bluuebunny/crossref_metadata_2025_split huggingface dataset:
Present‐Day Stress Field Influences Bedrock Fracture Openness Deep Into the Subsurface
Authors: Moon Seulgi , Perron J. Taylor , Martel Stephen J. , Goodfellow Bradley W. , Mas Ivars Diego , Hall Adrian , Heyman Jakob , Munier Raymond , Näslund Jens‐Ove , Simeonov Assen , Stroeven Arjen P. 
Published: November 2020

AbstractFracturing of bedrock promotes water‐rock interactions and influences the formation of the life‐sustaining layer of soil at Earth's surface. Models predict that present‐day stress fields should influence bedrock fracture openness, but testing this prediction has proven difficult because comprehensive fracture data sets are rarely available. We model the three‐dimensional present‐day stress field beneath the deglaciated, low‐relief landscape of Forsmark, Sweden. We account for ambient regional stresses, pore pressure, topography, sediment weight, and seawater loading. We then compare the modeled stresses to a data set of ~50,000 fractures reaching depths of 600 m at Forsmark. We show that modeled failure proxies correlate strongly with the fraction of observed open fractures to depths of ~500 m. This result implies that the present‐day regional stress field, affected by surface conditions and pore pressure, influences fracture openness in bedrock hundreds of meters beneath the surface, thereby preparing the rock for further weathering.
Analysis and Attribution of Climate Change in the Upper Atmosphere From 1950 to 2015 Simulated by WACCM‐X
Authors: Cnossen I. 
Published: November 2020

AbstractMonitoring climatic changes in the thermosphere and ionosphere and understanding their causes is important for practical purposes. To support this effort and facilitate comparisons between observations and model results, a long transient simulation with the Whole Atmosphere Community Climate Model eXtension (WACCM‐X) from 1950 to 2015 was conducted. This simulation used realistic variations in solar and geomagnetic activity, main magnetic field changes, and trace gas emissions, including CO2, thereby including all known drivers of upper atmosphere climate change. Analysis of the full 1950–2015 interval with a standard multilinear regression approach demonstrated difficulties in removing solar cycle effects sufficiently to obtain reliable trends. Results improved when an (F10.7a)2 was included in the regression model, in addition to terms for F10.7a, KP, and the trend itself. Comparisons with previous studies and analysis of spatial variations in trend estimates confirmed that the increase in CO2 concentration is the main driver of trends in thermosphere temperature and density, but at high (magnetic) latitudes effects of main magnetic field changes play a role as well, especially in the Northern Hemisphere. Spatial patterns of trends in hmF2, NmF2, and total electron content indicate a superposition of CO2 and geomagnetic field effects, with the latter dominating trends in the region of ∼50–20°N, ∼60°W to 20°E. Additional model experiments to investigate the indirect dynamical effects of climate change in the lower atmosphere (<50 km) on the upper atmosphere (>100 km) suggested that these effects are small and insignificant. However, current model limitations could mean that these effects are underestimated.
Three‐Dimensional P Wave Velocity Structure of the Northern Hikurangi Margin From the NZ3D Experiment: Evidence for Fault‐Bound Anisotropy
Authors: Arai Ryuta , Kodaira Shuichi , Henrys Stuart , Bangs Nathan , Obana Koichiro , Fujie Gou , Miura Seiichi , Barker Daniel , Bassett Dan , Bell Rebecca , Mochizuki Kimihiro , Kellett Richard , Stucker Valerie , Fry Bill ,   NZ3D Team
Published: November 2020

