bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining candidate mRNA and protein EV biomarkers to discriminate ccRCC and pRCC from non-malignant renal cells in vitro
Authors: Zieren Richard C. , Dong Liang , Clark David J. , Kuczler Morgan D. , Horie Kengo , Moreno Leandro Ferreira , Lih Tung-Shing M. , Schnaubelt Michael , Vermeulen Louis , Zhang Hui , de Reijke Theo M. , Pienta Kenneth J. , Amend Sarah R.
Published: July 2021

Renal cell carcinoma (RCC) accounts for over 400,000 new cases and 175,000 deaths annually. Diagnostic RCC biomarkers may prevent overtreatment in patients with early disease. Extracellular vesicles (EVs) are a promising source of RCC biomarkers because EVs carry proteins and messenger RNA (mRNA) among other biomolecules. We aimed to identify biomarkers and assess biological functions of EV cargo from clear cell RCC (ccRCC), papillary RCC (pRCC), and benign kidney cell lines. EVs were enriched from conditioned cell media by size exclusion chromatography. The EV proteome was assessed using Tandem Mass Tag mass spectrometry (TMT-MS) and NanoString nCounter technology was used to profile 770 cancer-related mRNA present in EVs. The heterogeneity of protein and mRNA abundance and identification highlighted the heterogeneity of EV cargo, even between cell lines of a similar pathological group (e.g., ccRCC or pRCC). Overall, 1726 proteins were quantified across all EV samples, including 181 proteins that were detected in all samples. In the targeted profiling of mRNA by NanoString, 461 mRNAs were detected in EVs from at least one cell line, including 159 that were present in EVs from all cell lines. In addition to a shared EV cargo signature, pRCC, ccRCC, and/or benign renal cell lines also showed unique signatures. Using this multi-omics approach, we identified 34 protein candidate pRCC EV biomarkers and 20 protein and 8 mRNA candidate ccRCC EV biomarkers for clinical validation.
Submicron particle docetaxel intratumoral injection in combination with anti-mCTLA-4 into 4T1-Luc orthotopic implants reduces primary tumor and metastatic pulmonary lesions
Authors: Maulhardt Holly , Marin Alyson , Hesseltine Holly , diZerega Gere
Published: July 2021

We describe here characterization of the response of local and metastatic disease and immunomodulation following intratumoral (IT) injection of submicron particle docetaxel (SPD) administered alone or in combination with systemic antibody anti-mCTLA-4 (anti-mCTLA-4) in the metastatic 4T1-Luc2-1A4 (4T1) murine breast cancer model. In-life assessments of treatment tolerance, tumor volume (TV), and metastasis were performed (n = 10 animals/group). At study end, immune cell populations in tumor-site tissues and peripheral blood were analyzed using flow cytometry. Signs of distress typical of this aggressive tumor model occurred across all animals except for the combination treated which were asymptomatic and gained weight. TV at study end was significantly reduced in the combination group versus untreated [43% reduced (p < 0.05)] and vehicle controls [54% reduced (p < 0.0001)]. No evidence of thoracic metastasis was found in 40% of combination group animals and thoracic bioluminescence imaging (BLI) was reduced vs. untreated controls (p < 0.01). Significant elevations (p < 0.05) in CD4 + T, CD4 + helper T, Treg, and NKT cells were found in tumor and blood in SPD or combination treatment compared to controls or anti-mCTLA-4. Combination treatment increased tumor-associated CD8 + T cells (p < 0.01), peripheral B cells (p < 0.01), and tumor associated and circulating dendritic cells (DC) (p < 0.05). Tumor-associated NK cells were significantly increased in SPD ± anti-mCTLA-4 treatments (p < 0.01). Myeloid-derived suppressor cells (MDSC) were reduced in bloods in SPD ± anti-mCTLA-4 groups (p < 0.05). These data demonstrate that both SPD and anti-mCTLA-4 produce local anti-tumor effects as well as reductions in metastasis which are significantly enhanced when administered in combination.
Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats
Authors: Ahlström F.H.G. , Mätlik K. , Viisanen H. , Blomqvist K.J. , Liu X. , Lilius T.O. , Sidorova Y. , Kalso E.A. , Rauhala P.V.
Published: July 2021

Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.
Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief
Authors: Mousa Shaaban A. , Shaqura Mohammed , Khalefa Baled I. , Li Li , Al-Madol Mohammed , Treskatsch Sascha , Schäfer Michael
Published: July 2021

