bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viscoplastic Interpretation of Localized Compaction Creep in Porous Rock
Authors: Shahin Ghassan , Marinelli Ferdinando , Buscarnera Giuseppe 
Published: July 2019

AbstractRecent laboratory evidence shows that compaction creep in porous rocks may develop through stages of acceleration, especially if the material is susceptible to strain localization. This paper provides a mechanical interpretation of compaction creep based on viscoplasticity and nonlinear dynamics. For this purpose, a constitutive operator describing the evolution of compaction creep is defined to evaluate the spontaneous accumulation of pore collapse within an active compaction band. This strategy enables the determination of eigenvalues associated with the stability of the response which is able to differentiate decelerating from accelerating strain. This mathematical formalism was linked to a constitutive law able to simulate compaction localization. Material point simulations were then used to identify the region of the stress space where unstable compaction creep is expected, showing that accelerating strains correspond to pulses of inelastic strain rate. Such pulses were also found in full‐field numerical analyses of delayed compaction, revealing that they correspond to stages of inception and propagation of new bands across the volume of the simulated sample. These results illustrate the intimate relation between the spatial patterns of compaction and their temporal dynamics, showing that while homogeneous compaction develops with decaying rates of accumulation, localized compaction occurs through stages of accelerating deformation caused by the loss of strength taking place during the formation of a band. In addition, they provide a predictive modeling framework to simulate and explain the spatio‐temporal dynamics of compaction in porous sedimentary formations.
Global Soil Moisture‐Air Temperature Coupling Based on GRACE‐Derived Terrestrial Water Storage
Authors: Chen Ajiao , Guan Huade , Batelaan Okke , Zhang Xinping , He Xinguang 
Published: July 2019

AbstractUnderstanding global soil moisture‐air temperature (θ‐Ta) coupling is needed to improve the representation of land‐atmosphere interactions in Earth system models. Most studies on θ‐Ta coupling have focused on hot extremes, where precipitation‐related indices and model‐derived soil moisture products are commonly used. In this study, global θ‐Ta coupling is examined based on monthly air temperature anomalies and the Gravity Recovery and Climate Experiment (GRACE) terrestrial water storage (TWS). A discrete wavelet decomposition is used to partition the TWS into different components. The results show that TWS is useful in revealing the spatial patterns of θ‐Ta coupling. Decomposed GRACE TWS shows improved skill compared to raw TWS in explaining temporal variability of monthly air temperature, which likely reflects different roles of soil moisture at different depths in the θ‐Ta coupling. The explanatory power improves further by using a combination of decomposed GRACE TWS and precipitation. Such improvement is observed particularly in places where vegetation tends to have a deeper rooting system, such as eastern region of South America, the southern tip of Africa, and north of the Tropic of Capricorn in Australia. The occurrence of θ‐Ta coupling is mainly constrained by the coupling of root zone moisture and land surface temperature. In addition to deeper rooting systems, clear wet and dry season alternation is another favorable factor for developing significant monthly θ‐Ta coupling.
Landscape Response to Lateral Advection in Convergent Orogens Over Geologic Time Scales
Authors: Eizenhöfer Paul R. , McQuarrie Nadine , Shelef Eitan , Ehlers Todd A. 
Published: July 2019

AbstractConvergent orogens exhibit high elevations and relief, features characteristic of active rock uplift, the latter influencing normalized channel steepness (Ksn). In systems with significant horizontal displacement, Ksn values and interfluves are elevated over a region of tens of kilometers and gradually decline in the direction of rock advection. To evaluate potential relationships between elevated Ksn, a gradual decline in interfluve elevation (i.e., tapered topography), and lateral advection, we integrated kinematic models that simulate advection over a midcrustal ramp with a 2‐D surface processes model. Varying convergence rate, bedrock erodibility, and ramp angle, we tracked topographic evolution over time. The process of advection through the region of active rock uplift above a midcrustal ramp is preserved in the geomorphic record through transient legacy landscapes characterized by (i) high‐relief, advection‐parallel interfluves, (ii) tapered topography, (iii) elevated and gradually declining Ksn values, and (iv) higher Ksn in trunk relative to tributary streams likely reflecting the influence of increased sediment flux, elevated interfluves, and changes in drainage area. The width of legacy landscapes provides a minimum constraint on the total lateral displacement, controlled by the duration of ramp activity and the rates of advection and erosion. The development of legacy landscapes is facilitated by spatial variations in flow convergence that occur in a 2‐D setting but are not captured in idealized 1‐D approaches. The presence of elevated Ksn and high relief, advection‐parallel interfluves beyond the region of active rock uplift likely reflects the horizontal advection component inherent to convergent orogenic systems.
Counter‐Electrojet Occurrence as Observed From C/NOFS Satellite and Ground‐Based Magnetometer Data Over the African and American Sectors
Authors: Habarulema John Bosco , Lefebvre Gabrielle , Moldwin Mark B. , Katamzi‐Joseph Zama T , Yizengaw Endawoke 
Published: July 2019