AbstractWe present a high‐resolution three‐dimensional (3‐D) anisotropic P wave velocity (Vp) model in the northern Hikurangi margin offshore Gisborne, New Zealand, constructed by tomographic inversion of over 430,000 first arrivals recorded by a dense grid of ocean bottom seismometers. Since the study area covers a region where shallow slow slip events (SSEs) occur repeatedly and the subduction of a seamount is proposed, it offers an ideal location to link our understanding of structural and hydrogeologic properties at megathrust faults to slip behavior. The Vp model reveals an ~30‐km‐wide, low‐velocity accretionary wedge at the toe of the overriding plate, where previous seismic reflection studies show a series of active thrust faults branching from the plate interface. We find some locations with significant Vp azimuthal anisotropy >5% near the branching faults and the deformation front. This finding suggests that the anisotropy is not ubiquitous and homogeneous within the overriding plate, but more localized in the vicinity of active thrust faults. The fast axes of Vp within the accretionary wedge are mostly oriented to the plate convergence direction, which is interpreted as preferentially oriented cracks in a compressional stress regime associated with plate subduction. We find that the magnitudes of anisotropy are roughly equivalent to values found at oceanic spreading centers, where the extensional stress regime is dominant and the crack density is expected to be higher than subduction zones. This consideration may indicate that additional effects such as fault foliation and clay mineral alignment also contribute to upper plate anisotropy along subduction margins.
Understanding the Asymmetry of Annual Streamflow Responses to Seasonal Warming in the Western United States
Authors: Ban Zhaoxin , Das Tapash , Cayan Dan , Xiao Mu , Lettenmaier Dennis P. 
Published: November 2020

AbstractThe response of annual runoff volume to sub‐annual climate warming is highly uncertain, and the governing mechanisms remain poorly understood, challenging adaptive water management. A typical exemplar is the Western United States, where climate models project substantially stronger warming in the warm season (April to September) than in the cool season (October to March). We investigate the asymmetrical responses of annual and seasonal streamflow changes to warm season and cool season warming for four regionally important basins in the Western United States using an ensemble of four land surface (hydrological) models. Our results show that (i) the general features of seasonal and annual streamflow responses to asymmetrical warming are consistent across models, although the magnitudes vary. The multi‐model mean shows annual runoff declining from 2.0% up to 7.5% under 3°C warm season warming, and from 2.2% up to 4.7% under 3°C cool season warming across the four basins. (ii) The asymmetry of the seasonal evapotranspiration sensitivity to temperature constrains the asymmetry of annual streamflow responses to seasonal warming; and (iii) basins with characteristics such as high ratios of warm to cool season gross incoming water, cooler summers, and colder winters have the strongest relative annual streamflow decreases for warm season warming relative to cool season warming. The pattern in (iii) is explained by the variation of evapotranspiration‐temperature sensitivity in response to a compound set of processes, including the enhanced rate of water holding capacity increase with warmer temperatures, temperature‐related snowmelt‐albedo feedback, and enhanced surface resistance with warmer temperatures.
Modeling the Unfrozen Water Content of Frozen Soil Based on the Absorption Effects of Clay Surfaces
Authors: Jin Xiao , Yang Wen , Gao Xiaoqing , Zhao Jian‐Qi , Li Zhenchao , Jiang Junxia 
Published: November 2020

AbstractUnfrozen water content significantly affects the thermal‐hydro‐mechanical characteristics of frozen soil. Currently, theoretical explanations for the presence of unfrozen water include capillary action, surface effects, adsorption forces, and the electrical double layer. However, the relationships between unfrozen water and these actions are not well explained, except for capillary forces. In addition, although frost heave experiments indicate that the electrical double‐layer solution on a clay particle contains the main portion of unfrozen water, the electrical double‐layer theory which produces a cation solution has not previously been used to calculate unfrozen water content. In this paper, it is assumed that the residual unfrozen water at very low temperatures (below −18°C) is held within the adsorption‐layer solution and that the remaining unfrozen water within the influence of surface effects is the cationic solution in the diffuse layer. Based on these assumptions, a theoretical model of unfrozen water is established with independent variables of temperature, specific surface area, and electrical double‐layer parameters. While the input parameters of the theoretical model are numerous and difficult to obtain, the theoretical model is simplified as a parametric model. Results of the parametric model are strongly consistent with experimental data within a certain temperature range, supporting the hypothetical conditions. The similarity in the underlying mathematical structure of the derived theoretical and parametric models to current semi‐empirical models further suggests that the surface effects of clay are the main causes of unfrozen water in frozen soil.
Hollow silica reinforced magnesium nanocomposites with enhanced mechanical and biological properties with computational modeling analysis for mandibular reconstruction
Authors: Prasadh Somasundaram , Manakari Vyasaraj , Parande Gururaj , Wong Raymond Chung Wen , Gupta Manoj 
Published: November 2020

