bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geomorphic processes influence human settlement on two islands in the Islands of Four Mountains, Alaska
Authors: Persico Lyman , Lanman Henry , Loopesko Lydia , Bruner Kale , Nicolaysen Kirsten 
Published: December 2018

AbstractThe Islands of Four Mountains island group of the Aleutian island arc is remote and difficult to access. Consequently, little fieldwork has focused on geomorphic processes and their relationship to island morphology, climatic change, and human settlement. We investigated glacial, fluvial, and slope processes on the morphologically different Carlisle, Cleveland, and Tana volcanoes. The islands were extensively glaciated at the last glacial maximum (LGM), and there is evidence for a Neoglacial advance. On the highly dissected Tana volcano, a large basin is likely the result of a pre-LGM sector collapse and subsequent glacial erosion into weak hydrothermally altered rock. Valley and moraine morphology is also influenced by hydrothermal alteration. On both Tana and Carlisle, there are sediment fans composed dominantly of thick debris flow deposits mantled by ~3 m of layered tephras, fine-grained alluvium, and anthropogenic deposits. Debris flow deposition was favored during the unstable paraglacial landscape of the early Holocene–latest Pleistocene. The earliest direct archaeological evidence for settlement is 3.8 cal ka BP, but soil geochemical evidence suggests that the islands were inhabited by 7.3 cal ka BP. This discrepancy in the archaeological record may be explained by geomorphic processes including coastal erosion and unstable geomorphic surfaces.
Translating GWAS findings into therapies for depression and anxiety disorders: gene-set analyses reveal enrichment of psychiatric drug classes and implications for drug repositioning
Authors: So Hon-Cheong , Chau Carlos Kwan-Long , Lau Alexandria , Wong Sze-Yung , Zhao Kai 
Published: December 2018

AbstractBackgroundDepression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders.MethodsHere we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD2018 and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on AD, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes.ResultsImportantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzedpvalues was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase.ConclusionTaken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and AD.
THE FORMATIVE TO CLASSIC PERIOD TRANSITION AT IZAPA: UPDATES FROM THE IZAPA HOUSEHOLD ARCHAEOLOGY PROJECT
Authors: Mendelsohn Rebecca R. 
Published: December 2018

AbstractIn southern Mesoamerica, the period between 100b.c.anda.d.400 saw both the apogee and fall of several powerful Formative-period cities. Previous reports have suggested that conquest from the southeast may have prompted a unique decline at Izapa around 100b.c., when many neighboring cities were prospering. Over the last five years, new archaeological data has emerged for the Formative to Classic period transition at Izapa. The present work summarizes these updates and highlights recent deposits excavated during the Izapa Household Archaeology Project. These updates raise questions about the Hato-phase intrusion hypothesis proposed by Lowe and colleagues (1982). I close with an alternative proposal that, beginning around 100b.c., increased network participation and a change in the institution of kingship produced some of the dramatic changes in ceramics and burial patterns observed at the site.
TRANSISTHMIAN TIES: EPI-OLMEC AND IZAPAN INTERACTION
Authors: Pool Christopher A. , Loughlin Michael L. , Ortiz Ceballos Ponciano 
Published: December 2018

AbstractIn 1943, Matthew Stirling (1943:72) once opined, “Izapa appears to be much more closely related to the earth-mound sites of southern Veracruz … than it does with sites in the Maya area.” Since then, scholars have postulated ties of varying strength between Late Formative polities on either side of the Isthmus of Tehuantepec. Ceramic similarities have been noted between southern Chiapas and the Gulf Coast, but discussion of Late Formative transisthmian interaction has focused primarily on sculptural similarities between Izapa and sites of the lower Papaloapan basin, including Tres Zapotes, El Mesón, and Alvarado. Indeed, Michael Coe (1965b:773) suggested that the Izapan art style may have originated on the Gulf Coast rather than on the Pacific slope. In this article, we reexamine Late Formative interaction between Izapa and Epi-Olmec polities with an expanded data set based on recent iconographic studies and archaeological investigations in and around Tres Zapotes.
INTRODUCING IZAPA
Authors: Rosenswig Robert M. , Guernsey Julia 
Published: December 2018

AbstractThis paper introduces the articles that comprise this Special Issue on Izapa. First, we review early reporting and assessments of Izapa's monuments as well as archaeological investigations undertaken at the site during the twentieth century. Next, we describe more recent developments in interpretation and new archeological excavations and survey data collected during the past two decades. The papers in this Special Issue present new information that contribute to our evolving understanding of Izapa during the millennium that stretches from the Middle Formative period through the Middle Classic period (700b.c.–a.d.600). They serve as a status report on our understanding of the still largely enigmatic ancient kingdom, its regional structure, and connections to contemporaneous Isthmian sites.
A Defense of Limited Regulation of Human Genetic Therapies
Authors: HUGHES JAMES J. 
Published: December 2018

