bluuebunny/crossref_metadata_2025 huggingface dataset:
Facies analyses and depositional setting of the Lower Cretaceous Shurijeh–Shatlyk formations in the Kopeh Dagh–Amu Darya Basin (Iran and Turkmenistan)
Authors: Hosseinyar Gholamreza , Moussavi‐Harami Reza , Abdollahie Fard Iraj , Mahboubi Asadollah , Noemani Rad Rooholah , Ebrahimi Mohammad‐Hassan
Published: July 2018

The Lower Cretaceous siliciclastic fluvial to shallow marine Shurijeh–Shatlyk formations together form one of the main reservoir successions in the Kopeh Dagh–Amu Darya Basin (NE Iran, Turkmenistan, and north of Afghanistan). Sedimentary facies and thickness changes in the Shurijeh–Shatlyk formations show complex variations throughout the basin, which highlight the importance of understanding the controlling factors on facies distribution and depositional setting for future hydrocarbon exploration. Integration of 3D seismic data, 13 boreholes, and five surface stratigraphic sections led to identification of lithofacies and facies associations. The results allow subdivision of this siliciclastic succession into four stratigraphic units (A, B, C, and D). Our study indicates that base‐level changes interacted with palaeotopography inherited from Middle Jurassic basin rifting, Upper Jurassic carbonate reefs/patch reef distributions, and reactivation of the deep basin faults, to control the Shurijeh–Shatlyk depositional setting and sedimentary facies distribution. Our findings show that the Aghdarband and Badkhyz–Maimana palaeo‐highs affected the Kopeh Dagh–Amu Darya Basin throughout deposition of the Shurijeh–Shatlyk formations. Allogeneic processes and active tectonics, related to the Valanginian Late Cimmerian Orogeny, caused a base‐level fall, exposure of Upper Jurassic carbonate sediments, and deposition of a carbonate pebbly conglomerate unit in the western part of the study area. This base‐level fall led to the deposition of thick evaporites in the western area and conglomerate in the eastern parts of the Kopeh Dagh. Due to a Hauterivian sea‐/base‐level rise, several deltas formed in the basin, which form the main reservoir zone in the Murgab Depression and Khangiran Field in Turkmenistan and Iran.
Photobiomodulation therapy promotes in vitro wound healing in nicastrin KO HaCaT cells
Authors: Tricarico Paola M. , Zupin Luisa , Ottaviani Giulia , Pacor Sabrina , Jean‐Louis Francette , Boniotto Michele , Crovella Sergio
Published: July 2018

Mutations in NCSTN gene (encoding for nicastrin protein) are associated with hidradenitis suppurativa (HS), a chronic inflammatory disease involving hair follicles. HS is clinically handled with drugs but the most severe cases are treated with surgery. Photobiomodulation (PBM) therapy, already used in the treatment of skin diseases such as acne, herpes virus lesions, ultraviolet damage, vitiligo, hypertrophic scar, keloid, burn, psoriasis and diabetic chronic wounds, could be beneficial as an adjuvant supportive treatment to promote and foster the healing process after skin excision in HS. The effects of PBM therapy in promoting the wound closure are evaluated in a HaCaT cells NCSTN−/−, assessing cell metabolism, migration rate, proliferation and cell cycle progression. In our experimental model, PBM exerts a potent action on metabolism of mutated keratinocytes, incrementing adenosine triphosphate (ATP) production at 2 hours, while after 24 hours an increase of metabolism with a decrement of intracellular ATP levels were recorded. Moreover, PBM speeds up the wound closure, inducing cells' migration without affecting their proliferation.Based on our findings, we suggest the use of PBM in HS patients, who undergo major surgery with large skin excision.
Epithelial‐to‐mesenchymal transition and cancer stem cells contribute to breast cancer heterogeneity
Authors: Hong Deli , Fritz Andrew J. , Zaidi Sayyed K. , van Wijnen Andre J. , Nickerson Jeffrey A. , Imbalzano Anthony N. , Lian Jane B. , Stein Janet L. , Stein Gary S.
Published: July 2018

Breast cancer is the most common cancer in women, and accounts for ~30% of new cancer cases and 15% of cancer‐related deaths. Tumor relapse and metastasis are primary factors contributing to breast cancer‐related deaths. Therefore, the challenge for breast cancer treatment is to sustain remission. A driving force behind tumor relapse is breast cancer heterogeneity (both intertumor, between different patients, and intratumor, within the same tumor). Understanding breast cancer heterogeneity is necessary to develop preventive interventions and targeted therapies. A recently emerging concept is that intratumor heterogeneity is driven by cancer stem cells (CSCs) that are capable of giving rise to a multitude of different cells within a tumor. Studies have highlighted linkage of CSC formation with epithelial‐to‐mesenchymal transition (EMT). In this review, we summarize the current understanding of breast cancer heterogeneity, links between EMT and CSCs, regulation of EMT by Runx transcription factors, and potential therapeutic strategies targeting these processes.
The protective role of curcumin in myocardial ischemia–reperfusion injury
Authors: Mokhtari‐Zaer Amin , Marefati Narges , Atkin Stephen L. , Butler Alexandra E. , Sahebkar Amirhossein
Published: July 2018

