bluuebunny/crossref_metadata_2025 huggingface dataset:
Level of and Motivation for Extracurricular Activity Are Associated with Academic Performance in the Veterinary Curriculum
Authors: Jones Meredyth L. , Rush Bonnie R. , Elmore Ronnie G. , White Brad J.
Published: July 2014

The objectives of this project were to determine the number of school-sanctioned extracurricular opportunities available to veterinary students and characterize the policies of school administrations toward extracurricular involvement and academic standing. Further, we sought to describe the level of extracurricular involvement of veterinary students, determine the association between extracurricular activity involvement and academic performance, and determine the motivation for extracurricular involvement of veterinary students. Survey data were obtained from 18 associate deans of colleges of veterinary medicine regarding the number of extracurricular student organizations within their school and administrative recommendations regarding student involvement. Another survey was administered and responded to by 665 veterinary students enrolled in curricular years 1–3 at Kansas State University and Texas A&M University regarding their extracurricular involvement. Associate deans of 11 schools responded that they make formal or informal recommendations to students about extracurricular activities, workload, and academic priority (61.1%). In a multivariate model, students who participated two times per week or more had a significantly higher overall grade point average (GPA) than students participating once per week (p<.0500). Students for whom the primary reason for participation was networking or social enhancement had a significantly lower overall GPA than students for whom the primary reason was gaining new knowledge and skills (p<.0500). These results indicate that student extracurricular involvement is a consideration for administrators when counseling students in academic difficulty. Moderate levels of extracurricular involvement can contribute to the academic success of students, but students should temper their level of involvement based upon their own motivations.
Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 15: Electrophysiological monitoring and lumbar fusion
Authors: Sharan Alok , Groff Michael W. , Dailey Andrew T. , Ghogawala Zoher , Resnick Daniel K. , Watters William C. , Mummaneni Praveen V. , Choudhri Tanvir F. , Eck Jason C. , Wang Jeffrey C. , Dhall Sanjay S. , Kaiser Michael G.
Published: July 2014

Intraoperative monitoring (IOM) is commonly used during lumbar fusion surgery for the prevention of nerve root injury. Justification for its use stems from the belief that IOM can prevent nerve root injury during the placement of pedicle screws. A thorough literature review was conducted to determine if the use of IOM could prevent nerve root injury during the placement of instrumentation in lumbar or lumbosacral fusion. There is no evidence to date that IOM can prevent injury to the nerve roots. There is limited evidence that a threshold below 5 mA from direct stimulation of the screw can indicate a medial pedicle breach by the screw. Unfortunately, once a nerve root injury has taken place, changing the direction of the screw does not alter the outcome. The recommendations formulated in the original guideline effort are neither supported nor refuted with the evidence obtained with the current studies.
Response Characterization of a Fiber Optic Sensor Array with Dye-Coated Planar Waveguide for Detection of Volatile Organic Compounds
Authors: Lee Jae-Sung , Yoon Na-Rae , Kang Byoung-Ho , Lee Sang-Won , Gopalan Sai-Anand , Jeong Hyun-Min , Lee Seung-Ha , Kwon Dae-Hyuk , Kang Shin-Won
Published: July 2014

We have developed a multi-array side-polished optical-fiber gas sensor for the detection of volatile organic compound (VOC) gases. The side-polished optical-fiber coupled with a polymer planar waveguide (PWG) provides high sensitivity to alterations in refractive index. The PWG was fabricated by coating a solvatochromic dye with poly(vinylpyrrolidone). To confirm the effectiveness of the sensor, five different sensing membranes were fabricated by coating the side-polished optical-fiber using the solvatochromic dyes Reinhardt’s dye, Nile red, 4-aminophthalimide, 4-amino-N-methylphthalimide, and 4-(dimethylamino)cinnamaldehyde, which have different polarities that cause changes in the effective refractive index of the sensing membrane owing to evanescent field coupling. The fabricated gas detection system was tested with five types of VOC gases, namely acetic acid, benzene, dimethylamine, ethanol, and toluene at concentrations of 1, 2,…,10 ppb. Second-regression and principal component analyses showed that the response properties of the proposed VOC gas sensor were linearly shifted bathochromically, and each gas showed different response characteristics.
Bridging Research and Game Development
Authors: Chamberlin Barbara , Trespalacios Jesús , Gallagher Rachel
Published: July 2014

Over the past 20 years, instructional designers in the Learning Games Lab at New Mexico State University have developed a design model for game development that brings researchers, educators, and game developers together throughout the design process. Using this approach, game developers and content experts (a) work collaboratively to ensure educational goals and outcomes are appropriate for the learner and the learning environment, (b) immerse themselves in both content and game design, and (c) test extensively throughout development with members of the target audience. In this chapter, the authors describe the model as it was used in development of several math games during a four-year development cycle for the Math Snacks project. They discuss the implications of this approach for the creation of other educational games or suites of games and share recommendations for expansion of the model to other developers.
A recursive construction of the regular exceptional graphs with least eigenvalue –2
Authors: Barbedo Inês , Cardoso Domingos M. , Cvetković Dragoš , Rama Paula , Simić Slobodan K.
Published: July 2014

In spectral graph theory a graph with least eigenvalue

-2

is exceptional if it is connected, has least eigenvalue greater than or equal to

-2

, and it is not a generalized line graph. A

(\kappa,\tau)

