bluuebunny/crossref_metadata_2025_split huggingface dataset:
A receptor theory‐based semimechanistic PD model for the CCR5 noncompetitive antagonist maraviroc
Authors: Jacqmin Philippe , McFadyen Lynn , Wade Janet R. 
Published: March 2008

AIMTo develop a novel combined viral dynamics/operational model of (ant‐)agonism that describes the pharmacodynamic effects of maraviroc, a noncompetitive CCR5 inhibitor, on viral load.METHODSA common theoretical framework based on receptor theory and the operational model of (ant‐)agonism has been developed to describe the binding of maraviroc to the CCR5 receptor and the subsequent decrease in viral load. The anchor point of the operational model in the differential equations of the viral dynamic model is the infection rate constant; this is assumed to be dependent on the number of free activated receptors on each target cell.RESULTSThe new model provides one explanation for the apparent discrepancy between thein vivobinding of maraviroc to the CCR5 receptor (KD = 0.089 ng ml−1) and the estimatedin vivoinhibition (IC50 = 8 ng ml−1) of the infection rate. The estimatedKEvalue of the operational model indicates that only 1.2% of free activated receptors are utilized to elicit 50% of the maximum infection rate.CONCLUSIONSThe developed model suggests that the target cells, when activated, express more receptors (spare receptors) than needed. In the presence of maraviroc these spare receptors first require blocking before any decrease in the infection rate, and consequently in the viral load at equilibrium, can be detected. The model allows the simultaneous simulation of the binding of maraviroc to the CCR5 receptor and the change in viral load after both short‐ and long‐term treatment.
Associations with multiple pituitary hormone deficiency in patients with an ectopic posterior pituitary gland
Authors: Murray P. G. , Hague C. , Fafoula O. , Patel L. , Raabe A. L. , Cusick C. , Hall C. M. , Wright N. B. , Amin R. , Clayton P. E. 
Published: March 2008

SummaryIntroduction  The presence of an ectopic posterior pituitary gland (EPP) on magnetic resonance imaging (MRI) is associated with hypopituitarism with one or more hormone deficiencies. We aimed to identify risk factors for having multiple pituitary hormone deficiency (MPHD) compared to isolated growth hormone deficiency (IGHD) in patients with an EPP.Methods  In 67 patients (45 male) with an EPP on MRI, the site (hypothalamic vs. stalk) and surface area (SA) [ × (maximum diameter/2) × (maximum height/2), mm2] of the EPP were recorded and compared in patients with IGHD and MPHD in relation to clinical characteristics.Results  In MPHD (n = 32) compared to IGHD (n = 35) patients: age of presentation was younger (1·4 [0·1–10·7]vs. 4·0 [0·1–11·3] years, P = 0·005), major incidents during pregnancy were increased (47%vs. 20%, P = 0·02) as were admissions to a neonatal intensive care unit (NICU) (60%vs. 26%, P = 0·04), whilst EPP SA was lower (12·3 [2·4–34·6]vs. 25·7 [6·9–48·2] mm2, P < 0·001). In patients with a hypothalamic (n = 56) compared to a stalk sited EPP (n = 11): prevalence of MPHD was greater (55%vs. 9%,P = 0·05) and EPP surface area was smaller (17·3 [2·4–48·2]vs. 25·3 [11·8–38·5] mm2, P < 0·001). In regression analysis, after adjusting for age, presence of MPHD was associated with: major incidents during pregnancy (RR 6·8 [95%CI 1·2–37·7]), hypothalamic EPP site (RR 10·9 [1·0–123·9]) and small EPP SA (RR 2·5 [1·0–5·0] for tertiles of SA).Conclusion  In patients with an EPP, adverse antenatal events, size (small) and position (hypothalamic) of the posterior pituitary gland on MRI were associated with MPHD. These findings suggest that adverse factors during pregnancy may be important for the development of an EPP.
A cyanobacterial bloom prevents fish trophic cascades
Authors: RONDEL CAROLINE , ARFI ROBERT , CORBIN DANIEL , LE BIHAN FRÉDÉRIC , NDOUR EL HADJI , LAZZARO XAVIER 
Published: March 2008

