bluuebunny/crossref_metadata_2025 huggingface dataset:
An Intein‐Mediated Site‐Specific Click Conjugation Strategy for Improved Tumor Targeting of Nanoparticle Systems
Authors: Elias Drew R. , Cheng Zhiliang , Tsourkas Andrew
Published: October 2010

The ability to modify and directly target nanoparticulate carriers has greatly increased their applicability in diagnostic and therapeutic studies. Generally essential to the targeting of nanoparticles is the bioconjugation of targeting ligands to the agent's surface. While bioconjugation techniques have steadily improved in recent years, the field is still plagued with inefficient conjugations reactions and/or the lack of site‐specific coupling. To overcome these limitations, click chemistry and expressed protein ligation (EPL) are combined to produce a highly efficient, site‐specific reaction. This new EPL–click conjugation strategy is applied to create superparamagnetic iron oxide nanoparticles (SPIO) labeled with HER2/neu affibodies. These HER2‐SPIO nanoparticles prove to be highly potent and receptor‐specific in both in vitro cell studies and murine tumor models. Moreover, when EPL–click‐derived HER2‐SPIO are compared with SPIO that had been labeled with HER2 affibodies using other popular bioconjugation methods, they produce a statistically significant improvement in contrast enhancement upon cell binding. The EPL–click system is also successfully extended to other nanoparticle platforms (i.e., liposomes and dendrimers) highlighting the versatility of the approach.
Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China
Authors: Wang Fei , Han Lianshu , Yang Yanling , Gu Xuefan , Ye Jun , Qiu Wenjuan , Zhang Huiwen , Zhang Yafen , Gao XiaoLan , Wang Yu
Published: October 2010

The most common inborn error of cobalamin (cbl) metabolism in China is the cblC type characterized by combined methylmalonic acidemia and hyperhomocysteinemia. The clinical presentation is relatively nonspecific, such as feeding difficulty, recurrent vomiting, hypotonia, lethargy, seizures, progressive developmental delay, and mental retardation, together with anemia and metabolic acidosis. More specific biochemical findings include high levels of propionylcarnitine (C3), free carnitine (C3/C0), and acetylcarnitine (C3/C2) measured by tandem mass spectrometry (MS/MS), elevation of methylmalonic acid (MMA) measured by gas chromatography–mass spectrometry (GC‐MS), and increased total homocysteine with normal or decreased methionine. We report on 50 Chinese patients with combined methylmalonic acidemia and hyperhomocysteinemia. Forty‐six belonged to the cblC complementation group. Mutation analysis of the MMACHC gene was performed to characterize the mutational spectrum of cblC deficiency, and 17 different mutations were found. Most were clustered in exons 3 and 4, accounting for 91.3% of all mutant alleles. Two mutations were novel, namely, c.315 C>G (p.Y105X) and c.470 G>C(p.W157S). In terms of genotype–phenotype correlation, the c.609 G>A mutation was associated with early‐onset disease when homozygous. Unlike previous reports from other populations, c.609 G>A (p.W203X) was the most frequent cblC mutation detected in our study of Chinese patients #Affecting 51 of 92 MMACHC alleles (55.4%). The high prevalence of this nonsense mutation could have potential therapeutic significance for Chinese cblC patients. Besides traditional approaches consisting of hydroxocobalamin injections, carnitine, betaine, and protein restriction, novel drugs that target premature termination codons may have a role in the future.
Stratum Corneum Lipid Structure Investigated by EPR Spin‐Probe Method: Application of Terpenes
Authors: Nakagawa Kouichi , Anzai Kazunori
Published: October 2010

Electron paramagnetic resonance (EPR) in conjunction with a slow‐tumbling simulation was utilized for defining stratum corneum (SC) lipid structure. SC from the back of hairless mouse (HOS:HR‐1) was stripped consecutively from one to three or four times using a glass plate coated with a cyanoacrylate resin. Aliphatic spin probes, 5‐doxylstearic acid (5‐DSA) and 3β‐doxyl‐5α‐cholestane (CHL), were used to evaluate the SC ordering. EPR spectrum of 5‐DSA incorporated in the SC demonstrated a characteristic peak for the first strip. A slow‐tumbling simulation for 5‐DSA showed clear differences in EPR intensities as well as ordering values (S0) of the SC for control and terpenes treated SC. The α‐terpineol enhanced the permeation of the single chain 5‐DSA about three times more than that of the control. However, EPR spectra of CHL in the SC did not show a clear difference for each strip, except for the signal intensity. The results imply that CHL permeates into SC lipid differently from 5‐DSA. The enhancement of the 5‐DSA is more significant than that of CHL. Therefore, the present results can be useful for various drug administrations via the skin.
Application of a conceptual framework to interpret variability in rangeland responses to atmospheric CO2enrichment
Authors: POLLEY H. W. , MORGAN J. A. , FAY P. A.
Published: October 2010

