bluuebunny/crossref_metadata_2025 huggingface dataset:
Koopman analysis of the long-term evolution in a turbulent convection cell
Authors: Giannakis Dimitrios , Kolchinskaya Anastasiya , Krasnov Dmitry , Schumacher Jörg
Published: May 2018

We analyse the long-time evolution of the three-dimensional flow in a closed cubic turbulent Rayleigh–Bénard convection cell via a Koopman eigenfunction analysis. A data-driven basis derived from diffusion kernels known in machine learning is employed here to represent a regularized generator of the unitary Koopman group in the sense of a Galerkin approximation. The resulting Koopman eigenfunctions can be grouped into subsets in accordance with the discrete symmetries in a cubic box. In particular, a projection of the velocity field onto the first group of eigenfunctions reveals the four stable large-scale circulation (LSC) states in the convection cell. We recapture the preferential circulation rolls in diagonal corners and the short-term switching through roll states parallel to the side faces which have also been seen in other simulations and experiments. The diagonal macroscopic flow states can last as long as 1000 convective free-fall time units. In addition, we find that specific pairs of Koopman eigenfunctions in the secondary subset obey enhanced oscillatory fluctuations for particular stable diagonal states of the LSC. The corresponding velocity-field structures, such as corner vortices and swirls in the midplane, are also discussed via spatiotemporal reconstructions.
Vortex-induced vibration of a transversely rotating sphere
Authors: Rajamuni Methma M. , Thompson Mark C. , Hourigan Kerry
Published: May 2018

The effects of transverse rotation on the vortex-induced vibration (VIV) of a sphere in a uniform flow are investigated numerically. The one degree-of-freedom sphere motion is constrained to the cross-stream direction, with the rotation axis orthogonal to flow and vibration directions. For the current simulations, the Reynolds number of the flow, $Re=UD/\unicode[STIX]{x1D708}$, and the mass ratio of the sphere, $m^{\ast }=\unicode[STIX]{x1D70C}_{s}/\unicode[STIX]{x1D70C}_{f}$, were fixed at 300 and 2.865, respectively, while the reduced velocity of the flow was varied over the range $3.5\leqslant U^{\ast }~(\equiv U/(f_{n}D))\leqslant 11$, where, $U$ is the upstream velocity of the flow, $D$ is the sphere diameter, $\unicode[STIX]{x1D708}$ is the fluid viscosity, $f_{n}$ is the system natural frequency and $\unicode[STIX]{x1D70C}_{s}$ and $\unicode[STIX]{x1D70C}_{f}$ are solid and fluid densities, respectively. The effect of sphere rotation on VIV was studied over a wide range of non-dimensional rotation rates: $0\leqslant \unicode[STIX]{x1D6FC}~(\equiv \unicode[STIX]{x1D714}D/(2U))\leqslant 2.5$, with $\unicode[STIX]{x1D714}$ the angular velocity. The flow satisfied the incompressible Navier–Stokes equations while the coupled sphere motion was modelled by a spring–mass–damper system, under zero damping. For zero rotation, the sphere oscillated symmetrically through its initial position with a maximum amplitude of approximately 0.4 diameters. Under forced rotation, it oscillated about a new time-mean position. Rotation also resulted in a decreased oscillation amplitude and a narrowed synchronisation range. VIV was suppressed completely for $\unicode[STIX]{x1D6FC}>1.3$. Within the $U^{\ast }$ synchronisation range for each rotation rate, the drag force coefficient increased while the lift force coefficient decreased from their respective pre-oscillatory values. The increment of the drag force coefficient and the decrement of the lift force coefficient reduced with increasing reduced velocity as well as with increasing rotation rate. In terms of wake dynamics, in the synchronisation range at zero rotation, two equal-strength trails of interlaced hairpin-type vortex loops were formed behind the sphere. Under rotation, the streamwise vorticity trail on the advancing side of the sphere became stronger than the trail in the retreating side, consistent with wake deflection due to the Magnus effect. This symmetry breaking appears to be associated with the reduction in the observed amplitude response and the narrowing of the synchronisation range. In terms of variation with Reynolds number, the sphere oscillation amplitude was found to increase over the range $Re\in [300,1200]$ at $U^{\ast }=6$ for each of $\unicode[STIX]{x1D6FC}=0.15$, 0.75 and 1.5. The VIV response depends strongly on Reynolds number, with predictions indicating that VIV will persist for higher rotation rates at higher Reynolds numbers.
Establishing social cooperation: The role of hubs and community structure
Authors: COOPER BARRY , LEWIS-PYE ANDREW E. M. , LI ANGSHENG , PAN YICHENG , YONG XI
Published: May 2018

