bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Interactions between Hepatitis B Virus RNase H Antagonists and Other Inhibitors
Authors: Lomonosova Elena , Zlotnick Adam , Tavis John E. 
Published: December 2016

ABSTRACT

Combination therapies are standard for management of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections; however, no such therapies are established for human hepatitis B virus (HBV). Recently, we identified several promising inhibitors of HBV RNase H (here simply RNase H) activity that have significant activity against viral replication
in vitro
. Here, we investigated the
in vitro
antiviral efficacy of combinations of two RNase H inhibitors with the current anti-HBV drug nucleoside analog lamivudine, with HAP12, an experimental core protein allosteric modulator, and with each other. Anti-HBV activities of the compounds were tested in a HepG2-derived cell line by monitoring intracellular core particle DNA levels, and cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. The antiviral efficiencies of the drug combinations were evaluated using the median-effect equation derived from the mass-action law principle and combination index theorem of Chou and Talalay. We found that combinations of two RNase H inhibitors from different chemical classes were synergistic with lamivudine against HBV DNA synthesis. Significant synergism was also observed for the combination of the two RNase H inhibitors. Combinations of RNase H inhibitors with HAP12 had additive antiviral effects. Enhanced cytotoxicity was not observed in the combination experiments. Because of these synergistic and additive effects, the antiviral activity of combinations of RNase H inhibitors with drugs that act by two different mechanisms and with each other can be achieved by administering the compounds in combination at doses below the respective single drug doses.
The Master Regulators of the Fla1 and Fla2 Flagella of Rhodobacter sphaeroides Control the Expression of Their Cognate CheY Proteins
Authors: Hernandez-Valle José , Domenzain Clelia , de la Mora Javier , Poggio Sebastian , Dreyfus Georges , Camarena Laura 
Published: December 2016

ABSTRACT

Rhodobacter sphaeroides
is an alphaproteobacterium that has two complete sets of flagellar genes. The
fla1
set was acquired by horizontal transfer from an ancestral gammaproteobacterium and is the only set of flagellar genes that is expressed during growth under standard laboratory conditions. The products of these genes assemble a single, subpolar flagellum. In the absence of the Fla1 flagellum, a gain-of-function mutation in the histidine kinase CckA turns on the expression of the
fla2
flagellar genes through the response regulator CtrA. The rotation of the Fla1 and Fla2 flagella is controlled by different sets of chemotaxis proteins. Here, we show that the expression of the chemotaxis proteins that control Fla2, along with the expression of the
fla2
genes, is coordinated by CtrA, whereas the expression of the chemotaxis genes that control Fla1 is mediated by the master regulators of the Fla1 system. The coordinated expression of the chemosensory proteins with their cognate flagellar genes highlights the relevance of integrating the expression of the horizontally acquired
fla1
genes with a chemosensory system independently of the regulatory proteins responsible for the expression of
fla2
and its cognate chemosensory system.

IMPORTANCE
Gene acquisition via horizontal transfer represents a challenge to the recipient organism to adjust its metabolic and genetic networks to incorporate the new material in a way that represents an adaptive advantage. In the case of
Rhodobacter sphaeroides
, a complete set of flagellar genes was acquired and successfully coordinated with the native flagellar system. Here we show that the expression of the chemosensory proteins that control flagellar rotation is dependent on the master regulators of their corresponding flagellar system, minimizing the use of transcription factors required to express the native and horizontally acquired genes along with their chemotaxis proteins.
Large subglacial meltwater features in the central Barents Sea
Authors: Bjarnadóttir L.R. , Winsborrow M.C.M. , Andreassen K. 
Published: December 2016

