bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody Protection against Botulinum Neurotoxin Intoxication in Mice
Authors: Cheng Luisa W. , Stanker Larry H. , Henderson Thomas D. , Lou Jianlong , Marks James D.
Published: August 2009

Adulteration of food or feed with any of the seven serotypes of botulinum neurotoxin (BoNT) is a potential bioterrorism concern. Currently, there is strong interest in the development of detection reagents, vaccines, therapeutics, and other countermeasures. A sensitive immunoassay for detecting BoNT serotype A (BoNT/A), based on monoclonal antibodies (MAbs) F1-2 and F1-40, has been developed and used in complex matrices. The epitope for F1-2 has been mapped to the heavy chain of BoNT/A, and the epitope of F1-40 has been mapped to the light chain. The ability of these MAbs to provide therapeutic protection against BoNT/A intoxication in mouse intravenous and oral intoxication models was tested. High dosages of individual MAbs protected mice well both pre- and postexposure to BoNT/A holotoxin. A combination therapy consisting of antibodies against both the light and heavy chains of the toxin, however, significantly increased protection, even at a lower MAb dosage. An in vitro peptide assay for measuring toxin activity showed that pretreatment of toxin with these MAbs did not block catalytic activity but instead blocked toxin entry into primary and cultured neuronal cells. The timing of antibody rescue in the mouse intoxication models revealed windows of opportunity for antibody therapeutic treatment that correlated well with the biologic half-life of the toxin in the serum. Knowledge of BoNT intoxication and antibody clearance in these mouse models and understanding of the pharmacokinetics of BoNT are invaluable for future development of antibodies and therapeutics against intoxication by BoNT.
Perforin and Gamma Interferon Expression Are Required for CD4+and CD8+T-Cell-Dependent Protective Immunity against a Human Parasite,Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination
Authors: de Alencar Bruna C. G. , Persechini Pedro M. , Haolla Filipe A. , de Oliveira Gabriel , Silverio Jaline C. , Lannes-Vieira Joseli , Machado Alexandre V. , Gazzinelli Ricardo T. , Bruna-Romero Oscar , Rodrigues Mauricio M.
Published: August 2009

A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4+and CD8+T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4+and CD8+T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection withTrypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-γ) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. In spite of a normal numeric expansion, specific CD8+T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-γ or IFN-γ/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-γ in the presence of highly cytotoxic T cells. Vaccinated IFN-γ-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-γ in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy.
Seismic activity and structural features in the Charlevoix region, Quebec
Authors: Lamontagne Maurice
Published: August 2009

The Charlevoix region is historically the most active earthquake zone in eastern Canada. Understanding the links between its seismicity and the faults of the region is important for the assessment of earthquake risk along the St. Lawrence Valley. The region has been monitored by a microseismic array since 1977, yielding accurate locations of the hypocentres. Previous analyses of data from the array indicated a relationship between the earthquakes and the St. Lawrence Valley paleorift faults. As a sequel to previous studies, the relationships between the seismic activity and the faults of the region were reexamined through the use of the composite P-nodal solutions, in an effort to clarify the nature of faulting in the seismic zone. The microseisms were partitioned into subsets of events on the basis of geological and hypocentre-trend considerations. The main objectives of this paper are to delineate the details of faulting within the Charlevoix region and to determine the effect of the impact crater on the nature of faulting in this area.Assuming a constant 6.2 km/s velocity model and using a data set of 107 events, composite fault-plane solutions were computed. The composite P-nodal solutions indicated that the Charlevoix impact crater modifies to a certain extent the focal-mechanism characteristics. Events outside the impact crater were found to be quite consistent in their polarity distribution on the focal sphere, suggesting similarity in their focal mechanisms. The composite mechanism of these events suggests a relationship between the earthquakes and the north–south faults mapped outside the impact crater. The magnitude mb (Lg) 5.0 earthquake of August 19, 1979, the largest event in the selected time window, had different fault planes than some of its aftershocks. Nevertheless, the polarity distribution of the aftershocks was in agreement with the average trend for the events outside the crater. Events inside the impact crater were found to be produced along more variable fault orientations, with an average trend similar to that of the rift fault system. It is proposed that the meteor impact weakened the rift faults and introduced its own fractures. The present earthquake activity probably occurs along these weak fault surfaces. The effect of the impact crater on the type of faulting versus depth is not readily discernible from available data. In general, meteor impacts do not leave neotectonic seismic signatures: the Charlevoix impact crater might represent a different case because of the presence of weakened paleorift faults.
Depositional environments during a glaciolacustrine to marine transition in the Richardson and Rae River basin, N.W.T.
Authors: Kerr Daniel E.
Published: August 2009

