bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimates of sea surface height and near‐surface alongshore coastal currents from combinations of altimeters and tide gauges
Authors: Saraceno M. , Strub P. T. , Kosro P. M.
Published: November 2008

Present methods used to retrieve altimeter data do not provide reliable estimates of sea surface height (SSH) in the nearshore region, resulting in a measurement gap of 25–50 km next to the coast. In the present work, gridded SSH fields produced by Archiving, Validation, and Interpretation of Satellite Oceanographic data (AVISO) in the offshore region are combined with coastal tide gauge time series of SSH to improve estimation in that gap along the west coast of the United States in the northern California Current System between 40° and 45°N and 123.8° and 126°W. To assess the increase in skill provided by this procedure, the geostrophic alongshore currents, calculated from the new SSH fields in the gap region, are compared to three in situ, nearshore current measurements, resulting in correlation coefficients of 0.73–0.83 and standard deviations of the differences of 11.6–12.6 cm/s, substantially improved from the AVISO‐only results. When the Ekman current components are estimated and added to the geostrophic currents, comparisons to the 10 m deep acoustic Doppler current profiler velocities are only slightly improved. The Ekman components make a more significant contribution when compared to HF radar surface current measurements, providing correlations of 0.94 and standard deviations of the differences of 6.4–9.5 cm/s. These results represent a dramatic improvement in the quality of the SSH fields and estimated alongshore currents when additional, realistic SSH data from the coastal region are added. Here we use coastal tide gauges to provide the additional SSH data but also discuss more general approaches for altimeter SSH retrievals in coastal regions where tide gauge data are not available.
An ensemble‐based explicit four‐dimensional variational assimilation method
Authors: Tian Xiangjun , Xie Zhenghui , Dai Aiguo
Published: November 2008

The adjoint and tangent linear models in the traditional four‐dimensional variational data assimilation (4DVAR) are difficult to obtain if the forecast model is highly nonlinear or the model physics contains parameterized discontinuities. A new method (referred to as POD‐E4DVAR) is proposed in this paper by merging the Monte Carlo method and the proper orthogonal decomposition (POD) technique into 4DVAR to transform an implicit optimization problem into an explicit one. The POD method is used to efficiently approximate a forecast ensemble produced by the Monte Carlo method in a 4‐dimensional (4‐D) space using a set of base vectors that span the ensemble and capture its spatial structure and temporal evolution. After the analysis variables are represented by a truncated expansion of the base vectors in the 4‐D space, the control (state) variables in the cost function appear explicit so that the adjoint model, which is used to derive the gradient of the cost function with respect to the control variables in the traditional 4DVAR, is no longer needed. The application of this new technique significantly simplifies the data assimilation process and retains the two main advantages of the traditional 4DVAR method. Assimilation experiments show that this ensemble‐based explicit 4DVAR method performs much better than the traditional 4DVAR and ensemble Kalman filter (EnKF) method. It is also superior to another explicit 4DVAR method, especially when the forecast model is imperfect and the forecast error comes from both the noise of the initial field and the uncertainty in the forecast model. Computational costs for the new POD‐E4DVAR are about twice as the traditional 4DVAR method but 5% less than the other explicit 4DVAR and much lower than the EnKF method. Another assimilation experiment conducted within the Lorenz model indicates potential wider applications of this new POD‐E4DVAR method.
Investigating the ability of general circulation models to capture the effects of Eurasian snow cover on winter climate
Authors: Hardiman Steven C. , Kushner Paul J. , Cohen Judah
Published: November 2008

The ability of general circulation models (GCMs) to reproduce the observed strong correlations of Eurasian snow extent in the fall to wave activity and Northern Annular Mode anomalies in the following winter is studied. The observed correlations have been hypothesized to involve two parts: a Rossby wave pulse generated in the troposphere in response to snow‐forced surface cooling and a coupled zonal‐mean stratosphere‐troposphere response to this Rossby wave pulse involving eddy mean flow interactions. It is found that all coupled ocean atmosphere GCMs used within the Coupled Model Intercomparison Project 3 (CMIP3) fail to capture the observed correlations. Using the CMIP3 GCMs and two versions of a particular GCM forced by prescribed sea surface temperatures, possible reasons for this are considered. The snow forcing, as represented in the spatial extent and interannual variability of snow cover area, is found to be reasonable although somewhat weak in the GCMs, as is the relationship between snow cover and the zonal‐mean circulation. However, the anomaly of eddy geopotential height associated with Eurasian snow cover anomalies is found to be too localized longitudinally in the GCMs. It is proposed that the reduced longitudinal scale of the snow‐forced Rossby wave pulse prevents it from propagating into the stratosphere, thus inhibiting the observed wave‐driven stratosphere‐troposphere response to the pulse.
Boreal soil carbon dynamics under a changing climate: A model inversion approach
Authors: Fan Zhaosheng , Neff Jason C. , Harden Jennifer W. , Wickland Kimberly P.
Published: November 2008

