bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stressing Rates and Seismicity on the Major Faults in Eastern Tibetan Plateau
Authors: Luo Gang , Liu Mian 
Published: November 2018

AbstractIntensive studies following the 2008 Wenchuan and 2013 Lushan earthquakes have shown that these two events have changed stresses on major faults in eastern Tibetan Plateau. However, these stress changes are small perturbations to total stresses on these faults. To evaluate full stress evolution on faults and the associated earthquake hazard, we need to consider the effects of all regional large earthquakes and tectonic stressing on faults. Here we use a three‐dimensional viscoelastoplastic finite element model to investigate stress evolution and long‐term temporal patterns of seismicity on major faults in eastern Tibet. We first simulate stress changes due to coseismic slips and postseismic viscoelastic stress relaxation by regional 28 big earthquakes since 1327 and find that nine events, including the Wenchuan earthquake, occurred where Coulomb stress was decreased by the preceding events. We then evaluate interseismic stressing rates using the geodynamic model and GPS data and find the highest rate on Xianshuihe fault (~1,000–4,950 Pa/yr) and the lowest rate on Longmenshan fault (~150–1,133 Pa/yr). Including interseismic stressing in stress evolution shows that the Wenchuan earthquake ruptured where Coulomb stress had increased since 1327 and stresses on southern Xianshuihe and central Anninghe faults would have reached prerupture stress levels of their preceding ruptures. Finally, we analyze synthetic seismicity on faults and find that earthquakes on each fault tend to occur in clusters, separated by quiescent periods whose lengths are inversely related with fault slip rates. The time spans of earthquake clusters are affected by fault slip rates, fault configuration, and rheology.
Seismic Imprints of Plume‐Lithosphere Interaction Beneath the Northwestern Deccan Volcanic Province
Authors: Sharma Jyoti , Kumar M. Ravi , Roy Ketan Singha , Roy P. N. S. 
Published: November 2018

AbstractThe interaction of the Indian continental lithosphere with the Reunion plume resulted in massive outpouring of basalts manifested in the Deccan Volcanic Province. Although it is postulated that preexisting weak rift zones facilitated the eruption, deeper signatures of the plume remain contentious. In this study, we investigate the shear wave velocity (Vs) structure of the crust and upper mantle by inverting regionalized group velocity dispersion data in the period range of 6 to 100 s, down to 220 km depth, using the genetic algorithm technique. We used 1,286 dispersion curves derived from waveforms of 77 regional earthquakes recorded at 38 broadband stations. Our results reveal distinct intracrustal layers, Moho, mantle lid, and asthenospheric low‐velocity layer. Signatures of magmatic underplating are recognized in terms of high Vs and a thick crust beneath the Kutch seismic zone and Western Ghats. The lithospheric thickness varies from 80 to 124 km, being thinnest at the junction of Cambay and Narmada rifts, which could be the source zone of volcanic eruption. A thin lithosphere has also been observed beneath the Kutch seismic zone. A low‐velocity zone at depths ~80 km can be related with upwarping of the asthenosphere and/or presence of partial melts. A predominant low‐velocity zone beneath the Cambay, Saurashtra, and adjoining regions may be due to the effect of a residual thermal anomaly. A thin lithosphere beneath northwestern Deccan Volcanic Province could be the result of weakening due to plume‐lithosphere interaction, which facilitated volcanism through preexisting rift zones.
Connectivity of the Aleutian North Slope Current and Bering Sea Basin Waters at the Level of the Subsurface Temperature Maximum: A Modeling Study
Authors: Mauch M. , Durski S. M. , Kurapov A. L. 
Published: November 2018