AbstractAn analysis of the counter‐electrojet occurrence (CEJ) during 2008–2014 is presented for the African and American sectors based on local daytime (0700–1700 LT) observations from the Communications and Navigation Outage Forecasting System (C/NOFS) vertical ion plasma drift (equivalent to vertical E×B at an altitude of about 400 km) and ground‐based magnetometers. Using quiet time (Kp≤ 3) data, differences and/or similarities between the two data sets with reference to local time and seasonal dependence are established. For the first time, it is shown that C/NOFS satellite data are consistent with magnetometer observations in identifying CEJ occurrences during all seasons. However, C/NOFS satellite data show higher CEJ occurrence rate for almost all seasons. With respect to local time, C/NOFS satellite observes more CEJ events than magnetometer observations by average of about 20% and 40% over the American and African sectors, respectively, despite both data sets showing similar trends in CEJ identification. Therefore, when a space weather event occurs, it is important to first establish the original variability nature and/or magnitude of the eastward electric field in equatorial regions before attributing the resulting changes to solar wind‐magnetosphere and ionosphere coupling processes since CEJ events can be present even during quiet conditions.
Target preference of Type III-A CRISPR-Cas complexes at the transcription bubble
Authors: Liu Tina Y. , Liu Jun-Jie , Aditham Abhishek J. , Nogales Eva , Doudna Jennifer A. 
Published: July 2019

AbstractType III-A CRISPR-Cas systems are prokaryotic RNA-guided adaptive immune systems that use a protein-RNA complex, Csm, for transcription-dependent immunity against foreign DNA. Csm can cleave RNA and single-stranded DNA (ssDNA), but whether it targets one or both nucleic acids during transcription elongation is unknown. Here, we show that binding of a Thermus thermophilus (T. thermophilus) Csm (TthCsm) to a nascent transcript in a transcription elongation complex (TEC) promotes tethering but not direct contact of TthCsm with RNA polymerase (RNAP). Biochemical experiments show that both TthCsm and Staphylococcus epidermidis (S. epidermidis) Csm (SepCsm) cleave RNA transcripts, but not ssDNA, at the transcription bubble. Taken together, these results suggest that Type III systems primarily target transcripts, instead of unwound ssDNA in TECs, for immunity against double-stranded DNA (dsDNA) phages and plasmids. This reveals similarities between Csm and eukaryotic RNA interference, which also uses RNA-guided RNA targeting to silence actively transcribed genes.
Zero-field nuclear magnetic resonance of chemically exchanging systems
Authors: Barskiy Danila A. , Tayler Michael C. D. , Marco-Rius Irene , Kurhanewicz John , Vigneron Daniel B. , Cikrikci Sevil , Aydogdu Ayca , Reh Moritz , Pravdivtsev Andrey N. , Hövener Jan-Bernd , Blanchard John W. , Wu Teng , Budker Dmitry , Pines Alexander 
Published: July 2019

AbstractZero- to ultralow-field (ZULF) nuclear magnetic resonance (NMR) is an emerging tool for precision chemical analysis. In this work, we study dynamic processes and investigate the influence of chemical exchange on ZULF NMR J-spectra. We develop a computational approach that allows quantitative calculation of J-spectra in the presence of chemical exchange and apply it to study aqueous solutions of [15N]ammonium (15N$${\mathrm{H}}_4^ +$$