Several fundamental but important factors controlling the feedback of boreal organic carbon (OC) to climate change were examined using a mechanistic model of soil OC dynamics, including the combined effects of temperature and moisture on the decomposition of OC and the factors controlling carbon quality and decomposition with depth. To estimate decomposition rates and evaluate their variations with depth, the model was inverted using a global optimization algorithm. Three sites with different drainage conditions that represent a broad diversity of boreal black spruce ecosystems were modeled. The comparison among the models with different depth patterns of decomposition rates (i.e., constant, linear, and exponential decrease) revealed that the model with constant inherent decomposition rates through the soil profile was able to fit the observed data in the most efficient way. There were also lower turnover times in the wettest site compared to the drier site even after accounting for moisture and temperature differences. Taken together, these results indicate that decomposition (especially for the wetter site) was not accurately represented with standard moisture and temperature controls and that other important protection mechanisms (e.g., limitation of O2, redox conditions, and permafrost) rather than low inherent decomposition rates are responsible for the recalcitrance of deep OC. The simulation results also showed that most of the soil CO2 efflux is generated from subsurface layers of OC because of the large OC stocks and optimal moisture conditions, suggesting that these deeper soil OC stocks are likely to be critically important to the future carbon dynamics.
Benchmarking in water project analysis
Authors: Griffin Ronald C.
Published: November 2008

The with/without principle of cost‐benefit analysis is examined for the possible bias that it brings to water resource planning. Theory and examples for this question are established. Because benchmarking against the demonstrably low without‐project hurdle can detract from economic welfare and can fail to promote efficient policy, improvement opportunities are investigated. In lieu of the traditional, without‐project benchmark, a second‐best‐based “difference‐making benchmark” is proposed. The project authorizations and modified review processes instituted by the U.S. Water Resources Development Act of 2007 may provide for renewed interest in these findings.
Environmental microarray analyses of Antarctic soil microbial communities
Authors: Yergeau Etienne , Schoondermark-Stolk Sung A , Brodie Eoin L , Déjean Sébastien , DeSantis Todd Z , Gonçalves Olivier , Piceno Yvette M , Andersen Gary L , Kowalchuk George A
Published: November 2008

Antarctic ecosystems are fascinating in their limited trophic complexity, with decomposition and nutrient cycling functions being dominated by microbial activities. Not only are Antarctic habitats exposed to extreme environmental conditions, the Antarctic Peninsula is also experiencing unequalled effects of global warming. Owing to their uniqueness and the potential impact of global warming on these pristine systems, there is considerable interest in determining the structure and function of microbial communities in the Antarctic. We therefore utilized a recently designed 16S rRNA gene microarray, the PhyloChip, which targets 8741 bacterial and archaeal taxa, to interrogate microbial communities inhabiting densely vegetated and bare fell-field soils along a latitudinal gradient ranging from 51 °S (Falkland Islands) to 72 °S (Coal Nunatak). Results indicated a clear decrease in diversity with increasing latitude, with the two southernmost sites harboring the most distinct Bacterial and Archaeal communities. The microarray approach proved more sensitive in detecting the breadth of microbial diversity than polymerase chain reaction-based bacterial 16S rRNA gene libraries of modest size (∼190 clones per library). Furthermore, the relative signal intensities summed for phyla and families on the PhyloChip were significantly correlated with the relative occurrence of these taxa in clone libraries. PhyloChip data were also compared with functional gene microarray data obtained earlier, highlighting numerous significant relationships and providing evidence for a strong link between community composition and functional gene distribution in Antarctic soils. Integration of these PhyloChip data with other complementary methods provides an unprecedented understanding of the microbial diversity and community structure of terrestrial Antarctic habitats.
Gene transfer agent (GTA) genes reveal diverse and dynamic Roseobacter and Rhodobacter populations in the Chesapeake Bay
Authors: Zhao Yanlin , Wang Kui , Budinoff Charles , Buchan Alison , Lang Andrew , Jiao Nianzhi , Chen Feng
Published: November 2008

Within the bacterial class Alphaproteobacteria, the order Rhodobacterales contains the Roseobacter and Rhodobacter clades. Roseobacters are abundant and play important biogeochemical roles in marine environments. Roseobacter and Rhodobacter genomes contain a conserved gene transfer agent (GTA) gene cluster, and GTA-mediated gene transfer has been observed in these groups of bacteria. In this study, we investigated the genetic diversity of these two groups in Chesapeake Bay surface waters using a specific PCR primer set targeting the conserved Rhodobacterales GTA major capsid protein gene (g5). The g5 gene was successfully amplified from 26 Rhodobacterales isolates and the bay microbial communities using this primer set. Four g5 clone libraries were constructed from microbial assemblages representing different regions and seasons of the bay and yielded diverse sequences. In total, 12 distinct g5 clusters could be identified among 158 Chesapeake Bay clones, 11 fall within the Roseobacter clade, and one falls in the Rhodobacter clade. The vast majority of the clusters (10 out of 12) lack cultivated representatives. The composition of g5 sequences varied dramatically along the bay during the wintertime, and a distinct Roseobacter population composition between winter and summer was observed. The congruence between g5 and 16S rRNA gene phylogenies indicates that g5 may serve as a useful genetic marker to investigate diversity and abundance of Roseobacter and Rhodobacter in natural environments. The presence of the g5 gene in the natural populations of Roseobacter and Rhodobacter implies that genetic exchange through GTA transduction could be an important mechanism for maintaining the metabolic flexibility of these groups of bacteria.
Difference in upper airway collapsibility during wakefulness between men and women in response to lower-body positive pressure
Authors: Su Mao-Chang , Chiu Kuo-Liang , Ruttanaumpawan Pimon , Shiota Satomi , Yumino Dai , Redolfi Stefania , Haight James S. , Yau Brian , Lam Jennifer , Bradley T. Douglas
Published: November 2008

