bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revised stratigraphic framework of pre-Westphalian Carboniferous petroleum system elements from the Outer Moray Firth to the Silverpit Basin, North Sea, UK
Authors: Kearsey T. I. , Millward D. , Ellen R. , Whitbread K. , Monaghan A. A. 
Published: May 2018

Abstract
Spatially and temporally variable Tournaisian to Namurian Carboniferous fluvial, fluvio-deltaic, platform carbonate and shale-dominated basin sedimentary successions up to 3.5 km thick are preserved in a complex series of basins from the Outer Moray Firth (Quadrant 14) to the Silverpit Basin (Quadrant 44). Differences in stratigraphic nomenclature in the areas surrounding the Mid North Sea High and onshore, combined with sparse biostratigraphic data, have hindered the systematic regional understanding of the timing and controls on stacked source and reservoir rock intervals. Over 125 well reinterpretations, tied to seismic interpretations, provide evidence of the inception and extent of a delta system. Regional time slices highlight a long-lived laterally equivalent basinal, mud-rich succession across Quadrants 41–44. They also show that the area from the Outer Moray Firth to the Silverpit Basin was part of the same sedimentary system up to at least Namurian times. All of this is placed within a simplified stratigraphic framework.
Sediment mass movement of a particle-laden turbidity current based on ultrasound velocity profiling and the distribution of sediment concentration
Authors: Nomura Shun , Hitomi Jumpei , De Cesare Giovanni , Takeda Yasushi , Yamamoto Yuzuru , Sakaguchi Hide 
Published: May 2018

Abstract
Particle-laden flows or turbidity currents along the seafloor are important to the formation and erosion of submarine topography. To understand the mass-transport process, flume tests were carried out with a continuous supply of quartz-laden suspension. The vertical and horizontal velocities were extracted by two pairs of ultrasound Doppler velocity profilers installed at different angles with respect to the bed-normal direction. Due to the head intrusion into the ambient water, the sediment in the suspension was continuously lifted up and mixed, leaving lobes and clefts. The velocity-maximum layer acted as the main sediment conveyor and divided the body into wall and jet regions. The concentration distribution was also quantified based on the relationship between the fluid density and the intensity of light attenuation obtained using a video recording. An area of high sediment concentration was observed just behind the head frontal area. Analysis of the velocity and concentration distribution demonstrated that sediment in the turbidity current was transported mainly by head movement and that continuous sedimentation took place in the wall region. The results indicate that a turbidity current proceeds while maintaining an ordered inner dynamic structure.
Stratal architecture and evolution of a slope mass-transport complex, Isaac Formation, Neoproterozoic Windermere Supergroup, southern Canadian Cordillera, British Columbia, Canada
Authors: Navarro Lilian , Arnott R. William C. 
Published: May 2018

Abstract

Detailed sedimentological and stratigraphic analyses of a
c.
1500 m thick, siliciclastic-dominated slope succession in the Neoproterozoic Isaac Formation at the Castle Creek study area (southern Canadian Cordillera) reveals the occurrence of four well-preserved mass-transport complexes (MTCs) composed principally of slide/slump and debris-flow deposits. The stratigraphically lowest of these complexes is about 60 m thick and crops out for >2.5 km laterally, consisting of slide and debrite. The slide has an irregular erosive base with ramp-and-flat geometry. This is overlain locally by boulder-sized blocks of slightly to moderately deformed strata, bounded by shear surfaces. The slide is overlain by a debrite that pinches and swells laterally, consisting of matrix-supported conglomerate with common metre-scale clasts of mudstone and coarse-grained sandstone embedded in a mudstone-rich matrix with dispersed, pebble quartz grains. Based on its stratigraphic position at the base of the slope, vertical stacking of slide-debrite, lithological distribution, considerable thickness and lateral extent, this MTC is interpreted to be associated with a major episode of continental slope instability and submarine mass-wasting. The close association between the MTC and underlying/overlying mixed carbonate-siliciclastic strata suggests that sea level most likely exerted a key control on sediment supply, which ultimately led to the emplacement of this MTC.
Three modes of isograd formation in the northern Monashee Complex of the Canadian Cordillera
Authors: Gervais Félix 
Published: May 2018