Plant productivity and other ecosystem processes vary widely in their responses to experimental increases in atmospheric carbon dioxide (CO2) concentration. A conceptual framework first suggested by Chapinet al.(1996) was adapted to address the question of why CO2effects on primary productivity vary so greatly among rangelands and among years for a given ecosystem. The ‘interactive controls’ framework is based on the premise that the influence of elevated CO2on productivity is governed by a set of internal variables that interact dynamically with ecosystem processes. These interactive controls, which include regional climate, soil resource supply, major functional groups of organisms and disturbance regimes, both regulate CO2effects on ecosystems and respond to CO2effects. Changes in interactive controls resulting from CO2enrichment may feed back to dampen or amplify ecosystem responses to CO2. Most feedbacks from interactive controls will be negative and dampen CO2effects on ecosystems. Negative feedbacks promote homeostasis in ecosystem processes and reduce the response of plant productivity to CO2. Positive feedbacks on CO2responses are fewer, but can sustain or even increase benefits of CO2enrichment for productivity. Positive feedbacks on CO2responses occur most frequently through changes in plant species and functional group composition. Understanding positive and negative feedbacks on CO2responses could be one key to predicting consequences of CO2enrichment for rangeland productivity and other processes.
When Is Shuttle Diplomacy Worth the Commute? Information Sharing through Mediation
Authors: Fey Mark , Ramsay Kristopher W.
Published: October 2010

The authors study the conflict mediation problem, sometimes called “shuttle diplomacy,” when the mediator acts as a go-between and must gather information from the disputants. In the context of a general model of information mediation, they show that the incentive that disputants have to lie to the mediator undoes any advantage that might be gained by adding communication with a third party. In fact, the main result shows that any equilibrium outcome that is achievable through mediation is also achievable as an equilibrium outcome of a game with unmediated preplay communication. This is true even when the mediator is allowed to have arbitrary preferences or biases. The authors then test their empirical prediction on dispute management efforts between 1937 and 1985. The analysis supports the hypothesis that information mediation has no effect in environments where the mediator has no independent source of information.
Organizational Determinants of Wage Moderation
Authors: Baccaro Lucio , Simoni Marco
Published: October 2010

This article contributes to the political economic literature regarding the effects of industrial relations institutions on national economic outcomes. Based on an econometric analysis of the determinants of wage moderation in sixteen industrialized countries between 1974 and 2000, it argues that the organizational characteristics of trade unions have a significant impact on wage dynamics. Controlling for a number of institutional and economic factors, the countries in which trade union confederations directly involve workers in the process of collective bargaining ratification have on average lower wage growth relative to productivity than others. The authors also find that collective bargaining coordination and contract ratification magnify each other's wage-dampening effect. Through case studies of Ireland and Italy, the article examines the causal mechanisms underlying the uncovered statistical regularities and concludes that, particularly at a time in which classic political exchange is waning, worker involvement in contract ratification allows confederation leaders to resolve conflicting claims inside their organizations at lower wage levels than are achieved by a less participatory governance process.
Varieties of Electioneering: Success Contagion and Presidential Campaigns in Latin America
Authors: Boas Taylor C.
Published: October 2010

Existing theories of change in campaign strategies predict cross-national convergence in candidates' linkages to voters and the degree of policy focus and cleavage priming in their appeals. However, the prevailing national patterns of electioneering in Chile, Brazil, and Peru have actually diverged from one another since their transitions from authoritarian rule. Based upon content analysis of television advertising, interviews with campaign staff, and case studies of specific elections in these three countries, this article develops a theory of success contagion that can explain the evolution of presidential campaign strategy in third-wave democracies. The author argues that the first politician to combine a victorious campaign with a successful term as president establishes a model of electioneering that candidates across the ideological spectrum are likely to adopt in the future. Such contagion can occur directly, through politicians' imitation of each other's strategies, or indirectly, with communities of campaign professionals playing an intermediary role. Strategic convergence is less likely in cases of repeatedly poor governing performance. Instead, candidates tend to choose strategies through an inward-oriented process of reacting against previous errors. Initial testing suggests the theory is generalizable to other new democracies with at least moderate organizational continuity across elections.
Mobilizing Restraint: Economic Reform and the Politics of Industrial Protest in South Asia
Authors: Teitelbaum Emmanuel
Published: October 2010

The study draws on evidence from South Asia to explore how union partisan ties condition industrial protest in the context of rapid economic change. It argues that unions controlled by major political parties respond to the economic challenges of the postreform period by facilitating institutionalized grievance resolution and encouraging restraint in the collective bargaining arena. By contrast, politically independent unions and those controlled by small parties are more likely to ratchet up militancy and engage in extreme or violent forms of protest. The difference between the protest behavior of major party unions and other types of unions is explained by the fact that major political parties are encompassing organizations that internalize the externalities associated with the protest of their affiliated unions. Using original survey data from four regions in South Asia, the study shows that party encompassment is a better predictor of worker protest than other features of the affiliated party or the union, including whether the party is in or out of power, the ideological orientation of the party, or the degree of union encompassment. The analysis has implications for the policy debate over whether successful economic reform is contingent upon the political exclusion or repression of organized labor.
Palinspastic restoration of NAVDat and implications for the origin of magmatism in southwestern North America
Authors: McQuarrie Nadine , Oskin Michael
Published: October 2010