Fluid shift from the legs to the neck induced by LBPP (lower-body positive pressure) increases UA (upper airway) collapsibility in healthy men. Rostral fluid displacement during recumbency may therefore contribute to the pathogenesis of OSA (obstructive sleep apnoea). There is a higher prevalence of OSA in men than in women. We therefore hypothesized that UA collapsibility increases more in men in response to rostral fluid displacement than in women. UA collapsibility was assessed in healthy, non-obese men and women while awake by determining UA Pcrit (critical closing pressure) during application of different suction pressures to the UA. Subjects were randomized to 5 min control or LBPP arms after which they crossed-over into the other arm following a 30 min washout. LBPP was applied by inflating anti-shock trousers wrapped around both legs to 40 mmHg. Pcrit, leg fluid volume and neck circumference were measured at baseline and after 5 min of both control and LBPP periods. LBPP caused a decrease in leg fluid volume and an increase in neck circumference that did not differ between men and women. However, compared with the control period, LBPP induced a much greater increase in Pcrit in men than in women (7.2±1.8 compared with 2.0±1.5 cmH2O, P=0.035). We conclude that rostral fluid displacement by LBPP increases UA collapsibility more in healthy, non-obese men than in women. This may be one mechanism contributing to the higher prevalence of OSA in men than in women.
The Distinctive City: Pitfalls in the Pursuit of Differential Advantage
Authors: Turok Ivan
Published: November 2008

In the face of growing competitive pressures, cities in Britain and elsewhere have been exploring new ways of promoting their distinctiveness in order to increase local prosperity. I analyse the main approaches used for this purpose and consider their underlying rationale. I argue that there is some justification for developing more specialised activities and sources of differential advantage that other cities cannot reproduce. However, many cities appear to be pursuing the same policy formula comprising one or more of the following elements: nascent industries, high-level occupations, signature buildings, and consumer identities. I discuss the limitations of each of these. I conclude with some constructive suggestions for what cities might do to develop more original and distinctive advantages.
Challenging Tradition: Unlocking New Paths to Regional Industrial Upgrading
Authors: Lowe Nichola J
Published: November 2008

Globalization is expected to benefit developing country manufacturers through exposure to quality-demanding markets and global buyers. Yet, its contribution to the process of local upgrading depends on the ability of these manufacturers to have access to and learn from global transactions. Growing awareness of the exclusion of smaller sized manufacturers from buyer-driven upgrading arrangements has led development scholars to document alternative strategies for global market insertion that are locally coordinated. But what happens when these alternative upgrading paths are themselves hindered by development-inhibiting relational dynamics at the local level? What options exist for unlocking entrenched social roles and practices in order to promote regional upgrading and with it the repositioning of an established manufacturing district? This paper explores this policy challenge within the context of a historic apparel-making district in West Central Mexico. It looks at the innovative steps taken by development practitioners to promote relational deepening between established manufacturing elites and their traditional subcontractors and, in turn, to encourage joint upgrading as a regional strategy for new market access.
(Dis)connecting Milan(ese): Deterritorialised Urbanism and Disempowering Politics in Globalising Cities
Authors: González Sara
Published: November 2008

This paper contributes to the debates on relational conceptualisations of space by focusing on how these notions are used by policy makers in particular governance contexts. It uses the example of Milan, where recent urban interventions and a particular fragmented governance structure demonstrate how overstated accounts of relationality can take hold in disempowering ways. It argues that, as Milan tries to become connected into the global flows of capital by ‘going up’ the city league, most Milanese are becoming disconnected from the democratic government of their city. As such, an excessive emphasis on connectivity and fluid conceptions of space risks losing sight of the particularities and uniqueness of places and the territorial nature of problems in cities today. It concludes that, theoretically, we still need a relational concept of space but one which denounces unevenness and spatial injustice.
From Manufacturing Garments for Ready-to-Wear to Designing Collections for Fast Fashion: Evidence from Turkey
Authors: Tokatli Nebahat , Kızılgün Ömür
Published: November 2008

In this paper we discuss two distinct sets of advantages which have helped Turkey to become the world's second-largest clothing exporter: the competency-related advantages of the last decade; and the trade-and-currency-related advantages of the earlier decades. In the late 1980s and 1990s, some fortunate developments in the international currency markets, together with an unofficial trade with Russia following the collapse of the Soviet Union, resulted in windfall trade gains for Turkey. During the last decade, a shift in the culture of fashion, from ready-to-wear to fast fashion pushed Turkish suppliers to upgrade into higher value-added activities such as design. While our focus is on the latter advantage, we point out that both sets of advantages have a commonality: namely, a sustainability problem.
Developing an Evaluation for Crosscutting Policy Goals: The Accessibility Policy Assessment Tool
Authors: Bristow Gillian , Farrington John , Shaw Jon , Richardson Tim
Published: November 2008

