bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basal cytokeratins in breast tumours among BRCA1, BRCA2and mutation-negative breast cancer families
Authors: Eerola Hannaleena , Heinonen Mira , Heikkilä Päivi , Kilpivaara Outi , Tamminen Anitta , Aittomäki Kristiina , Blomqvist Carl , Ristimäki Ari , Nevanlinna Heli 
Published: February 2008

Abstract
Introduction
Finding new immunohistochemical markers that are specific to hereditary breast cancer could help us to select candidates for BRCA1/BRCA2 mutation testing and to understand the biological pathways of tumour development.

Methods
Using breast cancer tumour microarrays, immunohistochemical expression of cytokeratin (CK)-5/6, CK-14 and CK-17 was evaluated in breast tumours from BRCA1 families (n = 46), BRCA2 families (n = 40), non-BRCA1/BRCA2 families (n = 358) and familial breast cancer patients with one first-degree relative affected by breast or ovarian cancer (n = 270), as well as from patients with sporadic breast cancer (n = 364). Staining for CK-5/6, CK-14 and CK-17 was compared between these groups and correlated with other clinical and histological factors.

Results
CK-5/6, CK-14 and CK-17 were detected mostly among oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative and high-grade tumours. We found the highest percentages of samples positive for these CKs among ER-negative/HER2-negative tumours. In univariate analysis, CK-14 was significantly associated with tumours from BRCA1 (39%; P < 0.0005), BRCA2 (27%; P = 0.011), and non-BRCA1/BRCA2 (21%; P < 0.005) families, as compared with sporadic tumours (10%). However, in multivariate analysis, CKs were not found to be independently associated with BRCA1 or BRCA2 mutation status, and the most effective predictors of BRCA1 mutations were age at onset, HER2 status, and either ER or PR status.

Conclusion
Although our study confirms that basal CKs can help to identify BRCA1 mutation carriers, this effect was weaker than previously suggested and CKs did not independently predict BRCA1 mutation either from sporadic or familial breast cancer cases. The most effective, independent predictors of BRCA1 mutations were age at onset, HER2 status, and either ER or PR status, as compared with sporadic or non-BRCA1/BRCA2 cancers.
Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes
Authors: Cullingford Timothy E , Markou Thomais , Fuller Stephen J , Giraldo Alejandro , Pikkarainen Sampsa , Zoumpoulidou Georgia , Alsafi Ali , Ekere Collins , Kemp Timothy J , Dennis Jayne L , Game Laurence , Sugden Peter H , Clerk Angela 
Published: February 2008

Abstract
Background
Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown.

Results
Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated.

Conclusion
The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response.
LRG-accelerated differentiation defines unique G-CSFR signaling pathways downstream of PU.1 and C/EBPε that modulate neutrophil activation
Authors: Ai Jing , Druhan Lawrence J , Hunter Melissa G , Loveland Megan J , Avalos Belinda R 
Published: February 2008

AbstractExpression of leucine-rich α2 glycoprotein (LRG), a member of the leucine-rich repeat family of proteins, was recently shown to be up-regulated during neutrophil differentiation. Its precise role in granulopoiesis, however, remains unknown. In this paper, we show that the transcription factors PU.1 and C/EBPε that regulate the expression of multiple myeloid-specific genes also bind to the LRG promoter. We also demonstrate that LRG localizes to the same cytoplasmic compartment as myeloperoxidase and that G-CSF treatment of the 32Dcl3 myeloid cell line induces nuclear translocation of LRG. Stable transfection of LRG into 32Dcl3 cells resulted in accelerated, G-CSF-mediated neutrophil differentiation and induction of CD11b expression. In contrast, constitutive expression of LRG in 32Dwt18 cells, expressing a chimeric erythropoietin (Epo)/G-CSFR consisting of the EpoR extracellular domain fused to the G-CSFR transmembrane and cytoplasmic domains, failed to induce accelerated neutrophil differentiation and CD11b expression in response to Epo stimulation. LRG-mediated accelerated differentiation and CD11b expression were found to correlate with an increased level of phospho-Stat3 but not with PU.1 or p27kip1 levels. Hence, similar to other genes involved in neutrophil differentiation, the expression of LRG also appears to be regulated by PU.1 and C/EBPε. Collectively, these findings suggest a role for LRG in modulating neutrophil differentiation and expression of CD11b via nonredundant G-CSFR signals.
Pharmaceutical Expenditures as a Correlate of Population Health in Industrialized Nations
Authors: Liu Li , Cline Richard R , Schondelmeyer Stephen W , Schommer Jon C 
Published: February 2008