Abstract
During the last glacial period large parts of the Arctic, including the Barents Sea, north of Norway and Russia, were covered by ice sheets. Despite several studies indicating that melting occurred beneath much of the Barents Sea ice sheet, very few meltwater-related landforms have been identified. We document ∼200 seafloor valleys in the central Barents Sea and interpret them to be tunnel valleys formed by meltwater erosion beneath an ice sheet. This is the first account of widespread networks of tunnel valleys in the Barents Sea, and confirms previous predictions that large parts of the ice sheet were warm based. The tunnel valleys are interpreted to be formed through a combination of steady-state drainage and outburst floods close to the ice margin, as a result of increased melting within a period of rapid climate warming during late deglaciation. This is the first study documenting widespread tunnel valley formation at the northern reaches of a Northern Hemisphere paleo–ice sheet, during advanced deglaciation and beneath a much reduced ice sheet. This indicates that suitable conditions for tunnel valley formation may have occurred more widely than previously reported, and emphasizes the need to properly incorporate hydrological processes in current efforts to model ice sheet response to climate warming. This study provides valuable empirical data, to which modeling results can be compared.
Regional variability in the frequency and magnitude of large explosive volcanic eruptions
Authors: Sheldrake Tom , Caricchi Luca 
Published: December 2016

Abstract
Quantifying the frequency at which volcanic eruptions of different size occurs is important for hazard assessment. Volcanic records can be used to estimate the recurrence rate of large-magnitude eruptions (magnitude ≥4), but recording biases that impact data completeness complicate analysis. To overcome these biases, we conceptualize the volcanic record as a series of individual and unique time series associated by a common behavior. Thus, we approach issues of completeness on a volcano-by-volcano basis and use a hierarchical Bayesian approach to characterize the common frequency-magnitude (f-M) behavior for different groups of volcanoes. We identify variations in the f-M relationship between different volcano types and between different volcanic arcs. By accounting for systematic under-recording in the volcanic record, we also calculate the global recurrence rates for large-magnitude eruptions during the Holocene, which are similar to previous estimates. However, higher recurrence rates for smaller-magnitude events are observed, which is a result of our adjustments for data completeness. Quantifying how the f-M relationship varies between different groups of volcanoes provides an opportunity to understand how the tectonic setting influences f-M behavior, which is important to quantify long-term regional volcanic hazard.
A probabilistic analysis of meteorically altered δ13C chemostratigraphy from late Paleozoic ice age carbonate platforms
Authors: Dyer Blake , Higgins John A. , Maloof Adam C. 
Published: December 2016

Abstract
The stratigraphic expression of meteoric diagenesis in carbonates is a glimpse into the weathering, fluid transport, and biological productivity of the ancient near-surface terrestrial environment. To infer this environmental information, we use a probabilistic approach to merge an isotope-based reactive transport model with chemostratigraphic data from carbonates that were subaerially exposed during an expansion of the late Paleozoic ice age in the middle Carboniferous. The rate of carbon flowing through the carbonate platform relative to the rate of carbon reacting between mineral and fluid phases controls the length scale, curvature, and magnitude of the diagenetic carbon isotope profiles. The ratio of advection to reaction is determined for seven stratigraphic sections, and the advection rate is used to estimate the minimum carbonate weathering associated with each profile. These carbonate weathering rates extrapolated over the expansive shallow carbonate platforms of the middle Carboniferous indicate that glacioeustatic fall may have caused a 20%–50% increase in the dissolved CaCO3 flux to the ocean. The complex feedbacks among carbonate weathering and accumulation, atmospheric pCO2, glacioeustasy, and passive margin subsidence may have played an unexplored role in the glacial-interglacial climate dynamics of the late Paleozoic ice age.
Early Cenozoic drainage reorganization of the United States Western Interior–Gulf of Mexico sediment routing system
Authors: Sharman Glenn R. , Covault Jacob A. , Stockli Daniel F. , Wroblewski Anton F.-J. , Bush Meredith A. 
Published: December 2016

