bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rock elasticity as a function of the uniaxial stress: laboratory measurements and theoretical modelling of vertical transversely isotropic and orthorhombic shales
Authors: Sviridov V.A. , Mayr S.I. , Shapiro S.A. 
Published: May 2019

ABSTRACTWe apply a rock‐physics model that describes the relationship between the effective stress and rock elasticity. We experimentally obtain and analyse a data set containing one vertical transversely isotropic and one orthorhombic shale sample. The vertical transversely isotropic symmetry of the first sample is caused by the layered structure of the rock. The seismic orthorhombicity of the second sample could be explained after microscopic analysis of thin section, which demonstrates an imperfect disorder of inhomogeneities. Both samples were loaded uniaxially in a quasi‐static regime. During the loading, we measured stress‐dependent seismic velocities and sample deformations. For the analysis of the stress‐dependent velocities and stiffnesses, we modelled the measured data set using a recent generalization of the porosity deformation approach. Comparison of the experimentally determined and numerically modelled data supports the applicability of the theory and helps in the interpretation of experimentally obtained data. In agreement with the theory, uniaxial stress increases the elliptic component of the seismic anisotropy and does not impact the anellipticity parameter. We demonstrate the distinct influence of the stiff and compliant porosities on the stress sensitivity of the elastic properties.
Integrated metabolic strategy: A framework for predicting the evolution of carbon‐water tradeoffs within plant clades
Authors: Goud Ellie M. , Sparks Jed P. , Fishbein Mark , Agrawal Anurag A. 
Published: May 2019

Abstract

The fundamental tradeoff between carbon gain and water loss has long been predicted as an evolutionary driver of plant strategies across environments. Nonetheless, challenges in measuring carbon gain and water loss in ways that integrate over leaf lifetime have limited our understanding of the variation in and mechanistic bases of this tradeoff. Furthermore, the microevolution of plant traits within species versus the macroevolution of strategies among closely related species may not be the same, and accordingly, the latter must be addressed using comparative phylogenetic analyses.

Here we introduce the concept of ‘integrated metabolic strategy’ (IMS) to describe the ratio between carbon isotope composition (δ13C) and oxygen isotope composition above source water (Δ18O) of leaf cellulose. IMS is a measure of leaf‐level conditions that integrate several mechanisms contributing to carbon gain (δ13C) and water loss (Δ18O) over leaf lifespan, with larger values reflecting higher metabolic efficiency and hence less of a tradeoff. We tested how IMS evolves among closely related yet ecologically diverse milkweed species, and subsequently addressed phenotypic plasticity in response to water availability in species with divergent IMS.

Integrated metabolic strategy varied strongly among 20 Asclepias species when grown under controlled conditions, and phylogenetic analyses demonstrate species‐specific tradeoffs between carbon gain and water loss. Larger IMS values were associated with species from dry habitats, with larger carboxylation capacity, smaller stomatal conductance and smaller leaves; smaller IMS was associated with wet habitats, smaller carboxylation capacity, larger stomatal conductance and larger leaves. The evolution of IMS was dominated by changes in species’ demand for carbon (δ13C) more so than water conservation (Δ18O). Although some individual physiological traits showed phylogenetic signal, IMS did not.

In response to experimental decreases in soil moisture, three species maintained similar IMS across levels of water availability because of proportional increases in δ13C and Δ18O (or little change in either), while one species increased IMS due to disproportional changes in δ13C relative to Δ18O.

