bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-Activity Relationship of 39 Analogs of Laetispicine with Antidepressant Properties
Authors: Xie Hui , Liu Juan , Yu Min , Wang Yong , Yao Chunyan , Yao Shuyi , Jin Di , Hu Dingyu , Wang Yanlin , Shen Jingkang , Pan Shengli
Published: November 2013

The natural product Laetispicine ( N -isobutyl-(3,4-methylendioxyphenyl)-2E, 4E, 9E-undecatrienoamide), was isolated from the Piper laetispicum C. DC and screened, for its antidepressant activity and antinociceptive effects. Structure-functional activities of five natural products indicated that biological activity is dependent on double bonds present within the benzene ring and a conjugated double bond located at positions 2–3 and 4–5 in the molecular structure. To further understand the structural-activity relationship of Laetispicine as a new potent and safe antidepressant, the structural-activity relationship of 39 analogs of Laetispicine were synthetized and tested in forced swimming tests in mice whilst also in protective effects against glutamate or H 2 O 2 induced apoptosis in PC12 cells. The results show that the compound 30 — N -isobutyl-11-(4-chlorophenyl) undeca-2E,4E,9E-trienamide exhibited the same activity as the parental compound Laetispicine, and furthermore, the effective dose of this compound is lower than Laetispicine. Therefore, the compound 30 might be a potentially useful therapy in the treatment of depression. For structure, the conjugated double bonds located at 2-3, 4-5 and isolated double bonds from benzene ring are necessary for the antidepressant activities no matter the different length of carbon chain; the isobutyl connected with acylamino also are necessary; and the benzodioxole moiety is replaceable, the halogen atom in phenyl ring at the para-position could enhance this kind of activity.
Endothelial nitric oxide synthase uncoupling and microvascular dysfunction in the mesentery of mice deficient in α-galactosidase A
Authors: Kang Justin J. , Shu Liming , Park James L. , Shayman James A. , Bodary Peter F.
Published: November 2013

A defect in the gene for the lysosomal enzyme α-galactosidase A (Gla) results in globotriaosylceramide (Gb3) accumulation in Fabry disease and leads to premature death from cardiac and cerebrovascular events. However, gastrointestinal symptoms are often first observed during childhood in these patients and are not well understood. In this study, we demonstrate an age-dependent microvasculopathy of the mesenteric artery (MA) in a murine model of Fabry disease (Gla-knockout mice) resulting from dysregulation of the vascular homeostatic enzyme endothelial nitric oxide synthase (eNOS). The progressive accumulation of Gb3 in the MA was confirmed by thin-layer chromatographic analysis. A total absence of endothelium-dependent dilation was observed in MAs from mice at 8 mo of age, while suppression of ACh-mediated vasodilation was evident from 2 mo of age. Endothelium-independent dilation with sodium nitroprusside was normal compared with age-matched wild-type mice. The microvascular defect in MAs from Fabry mice was endothelium-dependent and associated with suppression of the active homodimer of eNOS. Phosphorylation of eNOS at the major activation site (Ser1179) was significantly downregulated, while phosphorylation at the major inhibitory site (Thr495) was remarkably enhanced in MAs from aged Fabry mice. These profound alterations in eNOS bioavailability at 8 mo of age were observed in parallel with high levels of 3-nitrotyrosine, suggesting increased reactive oxygen species along with eNOS uncoupling in this vascular bed. Overall, the mesenteric microvessels in the setting of Fabry disease were observed to have an early and profound endothelial dysfunction associated with elevated reactive nitrogen species and decreased nitric oxide bioavailability.
Changes in breath sound power spectra during experimental oleic acid-induced lung injury in pigs
Authors: Räsänen Jukka , Nemergut Michael E. , Gavriely Noam
Published: November 2013

To evaluate the effect of acute lung injury on the frequency spectra of breath sounds, we made serial acoustic recordings from nondependent, midlung and dependent regions of both lungs in ten 35- to 45-kg anesthetized, intubated, and mechanically ventilated pigs during development of acute lung injury induced with intravenous oleic acid in prone or supine position. Oleic acid injections rapidly produced severe derangements in the gas exchange and mechanical properties of the lung, with an average increase in venous admixture from 16 ± 12 to 62 ± 16% ( P < 0.01), and a reduction in dynamic respiratory system compliance from 25 ± 4 to 14 ± 4 ml/cmH2O ( P < 0.01). A concomitant increase in sound power was seen in all lung regions ( P < 0.05), predominantly in frequencies 150–800 Hz. The deterioration in gas exchange and lung mechanics correlated best with concurrent spectral changes in the nondependent lung regions. Acute lung injury increases the power of breath sounds likely secondary to redistribution of ventilation from collapsed to aerated parts of the lung and improved sound transmission in dependent, consolidated areas.
Determinants of resting lipid oxidation in response to a prior bout of endurance exercise
Authors: Henderson Gregory C. , Alderman Brandon L.
Published: November 2013