This paper describes the principal glaciolacustrine deposits of a sequence of overlapping ice-marginal lakes known as glacial Lake Richardson and its transition to a postglacial sea following the retreat of a lobe of the Laurentide ice sheet from the Richardson and Rae River basin. The glaciolacustrine to marine transition is characterized by an upward-fining sequence of facies deposited in proglacial lacustrine environments, succeeded by an upward-coarsening trend corresponding to a regressive marine sequence. A composite stratigraphic section includes (a) basal diamicton, (b) stratified subaqueous sand and gravel, (c) glaciolacustrine silty clay rhythmites, (d) massive marine silty clay, and (e) littoral marine sands. The sudden passage from lacustrine to marine environments is reflected in the abrupt change in depositional mechanisms. Turbidity currents prevailed in the proglacial lake as inferred from thick sequences of varve-like couplets, whereas the salinity of marine waters, impeding the sedimentation of fines by density underflows, led to the deposition of massive structureless marine silty clays by flocculation.
The Holocene evolution of permafrost near the tree line, on the eastern coast of Hudson Bay (northern Quebec)
Authors: Allard Michel , Seguin Maurice K.
Published: August 2009

Permafrost evolution in postglacial marine silts near the tree line was reconstructed using landform analysis, 14C dating, and palynostratigraphic analysis of peat sections. In the forest–tundra, below the tree line, four sites in peat plateaus have a stratigraphic sequence indicating an alluvial plain environment from 6000 to 4800 BP followed by a wetland supporting trees and shrubs with deep snow accumulation and without permafrost. Ground heave occurred between 1900 and 1200 BP as peat plateaus and palsas were formed. In the shrub–tundra, above the tree line, three permafrost sites with buried peat beds suggest that climatic conditions were cold enough for discontinuous permafrost in the surrounding landscape starting from land emergence, about 5800 BP; however, fen expansion and sedge peat accumulation continued over unfrozen ground until 2300, 1560, and 1400 BP. At these dates, the sites were buried with silt, probably as a result of mass wasting on nearby permafrost mounds and then permafrost aggraded under the sites. Generally, the palynostratigraphic data reflect a marked cooling of climate starting by 3200–2700 BP and culminating in a major period of permafrost aggradation between 1900 and 1200 BP. Permafrost degradation has been dominant since then despite other possible cold intervals. Nowadays, the permafrost in marine silts is twice as thick and three times more widespread in the shrub–tundra than in the forest–tundra.
Field evidence for successive mixing and mingling between the Piolard Diorite and the Saint-Julien-la-Vêtre Monzogranite (Nord–Forez, Massif Central, France)
Authors: Barbarin Bernard
Published: August 2009

Recent mapping of the Nord–Forez region, Massif Central, France, reveals a variety of complex field relationships along contacts between a large enclave of diorite and its enclosing monzogranite. Field relations, hybrid rocks, and a wide variety of mafic magmatic enclaves can be explained by a succession of processes between coexisting mafic and felsic magmas that either prevent or promote exchanges. The large volume of mafic magma, and consequently the large amount of heat it brought with it, favored exchange processes. Because the distribution of heat varied with both time and place, the nature and intensity of the compositional exchange processes also varied.Most of the features attributed to exchange are related to processes that occurred at the level of emplacement and after the beginning of crystallization of the two magmas. These processes affected both the granitic and dioritic magmas already thoroughly hybridized by nearly similar processes that took place earlier at depth.
Geochemistry, geochronology, and tectonic implications of two quartz monzonite intrusions, Purcell Mountains, southeastern British Columbia
Authors: Höy Trygve , Heyden P. van der
Published: August 2009

The Reade Lake and Kiakho stocks are posttectonic mesozonal quartz monzonite porphyries that intrude dominantly Middle Proterozoic Purcell Supergroup rocks in southeastern British Columbia. K–Ar dates of hornblende from the Reade Lake stock range from 103 to 143 Ma. However, a U–Pb date of 94 Ma from zircon concentrates is interpreted to be the age of emplacement of the stock, suggesting the range and older K–Ar dates are due to excess 40Ar. A K–Ar date of 122 Ma for the hornblende from the Kiakho stock is believed to be a more reliable intrusive age.Both stocks cut across and apparently seal two faults that have played roles in the tectonic evolution of the Purcell anticlinorium and Rocky Mountain thrust belt. The Reade Lake stock cuts the St. Mary fault, an east-trending reverse thrust that crosses the Rocky Mountain trench and links with thrusts in the Rocky Mountains; the Kiakho stock cuts the Cranbrook fault, an older east-trending normal fault. Hence, the 94 Ma date on the Reade Lake stock constrains the latest movement on the St. Mary fault to early Late Cretaceous; and the 122 Ma date on the Kiakho stock appears to limit latest movement on the Cranbrook fault to Early Cretaceous. These faults and the intrusions are part of an allochthonous package, displaced eastward by underlying thrust faults during formation of the Purcell anticlinorium and more eastern thrusts in the Rocky Mountains.
Evidence for contrasting compositional spectra in comagmatic intrusive and extrusive rocks of the late Archean Blake River Group, Abitibi, Quebec
Authors: Paradis Suzanne , Ludden John , Gélinas Léopold
Published: August 2009

