bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Periodic Ribs on the Local Aerodynamic and Heat Transfer Performance of a Straight Cooling Channel
Authors: Rau G. , Çakan M. , Moeller D. , Arts T.
Published: February 2015

The local aerodynamic and heat transfer performance were measured in a rib-roughened square duct as a function of the rib pitch to beight ratio. The blockage ratio of these square obstacles was 10% or 20% depending on whether they were placed on one single (1s) or on two opposite walls (2s). The Reynolds number, based on the channel mean velocity and hydraulic diameter, was fixed at 30000.

The aerodynamic description of the flow field was based on local pressure distributions along the ribbed and adjacent smooth walls as well as on 2D LDV explorations in the channel symmetry plane and in two planes parallel to the ribbed wall(s). Local heat transfer distributions were obtained on the floor, between the ribs, and on the adjacent smooth side wall. Averaged parameters, such as friction factor and averaged heat transfer enhancement factor, were calculated from the local results and compared to correlations given in literature.

This contribution showed that simple correlations derived from the law of the wall similarity and from the Reynolds analogy could not be applied for the present rib height-to-channel hydraulic diameter ratio (e/Dh=0.1). The strong secondary flows resulted in a three-dimensional flow field with high gradients in the local heat transfer distributions on the smooth side walls.
Simulation and Validation of Mach Number Effects on Secondary Flow in a Transonic Turbine Using a Multigrid, k-ε Solver
Authors: Koiro M. , Lakshminarayana B.
Published: February 2015

An existing three dimensional Navier-Stokes flow solver with an explicit Runge-Kutta algorithm and a low Reynolds number k-ε turbulence model has been modified in order to simulate turbomachinery flows in a more efficient manner. The solver has been made to converge more rapidly through use of the mutligrid technique. Stability problems associated with use of multigrid in conjunction with two equation turbulence models are addressed and techniques to alleviate instability are investigated. Validation for the new code was performed with a transonic turbine cascade tested by Perdichizzi. In the fully three dimensional turbulent cascade, real convergence (i.e. CPU time) was improved nearly two times the original code. Robustness was enhanced with the full multigrid initialization procedure. The same test case was then used to perform a series of simulations that investigated the effect of different exit Mach numbers on secondary flow features. This permitted an in depth study into the mechanisms of secondary flow formation and secondary losses at high Mach numbers. In this cascade, it was found that secondary losses and secondary flow deviation, which are fairly constant in incompressible flows with similar geometries, underwent a large reduction in the compressible flow range. The structure of the trailing edge shock system and the reduced endwall boundary layer at supersonic exit conditions were shown to be very significant in reducing the amount of secondary flow and losses.
A Computational Assessment of Surge-Induced Inlet Overpressure Distribution for Preliminary Design
Authors: Miller Daniel N. , Hamstra Jeffrey W.
Published: February 2015

Emphasis on tactical aircraft cost reduction has motivated efforts to reduce air induction system cost, which is mainly driven by structural weight. Historically, inlet structural weight has been set by the peak loads associated with engine surge-induced hammershocks. Therefore, an accurate assessment of peak inlet pressure distribution occurring during an engine surge is critical to successful design of next-generation inlet structure for minimum weight and adequate safety margin. Current methods to quantify these inlet loads during preliminary design stages of an advanced inlet are inadequate. A cost-effective, computational methodology was developed to address this issue. This methodology predicted F-16 Normal Shock Inlet overpressure design loads to within 3% of existing methods. The sensitivity of inlet overpressure distribution to the engine face waveform and inlet geometry was investigated. This technique was also applied to an advanced inlet to study the effects of serpentine ducts and 3-D inlet apertures on hammershock loads.
Two-Dimensional Computational Model for Wave Rotor Flow Dynamics
Authors: Welch Gerard E.
Published: February 2015

A two-dimensional (θ,z) Navier-Stokes solver for multi-port wave rotor flow simulation is described. The finite-volume form of the unsteady thin-layer Navier-Stokes equations arc integrated in time on multi-block grids that represent the stationary inlet and outlet ports and the moving rotor passages of the wave rotor. Computed results are compared with three-port wave rotor experimental data. The model is applied to predict the performance of a planned four-port wave rotor experiment. Two-dimensional flow features that reduce machine performance and influence rotor blade and duct wall thermal loads are identified. The performance impact of rounding the inlet port wall, to inhibit separation during passage gradual opening, is assessed.
Multivariate ToF-SIMS image analysis of polymer microarrays and protein adsorption
Authors: Hook Andrew L. , Williams Philip M. , Alexander Morgan R. , Scurr David J.
Published: February 2015

The complexity of hyperspectral time of flight secondary ion mass spectrometry (ToF-SIMS) datasets makes their subsequent analysis and interpretation challenging, and is often an impasse to the identification of trends and differences within large sample-sets. The application of multivariate data analysis has become a routine method to successfully deconvolute and analyze objectively these datasets. The advent of high-resolution large area ToF-SIMS imaging capability has enlarged further the data handling challenges. In this work, a modified multivariate curve resolution image analysis of a polymer microarray containing 70 different poly(meth)acrylate type spots (over a 9.2 × 9.2 mm area) is presented. This analysis distinguished key differences within the polymer library such as the differentiation between acrylate and methacrylate polymers and variance specific to side groups. Partial least squares (PLS) regression analysis was performed to identify correlations between the ToF-SIMS surface chemistry and the protein adsorption. PLS analysis identified a number of chemical moieties correlating with high or low protein adsorption, including ions derived from the polymer backbone and polyethylene glycol side-groups. The retrospective validation of the findings from the PLS analysis was also performed using the secondary ion images for those ions found to significantly contribute to high or low protein adsorption.
Mixing time prediction using spherical microphone arrays
Authors: Götz Philipp , Kowalczyk Konrad , Silzle Andreas , Habets Emanuël A. P.
Published: February 2015