Coronary artery disease (CAD) is a well‐known pathological condition that is characterized by high morbidity and mortality. The main pathological manifestation of CAD is myocardial injury due to ischemia–reperfusion (I–R). Currently, no efficacious treatment of protecting the heart against myocardial I–R exists. Hence, it is necessary to discover or develop novel strategies to prevent myocardial‐reperfusion injury to improve clinical outcomes in patients with CAD. A large body of experimental evidence supports cardioprotective properties of curcumin and the ability of this phytochemical to modify some cardiovascular risk factors. However, the detailed effects of curcumin in myocardial I–R injury are still unclear and there is a lack of evidence concerning which curcumin regimen may be ideal for myocardial I–R injury. This paper presents a brief review of the pathophysiology of myocardial I–R injury and the mechanisms of action of curcumin in reducing myocardial I–R injury.
Cistanche deserticola polysaccharide attenuates osteoclastogenesis and bone resorption via inhibiting RANKL signaling and reactive oxygen species production
Authors: Song Dezhi , Cao Zhen , Liu Zaibing , Tickner Jennifer , Qiu Heng , Wang Chao , Chen Kai , Wang Ziyi , Dong Shiwu , Xu Jiake
Published: July 2018

Osteoporosis is a metabolic disease characterized by osteopenia and bone microstructural deterioration. Osteoclasts are the primary effector cells that degrade bone matrix and their abnormal function leads to the development of osteoporosis. Reactive oxygen species (ROS) accumulation during cellular metabolism promotes osteoclast proliferation and differentiation, therefore, playing an important role in osteoporosis. Cistanche deserticola polysaccharide (CDP) possesses antitumor, anti‐inflammatory, and antioxidant activity. However, the impact of CDP on osteoclasts is unclear. In this study, tartrate‐resistant acid phosphatase staining, immunofluorescence, reverse transcription‐polymerase chain reaction, and western blot analysis were utilized to demonstrate that CDP inhibited osteoclastogenesis and hydroxyapatite resorption. In addition, CDP also inhibited the expression of osteoclast maker genes including Ctsk, Mmp9, and Acp5 and had no effect on receptor activator of nuclear factor κB (RANK) expression. Mechanistic analyses revealed that CDP increases the expression of antioxidant enzymes to attenuate RANKL‐mediated ROS production in osteoclasts and inhibits nuclear factor of activated T cells and mitogen‐activated protein kinase activation. These results suggest that CDP may represent a candidate drug for the treatment of osteoporosis caused by excessive osteoclast activity.
Applications of PET‐MRI in musculoskeletal disease
Authors: Kogan Feliks , Broski Stephen M. , Yoon Daehyun , Gold Garry E.
Published: July 2018

New integrated PET‐MRI systems potentially provide a complete imaging modality for diagnosis and evaluation of musculoskeletal disease. MRI is able to provide excellent high‐resolution morphologic information with multiple contrast mechanisms that has made it the imaging modality of choice in evaluation of many musculoskeletal disorders. PET offers incomparable abilities to provide quantitative information about molecular and physiologic changes that often precede structural and biochemical changes. In combination, hybrid PET‐MRI can enhance imaging of musculoskeletal disorders through early detection of disease as well as improved diagnostic sensitivity and specificity. The purpose of this article is to review emerging applications of PET‐MRI in musculoskeletal disease. Both clinical applications of malignant musculoskeletal disease as well as new opportunities to incorporate the molecular capabilities of nuclear imaging into studies of nononcologic musculoskeletal disease are discussed. Lastly, we discuss some of the technical considerations and challenges of PET‐MRI as they specifically relate to musculoskeletal disease.

Level of Evidence

5

Technical Efficacy

Stage 3 J. Magn. Reson. Imaging 2018;48:27–47.
A feature extraction method for predictive maintenance with time‐lagged correlation–based curve‐registration model
Authors: Zhang Shouli , Liu Chen , Su Shen , Han Yanbo , Li XiaoHong
Published: July 2018

With the prevalent development and use of predictive maintenance models for Internet‐of‐Things scenarios, the deep learning technology is gaining momentum. Feature extraction helps to increase efficiency in training the deep‐learning–based predictive maintenance model. However, there are common situations of time‐lagged correlations among industrial sensor data, resulting in reduction the effect of feature extraction. In this paper, we propose a feature extraction method for multisensors data with time‐lagged correlation. A curve‐registration method of correlation maximization algorithm is used to solve the problem of time‐lagged correlation for multi sensors. Then we apply a recurrent neural network, namely, long short‐term memory to develop a lightweight predictive maintenance model with the help of proposed feature extraction method. The effectiveness of the proposed feature extraction approach is demonstrated by examining real cases in a power plant. The experimental results indicate that our method can (1) effectively improve the accuracy of prediction and (2) improve the performance of the prediction model.
ManIoT: A 2‐tier management platform for heterogeneous IoT devices and applications
Authors: Antunes Josué B. , Denés István L. , Castro Tiago O. , Macedo Daniel F. , dos Santos Aldri L.
Published: July 2018

The Internet of Things (IoT) is a paradigm where devices can interact with each other via an Internet connection. One of the challenges of IoT is the heterogeneity of the devices and applications comprising the network. Each object can have different processing capabilities or employ different communication standards. Further, applications can control different sensors, and each application may have conflicting goals. Thus, IoT systems must employ a context‐aware platform that supports a variety of sensor protocols and is able to cope with many applications and devices at the same time. This paper presents a platform for managing devices and applications on the IoT, called Management for Internet of Things, which operates in local and global levels and considers the perception of context. A 2‐level approach allows the adoption of the platform for Mobile‐Edge Computing use cases, as well for the operation of large scale IoT applications. The evaluation of a prototype shows that Management for Internet of Things supports many applications and devices with a reduced resource usage.
Generalized radial‐return mapping algorithm for anisotropic von Mises plasticity framed in material eigenspace
Authors: Versino Daniele , Bennett Kane C.
Published: July 2018