The Flavrian pluton is a sill-shaped intrusion in the Blake River Group (BRG) volcanic rocks in the Noranda region of the Abitibi greenstone belt. The pluton is dominated by trondhjemites and tonalites, with minor peripheral quartz gabbro and hybrid phases. The BRG volcanic rocks consist of a bimodal suite of basalt–andesite and rhyolite. The Flavrian trondhjemites are geochemically identical to the rhyolitic lavas of the BRG (SiO2 ≥ 72%, La/Sm = 3.4, La/Yb = 3.6, Zr/Y = 3.9, Y/Nb = 3.1), and the Flavrian gabbroic and dioritic rocks are identical to the BRG basalts and andesites (SiO2 < 58%, La/Sm = 3.0, La/Yb = 5.5, Zr/Y = 4.2, Y/Nb = 3.3). However, the tonalitic rocks of the Flavrian pluton have no extrusive equivalents in the BRG. The different compositional spectra of the extrusive and intrusive rocks are interpreted as being a result of a transition in magma-chamber evolution from a zoned open system that was active during the evolution of the volcanic rocks to closed-system plutonic crystallization. The latter destroyed the compositional bimodality of the magma chamber and resulted in the evolution of intermediate compositions (tonalites) generated by both fractional crystallization and magma mixing.
8000 year old wood from the Athabasca Glacier, Alberta
Authors: Luckman B. H.
Published: August 2009

Several wood fragments of Pinus sp. (dated at 8230 ± 80 and 8000 ± 90 years BP) and Abies sp. were recovered from the snout of the Athabasca Glacier. This wood, derived from an unknown source up valley, indicates that the glacier was less extensive than at present during the Hypsithermal and that an area up valley of the present snout was tree covered ca. 8000–8300 years BP.
Strontium isotopic composition of Pliocene and Pleistocene molluscs from emerged marine deposits, North American Arctic
Authors: Kaufman Darrell , Carter L. David , Miller Gifford H. , Farmer G. Lang , Budd David A.
Published: August 2009

High-precision strontium (Sr) isotopic measurements were obtained for 53 Pliocene and Pleistocene molluscan shells from emerged marine deposits around the coasts of Arctic North America to test whether such data can be used for chronostratigraphic purposes. 87Sr/86Sr ratios from Sr isotopic measurements on many marine fossils from Arctic Ocean borderland sites are broadly consistent with their expected values based on independent age control and on a comparison with the Sr isotopic evolution of seawater recorded in deep-sea cores. All 87Sr/86Sr ratios measured for shells from Middle and Late Pleistocene deposits are consistent with expected values, but only 9 of 22 ratios in shells from older deposits are consistent with independent age estimates. Aberrant 87Sr/86Sr ratios are consistently higher than expected. At Nome, Alaska, and Baffin Island, Canada, all 87Sr/86Sr ratios are higher than expected. Because these shells were formed along the Pacific Ocean and Atlantic Ocean margins, respectively, their high 87Sr/86Sr ratios cannot be attributed to possible differences in the Sr isotopic evolution of the Arctic Ocean relative to that of remainder of the world's oceans. Radiogenic Sr from proximal river-water input, or leaching of detritus within the shell matrix, may have changed the 87Sr/86Sr ratios by as much as about 5 × 10−5, but these mechanisms cannot account for the very high 87Sr/86Sr values (from 20 × 10−5 to 200 × 10−5 higher than those of modern seawater) measured for some shells. Alteration by diagenetic fluids rich in radiogenic Sr is the most plausible explanation for the aberrant results. Diagenesis is recognized petrographically in the most altered shells by micritic overprinting of the original shell microstructure; in addition, one shell enriched in 87Sr from Baffin Island exhibits a broad range (170 × 10−5) of 87Sr/86Sr ratios across the shell, and an oxygen isotopic gradient (l.6‰) that is greater than the expected primary variability. Although our data suggest that Sr isotopic data from young Arctic molluscan fossils may offer a viable dating method, criteria for screening altered shells must be devised before the technique can be considered a reliable chronostratigraphic tool.
Quaternary sedimentation and marine placers along the North Shore, Gulf of St. Lawrence
Authors: Hein Frances J. , Syvitski James P. M. , Dredge Lynda A. , Long Bernard F.
Published: August 2009

