bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using artificial burrows to evaluate inhalation risks to burrowing mammals
Authors: Markwiese James T , Tiller Brett , Ryti Randall T , Bauer Roy 
Published: July 2008

Abstract
Since the onset of plutonium production at the US Department of Energy's Hanford Site, several hundred cubic meters of carbon tetrachloride (CCl4) has been discharged to the soil column, resulting in a dispersed CCl4 vapor plume in the subsurface. Inhalation of volatile organic chemicals could be an important exposure pathway for burrowing animals there. Historical levels of CCl4 in soil pore gas exceeded the inhalation ecological screening level for CCl4. Thus, the inhalation exposure pathway was evaluated with the use of artificial burrows deployed at locations that had elevated levels of CCl4 in soil gas. Artificial burrows were designed on the basis of information available for Hanford Site fossorial wildlife. After installation, the artificial burrow atmosphere was sampled and analyzed for CCl4 and its degradation products: chloroform, methylene chloride, and chloromethane. Sampling was repeated on 3 occasions to capture varying atmospheric conditions affecting exposure concentrations. CCl4 was detected in the artificial burrows, and maximum exposures were observed during relatively low barometric conditions. The highest CCl4 detections were still well below the inhalation-based ecological screening level and CCl4 degradation products were never detected. This study shows that artificial burrows are an efficient method for obtaining relevant exposure data and illustrates the utility of directly measuring the medium for exposure under ecologically realistic conditions.
What is meant by risk-based environmental quality criteria?
Authors: Suter Glenn W , Cormier Susan M 
Published: July 2008

Abstract
Criteria for the quality of water and other media are often said to be risk based. However, the relationship between the process of criterion setting and risk assessment has not been clear. This article shows that the conventional framework for risk assessment may be easily modified to represent criterion development. The critical difference is that conventional risk assessments solve an exposure-response model for an expected exposure to estimate an effect, but criterion assessments solve the same model for a benchmark effect to estimate an upper limit to acceptable exposures. Hence, the critical step in criterion setting is the determination of an effect metric that can be modeled and that represents the environmental goal. The same process applies to equivalent assessments, such as deriving screening benchmarks and remedial goals.
Pour Une Évaluation Normative De La Compétence De Traduction
Authors: Anckaert Philippe , Eyckmans June , Segers Winibert 
Published: July 2008

Résumé
Après un bref aperçu des risques d’infidélité d’une évaluation critériée de la compétence de traduction, liés principalement à la subjectivité du correcteur, nous mettons en évidence les limites des tentatives d’objectivation du processus d’évaluation au moyen de grilles de correction ou d’évaluation de la qualité telles qu’utilisées dans les écoles de traduction et le monde professionnel. Pour pallier le manque de fidélité des épreuves de traduction traditionnelles, nous proposons une méthode d’évaluation normative qui permet de neutraliser complètement la subjectivité du correcteur. Dans cet article, nous décrivons et illustrons par un exemple concret les différentes étapes de la confection d’une épreuve standardisée. De cette description, il ressort que notre méthode naît du mariage des principes de la docimologie, qui fournit les instruments de contrôle de la fidélité, et des acquis de la traductologie, indispensables pour se prononcer sur la validité des épreuves.
Automated User-Centred Task Selection and Input Modification in Language Learning
Authors: van der Werf Rintse , Hootsen Geke , Vermeer Anne 
Published: July 2008

AbstractThis article presents the results of a CALL-experiment in which reading material is selected dynamically, based on the “fit” between the vocabulary proficiency of individual students and the relative difficulty of texts. The texts were analysed, selected and presented online, together with a personalized electronic dictionary with words that were assumed to be unknown. In a pre-test – treatment – post-test design in which 32 Dutch L2-students took part, the vocabulary learned implicitly while reading the texts was measured. The relation between user-initiated noticing and word retention was also examined.We found an average word-learning improvement of 10.8%. On the basis of the non-significant differences between various proficiency groups, we concluded that the method we propose for the automated adaptive selection of reading texts ensures that learners of different proficiency levels receive linguistic input that is best fitted to their abilities. Using frequency information for both automated analysis of texts and the compilation of a personalized dictionary has great potential for more user-centred task selection and guidance. We also found a relation between user-initiated dictionary use and word retention, which was strong for the lowest proficiency level. With respect to the words looked up in the dictionary, a strong correlation was found between noticing and retention.
‘I me Mine’ The Acquisition of Dutch Pronominal Possessives by L1 Children, L2 Children and L2 Adults
Authors: Nap-Kolhoff Elma , Broeder Peter 
Published: July 2008