Human perception of room acoustics depends among others on the time of transition from early reflections to late reverberation in room impulse responses, which is known as mixing time. In this letter, a multi-channel mixing time prediction method is proposed, which in contrast to state-of-the-art channel-based predictors accounts for spatiotemporal properties of the sound field. The proposed diffuseness-based method is compared with existing model- and channel-based prediction methods through measurements and acoustic simulations, and is shown to correlate well with the perceptual mixing time. Furthermore, insights into relations between prediction methods and mixing time definitions based on reflection density are presented.
Two- and Three-Dimensional Relationships Between Knee and Hip Kinematic Motion Analysis: Single-Leg Drop-Jump Landings
Authors: Sorenson Bryan , Kernozek Thomas W. , Willson John David , Ragan Robert , Hove Jordan
Published: February 2015

Context:

Hip- and knee-joint kinematics during drop landings are relevant to lower-extremity injury mechanisms. In clinical research the “gold standard” for joint kinematic assessment is 3-dimensional (3D) motion analysis. However, 2-dimensional (2D) kinematic analysis is an objective and feasible alternative.

Objective:

To quantify the relationship between 2D and 3D hip and knee kinematics in single-leg drop landings and test for a set of 3D hip and knee kinematics that best predicts 2D kinematic measures during single-leg drop landings Design: Descriptive, comparative laboratory study.

Participants:

31 healthy college-age women (65.5 kg [SD 12.3], 168.1 cm [SD 6.7]).

Methods:

Participants performed five 40-cm single-leg landings during motion capture at 240 Hz. Multiple regressions were used to predict relationships for knee and hip between 2D frontal-plane projection angles (FPPA) and 3D measurements.

Results:

2D knee FPPA had a strong relationship with 3D frontal-plane knee kinematics at initial contact (IC) (r2 = .72), which was only minimally improved with the addition of knee sagittal-plane and hip transverse-plane positions at IC (r2 = .77). In contrast, 2D knee FPPA had a low relationship with 3D knee-abduction excursion (r2 = .06). The addition of knee sagittal-plane and hip transverse-plane motions did not improve this relationship (r2 = .14). 2D hip FPPA had a moderate relationship with 3D frontal-plane hip position at IC (r2 = .52), which was strengthened with the addition of hip sagittal-plane position (r2 = .60). In addition, hip 2D FPPA into adduction excursion had a strong association with 3D hip-adduction excursion (r2 = .70).

Conclusion:

2D kinematics can predict 3D frontal-plane hip and knee position at IC during a single-leg landing but predict 3D frontal-plane knee excursion with far less accuracy.
Disruption of the head direction cell network impairs the parahippocampal grid cell signal
Authors: Winter Shawn S. , Clark Benjamin J. , Taube Jeffrey S.
Published: February 2015

Are we heading in the right direction?

Some neurons, called grid cells, discharge at multiple locations to form a regular pattern that represents the animal's environment. These cells use information about the animal's running speed and direction of movement to constantly update its location. The so-called head direction cells provide the direction-of-movement signal. Winter
et al.
recorded neuronal activity in awake behaving rats. When they disabled the input from the head direction cells, the grid cells lost their normal function. These findings provide experimental confirmation of theoretical predictions that grid cells will no longer exhibit their characteristic firing pattern when the head direction signal is disturbed.

Science
, this issue p.
870
Genome Sequences of Two Pandoraea pnomenusa Isolates Recovered 11 Months Apart from a Cystic Fibrosis Patient
Authors: Ee Robson , Ambrose Mark , Lazenby James , Williams Paul , Chan Kok-Gan , Roddam Louise
Published: February 2015

Pandoraea is an emerging respiratory pathogen capable of causing chronic lung infections in people with cystic fibrosis (CF), but the clinical significance of this infection is ambiguous. We have sequenced and annotated the genomes of two multidrug-resistant
Pandoraea pnomenusa
isolates recovered 11 months apart from the same CF patient.
Draft Genome Sequences of the Enteroinvasive Escherichia coli Strains M4163 and 4608-58
Authors: Leonard Susan R. , Lacher David W. , Lampel Keith A.
Published: February 2015

We report here the draft genome sequences of enteroinvasive
Escherichia coli
(EIEC) O124:H30 strain M4163 isolated from imported French cheese and EIEC O143:H26 strain 4608-58. The assembled data determined that both strains contain multiple copies of the
ipaH
gene, as well as the pINV A form of the invasion plasmid.
Draft Genome Sequence of Acinetobacter oleivorans PF1, a Diesel-Degrading and Plant-Growth-Promoting Endophytic Strain Isolated from Poplar Trees Growing on a Diesel-Contaminated Plume
Authors: Gkorezis Panagiotis , Rineau Francois , Van Hamme Jonathan , Franzetti Andrea , Daghio Matteo , Thijs Sofie , Weyens Nele , Vangronsveld Jaco
Published: February 2015