Simultaneous palinspastic restoration of deformation and volcanism illuminates relationships between magmatism and tectonics in western North America. Using ArcGIS, we retrodeformed the NAVDat (North American Volcanic Database, navdat.geongrid.org) using the western North America reconstruction of McQuarrie and Wernicke (2005). From these data sets we quantitatively compare rates of magmatism and deformation and evaluate the age, composition, and migration of Cenozoic volcanism from 36 Ma to present. These relationships are shown in a series of palinspastic maps as well as animations that highlight migrating extension and volcanism with time. Western North America is grouped into eight different regions with distinct relationships between strain and volcanism to evaluate competing hypotheses regarding the relationship of extension to continental magmatism. A first‐order observation from this study is that magmatism throughout the Basin and Range appears to be primarily driven by plate boundary effects, notably subducting and foundering slabs as well as slab windows. Exceptions include the Yellowstone hotspot system along the northern border of our study area and late‐stage (<8 Ma) passive, extension‐related asthenospheric upwelling along the eastern and western margins of the Basin and Range. The palinspastic reconstructions presented here highlight that the classic, high‐angle, Basin and Range faulting that comprises most of the physiographic Basin and Range Province commenced during a magmatic lull. More broadly, with the exception of the Rio Grande rift we find that pulses of magmatism lag the onset of extension. These observations largely contradict the active rifting model where magmatism triggers Basin and Range extension.
Vertical distribution of water within the polythermal Storglaciären, Sweden
Authors: Gusmeroli Alessio , Murray Tavi , Jansson Peter , Pettersson Rickard , Aschwanden Andy , Booth Adam D.
Published: October 2010

Knowledge of water content and its distribution in polythermal glaciers is required to model their flow and thermal state. However, observations of water content variations with depth in polythermal glaciers are scarce. Water content can be estimated from radio wave speed because they depend on one another. We obtained continuous profiles of radio wave speed variations with depth from zero‐offset radar profiles collected in boreholes approximately 80 m deep in the upper ablation area of Storglaciären, northern Sweden. These profiles show that the microcrystalline water system in the temperate ice is relatively homogeneous. The overall hydrothermal structure at this location is composed of a 20 m thick upper layer of cold, water‐free ice, underlain by a temperate ice layer whose average water content is 0.6% ± 0.3%. These results are corroborated by surface radar and thermistor measurements, which show that the depth of the cold temperate transition is 21 m and the calculated water content at that transition is 0.6% ± 0.1%. These findings imply that the whole temperate ice layer is from 3 to 4 times softer than the cold ice and, consequently, that realistic ice flow models of polythermal glaciers should include the effect of water content on viscosity.
ForCent model development and testing using the Enriched Background Isotope Study experiment
Authors: Parton William J. , Hanson Paul J. , Swanston Chris , Torn Margaret , Trumbore Susan E. , Riley William , Kelly Robin
Published: October 2010

The ForCent forest ecosystem model was developed by making major revisions to the DayCent model including: (1) adding a humus organic pool, (2) incorporating a detailed root growth model, and (3) including plant phenological growth patterns. Observed plant production and soil respiration data from 1993 to 2000 were used to demonstrate that the ForCent model could accurately simulate ecosystem carbon dynamics for the Oak Ridge National Laboratory deciduous forest. A comparison of ForCent versus observed soil pool 14C signature (Δ 14C) data from the Enriched Background Isotope Study 14C experiment (1999–2006) shows that the model correctly simulates the temporal dynamics of the 14C label as it moved from the surface litter and roots into the mineral soil organic matter pools. ForCent model validation was performed by comparing the observed Enriched Background Isotope Study experimental data with simulated live and dead root biomass Δ 14C data, and with soil respiration Δ 14C (mineral soil, humus layer, leaf litter layer, and total soil respiration) data. Results show that the model correctly simulates the impact of the Enriched Background Isotope Study 14C experimental treatments on soil respiration Δ 14C values for the different soil organic matter pools. Model results suggest that a two‐pool root growth model correctly represents root carbon dynamics and inputs to the soil. The model fitting process and sensitivity analysis exposed uncertainty in our estimates of the fraction of mineral soil in the slow and passive pools, dissolved organic carbon flux out of the litter layer into the mineral soil, and mixing of the humus layer into the mineral soil layer.
Land‐use effects on the chemical attributes of low‐order streams in the eastern Amazon
Authors: Figueiredo Ricardo O. , Markewitz Daniel , Davidson Eric A. , Schuler Azeneth E. , dos S. Watrin Orlando , de Souza Silva Patrício
Published: October 2010

Deforestation is altering small catchment hydrobiogeochemistry in the Amazon. To evaluate land use change effects on water chemistry and other measures of water quality, five low‐order streams were studied in the eastern Amazon from April 2003 to October 2005. It was hypothesized that 1) cation loads would increase downstream as the area of cleared forest increased, particularly during the wet season, 2) increasing forest to pasture conversion would increase total solute loads, and 3) nitrate concentrations, which are high under mature forest, would decline with conversion to pasture, but would increase with increasing row crop agriculture. The first hypothesis was generally not supported, as there was no consistent observed increase in conductivity or cation concentrations from upstream to downstream. However, elevated wet‐season measures of conductivity, alkalinity, and turbidity indicated increased wet season surface runoff of these constituents, with seasonal changes largest in the watersheds that had experienced the most deforestation. The second hypothesis was supported when all data were pooled in a mixed‐model analysis such that conductivity declined with increasing percent forest or increased with increasing percent pasture; however, similar correlations with cations were not significant. The third hypothesis was supported, with decreasing nitrate concentrations observed as forest cover declined and pasture cover increased from upstream to downstream positions, except where crops were grown near the stream, which was associated with increased stream nitrate. In addition, stream temperature, dissolved oxygen, and pH were negatively correlated with percent forest cover while sodium, chloride, and turbidity also increased with percent crop cover. Turbidity, temperature, pH, and dissolved oxygen appear to be the simplest and most indicative parameters for detecting effects of land‐use change on water quality in this region.
Tundra burning in Alaska: Linkages to climatic change and sea ice retreat
Authors: Hu Feng Sheng , Higuera Philip E. , Walsh John E. , Chapman William L. , Duffy Paul A. , Brubaker Linda B. , Chipman Melissa L.
Published: October 2010

