bluuebunny/crossref_metadata_2025_split huggingface dataset:
Belief and Counterfactuality
Authors: Rafetseder Eva , Perner Josef 
Published: March 2018

Abstract. The development and relation of counterfactual reasoning and false belief understanding were examined in 3- to 7-year-old children (N = 75) and adult controls (N = 14). The key question was whether false belief understanding engages counterfactual reasoning to infer what somebody else falsely believes. Findings revealed a strong correlation between false belief and counterfactual questions even in conditions in which children could commit errors other than the reality bias (rp = .51). The data suggest that mastery of belief attribution and counterfactual reasoning is not limited to one point in development but rather develops over a longer period. Moreover, the rare occurrence of reality errors calls into question whether young children’s errors in the classic false belief task are indeed the result of a failure to inhibit what they know to be actually the case. The data speak in favor of a teleological theory of belief attribution and challenges established theories of belief attribution.
Controlled drug delivery vehicles for cancer treatment and their performance
Authors: Senapati Sudipta , Mahanta Arun Kumar , Kumar Sunil , Maiti Pralay 
Published: March 2018

AbstractAlthough conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments.
Automatic detection of image manipulations in the biomedical literature
Authors: Bucci Enrico M. 
Published: March 2018

AbstractImages in scientific papers are used to support the experimental description and the discussion of the findings since several centuries. In the field of biomedical sciences, in particular, the use of images to depict laboratory results is widely diffused, at such a level that one would not err in saying that there is barely any experimental paper devoid of images to document the attained results. With the advent of software for digital image manipulation, however, even photographic reproductions of experimental results may be easily altered by researchers, leading to an increasingly high rate of scientific papers containing unreliable images. In this paper I introduce a software pipeline to detect some of the most diffuse misbehaviours, running two independent tests on a random set of papers and on the full publishing record of a single journal. The results obtained by these two tests support the feasibility of the software approach and imply an alarming level of image manipulation in the published record.
circHECTD1 promotes the silica-induced pulmonary endothelial–mesenchymal transition via HECTD1
Authors: Fang Shencun , Guo Huifang , Cheng Yusi , Zhou Zewei , Zhang Wei , Han Bing , Luo Wei , Wang Jing , Xie Weiping , Chao Jie 
Published: March 2018

AbstractExcessive proliferation and migration of fibroblasts contribute to pulmonary fibrosis in silicosis, and both epithelial cells and endothelial cells participate in the accumulation of fibroblasts via the epithelial–mesenchymal transition (EMT) and the endothelial–mesenchymal transition (EndMT), respectively. A mouse endothelial cell line (MML1) was exposed to silicon dioxide (SiO2, 50 μg/cm2), and immunofluorescence and western blot analyses were performed to evaluate levels of specific endothelial and mesenchymal markers and to elucidate the mechanisms by which SiO2 induces the EndMT. Functional changes were evaluated by analyzing cell migration and proliferation. The mRNA and circular RNA (circRNA) levels were measured using qPCR and fluorescent in situ hybridization (FISH). Lung tissue samples from both Tie2-GFP mice exposed to SiO2 and silicosis patients were applied to confirm the observations from in vitro experiments. Based on the results from the current study, SiO2 increased the expression of mesenchymal markers (type I collagen (COL1A1), type III collagen (COL3A1) and alpha smooth muscle actin (α-SMA/Acta2)) and decreased the expression of endothelial markers (vascular endothelial cadherin (VE-Cad/Cdh 5) and platelet endothelial cell adhesion molecule-1 (PECAM1)), indicating the occurrence of the EndMT in response to SiO2 exposure both in vivo and in vitro. SiO2 concomitantly increased circHECTD1 expression, which, in turn, inhibited HECTD1 protein expression. SiO2-induced increases in cell proliferation, migration, and changes in marker levels were restored by either a small interfering RNA (siRNA) targeting circHECTD1 or overexpression of HECTD1 via the CRISPR/Cas9 system, confirming the involvement of the circHECTD1/HECTD1 pathway in the EndMT. Moreover, tissue samples from SiO2-exposed mice and silicosis patients confirmed the EndMT and change in HECTD1 expression. Our findings reveal a potentially new function for the circHECTD1/HECTD1 pathway and suggest a possible mechanism of fibrosis in patients with pulmonary silicosis.
TRIP13 promotes tumor growth and is associated with poor prognosis in colorectal cancer
Authors: Sheng Nengquan , Yan Li , Wu Kai , You Weiqiang , Gong Jianfeng , Hu Landian , Tan Gewen , Chen Hongqi , Wang Zhigang 
Published: March 2018