Abstract
This contribution re-examines textural relationships in metapelitic schist from five metamorphic zones separated by four isograds along the west flank of the Frenchman Cap dome in the southeastern Canadian Cordillera. There is a muscovite-out isograd formed by muscovite-dehydration melting in the kyanite-field. Two others, including one coinciding with the muscovite-out isograd, mark the appearance of sillimanite, which was produced along with biotite by garnet breakdown in the presence of melt. Two others mark the disappearance of kyanite: one formed during retrogression, the other coinciding with a shear zone (the Monashee décollement). Only the muscovite-out isograd, therefore, corresponds with the classical definition of an intersection of the topography with a prograde, isogradic-surface. This contribution exemplifies the need to use a descriptive definition of isograd as the trace of a surface across which a specific change in metamorphic mineralogy takes place. It is further proposed to specify their origin whenever possible with terms such as prograde-, retrograde- and structural-isograds. This revised terminology for isograds will improve our understanding of metamorphic terrains by helping to localize cryptic shear zones, gain a better understanding of the retrograde path and put firmer constraints on viable tectonic models.
Microvascular permeability of skeletal muscle after eccentric contraction-induced muscle injury: in vivo imaging using two-photon laser scanning microscopy
Authors: Hotta Kazuki , Behnke Bradley Jon , Masamoto Kazuto , Shimotsu Rie , Onodera Naoya , Yamaguchi Akihiko , Poole David C. , Kano Yutaka 
Published: May 2018

Via modulation of endothelial integrity and vascular permeability in response to damage, skeletal muscle microvessels play a crucial permissive role in tissue leukocyte invasion. However, direct visual evidence of altered microvascular permeability of skeletal muscle has not been technically feasible, impairing mechanistic understanding of these responses. Two-photon laser scanning microscopy (TPLSM) allows three-dimensional in vivo imaging of skeletal muscle microcirculation. We hypothesized that the regulation of microvascular permeability in vivo is temporally related to acute inflammatory and regenerative processes following muscle injury. To test our hypothesis, tibialis anterior muscles of anesthetized male Wistar rats were subjected to eccentric contractions (ECCs) via electrical stimulation. The skeletal muscle microcirculation was imaged by an intravenously infused fluorescent dye (rhodamine B isothiocyanate-dextran) to assess microvascular permeability via TPLSM 1, 3, and 7 days after ECC. Immunohistochemistry on serial muscle sections was performed to determine the proportion of VEGF-A-positive muscle fibers in the damaged muscle. Compared with control rats, the volumetrically determined interstitial leakage of fluorescent dye (5.1 ± 1.4, 5.3 ± 1.2 vs. 0.51 ± 0.14 μm3 × 106; P < 0.05, days 1 and 3, respectively, vs. control) and percentage of VEGF-A-positive fibers in the damaged muscle (10 ± 0.4%, 22 ± 1.1% vs. 0%; days 1 and 3, respectively, vs. control) were significantly higher on days 1 and 3 after ECC. The interstitial leakage volume returned to control by day 7. These results suggest that microvascular hyperpermeability assessed by in vivo TPLSM imaging is associated with ECC-induced muscle damage and increased VEGF expression. NEW & NOTEWORTHY This investigation employed a novel in vivo imaging technique for skeletal muscle microcirculation using two-photon laser scanning microscopy that enabled microvascular permeability to be assessed by four-dimensional image analysis. By combining in vivo imaging and histological analysis, we found the temporal profile of microvascular hyperpermeability to be related to that of eccentric contraction-induced skeletal muscle injury and pronounced novel myocyte VEGF expression.
Blood flow occlusion-related O2 extraction “reserve” is present in different muscles of the quadriceps but greater in deeper regions after ramp-incremental test
Authors: Iannetta Danilo , Okushima Dai , Inglis Erin Calaine , Kondo Narihiko , Murias Juan M , Koga Shunsaku 
Published: May 2018

