bluuebunny/crossref_metadata_2025_split huggingface dataset:
The return of truth: defending the correspondence theory after the liberal/postliberal divide
Authors: KNIGHT JOHN ALLAN 
Published: February 2019

AbstractThis article defends the correspondence theory of truth against criticisms of three theologians: Stephen Long, Kevin Hector, and Bruce Marshall. Long's criticisms arise from his metaphysical commitments, Hector's from his anti-metaphysical commitments, and Marshall's from his methodological commitments. I treat Long and Hector briefly, before giving a more extended treatment of Bruce Marshall's attack on the correspondence theory using the slingshot argument of Donald Davidson. I argue that correspondence theories withstand their criticisms. They therefore pose no obstacle to using them in theology.
Vitamin C improves liver and renal functions in hypothyroid rats by reducing tissue oxidative injury
Authors: Esmaeilizadeh Mahdi , Hosseini Mahmoud , Beheshti Farimah , Alikhani Vajihe , Keshavarzi Zakieh , Shoja Mohsen , Mansoorian Mozhgan , Sadeghnia Hamid Reza 
Published: February 2019

Abstract. Background: The effects of Vit C on liver and renal function and the tissues oxidative damage was investigated in hypothyroid rats. Materials and methods: The pregnant rats were divided into 5 groups (n=6): (1) Control; (2) Propylthiouracil (PTU; 0.005%), (3–5) PTU plus 10, 100 or 500 mg/kg b.w. Vit C. The drugs were added to the drinking water of the dams and their pups during lactation period and then continued for the offspring through the ﬁrst 8 weeks of their life. Finally, 7 male offspring from each group were randomly selected. Results: Thyroxine, protein and albumin concentrations in the serum and thiol content and superoxide dismutase (SOD) and catalase (CAT) activities in renal and liver tissues of hypothyroid group was lower (all P<0.001) while, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALK-P), creatinine and blood urea nitrogen (BUN) concentrations in the serum and malondialdehyde (MDA) in the liver and renal tissues were higher than the control (all P<0.001). All doses of Vit C increased thyroxine, protein and albumin and thiol content in in renal and liver tissues while, decreased AST, ALT and ALK-P concentration and MDA in liver and renal tissues compared to PTU group (P<0.05–P<0.001). Creatinine, BUN and SOD and CAT were improved by both 100 and 500 mg/kg of Vit C in the renal (P<0.05–P<0.001) and by 100 mg/kg in the liver (P<0.05–P<0.001). Conclusion: Vit C improved liver and renal function of hypothyroid rats which might be due to its protective effects against tissues oxidative damage.
A New Definition of the South‐East Madagascar Bloom and Analysis of Its Variability
Authors: Dilmahamod A. F. , Penven P. , Aguiar‐González B. , Reason C. J. C. , Hermes J. C. 
Published: February 2019

AbstractThe South‐East Madagascar Bloom occurs in an oligotrophic region of the southwest Indian Ocean. Phase locked to austral summer, this sporadic feature exhibits substantial temporal and spatial variability. Several studies, with different hypotheses, have focused on the initiation mechanism triggering the bloom, but none has been as yet clearly substantiated. With 19 years of ocean color data set available as well as in situ measurements (Argo profiles), the time is ripe to review this feature. The bloom is characterized in a novel manner, and a new bloom index is suggested, yielding 11 bloom years, including 3 major bloom years (1999, 2006, and 2008). Spatially, the bloom varies from a mean structure (22–32°S; 50–70°E) both zonally and meridionally. A colocation analysis of Argo profiles and chlorophyll‐a data revealed a bloom occurrence in a shallow‐stratified layer, with low‐salinity water in the surface layers. Additionally, a quantitative assessment of the previous hypotheses is performed and bloom occurrence is found to coincide with La Niña events and reduced upwelling intensity south of Madagascar. A stronger South‐East Madagascar Current during La Niña may support a detachment of the current from the coasts, dampening the upwelling south of Madagascar, and feeding low‐salinity waters into the Madagascar Basin, hence increasing stratification. Along with abundance of light, these provide the right conditions for a nitrogen‐fixing cyanobacterial phytoplankton bloom onset.
Temporal and Spatial Hydrodynamic Variability in the Mallorca Channel (Western Mediterranean Sea) From 8 Years of Underwater Glider Data
Authors: Barceló‐Llull Bàrbara , Pascual Ananda , Ruiz Simón , Escudier Romain , Torner Marc , Tintoré Joaquín 
Published: February 2019