H

4

+

) as a model system. We show that pH-dependent chemical exchange substantially affects the J-spectra and, in some cases, can lead to degradation and complete disappearance of the spectral features. To demonstrate potential applications of ZULF NMR for chemistry and biomedicine, we show a ZULF NMR spectrum of [2-13C]pyruvic acid hyperpolarized via dissolution dynamic nuclear polarization (dDNP). We foresee applications of affordable and scalable ZULF NMR coupled with hyperpolarization to study chemical exchange phenomena in vivo and in situations where high-field NMR detection is not possible to implement.
Metformin induces lipogenic differentiation in myofibroblasts to reverse lung fibrosis
Authors: Kheirollahi Vahid , Wasnick Roxana M. , Biasin Valentina , Vazquez-Armendariz Ana Ivonne , Chu Xuran , Moiseenko Alena , Weiss Astrid , Wilhelm Jochen , Zhang Jin-San , Kwapiszewska Grazyna , Herold Susanne , Schermuly Ralph T. , Mari Bernard , Li Xiaokun , Seeger Werner , Günther Andreas , Bellusci Saverio , El Agha Elie 
Published: July 2019

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal disease in which the intricate alveolar network of the lung is progressively replaced by fibrotic scars. Myofibroblasts are the effector cells that excessively deposit extracellular matrix proteins thus compromising lung structure and function. Emerging literature suggests a correlation between fibrosis and metabolic alterations in IPF. In this study, we show that the first-line antidiabetic drug metformin exerts potent antifibrotic effects in the lung by modulating metabolic pathways, inhibiting TGFβ1 action, suppressing collagen formation, activating PPARγ signaling and inducing lipogenic differentiation in lung fibroblasts derived from IPF patients. Using genetic lineage tracing in a murine model of lung fibrosis, we show that metformin alters the fate of myofibroblasts and accelerates fibrosis resolution by inducing myofibroblast-to-lipofibroblast transdifferentiation. Detailed pathway analysis revealed a two-arm mechanism by which metformin accelerates fibrosis resolution. Our data report an antifibrotic role for metformin in the lung, thus warranting further therapeutic evaluation.
Survival probability of stochastic processes beyond persistence exponents
Authors: Levernier N. , Dolgushev M. , Bénichou O. , Voituriez R. , Guérin T. 
Published: July 2019

AbstractFor many stochastic processes, the probability$$S(t)$$S(t)of not-having reached a target in unbounded space up to time$$t$$tfollows a slow algebraic decay at long times,$$S(t) \sim {S}_{0}/{t}^{\theta }$$S(t)~S0∕tθ. This is typically the case of symmetric compact (i.e. recurrent) random walks. While the persistence exponent$$\theta$$θhas been studied at length, the prefactor$${S}_{0}$$S0, which is quantitatively essential, remains poorly characterized, especially for non-Markovian processes. Here we derive explicit expressions for$${S}_{0}$$S0for a compact random walk in unbounded space by establishing an analytic relation with the mean first-passage time of the same random walk in a large confining volume. Our analytical results for$${S}_{0}$$S0are in good agreement with numerical simulations, even for strongly correlated processes such as Fractional Brownian Motion, and thus provide a refined understanding of the statistics of longest first-passage events in unbounded space.
Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling
Authors: Robinson Brian D. , Vlachostergios Panagiotis J. , Bhinder Bhavneet , Liu Weisi , Li Kailyn , Moss Tyler J. , Bareja Rohan , Park Kyung , Tavassoli Peyman , Cyrta Joanna , Tagawa Scott T. , Nanus David M. , Beltran Himisha , Molina Ana M. , Khani Francesca , Miguel Mosquera Juan , Xylinas Evanguelos , Shariat Shahrokh F. , Scherr Douglas S. , Rubin Mark A. , Lerner Seth P. , Matin Surena F. , Elemento Olivier , Faltas Bishoy M. 
Published: July 2019

