bluuebunny/crossref_metadata_2025 huggingface dataset:
Weibull Distribution Function for Wind Energy Estimation of Gharo (Sindh)
Authors: Muhammad Shoaib  , Imran Siddiqui  , Firoz Ahmed  , Saif ur Rehman  , Muhammad Rashid Tanveer  , Saif Uddin Jilani
Published: February 2015

Weibull distribution function is fitted to a measured wind speed data set at mast height of 30 m and Gharo-Sindh (Pakistan) is selected as a case site under study. Wind speed data recorded in one minute interval for the year 2004 is used to estimate Weibull parameters (k and c). Weibull parameters are calculated using Modified Maximum Likelihood Method (MMLM), Maximum likelihood Method (MLM) and Method of Moment (MoM) and the results obtained are compared. Kolomogorov-Smirnov test, Root Mean Square Error (RMSE) and R2 tests are performed to test the goodness-of-fit of the Weibull distribution function. The analysis is based on recorded monthly and yearly wind speed data. Goodness-of-fit tests indicate a better performance of MMLM and MLM as compared to MoM. Wind power density is estimated for the site under study using MMLM and Weibull function estimator. A lowest Weibull mean wind speed of 3.73 m/s in the month of October and highest value of 7.90 m/s for August are observed and correspondingly power densities of 80.95 W/m2 and 425.87 W/m2 are obtained. Descriptive statistics for the measured wind speed data is also evaluated.
Duration and Magnitude of Myofascial Release in 3-Dimensional Bioengineered Tendons: Effects on Wound Healing
Authors: Cao Thanh V. , Hicks Michael R. , Zein-Hammoud Manal , Standley Paul R.
Published: February 2015

Context:Myofascial release (MFR) is one of the most commonly used manual manipulative treatments for patients with soft tissue injury. However, a paucity of basic science evidence has been published to support any particular mechanism that may contribute to reported clinical efficacies of MFR.

Objective:To investigate the effects of duration and magnitude of MFR strain on wound healing in bioengineered tendons (BETs) in vitro.

Methods:The BETs were cultured on a deformable matrix and then wounded with a steel cutting tip. Using vacuum pressure, they were then strained with a modeled MFR paradigm. The duration of MFR dose consisted of a slow-loading strain that stretched the BETs 6% beyond their resting length, held them for 0, 1, 2, 3, 4, or 5 minutes, and then slowly released them back to baseline. To assess the effects of MFR magnitude, the BETs were stretched to 0%, 3%, 6%, 9%, or 12% beyond resting length, held for 90 seconds, and then released back to baseline. Repeated measures of BET width and the wound's area, shape, and major and minor axes were quantified using microscopy over a 48-hour period.

Results:An 11% and 12% reduction in BET width were observed in groups with a 9% (0.961 mm;P<.01) and 12% (0.952 mm;P<.05) strain, respectively. Reduction of the minor axis of the wound was unrelated to changes in BET width. In the 3% strain group, a statistically significant decrease (−40%;P<.05) in wound size was observed at 24 hours compared with 48 hours in the nonstrain, 6% strain, and 9% strain groups. Longer duration of MFR resulted in rapid decreases in wound size, which were observed as early as 3 hours after strain.

Conclusion:Wound healing is highly dependent on the duration and magnitude of MFR strain, with a lower magnitude and longer duration leading to the most improvement. The rapid change in wound area observed 3 hours after strain suggests that this phenomenon is likely a result of the modification of the existing matrix protein architecture. These data suggest that MFR's effect on the extracellular matrix can potentially promote wound healing.
Seismic observation of an extremely magmatic accretion at the ultraslow spreading Southwest Indian Ridge
Authors: Li Jiabiao , Jian Hanchao , Chen Yongshun John , Singh Satish C. , Ruan Aiguo , Qiu Xuelin , Zhao Minghui , Wang Xianguang , Niu Xiongwei , Ni Jianyu , Zhang Jiazheng
Published: February 2015

