bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of avoidance: political questions before international courts
Authors: Odermatt Jed 
Published: May 2018

AbstractInternational courts (ICs) have found themselves dealing with issues that are ‘political’ in nature. This paper discusses the techniques of avoidance ICs have developed to navigate such highly political or sensitive issues. The first part discusses some of the key rationales for avoidance. Drawing on the discussion of the political question doctrine in US constitutional law, it shows how ICs may justify avoidance on both principled and pragmatic grounds. It then discusses the different types of avoidance strategies employed by ICs, based on examples from the Court of Justice of the European Union, the International Court of Justice and the East African Court of Justice. ICs are rarely upfront about avoidance strategies. Rather, ICs tend to avoid cases in a more subtle fashion, relying on procedural rules to exclude a case, or by resolving the dispute in a way that avoids the most politically sensitive questions and controversies.
An Economical Model for Simulating Turbulence Enhancement of Droplet Collisions and Coalescence
Authors: Krueger Steven K. , Kerstein Alan R. 
Published: May 2018

AbstractClusColl, an economical simulation method for droplet motions and collisions in turbulent flows, has been developed, implemented, tested, and applied. In the Linear Eddy Model, permutations called triplet maps representing individual turbulent eddies implement turbulent advection of fluid in 1‐D. This captures flow processes down to the smallest turbulent eddy (Kolmogorov microscale), but the inertial response of small Stokes number droplets to turbulence has important features at scales down to the droplet radius, notably sub‐Kolmogorov‐scale clustering of finite‐inertia droplets that can increase collision rates significantly. Additionally, shear due to the smallest scales of turbulence increases collision rates of zero‐inertia droplets. In ClusColl, a 3‐D triplet map for droplets captures both effects. We implemented collision detection, enabling simulation of droplet collisions and coalescence, and a sedimentation treatment in ClusColl. Published direct numerical simulations (DNSs) of monodispersions were used to tune parameters. For sedimenting droplets in turbulence, ClusColl's turbulent enhancement of bidisperse collision kernels agrees reasonably well with published DNS results. We compared ClusColl and DNS coalescence growth results. For weak turbulence (ε≤100 cm2/s3), ClusColl's turbulent enhancement of coalescence growth closely matches that of the DNS. For ε≥200 cm2/s3, lack of accurate collision efficiencies precludes definitive quantitative evaluation of ClusColl's coalescence growth. In a comparison of coalescence growth dependence on the droplet size distribution width and on turbulent enhancement, ClusColl indicates that the latter dramatically accelerates cloud droplet conversion into raindrops, while the former has significantly less impact.
Improving Representation of Crop Growth and Yield in the Dynamic Land Ecosystem Model and Its Application to China
Authors: Zhang Jingting , Tian Hanqin , Yang Jia , Pan Shufen 
Published: May 2018

AbstractTo accurately assess the roles of agriculture in securing food security and maintaining environmental sustainability, it is essential to improve the representation of crop growth, development, and yield formation in global land models that traditionally focus on energy, water, carbon, and nitrogen exchanges between land and the atmosphere. In this study, a process‐based agricultural module has been coupled with the Dynamic Land Ecosystem Model (DLEM‐AG2.0) for assessing how multiple environmental factors (climate change, atmospheric CO2 concentration, tropospheric O3, and nitrogen deposition) and human activities (land use/cover change, nitrogen fertilizer use, and irrigation) have affected the crop growth, development, yield, carbon (C), nitrogen (N), and water cycles in agroecosystems. Here we describe the model structure for simulating crop growth, development, and yield formation in the DLEM‐AG2.0, and then we validate the model using field observations and a national yield survey for three major crops (wheat, maize, and rice) in China during 1980–2012. Results show that the DLEM‐AG2.0 is capable of simulating the dynamic processes of phenological development, leaf growth expansion, biomass accumulation, biomass allocation, and yield formation for wheat, maize, and rice with normalized root mean square errors of the simulations of less than 20%. Our model‐based yield estimation for the three major crops at the national scale for the period 1980–2012 is generally consistent with the national yield survey in China. The crop representation in the DLEM‐AG2.0 is flexible for extrapolating to a global scale after rigorous testing with both site‐specific and regional observations. Further advancement of agricultural modeling within the global land modeling framework will require consideration of human perception and behavior for adapting and mitigating global change.
Peruvian Altiplano Stratigraphy Highlights Along‐Strike Variability in Foreland Basin Evolution of the Cenozoic Central Andes
Authors: Sundell Kurt E. , Saylor Joel E. , Lapen Thomas J. , Styron Richard H. , Villarreal Dustin P. , Usnayo Paola , Cárdenas José 
Published: May 2018