AbstractEight years of glider data are used to characterize the temporal and spatial variability of a region in the western Mediterranean that will constitute one of the targets for the calibration phase of the Surface Water and Ocean Topography (SWOT) satellite mission. The characteristic horizontal dimension of mesoscale instabilities in the Mallorca channel is 6.0 km. The temporal evolution of intermediate water masses is dominated by an increase over time of the characteristic temperature values. Western Mediterranean and Levantine Intermediate waters display an increase of the temperature extrema of 0.064 ± 0.002 and 0.044 ± 0.002 °C/year between 2011 and 2018, respectively. At the layer of Levantine Intermediate water the salinity temporal regression reveals a mean trend of 0.010 year−1. Temperature annual cycle shows an averaged temperature gradient of ∼6 °C in 6 months at the upper layer, with a disconnection with the annual cycle at 100‐m depth. The circulation across the channel is dominated by high‐frequency variability. The signature of eddies with radius ranging from 5 to 18 km is apparent in 16% of the transects analyzed and mainly in spring and summer, with a dominance of subsurface cyclonic eddies. Two‐way flow controls the annual cycle of the water transport through the channel with prevalence of the inflow of Atlantic water. Variations of water transport over timescales of weeks to months can be similar to those identifiable as seasonal changes.
Modulation of Economic Losses From European Floods by the North Atlantic Oscillation
Authors: Zanardo Stefano , Nicotina Ludovico , Hilberts Arno G. J. , Jewson Stephen P. 
Published: February 2019

AbstractThe space‐time structure of flood losses is arguably related to large‐scale climatic patterns; however, this interconnection is not always well understood. Here we show that the North Atlantic Oscillation (NAO) correlates with the occurrence of catastrophic floods across Europe and the associated economic losses. The analysis reveals that in Northern Europe the majority of historic winter floods occurred during a positive NAO state, whereas the majority of summer floods occurred during a negative state. Analogous, but stronger, patterns can be observed in individual Atlantic countries. Through the application of a state‐of‐the‐art catastrophe model, we find that there is a statistically significant relationship between the NAO and flood losses. Critically, we observe that the average flood loss during opposite NAO states can differ by up to 50%. These results can inform financial preparedness and disaster fund allocation, as stakeholders, such as governments and insurance companies, can distribute resources more effectively.
Downregulation of Npas4 in parvalbumin interneurons and cognitive deficits after neonatal NMDA receptor blockade: relevance for schizophrenia
Authors: Shepard Ryan , Heslin Kelsey , Hagerdorn Payton , Coutellier Laurence 
Published: February 2019

AbstractDysfunction of prefrontal parvalbumin (PV+) interneurons has been linked with severe cognitive deficits as observed in several neurodevelopmental disorders including schizophrenia. However, whether a specific aspect of PV+ neurons deregulation, or a specific molecular mechanism within PV+ neurons is responsible for cognitive deficits and other behavioral impairments remain to be determined. Here, we induced cognitive deficits and altered the prefrontal PV system in mice by exposing them neonatally to the NMDA receptor antagonist ketamine. We observed that the cognitive deficits and hyperactivity induced by neonatal ketamine were associated with a downregulation of Npas4 expression specifically in PV+ neurons. To determine whether Npas4 downregulation-induced dysfunction of PV+ neurons could be a molecular contributor to the cognitive and behavioral impairments reported after neonatal ketamine, we used a transgenic Cre-Lox approach. Reduced Npas4 expression within PV+ neurons replicates deficits in short-term memory observed after neonatal ketamine, but does not reproduce disturbances in general activity. Our data show for the first time that the brain-specific transcription factor Npas4 may be an important contributor to PV+ neurons dysfunction in neurodevelopmental disorders, and thereby could contribute to the cognitive deficits observed in diseases characterized by abnormal functioning of PV+ neurons such as schizophrenia. These findings provide a potential novel therapeutic target to rescue the cognitive impairments of schizophrenia that remain to date unresponsive to treatments.
miR-29a contributes to breast cancer cells epithelial–mesenchymal transition, migration, and invasion via down-regulating histone H4K20 trimethylation through directly targeting SUV420H2
Authors: Wu You , Shi Wanyue , Tang Tingting , Wang Yidong , Yin Xin , Chen Yanlin , Zhang Yanfeng , Xing Yun , Shen Yumeng , Xia Tiansong , Guo Changying , Pan Yi , Jin Liang 
Published: February 2019