Summary1. We experimentally compared the impacts of visually feeding zooplanktivorous fish and filter‐feeding omnivorous fish in shallow tropical Dakar Bango reservoir, Senegal. We provoked a cyanobacterial Anabaena bloom under mesotrophic to eutrophic N‐limited conditions in 18 enclosures assigned to six Nile tilapia life‐stage treatments, at typical biomasses: fishless control (C), zooplanktivorous fry (Z), omnivorous juveniles (O), herbivorous fingerlings (H) and two combinations (OZ, OH).2. All fish grew well, but as prevalent inedible phytoplankton dampened fish effects, community‐level trophic cascades did not occur. Planktivore types acted independently and affected differentially the biomasses of total zooplankton, cyclopoids, nauplii, cladocerans, invertebrate carnivores, large herbivores, colonial cyanobacteria and Chlorophyta. They neither influenced the total biomass of phytoplankton, nor most water chemistry characteristics. Responses were apparently not fish‐biomass related. The bloom collapsed synchronously in all enclosures, coinciding with enrichment ending, with a return to clear water within 12 days.3. Our results support the hypothesis that excess nutrients and prevalent inedible cyanobacteria inhibit the cascading effects of natural biomass levels of both visually feeding zooplanktivores and filter‐feeding omnivores. In N‐limited meso‐eutrophic shallow tropical lakes with predominantly small herbivorous zooplankton, neither the type nor the biomass of planktivorous fish present seems likely to prevent the transient outburst of cyanobacterial blooms. Such fragile ecosystems may thus not sustain a trophic state suitable for drinking water production, unless human impacts are restricted. The generality of restoration approaches based on ecological engineering should be further explored.
Warming and depth interact to affect carbon dioxide concentration in aquatic mesocosms
Authors: FLANAGAN KYLA M. , MCCAULEY EDWARD 
Published: March 2008

Summary1. Climate change may significantly influence lake carbon dynamics and consequently the exchange of CO2 with the atmosphere. Warming will accelerate multiple processes that either absorb or release CO2, making predicting the net effect of warming on CO2 exchange with the atmosphere difficult. Here we experimentally test how the CO2 flux of deep and shallow systems responds to warming. To do this, we conducted a greenhouse experiment using mesocosms of two depths, experiencing either ambient or warmed temperatures.2. Deeper mesocosms were found to have a lower average CO2 concentration than shallower mesocosms under ambient temperature conditions. In addition, warming interacts with mesocosm depth to affect the average CO2 concentration; there was no effect of warming on the average CO2 concentration of deep mesocosms, but shallow mesocosms had significantly lower average CO2 concentrations when warmed.3. The difference in CO2 concentration resulting from the depth manipulation was due to varying loss rates of particulate carbon to the sediments. There was a strong negative correlation between CO2 and sedimentation rates in the deep mesocosms suggesting that high particulate carbon loss to the sediments lowered the CO2 concentration in the water column. There was no correlation between CO2 and sedimentation rates observed for shallow mesocosms suggesting enhanced carbon regeneration from the sediments was maintaining higher CO2 concentrations in the water column.4. Relationships between CO2 and algal concentrations indicate that the reduction in CO2 concentrations resulting from warming is due to increased per capita algal turnover rates depleting CO2 in the water column. Our results suggest that the carbon dynamics and CO2 flux of shallow systems will be affected more by climate warming than deep systems and the net effect of warming is to increase CO2 uptake.
Methane emission from Siberian arctic polygonal tundra: eddy covariance measurements and modeling
Authors: WILLE CHRISTIAN , KUTZBACH LARS , SACHS TORSTEN , WAGNER DIRK , PFEIFFER EVA‐MARIA 
Published: March 2008