A computationally efficient integration algorithm for anisotropic plasticity is proposed, which is identified as a generalization of the radial‐return mapping algorithm to anisotropy. The algorithm is based upon formulation within the eigenspace of a material anisotropy tensor associated with anisotropic quadratic von Mises (J2) plasticity (also called Hill plasticity), for which it is shown to ensure that the flow rule remains associative, ie, the normality condition is satisfied. Extension of the algorithm to include anisotropic elasticity (anisotropic elastoplasticity) is further provided, made possible by the identification of a certain fourth‐order material tensor dependent on both the elastic and plastic anisotropy. The derivation of the fully elastoplastically anisotropic algorithm involves further complexity, but the resulting algorithm is shown to closely resemble the purely plastically anisotropic one once the appropriate eigenspace is identified. The proposed generalized radial‐return algorithm is compared to a classical closest‐point projection algorithm, for which it is shown to provide considerable advantage in computational cost. The efficiency, accuracy, and robustness of the algorithm are demonstrated through various illustrative test cases and in the finite element simulation of Taylor impact tests on tantalum.
Carbon Nanotube‐Silicone Rubber on Active Thin‐Film Implants
Authors: Behrens Ailke , Foremny Katharina , Doll Theodor
Published: July 2018

To improve interfacing with neurites, flexible electrode materials consisting of carbon nanotubes (CNTs) and silicone rubber are investigated. Here, the authors present a method for defined application of CNT‐silicone rubber on electrode surfaces. However, for low impedance as well as intimate contact between nerve cells and electrodes, additional reduction of the silicone rubber layer via etching at the interface is necessary. This requires protection of the electrodes using photoresist. The etching methods are optimized for application on ready‐to‐use electrode arrays and characterized using impedance spectroscopy and scanning electron microscopy.
A Benzooxazole‐Based Probe for the Sensitive Detection of Hydrogen Sulfide: Kinetic and Transition‐State Studies and In Vitro Application in HepG2 Cells
Authors: Pal Kaberi , Islam Abu Saleh Musha , Prodhan Chandraday , Bhunya Sourav , Paul Ankan , Ali Mahammad
Published: July 2018

A benzooxazole based probe, 2‐[4‐(2, 4‐dinitrophenoxy)‐phenyl]‐benzooxazole has been synthesized and thoroughly characterized by mass, 1H‐NMR and FT‐IR spectroscopy. The probe exhibits sensitive and selective response towards H2S in DMSO:PBS buffer (6:4, v/v, pH 7.4) over the other reactive sulfur species especially the biological thiols like cysteine, homocysteine and glutathione. Due to thiolysis of dinitrophenyl ether, this probe displays turn‐on fluorescence response where the sensing mechanism follows inhibited photoinduced electron transfer (d‐PET) process. This thiolysis reaction proceeds through aromatic nucleophilic substitution (SNAr) type mechanism. Moreover, the transition state study shows that this process is exoergic with favorable energy barrier of 5.0 kcal/mol. The kinetic studies of the probe with HS– at various pH assist to evaluate the acid dissociation constant value (Ka1 =1.09 × 10−8 M−1) of H2S that illustrate a reasonable agreement with the literature value, Ka (9.5 x 10−8 M−1). Finally, this probe is cell permeable, non‐cytotoxic and suitable for intracellular cytoplasmic HS– sensing in live cells with a very low detection limit (51.8 nM).
Lifshitz entanglement entropy from holographic cMERA
Authors: Gentle Simon A. , Vandoren Stefan
Published: July 2018

Abstract

We study entanglement entropy in free Lifshitz scalar field theories holographically by employing the metrics proposed by Nozaki, Ryu and Takayanagi in [1] obtained from a continuous multi-scale entanglement renormalisation ansatz (cMERA). In these geometries we compute the minimal surface areas governing the entanglement entropy as functions of the dynamical exponent z and we exhibit a transition from an area law to a volume law analytically in the limit of large z. We move on to explore the effects of a massive deformation, obtaining results for any z in arbitrary dimension. We then trigger a renormalisation group flow between a Lifshitz theory and a conformal theory and observe a monotonic decrease in entanglement entropy along this flow. We focus on strip regions but also consider a disc in the undeformed theory.
What Patients Look for When Browsing Online for Pancreatic Cancer: The Bait Behind the Byte
Authors: Storino Alessandra , Guetter Camila , Castillo‐Angeles Manuel , Watkins Ammara A. , Mancias Joseph D. , Bullock Andrea , James Moser A. , Kent Tara S.
Published: July 2018

Background

Suitability is a patient‐centered metric defined as how appropriately health information is targeted to specific populations to increase knowledge. However, suitability is most commonly evaluated exclusively by healthcare professionals without collaboration from intended audiences. Suitability (as rated by intended audiences), accuracy and readability have not been evaluated on websites discussing pancreatic cancer.

Methods

Ten healthy volunteers evaluated fifty pancreatic cancer websites using the suitability assessment of materials (SAM instrument) for the materials’ overall suitability. Readability and accuracy were correlated.