Recent climatic warming has resulted in pronounced environmental changes in the Arctic, including shrub cover expansion and sea ice shrinkage. These changes foreshadow more dramatic impacts that will occur if the warming trend continues. Among the major challenges in anticipating these impacts are “surprises” stemming from changes in system components that have remained relatively stable in the historic record. Tundra burning is potentially one such component. Here we report paleoecological evidence showing that recent tundra burning is unprecedented in the central Alaskan Arctic within the last 5000 years. Analysis of lake sediment cores reveals peak values of charcoal accumulation corresponding to the Anaktuvuk River Fire in 2007, with no evidence of other fire events throughout the past five millennia in that area. Atmospheric reanalysis suggests that the fire was favored by exceptionally warm and dry weather conditions in summer and early autumn. Boosted regression tree modeling shows that such conditions also explain 95% of the interannual variability in tundra area burned throughout Alaska over the past 60 years and that the response of tundra burning to climatic warming is nonlinear. These results contribute to an emerging body of evidence suggesting that tundra ecosystems can burn more frequently under suitable climatic and fuel conditions. The Anaktuvuk River Fire coincides with extreme sea ice retreat, and tundra area burned in Alaska is moderately correlated with sea ice extent from 1979 to 2009 (r = −0.43, p = 0.02). Recurrences of large tundra fires as a result of sea ice disappearance may represent a novel manifestation of coupled marine‐terrestrial responses to climatic warming.
Catchments as simple dynamical systems: Experience from a Swiss prealpine catchment
Authors: Teuling A. J. , Lehner I. , Kirchner J. W. , Seneviratne S. I.
Published: October 2010

Heterogeneity in small‐scale subsurface flow processes does not necessarily lead to complex system behavior at larger scales. Here we use the simple dynamical systems approach recently proposed by Kirchner (WRR, 2009) to analyze, characterize, and simulate streamflow dynamics in the Swiss Rietholzbach catchment. The Rietholzbach data set used here provides 32 years of continuous and high‐quality observations, which include a soil moisture profile and unique observations of storage changes and evapotranspiration measured by a weighing lysimeter. Streamflow recession at the daily time scale shows a marked seasonal cycle and is fastest in summer due to the higher evapotranspiration losses. The discharge sensitivity function linking storage and discharge is nonlinear and slightly downward‐curving in double‐logarithmic space. Small diurnal discharge fluctuations prevent application of the approach at the hourly resolution for low‐discharge conditions. The vast majority of runoff peaks can be explained by storage variations, except peaks that follow events with extreme precipitation intensity (30–40 mm h−1). Storage change dynamics inferred from streamflow variations compare well to observations from the lysimeter and simulations with a land surface model but become very uncertain under dry conditions. Good results can be obtained when the discharge sensitivity function is calibrated on a monthly time scale to avoid the effect of the diurnal discharge fluctuations. Our analysis highlights the importance of evapotranspiration for catchment hydrology, as it is the main driver of changes in streamflow at Rietholzbach for 21% of the time.
Groundwater uptake by woody vegetation in a semiarid oak savanna
Authors: Miller Gretchen R. , Chen Xingyuan , Rubin Yoram , Ma Siyan , Baldocchi Dennis D.
Published: October 2010

Groundwater can serve as an important resource for woody vegetation in semiarid landscapes, particularly when soil water is functionally depleted and unavailable to plants. This study examines the uptake of groundwater by deciduous blue oak trees (Quercus douglasii) in a California oak savanna. Here we present a suite of direct and indirect methods that demonstrate its occurrence and quantify its rates. The study site is underlain by a thin soil layer and fractured metavolcanic bedrock. Typical depth to groundwater is approximately 8 m. A variety of water storage and flux measurements were collected from 2005 to 2008, including groundwater levels, soil moisture contents, sap flows, and latent heat fluxes. During the dry season, groundwater uptake rates ranged from 4 to 25 mm month−1 and approximately 80% of total ET during June, July, and August came from groundwater. Leaf and soil water potentials supported these results, indicating that groundwater uptake was thermodynamically favorable over soil water uptake for key portions of the growing season. These findings strongly suggest that blue oaks should be considered obligate phreatophytes and that groundwater reserves provide a buffer to rapid changes in their hydroclimate, if these assets are not otherwise depleted by prolonged drought or human consumption. While groundwater uptake may provide for short‐term protection, it should be viewed not as a mechanism for continued plant growth. It allows the woody vegetation to subsist during the summer but not to flourish.
Volcanic ash fuels anomalous plankton bloom in subarctic northeast Pacific
Authors: Hamme Roberta C. , Webley Peter W. , Crawford William R. , Whitney Frank A. , DeGrandpre Michael D. , Emerson Steven R. , Eriksen Charles C. , Giesbrecht Karina E. , Gower Jim F. R. , Kavanaugh Maria T. , Peña M. Angelica , Sabine Christopher L. , Batten Sonia D. , Coogan Laurence A. , Grundle Damian S. , Lockwood Deirdre
Published: October 2010