AbstractColorectal cancer (CRC) is one of the most common neoplasms worldwide. However, the mechanisms underlying its development are still poorly understood. Thyroid hormone Receptor Interactor 13 (TRIP13) is a key mitosis regulator, and recent evidence has shown that it is an oncogene. Here, we report that TRIP13, which is overexpressed in CRC, is correlated with the CEA (carcino-embryonic antigen), CA19-9 (carbohydrate antigen 19-9) and pTNM (pathologic primary tumor, lymph nodes, distant metastasis) classification. Multivariate analyses showed that TRIP13 might serve as an independent prognostic marker of CRC. We also found that TRIP13 promoted CRC cell proliferation, invasion and migration in vitro and subcutaneous tumor formation in vivo. Furthermore, the potential mechanism underlying these effects involves the interaction of TRIP13 with a 14-3-3 protein, YWHAZ, which mediates G2-M transition and epithelial-mesenchymal transition (EMT). Together, these findings suggest that TRIP13 may be a potential biomarker and therapeutic target for CRC.
Inhibition of p70 S6 kinase activity by A77 1726 induces autophagy and enhances the degradation of superoxide dismutase 1 (SOD1) protein aggregates
Authors: Sun Jing , Mu Yarong , Jiang Yuanyuan , Song Ruilong , Yi Jianxin , Zhou Jingsong , Sun Jun , Jiao Xinan , Prinz Richard A. , Li Yi , Xu Xiulong 
Published: March 2018

AbstractAutophagy plays a central role in degrading misfolded proteins such as mutated superoxide dismutase 1 (SOD1), which forms aggregates in motor neurons and is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is activated when UNC-51-like kinase 1 (ULK1) is phosphorylated at S555 and activated by AMP-activated protein kinase (AMPK). Autophagy is suppressed when ULK1 is phosphorylated at S757 by the mechanistic target of rapamycin (mTOR). Whether p70 S6 kinase 1 (S6K1), a serine/threonine kinase downstream of mTOR, can also regulate autophagy remains uncertain. Here we report that inhibition of S6K1 by A77 1726, the active metabolite of an anti-inflammatory drug leflunomide, induced mTOR feedback activation and ULK1S757phosphorylation in NSC34 cells, a hybrid mouse motoneuron cell line. Unexpectedly, A77 1726 did not suppress but rather induced autophagy by increasing AMPKT172and ULK1S555phosphorylation. Similar observations were made with PF-4708671, a specific S6K1 inhibitor, or with S6K1 siRNA. Further studies showed that A77 1726 induced AMPK phosphorylation by activating the TGF-β-activated kinase 1 (TAK1). Functional studies revealed that A77 1726 induced co-localization of mutant SOD1G93Aprotein aggregates with autophagosomes and accelerated SOD1G93Aprotein degradation, which was blocked by inhibition of autophagy through autophagy-related protein 7 (ATG7) siRNA. Our study suggests that S6K1 inhibition induces autophagy through TAK1-mediated AMPK activation in NSC34 cells, and that blocking S6K1 activity by a small molecule inhibitor such as leflunomide may offer a new strategy for ALS treatment.
Myocardial Bmp2 gain causes ectopic EMT and promotes cardiomyocyte proliferation and immaturity
Authors: Prados Belén , Gómez-Apiñániz Paula , Papoutsi Tania , Luxán Guillermo , Zaffran Stephane , Pérez-Pomares José María , de la Pompa José Luis 
Published: March 2018

