bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extremely Energetic Rockfalls
Authors: De Blasio Fabio Vittorio , Dattola Giuseppe , Crosta Giovanni Battista 
Published: September 2018

AbstractExtremely energetic rockfalls (EERs) are defined here as rockfalls for which a combination of both large volume and free fall height of hundreds of meters results in energy larger than about 80 GJ released in a short time. Examples include several events worldwide. In contrast to low energy rockfalls where block disintegration is limited, in EERs the impact after free fall causes immediate release of energy much like an explosion. The resulting air blast can snap trees hundreds of meters ahead of the fall area. Pulverized rock at high speed can abrade vegetation in a process of sandblasting, and particles suspended by the blast and the subsequent debris cloud may travel farther than the impact zone, blanketing vast areas. Using published accounts and new data, we introduce physically based models formulated on analogies with explosions and explosive fragmentation to describe EERs. Results indicate that a portion of the initial potential energy of the block is spent in rock disintegration at impact (typically 0.2%–18%), while other sources of energy loss (air drag, seismic, sound, and ground deformation) are negligible; consequently, more than 80% of the potential energy is converted to kinetic energy of the fragmented block (ballistic projection, shock wave, sand blast, and dust cloud). We also propose simple estimates for the flow of the dust cloud associated with an EER and its long settling time. The areal extent of the affected zone is estimated from the energy balance and an empirical power law relationship.
Toward Robust Interpretation of Low‐Temperature Thermochronometers in Magmatic Terranes
Authors: Murray Kendra E. , Braun Jean , Reiners Peter W. 
Published: September 2018

AbstractMany regions central to our understanding of tectonics and landscape evolution are active or ancient magmatic terranes, and robust interpretation of low‐temperature thermochronologic ages in these settings requires careful attention to the drivers of rock heating and cooling, including magmatism. However, we currently lack a quantitative framework for evaluating the potential role of magmatic cooling—that is, post‐magmatic thermal relaxation—in shaping cooling age patterns in regions with a history of intrusive magmatism. Here we use analytical approximations and numerical models to characterize how low‐temperature thermochronometers document cooling inside and around plutons in steadily exhuming environments. Our models predict that the thermal field a pluton intrudes into, specifically the ambient temperatures relative to the closure temperature of a given thermochronometer, is as important as the pluton size and temperature in controlling the pattern and extent of thermochronometer resetting in the country rocks around a pluton. We identify one advective and several conductive timescales that govern the relationship between the crystallization and cooling ages inside a pluton. In synthetic vertical age‐elevation relationships (AERs), resetting next to plutons results in changes in AER slope that could be misinterpreted as past changes in exhumation rate if the history of magmatism is not accounted for. Finally, we find that large midcrustal plutons, such as those emplaced at ~10–15‐km depth, can reset the low‐temperature thermochronometers far above them in the upper crust—a result with considerable consequences for thermochronology in arcs and regions with a history of magmatic activity that may not have a surface expression.
Quartz Solubility in the Two‐Phase Region of the NaCl‐H2O System: An Experimental Study With Application to the Piccard Hydrothermal Field, Mid‐Cayman Rise
Authors: Scheuermann Peter P. , Tan Chunyang , Seyfried William E. 
Published: September 2018