AbstractThe present study investigates Mg-SiO2 nanocomposites as biodegradable implants for orthopedic and maxillofacial applications. The effect of presence and progressive addition of hollow silica nanoparticles (0.5, 1, and 1.5) vol.% on the microstructural, mechanical, degradation, and biocompatibility response of pure Mg were investigated. Results suggest that the increased addition of hollow silica nanoparticles resulted in a progressive increase in yield strength and ultimate compressive strength with Mg-1.5 vol.% SiO2 exhibiting superior enhancement. The response of Mg-SiO2 nanocomposites under the influence of Hanks’ balanced salt solution revealed that the synthesized composites revealed lower corrosion rates, indicating rapid dynamic passivation when compared with pure Mg. Furthermore, cell adhesion and proliferation of osteoblast cells were noticeably higher than pure Mg with the addition of 1 vol.% SiO2 nanoparticle. The biocompatibility and the in vitro biodegradation of the Mg-SiO2 nanocomposites were influenced by the SiO2 content in pure Mg with Mg-0.5 vol.% SiO2 nanocomposite exhibiting the best corrosion resistance and biocompatibility when compared with other nanocomposites. Enhancement in mechanical, corrosion, and biocompatibility characteristics of Mg-SiO2 nanocomposites developed in this study are also compared with properties of other metallic biomaterials used in alloplastic mandibular reconstruction in a computational model.
Phase 1 randomized study on the safety, tolerability, and pharmacodynamic cognitive and electrophysiological effects of a dopamine D1 receptor positive allosteric modulator in patients with schizophrenia
Authors: Desai Amit , Benner Lauren , Wu Ruishan , Gertsik Lev , Maruff Paul , Light Gregory A. , Uz Tolga , Marek Gerard J. , Zhu Tong 
Published: November 2020

AbstractASP4345, a novel dopamine D1 receptor positive allosteric modulator, is being evaluated for the treatment of cognitive impairment associated with schizophrenia (CIAS). This phase 1 multiple ascending-dose study (NCT02720263) assessed the safety, tolerability, and pharmacodynamics of ASP4345 in patients with schizophrenia/schizoaffective disorder. Pharmacodynamic assessments were Cogstate cognitive tests and electrophysiological biomarkers, including gamma-band power and phase synchronization in response to 40-Hz auditory steady-state stimulation, as well as mismatch negativity (MMN) and P3a event-related potentials. The sample size determination was based on standard practice in assessing safety and tolerability of a new chemical entity. Data were summarized by conversion of this data into effect sizes using descriptive and inferential statistics. A total of 36 randomized patients received ASP4345 (3, 15, 50, and 150 mg; n = 9 each dose) and 12 patients received placebo. Patients in the ASP4345 group experienced 73 treatment-emergent adverse events (TEAEs) and 34 TEAEs were reported for the placebo group. The most common TEAEs were headache and somnolence and nearly all TEAEs were mild in severity. No changes in mood or self-reports of suicidal ideation/behavior were observed. Improvements in performance on cognitive tests were noted, which suggests a potential improvement in psychomotor function and visual attention. Furthermore, positive changes in neurophysiological biomarkers (auditory steady-state response [ASSR] and MMN) suggest improvement in information processing. The findings need to be confirmed in studies with a larger patient population. Nonetheless, the trends in safety and pharmacodynamic data support further clinical development of ASP4345 for the treatment of CIAS.
Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity
Authors: Yi Xin , Wright Laura E. , Pagnotti Gabriel M. , Uzer Gunes , Powell Katherine M. , Wallace Joseph M. , Sankar Uma , Rubin Clinton T. , Mohammad Khalid , Guise Theresa A. , Thompson William R. 
Published: November 2020

AbstractExercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression. We examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of vibration. Low-magnitude, high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration (LIV). LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH, IL-11, and RANKL. Furthermore, paracrine signals from mechanically stimulated cancer cells, reduced osteoclast differentiation and resorptive capacity. Disconnecting the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor secretion. LIV increased cell stiffness; an effect dependent on the LINC complex. These data show that mechanical vibration reduces the metastatic potential of human breast cancer cells, where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling.
Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project
Authors:   on behalf of the Sloane Project Steering Committee, Shaaban Abeer M. , Hilton Bridget , Clements Karen , Provenzano Elena , Cheung Shan , Wallis Matthew G. , Sawyer Elinor , Thomas Jeremy S. , Hanby Andrew M. , Pinder Sarah E. , Thompson Alastair M. 
Published: November 2020

Abstract
Background
The Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes.

Methods
This was a national, prospective cohort study of DCIS diagnosed during 2003–2012.

Results
Among 11,337 patients, 7204 (64%) had high-grade DCIS. Over time, the proportion of high-grade disease increased (from 60 to 65%), low-grade DCIS decreased (from 10 to 6%) and mean size increased (from 21.4 to 24.1 mm). Mastectomy was more common for high-grade (36%) than for low-grade DCIS (15%). Few (6%) patients treated with breast-conserving surgery (BCS) had a surgical margin <1 mm. Of the 9191 women diagnosed in England (median follow-up 9.4 years), 7% developed DCIS or invasive malignancy in the ipsilateral and 5% in the contralateral breast. The commonest ipsilateral event was invasive carcinoma (n = 413), median time 62 months, followed by DCIS (n = 225), at median 37 months. Radiotherapy (RT) was most protective against recurrence for high-grade DCIS (3.2% for high-grade DCIS with RT compared to 6.9% without, compared with 2.3 and 3.0%, respectively, for low/intermediate-grade DCIS). Ipsilateral DCIS events lessened after 5 years, while the risk of ipsilateral invasive cancer remained consistent to beyond 10 years.

Conclusion
DCIS pathology informs patient management and highlights the need for prolonged follow-up of screen-detected DCIS.
Migrant birds and mammals live faster than residents
Authors: Soriano-Redondo Andrea , Gutiérrez Jorge S. , Hodgson Dave , Bearhop Stuart 
Published: November 2020

AbstractBillions of vertebrates migrate to and from their breeding grounds annually, exhibiting astonishing feats of endurance. Many such movements are energetically costly yet there is little consensus on whether or how such costs might influence schedules of survival and reproduction in migratory animals. Here we provide a global analysis of associations between migratory behaviour and vertebrate life histories. After controlling for latitudinal and evolutionary patterns, we find that migratory birds and mammals have faster paces of life than their non-migratory relatives. Among swimming and walking species, migrants tend to have larger body size, while among flying species, migrants are smaller. We discuss whether pace of life is a determinant, consequence, or adaptive outcome, of migration. Our findings have important implications for the understanding of the migratory phenomenon and will help predict the responses of bird and mammal species to environmental change.
Young adult-born neurons improve odor coding by mitral cells
Authors: Shani-Narkiss H. , Vinograd A. , Landau I. D. , Tasaka G. , Yayon N. , Terletsky S. , Groysman M. , Maor I. , Sompolinsky H. , Mizrahi A. 
Published: November 2020

AbstractNew neurons are continuously generated in the adult brain through a process called adult neurogenesis. This form of plasticity has been correlated with numerous behavioral and cognitive phenomena, but it remains unclear if and how adult-born neurons (abNs) contribute to mature neural circuits. We established a highly specific and efficient experimental system to target abNs for causal manipulations. Using this system with chemogenetics and imaging, we found that abNs effectively sharpen mitral cells (MCs) tuning and improve their power to discriminate among odors. The effects on MCs responses peaked when abNs were young and decreased as they matured. To explain the mechanism of our observations, we simulated the olfactory bulb circuit by modelling the incorporation of abNs into the circuit. We show that higher excitability and broad input connectivity, two well-characterized features of young neurons, underlie their unique ability to boost circuit computation.
PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts
Authors: Piberger Ann Liza , Bowry Akhil , Kelly Richard D. W. , Walker Alexandra K. , González-Acosta Daniel , Bailey Laura J. , Doherty Aidan J. , Méndez Juan , Morris Joanna R. , Bryant Helen E. , Petermann Eva 
Published: November 2020

