bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermohaline Suppression of Upper Circumpolar Deep Water Eddies in the Ross Gyre
Authors: Bebieva Yana , Speer Kevin 
Published: September 2021

AbstractTemperature and salinity measurements of a warm‐core eddy at the northern flank of the Ross Gyre are analyzed for dominant mixing mechanisms. The eddy is centered at the depths of the Circumpolar Deep Water and carries heat towards the gyre. Vertical and horizontal heat fluxes out of the eddy associated with internal wave turbulent mixing and thermohaline intrusions are estimated. Upward internal wave turbulent heat flux is W, whereas, the lateral intrusive heat flux is of the order of W. The horizontal flux due to intrusions is suggested to be the dominant mechanism for eddy decay and yields an eddy lifetime of about 6 months. The thermohaline intrusion‐eddy suppression mechanism is proposed and shown to be effective in suppressing the eddy field at the northern flank of the Ross Gyre. This effect has important implications for setting the basin‐wide heat budget and regulating sea‐ice cover.
Changes in the Tropical Lapse Rate due to Entrainment and Their Impact on Climate Sensitivity
Authors: Bao Jiawei , Stevens Bjorn , Kluft Lukas , Jiménez‐de‐la‐Cuesta Diego 
Published: September 2021

AbstractThe tropical temperature in the free troposphere deviates from a theoretical moist‐adiabat. The overall deviations are attributed to the entrainment of dry surrounding air. The deviations gradually approach zero in the upper troposphere, which we explain with a buoyancy‐sorting mechanism: the height to which individual convective parcels rise depends on parcel buoyancy, which is closely tied to the impact of entrainment during ascent. In higher altitudes, the temperature is increasingly controlled by the convective parcels that are warmer and more buoyant because of weaker entrainment effects. We represent such temperature deviations from moist‐adiabats in a clear‐sky one‐dimensional radiative‐convective equilibrium model. Compared with a moist‐adiabatic adjustment, having the entrainment‐induced temperature deviations lead to higher clear‐sky climate sensitivity. As the impact of entrainment depends on the saturation deficit, which increases with warming, our model predicts even more amplified surface warming from entrainment in a warmer climate.
Further Evidence of High Intensity During the Levantine Iron Age Anomaly in Southwestern Europe: Full Vector Archeomagnetic Dating of an Early Iron Age Dwelling From Western Spain
Authors: García‐Redondo N. , Calvo‐Rathert M. , Carrancho Á. , Goguitchaichvili A. , Iriarte E. , Blanco‐González A. , Dekkers M. J. , Morales‐Contreras J. , Alario‐García C. , Macarro‐Alcalde C. 
Published: September 2021

AbstractWe report an archeomagnetic study from the Early Iron Age archeological site of Cerro de San Vicente (Salamanca, Spain). The studied materials were sampled from one roundhouse and its central fireplace, a surrounding burnt floor, and slags with a twofold objective. First, to archeomagnetically determine the last use of the central fireplace, because dating with other methods was imprecise. Second, to retrieve information about the Earth's magnetic field in Western Europe from a period when the Levantine Iron Age Anomaly (LIAA) has been occasionally reported. This study includes mineralogical, archeomagnetic directional analyses, and multimethod archeointensity determinations. Paleomagnetic analyses of the central fireplace yield a mean direction: declination D = 15.1°, inclination I = 52.5°; k = 477.1, and α95 = 5.6°. Archeointensity determinations yield a mean anisotropy‐corrected archeointensity of 72.4 ± 2.0 μT (74.7 ± 4.3 μT if a pTRM‐check correction is applied) on the central fireplace and 48.2 ± 2.0 μT on slags. A full‐vector archeomagnetic dating was performed with the SHA.DIF.4k geomagnetic field model which yielded an age interval of last use of the central fireplace between 644 and 575 BCE (654–575 BCE with the pTRM‐check corrected data) at 95% confidence level. This date agrees with the archeological context. Results allows to place the high paleointensity obtained near the maximum observed in Iberia at this age, confirming the existence of this peak related to the LIAA in Western Europe where records of this feature are still scarce.
Controls on Post‐Seismic Landslide Behavior in Brittle Rocks
Authors: Brain Matthew J. , Moya Sebastian , Kincey Mark E. , Tunstall Neil , Petley David N. , Sepúlveda Sergio A. 
Published: September 2021