Results

Ten recruited volunteers (ages 23–63, 50% female) found websites to be on average “adequate” or “superior” in suitability. Surgery, radiotherapy and nonprofit websites had higher suitability scores as compared to counterparts (p ≤ 0.03). There was no correlation between readability and accuracy levels and suitability scores (p ≥ 0.3). Presence of visual aids was associated with better suitability scores after controlling for website quality (p ≤ 0.01).

Conclusion

Suitability of websites discussing pancreatic cancer treatments as rated by lay audiences differed based on therapy type and website affiliation, and was independent of readability level and accuracy of information. Nonprofit affiliation websites focusing on surgery or radiotherapy were most suitable. Online information should be assessed for suitability by target populations, in addition to readability level and accuracy, to ensure information reaches the intended audience.
“I Am Uncertain About What My Uncertainty Even Is”: Men's Uncertainty and Information Management of Their BRCA‐Related Cancer Risks
Authors: Rauscher Emily A. , Dean Marleah , Campbell‐Salome Gemme M.
Published: July 2018

Men with a germline pathogenic BRCA1 or BRCA2 variant have increased risks for developing breast, pancreatic, prostate, and melanoma cancers, but little is known about how they understand and manage their cancer risks. This study examines how men with BRCA‐related cancer risks manage uncertainty and information about their risks. Twenty‐five men who were either a BRCA carrier or have a BRCA‐positive first‐degree family member that put the participant at 50% chance of also being a BRCA carrier were interviewed for this study. Using uncertainty management theory as a theoretical framework, this study demonstrates that men manage uncertainty by seeking information from female family members, websites, and healthcare providers, and are under‐informed about their cancer risks. Further, in handling their information, men prefer information about cancer risk percentages and screening recommendations in the form of lists presented to them via websites, printed literature, proactive healthcare providers, and an identifiable male spokesperson. Finally, men used BRCA‐related cancer risk information to make decisions about whether or not to engage in screening and prevention, manage their BRCA‐related cancer risks, and overall family well‐being—yet often at the expense of their own individual risks. Implications for genetic counseling and family conversations are discussed.
Extrinsic environmental factors, not resident diversity itself, lead to invasion of Ageratum conyzoides L. in diverse communities
Authors: Luo Zhengrong , Chen Xiaorong , Xia Gengshou , Chen Xubo
Published: July 2018

The relationship between diversity and invasibility might be confounded by extrinsic environmental factors and the evolutionary structure of the resident community. To examine the role of extrinsic environmental factors, species and phylogenetic diversity in regulating community susceptibility to invasion, we established 109 plots either with or without Ageratum conyzoides L. in Liandu, China. We identified all the species in our samples, weighed the aboveground biomass of each species, and measured environmental variables. For all species recorded in our survey, we constructed a community phylogeny using PhytoPhylo mega‐phylogeny as a backbone. We selected the best‐fit environment model based on the minimum corrected Akaike information criteria score to examine the effect of extrinsic environmental variables on the relative abundance of A. conyzoides. Relationship between biodiversity and invasion of A. conyzoides was examined by a multiple regression, in which extrinsic ecological factors and biodiversity were combined to predict the relative abundance of A. conyzoides. To reduce the number of extrinsic variables, the first six components produced by a principal component analysis of environmental variables were used as predictive variables in the multiple regression. The best‐fit environment model indicated that the relative abundance of A. conyzoides was higher in summer and in communities with lower total organic matter and higher total nitrogen in the soil. The multiple regression indicated that only the positive relationship between the Shannon–Wiener diversity of exotics and the relative abundance of A. conyzoides was significant. This result challenges the importance of diversity–resistance to plant invasion. Generalist facilitation might exist between A. conyzoides and other exotic species, although mechanisms for such facilitation are unclear. Overall, our finding suggests the extrinsic factors covarying with diversity are more important than diversity itself in regulating community susceptibility to invasion.
Presentation and diagnosis of patients with type 3 von Willebrand disease in resourceslimited laboratory
Authors: Abdulsalam Abbas Hashim , Ghiath Yusra , Alrahal Nidhal
Published: July 2018

Von Willebrand disease (VWD) is a bleeding disorder that results from decreased von Willebrand factor (VWF) activity <0.30 iu/mL. Therefore, the diagnosis of type 3 VWD in patients with bleeding requires finding a VWF:Ag and/or VWF:platelet ristocetin cofactor (RiCof) <0.03 iu/mL, no further testing is usually necessary. This is a cohort study that included 64 patients with type 3 VWD who were presented and diagnosed at the National Center of Hematology (NCH) from October 2014 to October 2016. In this study the sensitivity of VWF:Ag is only 78%, the sensitivity of VWF:RiCof is 92% of diagnosed cases. From our results it can be concluded that patients with type 3 VWD are usually presented with moderate/severe mucocutaneous bleeding that is associated with prolonged bleeding time test of >10 min and a family history of similar type of bleeding. This fact was frequently utilized to provisionally diagnose several members of the same family, forming a cohort of patients that is larger than the number of objectivelydiagnosed patients included in this study, when they cannot afford to be all tested with VWF:Ag/VWF:RiCof.
The Sociology of Morality as Ecology of Mind
Authors: Bargheer Stefan
Published: July 2018

