bluuebunny/crossref_metadata_2025_split huggingface dataset:
The application of physiologically based pharmacokinetic modelling to assess the impact of antiretroviral‐mediated drug–drug interactions on piperaquine antimalarial therapy during pregnancy
Authors: Olafuyi Olusola , Coleman Michael , Badhan Raj K.S. 
Published: July 2017

AbstractAntimalarial therapy during pregnancy poses important safety concerns due to potential teratogenicity and maternal physiological and biochemical changes during gestation. Piperaquine (PQ) has gained interest for use in pregnancy in response to increasing resistance towards sulfadoxine–pyrimethamine in sub‐Saharan Africa. Coinfection with HIV is common in many developing countries, however, little is known about the impact of antiretroviral (ARV) mediated drug–drug interaction (DDI) on piperaquine pharmacokinetics during pregnancy. This study applied mechanistic pharmacokinetic modelling to predict pharmacokinetics in non‐pregnant and pregnant patients, which was validated in distinct customised population groups from Thailand, Sudan and Papua New Guinea. In each population group, no significant differences in day 7 concentrations were observed during different gestational weeks (GW) (weeks 10–40), supporting the notion that piperaquine is safe throughout pregnancy with consistent pharmacokinetics, although possible teratogenicity may limit this. Antiretroviral‐mediated DDIs (efavirenz and ritonavir) had moderate effects on piperaquine during different gestational weeks with a predicted AUCratio in the range 0.56–0.8 and 1.64–1.79 for efavirenz and ritonavir, respectively, over GW 10–40, with a reduction in circulating human serum albumin significantly reducing the number of subjects attaining the day 7 (post‐dose) therapeutic efficacy concentrations under both efavirenz and ritonavir DDIs. This present model successfully mechanistically predicted the pharmacokinetics of piperaquine in pregnancy to be unchanged with respect to non‐pregnant women, in the light of factors such as malaria/HIV co‐infection. However, antiretroviral‐mediated DDIs could significantly alter piperaquine pharmacokinetics. Further model refinement will include collation of relevant physiological and biochemical alterations common to HIV/malaria patients.
ROS mediated selection for increased NADPH availability in Escherichia coli
Authors: Reynolds Thomas S. , Courtney Colleen M. , Erickson Keesha E. , Wolfe Lisa M. , Chatterjee Anushree , Nagpal Prashant , Gill Ryan T. 
Published: July 2017

AbstractThe economical production of chemicals and fuels by microbial processes remains an intense area of interest in biotechnology. A key limitation in such efforts concerns the availability of key co‐factors, in this case NADPH, required for target pathways. Many of the strategies pursued for increasing NADPH availability in Escherichia coli involve manipulations to the central metabolism, which can create redox imbalances and overall growth defects. In this study we used a reactive oxygen species based selection to search for novel methods of increasing NADPH availability. We report a loss of function mutation in the gene hdfR appears to increase NADPH availability in E. coli. Additionally, we show this excess NADPH can be used to improve the production of 3HP in E. coli.
High glucose induces O‐GlcNAc glycosylation of the vitamin D receptor (VDR) in THP1 cells and in human macrophages derived from monocytes
Authors: Hernández‐Sánchez Fernando , Guzmán‐Beltrán Silvia , Herrera María Teresa , Gonzalez Yolanda , Salgado Manuel , Fabian Guadalupe , Torres Martha 
Published: July 2017