Prisoner's Dilemma (PD) games have become a well-established paradigm for studying the mechanisms by which cooperative behavior may evolve in societies consisting of selfish individuals. Recent research has focused on the effect of spatial and connectivity structure in promoting the emergence of cooperation in scenarios where individuals play games with their neighbors, using simple “memoryless” rules to decide their choice of strategy in repeated games. While heterogeneity and structural features such as clustering have been seen to lead to reasonable levels of cooperation in very restricted settings, no conditions on network structure have been established, which robustly ensure the emergence of cooperation in a manner that is not overly sensitive to parameters such as network size, average degree, or the initial proportion of cooperating individuals. Here, we consider a natural random network model, with parameters that allow us to vary the level of “community” structure in the network, as well as the number of high degree hub nodes. We investigate the effect of varying these structural features and show that, for appropriate choices of these parameters, cooperative behavior does now emerge in a truly robust fashion and to a previously unprecedented degree. The implication is that cooperation (as modelled here by PD games) can become the social norm in societal structures divided into smaller communities, and in which hub nodes provide the majority of inter-community connections.
The Future of Canadian Political Science: Boundary Transgressions, Gender and Anti-Oppression Frameworks
Authors: Nath Nisha , Tungohan Ethel , Gaucher Megan
Published: May 2018

In light of theCanadian Journal of Political Science(CJPS) self-reflexive “50thAnniversary” issue on the state of Canadian political science (CPS), this article maps the discipline's engagement with intersectional anti-oppression scholarship. Analyzing abstracts inCJPSand theCanadian Political Science Review,we argue while these journals—and mainstream CPS more generally—tackle questions of diversity, there remains a gap between conversations recognized in these particular forums and the incorporation of what we term an intersectional anti-oppression lens. In its deconstruction of systems of power and privilege, we explore analytic and pedagogical possibilities this lens presents for mainstream CPS.
Hausdorff dimension and uniform exponents in dimension two
Authors: BUGEAUD YANN , CHEUNG YITWAH , CHEVALLIER NICOLAS
Published: May 2018

In this paper we prove that the Hausdorff dimension of the set of (nondegenerate) singular two-dimensional vectors with uniform exponentμin (1/2, 1) is equal to 2(1 −μ) forμ⩾$\sqrt2/2$, whereas forμ<$\sqrt2/2$it is greater than 2(1 −μ) and at most equal to (3 − 2μ)(1 − μ)/(1 −μ+μ2). We also establish that this dimension tends to 4/3 (which is the dimension of the set of singular two-dimensional vectors) whenμtends to 1/2. These results improve upon previous estimates of R. Baker, joint work of the first author with M. Laurent, and unpublished work of M. Laurent. Moreover, we prove a lower bound for the packing dimension, which appears to be strictly greater than the Hausdorff dimension for μ ⩾ 0.565. . . .
Habit strength and between-meal snacking in daily life: the moderating role of level of education
Authors: Wouters Saskia , Thewissen Viviane , Duif Mira , van Bree Rob JH , Lechner Lilian , Jacobs Nele
Published: May 2018

Objective

Recent research emphasizes the importance of habit in explaining patterns of energy intake and choices of consumption. However, the nature of the association between habit strength and snacking has not been explored for all types of between-meal snacks.

Design

Multilevel linear techniques were used to: (i) examine the association between habit strength and moment-to-moment energy intake (kilocalories) from snacks in daily life; and (ii) determine whether gender, age, level of education and BMI moderate the association between habit strength and moment-to-moment energy intake from snacks. A smartphone application based on the experience sampling method was used to map momentary between-meal snack intake in the context of daily life. Demographics and habit strength were assessed with an online composite questionnaire.

Setting

This research was performed in the Netherlands in the natural environment of participants’ daily life.

Subjects

Adults (n 269) aged 20–50 years.

Results

Habit strength was significantly associated with moment-to-moment energy intake from between-meal snacks in daily life: the higher the strength of habit to snack between meals, the higher the amount of momentary energy intake from snacks. The association between habit strength and moment-to-moment energy intake from snacks was moderated by education level. Additional analyses showed that habit strength was significantly associated with moment-to-moment energy intake from between-meal snacks in the low to middle level of education group.

