bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect on gene expression of three allelic variants in GATA motifs of ABO, RHD, and RHCE regulatory elements
Authors: Fennell Katie , Hoffman Roser , Yoshida Ken , Iwamoto Sadahiko , Govender Lavendri , Vather Kuben , Sookraj Ashika , Jentsch Ute , Pambrun Chantale , McAuley Catherine , Keller Margaret A. , Ochoa‐Garay Gorka 
Published: August 2017

BACKGROUNDOnly a few genetic variants have been reported in regulatory elements of blood group genes. Most of them affect GATA motifs, binding sites for the GATA‐1 transcription factor.STUDY DESIGN AND METHODSSamples from two patients and one donor with unusual or discrepant serology for ABO, RhD, and RhCE antigens were analyzed by DNA sequencing. Analyzed regions included the coding sequence and portions of regulatory elements. The effect of some variants on gene expression was evaluated in reporter gene assays.RESULTSThree new alleles were identified. Their key variants are located in the ABO Intron 1 enhancer, the RHD proximal promoter, and the RHCE proximal promoter. IVS1 + 5859A was found in an African American patient with a group O forward type and a group B reverse type. 5′UTR‐115C was the only RHD variant sequence found in a mixed‐race black and Caucasian prenatal patient showing mixed‐field agglutination with anti‐D. 5′UTR‐83T was found in several black donors and patients in the context of the genetically related RHCE*ceBI and RHCE*ceSM alleles. Reporter assays of promoter constructs including 5′UTR‐115C or 5′UTR‐83T showed a significant reduction in RH gene expression.CONCLUSIONThree new alleles in the ABO, RHD, and RHCE genes consist of single‐nucleotide changes within GATA motifs, emphasizing the key role of GATA transcription factors in the expression of blood group genes.
The impact of intergenerational transfers on wealth inequality in Japan and the United States
Authors: Niimi Yoko , Horioka Charles Yuji 
Published: August 2017

AbstractOur paper sheds light on the implications of intergenerational transfers for wealth inequality by examining whether or not individuals who receive intergenerational transfers from their parents are more likely to leave bequests to their children than those who do not using microdata for Japan and the United States. The estimation results show that the receipt of intergenerational transfers from parents and/or parents‐in‐law increases the likelihood of individuals leaving bequests to their children in both Japan and the United States, which in turn is likely to contribute to the persistence or widening of wealth disparities. However, such a tendency is found to be stronger among less better‐off households in both countries, and this may help alleviate the disequalising effect of intergenerational transfers on the distribution of wealth, at least to some extent.
Infection with a novel derogenid trematode in a Flap‐necked chameleon (Chamaeleo dilepis)
Authors: Collicutt Nancy B. , Stacy Nicole I. , Walden Heather Stockdale , Childress April , Dill Jennifer , Anderson Marita , Wellehan James F.X. 
Published: August 2017

AbstractA 2‐year‐old female Flap‐necked chameleon (Chamaeleo dilepis) was presented with a history of anorexia. On physical examination, three 11×4×2 mm, light tan‐pink, raised, gelatinous, freely movable, poorly demarcated, raised nodules were identified within the oral cavity. An impression smear contained multiple, light blue to green structures exhibiting an 18×35 μm, elliptical‐shaped anterior portion and a single 1×150 μm filament with a tapered end. Initial differential etiologies included trematode ova, flagellate protozoa, fungal sporangia, plant material, and sperm. Fungal culture yielded no growth. The structures described above did not stain with Gomori methenamine silver stain. A calcofluor white stain yielded positive fluorescence. The DNA was extracted from the impression smears and pan‐trematode PCR was performed; products were directly sequenced and phylogenetic analysis revealed maximum similarity with a digenean trematode in the family Derogenidae that was distinct from other trematodes for which a reference sequence was available. To our knowledge, this is the first description of cytologic features of trematode ova from an oral lesion in a chameleon.
Pullout strength of 2.0 mm cancellous and cortical screws in synthetic bone
Authors: Moser John E. , Kunkel Kevin A. R. , Gerard Patrick D. 
Published: August 2017