Synthesis. IMS is a broadly applicable mechanistic tool; IMS variation among and within species may shed light on unresolved questions relating to the evolution and ecology of plant ecophysiological strategies.
How Busyness Influences SEC Compliance Activities: Evidence from the Filing Review Process and Comment Letters
Authors: Gunny Katherine A. , Hermis Judith M. 
Published: May 2019

ABSTRACTThe SEC reviews firm filings and issues comment letters on those filings. These comment letters play an important role in the assessment of firm value. These activities are seasonally compressed because over 70 percent of registrants have a December fiscal year‐end. Research in other settings finds that busyness leads to negative outcomes. We examine how busyness impacts the frequency, scope, and timeliness of comment letters. We find that the SEC issues fewer comment letters when busy, focuses its limited resources on the most severe cases of disclosure noncompliance, and extends the amount of time between receiving a firm's filing and issuing a comment letter. Despite this, we find no evidence that the SEC misses more serious compliance issues when busy. Our results have implications for policymakers responsible for allocating resources to the SEC.
A comparative analysis of common methods to identify waterbird hotspots
Authors: Sussman Allison L. , Gardner Beth , Adams Evan M. , Salas Leo , Kenow Kevin P. , Luukkonen David R. , Monfils Michael J. , Mueller William P. , Williams Kathryn A. , Leduc‐Lapierre Michele , Zipkin Elise F. 
Published: May 2019

Abstract

Hotspot analysis is a commonly used method in ecology and conservation to identify areas of high biodiversity or conservation concern. However, delineating and mapping hotspots is subjective and various approaches can lead to different conclusions with regard to the classification of particular areas as hotspots, complicating long‐term conservation planning.

We present a comparative analysis of recent approaches for identifying waterbird hotspots, with the goal of developing insights about the appropriate use of these methods. We selected four commonly used measures to identify persistent areas of high use: kernel density estimation, Getis‐Ord Gi*, hotspot persistence and hotspots conditional on presence, which represent the range of quantitative hotspot estimation approaches used in waterbird analyses. We applied each of the methods to aerial survey waterbird count data collected in the Great Lakes from 2012–2014. For each approach, we identified areas of high use for seven species/species groups and then compared the results across all methods and to mean effort‐corrected counts.

Our results indicate that formal hotspot analysis frameworks do not always lead to the same conclusions. The kernel density and Getis‐Ord Gi* methods yielded the most similar results across all species analysed and were generally correlated with mean effort‐corrected count data. We found that these two models can differ substantially from the hotspot persistence and hotspots conditional on presence estimation approaches, which were not consistently similar to one another. The hotspot persistence approach differed most significantly from the other methods but is the only method to explicitly account for temporal variation.

We recommend considering the ecological question and scale of conservation or management activities prior to designing survey methodologies. Deciding the appropriate definition and scale for analysis is critical for interpretation of hotspot analysis results as is inclusion of important covariates. Combining hotspot analysis methods using an integrative approach, either within a single analysis or post hoc, could lead to greater consistency in the identification of waterbird hotspots.
Body of evidence and approaches applied in the clinical development programme of fixed‐dose combinations in the European Union from 2010 to 2016
Authors: Nøhr‐Nielsen Asbjørn , De Bruin Marie Louise , Thomsen Mikael , Pipper Christian Bressen , Lange Theis , Bjerrum Ole Jannik , Lund Trine Meldgaard 
Published: May 2019

AimsTo provide insights into the clinical development pathway for fixed‐dose combinations (FDCs), to consider strategies, and to elucidate the path to approval by assessing the body of evidence, as summarized in the European Public Assessment Reports.MethodsThe main resource was the European Public Assessment Reports for 36 FDCs, which included 239 clinical trials with 157 514 patients. The analyses focused on how prior knowledge of the active substances or combination, use of pharmacokinetic–pharmacodynamic modelling, and clinical trial design choice impact the size and strategy of the clinical development programme.ResultsFDC products primarily comprised 2 previously approved components (21/36, 71%) and had only 1 approved combination (21/36, 71%). Utilizing previously approved active substances resulted in fewer clinical trials, arms and patients, but FDC doses studied in the clinical development programme. Furthermore, dose‐finding trials were performed for less than half of FDCs consisting of 2 previously approved active substances. The standard approach to demonstrate contribution of active substances was through a factorial or single combination study. Finally, the use of pharmacokinetic modelling showed a significant decrease in the number of FDC doses studied.ConclusionsThe field of FDCs seems to be on the rise, utilizing new molecular entities, prior knowledge and re‐profiling drugs. However, a way to move FDC development forward might be through new regulatory and scientific paradigms, in which it is encouraged to utilize model‐based approaches to develop FDCs with multiple dose levels and dose ratios for exposure‐based treatment that will enable personalization.
Ursodeoxycholic acid accelerates bile acid enterohepatic circulation
Authors: Zhang Yunjing , Jiang Runqiu , Zheng Xiaojiao , Lei Sha , Huang Fengjie , Xie Guoxiang , Kwee Sandi , Yu Herbert , Farrar Christine , Sun Beicheng , Zhao Aihua , Jia Wei 
Published: May 2019