AbstractDuring mammalian heart development, restricted myocardial Bmp2 expression is a key patterning signal for atrioventricular canal specification and the epithelial–mesenchyme transition that gives rise to the valves. Using a mouse transgenic line conditionally expressing Bmp2, we show that widespread Bmp2 expression in the myocardium leads to valve and chamber dysmorphogenesis and embryonic death by E15.5. Transgenic embryos show thickened valves, ventricular septal defect, enlarged trabeculae and dilated ventricles, with an endocardium able to undergo EMT both in vivo and in vitro. Gene profiling and marker analysis indicate that cellular proliferation is increased in transgenic embryos, whereas chamber maturation and patterning are impaired. Similarly, forced Bmp2 expression stimulates proliferation and blocks cardiomyocyte differentiation of embryoid bodies. These data show that widespread myocardial Bmp2 expression directs ectopic valve primordium formation and maintains ventricular myocardium and cardiac progenitors in a primitive, proliferative state, identifying the potential of Bmp2 in the expansion of immature cardiomyocytes.
Land use change and El Niño-Southern Oscillation drive decadal carbon balance shifts in Southeast Asia
Authors: Kondo Masayuki , Ichii Kazuhito , Patra Prabir K. , Canadell Joseph G. , Poulter Benjamin , Sitch Stephen , Calle Leonardo , Liu Yi Y. , van Dijk Albert I. J. M. , Saeki Tazu , Saigusa Nobuko , Friedlingstein Pierre , Arneth Almut , Harper Anna , Jain Atul K. , Kato Etsushi , Koven Charles , Li Fang , Pugh Thomas A. M. , Zaehle Sönke , Wiltshire Andy , Chevallier Frederic , Maki Takashi , Nakamura Takashi , Niwa Yosuke , Rödenbeck Christian 
Published: March 2018

AbstractAn integrated understanding of the biogeochemical consequences of climate extremes and land use changes is needed to constrain land-surface feedbacks to atmospheric CO2 from associated climate change. Past assessments of the global carbon balance have shown particularly high uncertainty in Southeast Asia. Here, we use a combination of model ensembles to show that intensified land use change made Southeast Asia a strong source of CO2 from the 1980s to 1990s, whereas the region was close to carbon neutral in the 2000s due to an enhanced CO2 fertilization effect and absence of moderate-to-strong El Niño events. Our findings suggest that despite ongoing deforestation, CO2 emissions were substantially decreased during the 2000s, largely owing to milder climate that restores photosynthetic capacity and suppresses peat and deforestation fire emissions. The occurrence of strong El Niño events after 2009 suggests that the region has returned to conditions of increased vulnerability of carbon stocks.
Memory effects can make the transmission capability of a communication channel uncomputable
Authors: Elkouss David , Pérez-García David 
Published: March 2018

AbstractMost communication channels are subjected to noise. One of the goals of information theory is to add redundancy in the transmission of information so that the information is transmitted reliably and the amount of information transmitted through the channel is as large as possible. The maximum rate at which reliable transmission is possible is called the capacity. If the channel does not keep memory of its past, the capacity is given by a simple optimization problem and can be efficiently computed. The situation of channels with memory is less clear. Here we show that for channels with memory the capacity cannot be computed to within precision 1/5. Our result holds even if we consider one of the simplest families of such channels—information-stable finite state machine channels—restrict the input and output of the channel to 4 and 1 bit respectively and allow 6 bits of memory.
The human cortex possesses a reconfigurable dynamic network architecture that is disrupted in psychosis
Authors: Reinen Jenna M. , Chén Oliver Y. , Hutchison R. Matthew , Yeo B. T. Thomas , Anderson Kevin M. , Sabuncu Mert R. , Öngür Dost , Roffman Joshua L. , Smoller Jordan W. , Baker Justin T. , Holmes Avram J. 
Published: March 2018

AbstractHigher-order cognition emerges through the flexible interactions of large-scale brain networks, an aspect of temporal coordination that may be impaired in psychosis. Here, we map the dynamic functional architecture of the cerebral cortex in healthy young adults, leveraging this atlas of transient network configurations (states), to identify state- and network-specific disruptions in patients with schizophrenia and psychotic bipolar disorder. We demonstrate that dynamic connectivity profiles are reliable within participants, and can act as a fingerprint, identifying specific individuals within a larger group. Patients with psychotic illness exhibit intermittent disruptions within cortical networks previously associated with the disease, and the individual connectivity profiles within specific brain states predict the presence of active psychotic symptoms. Taken together, these results provide evidence for a reconfigurable dynamic architecture in the general population and suggest that prior reports of network disruptions in psychosis may reflect symptom-relevant transient abnormalities, rather than a time-invariant global deficit.
Robustness of anthropogenically forced decadal precipitation changes projected for the 21st century
Authors: Zhang Honghai , Delworth Thomas L. 
Published: March 2018