A single bout of exercise can alter subsequent resting metabolism for many hours and into the next day. However, differences between men and women, effects of nutritional state, and relative effects of resting metabolic rate (RMR) and respiratory exchange ratio (RER) in controlling the increase in lipid oxidation (Lox) after exercise are not yet clear. Effects of aerobic capacity (V̇o2 peak) and exercise bout parameters (intensity and volume) also remain to be clearly elucidated as does the time course of changes after exercise. We performed a meta-analysis to assess these potential moderators of the impact of endurance exercise [effect sizes (ESs)] on subsequent Lox at rest (ES = 0.91; 95% CI: 0.69–1.12), on the day of exercise (ES = 1.22; 95% CI: 0.89–1.55), and on the following day (ES = 0.60; 95% CI: 0.35–0.85). ES for the exercise-related increase in resting Lox was significantly greater in men than women in the postabsorptive state but similar in the postprandial state. The ES for depression of RER after exercise was similar between men and women, while the ES for RMR in the postabsorptive state tended to be higher in men than women. Finally, V̇o2 peakand exercise energy expenditure (EEE), but not intensity, were predictive of postexercise Lox. The findings indicate importance of EEE and fitness for ability to achieve robust enhancement of Lox after exercise. The results additionally indicate a gender difference in postexercise Lox that is dependent on nutritional state, as the ES for Lox was lower in women only in the postabsorptive state.
Optimal Color Stability for White Organic Light-Emitting Diode (WOLED) by Using Multiple-Ultra-Thin Layers (MUTL)
Authors: Chen Kan-Lin , Huang Chien-Jung , Chen Wen-Ray , Lin Fong-Yi , Meen Teen-Hang , Kang Chih-Chieh
Published: November 2013

The work demonstrates the improvement of color stability for white organic light-emitting diode (WOLED). The devices were prepared by vacuum deposition on ITO-glass substrates. These guest materials of 5,6,11,12-tetraphenylnaphthacene (Rubrene) were deposited in 4,4′-bis(2,2-diphenyl vinyl)-1,1′-biphenyl (DPVBi), resulting in an emitting layer. Experimental results reveal that the properties in the multiple-ultra-thin layer (MUTL) are better than those of the emitting layer with a single guest material, reaching the commercial white-light wavelength requirement of 400–700 nm. The function of the MUTL is as the light-emitting and trapping layer. The results show that the MUTL has excellent carrier capture effect, leading to high color stability of the device at various applied voltages. The Commissions Internationale De L’Eclairage (CIE) coordinate of this device at 3~7 V is few displacement and shows a very slight variation of (0.016, 0.009). The CIE coordinates at a maximal luminance of 9980 cd/m2are (0.34, 0.33).
Design and Analysis of a Novel Speed-Changing Wheel Hub with an Integrated Electric Motor for Electric Bicycles
Authors: Wu Yi-Chang , Sun Zi-Heng
Published: November 2013

The aim of this paper is to present an innovative electromechanical device which integrates a brushless DC (BLDC) hub motor with a speed-changing wheel hub stored on the rear wheel of an electric bicycle. It combines a power source and a speed-changing mechanism to simultaneously provide functions of power generation and transmission for electric bicycles. As part of the proposed integrated device, the wheel hub consists of a basic planetary gear train providing three forward speeds including a low-speed gear, a direct drive, and a high-speed gear. Each gear is manually controlled by the shift control sleeve to selectively engage or disengage four pawl-and-ratchet clutches based on its clutching sequence table. The number of gear teeth of each gear element of the wheel hub is synthesized. The BLDC hub motor is an exterior-rotor-type permanent-magnet synchronous motor. Two-dimensional finite-element analysis (FEA) software is employed to facilitate the motor design and performance analysis. An analysis of the power transmission path at each gear is provided to verify the validity of the proposed design. The results of this work are beneficial to the embodiment, design, and development of novel electromechanical devices for the power and transmission systems of electric bicycles.
A Novel CT Imaging System with Adjacent Double X-Ray Sources
Authors: An Mou , Xie Yaoqin
Published: November 2013

Current computed tomography (CT) scanners rotate fast to reduce motion artifact. X-ray tube must work in a high power to make the image clear under short exposure time. However, the life span of such a tube may be shortened. In this paper, we propose a novel double sources CT imaging system, which puts two of the same X-ray sources closely with each other. The system is different from current dual source CT with orthogonal X-ray sources. In our system, each projection is taken twice by these two sources to enhance the exposure value and then recovered to a single source projection for image reconstruction. The proposed system can work like normal single source CT system, while halving down the working power for each tube.
Optimal Design for the Diffusion Plate with Nanoparticles in a Diffusive Solar Cell Window by Mie Scattering Simulation
Authors: Chen Ruei-Tang , Kang Chih-Chieh , Lin Jeng-Feng , Lin Tzu-Chi , Lai Chih-Wen
Published: November 2013

A diffusive solar cell window comprises a diffusion plate with TiO2nanoparticles sandwiched between two glass layers. It is a simple, inexpensive, easy-to-made, and highly reliable transparent solar energy module. To improve its power generation efficiency as well as maintain indoor natural lighting, we examined the scattering mechanism in the diffusion plate with TiO2nanoparticles within a diffusive solar cell window by Mie scattering simulations. In this work, a multiwavelength ASAP ray tracing model for a diffusive solar cell window with acceptable accuracy was developed to investigate the influence of the diffusion plate design parameter, mainly concentration of a diffusion plate with determined particle size distribution, on power generation efficiency and color shift of transmitted sun light. A concept of “effective average radius” was proposed to account for the equivalent scattering effect of a size distribution of quasispherical particles. Simulation results demonstrated that both the transmitted light and its correlated color temperature decreased as the concentration increased for a large-size diffusive solar cell window. However, there existed a maximum power generation efficiency at around 160 ppm concentration. The optimal design for a large-size diffusion plate inside a diffusive solar cell window by taking indoor lighting into account was suggested based on the simulation results.
Millimeter Wave on Chip Antenna Using Dogbone Shape Artificial Magnetic Conductor
Authors: Luo Guo Qing , Song Zheng Zheng , Zhang Xiao Hong , Hu Xiao Ping
Published: November 2013