AbstractThis study compares pronominal possessive constructions in Dutch first language (L1) acquisition, second language (L2) acquisition by young children, and untutored L2 acquisition by adults. The L2 learners all have Turkish as L1. In longitudinal spontaneous speech data for four L1 learners, seven child L2 learners, and two adult learners, remarkable differences and similarities between the three learner groups were found. In some respects, the child L2 learners develop in a way that is similar to child L1 learners, for instance in the kind of overgeneralisations that they make. However, the child L2 learners also behave like adult L2 learners; i.e., in the pace of the acquisition process, the frequency and persistence of non-target constructions, and the difficulty in acquiring reduced pronouns. The similarities between the child and adult L2 learners are remarkable, because the child L2 learners were only two years old when they started learning Dutch. L2 acquisition before the age of three is often considered to be similar to L1 acquisition. The findings might be attributable to the relatively small amount of Dutch language input the L2 children received.
Reduction of Ptf1a Gene Dosage Causes Pancreatic Hypoplasia and Diabetes in Mice
Authors: Fukuda Akihisa , Kawaguchi Yoshiya , Furuyama Kenichiro , Kodama Sota , Horiguchi Masashi , Kuhara Takeshi , Kawaguchi Michiya , Terao Mami , Doi Ryuichiro , Wright Christopher V.E. , Hoshino Mikio , Chiba Tsutomu , Uemoto Shinji 
Published: July 2008

OBJECTIVE—Most pancreatic endocrine cells derive from Ptf1a-expressing progenitor cells. In humans, nonsense mutations in Ptf1a have recently been identified as a cause of permanent neonatal diabetes associated with pancreatic agenesis. The death of Ptf1a-null mice soon after birth has not allowed further insight into the pathogenesis of the disease; it is therefore unclear how much pancreatic endocrine function is dependent on Ptf1a in mammals. This study aims to investigate gene-dosage effects of Ptf1a on pancreas development and function in mice.
RESEARCH DESIGN AND METHODS—Combining hypomorphic and null alleles of Ptf1a and Cre-mediated lineage tracing, we followed the cell fate of reduced Ptf1a-expressing progenitors and analyzed pancreas development and function in mice.
RESULTS—Reduced Ptf1a dosage resulted in pancreatic hypoplasia and glucose intolerance with insufficient insulin secretion in a dosage-dependent manner. In hypomorphic mutant mice, pancreatic bud size was small and substantial proportions of pancreatic progenitors were misspecified to the common bile duct and duodenal cells. Growth with branching morphogenesis and subsequent exocrine cytodifferentiation was reduced and delayed. Total β-cell number was decreased, proportion of non-β islet cells was increased, and α-cells were abnormally intermingled with β-cells. Interestingly, Pdx1 expression was decreased in early pancreatic progenitors but elevated to normal level at the mid-to-late stages of pancreatogenesis.
CONCLUSIONS—The dosage of Ptf1a is crucial for pancreas specification, growth, total β-cell number, islet morphogenesis, and endocrine function. Some neonatal diabetes may be caused by mutation or single nucleotide polymorphisms in the Ptf1a gene that reduce gene expression levels.
Physical Activity and Insulin Sensitivity
Authors: Balkau Beverley , Mhamdi Leila , Oppert Jean-Michel , Nolan John , Golay Alain , Porcellati Francesca , Laakso Markku , Ferrannini Ele ,   on behalf of the EGIR-RISC Study Group
Published: July 2008