AbstractChronic hyperglycemia increases the carbon flux through the hexosamine pathway, allowing the accumulation of UDP‐GlcNAc. UDP‐GlcNAc is the sugar donor for the enzyme‐mediated protein glycosylation event known as OGlcNAcylation. This posttranslational modification targets several transcription factors implicated in glucose toxicity, insulin resistance, and diabetes. Vitamin D plays an important role in glucose homeostasis and insulin secretion through transcriptional mechanisms mediated by its receptor (VDR). Vitamin D deficiency has been associated with higher susceptibility to bacterial diseases in diabetic patients. However, it has not been explored whether VDR is subject to OGlcNAcylation or whether high glucose affects its transcriptional or biological activities. The aim of this study was to evaluate the effect of hyperglycemia on VDR OGlcNAcylation and its effects on vitamin D‐mediated transcription. We predicted potential OGlcNAcylation sites using free software. Our results showed that hyperglycemia (30 mM) induces the OGlcNAcylation of VDR in THP1 cells and in human macrophages derived from monocytes (MDM). This condition did not hamper the vitamin D‐dependent activation of LL‐37 gene expression, and even did not impair the macrophage bactericidal activity. Our study provides new insight into vitamin D receptor posttranslational modification that may have relevance on the physiological responses of long‐term hyperglycemia.
Active Site Elucidation and Optimization in Pt Co‐catalysts for Photocatalytic Hydrogen Production over Titania
Authors: Jiang Zhi , Isaacs Mark A. , Huang Zheng Wen , Shangguan Wenfeng , Deng Yifeng , Lee Adam F. 
Published: July 2017

AbstractPlatinum co‐catalysts play a critical role in promoting the photocatalytic performance of inorganic semiconductors, yet despite intensive investigation, the active platinum species responsible remains controversial. Here, the physicochemical properties of Pt nanoparticles introduced into anatase titania through three different synthetic protocols are investigated by porosimetry, XRD, X‐ray photoelectron spectroscopy (XPS), and X‐ray absorption spectroscopy (XAS) and correlated with their corresponding activity for aqueous photocatalytic hydrogen production. Conventional wet impregnation produces small but highly oxidized platinum nanoparticles owing to the classical strong metal–support interaction with titania during high‐temperature processing. Photodeposition yields predominantly metallic but large and inhomogeneous (1.5–7.5 nm) Pt nanoparticles. In contrast, a modified in situ polyol route affords metallic and highly dispersed (<2 nm) nanoparticles with minimal PtOx. Photocatalytic H2 evolution is directly proportional to the surface concentration of Pt metal, conclusively demonstrating metallic platinum as the active co‐catalyst, and offering a simple parameter to quantitatively predict the photocatalytic performance of Pt/TiO2 in H2 production. The modified in situ polyol synthesis is optimal for co‐catalyst formation, delivering rate enhancements of 25–80 % compared with the other syntheses.
Aromatic Micelles as a New Class of Aqueous Molecular Flasks
Authors: Kondo Kei , Klosterman Jeremy K. , Yoshizawa Michito 
Published: July 2017

AbstractMicelles are a versatile class of molecular assemblies typically composed of aliphatic molecules with hydrophilic groups. Polyaromatic molecules with hydrophilic groups, on the other hand, usually do not assemble into micellar structures in water but rather form columnar, π‐stacked architectures. This Minireview article focuses on the recent development of aqueous micellar nanostructures with multiple oligoarylene rods or polyaromatic panels. The new micelles with spherical polyaromatic shells, which we name “aromatic micelles”, serve as functional molecular flasks with superior binding abilities for medium to very large molecules in water.
A Review on Bimetallic Nickel‐Based Catalysts for CO2 Reforming of Methane
Authors: Bian Zhoufeng , Das Sonali , Wai Ming Hui , Hongmanorom Plaifa , Kawi Sibudjing 
Published: July 2017

AbstractIn recent years, CO2 reforming of methane (dry reforming of methane, DRM) has become an attractive research area because it converts two major greenhouse gasses into syngas (CO and H2), which can be directly used as fuel or feedstock for the chemical industry. Ni‐based catalysts have been extensively used for DRM because of its low cost and good activity. A major concern with Ni‐based catalysts in DRM is severe carbon deposition leading to catalyst deactivation, and a lot of effort has been put into the design and synthesis of stable Ni catalysts with high carbon resistance. One effective and practical strategy is to introduce a second metal to obtain bimetallic Ni‐based catalysts. The synergistic effect between Ni and the second metal has been shown to increase the carbon resistance of the catalyst significantly. In this review, a detailed discussion on the development of bimetallic Ni‐based catalysts for DRM including nickel alloyed with noble metals (Pt, Ru, Ir etc.) and transition metals (Co, Fe, Cu) is presented. Special emphasis has been provided on the underlying principles that lead to synergistic effects and enhance catalyst performance. Finally, an outlook is presented for the future development of Ni‐based bimetallic catalysts.
No obvious genetic erosion, but evident relict status at the westernmost range edge of the Pontic‐Pannonian steppe plant Linum flavum L. (Linaceae) in Central Europe
Authors: Plenk Kristina , Bardy Katharina , Höhn Maria , Thiv Mike , Kropf Matthias 
Published: July 2017