We report the 3.7-Mb draft genome of Acinetobacter oleivorans strain PF1, a hydrocarbonoclastic Gram-negative bacterium in the class Gammaproteobacteria, isolated from poplar trees growing on a diesel-contaminated plume at the Ford Motor Company site in Genk, Belgium. Strain PF1 is a potent plant-growth promoter, useful for diesel fuel phytoremediation applications.
Draft Genome Sequence of High-Temperature-Adapted Protochlamydia sp. HS-T3, an Amoebal Endosymbiotic Bacterium Found in Acanthamoeba Isolated from a Hot Spring in Japan
Authors: Yamaguchi Hiroyuki , Matsuo Junji , Yamazaki Tomohiro , Ishida Kasumi , Yagita Kenji
Published: February 2015

Here, we report the draft genome sequence of high-temperature-adapted Protochlamydia sp. strain HS-T3, an environmental chlamydia. This bacterium is an amoebal endosymbiont, found in Acanthamoeba isolated from a hot spring in Japan. Strain HS-T3 readily grew in mammalian cells at 37°C, a characteristic not previously reported for environmental chlamydiae.
Draft Genome Sequence of Streptomyces sp. Strain CT34, Isolated from a Ghanaian Soil Sample
Authors: Zhai Yin , Cheng Bin , Hu Juan , Kyeremeh Kwaku , Wang Xiaoling , Jaspars Marcel , Deng Hai , Deng Zi-Xin , Hong Kui
Published: February 2015

Presented here is a draft genome sequence of Streptomyces sp. strain CT34, which produces a novel ribosomally synthesized and posttranslationally modified peptide (RiPP). Analysis of the deduced open reading frame set identified the putative RiPP biosynthesis gene cluster, as well as other secondary metabolite gene clusters.
Draft Genome Sequences of Five New Strains of Methylophilaceae Isolated from Lake Washington Sediment
Authors: McTaggart Tami L. , Benuska Gabrielle , Shapiro Nicole , Woyke Tanja , Chistoserdova Ludmila
Published: February 2015

We sequenced the genomes of five new Methylophilaceae strains isolated from Lake Washington sediment. We used the new sequences to sort these new strains into specific Methylophilaceae ecotypes, including one novel ecotype. The new genomes expand the known diversity of Methylophilaceae and provide new models for studying the ecology of methylotrophy.
Complete Genome Sequences of a Mycobacterium smegmatis Laboratory Strain (MC
2
155) and Isoniazid-Resistant (4XR1/R2) Mutant Strains
Authors: Mohan Abhilash , Padiadpu Jyothi , Baloni Priyanka , Chandra Nagasuma
Published: February 2015

We report the whole genome sequences of a
Mycobacterium smegmatis
laboratory wild-type strain (MC
2
155) and mutants (4XR1, 4XR2) resistant to isoniazid. Compared to
Mycobacterium smegmatis
MC
2
155 (NC_008596), a widely used strain in laboratory experiments, the MC
2
155, 4XR1, and 4XR2 strains are 60, 128 and 93 bp longer, respectively.
Avian Influenza Virus with Hemagglutinin-Neuraminidase Combination H3N6, Isolated from a Domestic Pigeon in Guangxi, Southern China
Authors: Liu Tingting , Xie Zhixun , Wang Guoli , Song Degui , Huang Li , Xie Zhiqing , Deng Xianweng , Luo Sisi , Huang Jiaoling , Zeng Tingting
Published: February 2015

The H3 subtype of avian influenza virus can provide genes for human influenza virus through gene reassortment, which has raised great concerns about its potential threat to human health. An H3N6 subtype of avian influenza virus was isolated from Guangxi Province, China, in 2009. All eight gene segments of the strain were sequenced. The sequence analysis indicated that this H3N6 virus was a nature reassortant virus. The genome sequences now can be used to understand the epidemiological and molecular characteristics of the H3N6 influenza virus in southern China.
Giant epidermal cyst with intramuscular extension: a rare occurrence
Authors: Low Soo Fin , Sridharan Radhika , Ngiu Chai Soon
Published: February 2015

An epidermal cyst is the most common type of cyst to occur in subcutaneous tissue. When its size is greater than 5 cm, it is recognised as a giant epidermal cyst. A subcutaneous giant epidermal cyst with intramuscular extension is extremely rare. The authors report a case of a 74-year-old man who presented with a painless, slow-growing left gluteal mass of 6-month duration. Examination revealed a large left gluteal mass that was fixed to the underlying structures. A small epidermal cyst with visible punctum was noted at the medial aspect of the mass. MRI demonstrated a large, lobulated left gluteal lesion measuring 20 cm×16 cm×10 cm. The lesion was partly within the gluteal maximus muscle and partly within the subcutaneous tissue. MRI and ultrasound features of the lesion were consistent with a giant epidermal cyst with intramuscular extension. The lesion was excised and histology confirmed the diagnosis.
Ischaemia-modified albumin during experimental apnoea
Authors: Joulia Fabrice , Coulange Mathieu , Lemaitre Frederic , Desplantes Agnelys , Costalat Guillaume , Bruzzese Laurie , Franceschi Frederic , Barberon Bruno , Kipson Nathalie , Jammes Yves , Guieu Régis
Published: February 2015