Background: In recent years, healthcare spending has outpaced economic growth in developed countries, with pharmaceutical expenditures being a key driver of this trend. While a significant number of studies investigating the effect of healthcare resource productivity on health status have been done, only a few have disaggregated pharmaceutical expenditures from total healthcare expenditures. Objective: To assess the independent association between pharmaceutical expenditures and health outcomes in 14 industrialized countries. Methods: We used data from the Organisation for Economic Co-operation and Development to construct a panel data set covering the years from 1985 to 2001. These data contain information on pharmaceutical expenditures, other healthcare expenditures, environmental health determinants, lifestyle health determinants, potential years of life lost, and life expectancy at ages 65 and 80 years across 14 industrialized nations. We estimated the relationship between pharmaceutical expenditures and potential years of life lost and life expectancy at ages 65 and 80 years for both males and females, using nonlinear fixed-effects regression models that corrected for serial correlation. All explanatory variables were lagged by 5 years to account for their cumulative effect on population health outcomes. Results: Pharmaceutical expenditures proved to be a robust correlate of health outcomes from 1985 to 2001 in this sample of nations, when controlling for the effects of other variables likely to impact population health outcomes. Our estimates imply that a 10% increase in pharmaceutical expenditures during these years was associated with a 0.3% (95% CI 0.1% to 0.5%; ~21 days) increase in female life expectancy at age 65 years (p < 0.05), while a similar increase was associated with a 0.4% (95% CI 0.1 to 0.7; ~24 days) increase in male life expectancy at age 65 years (p < 0.05) and a 0.5% increase (95% CI 0.03 to 1.0; ~14 days) at age 80 years (p < 0.05). Conclusions: Our results suggest that significant, but small, marginal gains in population health outcomes were associated with increased pharmaceutical expenditures in developed nations during the period studied.
Interaction Between Levodopa and Enteral Nutrition
Authors: Cooper Mandelin K , Brock David G , McDaniel Cara M 
Published: February 2008

Objective: To report and discuss a drug–nutrient interaction involving levodopa and protein in enteral nutrition. Case Summary: A 77-year-old male with Parkinson's disease was admitted to an intensive care unit for an intracerebral hemorrhage. To provide nutritional support, an oral gastric tube was placed and continuous enteral nutrition was initiated, with 1.4 g/kg of protein administered daily. The following medications were continued during hospitalization: immediate-release carbidopa/levodopa 25 mg/100 mg, with 1.5 tablets administered 4 times daily; pramipexole 1.5 mg 3 times daily; and entacapone 200 mg 4 times daily. Despite this drug therapy, the patient developed severe rigidity. A review of the literature revealed a potential interaction between levodopa and protein intake. To resolve this interaction, the amount of protein in the enteral nutrition was decreased to 0.9 g/kg/day and the nutritional administration was changed from continuous enteral feeding to bolus feeding, with levodopa given between boluses. After these adjustments, the patient showed marked improvement of parkinsonian symptoms. Discussion: The drug–nutrient interaction between protein and levodopa in outpatient settings has been reported widely in the literature; however, this interaction has not been previously reported with continuous enteral nutrition. Decreased parkinsonian symptom control, despite adherence to an established medication regimen, together with dramatic improvement observed after manipulation of enteral nutrition delivery and content, strongly suggest interference with levodopa absorption. Use of the Naranjo probability scale supports a probable interaction between the protein content in tube feeds and levodopa, resulting in decreased levodopa efficacy. Conclusions: Clinicians should be cognizant of the potential drug–nutrient interaction between levodopa and enteral nutrition.
Cladding Tube Deformation Test for Stress Reorientation of Hydrides
Authors: Alam Adil M. , Hellwig Christian 
Published: February 2008

Abstract
The phenomenon of stress reorientation of hydrides in fuel cladding tubes was studied with the help of a test technique named as the “cladding tube deformation test” (CTDT). Unirradiated Zircaloy-2 (Zry-2) cladding tube specimens charged with 250 ppm of hydrogen were tested. The test consisted of heating specimens to 400°C and then cooling them down to room temperature at cooling rates of 0.7°C/min and 2°C/min. During the cooling phase, a constant tensile load was applied to specimens with the help of two inner cylinder halves. The stress-strain fields developed in the tube specimen were calculated with the help of the finite element method (FEM). Post-testing metallographic observations revealed considerable amount of hydrides oriented radially as a result of loading. Lengths and relative position of all hydride bands were determined through a semi-automatic image processing technique. Mapping of FEM calculated stress field on the metallographic section helped to determine a stress threshold value of 72 MPa. Tests performed with a cooling rate 2°C/min showed a considerably lower extent of hydride reorientation. The above test technique was validated by performing internal pressurization tests using pre-hydrided Zry-2 cladding tubes. The external diameter of the tube was tapered by fine turning in order to exert different uniform hoop stress values on different cross sections of the tube. Internal pressurization tests were performed with a maximum temperature of 400°C and a cooling rate of 0.5°C/min. Post-testing metallographic observations on several cross sections of the specimen revealed a stress reorientation threshold of 65 MPa. Percentage of radially oriented hydrides as well as their lengths increased with the stress level until it reached a plateau. Further tests were carried out with the CTDT technique on specimens with H2 content ranging from 560 ppm to 750 ppm. These results revealed a reorientation stress threshold of around 120 MPa for higher hydrogen content.
Landscape Effects on Growth of Age‐0 Arctic Grayling in Tundra Streams
Authors: Luecke Chris , MacKinnon Peter 
Published: February 2008