-regular set

S

of a graph is a vertex subset, inducing a

\kappa

-regular subgraph such that every vertex not in

S

has

\tau

neighbors in

S

. We present a recursive construction of all regular exceptional graphs as successive extensions by regular sets.
An untwisted cube of resolutions for knot Floer homology
Authors: Manolescu Ciprian
Published: July 2014

Ozsváth and Szabó gave a combinatorial description of knot Floer homology based on a cube of resolutions, which uses maps with twisted coefficients. We study the

t=1

specialization of their construction. The associated spectral sequence converges to knot Floer homology, and we conjecture that its

E_1

page is isomorphic to the HOMFLY-PT chain complex of Khovanov and Rozansky. At the level of each

E_1

summand, this conjecture can be stated in terms of an isomorphism between certain Tor groups. As evidence for the conjecture, we prove that such an isomorphism exists in degree zero.
Intercalibration of GOES Imager visible channels over the Sonoran Desert
Authors: Yu Fangfang , Wu Xiangqian , Grotenhuis Michael , Qian Haifeng
Published: July 2014

The Geostationary Operational Environmental Satellites (GOES) have been observing the Western Hemisphere since the late 1970s, providing valuable information for weather forecast and climate change studies. Due to the lack of an onboard calibration device for the visible channel, accurate reflectance of the visible channel data depends on vicarious calibration methods to provide postlaunch calibration coefficients to compensate for the degraded responsivity. In this study, the Sonoran Desert, which can be viewed by both GOES‐East and GOES‐West satellites, is used to intercalibrate the visible channels on board the three‐axis stabilized GOES satellite Imagers traceable to the Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 6 (C6) calibration standard. It was found that when the anomalous reflectance in 2004 and 2005 are excluded, the Sonoran Desert is radiometrically, spatially, and spectrally stable at the GOES viewing geometries and thus can be considered as a pseudo‐invariant calibration site to develop long‐term GOES Imager visible data set. To characterize the desert target reflectance with the MODIS data, GOES observations over 1 year period are used to convert the MODIS reflectance to the GOES viewing and solar illumination geometries. The spectral band adjustment factor for each GOES Imager visible channel is generated with a set of clear‐sky Hyperion measurements. A trending algorithm, which consists of a polynomial function for the description of instrument degradation performance and two sine terms for the impacts of the seasonal variations of the solar zenith angle and atmospheric components, is applied to fit the time series of prelaunch calibrated reflectance. The combined calibration uncertainty of the desert calibration method is less than 4% at the Aqua MODIS C6 calibration standard. The difference of the postlaunch calibration coefficients between the desert calibration and the current GOES visible operational calibration methods is mainly within 5%.
Water resources of the Black Sea Basin at high spatial and temporal resolution
Authors: Rouholahnejad Elham , Abbaspour Karim C. , Srinivasan Raghvan , Bacu Victor , Lehmann Anthony
Published: July 2014

The pressure on water resources, deteriorating water quality, and uncertainties associated with the climate change create an environment of conflict in large and complex river system. The Black Sea Basin (BSB), in particular, suffers from ecological unsustainability and inadequate resource management leading to severe environmental, social, and economical problems. To better tackle the future challenges, we used the Soil and Water Assessment Tool (SWAT) to model the hydrology of the BSB coupling water quantity, water quality, and crop yield components. The hydrological model of the BSB was calibrated and validated considering sensitivity and uncertainty analysis. River discharges, nitrate loads, and crop yields were used to calibrate the model. Employing grid technology improved calibration computation time by more than an order of magnitude. We calculated components of water resources such as river discharge, infiltration, aquifer recharge, soil moisture, and actual and potential evapotranspiration. Furthermore, available water resources were calculated at subbasin spatial and monthly temporal levels. Within this framework, a comprehensive database of the BSB was created to fill the existing gaps in water resources data in the region. In this paper, we discuss the challenges of building a large‐scale model in fine spatial and temporal detail. This study provides the basis for further research on the impacts of climate and land use change on water resources in the BSB.
The influence of the large‐scale atmospheric circulation on Antarctic sea ice during ice advance and retreat seasons
Authors: Raphael Marilyn N. , Hobbs Will
Published: July 2014

Antarctic sea ice, a key component of the Southern Hemisphere climate system, is influenced by several large‐scale modes of the atmospheric circulation. Antarctic sea ice variability is spatially heterogeneous, and links between the atmospheric circulation modes and the sea ice variability are unclear. Using the observed sea ice concentration data, this research isolates distinct regions of sea ice variability around Antarctica and determines the advance and retreat periods for each of them. The latter are then statistically linked with the observed geopotential height data to determine the atmospheric circulation pattern associated with the variability in the sea ice for each period and region. The results clarify which circulation mechanism is of primary importance to sea ice variability during critical periods of the ice lifecycle in the different regions around Antarctica and have potential for making estimates of past sea ice extent using the observed geopotential height data.
High‐speed video evidence of a dart leader with bidirectional development
Authors: Jiang Rubin , Wu Zhijun , Qie Xiushu , Wang Dongfang , Liu Mingyuan
Published: July 2014