This paper reports upon the development of a policy assessment tool designed to evaluate the outcomes of policies promoting increased accessibility to services in rural areas. Much public policy is now concerned with addressing issues (such as accessibility) that span traditional organisational responsibilities and boundaries and thus require ‘joined-up’ thinking. At the same time, public policy is also increasingly required to be ‘evidence based’. As a consequence, it becomes necessary to develop appraisal and evaluation tools capable of assessing the achievements of joined-up policy interventions and their broader impacts on decision making and delivery across a diverse number of stakeholders. The Accessibility Policy Assessment Tool has been developed as a way of focusing more on the wider impacts of policy initiatives and is based upon a realist synthesis and multimethod approach to policy assessment. Through this focus, it has the potential to contribute to broader evaluation practice.
Dynamic NMR effects in breast cancer dynamic-contrast-enhanced MRI
Authors: Li Xin , Huang Wei , Morris Elizabeth A. , Tudorica Luminita A. , Seshan Venkatraman E. , Rooney William D. , Tagge Ian , Wang Ya , Xu Jingang , Springer Charles S.
Published: November 2008

The passage of a vascular-injected paramagnetic contrast reagent (CR) bolus through a region-of-interest affects tissue
1
H
2
O relaxation and thus MR image intensity. For longitudinal relaxation [
R
1
≡ (
T
1
)
−1
], the CR must have transient molecular interactions with water. Because the CR and water molecules are never uniformly distributed in the histological-scale tissue compartments, the kinetics of equilibrium water compartmental interchange are competitive. In particular, the condition of the equilibrium trans cytolemmal water exchange NMR system sorties through different domains as the interstitial CR concentration, [CR
o
], waxes and wanes. Before CR, the system is in the fast-exchange-limit (FXL). Very soon after CR
o
arrival, it enters the fast-exchange-regime (FXR). Near maximal [CR
o
], the system could enter even the slow-exchange-regime (SXR). These conditions are defined herein, and a comprehensive description of how they affect quantitative pharmacokinetic analyses is presented. Data are analyzed from a population of 22 patients initially screened suspicious for breast cancer. After participating in our study, the subjects underwent biopsy/pathology procedures and only 7 (32%) were found to have malignancies. The transient departure from FXL to FXR (and apparently not SXR) is significant in only the malignant tumors, presumably because of angiogenic capillary leakiness. Thus, if accepted, this analysis would have prevented the 68% of the biopsies that proved benign.
The G-protein-coupled receptor kinase 5 inhibits NFκB transcriptional activity by inducing nuclear accumulation of IκBα
Authors: Sorriento Daniela , Ciccarelli Michele , Santulli Gaetano , Campanile Alfonso , Altobelli Giovanna Giuseppina , Cimini Vincenzo , Galasso Gennaro , Astone Dalila , Piscione Federico , Pastore Lucio , Trimarco Bruno , Iaccarino Guido
Published: November 2008

G-protein-coupled receptor (GPCR) kinases, GRKs, are known as serine/threonine kinases that regulate GPCR signaling, but recent findings propose functions for these kinases besides receptor desensitization. Indeed, GRK5 can translocate to the nucleus by means of a nuclear localization sequence, suggesting that this kinase regulates transcription events in the nucleus. To evaluate the effect of GRK5–IκBα interaction on NFκB signaling, we induced the overexpression and the knockdown of GRK5 in cell cultures. GRK5 overexpression causes nuclear accumulation of IκBα, leading to the inhibition of NFκB transcriptional activity. Opposite results are achieved by GRK5 knockdown through siRNA. A physical interaction between GRK5 and IκBα, rather than phosphorylative events, appears as the underlying mechanism. We identify the regulator of gene protein signaling homology domain of GRK5 (RH) and the N-terminal domain of IκBα as the regions involved in such interaction. To confirm the biological relevance of this mechanism of regulation for NFκB, we evaluated the effects of GRK5-RH on NFκB-dependent phenotypes. In particular, GRK5-RH overexpression impairs apoptosis protection and cytokine production in vitro and inflammation and tissue regeneration in vivo. Our results reveal an unexpected role for GRK5 in the regulation of NFκB transcription activity. Placing these findings in perspective, this mechanism may represent a therapeutic target for all those conditions involving excessive NFκB activity.
Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes
Authors: Haanstra Jurgen R. , van Tuijl Arjen , Kessler Peter , Reijnders Willem , Michels Paul A. M. , Westerhoff Hans V. , Parsons Marilyn , Bakker Barbara M.
Published: November 2008

ATP generation by both glycolysis and glycerol catabolism is autocatalytic, because the first kinases of these pathways are fuelled by ATP produced downstream. Previous modeling studies predicted that either feedback inhibition or compartmentation of glycolysis can protect cells from accumulation of intermediates. The deadly parasite
Trypanosoma brucei
lacks feedback regulation of early steps in glycolysis yet sequesters the relevant enzymes within organelles called glycosomes, leading to the proposal that compartmentation prevents toxic accumulation of intermediates. Here, we show that glucose 6-phosphate indeed accumulates upon glucose addition to PEX14 deficient trypanosomes, which are impaired in glycosomal protein import. With glycerol catabolism, both in silico and in vivo, loss of glycosomal compartmentation led to dramatic increases of glycerol 3-phosphate upon addition of glycerol. As predicted by the model, depletion of glycerol kinase rescued PEX14-deficient cells of glycerol toxicity. This provides the first experimental support for our hypothesis that pathway compartmentation is an alternative to allosteric regulation.
Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis
Authors: Wittmeier Steffen , Song Gang , Duffin James , Poon Chi-Sang
Published: November 2008