Offshore areas, along the North Shore of the St. Lawrence Estuary, have major lithostratigraphic and seismostratigraphic units that relate to the advance or retreat of the Late Wisconsinan Ice Sheet, subsequent marine transgression or regression, and reworking of postglacial deposits. Glacial diamicton and glaciomarine units (acoustic units 1 and 2) were emplaced between >18 and 14.5 ka, by basal meltout or ice-marginal sedimentation; they reflect ice-proximal sedimentation associated with ice-terminal stillstands. Deep-water muds (acoustic unit 3) represent ice-distal accumulation of glaciomarine sediment from glaciofluvial plumes between 13.5 and 11 ka. After this time exceptionally thick nearshore coarse-grained deltaic and estuarine successions (acoustic unit 4) were deposited. The uppermost postglacial sediment (acoustic unit 5) forms the seabed and reflects a reworking phase concomitant with a lowering sea level and ablating Late Wisconsinan ice sheets.Glacioisostatic rebound, which occurred about 23 ka to the present, uplifted glacial and marine deposits and resulted in extensive reworking and production of modern placers. Heavy-mineral concentrations vary as follows: terrestrial tills, 9–20%; modem storm-berm and delta top deposits, 43–60%; delta slope deposits, 25–55%; and deep (170+ m) offshore sediments, 0–2%. Three stages occurred in marine placer formation: (1) 6700 BP, fluvial discharge was high, and fluvial-dominated deltas were built; marine limit was 30 m asl, with progradation of deltas and delivery of sediments with at most 2% heavy minerals; (2) 5200 BP, fluvial discharge was reduced; marine limit was 15 m asl, deltaic sediments were reworked, increasing heavy mineral concentration to 2–8%; (3) 2800 BP, fluvial input was greatly reduced, waves and tides were more influential, a strong littoral current system developed, causing significant reworking of nearshore sediments, heavy mineral concentrations increased, with values exceeding 20% locally. Mass budget calculations show that the second-cycle reworked sediment (acoustic unit 5) is a potential economic target (1 km3, or 1700 Mt). If 7% (using atomic weights) of this target sediment is ilmenite (FeTiO3). then 27 Mt of titanium may be available.
Lower Silurian reefs and post-reef beds of the Attawapiskat Formation, Hudson Bay Platform, northern Ontario
Authors: Suchy Daniel R. , Stearn Colin W.
Published: August 2009

Outcrop exposures along the Attawapiskat River in the Hudson Bay Lowlands of northern Ontario clearly reveal the morphology of Silurian (upper Llandoverian) reefs of the Attawapiskat Formation and the relationships between reef cores, flanking beds, and post-reef beds. These relationships indicate that the reefs had a syndepositional relief of at least 8–10 m. The relief of the reefs is indicated by debris-flow lenses encased within flanking beds, a debris-flow fan at the base of a reef, thin reef-flanking beds truncated against a vertical reef face, penecontemporaneous brachiopod beds on the flanks of reefs, and three large slide blocks that apparently slid over the side of a reef.Reefs of the Attawapiskat Formation are largely limestones with a wide range of lithologies, from stromatoporoid-, coral-, and cement-rich boundstones to alga–cement-rich boundstones. Thick, laterally extensive Nuia grainstone beds, a product of widespread Nuia monocultures in supratidal to intertidal ponds, are present above the reefs. The most important diagenetic processes were early marine cementation (predominantly radial-fibrous calcite), shallow burial diagenesis, and pervasive neomorphism.Schematic reconstructions of the depositional history of the Attawapiskat Formation in outcrop, constructed from observations of outcrop relationships, show a stratigraphic succession that was controlled by relative-sea-level changes. Reefs growth was terminated by a relative-sea-level fall, but subsequent minor relative-sea-level fluctuations resulted in alternating deposition of supratidal to shallow subtidal sediments for a short time before the final retreat of the Silurian seas from the Hudson Bay Platform; only supratidal evaporite facies are present in the remainder of the Silurian section above the Attawapiskat Formation.
FRAMEWORK FOR DATA QUALITY ASSURANCE BETWEEN COMPOSITE SERVICES
Authors: LEE JUNG-WON , CHOI BYOUNGJU
Published: August 2009

Today, businesses have to respond with flexibility and speed to ever-changing customer demand and market opportunities. Service-Oriented Architecture (SOA) is the best methodology for developing new services and integrating them with adaptability — the ability to respond to changing and new requirements. In this paper, we propose a framework for ensuring data quality between composite services, which solves semantic data transformation problems during service composition and detects data errors during service execution at the same time. We also minimize the human intervention by learning data constraints as a basis of data transformation and error detection. We developed a data quality assurance service based on SOA, which makes it possible to improve the quality of services and to manage data effectively for a variety of SOA-based applications. As an empirical study, we applied the service to detect data errors between CRM and ERP services and showed that the data error rate could be reduced by more than 30%. We also showed automation rate for setting detection rule is over 41% by learning data constraints from multiple registered services in the field of business.
REQUIREMENT BASED SYSTEM TEST CASE PRIORITIZATION OF NEW AND REGRESSION TEST CASES
Authors: KRISHNAMOORTHI R. , SAHAAYA ARUL MARY S. A.
Published: August 2009