An artificial magnetic conductor (AMC) applied in millimeter wave on chip antenna design based on a standard 0.18 μm CMOS technology is studied. The AMC consisting of two-dimensional periodic dogbone shape elements is constructed at one metal layer of the CMOS structure. After its performance has been completely investigated, it has been used in an on chip dipole antenna design as an artificial background to enhance efficiency of the dipole antenna. The result shows that 0.72 dB gain has been achieved at 75 GHz when the AMC is constructed by a 4*6 dogbone array.
Boundedness of Oscillatory Integrals with Variable Calderón-Zygmund Kernel on Weighted Morrey Spaces
Authors: Pan Yali , Li Changwen , Wang Xinsong
Published: November 2013

Oscillatory integral operators play a key role in harmonic analysis. In this paper, the authors investigate the boundedness of the oscillatory singular integrals with variable Calderón-Zygmund kernel on the weighted Morrey spacesLp,k(ω). Meanwhile, the corresponding results for the oscillatory singular integrals with standard Calderón-Zygmund kernel are established.
Use ofFrankiaand Actinorhizal Plants for Degraded Lands Reclamation
Authors: Diagne Nathalie , Arumugam Karthikeyan , Ngom Mariama , Nambiar-Veetil Mathish , Franche Claudine , Narayanan Krishna Kumar , Laplaze Laurent
Published: November 2013

Degraded lands are defined by soils that have lost primary productivity due to abiotic or biotic stresses. Among the abiotic stresses, drought, salinity, and heavy metals are the main threats in tropical areas. These stresses affect plant growth and reduce their productivity. Nitrogen-fixing plants such as actinorhizal species that are able to grow in poor and disturbed soils are widely planted for the reclamation of such degraded lands. It has been reported that association of soil microbes especially the nitrogen-fixing bacteriaFrankiawith these actinorhizal plants can mitigate the adverse effects of abiotic and biotic stresses. Inoculation of actinorhizal plants withFrankiasignificantly improves plant growth, biomass, shoot and root N content, and survival rate after transplanting in fields. However, the success of establishment of actinorhizal plantation in degraded sites depends upon the choice of effective strains ofFrankia. Studies related to the beneficial role ofFrankiaon the establishment of actinorhizal plants in degraded soils are scarce. In this review, we describe some examples of the use ofFrankiainoculation to improve actinorhizal plant performances in harsh conditions for reclamation of degraded lands.
Boosted Rat Natural Xenoantibodies Cross-React with Enterococcus faecalis by Targeting Melibiose and L-Rhamnose
Authors: Perez-Cruz Magdiel , Costa Cristina , Mañez Rafael
Published: November 2013

Natural antibodies include a subset described as xenoantibodies considered to be directed at microorganisms and also cross-react with antigens of unrelated species. In this study, we generated T-cell-independent (TI) and T-cell-dependent (TD) xenoantibodies in Lewis rats with hamster and pig blood injections. TI anti-hamster and anti-pig IgM and IgG xenoantibodies cross-reacted with Enterococcus faecalis but not with Escherichia coli isolated from the blood of Lewis rats after cecal ligation and puncture (CLP). TI anti-pig IgM xenoantibodies also showed some reactivity with two human blood isolates of E. faecalis. In contrast, TD xenoantibodies did not show any reactivity with rat or human bacteria. TI and TD anti-hamster and anti-pig IgM and IgG xenoantibodies showed cross-reactivity with lymphocytes and endothelial cells from species distinct to that used for immunization. Glycan array analysis and inhibition assays identified antibodies against melibiose and L-rhamnose as mediators of anti-hamster and anti-porcine xenoantibody cross-reactivity with E. faecalis. A rise in TI anti-hamster and anti-pig xenoantibodies was accompanied by decreased survival of Lewis rats in a low-severity sepsis model of CLP. Therefore, TI xenoantibodies in the rat include anti-carbohydrate antibodies reactive to bacteria of endogenous flora. Enhancement of these antibodies may result in more severe infectious diseases caused by these microorganisms.
Evaluation of Superficial Oral Squamous Cell Malignancy Based on Morphometry and Immunoexpression of Cytokeratin 13 and Cytokeratin 17
Authors: Yamashina Mitsumasa , Sato Kazumichi , Tonogi Morio , Tanaka Yoichi , Yamane Gen-yuki , Katakura Akira
Published: November 2013

Objective: Evaluation of combined morphometry and immunoexpression of cytokeratin 13 (CK13) and cytokeratin 17 (CK17) for cytological identification of superficial oral squamous cells. Study Design: Smears from 11 tongue squamous cell carcinoma patients were processed by liquid-based cytology, stained via the Papanicolaou method and divided into multiple specimens by cell transfer. Morphometric indices, including nuclear area, nuclear perimeter, nuclear circular rate, largest-to-smallest dimension ratio of the nucleus and nucleocytoplasmic ratio, were measured using a computerized analysis system. CK13 and CK17 were detected by immunostaining. Morphometric values were compared between cell populations with distinct staining and immunoexpression patterns. Results: Most orange G-stained superficial cells were negative for CK13 (99.4%) and CK17 (98.6%). For light green-stained superficial cells, loss of CK13 was associated with greater cellular atypia in the nuclear area, nuclear perimeter and nucleocytoplasmic ratio (p < 0.01), while expression of CK17 was related to higher-grade cellular atypia in the same parameters (p < 0.01) as well as the nuclear circular rate (p < 0.05). Conclusion: Immunoexpression of CK13 and CK17 in light green-stained superficial cells was associated with more severe morphological atypia. Combined morphometry and immunoexpression of CK13 and CK17 might be useful for cytological diagnosis of this cell population.
Methionine Sulfoxide Reductases Protect against Oxidative Stress in Staphylococcus aureus Encountering Exogenous Oxidants and Human Neutrophils
Authors: Pang Yun Yun , Schwartz Jamie , Bloomberg Sarah , Boyd Jeffrey M. , Horswill Alexander R. , Nauseef William M.
Published: November 2013