An upward negative cloud‐to‐ground lightning flash initiated from a high structure was detected by a high‐speed camera operated at 10,000 fps, together with the coordinated measurement of electric field changes. Bidirectional propagation of a dart leader developing through the preconditioned channel was observed for the first time by optical means. The leader initially propagated downward through the upper channel with decreasing luminosity and speed and terminated at an altitude of about 2200 m. Subsequently, it restarted the development with both upward and downward channel extensions. The 2‐D partial speed of the leader's upward propagation with positive polarity ranged between 3.2 × 106 m/s and 1.1 × 107 m/s with an average value of 6.4 × 106 m/s, while the speeds of the downward propagation with negative polarity ranged between 1.0 and 3.2 × 106 m/s with an average value of 2.2 × 106 m/s. The downward propagation of the bidirectional leader eventually reached the ground and induced a subsequent return stroke.
Simultaneous estimation of both hydrological and ecological parameters in an ecohydrological model by assimilating microwave signal
Authors: Sawada Yohei , Koike Toshio
Published: July 2014

To improve the skill of reproducing land‐atmosphere interactions in weather, seasonal, and climate prediction systems, it is necessary to simulate correctly and simultaneously the surface soil moisture (SSM) and terrestrial biomass in land surface models. Despite the performance of hydrological and ecosystem models depends highly on parameter calibration, a method for parameter estimation in ungauged areas has yet to be established. We develop an autocalibration system that can simultaneously estimate both hydrological and ecological parameters by assimilating a microwave signal that is sensitive to both SSM and terrestrial biomass. This system comprises a hydrological model that has a physically based, sophisticated soil hydrology scheme, a dynamic vegetation model that can estimate vegetation growth and senescence, and a radiative transfer model that can convert land surface condition into brightness temperatures in the microwave region. By assimilating microwave signals from the Advanced Microwave Scanning Radiometer for Earth Observing System, the system simultaneously optimizes the parameters of these models. We test this approach at three in situ observation sites under different hydroclimatic conditions. Estimated SSM exhibits good agreement with ground‐based in situ observed SSM, and estimated leaf area index (LAI) is also improved by the optimization, compared with satellite‐observed LAI. The root‐mean‐square error of SSM and LAI at all sites, estimated by the model with optimized parameters, is much less than that estimated by the model with default parameters. Using microwave satellite brightness temperature data sets, this system offers the potential to calibrate parameters of both hydrological and ecosystem models globally.
Attorneys' Questions and Children's Productivity in Child Sexual Abuse Criminal Trials
Authors: Klemfuss J. Zoe , Quas Jodi A. , Lyon Thomas D.
Published: July 2014

We investigated the links between questions child witnesses are asked in court, children's answers, and case outcome. Samples of acquittals and convictions were matched on child age, victim–defendant relationship, and allegation count and severity. Transcripts were coded for question types, including a previously under‐examined type of potentially suggestive question, declarative questions. Children's productivity was conceptualized in a novel way by separating new from repeated content and by adjusting the definition based on the linguistic demands of the questions. Attorneys frequently used declarative questions, and disconcertingly, attorneys who used these and other suggestive questions more frequently were more likely to win their case. Open‐ended and closed‐ended questions elicited similar levels of productivity from children, and both elicited more productivity compared with suggestive questions. Results highlight how conceptualization of questions and answers can influence conclusions, and demonstrate the important real‐world implications of attorney questioning strategies on legal cases with child witnesses Copyright © 2014 John Wiley & Sons, Ltd.
Multiphoton Excited Fluorescent Materials for Frequency Upconversion Emission and Fluorescent Probes
Authors: Guo Lei , Wong Man Shing
Published: July 2014

Recent progress in developing various strategies for exploiting efficient MPA fluorophores for two emerging technological MPA applications including frequency upconversion photoluminescence and lasing as well as 2PA fluorescence bioimaging and biosensing are presented. An intriguing application of MPA frequency‐upconverted lasing offers opportunity for the fabrication of high‐energy coherent light sources in the blue region which could create new advantages and breakthroughs in various laser‐based applications. In addition, multiphoton excitation has led to considerable progress in the development of advanced diagnostic and therapeutic treatments; further advancement is anticipated with the emergence of various versatile 2PA fluorescence probes. It is widely appreciated that the two‐photon excitation offers significant advantages for the biological fluorescence imaging and sensing which includes higher spatial resolution, less photobleaching and photodamage as well as deeper tissue penetration as compared to the one‐photon excited microscopy. To be practically useful, the 2PA fluorescent probes for biological applications are required to have a site‐specificity, a high fluorescence quantum yield, proper two‐photon excitation and subsequent emission wavelengths, good photodecomposition stability, water solubility, and biocompatibility besides large 2PA action cross‐sections.
Polarization Orientation, Piezoelectricity, and Energy Harvesting Performance of Ferroelectric PVDF‐TrFE Nanotubes Synthesized by Nanoconfinement
Authors: Bhavanasi Venkateswarlu , Kusuma Damar Yoga , Lee Pooi See
Published: July 2014