Corticotropin-releasing factor (CRF) orchestrates our body’s response to stressful stimuli. Pain is often stressful and counterbalanced by activation of CRF receptors along the nociceptive pathway, although the involvement of the CRF receptor subtypes 1 and/or 2 (CRF-R1 and CRF-R2, respectively) in CRF-induced analgesia remains controversial. Thus, the aim of the present study was to examine CRF-R1 and CRF-R2 expression within the spinal cord of rats with Freund’s complete adjuvant-induced unilateral inflammation of the hind paw using reverse transcriptase polymerase chain reaction, Western blot, radioligand binding, and immunofluorescence confocal analysis. Moreover, the antinociceptive effects of intrathecal (i.t.) CRF were measured by paw pressure algesiometer and their possible antagonism by selective antagonists for CRF-R1 and/or CRF-R2 as well as for opioid receptors. Our results demonstrated a preference for the expression of CRF-R2 over CRF-R1 mRNA, protein, binding sites and immunoreactivity in the dorsal horn of the rat spinal cord. Consistently, CRF as well as CRF-R2 agonists elicited potent dose-dependent antinociceptive effects which were antagonized by the i.t. CRF-R2 selective antagonist K41498, but not by the CRF-R1 selective antagonist NBI35965. In addition, i.t. applied opioid antagonist naloxone dose-dependently abolished the i.t. CRF- as well as CRF-R2 agonist-elicited inhibition of somatic pain. Importantly, double immunofluorescence confocal microscopy of the spinal dorsal horn showed CRF-R2 on enkephalin (ENK)-containing inhibitory interneurons in close opposition of incoming mu-opioid receptor-immunoreactive nociceptive neurons. CRF-R2 was, however, not seen on pre- or on postsynaptic sensory neurons of the spinal cord. Taken together, these findings suggest that i.t. CRF or CRF-R2 agonists inhibit somatic inflammatory pain predominantly through CRF-R2 receptors located on spinal enkephalinergic inhibitory interneurons which finally results in endogenous opioid-mediated pain inhibition.
Effects of water salinity on the foam dynamics for EOR application
Authors: Rudyk Svetlana , Al-Khamisi Sami , Al-Wahaibi Yahya
Published: July 2021

Factors limiting foam injection for EOR application are exceptionally low rock permeability and exceedingly high salinity of the formation water. In this regard, foam formation using internal olefin sulfonate is investigated over a wide salinity range (1, 5, 8, 10, and 12% NaCl) through 10 mD limestone. The relationships between pressure drop (dP), apparent viscosity, liquid flow rate, total flow rate, salinity, foam texture, and length of foam drops at the outlet used as an indicator of viscosity are studied. Foaming is observed up to 12% NaCl, compared to a maximum of 8% NaCl in similar core-flooding experiments with 50 mD limestone and 255 mD sandstone. Thus, the salinity limit of foam formation has increased significantly due to the low permeability, which can be explained by the fact that the narrow porous system acts like a membrane with smaller holes. Compared to the increasing dP reported for highly permeable rocks, dP linearly decreases in almost the entire range of gas fraction (fg) at 1–10% NaCl. As fg increases, dP at higher total flow rate is higher at all salinities, but the magnitude of dP controls the dependence of apparent viscosity on total flow rate. Low dP is measured at 1% and 10% NaCl, and high dP is measured at 5, 8, and 12% NaCl. In the case of low dP, the apparent viscosity is higher at higher total flow rate with increasing gas fraction, but similar at two total flow rates with increasing liquid flow rate. In the case of high dP, the apparent viscosity is higher at lower total flow rate, both with an increase in the gas fraction and with an increase in the liquid flow rate. A linear correlation is found between dP or apparent viscosity and liquid flow rate, which defines it as a governing factor of foam flow and can be considered when modeling foam flow.
Designing a unique feedback mechanism for hydrogel-forming microneedle array patches: a concept study
Authors: Hutton Aaron R. J. , Kirkby Melissa , Larrañeta Eneko , Donnelly Ryan F.
Published: July 2021

Although microneedle array patch (MAP) technology is reaching ever closer to regulatory approval, it remains imperative that approaches to further improve patient acceptance are still explored. Addressing this perception, a water-filled reservoir was incorporated into a hydrogel-forming MAP system to provide a novel feedback mechanism. To confirm successful MAP skin insertion, the end user would both hear and feel the rupture of the water-filled reservoir. Interestingly, a 50-µL water-filled reservoir ruptured at 30.27 ± 0.39 N, which has previously been shown as the mean application force for MN insertion in human subjects following appropriate instruction. Importantly, no significant difference in % cumulative permeation of FITC-dextran 10 kDa and fluorescein sodium after 24 h was observed between a 50-µL reservoir and the current method of application that has been successfully used in both in vitro and in vivo studies (p > 0.05). Therefore, as drug delivery was not affected, this proof-of-concept study has shown that a water-filled reservoir feedback mechanism has the potential to serve as a viable tool for consistent MAP skin insertion.

Graphical abstract
Feasibility of hydrogen fuel cell technology for railway intercity services: a case study for the Piedmont in North Carolina
Authors: Madovi Orwell , Hoffrichter Andreas , Little Nick , Foster Shanelle N. , Isaac Raphael
Published: July 2021

Diesel fuel combustion results in exhaust containing air pollutants and greenhouse gas emissions. Many railway vehicles use diesel fuel as their energy source. Exhaust emissions, as well as concerns about economical, alternative power supply, have driven efforts to move to hydrogen motive power. Hydrogen fuel cell technology applied to railways offers the opportunity to eliminate harmful exhaust emissions and the potential for a low- or zero-emission energy supply chain. Currently, only multiple-unit trains with hydrail technology operate commercially. Development of an Integrated Hybrid Train Simulator for intercity railway is presented. The proposed tool incorporates the effect of powertrain components during the wheel-to-tank process. Compared to its predecessors, the proposed reconfigurable tool provides high fidelity with medium requirements and minimum computation time. Single train simulation and the federal government’s Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREET®) model are used in combination to evaluate the feasibility of various train and powertrain configurations. The Piedmont intercity service operating in North Carolina is used as a case study. The study includes six train configurations and powertrain options as well as nine hydrogen supply options in addition to the diesel supply. The results show that a hydrail option is not only feasible, but a low- or zero-carbon hydrogen supply chain could be possible.
Bio-inspired smart surface to achieve controllable locomotion through adjustable anisotropic friction
Authors: Ji Zhongying , Qin Shiyu , Ma Shuanhong , Jia Xin , Wang Xiaolong , Zhou Feng
Published: July 2021

