pinecone/core-2020-05-10-deduplication huggingface dataset:
Pharmacokinetic Profiles of Active Components After Oral Administration of a Kampo Medicine, Shakuyakukanzoto, to Healthy Adult Japanese Volunteers

ABSTRACTShakuyakukanzoto (SKT), a traditional Japanese (Kampo) medicine, has been used by patients with muscle cramps and abdominal pains. In this trial, we analyzed plasma concentrations of active components after SKT was administered as a single oral dose of 2.5 or 5.0g/day per person. The study was a randomized, open-label, two-arm, two-period, crossover trial conducted in healthy Japanese volunteers. Albiflorin (ALB), paeoniflorin (PAE), glycycoumarin (GCM), isoliquiritigenin (ILG), glycyrrhetic acid (GA), and glycyrrhetic acid-3-O-monoglucuronide were targeted, and the plasma concentration of each component was measured using a liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were calculated, and the linearity was assessed. All targeted components were detected in the plasma after oral administration of SKT. ALB, PAE, GCM, and ILG were detected at an early stage. The linearity was observed for the maximum plasma concentration of GCM, ILG, and GA and for the area under the plasma concentration-time curve of GA. In this trial, we demonstrated for the first time in humans that these components were absorbed into the blood after oral administration of SKT. The results of this pharmacokinetic trial in humans are also important and useful for understanding the mechanism of action of SKT, verifying the active components predicted in basic research, and conducting pharmacokinetics and safety studies in the future
Characterization of Human Duodenal Fluids in Fasted and Fed State Conditions

This work provides an elaborate characterization of human intestinal fluids (HIF) collected in fasted- and fed-state conditions. HIF from 20 healthy volunteers (10 M/F) were aspirated by intubation near the ligament of Treitz in a time-dependent manner (10-min intervals) and characterized for pH, bile salts, phospholipids, cholesterol, triacylglycerides (TAG), diacylglycerides (DAG), monoacylglycerides (MAG), free fatty acids (FFA), pancreatic lipase, phospholipase A2, and nonspecific esterase activity. For almost all parameters, a food-induced effect was observed. Results were characterized by a high variability, as illustrated by the broad ranges observed for each parameter: pH (fasted: 3.4-8.3; fed: 4.7-7.1), bile salts (fasted: 0.03-36.18 mM; fed: 0.74-86.14 mM), phospholipids (fasted: 0.01-6.33 mM; fed: 0.16-14.39 mM), cholesterol (fasted: 0-0.48 mM; fed: 0-3.29 mM), TAG (fed: 0-6.76 mg/mL), DAG (fed: 0-3.64 mg/mL), MAG (fasted: 0-1.09 mg/mL; fed: 0-11.36 mg/mL), FFA (fasted: 0-3.86 mg/mL; fed: 0.53-15.0 mg/mL), pancreatic lipase (fasted: 26-86 μg/mL; fed: 146-415 μg/mL), phospholipase A2 (fasted: 3-6 ng/mL; fed: 4.3-27.7 ng/mL), and nonspecific esterase activity (fasted: 270-4900 U/mL; fed: 430-4655 U/mL). This comprehensive overview may serve as reference data for physiologically based pharmacokinetic modeling and the optimization of biorelevant simulated intestinal fluids for the use in in vitro dissolution, solubility, and permeability profiling. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.status: publishe
Elemental Impurities in Pharmaceutical Excipients

ABSTRACTControl of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to control based on permitted daily exposures in drug products. Within the pharmaceutical community, there is uncertainty regarding the impact of these changes on manufactures of drug products. This uncertainty is fueled in part by a lack of publically available information on elemental impurity levels in common pharmaceutical excipients. This paper summarizes a recent survey of elemental impurity levels in common pharmaceutical excipients as well as some drug substances. A widely applicable analytical procedure was developed and was shown to be suitable for analysis of elements that are subject to United States Pharmacopoeia Chapter <232>and International Conference on Harmonization’s Q3D Guideline on Elemental Impurities. The procedure utilizes microwave-assisted digestion of pharmaceutical materials and inductively coupled plasma mass spectrometry for quantitative analysis of these elements. The procedure was applied to 190 samples from 31 different excipients and 15 samples from eight drug substances provided through the International Pharmaceutical Excipient Council of the Americas. The results of the survey indicate that, for the materials included in the study, relatively low levels of elemental impurities are present
Pathway Distribution Model for Solute Transport in Stratum Corneum