AbstractEarthquakes trigger widespread landsliding in tectonically active landscapes. The effects of strong ground shaking on hillslope stability persist into the post‐seismic stage; rates of landsliding remain elevated in the years following an earthquake. The mechanisms that control the spatial pattern and rate of ongoing landsliding are poorly constrained, hindering our ability to reliably forecast how landscapes and landslide hazard evolve. To address this, we undertook a detailed geotechnical investigation in which we subjected representative rock samples to dynamic loading, simulating the effects of earthquake ground shaking on hillslopes of different configuration. Our results indicate that post‐seismic hillslope strength is not an intrinsic rock property; rather, it responds to the amplitude of imposed dynamic loads and the degree of pre‐existing shear surface formation within the rock. This path‐dependent behavior results from differences in the character of fractures generated by dynamic loads of different amplitude, and the ways in which apertures are mobilized or degraded in subsequent (post‐seismic) shearing. Sensitivity to dynamic loading amplitude is greater in shallow landslides in which shear surfaces are yet to fully form; such hillslopes can be strengthened or weakened by earthquake events, depending on their characteristics. In contrast, deeper landslides on steeper hillslopes in which shear surfaces have largely developed are less likely to display differences in behavior in response to dynamic loading because strain accumulation along pre‐existing fractures is dominant. Our results demonstrate the need to consider path‐dependent hillslope stability in numerical models used to forecast how landscapes respond to earthquakes and how post‐seismic hazard evolves.
Evidence of a South Asian Proto‐Monsoon During the Oligocene‐Miocene Transition
Authors: Beasley C. , Kender S. , Giosan L. , Bolton C. T. , Anand P. , Leng M. J. , Nilsson‐Kerr K. , Ullmann C. V. , Hesselbo S. P. , Littler K. 
Published: September 2021

AbstractThe geological history of the South Asian monsoon (SAM) before the Pleistocene is not well‐constrained, primarily due to a lack of available continuous sediment archives. Previous studies have noted an intensification of SAM precipitation and atmospheric circulation during the middle Miocene (∼14 Ma), but no records are available to test how the monsoon changed prior to this. In order to improve our understanding of monsoonal evolution, geochemical and sedimentological data were generated for the Oligocene‐early Miocene (30–20 Ma) from Indian National Gas Hydrate Expedition 01 Site NGHP‐01‐01A in the eastern Arabian Sea, at 2,674 m water depth. We find the initial glaciation phase (23.7–23.0 Ma) of the Oligocene‐Miocene transition (OMT) to be associated with an increase in water column ventilation and water mass mixing, suggesting an increase in winter monsoon type atmospheric circulation, possibly driven by a relative southward shift of the intertropical convergence zone. During the latter part of the OMT, or “deglaciation” phase (23.0–22.7 Ma), a long‐term decrease in Mn (suggestive of deoxygenation), increase in Ti/Ca and dissolution of the biogenic carbonate fraction suggest an intensification of a proto‐summer SAM system, characterized by the formation of an oxygen minimum zone in the eastern Arabian Sea and a relative increase of terrigenous material delivered by runoff to the site. With no evidence at this site for an active SAM prior to the OMT we suggest that changes in orbital parameters, as well as possibly changing Tethyan/Himalayan tectonics, caused this step change in the proto‐monsoon system at this intermediate‐depth site.
Connection Between a Subcontinental Plume and the Mid‐Lithospheric Discontinuity Leads to Fast and Intense Craton Lithospheric Thinning
Authors: Shi Ya‐Nan , Li Zhong‐Hai , Chen Ling , Morgan Jason P. 
Published: September 2021