Anisotropic friction generated by microstructured surfaces is crucial for performing functions such as directional locomotion and adhesion in biological systems. Hence, an epoxy-based shape memory polymer (SMP) incorporating Fe3O4 nanoparticles is used in this study to create a smart surface with oriented structures to mimic anisotropic friction and exploit human-developed controllable locomotion systems. Applying the specific properties of the epoxy-based SMP, fast switching friction can be achieved by adjusting the topography and stiffness of the microstructures on the surface. In addition, the photothermogenesis effect of Fe3O4 nanoparticles induces changes in the asymmetric topography and stiffness on the SMP surface under the irradiation of near-infrared (NIR) light, thereby inducing a rapid switching of the friction force. Furthermore, a microbot is created to demonstrate remotely controlled locomotion, such as unidirectional and round-trip movements, and braking by switching the friction force under NIR light. These results are promising for the design of new intelligent surfaces and interfaces; additionally, they may facilitate the investigation of biological structures and processes.
Learning quantized neural nets by coarse gradient method for nonlinear classification
Authors: Long Ziang , Yin Penghang , Xin Jack
Published: July 2021

Quantized or low-bit neural networks are attractive due to their inference efficiency. However, training deep neural networks with quantized activations involves minimizing a discontinuous and piecewise constant loss function. Such a loss function has zero gradient almost everywhere (a.e.), which makes the conventional gradient-based algorithms inapplicable. To this end, we study a novel class of biased first-order oracle, termed coarse gradient, for overcoming the vanished gradient issue. A coarse gradient is generated by replacing the a.e. zero derivative of quantized (i.e., staircase) ReLU activation composited in the chain rule with some heuristic proxy derivative called straight-through estimator (STE). Although having been widely used in training quantized networks empirically, fundamental questions like when and why the ad hoc STE trick works, still lack theoretical understanding. In this paper, we propose a class of STEs with certain monotonicity and consider their applications to the training of a two-linear-layer network with quantized activation functions for nonlinear multi-category classification. We establish performance guarantees for the proposed STEs by showing that the corresponding coarse gradient methods converge to the global minimum, which leads to a perfect classification. Lastly, we present experimental results on synthetic data as well as MNIST dataset to verify our theoretical findings and demonstrate the effectiveness of our proposed STEs.
Computing models for quotients of modular curves
Authors: Box Josha
Published: July 2021

We describe an algorithm for computing a$${\mathbb {Q}}$$Q-rational model for the quotient of a modular curve by an automorphism group, under mild assumptions on the curve and the automorphisms, by determiningq-expansions for a basis of the corresponding space of cusp forms. We also give a moduli interpretation for general morphisms between modular curves.
Sport for a Livelihood and Well-being: From Leisure Activity to Occupational Devotion
Authors: Hallmann Kirstin , Bogner Laura , Sander Kathrin , Reuß Konrad
Published: July 2021

This study explored the occupational devotion of lifestyle entrepreneurs and their well-being. Although the number of enterprises in the sports industry increased over the past years, limited literature exists on this topic. Therefore, this paper focused on lifestyle entrepreneurs who turned their sports into their occupations. We conducted semi-structured interviews and a follow-up survey with lifestyle entrepreneurs (N = 13) from various sports (e.g., yoga, kiting, football). The thematic analysis revealed a strong connection between the individuals’ choice of career and well-being. Other themes (and sub-themes), such as mental and physical health and value (co-)creation, were identified, corroborating the authors’ assumption that these lifestyle entrepreneurs started a career in their sports to reach a higher quality of life. The results uncovered that well-being and occupational devotion are closely linked. Co-creation is connected to well-being, and this can accrue social capital in the community. Thus, the results recommended support for lifestyle entrepreneurs as they provide community benefits.
Unsteady pressure measurement and numerical simulations in an end-wall region of a linear blade cascade
Authors: Flídr Erik , Straka Petr , Kladrubský Milan , Jelínek Tomáš
Published: July 2021

This contribution describes experimental and numerical research of an unsteady behaviour of a flow in an end-wall region of a linear nozzle cascade. Effects of compressibility ($$M_\mathrm {2,is}$$

M

2
,
is

) and inlet flow angle ($$\alpha _1$$

α
1

) were investigated. Reynolds number ($$Re_\mathrm {2,is}$$

R

e

2
,
is

$$=8.5\times 10^5$$

=
8.5
×

10
5

) was held constant for all tested cases. Unsteady pressure measurement was performed at the blade mid-span in the identical position $${\mathfrak {s}}$$
s
to obtain reference data. Surface flow visualizations were performed as well as the steady pressure measurement to support conclusions obtained from the unsteady measurements. Comparison of the surface Mach number distributions obtained from the experiments and from the numerical simulations are presented. Flow visualizations are then compared with calculated limiting streamlines on the blade suction surface. It was shown, that the flow structures in the end-wall region were not affected by the primary flow at the blade mid-span, even when the shock wave formed. This conclusion was made from the experimental, numerical, steady as well as unsteady points of view. Three significant frequencies in the power spectra suggested that there was a periodical interaction between the vortex structures in the end-wall region. Based on the data analyses, anisotropic turbulence was observed in the cascade.
Preventing Pressure Oscillations Does Not Fix Local Linear Stability Issues of Entropy-Based Split-Form High-Order Schemes
Authors: Ranocha Hendrik , Gassner Gregor J.
Published: July 2021