OBJECTIVE— Physical activity is a modifiable risk factor for type 2 diabetes, partly through its action on insulin sensitivity. We report the relation between insulin sensitivity and physical activity measured by accelerometry.
RESEARCH DESIGN AND METHODS— This is a cross-sectional study of 346 men and 455 women, aged 30–60 years, without cardiovascular disease and not treated by drugs for diabetes, hypertension, dyslipidemia, or obesity. Participants were recruited in 18 clinical centers from 13 European countries. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Physical activity was recorded by accelerometry for a median of 6 days. We studied the relationship of insulin sensitivity with total activity (in counts per minute), percent of time spent sedentary, percent of time in light activity, and activity intensity (whether the participant recorded some vigorous or some moderate activity).
RESULTS— In both men and women, total activity was associated with insulin sensitivity (P &lt; 0.0001). Time spent sedentary, in light activity, and activity intensity was also associated with insulin sensitivity (P &lt; 0.0004/0.01, 0.002/0.03, and 0.02/0.004, respectively, for men/women) but lost significance once adjusted for total activity. Adjustment for confounders such as adiposity attenuated the relationship with total activity; there were no interactions with confounders. Even in the 25% most sedentary individuals, total activity was significantly associated with better insulin sensitivity (P &lt; 0.0001).
CONCLUSIONS— Accumulated daily physical activity is a major determinant of insulin sensitivity. Time spent sedentary, time spent in light-activity, and bouts of moderate or vigorous activity did not impact insulin sensitivity independently of total activity.
miR-375 Targets 3′-Phosphoinositide–Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic β-Cells
Authors: El Ouaamari Abdelfattah , Baroukh Nadine , Martens Geert A. , Lebrun Patricia , Pipeleers Daniel , van Obberghen Emmanuel 
Published: July 2008

OBJECTIVE—MicroRNAs are short, noncoding RNAs that regulate gene expression. We hypothesized that the phosphatidylinositol 3-kinase (PI 3-kinase) cascade known to be important in β-cell physiology could be regulated by microRNAs. Here, we focused on the pancreas-specific miR-375 as a potential regulator of its predicted target 3′-phosphoinositide–dependent protein kinase-1 (PDK1), and we analyzed its implication in the response of insulin-producing cells to elevation of glucose levels.
RESEARCH DESIGN AND METHODS—We used insulinoma-1E cells to analyze the effects of miR-375 on PDK1 protein level and downstream signaling using Western blotting, glucose-induced insulin gene expression using quantitative RT-PCR, and DNA synthesis by measuring thymidine incorporation. Moreover, we analyzed the effect of glucose on miR-375 expression in both INS-1E cells and primary rat islets. Finally, miR-375 expression in isolated islets was analyzed in diabetic Goto-Kakizaki (GK) rats.
RESULTS—We found that miR-375 directly targets PDK1 and reduces its protein level, resulting in decreased glucose-stimulatory action on insulin gene expression and DNA synthesis. Furthermore, glucose leads to a decrease in miR-375 precursor level and a concomitant increase in PDK1 protein. Importantly, regulation of miR-375 expression by glucose occurs in primary rat islets as well. Finally, miR-375 expression was found to be decreased in fed diabetic GK rat islets.
CONCLUSIONS—Our findings provide evidence for a role of a pancreatic-specific microRNA, miR-375, in the regulation of PDK1, a key molecule in PI 3-kinase signaling in pancreatic β-cells. The effects of glucose on miR-375 are compatible with the idea that miR-375 is involved in glucose regulation of insulin gene expression and β-cell growth.
Neuronatin: A New Inflammation Gene Expressed on the Aortic Endothelium of Diabetic Mice
Authors: Mzhavia Nino , Yu Shuiqing , Ikeda Shota , Chu Tehua T. , Goldberg Ira , Dansky Hayes M. 
Published: July 2008

OBJECTIVE—Identification of arterial genes and pathways altered in obesity and diabetes.RESEARCH DESIGN AND METHODS—Aortic gene expression profiles of obese and diabetic db/db, high-fat diet–fed C57BL/6J, and control mice were obtained using mouse Affymetrix arrays. Neuronatin (Nnat) was selected for further analysis. To determine the function of Nnat, a recombinant adenovirus (Ad-Nnat) was used to overexpress the Nnat gene in primary endothelial cells and in the mouse aorta in vivo.RESULTS— Nnat, a gene of unknown vascular function, was upregulated in the aortas of db/db and high-fat diet–fed mice. Nnat gene expression was increased in db/db mouse aorta endothelial cells. Nnat protein was localized to aortic endothelium and was selectively increased in the endothelium of db/db mice. Infection of primary human aortic endothelial cells (HAECs) with Ad-Nnat increased expression of a panel of nuclear factor-κB (NF-κB)-regulated genes, including inflammatory cytokines, chemokines, and cell adhesion molecules. Infection of mouse carotid arteries in vivo with the Ad-Nnat increased expression of vascular cell adhesion molecule 1 protein. Nnat activation of NF-κB and inflammatory gene expression in HAECs was mediated through pathways distinct from tumor necrosis factor-α. Nnat expression stimulated p38, Jun NH2-terminal kinase, extracellular signal–related kinase, and AKT kinase phosphorylation. Phosphatidylinositol 3-kinase and p38 inhibitors prevented Nnat-mediated activation of NF-κB–induced gene expression.CONCLUSIONS—Nnat expression is increased in endothelial cells of obese and diabetic mouse blood vessels. The effects of Nnat on inflammatory pathways in vitro and in vivo suggest a pathophysiological role of this new gene in diabetic vascular diseases.
Cytokine-Induced β-Cell Death Is Independent of Endoplasmic Reticulum Stress Signaling
Authors: Åkerfeldt Mia C. , Howes Jennifer , Chan Jeng Yie , Stevens Veronica A. , Boubenna Nacer , McGuire Helen M. , King Cecile , Biden Trevor J. , Laybutt D. Ross 
Published: July 2008