Ischaemia-modified albumin (IMA) is a marker of the release of reactive oxygen species (ROS) during hypoxaemia. In elite divers, breath-hold induces ROS production. Our aim was to evaluate the kinetics of IMA serum levels during apnea. Twenty breath-hold divers were instructed to perform a submaximal static breath-hold. Twenty non-diver subjects served as controls. Blood samples were collected at rest, every minute, at the end of breath-hold, and 10 min after recovery. The IMA level increased after 1 min of breath-hold (p < 0.003) and remained high until recovery. Divers were separated into 2 groups: subjects who held their breath for less than 4 min (G–4) and those who held it for more than 4 min (G+4). After 3 min of apnoea, the increase of IMA was higher in the G–4 group than in the G+4 group (p < 0.008). However, at the end of apnoea, the IMA level did not differ between groups. If IMA level was globally correlated with the apnoea duration, it is interesting to note that the higher IMA level was not found in the best divers. Similarly, if arterial blood oxygen saturation (SpO2) was globally inversely correlated with apnoea duration, the lowest SpO2 at the end of breath-hold was not found in the divers that performed the best apnoea. We concluded that these divers save their oxygen. The IMA level provides a useful measure of resistance to hypoxaemia.
On the Trace of Scatter Matrix Difference: A Convex Approximate Discriminant Analysis Formulation and Its Mechanism Research in Imperial Examination System
Authors: Li Kun , Qian Yongsheng , Xu Dejie , Zeng Junwei , Wang Min , Zhang Jijing
Published: February 2015

In this paper, we present a convex discriminant analysis formulation, which is extended to solve multi-label classification problems. The original Linear Discriminant Analysis energy optimization function is turned into another form as a convex formulation (namely, convex Approximate LDA, denoted as “convexALDA” for short) using the generalized eigen-decomposition. We give applications by incorporating convexALDA as a regularizer into discriminant regression analysis. Extensive experimental results on multi-label classification tasks and an extensive application scenario on communication characteristics of imperial examination system are provided. In this way we have a brand-new comprehension for it, and a new idea and method was also put forward for studying the system.
Automatic Pharynx Segmentation from MRI Data for Analysis of Sleep Related Disorders
Authors: Ivanovska Tatyana , Laqua René , Shahid Muhammad Laiq , Linsen Lars , Hegenscheid Katrin , Völzke Henry
Published: February 2015

In our project, we analyse throat structures using magnetic resonance imaging (MRI) to associate anatomic risk factors with sleep related disorders. Pharynx segmentation is the first step in the three-dimensional analysis of throat tissues.

We present a pipeline for automatic pharynx segmentation. The automatic part of the approach consists of three steps: smoothing, thresholding, 2D and 3D connected component analysis. Whereas two first steps are rather common, the third step provides a set of general rules for the automatic extraction of the pharyngeal component. Our method requires less than one minute to extract the pharyngeal structures. The approach is evaluated quantitatively on 30 data sets using region-based and edge-based measures.
Curved spacetimes and curved graphene: A status report of the Weyl symmetry approach
Authors: Iorio Alfredo
Published: February 2015

This is a status report about the ongoing work on the realization of quantum field theory on curved graphene spacetimes that uses Weyl symmetry. The programme is actively pursued from many different perspectives. Here we point to what has been done, and to what needs to be done.
Applicability of the systematic helium-3 potential for triton-nucleus reactions
Authors: Xu Yong-Li , Guo Hai-Rui , Han Yin-Lu , Shen Qing-Biao
Published: February 2015

The elastic scattering angular distributions of triton are calculated by the obtained systematic helium-3 global optical model potential parameters and compared with the available experimental data. These results show that the present global optical model potential can give a reasonable description of the elastic scattering of triton. The total reaction cross-sections of triton as a function of energy per nucleon are also further investigated and the reasonable results are presented.
ALGORITHMIC COUNTERPARTY CREDIT EXPOSURE FOR MULTI-ASSET BERMUDAN OPTIONS
Authors: SHEN YANBIN , ANDERLUH J. H. M. , VAN DER WEIDE J. A. M.
Published: February 2015

For an efficient computation of the counterparty credit exposure profiles of the multi-asset options, a simulation-based method, named the Stochastic Grid Bundling Method (SGBM), is applied. The method is based on a 'regression later' technique used for the conditional expectation approximation and a bundling (or 'binning') technique used for state space partitioning. In the case of high-dimensional underlying asset processes, by using the bundling technique, the accuracy of exposure profiles is improved significantly, and the computation speed is reasonably fast. A detailed analysis for the bundling technique and regression approximation technique used in SGBM is given via various numerical examples. We provide an efficiency comparison of SGBM, the Standard Regression Method (SRM), and the Standard Regression Bundling Method (SRBM). We also show that for discontinuous payoffs, such as digital options, by using the bundling technique appropriately, SGBM can get accurate and stable results of option prices and exposure profiles. Compared with the benchmark results of one-dimensional European and Bermudan options, the SGBM has high accuracy in the computation of exposure profiles. The efficient calculation of the expected exposure (EE) by using SGBM forms the basis of the credit value adjustment (CVA) for multi-asset portfolios.
The study of composition and surface electron structure of nitrogen-doped DLC film prepared by PIII-D
Authors: Li Haiguang , Wen Feng , Pan Changjiang , Ding Hongyan , Huang Nan , Leng Yongxiang
Published: February 2015

Nitrogen-doped diamond-like carbon (N-DLC) films were synthesized by plasma immersion ion implantation and deposition (PIII-D) at room temperature (RT). During the process of deposition, N 2 flow was changed from 0 to 10 sccm. Lifshitz–van der Waals/acid–base (LW-AB) approach was employed to study the surface electronic state of the films, X-ray photoelectron spectroscopic (XPS) and valence band spectra (VBS) were used to study chemical bonds and electron structure information inside the films. Bandgap of the films were calculated by the data from ultraviolet spectrophotometer. The results showed that synthesized films were n-type semiconductors and doping of nitrogen element will affect the accepted–electron capability of the film. The change tendency of the bandgap coincides with that of the ratio of acidic to alkaline component of the polar acid-alkali surface energy. There was much sp hybrid electronic state existed in the films, which mainly sp2 C=C / C=N and sp3 C–C / C–N bonds.
A novel high color purity yellow luminescent material NaBaBO3:Sm3+
Authors: Zheng Jianghui , Feng Jia , Cheng Qijin , Guo Ziquan , Cai Lihan , Chen Chao
Published: February 2015