AbstractBreast cancer is the most prevalent cancer in women worldwide, which remains incurable once metastatic. Breast cancer stem cells (BCSCs) are a small subset of breast cancer cells which are essential in tumor formation, metastasis, and drug resistance. microRNAs (miRNAs) play important roles in the breast cancer cells and BCSCs by regulating specific genes. In this study, we found that miR-29a was up-regulated in BCSCs, in aggressive breast cancer cell line and in breast cancer tissues. We also confirmed suppressor of variegation 4–20 homolog 2 (SUV420H2), which is a histone methyltransferase that specifically trimethylates Lys-20 of histone H4 (H4K20), as the target of miR-29a. Both miR-29a overexpression and SUV420H2 knockdown in breast cancer cells promoted their migration and invasion in vitro and in vivo. Furthermore, we discovered that SUV420H2-targeting miR-29a attenuated the repression of connective tissue growth factor (CTGF) and growth response protein-1 (EGR1) by H4K20 trimethylation and promoted the EMT progress of breast cancer cells. Taken together, our findings reveal that miR-29a plays critical roles in the EMT and metastasis of breast cancer cells through targeting SUV420H2. These findings may provide new insights into novel molecular therapeutic targets for breast cancer.
The shape of human squalene epoxidase expands the arsenal against cancer
Authors: Brown Andrew J. , Chua Ngee Kiat , Yan Nieng 
Published: February 2019

AbstractSqualene epoxidase (also known as squalene monooxygenase, EC 1.14.99.7) is a key rate-limiting enzyme in cholesterol biosynthesis. Anil Padyana and colleagues report the long awaited structure of human squalene epoxidase (SQLE). They solved the crystal structure of the catalytic domain of human SQLE alone and in complex with two similar pharmacological inhibitors and elucidate their mechanism of action. SQLE is the target of fungicides and of increasing interest in human health and disease, particularly as a new anti-cancer target. Indeed, in a companion paper, Christopher Mahoney and colleagues performed an inhibitor screen with cancer cell lines and identified SQLE as an unique vulnerability in a subset of neuroendocrine tumours, where SQLE inhibition caused a toxic accumulation of the substrate squalene. The SQLE structure will facilitate the development of improved inhibitors. Here, we comment on these two studies in the wider context of the field and discuss possible future directions.
Composition change-driven texturing and doping in solution-processed SnSe thermoelectric thin films
Authors: Heo Seung Hwae , Jo Seungki , Kim Hyo Seok , Choi Garam , Song Jae Yong , Kang Jun-Yun , Park No-Jin , Ban Hyeong Woo , Kim Fredrick , Jeong Hyewon , Jung Jaemin , Jang Jaeyoung , Lee Won Bo , Shin Hosun , Son Jae Sung 
Published: February 2019

AbstractThe discovery of SnSe single crystals with record high thermoelectric efficiency along the b-axis has led to the search for ways to synthesize polycrystalline SnSe with similar efficiencies. However, due to weak texturing and difficulties in doping, such high thermoelectric efficiencies have not been realized in polycrystals or thin films. Here, we show that highly textured and hole doped SnSe thin films with thermoelectric power factors at the single crystal level can be prepared by solution process. Purification step in the synthetic process produced a SnSe-based chalcogenidometallate precursor, which decomposes to form the SnSe2 phase. We show that the strong textures of the thin films in the b–c plane originate from the transition of two dimensional SnSe2 to SnSe. This composition change-driven transition offers wide control over composition and doping of the thin films. Our optimum SnSe thin films exhibit a thermoelectric power factor of 4.27 μW cm−1 K−2.
Geometrical Perturbation Techniques and Approximate Analysis for Eigenmode Splitting and Shifting in Electromagnetic Planar Dual-Mode Resonators
Authors: Naji Adham , Warr Paul A. 
Published: February 2019