To establish infection successfully, Staphylococcus aureus must evade clearance by polymorphonuclear neutrophils (PMN). We studied the expression and regulation of the methionine sulfoxide reductases (Msr) that are involved in the repair of oxidized staphylococcal proteins and investigated their influence on the fate of S. aureus exposed to oxidants or PMN. We evaluated a mutant deficient in msrA1 and msrB for susceptibility to hydrogen peroxide, hypochlorous acid and PMN. The expression of msrA1 in wild-type bacteria ingested by human PMN was assessed by real-time PCR. The regulation of msr was studied by screening a library of two-component regulatory system (TCS) mutants for altered msr responses. Relative to the wild-type bacteria, bacteria deficient in Msr were more susceptible to oxidants and PMN. Upregulation of staphylococcal msrA1 occurred within the phagosomes of normal PMN and PMN deficient in NADPH oxidase activity. Furthermore, PMN granule-rich extract stimulated the upregulation of msrA1. Modulation of msrA1 within PMN was shown to be partly dependent on the VraSR TCS. Msr contributes to staphylococcal responses to oxidative attack and PMN. Our study highlights a novel interaction between the oxidative protein repair pathway and the VraSR TCS that is involved in cell wall homeostasis.
Inflammatory Stress Induces Statin Resistance by Disrupting 3-Hydroxy-3-Methylglutaryl-CoA Reductase Feedback Regulation
Authors: Chen Yaxi , Ku Halcyon , Zhao Lei , Wheeler David C. , Li Lung-Chih , Li Qing , Varghese Zac , Moorhead John F. , Powis Stephen H. , Huang Ailong , Ruan Xiong Z.
Published: November 2013

Objective—

The risk of cardiovascular disease is increased by up to 33 to 50× in chronic inflammatory states and convention doses of statins may not provide the same cardiovascular protection as in noninflamed patients. This study investigated whether the increase in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA-R)–mediated cholesterol synthesis observed under inflammatory stress was resistant to the action of statins and if so, whether this was because of interference with the sterol regulatory element binding protein cleavage–activating protein pathway.

Approach and Results—

Inflammatory stress was induced by adding cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6) and lipopolysaccharides to vascular smooth muscle cells in vitro and by subcutaneous casein injection in apolipoprotein E/scavenger receptors class A/CD36 triple knockout mice in vivo. Inflammatory stress exacerbated cholesterol ester accumulation and was accompanied in vitro and in vivo by increased HMGCoA-R mRNA and protein expression mediated via activation of the sterol regulatory element binding protein cleavage–activating protein/sterol regulatory element binding protein-2 pathway. Atorvastatin reduced HMGCoA-R enzymatic activity and intracellular cholesterol synthesis in vitro. However, inflammatory stress weakened these suppressive effects. Atorvastatin at concentrations of 16 μmol/L inhibited HMGCoA-R activity by 50% in vascular smooth muscle cells, but the same concentration resulted in only 30% of HMGCoA-R activity in vascular smooth muscle cells in the presence of interleukin-1β. Knocking down sterol regulatory element binding protein cleavage–activating protein prevented statin resistance induced by interleukin-1β, and overexpression of sterol regulatory element binding protein cleavage–activating protein induced statin resistance even without inflammatory stress. In vivo, the amount of atorvastatin required to lower serum cholesterol and decrease aortic lipid accumulation rose from 2 to 10 mg/kg per day in the presence of inflammatory stress.

Conclusions—

Increased cholesterol synthesis mediated by HMGCoA-R under inflammatory stress may be one of the mechanisms for intracellular lipid accumulation and statin resistance.
Protein S Is a Cofactor for Platelet and Endothelial Tissue Factor Pathway Inhibitor-α but Not for Cell Surface–Associated Tissue Factor Pathway Inhibitor
Authors: Wood Jeremy P. , Ellery Paul E. R. , Maroney Susan A. , Mast Alan E.
Published: November 2013

Objective—

Tissue factor pathway inhibitor (TFPI) is produced in 2 isoforms: TFPIα, a soluble protein in plasma, platelets, and endothelial cells, and TFPIβ, a glycosylphosphatidylinositol-anchored protein on endothelium. Protein S (PS) functions as a cofactor for TFPIα, enhancing the inhibition of factor Xa. However, PS does not alter the inhibition of prothrombinase by TFPIα, and PS interactions with TFPIβ are undescribed. Thus, the physiological role and scope of the PS–TFPI system remain unclear.

Approach and Results—

Here, the cofactor activity of PS toward platelet and endothelial TFPIα and endothelial TFPIβ was quantified. PS enhanced the inhibition of factor Xa by TFPIα from platelets and endothelial cells and stabilized the TFPIα/factor Xa inhibitory complex, delaying thrombin generation by prothrombinase. By contrast, PS did not enhance the inhibitory activity of TFPIβ or a membrane-anchored form of TFPI containing the PS-binding third Kunitz domain (K1K2K3) although PS did function as a cofactor for K1K2K3 enzymatically released from the cell surface.