AbstractEddy covariance measurements of methane flux were carried out in an arctic tundra landscape in the central Lena River Delta at 72°N. The measurements covered the seasonal course of mid‐summer to early winter in 2003 and early spring to mid‐summer in 2004, including the periods of spring thaw and autumnal freeze back. The study site is characterized by very cold and deep permafrost and a continental climate with a mean annual air temperature of −14.7 °C. The surface is characterized by wet polygonal tundra, with a micro‐relief consisting of raised moderately dry sites, depressed wet sites, polygonal ponds, and lakes. We found relatively low fluxes of typically 30 mg CH4 m−2 day−1 during mid‐summer and identified soil temperature and near‐surface atmospheric turbulence as the factors controlling methane emission. The influence of atmospheric turbulence was attributed to the high coverage of open water surfaces in the tundra. The soil thaw depth and water table position were found to have no clear effect on methane fluxes. The excess emission during spring thaw was estimated to be about 3% of the total flux measured during June–October. Winter emissions were modeled based on the functional relationships found in the measured data. The annual methane emission was estimated to be 3.15 g m−2. This is low compared with values reported for similar ecosystems. Reason for this were thought to be the very low permafrost temperature in the study region, the sandy soil texture and low bio‐availability of nutrients in the soils, and the high surface coverage of moist to dry micro‐sites. The methane emission accounted for about 14% of the annual ecosystem carbon balance. Considering the global warming potential of methane, the methane emission turned the tundra into an effective greenhouse gas source.
Storage, patterns and controls of soil organic carbon in the Tibetan grasslands
Authors: YANG YUANHE , FANG JINGYUN , TANG YANHONG , JI CHENGJUN , ZHENG CHENGYANG , HE JINSHENG , ZHU BIAO 
Published: March 2008

AbstractThe soils of the Qinghai‐Tibetan Plateau store a large amount of organic carbon, but the magnitude, spatial patterns and environmental controls of the storage are little investigated. In this study, using data of soil organic carbon (SOC) in 405 profiles collected from 135 sites across the plateau and a satellite‐based dataset of enhanced vegetation index (EVI) during 2001–2004, we estimated storage and spatial patterns of SOC in the alpine grasslands. We also explored the relationships between SOC density (soil carbon storage per area) and climatic variables and soil texture. Our results indicated that SOC storage in the top 1 m in the alpine grasslands was estimated at 7.4 Pg C (1 Pg=1015 g), with an average density of 6.5 kg m−2. The density of SOC decreased from the southeastern to the northwestern areas, corresponding to the precipitation gradient. The SOC density increased significantly with soil moisture, clay and silt content, but weakly with mean annual temperature. These variables could together explain about 72% of total variation in SOC density, of which 54% was attributed to soil moisture, suggesting a key role of soil moisture in shaping spatial patterns of SOC density in the alpine grasslands.
Changes in the composition of British butterfly assemblages over two decades
Authors: GONZÁLEZ‐MEGÍAS ADELA , MENÉNDEZ ROSA , ROY DAVID , BRERETON TOM , THOMAS CHRIS D. 
Published: March 2008

AbstractChanges in the abundance and distribution of individual species have been widely documented in Britain and other countries in recent decades, but little has been done to determine changes in community composition over broad geographic areas. Here, we studied species turnover in 51 butterfly assemblages in Britain since 1976, examining extinction and colonisation events together with variation in the abundances of the species. We showed that the species turnover that occurred over 20 years in Britain was associated with colonisation and extinction events and also with variability in the abundance of the species. These changes in community composition differed according to the habitat requirements of the species and their previous distributions, being more evident for habitat specialists and for southerly distributed species. Colonising species often became abundant components of the communities they joined, although this was more evident for generalist than for specialist species. The abundance of species following their arrival, increased with time since colonisation. Species turnover associated with southerly species expanding northwards is consistent with being a response to climate change. The results suggest that climate‐ and habitat‐driven changes in the identity and abundance of species within communities are widespread, and probably ubiquitous. Similar changes are likely to be occurring in other groups of organisms that are similarly undertaking major range shifts associated with climate change.
Rice production in a changing climate: a meta‐analysis of responses to elevated carbon dioxide and elevated ozone concentration
Authors: AINSWORTH ELIZABETH A. 
Published: March 2008