Test case prioritization schedules the test cases in an order that increases the effectiveness in achieving some performance goals. One of the most important performance goals is the rate of fault detection. Test cases should run in an order that increases the possibility of fault detection and also detects the most severe faults at the earliest in its testing life cycle. Test case prioritization techniques have proved to be beneficial for improving regression testing activities. While code coverage based prioritization techniques are found to be studied by most scholars, test case prioritization based on requirements in a cost effective manner has not been used for studies so far. Hence, in this paper, we propose to put forth a model for system level Test Case Prioritization (TCP) from software requirement specification to improve user satisfaction with quality software that can also be cost effective and to improve the rate of severe fault detection. The proposed model prioritizes the system test cases based on six factors: customer priority, changes in requirement, implementation complexity, usability, application flow and fault impact. The proposed prioritization technique is experimented in three phases with student projects and two sets of industrial projects and the results show convincingly that the proposed prioritization technique improves the rate of severe fault detection.
From business process models to process-oriented software systems
Authors: Ouyang Chun , Dumas Marlon , Aalst Wil M. P. Van Der , Hofstede Arthur H. M. Ter , Mendling Jan
Published: August 2009

Several methods for enterprise systems analysis rely on flow-oriented representations of business operations, otherwise known as business process models. The Business Process Modeling Notation (BPMN) is a standard for capturing such models. BPMN models facilitate communication between domain experts and analysts and provide input to software development projects. Meanwhile, there is an emergence of methods for enterprise software development that rely on detailed process definitions that are executed by process engines. These process definitions refine their counterpart BPMN models by introducing data manipulation, application binding, and other implementation details. The de facto standard for defining executable processes is the Business Process Execution Language (BPEL). Accordingly, a standards-based method for developing process-oriented systems is to start with BPMN models and to translate these models into BPEL definitions for subsequent refinement. However, instrumenting this method is challenging because BPMN models and BPEL definitions are structurally very different. Existing techniques for translating BPMN to BPEL only work for limited classes of BPMN models. This article proposes a translation technique that does not impose structural restrictions on the source BPMN model. At the same time, the technique emphasizes the generation of readable (block-structured) BPEL code. An empirical evaluation conducted over a large collection of process models shows that the resulting BPEL definitions are largely block-structured. Beyond its direct relevance in the context of BPMN and BPEL, the technique presented in this article addresses issues that arise when translating from graph-oriented to block-structure flow definition languages.
Regulation Mechanisms and Signaling Pathways of Autophagy
Authors: He Congcong , Klionsky Daniel J.
Published: August 2009

Autophagy is a process of self-degradation of cellular components in which double-membrane autophagosomes sequester organelles or portions of cytosol and fuse with lysosomes or vacuoles for breakdown by resident hydrolases. Autophagy is upregulated in response to extra- or intracellular stress and signals such as starvation, growth factor deprivation, ER stress, and pathogen infection. Defective autophagy plays a significant role in human pathologies, including cancer, neurodegeneration, and infectious diseases. We present our current knowledge on the key genes composing the autophagy machinery in eukaryotes from yeast to mammalian cells and the signaling pathways that sense the status of different types of stress and induce autophagy for cell survival and homeostasis. We also review the recent advances on the molecular mechanisms that regulate the autophagy machinery at various levels, from transcriptional activation to post-translational protein modification.
The Detection and Attribution of Human Influence on Climate
Authors: Stone Dáithí A. , Allen Myles R. , Stott Peter A. , Pall Pardeep , Min Seung-Ki , Nozawa Toru , Yukimoto Seiji
Published: August 2009

This article describes the field of the detection and attribution of climate change and highlights recent progress, major issues, and future directions. The attribution of global temperature variations over the past century to a combination of anthropogenic and natural influences is now well established, with the anthropogenic factors dominating. Other aspects of the climate system, including regional quantities, are increasingly being found to also show a detectable signal of human influence. Of particular interest, though, is the attribution of changes in nonmeteorological quantities, such as hydrological and ecological measures, and of changes in the risk of extreme weather events to anthropogenic emissions. Methods are being developed for tackling these two problems but are still in the early stages. As the field gradually includes a service focus, the biggest challenges will become the integration of various approaches into an overall framework and the communication of the capabilities and limitations of that framework to the outside community.
On the Increasing Vulnerability of the World Ocean to Multiple Stresses
Authors: Miles Edward L.
Published: August 2009

This review focuses on the increasing vulnerability of the world ocean to multiple anthropogenic stresses in the latter half of the twentieth century and the first decade of the twenty-first century. The multiple stresses, which affected the world ocean in the latter half of the twentieth century, could have been controlled on a timescale of decades, had governments and their subjects chosen to do so. In the twenty-first century, the timescale of remediability has been observed to shift from decades to centuries and even to millennia. The major additions to the suite of multiple stresses consist of the combined impacts of changing ocean thermal structure and increasing acidification, both of which are the results of increased anthropogenic CO2 emissions. The consequences of these recent changes are assessed. The assessment makes clear collectively what is known and unknown and what responses are available to human social systems to adapt to these accelerating changes.
Public Support for Civil Liberties Pre- and Post-9/11
Authors: Sullivan John L. , Hendriks Henriët
Published: August 2009

