bluuebunny/crossref_metadata_2025_split huggingface dataset:
Terrestrial microbialites provide constraints on the mesoproterozoic atmosphere
Authors: Hren Michael T. , Sheldon Nathan D. 
Published: July 2019

AbstractPalaeoclimate data indicate that Earth surface temperatures have remained largely temperate for the past 3.5 Byr despite significantly lower solar luminosity over this time relative to the present day. There is evidence for episodic early and late Proterozoic glaciation, but little evidence of glaciation in the intervening billion years. A prolonged equable Mesoproterozoic Earth requires elevated greenhouse gas concentrations. Two endmember scenarios have been proposed for maintaining global warmth. These include extremely high pCO2 or more modest pCO2 with higher methane concentrations. This paper reports on the δ13C of organic matter in 1.1 Ga stromatolites from the Copper Harbor Conglomerate (CHC) of the Mesoproterozoic Midcontinent Rift (North America) and δ18O and Δ47 temperatures of inorganic stromatolite carbonate to constrain formation and burial conditions and the magnitude of ancient carbon isotope discrimination. CHC sediments have never been heated above ~125–155°C, providing a novel geochemical archive of the ancient environment. Stromatolite Δ47 data record moderate alteration, and therefore, the occluded organic matter was unlikely to have experienced significant thermal alteration after deposition. The δ13C values of ancient mat organic matter and inorganic carbonate show isotope discrimination (εp) values ~15.5–18.5‰, similar to modern microbial mats formed in equilibrium with low concentrations of dissolved inorganic carbon. In combination, these data are consistent with a temperate climate Mesoproterozoic biosphere supported by relatively modest pCO2. This result agrees with Atmosphere‐Ocean Global Circulation Model reconstructions for Mesoproterozoic climate using 5–10 times present atmospheric levels pCO2 and pCH4 of >28 ppmv. However, given marine modelling constraints of CH4 production that suggest pCH4 was below 10 ppm, this creates a methane paradox. Either an additional source of CH4 (e.g. from terrestrial ecosystems) or another greenhouse gas, such as N2O, would have been necessary to maintain equable conditions in the Mesoproterozoic.
Phenethylamine‐derived new psychoactive substances 2C‐E‐FLY, 2C‐EF‐FLY, and 2C‐T‐7‐FLY: Investigations on their metabolic fate including isoenzyme activities and their toxicological detectability in urine screenings
Authors: Wagmann Lea , Hempel Nora , Richter Lilian H.J. , Brandt Simon D. , Stratford Alexander , Meyer Markus R. 
Published: July 2019

AbstractPsychoactive substances of the 2C‐series are phenethylamine‐based designer drugs that can induce psychostimulant and hallucinogenic effects. The so‐called 2C‐FLY series contains rigidified methoxy groups integrated in a 2,3,6,7‐tetrahydrobenzo[1,2‐b:4,5‐b']difuran core. The aim of the presented work was to investigate the in vivo and in vitro metabolic fate including isoenzyme activities and toxicological detectability of the three new psychoactive substances (NPS) 2C‐E‐FLY, 2C‐EF‐FLY, and 2C‐T‐7‐FLY to allow clinical and forensic toxicologists the identification of these novel compounds. Rat urine, after oral administration, and pooled human liver S9 fraction (pS9) incubations were analyzed by liquid chromatography−high‐resolution tandem mass spectrometry (LC−HRMS/MS). By performing activity screenings, the human isoenzymes involved were identified and toxicological detectability in rat urine investigated using standard urine screening approaches (SUSAs) based on gas chromatography (GC)−MS, LC−MSn, and LC−HRMS/MS. In total, 32 metabolites were tentatively identified. Main metabolic steps consisted of hydroxylation and N‐acetylation. Phase I metabolic reactions were catalyzed by CYP2D6, 3A4, and FMO3 and N‐acetylation by NAT1 and NAT2. Methoxyamine was used as a trapping agent for detection of the deaminated metabolite formed by MAO‐A and B. Interindividual differences in the metabolism of the 2C‐FLY drugs could be caused by polymorphisms of enzymes involved or drug–drug interactions. All three SUSAs were shown to be suitable to detect an intake of these NPS but common metabolites of 2C‐E‐FLY and 2C‐EF‐FLY have to be considered during interpretation of analytical findings.
Reduced maternal vitamin A status increases the incidence of normal aortic arch variants
Authors: Sugrue Kelsey F. , Zohn Irene E. 
Published: July 2019