The oceanic crust is formed by a combination of magmatic and tectonic processes at mid‐ocean spreading centers. Under ultraslow spreading environment, however, observations of thin crust and mantle‐derived peridotites on the seafloor suggest that a large portion of crust is formed mainly by tectonic processes, with little or absence of magmatism. Using three‐dimensional seismic tomography at an ultraslow spreading Southwest Indian Ridge segment containing a central volcano at 50°28′E, here we report the presence of an extremely magmatic accretion of the oceanic crust. Our results reveal a low‐velocity anomaly (−0.6 km/s) in the lower crust beneath the central volcano, suggesting the presence of partial melt, which is accompanied by an unusually thick crust (~9.5 km). We also observe a strong along‐axis variation in crustal thickness from 9.5 to 4 km within 30–50 km distance, requiring a highly focused melt delivery from the mantle. We conclude that the extremely magmatic accretion is due to localized melt flow toward the central volcano, which was enhanced by the significant along‐axis variation in lithosphere thickness at the ultraslow spreading Southwest Indian Ridge.
Investigation of scaling properties of a thin current sheet by means of particle trajectories study
Authors: Sasunov Yu. L. , Khodachenko M. L. , Alexeev I. I. , Belenkaya E. S. , Semenov V. S. , Kubyshkin I. V. , Mingalev O. V.
Published: February 2015

A thin current sheet (TCS), with the width of an order of thermal proton gyroradius, appears a fundamental physical object which plays an important role in structuring of major magnetospheric current systems (magnetotail, magnetodisk, etc.). The TCSs are nowadays under extensive study by means of space missions and theoretical models. We consider a simple model of the TCS separating two half‐spaces occupied by a homogenous magnetic field of opposite sign tangential to the TCS; a small normal component of the magnetic field is prescribed. An analytical solution for the electric current and plasma density in the close vicinity of the TCS has been obtained and compared with numerical simulation. The number density and the electric current profiles have two maxima each. The characteristic spatial scale zS of the maxima location was investigated as a function of initial pitch angle of an incoming charge particle. The effect of the thermal dispersion of the incoming proton beam have been taken into consideration.
New fully kinetic model for the study of electric potential, plasma, and dust above lunar landscapes
Authors: Dyadechkin S. , Kallio E. , Wurz P.
Published: February 2015

We have developed a new fully kinetic electrostatic simulation, HYBes, to study how the lunar landscape affects the electric potential and plasma distributions near the surface and the properties of lifted dust. The model embodies new techniques that can be used in various types of physical environments and situations. We demonstrate the applicability of the new model in a situation involving three charged particle species, which are solar wind electrons and protons, and lunar photoelectrons. Properties of dust are studied with test particle simulations by using the electric fields derived from the HYBes model. Simulations show the high importance of the plasma and the electric potential near the surface. For comparison, the electric potential gradients near the landscapes with feature sizes of the order of the Debye length are much larger than those near a flat surface at different solar zenith angles. Furthermore, dust test particle simulations indicate that the landscape relief influences the dust location over the surface. The study suggests that the local landscape has to be taken into account when the distributions of plasma and dust above lunar surface are studied. The HYBes model can be applied not only at the Moon but also on a wide range of airless planetary objects such as Mercury, other planetary moons, asteroids, and nonactive comets.
Seasonal evolution of an ice‐shelf influenced fast‐ice regime, derived from an autonomous thermistor chain
Authors: Hoppmann M. , Nicolaus M. , Hunkeler P. A. , Heil P. , Behrens L.‐K. , König‐Langlo G. , Gerdes R.
Published: February 2015

Ice shelves strongly interact with coastal Antarctic sea ice and the associated ecosystem by creating conditions favorable to the formation of a sub‐ice platelet layer. The close investigation of this phenomenon and its seasonal evolution remains a challenge due to logistical constraints and a lack of suitable methodology. In this study, we characterize the seasonal cycle of Antarctic fast ice adjacent to the Ekström Ice Shelf in the eastern Weddell Sea. We used a thermistor chain with the additional ability to record the temperature response induced by cyclic heating of resistors embedded in the chain. Vertical sea‐ice temperature and heating profiles obtained daily between November 2012 and February 2014 were analyzed to determine sea‐ice and snow evolution, and to calculate the basal energy budget. The residual heat flux translated into an ice‐volume fraction in the platelet layer of 0.18 ± 0.09, which we reproduced by a independent model simulation and agrees with earlier results. Manual drillings revealed an average annual platelet‐layer thickness increase of at least 4 m, and an annual maximum thickness of 10 m beneath second‐year sea ice. The oceanic contribution dominated the total sea‐ice production during the study, effectively accounting for up to 70% of second‐year sea‐ice growth. In summer, an oceanic heat flux of 21 W m−2 led to a partial thinning of the platelet layer. Our results further show that the active heating method, in contrast to the acoustic sounding approach, is well suited to derive the fast‐ice mass balance in regions influenced by ocean/ice‐shelf interaction, as it allows subdiurnal monitoring of the platelet‐layer thickness.
Modeled alongshore circulation and force balances onshore of a submarine canyon
Authors: Hansen Jeff E. , Raubenheimer Britt , List Jeffrey H. , Elgar Steve
Published: February 2015