The article engages in a comparative analysis of efforts to pass international legislation for the conservation of wild birds in turn-of-the-century Europe. Obstacles to this project were not merely incompatible laws already existing in the involved countries, but the different ways of relating economic, moral, and aesthetic evaluations of wildlife to each other. Focusing on the stark differences between German and British approaches to the topic, the article shows how the way these categories were related to each other was a product of the involved practices shaping the experience of the natural environment. As a result of different practices, moral justifications in Britain were one form of argument among many others formulated by conservationists. The logic of discourse was cumulative, comprising of different arguments that were presented as compatible with each other. In Germany, by contrast, conservationists recognized the existence of a variety of arguments for conservation, yet emphasized the incommensurability of these arguments and commonly advanced only one argument as a valid justification. Taking the centrality of the experience of nature into account, the article argues for the expansion of the classical sociology of morality into an ecology of mind.
Do markets make good commissioners?: A quasi-experimental analysis of retail electric restructuring in Ohio
Authors: Dormady Noah , Jiang Zhongnan , Hoyt Matthew
Published: July 2018

Empirical support for the purported benefits of retail electric deregulation is mixed at best. Prior studies that identify states as simply “retail deregulated” overlook complex policy environments in which deregulation is implemented by regulators with a high degree of discretion. Prior studies also rely on Energy Information Administration data that do not account for core regulatory interventions that can take place during the process of implementing deregulation. Using robust time series household final bill survey data from the Public Utilities Commission of Ohio, this article provides a quasi-experimental analysis of the price impacts of retail electric restructuring in Ohio. The results suggest that residential electricity prices have increased following retail restructuring in all service territories in Ohio, with significant favourable welfare effects observed only in the Cincinnati area, where key policy implementation stages were not circumvented.
NONPARAMETRIC STOCHASTIC VOLATILITY
Authors: Bandi Federico M. , Renò Roberto
Published: July 2018

We provide nonparametric methods for stochastic volatility modeling. Our methods allow for the joint evaluation of return and volatility dynamics with nonlinear drift and diffusion functions, nonlinear leverage effects, and jumps in returns and volatility with possibly state-dependent jump intensities, among other features. In the first stage, we identify spot volatility by virtue of jump-robust nonparametric estimates. Using observed prices and estimated spot volatilities, the second stage extracts the functions and parameters driving price and volatility dynamics from nonparametric estimates of the bivariate process’infinitesimal moments. For these infinitesimal moment estimates, we report an asymptotic theory relying onjointin-fill and long-span arguments which yields consistency and weak convergence under mild assumptions.
Race, Gender, and the 2016 Presidential Election
Authors: Philpot Tasha S.
Published: July 2018

With the first female presidential candidate at the top of the Democratic ticket, the gender gap in 2016 was predicted to be the largest ever. Although the gender gap proved to be bigger than any other in recent history, with a majority of women voting for Hillary Clinton, a disaggregation of the vote by race indicated that not all women equally supported the female presidential candidate. This suggests the existence of a racialized gender gap not previously explored by extant research. Thus, this article explores the nature of this interracial gender gap by examining the political evaluations of men and women, by race, in the 2016 presidential election. Using data from the 2016 American National Election Study (ANES) Time Series Study merged with the ANES Cumulative Data File (1948–2012), predictors of the gender gap were explored and the circumstances under which an interracial gender gap can be narrowed were examined.
Data Access, Transparency, and Replication: New Insights from the Political Behavior Literature
Authors: Stockemer Daniel , Koehler Sebastian , Lentz Tobias
Published: July 2018

Do researchers share their quantitative data and are the quantitative results that are published in political science journals replicable? We attempt to answer these questions by analyzing all articles published in the 2015 issues of three political behaviorist journals (i.e., Electoral Studies, Party Politics, and Journal of Elections, Public Opinion & Parties)—all of which did not have a binding data-sharing and replication policy as of 2015. We found that authors are still reluctant to share their data; only slightly more than half of the authors in these journals do so. For those who share their data, we mainly confirmed the initial results reported in the respective articles in roughly 70% of the times. Only roughly 5% of the articles yielded significantly different results from those reported in the publication. However, we also found that roughly 25% of the articles organized the data and/or code so poorly that replication was impossible.
Laws for Metaphysical Explanation
Authors: Schaffer Jonathan
Published: July 2018

I argue that, just like causal explanation requires laws of nature, so metaphysical explanation requires laws of metaphysics. I offer a minimal rendition of the argument for laws of metaphysics, assuming nothing about grounding or essences, and little about explanation. And I offer a positive and minimal functional conception of the laws of metaphysics, coupled with an argument that some laws of metaphysics are fundamental.
Irrealism about Grounding
Authors: Thompson Naomi
Published: July 2018

Grounding talk has become increasingly familiar in contemporary philosophical discussion. Most discussants of grounding think that grounding talk is useful, intelligible, and accurately describes metaphysical reality. Call themrealistsabout grounding. Some dissenters reject grounding talk on the grounds that it is unintelligible, or unmotivated. They would prefer to eliminate grounding talk from philosophy, so we can call themeliminitivistsabout grounding. This paper outlines a new position in the debate about grounding, defending the view that grounding talk is (or at least can be) intelligible and useful. Grounding talk does not, however, provide a literal and veridical description of mind-independent metaphysical reality. This (non-eliminative)irrealismabout grounding treads a path between realism and eliminativism.
Interplate Coupling State at the Nansei‐Shoto (Ryukyu) Trench, Japan, Deduced From Seafloor Crustal Deformation Measurements
Authors: Tadokoro Keiichi , Nakamura Mamoru , Ando Masataka , Kimura Hiroshi , Watanabe Tsuyoshi , Matsuhiro Kenjiro
Published: July 2018