AbstractRemoval and thinning of cratonic lithosphere is believed to have occurred under different tectonic settings, for example, near subduction zones and above mantle plumes. Subduction‐induced cratonic modification has been widely discussed; however, the mechanisms and dynamic processes of plume‐induced lithospheric removal remain elusive and require further systematic investigation. In this study, we use a series of 2‐D thermo‐mechanical models to explore the dynamics of the removal and thinning of cratonic lithosphere due to the interaction between a mantle plume and a weak mid‐lithosphere discontinuity (MLD) layer. Our modeling results suggest that the interaction between a mantle plume and weak MLD layer can lead to a large‐scale removal of the cratonic lithosphere once a connection between the hot upwelling and weak MLD layer is established. The presence of a vertical lithospheric weak zone and its closeness to the plume center play critical roles in creating a connection between the weak MLD and hot plume/asthenosphere. Furthermore, delamination of cratonic lithosphere is favored by a larger plume radius/volume, a higher plume temperature anomaly, and a lower viscosity of the MLD layer. A systematic comparison between subduction‐induced and plume‐induced lithospheric thinning patterns was also conducted. We summarize their significant differences on the origin and migration of melt generation, the water content in melts, and topographic evolution. The combination of numerical models and geological/geophysical observations indicates that mantle plume‐MLD interactions may have played a crucial role in lithospheric removal beneath the South Indian, South American, and North Siberian Cratons.
Climate Uncertainty and Optimal Groundwater Augmentation
Authors: Tran Dat Q. , Kovacs Kent F. 
Published: September 2021

AbstractTwo approaches to augment irrigation water supply are managed aquifer recharge (MAR) and on‐farm reservoirs with tail‐water recovery (OFS‐TWR). We explore the joint use of MAR and OFS‐TWR to sustain groundwater and agricultural income with climate variability by farmer risk preference. We find that MAR use declines slightly with greater risk aversion and declines rapidly with MAR cost. The use of OFS‐TWR increases with risk aversion. The use of MAR increases income by a larger percentage for risk‐neutral than very risk‐averse producers. Across risk aversion degree, the use of MAR leads to a percentage increase in income that is double the percentage increase in the standard deviation of income (i.e., income risk). At a low cost of MAR, there is little difference in MAR use between a very risk‐averse and a risk‐neutral producer across scenarios of crop profit margin and the initial depth to water. Large differences in OFS‐TWR use between a very risk‐averse and a risk‐neutral producer occur when there are relatively high crop profit margin, low initial water depth, or a low discount rate.
Rare GATA6 variants associated with risk of congenital heart disease phenotypes in 200,000 UK Biobank exomes
Authors: Williams Simon G. , Byrne Dominic J. F. , Keavney Bernard D. 
Published: September 2021

AbstractCongenital heart disease (CHD) has a complex and largely uncharacterised genetic etiology. Using 200,000 UK Biobank (UKB) exomes, we assess the burden of ultra-rare, potentially pathogenic variants in the largest case/control cohort of predominantly mild CHD to date. We find an association with GATA6, a member of the GATA family of transcription factors that play an important role during heart development and has been linked with several CHD phenotypes previously. Several identified GATA6 variants are previously unreported and their roles in conferring risk to CHD warrants further study. We demonstrate that despite limitations regarding detailed familial phenotype information in large-scale biobank projects, through careful consideration of case and control cohorts it is possible to derive important associations.
Loss of Sirt6 in adipocytes impairs the ability of adipose tissue to adapt to intermittent fasting
Authors: Wu Dandan , Bang In Hyuk , Park Byung-Hyun , Bae Eun Ju 
Published: September 2021

AbstractIntermittent fasting (IF) is gaining popularity for its effectiveness in improving overall health, including its effectiveness in achieving weight loss and euglycemia. The molecular mechanisms of IF, however, are not well understood. This study investigated the relationship between adipocyte sirtuin 6 (Sirt6) and the metabolic benefits of IF. Adipocyte-specific Sirt6-knockout (aS6KO) mice and wild-type littermates were fed a high-fat diet (HFD) ad libitum for four weeks and then subjected to 12 weeks on a 2:1 IF regimen consisting of two days of feeding followed by one day of fasting. Compared with wild-type mice, aS6KO mice subjected to HFD + IF exhibited a diminished response, as reflected by their glucose and insulin intolerance, reduced energy expenditure and adipose tissue browning, and increased inflammation of white adipose tissue. Sirt6 deficiency in hepatocytes or in myeloid cells did not impair adaptation to IF. Finally, the results indicated that the impaired adipose tissue browning and reduced expression of UCP1 in aS6KO mice were accompanied by downregulation of p38 MAPK/ATF2 signaling. Our findings indicate that Sirt6 in adipocytes is critical to obtaining the improved glucose metabolism and metabolic profiles conferred by IF and that maintaining high levels of Sirt6 in adipocytes may mimic the health benefits of IF.
Ultrasensitive detection of endocrine disruptors via superfine plasmonic spectral combs
Authors: Liu Lanhua , Zhang Xuejun , Zhu Qian , Li Kaiwei , Lu Yun , Zhou Xiaohong , Guo Tuan 
Published: September 2021