Recently, it was discovered that the entropy-conserving/dissipative high-order split-form discontinuous Galerkin discretizations have robustness issues when trying to solve the simple density wave propagation example for the compressible Euler equations. The issue is related to missing local linear stability, i.e., the stability of the discretization towards perturbations added to a stable base flow. This is strongly related to an anti-diffusion mechanism, that is inherent in entropy-conserving two-point fluxes, which are a key ingredient for the high-order discontinuous Galerkin extension. In this paper, we investigate if pressure equilibrium preservation is a remedy to these recently found local linear stability issues of entropy-conservative/dissipative high-order split-form discontinuous Galerkin methods for the compressible Euler equations. Pressure equilibrium preservation describes the property of a discretization to keep pressure and velocity constant for pure density wave propagation. We present the full theoretical derivation, analysis, and show corresponding numerical results to underline our findings. In addition, we characterize numerical fluxes for the Euler equations that are entropy-conservative, kinetic-energy-preserving, pressure-equilibrium-preserving, and have a density flux that does not depend on the pressure. The source code to reproduce all numerical experiments presented in this article is available online (https://doi.org/10.5281/zenodo.4054366).
The Nature of Fear Among Farmers Working with Animal Production
Authors: Ceccato Vania , Lundqvist Peter , Abraham Jonatan , Göransson Eva , Alwall Svennefelt Catharina
Published: July 2021

In this article, we investigate the nature of fear among farmers working with animal production with particular focus on the impact of harassment and crimes linked to animal rights activism. The study is based on responses from 3815 animal farmers to a national survey in 2020 in Sweden. Cross-table analysis and logistic regression models underlie the methodology of the study. Findings show that three out of ten of those farmers feel afraid of being victimized by the actions of animal rights activists; the proportion is two-thirds among farmers with previous experience of victimization, and fear of victimization varies across Sweden and by type of activity. Perceived lack of support from the police, exacerbated by geographical isolation, are common determinants of farmers’ declared fear, particularly those whose families live on the farms and who have employees. While understanding the factors that affect farmers’ safety perceptions is important, the article ends by calling for further research on the ways by which fear of animal activism impacts farmers’ personal lives, those of their family and employees, and not least their livelihood.
Examining the relationship between anhedonia symptoms and trait positive appraisal style in adolescents: A longitudinal survey study
Authors: Yilmaz Merve , Psychogiou Lamprini , Ford Tamsin , Dunn Barnaby D.
Published: July 2021

Introduction

Anhedonia, defined as a loss of interest and pleasure in previously enjoyable activities, is a core symptom of depression that predicts a poor treatment response in adolescents. We know little about the cognitive vulnerability factors that contribute to the development of anhedonia in youth. This cross‐sectional and longitudinal survey study investigated the link between anhedonia symptoms and cognitive appraisal of positive affect.

Methods

Baseline data were collected from 392 secondary school students in the UK (aged 13–16, 54 % Female), 170 of whom went on to complete the three‐month follow‐up assessment (a 43 % response rate). Participants rated their anhedonia symptoms and appraisal styles which were measured in terms of use of amplifying appraisals, dampening appraisals, and fear of positive emotion.

Results

At baseline, greater anhedonia was significantly associated with increased levels of dampening and reduced levels of amplifying but was not significantly related to fear of positive emotion. Prospectively, greater baseline levels of amplifying uniquely predicted lower anhedonia severity at three‐month follow‐up, and vice‐versa. There was no evidence for reciprocal prospective associations between anhedonia and, appraisal styles of dampening and fear of positive emotion.

Conclusion

These results indicate that cognitive appraisal of positive affect is associated with concurrent and to some extent can predict future symptoms of anhedonia in youth.
Development of Environmental Laws in India
Authors: Kohli Kanchi , Menon Manju
Published: July 2021

Development of Environmental Laws in India highlights the dynamic nature of environmental law-making in India between the judiciary, the executive and the parliament. This has led to the creation of a wide range of environmental institutions and bodies with varied roles and responsibilities. The book contains a large volume of materials from the late 1990s, which show a marked shift in the nature of environmental governance in India. These materials offer an understanding of the contemporary debates in environment law in the context of India's economic liberalisation. The materials are thematically organized and presented in an accessible manner. The chapters contain definitions and specific clauses from the legal instruments and refer to court orders and judgements on these themes.
Advanced Grid Model of Weighted Mean Temperature Based on Feedforward Neural Network Over China
Authors: Zhu Mingchen , Hu Wusheng , Sun Wei
Published: July 2021