Using multiple lines of evidence, we demonstrate that volcanic ash deposition in August 2008 initiated one of the largest phytoplankton blooms observed in the subarctic North Pacific. Unusually widespread transport from a volcanic eruption in the Aleutian Islands, Alaska deposited ash over much of the subarctic NE Pacific, followed by large increases in satellite chlorophyll. Surface ocean pCO2, pH, and fluorescence reveal that the bloom started a few days after ashfall. Ship‐based measurements showed increased dominance by diatoms. This evidence points toward fertilization of this normally iron‐limited region by ash, a relatively new mechanism proposed for iron supply to the ocean. The observations do not support other possible mechanisms. Extrapolation of the pCO2 data to the area of the bloom suggests a modest ∼0.01 Pg carbon export from this event, implying that even large‐scale iron fertilization at an optimum time of year is not very efficient at sequestering atmospheric CO2.
On the occurrence of open ocean particle production and growth events
Authors: O'Dowd Colin , Monahan Ciaran , Dall'Osto Manuel
Published: October 2010

We present new results from the Mace Head coastal station illustrating that open ocean new particle production and growth events occur frequently during periods of high oceanic productivity over the N.E. Atlantic. For the first time, we report events during which a recently‐formed nucleation mode (∼15 nm diameter) is detected and is observed to grow into an Aitken mode (∼50 nm diameter) over periods up to 48 hours. A growth rate of 0.8 nm hour−1 is estimated in a typical case study, pointing to a source region ∼700 km off‐shore. The duration of the growth also suggests the particle production events are occurring over large spatial scales. Analysis of seven years of data show occurrence of extended growth events (lasting at least 24 hours) from March to September, with a peak occurrence in May. The events suggest that secondary marine boundary layer aerosol formation contributes to the marine aerosol population.
Regional and grain size influences on the geochemistry of soil at Gusev crater, Mars
Authors: Karunatillake Suniti , McLennan Scott , Herkenhoff Ken E.
Published: October 2010

Congruous with earlier work, Martian soil along the Spirit Rover's traverse at Gusev crater can be divided into three broad groups by size: fines (<150 μm), sand, and a mix of various grain sizes. The key chemical observation is greater homogeneity in fines relative to the other two, consistent with regional‐ and global‐scale sampling of chemical compositions by finer particle sizes. The mix class is generally more heterogeneous as are samples from the Columbia Hills within each class. Variation in the trace element Ni is consistent with a CI contribution not exceeding 3%, while that of Ti is compatible with Fe‐Ti oxide enrichment not exceeding 3%. Physical mixing models are poorly supported. Among many potential binary and three‐component mixing models, only two show some consistency with the soil data: typical fines with the opaline Si end‐member identified at Home Plate and typical fines with sulfates (bearing a variable mix of Ca, Fe, and Mg cations). We also infer that binary mixing transcends classes, contrasting strongly with terrestrial sediments, and that mixing trends are consistent with significant nonmixing contributions, perhaps including localized chemical alteration. The decoupling between chemistry and grain size classes also suggests that processes linking composition with grain size, such as heavy mineral sorting, may have been minimal or absent entirely. The primary exception to this is the correlation between Cl and Si, Cl‐S, and Al‐Si, which is strongest in the fines class.
A physically based model to predict hydraulic erosion of fine‐grained riverbanks: The role of form roughness in limiting erosion
Authors: Darby Stephen E. , Trieu Hai Q. , Carling Paul A. , Sarkkula Juha , Koponen Jorma , Kummu Matti , Conlan Iwona , Leyland Julian
Published: October 2010

Hydraulic erosion of bank toe materials is the dominant factor controlling the long‐term rate of riverbank retreat. In principle, hydraulic bank erosion can be quantified using an excess shear stress model, but difficulties in estimating input parameters seriously inhibit the predictive accuracy of this approach. Herein a combination of analytical modeling and novel field measurement techniques is employed to improve the parameterization of an excess shear stress model as applied to the Lower Mekong River. Boundary shear stress is estimated using a model (Kean and Smith, 2006a, 2006b) for flow over the irregular bank topography that is characteristic of fine‐grained riverbanks. Bank erodibility parameters were obtained using a cohesive strength meter (Tolhurst et al., 1999). The new model was used to estimate annual bank erosion rates via integration across the Mekong's annual flow regime. Importantly, the simulations represent the first predictions of hydraulic bank erosion that do not require recourse to calibration, thereby providing a stronger physical basis for the simulation of bank erosion. Model predictions, as evaluated by comparing simulated annual rates of bank toe retreat with estimates of bank retreat derived from analysis of aerial photographs and satellite imagery, indicate a tendency to overpredict erosion (root‐mean‐square error equals ±0.53 m/yr). Form roughness induced by bank topographic features is shown to be a major component (61%–85%) of the spatially averaged total shear stress, and as such it can be viewed as an important factor that self‐limits bank erosion.
Cell‐type specific analysis of translating RNAs in developing flowers reveals new levels of control
Authors: Jiao Yuling , Meyerowitz Elliot M
Published: October 2010