AbstractDual-mode electromagnetic resonators are used in numerous systems and applications in physics and engineering. They rely on degenerate-mode splitting to control the spectral properties of the system that employs them. Controlling (splitting or shifting) these eigenvalues to fully tune the frequency response, however, is a nontrivial problem that involves the use of geometrical perturbation theory as well as lossy electronic elements that enable the tuning process. In this paper we present novel geometrical techniques to control the eigenmodes of dual-mode resonators, highlighting the strong connection between the chosen geometry and performance (measured by the unloaded quality factor, Q0). Key advantages of the presented structures include electronic geometric tunability for frequency splitting and shifting, as well as the use of buried feeds to improve insertion loss and return loss performance. Field analysis is used to show how the performance is degraded by geometry itself, rather than by the tuning elements. The discussion includes derivation of approximate analytical models that highlight the sources of performance degradation in the geometry even before any tuning elements are inserted. The presented concepts are verified by measurements on perturbed microwave resonators.
Large-scale all-atom molecular dynamics alanine-scanning of IAPP octapeptides provides insights into the molecular determinants of amyloidogenicity
Authors: Tambi Richa , Morimoto Gentaro , Kosuda Satoshi , Taiji Makoto , Kuroda Yutaka 
Published: February 2019

AbstractIn order to investigate the early phase of the amyloid formation by the short amyloidogenic octapeptide sequence (‘NFGAILSS’) derived from IAPP, we carried out a 100ns all-atom molecular dynamics (MD) simulations of systems that contain 27 peptides and over 30,000 water molecules. The large-scale calculations were performed for the wild type sequence and seven alanine-scanned sequences using AMBER 8.0 on RIKEN’s special purpose MD-GRAPE3 supercomputer, using the all-atom point charge force field ff99, which do not favor β-structures. Large peptide clusters (size 18–26 mers) were observed for all simulations, and our calculations indicated that isoleucine at position 5 played important role in the formation of β-rich clusters. In the oligomeric state, the wild type and the S7A sequences had the highest β-structure content (~14%), as calculated by DSSP, in line with experimental observations, whereas I5A and G3A had the highest helical content (~20%). Importantly, the β-structure preferences of wild type IAPP originate from its association into clusters and are not intrinsic to its sequence. Altogether, the results of this first large-scale, multi-peptide all-atom molecular dynamics simulation appear to provide insights into the mechanism of amyloidogenic and non-amyloidogenic oligomers that mainly corroborate previous experimental observations.
A genome-wide enhancer/suppressor screen for Dube3a interacting genes in Drosophila melanogaster
Authors: Hope Kevin A. , McGinn Addison , Reiter Lawrence T. 
Published: February 2019

AbstractThe genetics underlying autism spectrum disorder (ASD) are complex. Approximately 3–5% of ASD cases arise from maternally inherited duplications of 15q11.2-q13.1, termed Duplication 15q syndrome (Dup15q). 15q11.2-q13.1 includes the gene UBE3A which is believed to underlie ASD observed in Dup15q syndrome. UBE3A is an E3 ubiquitin ligase that targets proteins for degradation and trafficking, so finding UBE3A substrates and interacting partners is critical to understanding Dup15q ASD. In this study, we take an unbiased genetics approach to identify genes that genetically interact with Dube3a, the Drosophila melanogaster homolog of UBE3A. We conducted an enhancer/suppressor screen using a rough eye phenotype produced by Dube3a overexpression with GMR-GAL4. Using the DrosDel deficiency kit, we identified 3 out of 346 deficiency lines that enhanced rough eyes when crossed to two separate Dube3a overexpression lines, and subsequently identified IA2, GABA-B-R3, and lola as single genes responsible for rough eye enhancement. Using the FlyLight GAL4 lines to express uas-Dube3a + uas-GFP in the endogenous lola pattern, we observed an increase in the GFP signal compared to uas-GFP alone, suggesting a transcriptional co-activation effect of Dube3a on the lola promoter region. These findings extend the role of Dube3a/UBE3A as a transcriptional co-activator, and reveal new Dube3a interacting genes.
Targeted editing of the PSIP1 gene encoding LEDGF/p75 protects cells against HIV infection
Authors: Lampi Yulia , Van Looveren Dominique , Vranckx Lenard S. , Thiry Irina , Bornschein Simon , Debyser Zeger , Gijsbers Rik 
Published: February 2019