AbstractUpper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.
Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma
Authors: Hu Xin , Fujimoto Junya , Ying Lisha , Fukuoka Junya , Ashizawa Kazuto , Sun Wenyong , Reuben Alexandre , Chow Chi-Wan , McGranahan Nicholas , Chen Runzhe , Hu Jinlin , Godoy Myrna C. , Tabata Kazuhiro , Kuroda Kishio , Shi Lei , Li Jun , Behrens Carmen , Parra Edwin Roger , Little Latasha D. , Gumbs Curtis , Mao Xizeng , Song Xingzhi , Tippen Samantha , Thornton Rebecca L. , Kadara Humam , Scheet Paul , Roarty Emily , Ostrin Edwin Justin , Wang Xu , Carter Brett W. , Antonoff Mara B. , Zhang Jianhua , Vaporciyan Ara A. , Pass Harvey , Swisher Stephen G. , Heymach John V. , Lee J. Jack , Wistuba Ignacio I. , Hong Waun Ki , Futreal P. Andrew , Su Dan , Zhang Jianjun 
Published: July 2019

AbstractThere has been a dramatic increase in the detection of lung nodules, many of which are preneoplasia atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (ADC). The molecular landscape and the evolutionary trajectory of lung preneoplasia have not been well defined. Here, we perform multi-region exome sequencing of 116 resected lung nodules including AAH (n = 22), AIS (n = 27), MIA (n = 54) and synchronous ADC (n = 13). Comparing AAH to AIS, MIA and ADC, we observe progressive genomic evolution at the single nucleotide level and demarcated evolution at the chromosomal level supporting the early lung carcinogenesis model from AAH to AIS, MIA and ADC. Subclonal analyses reveal a higher proportion of clonal mutations in AIS/MIA/ADC than AAH suggesting neoplastic transformation of lung preneoplasia is predominantly associated with a selective sweep of unfit subclones. Analysis of multifocal pulmonary nodules from the same patients reveal evidence of convergent evolution.
Relaxin gene delivery mitigates liver metastasis and synergizes with check point therapy
Authors: Hu Mengying , Wang Ying , Xu Ligeng , An Sai , Tang Yu , Zhou Xuefei , Li Jingjing , Liu Rihe , Huang Leaf 
Published: July 2019

AbstractActivated hepatic stellate cell (aHSC)-mediated liver fibrosis is essential to the development of liver metastasis. Here, we discover intra-hepatic scale-up of relaxin (RLN, an anti-fibrotic peptide) in response to fibrosis along with the upregulation of its primary receptor (RXFP1) on aHSCs. The elevated expression of RLN serves as a natural regulator to deactivate aHSCs and resolve liver fibrosis. Therefore, we hypothesize this endogenous liver fibrosis repair mechanism can be leveraged for liver metastasis treatment via enforced RLN expression. To validate the therapeutic potential, we utilize aminoethyl anisamide-conjugated lipid-calcium-phosphate nanoparticles to deliver plasmid DNA encoding RLN. The nanoparticles preferentially target metastatic tumor cells and aHSCs within the metastatic lesion and convert them as an in situ RLN depot. Expressed RLN reverses the stromal microenvironment, which makes it unfavorable for established liver metastasis to grow. In colorectal, pancreatic, and breast cancer liver metastasis models, we confirm the RLN gene therapy results in significant inhibition of metastatic progression and prolongs survival. In addition, enforced RLN expression reactivates intra-metastasis immune milieu. The combination of the RLN gene therapy with PD-L1 blockade immunotherapy further produces a synergistic anti-metastatic efficacy. Collectively, the targeted RLN gene therapy represents a highly efficient, safe, and versatile anti-metastatic modality, and is promising for clinical translation.
Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes
Authors: Koedoot Esmee , Fokkelman Michiel , Rogkoti Vasiliki-Maria , Smid Marcel , van de Sandt Iris , de Bont Hans , Pont Chantal , Klip Janna E. , Wink Steven , Timmermans Mieke A. , Wiemer Erik A. C. , Stoilov Peter , Foekens John A. , Le Dévédec Sylvia E. , Martens John W. M. , van de Water Bob 
Published: July 2019

AbstractTtriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential for cancer cell migration, amplified in human primary breast tumors and associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF causes primarily down regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B is essential for TNBC metastasis formation in vivo, making PRPF4B a candidate for further drug development.
Divergent changes in the elevational gradient of vegetation activities over the last 30 years
Authors: Gao Mengdi , Piao Shilong , Chen Anping , Yang Hui , Liu Qiang , Fu Yongshuo H. , Janssens Ivan A. 
Published: July 2019