Inspiratory and expiratory rhythms in mammals are thought to be generated by pacemaker-like neurons in 2 discrete brainstem regions: pre-Bötzinger complex (preBötC) and parafacial respiratory group (pFRG). How these putative pacemakers or pacemaker networks may interact to set the overall respiratory rhythm in synchrony remains unclear. Here, we show that a pacemakers 2-way “handshake” process comprising pFRG excitation of the preBötC, followed by reverse inhibition and postinhibitory rebound (PIR) excitation of the pFRG and postinspiratory feedback inhibition of the preBötC, can provide a phase-locked mechanism that sequentially resets and, hence, synchronizes the inspiratory and expiratory rhythms in neonates. The order of this handshake sequence and its progression vary depending on the relative excitabilities of the preBötC vs. the pFRG and resultant modulations of the PIR in various excited and depressed states, leading to complex inspiratory and expiratory phase-resetting behaviors in neonates and adults. This parsimonious model of pacemakers synchronization and mutual entrainment replicates key experimental data in vitro and in vivo that delineate the developmental changes in respiratory rhythm from neonates to maturity, elucidating their underlying mechanisms and suggesting hypotheses for further experimental testing. Such a pacemakers handshake process with conjugate excitation–inhibition and PIR provides a reinforcing and evolutionarily advantageous fail-safe mechanism for respiratory rhythmogenesis in mammals.
A CATALOG OF EXTENDED GREEN OBJECTS IN THE GLIMPSE SURVEY: A NEW SAMPLE OF MASSIVE YOUNG STELLAR OBJECT OUTFLOW CANDIDATES
Authors: Cyganowski C. J. , Whitney B. A. , Holden E. , Braden E. , Brogan C. L. , Churchwell E. , Indebetouw R. , Watson D. F. , Babler B. L. , Benjamin R. , Gomez M. , Meade M. R. , Povich M. S. , Robitaille T. P. , Watson C.
Published: November 2008

Using images from the Spitzer Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE), we have identified more than 300 extended 4.5 μm sources (Extended Green Objects (EGOs), for the common coding of the [4.5] band as green in three-color composite InfraRed Array Camera images). We present a catalog of these EGOs, including integrated flux density measurements at 3.6, 4.5, 5.8, 8.0, and 24 μm from GLIMPSE and the Multiband Imaging Photometer for Spitzer Galactic Plane Survey. The average angular separation between a source in our sample and the nearest IRAS point source is greater than 1′. The majority of EGOs are associated with infrared dark clouds (IRDCs), and where high-resolution 6.7 GHz CH3OH maser surveys overlap the GLIMPSE coverage, EGOs and 6.7 GHz CH3OH masers are strongly correlated. Extended 4.5 μm emission is thought to trace shocked molecular gas in protostellar outflows; the association of EGOs with IRDCs and 6.7 GHz CH3OH masers suggests that the extended 4.5 μm emission may pinpoint outflows specifically from massive protostars. The mid-IR colors of EGOs lie in regions of color–color space occupied by young protostars still embedded in infalling envelopes.
Predicting DNA recognition by Cys2His2 zinc finger proteins
Authors: Persikov Anton V. , Osada Robert , Singh Mona
Published: November 2008

Motivation: Cys2His2 zinc finger (ZF) proteins represent the largest class of eukaryotic transcription factors. Their modular structure and well-conserved protein-DNA interface allow the development of computational approaches for predicting their DNA-binding preferences even when no binding sites are known for a particular protein. The ‘canonical model’ for ZF protein-DNA interaction consists of only four amino acid nucleotide contacts per zinc finger domain.

Results: We present an approach for predicting ZF binding based on support vector machines (SVMs). While most previous computational approaches have been based solely on examples of known ZF protein–DNA interactions, ours additionally incorporates information about protein–DNA pairs known to bind weakly or not at all. Moreover, SVMs with a linear kernel can naturally incorporate constraints about the relative binding affinities of protein-DNA pairs; this type of information has not been used previously in predicting ZF protein-DNA binding. Here, we build a high-quality literature-derived experimental database of ZF–DNA binding examples and utilize it to test both linear and polynomial kernels for predicting ZF protein–DNA binding on the basis of the canonical binding model. The polynomial SVM outperforms previously published prediction procedures as well as the linear SVM. This may indicate the presence of dependencies between contacts in the canonical binding model and suggests that modification of the underlying structural model may result in further improved performance in predicting ZF protein–DNA binding. Overall, this work demonstrates that methods incorporating information about non-binding and relative binding of protein–DNA pairs have great potential for effective prediction of protein–DNA interactions.

Availability: An online tool for predicting ZF DNA binding is available at http://compbio.cs.princeton.edu/zf/.

Contact:  mona@cs.princeton.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Decomposition of complex microbial behaviors into resource-based stress responses
Authors: Carlson Ross P.
Published: November 2008

Motivation: Highly redundant metabolic networks and experimental data from cultures likely adapting simultaneously to multiple stresses can complicate the analysis of cellular behaviors. It is proposed that the explicit consideration of these factors is critical to understanding the competitive basis of microbial strategies.