AbstractPrecipitation is characterized by substantial natural variability, including on regional and decadal scales. This relatively large variability poses a grand challenge in assessing the significance of anthropogenically forced precipitation changes. Here we use multiple large ensembles of climate change experiments to evaluate whether, on regional scales, anthropogenic changes in decadal precipitation mean state are distinguishable. Here, distinguishable means the anthropogenic change is outside the range expected from natural variability. Relative to the 1950–1999 period, simulated anthropogenic shifts in precipitation mean state for the 2000–2009 period are already distinguishable over 36–41% of the globe—primarily in high latitudes, eastern subtropical oceans, and the tropics. Anthropogenic forcing in future medium-to-high emission scenarios is projected to cause distinguishable shifts over 68–75% of the globe by 2050 and 86–88% by 2100. Our findings imply anthropogenic shifts in decadal-mean precipitation will exceed the bounds of natural variability over most of the planet within several decades.
Automated generation and ensemble-learned matching of X-ray absorption spectra
Authors: Zheng Chen , Mathew Kiran , Chen Chi , Chen Yiming , Tang Hanmei , Dozier Alan , Kas Joshua J. , Vila Fernando D. , Rehr John J. , Piper Louis F. J. , Persson Kristin A. , Ong Shyue Ping 
Published: March 2018

AbstractX-ray absorption spectroscopy (XAS) is a widely used materials characterization technique to determine oxidation states, coordination environment, and other local atomic structure information. Analysis of XAS relies on comparison of measured spectra to reliable reference spectra. However, existing databases of XAS spectra are highly limited both in terms of the number of reference spectra available as well as the breadth of chemistry coverage. In this work, we report the development of XASdb, a large database of computed reference XAS, and an Ensemble-Learned Spectra IdEntification (ELSIE) algorithm for the matching of spectra. XASdb currently hosts more than 800,000 K-edge X-ray absorption near-edge spectra (XANES) for over 40,000 materials from the open-science Materials Project database. We discuss a high-throughput automation framework for FEFF calculations, built on robust, rigorously benchmarked parameters. FEFF is a computer program uses a real-space Green’s function approach to calculate X-ray absorption spectra. We will demonstrate that the ELSIE algorithm, which combines 33 weak “learners” comprising a set of preprocessing steps and a similarity metric, can achieve up to 84.2% accuracy in identifying the correct oxidation state and coordination environment of a test set of 19 K-edge XANES spectra encompassing a diverse range of chemistries and crystal structures. The XASdb with the ELSIE algorithm has been integrated into a web application in the Materials Project, providing an important new public resource for the analysis of XAS to all materials researchers. Finally, the ELSIE algorithm itself has been made available as part of veidt, an open source machine-learning library for materials science.
An effective method to screen sodium-based layered materials for sodium ion batteries
Authors: Zhang Xu , Zhang Zihe , Yao Sai , Chen An , Zhao Xudong , Zhou Zhen 
Published: March 2018

AbstractDue to the high cost and insufficient resource of lithium, sodium-ion batteries are widely investigated for large-scale applications. Typically, insertion-type materials possess better cyclic stability than alloy-type and conversion-type ones. Therefore, in this work, we proposed a facile and effective method to screen sodium-based layered materials based on Materials Project database as potential candidate insertion-type materials for sodium ion batteries. The obtained Na-based layered materials contains 38 kinds of space group, which reveals that the credibility of our screening approach would not be affected by the space group. Then, some important indexes of the representative materials, including the average voltage, volume change and sodium ion mobility, were further studied by means of density functional theory computations. Some materials with extremely low volume changes and Na diffusion barriers are promising candidates for sodium ion batteries. We believe that our classification algorithm could also be used to search for other alkali and multivalent ion-based layered materials, to accelerate the development of battery materials.
De Novo Design of Potent, Insecticidal Synthetic Mimics of the Spinosyn Macrolide Natural Products
Authors: Crouse Gary D. , Demeter David A. , Samaritoni Geno , McLeod Casandra L. , Sparks Thomas C. 
Published: March 2018