Conclusions—

The PS–TFPI anticoagulant system is limited to plasma TFPIα and TFPIα released from platelets and endothelial cells. PS likely functions to localize solution-phase TFPIα to the cell surface, where factor Xa is bound. PS does not alter the activity of membrane-associated TFPI. Because activated platelets release TFPIα and PS, the PS–TFPIα anticoagulant system may act physiologically to dampen thrombin generation at the platelet surface.
Preliminary Biomarkers for Identification of Human Ascending Thoracic Aortic Aneurysm
Authors: Black Kendra M. , Masuzawa Akihiro , Hagberg Robert C. , Khabbaz Kamal R. , Trovato Mary E. , Rettagliati Verna M. , Bhasin Manoj K. , Dillon Simon T. , Libermann Towia A. , Toumpoulis Ioannis K. , Levitsky Sidney , McCully James D.
Published: November 2013

Background

Human ascending thoracic aortic aneurysms (
ATAAs
) are life threatening and constitute a leading cause of mortality in the
United States
. Previously, we demonstrated that collagens α2(V) and α1(XI)
mRNA
and protein expression levels are significantly increased in
ATAAs
.

Methods and Results

In this report, the authors extended these preliminary studies using high‐throughput proteomic analysis to identify additional biomarkers for use in whole blood real‐time
RT
‐
PCR
analysis to allow for the identification of
ATAAs
before dissection or rupture. Human
ATAA
samples were obtained from male and female patients aged 65±14 years. Both bicuspid and tricuspid aortic valve patients were included and compared with nonaneurysmal aortas (mean diameter 2.3 cm). Five biomarkers were identified as being suitable for detection and identification of
ATAAs
using q
RT
‐
PCR
analysis of whole blood. Analysis of 41 samples (19 small, 13 medium‐sized, and 9 large
ATAAs
) demonstrated the overexpression of 3 of these transcript biomarkers correctly identified 79.4% of patients with
ATAA
of ≥4.0 cm (
P
<0.001, sensitivity 0.79,
CI
=0.62 to 0.91; specificity 1.00, 95%
CI
=0.42 to 1.00).

Conclusion

A preliminary transcript biomarker panel for the identification of
ATAAs
using whole blood q
RT
‐
PCR
analysis in men and women is presented.
Protective Effect of Time Spent Walking on Risk of Stroke in Older Men
Authors: Jefferis Barbara J. , Whincup Peter H. , Papacosta Olia , Wannamethee S. Goya
Published: November 2013

Background and Purpose—

Older adults have the highest risks of stroke and the lowest physical activity levels. It is important to quantify how walking (the predominant form of physical activity in older age) is associated with stroke.

Methods—

A total of 4252 men from a UK population-based cohort reported usual physical activity (regular walking, cycling, recreational activity, and sport) in 1998 to 2000. Nurses took fasting blood samples and made anthropometric measurements.

Results—

Among 3435 ambulatory men free from cardiovascular disease and heart failure in 1998 to 2000, 195 first strokes occurred during 11-year follow-up. Men walked a median of 7 (interquartile range, 3–12) hours/wk; walking more hours was associated with lower heart rate, D-dimer, and higher forced expiratory volume in 1 second. Compared with men walking 0 to 3 hours/wk, men walking 4 to 7, 8 to 14, 15 to 21, and >22 hours had age- and region-adjusted hazard ratios (95% confidence intervals) for stroke of 0.89 (0.60–1.31), 0.63 (0.40–1.00), 0.68 (0.35–1.32), and 0.36 (0.14–0.91), respectively,
P
(trend)=0.006. Hazard ratios were somewhat attenuated by adjustment for established and novel risk markers (inflammatory and hemostatic markers and cardiac function [N-terminal pro-brain natriuretic peptide]) and walking pace, but linear trends remained. There was little evidence for a dose–response relationship between walking pace and stroke; comparing average pace or faster to a baseline of slow pace, the hazard ratio for stroke was 0.65 (95% confidence interval, 0.44–0.97), which was fully mediated by time spent walking.

Conclusions—

Time spent walking was associated with reduced risk of onset of stroke in dose–response fashion, independent of walking pace. Walking could form an important part of stroke-prevention strategies in older people.
Time to Brain Imaging in Acute Stroke Is Improving
Authors: Sauser Kori , Burke James F. , Levine Deborah A. , Scott Phillip A. , Meurer William J.
Published: November 2013

Background and Purpose—

Patients with acute ischemic stroke benefit from rapid evaluation and treatment, and timely brain imaging is a necessary component. We determined the effect of a targeted behavioral intervention on door-to-imaging time (DIT) among patients with ischemic stroke treated with tissue-type plasminogen activator. Second, we examined the variation in DIT accounted for by patient-level and hospital-level factors.

Methods—

The Increasing Stroke Treatment through Interventional behavioral Change Tactics (INSTINCT) trial was a cluster-randomized, controlled trial involving 24 Michigan hospitals. The intervention aimed to increase tissue-type plasminogen activator utilization. Detailed chart abstractions collected data for 557 patients with ischemic stroke. We used a series of hierarchical linear mixed-effects models to evaluate the effect of the intervention on DIT (difference-in-differences analysis) and used patient-level and hospital-level explanatory variables to decompose variation in DIT.

Results—

DIT improved over time, without a difference between intervention and control hospitals (intervention: 23.7–19.3 minutes, control: 28.9–19.2 minutes;
P
=0.56). Adjusted DIT was faster in patients who arrived by ambulance (7.2 minutes; 95% confidence interval, 4.1–10.2), had severe strokes (1.0 minute per +5-point National Institutes of Health Stroke Scale; 95% confidence interval, 0.1–2.0), and presented in the postintervention period (4.9 minutes; 95% confidence interval, 2.3–7.4). After accounting for these factors, 13.8% of variation in DIT was attributable to hospital. Neither hospital stroke volume nor stroke center status was associated with DIT.