We performed observations of seafloor crustal deformation employing the Global Navigation Satellite System/Acoustic technique at two stations installed at about 45 and 70 km from the axis of the Nansei‐Shoto (Ryukyu) Trench, to the southeast off the Okinawa Main Island. The observations for 3‐ and 6‐year survey periods indicate that the two stations moved landward, in the opposite direction to the trench, by 63 and 21 mm/year relative to the Ryukyu Arc, suggesting interplate coupling around the stations. The observational results reveal the strong coupling state on the plate interface with coupling ratios of 0.9–1.0 at the slab depths of 10–13 km or 0.7–0.8 at slab depth ranging from 13 km up to the seafloor. The strongly coupled segment completely coincides with the source area of the 1791 tsunami event and does not overlap with the activity area of slow slip events.
The Relation Between the Seasonal Changes in Jet Characteristics and the Pacific Midwinter Minimum in Eddy Activity
Authors: Yuval J. , Afargan H. , Kaspi Y.
Published: July 2018

This study relates the occurrence of the midwinter minimum in eddy activity over the North Pacific with the seasonality in jet characteristics. During winter, the Pacific jet core is typically around latitude 32°N and has features of a merged subtropical eddy‐driven jet. On the other hand, during transition seasons, the jet is at higher latitudes (≈40°N) and resembles more an eddy‐driven jet. We find that these differences in jet characteristics play a role in the occurrence of the midwinter minimum. It is found that a midwinter minimum‐like behavior in eddy activity, as observed, is obtained in idealized simulations where zonally symmetric temperature profiles are adjusted to mimic the seasonality of longitudinally averaged temperature observed across the North Pacific. Furthermore, we find in both reanalysis data and the idealized simulations that a poleward shift of the January jet leads to an increase in eddy kinetic energy.
Thin is required for cell death in the Drosophila abdominal muscles by targeting DIAP1
Authors: Vishal Kumar , Bawa Simranjot , Brooks David , Bauman Kenneth , Geisbrecht Erika R.
Published: July 2018

In holometabolous insects, developmentally controlled programmed cell death (PCD) is a conserved process that destroys a subset of larval tissues for the eventual creation of new adult structures. This process of histolysis is relatively well studied in salivary gland and midgut tissues, while knowledge concerning larval muscle destruction is limited. Here, we have examined the histolysis of a group of Drosophila larval abdominal muscles called the dorsal external oblique muscles (DEOMs). Previous studies have defined apoptosis as the primary mediator of DEOM breakdown, whose timing is controlled by ecdysone signaling. However, very little is known about other factors that contribute to DEOM destruction. In this paper, we examine the role of thin (tn), which encodes for the Drosophila homolog of mammalian TRIM32, in the regulation of DEOM histolysis. We find that loss of Tn blocks DEOM degradation independent of ecdysone signaling. Instead, tn genetically functions in a pathway with the death-associated inhibitor of apoptosis (DIAP1), Dronc, and death-associated APAF1-related killer (Dark) to regulate apoptosis. Importantly, blocking Tn results in the absence of active Caspase-3 immunostaining, upregulation of DIAP1 protein levels, and inhibition of Dronc activation. DIAP1 and Dronc mRNA levels are not altered in tn mutants, showing that Tn acts post-transcriptionally on DIAP1 to regulate apoptosis. Herein, we also find that the RING domain of Tn is required for DEOM histolysis as loss of this domain results in higher DIAP1 levels. Together, our results suggest that the direct control of DIAP1 levels, likely through the E3 ubiquitin ligase activity of Tn, provides a mechanism to regulate caspase activity and to facilitate muscle cell death.
The novel long noncoding RNA u50535 promotes colorectal cancer growth and metastasis by regulating CCL20
Authors: Yu Xihu , Yuan Zixu , Yang Zuli , Chen Daici , Kim Taewan , Cui Yanmei , Luo Qianxin , Liu Zhihang , Yang Zihuan , Fan Xinjuan , Chen DianKe , Wang Lei
Published: July 2018

Long noncoding RNAs (lncRNAs) have been emerging as master regulators of tumor growth and metastasis, but the functions and underlying mechanisms of lncRNAs in colorectal cancer (CRC) still need to be clarified. Here, we found a novel lncRNA u50535, which was greatly overexpressed in CRC tissues and was associated with poor prognosis in CRC patients. Function studies showed that u50535 was an oncogene in CRC both in vitro and in vivo. In mechanism, through RNA sequencing and rescue assay, we found that u50535 activates CCL20 signaling to promote cell proliferation and migration in CRC. Taken together, these findings suggest that u50535 can promote CRC growth and metastasis and may serve as a potential biomarker in CRC.
SOX17 restrains proliferation and tumor formation by down-regulating activity of the Wnt/β-catenin signaling pathway via trans-suppressing β-catenin in cervical cancer
Authors: Li Lu , Yang Wen-Ting , Zheng Peng-Sheng , Liu Xiao-Fang
Published: July 2018