AbstractHydrothermal experiments were performed at elevated temperature (420–500 °C) and pressure (31.0–51.0 MPa) in the NaCl‐H2O system to measure quartz solubility in coexisting vapor and liquid and extend the calibrated range of the Si‐Cl geothermobarometer. In the vapor, the density‐based equations for quartz solubility of Fournier (1983, http://doi.org/10.1016/0016‐7037(83)90279‐X) and Von Damm et al. (1991, http://doi.org/10.2475/ajs.291.10.977) agree well with the experimental data, while the equation of Fournier (1983) also accurately predicts SiO2(aq) concentrations in the liquid. Importantly, the equations of Fournier (1983) and Von Damm et al. (1991) were calibrated based on quartz solubility in single phase fluids (no coexisting vapor‐liquid) at higher pressure than investigated here. The new experimental data therefore extend the pressure range of the density‐equations and demonstrate that quartz solubility in either vapor or liquid can be treated independently as a function of temperature, pressure, and fluid density. The Si‐Cl geothermobarometer indicates that fluids venting from Piccard reach 540 ± 15 °C, 62.5 ± 3.0 MPa. These are the hottest and deepest conditions yet recorded by an actively venting seafloor hydrothermal fluid. Based on the calculated enthalpy differences between the subsurface fluid and that venting at the seafloor, approximately one third of the heat extracted at depth is lost during conductive cooling of the hydrothermal fluid. Incorporating the heat lost during conductive cooling into the overall budget at Piccard yields a flux of 100 ± 37 MW and an associated hydrothermal fluid flux of 1.2 ± 0.4 × 109 kg/year. The newly calibrated Si‐Cl geothermobarometer provides important constraints for accurate determination of heat and mass fluxes at axial vent sites.
HDAC6 inhibitor TST strengthens the antiproliferative effects of PI3K/mTOR inhibitor BEZ235 in breast cancer cells via suppressing RTK activation
Authors: Sun Shixiu , Zhang Yujie , Zheng Jianchao , Duan Biao , Cui Jie , Chen Yan , Deng Wenjie , Ye Bixing , Liu Lei , Chen Yongchang , Du Jun , Gu Luo 
Published: September 2018

AbstractNVP-BEZ235 (BEZ235), an available dual PI3K/mTOR inhibitor, showed antitumor effect and provided a therapy strategy in carcinomas. However, the acquired upregulation of multiple receptor tyrosine kinases (RTKs) by NVP-BEZ235 in tumors limits its clinical efficacy. HDAC6, a class II histone deacetylase, is associated with expressions of multiple RTKs. The aim of this study was to detect whether co-treatment with HDAC6 inhibitor Tubastatin A (TST) would enhance the anticancer effects of BEZ235 in breast cancer cells. In this study, we described that treatment of breast cancer cell lines (T47D, BT474, and MDA-MB-468) with BEZ235 significantly triggered PI3K/mTOR signaling inactivation and increased multiple RTK expression, including EGFR, HER2, HER3, IGF-1 receptor, insulin receptor, and their phosphorylation levels. The adding of TST destabilized these RTKs in those breast cancer cells. Co-treatment with BEZ235 and TST reduced cell proliferative rate by strengthening Akt inactivation. In addition, the combination of these two drugs also cooperatively arrested cell cycle and DNA synthesis. In conclusion, the co-treatment with PI3K/mTOR inhibitor BEZ235 and HDAC6 inhibitor TST displayed additive antiproliferative effects on breast cancer cells through inactivating RTKs and established a rationable combination therapy to treat breast cancer.
Melanoma cells resistant towards MAPK inhibitors exhibit reduced TAp73 expression mediating enhanced sensitivity to platinum-based drugs
Authors: Makino Elena , Gutmann Vanessa , Kosnopfel Corinna , Niessner Heike , Forschner Andrea , Garbe Claus , Sinnberg Tobias , Schittek Birgit 
Published: September 2018

AbstractThe efficacy of targeted MAPK signalling pathway inhibitors (MAPKi) in metastatic melanoma therapy is limited by the development of resistance mechanisms that results in disease relapse. This situation still requires treatment alternatives for melanoma patients with acquired resistance to targeted therapy. We found that melanoma cells, which developed resistance towards MAPKi show an enhanced susceptibility to platinum-based drugs, such as cisplatin and carboplatin. We found that this enhanced susceptibility inversely correlates with the expression level of the p53 family member TAp73. We show that the lower expression of the TAp73 isoform in MAPKi-resistant melanoma cells enhances accumulation of DNA double-strand breaks upon cisplatin and carboplatin treatment by reducing the efficiency of nucleotide excision repair. These data suggest that a subgroup of melanoma patients with acquired resistance to MAPKi treatment and low TAp73 expression can benefit from chemotherapy with platinum-based drugs as a second-line therapy.
Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in acute promyelocytic leukemia (APL)☆
Authors: Holloway Ryan W. , Thomas Margaret L. , Cohen Alejandro M. , Bharadwaj Alamelu G. , Rahman Mushfiqur , Marcato Paola , Marignani Paola A. , Waisman David M. 
Published: September 2018