OBJECTIVE—Cytokines contribute to β-cell destruction in type 1 diabetes. Endoplasmic reticulum (ER) stress–mediated apoptosis has been proposed as a mechanism for β-cell death. We tested whether ER stress was necessary for cytokine-induced β-cell death and also whether ER stress gene activation was present in β-cells of the NOD mouse model of type 1 diabetes.
RESEARCH DESIGN AND METHODS—INS-1 β-cells or rat islets were treated with the chemical chaperone phenyl butyric acid (PBA) and exposed or not to interleukin (IL)-1β and γ-interferon (IFN-γ). Small interfering RNA (siRNA) was used to silence C/EBP homologous protein (CHOP) expression in INS-1 β-cells. Additionally, the role of ER stress in lipid-induced cell death was assessed.
RESULTS—Cytokines and palmitate triggered ER stress in β-cells as evidenced by increased phosphorylation of PKR-like ER kinase (PERK), eukaryotic initiation factor (EIF)2α, and Jun NH2-terminal kinase (JNK) and increased expression of activating transcription factor (ATF)4 and CHOP. PBA treatment attenuated ER stress, but JNK phosphorylation was reduced only in response to palmitate, not in response to cytokines. PBA had no effect on cytokine-induced cell death but was associated with protection against palmitate-induced cell death. Similarly, siRNA-mediated reduction in CHOP expression protected against palmitate- but not against cytokine-induced cell death. In NOD islets, mRNA levels of several ER stress genes were reduced (ATF4, BiP [binding protein], GRP94 [glucose regulated protein 94], p58, and XBP-1 [X-box binding protein 1] splicing) or unchanged (CHOP and Edem1 [ER degradation enhancer, mannosidase α–like 1]).
CONCLUSIONS—While both cytokines and palmitate can induce ER stress, our results suggest that, in contrast to lipoapoptosis, the PERK-ATF4-CHOP ER stress–signaling pathway is not necessary for cytokine-induced β-cell death.
Evidence for Interindividual Heterogeneity in the Glucose Gradient Across the Human Red Blood Cell Membrane and Its Relationship to Hemoglobin Glycation
Authors: Khera Paramjit K. , Joiner Clinton H. , Carruthers Anthony , Lindsell Christopher J. , Smith Eric P. , Franco Robert S. , Holmes Yancey R. , Cohen Robert M. 
Published: July 2008

OBJECTIVE—To determine whether interindividual heterogeneity in the erythrocyte (red blood cell [RBC]) transmembrane glucose gradient might explain discordances between A1C and glycemic control based on measured fructosamine.
RESEARCH DESIGN AND METHODS—We modeled the relationship between plasma glucose and RBC glucose as the concentration distribution (Ci-to-Co ratio) of a nonmetabolizable glucose analog 14C-3-O-methyl glucose (14C-3OMG) inside (Ci) and outside (Co) RBCs in vitro. We examined the relationship between that distribution and the degree of glycation of hemoglobin in comparison with glycation of serum proteins (fructosamine), the glycation gap. A1C, fructosamine, and in vitro determination of the 14C-3OMG distribution in glucose-depleted RBCs were measured in 26 fasted subjects.
RESULTS—The Ci-to-Co ratio 0.89 ± 0.07 for 3-O-methyl-d-glucopyranose (3OMG) ranged widely (0.72–1.04, n = 26). In contrast, urea Ci-to-Co (1.015 ± 0.022 [range 0.98–1.07], P &lt; 0.0001) did not. Concerning mechanism, in a representative subset of subjects, the Ci-to-Co ratio was retained in RBC ghosts, was not dependent on ATP or external cations, and was reestablished after reversal of the glucose gradient. The 3OMG Ci-to-Co ratio was not correlated with serum fructosamine, suggesting that it was independent of mean plasma glucose. However, Ci-to-Co did correlate with A1C (R2 = 0.19) and with the glycation gap (R2 = 0.20), consistent with a model in which differences in internal glucose concentration at a given mean plasma glucose contribute to differences in A1C for given level of glycemic control.
CONCLUSIONS—The data demonstrate interindividual heterogeneity in glucose gradients across RBC membranes that may affect hemoglobin glycation and have implications for diabetes complications risk and risk assessment.
Decreased Fetal Size Is Associated With β-Cell Hyperfunction in Early Life and Failure With Age
Authors: Chakravarthy Manu V. , Zhu Yimin , Wice Mitchell B. , Coleman Trey , Pappan Kirk L. , Marshall Connie A. , McDaniel Michael L. , Semenkovich Clay F. 
Published: July 2008