The SRY-box containing gene 17 (SOX17) is considered as a regulator in stemness maintenance and a suppressor in some malignant tumors. However, the biological function and molecular mechanism of SOX17 in the process of initiation and progression of cervical cancer remain obscure. In this study, immunohistochemistry showed that the expression of SOX17 was high in the normal cervix, moderate in the high-grade squamous intraepithelial lesion, and low in the cervical cancer. SOX17 inhibited the proliferation and viability of cervical cancer cells in vitro as well as tumor formation in vivo. Additionally, SOX17 induced the cell cycle arrest at the transition from the G0/G1 phase to the S phase. The TOP/ FOP-Flash reporter assay and Western blotting showed SOX17 inhibited the activity of the Wnt/β-catenin signaling pathway in cervical cancer. Further, firefly luciferase reporter assay and quantitative chromatin immunoprecipitation (qChIP) assays confirmed that SOX17 trans-suppressed the expression of β-catenin by directly binding to the specific region of the β-catenin promoter. Together, our data demonstrated that SOX17 restrained the proliferation and tumor formation by down-regulating the activity of the Wnt/β-catenin signaling pathway via trans-suppression of β-catenin in cervical cancer.
Retraction Note: Liver X receptors constrain tumor development and metastasis dissemination in PTEN-deficient prostate cancer
Authors: Alioui Anthony , Dufour Julie , Leoni Valerio , Loregger Anke , Moeton Martina , Iuliano Luigi , Zerbinati Chiara , Septier Amandine , Val Pierre , Fouache Allan , Russo Vincenzo , Volle David H. , Lobaccaro Jean-Marc A. , Zelcer Noam , Baron Silvère
Published: July 2018

This paper has been retracted at the request of the authors.
Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development
Authors: Painter Heather J. , Chung Neo Christopher , Sebastian Aswathy , Albert Istvan , Storey John D. , Llinás Manuel
Published: July 2018

Genome-wide analysis of transcription in the malaria parasite Plasmodium falciparum has revealed robust variation in steady-state mRNA abundance throughout the 48-h intraerythrocytic developmental cycle (IDC), suggesting that this process is highly dynamic and tightly regulated. Here, we utilize rapid 4-thiouracil (4-TU) incorporation via pyrimidine salvage to specifically label, capture, and quantify newly-synthesized RNA transcripts at every hour throughout the IDC. This high-resolution global analysis of the transcriptome captures the timing and rate of transcription for each newly synthesized mRNA in vivo, revealing active transcription throughout all IDC stages. Using a statistical model to predict the mRNA dynamics contributing to the total mRNA abundance at each timepoint, we find varying degrees of transcription and stabilization for each mRNA corresponding to developmental transitions. Finally, our results provide new insight into co-regulation of mRNAs throughout the IDC through regulatory DNA sequence motifs, thereby expanding our understanding of P. falciparum mRNA dynamics.
Attentional fluctuations induce shared variability in macaque primary visual cortex
Authors: Denfield George H. , Ecker Alexander S. , Shinn Tori J. , Bethge Matthias , Tolias Andreas S.
Published: July 2018

Variability in neuronal responses to identical stimuli is frequently correlated across a population. Attention is thought to reduce these correlations by suppressing noisy inputs shared by the population. However, even with precise control of the visual stimulus, the subject’s attentional state varies across trials. While these state fluctuations are bound to induce some degree of correlated variability, it is currently unknown how strong their effect is, as previous studies generally do not dissociate changes in attentional strength from changes in attentional state variability. We designed a novel paradigm that does so and find both a pronounced effect of attentional fluctuations on correlated variability at long timescales and attention-dependent reductions in correlations at short timescales. These effects predominate in layers 2/3, as expected from a feedback signal such as attention. Thus, significant portions of correlated variability can be attributed to fluctuations in internally generated signals, like attention, rather than noise.
Gut microbiota associations with common diseases and prescription medications in a population-based cohort
Authors: Jackson Matthew A. , Verdi Serena , Maxan Maria-Emanuela , Shin Cheol Min , Zierer Jonas , Bowyer Ruth C. E. , Martin Tiphaine , Williams Frances M. K. , Menni Cristina , Bell Jordana T. , Spector Tim D. , Steves Claire J.
Published: July 2018

The human gut microbiome has been associated with many health factors but variability between studies limits exploration of effects between them. Gut microbiota profiles are available for >2700 members of the deeply phenotyped TwinsUK cohort, providing a uniform platform for such comparisons. Here, we present gut microbiota association analyses for 38 common diseases and 51 medications within the cohort. We describe several novel associations, highlight associations common across multiple diseases, and determine which diseases and medications have the greatest association with the gut microbiota. These results provide a reference for future studies of the gut microbiome and its role in human health.
Interleukin 10 mutant zebrafish have an enhanced interferon gamma response and improved survival against a Mycobacterium marinum infection
Authors: Harjula Sanna-Kaisa E. , Ojanen Markus J. T. , Taavitsainen Sinja , Nykter Matti , Rämet Mika
Published: July 2018