Abstract:There is a role for regulatory oversight over new genetic technologies. Research must ensure the rights of human subjects, and all medical products and techniques should be ensured to be safe and effective. In the United States, these forms of regulation are largely the purview of the National Institutes of Health and the Food and Drug Administration. Some have argued, however, that human genetic therapies require new regulatory agencies empowered to enforce cultural norms, protect against hypothetical social harms, or ensure that the human genome remains unchanged. Focusing on the United States, this essay will briefly review these arguments and argue that the current limited regulatory role over human gene therapies is sufficient to protect public health, bodily autonomy, and reproductive freedom.
Involving Patients in Research? Responsible Research and Innovation in Small- and Medium-Sized European Health Care Enterprises*
Authors: IORDANOU KALYPSO 
Published: December 2018

Abstract:Health research is generally undertaken to resolve existing health problems or enhance existing solutions. Research ethics committees have been the main governance tool for research for more than half a century. Their role is to ensure that research is undertaken ethically. To close the increasing gap between science and society, other governance tools are required. The European Commission recommends and actively promotes the policy of responsible research and innovation (RRI). In addition to sound research ethics, a key feature of RRI is the involvement of different societal stakeholders throughout the research process.But how accepted is the involvement of societal stakeholders in the research of small- and medium-sized enterprises (SMEs) in the health care sector? This question is examined based on 18 in-depth interviews with private health care industry representatives from across Europe in companies focusing on developing medical device technology. Findings suggest that SMEs are reluctant to undertake research involving patients, especially in the early stages of the research and innovation process. For some SMEs this is due to concerns about the dangers of raising expectations they cannot meet, while for others the main concerns are increasing costs and producing less competitive products. Implications of the research findings are discussed.
CATEGORICAL PROOF OF HOLOMORPHIC ATIYAH–BOTT FORMULA
Authors: Kondyrev Grigory , Prikhodko Artem 
Published: December 2018

Given a $2$-commutative diagramin a symmetric monoidal $(\infty ,2)$-category $\mathscr{E}$ where $X,Y\in \mathscr{E}$ are dualizable objects and $\unicode[STIX]{x1D711}$ admits a right adjoint we construct a natural morphism $\mathsf{Tr}_{\mathscr{E}}(F_{X})\xrightarrow[{}]{~~~~~}\mathsf{Tr}_{\mathscr{E}}(F_{Y})$ between the traces of $F_{X}$ and $F_{Y}$, respectively. We then apply this formalism to the case when $\mathscr{E}$ is the $(\infty ,2)$-category of $k$-linear presentable categories which in combination of various calculations in the setting of derived algebraic geometry gives a categorical proof of the classical Atiyah–Bott formula (also known as the Holomorphic Lefschetz fixed point formula).
Addressing perceived economic obstacles to genetic testing as a way to mitigate disparities in family health history for adoptees
Authors: May Thomas , Evans James P. 
Published: December 2018

AbstractIn this paper, we ask whether or not we can afford to realize the potential benefits of genetic testing as a screening tool for adoptees. Our method is to provide reasonable cost and savings estimates. We argue that the prospect of cost neutrality should be sufficient to explore the targeted screening for a population who will otherwise suffer an avoidable health disparity in access to inherited disease information. Our goal here is to establish that the investment needed to attain these benefits is not beyond our means.
Constraining the Fluid History of a CO2‐H2S Reservoir: Insights From Stable Isotopes, REE, and Fluid Inclusion Microthermometry
Authors: Zwahlen Carmen , Hollis Cathy , Lawson Michael , Becker Stephen P. , Boyce Adrian , Zhou Zheng , Holland Greg 
Published: December 2018

AbstractReservoirs that host CO2‐H2S‐bearing gases provide a key insight into crustal redox reactions such as thermochemical sulfate reduction (TSR). Despite this, there remains a poor understanding of the extent, duration, and the factors limiting this process on a reservoir scale. Here we show how a combination of petrography, fluid inclusion, rare earth element (REE), and carbon (δ13C), oxygen (δ18O), and sulfur (δ34S) stable isotope data can disentangle the fluid history of the world's largest CO2accumulation, the LaBarge Field in Wyoming, USA. The carbonate‐hosted LaBarge Field was charged with oil around 80 Ma ago, which together with nodular anhydrite represent the reactants for TSR. The nodules exhibit two distinct trends of evolution in δ13C with both δ34S and δ18O that may be coupled to two different processes. The first trend was interpreted to reflect the coupled dissolution of anhydrite and reduction to elemental sulfur and the oxidation of organic compounds and associated precipitation of calcite during TSR. In contrast, the second trend was interpreted to be the result of the hydrothermal CO2influx after the cessation of TSR. In addition, mass balance calculations were performed to estimate an approximate TSR reaction duration of 80 ka and to identify the availability of organic compounds as the limiting factor of the TSR process. Such an approach provides a tool for the prediction of TSR occurrence elsewhere and advancing our understanding of crustal fluid interactions.
Multispacecraft Analysis of Electron Holes
Authors: Steinvall K. , Khotyaintsev Yu. V. , Graham D. B. , Vaivads A. , Lindqvist P.‐A. , Russell C. T. , Burch J. L. 
Published: December 2018