Alongshore force balances, including the role of nonlinear advection, in the shoaling and surf zones onshore of a submarine canyon are investigated using a numerical modeling system (Delft3D/SWAN). The model is calibrated with waves and alongshore flows recorded over a period of 1.5 months at 26 sites along the 1.0, 2.5, and 5.0 m depth contours spanning about 2 km of coast. Field observation‐based estimates of the alongshore pressure and radiation‐stress gradients are reproduced well by the model. Model simulations suggest that the alongshore momentum balance is between the sum of the pressure and radiation‐stress gradients and the sum of the nonlinear advective terms and bottom stress, with the remaining terms (e.g., wind stress and turbulent mixing) being negligible. The simulations also indicate that unexplained residuals in previous field‐based estimates of the momentum balance may be owing to the neglect of the nonlinear advective terms, which are similar in magnitude to the sum of the forcing (pressure and radiations stress gradients) and to the bottom stress.
Intercomparison of total precipitable water measurements made by satellite‐borne microwave radiometers and ground‐based GPS instruments
Authors: Mears Carl A. , Wang Junhong , Smith Deborah , Wentz Frank J.
Published: February 2015

High‐quality, high temporal resolution measurements of total precipitable water (TPW) can be made by evaluating the vapor‐dependent delay of radio signals reaching land‐based Global Positioning System (GPS) receivers from GPS satellites. These measurements are available since the mid‐1990s when the GPS system became operational. Over the world's oceans, satellite‐borne microwave imaging radiometers have been making measurements of TPW for more than 25 years. In this work, we perform an intercomparison of collocated TPW measurements made by these two disparate systems using measurements from 26 GPS stations located on small islands. The two types of measurements agree well, with typical satellite‐station mean differences of less than 1.0 kg m−2. Analysis revealed several cases of inhomogeneities in the GPS data set, and two deficiencies in the Remote Sensing Systems satellite data, demonstrating the usefulness of intercomparison for improving the accuracy of both types of data. After the individual station, biases were removed, the standard deviation of the overall differences between individual satellites and GPS measurements ranged between 1.60 and 1.94 kg m−2. Twelve GPS stations had overlap time periods long enough to evaluate difference trends, yielding 59 satellite‐station pairs when paired with different satellites. More than half of the pairs (39 of 59) did not show a significant trend. The 20 pairs with significant trends did not show trends of predominantly one sign, suggesting that neither system is plagued by a system‐wide drift in TPW.
Sulfuric acid nucleation: An experimental study of the effect of seven bases
Authors: Glasoe W. A. , Volz K. , Panta B. , Freshour N. , Bachman R. , Hanson D. R. , McMurry P. H. , Jen C.
Published: February 2015

Nucleation of particles with sulfuric acid, water, and nitrogeneous bases was studied in a flow reactor. Sulfuric acid and water levels were set by flows over sulfuric acid and water reservoirs, respectively, and the base concentrations were determined from measured permeation rates and flow dilution ratios. Particle number distributions were measured with a nano‐differential‐mobility‐analyzer system. Results indicate that the nucleation capability of NH3, methylamine, dimethylamine, and trimethylamine with sulfuric acid increases from NH3 as the weakest, methylamine next, and dimethylamine and trimethylamine the strongest. Three other bases were studied, and experiments with triethylamine showed that it is less effective than methylamine, and experiments with urea and acetamide showed that their capabilities are much lower than the amines with acetamide having basically no effect. When both NH3 and an amine were present, nucleation was more strongly enhanced than with just the amine present. Comparisons of nucleation rates to predictions and previous experimental work are discussed, and the sulfuric acid‐base nucleation rates measured here are extrapolated to atmospheric conditions. The measurements suggest that atmospheric nucleation rates are significantly affected by synergistic interactions between ammonia and amines.
Multiyear ice replenishment in the Canadian Arctic Archipelago: 1997–2013
Authors: Howell Stephen E. L. , Derksen Chris , Pizzolato Larissa , Brady Michael
Published: February 2015