Conclusions

It is recommended to address habitual between-meal snacking in future interventions targeting low- to middle-educated individuals.
Refining and implementing the Food Assortment Scoring Tool (FAST) in food pantries
Authors: Caspi Caitlin E , Grannon Katherine Y , Wang Qi , Nanney Marilyn S , King Robert P
Published: May 2018

Objective

Hunger relief agencies have a limited capacity to monitor the nutritional quality of their food. Validated measures of food environments, such as the Healthy Eating Index-2010 (HEI-2010), are challenging to use due to their time intensity and requirement for precise nutrient information. A previous study used out-of-sample predictions to demonstrate that an alternative measure correlated well with the HEI-2010. The present study revised the Food Assortment Scoring Tool (FAST) to facilitate implementation and tested the tool’s performance in a real-world food pantry setting.

Design

We developed a FAST measure with thirteen scored categories and thirty-one sub-categories. FAST scores were generated by sorting and weighing foods in categories, multiplying each category’s weight share by a healthfulness parameter and summing the categories (range 0–100). FAST was implemented by recording all food products moved over five days. Researchers collected FAST and HEI-2010 scores for food availability and foods selected by clients, to calculate correlations.

Setting

Five food pantries in greater Minneapolis/St. Paul, Minnesota, USA.

Subjects

Food carts of sixty food pantry clients.

Results

The thirteen-category FAST correlated well with the HEI-2010 in prediction models (r= 0·68). FAST scores averaged 61·5 for food products moved, 63·8 for availability and 62·5 for client carts. As implemented in the real world, FAST demonstrated good correlation with the HEI-2010 (r= 0·66).

Conclusions

The FAST is a flexible, valid tool to monitor the nutritional quality of food in pantries. Future studies are needed to test its use in monitoring improvements in food pantry nutritional quality over time.
Deep and Not Comprehensive? What the WTO Rules Permit for a UK–EU FTA
Authors: LYDGATE EMILY , WINTERS L. ALAN
Published: May 2018

WTO rules prohibit Free Trade Areas (FTAs) that provide tariff-free access or services liberalization in only one or a few sectors. In this sense, a narrow, sectoral approach to concluding an FTA between the EU and the UK would contravene WTO law. However, assuming the EU and the UK were able to agree a substantially broad tariff-free FTA, WTO rules would not prevent them from moving further to maintain the bulk of the benefits of the Customs Union and the Single Market in a few key sectors. They could establish customs union-like conditions by coordinating external tariffs in some sectors and agreeing on relaxed Rules of Origin (RoOs) administered lightly and Single Market-like access could be approximated through sectoral Mutual Recognition Agreements. Such an approach would enable continued deep integration, whose desirability has been signalled on both sides. It would fall short of current market access levels even in the selected sectors, and, in the case of tariff coordination, re-create some of the limits to an independent trade policy that Brexit aimed to remove. If the trade-off were deemed desirable, however, the approach could be reconciled with WTO rules including the ‘Most Favoured Nation’ requirement that equal treatment be awarded to all WTO Member States.
Researching children's perspectives in pediatric palliative care: A systematic review and meta-summary of qualitative research
Authors: Ghirotto Luca , Busani Elena , Salvati Michela , Di Marco Valeria , Caldarelli Valeria , Artioli Giovanna
Published: May 2018

Objective

Qualitative research is pivotal in gaining understanding of individuals’ experiences in pediatric palliative care. In the past few decades, the number of qualitative studies on pediatric palliative care has increased slightly, as has interest in qualitative research in this area. Nonetheless, a limited number of such studies have included the first-person perspective of children. The aim of this article is to understand the contribution of previous qualitative research on pediatric palliative care that included the voices of children.

Method

A systematic review of qualitative studies and a meta-summary were conducted. MEDLINE, CINAHL, PsycINFO, PsycARTICLES, and ERIC were searched without limitations on publication date or language. Eligible articles were qualitative research articles in which the participants were children ranging in age from 3 to 18 years.

Result

We retrieved 16 qualitative research articles reporting on 12 unique studies, and we selected two mixed-method articles. The meta-summary shows eight themes: the relationship with professional caregivers, pain and its management, “living beyond pain,” the relationship between pediatric patients and their families, children's view on their treatment and service provision, meanings children give to their end-of-life situation, consequences of clinical decisions, and the relationships among children in pediatric palliative care and their peers.