Determining both the expression levels of mRNA and the regulation of its translation is important in understanding specialized cell functions. In this study, we describe both the expression profiles of cells within spatiotemporal domains of the Arabidopsis thaliana flower and the post‐transcriptional regulation of these mRNAs, at nucleotide resolution. We express a tagged ribosomal protein under the promoters of three master regulators of flower development. By precipitating tagged polysomes, we isolated cell type‐specific mRNAs that are probably translating, and quantified those mRNAs through deep sequencing. Cell type comparisons identified known cell‐specific transcripts and uncovered many new ones, from which we inferred cell type‐specific hormone responses, promoter motifs and coexpressed cognate binding factor candidates, and splicing isoforms. By comparing translating mRNAs with steady‐state overall transcripts, we found evidence for widespread post‐transcriptional regulation at both the intron splicing and translational stages. Sequence analyses identified structural features associated with each step. Finally, we identified a new class of noncoding RNAs associated with polysomes. Findings from our profiling lead to new hypotheses in the understanding of flower development.
The Discovery of Vorapaxar (SCH 530348), a Thrombin Receptor (Protease Activated Receptor-1) Antagonist with Potent Antiplatelet Effects
Authors: Chackalamannil Samuel
Published: October 2010

The coagulation and platelet activation mechanisms synergize in hemostasis and thrombosis. Thrombin plays a key dual role in these by generation of fibrin from fibrinogen and by activation of platelets via protease activated receptors (PARs). Human platelets contain the high affinity PAR-1, also know as the thrombin receptor, and the low affinity PAR-4. Among the various platelet activating mechanisms, PAR-1 stimulation is the most potent one, and as such, a PAR-1 antagonist is expected to confer potent antiplatelet effects. Additionally, a PAR-1 antagonist is expected to produce less bleeding side effect than currently available antithrombotic agents, since fibrin generation would be unaffected, and platelet activation by other mechanisms needed for normal hemostasis would be maintained.

SCH 530348 is a potent thrombin receptor antagonist that was discovered by optimization of a lead derived from the natural product himbacine. It is a competitive antagonist of PAR-1 with a Ki of 8.1 nM and it was highly potent in multiple functional assays. In a preclinical ex vivo platelet aggregation model in cynomolgus monkeys, SCH 530348 showed complete and sustained inhibition of platelet aggregation for greater than 24 hours after an oral administration of 0.1 mg/kg. In phase I clinical trials, SCH 53048 demonstrated excellent safety and tolerability, and exhibited potent pharmacodynamic effects in human plasma. In a phase II clinical trial (TRA-PCI) in patients who underwent non-emergent percutaneous coronary intervention, SCH 530348 was not associated with increased TIMI major plus minor bleeding when compared with placebo, and therefore met its primary end point. For the secondary outcome endpoint, SCH 530348 was associated with a numerical reduction in periprocedural myocardial infarction and an overall reduction in arterial thrombotic events. SCH 530348 is currently undergoing two large Phase III studies in patients with acute coronary syndrome (TRA*CER) and in patients who are at risk of atherothrombotic events (TRA*2P).
The Genesis of the Antibody Conjugate Gemtuzumab Ozogamicin (Mylotarg®) for Acute Myeloid Leukemia
Authors: Hamann Philip R.
Published: October 2010

Gemtuzumab ozogamicin is an antibody conjugate of calicheamicin that targets the CD33 antigen on differentiating myeloid cells and which is over-expressed on acute myeloid leukemia cells in most patients. It carries a DNA-active calicheamicin derivative selected during preclinical work with various antibodies. The calicheamicin derivative is attached to the hP67.6 antibody via the bifunctional AcBut linker, which allows for hydrolytic release of the calicheamicin in the acidic lysosomes. This conjugate, hP67.6-NAc-gamma calicheamicin DMH AcBut, is potently cytotoxic to most CD33-positive cells in tissue culture with high selectivity versus CD33-negative cells. It is curative of the CD33-expressing HL-60 xenografts and shows selective cytotoxicity in a significant proportion of AML bone marrow samples in a colony-forming assay.

Gemtuzumab ozogamicin has shown significant activity in various clinical trials. In pivotal Phase 2 trials, the remission rate was 26% and the medium recurrence-free survival in a heavily pre-treated patient population was 5.5 months. It was approved by the FDA in May 2000 for use in patients with CD33-positive AML in first relapse who are ≥60 years of age and are not candidates for cytotoxic chemotherapy. In a key on-going study combining it with daunorubicin and cytarabine for first indication, a complete response (CR) rate of 84% with gemtuzumab ozogamicin vs. 55% without has been seen so far with a median duration of CR >6 months. Such studies promise to expand the role of gemtuzumab ozogamicin in the treatment of AML and to give patients more options for the treatment of this commonly fatal disease.
Polymer Nanocomposites in Emulsion and Suspension: an Overview
Authors: Mittal Vikas
Published: October 2010