Conclusions—

Performance on DIT improved similarly in intervention and control hospitals, suggesting that nonintervention factors explain the improvement. Hospital-level factors explain a modest proportion of variation in DIT, but further research is needed to identify the hospital-level factors responsible.
Zonal Gradients in the Lower Atmosphere and Upper Ocean across the Windward Antilles during Midsummer 2012
Authors: Jury Mark R.
Published: November 2013

This observational study examines zonal gradients in the lower atmosphere and upper ocean across the windward Antilles during midsummer 2012. While earlier work reported on meridional confluence, here the focus is on the zonal enrichment of trade winds by upstream shallow seas and islands. Intercomparisons along 18.2°N are made between modern reanalysis and satellite estimates, and coastal station, moored buoy, aircraft, and radiosonde observations for one case and as a June–July 2012 average. Mean gradients per 100 km east of Puerto Rico were 0.2 g kg−1 for 925-hPa specific humidity, 0.16°C for SST, 0.01 m for sea level, and 2.0 × 10−3 g kg−1 for cloud water. Zonal changes in the lower atmosphere occur in three stages: 1) Atlantic, where westward ocean currents, strong trade winds, and subsidence prevail; 2) Antilles, where ocean currents diminish and sea temperatures increase; and 3) island, where trade winds abate [−1 m s−1 (100 km)−1] and diurnal evapotranspiration greater than 10 mm day−1 offsets large-scale subsidence producing a localized convection.
Probability of Convectively Induced Turbulence Associated with Geostationary Satellite–Inferred Cloud-Top Cooling
Authors: Monette Sarah A. , Sieglaff Justin M.
Published: November 2013

The probability of turbulence in the region of identified cloud-top cooling (CTC) from a satellite-based algorithm is calculated. It is found that the overall turbulence probability is low, with only 3.93% of 738 Boeing 737s and 757s experiencing light or greater turbulence. Predicting the probability of turbulence is done using a Bayesian scheme. This prediction scheme relies on the CTC magnitude as well as the relationship between the CTC and aircraft. At higher CTC magnitudes [≤−16 K (15 min)−1], turbulence is more common, with the conditional probability of turbulence exceeding the conditional probability of no turbulence. Aircraft with flight levels that are less than 8000 ft (~2440 m) above the cloud height also have a higher conditional probability of turbulence than no turbulence. Overall, the Bayesian scheme is found to be more skillful when compared with use of climatological information alone.
Performance properties of biocomposites from renewable natural resource
Authors: Avci Erkan , Candan Zeki , Gonultas Oktay
Published: November 2013

Hazelnut husk is widely available as a biowaste in the northeast of Turkey. In this study, biocomposites were manufactured using hazelnut husk, polypropylene, and coupling agent. Density, thickness swelling, water absorption, modulus of rupture, modulus of elasticity, tensile strength, tensile modulus, and elongation at break tests were carried out to determine its performance properties. The results obtained in this study indicated that the performance properties of the biocomposites manufactured from hazelnut husk could be comparable to neat PP composites. The biowaste-loading level positively affected the modulus properties of the biocomposites. It could be concluded that the hazelnut husk could be used as an alternative raw material to produce new biocomposites so that biowaste could be recycled. It can also help sustainable protection of nature.
The “Silent Majority” in Black and White
Authors: Fortner Michael Javen
Published: November 2013

Over the past decade, mass incarceration has received much scholarly attention from historians, social scientists, and legal scholars. Despite the substantive contributions of this research, the overreliance on functionalist and top–down political explanations has undermined its descriptive force and explanatory power. Many accounts fold the peculiarities and nuances of the “law and order” discourse of the late 1960s and early 1970s—the period during which the seeds of mass incarceration were sown—into neat, imprecise narratives that render black politics invisible and relegate white politics to the stifling abyss of whiteness. Consequently, in order to understand the miscellany of law and order concerns and identify the role African Americans played in the construction of this discourse, this essay returns to the social and cultural context of the late 1960s and early 1970s. It situates the cultural concepts of law and order within local contexts in order to excavate their meanings, relative importance, and relationships. It describes the “black silent majority” and argues that the individual components of law and order were united by class considerations rather than racial motivations.
Inconclusive Evidence for Allergic Rhinitis to Predict a Prolonged or Chronic Course of Acute Rhinosinusitis
Authors: Frerichs Kristine A. , Nigten Gea , Romeijn Kalynda , Kaper Nina M. , Grolman Wilko , van der Heijden Geert J. M. G.
Published: November 2013

Objective

To systematically review the evidence on allergic rhinitis as a predictor for a prolonged or chronic course in adult patients with acute rhinosinusitis.

Data Sources

Pubmed, EMBASE, and the Cochrane library.

Review Methods

A systematic literature search was performed on March 15, 2013. During screening of title and abstract, 3 authors independently selected studies on allergic rhinitis as a predictor for the course of acute rhinosinusitis in adults. The reported study design was assessed for directness of evidence and risk of bias. We aimed to extract prior and posterior probabilities for a prolonged or chronic course of acute rhinosinusitis.