AbstractA 2‐km resolution ocean circulation model for the Eastern Bering Sea is utilized to understand whether and where slope‐interior exchange along the path of the Aleutian North Slope Current helps maintain the subsurface temperature maximum on the 26.8‐kg/m3 isopycnal surface in the Bering Sea Basin, at approximately 300–400‐m depths. A simulation for June–October 2009 shows warmer water advecting westward on this isopycnal along the southern slope of the Aleutian Islands, through Amchitka Pass (180°W), and then eastward along the northern slope as the season progresses, reaching the Bering Canyon. However, Lagrangian particle tracking on this surface shows that very few floats released over the slope south of Amukta Pass (172°W) will end up in the Aleutian North Slope Current. The warming in the Aleutian North Slope Current at the depth of the 26.8‐kg/m3 isopycnal can be explained as resulting from a tidally enhanced downward vertical turbulent flux of warmer water which has been advected eastward in faster flowing waters at shallower depths. This hypothesis is confirmed by the heat equation term balance analysis and Lagrangian particle tracking on the 26.8‐kg/m3 surface and a shallower, 26.4‐kg/m3 surface. The model shows that the warm slope current separates into the basin near several topographical features, particularly at 178°W (just east of Amchitka Pass) and 174°W (Atka Island). North of Amukta Pass, the warmer pattern is strongly modulated at the tidal and fortnightly time scales and is associated with mixing in and transport through the pass.
Revisiting the Basis of Sensitivity Analysis for Dynamical Earth System Models
Authors: Gupta Hoshin V. , Razavi Saman 
Published: November 2018

AbstractThis paper investigates the problem of global sensitivity analysis (GSA) of Dynamical Earth System Models and proposes a basis for how such analyses should be performed. We argue that (a) performance metric‐based approaches to parameter GSA are actually identifiability analyses, (b) the use of a performance metric to assess sensitivity unavoidably distorts the information provided by the model about relative parameter importance, and (c) it is a serious conceptual flaw to interpret the results of such an analysis as being consistent and accurate indications of the sensitivity of the model response to parameter perturbations. Further, because such approaches depend on availability of system state/output observational data, the analysis they provide is necessarily incomplete. Here we frame the GSA problem from first principles, using trajectories of the partial derivatives of model outputs with respect to controlling factors as the theoretical basis for sensitivity, and construct a global sensitivity matrix from which statistical indices of total period time‐aggregateparameter importance, and time series of time‐varying parameter importance, can be inferred. We demonstrate this framework using theHBV‐SASKconceptual hydrologic model applied to the Oldman basin in Canada and show that it disagrees with performance metric‐based methods regarding which parameters exert the strongest controls on model behavior. Further, it is highly efficient, requiring less than 1,000 base samples to obtain stable and robust parameter importance assessments for our 10‐parameter example.
Sofosbuvir-Based Therapy in Hepatitis C Virus-Infected Cancer Patients: A Prospective Observational Study
Authors: Torres Harrys A. , Economides Minas P. , Angelidakis Georgios , Hosry Jeff , Kyvernitakis Andreas , Mahale Parag , Jiang Ying , Miller Ethan , Blechacz Boris , Naing Aung , Samaniego Felipe , Kaseb Ahmed , Raad Issam I. , Granwehr Bruno P. 
Published: November 2018

BACKGROUND:
Data are sparse on treatment of chronic hepatitis C virus (HCV) in cancer patients. We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in cancer patients.

METHODS:
Patients treated with SOFBT at our center during 2014–2017 were included in a prospective observational study. Efficacy [sustained virologic response at 12 weeks after the end of treatment (SVR12)], cancer-related outcomes and adverse events (AEs) were assessed.

RESULTS:
We included 153 patients. Most were men (109; 71%), white (92; 60%), non-cirrhotic (105; 69%), and with HCV genotype 1 (110; 72%). The most common cancers were hepatocellular carcinoma (HCC) (27; 18%) and multiple myeloma (14; 9%). The overall SVR12 rate was 91% (128/141). SVR12 was 100% in patients treated with ledipasvir/sofosbuvir for 8 weeks. Of the 32 patients initially excluded from cancer clinical trials because of HCV, 27 (84%) were granted cancer therapy access after starting SOFBT. Six patients with indolent non-Hodgkin’s lymphoma (NHL) received SOFBT without cancer treatment. Two achieved complete remission, one had partial remission, and two had stable cancer. Within 6 months after SOFBT, 5% (6/121) of patients in remission or with stable cancer, had progression or recurrence (two with HCC and one each with esophageal cancer, cholangiocarcinoma, NHL, and tonsillar cancer). No de novo HCCs occurred. AEs were most commonly grade 1–2 (90%).