Polymer nanocomposites have been a subject of intense research in the recent yeas. By nanoscale dispersion of inorganic fillers in the polymer matrices, significant enhancements in the properties of the materials have been achieved at very low filler volume fractions. Different modes of nanocomposite synthesis have been developed in the recent years which include template synthesis, in-situ polymerization, melt intercalation and polymer or prepolymer adsorption from solution. The last methodology also covers emulsion and suspension polymerization techniques for the synthesis of nanocomposites. These emulsion and suspension modes of polymer nanocomposite synthesis have the advantage that the polymerization is carried out in the presence of water which does not allow buildup of viscosity and the heat dissipation from the system is also easily achieved. The potential thermal damage to the polymer and the organic modification usually encountered in the melt intercalation is also avoided in the case of emulsion and suspension polymerization. Different polymer systems have been reported like polystyrene, polyurethanes, epoxy, poly(methyl methacrylate), poly(N-isopropylacrylamide), poly(butyl acrylate) etc. Specific synthetic methodologies like surfactant free polymerization, controlled living polymerization etc. have also been reported to successfully achieve nanocomposites with superior properties than the pure polymers. Majority of the studies bring home the conclusion that the amount of clay as well as surface modification present on clay surface significantly affect the microstructure and properties of the nanocomposite particles. Apart from clay as filler, many studies also have used the spherical inorganic particles as reinforcements.
PMMA-based Montmorillonite Nanocomposites by Soap-free Emulsion Polymerization
Authors: Lin King-Fu , Lin Keng-Jen
Published: October 2010

This chapter introduces the current development in the exfoliated montmorillonite (MMT)/poly(methyl methacrylate) (PMMA)-based nanocomposites fabricated by soap-free emulsion polymerization. MMT is hydrophilic in nature and MMA monomer is slightly soluble in water. By using the soap-free emulsion polymerization of MMA in the presence of MMT, MMT can be exfoliated during micellation stage, resulting in the formation of exfoliated MMT/PMMA nanocomposite latex particles. To lower Tg of the MMT/PMMA nanocomposites by copolymerizing with methylacrylate, the resulting nanocomposite latices can be cast into films, which were found to have superior tensile properties, low permeability and high flame retardation. This chapter will illustrate their fabrication methods, structure, novel properties and applications.
Polymer Nanocomposites Prepared by Suspension Polymerization of Inverse Emulsion
Authors: Yang Jintao , Zhu Bin , James Lee L.
Published: October 2010

Compared to emulsion polymerization and suspension polymerization, the manufacturing process of suspension polymerization of inverse emulsion is more complicated. The advantage of using this technology is to make capsular structure which has a polymer shell and liquid inner phase. The polymer shell can provide protection by preventing the inner phase from leaking out. When nanoparticles were added into the polymer shell, they can inhibit the mass transfer and reinforce the polymer matrix to make the nanocomposites stronger or thermally stable. More importantly, the presence of nanoparticle can partially replace or completely eliminate the use of emulsifiers in the nanocomposite bead synthesis process. One application as mentioned before is to make PS nanocomposite particles containing water as a physical blowing agent for PS foam. Other applications include drug delivery and functional particle preparation.
Polymer–Clay Nanocomposites Prepared in Miniemulsion Using the RAFT Process
Authors: Zengeni Eddson , Samakande Austin , Hartmann Patrice C.
Published: October 2010

This chapter is a review on polymer-clay nanocomposites (PCNs) prepared in miniemulsion using the reversible addition-fragmentation chain transfer (RAFT) process.

One of the most interesting research areas in nanotechnology is the inclusion of nanoparticles in polymers in order to enhance their physical properties e.g. thermal stability, barrier properties and mechanical properties. In the early 1990s the Toyota research group showed that the hydrated cations within the clay layers can be replaced by alkyl ammonium compounds. A reactive clay modifier leads to a strong interfacial adhesion between the clay and the polymer, and subsequently the exceptional mechanical properties during load bearing. The use of tailor-made transfer agents in free-radical polymerisation reactions allows one to achieve control of the polymerisation process. This results in polymers with low polydispersity indices and predictable molar masses. The discovery of the controlled polymerisation techniques, and in particular RAFT agents, was a milestone achievement. RAFT polymerisation now allows the preparation of polymer architectures that were never before envisaged to be possible. Thus, a combination of RAFT technology and clay nanotechnology for the synthesis of PCNs by RAFT-mediated polymerisation can allow the preparation of tailor-made materials with specific properties for niche applications.
Use of the LENA Tool to Evaluate the Effectiveness of a Parent Intervention Program
Authors: Weil Lisa Wisman , Middleton Laura
Published: October 2010

This article describes a study investigating the language environment analysis (LENA) tool to measure the effectivenes of a parent intervention training program with children with language delays. In addition to the effects of parent training on the language development of participating children, the contributions of using LENA to measure growth also is discussed.
Transcranial Doppler ultrasonography in siblings with sickle cell disease
Authors: Kwiatkowski Janet L. , Hunter Jill V. , Smith‐Whitley Kim , Katz Mira L. , Shults Justine , Ohene‐Frempong Kwaku
Published: October 2010