AbstractElectron holes (EHs) are nonlinear electrostatic structures in plasmas. Most previous in situ studies of EHs have been limited to single‐ and two‐spacecraft methods. We present statistics of EHs observed by Magnetospheric Multiscale on the magnetospheric side of the magnetopause during October 2016 when the spacecraft separation was around 6 km. Each EH is observed by all four spacecraft, allowing EH properties to be determined with unprecedented accuracy. We find that the parallel length scale, l∥, scales with the Debye length. The EHs can be separated into three groups of speed and potential based on their coupling to ions. We present a method for calculating the perpendicular length scale, l⊥. The method can be applied to a small subset of the observed EHs for which we find shapes ranging from almost spherical to more oblate. For the remaining EHs we use statistical arguments to find l⊥/l∥≈5, implying dominance of oblate EHs.
Magnetic Connectivity in the Corona as a Source of Structure in the Solar Wind
Authors: Burkholder B. L. , Otto A. , Delamere P. A. , Borovsky J. E. 
Published: December 2018

AbstractFive decades of satellite data confirm that the solar wind contains many boundaries separating flow with distinct magnetic and plasma properties. Some speculate the boundaries in the solar wind found at Earth originate at the solar surface and are carried along with the expanding solar wind as fossil structures to 1 AU. This begs the question, is it the physics and magnetic structure above the photosphere that creates well‐defined boundaries between different magnetic flux regions at 1 AU in the solar wind? Magnetic boundaries in the corona exist all the time as topological features of null points in the field. These topological magnetic boundaries seem to be likely locations for plasma boundaries. It can be expected that these boundaries are typical locations where field line‐integrated quantities, such as field‐aligned current, experience large and abrupt changes. We perform three‐dimensional resistive magnetohydrodynamic simulations of the solar corona driven by photospheric foot point motions. We find that large and abrupt changes occur for field line‐integrated quantities across a magnetic topological boundary and the cause for these changes is the discontinuous mapping for magnetic field lines and thus for Alfvén waves across these boundaries. It is also demonstrated via in situ properties that thin layers of field‐aligned and perpendicular currents are frequently located at or close to topological boundaries.
Evaluation of Temporally Correlated Noise in Global Navigation Satellite System Time Series: Geodetic Monument Performance
Authors: Langbein John , Svarc Jerry L. 
Published: December 2018

AbstractEstimates of background noise of Global Positioning System‐derived time series of positions for 740 sites in the western United States are examined. These data consist of daily epochs of three components of displacements that are at least 9.75 years long within the interval between 2000 and 2018. We find that these time series have significant temporal correlations that could be represented as a combination of white, flicker, random‐walk, and band‐pass filtered noise. From this noise model, two other metrics are computed: the root‐mean‐square of seasonal noise, that is, the integrated power spectrum between 0.5 and 2 cycles per year, and the standard error in position rate for a 10‐year‐long time series. These two metrics are used to evaluate potential correlations with different geographic regions and with different methods of construction of monuments used to attach the Global Positioning System antenna to the Earth's surface. The sites with the lowest noise, both in terms of rate error and seasonal root‐mean‐square, are located in semiarid regions east of the rain shadow provided by the Cascade and Sierra Nevada mountain ranges. In addition, according to statistical rank tests, monuments known as drilled‐braced monuments perform 30% to 50% better than other monument types (buildings, boreholes, piers, etc.) in terms of having smaller rate errors and lower seasonal noise.
Controls on Carbonate System Dynamics in a Coastal Plain Estuary: A Modeling Study
Authors: Shen Chunqi , Testa Jeremy M. , Li Ming , Cai Wei‐Jun , Waldbusser George G. , Ni Wenfei , Kemp W. Michael , Cornwell Jeffrey , Chen Baoshan , Brodeur Jean , Su Jianzhong 
Published: December 2018

