bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the links between sediment character, bed material erosion and landscape: implications from a laboratory study of gravels and sand-gravel mixtures
Authors: Frostick Lynne , Murphy Brendan , Middleton Richard 
Published: February 2008

Abstract
Rates of landscape evolution and landform development depend on the capacity of the main transporting medium, predominantly water and the river system, to move material away from the site of production in the upland slopes. In upland areas the main river bed material is coarse gravels, with various admixtures of finer sand and silt. This paper reports a series of flume experiments to investigate the impact of admixtures of finer material on the entrainment of coarse particles. In all experiments the main framework of the bed was made up of quartz-density gravels with a mean particle size of 8 mm. In some of the experiments unimodal, 0.09 mm mean particle size, quartz sands were introduced upstream of the experimental section and transported into place in order to simulate a common condition in natural river beds, of sand migrating over a static gravel bed. New image analysis techniques were developed to extract data from video recordings of the experimental runs. These revealed important differences in entrainment processes among the experiments with a distinctive contrast between the clean gravel and sand–gravel runs. Observations suggest that the presence of sand increases the rates of gravel entrainment and leads to a distinctive patchiness in bed break-up which will encourage bed form development. In the mixtures, sand removal prior to gravel entrainment destabilizes the bed and allows large areas to become entrained. This contrasts with clean gravels where grains tend to entrain individually. These observations show the importance of bed material character in controlling river form and process and point to its role in controlling sediment flux through the landscape.
Targeting the p27 E3 ligase SCFSkp2 results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy
Authors: Chen Qing , Xie Weilin , Kuhn Deborah J. , Voorhees Peter M. , Lopez-Girona Antonia , Mendy Derek , Corral Laura G. , Krenitsky Veronique Plantevin , Xu Weiming , Moutouh-de Parseval Laure , Webb David R. , Mercurio Frank , Nakayama Keiichi I. , Nakayama Keiko , Orlowski Robert Z. 
Published: February 2008

AbstractDecreased p27Kip1 levels are a poor prognostic factor in many malignancies, and can occur through up-regulation of SCFSkp2 E3 ligase function, resulting in enhanced p27 ubiquitination and proteasome-mediated degradation. While proteasome inhibitors stabilize p27Kip1, agents inhibiting SCFSkp2 may represent more directly targeted drugs with the promise of enhanced efficacy and reduced toxicity. Using high-throughput screening, we identified Compound A (CpdA), which interfered with SCFSkp2 ligase function in vitro, and induced specific accumulation of p21 and other SCFSkp2 substrates in cells without activating a heat-shock protein response. CpdA prevented incorporation of Skp2 into the SCFSkp2 ligase, and induced G1/S cell-cycle arrest as well as SCFSkp2- and p27-dependent cell killing. This programmed cell death was caspase-independent, and instead occurred through activation of autophagy. In models of multiple myeloma, CpdA overcame resistance to dexamethasone, doxorubicin, and melphalan, as well as to bortezomib, and also acted synergistically with this proteasome inhibitor. Importantly, CpdA was active against patient-derived plasma cells and both myeloid and lymphoblastoid leukemia blasts, and showed preferential activity against neoplastic cells while relatively sparing other marrow components. These findings provide a rational framework for further development of SCFSkp2 inhibitors as a novel class of antitumor agents.
The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse
Authors: Huang Yanping , Comiskey Erin O. , Dupree Renell S. , Li Shuixing , Koleske Anthony J. , Burkhardt Janis K. 
Published: February 2008