AbstractStalled replication forks can be restarted and repaired by RAD51-mediated homologous recombination (HR), but HR can also perform post-replicative repair after bypass of the obstacle. Bulky DNA adducts are important replication-blocking lesions, but it is unknown whether they activate HR at stalled forks or behind ongoing forks. Using mainly BPDE-DNA adducts as model lesions, we show that HR induced by bulky adducts in mammalian cells predominantly occurs at post-replicative gaps formed by the DNA/RNA primase PrimPol. RAD51 recruitment under these conditions does not result from fork stalling, but rather occurs at gaps formed by PrimPol re-priming and resection by MRE11 and EXO1. In contrast, RAD51 loading at double-strand breaks does not require PrimPol. At bulky adducts, PrimPol promotes sister chromatid exchange and genetic recombination. Our data support that HR at bulky adducts in mammalian cells involves post-replicative gap repair and define a role for PrimPol in HR-mediated DNA damage tolerance.
Polycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window
Authors: Wang Xu , Wilhelm Jonathan , Li Wei , Li Suxin , Wang Zhaohui , Huang Gang , Wang Jian , Tang Houliang , Khorsandi Sina , Sun Zhichen , Evers Bret , Gao Jinming 
Published: November 2020

AbstractStimuli-sensitive nanomaterials with cooperative response are capable of converting subtle and gradual biological variations into robust outputs to improve the precision of diagnostic or therapeutic outcomes. In this study, we report the design, synthesis and characterization of a series of degradable ultra-pH sensitive (dUPS) polymers that amplify small acidic pH changes to efficacious therapeutic outputs. A hydrolytically active polycarbonate backbone is used to construct the polymer with pH-dependent degradation kinetics. One dUPS polymer, PSC7A, can achieve activation of the stimulator of interferon genes and antigen delivery upon endosomal pH activation, leading to T cell-mediated antitumor immunity. While a non-degradable UPS polymer induces granulomatous inflammation that persists over months at the injection site, degradable PSC7A primes a transient acute inflammatory response followed by polymer degradation and complete tissue healing. The improved therapeutic window of the dUPS polymers opens up opportunities in pH-targeted drug and protein therapy.
Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly
Authors: Cicconi Alessandro , Rai Rekha , Xiong Xuexue , Broton Cayla , Al-Hiyasat Amer , Hu Chunyi , Dong Siying , Sun Wenqi , Garbarino Jennifer , Bindra Ranjit S. , Schildkraut Carl , Chen Yong , Chang Sandy 
Published: November 2020

AbstractTelomeres protect chromosome ends from inappropriately activating the DNA damage and repair responses. Primary microcephaly is a key clinical feature of several human telomere disorder syndromes, but how microcephaly is linked to dysfunctional telomeres is not known. Here, we show that the microcephalin 1/BRCT-repeats inhibitor of hTERT (MCPH1/BRIT1) protein, mutated in primary microcephaly, specifically interacts with the TRFH domain of the telomere binding protein TRF2. The crystal structure of the MCPH1–TRF2 complex reveals that this interaction is mediated by the MCPH1 330YRLSP334 motif. TRF2-dependent recruitment of MCPH1 promotes localization of DNA damage factors and homology directed repair of dysfunctional telomeres lacking POT1-TPP1. Additionally, MCPH1 is involved in the replication stress response, promoting telomere replication fork progression and restart of stalled telomere replication forks. Our work uncovers a previously unrecognized role for MCPH1 in promoting telomere replication, providing evidence that telomere replication defects may contribute to the onset of microcephaly.