One of the main functions of the skin is to reduce the amount of water evaporating from the surface of a human body with outermost layer of the epidermis, stratum corneum (SC), forming a barrier, which protects underlying tissue from dehydration. Empirical data obtained for water penetration in SC are normally analysed using mathematical models, among which the homogeneous membrane (HM) model is commonly employed to describe transport kinetics in SC. However, the HM model failed to fit simultaneously the experimental data for water permeation and desorption (Anissimov YG, Roberts MS. 2009. J Pharm Sci 98:772–781), as the model does not account for a complex structure of SC and irregular distribution of corneocytes. Our previous work (Anissimov YG, Roberts MS. 2009. J Pharm Sci 98:772–781) introduced a slow binding (SB) model that is more aligned with the true biological structure of SC. This report provides an alternative/additional model to both the HM and SB models and takes into account the distribution of effective pathways across SC for water transport.Griffith Sciences, School of Natural SciencesFull Tex
The Palaeolithic occupation of Europe as revealed\ud
by evidence from the rivers: data from IGCP 449

IGCP 449 (2000–2004), seeking to correlate fluvial records globally, has compiled a\ud
dataset of archaeological records from Pleistocene fluvial sequences. Many terrace sequences can\ud
now be reliably dated and correlated with marine oxygen isotope stages (MIS), allowing potentially\ud
useful patterns in artefact distribution to be recognised. This review, based on evidence from\ud
northwest European and German sequences (Thames, Somme, Ilm, Neckar and Wipper), makes\ud
wider comparisons with rivers further east, particularly the Vltava, and with southern Europe,\ud
especially Iberia. The northwest and southern areas have early assemblages dominated by handaxes,\ud
in contrast with flake-core industries in Germany and further east. Fluvial sequences can provide\ud
frameworks for correlation, based on markers within the Palaeolithic record. In northwest Europe the\ud
first appearance of artefacts in terrace staircases, the earliest such marker, dates from the mid–late\ud
Cromerian Complex. Flake-core industries may have significantly preceded handaxe industries in\ud
southern Europe. An important technological innovation—Levallois technique—occurs at the\ud
Lower-Middle Palaeolithic boundary, correlated with MIS 9–8. Humans deserted northern Europe\ud
during MIS 6, apparently returning to central Germany and northern France (Somme valley) by MIS 5e\ud
but not reaching southern England until the appearance of Mousterian culture during MIS 4–3
Geomorphological signature and flow dynamics of The Minch palaeo-ice stream, NW Scotland

Large-scale streamlined glacial landforms are identified in 11 areas of northwest Scotland, from the Isle of Skye in the south to the Butt of Lewis in the north. These ice-directional features occur in bedrock and superficial deposits, generally below 350 m above sea level, and where best developed have elongation ratios of >20:1. Sidescan sonar and multibeam echo-sounding data from The Minch show elongate streamlined ridges and grooves on the seabed, with elongation ratios of up to 70:1. These bedforms are interpreted as mega-scale glacial lineations. All the features identified formed beneath The Minch palaeo-ice stream which was ca. 200 km long, up to 50 km wide and drained ca. 15 000 km2 of the northwest sector of the last British-Irish Ice Sheet (Late Devensian Glaciation). Nine ice-stream tributaries and palaeo-onset zones are also identified, on the basis of geomorphological evidence. The spatial distribution and pattern of streamlined bedforms around The Minch has enabled the catchment, flow paths and basal shear stresses of the palaeo-ice stream and its tributaries to be tentatively reconstructed
The paleohydrological evolution of Lago Chungará Andean Altiplano, northern Chile) during the Lateglacial and early Holocene using oxigen isotopes in diatom silica