AbstractObjectiveTo determine whether 2.0 mm cancellous screws are superior to 2.0 mm cortical screws when inserted into cancellous and bicortical bone.Study designBiomechanical study.MethodsThe 2.0 mm cancellous screws and 2.0 mm cortical screws were inserted according to the recommended guidelines in synthetic cancellous and bicortical blocks. Fifteen screw‐block constructs per group were tested to failure in axial pullout. Axial pullout strength and yield strength were calculated. Data were analyzed using a one‐way ANOVA.ResultsThe 2.0 mm cortical screws achieved lower axial pullout strength than 2.0 mm cancellous screws in cancellous blocks. The 2.0 mm cortical screws achieved greater pullout strength than 2.0 mm cancellous screws in bicortical blocks.ConclusionThe 2.0 mm cancellous screws may offer a biomechanical advantage in bone with thin cortices (<1 mm thick), whereas 2.0 mm cortical screws may be preferred in cortical bone with cortices measuring at least 1 mm in thickness.
Cardiac action potential repolarization revisited: early repolarization shows all‐or‐none behaviour
Authors: Trenor Beatriz , Cardona Karen , Saiz Javier , Noble Denis , Giles Wayne 
Published: August 2017

AbstractIn healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate‐dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q–T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J‐wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time‐ and voltage‐dependent thresholds, and also demonstrating that both can show regenerative all‐or‐none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as ‘repolarization reserve’. For example, the complex pattern of cell‐to‐cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q–T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti‐arrhythmic drugs).
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Chronic morphine reduces the readily releasable pool of GABA, a presynaptic mechanism of opioid tolerance
Authors: Wilson‐Poe Adrianne R. , Jeong Hyo‐Jin , Vaughan Christopher W. 
Published: August 2017

Key points
Chronic treatment with opioids, such as morphine, leads to analgesic tolerance.
While postsynaptic opioid tolerance is well documented, the involvement of presynaptic mechanisms remains unclear.
We show that chronic morphine reduces the ability of periaqueductal grey (PAG) neurons to maintain GABAergic transmission.
This depression of GABAergic transmission was due to a reduction in the effective size of the readily releasable pool.
This also led to a reduction in opioid presynaptic inhibition; these presynaptic adaptations need to be considered in the development of strategies to reduce opioid tolerance.
AbstractThe midbrain periaqueductal grey (PAG) plays a critical role in tolerance to the analgesic actions of opioids such as morphine. While numerous studies have identified the postsynaptic adaptations induced by chronic morphine treatment in this and other brain regions, the presence of presynaptic adaptations remains uncertain. We examined GABAergic synaptic transmission within rat PAG brain slices from animals which underwent a low dose morphine treatment protocol which produces tolerance, but not withdrawal. Evoked GABAergic IPSCs (inhibitory postsynaptic currents) were less in morphine compared to control saline treated animals. Postsynaptic GABAA receptor mediated currents and desensitization, presynaptic release probability (Pr), and inhibition by endogenous neurotransmitters were similar in morphine and saline treated animals. By contrast, the effective size of the readily releasable pool (RRP) was smaller in morphine treated animals. While the μ‐opioid agonist DAMGO produced a reduction in Pr and RRP size in saline treated animals, it only reduced Pr in morphine treated animals. Consequently, DAMGO‐induced inhibition of evoked IPSCs during short burst stimulation was less in morphine, compared to saline treated animals. These results indicate that low dose chronic morphine treatment reduces presynaptic μ‐opioid inhibition by reducing the size of the pool of vesicles available for action potential dependent release. This novel presynaptic adaptation may provide important insights into the development of efficacious pain therapies that can circumvent the development of opioid tolerance.
Pulmonary artery wave propagation and reservoir function in conscious man: impact of pulmonary vascular disease, respiration and dynamic stress tests
Authors: Su Junjing , Manisty Charlotte , Simonsen Ulf , Howard Luke S. , Parker Kim H. , Hughes Alun D. 
Published: August 2017