AbstractS100A10 (p11), a member of the S100 family of small dimeric EF-hand-type Ca2+-binding proteins, plays a role in a variety of both intracellular and extracellular processes. Previous studies have suggested that p11 is intrinsically unstable and requires binding to annexin A2 (p36) to prevent its rapid ubiquitylation and degradation. Our laboratory has shown that p11 levels are stimulated by the expression of the oncoprotein, PML/RARα. Furthermore, treatment of the APL cell line, NB4 with all-trans retinoic acid (ATRA) causes the rapid loss of p36 and p11 protein. However, the mechanism by which ATRA regulates p11 levels has not been established. Here, we show that the proteasomal inhibitor, lactacystin reversed the ATRA-dependent loss of p11, but did not cause an accumulation of ubiquitylated forms of p11, suggesting that ATRA promotes the proteasomal degradation of p11 in an ubiquitin-independent manner. ATRA treatment of MCF-7 breast cancer cells reduced p11 but not p36 transcript and protein levels, thus indicating that ATRA can regulate p11 levels independently of PML/RARα and p36. Overexpression of p36 upregulated p11 protein but not mRNA levels, indicating that p36 affects p11 post translationally. The forced expression of ubiquitin and p11 in 293 T cells resulted in ubiquitylation of p11 that was blocked by mutagenesis of lysine 57. This study highlights the complex regulation of p11 by retinoid signaling and challenges the hypothesis that ubiquitin-mediated proteasomal degradation of p11 represents a universal mechanism of regulation of this protein.
KLLN-mediated DNA damage-induced apoptosis is associated with regulation of p53 phosphorylation and acetylation in breast cancer cells
Authors: Sankunny Madhav , Eng Charis 
Published: September 2018

AbstractKLLN is a target of p53 involved in S-phase cell cycle regulation deemed necessary and sufficient for p53-mediated apoptosis. Germline promoter hypermethylation of KLLN is associated with a cancer-predisposition syndrome, Cowden syndrome. KLLN’s DNA-binding ability is associated with transcription regulation and maintenance of genomic stability. Here, we report on KLLN’s role in DNA damage response (DDR) mediated through apoptosis in breast cells with and without a cancer phenotype. KLLN expression was upregulated after doxorubicin-induced DNA damage and this upregulation can be abrogated using RNAi-mediated gene silencing. Silencing KLLN after doxorubicin treatment effected DDR shown by decreased γ-H2AX foci and expression, and apoptosis assessed by decreased frequency of apoptotic nuclei and decreased expression of definitive markers of apoptosis. Contrary to expectations, there was no change in cell cycle regulation after KLLN silencing. These results were observed in breast cells with wildtype and mutant p53. At early timepoints after doxorubicin treatment, knocking down KLLN resulted in decreased Ser15-phosphorylation of p53 but not Thr68-phosphorylation of CHK2 or the phosphorylation of upstream regulators such as ATM and ATR. Interestingly, a second pathway for p53 activation was also affected by knockdown of KLLN. After doxorubicin treatment, Thr454-phosphorylation of DBC1, required to inhibit deacetylation of p53 by SIRT1, was decreased and therefore acetylation of p53 was also decreased with KLLN knockdown. Therefore, our observations suggest that KLLN’s role in DNA damage-induced apoptosis is likely independent of p53 and is associated with a two-pronged regulation of p53 activation.
BTK modulates p73 activity to induce apoptosis independently of p53
Authors: Rada Miran , Barlev Nickolai , Macip Salvador 
Published: September 2018

AbstractBruton’s tyrosine kinase (BTK) is a key component of B cell receptor signalling. Because of this, BTK plays an important role in cell proliferation and survival in various B cell malignancies. However, in certain contexts, BTK can also have tumour suppressor functions. We have previously shown that BTK activates the p53 transcriptional activity by binding to and phosphorylating p53, as well as acting on MDM2 to reduce its inhibitory effects. This results in increased p53 functions, including enhanced cell death. Here, we report that BTK can also induce cell death and increase responses to DNA damage independently of p53. This is concomitant to the induction of p21, PUMA and MDM2, which are classic target genes of the p53 family of proteins. Our results show that these p53-independent effects of BTK are mediated through p73. Similar to what we observed in the p53 pathway, BTK can upregulate p73 after DNA damage and induce expression of its target genes, suggesting that BTK is a modulator of p73 functions and in the absence of p53. This effect allows BTK to have pro-apoptotic functions independently of its effects on the p53 pathway and thus play an important role in the DNA damage-related induction of apoptosis in the absence of p53. This provides a novel role of BTK in tumour suppression and contributes to the understanding of its complex pleiotropic functions
ADRB2 polymorphism Arg16Gly modifies the natural outcome of heart failure and dictates therapeutic response to β-blockers in patients with heart failure
Authors: Huang Jin , Li Chenze , Song Ying , Fan Xiaohan , You Ling , Tan Lun , Xiao Lei , Li Qing , Ruan Guoran , Hu Senlin , Cui Wei , Li Zongzhe , Ni Li , Chen Chen , Woo Anthony Yiu-Ho , Xiao Rui-Ping , Wang Dao Wen 
Published: September 2018