Results: Wide ranging, seemingly unrelated Escherichia coli physiological fluxes can be simply and accurately described as linear combinations of a few ecologically relevant stress adaptations. These strategies were identified by decomposing the central metabolism of E.coli into elementary modes (mathematically defined biochemical pathways) and assessing the resource investment cost–benefit properties for each pathway. The approach capitalizes on the inherent tradeoffs related to investing finite resources like nitrogen into different pathway enzymes when the pathways have varying metabolic efficiencies. The subset of ecologically competitive pathways represented 0.02% of the total permissible pathways. The biological relevance of the assembled strategies was tested against 10 000 randomly constructed pathway subsets. None of the randomly assembled collections were able to describe all of the considered experimental data as accurately as the cost-based subset. The results suggest these metabolic strategies are biologically significant. The current descriptions were compared with linear programming (LP)-based flux descriptions using the Euclidean distance metric. The current study's pathway subset described the experimental fluxes with better accuracy than the LP results without having to test multiple objective functions or constraints and while providing additional ecological insight into microbial behavior. The assembled pathways seem to represent a generalized set of strategies that can describe a wide range of microbial responses and hint at evolutionary processes where a handful of successful metabolic strategies are utilized simultaneously in different combinations to adapt to diverse conditions.

Contact:  rossc@biofilms.montana.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Statistical properties of measured X-ray intensities affected by counting loss
Authors: Ida T.
Published: November 2008

The statistical properties of X-ray intensities measured with counting systems have been experimentally investigated. A formula of statistical variance for the intermediately extended dead-time model is proposed and compared with the experimentally evaluated variance obtained from repeated measurements based on Chipman's foil method applied to X-ray detection systems of laboratory and synchrotron powder diffractometers. It has been found that the variance of the observed intensities is smaller than the average of count, as has been suggested by conventional theoretical models for counting loss. It is shown that the statistical errors can be predicted by applying an intermediately extended dead-time model including dead-time τ and degree of extension ρ as fixed parameters.
A Role for the ESCRT System in Cell Division in Archaea
Authors: Samson Rachel Y. , Obita Takayuki , Freund Stefan M. , Williams Roger L. , Bell Stephen D.
Published: November 2008

Archaea are prokaryotic organisms that lack endomembrane structures. However, a number of hyperthermophilic members of the Kingdom
Crenarchaea
, including members of the
Sulfolobus
genus, encode homologs of the eukaryotic endosomal sorting system components Vps4 and ESCRT-III (endosomal sorting complex required for transport–III). We found that
Sulfolobus
ESCRT-III and Vps4 homologs underwent regulation of their expression during the cell cycle. The proteins interacted and we established the structural basis of this interaction. Furthermore, these proteins specifically localized to the mid-cell during cell division. Overexpression of a catalytically inactive mutant Vps4 in
Sulfolobus
resulted in the accumulation of enlarged cells, indicative of failed cell division. Thus, the archaeal ESCRT system plays a key role in cell division.
Direct Imaging of Multiple Planets Orbiting the Star HR 8799
Authors: Marois Christian , Macintosh Bruce , Barman Travis , Zuckerman B. , Song Inseok , Patience Jennifer , Lafrenière David , Doyon René
Published: November 2008

Direct imaging of exoplanetary systems is a powerful technique that can reveal Jupiter-like planets in wide orbits, can enable detailed characterization of planetary atmospheres, and is a key step toward imaging Earth-like planets. Imaging detections are challenging because of the combined effect of small angular separation and large luminosity contrast between a planet and its host star. High-contrast observations with the Keck and Gemini telescopes have revealed three planets orbiting the star HR 8799, with projected separations of 24, 38, and 68 astronomical units. Multi-epoch data show counter clockwise orbital motion for all three imaged planets. The low luminosity of the companions and the estimated age of the system imply planetary masses between 5 and 13 times that of Jupiter. This system resembles a scaled-up version of the outer portion of our solar system.
Optical Images of an Exosolar Planet 25 Light-Years from Earth
Authors: Kalas Paul , Graham James R. , Chiang Eugene , Fitzgerald Michael P. , Clampin Mark , Kite Edwin S. , Stapelfeldt Karl , Marois Christian , Krist John
Published: November 2008

Fomalhaut, a bright star 7.7 parsecs (25 light-years) from Earth, harbors a belt of cold dust with a structure consistent with gravitational sculpting by an orbiting planet. Here, we present optical observations of an exoplanet candidate, Fomalhaut b. Fomalhaut b lies about 119 astronomical units (AU) from the star and 18 AU of the dust belt, matching predictions of its location. Hubble Space Telescope observations separated by 1.73 years reveal counterclockwise orbital motion. Dynamical models of the interaction between the planet and the belt indicate that the planet's mass is at most three times that of Jupiter; a higher mass would lead to gravitational disruption of the belt, matching predictions of its location. The flux detected at 0.8 μm is also consistent with that of a planet with mass no greater than a few times that of Jupiter. The brightness at 0.6 μm and the lack of detection at longer wavelengths suggest that the detected flux may include starlight reflected off a circumplanetary disk, with dimension comparable to the orbits of the Galilean satellites. We also observe variability of unknown origin at 0.6 μm.
Flow-induced vascular remodeling in the mesenteric artery of spontaneously hypertensive rats
Authors: Gao Yu-Jing , Yang Lu-Fang , Stead Shelley , Lee Robert M.K.W.
Published: November 2008