Yellow emitting Sm 3+-doped NaBa 1-x BO 3(0.01 ≤ x ≤ 0.13) phosphors were synthesized by conventional solid state reaction method. The phase structure and luminescence properties of the as-prepared phosphors were investigated. These phosphors can be effectively excited by 403 nm near-ultraviolet light and feature a satisfactory yellow performance. The emission peaks are observed at 560 nm, 603 nm and 650 nm, originating from the transitions of 4G5∕2→6H5∕2, 4G5∕2→6H7∕2 and 4G5∕2→6H9∕2 respectively. Investigation of Sm 3+ concentration-dependent emission spectra indicates that the NaBa 0.95 BO 3:0.05 Sm 3+ phosphor shows the strongest yellow emission intensity and exhibits the CIE value of x = 0.4760 and y = 0.5090. Through the theoretical calculation, a high color purity of 96.0% was determined for the NaBaBO 3: Sm 3+ phosphor, and the color purity of NaBaBO 3: Sm 3+ is much higher than that of the commercial yellow phosphor YAG : Ce 3+. This work is highly relevant to the development of a new type of potential down-conversion (DC) yellow phosphor for near ultraviolet white or yellow light-emitting diodes (LEDs).
Ferritin-mediated biomimetic synthesis of bimetallic Au–Ag nanoparticles on graphene nanosheets for electrochemical detection of hydrogen peroxide
Authors: Wang Li , Wang Jiku , Ni Pengjuan , Li Zhuang
Published: February 2015

We demonstrated a biomimetic green synthesis of bimetallic Au – Ag nanoparticles (NPs) on graphene nanosheets (GNs). The spherical protein, ferritin ( Fr ), was bound onto GNs and served as the template for the synthesis of GN / Au – Ag nanohybrids. The created GN / Au – Ag nanohybrids were further utilized to fabricate a non-enzymatic amperometric biosensor for the sensitive detection of hydrogen peroxide ( H 2 O 2), and this biosensor displayed high performances to determine H 2 O 2 with a detection limit of 20.0 × 10-6 M and a linear detection range from 2.0 μM to 7.0 mM.
Design of poly(ether block amide)/polyacrylonitrile composite membrane for carbon dioxide capture
Authors: Wang Lianjun , Ji Pengfei , Li Yang , Di Mingming , Lv Quan , Li Shuguang
Published: February 2015

In this study, poly(ether block amide) was used as coating material to develop a novel composite polymer membrane for CO 2 capture. Polyacrylonitrile (PAN) ultrafiltration membrane was applied as substrate. Between them, a gutter layer prepared from cross-linked polydimethylsiloxane (PDMS) blending with amino silicone was introduced to improve separation performance of the composite membrane. The separation properties of resultant triple layer composite membrane was characterized using pure CO 2 and N 2 gases. It was found that the crosslinking degree of the gutter layer had great influence on membrane performance, which could be significantly improved with the help of amino-PDMS gutter layer compared with that of the membrane having Pebax coating directly onto PAN substrate. Using 2 wt.% Pebax coating solution and properly cross-linked gutter layer, the designed Pebax/amino-PDMS/PAN composite membrane showed CO 2 permeance of 147 GPU and CO 2/ N 2 selectivity of 62.
Next generation of ALDH substrates and their potential to study maturational lineage biology in stem and progenitor cells
Authors: Dollé Laurent , Boulter Luke , Leclercq Isabelle A. , van Grunsven Leo A.
Published: February 2015

High aldehyde dehydrogenase (ALDH) activity is a feature of stem cells from normal and cancerous tissues and a reliable universal marker used to isolate them. There are numerous ALDH isoforms with preferred substrate specificity variably expressed depending on tissue, cell type, and organelle and cell status. On the other hand, a given substrate may be metabolized by several enzyme isoforms. Currently ALDH activity is evidenced by using Aldefluor, a fluorescent substrate likely to be metabolized by numerous ALDH isoforms. Therefore, isolation techniques based on ALDH activity detection select a heterogeneous population of stem or progenitor cells. Despite active research in the field, the precise role(s) of different ALDH isoforms in stem cells remains enigmatic. Understanding the metabolic role of different ALDH isoform in the control of stem cell phenotype and cell fate during development, tissue homeostasis, or repair, as well as carcinogenesis, should open perspectives to significant discoveries in tissue biology. In this perspective, novel ALDH substrates are being developed. Here we describe how new substrates could be instrumental for better isolation of cell population with stemness potential and for defining hierarchy of cell populations in tissue. Finally, we speculate on other potential applications.
Conditionally immortalized human proximal tubular epithelial cells isolated from the urine of a healthy subject express functional calcium-sensing receptor
Authors: Di Mise Annarita , Tamma Grazia , Ranieri Marianna , Svelto Maria , Heuvel Bert van den , Levtchenko Elena N. , Valenti Giovanna
Published: February 2015