OBJECTIVE—Low birth weight is associated with diabetes in adult life. Accelerated or “catch-up” postnatal growth in response to small birth size is thought to presage disease years later. Whether adult disease is caused by intrauterine β-cell–specific programming or by altered metabolism associated with catch-up growth is unknown.
RESEARCH DESIGN AND METHODS—We generated a new model of intrauterine growth restriction due to fatty acid synthase (FAS) haploinsufficiency (FAS deletion [FASDEL]). Developmental programming of diabetes in these mice was assessed from in utero to 1 year of age.
RESULTS—FASDEL mice did not manifest catch-up growth or insulin resistance. β-Cell mass and insulin secretion were strikingly increased in young FASDEL mice, but β-cell failure and diabetes occurred with age. FASDEL β-cells had altered proliferative and apoptotic responses to the common stress of a high-fat diet. This sequence appeared to be developmentally entrained because β-cell mass was increased in utero in FASDEL mice and in another model of intrauterine growth restriction caused by ectopic expression of uncoupling protein-1. Increasing intrauterine growth in FASDEL mice by supplementing caloric intake of pregnant dams normalized β-cell mass in utero.
CONCLUSIONS—Decreased intrauterine body size, independent of postnatal growth and insulin resistance, appears to regulate β-cell mass, suggesting that developing body size might represent a physiological signal that is integrated through the pancreatic β-cell to establish a template for hyperfunction in early life and β-cell failure with age.
Evaluating the Role of LPIN1 Variation in Insulin Resistance, Body Weight, and Human Lipodystrophy in U.K. Populations
Authors: Fawcett Katherine A. , Grimsey Neil , Loos Ruth J.F. , Wheeler Eleanor , Daly Allan , Soos Maria , Semple Robert , Syddall Holly , Cooper Cyrus , Siniossoglou Symeon , O'Rahilly Stephen , Wareham Nicholas J. , Barroso Inês 
Published: July 2008

OBJECTIVE— Loss of lipin 1 activity causes lipodystrophy and insulin resistance in the fld mouse, and LPIN1 expression and common genetic variation were recently suggested to influence adiposity and insulin sensitivity in humans. We aimed to conduct a comprehensive association study to clarify the influence of common LPIN1 variation on adiposity and insulin sensitivity in U.K. populations and to examine the role of LPIN1 mutations in insulin resistance syndromes.
RESEARCH DESIGN AND METHOD— Twenty-two single nucleotide polymorphisms tagging common LPIN1 variation were genotyped in Medical Research Council (MRC) Ely (n = 1,709) and Hertfordshire (n = 2,901) population-based cohorts. LPIN1 exons, exon/intron boundaries, and 3′ untranslated region were sequenced in 158 patients with idiopathic severe insulin resistance (including 23 lipodystrophic patients) and 48 control subjects.
RESULTS— We found no association between LPIN1 single nucleotide polymorphisms and fasting insulin but report a nominal association between rs13412852 and BMI (P = 0.042) in a meta-analysis of 8,504 samples from in-house and publicly available studies. Three rare nonsynonymous variants (A353T, R552K, and G582R) were detected in severely insulin-resistant patients. However, these did not cosegregate with disease in affected families, and Lipin1 protein expression and phosphorylation in patients with variants were indistinguishable from those in control subjects.
CONCLUSIONS— Our data do not support a major effect of common LPIN1 variation on metabolic traits and suggest that mutations in LPIN1 are not a common cause of lipodystrophy in humans. The nominal associations with BMI and other metabolic traits in U.K. cohorts require replication in larger cohorts.