AbstractRetroarc foreland basins in the Andean plateau contain critical information on geodynamic processes driving plateau development by providing a record of exhumation and sediment sourcing, as well as the timing, location, and magnitude of basin subsidence. However, this record is incomplete along orogenic strike and particularly limited in southern Peru. We measured ~6,200 m of nonmarine clastic strata in the northern Peruvian Altiplano, documented through lithofacies characterization and paleocurrent analysis, conglomerate clast counts, sandstone petrography, and detrital zircon U‐Pb geochronology; for the latter we employ quantitative detrital zircon interpretation methods including multidimensional scaling, mixture modeling, and quantification of zircon roundness. Results show dominant sediment sourcing from the Western Cordillera and/or western Altiplano. Sediment accumulation rates define an upward‐convex Paleogene subsidence profile consistent with deposition in a northeastward‐migrating flexural foreland basin system, with lithospheric loading from an increasingly proximal Western Cordilleran hinterland. Basin deposition following a 23–9 Ma angular unconformity shows a marked increase in sediment accumulation rates >800 m/Myr, interpreted as a departure from flexural subsidence. Results highlight along‐strike variability in Andean foreland basin evolution, as foredeep deposits are thicker, and the onset of rapid sediment accumulation occurs earlier in southern Peru compared to Bolivia and Argentina. Results tentatively support models of orogenic cyclicity and reveal that episodes of high‐flux magmatism in southern Peru are slightly out of phase with those documented in northwest Argentina, which may be controlled by preexisting Paleozoic‐Mesozoic structural and stratigraphic fabrics and the rate of underthrusting of melt‐fertile continental lower crust and mantle lithosphere.
Neogene 3‐D Structural Architecture of The North‐West Apennines: The Role of the Low‐Angle Normal Faults and Basement Thrusts
Authors: Molli G. , Carlini M. , Vescovi P. , Artoni A. , Balsamo F. , Camurri F. , Clemenzi L. , Storti F. , Torelli L. 
Published: May 2018

AbstractThe northern Apennines of Italy are a classical site for studying fundamental issues in tectonic studies, such as ophiolite formation and emplacement, kinematics of thrust wedges, role of in‐sequence and out‐of‐sequence thrusting, and of along strike segmentation, synorogenic versus postorogenic extension, and interplay between tectonics, erosion, and sedimentation. Accordingly, the northern Apennines have been extensively studied since more than two centuries ago. Despite the huge amount of available data with different resolution, a 3‐D comprehensive regional view combining in a modern framework all available surface and subsurface information for contiguous sectors of the chain is still lacking. We performed such an attempt in the area framed between the Taro valley to the north and the northern termination of the Alpi Apuane to the south. The region includes the main morphostructural zones of the north‐west Apennines from the Tyrrhenian coast (SSW of La Spezia), through the main topographic divide of the Apennines, up to the foothills range of the chain to the north. The area has been investigated through a multidisciplinary approach that integrated surface geological data, collected during the last two decades of structural and stratigraphic field works, and subsurface geological data. The construction of two regional NE‐SW trending cross sections (the Levanto‐Pontremoli‐Parma to the north and the La Spezia‐ Sarzana‐North Apuane‐Cerreto to the south), intersected by a NW‐SE trending Taro‐Lunigiana‐Alpi Apuane composite section, allowed us to illustrate (i) the role of out‐of‐sequence blind thrusting in the basement and (ii) the presence of low‐angle normal faulting and its relationships with recent to active high‐angle normal faulting. Both extensional and contractional systems have relevant implications for the tectonics of the northern Apennines as well as the seismotectonics of the studied region.
HMGB1 released by irradiated tumor cells promotes living tumor cell proliferation via paracrine effect
Authors: He Sijia , Cheng Jin , Sun Lianhui , Wang Yiwei , Wang Chuangui , Liu Xinjian , Zhang Zhengxiang , Zhao Minghui , Luo Yuntao , Tian Ling , Li Chuanyuan , Huang Qian 
Published: May 2018