SummaryWhile common in the general population, the developmental origins of “normal” anatomic variants of the aortic arch remain unknown. Aortic arch development begins with the establishment of the second heart field (SHF) that contributes to the pharyngeal arch arteries (PAAs). The PAAs remodel during subsequent development to form the mature aortic arch and arch vessels. Retinoic acid signaling involving the biologically active metabolite of vitamin A, plays a key role in multiple steps of this process. Recent work from our laboratory indicates that the E3 ubiquitin ligase Hectd1 is required for full activation of retinoic acid signaling during cardiac development. Furthermore, our study suggested that mild alterations in retinoic acid signaling combined with reduced gene dosage of Hectd1, results in a benign aortic arch variant where the transverse aortic arch is shortened between the brachiocephalic and left common carotid arteries. These abnormalities are preceded by hypoplasia of the fourth PAA. To further explore this interaction, we investigate whether reduced maternal dietary vitamin A intake can similarly influence aortic arch development. Our findings indicate that the incidence of hypoplastic fourth PAAs, as well as the incidence of shortened transverse arch are increased with reduced maternal vitamin A intake during pregnancy. These studies provide new insights as to the developmental origins of these benign aortic arch variants.
Generated output increase control with consideration of the influence of wake for wind farm
Authors: Kondo Shinichi , Inage Shinichi 
Published: July 2019

AbstractPresently, many wind turbine generators (WTGs) are connected to the power grid. While the penetration of wind power to the power system is increasing, FIT price is decreasing. Therefore, wind generation companies want to increase the electric power output from wind farms (WFs). In this article, we propose a control technique to reduce the influence of the wake by changing a power coefficient of each WTG in a WF for the purpose of improving electric power output of WFs. We showed the optimization technique of a power coefficient of each WTG and the effect of reducing the influence of the wake using measurement data from WFs. In addition, we formulated the wake effect as a function of distance between WTGs. We verified 1% improvement of generated energy in a year compared to the conventional control method by simulation. Furthermore, we quantified the improvement of generated energy output, using the distance between WTGs and the occurrence rate of the direction of the wind as a variable.
Use of Cucurbit[6]uril as Ionophore in Ion Selective Electrodes for Etilefrine Determination in Pharmaceuticals
Authors: Gomes Amorim Célia , Araújo Alberto , da Conceição Montenegro Maria 
Published: July 2019

AbstractCucurbiturils are macrocyclic molecules and have been used with promising results in the development of electrochemical sensors and biosensors due to their main properties such as shape, selectivity, binding interactions and solubility. However, its application for the development of ion selective electrodes has been scarce. In this work, cucurbit[6]uril was used as molecular‐recognition compound for etilefrine sensing membrane with potentiometric transduction. The etilefrine selective electrode was evaluated and proposed as an alternative methodology for pharmaceutical quality control. Different membranes composition were evaluated, considering the use of different solvent mediators and the presence of anionic additives. The best membrane comprises 9.24 mmol.Kg−1 of cucurbit[6]uril, 68.90 % (w/w) of dibutylsebacate and 30.18 % (w/w) of carboxylated polyvinyl chloride. The electrode exhibited selective cationic response toward the etilefrine in a concentration interval of more than four decades, with an slope of 57.4±0.5 mV dec−1, a practical detection limit of (8±1)×10−7 mol L−1 and a low limit of linear range of (1.25±0.28)×10−6 mol L−1. The selectivity of the electrode towards different interfering was high. A comparative evaluation of the accuracy and precision of both procedures was done using the t‐student test (t4,12=1.135) and the Fischer test (F12,4=2.42) and compared with the tabulated ones (t4,12=1.135, F11,3=5.91) for the level of confidence of 95 %.
Longitudinal increases in structural connectome segregation and functional connectome integration are associated with better recovery after mild TBI
Authors: Kuceyeski Amy F. , Jamison Keith W. , Owen Julia P. , Raj Ashish , Mukherjee Pratik 
Published: July 2019