Background and PurposeUrsodeoxycholic acid (UDCA) is the first‐line treatment for primary biliary cholangitis, but its effects on the enterohepatic circulation of bile acid (BA) have been under‐investigated. Therefore, we studied the influence of UDCA on BA enterohepatic circulation in vivo and the mechanisms by which UDCA affects the BA kinetics.Experimental ApproachMice were treated with UDCA and other BAs to observe changes in BA pool and BA transporters involved in enterohepatic circulation. Isotope dilution techniques and biochemical analyses were applied to study BA kinetics after oral administration of UDCA, and the mechanism involved.Key ResultsOral administration of UDCA in mice reduced the overall BA pool and produced a unique BA profile with high‐abundance conjugated UDCA species, including tauroursodeoxycholic acid (TUDCA) and GUDCA. We found increased expression of several main BA transporters in the ileum and liver. BA kinetic experiment showed that feeding UDCA shortened cycling time of BA and accelerated BA enterohepatic circulation. Additionally, we found evidence that the effect of UDCA administration on accelerating BA enterohepatic circulation was due to the inhibition of farnesoid X receptor (FXR) signalling in the ileum and FGF15/19 in the liver.Conclusion and ImplicationsOral administration of UDCA produced a unique BA profile with high‐abundance TUDCA and GUDCA and significantly accelerated BA enterohepatic circulation through the inhibition of intestinal FXR signalling and reduced level of FGF15/19, which in turn, induced the expression of BA transporters in the liver. These findings highlight a critical role for UDCA in maintaining the homeostasis of BA enterohepatic circulation in vivo.
Evolution of drainage, sediment‐flux and fluvio‐deltaic sedimentary systems response in hanging wall depocentres in evolving non‐marine rift basins: Paleogene of Raoyang Sag, Bohai Bay Basin, China
Authors: Chen Hehe , Zhu Xiaomin , Wood Lesli J. , Shi Ruisheng 
Published: May 2019

AbstractThe dynamics of sediment feeding into rift basins and the geomorphologic nature of source areas are critical elements in understanding the evolution of rifted basins. This study integrates seismic, well and geochronologic data on the western dipslope of the Raoyang Sag, a rift associated sub‐basin to the larger Bohai Bay Basin of China to define the history of drainage development for the basin and to assess the sedimentologic response to drainage evolution events. In the Paleogene‐age Lixian Slope, as indicated by paleo‐drainage configuration, progradational seismic geometries, compositional maturity and zircon‐tourmaline‐rutile maturity index trends, three drainages; the paleo‐Daqing River, paleo‐Tang River and paleo‐Dasha River drainages were feeding three closely spaced hanging wall deltaic depositional systems; Delta A fed from the northwest, Delta B fed from the west and Delta C fed from the southwest, respectively. From the late Eocene to early Oligocene, a decrease in sediment‐flux into the hanging wall is documented and petrographic analysis is used to link these changes to stream‐capture in the upstream catchment of the Daqing River. This change is coupled with morphologic changes in the geometries of Deltas A and C, both of which show decreasing deltaic areas, changes in lobe geometry and changes in distributary channel sizes. In addition, the progradational direction of Delta C changes from perpendicular‐to‐the‐rift axis to prograding oblique‐to‐the‐rift axis. It is apparent that the progradation and retrogradational changes in rift margin deltas do not happen in isolation, but such changes can affect growth and progradation direction in adjacent deltas. This work shows that the decrease in sediment‐flux, caused by a drainage capture, will result in a decrease in distributary channel size and delta size and may result in upstream deltas taking advantage of such decreasing confinement to prograde more obliquely to the rift axis.
Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice
Authors: Longworth Sarah A. , Daly Jennifer S. ,   the AST Infectious Diseases Community of Practice
Published: May 2019