Oxygen isotopes of diatom silica and petrographical characterisation of diatomaceous laminated sediments of Lago Chungara´ (northern Chilean Altiplano) have allowed us to establish its palaeohydrological evolution during the Lateglacial-early Holocene (ca. 12 000-9400 cal. yr BP). These laminated sediments are composed of light and dark pluriannual couplets of diatomaceous ooze formed by different processes. Light sediment laminae accumulated during short-term diatom blooms whereas dark sediment laminae represent the baseline limnological conditions during several years of deposition. Oxygen isotope analysis of the dark diatom laminae show a general d18Oenrichment trend during the studied period. Comparison of these d18Odiatom values with the previously published lake-level evolution suggests a correlation between d18Odiatom and the precipitation:evaporation ratio, but also with the evolution of other local hydrological factors as changes in the groundwater outflow as well as shifts in the surface:volume ratio of Lago Chungara´. The lake expanded (probably increasing this ratio) during the rising lake-level trend due to changes in its morphology, enhancing evaporation. Furthermore, the lake's hydrology was probably modified as the groundwater outflow became sealed by sediments, increasing lake water residence time and potential evaporation. Both factors could cause isotope enrichment. # Natural Environment Research Council (NERC) copyright 2008. Reproduced with the permission of NERC
Ice caps existed throughout the Lateglacial Interstadial in northern Scotland

We constrain, in detail, fluctuations of two former ice caps in NW Scotland with multibeam seabed surveys, geomorphological mapping and cosmogenic 10Be isotope analyses. We map a continuous sequence of 40 recessional moraines stretching from ~10 km offshore to the Wester Ross mountains. Surface-exposure ages from boulders on moraine ridges in Assynt and the Summer Isles region show that substantial, dynamic, ice caps existed in NW Scotland between 13–14 ka BP. We interpret this as strong evidence that large active glaciers probably survived throughout the Lateglacial Interstadial, and that during the Older Dryas period (c.14 ka BP) ice caps in NW Scotland were thicker and considerably more extensive than in the subsequent Younger Dryas Stadial. By inference, we suggest that Lateglacial ice-cap oscillations in Scotland reflect the complex interplay between changing temperature and precipitation regimes during this climatically unstable period (~15–11 ka BP). \ud
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Isotope offsets in marine diatom [delta]18O over the last 200 ka

Previous work has suggested that a species effect may be present in diatom oxygen isotope ratios (18Odiatom). While predominantly attributed to be a size-related species effect, currently the precise mechanism remains unknown. Here, two size fractions of diatoms (38-75 µm and >100 µm) covering the last 200 ka are analysed for 18O from ODP Site 882 in the North-West Pacific Ocean. Synchronous variations of up to 13 occur in both size fractions. However, large isotope offsets (mean = 2.02) exist between the two fractions with no relationship between their magnitude and the overlying palaeoenvironmental conditions. In contrast to earlier work from the same site, no one size fraction is constantly higher or lower in 18O relative to the other. As such, the dominant mechanism is most likely separate to the size effect previously detected. In addition, no relationship exists between the magnitude of the offsets and the species composition of the two size fractions. The presence of these isotope offsets imposes significant constraints upon the future use of 18Odiatom in palaeoceanographic reconstructions and reiterates the need to extract and analyse only species- and size-specific diatom samples
The last deglaciation in the Picos de Europa National Park (Cantabrian Mountains, northern Spain)