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor, which plays an essential role in regulating Ca2+homeostasis. Here we show that conditionally immortalized proximal tubular epithelial cell line (ciPTEC) obtained by immortalizing and subcloning cells exfoliated in the urine of a healthy subject expresses functional endogenous CaSR. Immunolocalization studies of polarized ciPTEC revealed the apical localization of the receptor. By Western blotting of ciPTEC lysates, both monomeric and dimeric forms of CaSR at 130 and ∼250 kDa, respectively, were detected. Functional studies indicated that both external calcium and the positive CaSR allosteric modulator, NPS-R568, induced a significant increase in cytosolic calcium, proving a high sensitivity of the endogenous receptor to its agonists. Calcium depletion from the endoplasmic reticulum using cyclopiazonic acid abolished the increase in cytosolic calcium elicited by NPS-R568, confirming calcium exit from intracellular stores. Activation of CaSR by NPS-R significantly reduced the increase in cAMP elicited by forskolin (FK), a direct activator of adenylate cyclase, further confirming the functional expression of the receptor in this cell line. CaSR expressed in ciPTEC was found to interact with Gqas a downstream effector, which in turn can cause release of calcium from intracellular stores via phospholipase C activation. We conclude that human proximal tubular ciPTEC express functional CaSR and respond to its activation with a release of calcium from intracellular stores. These cell lines represent a valuable tool for research into the disorder associated with gain or loss of function of the CaSR by producing cell lines from patients.
Expiratory load compensation is associated with electroencephalographic premotor potentials in humans
Authors: Morawiec Elise , Raux Mathieu , Kindler Felix , Laviolette Louis , Similowski Thomas
Published: February 2015

In normal humans during quiet breathing, expiration is mostly driven by elastic recoil of the lungs. Expiration becomes active when ventilation must be increased to meet augmented metabolic demands, or in response to expiratory loading, be it experimental or disease-related. The response to expiratory loading is considered to be mediated by both reflex and cortical mechanisms, but the latter phenomenon have not been neurophysiologically characterized. We recorded the EEG in 20 healthy volunteers (9 men, 11 women, age: 22 to 50 yr) during unloaded breathing, voluntary expirations, and in response to 50 cmH2O·l−1·s expiratory resistive load (ERL), 20 cmH2O expiratory threshold load (high ETL), and 10 cmH2O expiratory threshold load (low ETL). EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration involving the supplementary motor area. Four subjects were excluded because of technical EEG problems. Pre-expiratory potentials were present in one subject at baseline and in all subjects during voluntary expirations. They were present in eight subjects during low ETL, in 15 subjects during high ETL, and in 13 subjets during ERL (control vs. low ETL, P = 0.008; control vs. high ETL, P < 0.001; and control vs. ERL, P < 0.001). Respiratory discomfort was more intense in the presence of pre-expiratory potentials ( P < 0.001). These results provide a neurophysiological substrate to a cortical component of the physiological response to experimental expiratory loads in humans.
MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial
Authors: Weller Michael , Tabatabai Ghazaleh , Kästner Bärbel , Felsberg Jörg , Steinbach Joachim P. , Wick Antje , Schnell Oliver , Hau Peter , Herrlinger Ulrich , Sabel Michael C. , Wirsching Hans-Georg , Ketter Ralf , Bähr Oliver , Platten Michael , Tonn Jörg C. , Schlegel Uwe , Marosi Christine , Goldbrunner Roland , Stupp Roger , Homicsko Krisztian , Pichler Josef , Nikkhah Guido , Meixensberger Jürgen , Vajkoczy Peter , Kollias Spyros , Hüsing Johannes , Reifenberger Guido , Wick Wolfgang
Published: February 2015

Purpose: Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen.

Experimental Design: Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m2 per day)/one week off] or Arm B [3 weeks on (80 mg/m2 per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR.

Results: Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8–3.2 vs. B: 2.0 months; 95% CI, 1.8–3.5] and overall survival [A: 9.8 months (95% CI, 6.7–13.0) vs. B: 10.6 months (95% CI, 8.1–11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8–7.4) versus 1.8 months (95% CI, 1.8–2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation.

Conclusions: Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation. Clin Cancer Res; 21(9); 2057–64. ©2015 AACR.
Nonclinical Safety Evaluation of VX15/2503, a Humanized IgG4 Anti-SEMA4D Antibody
Authors: Leonard John E. , Fisher Terrence L. , Winter Laurie A. , Cornelius Chad A. , Reilly Christine , Smith Ernest S. , Zauderer Maurice
Published: February 2015

The humanized IgG4 monoclonal antibody VX15/2503 bound with 1 to 5 nmol/L affinity to purified recombinant semaphorin 4D (SEMA4D; CD100) produced using murine, rat, cynomolgus macaque, and human sequences. The affinity for native SEMA4D expressed on macaque T lymphocytes was approximately 0.6 nmol/L. Tissues from rats and cynomolgus macaques demonstrated specific staining only with resident lymphocytes. Single-dose and one-month toxicology/PK studies used VX15/2503 dose levels of 0 to 100 mg/kg. No toxicity was observed with either species in these studies, thus the no observed adverse effect level (NOAEL) was 100 mg/kg. Cmax, exposure, and half-life values were similar for both rats and macaques. The NOAEL in a primate maximum feasible dose study was 200 mg/kg. Saturation of T-cell–associated SEMA4D occurred following administration of single doses of 0.1 mg/kg and above; five weekly injections of VX15/2503 at a dose level of 100 mg/kg produced saturation lasting for more than 120 and 130 days, respectively, for rats and primates. Macaques administered five weekly doses of VX15/2503 showed dose-dependent reductions of 2- to 3-fold in T-cell SEMA4D (cSEMA4D) expression levels compared with controls. Reduced cSEMA4D expression levels continued until serum antibody concentrations were 2 to 5 μg/mL, and thereafter normal cSEMA4D levels were restored. On the basis of these data, a phase I clinical study of the safety and tolerability of VX15/2503 was conducted, enrolling adult patients with advanced solid tumor diseases; a single-dose, dose escalation, phase I safety study was also initiated with subjects with multiple sclerosis. Mol Cancer Ther; 14(4); 964–72. ©2015 AACR.
Metabolomic Markers of Altered Nucleotide Metabolism in Early Stage Adenocarcinoma
Authors: Wikoff William R. , Grapov Dmitry , Fahrmann Johannes F. , DeFelice Brian , Rom William N. , Pass Harvey I. , Kim Kyoungmi , Nguyen UyenThao , Taylor Sandra L. , Gandara David R. , Kelly Karen , Fiehn Oliver , Miyamoto Suzanne
Published: February 2015