Public support for civil liberties has undergone important changes in the past 50 years, as has scholarship on this topic. Whereas the American public was very intolerant of communists, socialists, and atheists in the 1950s and 1960s, current intolerance is now focused more on Muslim Americans and right-wing racists, among other groups. What has remained consistent is the important role played in shaping citizens’ tolerant and intolerant attitudes by their individual characteristics, such as education, authoritarianism, dogmatism, religiosity, and race. Although threat perceptions have always played an important role in explaining citizens’ support for civil liberties, this variable has gained new meaning in the aftermath of the terrorist attacks of September 11, 2001. Meanwhile, improved survey methodology now allows us to understand better the extent of democratic tolerance among Americans. In this article, we review the state of the literature on public support for civil liberties prior to 9/11 and, because we believe the terrorist attacks dramatically changed the political context, after 9/11.
Inhibition of hepatic Niemann-Pick C1-like 1 improves hepatic insulin resistance
Authors: Nomura Mitsunori , Ishii Hideto , Kawakami Akio , Yoshida Masayuki
Published: August 2009

The present study attempted to define the role of hepatic Niemann-Pick C1-like 1 (NPC1L1), a cholesterol transporter, in hepatic insulin resistance as well as hepatic steatosis. The inhibition of NPC1L1 and its molecular consequences were examined in Zucker obese fatty (ZOF) rats and cultured steatotic hepatocytes using ezetimibe, a pharmacoloigcal inhibitor of NPC1L1, and short hairpin RNA (shRNA) of NPC1L1. Ezetimibe improved hepatic insulin signaling as well as hepatic steatosis in ZOF rats. It also restored insulin sensitivity in steatotic hepatocytes in vitro through a reduction in hepatic reactive oxygen species (ROS) generation, JNK activation, and ER stress. In addition, ezetimibe recovered insulin-induced Akt activation and reduced gluconeogenic genes in the liver of ZOF rats and cultured steatotic hepatocytes. Transfection of NPC1L1 shRNA into hepatocytes also reduced ROS generation and ER stress. These results indicate that NPC1L1 contributes to hepatic insulin resistance through cholesterol accumulation, and its inhibition could be a potential therapeutic target of hepatic insulin resistance.
Biochemical and pharmacokinetic characterisation of two PEGylated variants of dipetarudin
Authors: Koehler Anne , Nowak Goetz , López Mercedes
Published: August 2009

Dipetarudin was coupled to polyethylene glycol (PEG)-5000 residues in order to improve its pharmacokinetic profile and to enhance its anticoagulant efficacy. The resulting compounds, mono-and di-PEGylated dipetarudin were purified by gel filtration. Mono-PEGylated dipetarudin exhibited similar activity like its non-conjugated equivalent both in vitro and in vivo. However, di-PEGylated dipetarudin showed longer distribution and elimination half-lives and higher area under the time-concentration curve in comparison with the unmodified inhibitor which may be attributed to decreased renal clearance. Futhermore, ratio k
12/k
21 decreased when the number of PEG chains coupled to dipetarudin increased. It means that the intercompartment transfer of dipetarudin, characterised by a fast distribution and a high retention in the peripheral compartment, is reverted by coupling to PEG. Thus, the transfer of mono-PEGylated dipetarudin between these compartments is similar in both senses and the transfer of di-PEGylated dipetarudin is slower from vascular to extravascular compartment than vice versa. Our results show that di-PEGylated dipetarudin produces a better and longer anticoagulant effect than unmodified dipetarudin which is a desirable attribute for future therapeutic application.
The effects of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor
Authors: Verkleij Chantal J. N. , Nieuwdorp Max , Gerdes Victor E. A. , Mörgelin Matthias , Meijers Joost C. M. , Marx Pauline F.
Published: August 2009

Epidemiological studies have shown a strong association between type 2 diabetes mellitus and cardiovascular diseases, and hypofibrinolysis may contribute to this phenomenon. The aim of this study was to determine the effect of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor (TAFI). Hyperglycaemia was mimicked in vitro by incubation of TAFI with glyceraldehyde and in vivo by hyperglycaemic clamping of healthy volunteers. The effects of long-term hyperglycaemia in vivo on TAFI were investigated by comparing TAFI from poorly regulated and tightly regulated patients with type 2 diabetes. In vitro glycated TAFI showed an altered migration pattern on SDS-PAGE due to aggregation. Glycated TAFI showed decreased activity after activation by thrombin-thrombomodulin in a glyceraldehyde-dosedependent manner and a reduced anti-fibrinolytic potential. In vivo, no differences in TAFI parameters were found after hyper-glycaemic clamping of healthy volunteers and between tightly and poorly regulated patients with type 2 diabetes. Moreover, TAFI purified from poorly regulated and tightly regulated patients with type 2 diabetes migrated similarly on SDS-PAGE, indicating little or no glycation of the protein. Despite the deleterious effects of glycation of TAFI in vitro on its function, TAFI was neither affected by hyperglycaemic clamping, nor by long-term hyperglycaemia in patients with type 2 diabetes. This is in contrast to fibrinolytic factors as plasminogen-activator inhibitor I and tissue-type plasminogen activator, which are affected. We therefore hypothesise that a normally functioning TAFI under hyperglycaemic conditions may tip the haemostatic balance towards hypofibrinolysis, which may contribute to the development of cardiovascular diseases in type 2 diabetic patients.
Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: Results from the OPTIMEV study
Authors: Sevestre-Pietri Marie-Antoinette , Bosson Jean-Luc , Laroche Jean-Pieere , Righini Marc , Brisot Dominique , Boge Gudrun , van Kien Aaurelie , Gattolliat Olivier , Bettarel-Binon Catherine , Gris Jean-Christophe , Genty Celine , Quere Isabelle , Galanaud Jean-Philippe ,   The OPTIMEV-SFMV Investigators
Published: August 2009