Abstract
Continental-scale drainages host the world’s largest rivers and offshore sediment accumulations, many of which contain significant petroleum reserves. Rate of sediment supply in these settings may be a signal of external controls (e.g., tectonics) on landscape evolution, yet deciphering these controls remains a major challenge in interpreting the ancient stratigraphic record. Integration of new and published detrital zircon U-Pb ages from the United States Rocky Mountain region and Gulf of Mexico (GOM) sedimentary basin demonstrates profound changes in the U.S. continental drainage divide that controlled the rate of sediment delivery to the northern GOM during Paleocene–Eocene time. Sedimentation rate increased dramatically during deposition of the lower Wilcox Group, reaching approximately three times the Cenozoic average, accompanied by pronounced shoreline regression and delivery of a large volume of sand to the basin floor. We hypothesize that this increase in sediment delivery to the GOM resulted from drainage capture of a significant portion of the Sevier-Laramide structural province (∼900,000 km2) that included the headwaters of the California and Idaho Rivers. Capture of the California River drainage may have occurred in the vicinity of the Hanna Basin of eastern Wyoming that previously emptied northward into a shallow seaway, but was subsequently diverted southward to the Rockdale delta, which accumulated within the Houston embayment during the time of deposition of the lower Wilcox Group. Detrital zircon U-Pb ages from Wilcox samples within the Rockdale delta show a remarkable similarity with contemporaneous Laramide synorogenic units, including enrichment in detritus derived from the Cordilleran arc and basement terranes of western North America relative to older and younger units in the Houston embayment. A subsequent order of magnitude decline in sedimentation rate to the GOM can be partly attributed to well-documented drainage closure (∼800,000 km2) that accompanied lake formation in interior Laramide basins (ca. 53–51.8 Ma). Our results demonstrate that tectonically induced drainage migration in the high-relief segments of continental-scale drainages can have a pronounced effect on the rate of sediment transfer to continental margins.
Functional Assessment of Coronary Artery Disease Using Whole-Heart Dynamic Computed Tomographic Perfusion
Authors: Hubbard Logan , Ziemer Benjamin , Lipinski Jerry , Sadeghi Bahman , Javan Hanna , Groves Elliott M. , Malkasian Shant , Molloi Sabee 
Published: December 2016

Background—
Computed tomographic (CT) angiography is an important tool for the evaluation of coronary artery disease but often correlates poorly with myocardial ischemia. Current dynamic CT perfusion techniques can assess ischemia but have limited accuracy and deliver high radiation dose. Therefore, an accurate, low-dose, dynamic CT perfusion technique is needed.

Methods and Results—

A total of 20 contrast-enhanced CT volume scans were acquired in 5 swine (40±10 kg) to generate CT angiography and perfusion images. Varying degrees of stenosis were induced using a balloon catheter in the proximal left anterior descending coronary artery, and a pressure wire was used for reference fractional flow reserve (FFR) measurement. Perfusion measurements were made with only 2 volume scans using a new first-pass analysis (FPA) technique and with 20 volume scans using an existing maximum slope model (MSM) technique. Perfusion (P) and FFR measurements were related by P
FPA
=1.01 FFR−0.03 (
R
2
=0.85) and P
MSM
=1.03 FFR−0.03 (
R
2
=0.80) for FPA and MSM techniques, respectively. Additionally, the effective radiation doses were calculated to be 2.64 and 26.4 mSv for FPA and MSM techniques, respectively.

Conclusions—
A new FPA-based dynamic CT perfusion technique was validated in a swine animal model. The results indicate that the FPA technique can potentially be used for improved anatomical and functional assessment of coronary artery disease at a relatively low radiation dose.
On the longevity, growth and reproductive characteristics of Lichtenstein’s Toadhead Agama, Phrynocephalus interscapularis Lichtenstein, 1856 (Agamidae, Sauria)
Authors: Smirina Ella , Ananjeva Natalia 
Published: December 2016

We aimed to analyze growth and longevity in relation to reproductive characteristics in a population of smallest species of agamid lizard, Phrynocephalus interscapularis using skeletochronology. Growth layers in the humerus were examined to estimate lizard age and growth, and to check the hypothesis of an annual turnover of short-term life of arid small lizards. Individual age of lizards in a sample of 50 individuals was determined. Ageing by skeletochronology showed the maximum age of lizards in the population as about three years and determined the following age structure of the sample: 18 one-year-old individuals (after the first hibernation), 19 two-year old individuals and 11 three-year old ones. It was shown that in studied population the largest specimen (a male of 37 mm) is not the oldest. The problem of ephemeral annual lizards is discussed.
Hydrological Modeling and Capacity Building in the Republic of Namibia
Authors: Clark Robert A. , Flamig Zachary L. , Vergara Humberto , Hong Yang , Gourley Jonathan J. , Mandl Daniel J. , Frye Stuart , Handy Matthew , Patterson Maria 
Published: December 2016