AbstractActin dynamics during T-cell activation are controlled by the coordinate action of multiple actin regulatory proteins, functioning downstream of a complex network of kinases and other signaling molecules. The c-Abl nonreceptor tyrosine kinase regulates actin responses in nonhematopoietic cells, but its function in T cells is poorly understood. Using kinase inhibitors, RNAi, and conditional knockout mice, we investigated the role of c-Abl in controlling the T-cell actin response. We find that c-Abl is required for normal actin polymerization and lamellipodial spreading at the immune synapse, and for downstream events leading to efficient interleukin-2 production. c-Abl also plays a key role in signaling chemokine-induced T-cell migration. c-Abl is required for the appropriate function of 2 proteins known to be important for controlling actin responses to T-cell receptor (TCR) engagement, the actin-stabilizing adapter protein HS1, and the Rac1-dependent actin polymerizing protein WAVE2. c-Abl binds to phospho-HS1 via its SH2 domains and is required for full tyrosine phosphorylation of HS1 during T-cell activation. In addition, c-Abl is required for normal localization of WAVE2 to the immune synapse (IS). These studies identify c-Abl as a key player in the signaling cascade, leading to actin reorganization during T-cell activation.
Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma
Authors: Qiang Ya-Wei , Chen Yu , Stephens Owen , Brown Nathan , Chen Bangzheng , Epstein Joshua , Barlogie Bart , Shaughnessy John D. 
Published: February 2008

AbstractMultiple myeloma (MM) is characterized by osteolytic bone lesions (OBL) that arise as a consequence of osteoblast inactivation and osteoclast activation adjacent to tumor foci within bone. Wnt signaling in osteoblasts regulates osteoclastogenesis through the differential activation and inactivation of Receptor Activator of Nuclear factor Kappa B Ligand (RANKL) and osteoprotegerin (OPG), positive and negative regulators of osteoclast differentiation, respectively. We demonstrate here that MM cell–derived DKK1, a soluble inhibitor of canonical Wnt signaling, disrupted Wnt3a-regulated OPG and RANKL expression in osteoblasts. Confirmed in multiple independent assays, we show that pretreatment with rDKK1 completely abolished Wnt3a-induced OPG mRNA and protein production by mouse and human osteoblasts. In addition, we show that Wnt3a-induced OPG expression was diminished in osteoblasts cocultured with a DKK1-expressing MM cell line or primary MM cells. Finally, we show that bone marrow sera from 21 MM patients significantly suppressed Wnt3a-induced OPG expression and enhanced RANKL expression in osteoblasts in a DKK1-dependent manner. These results suggest that DKK1 may play a key role in the development of MM-associated OBL by directly interrupting Wnt-regulated differentiation of osteoblasts and indirectly increasing osteoclastogenesis via a DKK1-mediated increase in RANKL-to-OPG ratios.
Sampling and sensitivity analyses tools (SaSAT) for computational modelling
Authors: Hoare Alexander , Regan David G , Wilson David P 
Published: February 2008

AbstractSaSAT (Sampling and Sensitivity Analysis Tools) is a user-friendly software package for applying uncertainty and sensitivity analyses to mathematical and computational models of arbitrary complexity and context. The toolbox is built in Matlab®, a numerical mathematical software package, and utilises algorithms contained in the Matlab®Statistics Toolbox. However, Matlab®is not required to use SaSAT as the software package is provided as an executable file with all the necessary supplementary files. The SaSAT package is also designed to work seamlessly with Microsoft Excel but no functionality is forfeited if that software is not available. A comprehensive suite of tools is provided to enable the following tasks to be easily performed: efficient and equitable sampling of parameter space by various methodologies; calculation of correlation coefficients; regression analysis; factor prioritisation; and graphical output of results, including response surfaces, tornado plots, and scatterplots. Use of SaSAT is exemplified by application to a simple epidemic model. To our knowledge, a number of the methods available in SaSAT for performing sensitivity analyses have not previously been used in epidemiological modelling and their usefulness in this context is demonstrated.
Absence of Secondary Malignant Neoplasms in Children With High-Risk Acute Lymphoblastic Leukemia Treated With Dexrazoxane
Authors: Barry Elly V. , Vrooman Lynda M. , Dahlberg Suzanne E. , Neuberg Donna S. , Asselin Barbara L. , Athale Uma H. , Clavell Luis A. , Larsen Eric C. , Moghrabi Albert , Samson Yvan , Schorin Marshall A. , Cohen Harvey J. , Lipshultz Steven E. , Sallan Stephen E. , Silverman Lewis B. 
Published: February 2008