1D nanostructures of soft ferroelectric materials exert promising potential in the fields of energy harvesting and flexible and printed nanoelectronics. Here, improved piezoelectric properties, energy‐harvesting performance, lower coercive fields, and the polarization orientation of poly(vinylidene fluoride–trifluoroethylene) (PVDF‐TrFE) nanotubes synthesized with nanoconfinement effect are reported. X‐ray diffraction (XRD) patterns of the nanotubes show the peak corresponding to the planes of (110)/(200), which is a signature of ferroelectric beta phase formation. Piezoforce spectroscopy measurements on the free‐standing horizontal nanotubes bundles reveal that the effective polarization direction is oriented at an inclination to the long axis of the nanotubes. The nanotubes exhibit a coercive field of 18.6 MV m−1 along the long axis and 40 MV m−1 (13.2 MV m−1 considering the air gap) in a direction perpendicular to the long axis, which is lower than the film counterpart of 50 MV m−1. The poled 200 nm nanotubes, with 40% reduction in poling field, give larger piezoelectric d33 coefficient values of 44 pm V−1, compared to poled films (≈20 pm V−1). The ferroelectric nanotubes deliver superior energy harvesting performance with an output voltage of ≈4.8 V and power of 2.2 μW cm−2, under a dynamic compression pressure of 0.075 MPa at 1 Hz.
High‐throughput packed‐bed microreactors with in‐line analytics for the discovery of asphaltene deposition mechanisms
Authors: Hu Chuntian , Hartman Ryan L.
Published: July 2014

Understanding asphaltene nanoaggregation kinetics is a key to predicting the deposition in pure quartz‐grain porous media. High‐throughput quartz packed‐bed microreactors (μPBRs) were, therefore, designed to provide mechanistic insights by merging oilfield chemistry and microchemical systems. In‐line UV‐Vis spectroscopy and pressure transducer were used to characterize the stable packing of quartz particles with porosity of ∼40% and permeability of ∼5.5 × 10−13 m2. Temperature (25.0–90.0°C), n‐heptane composition (50.0–80.0 vol %), and n‐alkane (n‐C5 to n‐C9) were all observed to influence asphaltenes deposition in the porous media, and reduced dispersion was obtained in the damaged packed‐bed by estimating dispersion coefficients and the Bodenstein number. Deposition by mechanical entrapment dominated the mechanism in all scenarios, as discovered by the simplified Kozeny–Carman and Civan's permeability‐porosity relationships. The results could aid in the design of remediations that minimize production losses of considerable economic magnitude. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3534–3546, 2014
Flow and temperature patterns in an inductively coupled plasma reactor: Experimental measurements and CFD simulations
Authors: Punjabi Sangeeta B. , Sahasrabudhe Sunil N. , Ghorui S. , Das A. K. , Joshi Narendra K. , Kothari Dushyant C. , Ganguli Arijit A. , Joshi Jyeshtharaj B.
Published: July 2014

Measurements of temperature patterns in an inductively coupled plasma (ICP) have been carried out experimentally. Plasma torch was operated at different RF powers in the range of 3–14 kW at near atmospheric pressure and over a wide range of sheath gas flow rate (3–25 lpm). Measurements were made at five different axial positions in ICP torch. The chordal intensities were converted into a radial intensity profile by Abel Inversion technique. Typical radial temperature profile shows an off‐axis temperature peak, which shifts toward the wall as the power increases. Temperatures in the range of 6000–14,000 K were recorded by this method. The temperature profiles in the plasma reactor were simulated using computational fluid dynamics (CFD). A good agreement was found between the CFD predictions of the flow and temperature pattern with those published in the literature as well as the temperature profiles measured in the present work. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3647–3664, 2014
Cerebrospinal fluid aquaporin‐4 antibody levels in neuromyelitis optica attacks
Authors: Sato Douglas Kazutoshi , Callegaro Dagoberto , de Haidar Jorge Frederico M. , Nakashima Ichiro , Nishiyama Shuhei , Takahashi Toshiyuki , Simm Renata Faria , Apostolos‐Pereira Samira Luisa , Misu Tatsuro , Steinman Lawrence , Aoki Masashi , Fujihara Kazuo
Published: July 2014

To elucidate immunopathogenetic roles of aquaporin‐4 antibodies in the cerebrospinal fluid (CSF) of neuromyelitis optica spectrum disorders (NMOSD), we analyzed aquaporin‐4 antibody titers, cellular and inflammatory markers in the CSF collected from 11 aquaporin‐4 antibody seropositive patients. The CSF aquaporin‐4 antibody levels during attacks (but not in sera) closely correlated with pleocytosis, inflammatory cytokines including interleukin‐6 that can regulate antibody‐producing plasmablasts, and glial fibrillary acidic protein levels in the CSF. The amount of aquaporin‐4 antibodies present in the central nervous system may have therapeutic implications, as it is associated with astrocyte injury and inflammatory responses during NMOSD attacks. Ann Neurol 2014;76:305–309
Efficient and Modular Synthesis of New Structurally Diverse Functionalized [n]Paracyclophanes by a Ring‐Distortion Strategy
Authors: Krieger Jean‐Philippe , Ricci Gino , Lesuisse Dominique , Meyer Christophe , Cossy Janine
Published: July 2014

With the goal of synthesizing new [n]paracyclophanes, the expansion of the scope of a strategy originally disclosed by Winterfeldt et al., was investigated. This approach involves sequential Diels–Alder/retro‐Diels–Alder reactions, the applications of which have been constrained so far to steroid derivatives. An efficient access to new functionalized [9]‐, [10]‐, and [16]paracyclophanes, including original cage architectures, was developed from readily available building blocks using thermal electrocyclization and a cycloaddition/cycloreversion sequence as the key steps.
Tantalum Oxide Nanoparticles for the Imaging of Articular Cartilage Using X‐Ray Computed Tomography: Visualization of Ex Vivo/In Vivo Murine Tibia and Ex Vivo Human Index Finger Cartilage
Authors: Freedman Jonathan D. , Lusic Hrvoje , Snyder Brian D. , Grinstaff Mark W.
Published: July 2014