AbstractTraumatic brain injury damages white matter pathways that connect brain regions, disrupting transmission of electrochemical signals and causing cognitive and emotional dysfunction. Connectome‐level mechanisms for how the brain compensates for injury have not been fully characterized. Here, we collected serial MRI‐based structural and functional connectome metrics and neuropsychological scores in 26 mild traumatic brain injury subjects (29.4 ± 8.0 years, 20 males) at 1 and 6 months postinjury. We quantified the relationship between functional and structural connectomes using network diffusion (ND) model propagation time, a measure that can be interpreted as how much of the structural connectome is being utilized for the spread of functional activation, as captured via the functional connectome. Overall cognition showed significant improvement from 1 to 6 months (t25 = −2.15, p = .04). None of the structural or functional global connectome metrics was significantly different between 1 and 6 months, or when compared to 34 age‐ and gender‐matched controls (28.6 ± 8.8 years, 25 males). We predicted longitudinal changes in overall cognition from changes in global connectome measures using a partial least squares regression model (cross‐validated R2 = .27). We observe that increased ND model propagation time, increased structural connectome segregation, and increased functional connectome integration were related to better cognitive recovery. We interpret these findings as suggesting two connectome‐based postinjury recovery mechanisms: one of neuroplasticity that increases functional connectome integration and one of remote white matter degeneration that increases structural connectome segregation. We hypothesize that our inherently multimodal measure of ND model propagation time captures the interplay between these two mechanisms.
Design, synthesis and photocytotoxicity of upconversion nanoparticles: Potential applications for near‐infrared photodynamic and photothermal therapy
Authors: Hu Yang , Honek John F. , Wilson Brian C. , Lu Qing‐Bin 
Published: July 2019

AbstractPhotodynamic therapy (PDT) and photothermal therapy (PTT) are emerging modalities for the treatment of tumors and nonmalignant conditions, based on the use of photosensitizers to generate singlet oxygen or heat, respectively, upon light (laser) irradiation. They have potential advantages over conventional treatments, being minimally invasive with precise spatial‐temporal selectivity and reduced side effects. However, most clinically employed PDT agents are activated at visible (vis) wavelengths for which the tissue penetration and, hence, effective treatment depth are compromised. In addition, the lipophilicity of near‐infrared (NIR) photothermal agents limits their use and efficiency. To achieve combined PDT/PTT effects, both excitation wavelengths need to be tuned into the NIR spectral window of biological tissues. This paper reports the synthesis of neodymium‐doped upconversion nanoparticles (NaYF4:Yb,Er,Nd@NaYF4:Nd) that convert 800 nm light into vis wavelengths, which can then activate conventional photosensitizers on the nanoparticle surface for PDT. Covalently bonded IR‐780 dyes can readily be activated by 800 nm laser irradiation. The PEGylated nanoplatform exhibited a narrow size distribution, good stability and efficient generation of singlet oxygen under laser irradiation. The in vitro photocytotoxicity of this engineered nanoplatform as either a PDT or PTT agent in HeLa cells is demonstrated, while fluorescence microscopy in nanoplatform‐incubated cells highlights its potential for bioimaging.
Absence of Dipeptidyl Peptidase 3 Increases Oxidative Stress and Causes Bone Loss
Authors: Menale Ciro , Robinson Lisa J , Palagano Eleonora , Rigoni Rosita , Erreni Marco , Almarza Alejandro J , Strina Dario , Mantero Stefano , Lizier Michela , Forlino Antonella , Besio Roberta , Monari Marta , Vezzoni Paolo , Cassani Barbara , Blair Harry C , Villa Anna , Sobacchi Cristina 
Published: July 2019

ABSTRACT
Controlling oxidative stress through the activation of antioxidant pathways is crucial in bone homeostasis, and impairments of the cellular defense systems involved contribute to the pathogenesis of common skeletal diseases. In this work we focused on the dipeptidyl peptidase 3 (DPP3), a poorly investigated ubiquitous zinc-dependent exopeptidase activating the Keap1-Nrf2 antioxidant pathway. We showed Dpp3 expression in bone and, to understand its role in this compartment, we generated a Dpp3 knockout (KO) mouse model and specifically investigated the skeletal phenotype. Adult Dpp3 KO mice showed a mild growth defect, a significant increase in bone marrow cellularity, and bone loss mainly caused by increased osteoclast activity. Overall, in the mouse model, lack of DPP3 resulted in sustained oxidative stress and in alterations of bone microenvironment favoring the osteoclast compared to the osteoblast lineage. Accordingly, in vitro studies revealed that Dpp3 KO osteoclasts had an inherent increased resorptive activity and ROS production, which on the other hand made them prone to apoptosis. Moreover, absence of DPP3 augmented bone loss after estrogen withdrawal in female mice, further supporting its relevance in the framework of bone pathophysiology. Overall, we show a nonredundant role for DPP3 in the maintenance of bone homeostasis and propose that DPP3 might represent a possible new osteoimmunological player and a marker of human bone loss pathology. © 2019 American Society for Bone and Mineral Research.
Expression of miR‐Let‐7a, miR‐15a, miR‐16‐1, and their target genes in fresh and vitrified embryos and its surrounding culture media for noninvasive embryo assessment
Authors: Heidari Fezzeh , Hosseini Sara , Yeganeh Samira M. , Salehi Mohammad 
Published: July 2019