42 páginas, 8 figuras, 4 tablas.-- El PDF del artículo esta en formato pre-print.A sedimentological and geochemical study of the Lago Enol sequence (Cantabrian Mountains, northern Spain), together with detailed geomorphological mapping, provides a first record of glacier evolution and climate change over the last 40 ka in the Picos de Europa National Park. The Enol glacier retreated from its maximum extent prior to 40 ka BP as demonstrated by the onset of proglacial lacustrine sedimentation in two glaciated depressions: the Comella hollow to the north (before 40 ka BP) and the Lago Enol (before 38 ka BP). These results support previous evidence that the maximum extent of southern European glaciers occurred earlier than in northern Europe. Alternation of homogeneous and laminated proglacial sediments during the glacier retreat illustrate a dynamic glacial evolution during the Marine Isotope Stage (MIS) 3 (40–26 ka BP). A slight warming is detected at 26 ka ago with the change from proglacial sediments (in a lake located in contact to the glacier) to glaciolacustrine sedimentation (in a non-contact or distal lake). Finally, the onset of organic-rich sediments took place at 18 ka ago. This last transition occurred in two phases, similarly to the North Atlantic Last Termination, suggesting a link between North Atlantic Deep Water formation oscillations and palaeohydrological variability in the Cantabrian Mountains.This research has been funded through the projects LIMNOCLIBER (REN2003-09130-C02-02), IBERLIMNO (CGL2005-20236-E/CLI), LIMNOCAL (CGL2006-13327-C04-01) and GRACCIE (CSD2007-00067), provided by the Spanish Inter-Ministry Commission of Science and Technology (CICYT). Additional funding was provided by the Spanish National Parks Agency through the project ‘Evolución climática y ambiental del Parque Nacional de Picos de Europa desde el último máximo glaciar – ref: 53/2006’. A. Moreno acknowledges funding from the European Commission's Sixth Framework Program (Marie Curie Outgoing International Fellowships, proposal 021673-IBERABRUPT).Peer reviewe
The Antarctic palaeo record and its role in improving predictions of future Antarctic Ice Sheet change.

This paper reviews the ways in which the palaeo record of Antarctic Ice Sheet change can be used to improve understanding of contemporary ice sheet behaviour, and thus enhance predictions of future sea-level change. The main areas where the palaeo ice sheet record can contribute are understanding long-term ice sheet trajectory; providing data against which ice sheet models can be tested; to identify and understand the range and types of natural ice sheet behaviour; to balance the global water budget; to correct contemporary glaciological measurements of mass change; and to understand the relationship between polar ecosystems and the ice sheet. I review each in turn and argue that research priorities include understanding past West Antarctic Ice Sheet collapse and its timing; a focus on the palaeo record of rapid retreat events and how these unfolded in the geological past; improving the number and range of ice sheet reconstructions, particularly through the Holocene; continuing to investigate the potential for using sediments and landforms to parameterise basal conditions in ice sheet models; and understanding past East Antarctic Ice Sheet dynamics, particularly the evidence for partial deglaciation
A Record of Lateglacial and Early Holocene Environmental and Ecological Change from Southwestern Connecticut, USA

Analyses of a sediment core from Highstead Swamp in southwestern Connecticut, USA, reveal Lateglacial and early Holocene ecological and hydrological changes. Lateglacial pollen assemblages are dominated by Picea  and Pinus subg. Pinus, and the onset of the Younger Dryas (YD) cold interval is evidenced by higher abundance of Abies and Alnus viridis subsp. crispa. As climate warmed at the end of the YD, Picea and Abies declined and Pinus strobus  became the dominant upland tree species. A shift from lacustrine sediment to organic peat at the YD-Holocene boundary suggests that the lake that existed in the basin during the Lateglacial interval developed into a swamp in response to reduced effective moisture. A change in wetland vegetation from Myrica gale to Alnus incana subsp. rugosa and Sphagnum is consistent with this interpretation of environmental changes at the beginning of the HoloceneOther Research Uni
A Last Glacial Maximum Pollen Record from Bodmin Moor Showing a Possible Cryptic Northern Refugium in Southwest England