The synthesis and characterization of tantalum oxide (Ta2O5) nanoparticles (NPs) as new X‐ray contrast media for microcomputed tomography (μCT) imaging of articular cartilage are reported. NPs, approximately 5–10 nm in size, and possessing distinct surface charges, were synthesized using phosphonate (neutral), ammonium (cationic), and carboxylate (anionic) ligands as end functional groups. Assessment of a cartilage defect in a human cadaver distal metacarpophalangeal (MCP) joint with the ammonium nanoparticles showed good visualization of damage and preferential uptake in areas surrounding the defect. Finally, an optimized nontoxic cationic NP contrast agent was evaluated in an in vivo murine model and the cartilage was imaged. These nanoparticles represent a new type of contrast agent for imaging articular cartilage, and the results demonstrate the importance of surface charge in the design of nanoparticulate agents for targeting the surface or interior zones of articular cartilage.
Isolation of a Bis(oxazol‐2‐ylidene)–Phenylborylene Adduct and its Reactivity as a Boron‐Centered Nucleophile
Authors: Kong Lingbing , Li Yongxin , Ganguly Rakesh , Vidovic Dragoslav , Kinjo Rei
Published: July 2014

An isolable phenylborylene species supported by two oxazol‐2‐ylidene ligands was synthesized and structurally characterized. Computational studies revealed the presence of lone‐pair electrons on the boron atom in this molecule; therefore, there are eight electrons around the three‐coordinate boron center. The nucleophilic property was confirmed by the reactions with trifluoromethanesulfonic acid and [(thf)Cr(CO)5], which gave the corresponding conjugate acid and a chromium–borylene complex, respectively.
Behavior of UV‐cured print inks on LDPE and PBAT/TPS blend substrates during curing, postcuring, and accelerated degradation
Authors: Gonçalves Bardi Marcelo Augusto , Leite Munhoz Mara de Mello , Oliveira Henrique Alves de , Auras Rafael , Machado Luci Diva Brocardo
Published: July 2014

During radiation curing, a reactive formulation is converted into a highly crosslinked coating film by means of polymerization reactions. This three‐dimensional (3D) network is resistant to external degrading factors as it cannot be undone by any physical–chemical means. In this study, various ultraviolet (UV)‐curable ink formulations with different pigments were developed. The behavior of the UV‐curable inks was evaluated during UV curing in a photocalorimeter or in a UV tunnel. Inks were exposed to accelerated aging in an accelerated weathering chamber and their physical–chemical properties were investigated. The presence of residual fractions of unreacted species trapped in the 3D network formed during UV curing interferes with the degradation of the main structure during exposure in the weathering chamber. The ink formulations that did not easily absorb UV light increased in gloss and hardness, indicating that residual crosslinking is taking place at the same time that degradation is occurring. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41116.
Induced CD8+FoxP3+ Treg Cells in Rheumatoid Arthritis Are Modulated by p38 Phosphorylation and Monocytes Expressing Membrane Tumor Necrosis Factor α and CD86
Authors: Ellis Shawn D. P. , McGovern Jenny L. , van Maurik André , Howe David , Ehrenstein Michael R. , Notley Clare A.
Published: July 2014

Objective

Limiting the severity of inflammation and promoting its eventual resolution are vital for protecting host tissues both in autoimmunity and chronic infection. The aim of this study was to determine the suitability of repurposing anti‐CD3 monoclonal antibody (mAb) therapy for rheumatoid arthritis (RA) by analyzing its ability to induce CD8+FoxP3+ Treg cells from peripheral blood mononuclear cells (PBMCs).

Methods

Anti‐CD3 mAb was cultured with RA PBMCs to induce CD8+FoxP3+ Treg cells, which were analyzed by flow cytometry to determine their phenotype. Treg cell induction was investigated via neutralization or blocking antibodies, cellular depletion, or ImageStream technology. Blotting was used to determine the signaling pathways involved in CD8+FoxP3+ Treg cell induction. Suppression of CD4+ T cell effector responses was assessed by Treg cell suppression assays and Mosaic enzyme‐linked immunosorbent assay.

Results

Potent CD8+FoxP3+ Treg cells were induced from RA PBMCs by anti‐CD3 mAb. Unlike their CD4+ counterparts, CD8+FoxP3+ Treg cells inhibited Th17 responses in a contact‐dependent manner, thereby functioning to limit a wider range of inflammatory pathways. CD8+FoxP3+ Treg cell induction was supported both by p38 phosphorylation intrinsic to naive CD8+ T cells and by monocytes via CD86 and membrane tumor necrosis factor α (TNFα). Artificially increasing monocyte membrane TNFα or inhibiting CD8+ T cell p38 phosphorylation drove FoxP3 expression in a subset of initially unresponsive CD8+ T cells.