It was recently demonstrated that an O2 extraction reserve, as assessed by the near-infrared spectroscopy (NIRS)-derived deoxygenation signal ([HHb]), exists in the superficial region of vastus lateralis (VL) muscle during an occlusion performed at the end of a ramp-incremental test. However, it is unknown whether this reserve is present and/or different in magnitude in other portions and depths of the quadriceps muscles. We tested the hypothesis that an O2 extraction reserve would exist in other regions of this muscle but is greater in deep compared with more superficial portions. Superficial (VL-s) and deep VL (VL-d) as well as superficial rectus femoris (RF-s) were monitored by a combination of low- and high-power time-resolved (TRS) NIRS. During the occlusion immediately post-ramp-incremental test there was a significant overshoot in the [HHb] signal ( P < 0.05). However, the magnitude of this increase was greater in VL-d (93.2 ± 42.9%) compared with VL-s (55.0 ± 19.6%) and RF-s (47.8 ± 14.0%) ( P < 0.05). The present study demonstrated that an O2 extraction reserve exists in different pools of active muscle fibers of the quadriceps at the end of a ramp exercise to exhaustion. The greater magnitude in the reserve observed in the deeper portion of VL, however, suggests that this portion of muscle may present a greater surplus of oxygenated blood, which is likely due to a greater population of slow-twitch fibers. These findings add to the notion that the plateau in the [HHb] signal toward the end of a ramp-incremental exercise does not indicate the upper limit of O2 extraction. NEW & NOTEWORTHY Different portions of the quadriceps muscles exhibited an untapped O2 extraction reserve during a blood flow occlusion performed at the end of a ramp-incremental exercise. In the deeper portion of the vastus lateralis muscle, this reserve was greater compared with superficial vastus lateralis and rectus femoris. These data suggest that the O2 extraction reserve may be dependent on the vascular and/or oxidative capacities of the muscles.
Elevated extracellular potassium prior to muscle contraction reduces onset and steady-state exercise hyperemia in humans
Authors: Terwoord Janée D. , Hearon Christopher M. , Luckasen Gary J. , Richards Jennifer C. , Joyner Michael J. , Dinenno Frank A. 
Published: May 2018

The increase in interstitial potassium (K+) during muscle contractions is thought to be a vasodilatory signal that contributes to exercise hyperemia. To determine the role of extracellular K+in exercise hyperemia, we perfused skeletal muscle with K+before contractions, such that the effect of any endogenously-released K+would be minimized. We tested the hypothesis that local, intra-arterial infusion of potassium chloride (KCl) at rest would impair vasodilation in response to subsequent rhythmic handgrip exercise in humans. In 11 young adults, we determined forearm blood flow (FBF) (Doppler ultrasound) and forearm vascular conductance (FVC) (FBF/mean arterial pressure) during 4 min of rhythmic handgrip exercise at 10% of maximal voluntary contraction during 1) control conditions, 2) infusion of KCl before the initiation of exercise, and 3) infusion of sodium nitroprusside (SNP) as a control vasodilator. Infusion of KCl or SNP elevated resting FVC similarly before the onset of exercise (control: 39 ± 6 vs. KCl: 81 ± 12 and SNP: 82 ± 13 ml·min−1·100 mmHg−1; both P < 0.05 vs. control). Infusion of KCl at rest diminished the hyperemic (ΔFBF) and vasodilatory (ΔFVC) response to subsequent exercise by 22 ± 5% and 30 ± 5%, respectively (both P < 0.05 vs. control), whereas SNP did not affect the change in FBF ( P = 0.74 vs. control) or FVC ( P = 0.61 vs. control) from rest to steady-state exercise. These findings implicate the K+ion as an essential vasodilator substance contributing to exercise hyperemia in humans.NEW & NOTEWORTHY Our findings support a significant and obligatory role for potassium signaling in the local vasodilatory and hyperemic response to exercise in humans.
Effect of dietary nitrate supplementation on conduit artery blood flow, muscle oxygenation, and metabolic rate during handgrip exercise
Authors: Craig Jesse C. , Broxterman Ryan M. , Smith Joshua R. , Allen Jason D. , Barstow Thomas J. 
Published: May 2018