Adenocarcinoma, a type of non–small cell lung cancer, is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarcinoma remains largely unknown. Herein, we describe the application of mass spectrometry and multivariate statistical analysis in one of the largest biomarker research studies to date aimed at distinguishing metabolic differences between malignant and nonmalignant lung tissue. Gas chromatography time-of-flight mass spectrometry was used to measure 462 metabolites in 39 malignant and nonmalignant lung tissue pairs from current or former smokers with early stage (stage IA–IB) adenocarcinoma. Statistical mixed effects models, orthogonal partial least squares discriminant analysis and network integration, were used to identify key cancer-associated metabolic perturbations in adenocarcinoma compared with nonmalignant tissue. Cancer-associated biochemical alterations were characterized by (i) decreased glucose levels, consistent with the Warburg effect, (ii) changes in cellular redox status highlighted by elevations in cysteine and antioxidants, alpha- and gamma-tocopherol, (iii) elevations in nucleotide metabolites 5,6-dihydrouracil and xanthine suggestive of increased dihydropyrimidine dehydrogenase and xanthine oxidoreductase activity, (iv) increased 5′-deoxy-5′-methylthioadenosine levels indicative of reduced purine salvage and increased de novo purine synthesis, and (v) coordinated elevations in glutamate and UDP-N-acetylglucosamine suggesting increased protein glycosylation. The present study revealed distinct metabolic perturbations associated with early stage lung adenocarcinoma, which may provide candidate molecular targets for personalizing therapeutic interventions and treatment efficacy monitoring. Cancer Prev Res; 8(5); 410–8. ©2015 AACR.
Metabolic Syndrome Individuals With and Without Type 2 Diabetes Mellitus Present Generalized Vascular Dysfunction
Authors: Walther Guillaume , Obert Philippe , Dutheil Frédéric , Chapier Robert , Lesourd Bruno , Naughton Geraldine , Courteix Daniel , Vinet Agnès
Published: February 2015

Objectives—

The first objective of this study was to demonstrate differences within endothelial-dependent and endothelial-independent vasoreactivity in macro- and microcirculation beds among patients with metabolic syndrome (MetS) with and without type 2 diabetes mellitus (T2D) compared with healthy counterparts. The second objective was to determine relationships among the function of macro- and microvascular systems and abdominal adiposity, as well as inflammatory markers in the 3 groups.

Approach and Results—

Cross-sectional analyses of 53 patients with MetS without T2D and 25 with T2D, as well as aged 40 years and sex-matched healthy controls included microvascular (cutaneous blood flow measured with laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside), and macrovascular reactivity (flow-mediated dilation and nitrate-mediated dilation) along with anthropometric measures, plasma glucose, and insulin and inflammatory markers. Compared with controls, MetS participants showed depressed endothelial function of both micro- and macrocirculation beds. T2D in patients with MetS revealed an exacerbated vascular smooth muscle dysfunction in micro- and macrocirculation compared with MetS without T2D. Indices of micro- and macrocirculation were predominantly inversely related to abdominal fat and inflammatory markers.

Conclusions—

MetS was associated with endothelial-dependent and endothelial-independent dysfunction, affecting both the macro- and the microvascular systems. Participants with diabetes mellitus demonstrated the most severe smooth muscle dysfunction. The presence of central abdominal fat and systemic inflammation seems implicated in the pathogenesis of vascular dysfunctions in MetS.
Nanoparticle-Mediated Expression of a Wnt Pathway Inhibitor Ameliorates Ocular Neovascularization
Authors: Wang Zhongxiao , Cheng Rui , Lee Kyungwon , Tyagi Puneet , Ding Lexi , Kompella Uday B. , Chen Jing , Xu Xun , Ma Jian-xing
Published: February 2015

Objective—

The deficiency of very low-density lipoprotein receptor resulted in Wnt signaling activation and neovascularization in the retina. The present study sought to determine whether the very low-density lipoprotein receptor extracellular domain (VLN) is responsible for the inhibition of Wnt signaling in ocular tissues.