Conclusion

These data define an unknown mechanism of CD8+FoxP3+ Treg cell induction by anti‐CD3 mAb, which could be combined with a p38 inhibitor to improve therapeutic efficacy in RA patients and resolve chronic inflammation via the restoration of tolerance.
Role of Protein Phosphatase Magnesium‐Dependent 1A and Anti–Protein Phosphatase Magnesium‐Dependent 1A Autoantibodies in Ankylosing Spondylitis
Authors: Kim Yong‐Gil , Sohn Dong Hyun , Zhao Xiaoyan , Sokolove Jeremy , Lindstrom Tamsin M. , Yoo Bin , Lee Chang‐Keun , Reveille John D. , Taurog Joel D. , Robinson William H.
Published: July 2014

Objective

Although ankylosing spondylitis (AS) is driven by immune‐mediated processes, little is known about the presence and role of autoantibodies in this disease. This study was undertaken to investigate whether autoantibodies occur in and are involved in AS.

Methods

We performed human protein microarray analysis of sera derived from patients with AS or other autoimmune disorders to identify autoantibodies associated specifically with AS, and identified autoantibody targeting of protein phosphatase magnesium‐dependent 1A (PPM1A) in AS. We performed enzyme‐linked immunosorbent assay (ELISA) analysis of sera from 2 independent AS cohorts to confirm autoantibody targeting of PPM1A, and to assess associations between levels of anti‐PPM1A antibodies and AS disease severity or response to anti–tumor necrosis factor (anti‐TNF) therapy (as measured by Bath AS Disease Activity Index [BASDAI] score). Levels of anti‐PPM1A antibodies were also evaluated in sera from rats transgenic for HLA–B27 and human β2‐microglobulin. The expression of PPM1A was assessed by immunohistochemistry in synovial tissue samples from patients with AS, rheumatoid arthritis, or osteoarthritis. The role of PPM1A in osteoblast differentiation was investigated by gene knockdown and overexpression.

Results

AS was associated with autoantibody targeting of PPM1A, and levels of anti‐PPM1A autoantibodies were significantly higher in patients with more advanced sacroiliitis and correlated positively with BASDAI score after treatment with anti‐TNF agents. The levels of anti‐PPM1A autoantibodies were also higher in the sera of transgenic rats that are prone to develop spondyloarthritis than in those that are not. PPM1A was expressed in AS synovial tissue, and PPM1A overexpression promoted osteoblast differentiation, whereas PPM1A knockdown suppressed it.

Conclusion

Anti‐PPM1A autoantibodies are present in AS, and our findings suggest that PPM1A may contribute to the pathogenic bone ankylosis characteristic of AS.
Evaluation of Developmental Toxicity of Propylthiouracil and Methimazole
Authors: Mallela Murali K. , Strobl Marie , Poulsen Ryan R. , Wendler Christopher C. , Booth Carmen J. , Rivkees Scott A.
Published: July 2014

BACKGROUND

Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs.

METHODS

We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague‐Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20.

RESULTS

In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown‐rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed.

CONCLUSION

We did not observe either gross external malformations or histopathological malformations in mice or rats treated long‐term with high doses of PTU or MMI during pregnancy
Short-term complications and long-term morbidity of laparoscopic and open appendicectomy in a national cohort
Authors: Andersson R E
Published: July 2014

Background

Laparoscopic appendicectomy has been proposed as the standard for surgical treatment of acute appendicitis, based on controversial evidence. This study compared outcomes after open and laparoscopic appendicectomy in a national, population-based cohort.

Methods

All patients who underwent open or intended laparoscopic appendicectomy in Sweden between 1992 and 2008 were identified from the Swedish National Patient Register. The outcomes were analysed according to intention to treat with multivariable adjustment for confounding factors and survival analytical techniques where appropriate.

Results

A total of 169 896 patients underwent open (136 754) or intended laparoscopic (33 142) appendicectomy. The rate of intended laparoscopic appendicectomy increased from 3·8 per cent (425 of 11 175) in 1992 to 32·9 per cent (3066 of 9329) in 2008. Laparoscopy was used most frequently in middle-aged patients, women and patients with no co-morbidity. The rate of conversion from laparoscopy to open appendicectomy decreased from 75·3 per cent (320 of 425) in 1992 to 19·7 per cent (603 of 3066) in 2008. Conversion was more frequent in women and those with perforated appendicitis, and the rate increased with age and increasing co-morbidity. After adjustment for co-variables, compared with open appendicectomy, laparoscopy was associated with a shorter length of hospital stay (by 0·06 days), a lower frequency of negative appendicectomy (adjusted odds ratio (OR) 0·59; P < 0·001), wound infection (adjusted OR 0·54; P = 0·004) and wound rupture (adjusted OR 0·44; P = 0·010), but higher rates of intestinal injury (adjusted OR 1·32; P = 0·042), readmission (adjusted OR 1·10; P < 0·001), postoperative abdominal abscess (adjusted OR 1·58; P < 0·001) and urinary infection (adjusted OR 1·39; P = 0·020). Laparoscopy had a lower risk of postoperative small bowel obstruction during the first 2 years after surgery, but not thereafter.

Conclusion

The outcomes of laparoscopic and open appendicectomy showed a complex and contrasting pattern and small differences of limited clinical importance. The choice of surgical method therefore depends on the local situation, the surgeon's experience and the patient's preference.
Randomized clinical trial of endovenous laser ablation versus steam ablation (LAST trial) for great saphenous varicose veins
Authors: van den Bos R R , Malskat W S J , De Maeseneer M G R , de Roos K P , Groeneweg D A G , Kockaert M A , Neumann H A M , Nijsten T
Published: July 2014

Background

The aim was to compare endovenous laser ablation (EVLA) and endovenous steam ablation (EVSA) for great saphenous varicose veins in a non-inferiority study.