AbstractTumor repopulation during therapy is an important cause of treatment failure. Strategies to overcome repopulation are arising in parallel with advances in the comprehension of underlying biological mechanisms. Here, we reveal a new mechanism by which high mobility group box 1 (HMGB1) released by dying cells during radiotherapy or chemotherapy could stimulate living tumor cell proliferationInhibition or genetic ablation of HMGB1 suppressed tumor cell proliferation. This effect was due to binding of HMGB1with the member receptor for advanced glycation end-products (RAGE), which activated downstream ERK and p38 signaling pathway and promoted cell proliferation. Furthermore, higher HMGB1 expression in tumor tissue correlated with poor overall survival and higher HMGB1 concentration was detected in serum of patients who accepted radiotherapy. Collectively, the results from this study suggested that interaction between dead cells and surviving cells might influence the fate of tumor. HMGB1 could be a novel tumor promoter with therapeutic and prognostic relevance in cancers.
DSGOST regulates resistance via activation of autophagy in gastric cancer
Authors: Kim Tae Woo , Lee Seon Young , Kim Mia , Cheon Chunhoo , Jang Bo-Hyoung , Shin Yong Cheol , Ko Seong-Gyu 
Published: May 2018

AbstractDanggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST in Korean, Danggui-Sini-Jia-Wuzhuyu-Shengian-Tang in Chinese, and Tokishigyakukagoshuyushokyoto (TJ-38) in Japanese), a well-known traditional Korean/Chinese/Japanese medicine, has long been used to treat vascular diseases such as Raynaud’s phenomenon (RP). However, anticancer effect of DSGOST remains elusive. In this study, we checked if DSGOST has an anticancer effect against gastric cancer cells, and investigated the mechanisms underlying DSGOST resistance. Moreover, DSGOST regulates chemoresistance in cisplatin-treated gastric cancer cells. Interestingly, DSGOST treatment induced the accumulation of GFP-LC3 puncta and increased the level of autophagy markers, such as LC3-II, ATG5, and Beclin-1, indicating activated autophagy. Furthermore, DSGOST could activate epithelial-to-mesenchymal transition (EMT) and exosomes via induction of autophagy. DSGOST in combination with TGFβ also induced autophagy and EMT. However, autophagy inhibition induces DSGOST-mediated cell death in gastric cancer cells. In addition, autophagy inhibition blocks the activation of DSGOST-mediated EMT markers including N-cadherin, Snail, Slug, vimentin, β-catenin, p-Smad2, and p-Smad3. Taken together, these findings indicated that prosurvival autophagy was one of the mechanisms involved in the resistance of gastric cancer to DSGOST. Targeting the inhibition of autophagy could be an effective therapeutic approach to overcome resistance to DSGOST in gastric cancer.
S100A11 protects against neuronal cell apoptosis induced by cerebral ischemia via inhibiting the nuclear translocation of annexin A1
Authors: Xia Qian , Li Xing , Zhou Huijuan , Zheng Lu , Shi Jing 
Published: May 2018

AbstractThe subcellular location of annexin A1 (ANXA1) determines the ultimate fate of neurons after ischemic stroke. ANXA1 nuclear translocation is involved in neuronal apoptosis after cerebral ischemia, and extracellular ANXA1 is also associated with regulation of inflammatory responses. As the factors and mechanism that influence ANXA1 subcellular translocation remain unclear, studies aiming to determine and clarify the role of ANXA1 as a cell fate ‘regulator’ within cells are critically needed. In this study, we found that intracerebroventricular injection of the recombinant adenovirus vector Ad-S100A11 (carrying S100A11) strongly improved cognitive function and induced robust neuroprotective effects after ischemic stroke in vivo. Furthermore, upregulation of S100A11 protected against neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro. Surprisingly, S100A11 overexpression markedly decreased ANXA1 nuclear translocation and subsequently alleviated OGD/R-induced neuronal apoptosis. Notably, S100A11 exerted its neuroprotective effect by directly binding ANXA1. Importantly, S100A11 directly interacted with ANXA1 through the nuclear translocation signal (NTS) of ANXA1, which is essential for ANXA1 to import into the nucleus. Consistent with our previous studies, ANXA1 nuclear translocation after OGD/R promoted p53 transcriptional activity, induced mRNA expression of the pro-apoptotic Bid gene, and activated the caspase-3 apoptotic pathway, which was almost completely reversed by S100A11 overexpression. Thus, S100A11 protects against cell apoptosis by inhibiting OGD/R-induced ANXA1 nuclear translocation. This study provides a novel mechanism whereby S100A11 protects against neuronal cells apoptosis, suggesting the potential for a previously unidentified treatment strategy in minimizing apoptosis after ischemic stroke.
The novel histone de acetylase 6 inhibitor, MPT0G211, ameliorates tau phosphorylation and cognitive deficits in an Alzheimer’s disease model
Authors: Fan Sheng-Jun , Huang Fang-I , Liou Jing-Ping , Yang Chia-Ron 
Published: May 2018