CONCLUSIONS:
SOFBT in HCV-infected cancer patients is effective and safe, may permit access to investigational cancer therapy expanding treatment options, may induce remission of NHL, and may be used for 8 weeks.
Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts
Authors: Faict Sylvia , Muller Joséphine , De Veirman Kim , De Bruyne Elke , Maes Ken , Vrancken Louise , Heusschen Roy , De Raeve Hendrik , Schots Rik , Vanderkerken Karin , Caers Jo , Menu Eline 
Published: November 2018

AbstractProgression of multiple myeloma (MM) is largely dependent on the bone marrow (BM) microenvironment wherein communication through different factors including extracellular vesicles takes place. This cross-talk not only leads to drug resistance but also to the development of osteolysis. Targeting vesicle secretion could therefore simultaneously ameliorate drug response and bone disease. In this paper, we examined the effects of MM exosomes on different aspects of osteolysis using the 5TGM1 murine model. We found that 5TGM1 sEVs, or ‘exosomes’, not only enhanced osteoclast activity, they also blocked osteoblast differentiation and functionality in vitro. Mechanistically, we could demonstrate that transfer of DKK-1 led to a reduction in Runx2, Osterix, and Collagen 1A1 in osteoblasts. In vivo, we uncovered that 5TGM1 exosomes could induce osteolysis in a similar pattern as the MM cells themselves. Blocking exosome secretion using the sphingomyelinase inhibitor GW4869 not only increased cortical bone volume, but also it sensitized the myeloma cells to bortezomib, leading to a strong anti-tumor response when GW4869 and bortezomib were combined. Altogether, our results indicate an important role for exosomes in the BM microenvironment and suggest a novel therapeutic target for anti-myeloma therapy.
miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer
Authors: Yan Meina , Yang Xinxin , Shen Rong , Wu Chengjiang , Wang Hui , Ye Qing , Yang Peifang , Zhang Lubin , Chen Miao , Wan Bing , Zhang Qinqin , Xia Sheng , Lu Xiaodong , Shao Genbao , Zhou Xiaoming , Yu Jun , Shao Qixiang 
Published: November 2018

AbstractEpithelial ovarian carcinoma (EOC) is the most lethal gynecologic malignancy. However, the molecular mechanisms remain unclear. In this study, we found that miR-146b was downregulated in EOC and its expression level was negatively correlated with the pathological staging. Follow-up functional experiments illustrated that overexpression of miR-146b significantly inhibited cell migration and invasion, and increased cell proliferation, but it also improved the response to chemotherapeutic agents. Mechanistically, we demonstrated that miR-146b exerted its function mainly through inhibiting F-box and leucine-rich repeat protein 10 (FBXL10), and upregulated the Cyclin D1, vimentin (VIM), and zona-occludens-1 (ZO-1) expression in EOC. These findings indicate that miR-146b–FBXL10 axis is an important epigenetic regulation pathway in EOC. Low miR-146b may contribute to cancer progression from primary stage to advanced stage, and may be the promising therapeutic target of EOC.
Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and presynaptic plasticity
Authors: Barthet Gaël , Jordà-Siquier Tomàs , Rumi-Masante Julie , Bernadou Fanny , Müller Ulrike , Mulle Christophe 
Published: November 2018

AbstractMutations of the intramembrane protease presenilin (PS) or of its main substrate, the amyloid precursor protein (APP), cause early-onset form of Alzheimer disease. PS and APP interact with proteins of the neurotransmitter release machinery without identified functional consequences. Here we report that genetic deletion of PS markedly decreases the presynaptic levels of the Ca2+sensor synaptotagmin-7 (Syt7) leading to impaired synaptic facilitation and replenishment of synaptic vesicles. The regulation of Syt7 expression by PS occurs post-transcriptionally and depends on γ-secretase proteolytic activity. It requires the substrate APP as revealed by the combined genetic invalidation of APP and PS1, and in particular the APP-Cterminal fragments which interact with Syt7 and accumulate in synaptic terminals under pharmacological or genetic inhibition of γ-secretase. Thus, we uncover a role of PS in presynaptic mechanisms, through APP cleavage and regulation of Syt7, that highlights aberrant synaptic vesicle processing as a possible new pathway in AD.
Conformational ensemble of the human TRPV3 ion channel
Authors: Zubcevic Lejla , Herzik Mark A. , Wu Mengyu , Borschel William F. , Hirschi Marscha , Song Albert S. , Lander Gabriel C. , Lee Seok-Yong 
Published: November 2018