AbstractWe sought to investigate the association of single nucleotide polymorphisms (SNPs) of the genes involved in βAR signaling with the response of patients to βAR blockers. A total of 2403 hospitalized patients with chronic heart failure (HF) were enrolled in a multicenter observational study as the first cohort and followed up for a mean period of 20 months. Genes for β1AR, β2AR, and the major cardiac G-protein-coupled receptor kinases (GRKs) GRK2 and GRK5 were analyzed to identify SNPs, and patients were stratified according to genotypes. A second independent cohort enrolling 919 patients with chronic HF was applied to validate the observed associations. The signaling properties of the key identified SNPs were assessed in vitro. Our data showed that HF patients harboring the Gly16 allele in the gene for β2AR (ADRB2) had an increased risk of the composite end point relative to patients who were homozygous for Arg16. Notably, these patients showed a beneficial response to βAR-blocker treatment in a G allele-dose-dependent manner, whereas Arg16 homozygotes had no response to βAR-blocker therapy. This Arg16Gly genotype-dependent heterogeneity in clinical outcomes of HF was successfully validated in the second independent population. Besides, the in vitro experiments revealed that G allele carriers were defective in β2AR-coupled inhibitory adenylate cyclase g (Gi) protein signaling.
A plant Bro1 domain protein BRAF regulates multivesicular body biogenesis and membrane protein homeostasis
Authors: Shen Jinbo , Zhao Qiong , Wang Xiangfeng , Gao Caiji , Zhu Ying , Zeng Yonglun , Jiang Liwen 
Published: September 2018

AbstractPlant development, defense, and many physiological processes rely on the endosomal sorting complex required for transport (ESCRT) machinery to control the homeostasis of membrane proteins by selective vacuolar degradation. Although ESCRT core components are conserved among higher eukaryotes, the regulators that control the function of the ESCRT machinery remain elusive. We recently identified a plant-specific ESCRT component, FREE1, that is essential for multivesicular body/prevacuolar compartment (MVB/PVC) biogenesis and vacuolar sorting of membrane proteins. Here we identify a plant-specific Bro1-domain protein BRAF, which regulates FREE1 recruitment to the MVB/PVC membrane by competitively binding to the ESCRT-I component Vps23. Altogether, we have successfully identified a role for BRAF, whose function as a unique evolutionary ESCRT regulator in orchestrating intraluminal vesicle formation in MVB/PVCs and the sorting of membrane proteins for degradation in plants makes it an important regulatory mechanism underlying the ESCRT machinery in higher eukaryotes.
14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface
Authors: Karlberg Tobias , Hornyak Peter , Pinto Ana Filipa , Milanova Stefina , Ebrahimi Mahsa , Lindberg Mikael , Püllen Nikolai , Nordström Axel , Löverli Elinor , Caraballo Rémi , Wong Emily V. , Näreoja Katja , Thorsell Ann-Gerd , Elofsson Mikael , De La Cruz Enrique M. , Björkegren Camilla , Schüler Herwig 
Published: September 2018

AbstractPseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3β:ExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.
A spin torque meter with magnetic facet domains
Authors: Moon Kyoung-Woong , Kim Changsoo , Yoon Jungbum , Choi Jun Woo , Kim Dong-Ok , Song Kyung Mee , Kim Dongseuk , Chun Byong Sun , Hwang Chanyong 
Published: September 2018