Weighted mean temperature (Tm) is a key parameter in Global Navigation Satellite System meteorology. In this study, European Centre for Medium‐Range Weather Forecasts Re‐Analysis product with a spatial resolution of 0.5° × 0.5° from 1999 to 2018 was used to study the spatiotemporal behaviors of Tm in China. Decomposed by Fast Fourier Transformation, Tm and lapse rate (β) variations are highly latitude‐dependent and exhibit periodicities on annual, semi‐annual, and diurnal scales. Meanwhile, Tm keeps increasing at a rate of 0.25 K per decade across China. Based on these discoveries, this study build a new grid Tm model based on feedforward neural network (FNN) with a spatial resolution of 0.5° × 0.5°, known as Grid‐FNN model. FNN is applied to each grid point to compensate the residual error of the corresponding periodic functions. And the fitting accuracy at each grid is improved by the FNN algorithm. ERA‐Interim product with a spatial resolution of 0.4° × 0.4° and Radiosonde data in 2018 are used to validate the new model, and the accuracy of Grid‐FNN model is proved 8.6% and 10.9% better than GPT2w‐Tm model, respectively. The Grid‐FNN model also shows better performance than IGPT2w, GTm‐III, and GTrop model in autumn and winter and in high‐altitude regions.
The Spatial Characteristics of Hourly Rainfall Induced by Tropical Cyclones Along the South China Coast
Authors: Ali Riaz , Li Qinglan , Chen Ji , Huang Dian , Lu Xiaoxiong
Published: July 2021

Accurate prediction of tropical cyclone (TC) induced rainfall is of great importance to disaster prevention but quite challenging to operational forecasters. This study quantifies the spatial characteristics of the hourly rainfall caused by TCs at several individual weather stations over the south China coast. We use the historical TC datasets from 2004 to 2018 and the hourly rainfall data from six weather stations to investigate the stations' rainfall distribution characteristics induced by TCs within a distance of 700 km to the weather stations. The hourly rainfall data during the study period from six coastal stations: Zhuzilin (ZZL), Shekou Ferry Terminal (SFT), and Wutong Village (WTV) in Shenzhen, and Hong Kong Observatory (HKO), Sha Tin (SHA), and Tai Mo Shan (TMS) in Hong Kong are used to investigate the statistical relationship. Results show that the most hazardous areas for TC‐induced rainfall are TCs within a distance of 200 km relative to the stations. High intensity TCs in the southwest quadrant may bring torrential rainfall to stations within 500 km distance, and low intensity TCs are likely to induce torrential rainfall to stations within 300 km distance when they are in the northeast and northwest quadrants. If TCs are over the region with the azimuth of 60–150° and distance out of 200 km to the six stations, there is almost no rainfall influence on those stations. The findings of this study are valuable to provide information for the local operational forecasters when predicting the potential rainfall along the south China coast due to future TCs.
Exhumation of the Coastal Metamorphic Belt Above the Subduction‐to‐Transform Transition, in the Southeast Caribbean Plate Corner
Authors: Arkle Jeanette C. , Weber John , Enkelmann Eva , Owen Lewis A. , Govers Rob , Jess Scott , Denison Chris , O'Sullivan Paul B. , Donelick Raymond A.
Published: July 2021

Plate corners that transition from subduction to transform motion can result in complex deformation. The southeastern corner of the Caribbean plate is a site where active westward subduction of the oceanic South American plate transitions to transform motion along continental South America. The Northern Range (Trinidad) and Paria (Venezuela) metamorphic mountains are located directly above this eastward propagating plate transition zone. We examined the exhumation history of the Northern Range and eastern Paria using apatite fission track (AFT) and apatite and zircon (U‐Th)/He (AHe and ZHe, respectively) thermochronology on 21 bedrock samples. These samples yield ages of ∼43–6 Ma (ZHe: aliquots), ∼20–4 Ma (AFT: pooled) and ∼5–2 Ma (AHe: aliquots). Along strike of the mountains, our new and published samples show a gradual eastward increase in age. Thermal modeling reveals two phases of rapid cooling and inferred exhumation that post‐dates oblique collision and that migrated from west to east. We record an ∼six‐fold increase in cooling and exhumation between ∼13–9 Ma in the Paria Peninsula and western Northern Range; a deceleration followed this rapid exhumation at ∼7 and 5 Ma. Synchronous with the deceleration in the west, exhumation of the eastern Northern Range increased ∼4 Ma. These post‐collisional changes in exhumation constrain the inversion to east‐side‐up tilting of the Northern Range to ∼4 Ma. We interpret the timing and pattern of exhumation since the mid‐Miocene to be consistent with the time‐transgressive processes produced by an eastward propagating lithospheric subduction‐transform edge propagator fault.
Estimation of the Slip Rate Along the Unruptured Fault Segment of the M7.2 1896 Rikuu Earthquake, Northeast Japan
Authors: Arora Shreya , Kondo Hisao , Kurosawa Hideki , Koshika Kouta
Published: July 2021

The Ou Backbone Range (OBR) is one of the most seismically active intraplate regions in northeast Japan. Over the past 200 years, it has been the locus of five large magnitude earthquakes, including the M7.2 1896 Rikuu earthquake, which produced coseismic surface deformation along the northern segment of the Eastern Margin Fault Zone of Yokote Basin (EFZYB), while the southern segment remained unruptured. Despite the extensive paleoseismic investigations along the ruptured segment, the slip rate estimates, and the recurrence interval remained largely unresolved along the southern unruptured segment. This study reports the long‐term slip rate, and recurrence interval along the Higashi Chokai san Fault and the signatures of active faulting along the Kanazawa and Omoriyama Faults. Based on the seismic reflection and borehole survey, we have estimated a vertical displacement of 29.3–36.1 m across the Higashi Chokai san Fault, a long‐term slip rate of 1.6–1.9 mm/yr over the past 35 ka, and a recurrence interval of about 3,800–4,600 years.