AbstractWe investigate patterns of genetic variation along an east–west transect of Central European populations of Linum flavum and interpret the Quaternary history of its peripheral populations, especially those at the westernmost isolated range edge, discussing their migrations and possible relict status. We defined our peripheral transect across three study regions from Central Hungary, eastern Austria to southwestern Germany. Using AFLP fingerprinting and cpDNA sequence variation (rpL16 intron, atpI‐H), we analyzed 267 and 95 individuals, respectively, representing each study region by four populations. Hierarchical AMOVA (AFLPs) indicated significant variation among study regions (12% of total variance) and moderate differentiation between populations (10%). Population differentiation was high at the westernmost range edge (11.5%, Germany), but also in the east (13.4%, Hungary), compared to the Austrian study region (8.6%). Correspondingly, AFLP diversity was highest in the center of the study transect in eastern Austria. CpDNA haplotypes support a pattern of regional structuring with the strongest separation of the westernmost range edge, and some haplotype sharing among Austrian and Hungarian individuals. Equilibrating nucleotide versus haplotype diversity patterns, the highly diverse populations at the Pannonian range edge (Austria) indicate long‐term persistence, while Central Pannonian populations are obviously effected by recent bottlenecks. Intermediate nucleotide, but high haplotype diversity within the westernmost exclave (Swabian Alb), is indicative of a founder bottleneck during its pre‐LGM or early postglacial migration history, followed by sufficient time to accumulate cpDNA variation. The not obviously reduced genetic diversity and distinctiveness of L. flavum at the westernmost range edge suggest a long‐term persistence (relict status) of populations in this region, where the species has survived probably even the Würm glaciation in extra‐Mediterranean refugia. This genetic relict variation represents an important part of the overall genetic diversity found in the western periphery of this steppe plant and highlights the high conservation priority of respective gene pools.
Interactions among salt marsh plants vary geographically but not latitudinally along the California coast
Authors: Noto Akana E. , Shurin Jonathan B. 
Published: July 2017

AbstractThe strength of species interactions often varies geographically and locally with environmental conditions. Competitive interactions are predicted to be stronger in benign environments while facilitation is expected to be stronger in harsh ones. We tested these ideas with an aboveground neighbor removal experiment at six salt marshes along the California coast. We determined the effect of removals of either the dominant species, Salicornia pacifica, or the subordinate species on plant cover, aboveground biomass and community composition, as well as soil salinity and moisture. We found that S. pacifica consistently competed with the subordinate species and that the strength of competition varied among sites. In contrast with other studies showing that dominant species facilitate subordinates by moderating physical stress, here the subordinate species facilitated S. pacifica shortly after removal treatments were imposed, but the effect disappeared over time. Contrary to expectations based on patterns observed in east coast salt marshes, we did not see patterns in species interactions in relation to latitude, climate, or soil edaphic characteristics. Our results suggest that variation in interactions among salt marsh plants may be influenced by local‐scale site differences such as nutrients more than broad latitudinal gradients.
Dissociation of spatial memory systems in Williams syndrome
Authors: Bostelmann Mathilde , Fragnière Emilie , Costanzo Floriana , Di Vara Silvia , Menghini Deny , Vicari Stefano , Lavenex Pierre , Lavenex Pamela Banta 
Published: July 2017