Dietary nitrate supplementation has positive effects on mitochondrial and muscle contractile efficiency during large muscle mass exercise in humans and on skeletal muscle blood flow (Q̇) in rats. However, concurrent measurement of these effects has not been performed in humans. Therefore, we assessed the influence of nitrate supplementation on Q̇ and muscle oxygenation characteristics during moderate- (40 %peak) and severe-intensity(85% peak) handgrip exercise in a randomized, double-blind, crossover design. Nine healthy men (age: 25 ± 2 yr) completed four constant-power exercise tests (2/intensity) randomly assigned to condition [nitrate-rich (nitrate) or nitrate-poor (placebo) beetroot supplementation] and intensity (40 or 85% peak). Resting mean arterial pressure was lower after nitrate compared with placebo (84 ± 4 vs. 89 ± 4 mmHg, P < 0.01). All subjects were able to sustain 10 min of exercise at 40% peak in both conditions. Nitrate had no effect on exercise tolerance during 85% peak (nitrate: 358 ± 29; placebo: 341 ± 34 s; P = 0.3). Brachial artery Q̇ was not different after nitrate at rest or any time during exercise. Deoxygenated [hemoglobin + myoglobin] was not different for 40% peak ( P > 0.05) but was elevated throughout 85% peak ( P < 0.05) after nitrate. The metabolic cost (V̇o2) was not different at the end of exercise; however, the V̇o2 primary amplitude at the onset of exercise was elevated after nitrate for the 85% peak work rate (96 ± 20 vs. 72 ± 12 ml/min, P < 0.05) and had a faster response. These findings suggest that an acute dose of nitrate reduces resting blood pressure and speeds V̇o2 kinetics in young adults but does not augment Q̇ or reduce steady-state V̇o2 during small muscle mass handgrip exercise. NEW & NOTEWORTHY We show that acute dietary nitrate supplementation via beetroot juice increases the amplitude and speed of local muscle V̇o2 on kinetics parameters during severe- but not moderate-intensity handgrip exercise. These changes were found in the absence of an increased blood flow response, suggesting that the increased V̇o2 was attained via improvements in fractional O2 extraction and/or spatial distribution of blood flow within the exercising muscle.
SETD2 Is Recurrently Mutated in Whole-Exome Sequenced Canine Osteosarcoma
Authors: Sakthikumar Sharadha , Elvers Ingegerd , Kim Jaegil , Arendt Maja L. , Thomas Rachael , Turner-Maier Jason , Swofford Ross , Johnson Jeremy , Schumacher Steven E. , Alföldi Jessica , Axelsson Erik , Couto C. Guillermo , Kisseberth William C. , Pettersson Mats E. , Getz Gad , Meadows Jennifer R.S. , Modiano Jaime F. , Breen Matthew , Kierczak Marcin , Forsberg-Nilsson Karin , Marinescu Voichita D. , Lindblad-Toh Kerstin 
Published: May 2018

Abstract
Osteosarcoma is a debilitating bone cancer that affects humans, especially children and adolescents. A homologous form of osteosarcoma spontaneously occurs in dogs, and its differential incidence observed across breeds allows for the investigation of tumor mutations in the context of multiple genetic backgrounds. Using whole-exome sequencing and dogs from three susceptible breeds (22 golden retrievers, 21 Rottweilers, and 23 greyhounds), we found that osteosarcoma tumors show a high frequency of somatic copy-number alterations (SCNA), affecting key oncogenes and tumor-suppressor genes. The across-breed results are similar to what has been observed for human osteosarcoma, but the disease frequency and somatic mutation counts vary in the three breeds. For all breeds, three mutational signatures (one of which has not been previously reported) and 11 significantly mutated genes were identified. TP53 was the most frequently altered gene (83% of dogs have either mutations or SCNA in TP53), recapitulating observations in human osteosarcoma. The second most frequently mutated gene, histone methyltransferase SETD2, has known roles in multiple cancers, but has not previously been strongly implicated in osteosarcoma. This study points to the likely importance of histone modifications in osteosarcoma and highlights the strong genetic similarities between human and dog osteosarcoma, suggesting that canine osteosarcoma may serve as an excellent model for developing treatment strategies in both species.
Significance: Canine osteosarcoma genomics identify SETD2 as a possible oncogenic driver of osteosarcoma, and findings establish the canine model as a useful comparative model for the corresponding human disease. Cancer Res; 78(13); 3421–31. ©2018 AACR.
Modulation of LIN28B/Let-7 Signaling by Propranolol Contributes to Infantile Hemangioma Involution
Authors: Mong Ezinne Francess , Akat Kemal Marc , Canfield John , Lockhart John , VanWye Jeffrey , Matar Andrew , Tsibris John C.M. , Wu June K. , Tuschl Thomas , Totary-Jain Hana 
Published: May 2018