In the Canadian Arctic Archipelago (CAA), multiyear ice (MYI) replenishment from first‐year ice aging (CAAMYI‐Oct‐1) and Arctic Ocean MYI exchange (CAAMYI‐exchange) contribute to the CAA's relatively heavy sea ice conditions at the end of the summer melt season. We estimate these components using RADARSAT and the Canadian Ice Service Digital Archive and explore processes responsible for interannual variability from 1997 to 2013. CAAMYI‐Oct‐1 (52 ± 36 × 103 km2) provides a larger contribution than CAAMYI‐exchange (13 ± 11 × 103 km2). CAAMYI‐Oct‐1 represents ∼10% of the amount that occurs in the Arctic Ocean. CAAMYI‐exchange represents ∼50% of Nares Strait MYI export to Baffin Bay and ∼12% of Fram Strait MYI export to the Greenland Sea. CAAMYI‐Oct‐1 exhibits dependence on warmer (cooler) summers that increase (decrease) melt evident from strong relationships to surface air temperature (SAT), albedo and total absorbed solar radiation (Qtotal). CAAMYI‐exchange is influenced by summer sea level pressure (SLP) anomalies over the Beaufort Sea and Canadian Basin which shifts the primary source of CAAMYI‐exchange between less obstructed M'Clure Strait (low SLP anomalies) and the more obstructed Queen Elizabeth Islands (high SLP anomalies). Over the 17‐record, appreciable replenishment occurred for most years from 1997 to 2004, reduced replenishment from 2005 to 2012, and large replenishment in 2013. The reduced replenishment period was associated with positive SAT, negative albedo, and positive Qtotal anomalies that facilitated more melt and less CAAMYI‐Oct‐1, together with high SLP anomalies that facilitated less CAAMYI‐exchange. Large replenishment in 2013 was primarily from CAAMYI‐Oct‐1 attributed to strongly negative SAT and Qtotal anomalies and strongly positive albedo that impeded melt.
Rapid Self‐Assembly of Macroscale Tissue Constructs at Biphasic Aqueous Interfaces
Authors: Frampton John P. , Leung Brendan M. , Bingham Eve L. , Lesher‐Perez Sasha Cai , Wang Jack D. , Sarhan Hady T. , El‐Sayed Mohamed E. H. , Feinberg Stephen E. , Takayama Shuichi
Published: February 2015

An entirely new approach to tissue engineering is presented that uses the interfacial forces between aqueous solutions of phase‐separating polymers to confine cells and promote their assembly into interconnected, macroscopic tissue constructs. This simple and inexpensive general procedure creates free‐standing, centimeter‐scale constructs from cell suspensions at the interface between poly(ethylene glycol) and dextran aqueous two‐phase systems in as little as 2 h. Using this method, skin constructs are produced that integrate with decellularized dermal matrices, on which they differentiate and stratify into skin equivalents. It is demonstrated that the constructs produced by this method have appropriate integrity and mechanical properties for use as in vitro tissue models.
Organic/Inorganic Hybrid Nanochannels Based on Polypyrrole‐Embedded Alumina Nanopore Arrays: pH‐ and Light‐Modulated Ion Transport
Authors: Zhang Qianqian , Liu Zhaoyue , Wang Kefeng , Zhai Jin
Published: February 2015