Methods

Patients with primary great saphenous vein reflux were randomized to EVLA (940 nm) or EVSA (SVS™). Primary outcomes were treatment success (vein obliteration) at 52 weeks, and Venous Clinical Severity Score (VCSS) at 12 weeks. Secondary outcomes were pain, satisfaction with treatment, duration of analgesia use and days lost from daily activities, changes in Aberdeen Varicose Vein Questionnaire (AVVQ) and EQ-5D™ scores after 12 weeks, and complications at 2 and 12 weeks.

Results

A total of 227 legs were treated (EVSA, 117; EVLA, 110); 36 legs treated with EVSA received a low dose and the remaining 81 a higher dose. At 1 year, the treatment success rate after high-dose EVSA was not inferior to that of EVLA: 92 (95 per cent confidence interval (c.i.) 86 to 98) versus 96 (92 to 100) per cent respectively. Changes in VCSS after 12 weeks were similar: −2·69 (95 per cent c.i. −2·34 to −3·04) and −2·51 (−2·10 to −2·93). AVVQ, EQ-5D™ and EQ VAS scores improved equally 12 weeks after both treatments. Patients treated with EVSA reported less postprocedural pain, fewer days of analgesia use, were more satisfied with therapy, and had a shorter convalescence. Complication rates were comparable.

Conclusion

The 1-year treatment success of high-dose EVSA was not inferior to that of EVLA. Several secondary outcomes were in favour of EVSA. Registration number NCT02046967 (http://www.clinicaltrials.gov).
The use of whole‐mount in situ hybridization to illustrate gene expression regulation
Authors: Llamusí Beatriz , Muñoz‐Soriano Verónica , Paricio Nuria , Artero Rubén
Published: July 2014

In situ hybridization is a widely used technique for studying gene expression. Here, we describe two experiments addressed to postgraduate genetics students in which the effect of transcription factors on gene expression is analyzed in Drosophila embryos of different genotypes by whole‐mount in situ hybridization. In one of the experiments, students analyzed the repressive effect of Snail over rhomboid expression using reporter lines containing different constructs of the rhomboid neuroectodermal enhancer fused to the lacZ gene. In the second experiment, the epistatic relationship between the cabut and decapentaplegic genes was analyzed. These simple experiments allowed students to (1) understand the role of transcription factors and cis‐regulatory elements over gene expression regulation and (2) practice a widespread laboratory technique, in situ hybridization with nonradioactive labeled probes, to detect gene expression patterns. These experiments required 12 hr and were organized into four daily sessions that included the discussion of the results with students. Examples of the results obtained and their relevance are shown and discussed herein. The methods described in these laboratory exercises can be easily adapted to model organisms other than Drosophila. © 2014 by The International Union of Biochemistry and Molecular Biology, 42(4):339–347, 2014.
Carbonaceous Hydrogen‐Evolution Catalyst Containing Cobalt Surrounded by a Tuned Local Structure
Authors: Maruyama Jun , Ioroi Tsutomu , Hasegawa Takahiro , Mori Takuya , Orikasa Yuki , Uchimoto Yoshiharu
Published: July 2014

The low activity and durability of noble‐metal‐free catalysts in acidic media are major problems that hinder their practical use. This study reports significantly enhanced activity of a cobalt‐containing carbonaceous catalyst used for the hydrogen‐evolution reaction in a water electrolyzer by using a proton‐exchange membrane (PEM), which is an efficient energy‐conversion device that is suitable for intermittent renewable energy sources. On the basis of X‐ray absorption near‐edge structure, the enhancement in activity was attributed to a change in the local structure surrounding the Co atom. The PEM water electrolyzer formed by using the catalyst with an optimized structure and Co surface concentration showed an enthalpy efficiency of 80 % at 1 A cm−2.
Purification of Lysozyme from Protein Mixtures by Solvent‐Freeze‐Out Technology
Authors: Yu Xiaoxi , Wang Jingkang , Ulrich Joachim
Published: July 2014

The purification of hen egg white lysozyme from a lysozyme/crude extract mixture was carried out by the solvent‐freeze‐out (SFO) technology on the laboratory scale. Compared to previous works, this investigation focuses on the crystallization of lysozyme from a complicated system. The crystallization conditions were determined by screening tests. Based on these results, the crystallization process was performed in basic buffer solution in which the formation of tetragonal lysozyme crystals is considered to be difficult. The protein composition and purity of the crystals were evaluated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. The enzymatic activity was also measured by the use of a spectrophotometer. The results show that lysozyme retained its original enzyme activity.
Formation and Properties of a Bicyclic Silylated Digermene
Authors: Hlina Johann , Baumgartner Judith , Marschner Christoph , Albers Lena , Müller Thomas , Jouikov Viatcheslav V.
Published: July 2014

In the presence of PMe3 or N‐heterocyclic carbenes, the reaction of oligosilanylene dianions with GeCl2⋅dioxane gives germylene–base adducts. After base abstraction, the free germylenes can dimerize by formation of a digermene. An electrochemical and theoretical study of a bicyclic tetrasilylated digermene revealed formation of a comparably stable radical anion and a more reactive radical cation, which were characterized further by UV/Vis and ESR spectroscopy.
The Discovery and Development of the N‐Substituted trans‐3,4‐Dimethyl‐4‐(3′‐hydroxyphenyl)piperidine Class of Pure Opioid Receptor Antagonists
Authors: Carroll F. Ivy , Dolle Roland E.
Published: July 2014