AbstractThe study of acidification in Chesapeake Bay is challenged by the complex spatial and temporal patterns of estuarine carbonate chemistry driven by highly variable freshwater and nutrient inputs. A new module was developed within an existing coupled hydrodynamic‐biogeochemical model to understand the underlying processes controlling variations in the carbonate system. We present a validation of the model against a diversity of field observations, which demonstrated the model's ability to reproduce large‐scale carbonate chemistry dynamics of Chesapeake Bay. Analysis of model results revealed that hypoxia and acidification were observed to cooccur in midbay bottom waters and seasonal cycles in these metrics were regulated by aerobic respiration and vertical mixing. Calcium carbonate dissolution was an important buffering mechanism for pH changes in late summer, leading to stable or slightly higher pH values in this season despite persistent hypoxic conditions. Model results indicate a strong spatial gradient in air‐sea CO2 fluxes, where the heterotrophic upper bay was a strong CO2 source to atmosphere, the mid bay was a net sink with much higher rates of net photosynthesis, and the lower bay was in a balanced condition. Scenario analysis revealed that reductions in riverine nutrient loading will decrease the acid water volume (pH < 7.5) as a consequence of reduced organic matter generation and subsequent respiration, while bay‐wide dissolved inorganic carbon (DIC) increased and pH declined under scenarios of continuous anthropogenic CO2 emission. This analysis underscores the complexity of carbonate system dynamics in a productive coastal plain estuary with large salinity gradients.
The Traditional Chinese Medicine MLC901 inhibits inflammation processes after focal cerebral ischemia
Authors: Widmann C. , Gandin C. , Petit-Paitel A. , Lazdunski M. , Heurteaux C. 
Published: December 2018

AbstractInflammation is considered as a major contributor to brain injury following cerebral ischemia. The therapeutic potential of both MLC601/MLC901, which are herbal extract preparations derived from Chinese Medicine, has been reported both in advanced stroke clinical trials and also in animal and cellular models. The aim of this study was to investigate the effects of MLC901 on the different steps of post-ischemic inflammation in focal ischemia in mice. In vivo injury was induced by 60 minutes of middle cerebral artery occlusion (MCAO) followed by reperfusion. MLC901 was administered in post-treatment 90 min after the onset of ischemia and once a day during reperfusion. MLC901 treatment resulted in a reduction in infarct volume, a decrease of Blood Brain Barrier leakage and brain swelling, an improvement in neurological scores and a reduction of mortality rate at 24 hours after MCAO. These beneficial effects of MLC901 were accompanied by an inhibition of astrocytes and microglia/macrophage activation, a drastically decreased neutrophil invasion into the ischemic brain as well as by a negative regulation of pro-inflammatory mediator expression (cytokines, chemokines, matrix metalloproteinases). MLC901 significantly inhibited the expression of Prx6 as well as the transcriptional activity of NFκB and the activation of Toll-like receptor 4 (TLR4) signaling, an important pathway in the immune response in the ischemic brain. MLC901 effects on the neuroinflammation cascade induced by cerebral ischemia probably contribute, in a very significant way, in its potential therapeutic value.
OATP1B3 (699G>A) and CYP2C9*2, *3 significantly influenced the transport and metabolism of glibenclamide and glipizide
Authors: Yang Fayou , Liu Linlin , Chen Lin , Liu Mingyi , Liu Fanglan , Xiong Yuqing , Hu Xiao , Xia Chunhua 
Published: December 2018

AbstractGlibenclamide and glipizide show large substantial inter-individual variation in clinical efficacy, which may be resulted from the genetic differences of metabolic enzymes and transporters in individuals. This study purposed to investigate the effect of OATP1B3 and CYP2C9 genetic polymorphisms on the transport and metabolism of glibenclamide and glipizide in human. An LC-MS method was used to determine the uptake of glibenclamide and glipizide in OATP1B3, OATP1B3 (344T > G) and OATP1B3 (699G > A)-HEK293T cells and their metabolism in CYP2C9*1, *2 and *3 recombinase system. Glibenclamide can be taken in OATP1B3 (wild-type), OATP1B3 (344T > G) and OATP1B3 (699G > A)-HEK293T cells with the Vmax values of 44.91 ± 7.97, 46.08 ± 8.69, and 37.31 ± 5.04 pmol/min/mg, while glipizide was taken in with Vmax of 16.50 ± 3.64, 16.87 ± 4.23, and 13.42 ± 2.79 pmol/min/mg, respectively. The internal clearance of glibenclamide and glipizide in OATP1B3 (699G > A) was less than that in wild-type. Glibenclamide can be metabolized in CYP2C9*1, *2 and *3 recombinase system with the Vmax values of 1.58 ± 0.71, 0.69 ± 0.25, and 0.41 ± 0.13 nmol/min/mg protein, while glipizide was metabolized with Vmax of 8.82 ± 2.78, 5.99 ± 1.95, and 2.87 ± 1.03 nmol/min/mg protein, respectively. The internal clearance of glibenclamide and glipizide in CYP2C9*2 and *3 was markedly reduced compared to that in CYP2C9*1. These results collectively demonstrate that OATP1B3 (699G > A) and CYP2C9*2 and *3 have a significant influence on the transport and metabolism of glibenclamide and glipizide.