AbstractAlzheimer’s disease (AD) is a dreadful neurodegenerative disease that leads to severe impairment of cognitive function, leading to a drastic decline in the quality of life. The primary pathological features of AD include senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs), comprising aggregated amyloid β (Aβ) and hyperphosphorylated tau protein, respectively, in the hippocampus of AD patients. Histone deacetylase 6 (HDAC6) is a key enzyme in this neurodegenerative disease, in particular, as it relates to tau hyperphosphorylation. This study aimed to investigate the protective effects and mechanism of the novel HDAC6 inhibitor, MPT0G211, using an AD model. Our results indicated that MPT0G211 significantly reduced tau phosphorylation and aggregation, the processes highly correlated with the formation of NFTs. This HDAC6 inhibitory activity resulted in an increase in acetylated Hsp90, which decreased Hsp90 and HDAC6 binding, causing ubiquitination of phosphorylated tau proteins. In addition, a significant increase of phospho-glycogen synthase kinase-3β (phospho-GSK3β) on Ser9 (the inactive form) through Akt phosphorylation was associated with the inhibition of phospho-tau Ser396 in response to MPT0G211 treatment. In AD in vivo models, MPT0G211 appeared to ameliorate learning and memory impairment in animals. Furthermore, MPT0G211 treatment reduced the amount of phosphorylated tau in the hippocampal CA1 region. In summary, MPT0G211 treatment appears to be a promising strategy for improving the AD phenotypes, including tau hyperphosphorylation and aggregation, neurodegeneration, and learning and memory impairment, making it a valuable agent for further investigation.
The cyclohexene derivative MC-3129 exhibits antileukemic activity via RhoA/ROCK1/PTEN/PI3K/Akt pathway-mediated mitochondrial translocation of cofilin
Authors: Zheng Yi , Ouyang Qin , Fu Ruoqiu , Liu Lei , Zhang Hongwei , Hu Xiaoye , Liu Yanxia , Chen Yingchun , Gao Ning 
Published: May 2018

AbstractThe effects of MC-3129, a synthetic cyclohexene derivative, on cell viability and apoptosis have been investigated in human leukemia cells. Exposure of leukemia cells to MC-3129 led to the inhibition of cell viability and induction of apoptosis through the dephosphorylation and mitochondrial translocation of cofilin. A mechanistic study revealed that interruption of the RhoA/ROCK1/PTEN/PI3K/Akt signaling pathway plays a crucial role in the MC-3129-mediated dephosphorylation and mitochondrial translocation of cofilin and induction of apoptosis. Our in vivo study also showed that the MC-3129-mediated inhibition of the tumor growth in a mouse leukemia xenograft model is associated with the interruption of ROCK1/PTEN/PI3K/Akt signaling and apoptosis. Molecular docking suggested that MC-3129 might activate the RhoA/ROCK1 pathway by targeting LPAR2. Collectively, these findings suggest a hierarchical model, in which the induction of apoptosis by MC-3129 primarily results from the activation of RhoA/ROCK1/PTEN and inactivation of PI3K/Akt, leading to the dephosphorylation and mitochondrial translocation of cofilin, and culminating in cytochrome c release, caspase activation, and apoptosis. Our study reveals a novel role for RhoA/ROCK1/PTEN/PI3K/Akt signaling in the regulation of mitochondrial translocation of cofilin and apoptosis and suggests MC-3129 as a potential drug for the treatment of human leukemia.
Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing
Authors: Ishihara Jun , Ishihara Ako , Fukunaga Kazuto , Sasaki Koichi , White Michael J. V. , Briquez Priscilla S. , Hubbell Jeffrey A. 
Published: May 2018