Results

Of 13,202 retrieved articles, 2 articles were eligible for study assessment. They provided a high directness of evidence but carried a high risk of bias. The studies showed an incidence of a prolonged and chronic course of, respectively,. 19 (95% confidence interval [CI]. 16‐.23) and. 05 (95% CI,. 02‐.13). In patients with allergic rhinitis, the incidence was. 25 (95% CI,. 18‐.35) and. 14 (95% CI,. 04‐.34), so the added value of allergic rhinitis to predict a prolonged course is 6% and to predict a chronic course 8%.

Conclusion and Recommendation

While the 2 included studies suggest that allergic rhinitis adds little to the prediction of a prolonged or chronic course in patients with acute rhinosinusitis, they carry a high risk of bias. As the available evidence does not provide grounds for different management of patients with and without allergic rhinitis, namely, according to clinical practice guidelines, both can be managed with expectant observation and symptomatic treatment.
Dexamethasone Otoprotection in a Multidose Cisplatin Ototoxicity Mouse Model
Authors: Hughes Amy Lawrason , Hussain Nighat , Pafford Ryan , Parham Kourosh
Published: November 2013

Objective

To develop a murine model for multidose administration of cisplatin that produces significant hearing threshold elevations and to use this model to assess the protective properties of intratympanic (IT) dexamethasone against cisplatin ototoxicity.

Study Design

Controlled repeated measures design.

Setting

Translational research laboratory.

Subjects and Methods

Intraperitoneal (IP) cisplatin, 2 or 3 mg/kg/day, was administered for a total of 5 or 10 days in young CBA/J mice. Pure‐tone evoked auditory brainstem response (ABR) thresholds were performed on days 7, 14, 21, and 28 to evaluate hearing threshold shifts. After development of the optimal dosing regimen, 15 mice received IT dexamethasone (24 mg/ml) in one ear and IT saline in the contralateral ear.

Results

Significant threshold elevations were obtained for the 2 and 3 mg/kg/day 10 day groups, but both had high mortality rates and were excluded as potential multidose murine models. The 3 mg/kg/day 5 day group had a lower mortality rate and significant ABR threshold elevations for all frequencies on days 7, 14, 21, and 28. Using this dosing model, no statistically significant difference between IT dexamethasone and saline treated ears was found.

Conclusions

Unlike previous single dose models, IT dexamethasone did not have an otoprotective effect in a multidose murine model of cisplatin ototoxicity.
Applications of Pathology-Assisted Image Analysis of Immunohistochemistry-Based Biomarkers in Oncology
Authors: Shinde V. , Burke K. E. , Chakravarty A. , Fleming M. , McDonald A. A. , Berger A. , Ecsedy J. , Blakemore S. J. , Tirrell S. M. , Bowman D.
Published: November 2013

Immunohistochemistry-based biomarkers are commonly used to understand target inhibition in key cancer pathways in preclinical models and clinical studies. Automated slide-scanning and advanced high-throughput image analysis software technologies have evolved into a routine methodology for quantitative analysis of immunohistochemistry-based biomarkers. Alongside the traditional pathology H-score based on physical slides, the pathology world is welcoming digital pathology and advanced quantitative image analysis, which have enabled tissue- and cellular-level analysis. An automated workflow was implemented that includes automated staining, slide-scanning, and image analysis methodologies to explore biomarkers involved in 2 cancer targets: Aurora A and NEDD8-activating enzyme (NAE). The 2 workflows highlight the evolution of our immunohistochemistry laboratory and the different needs and requirements of each biological assay. Skin biopsies obtained from MLN8237 (Aurora A inhibitor) phase 1 clinical trials were evaluated for mitotic and apoptotic index, while mitotic index and defects in chromosome alignment and spindles were assessed in tumor biopsies to demonstrate Aurora A inhibition. Additionally, in both preclinical xenograft models and an acute myeloid leukemia phase 1 trial of the NAE inhibitor MLN4924, development of a novel image algorithm enabled measurement of downstream pathway modulation upon NAE inhibition. In the highlighted studies, developing a biomarker strategy based on automated image analysis solutions enabled project teams to confirm target and pathway inhibition and understand downstream outcomes of target inhibition with increased throughput and quantitative accuracy. These case studies demonstrate a strategy that combines a pathologist’s expertise with automated image analysis to support oncology drug discovery and development programs.
Toll-like receptor 4 gene polymorphism 1196 C/T does not influence the risk of neuropsychiatric systemic lupus erythematosus in Polish population – a preliminary report
Authors: Bogaczewicz A , Sobow T , Bogaczewicz J , Kaleta B , Sysa-Jedrzejowska A , Robak E , Lukaszkiewicz J , Dariusz S , Wozniacka A
Published: November 2013

Objective

Recent data indicate that Toll-like receptors (TLRs) participate in various neuropathologic conditions, including ictogenesis, myelin disruptions associated with chronic alcohol abuse, behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage, and activation of microglia to reduce amyloid β deposits. As seizures and depression are well known neuropsychiatric syndromes in systemic lupus erythematosus (SLE) the aim of the study was to investigate whether TLR4 gene polymorphism 1196C/T (rs4986791, Thr399Ile) was a candidate for susceptibility of development of neuropsychiatric systemic lupus erythematosus (NPSLE).

Methods

The study covered 60 patients with SLE and 100 healthy individuals. TLR4 1196C/T genotyping was performed by real-time polymerase chain reaction with the SimpleProbe.