AbstractmicroRNAs (miRNAs) play a critical role in implantation and development of mouse embryos. In this study, we aim to evaluate the possibility of miRNAs as potential biomarkers in the blastocyst culture to assess embryo quality. We also intend to investigate whether improved clinical outcomes of vitrified embryos agree with altered miRNA expressions. Mouse embryos from in vitro fertilization were vitrified at the two‐cell stage. After thawing, the embryos were individually cultured and developed to the blastocyst stage. We used quantitative real‐time polymerase chain reaction to evaluate miRNA expression levels in both vitrified and fresh groups, and culture medium (CM). The fibronectin binding assay was performed to examine for blastocyst attachment. The findings showed reduced expressions of miR‐16‐1 (0.2 ± 0.06) and miR‐Let‐7a (0.65 ± 0.1) after vitrification compared to fresh embryos. We observed significant upregulation of the target genes Vav3 (4.33 ± 0.25), integrin β‐3 (Itg β3; 4.73 ± 0.2), and Bcl2 (2.29 ± 0.16) in the vitrified embryos compared to the fresh groups. Evaluation of blastocyst CM showed upregulation of miR‐Let‐7a (15.68 ± 0.89), miR‐16‐1 (16.18 ± 0.75), and miR‐15a (13.36 ± 0.73) in the vitrified group in comparison to the fresh blastocysts (P < .05). The expression levels of miR‐16‐1 (3.28 ± 0.63), miR‐15a (5.91 ± 0.38), and miR‐Let‐7a (9.07 ± 0.6) in CM of the vitrified blastocysts conducted on fibronectin were significantly higher than the fresh group (P < .05).This study showed that vitrification of embryos changes implantation and proliferation biomarkers. In addition, upregulated miRNAs in CM could be potentially used for noninvasive early assessment of embryo quality.
Screening and evaluation of potential inhibitors against vaccinia virus from 767 approved drugs
Authors: Wu Jiajing , Liu Qiang , Xie Hui , Chen Ruifeng , Huang Weijin , Liang Chunnan , Xiao Xinyue , Yu Yongxin , Wang Youchun 
Published: July 2019

AbstractThe development of therapies for human smallpox is needed due to the increasing concern over the potential use of smallpox virus as a biological weapon. Here, we report a high‐throughput screening for anti‐smallpox virus drugs from a 767‐small‐molecule library, employing two vaccinia virus (VACV) strains containing firefly luciferase (VTT‐Fluc and VG9‐Fluc) as surrogate viruses. Using an eight‐point dose response format assay, 26 compounds of different pharmacological classes were identified with in vitro anti‐VACV activities. Mycophenolate mofetil (MMF) and tranilast (TRA) were detected to possess the highest anti‐VACV potency (selectivity index values of >334 and >74, respectively); they could inhibit VTT‐Fluc replication in nude mice at 5 days post‐infection by 99% (10 mg/kg, P < .01) and 59% (45 mg/kg, P = .01), respectively, as indicated by bioluminescent intensity. In conclusion, MMF and TRA are promising anti‐smallpox virus candidates for further optimization and repurposing for use in clinical practice.
Correlation between the left atrial low‐voltage area and the cardiac function improvement after catheter ablation for paroxysmal atrial fibrillation
Authors: Nakatani Yosuke , Sakamoto Tamotsu , Yamaguchi Yoshiaki , Tsujino Yasushi , Kataoka Naoya , Nishida Kunihiro , Mizumaki Koichi , Kinugawa Koichiro 
Published: July 2019