Significance of results

This meta-summary presents the “state of the art” of pediatric palliative care qualitative research on children and highlights additional research areas that warrant qualitative study.
Backlash against international courts: explaining the forms and patterns of resistance to international courts
Authors: Madsen Mikael Rask , Cebulak Pola , Wiebusch Micha
Published: May 2018

The paper investigates and theorises different forms and patterns of resistance to international courts (ICs) and develops an analytical framework for explaining their variability. In order to make intelligible the resistance that many ICs are currently facing, the paper first unpacks the concept of resistance. It then introduces a key distinction between mere pushback from individual Member States or other actors, seeking to influence the future direction of a court's case-law, and actual backlash – a critique triggering significant institutional reform or even the dismantling of tribunals. On the basis on the proposed theoretical framework, the paper provides a roadmap for empirical studies of resistance to ICs, considering the key contextual factors necessary to take into account in such studies.
Patterns of avoidance: political questions before international courts
Authors: Odermatt Jed
Published: May 2018

International 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.
Interdisziplinarität – (k)ein Thema im Unterricht an Gesundheitsfachschulen
Authors: Diefenbach Sabine , Höhle Dörthe
Published: May 2018

Zusammenfassung. Interdisziplinarität im Gesundheitswesen ist notwendig, um Menschen in komplexen Pflege- und Therapiesituationen adäquat unterstützen zu können. Dies setzt voraus, dass Auszubildende in den Gesundheitsfachberufen in institutionalisierten Lernprozessen notwendiges Wissen erwerben und Erfahrungen reflektiert werden. Formelle Lernangebote zu dieser Thematik finden überwiegend berufsspezifisch in den jeweiligen Ausbildungen statt. Diese Lernsituation dient als Anregung, Interdisziplinarität in der Ausbildung an konkreten beruflichen Situationen festzumachen.
An Economical Model for Simulating Turbulence Enhancement of Droplet Collisions and Coalescence
Authors: Krueger Steven K. , Kerstein Alan R.
Published: May 2018

ClusColl, 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

To 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

Retroarc 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

The 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

Tumor 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.
Correction: MicroRNA-27a promotes podocyte injury via PPARγ-mediated β-catenin activation in diabetic nephropathy
Authors: Zhou Zhanmei , Wan Jiao , Hou Xiaoyan , Geng Jian , Li Xiao , Bai Xiaoyan
Published: May 2018

Correction to:Cell Death and Disease8, e2658 (2017); https://doi.org/10.1038/cddis.2017.74; published online 9 March 2017
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

Danggui-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

The 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

Alzheimer’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

The 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

Laminin, 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

Large 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

Development 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

The 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.
Resolving molecule-specific information in dynamic lipid membrane processes with multi-resonant infrared metasurfaces
Authors: Rodrigo Daniel , Tittl Andreas , Ait-Bouziad Nadine , John-Herpin Aurelian , Limaj Odeta , Kelly Christopher , Yoo Daehan , Wittenberg Nathan J. , Oh Sang-Hyun , Lashuel Hilal A. , Altug Hatice
Published: May 2018

A multitude of biological processes are enabled by complex interactions between lipid membranes and proteins. To understand such dynamic processes, it is crucial to differentiate the constituent biomolecular species and track their individual time evolution without invasive labels. Here, we present a label-free mid-infrared biosensor capable of distinguishing multiple analytes in heterogeneous biological samples with high sensitivity. Our technology leverages a multi-resonant metasurface to simultaneously enhance the different vibrational fingerprints of multiple biomolecules. By providing up to 1000-fold near-field intensity enhancement over both amide and methylene bands, our sensor resolves the interactions of lipid membranes with different polypeptides in real time. Significantly, we demonstrate that our label-free chemically specific sensor can analyze peptide-induced neurotransmitter cargo release from synaptic vesicle mimics. Our sensor opens up exciting possibilities for gaining new insights into biological processes such as signaling or transport in basic research as well as provides a valuable toolkit for bioanalytical and pharmaceutical applications.
Pancharatnam–Berry phase in condensate of indirect excitons
Authors: Leonard J. R. , High A. A. , Hammack A. T. , Fogler M. M. , Butov L. V. , Campman K. L. , Gossard A. C.
Published: May 2018

The Pancharatnam–Berry phase is a geometric phase acquired over a cycle of parameters in the Hamiltonian governing the evolution of the system. Here, we report on the observation of the Pancharatnam–Berry phase in a condensate of indirect excitons (IXs) in a GaAs-coupled quantum well structure. The Pancharatnam–Berry phase is directly measured by detecting phase shifts of interference fringes in IX interference patterns. Correlations are found between the phase shifts, polarization pattern of IX emission, and onset of IX spontaneous coherence. The evolving Pancharatnam–Berry phase is acquired due to coherent spin precession in IX condensate and is observed with no decay over lengths exceeding 10 μm indicating long-range coherent spin transport.
Precipitation and ectoparasitism reduce reproductive success in an arctic-nesting top-predator
Authors: Lamarre Vincent , Legagneux Pierre , Franke Alastair , Casajus Nicolas , Currie Douglas C. , Berteaux Dominique , Bêty Joël
Published: May 2018