AbstractThe growth of age‐0 Arctic grayling Thymallus arcticus in two adjacent watersheds with differing numbers of lakes was compared. Age‐0 Arctic grayling grew faster in the watershed with numerous lakes (eight) than in the watershed with only one lake. The presence of lakes along the stream courses in both watersheds decreased stream temperatures in the spring but increased temperatures in summer. The size of substrates was greater in streams below lakes than in inlet stream reaches. Growth rates of discrete populations of age‐0 Arctic grayling were positively related to stream temperature. No relationship between fish growth rate and the biomass of invertebrate drift was apparent. We conclude that the summer increase in stream temperatures attributable to the presence of lakes resulted in increased growth of Arctic grayling in the watershed with numerous lakes. A simulation model of the temperature‐dependent growth of age‐0 Arctic grayling indicated that the abundance of lakes in one of the watersheds enhanced the potential production of Arctic grayling almost sixfold.
Climate Regime Effects on Pacific Herring Growth Using Coupled Nutrient‐Phytoplankton‐Zooplankton and Bioenergetics Models
Authors: Rose Kenneth A. , Megrey Bernard A. , Hay Douglas , Werner Francisco , Schweigert Jake 
Published: February 2008

AbstractWe used a nutrient‐phytoplankton‐zooplankton (NPZ) model coupled to a fish bioenergetics model to simulate the weight‐at‐age responses of Pacific herring Clupea pallasii to climate regimes. The NPZ model represents the daily dynamics of the lower trophic levels by simulating the uptake and recycling dynamics of nitrogen and silicon and the photosynthesis and grazing interactions of multiple functional groups of phytoplankton and zooplankton. The bioenergetics model simulates the number and mean weight of Pacific herring for each of 10 age‐classes. Three zooplankton groups simulated in the NPZ model provide estimates of the prey used to determine the consumption component of the herring bioenergetics model. We used a spawner‐recruit relationship to estimate the number of new age‐1 individuals joining the herring population every year. The coupled models were applied to the coastal upwelling area off the west coast of Vancouver Island. Model simulations were performed to isolate the effects of each of four documented climate regimes on Pacific herring weights at age. The climate regimes differed in the environmental variables used in the spawner‐recruit relationship as well as in the water temperature, mixed‐layer depth, and nutrient influxing rate used by the NPZ model. In agreement with general opinion and with the Pacific herring data from the west coast of Vancouver Island, the model‐predicted estimates of weight at age, recruitment, and spawning stock biomass were highest in regime 1 (1962‐1976), intermediate in regime 2 (1977‐1988), and lowest in regime 3 (1989‐1999). Insufficient time has passed to adequately document the conditions and herring responses in regime 4 (1998‐2002). The overall regime effect on weights at age was a mix of recruitment effects and lower trophic level effects that varied in direction and magnitude among the four regimes. Coupling bioenergetics models to physics and food web models is the next challenge in understanding and forecasting how climate change will affect fish growth and population dynamics.
Bioenergetics Modeling in the 21st Century: Reviewing New Insights and Revisiting Old Constraints
Authors: Chipps Steven R. , Wahl David H. 
Published: February 2008

AbstractThe development and application of fish bioenergetics models have flourished in recent years, due in part to the complexity of the issues being faced by fisheries biologists. As with any model, the accuracy of bioenergetics models can be hampered by uncertainty in model parameters. A review of the literature showed that field and laboratory tests of bioenergetics models often result in poor agreement between model predictions and independent data. Nonetheless, bioenergetics modeling continues to be used to make important management decisions. Recent tests of model predictions have shown that parameter uncertainty is influenced by factors such as feeding rate, physiological adaptations, and prey composition and abundance. In an attempt to reduce the uncertainty in modeling applications, we propose a framework that highlights the importance of (1) model evaluation, (2) hypothesis‐based parameter testing, and (3) improved communication between model developers and model users. Adherence to this framework will help reduce uncertainty in modeling applications and simultaneously contribute to a broader knowledge of fish physiology and feeding ecology.
Enhancing Bioenergetics Models to Account for Dynamic Changes in Fish Body Composition and Energy Density
Authors: Breck James E. 
Published: February 2008