Inspired by the asymmetric structure and responsive ion transport in biological ion channels, organic/inorganic hybrid artificial nanochannels exhibiting pH‐modulated ion rectification and light‐regulated ion flux have been constructed by introducing conductive polymer into porous nanochannels. The hybrid nanochannels are achieved by partially modifying alumina (Al2O3) nanopore arrays with polypyrrole (PPy) layer using electrochemical polymerization, which results in an asymmetric component distribution. The protonation and deprotonation of Al2O3 and PPy upon pH variation break the surface charge continuity, which contributes to the pH‐tunable ion rectification. The ionic current rectification ratio is affected substantially by the pH value of electrolyte and the pore size of nanochannels. Furthermore, the holes (positive charges) in PPy layer induced by the cooperative effect of light and protons are used to regulate the ionic flux through the nanochannels, which results in a light‐responsive ion current. The magnitude of responsive ionic current could be amplified by optimizing this cooperation. This new type of stimuli‐responsive PPy/Al2O3 hybrid nanochannels features advantages of unique optical and electric properties from conducting PPy and high mechanical performance from porous Al2O3 membrane, which provide a platform for creating smart nanochannels system.
Synthesis of a Molecularly Imprinted Polymer for Melamine Analysis in Milk by HPLC with Diode Array Detection
Authors: Figueiredo Leandro , Santos Lúcia , Alves Arminda
Published: February 2015

A molecularly imprinted polymer (MIP) for melamine was prepared by suspension polymerization, using melamine as a template, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross‐linker. The optimal template/monomer and monomer/cross‐linker ratios were obtained, being defined as 1/15 and 1/12, respectively. Molecular recognition properties and binding capacity toward melamine were evaluated by adsorption tests. Compared with the nonimprinted polymer, the imprinted polymer showed higher affinity for melamine with a dissociation constant (Kd) and a maximum binding concentration of 568.4 ± 7.4 μmol/L and 96.8 ± 2.3 μmol/g, respectively. Under optimal conditions, the imprinted polymer was used as a dispersive extraction sorbent to extract melamine from different milk samples, before high performance liquid chromatography with diode array detection (HPLC‐DAD) analysis. The validated method presented a limit of detection of 0.6 mg/kg. From the analysis of six different milks, melamine was detected in two of the considered samples at a maximum concentration of 9.3 ± 0.3 mg/kg.
Twenty‐one new theoretically based cubic equations of state for athermal hard‐sphere chain pure fluids and mixtures
Authors: Gow Arthur S. , Kelly Robert B.
Published: February 2015

Eight new hard‐sphere equations of state (EOS's) were obtained from molecular simulation data for the pair correlation function gHS(σ) vs. packing fraction η and combined with three theoretical schemes to obtain 21 new cubic EOS's for athermal hard‐sphere chains (AHSC's). The eight new hard‐sphere EOS models successfully reproduced isotropic fluid compressibility factor ZHS and gHS(σ) vs. η simulation data and predicted metastable liquid ZHS vs. η and virial coefficients up through B10. Moreover, calculated Z vs. η and reduced second‐virial coefficient vs. chain length m were compared with molecular simulation data for chains up to m = 201 for a set of representative (eight of twenty‐one) chain equations. Z vs. η for three AHSC binary mixtures was also successfully predicted. The results indicate that the new cubic EOS's give a satisfactory representation of simulation data for chain fluids and can be used to develop theoretically based cubic EOS's for “real” fluids including attractive effects. © 2015 American Institute of Chemical Engineers AIChE J, 61: 1677–1690, 2015
Gas/liquid/liquid three‐phase flow patterns and bubble/droplet size laws in a double T‐junction microchannel
Authors: Wang Kai , Qin Kang , Lu Yangcheng , Luo Guangsheng , Wang Tao
Published: February 2015

The double T‐junction microchannel is a classical microstructured chemical device used to generate gas/liquid/liquid three‐phase microflows. An experimental study that focused on the three‐phase flow phenomena and bubble/droplet generation rules in a double T‐junction microchannel was introduced. Based on the published knowledge of gas/liquid and liquid/liquid two‐phase microflows, new flow patterns were carefully defined: bubble cutting flow, spontaneous break‐up and bubble cutting coupling flow, and bubble/droplet alternate break‐up flow. According to the classical correlations of bubble and droplet volumes and their generation frequency ratio, the operating criteria for creating different three‐phase flow patterns were established and a model for the dimensionless average bubble and droplet volumes in the three‐phase microflows was developed. These various three‐phase microflows have great application potential in material science and flow chemistry synthesis. © 2015 American Institute of Chemical Engineers AIChE J, 61: 1722–1734, 2015
Craniosynostosis and risk factors related to thyroid dysfunction
Authors: Carmichael S.L. , Ma C , Rasmussen S.A. , Cunningham M.L. , Browne M.L. , Dosiou C , Lammer E.J. , Shaw G.M.
Published: February 2015