Combining our results with the already published data along the OBR, revealed two seismic gaps, first along the western margin of the OBR, along the partial rupture zone of the 1970 Akita‐ken earthquake, and second, along the eastern margin of the OBR, north of the 2008 Iwate‐Miyagi Nairiku earthquake (IMEQ) rupture zone. Given most of the slip is released elastically, we propose that these seismic gaps have a potential to produce earthquakes with magnitudes Mw7.1 and Mw7.3, respectively if they were to rupture in a single event.
Buried Aseismic Slip and Off‐Fault Deformation on the Southernmost San Andreas Fault Triggered by the 2010 El Mayor Cucapah Earthquake Revealed by UAVSAR
Authors: Parker Jay , Donnellan Andrea , Bilham Roger , Ludwig Lisa Grant , Wang Jun , Pierce Marlon , Mowery Nicholas , Jänecke Susanne
Published: July 2021

We use UAVSAR interferograms to characterize fault slip, triggered by the Mw 7.2 El Mayor‐Cucapah earthquake on the 1 San Andreas Fault in the Coachella Valley providing comprehensive maps of short‐term geodetic surface deformation that complement in situ measurements. Creepmeters and geological mapping of fault offsets on Durmid Hill recorded 4 and 8 mm of average triggered slip respectively on the fault, in contrast to radar views that reveal significant off‐fault dextral deformation averaging 20 mm. Unlike slip in previous triggered slip events on the southernmost San Andreas fault, dextral shear in 2010 is not confined to transpressional hills in the Coachella valley. Edge detection and gradient estimation applied to the 50‐m‐sampled interferogram data identify the location (to 20 m) and local strike (to <4°) of secondary surface ruptures. Transverse curve fitting applied to these local detections provides local estimates of the radar‐projected dextral slip and a parameter indicating the transverse width of the slip, which we equate with the depth of subsurface shear. These estimates are partially validated by fault‐transverse interferogram profiles generated using the GeoGateway UAVSAR tool, and appear consistent for radar‐projected slip greater than about 5 mm. An unexpected finding is that creep and triggered slip on the San Andreas fault terminate in the shallow subsurface below a surface shear zone that resists the simple expression of aseismic fault slip. We introduce the notion of a surface locking depth above which fault slip is manifest as distributed shear, and evaluate its depth as 6–27 m.
Why Study Geysers?
Authors: Hurwitz Shaul , Manga Michael , Campbell Kathleen , Mu�oz-Saez Carolina , Eibl Eva
Published: July 2021

Aside from captivating our senses, geysers have much to tell us about subsurface fluids, climate change effects, and the occurrence and limits of life on Earth and elsewhere in the solar system.
Prompt Penetration and Substorm Effects Over Jicamarca During the September 2017 Geomagnetic Storm
Authors: Fejer B. G. , Navarro L. A. , Sazykin S. , Newheart A. , Milla M. A. , Condor P.
Published: July 2021

We used reanalyzed Jicamarca radar measurements to study the response of equatorial ionospheric electrodynamics and spread F during the main phase of the large September 2017 geomagnetic storm. Our observations near dusk on 7 September show very large upward drifts followed by a large short‐lived downward drift perturbation that completely suppressed the lower F region plasma irregularities and severely decreased the backscattered power from the higher altitude spread F. We suggest that this large short‐lived westward electric field perturbation is most likely of magnetospheric origin and is due to a sudden and very strong magnetic field reconfiguration. Later in the early night period, data indicate large, mostly upward, drift perturbations generally consistent with standard undershielding and overshielding electric field effects, but with amplitudes significantly larger than expected. Our analysis suggests that occurrence of storm‐time substorms is one of the major factors causing the large nighttime westward and eastward electric field perturbations observed at Jicamarca near the storm main phase. Our analysis also suggests that magnetospheric substorms play far more important roles on the electrodynamics of the equatorial nighttime ionosphere than has generally been thought.
Alteration‐Induced Volcano Instability at La Soufrière de Guadeloupe (Eastern Caribbean)
Authors: Heap Michael J. , Baumann Tobias S. , Rosas‐Carbajal Marina , Komorowski Jean‐Christophe , Gilg H. Albert , Villeneuve Marlène , Moretti Roberto , Baud Patrick , Carbillet Lucille , Harnett Claire , Reuschlé Thierry
Published: July 2021