AbstractTransient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as a key regulator of normal skin physiology through the release of pro-inflammatory messengers. Mutations in trpv3 have been identified as the cause of the congenital skin disorder, Olmsted syndrome. Unlike other members of the thermoTRPV channel family, TRPV3 sensitizes upon repeated stimulation, yet a lack of structural information about the channel precludes a molecular-level understanding of TRPV3 sensitization and gating. Here, we present the cryo-electron microscopy structures of apo and sensitized human TRPV3, as well as several structures of TRPV3 in the presence of the common thermoTRPV agonist 2-aminoethoxydiphenyl borate (2-APB). Our results show α-to-π-helix transitions in the S6 during sensitization, and suggest a critical role for the S4-S5 linker π-helix during ligand-dependent gating.
ΦCrAss001 represents the most abundant bacteriophage family in the human gut and infects Bacteroides intestinalis
Authors: Shkoporov Andrey N. , Khokhlova Ekaterina V. , Fitzgerald C. Brian , Stockdale Stephen R. , Draper Lorraine A. , Ross R. Paul , Hill Colin 
Published: November 2018

AbstractCrAssphages are an extensive and ubiquitous family of tailed bacteriophages, predicted to infect bacteria of the order Bacteroidales. Despite being found in ~50% of individuals and representing up to 90% of human gut viromes, members of this viral family have never been isolated in culture and remain understudied. Here, we report the isolation of a CrAssphage (ΦCrAss001) from human faecal material. This bacteriophage infects the human gut symbiont Bacteroides intestinalis, confirming previous in silico predictions of the likely host. DNA sequencing demonstrates that the bacteriophage genome is circular, 102 kb in size, and has unusual structural traits. In addition, electron microscopy confirms that ΦcrAss001 has a podovirus-like morphology. Despite the absence of obvious lysogeny genes, ΦcrAss001 replicates in a way that does not disrupt proliferation of the host bacterium, and is able to maintain itself in continuous host culture during several weeks.
Two-step self-assembly of a spider silk molecular clamp
Authors: Rat Charlotte , Heiby Julia C. , Bunz Jessica P. , Neuweiler Hannes 
Published: November 2018

AbstractWeb spiders synthesize silk fibers of unique strength and extensibility through the controlled self-assembly of protein building blocks, so-called spidroins. The spidroin C-terminal domain is highly conserved and connects two polypeptide chains through formation of an all-helical, intertwined dimer. Here we use contact-induced fluorescence self-quenching and resonance energy transfer in combination with far-UV circular dichroism spectroscopy as three orthogonal structural probes to dissect the mechanism of folding and dimerization of a spidroin C-terminal domain from the major ampullate gland of the nursery web spider Euprosthenops australis. We show that helices forming the dimer core assemble very rapidly and fold on association. Subsequently, peripheral helices fold and dock slowly onto the preformed core. Lability of outer helices facilitates formation of a highly expanded, partially folded dimer. The high end-to-end distance of chain termini in the partially folded dimer suggests an extensibility module that contributes to elasticity of spider silk.
Superconductivity in a 122-type Fe-based compound (La,Na,K)Fe2As2
Authors: Kawashima Kenji , Ishida Shigeyuki , Fujihisa Hiroshi , Gotoh Yoshito , Yoshida Yoshiyuki , Eisaki Hiroshi , Ogino Hiraku , Iyo Akira 
Published: November 2018