Approach and Results—

A plasmid expressing the soluble VLN was encapsulated with poly(lactide-co-glycolide acid) to form VLN nanoparticles (VLN-NP). Nanoparticles containing a plasmid expressing the low-density lipoprotein receptor extracellular domain nanoparticle were used as negative control. MTT, modified Boyden chamber, and Matrigel (™) assays were used to evaluate the inhibitory effect of VLN-NP on Wnt3a-stimulated endothelial cell proliferation, migration, and tube formation.
Vldlr
−/−
mice, oxygen-induced retinopathy, and alkali burn–induced corneal neovascularization models were used to evaluate the effect of VLN-NP on ocular neovascularization. Wnt reporter mice (BAT-gal), Western blotting, and luciferase assay were used to evaluate Wnt pathway activity. Our results showed that VLN-NP specifically inhibited Wnt3a-induced endothelial cell proliferation, migration, and tube formation. Intravitreal injection of VLN-NP inhibited abnormal neovascularization in
Vldlr
−/−
, oxygen-induced retinopathy, and alkali burn–induced corneal neovascularization models, compared with low-density lipoprotein receptor extracellular domain nanoparticle. VLN-NP significantly inhibited the phosphorylation of low-density lipoprotein receptor-related protein 6, the accumulation of β-catenin, and the expression of vascular endothelial growth factor in vivo and in vitro.

Conclusions—

Taken together, these results suggest that the soluble VLN is a negative regulator of the Wnt pathway and has antiangiogenic activities. Nanoparticle-mediated expression of VLN may thus represent a novel therapeutic approach to treat pathological ocular angiogenesis and potentially other vascular diseases affected by Wnt signaling.
Neuron-Derived Neurotrophic Factor Ameliorates Adverse Cardiac Remodeling After Experimental Myocardial Infarction
Authors: Joki Yusuke , Ohashi Koji , Yuasa Daisuke , Shibata Rei , Kataoka Yoshiyuki , Kambara Takahiro , Uemura Yusuke , Matsuo Kazuhiro , Hayakawa Satoko , Hiramatsu-Ito Mizuho , Kanemura Noriyoshi , Ito Masanori , Ogawa Hayato , Daida Hiroyuki , Murohara Toyoaki , Ouchi Noriyuki
Published: February 2015

Background—

Myocardial infarction (MI) is one of the major causes of death worldwide. Chronic heart failure is a serious complication of MI that leads to poor prognosis. We recently found that neuron-derived neurotrophic factor (NDNF) is a proangiogenic secretory protein that is upregulated in ischemic skeletal muscle. Here, we examined whether NDNF modulates cardiac remodeling in response to chronic ischemia.

Methods and Results—

C57BL/6J wild-type mice were subjected to the permanent ligation of the left anterior descending coronary artery to create MI. Adenoviral vectors expressing NDNF or β-galactosidase (control) were intramuscularly injected into mice 3 days before permanent left anterior descending coronary artery ligation. Intramuscular administration of adenoviral vectors expressing NDNF to mice resulted in increased levels of circulating NDNF. Adenoviral vectors expressing NDNF administration improved left ventricular systolic dysfunction and dilatation after MI surgery. Moreover, adenoviral vectors expressing NDNF enhanced capillary formation and reduced cardiomyocyte apoptosis and hypertrophy in the post-MI hearts. Treatment of cultured cardiomyocytes with recombinant NDNF protein led to reduced apoptosis under conditions of hypoxia. NDNF also promoted the phosphorylation of Akt and focal adhesion kinase in cardiomyocytes. Blockade of focal adhesion kinase activation blocked the stimulatory effects of NDNF on cardiomyocyte survival and Akt phosphorylation. Similarly, treatment of cultured endothelial cells with NDNF protein led to enhancement of network formation and Akt phosphorylation, which was diminished by focal adhesion kinase inhibition.

Conclusions—

These data suggest that NDNF ameliorates adverse myocardial remodeling after MI by its abilities to enhance myocyte survival and angiogenesis in the heart through focal adhesion kinase/Akt-dependent mechanisms.
Comparative Effectiveness and Safety of a Catheterization Laboratory–Only Eptifibatide Dosing Strategy in Patients Undergoing Percutaneous Coronary Intervention
Authors: Gurm Hitinder S. , Hosman Carrie , Bates Eric R. , Share David , Hansen Ben B.
Published: February 2015

Background—

Eptifibatide, a small-molecule glycoprotein IIb/IIIa inhibitor, is conventionally administered as a bolus plus infusion. A growing number of clinicians are using a strategy of catheterization laboratory–only eptifibatide (an off-label use) as procedural pharmacotherapy for patients undergoing percutaneous coronary intervention although the comparative effectiveness of this approach is unknown.

Methods and Results—

We compared the in-hospital outcome of patients undergoing percutaneous coronary intervention across 47 hospitals and treated with eptifibatide bolus plus infusion with those treated with a catheterization laboratory–only regimen. We used optimal matching to link the use of catheterization laboratory–only eptifibatide with clinical outcomes, including mortality, myocardial infarction, bleeding, and need for transfusion. Of the 84 678 percutaneous coronary interventions performed during 2010 to 2011, and meeting our inclusion criteria, eptifibatide was administered to 21 296 patients. Of these, a catheterization laboratory–only regimen was used in 4511 patients, whereas 16 785 patients were treated with bolus plus infusion. In the optimally matched analysis, compared with bolus plus infusion, a catheterization laboratory–only regimen was associated with a reduction in bleeding (optimally matched adjusted odds ratio, 0.74; 95% confidence interval, 0.58–0.93;
P
=0.014) and need for transfusion (optimally matched adjusted odds ratio, 0.70; 95% confidence interval, 0.52–0.92;
P
=0.012), with no difference in mortality or myocardial infarction.

Conclusions—

A catheterization laboratory–only eptifibatide regimen is commonly used in clinical practice and is associated with a significant reduction in bleeding complications in patients undergoing contemporary percutaneous coronary intervention.