AbstractLaminin, as a key component of the basement membrane extracellular matrix (ECM), regulates tissue morphogenesis. Here, we show that multiple laminin isoforms promiscuously bind to growth factors (GFs) with high affinity, through their heparin-binding domains (HBDs) located in the α chain laminin-type G (LG) domains. These domains also bind to syndecan cell-surface receptors, promoting attachment of fibroblasts and endothelial cells. We explore the application of these multifunctional laminin HBDs in wound healing in the type-2 diabetic mouse. We demonstrate that covalent incorporation of laminin HBDs into fibrin matrices improves retention of GFs and significantly enhances the efficacy of vascular endothelial cell growth factor (VEGF-A165) and platelet-derived growth factor (PDGF-BB) in promoting wound healing in vivo, under conditions where the GFs alone in fibrin are inefficacious. This laminin HBD peptide may be clinically useful by improving biomaterial matrices as both GF reservoirs and cell scaffolds, leading to effective tissue regeneration.
Model structures amplify uncertainty in predicted soil carbon responses to climate change
Authors: Shi Zheng , Crowell Sean , Luo Yiqi , Moore Berrien 
Published: May 2018

AbstractLarge model uncertainty in projected future soil carbon (C) dynamics has been well documented. However, our understanding of the sources of this uncertainty is limited. Here we quantify the uncertainties arising from model parameters, structures and their interactions, and how those uncertainties propagate through different models to projections of future soil carbon stocks. Both the vertically resolved model and the microbial explicit model project much greater uncertainties to climate change than the conventional soil C model, with both positive and negative C-climate feedbacks, whereas the conventional model consistently predicts positive soil C-climate feedback. Our findings suggest that diverse model structures are necessary to increase confidence in soil C projection. However, the larger uncertainty in the complex models also suggests that we need to strike a balance between model complexity and the need to include diverse model structures in order to forecast soil C dynamics with high confidence and low uncertainty.
Planar cell polarity signalling coordinates heart tube remodelling through tissue-scale polarisation of actomyosin activity
Authors: Merks Anne Margarete , Swinarski Marie , Meyer Alexander Matthias , Müller Nicola Victoria , Özcan Ismail , Donat Stefan , Burger Alexa , Gilbert Stephen , Mosimann Christian , Abdelilah-Seyfried Salim , Panáková Daniela 
Published: May 2018

AbstractDevelopment of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping. Although many molecular factors regulating the process of cardiac chamber ballooning have been identified, the cellular mechanisms underlying the chamber formation remain unclear. Here, we demonstrate that cardiac chambers remodel by cell neighbour exchange of cardiomyocytes guided by the planar cell polarity (PCP) pathway triggered by two non-canonical Wnt ligands, Wnt5b and Wnt11. We find that PCP signalling coordinates the localisation of actomyosin activity, and thus the efficiency of cell neighbour exchange. On a tissue-scale, PCP signalling planar-polarises tissue tension by restricting the actomyosin contractility to the apical membranes of outflow tract cells. The tissue-scale polarisation of actomyosin contractility is required for cardiac looping that occurs concurrently with chamber ballooning. Taken together, our data reveal that instructive PCP signals couple cardiac chamber expansion with cardiac looping through the organ-scale polarisation of actomyosin-based tissue tension.
Artificial strain of human prions created in vitro
Authors: Kim Chae , Xiao Xiangzhu , Chen Shugui , Haldiman Tracy , Smirnovas Vitautas , Kofskey Diane , Warren Miriam , Surewicz Krystyna , Maurer Nicholas R. , Kong Qingzhong , Surewicz Witold , Safar Jiri G. 
Published: May 2018

AbstractThe molecular mechanism that determines under physiological conditions transmissibility of the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD) is unknown. We report the synthesis of new human prion from the recombinant human prion protein expressed in bacteria in reaction seeded with sCJD MM1 prions and cofactor, ganglioside GM1. These synthetic human prions were infectious to transgenic mice expressing non-glycosylated human prion protein, causing neurologic dysfunction after 459 and 224 days in the first and second passage, respectively. The neuropathology, replication potency, and biophysical profiling suggest that a novel, particularly neurotoxic human prion strain was created. Distinct biological and structural characteristics of our synthetic human prions suggest that subtle changes in the structural organization of critical domains, some linked to posttranslational modifications of the pathogenic prion protein (PrPSc), play a crucial role as a determinant of human prion infectivity, host range, and targetting of specific brain structures in mice models.