Reproduced with permission of the publisher. The definitive version is available at www3.interscience.wiley.com. Copyright © 2009 John Wiley & Sons, LtdA late Devensian palynological record is presented from Dozmary Pool (Bodmin Moor, southwest England), beyond the southern limit of the Last Glacial Maximum (LGM) British Ice Sheet. The pollen assemblages indicate predominantly herbaceous tundra steppe communities but also include elevated levels (typically 10-20%) of conifer tree pollen (Picea, Pinus, Abies) and lower but persistent percentages of broadleaf tree pollen during the LGM. This record is seemingly at odds with the orthodox view of an entirely treeless tundra steppe environment for this region and elimination of tree species from the British Isles during glacial maxima. Long-distance pollen transport seems an unlikely explanation for the tree pollen considering distance to the nearest known refugia, except possibly for Pinus. Reworking of the tree pollen, often invoked in these circumstances, remains a possible alternative, especially given the abundance of these trees in the region during early Devensian interstadials. However, this explanation has been challenged by studies reporting plant macrofossil and faunal evidence for survival of temperate biota during glacial maxima and from climate modelling work that suggests some trees could have survived the glacial extremes in areas well beyond the recorded glacial refugia. Assuming reworking was not a major factor, the Dozmary Pool pollen record is consistent with the "apos;cryptic northern refugia hypothesis"apos; that invokes survival of trees in small, scattered populations under locally favourable conditions during glacial maxima
Provenance and depositional environments of Quaternary sediments from the western North Sea Basin

As the majority of the data on Quaternary sediments from the North Sea Basin are seismostratigraphical, we analysed the Elsterian Swarte Bank Formation, the Late Saalian Fisher Formation and the Late Weichselian (Dimlington Stadial) Bolders Bank Formation in order to determine genesis and provenance. The Swarte Bank Formation is a subglacial till containing palynomorphs from the Moray Forth and the northeastern North Sea, and metamorphic heavy minerals from the Scottish Highlands. The Fisher Formation was sampled from the northern and central North Sea. In the north, it is interpreted as a subglacial till, with glaciomarine sediments cropping out further south. These sediments exhibit a provenance signature consistent with the Midland Valley of Scotland, the Eocene of the North Sea Basin, the Grampian Highlands and northeast Scotland. The Bolders Bank Formation is a subglacial till containing palynomorphs from the Midland Valley of Scotland, northern Britain, and a metamorphic heavy-mineral suite indicative of the Grampian Highlands, Southern Uplands and northeast Scotland. These data demonstrate that there was repeated glaciation of the North Sea Basin during the Middle and Late Pleistocene, with ice sheets originating in northern Scotland. There was no evidence for a Scandinavian ice sheet in the western North Sea basin
Tropical cyclone activity and western North Atlantic stratification over the last millennium: a comparative review with viable connections

Tropical cyclones (TC) are recognized to modify the thermal structure of the upper ocean through the process of vertical mixing. Assessing the role this mixing plays in the overall stratification of the upper ocean is difficult, due to the relatively short and incomplete instrumental record. Proxy records for both TC landfalls and oceanographic stratification are preserved within the geological record and provide insight for how past changes in TC‐induced mixing have potentially affected water column structure prior to the instrumental record. Here we provide the first comparison between previously published paleo‐reconstructions of vertical ocean density and tropical cyclone activity from the western North Atlantic. A prominent lull in TC activity has been observed prior to approximately 1700 CE that extends back several centuries. This interval of low TC activity is shown to be concurrent with the timing of increased ocean stratification near Great Bahama Bank, potentially due in part to reduced TC‐induced mixing. To test whether this relationship is feasible, we present numerical results from a coarse‐resolution ocean general circulation model experiment isolating the effect of TC surface wind forcing on the upper ocean. An anomaly of roughly 0.12 kg m −3  in vertical stratification occurs above and below the mixed layer for model runs with and without TC mixing. This anomaly is roughly 25% of the entire paleo‐density signal observed just prior to 1700 CE. These results suggest that TC mixing alone cannot completely explain the density anomaly observed prior to 1700 CE, but support TC variability as an important contributor to enhancing oceanic stratification during this interval. Copyright © 2011 John Wiley & Sons, Ltd