Volcanoes are unstable structures that deform laterally and frequently experience mass wasting events. Hydrothermal alteration is often invoked as a mechanism that contributes significantly to volcano instability. We present a study that combines laboratory experiments, geophysical data, and large‐scale numerical modeling to better understand the influence of alteration on volcano stability, using La Soufrière de Guadeloupe (Eastern Caribbean) as a case study. Laboratory experiments on variably altered (advanced argillic alteration) blocks show that uniaxial compressive strength, Young's modulus, and cohesion decrease as a function of increasing alteration, but that the internal friction angle does not change systematically. Simplified volcano cross sections were prepared (a homogenous volcano, a volcano containing the alteration zone identified by a recent electrical survey, and a volcano with an artificially enlarged area of alteration) and mechanical properties were assigned to zones corresponding to unaltered and altered rock. Numerical modeling performed on these cross sections, using a hydro‐thermo‐mechanical modeling code, show (a) the importance of using upscaled values in large‐scale models and (b) that alteration significantly increases volcano deformation and collapse volume. Finally, we combined published muon tomography data with our laboratory data to create a 3D strength map, exposing a low‐strength zone beneath the southern flank of the volcano coincident with the hydrothermal system. We conclude that hydrothermal alteration decreases volcano stability and thus expedites volcano spreading and increases the likelihood of mass wasting events and associated volcanic hazards. Hydrothermal alteration, and its evolution, should therefore be monitored at active volcanoes worldwide.
Potential Impact of Photoinhibition on Microphytobenthic Primary Production on a Large Intertidal Mudflat
Authors: Savelli Raphaël , Serôdio João , Cugier Philippe , Méléder Vona , Polsenaere Pierre , Dupuy Christine , Le Fouest Vincent
Published: July 2021

Microphytobenthos (MPB) are a key primary producer of intertidal mudflats. MPB face strong variability in incident irradiance during low tides. Despite photoprotection and photoacclimation, such variations can translate into the photoinhibition of MPB cells. This study explores the effect of photoinhibition on MPB primary production (PP) over a large and productive temperate mudflat (Brouage mudflat, NW France). We used a regional and high‐resolution tri‐dimensional hydrodynamic model coupled to an MPB model with or without photoinhibition. Photoinhibition leads to a 20% (−0.79 × t C) decrease of the simulated MPB PP over the entire mudflat. As the upper shore is exposed to light more frequently and longer than the lower shore, the decrease of MPB PP is higher on the upper shore (−29%) than on the lower shore (−5%). With the highest photosynthetically active radiation cumulated over the mudflat, the decrease of MPB PP due to photoinhibition is the highest during spring and spring tides (−22% and −23%, respectively). The model suggests MPB photoinhibition is sensitive to the photoacclimation status of MPB cells through the light saturation parameter. This first modeling attempt to account for MPB photoinhibition is highly constrained by our current theoretical knowledge and limitations on the MPB growth physiology, but it suggests that this process can have a substantial impact on the MPB PP. As such, assessing the MPB photosynthetic response to the highly variable environmental conditions that prevail in large and productive intertidal mudflats is a real challenge for quantifying MPB PP from a synoptic to inter‐annual time scale.
AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms
Authors: Rejeski Kai , Duque-Afonso Jesús , Lübbert Michael
Published: July 2021

The chromosomal translocation t(8;21) and the resulting oncofusion gene AML1/ETO have long served as a prototypical genetic lesion to model and understand leukemogenesis. In this review, we describe the wide-ranging role of AML1/ETO in AML leukemogenesis, with a particular focus on the aberrant epigenetic regulation of gene transcription driven by this AML-defining mutation. We begin by analyzing how structural changes secondary to distinct genomic breakpoints and splice changes, as well as posttranscriptional modifications, influence AML1/ETO protein function. Next, we characterize how AML1/ETO recruits chromatin-modifying enzymes to target genes and how the oncofusion protein alters chromatin marks, transcription factor binding, and gene expression. We explore the specific impact of these global changes in the epigenetic network facilitated by the AML1/ETO oncofusion on cellular processes and leukemic growth. Furthermore, we define the genetic landscape of AML1/ETO-positive AML, presenting the current literature concerning the incidence of cooperating mutations in genes such as KIT, FLT3, and NRAS. Finally, we outline how alterations in transcriptional regulation patterns create potential vulnerabilities that may be exploited by epigenetically active agents and other therapeutics.
Integrating plant-to-plant communication and rhizosphere microbial dynamics: ecological and evolutionary implications and a call for experimental rigor
Authors: Howard Mia M , Bass Ethan , Chautá Alexander , Mutyambai Daniel , Kessler André
Published: July 2021

The perception of airborne chemical signals by plants can trigger reconfigurations of their metabolism that alter their biotic interactions. While plant-to-plant chemical communication has primarily been studied in the context of eliciting defenses to herbivores and pathogens, recent work suggests that it can also affect plants’ interactions with their rhizosphere microbiomes. In this perspective, we discuss the potential for integrating the fields of plant-to-plant communication and microbial ecology to understand the chemical ecology of plant−microbiome interactions. As an introduction for microbial ecologists, we highlight mechanistic knowledge gaps in plant volatile organic compound (VOC) perception and provide recommendations for avoiding common experimental errors that have plagued the plant communication field. Lastly, we discuss potential implications of plant VOCs structuring rhizosphere microbiomes, particularly effects on plant community and evolutionary dynamics. As we continue to discover links between plant metabolism and their microbiomes—from molecular to community scales—we hope that this perspective will provide both motivation and words of caution for researchers working at the intersection of these two fields.
Herpes simplex virus, early neuroimaging markers and incidence of Alzheimer’s disease
Authors: Linard Morgane , Baillet Marion , Letenneur Luc , Garrigue Isabelle , Catheline Gwenaëlle , Dartigues Jean-François , Peres Karine , Helmer Catherine
Published: July 2021