AbstractRice is arguably the most important food source on the planet and is consumed by over half of the world's population. Considerable increases in yield are required over this century to continue feeding the world's growing population. This meta‐analysis synthesizes the research to date on rice responses to two elements of global change, rising atmospheric carbon dioxide concentration ([CO2]) and rising tropospheric ozone concentration ([O3]). On an average, elevated [CO2] (627 ppm) increased rice yields by 23%. Modest increases in grain mass and larger increases in panicle and grain number contributed to this response. The response of rice to elevated [CO2] varied with fumigation technique. The more closely the fumigation conditions mimicked field conditions, the smaller was the stimulation of yield by elevated [CO2]. Free air concentration enrichment (FACE) experiments showed only a 12% increase in rice yield. The rise in atmospheric [CO2] will be accompanied by increases in tropospheric O3 and temperature. When compared with rice grown in charcoal‐filtered air, rice exposed to 62 ppb O3 showed a 14% decrease in yield. Many determinants of yield, including photosynthesis, biomass, leaf area index, grain number and grain mass, were reduced by elevated [O3]. While there have been too few studies of the interaction of CO2 and O3 for meta‐analysis, the interaction of temperature and CO2 has been studied more widely. Elevated temperature treatments negated any enhancement in rice yield at elevated [CO2], which suggests that identifying high temperature tolerant germplasm will be key to realizing yield benefits in the future.
Convergence in the relationship of CO2 and N2O exchanges between soil and atmosphere within terrestrial ecosystems
Authors: XU XIAOFENG , TIAN HANQIN , HUI DAFENG 
Published: March 2008

AbstractEcosystem CO2 and N2O exchanges between soils and the atmosphere play an important role in climate warming and global carbon and nitrogen cycling; however, it is still not clear whether the fluxes of these two greenhouse gases are correlated at the ecosystem scale. We collected 143 pairs of ecosystem CO2 and N2O exchanges between soils and the atmosphere measured simultaneously in eight ecosystems around the world and developed relationships between soil CO2 and N2O fluxes. Significant linear regressions of soil CO2 and N2O fluxes were found for all eight ecosystems; the highest slope occurred in rice paddies and the lowest in temperate grasslands. We also found the dominant role of growing season on the relationship of annual CO2 and N2O fluxes. No significant relationship between soil CO2 and N2O fluxes was found across all eight ecosystem types. The estimated annual global N2O emission based on our findings is 13.31 Tg N yr−1 with a range of 8.19–18.43 Tg N yr−1 for 1980–2000, of which cropland contributes nearly 30%. Our findings demonstrated that stoichiometric relationships may work on ecological functions at the ecosystem level. The relationship of soil N2O and CO2 fluxes developed here could be helpful in biogeochemical modeling and large‐scale estimations of soil CO2 and N2O fluxes.
Applying relationship theories to web site design: development and validation of a site‐communality scale
Authors: Tomiuk Daniel , Pinsonneault Alain 
Published: March 2008

AbstractOur study investigates whether relationship theories can be of help in designing web sites which foster greater customer loyalty. Based on literature reviews of Communal‐Relationship Theory from Social Psychology, communality from marketing research and related concepts (e.g. commercial friendships), we develop and refine a multidimensional measure of ‘site communality’ using a sample of 305 participants. Each visited one among several real web sites chosen across three industries (i.e. banking, pharmaceuticals and insurance). We define site communality as the extent to which web site content signals that a company's relationship with its customers goes beyond the formal, ‘tit for tat’ business dealings that are typically expected from purely commercial exchanges, and instead, more closely abide by the norms and behaviours evocative of friendships and/or family relations. Our results indicate that demonstration of caring, role spanning and authenticity/genuineness
are its most important dimensions. Preliminary, findings also show that site communality is positively related to the benevolence dimension of online trust which is an important antecedent of loyalty. The practical implications of our study are discussed in the form of recommendations to help companies in designing web sites high in site communality.
Pluralist action research: a review of the information systems literature*
Authors: Chiasson Mike , Germonprez Matt , Mathiassen Lars 
Published: March 2008

AbstractAction research (AR) has for many years been promoted and practised as one way to conduct field studies within the information systems (IS) discipline. Based on a review of articles published in leading journals, we explore how IS researchers practise AR. Our review suggests that AR lends itself strongly towards pluralist approaches which facilitate the production of both theoretical and practical knowledge. First, on the level of each study we analyse how research and problem‐solving activities are mixed, in three ways: the research dominant, the problem‐solving dominant and the interactive approaches. Second, in the context of the wider research programme in which the study is situated, we analyse how AR is mixed with other research methods, in two ways: the dominant and the sequential approaches. We argue that these pluralist practices of mixing types of research activities and types of research methods provide IS action researchers with a rich portfolio of approaches to knowledge production. This portfolio helps them address the risks involved in AR to ensure their efforts contribute to the literature as well as to practical problem‐solving.
Dysregulation of matrix metalloproteinases and their tissue inhibitors is related to abnormality of left ventricular geometry and function in streptozotocin‐induced diabetic minipigs
Authors: Lu Lin , Zhang Qi , Pu Li Jin , Peng Wen Hui , Yan Xiao Xiang , Wang Lin Jie , Chen Qiu Jing , Zhu Zheng Bing , Michel Jean‐Baptiste , Shen Wei Feng 
Published: March 2008