N‐Substituted trans‐3,4‐dimethyl‐4‐(3‐hydroxyphenyl)piperidines are a class of pure opioid receptor antagonists with a novel pharmacophore. This opioid receptor antagonist pharmacophore was used as a lead structure to design and develop several interesting and useful opioid receptor antagonists. In this review we describe: 1) early SAR studies that led to the discovery of LY255582 and analogues that are nonselective opioid receptor antagonists developed for the treatment of obesity; 2) the discovery and commercialization of LY246736 (alvimopan; ENTEREG®), a peripherally selective opioid receptor antagonist that accelerates the time to upper and lower GI recovery following surgeries that include partial bowel resection with primary anastomosis; and 3) the discovery and development of the potent and selective κ opioid receptor antagonist JDTic and analogues as potential pharmacotherapies for treating depression, anxiety, and substance abuse (nicotine, alcohol, and cocaine). In addition, the use of JDTic for obtaining the X‐ray structure of the human κ opioid receptor is discussed.
Noninvasive radiofrequency treatment effect on mitochondria in pancreatic cancer cells
Authors: Curley Steven A. , Palalon Flavio , Lu Xiaolin , Koshkina Nadezhda V.
Published: July 2014

BACKGROUND

The development of novel therapeutic approaches for cancer therapy is important, especially for tumors that have poor response or develop resistance to standard chemotherapy and radiation. We discovered that noninvasive radiofrequency (RF) fields can affect cancer cells but not normal cells, inhibit progression of tumors in mice, and enhance the anticancer effects of chemotherapy. However, it remains unclear what physiological and molecular mechanisms this treatment induces inside cells. Here, we studied the effect of RF treatment on mitochondria in human pancreatic cancer cells.

METHODS

The morphology of mitochondria in cells was studied via electron microscopy. The alteration of mitochondrial membrane potential (Δψ) was accessed using a Mitotracker probe. The respiratory activity of mitochondria was evaluated by analyzing changes in oxygen consumption rates determined with a Mito Stress Test Kit. The production of intracellular reactive oxygen species was performed using flow cytometry. The colocalization of mitochondria and autophagosome markers in cells was performed using fluorescence immunostaining and confocal microscopy analysis.

RESULTS

RF fields treatment changed the morphology of mitochondria in cancer cells, altered polarization of the mitochondrial membrane, substantially impaired mitochondrial respiration, and increased reactive oxygen species production, indicating RF‐induced stress on the mitochondria. We also observed frequent colocalization of the autophagosome marker LC3B with the mitochondrial marker Tom20 inside cancer cells after RF exposure, indicating the presence of mitochondria in the autophagosomes. This suggests that RF‐induced stress can damage mitochondria and induce elimination of damaged organelles via autophagy.

CONCLUSION

RF treatment impaired the function of mitochondria in cancer cells. Therefore, mitochondria can represent one of the targets of the RF treatment. Cancer 2014;120:3418–3425. © 2014 American Cancer Society.
The orexinergic neurons receive synaptic input from C1 cells in rats
Authors: Bochorishvili Genrieta , Nguyen Thanh , Coates Melissa B. , Viar Kenneth E. , Stornetta Ruth L. , Guyenet Patrice G.
Published: July 2014

The C1 cells, located in the rostral ventrolateral medulla (RVLM), are activated by pain, hypoxia, hypoglycemia, infection, and hypotension and elicit cardiorespiratory stimulation, adrenaline and adrenocorticotropic hormone (ACTH) release, and arousal. The orexin neurons contribute to the autonomic responses to acute psychological stress. Here, using an anatomical approach, we consider whether the orexin neurons could also be contributing to the autonomic effects elicited by C1 neuron activation. Phenylethanolamine N‐methyl transferase‐immunoreactive (PNMT‐ir) axons were detected among orexin‐ir somata, and close appositions between PNMT‐ir axonal varicosities and orexin‐ir profiles were observed. The existence of synapses between PNMT‐ir boutons labeled with diaminobenzidine and orexinergic neurons labeled with immunogold was confirmed by electron microscopy. We labeled RVLM neurons with a lentiviral vector that expresses the fusion protein ChR2‐mCherry under the control of the catecholaminergic neuron‐selective promoter PRSx8 and obtained light and ultrastructural evidence that these neurons innervate the orexin cells. By using a Cre‐dependent adeno‐associated vector and TH‐Cre rats, we confirmed that the projection from RVLM catecholaminergic neurons to the orexinergic neurons originates predominantly from PNMT‐ir catecholaminergic (i.e., C1 cells). The C1 neurons were found to establish predominantly asymmetric synapses with orexin‐ir cell bodies or dendrites. These synapses were packed with small clear vesicles and also contained dense‐core vesicles. In summary, the orexin neurons are among the hypothalamic neurons contacted and presumably excited by the C1 cells. The C1–orexin neuronal connection is probably one of several suprabulbar pathways through which the C1 neurons activate breathing and the circulation, raise blood glucose, and facilitate arousal from sleep. J. Comp. Neurol. 522:3834–3846, 2014. © 2014 Wiley Periodicals, Inc.