AbstractWilliams syndrome (WS), a genetic deletion syndrome, is characterized by severe visuospatial deficits affecting performance on both tabletop spatial tasks and on tasks which assess orientation and navigation. Nevertheless, previous studies of WS spatial capacities have ignored the fact that two different spatial memory systems are believed to contribute parallel spatial representations supporting navigation. The place learning system depends on the hippocampal formation and creates flexible relational representations of the environment, also known as cognitive maps. The spatial response learning system depends on the striatum and creates fixed stimulus‐response representations, also known as habits. Indeed, no study assessing WS spatial competence has used tasks which selectively target these two spatial memory systems. Here, we report that individuals with WS exhibit a dissociation in their spatial abilities subserved by these two memory systems. As compared to typically developing (TD) children in the same mental age range, place learning performance was impaired in individuals with WS. In contrast, their spatial response learning performance was facilitated. Our findings in individuals with WS and TD children suggest that place learning and response learning interact competitively to control the behavioral strategies normally used to support human spatial navigation. Our findings further suggest that the neural pathways supporting place learning may be affected by the genetic deletion that characterizes WS, whereas those supporting response learning may be relatively preserved. The dissociation observed between these two spatial memory systems provides a coherent theoretical framework to characterize the spatial abilities of individuals with WS, and may lead to the development of new learning strategies based on their facilitated response learning abilities.
Season‐specific habitat restriction in Asiatic black bears, Japan
Authors: Takahata Chihiro , Takii Akiko , Izumiyama Shigeyuki 
Published: July 2017

ABSTRACTUnderstanding habitat selection by wildlife, particularly in the vicinity of areas dominated by humans, is often important in identifying causes of human–wildlife conflict. With recent increases in the number of Asiatic black bears (Ursus thibetanus) in areas near settlements in Japan, there have been more human–bear conflicts. Because of the seasonal nature of these conflicts, we hypothesized that a season‐specific restriction in habitat may influence bears to select human‐settled areas. To confirm this, we focused on the estimate of seasonal differences in distributions of potential bear habitat. We collected global positioning system data from 14 female and 15 male bears in a 1,023‐km2 range located in the central Alps of Japan. We employed resource selection functions to model season‐specific habitat selection and quantified the spatial distribution of core habitat patches. Compared with other seasons, selected habitat of bears during summer was restricted to the narrow fringes of human‐dominated lands. Selection for younger forests, edges, and lowland red pine (Pinus densiflora) forests supporting diverse food resources indicated that Asiatic black bears were seasonally dependent on early successional stages. In summer when human–bear conflicts peaked, bear avoidance of plantations and the selection for remnant small forest openings and lowland forest combined was the major cause affecting bear proximity to settlements. We recommend that wildlife managers work to restore food‐producing habitat in dense, mature plantations to reduce negative interactions between humans and bears. © 2017 The Wildlife Society.
Vascular Pathology Causing Late Onset Generalized Chorea: A Clinico‐Pathological Case Report
Authors: Salgado Paula , Taipa Ricardo , Domingos Joana , Dias Daniel , Pires Manuel Melo , Magalhães Marina 
Published: July 2017

AbstractBackgroundChorea may occur as a manifestation of an acute stroke. Patients with vascular‐related chorea typically present with an acute or subacute onset of hemichorea, contralateral to the lesion.Methods and FindingsIn this clinico‐pathological case, we report a 90‐year‐old female who presented, at age 81, with a transient episode of generalized chorea. Over the years, the patient continued to have intermittent episodes of generalized chorea or hemichorea, followed by a progressive dementia syndrome with gait and sphincter disturbance. There was no family history of chorea or dementia. Laboratory tests for paraneoplastic or autoimmune disorders and genetic testing for Huntington's disease were normal or negative. Magnetic resonance imaging showed subcortical and basal ganglia atrophy associated with ischemic leukoencephalopathy and lacunar infarcts. The post‐mortem examination identified multiple lacunar infarcts (cortex, white matter, thalamus, basal ganglia) and minor Alzheimer′s disease neuropathological changes.ConclusionsVascular disease, affecting the basal ganglia, is included in most lists of causes of generalized chorea. Proven cases are difficult to find. We present a rare case of vascular pathology causing late onset generalized and intermittent chorea. We highlight the intermittent nature of the chorea that could be explained by cumulative vascular lesions or functional disconnection in a previous deficient circuit.
Detection and quantification of coronary calcium from dual energy chest x‐rays: Phantom feasibility study
Authors: Zhou Bo , Wen Di , Nye Katelyn , Gilkeson Robert C. , Eck Brendan , Jordan David , Wilson David L. 
Published: July 2017