AbstractThe reported progressive change of vegetation activity along elevational gradients has important aesthetic and conservation values. With climate change, cooler locations are suggested to warm faster than warmer ones, raising concerns of a more homogenized landscape along the elevation. Here, we use global satellite data to investigate the spatio-temporal dynamics of the elevational gradient (EG) in vegetation greenness (NDVImax3), spring (SOS) and autumn phenology (EOS) during 1982–2015. Although we find clear geographical patterns of the EG in NDVImax3 and SOS, there are no prevalent trends of vegetation homogenization or phenology synchronization along elevational gradients. Possible mechanisms, including spatially heterogeneous temperature lapse rate changes, different vegetation sensitivities to climate change, and human disturbances, may play diverse roles across different regions. Our finding of mixed EG trends and no general rules controlling EG dynamics poses challenges for mitigating possible adverse impacts of climate change on mountainous biological diversity and ecosystem services.
Enhancement of laccase activity by pre-incubation with organic solvents
Authors: Wu Meng-Hsuan , Lin Meng-Chun , Lee Cheng-Chung , Yu Su-May , Wang Andrew H.-J. , Ho Tuan-Hua David 
Published: July 2019

AbstractLaccases that are tolerant to organic solvents are powerful bio-catalysts with broad applications in biotechnology. Most of these uses must be accomplished at high concentration of organic solvents, during which proteins undergo unfolding, thereby losing enzyme activity. Here we show that organic-solvent pre-incubation provides effective and reversible 1.5- to 4.0-fold enhancement of enzyme activity of fungal laccases. Several organic solvents, including acetone, methanol, ethanol, DMSO, and DMF had an enhancement effect among all laccases studied. The enhancement was not substrate-specific and could be observed by using both phenolic and non-phenolic substrates. Laccase preincubated with organic solvents was sensitive to high temperature but remained stable at 25 °C, for an advantage for long-term storage. The acetone-pre-incubated 3-D structure of DLac, a high-efficiency fungal laccase, was determined and confirmed that the DLac protein structure remains intact and stable at a high concentration of organic solvent. Moreover, the turnover rates of fungal laccases were improved after organic-solvent pre-incubation, with DLac showing the highest enhancement among the fungal laccases examined. Our investigation sheds light on improving fungal laccase usage under extreme conditions and extends opportunities for bioremediation, decolorization, and organic synthesis.
Cathepsin Z as a novel potential biomarker for osteoporosis
Authors: Dera Ayed A. , Ranganath Lakshminarayan , Barraclough Roger , Vinjamuri Sobhan , Hamill Sandra , Barraclough Dong L. 
Published: July 2019

AbstractOsteoporosis, one of the most prevalent chronic ageing-related bone diseases, often goes undetected until the first fragility fracture occurs, causing patient suffering and cost to health/social care services. Osteoporosis arises from imbalanced activity of osteoclasts and osteoblasts. Since these cell lineages produce the protease, cathepsin Z, the aim of this study was to investigate whether altered cathepsin Z mRNA levels are associated with osteoporosis in clinical samples. Cathepsin Z mRNA in human peripheral blood mononuclear cells was significantly differentially-expressed among non-osteoporotic controls, osteopenia and osteoporosis patients (p < 0.0001) and in female osteoporosis patients over the age of 50 years (P = 0.0016). Cathepsin Z mRNA level strongly correlated with low bone mineral density (BMD) (g/cm2), lumbar spine L2-L4 and femoral neck (T-scores) (P = 0.0149, 0.0002 and 0.0139, respectively). Importantly, cathepsin Z mRNA was significantly associated with fragility fracture in osteoporosis patients (P = 0.0018). The levels of cathepsin Z mRNA were not significantly higher in patients with chronic inflammatory disorders in these two groups compared to those without (P = 0.774 and 0.666, respectively). ROC analysis showed that cathepsin Z mRNA has strong diagnostic value for osteoporosis and osteoporotic fracture. The results show for the first time that cathepsin Z could be a future diagnostic biomarker for osteoporosis including female osteoporosis patients over the age of 50 years.