affected when crude oil price decreases. Impact of crude oil price increase is insignificantly negative for all three countries during first year. In second year, impact is negative but smaller than first year for India, negative but larger for Bangladesh and positive for Pakistan.

Techno-economic Appraisal of Concentrating Solar Power Systems (CSP)

The diffusion of Concentrating Solar Power Systems (CSP) systems is currently taking place at a much slower pace than photovoltaic (PV) power systems. This is mainly because of the higher present cost of the solar thermal power plants, but also for the time that is needed in order to build them. Though economic attractiveness of different Concentrating technologies varies, still PV power dominates the market. The price of CSP is expected to drop significantly in the near future and wide spread installation of them will follow. The main aim of this project is the creation of different relevant case studies on solar thermal power generation and a comparison betwwen them. The purpose of this detailed comparison is the techno-economic appraisal of a number of CSP systems and the understanding of their behaviour under various boundary conditions. The CSP technologies which will be examined are the Parabolic Trough, the Molten Salt Power Tower, the Linear Fresnel Mirrors and the Dish Stirling. These systems will be appropriatly sized and simulated. All of the simulations aim in the optimization of the particular system. This includes two main issues. The first is the achievement of the lowest possible levelized cost of electricity and the second is the maximization of the annual energy output (kWh). The project also aims in the specification of these factors which affect more the results and more specifically, in what they contribute to the cost reduction or the power generation. Also, photovoltaic systems will be simulated under same boundary conditions to facolitate a comparison between the PV and the CSP systems. Last but not leats, there will be a determination of the system which performs better in each case study.

Economic Evaluation of a Solar Charged Thermal Energy Store for Space Heating

A thermal energy store corrects the misalignment of heating demand in the winter relative to solar thermal energy gathered in the summer. This thesis reviews the viability of a solar charged hot water tank thermal energy store for a school at latitude 56.25N, longitude -120.85W

The importance of body-mass exponent optimization for evaluation of performance capability in cross-country skiing

Introduction Performance in cross-country skiing is influenced by the skier’s ability to continuously produce propelling forces and force magnitude in relation to the net external forces. A surrogate indicator of the “power supply” in cross-country skiing would be a physiological variable that reflects an important performance-related capability, whereas the body mass itself is an indicator of the “power demand” experienced by the skier. To adequately evaluate an elite skier’s performance capability, it is essential to establish the optimal ratio between the physiological variable and body mass. The overall aim of this doctoral thesis was to investigate the importance of body-mass exponent optimization for the evaluation of performance capability in cross-country skiing. Methods In total, 83 elite cross-country skiers (56 men and 27 women) volunteered to participate in the four studies. The physiological variables of maximal oxygen uptake (V̇O2max) and oxygen uptake corresponding to a blood-lactate concentration of 4 mmol∙l-1 (V̇O2obla) were determined while treadmill roller skiing using the diagonal-stride technique; mean oxygen uptake (V̇O2dp) and upper-body power output (Ẇ) were determined during double-poling tests using a ski-ergometer. Competitive performance data for elite male skiers were collected from two 15-km classical-technique skiing competitions and a 1.25-km sprint prologue; additionally, a 2-km double-poling roller-skiing time trial using the double-poling technique was used as an indicator of upper-body performance capability among elite male and female junior skiers. Power-function modelling was used to explain the race and time-trial speeds based on the physiological variables and body mass. Results The optimal V̇O2max-to-mass ratios to explain 15-km race speed were V̇O2max divided by body mass raised to the 0.48 and 0.53 power, and these models explained 68% and 69% of the variance in mean skiing speed, respectively; moreover, the 95% confidence intervals (CI) for the body-mass exponents did not include either 0 or 1. For the modelling of race speed in the sprint prologue, body mass failed to contribute to the models based on V̇O2max, V̇O2obla, and V̇O2dp. The upper-body power output-to-body mass ratio that optimally explained time-trial speed was Ẇ ∙ m-0.57 and the model explained 63% of the variance in speed. Conclusions The results in this thesis suggest that V̇O2max divided by the square root of body mass should be used as an indicator of performance in 15-km classical-technique races among elite male skiers rather than the absolute or simple ratio-standard scaled expression. To optimally explain an elite male skier’s performance capability in sprint prologues, power-function models based on oxygen-uptake variables expressed absolutely are recommended. Moreover, to evaluate elite junior skiers’ performance capabilities in 2-km double-poling roller-skiing time trials, it is recommended that Ẇ divided by the square root of body mass should be used rather than absolute or simple ratio-standard scaled expression of power output.

Energy efficient and economic renovation of residential buildings with low-temperature heating and air heat recovery

With the building sector accounting for around 40% of the total energy consumption in the EU, energy efficiency in buildings is and continues to be an important issue. Great progress has been made in reducing the energy consumption in new buildings, but the large stock of existing buildings with poor energy performance is probably an even more crucial area of focus. This thesis deals with energy efficiency measures that can be suitable for renovation of existing houses, particularly low-temperature heating systems and ventilation systems with heat recovery. The energy performance, environmental impact and costs are evaluated for a range of system combinations, for small and large houses with various heating demands and for different climates in Europe. The results were derived through simulation with energy calculation tools. Low-temperature heating and air heat recovery were both found to be promising with regard to increasing energy efficiency in European houses. These solutions proved particularly effective in Northern Europe as low-temperature heating and air heat recovery have a greater impact in cold climates and on houses with high heating demands. The performance of heat pumps, both with outdoor air and exhaust air, was seen to improve with low-temperature heating. The choice between an exhaust air heat pump and a ventilation system with heat recovery is likely to depend on case specific conditions, but both choices are more cost-effective and have a lower environmental impact than systems without heat recovery. The advantage of the heat pump is that it can be used all year round, given that it produces DHW. Economic and environmental aspects of energy efficiency measures do not always harmonize. On the one hand, lower costs can sometimes mean larger environmental impact; on the other hand there can be divergence between different environmental aspects. This makes it difficult to define financial subsidies to promote energy efficiency measures.