The effect of an increased blood flow on vascular remodeling was studied in the mesenteric arteries of 11–12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar–Kyoto rats (WKY). Increased blood flow was induced by selective ligation of mesenteric arteries. Nearby arteries with normal blood flow were used as controls. 7–10 days after the ligation procedure, mesenteric arteries were fixed in situ at maximal relaxation by perfusion fixation. Morphometric measurement of vascular dimension was carried out with confocal microscopy. Apoptotic cells were detected by the TdT-mediated dUTP nick-end labelling method. Cell growth was quantified by using proliferating cell nuclear antigen (PCNA) in sections of paraffin-embedded vessels. In SHR, elevated blood flow increased the vessel wall dimension and the number of smooth muscle cell (SMC) layers and also increased the wall-to-lumen ratio and the number of PCNA-positive SMC, but did not change lumen size or number of apoptotic SMC. In WKY, on the other hand, increased blood flow resulted in an increase in lumen diameter, a reduction of apoptotic SMC, but no change in wall-to-lumen ratio, number of SMC layers, or number of PCNA-positive SMC. These results showed that mesenteric arteries from hypertensive and normotensive rats respond to an increase in blood flow differently: a lumen enlargement with reduced SMC apoptosis in WKY, but an increased wall-to-lumen ratio with enhanced SMC growth in SHR. Although it remains to be determined whether flow alteration is one of the initiating factors in the development of vascular remodeling in hypertension, we speculate that an increase in cardiac output, and therefore an increase in shear stress that occurs in young SHR, contributes to vascular remodelling in this model of hypertension.
Intracoronary endothelin receptor blockade improves endothelial function in patients with coronary artery disease
Authors: Böhm Felix , Jensen Jens , Svane Bertil , Settergren Magnus , Pernow John
Published: November 2008

Endothelin (ET)-1 receptor blockade improves endothelial function in the forearm of patients with atherosclerosis. The aim was to investigate whether intracoronary ET receptor blockade improves coronary endothelial function and increases blood flow in patients with coronary artery disease. Ten patients received a 60-minute infusion of either the selective ETAreceptor antagonist BQ123 (40 nmol/min, n = 6) or BQ123 + the ETBreceptor antagonist BQ788 (40 nmol/min, n = 4). In all patients, substance P, an endothelium-dependent vasodilator, did not increase baseline coronary flow reserve with thermodilution (CFRThermo) (0.71 ± 0.14 s during NaCl versus 0.59 ± 0.14 s during substance P) or baseline quantitative coronary angiography (QCA) (2.74 ± 0.16 mm versus 2.83 ± 0.20 mm). After ET receptor blockade, however, the response to substance P was significantly improved as determined both by CFRThermo(0.62 ± 0.14 s during NaCl versus 0.48 ± 0.10 s during substance P, p < 0.05) and by QCA (2.70 ± 0.18 mm versus 2.85 ± 0.19 mm, p < 0.05). In addition, ET blockade increased blood flow in all patients by 16% ± 10% (n = 10, p < 0.05) and in the BQ123 group by 22% ± 16% (n = 6, p < 0.05). Furthermore, ETAblockade increased blood flow significantly more than did dual ETA/ETBblockade (p < 0.05). These findings indicate that ET receptor blockade may be a new therapeutic strategy to improve coronary vascular function in patients with coronary artery disease.
Cardiovascular and airway relaxant activities of peony root extract
Authors: Ghayur Muhammad N. , Gilani Anwarul H. , Rasheed Huma , Khan Abdullah , Iqbal Zafar , Ismail Muhammad , Saeed Sheikh A. , Janssen Luke J.
Published: November 2008

Paeonia emodi (peony) is a well known plant used medicinally to treat hypertension, palpitations, and asthma. Despite its popularity, there are few reports in the scientific literature examining its use in such conditions. We prepared a 70% ethanolic extract of peony root (Pe.Cr) and applied it to segments of guinea pig atria and trachea and rat aorta suspended separately in tissue baths. Activity against arachidonic acid (AA)-induced platelet aggregation was measured in human platelet-rich plasma. Airway relaxant effect was evaluated against acetylcholine (ACh)-induced airway contraction in mouse lung slices loaded with fluo-4. Pe.Cr (0.3–10 mg/mL) showed an atropine-resistant negative inotropic effect in atria. In rat aorta, an endothelium-independent vasodilatory effect (0.3–10 mg/mL) was seen in phenylephrine- and high-K+-induced contractions. Pe.Cr (0.01–1 mg/mL) also inhibited AA-induced platelet aggregation. In isolated trachea, Pe.Cr (0.3–10 mg/mL) relaxed carbachol- and histamine-induced contractions independently of β-adrenergic receptors. In mouse lung slices, Pe.Cr (0.3–1 mg/mL) inhibited ACh-induced airway narrowing and oscillations of intracellular Ca2+in airway smooth muscle cells. The results showed cardiosuppressant, vasodilatory, antiplatelet, and tracheal and airway relaxant activities of peony, providing potential justification for its medicinal use in different hyperactive cardiovascular and respiratory disorders.
Influence of quinidine, fluvoxamine, and ketoconazole on the enantioselective pharmacokinetics of citalopram in rats
Authors: Rocha Adriana , Coelho Eduardo B. , Lanchote Vera L.
Published: November 2008