AbstractThese updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of nontuberculous mycobacterial infections in the pre‐ and post‐transplant period. NTM commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter‐associated infection, and lymphadenitis. Diagnosis of these infections can be challenging, particularly when they are isolated from nonsterile spaces, owing to their ubiquity in nature. Consequently, diagnosis of pulmonary infections with these pathogens requires fulfillment of microbiologic, radiographic, and clinical criteria to address this concern. A combination of culture and molecular diagnostic techniques is often required to make a species‐level identification. Treatment varies depending on the species isolated and is complex, owing to drug toxicities, need for long‐term multidrug regimens, and consideration of complex drug‐drug interactions between antimicrobials and immunosuppressive agents. Given these treatment challenges, efforts should be made in both the hospital and community settings to limit exposure to these pathogens to the extent feasible.
Export rivalry and exchange rate pass‐through
Authors: Sun Puyang , Tan Yong , Hou Xinyu 
Published: May 2019

AbstractIn this paper, we investigate the influence of market rivalry on firm‐level exchange rate pass‐through. Similar to Bloomet al. Econometrica,80, 1347–1393 (2013), we define market rivalry as product market proximity, and expect the cross market spillovers, that is, through leaked information or reputation, to affect firm‐level export price. Using a comprehensive dataset from Chinese exporters for the 2000–2007 period, we find that in response to a higher degree of market rivalry firms are less responsive to exchange fluctuations. This unresponsiveness suggests a higher degree of exchange rate pass‐through. The influence of market rivalry is stronger among firms that export consumption and heterogeneous products, and to developed countries. Our results are robust to different measures of market rivalry and specifications.
Gating in plant plasma membrane aquaporins: the involvement of leucine in the formation of a pore constriction in the closed state
Authors: Canessa Fortuna Agustina , Zerbetto De Palma Gerardo , Aliperti Car Lucio , Armentia Luciano , Vitali Victoria , Zeida Ari , Estrin Darío A. , Alleva Karina 
Published: May 2019

The control of water permeability in plant PIP2 aquaporins has become a paradigmatic case study of the capping mechanism for pore closure in water channels. From structural data, it has been postulated that the gating process in PIP2 involves a conformational rearrangement in cytosolic loopD that generates an obstruction to the transport of water molecules inside the aquaporin pore. BvPIP2;2 is a PIP2 aquaporin from Beta vulgaris whose pH response has been thoroughly characterized. In this work, we study the participation of Leu206 in BvPIP2;2 gating triggered by cytosolic acidification and show that this residue acts as a plug that blocks water transport. Based on data obtained from in silico and in vitro studies, we demonstrate that Leu206, one of the residues lining the pore, is responsible for ~ 60% of water blockage. Cell osmotic swelling experiments and atomistic molecular dynamics simulations indicate that the replacement of Leu206 by an Ala residue maintains high water permeability under conditions where the pore is expected to be closed. The present work demonstrates that Leu206, located at the cytoplasmic entry of the channel, constitutes a crucial pH‐sensitive steric gate regulating water transport in PIP aquaporins.
Modeling optimal responses and fitness consequences in a changing Arctic
Authors: Reimer Jody R. , Mangel Marc , Derocher Andrew E. , Lewis Mark A. 
Published: May 2019