Abstract
The Republic of Namibia, located along the arid and semiarid coast of southwest Africa, is highly dependent on reliable forecasts of surface and groundwater storage and fluxes. Since 2009, the University of Oklahoma (OU) and National Aeronautics and Space Administration (NASA) have engaged in a series of exercises with the Namibian Ministry of Agriculture, Water, and Forestry to build the capacity to improve the water information available to local decision-makers. These activities have included the calibration and implementation of NASA and OU’s jointly developed Coupled Routing and Excess Storage (CREST) hydrological model as well as the Ensemble Framework for Flash Flood Forecasting (EF5). Hydrological model output is used to produce forecasts of river stage height, discharge, and soil moisture.
To enable broad access to this suite of environmental decision support information, a website, the Namibia Flood Dashboard, hosted on the infrastructure of the Open Science Data Cloud, has been developed. This system enables scientists, ministry officials, nongovernmental organizations, and other interested parties to freely access all available water information produced by the project, including comparisons of NASA satellite imagery to model forecasts of flooding or drought. The local expertise needed to generate and enhance these water information products has been grown through a series of training meetings bringing together national government officials, regional stakeholders, and local university students and faculty. Aided by online training materials, these exercises have resulted in additional capacity-building activities with CREST and EF5 beyond Namibia as well as the initial implementation of a global flood monitoring and forecasting system.
Understanding the Sources of Satellite Passive Microwave Rainfall Retrieval Systematic Errors Over Land
Authors: Petković Veljko , Kummerow Christian D. 
Published: December 2016

AbstractAnalyses of the Tropical Rainfall Measuring Mission (TRMM) satellite rainfall estimates reveal a substantial disagreement between its active [Precipitation Radar (PR)] and passive [TRMM Microwave Imager (TMI)] sensors over certain regions. This study focuses on understanding the role of the synoptic state of atmosphere in these discrepancies over land regions where passive microwave (PMW) retrievals are limited to scattering signals. As such the variability in the relationship between the ice-induced scattering signal and the surface rainfall is examined. Using the Amazon River and central Africa regions as a test bed, it is found that the systematic difference seen between PR and TMI rainfall estimates is well correlated with both the precipitating system structure and the level of its organization. Relying on a clustering technique to group raining scenes into three broad but distinct organizational categories, it is found that, relative to the PR, deep-organized systems are typically overestimated by TMI while the shallower ones are underestimated. Results suggest that the storm organization level can explain up to 50% of the regional systematic difference between the two sensors. Because of its potential for retrieval improvement, the ability to forecast the level of systems organization is tested. The state of the atmosphere is found to favor certain storm types when constrained by CAPE, wind shear, dewpoint depression, and vertical humidity distribution. Among other findings, the observations reveal that the ratio between boundary layer and midtropospheric moisture correlates well with the organization level of convection. If adjusted by the observed PR-to-TMI ratio under a given environment, the differences between PMW and PR rainfall estimates are diminished, at maximum, by 30% in RMSE and by 40% in the mean.
Different Climatological Characteristics, Inner-Core Structures, and Intensification Processes of Simulated Intense Tropical Cyclones between 20-km Global and 5-km Regional Models
Authors: Kanada Sachie , Wada Akiyoshi 
Published: December 2016