Results

The SLE group comprised 86.7% of patients with wild-type homozygotes CC and 13.3% heterozygotes CT and no homozygotes TT. The control group consisted of 85% wild-type homozygotes CC, 15% heterozygotes CT and no homozygotes TT. The frequencies of genotype and allele distribution in SLE patients did not differ significantly from those of the control subjects. The probability of describing the possible risk of SLE imputed to genotype did not significantly differ in comparison with the healthy individuals ( p = 0.77, odds ratio = 0.87, 95% confidence interval 0.34–2.19). A significant genotype association of genotype CC with arthritis was found in SLE patients ( p = 0.02). It was further confirmed by a significant association of a dominant allele C with arthritis ( p = 0.02). No association between CC and CT genotypes of TLR4 1196C/T and NPSLE was found. Allele distribution of TLR4 1196C/T also was not associated with NPSLE. No other significant differences were found in genotype and allele frequencies regarding clinical manifestation of SLE patients.

Conclusion

In the Polish population of SLE patients, 1196C/T polymorphism of TLR4 gene does not increase the risk of development of NPSLE; however, genotype CC and a dominant allele C is associated with arthritis in the course of SLE.
Headache in the writings of Elizabeth Gaskell (1810–1865)
Authors: Larner AJ
Published: November 2013

Mrs Elizabeth Gaskell was a celebrated author of the Victorian era, a friend of both Charles Dickens and Charlotte Brontë and the latter’s first biographer. References to headache in Mrs Gaskell’s six major novels, published between 1848 and 1866 as well as some of her shorter fiction, have been collated. These multiple references suggest that Elizabeth Gaskell used headache as a narrative device, possibly based on her own experience of headache and that of female acquaintances, most notably Charlotte Brontë.
Clustering of 316 European Regions on Measures of Values
Authors: Minkov Michael , Hofstede Geert
Published: November 2013

The use of nations as units of analysis in cross-cultural studies is a controversial approach as nations may not be culturally homogeneous. However, a recent study by Minkov and Hofstede found that African, Asian, Latin American, and Anglo in-country regions tended to form homogeneous and distinct national clusters on World Values Survey (WVS) items. We extend this research to European regions, as well as randomly formed nationally homogeneous groups of European respondents, using value measures from the 2010 European Social Survey (ESS). We find that the regions of most European countries, as well as the randomly formed groups, tend to group into national clusters. We also find that large samples of randomly chosen individuals from diverse nations cannot be sorted into nations. Our findings have theoretical implications for the conceptualization of culture as something shared at the group level rather than the individual.
On (Not) Practicing What We Preach
Authors: Francis Ara , Bakehorn Jill
Published: November 2013

What should sociologists do when their everyday lives are at odds with their sociological values? Authors Ara Francis and Jill Bakehorn examine the contradictions that stem from trying to live sociologically and consider how scholars might put personal inconsistencies to good use.
Multidimensional approach to non-cystic fibrosis bronchiectasis: the FACED score
Authors: Martínez-García Miguel Á. , de Gracia Javier , Vendrell Relat Monserrat , Girón Rosa-Maria , Máiz Carro Luis , de la Rosa Carrillo David , Olveira Casilda
Published: November 2013

Bronchiectasis is a multidimensional disease and, therefore, its severity or prognosis cannot be adequately quantified by analysing one single variable. The objective of the present study was to develop a multidimensional score that classifies the severity of bronchiectasis according to its prognosis.

This is an observational multicentre study including 819 patients diagnosed with non-cystic fibrosis bronchiectasis using high-resolution computed tomography. 397 subjects were selected at random to construct the score while the remaining 422 were used for its validation. The outcome was 5-year all-cause mortality after radiological diagnosis. A logistic regression analysis was used to select the variables included in the final score.

The final seven-point score incorporated five dichotomised variables: forced expiratory volume in 1 s % predicted (F, cut-off 50%, maximum value 2 points); age (A, cut-off 70 years, maximum value 2 points); presence of chronic colonisation byPseudomonas aeruginosa(C, dichotomic, maximum value 1 point); radiological extension (E, number of lobes affected, cut-off two lobes, maximum value 1 point); and dyspnoea (D, cut-off grade II on the Medical Research Council scale, maximum value 1 point) to construct the FACED score. The validation cohort confirmed the score’s validity.

We conclude that this easy-to-use multidimensional grading system proved capable of accurately classifying the severity of bronchiectasis according to its prognosis.
emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension
Authors: Yorke Janelle , Corris Paul , Gaine Sean , Gibbs J. Simon R. , Kiely David G. , Harries Carl , Pollock Val , Armstrong Iain
Published: November 2013

The aim of this study was to develop a measure of the impact of pulmonary hypertension (PH) on health-related quality of life (HRQoL) as there is a need for a short, validated instrument that can be used in routine clinical practice.

Interviews were conducted with 30 PH patients to derive 32 statements, which were presented as a semantic differential six-point scale (0–5), with contrasting adjectives at each end. This item list was completed by patients attending PH clinics across the UK and Ireland. Rasch analysis was applied to identify items fitting a uni-dimensional model.

226 patients (mean age 55.6±14 years; 70% female) with PH (82% had pulmonary arterial hypertension) completed the study questionnaires. 10 of the 32 items demonstrated fit to the Rasch model (Chi-squared 16; p>0.05) and generated the emPHasis-10 questionnaire. Test–retest (intraclass correlation coefficient 0.95, n=33) and internal consistency (Chronbach’s α=0.9) were strong. emPHasis-10 scores correlated consistently with other relevant measures and discriminated subgroups of patients stratified by World Health Organization functional class (ANOVA F=1.73; p<0.001).

The emPHasis-10 is a short questionnaire for assessing HRQoL in pulmonary arterial hypertension. It has excellent measurement properties and is sensitive to differences in relevant clinical parameters. It is freely available for clinical and academic use.