Indirect impacts of climate change, mediated by new species interactions (including pathogens or parasites) will likely be key drivers of biodiversity reorganization. In addition, direct effects of extreme weather events remain understudied. Simultaneous investigation of the significance of ectoparasites on host populations and extreme weather events is lacking, especially in the Arctic. Here we document the consequences of recent black fly outbreaks and extreme precipitation events on the reproductive output of an arctic top predator, the peregrine falcon (Falco peregrinus tundrius) nesting at the northern range limit of ornithophilic black flies in Nunavut, Canada. Overall, black fly outbreaks and heavy rain reduced annual nestling survival by up to 30% and 50% respectively. High mortality caused by ectoparasites followed record-breaking spring snow precipitation, which likely increased stream discharge and nutrient runoff, two key parameters involved in growth and survival of black fly larvae. Using the RCP4.5 intermediate climate scenario run under the Canadian Global Climate Model, we anticipate a northward expansion of black fly distribution in Arctic regions. Our case study demonstrates that, in the context of climate change, extreme weather events can have substantial direct and indirect effects on reproductive output of an arctic top-predator population.
Seasonal variation in a diverse beetle assemblage along two elevational gradients in the Australian Wet Tropics
Authors: Wardhaugh C. W. , Stone M. J. , Stork N. E.
Published: May 2018

Altered abiotic conditions resulting from human-induced climate change are already driving changes in the spatial and temporal distributions of many organisms. For insects, how species are distributed across elevations is relatively well known, but data on their seasonality at different elevations are lacking. Here we show seasonal variation in beetle abundance and species richness along two spatially-distinct elevational transects (350–1000 m and 100–1000 m asl) in the rainforests of northern Australia. Temperature was the best predictor of temporal abundance and species richness patterns, while rainfall had little influence. Elevation had little effect on seasonal changes in abundance or diversity. Adults of most beetle species exhibited long season-lengths (>6 months of the year) with distinct peaks in abundance during the summer wet-season. We found evidence of phenotypic variation among the more widespread species, with seasonal peaks in abundance often not coinciding across elevations or transects. Due to the wide elevational range of most species, and the lack of consistency in the seasonality of wide-spread individual species, we suggest that many beetles inhabiting the low to mid-elevation mountains in the Wet Tropics, and potentially other tropical rainforests, are not as vulnerable to extinction due to climate change as many other organisms.
Protein kinase Cε regulates nuclear translocation of extracellular signal-regulated kinase, which contributes to bradykinin-induced cyclooxygenase-2 expression
Authors: Nakano Rei , Kitanaka Taku , Namba Shinichi , Kitanaka Nanako , Sugiya Hiroshi
Published: May 2018

The proinflammatory mediator bradykinin stimulated cyclooxygenase-2 (COX-2) expression and subsequently prostaglandin E2 synthesis in dermal fibroblasts. The involvement of B2 receptors and Gαq in the role of bradykinin was suggested by using pharmacological inhibitors. The PKC activator PMA stimulated COX-2 mRNA expression. Bradykinin failed to induce COX-2 mRNA expression in the presence of PKC inhibitors, whereas the effect of bradykinin was observed in the absence of extracellular Ca2+. Bradykinin-induced COX-2 mRNA expression was inhibited in cells transfected with PKCε siRNA. These observations suggest that the novel PKCε is concerned with bradykinin-induced COX-2 expression. Bradykinin-induced PKCε phosphorylation and COX-2 mRNA expression were inhibited by an inhibitor of 3-phosphoinositide-dependent protein kinase-1 (PDK-1), and bradykinin-induced PDK-1 phosphorylation was inhibited by phospholipase D (PLD) inhibitors, suggesting that PLD/PDK-1 pathway contributes to bradykinin-induced PKCε activation. Pharmacological and knockdown studies suggest that the extracellular signal-regulated kinase 1 (ERK1) MAPK signaling is involved in bradykinin-induced COX-2 expression. Bradykinin-induced ERK phosphorylation was attenuated in the cells pretreated with PKC inhibitors or transfected with PKCε siRNA. We observed the interaction between PKCε and ERK by co-immunoprecipitation experiments. These observations suggest that PKCε activation contributes to the regulation of ERK1 activation. Bradykinin stimulated the accumulation of phosphorylated ERK in the nuclear fraction, that was inhibited in the cells treated with PKC inhibitors or transfected with PKCε siRNA. Consequently, we concluded that bradykinin activates PKCε via the PLD/PDK-1 pathway, which subsequently induces activation and translocation of ERK1 into the nucleus, and contributes to COX-2 expression for prostaglandin E2 synthesis in dermal fibroblasts.