Purpose Dexrazoxane is a drug used to prevent anthracycline-induced cardiotoxicity. A recent report found an association between the use of dexrazoxane and the risk of developing secondary malignant neoplasms (SMNs) in children with Hodgkin's disease. We report the absence of an association of SMNs in children with acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute ALL Consortium Protocol 95-01. Patients and Methods Two hundred five children with high-risk (HR) ALL were randomly assigned to receive doxorubicin alone (n = 100) or doxorubicin with dexrazoxane (n = 105) during the induction and intensification phases of multiagent chemotherapy. We compared incidence of SMNs in these two groups. Results With a median follow-up of 6.2 years, no differences in the incidence of SMNs were noted between the group that received dexrazoxane and the group that did not (P = .66). One SMN (a melanoma located outside of the cranial radiation field) occurred in a patient who was randomly assigned to doxorubicin alone. No SMNs were observed in patients randomly assigned to receive dexrazoxane. Conclusion Dexrazoxane was not associated with an increased risk of SMNs in children treated for HR ALL. Given the potential importance of dexrazoxane as a cardioprotectant, we recommend that dexrazoxane continue to be used and studied in doxorubicin-containing pediatric regimens.
Concomitant Administration of Weekly Oxaliplatin, Fluorouracil Continuous Infusion, and Radiotherapy After 2 Months of Gemcitabine and Oxaliplatin Induction in Patients With Locally Advanced Pancreatic Cancer: A Groupe Coordinateur Multidisciplinaire en Oncologie Phase II Study
Authors: Moureau-Zabotto Laurence , Phélip Jean-Marc , Afchain Pauline , Mineur Laurent , André Thierry , Vendrely Veronique , Lledo Gerard , Dupuis Olivier , Huguet Florence , Touboul Emmanuel , Balosso Jacques , Louvet Christophe 
Published: February 2008

Background According to previously reported Groupe Coordinateur Multidisciplinaire en Oncologie (GERCOR) studies in locally advanced pancreatic cancer (LAPC), concomitant chemoradiotherapy (CCRT) may be recommended for patients who do not experience disease progression after systemic induction chemotherapy (CT). To further improve patient outcome with classical fluorouracil (FU)-based CCRT, this study was designed to prospectively investigate a CCRT with FU infusion and weekly oxaliplatin after 2 months of gemcitabine and oxaliplatin (GEMOX) induction chemotherapy. Patients and Methods Nonpretreated patients with LAPC having WHO performance status (PS) of 0 to 2 received four induction cycles of GEMOX (gemcitabine 1 g/m2 on day 1 and oxaliplatin 100 mg/m2 on day 2; day 1 of a 15-day cycle). One month after cycle 4, patients who did not experience disease progression with PS 0 to 2 received 45 Gy over 5 weeks + 10 Gy (as a concomitant boost during the last 2 weeks) of radiotherapy (RT), with daily 250 mg/m2 FU as a continuous infusion and 60 mg/m2of oxaliplatin weekly. Results Of 59 patients, 50 patients (84.7%) received CCRT, whereas nine patients did not because of disease progression (seven patients), CT toxicity (one patient), or personal decision (one patient). Forty-four patients (74.5%) completed the fully planned CCRT. Median progression-free survival and overall survival durations were 7.6 and 12.2 months, respectively, for the whole population and 9.4 and 12.6 months, respectively, for patients who completed CCRT. CCRT grade 3 to 4 toxicities (National Cancer Institute Common Toxicity Criteria) were neutropenia (10.4%), thrombocytopenia (8.4%), nausea and vomiting (16.7%), and diarrhea (12.5%). Conclusion Concomitant administration of weekly oxaliplatin, continuous-infusion FU, and RT in patients with LAPC is feasible, with an acceptable acute and late safety profile. The encouraging results observed despite a nonoptimal patient selection (owing to the short induction time) indicates that further randomized evaluation to better define the specific role of oxaliplatin in CCRT is deserved.
A survey of moisture distribution in two sets of Scots pine logs by NIR-spectroscopy
Authors: Karttunen Kyösti , Leinonen Asta , Sarén Matti-Paavo 
Published: February 2008