There is a lack of consensus on the value of detecting and treating symptomatic isolated distal deep-vein thrombosis (DVT) of the lower limbs. In our study, we compared the risk factors and outcomes in patients with isolated symptomatic distal DVT with those with proximal symptomatic DVT. We analysed the data of patients with objectively confirmed symptomatic isolated DVT enrolled in the national (France), multicenter, prospective OPTIMEV study.This sub-study outcomes were recurrent venous thromboembolism, major bleeding and death at three months. Among the 6141 patients with suspicion of isolated DVT included between November 2004 and January 2006, DVT was confirmed in 1643 patients (26.8%). Isolated distal DVT was more frequent than proximal DVT (56.8% vs. 43.2%, respectively; p=0.01). Isolated distal DVT was significantly more often associated with transient risk factors (recent surgery, recent plaster immobilisation, recent travel), whereas proximal DVT was significantly more associated with more chronic states (active cancer, congestive heart failure or respiratory insufficiency, age >75 years). Most patients (96.8%) with isolated distal DVT received anticoagulant therapies.There was no difference in the percentage of recurrent venous thromboembolism and major bleeding in patients with proximal DVT and isolated distal DVT. However, the mortality rate was significantly higher (p<0.01) in patients with proximal DVT (8.0%) than in those with isolated distal DVT (4.4%). Symptomatic isolated distal DVT differs from symptomatic proximal DVT both in terms of risk factors and clinical outcome. Whether these differences should influence the clinical management of these two events remains to be determined.
Tumor Suppressor Ras-Association Domain Family 1 Isoform A Is a Novel Regulator of Cardiac Hypertrophy
Authors: Oceandy Delvac , Pickard Adam , Prehar Sukhpal , Zi Min , Mohamed Tamer M.A. , Stanley Peter J. , Baudoin-Stanley Florence , Nadif Raja , Tommasi Stella , Pfeifer Gerd P. , Armesilla Angel L. , Cartwright Elizabeth J. , Neyses Ludwig
Published: August 2009

Background—

Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy.

Methods and Results—

A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A
−
/
−
) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A
−
/
−
mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras.

Conclusions—

Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway.
Blood Pressure Differences by Ethnic Group Among United States Children and Adolescents
Authors: Rosner Bernard , Cook Nancy , Portman Ron , Daniels Steve , Falkner Bonita
Published: August 2009

Large differences in blood pressure (BP) by ethnic group are apparent among adults. There is uncertainty as to whether similar differences by ethnic group exist among children and, if so, the age of onset. BP measurements were obtained from 58 698 children at 78 556 visits using Pediatric Task Force data, a collection of 11 studies with BP data from children and adolescents age 1 to 17 years. Generalized estimating equation methods were used to identify sex-specific differences in body mass index (BMI)–adjusted rates of BP elevation and prehypertension by ethnic group. Significant BMI-adjusted differences in rates of BP elevation were found between Hispanic boys versus white boys (odds ratio: 1.21; 95% CI: 1.07 to 1.37;
P
=0.002). No overall significant differences were found between black boys versus white boys (odds ratio: 1.03; 95% CI: 0.95 to 1.12;
P
=0.49); however, there was significant effect modification (
P
=0.01) with significant differences found for normal-weight boys (BMI: <85th percentile; OR black versus white: 1.14; 95% CI: 1.03 to 1.27;
P
=0.01) but not for overweight boys (BMI: ≥85th percentile; OR black versus white: 0.90; 95% CI: 0.78 to 1.05;
P
=0.20). No overall ethnic group differences in BMI-adjusted rates of hypertension were found for girls. Ethnic differences in prevalence rates of pediatric BP elevation that are not explained by obesity are present, primarily in boys. Whether these differences are attributable to genetic or environmental factors is unknown.
Trends in Twentieth-Century U.S. Extreme Snowfall Seasons
Authors: Kunkel Kenneth E. , Palecki Michael A. , Ensor Leslie , Easterling David , Hubbard Kenneth G. , Robinson David , Redmond Kelly
Published: August 2009

Temporal variability in the occurrence of the most extreme snowfall years, both those with abundant snowfall amounts and those lacking snowfall, was examined using a set of 440 quality-controlled, homogenous U.S. snowfall records. The frequencies with which winter-centered annual snowfall totals exceeded the 90th and 10th percentile thresholds at individual stations were calculated from 1900–01 to 2006–07 for the conterminous United States, and for 9 standard climate regions. The area-weighted conterminous U.S. results do not show a statistically significant trend in the occurrence of either high or low snowfall years for the 107-yr period, but there are regional trends. Large decreases in the frequency of low-extreme snowfall years in the west north-central and east north-central United States are balanced by large increases in the frequency of low-extreme snowfall years in the Northeast, Southeast, and Northwest. During the latter portion of the period, from 1950–51 to 2006–07, trends are much more consistent, with the United States as a whole and the central and northwest U.S. regions in particular showing significant declines in high-extreme snowfall years, and four regions showing significant increases in the frequency of low-extreme snowfall years (i.e., Northeast, Southeast, south, and Northwest).