Abstract
Climatological characteristics of simulated intense tropical cyclones (TCs) in the western North Pacific were explored with a 20-km-mesh atmospheric general circulation model (AGCM20) and a 5-km-mesh regional atmospheric nonhydrostatic model (ANHM5). From the AGCM20 climate runs, 34 intense TCs with a minimum central pressure (MCP) less than or equal to 900 hPa were sampled. Downscaling experiments were conducted with the ANHM5 for each intense TC simulated by the AGCM20. Only 23 developed into TCs with MCP ≤ 900 hPa. Most of the best-track TCs with an MCP ≤ 900 hPa underwent rapid intensification (RI) and attained maximum intensities south of 25°N. The AGCM20 simulated a similar number of intense TCs as the best-track datasets. However, the intense AGCM20 TCs tended to intensify longer and more gradually; only half of them underwent RI. The prolonged gradual intensification resulted in significant northward shifts of the location of maximum intensity compared with the location derived from two best-track datasets. The inner-core structure of AGCM20 TCs exhibited weak and shallow eyewall updrafts with maxima below an altitude of 6 km, while downscaling experiments revealed that most of the intense ANHM5 TCs underwent RI with deep and intense eyewall updrafts and attained their maximum intensity at lower latitudes. The altitudes of updraft maxima simulated by the AGCM20 descended rapidly during the phase of greatest intensification as midlevel warming markedly developed. The change in major processes responsible for precipitation in AGCM20 TCs before and after maximum intensification suggests close relationships between the large-scale cloud scheme and midlevel warming and prolonged gradual intensification.
Observed Basin-Scale Response of the North Atlantic Meridional Overturning Circulation to Wind Stress Forcing
Authors: Elipot Shane , Frajka-Williams Eleanor , Hughes Chris W. , Olhede Sofia , Lankhorst Matthias 
Published: December 2016

Abstract
The response of the North Atlantic meridional overturning circulation (MOC) to wind stress forcing is investigated from an observational standpoint, using four time series of overturning transports below and relative to 1000 m, overlapping by 3.6 yr. These time series are derived from four mooring arrays located on the western boundary of the North Atlantic: the RAPID Western Atlantic Variability Experiment (WAVE) array (42.5°N), the Woods Hole Oceanographic Institution Line W array (39°N), RAPID–MOC/MOCHA (26.5°N), and the Meridional Overturning Variability Experiment (MOVE) array (16°N). Using modal decompositions of the analytic cross-correlation between transports and wind stress, the basin-scale wind stress is shown to significantly drive the MOC coherently at four latitudes, on the time scales available for this study. The dominant mode of covariance is interpreted as rapid barotropic oceanic adjustments to wind stress forcing, eventually forming two counterrotating Ekman overturning cells centered on the tropics and subtropical gyre. A second mode of covariance appears related to patterns of wind stress and wind stress curl associated with the North Atlantic Oscillation, spinning anomalous horizontal circulations that likely interact with topography to form overturning cells.
Antiepileptic drugs in migraine and epilepsy: Who is at increased risk of adverse events?
Authors: Romoli Michele , Costa Cinzia , Siliquini Sabrina , Corbelli Ilenia , Eusebi Paolo , Bedetti Chiara , Caproni Stefano , Cupini Letizia Maria , Calabresi Paolo , Sarchielli Paola 
Published: December 2016

Background The impact of adverse events (AEs) of antiepileptic drugs (AEDs) have an impact on compliance and dropouts. We compared tolerability of AEs of AEDs among patients with migraine, epilepsy, or both. Methods Overall, 335 patients (epilepsy (n = 142), migraine (n = 131), and both (n = 62)), were evaluated with the Liverpool Adverse Events Profile (LAEP) to assess the magnitude, profile and occurrence rate of the AEs of valproate, topiramate, and lamotrigine. Results AEs were significantly more common with topiramate treatment (71.0%) and among migraineurs (69.5%), the latter being more prone to discontinue AEDs (46.6%). The profile of AEs with topiramate and valproate differed among groups. Moreover, treatment with both topiramate and valproate was associated, for all groups, with a worse tolerability profile compared to lamotrigine. Conclusion Our data suggest a specific drug and disease AE profile of AEDs. Specifically, migraineurs are the most affected by AEs, even though they receive very low dosages of AEDs. This finding might be considered a clinical implication of central sensitization mechanisms. Both the profile and tolerability of AEs, highly influencing quality of life, depended on the underlying conditions, and deeply impacted on treatment dropout. Therefore, before starting, switching or stopping AED treatment, all options need to be considered.