Key points
Wave travel plays an important role in cardiovascular physiology. However, many aspects of pulmonary arterial wave behaviour remain unclear.
Wave intensity and reservoir‐excess pressure analyses were applied in the pulmonary artery in subjects with and without pulmonary hypertension during spontaneous respiration and dynamic stress tests.
Arterial wave energy decreased during expiration and Valsalva manoeuvre due to decreased ventricular preload. Wave energy also decreased during handgrip exercise due to increased heart rate.
In pulmonary hypertension patients, the asymptotic pressure at which the microvascular flow ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by waves increased. The reservoir and excess pressures decreased during Valsalva manoeuvre but remained unchanged during handgrip exercise.
This study provides insights into the influence of pulmonary vascular disease, spontaneous respiration and dynamic stress tests on pulmonary artery wave propagation and reservoir function.
AbstractDetailed haemodynamic analysis may provide novel insights into the pulmonary circulation. Therefore, wave intensity and reservoir‐excess pressure analyses were applied in the pulmonary artery to characterize changes in wave propagation and reservoir function during spontaneous respiration and dynamic stress tests. Right heart catheterization was performed using a pressure and Doppler flow sensor tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in control subjects and patients with pulmonary arterial hypertension (PAH) at rest. In controls, recordings were also obtained during Valsalva manoeuvre and handgrip exercise. The asymptotic pressure at which the flow through the microcirculation ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by arterial waves increased in PAH patients compared to controls. The systolic and diastolic rate constants also increased, while the diastolic time constant decreased. The forward compression wave energy decreased by ∼8% in controls and ∼6% in PAH patients during expiration compared to inspiration, while the wave speed remained unchanged throughout the respiratory cycle. Wave energy decreased during Valsalva manoeuvre (by ∼45%) and handgrip exercise (by ∼27%) with unaffected wave speed. Moreover, the reservoir and excess pressures decreased during Valsalva manoeuvre but remained unaltered during handgrip exercise. In conclusion, reservoir‐excess pressure analysis applied to the pulmonary artery revealed distinctive differences between controls and PAH patients. Variations in the ventricular preload and afterload influence pulmonary arterial wave propagation as demonstrated by changes in wave energy during spontaneous respiration and dynamic stress tests.
Engineering defined membrane‐embedded elements of AMPA receptor induces opposing gating modulation by cornichon 3 and stargazin
Authors: Hawken Natalie M. , Zaika Elena I. , Nakagawa Terunaga 
Published: August 2017

Key points
The AMPA‐type ionotropic glutamate receptors (AMPARs) mediate the majority of excitatory synaptic transmission and their function impacts learning, cognition and behaviour.
The gating of AMPARs occurs in milliseconds, precisely controlled by a variety of auxiliary subunits that are expressed differentially in the brain, but the difference in mechanisms underlying AMPAR gating modulation by auxiliary subunits remains elusive and is investigated.
The elements of the AMPAR that are functionally recruited by auxiliary subunits, stargazin and cornichon 3, are located not only in the extracellular domains but also in the lipid‐accessible surface of the AMPAR.
We reveal that the two auxiliary subunits require a shared surface on the transmembrane domain of the AMPAR for their function, but the gating is influenced by this surface in opposing directions for each auxiliary subunit.
Our results provide new insights into the mechanistic difference of AMPAR modulation by auxiliary subunits and a conceptual framework for functional engineering of the complex.
AbstractDuring excitatory synaptic transmission, various structurally unrelated transmembrane auxiliary subunits control the function of AMPA receptors (AMPARs), but the underlying mechanisms remain unclear. We identified lipid‐exposed residues in the transmembrane domain (TMD) of the GluA2 subunit of AMPARs that are critical for the function of AMPAR auxiliary subunits, stargazin (Stg) and cornichon 3 (CNIH3). These residues are essential for stabilizing the AMPAR–CNIH3 complex in detergents and overlap with the contacts made between GluA2 TMD and Stg in the cryoEM structures. Mutating these residues had opposite effects on gating modulation and complex stability when Stg‐ and CNIH3‐bound AMPARs were compared. Specifically, in detergent the GluA2‐A793F formed an unstable complex with CNIIH3 but in the membrane the GluA2‐A793F–CNIH3 complex expressed a gain of function. In contrast, the GluA2‐A793F–Stg complex was stable, but had diminished gating modulation. GluA2‐C528L destabilized the AMPAR–CNIH3 complex but stabilized the AMPAR–Stg complex, with overall loss of function in gating modulation. Furthermore, loss‐of‐function mutations in this TMD region cancelled the effects of a gain‐of‐function Stg carrying mutation in its extracellular loop, demonstrating that both the extracellular and the TMD elements contribute independently to gating modulation. The elements of AMPAR functionally recruited by auxiliary subunits are, therefore, located not only in the extracellular domains but also in the lipid accessible surface of the AMPAR. The TMD surface we defined is a potential target for auxiliary subunit‐specific compounds, because engineering of this hotspot induces opposing functional outcomes by Stg and CNIH3. The collection of mutant‐phenotype mapping provides a framework for engineering AMPAR gating using auxiliary subunits.
High-Pressure Gas Turbine Vane Turbulent Flows and Heat Transfer Predicted by RANS/LES/DES
Authors: Dong Ping , Amano R. S. 
Published: August 2017