AbstractNew insect pest control agents are needed to meet the demands to feed an expanding global population, to address the desire for more environmentally-friendly insecticide tools, and to fill the loss of control options in some crop-pest complexes due to development of insecticide resistance. The spinosyns are a highly effective class of naturally occurring, fermentation derived insecticides, possessing a very favorable environmental profile. Chemically, the spinosyns are composed of a large complex macrolide tetracycle coupled to two sugars. As a means to further exploit this novel class of natural product-based insecticides, molecular modeling studies coupled with bioactivity-directed chemical modifications were used to define a less complex, synthetically accessible replacement for the spinosyn tetracycle. These studies lead to the discovery of highly insecticidal analogs, possessing a simple tri-aryl ring system as a replacement for the complex macrolide tetracycle.
Low Temperature-Mediated Enhancement of Photoacoustic Imaging Depth
Authors: Mahmoodkalayeh Sadreddin , Jooya Hossein Z. , Hariri Ali , Zhou Yang , Xu Qiuyun , Ansari Mohammad A. , Avanaki Mohammad R. N. 
Published: March 2018

AbstractWe study the temperature dependence of the underlying mechanisms related to the signal strength and imaging depth in photoacoustic imaging. The presented theoretical and experimental results indicate that imaging depth can be improved by lowering the temperature of the intermediate medium that the laser passes through to reach the imaging target. We discuss the temperature dependency of optical and acoustic properties of the intermediate medium and their changes due to cooling. We demonstrate that the SNR improvement of the photoacoustic signal is mainly due to the reduction of Grüneisen parameter of the intermediate medium which leads to a lower level of background noise. These findings may open new possibilities toward the application of biomedical laser refrigeration.
Predicting Binding Free Energies of PDE2 Inhibitors. The Difficulties of Protein Conformation
Authors: Pérez-Benito Laura , Keränen Henrik , van Vlijmen Herman , Tresadern Gary 
Published: March 2018

AbstractA congeneric series of 21 phosphodiesterase 2 (PDE2) inhibitors are reported. Crystal structures show how the molecules can occupy a ‘top-pocket’ of the active site. Molecules with small substituents do not enter the pocket, a critical leucine (Leu770) is closed and water molecules are present. Large substituents enter the pocket, opening the Leu770 conformation and displacing the waters. We also report an X-ray structure revealing a new conformation of the PDE2 active site domain. The relative binding affinities of these compounds were studied with free energy perturbation (FEP) methods and it represents an attractive real-world test case. In general, the calculations could predict the energy of small-to-small, or large-to-large molecule perturbations. However, accurately capturing the transition from small-to-large proved challenging. Only when using alternative protein conformations did results improve. The new X-ray structure, along with a modelled dimer, conferred stability to the catalytic domain during the FEP molecular dynamics (MD) simulations, increasing the convergence and thereby improving the prediction of ΔΔG of binding for some small-to-large transitions. In summary, we found the most significant improvement in results when using different protein structures, and this data set is useful for future free energy validation studies.
Contact geometry and mechanics predict friction forces during tactile surface exploration
Authors: Janko Marco , Wiertlewski Michael , Visell Yon 
Published: March 2018

AbstractWhen we touch an object, complex frictional forces are produced, aiding us in perceiving surface features that help to identify the object at hand, and also facilitating grasping and manipulation. However, even during controlled tactile exploration, sliding friction forces fluctuate greatly, and it is unclear how they relate to the surface topography or mechanics of contact with the finger. We investigated the sliding contact between the finger and different relief surfaces, using high-speed video and force measurements. Informed by these experiments, we developed a friction force model that accounts for surface shape and contact mechanical effects, and is able to predict sliding friction forces for different surfaces and exploration speeds. We also observed that local regions of disconnection between the finger and surface develop near high relief features, due to the stiffness of the finger tissues. Every tested surface had regions that were never contacted by the finger; we refer to these as “tactile blind spots”. The results elucidate friction force production during tactile exploration, may aid efforts to connect sensory and motor function of the hand to properties of touched objects, and provide crucial knowledge to inform the rendering of realistic experiences of touch contact in virtual reality.