AbstractBackgroundThe impact of the left atrial low‐voltage area (LVA) on the cardiac function improvement following ablation for atrial fibrillation (AF) is unclear.MethodsIn 49 patients with paroxysmal AF who underwent ablation, the left ventricular stroke volume index (SVI) was repeatedly measured using an impedance cardiography until 6 months after ablation. We defined the cardiac function improvement as a 20% increase in the SVI. The LVA (the area with the voltage amplitude of <0.5 mV) was assessed before ablation.ResultsThe reduced baseline SVI (<33 mL/m2) was observed in 18 (37%) patients. The SVI increased following ablation (from 36 ± 5 to 39 ± 6 mL/m2, P < .001). We observed the cardiac function improvement in 14 (29%) patients. The LVA was smaller in patients with the improved cardiac function than in those without (8.3% ± 5.2% vs 14.0% ± 8.5%, P = .026). The multivariate analysis revealed that only the LVA was independently associated with the cardiac function improvement (odds ratio, 0.878; 95% confidence interval: 0.778‐0.991, P = .036). Furthermore, LVAs of the anterior (7.9% ± 7.6% vs 18.2% ± 15.5%, P = .022), septal (12.0 ± 7.3% vs 20.7% ± 13.8%, P = .031), and roof walls (6.9% ± 6.0% vs 16.9% ± 15.2%, P = .022) were smaller in patients with the improved cardiac function than in those without.ConclusionsThe LVA was related to the cardiac function improvement following ablation in patients with paroxysmal AF.
phz1 contributes much more to phenazine‐1‐carboxylic acid biosynthesis than phz2 in Pseudomonas aeruginosa rpoS mutant
Authors: Sun Longshuo , Chi Xiaoyan , Feng Zhibin , Wang Kewen , Kai Le , Zhang Kailu , Cheng Shiwei , Hao Xiuying , Xie Weihai , Ge Yihe 
Published: July 2019

AbstractPseudomonas aeruginosa PAO1, a common opportunistic bacterial pathogen, contains two phenazine‐biosynthetic operons, phz1 (phzA1B1C1D1E1F1G1) and phz2 (phzA2B2C2D2E2F2G2). Each of two operons can independently encode a set of enzymes involving in the biosynthesis of phenazine‐1‐carboxylic acid. As a global transcriptional regulator, RpoS mediates a lot of genes involving secondary metabolites biosynthesis in many bacteria. In an other previous study, it was reported that RpoS deficiency caused overproduction of pyocyanin, a derivative of phenazine‐1‐carboxylic acid in P. aeruginosa PAO1. But it is not known how RpoS mediates the expression of each of two phz operons and modulates phenazine‐1‐carboxylic acid biosynthesis in detail. In this study, by deleting the rpoS gene in the mutant PNΔphz1 and the mutant PNΔphz2, we found that the phz1 operon contributes much more to phenazine‐1‐carboxylic acid biosynthesis than the phz2 operon in the absence of RpoS. With the construction of the translational and transcriptional fusion vectors with the truncated lacZ reporter gene, we demonstrated that RpoS negatively regulates the expression of phz1 and positively controls the expression of phz2, and the regulation of phenazine‐1‐carboxylic acid biosynthesis mediated by RopS occurs at the posttranscriptional level, not at the transcriptional level. Obviously, two copies of phz operons and their differential expression mediated by RpoS might help P. aeruginosa adapt to its diverse environments and establish infection in its hosts.
Variability and trends of landfalling atmospheric rivers along the Pacific Coast of northwestern North America
Authors: Sharma Aseem R. , Déry Stephen J. 
Published: July 2019

AbstractAtmospheric rivers (ARs), defined as narrow, transient corridors of strong moisture transport in the lower troposphere, are important phenomena for freshwater recharge and water resources, especially along the west coast of North America. This study presents the variability and trends of landfalling ARs (LARs) along the higher (53.5°–60.0°N) and lower (47.0°–53.5°N) latitudes of British Columbia and southeastern Alaska (BCSAK) during the 1948–2016 period. Moreover, we present the synoptic evolution and distribution of LARs in BCSAK during different phases of ocean–atmosphere climate variability using a six‐hourly AR catalogue from the Scripps Institution of Oceanography and reanalysis data from the National Centers for Environmental Prediction/National Center for Atmospheric Research. During 1948–2016, BCSAK averages 35 ± 5 LARs annually, with the highest frequency during fall (13 ± 2) and lowest during spring (5 ± 2). The frequency of LARs across BCSAK rises during the study period, and the increase between 1979 and 2016 is statistically significant (p < .05). A strong ridge over the Pacific Northwest and BC and a trough over the Gulf of Alaska and the Northeastern Pacific Ocean favours AR landfalls at the higher and lower latitudes, respectively. BCSAK experiences greater numbers of LARs during neutral phases of El Niño/Southern Oscillation, the 2013/2014 Pacific oceanic blob, and during the positive phases of the Pacific Decadal Oscillation and Pacific North American Pattern.