The lifetime of the modern gas turbines greatly depends on the durability of hot section components operating at high temperatures. Film cooling is key to air cooling technologies in modern gas turbine and widely used in high-temperature and high-pressure blades as an active cooling scheme.
The requirements of accurate prediction of aerodynamic flow and heat transfer in gas turbine blades lay the essential foundation of cooling effectiveness improvement and working life estimation. In recent days, Large Eddy Simulations (LES) is considered as a useful tool to predict turbulent flows and heat transfer around gas turbine blades, but, comparing to the Reynolds-Averaged Navier–Stokes (RANS) methods, the LES method usually needs more computing resource and depends on computational power and mesh quality.
In this paper, LES/DES (Detached Eddy Simulation) predictions were compared to RANS prediction with interest in the accuracy and improvement of turbulent flow and heat transfer phenomena around NASA’s C3X high-pressure gas turbine vane with leading edge cooling film. RANS/LES/DES were detailed and further investigated to assess their ability to predict flow and heat transfer in boundary layer around C3X vane.
The current predictions showed that the mix between film cooling injections and free stream resulted in complex flow and heat transfer in the boundary layer on the external vane surface. The predictions of the aerodynamic load along the C3X vane with RANS/LES/DES were almost identical and agreed well with the experimental results. However, the heat transfer predictions with RANS/LES/DES were different. The transition prediction showed the best agreement with the experiment data in the most region. The LES prediction only partially agreed with the experimental data before separation point on the suction side and mild pressure gradient region on the pressure side. The DES and RANS predictions agreed with the experiment data after separation point on the suction side and most region on the pressure side.
Short Helical Combustor: Flow Control in a Combustion System With Angular Air Supply
Authors: Ariatabar Behdad , Koch Rainer , Bauer Hans-Jörg 
Published: August 2017

The concept of the novel Short Helical Combustor (SHC) was investigated in our previous work [1, 2].
Based on the insight gained from these previous investigations, we propose a generic design improvement to address the tremendous loss of initial angular momentum as well as inhomogeneous flow and temperature field at the outlet of the SHC.
In the present paper, the main features of this design are introduced. It is shown that a three-dimensional shaping of the sidewalls, the dome, and the liners can effectively counteract the suboptimal interaction of the swirl flames with these surrounding walls.
As a result, the flow at the outlet of the combustor features a high angular momentum and exhibits a uniform flow angle and temperature field.
The insight gained from these generic investigations, and the resulting design optimization provides a useful framework for further industrial optimization of the SHC.
Response of a Compact Recuperator to Thermal Transients in a Supercritical Carbon Dioxide Brayton Cycle
Authors: Clementoni Eric M. , Cox Timothy L. , King Martha A. 
Published: August 2017

Supercritical carbon dioxide (sCO2) power cycle designs are typically highly recuperated, transferring heat from the high temperature turbine exhaust stream to the compressor discharge stream thereby increasing overall cycle efficiency. Compact heat exchangers are preferred for this application due to their high surface area-to-volume ratio enabling much smaller heat exchangers as compared to conventional designs. However, compact heat exchangers have a higher metal density than conventional heat exchangers which could result in thermal lag during rapid temperature transients.
The Naval Nuclear Laboratory has been operating the Integrated System Test (IST) with the objective of demonstrating the ability to operate and control an sCO2 Brayton power cycle over a wide range of conditions. Rapid turbomachinery startups and power transients result in thermal transients on the recuperator. This paper presents thermal transients observed in the IST recuperator during loop startup and power transients and illustrates the time to achieve thermal equilibrium following the transients.
Assessment of Real Turbine Blade Roughness Parameters for the Design of a Film Cooling Test Rig
Authors: Glasenapp Tobias , Puetz Franz , Schulz Achmed , Bauer Hans-Jörg 
Published: August 2017

The average roughness height Ra was used for characterizing surface roughness in many past investigations. In order to fully describe heat transfer and fluid flow over a rough surface, statistical parameters, however, are not sufficient. There is a lack of data in the literature in terms of three-dimensional real turbine roughness and the distribution of roughness parameters on the turbine airfoils. This study closes this gap and provides detailed surface roughness data of high-pressure turbine vanes that have been in service in land-based gas turbines and aero engines. Furthermore, samples of thermal barrier coatings from two different application techniques are investigated. High-resolution 3D profilometer and optical measurements are performed at various locations on both the pressure and suction side. Key parameters such as roughness shape and density are quantified. Equivalent sand grain roughness height (ks) values are obtained and related to the fluid flow by calculating the corresponding dimensionless roughness heights.
The results show that roughness parameters are spread over a wide range. No correlation with position on the vane surface is found. The distribution of the roughness heights deviates from a Gaussian distribution. Roughness on the suction side is generally smaller than on the pressure side. Dimensionless roughness heights are found to be mainly in the transitional regime and not in the fully rough regime as expected. The data presented in this paper is of great importance to the design of test surfaces for laboratory experiments and as input for numerical models.