AbstractAnimals must balance a series of costs and benefits while trying to maximize their fitness. For example, an individual may need to choose how much energy to allocate to reproduction versus growth, or how much time to spend on vigilance versus foraging. Their decisions depend on complex interactions between environmental conditions, behavioral plasticity, reproductive biology, and energetic demands. As animals respond to novel environmental conditions caused by climate change, the optimal decisions may shift. Stochastic dynamic programming provides a flexible modeling framework with which to explore these trade‐offs, but this method has not yet been used to study possible changes in optimal trade‐offs caused by climate change. We created a stochastic dynamic programming model capturing trade‐off decisions required by an individual adult female polar bear (Ursus maritimus) as well as the fitness consequences of her decisions. We predicted optimal foraging decisions throughout her lifetime as well as the energetic thresholds below which it is optimal for her to abandon a reproductive attempt. To explore the effects of climate change, we shortened the spring feeding period by up to 3 weeks, which led to predictions of riskier foraging behavior and higher reproductive thresholds. The resulting changes in fitness may be interpreted as a best‐case scenario, where bears adapt instantaneously and optimally to new environmental conditions. If the spring feeding period was reduced by 1 week, her expected fitness declined by 15%, and if reduced by 3 weeks, expected fitness declined by 68%. This demonstrates an effective way to explore a species' optimal response to a changing landscape of costs and benefits and highlights the fact that small annual effects can result in large cumulative changes in expected lifetime fitness.
Multiple KRAS mutations in the non‐mucinous epithelial lining in the majority of mucinous cystic neoplasms of the pancreas
Authors: An Soyeon , Kim Mi‐Ju , Kim Sung Joo , Sung You-Na , Kim Yeon Wook , Song Ki Byung , Hwang Dae Wook , Kim Song Cheol , Hruban Ralph H , Hong Seung‐Mo 
Published: May 2019

AimsMucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian‐type stroma. Although a non‐MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian‐type stroma and NMLE should be classified as MCNs or separately designated is debated.Methods and resultsTo test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low‐grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low‐grade dysplasia.ConclusionsClonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.
Fabrication and properties of porous anorthite/mullite ceramics with both high porosity and high strength
Authors: Wu Linghao , Li Cuiwei , Yang Jing , Li Hao 
Published: May 2019

AbstractPorous anorthite/mullite ceramics with both high porosity and high strength have been successfully fabricated by foam‐gelcasting and pressureless sintering technology, using α‐Al2O3, SiO2, and CaCO3 as starting materials and MnO2 as sintering aids. The porous mullite ceramics prepared in this study had 83.3% porosity and 0.3 W/m·K thermal conductivity, exhibited compressive strength value as high as 6.1 MPa. The samples fabricated with mullite content of 30 mol% possessed 79.4% porosity and 5.9 MPa compressive strength showed thermal conductivity as low as 0.19 W/m·K. With the addition of MnO2, the properties of the prepared materials varied slightly when mullite content changed in a large scale. The results showed that the addition of MnO2 promoted the reaction, affected sintering and grain growth, and contributed to high strength and low‐thermal conductivity.
Straddling medical specialties: should we have more comprehensive advanced training?
Authors: Learoyd Diana L. , Clarke Stephen J. 
Published: May 2019

AbstractOver careers spanning 35 years each, we have witnessed great advances in medicine especially in genetics, imaging, immunotherapies and targeted cancer therapies. Our respective specialties of endocrinology and medical oncology have come to overlap significantly necessitating better communication and skills across both specialties. We will highlight common scenarios that straddle endocrinology and medical oncology. The same broad issues apply to other closely related specialties, albeit with different clinical challenges. At present, we see expensive and inefficient cross‐referrals to other subspecialists or sometimes no referral at all, leading to significant clinical omissions. Opportunities for dual advanced training, or for more comprehensive single advanced training could more efficiently lead to enhanced patient care and communication.