While previous studies suggest the implication of herpes simplex virus (HSV) in the onset of Alzheimer’s disease (AD), no study has investigated its association with early neuroimaging markers of AD. In the Three-City and the AMI cohorts, the associations between HSV infection and (i) hippocampal volume (n = 349), (ii) white matter alterations in the parahippocampal cingulum and fornix using diffusion tensor imaging (n = 260), and (iii) incidence of AD (n = 1599) were assessed according to APOE4 status. Regardless of APOE4 status, infected subjects presented (i) significantly more microstructural alterations of the parahippocampal cingulum and fornix, (ii) lower hippocampal volumes only when their anti-HSV IgG level was in the highest tercile—reflecting possibly more frequent reactivations of the virus (p = 0.03 for subjects with a high anti-HSV IgG level while there was no association for all infected subjects, p = 0.19), and (iii) had no increased risk of developing AD. Nevertheless, among APOE4 carriers, infected subjects presented lower hippocampal volumes, although not significant (p = 0.09), and a two or three times higher risk of developing AD (adjusted Hazard ratio (aHR) = 2.72 [1.07–6.91] p = 0.04 for infected subjects and aHR = 3.87 [1.45–10.28] p = 0.007 for infected subjects with an anti-HSV IgG level in the highest tercile) while no association was found among APOE4 noncarriers. Our findings support an association between HSV infection and AD and a potential interaction between HSV status and APOE4. This reinforces the need to further investigate the infectious hypothesis of AD, especially the associated susceptibility factors and the possibility of preventive treatments.
High-throughput drug screening identifies the ATR-CHK1 pathway as a therapeutic vulnerability of CALR mutated hematopoietic cells
Authors: Jia Ruochen , Kutzner Leon , Koren Anna , Runggatscher Kathrin , Májek Peter , Müller André C. , Schuster Michael , Bock Christoph , Loizou Joanna I. , Kubicek Stefan , Kralovics Robert
Published: July 2021

Mutations of calreticulin (CALR) are the second most prevalent driver mutations in essential thrombocythemia and primary myelofibrosis. To identify potential targeted therapies for CALR mutated myeloproliferative neoplasms, we searched for small molecules that selectively inhibit the growth of CALR mutated cells using high-throughput drug screening. We investigated 89 172 compounds using isogenic cell lines carrying CALR mutations and identified synthetic lethality with compounds targeting the ATR-CHK1 pathway. The selective inhibitory effect of these compounds was validated in a co-culture assay of CALR mutated and wild-type cells. Of the tested compounds, CHK1 inhibitors potently depleted CALR mutated cells, allowing wild-type cell dominance in the co-culture over time. Neither CALR deficient cells nor JAK2V617F mutated cells showed hypersensitivity to ATR-CHK1 inhibition, thus suggesting specificity for the oncogenic activation by the mutant CALR. CHK1 inhibitors induced replication stress in CALR mutated cells revealed by elevated pan-nuclear staining for γH2AX and hyperphosphorylation of RPA2. This was accompanied by S-phase cell cycle arrest due to incomplete DNA replication. Transcriptomic and phosphoproteomic analyses revealed a replication stress signature caused by oncogenic CALR, suggesting an intrinsic vulnerability to CHK1 perturbation. This study reveals the ATR-CHK1 pathway as a potential therapeutic target in CALR mutated hematopoietic cells.
FBXO16-mediated hnRNPL ubiquitination and degradation plays a tumor suppressor role in ovarian cancer
Authors: Ji Mei , Zhao Zhao , Li Yue , Xu Penglin , Shi Jia , Li Zhe , Wang Kaige , Huang Xiaotian , Ji Jing , Liu Wei , Liu Bin
Published: July 2021

Heterogeneous nuclear ribonucleoprotein L (hnRNPL) is a type of RNA binding protein that highly expressed in a variety of tumors and plays a vital role in tumor progression. However, its post-translational regulation through ubiquitin-mediated proteolysis and the cellular mechanism responsible for its proteasomal degradation remains unclear. F-box proteins (FBPs) function as the substrate recognition subunits of SCF ubiquitin ligase complexes and directly bind to substrates. The aberrant expression or mutation of FBPs will lead to the accumulation of its substrate proteins that often involved in tumorigenesis. Here we discover FBXO16, an E3 ubiquitin ligase, to be a tumor suppressor in ovarian cancer, and patients with the relatively high expression level of FBXO16 have a better prognosis. Silencing or depleting FBXO16 significantly enhanced ovarian cancer cell proliferation, clonogenic survival, and cell invasion by activating multiple oncogenic pathways. This function requires the F-box domain of FBXO16, through which FBXO16 assembles a canonical SCF ubiquitin ligase complex that constitutively targets hnRNPL for degradation. Depletion of hnRNPL is sufficient to inactive multiple oncogenic signaling regulated by FBXO16 and prevent the malignant behavior of ovarian cancer cells caused by FBXO16 deficiency. FBXO16 interacted with the RRM3 domain of hnRNPL via its C-terminal region to trigger the proteasomal degradation of hnRNPL. Failure to degrade hnRNPL promoted ovarian cancer cell proliferation in vitro and tumor growth vivo, phenocopying the deficiency of FBXO16 in ovarian cancer.