AbstractCurrent-induced magnetic domain wall (DW) motion is an important operating principle of spintronic devices. Injected current generates spin torques (STs) on the DWs in two ways. One is the spin transfer from magnetic domains to the walls by the current flowing in the magnet. Current flow in attached heavy metals also generates another ST because of the spin-Hall effect. Both phenomena explain the wall motions well; therefore, their respective contribution is an important issue. Here, we show the simultaneous measurement of both torques by using magnetic facet domains that form mountain-shaped domains with straight walls. When the STs and the external magnetic field push the walls in opposite directions, the walls should have equilibrium angles to create balanced states. Such angles can be modulated by an additional in-plane magnetic field. Angle measurements distinguish the STs because each torque has a distinct mechanism related to the DW structure.
Hydrogen spillover through Matryoshka-type (ZIFs@)n−1ZIFs nanocubes
Authors: Zhan Guowu , Zeng Hua Chun 
Published: September 2018

AbstractHydrogen spillover phenomenon is well-documented in hydrogenation catalysis but still highly disputed in hydrogen storage. Until now, the existence of hydrogen spillover through metal–organic frameworks (MOFs) remains a topic of ongoing debate and how far the split hydrogen atoms diffuse in such materials is unknown. Herein we provide experimental evidence of the occurrence of hydrogen spillover in microporous MOFs at elevated temperatures, and the penetration depths of atomic hydrogen were measured quantitatively. We have made Matryoshka-type (ZIFs@)n−1ZIFs (where ZIFs = ZIF-8 or ZIF-67) nanocubes, together with Pt nanoparticles loaded on their external surfaces to produce atomic hydrogen. Within the (ZIFs@)n−1ZIFs, the ZIF-8 shell served as a ruler to measure the travelling distance of H atoms while the ZIF-67 core as a terminator of H atoms. In addition to the hydrogenolysis at normal pressure, CO2 hydrogenation can also trace the migration of H atoms over the ZIF-8 at high pressure.
Publisher Correction: Quantum coherence of multiple excitons governs absorption cross-sections of PbS/CdS core/shell nanocrystals
Authors: Tahara Hirokazu , Sakamoto Masanori , Teranishi Toshiharu , Kanemitsu Yoshihiko 
Published: September 2018

The original version of this Article contained an error in the seventh sentence of the second paragraph of the ‘TA amplitudes for double pump-pulse excitation” section of the Results, which incorrectly read ‘The absorption cross-sections of the transitions from the single exciton state to the biexciton and triexciton states are denoted by σ′ and σ'', respectively.’ The correct version states ‘σ′′’ in place of ‘σ''’.The ninth and tenth sentences of the same paragraph originally incorrectly read ‘The most important issue of this work is to clarify whether the multiple exciton absorption cross-sections σ′ and σ'' are equal to σ or not. The black dotted curves in Fig. 3b, c show the predicted results of the TA amplitudes by assuming identical cross-sections, i.e., σ = σ ′ = σ'' = .’ The correct version states ‘σ′ and σ′′ are equal” instead of ‘σ′ and σ'' are equal’ and ‘σ = σ′ = σ′′’ in place of ‘σ = σ ′ = σ'' = ’.This has been corrected in both the PDF and HTML versions of the Article.
In situ disentangling surface state transport channels of a topological insulator thin film by gating
Authors: Lüpke Felix , Just Sven , Eschbach Markus , Heider Tristan , Młyńczak Ewa , Lanius Martin , Schüffelgen Peter , Rosenbach Daniel , von den Driesch Nils , Cherepanov Vasily , Mussler Gregor , Plucinski Lukasz , Grützmacher Detlev , Schneider Claus M. , Tautz F. Stefan , Voigtländer Bert 
Published: September 2018

AbstractIn the thin film limit, the surface state of a three-dimensional topological insulator gives rise to two parallel conduction channels at the top and bottom surface of the film, which are difficult to disentangle in transport experiments. Here, we present gate-dependent multi-tip scanning tunneling microscope transport measurements combined with photoemission experiments all performed in situ on pristine BiSbTe3 thin films. To analyze the data, we develop a generic transport model including quantum capacitance effects. This approach allows us to quantify the gate-dependent conductivities, charge carrier concentrations, and mobilities for all relevant transport channels of three-dimensional topological insulator thin films (i.e., the two topological surface state channels, as well as the interior of the film). For the present sample, we find that the conductivity in the bottom surface state channel is minimized below a gate voltage of Vgate = −34 V and the top surface state channel dominates the transport through the film.