Abstract
Moisture content distributions of Scots pine logs in the green state were measured by a novel multi-step procedure. After sample preparation, the transverse sections of the wood surfaces were scanned by an automated scanning device with a fiber optical probe connected to a Fourier transform near-infrared spectroscope. In the course of the measurement sequences, several issues were addressed, such as surface drying, measurement geometry, ease of automation and interconnected data handling. The near-infrared (NIR) data were first modeled separately for heartwood and sapwood by means of multivariate partial least squares regression. The models for moisture content were evaluated by root mean square error of prediction, the result being 0.8% for heartwood and 10% for sapwood. The two models were then applied to the NIR data collected from sets of disks cut from nine logs. The results of the calculated moisture contents were evaluated by methods of descriptive statistics, and they indicated clear differences and trends in the distribution of moisture content in transverse or longitudinal regions of a log. Additionally, inter-tree variation in moisture content was detected.
Output Strategies for English‐Language Learners: Theory to Practice
Authors: Anthony Angela R. Beckman 
Published: February 2008

Language production, or output, is not simply a product to demonstrate learning but part of the learning process. The output hypothesis, a theoretical model of second‐language acquisition, proposes that second‐language learners must produce the language they are learning in order to obtain a level of proficiency similar to that of native speakers.The purpose of this article is to apply the principles of the output hypothesis to language and literacy instruction for English‐language learners (ELLs). A brief review of literature related to the input and output hypotheses is presented and is followed by application of the output theory to several common classroom practices. Emphasis is placed on the importance of moving beyond providing input for ELLs and intentionally targeting children's language production. Hypothetical examples of teacher talk and teaching strategies that encourage output are provided.
PTPN22 Trp620 Explains the Association of Chromosome 1p13 With Type 1 Diabetes and Shows a Statistical Interaction With HLA Class II Genotypes
Authors: Smyth Deborah J. , Cooper Jason D. , Howson Joanna M.M. , Walker Neil M. , Plagnol Vincent , Stevens Helen , Clayton David G. , Todd John A. 
Published: February 2008

OBJECTIVE—The disease association of the common 1858C&gt;T Arg620Trp (rs2476601) nonsynonymous single nucleotide polymorphism (SNP) of protein tyrosine phosphatase; nonreceptor type 22 (PTPN22) on chromosome 1p13 has been confirmed in type 1 diabetes and also in other autoimmune diseases, including rheumatoid arthritis and Graves’ disease. Some studies have reported additional associated SNPs independent of rs2476601/Trp620, suggesting that it may not be the sole causal variant in the region and that the relative risk of rs2476601/Trp620 is greater in lower risk by HLA class II genotypes than in the highest risk class II risk category.
RESEARCH DESIGN AND METHODS—We resequenced PTPN22 and used these and other data to provide &gt;150 SNPs to evaluate the association of the PTPN22 gene and its flanking chromosome region with type 1 diabetes in a minimum of 2,000 case subjects and 2,400 control subjects.
RESULTS—Due to linkage disequilibrium, we were unable to distinguish between rs2476601/Trp620 (P = 2.11 ×10−87) and rs6679677 (P = 3.21 ×10−87), an intergenic SNP between the genes putative homeodomain transcription factor 1 and round spermatid basic protein 1. None of the previously reported disease-associated SNPs proved to be independent of rs2476601/Trp620. We did not detect any interaction with age at diagnosis or sex. However, we found that rs2476601/Trp620 has a higher relative risk in type 1 diabetic case subjects carrying lower risk HLA class II genotypes than in those carrying higher risk ones (P = 1.36 × 10−4 in a test of interaction).
CONCLUSIONS—In our datasets, there was no evidence for allelic heterogeneity at the PTPN22 locus in type 1 diabetes, indicating that the SNP rs2476601/Trp620 remains the best candidate in this chromosome region in European populations. The heterogeneity of rs2476601/Trp620 disease risk by HLA class II genotype is consistent with previous studies, and the joint effect of the two loci is still greater in the high-risk group.
Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice
Authors: Cani Patrice D. , Bibiloni Rodrigo , Knauf Claude , Waget Aurélie , Neyrinck Audrey M. , Delzenne Nathalie M. , Burcelin Rémy 
Published: February 2008