PurposeWe have demonstrated the ability to identify coronary calcium, a reliable biomarker of coronary artery disease, using nongated, 2‐shot, dual energy (DE) chest x‐ray imaging. Here we will use digital simulations, backed up by measurements, to characterize DE calcium signals and the role of potential confounds such as beam hardening, x‐ray scatter, cardiac motion, and pulmonary artery pulsation. For the DE calcium signal, we will consider quantification, as compared to CT calcium score, and visualization.MethodsWe created stylized and anatomical digital 3D phantoms including heart, lung, coronary calcium, spine, ribs, pulmonary artery, and adipose. We simulated high and low kVp x‐ray acquisitions with x‐ray spectra, energy dependent attenuation, scatter, ideal detector, and automatic exposure control (AEC). Phantoms allowed us to vary adipose thickness, cardiac motion, etc. We used specialized dual energy coronary calcium (DECC) processing that includes corrections for scatter and beam hardening.ResultsBeam hardening over a wide range of adipose thickness (0–30 cm) reduced the change in intensity of a coronary artery calcification (ΔICAC) by < 3% in DECC images. Scatter correction errors of ±50% affected the calcium signal (ΔICAC) in DECC images ±9%. If a simulated pulmonary artery fills with blood between exposures, it can give rise to a residual signal in DECC images, explaining pulmonary artery visibility in some clinical images. Residual misregistration can be mostly compensated by integrating signals in an enlarged region encompassing registration artifacts. DECC calcium score compared favorably to CT mass and volume scores over a number of phantom perturbations.ConclusionSimulations indicate that proper DECC processing can faithfully recover coronary calcium signals. Beam hardening, errors in scatter estimation, cardiac motion, calcium residual misregistration etc., are all manageable. Simulations are valuable as we continue to optimize DE coronary calcium image processing and quantitative analysis.
Multivariate predictions of local reduced‐order‐model errors and dimensions
Authors: Moosavi Azam , Ştefănescu Răzvan , Sandu Adrian 
Published: July 2017

SummaryThis paper introduces multivariate input‐output models to predict the errors and bases dimensions of local parametric Proper Orthogonal Decomposition reduced‐order models. We refer to these mappings as the multivariate predictions of local reduced‐order model characteristics (MP‐LROM) models. We use Gaussian processes and artificial neural networks to construct approximations of these multivariate mappings. Numerical results with a viscous Burgers model illustrate the performance and potential of the machine learning‐based regression MP‐LROM models to approximate the characteristics of parametric local reduced‐order models. The predicted reduced‐order models errors are compared against the multifidelity correction and reduced‐order model error surrogates methods predictions, whereas the predicted reduced‐order dimensions are tested against the standard method based on the spectrum of snapshots matrix. Since the MP‐LROM models incorporate more features and elements to construct the probabilistic mappings, they achieve more accurate results. However, for high‐dimensional parametric spaces, the MP‐LROM models might suffer from the curse of dimensionality. Scalability challenges of MP‐LROM models and the feasible ways of addressing them are also discussed in this study.
Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Lee Won Hee , Chen Wen-Yi , Shao Ning-Yi , Xiao Dan , Qin Xulei , Baker Natalie , Bae Hye Ryeong , Wei Tzu-Tang , Wang Yongjun , Shukla Praveen , Wu Haodi , Kodo Kazuki , Ong Sang-Ging , Wu Joseph C. 
Published: July 2017

Abstract
Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because, unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future.