In almost all regions of the United States, temperature during November–March is more highly correlated than precipitation to the occurrence of extreme snowfall years. El Niño events are strongly associated with an increase in low-extreme snowfall years over the United States as a whole, and in the northwest, northeast, and central regions. A reduction in low-extreme snowfall years in the Southwest is also associated with El Niño. The impacts of La Niña events are strongest in the south and Southeast, favoring fewer high-extreme snowfall years, and, in the case of the south, more low-extreme snowfall years occur. The Northwest also has a significant reduction in the chance of a low-extreme snowfall year during La Niña. A combination of trends in temperature in the United States and changes in the frequency of ENSO modes influences the frequency of extreme snowfall years in the United States.
A Tracer-Contour Inverse Method for Estimating Ocean Circulation and Mixing
Authors: Zika Jan D. , McDougall Trevor J. , Sloyan Bernadette M.
Published: August 2009

A method is developed for estimating the along-isopycnal and vertical mixing coefficients (K and D) and the absolute velocity from time-averaged hydrographic data. The method focuses directly on transports down tracer gradients on isopycnals. When the tracer considered is salinity or an appropriate variable for heat, this downgradient transport constitutes the along-isopycnal component of the thermohaline overturning circulation. In the method, a geostrophic streamfunction is defined that is related on isopycnals by tracer contours and by the thermal wind relationship in the vertical. Volume and tracer conservation constraints are also included. The method is overdetermined and avoids much of the signal-to-noise error associated with differentiating hydrographic data in conventional inverse methods. The method is validated against output of a layered model. It is shown to resolve both K and D, the downgradient isopycnal transport, and the mean flow on isopycnals in the North Pacific and South Atlantic.

Importantly, an understanding is established of both the physics underlying the method and the circumstances necessary for an inverse method to determine the mixing rates and the absolute velocity. If mixing is neglected, the method is the Bernoulli inverse method. At the limit of zero weight on the tracer-contour equations the method is a conventional box inverse method. Comparisons are drawn between each method and their relative merits are discussed. A new closed expression for the absolute velocity is also presented.
Analytical Theory for the Quasi-Steady and Low-Frequency Equatorial Ocean Response to Wind Forcing: The “Tilt” and “Warm Water Volume” Modes
Authors: Clarke Allan J.
Published: August 2009

Analytical theory is used to examine the linear response of a meridionally unbounded stratified ocean to large-scale, low-frequency wind forcing. The following results, applied mainly to the equatorial Pacific, were obtained.

(i) Provided that the wind stress curl vanishes at large distance from the equator, a general Sverdrup solution is valid in the quasi-steady (frequency ω → 0) limit. The meridionally averaged zonal flow toward the western boundary layer is zero so that there is no net mass flow into the boundary layer and the large-scale boundary condition is therefore satisfied. This solution predicts a zero pycnocline response in the eastern equatorial Pacific. It therefore predicts that, for the eastern equatorial Pacific, a slow weakening of the equatorial trade winds will not lead to long-term El Niño conditions there.

(ii) Consistent with observations and other previous work, for finite but small frequencies there are two modes of equatorial motion. One is a “tilt” mode in which the equatorial sea level and thermocline are tilted by the in-phase zonal wind stress and the other is an equatorial warm water volume (WWV) mode in which the discharge of equatorial warm water (negative WWV anomaly) lags the wind stress forcing by a quarter of a period.

(iii) The amplitude of the WWV mode approaches zero like ω1/2. Therefore, as ω → 0, the equatorial solution reduces to the tilt mode.

(iv) The WWV mode is not due to a dominant meridional divergence driven by the wind, as suggested by some previous work. Meridional and zonal divergence approximately cancel. Reflection of energy at both ocean boundaries together with the strong dependence of long Rossby wave speed on latitude is crucial to the existence of the disequilibrium WWV mode. Because higher-latitude Rossby waves travel so much more slowly, the Rossby waves reflecting from the western ocean boundary are not in phase. This gives rise to a reflected equatorial Kelvin wave and a WWV that is not in phase with the wind stress forcing.

(v) Observations from past work have shown that much low-frequency wave energy, particularly westward propagating Rossby wave energy poleward of about 5°N and 5°S, is damped out before it reaches the western ocean boundary. In this way dissipation likely has a strong influence on the equatorial Kelvin wave reflection and hence the disequilibrium WWV.