AbstractFish proximate composition and energy density can influence growth, survival, and reproduction, so it is important to develop models to understand the patterns and predict dynamic changes. This paper presents three such models. Model 1 describes the general pattern of changes in lipid, protein, ash, and energy density that occur with changes in water content. The key assumption this model is that there is a fixed amount of water associated with each gram of protein and a much smaller fixed amount of water associated with each gram of lipid. In combination with a mass balance constraint, this explains the commonly observed linear relationship between the fraction lipid and the fraction water. Because energy density varies in direct proportion to the fractions lipid and protein, the linear relationship between body composition and fraction water makes energy density also a linear function of the fraction water. The model is fitted to data for lake trout Salvelinus namaycush and coho salmon Oncorhynchus kisutch for a limited range in wet weight. Model 2 describes the pattern of proximate composition and energy density that occurs with variation in body size. A strong pattern was found between the mass of water and the mass of protein, suggesting strict control of body water. The model is fitted to data for common carp Cyprinus carpio and bluegill Lepomis macrochirus. This analysis shows that the relationship between body composition, energy density, and fraction water is expected to vary with body size because both the water: Protein ratio and the fraction ash change with body size. Model 3 demonstrates how this approach can be used to predict changes in fish body composition and energy density during starvation, as might be done with a bioenergetics model. This model is fitted to data from a starvation experiment involving largemouth bass Micropterus salmoides.
Refinement and Testing of a Brook Trout Bioenergetics Model
Authors: Hartman Kyle J. , Cox M. Keith 
Published: February 2008

AbstractThe brook trout Salvelinus fontinalis is an important species across North America, being the focus of restoration and conservation efforts in the eastern United States and considered a threat to native salmonids in the western part of the country. Bioenergetics models have emerged as useful tools for studying the ecology and management of fish species, but these models should be critically evaluated prior to widespread application. We conducted laboratory experiments to refine model parameters (metabolism and the activity multiplier) and to test a model for brook trout. Brook trout metabolic rates increased with temperature up to 20°C, then declined sharply. Specific metabolism declined with increasing fish size. Validation experiments conducted for 7, 21, and 31 d at 12‐16°C showed that the model predicted consumption within 1.6 ± 3.6%, growth within 2.3 ± 12.5%, and final weight within 1.7 ± 5.1% of measured values. The results of this study will allow biologists to better use bioenergetics models to study the trophic dynamics of brook trout throughout their range.
Bioenergetics Modeling: Progress since the 1992 Symposium
Authors: Hartman Kyle J. , Kitchell James F. 
Published: February 2008

AbstractA symposium held at the annual meeting of the American Fisheries Society in Rapid City, South Dakota, in 1992 provided an overview of bioenergetics modeling and led to the publication of a series of papers in the Transactions of the American Fisheries Society the next year. Since then, Wisconsin Sea Grant has published a new version of its bioenergetics software (Fish Bioenergetics 3.0) and a manual to facilitate use of that model. Review of the more recent literature reveals continuing development and application of this modeling approach. A symposium held at the annual meeting in Madison, Wisconsin, in 2004 provided an opportunity for reporting progress and concerns about the “Wisconsin model.” This special section stems from the papers presented at that meeting.
Variable toxicity of ionic liquid–forming chemicals to Lemna mino and the influence of dissolved organic matter
Authors: Larson James H , Frost Paul C , Lamberti Gary A 
Published: February 2008

Abstract
Ionic liquids (ILs) are nonvolatile organic salts that remain liquid over a wide range of temperatures. Ionic liquids are promoted as environmentally friendly alternatives to the volatile organic solvents that are currently in widespread industrial usage. Although ILs are unlikely to contribute to air pollution, their potential effects on aquatic ecosystems are largely unknown. Furthermore, information is lacking on how ILs will interact with common features of aquatic environments, such as dissolved organic matter (DOM). We assessed the effect of five IL-forming chemicals on the growth of duckweed, Lemna minor, a common aquatic vascular plant. In general, 1-alkyl-3-methylimidazolium chemicals with longer alkyl chains were more toxic to L. minor than those with short alkyl chain lengths. The concentration that produced a 50% reduction (the EC50) in root growth was 8.56 ppm when a butyl chain was present but was 0.25 ppm (i.e., much more toxic) when an octyl chain was substituted. Butyl-substituted 3-methylpyridinium (root growth EC50 of 7.49 ppm) and 3-methylimidazolium cations had similar toxicity, whereas a tetrabutyl ammonium cation was considerably less toxic (root growth EC50 of 32.71 ppm). When we tested whether DOM reduced the toxicity of these cations, we saw no effect of a low-molecular-weight organic acid or commercial humic matter. In contrast, natural DOM reduced the toxicity of imidazolium, but only at low concentrations. Design and use of ILs and other new chemicals should incorporate not only standard toxicity tests but also information on how such chemicals will interact with other components of aquatic ecosystems.