AbstractTo fulfill a productive infection cycle the human immunodeficiency virus (HIV) relies on host-cell factors. Interference with these co-factors holds great promise in protecting cells against HIV infection. LEDGF/p75, encoded by the PSIP1 gene, is used by the integrase (IN) protein in the pre-integration complex of HIV to bind host-cell chromatin facilitating proviral integration. LEDGF/p75 depletion results in defective HIV replication. However, as part of its cellular function LEDGF/p75 tethers cellular proteins to the host-cell genome. We used site-specific editing of the PSIP1 locus using CRISPR/Cas to target the aspartic acid residue in position 366 and mutated it to asparagine (D366N) to disrupt the interaction with HIV IN but retain LEDGF/p75 cellular function. The resulting cell lines demonstrated successful disruption of the LEDGF/p75 HIV-IN interface without affecting interaction with cellular binding partners. In line with LEDGF/p75 depleted cells, D366N cells did not support HIV replication, in part due to decreased integration efficiency. In addition, we confirm the remaining integrated provirus is more silent. Taken together, these results support the potential of site-directed CRISPR/Cas9 mediated knock-in to render cells more resistant to HIV infection and provides an additional strategy to protect patient-derived T-cells against HIV-1 infection as part of cell-based therapy.
The 4717C > G polymorphism in periplakin modulates sensitivity to EGFR inhibitors
Authors: Lee Hui Mei , Kelly Gregory Michael , Zainal Nur Syafinaz , Yee Pei San , Fadlullah Muhammad Zaki Hidayatullah , Lee Bernard Kok Bang , Gan Chai Phei , Patel Vyomesh , Cheong Sok Ching 
Published: February 2019

AbstractThe use of EGFR inhibitors on oral squamous cell carcinoma (OSCC) as monotherapy yielded modest clinical outcomes and therefore would benefit from biomarkers that could predict which patient subsets are likely to respond. Here, we determined the efficacy of erlotinib in OSCC cell lines, and by comparing sensitive and resistant lines to identify potential biomarkers. We focused on the 4717C > G polymorphism in periplakin (PPL) where the CC genotype was associated with erlotinib resistance. To validate this, erlotinib-resistant cell lines harbouring CC genotype were engineered to overexpress the GG genotype and vice versa. Isogenic cell lines were then studied for their response to erlotinib treatment. We demonstrated that overexpression of the GG genotype in erlotinib-resistant lines sensitized them to erlotinib and inhibition of AKT phosphorylation. Similarly, the expression of the CC genotype conferred resistance to erlotinib with a concomitant increase in AKT phosphorylation. We also demonstrated that cell lines with the CC genotype generally are more resistant to other EGFR inhibitors than those with the GG genotype. Overall, we showed that a specific polymorphism in the PPL gene could confer resistance to erlotinib and other EGFR inhibitors and further work to evaluate these as biomarkers of response is warranted.
Strategic Eye Movements are Used to Support Object Authentication
Authors: Raymond Jane E. , Jones Scott P. 
Published: February 2019

AbstractAuthentication is an important cognitive process used to determine whether one’s initial identification of an object is corroborated by additional sensory information. Although authentication is critical for safe interaction with many objects, including food, websites, and valuable documents, the visual orienting strategies used to garner additional sensory data to support authentication remain poorly understood. When reliable visual cues to counterfeit cannot be anticipated, distributing fixations widely across an object’s surface might be useful. However, strategic fixation of specific object-defining attributes would be more efficient and should lead to better authentication performance. To investigate, we monitored eye movements during a repetitive banknote authentication task involving genuine and counterfeit banknotes. Although fixations were distributed widely across the note prior to authentication decisions, preference for hard-to mimic areas and avoidance of easily mimicked areas was evident. However, there was a strong tendency to initially fixate the banknote’s portrait, and only thereafter did eye movement control appear to be more strategic. Those who directed a greater proportion of fixations at hard-to-mimic areas and resisted more easily mimicked areas performed better on the authenticity task. The tendency to deploy strategic fixation improved with experience, suggesting that authentication benefits from precise visual orienting and refined categorisation criteria.