The importance of considering the evidence in the MTP 2014 Amendment debate in India - unsubstantiated arguments should not impede improved access to safe abortion

With the objective to improve access to safe abortion services in India, the Ministry of Health and Welfare, with approval of the Law Ministry, published draft amendments of the MTP Act on October 29, 2014. Instead of the expected support, the amendments created a heated debate within professional medical associations of India. In this commentary, we review the evidence in response to the current discourse with regard to the amendments. It would be unfortunate if unsubstantiated one-sided arguments would impede the intention of improving access to safe abortion care in India.

The Economic Effects of Ski Resorts on Communities in the State of Maine

Skiing and snowboarding is a fairly expensive activity for participant and one in which the industry as a whole makes handsome profits. In the 2005/06 season, resorts in the Northeast reported an average gross revenue of $18.5 million. (NSAA) With the current weather phenomenon of El Nino, however, resorts in New England especially, have been suffering economically. The gross revenue in New England in the ’05/’06 season was down 4% from the previous year, likely due to the fact the total snowfall declined by 16%. (NSAA) Much of this loss in revenue came during the Christmas to New Years vacation period. In the 2007 season, most mountains were less than half-opened during this peak week and the number of skiers and riders was especially low. With such a large decrease in profits, it is likely that many people will soon be affected (if they have not already been), including local employees. This project, therefore, seeks to analyze the impact that the resorts have on the local economies in order to determine the potential problems the changing snowfall patterns could have on locals’ well-being. It is hypothesized that there will be a strong correlation between the proximity of a community to a resort and the relative economic prosperity of that community; meaning that the ski industry is a pivotal part of their income and livelihood.

Enforcement in environmental law: an economic analysis of citizen suits

Previous to 1970, state and federal agencies held exclusive enforcement responsibilities over the violation of pollution control standards. However, recognizing that the government had neither the time nor resources to provide full enforcement, Congress created citizen suits. Citizen suits, first amended to the Clean Air Act in 1970, authorize citizens to act as private attorney generals and to sue polluters for violating the terms of their operating permits. Since that time, Congress has included citizen suits in 13 other federal statutes. The citizen suit phenomenon is sufficiently new that little is known about it. However, we do know that citizen suits have increased rapidly since the early 1980's. Between 1982 and 1986 the number of citizen suits jumped from 41 to 266. Obviously, they are becoming a widely used method of enforcing the environmental statutes. This paper will provide a detailed description, analysis and evaluation of citizen suits. It will begin with an introduction and will then move on to provide some historic and descriptive background on such issues as how citizen suit powers are delegated, what limitations are placed on the citizens, what parties are on each side of the suit, what citizens can enforce against, and the types of remedies available. The following section of the paper will provide an economic analysis of citizen suits. It will begin with a discussion of non-profit organizations, especially non-profit environmental organizations, detailing the economic factors which instigate their creation and activities. Three models will be developed to investigate the evolution and effects of citizen suits. The first model will provide an analysis of the demand for citizen suits from the point of view of a potential litigator showing how varying remedies, limitations and reimbursement procedures can effect both the level and types of activities undertaken. The second model shows how firm behavior could be expected to respond to citizen suits. Finally, a third model will look specifically at the issue of efficiency to determine whether the introduction of citizen enforcement leads to greater or lesser economic efficiency in pollution control. The database on which the analysis rests consists of 1205 cases compiled by the author. For the purposes of this project this list of citizen suit cases and their attributes were computerized and used to test a series of hypotheses derived from three original economic models. The database includes information regarding plaintiffs, defendants date notice and/or complaint was filed and statutes involved in the claim. The analysis focuses on six federal environmental statutes (Clean Water Act} Resource Conservation and Recovery Act, Comprehensive Environmental Response Compensation and Liability Act, Clean Air Act, Toxic Substances Control Act, and Safe Drinking Water Act) because the majority of citizen suits have occurred under these statutes.

The importance of common cyclical features in VAR analysis: a Monte-Carlo study

Despite the commonly held belief that aggregate data display short-run comovement, there has been little discussion about the econometric consequences of this feature of the data. We use exhaustive Monte-Carlo simulations to investigate the importance of restrictions implied by common-cyclical features for estimates and forecasts based on vector autoregressive models. First, we show that the ìbestî empirical model developed without common cycle restrictions need not nest the ìbestî model developed with those restrictions. This is due to possible differences in the lag-lengths chosen by model selection criteria for the two alternative models. Second, we show that the costs of ignoring common cyclical features in vector autoregressive modelling can be high, both in terms of forecast accuracy and efficient estimation of variance decomposition coefficients. Third, we find that the Hannan-Quinn criterion performs best among model selection criteria in simultaneously selecting the lag-length and rank of vector autoregressions.