Summary. The risk of stroke in sickle cell disease (SCD) may be influenced by either genetic or environmental factors. Elevated blood flow velocity in the large cerebral arteries, detected by transcranial Doppler (TCD) ultrasonography, predicts an increased stroke risk in children with SCD. We undertook this study to investigate the possibility of a familial predisposition to elevated cerebral blood flow velocity, a surrogate marker for stroke risk. We analysed the results of TCD studies performed on 63 children from 29 families that had more than one child with SCD. We assessed the association of elevated cerebral blood flow velocity with sibling TCD results as well as age and haemoglobin level, which are factors known to affect cerebral blood flow velocity. Positive or negative TCD results were highly correlated between family members (r = 0·61). The presence of a sibling with a positive TCD result was significantly associated with an elevated cerebral blood flow velocity in other siblings with SCD (odds ratio = 41·9, 95% confidence interval 8·2–214·7, P < 0·001). Furthermore, children who had a sibling with a positive TCD result had a significantly higher TCD velocity than children with SCD but without a sibling who were matched for age, sex, genotype and haemoglobin level. Our results are consistent with a familial predisposition to cerebral vasculopathy in SCD.
No effect of seasonal variation in training load on immuno‐endocrine responses to acute exhaustive exercise
Authors: Ronsen O. , Holm K. , Staff H. , Opstad P. K. , Pedersen B. K. , Bahr R.
Published: October 2010

This study was designed to examine the relationship between seasonal changes in training and competition load, and changes in leukocyte subsets, stress hormones, and interleukin‐6 (IL‐6) in response to a standardised bout of endurance exercise. In addition, changes in mood states were monitored. Ten male, international Nordic skiers, age 20–29, maximal oxygen uptake 70–82 ml  ·  kg−1  ·  min−1 performed the same incremental treadmill tests to exhaustion at the same time of day (±1 h), during the competitive season (in‐season HI test) and the recovery season (off‐season LO test). The subject filled out a training and competition log (TC score) for three weeks prior to each test and a 65‐item Profile of Mood State (POMS) test on arrival at the laboratory. Venous blood for haematological, hormonal, and IL‐6 analysis was drawn before and at 0, 15, 30, 60, 120 and 240 min after the test. TC score was more than twice as high during the competitive season (16.0±3.9) compared to the off‐season period (7.0±4.4). An ANOVA procedure for repeated measures showed no difference in exercise induced changes in concentrations of neutrocytes, lymphocytes, epinephrine, ACTH or cortisol between the in‐season HI and off‐season LO tests; however, norepinephrine and the IL‐6 concentrations were elevated at the in‐season HI test compared to the off‐season LO test. There were no significant differences in POMS global mood score or sub‐scores between the in‐season HI and the off‐season LO tests. Thus, in a group of elite Nordic skiers, we conclude that a doubling of the training and competition load during the winter season does not alter the leukocyte and stress hormone responses to an incremental exercise test to exhaustion.
Echocardiographic and ambulatory electrocardiographic findings in elite water‐polo athletes
Authors: Zakynthinos E. , Vassilakopoulos T. , Mavrommati I. , Filippatos G. , Roussos C. , Zakynthinos S.
Published: October 2010

The aim of this study was to investigate the echocardiographic and electrocardiographic findings in top water‐polo athletes and test the hypothesis that their hearts exhibit dilatation associated with hypertrophy secondary to the mixed type (isotonic and isometric) of exercise they are subjected to. Eighteen athletes of the Greek national water‐polo team and 15 healthy sedentary men serving as controls were studied. All underwent an echocardiogram, a standard 12‐lead ECG and 24‐h ECG monitoring. In athletes, as compared to healthy controls, an increase was detected in the following indices: left ventricular (LV) end‐diastolic diameter index (EDDI‐LV) (by 10%; P=0.02), interventricular septal thickness (IVS) (by 32%; P<0.001), thickness of the posterior wall (PW) (by 29%; P<0.001), relative wall thickness (IVS+PW/EDD‐LV) (by 12%; P<0.001) and LV mass index (by 82%; P<0.001). Mild asymmetric thickening of the septum (IVS/PW=1.40 and 1.37) was measured in two athletes. LV fractional shortening was normal. Standard 12‐lead ECG abnormalities (LV hypertrophy or abnormal repolarization pattern) were observed in 33% of athletes. Athletes had sinus bradycardia during day and night, respiratory arrhythmia (RA) (83% vs 40% of controls; P=0.03) and sinus pauses (SP) (39% vs 0% of controls; P=0.02), with occassional arrhythmias and conduction abnormalities. We conclude that top water‐polo athletes have dilatation combined with substantial hypertrophy and normal systolic function of the LV. In addition they present bradycardia, RA and SP, with occassional arrhythmias and conduction abnormalities.
Revision anterior cruciate ligament surgery. A review of the literature and results of our own revisions
Authors: Harilainen A. , Sandelin J.
Published: October 2010

Revision anterior cruciate ligament surgery has become a more commonly performed operation. Reasons for this are an increased number of first‐time operations, some with technical faults. Patients can also sustain a new injury severe enough to rupture their reconstructed ligament. Results of the revision operations are not as good as those of well executed primary reconstructions. Re‐reconstruction is usually technically feasible but the surgeon has to be prepared to encounter many demanding technical problems.