AbstractThe apparent increase in hormone-induced cancers and disorders of the reproductive tract has led to a growing demand for new technologies capable of detecting endocrine disruptors. However, a long-lasting challenge unaddressed is how to achieve ultrahigh sensitive, continuous, and in situ measurement with a portable device for in-field and remote environmental monitoring. Here we demonstrate a simple-to-implement plasmonic optical fiber biosensing platform to achieve an improved light–matter interaction and advanced surface chemistry for ultrasensitive detection of endocrine disruptors. Our platform is based on a gold-coated highly tilted fiber Bragg grating that excites high-density narrow cladding mode spectral combs that overlap with the broad absorption of the surface plasmon for high accuracy interrogation, hence enabling the ultrasensitive monitoring of refractive index changes at the fiber surface. Through the use of estrogen receptors as the model, we design an estradiol–streptavidin conjugate with the assistance of molecular dynamics, converting the specific recognition of environmental estrogens (EEs) by estrogen receptor into surface-based affinity bioassay for protein. The ultrasensitive platform with conjugate-induced amplification biosensing approach enables the subsequent detection for EEs down to 1.5 × 10−3 ng ml−1 estradiol equivalent concentration level, which is one order lower than the defined maximal E2 level in drinking water set by the Japanese government. The capability to detect EEs down to nanogram per liter level is the lowest limit of detection for any estrogen receptor-based detection reported thus far. Its compact size, flexible shape, and remote operation capability open the way for detecting other endocrine disruptors with ultrahigh sensitivity and in various hard-to-reach spaces, thereby having the potential to revolutionize environment and health monitoring.
Instrumental aversion coding in the basolateral amygdala and its reversion by a benzodiazepine
Authors: Jean-Richard-dit-Bressel Philip , Tran Jenny , Didachos Angelos , McNally Gavan P. 
Published: September 2021

AbstractPunishment involves learning the relationship between actions and their adverse consequences. Both the acquisition and expression of punishment learning depend on the basolateral amygdala (BLA), but how BLA supports punishment remains poorly understood. To address this, we measured calcium (Ca2+) transients in BLA principal neurons during punishment. Male rats were trained to press two individually presented levers for food; when one of these levers also yielded aversive footshock, responding on this punished lever decreased relative to the other, unpunished lever. In rats with the Ca2+indicator GCaMP6f targeted to BLA principal neurons, we observed excitatory activity transients to the footshock punisher and inhibitory transients to lever-presses earning a reward. Critically, as rats learned punishment, activity around the punished response transformed from inhibitory to excitatory and similarity analyses showed that these punished lever-press transients resembled BLA transients to the punisher itself. Systemically administered benzodiazepine (midazolam) selectively alleviated punishment. Moreover, the degree to which midazolam alleviated punishment was associated with how much punished response-related BLA transients reverted to their pre-punishment state. Together, these findings show that punishment learning is supported by aversion-coding of instrumental responses in the BLA and that the anti-punishment effects of benzodiazepines are associated with a reversion of this aversion coding.
Kynurenines increase MRS metabolites in basal ganglia and decrease resting-state connectivity in frontostriatal reward circuitry in depression
Authors: Chen Xiangchuan , Beltran Diana J. , Tsygankova Valeriya D. , Woolwine Bobbi J. , Patel Trusharth , Baer Wendy , Felger Jennifer C. , Miller Andrew H. , Haroon Ebrahim 
Published: September 2021