Tuberculosis ranks as one of the world’s deadliest infectious diseases causing more than a million casualties annually. IL10 inhibits the function of Th1 type cells, and IL10 deficiency has been associated with an improved resistance againstMycobacterium tuberculosisinfection in a mouse model. Here, we utilizedM. marinuminfection in the zebrafish (Danio rerio) as a model for studying Il10 in the host response against mycobacteria. Unchallenged, nonsenseil10e46/e46mutant zebrafish were fertile and phenotypically normal. Following a chronic mycobacterial infection,il10e46/e46mutants showed enhanced survival compared to the controls. This was associated with an increased expression of the Th cell markercd4-1and a shift towards a Th1 type immune response, which was demonstrated by the upregulated expression oftbx21andifng1, as well as the down-regulation ofgata3. In addition, at 8 weeks post infectionil10e46/e46mutant zebrafish had reduced expression levels of proinflammatory cytokinestnfbandil1b, presumably indicating slower progress of the infection. Altogether, our data show that Il10 can weaken the immune defense againstM. marinuminfection in zebrafish by restrictingifng1response. Importantly, our findings support the relevance ofM. marinuminfection in zebrafish as a model for tuberculosis.
Soluble interleukin-27 receptor alpha is a valuable prognostic biomarker for acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation
Authors: Liu Shuangzhu , Han Jingjing , Gong Huanle , Li Yongsheng , Bao Xiebing , Qi Jiaqian , Liu Hong , Chen Jia , Wu Xiaojin , Xu Yang , Ma Shoubao , Wu Depei
Published: July 2018

Acute graft-versus-host disease (aGVHD) is a major life-threatening complication after allogeneic haematopoietic stem cell transplantation. Interleukin-27 receptor alpha (IL-27Rα) is a co-receptor of IL-27, an inflammatory cytokine that possesses extensive immunological functions. It has been reported that IL-27Rα can exist in its soluble form (sIL-27Rα) in human serum and can function as a natural IL-27 antagonist. In this study, we examined serum sIL-27Rα levels and evaluated their prognostic value in aGVHD. A total of 152 subjects were prospectively recruited and separated into the training group (n = 72) and the validation group (n = 80). Serum sIL-27Rα at neutrophil engraftment was measured by ELISA. In the training set, a cut-off value of sIL-27Rα = 59.40 ng/ml was identified to predict grade II–IV aGVHD (AUC = 0.735, 95% CI 0.618–0.853, P = 0.001). Cumulative incidences of grade II–IV aGVHD (P = 0.004), relapse rate (P = 0.008), and non-relapse mortality (P = 0.008) in patients with low serum sIL-27Rα (≥59.40 ng/ml) were significantly higher than those of patients with high serum sIL-27Rα (<59.40 ng/ml). Multivariate analysis confirmed that low sIL-27Rα level (HR = 2.83 95% CI 1.29–6.19, P < 0.01) was an independent risk factor for predicting grade II-IV aGVHD. In addition, serum sIL-27Rα was positively correlated with IL-27 (R = 0.27, P = 0.029), IL-10 (R = 0.37, P = 0.0015) and HGF (R = 0.27, P = 0.0208), but was negatively correlated with TNFR1 (R = −0.365, P = 0.0022) and ST2 (R = −0.334, P = 0.0041), elafin (R = −0.29, P = 0.0117), and REG3α (R = −0.417, P = 0.0003). More importantly, the threshold value of sIL-27Rα was then validated in an independent cohort of 80 patients (AUC = 0.790, 95% CI 0.688–0.892, P < 0.001). Taken together, our findings suggested that serum sIL-27Rα at neutrophil engraftment maybe a valuable prognostic biomarker in predicting the incidence of moderate-to-severe aGVHD.
A power law distribution of metabolite abundance levels in mice regardless of the time and spatial scale of analysis
Authors: Sato Shumpei , Horikawa Makoto , Kondo Takeshi , Sato Tomohito , Setou Mitsutoshi
Published: July 2018

Biomolecule abundance levels change with the environment and enable a living system to adapt to the new conditions. Although, the living system maintains at least some characteristics, e.g. homeostasis. One of the characteristics maintained by a living system is a power law distribution of biomolecule abundance levels. Previous studies have pointed to a universal characteristic of biochemical reaction networks, with data obtained from lysates of multiple cells. As a result, the spatial scale of the data related to the power law distribution of biomolecule abundance levels is not clear. In this study, we researched the scaling law of metabolites in mouse tissue with a spatial scale of quantification that was changed stepwise between a whole-tissue section and a single-point analysis (25 μm). As a result, metabolites in mouse tissues were found to follow the power law distribution independently of the spatial scale of analysis. Additionally, we tested the temporal changes by comparing data from younger and older mice. Both followed similar power law distributions, indicating that metabolite composition is not diversified by aging to disrupt the power law distribution. The power law distribution of metabolite abundance is thus a robust characteristic of a living system regardless of time and space.
Integer-dimensional fractals of nonlinear dynamics, control mechanisms, and physical implications
Authors: He Zonglu
Published: July 2018

Fractal dimensionality is accepted as a measure of complexity for systems that cannot be described by integer dimensions. However, fractal control mechanisms, physical implications, and relations to nonlinear dynamics have not yet been fully clarified. Herein we explore these issues in a spacetime using a nonlinear integrated model derived by applying Newton’s second law into self-regulating systems. We discover that (i) a stochastic stable fixed point exhibits self-similarity and long-term memory, while a deterministic stable fixed point usually only exhibits self-similarity, if our observation scale is large enough; (ii) stochastic/deterministic period cycles and chaos only exhibit long-term memory, but also self-similarity for even restorative delays; (iii) fractal level of a stable fixed point is controlled primarily by the wave indicators that reflect the relative strength of extrinsic to intrinsic forces: a larger absolute slope (smaller amplitude) indicator leads to higher positive dependence (self-similarity), and a relatively large amplitude indicator or an even restorative delay could make the dependence oscillate; and (iv) fractal levels of period cycles and chaos rely on the intrinsic resistance, restoration, and regulative delays. Our findings suggest that fractals of self-regulating systems can be measured by integer dimensions.