OBJECTIVE—Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases.
RESEARCH DESIGN AND METHODS—We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect.
RESULTS—We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14−/− mutant mice mimicked the metabolic and inflammatory effects of antibiotics.
CONCLUSIONS—This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.
Quantifying the Excess Risk of Type 2 Diabetes by Body Habitus Measurements Among Australian Aborigines Living in Remote Areas
Authors: Kondalsamy-Chennakesavan Srinivas , Hoy Wendy E. , Wang Zhiqiang , Shaw Jonathan 
Published: February 2008

OBJECTIVE—To quantify the risk for type 2 diabetes by body habitus measurements among remote-living Australian Aborigines relative to that measured in the general Australian population (as characterized by the Australian Diabetes, Obesity and Lifestyle [AusDiab] study).
RESEARCH DESIGN AND METHODS—Anthropometric measurements and diabetes status were assessed by standard procedures among Aborigines (n = 1,456) and Australians aged ≥25 years (n = 11,247). Age-adjusted odds ratios (ORs) for diabetes among Aborigines relative to AusDiab participants were calculated by commonly used categories of body size measurements.
RESULTS—The OR (95% CI) values for diabetes among normal, overweight, and obese (by waist) Aboriginal women relative to AusDiab women were 2.6 (0.6–11.5), 13.1 (6.7–25.7), and 6.1 (4.6–8.0), respectively, and for Aboriginal men relative to AusDiab men, they were 7.6 (4.6–12.5), 7.6 (4.3–13.4), and 5.2 (3.4–8.0), respectively. Rates of diabetes were also excessive in Aborigines for each standard category of BMI.
CONCLUSIONS—Higher rates of diabetes, even at normal and lower body habitus measurements, among Aborigines suggest that strategies for prevention should expand beyond exclusive focus on diet and weight management.
Objectively Measured Time Spent Sedentary Is Associated With Insulin Resistance Independent of Overall and Central Body Fat in 9- to 10-Year-Old Portuguese Children
Authors: Sardinha Luis B. , Andersen Lars Bo , Anderssen Sigmund A. , Quitério Ana L. , Ornelas Rui , Froberg Karsten , Riddoch Chris J. , Ekelund Ulf 
Published: February 2008

OBJECTIVE—We examined the independent relationships between objectively measured physical activity and insulin resistance in Portuguese children.
RESEARCH DESIGN AND METHODS—This is a school-based, cross-sectional study in 147 randomly selected girls (aged 9.8 ± 0.3 years; 27.8 ± 9.3% body fat) and 161 boys (aged 9.8 ± 0.3 years; 22.0 ± 9.2% body fat). Physical activity was assessed by the Actigraph accelerometer for 4 days and summarized as time spent sedentary (accelerometer counts &lt;500/min), in light-intensity (accelerometer counts 500–2,000/min), and in moderate- and vigorous-intensity activity (accelerometer counts &gt;2,001/min). We measured total and central fat mass by dual-energy X-ray absorptiometry. Insulin resistance was expressed as the homeostasis model assessment score.
RESULTS—Time (min/day) spent sedentary was significantly and positively associated with insulin resistance (β-coefficient = 0.001 [95% CI 0.0002–0.002]; P = 0.013). Time spent in moderate- and vigorous-intensity physical activity (−0.002 [−0.003 to −0.001]; P = 0.0009) and overall physical activity (−0.001 [−0.008 to 0.003]; P &lt; 0.0001) were significantly and inversely associated with insulin resistance. All associations remained statistically significant, although they were attenuated after further adjustments for sex, birth weight, sexual maturity, and total or central fat mass (P &lt; 0.03).
CONCLUSIONS—Physical activity is associated with insulin resistance independent of total and central fat mass in children. Our results emphasize the importance of decreasing sedentary behavior and increasing time spent in moderate- and vigorous-intensity activity in children, which may have beneficial effects on metabolic risk factors regardless of the degree of adiposity.