AbstractInflammation is associated with the development of anhedonia in major depression (MD), but the pathway by which inflammatory molecules gain access to the brain and lead to anhedonia is not clear. Molecules of the kynurenine pathway (KP), which is activated by inflammation, readily influx into the brain and generate end products that alter brain chemistry, disrupt circuit functioning, and result in the expression of inflammatory behaviors such as anhedonia. We examined the impact of plasma and CSF KP metabolites on brain chemistry and neural function using multimodal neuroimaging in 49 depressed subjects. We measured markers of glial dysfunction and distress including glutamate (Glu) and myo-inositol in the left basal ganglia using magnetic resonance spectroscopy (MRS); metrics of local activity coherence (regional homogeneity, ReHo) and functional connectivity from resting-state functional MRI measures; and anhedonia from the Inventory for Depressive Symptoms-Self Report Version (IDS-SR). Plasma kynurenine/tryptophan (KYN/TRP) ratio and cerebrospinal fluid (CSF) 3-hydroxykynurenine (3HK) were associated with increases in left basal ganglia myo-inositol. Plasma kynurenic acid (KYNA) and KYNA/QA were associated with decreases and quinolinic acid (QA) with increases in left basal ganglia Glu. Plasma and CSF KP were associated with decreases in ReHo in the basal ganglia and dorsomedial prefrontal regions (DMPFC) and impaired functional connectivity between these two regions. DMPFC-basal ganglia mediated the effect of plasma and CSF KP on anhedonia. These findings highlight the pathological impact of KP system dysregulation in mediating inflammatory behaviors such as anhedonia.
Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study
Authors: Gambardella Valentina , Lombardi Pasquale , Carbonell-Asins Juan Antonio , Tarazona Noelia , Cejalvo Juan Miguel , González-Barrallo Inés , Martín-Arana Jorge , Tébar-Martínez Roberto , Viala Alba , Bruixola Gema , Hernando Cristina , Blasco Inma , Papaccio Federica , Martínez-Ciarpaglini Carolina , Alfaro-Cervelló Clara , Seda-García Enrique , Blesa Sebastián , Chirivella Isabel , Castillo Josefa , Montón-Bueno José Vicente , Roselló Susana , Huerta Marisol , Pérez-Fidalgo Alejandro , Martín-Martorell Paloma , Insa-Mollá Amelia , Fleitas Tania , Rentero-Garrido Pilar , Zúñiga-Trejos Sheila , Cervantes Andrés , Roda Desamparados 
Published: September 2021

Abstract
Introduction
Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution.

Methods
Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1).

Results
Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24–14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14–3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008).

Discussion
We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.
Effect of endothelial progenitor cell-derived extracellular vesicles on endothelial cell ferroptosis and atherosclerotic vascular endothelial injury
Authors: Li Lin , Wang Haining , Zhang Jing , Chen Xiao , Zhang Zhongwang , Li Qiang 
Published: September 2021

AbstractAtherosclerosis (AS) is a chronic inflammatory disorder characterized by endothelial dysfunction. Endothelial progenitor cells (EPCs) can overcome endothelial dysfunction and reduce AS risk. This study focused on the role of EPC-secreted extracellular vesicles (EPC-EVs) in AS. First, mouse EPCs and mouse aortic endothelial cells (MAECs) were isolated and identified. EVs were isolated from EPCs and identified. EPC-EVs were co-cultured with MAECs and the internalization of EVs was observed. Glutathione (GSH) consumption, reactive oxygen species (ROS) production, lipid peroxidation, and iron accumulation and cell death in endothelial cells were detected. The binding relationship between miR-199a-3p and specificity protein 1 (SP1) was confirmed using dual-luciferase and RIP assays. The mouse model of AS was established. The relationships between miR-199a-3p expression and aortic area plaque and serum pro-inflammatory factor were analyzed. The degree of atherosclerotic lesion was detected using oil red O staining and the serum inflammatory factors were detected using ELISA. Our results elicited that EPC-EVs inhibited cell death, GSH consumption, ROS production, lipid peroxidation, and iron accumulation in endothelial cells, thereby suppressing ferroptosis of endothelial cells. EPC-EVs transferred miR-199a-3p into endothelial cells. miR-199a-3p targeted SP1. Silencing miR-199a-3p or overexpression of SP1 in endothelial cells reversed the effect of EPC-EVs on ferroptosis of endothelial cells. In vivo experiments confirmed that EPC-EVs inhibited ferroptosis of endothelial cells and then alleviated the occurrence of AS via the miR-199a-3p/SP1 axis. To conclude, EPC-EVs transferred miR-199a-3p to inhibit SP1, thus repressing ferroptosis of endothelial cells and retarding the occurrence of AS.