SummaryThis study aimed to characterize matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in relation to changes in left ventricle (LV) geometry and function in a porcine model with streptozotocin (STZ)‐induced diabetes. In 15 Chinese Guizhou minipigs with STZ‐induced diabetes (diabetic group) and 15 age‐matched normal controls (control group), Doppler tissue imaging was performed at 6 months of diabetes. Serum MMP‐2, ‐9, TIMP‐1, ‐4 and B‐type natriuretic peptide (BNP) were determined. Expression of MMPs, TIMPs, urokinase type‐plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor‐1 (PAI‐1) in aortic intima and LV myocardium was evaluated, with gelatinolytic activities of tissue MMP‐2, ‐9 accessed by zymography. Left ventricle end‐diastolic septum thickness (P < 0.05) and mass (P < 0.05) were increased, whereas peak systolic mitral annulus velocity (Sm, P < 0.001), LV systolic (P = 0.01) and diastolic strain (P < 0.001) were significantly decreased in diabetic group than in controls. Diabetic group showed higher expression of TIMP‐1, ‐4 in aortic intima and LV myocardium (P < 0.01 or P < 0.05), with increased collagen content and elevated serum BNP level (P = 0.004) and lower gelatinolytic activities of tissue MMP‐2, ‐9 (all P < 0.05). Semi‐quantitative RT‐PCR of those diabetic tissues revealed elevated mRNA levels of major TIMPs, uPA, uPAR and PAI‐1. Reduction of serum MMP‐2 and ‐9 levels was observed in diabetic group vs. control group (both P < 0.05). This study features elevated levels of TIMP‐1, ‐4, uPA, uPAR and PAI‐1, and decreased activities of MMP‐2, ‐9 in aorta and myocardium in STZ‐induced diabetic minipigs, indicating that MMP–TIMP dysregulation is associated with LV hypertrophy, cardiac dysfunction and increased cardiovascular fibrosis in diabetes.
Serum FLT‐3 ligand in a busulphan‐induced model of chronic bone marrow hypoplasia in the female CD‐1 mouse
Authors: Molyneux Gemma , Gibson Frances M. , Whayman Matthew , Turton John A. 
Published: March 2008

SummaryThe concentration of the cytokine fms‐like tyrosine kinase‐3 ligand (FL) is elevated in the plasma of patients treated with chemotherapy or radiotherapy for malignant conditions. In addition, plasma FL is increased in patients with bone marrow failure resulting from stem‐cell defects (e.g. aplastic anaemia). Our goal in the present study was to measure the concentration of serum FL in mice treated with the chemotherapeutic agent busulphan (BU) to induce bone marrow depression and relate changes in FL to effects on haemopoiesis. Female CD‐1 mice were treated with BU (9.0 mg/kg) or vehicle by intraperitoneal injection on 10 occasions over 21 days. Animals were autopsied on days 1, 23, 72, 119 and 177 postdosing. A full blood count was performed, and serum prepared for FL analysis. Femoral marrow cell suspensions were prepared to assess the total femoral nucleated cell count (FNCC) and the number of committed haemopoietic progenitor cells (CFU‐C). On days 1 and 23 postdosing, significant decreases were evident in many peripheral blood parameters; the FNCC and CFU‐C were also reduced in BU‐treated mice, in conjunction with increases in serum FL levels. On days 72, 119 and 177 postdosing, several peripheral blood and bone marrow parameters remained reduced and the concentration of serum FL continued to be significantly increased. Linear regression analysis demonstrated significant correlations between the concentration of serum FL in BU‐treated mice and peripheral blood and bone marrow parameters; this suggests the possible use of serum FL as a potential biomarker for drug‐induced bone marrow injury.