Objective—
Infantile hemangiomas (IHs) are the most common benign vascular neoplasms of infancy, characterized by a rapid growth phase followed by a spontaneous involution, or triggered by propranolol treatment by poorly understood mechanisms. LIN28/let-7 axis plays a central role in the regulation of stem cell self-renewal and tumorigenesis. However, the role of LIN28B/let-7 signaling in IH pathogenesis has not yet been elucidated.

Approach and Results—
LIN28B is highly expressed in proliferative IH and is less expressed in involuted and in propranolol-treated IH samples as measured by immunofluorescence staining and quantitative RT-PCR. Small RNA sequencing analysis of IH samples revealed a decrease in microRNAs that target LIN28B, including let-7, and an increase in microRNAs in the mir-498(46) cistron. Overexpression of LIN28B in HEK293 cells induced the expression of miR-516b in the mir-498(46) cistron. Propranolol treatment of induced pluripotent stem cells, which express mir-498(46) endogenously, reduced the expression of both LIN28B and mir-498(46) and increased the expression of let-7. Furthermore, propranolol treatment reduced the proliferation of induced pluripotent stem cells and induced epithelial–mesenchymal transition.

Conclusions—
This work uncovers the role of the LIN28B/let-7 switch in IH pathogenesis and provides a novel mechanism by which propranolol induces IH involution. Furthermore, it provides therapeutic implications for cancers in which the LIN28/let-7 pathway is imbalanced.
Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity
Authors: van Leijsen Esther M.C. , Bergkamp Mayra I. , van Uden Ingeborg W.M. , Ghafoorian Mohsen , van der Holst Helena M. , Norris David G. , Platel Bram , Tuladhar Anil M. , de Leeuw Frank-Erik 
Published: May 2018

Background and Purpose—
White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normal-appearing white matter (NAWM) into WMH remains unknown. We examined whether and when progression of WMH was preceded by changes in fluid-attenuated inversion recovery and diffusion tensor imaging values, thereby taking into account differences between participants with mild versus severe baseline WMH.

Methods—
From 266 participants of the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort), we semiautomatically segmented WMH at 3 time points for 9 years. Images were registered to standard space through a subject template. We analyzed differences in baseline fluid-attenuated inversion recovery, fractional anisotropy, and mean diffusivity (MD) values and changes in MD values over time between 4 regions: (1) remaining NAWM, (2) NAWM converting into WMH in the second follow-up period, (3) NAWM converting into WMH in the first follow-up period, and (4) WMH.

Results—
NAWM converting into WMH in the first or second time interval showed higher fluid-attenuated inversion recovery and MD values than remaining NAWM. MD values in NAWM converting into WMH in the first time interval were similar to MD values in WMH. When stratified by baseline WMH severity, participants with severe WMH had higher fluid-attenuated inversion recovery and MD and lower fractional anisotropy values than participants with mild WMH, in all areas including the NAWM. MD values in WMH and in NAWM that converted into WMH continuously increased over time.

Conclusions—
Impaired microstructural integrity preceded conversion into WMH and continuously declined over time, suggesting a continuous disease process of white matter integrity loss that can be detected using diffusion tensor imaging even years before WMH become visible on conventional neuroimaging. Differences in microstructural integrity between participants with mild versus severe WMH suggest heterogeneity of both NAWM and WMH, which might explain the clinical variability observed in patients with similar small vessel disease severity.