AbstractWe synthesized a Fe-based superconductor (FeSC), (La,Na,K)Fe2As2, and characterized its superconducting properties. It was found that (La,Na,K)Fe2As2 has a 122-type (ThCr2Si2-type) structure with a space group I4/mmm (No. 139), identical to (Ba,K)Fe2As2 and (La,Na)Fe2As2 but distinct from so-called 1144-type FeSCs such as CaKFe4As4 and (La,Na)CsFe4As4. The results demonstrate that the formation of the 1144-type phase necessitates the large ionic radius mismatch among the so-called A-site constituent elements of the AFe2As2 formula. The lattice constants are a = 3.850(1) Å and c = 13.21(1) Å. The La, Na, and K ions occupy the same atomic site of Wyckoff position 1a. Electrical resistivity and magnetic susceptibility show the superconducting transition at 22.5 K. The transition temperature (Tc) of (La,Na,K)Fe2As2 is comparable with that of 122-type (La,Na)Fe2As2 and 1144-type (La,Na)AFe4As4 (A = Rb, Cs), while being more than 10 K lower than those of typical 122- and 1144-type FeSCs. The results suggest that the random distribution of La3+ and Na+ ions is the main reason for lower Tc in the AE = (La,Na) 122-type and 1144-type FeSCs.
Elevated ADAMTS13 Activity is Associated with Poor Postoperative Outcome in Patients Undergoing Liver Resection
Authors: Haegele Stefanie , Fuxsteiner Jennifer , Pereyra David , Koeditz Christoph , Rumpf Benedikt , Schuetz Clara , Schwarz Christian , Brostjan Christine , Gruenberger Thomas , Starlinger Patrick 
Published: November 2018

AbstractRecently, von-Willebrand-Factor (vWF) has been shown to correlate with postoperative liver dysfunction (LD). Accordingly, “disintegrin-like metalloprotease with thrombospondin type1 motif” (ADAMTS13) is known to cleave vWF in less active fragments. Thus, we aimed to evaluate the diagnostic potential of ADAMTS13-activity (ADAMTS13-AC) to identify patients with postoperative LD after hepatectomy. Accordingly 37 patients undergoing hepatectomy for different neoplastic entities were included in this study. Plasma ADAMTS13-AC and vWF-Ag were measured 1 day prior to (preOP), 1 and 5 days (POD1/5) after hepatectomy. In accordance to the ISGLS-criteria LD was prospectively recorded. In this context, perioperative ADAMTS13-AC- and vWF-Ag/ADAMTS13-AC-ratio- levels revealed a significant increase after hepatectomy. Accordingly, elevated vWF-Ag/ADAMTS13-AC-ratio significantly predicted LD (preOP AUC: 0.75, p = 0.02; POD1 AUC: 0.80, p = 0.03). Patients who fulfilled our perioperative vWF-Ag/ADAMTS13-AC-ratio cut-off-levels (preOP: ≥116, POD1: ≥165) suffered from significantly higher incidences of LD (preOP: 70% vs. 30%, p = 0.01; POD1: 83% vs. 17%, p = 0.001). In conclusion, perioperative ADAMTS13-AC measurement may serve as a useful parameter to early detect high-risk patients developing postoperative LD prior to liver resection in patients suffering from hepatic malignancies. Indeed, further investigations have to be performed to consolidate its role as a predictive marker for LD.
Integrated Population Modeling Provides the First Empirical Estimates of Vital Rates and Abundance for Polar Bears in the Chukchi Sea
Authors: Regehr Eric V. , Hostetter Nathan J. , Wilson Ryan R. , Rode Karyn D. , Martin Michelle St. , Converse Sarah J. 
Published: November 2018

AbstractLarge carnivores are imperiled globally, and characteristics making them vulnerable to extinction (e.g., low densities and expansive ranges) also make it difficult to estimate demographic parameters needed for management. Here we develop an integrated population model to analyze capture-recapture, radiotelemetry, and count data for the Chukchi Sea subpopulation of polar bears (Ursus maritimus), 2008–2016. Our model addressed several challenges in capture-recapture studies for polar bears by including a multievent structure reflecting location and life history states, while accommodating state uncertainty. Female breeding probability was 0.83 (95% credible interval [CRI] = 0.71–0.90), with litter sizes of 2.18 (95% CRI = 1.71–2.82) for age-zero and 1.61 (95% CRI = 1.46–1.80) for age-one cubs. Total adult survival was 0.90 (95% CRI = 0.86–0.92) for females and 0.89 (95% CRI = 0.83–0.93) for males. Spring on-ice densities west of Alaska were 0.0030 bears/km2(95% CRI = 0.0016–0.0060), similar to 1980s-era density estimates although methodological differences complicate comparison. Abundance of the Chukchi Sea subpopulation, derived by extrapolating density from the study area using a spatially-explicit habitat metric, was 2,937 bears (95% CRI = 1,552–5,944). Our findings are consistent with other lines of evidence suggesting the Chukchi Sea subpopulation has been productive in recent years, although it is uncertain how long this will continue given sea-ice loss due to climate change.