Citalopram (CITA) is available as a racemic mixture or as (+)-(S)-CITA. In humans, CITA is metabolized to demethylcitalopram (DCITA) by CYP2C19, CYP2D6, and CYP3A and to didemethylcitalopram by CYP2D6. There are no data regarding the enzymes involved in CITA and DCITA metabolism in rats. The present study investigated the influence of CYP inhibitors on the enantioselective metabolism of CITA in rats. Male Wistar rats (n = 6) received a single dose of 20 mg·kg–1CITA after pretreatment with 80 mg·kg–1quinidine, 10 mg·kg–1fluvoxamine, 50 mg·kg–1ketoconazole, or vehicle (control). Blood samples were collected up to 20 h after CITA administration. The CITA and DCITA enantiomers were analyzed by LC-MS/MS using a Chiralcel OD-R column. The kinetic disposition of CITA was enantioselective in rats (AUCS/Rratio = 0.4). Coadministration with quinidine resulted in non-enantioselective inhibition of the metabolism of CITA. Coadministration with fluvoxamine or ketoconazole, however, inhibited only the metabolism of (+)-(S)-CITA, but not of (–)-(R)-CITA when the racemic drug was administered to rats.
MAGNETOHYDRODYNAMIC MODELING OF RELATIVISTIC OUTFLOWS
Authors: VLAHAKIS NEKTARIOS
Published: November 2008

The main characteristics of relativistic, steady, ideal magnetohydrodynamic (MHD) outflows are discussed, focusing on their bulk acceleration and collimation. It is shown that the Bernoulli equation relates the bulk Lorentz factor with the shape of the flow, permitting an analytic estimation of the acceleration efficiency, while the transfield force-balance equation gives a simple relation of the bulk Lorentz factor to the distance.
MAGNETIC ACCELERATION OF ULTRARELATIVISTIC GRB AND AGN JETS
Authors: BARKOV M. V. , KOMISSAROV S. S.
Published: November 2008

We present numerical simulations of cold, axisymmetric, magnetically driven relativistic outflows. The outflows are initially sub-Alfvénic and Poynting-flux dominated, with total–to–rest-mass energy flux ratio up to μ ~ 620. To study the magnetic acceleration of jets we simulate flows confined within a funnel with a rigid wall of prescribed shape, which we take to be z ∝ ra (in cylindrical coordinates, with a ranging from 1 to 2). This allows us to eliminate the numerical dissipative effects induced by a free boundary with an ambient medium. We find that in all cases they converge to a steady state characterized by a spatially extended acceleration region. For the jet solutions the acceleration process is very efficient — on the outermost scale of the simulation more than half of the Poynting flux has been converted into kinetic energy flux, and the terminal Lorentz factor approached its maximum possible value (Γ∞ ≃ μ). The acceleration is accompanied by the collimation of magnetic field lines in excess of that dictated by the funnel shape. The numerical solutions are generally consistent with the semi-analytic self-similar jets solutions and the spatially extended acceleration observed in some astrophysical relativistic jets. In agreement with previous studies, we also find that the acceleration is significantly less effective for wind solutions suggesting that pulsar winds may remain Poynting dominated when they reach the termination shock.
3D RESISTIVE MHD SIMULATIONS OF MAGNETIC RECONNECTION AND THE TEARING MODE INSTABILITY IN CURRENT SHEETS
Authors: MURPHY G. C. , OUYED R. , PELLETIER G.
Published: November 2008

Magnetic reconnection plays a critical role in many astrophysical processes where high energy emission is observed, e.g. particle acceleration, relativistic accretion powered outflows, pulsar winds and probably in dissipation of Poynting flux in GRBs. The magnetic field acts as a reservoir of energy and can dissipate its energy to thermal and kinetic energy via the tearing mode instability. We have performed 3D nonlinear MHD simulations of the tearing mode instability in a current sheet. Results from a temporal stability analysis in both the linear regime and weakly nonlinear (Rutherford) regime are compared to the numerical simulations. We observe magnetic island formation, island merging and oscillation once the instability has saturated. The growth in the linear regime is exponential in agreement with linear theory. In the second, Rutherford regime the island width grows linearly with time. We find that thermal energy produced in the current sheet strongly dominates the kinetic energy. Finally preliminary analysis indicates a P(k) 4.8 power law for the power spectral density which suggests that the tearing mode vortices play a role in setting up an energy cascade.
LONG TERM EVOLUTION OF MAGNETIC TURBULENCE IN RELATIVISTIC COLLISIONLESS SHOCKS
Authors: CHANG PHILIP , SPITKOVSKY ANATOLY , ARONS JONATHAN
Published: November 2008

We study the long term evolution of magnetic fields generated by an initially unmagnetized collisionless relativistic e+e- shock. Our 2D particle-in-cell numerical simulations show that downstream of such a Weibel-mediated shock, particle distributions are approximately isotropic, relativistic Maxwellians, and the magnetic turbulence is highly intermittent spatially, non-propagating, and decaying. Using linear kinetic theory, we find a simple analytic form for these damping rates. Our theory predicts that the overall magnetic energy decays as (ωp t)-q with q ~ 1, which compares favorably with simulations, but predicts overly rapid damping of short-wavelength modes. The magnetic trapping of particles within the magnetic structures may be the origin of this discrepancy. We conclude that initially unmagnetized relativistic shocks in electron-positron plasmas are unable to form persistent downstream magnetic fields. These results put interesting constraints on synchrotron models for the prompt and afterglow emission from GRBs.