Thyroid disease is a common problem among women of reproductive age but often goes undiagnosed. Maternal thyroid disease has been associated with increased risk of craniosynostosis. We hypothesized that known risk factors for thyroid disease would be associated with risk of craniosynostosis among women not diagnosed with thyroid disease. Analyses included mothers of 1,067 cases and 8,494 population‐based controls who were interviewed for the National Birth Defects Prevention Study. We used multivariable logistic regression to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI). After excluding women with diagnosed thyroid disease, younger maternal age (AOR 0.7, 95% CI 0.6–0.9, for <25 years versus 25–29), black or other race‐ethnicity (AOR 0.3, 95% CI 0.2–0.4 and AOR 0.6, 95% CI 0.4–0.8, respectively, relative to non‐Hispanic whites), fertility medications or procedures (AOR 1.5, 95% CI 1.2–2.0), and alcohol consumption (AOR 0.8, 95% CI 0.7–0.9) were associated with risk of craniosynostosis, based on confidence intervals that excluded 1.0. These associations with craniosynostosis are consistent with the direction of their association with thyroid dysfunction (i.e., younger age, black race‐ethnicity and alcohol consumption are associated with reduced risk and fertility problems are associated with increased risk of thyroid disease). This study thus provides support for the hypothesis that risk factors associated with thyroid dysfunction are also associated with risk of craniosynostosis. Improved understanding of the potential association between maternal thyroid function and craniosynostosis among offspring is important given that craniosynostosis carries significant morbidity and that thyroid disease is under‐diagnosed and potentially modifiable. © 2015 Wiley Periodicals, Inc.
Revisiting mendelian randomization studies of the effect of body mass index on depression
Authors: Walter Stefan , Kubzansky Laura D. , Koenen Karestan C. , Liang Liming , Tchetgen Tchetgen Eric J , Cornelis Marilyn C. , Chang Shun‐Chiao , Rimm Eric , Kawachi Ichiro , Glymour M. Maria
Published: February 2015

Mendelian Randomization studies, which use genetic instrumental variables (IVs) as quasi‐experiments to estimate causal effects, report inconsistent findings regarding effects of body mass index (BMI) on mental health. We used genetic IV to estimate effects of BMI on depression and evaluated validity of a commonly used IV. Female Nurse's Health Study participants (n = 6989, average age 56.4, [Standard Deviation 6.91] years at first depression assessment) self‐reported BMI, which was averaged across eight reports prior to depression assessment (mean = 24.96, SD 4.50). Genetic instruments included fat mass and obesity‐associated protein (FTO) alleles, melanocortin receptor 4 (MC4R) alleles, and polygenic risk scores based on 32 established polymorphisms for BMI. Depression was assessed using multiple symptom measures, scaled to the Geriatric Depression Scale 15, averaged across up to 7 biennial waves. We used over‐identification tests to assess the validity of genetic IVs. In conventional estimates, each additional BMI point predicted 0.024 (95% Confidence Interval (CI): 0.020–0.029) higher average depression scores. Genetic IV estimates were not significant when based on FTO (beta: 0.064, CI: ‐0.014, 0.142), MC4R (beta: 0.005, CI: ‐0.146, 0.156), polygenic score excluding FTO (beta = ‐0.003, 95%‐CI ‐0.051, 0.045), or mechanism‐specific scores. The over‐identification test comparing IV estimates based on FTO to estimates based on the polygenic score excluding FTO rejected equality of estimated effects (P = 0.014). Results provide no evidence against a null effect of BMI on depression and call into question validity of FTO as an instrument for BMI in Mendelian Randomization studies. © 2015 Wiley Periodicals, Inc.
Genome‐wide association study of lymphoblast cell viability after clozapine exposure
Authors: de With S.A.J. , Pulit S.L. , Wang T. , Staal W.G. , Solinge W.W.van , de Bakker P.I.W. , Ophoff R.A.
Published: February 2015

Clozapine is an antipsychotic drug with proven efficacy in treatment‐resistant schizophrenia but also known to induce potentially lethal agranulocytosis (CIA) in 1% of patients. Genetic factors are likely to play a role in the molecular basis of CIA. We explored an in vitro system to study the genetic susceptibility of CIA. Cell viability was measured in 90 lymphoblast cell lines exposed to a series of increasing concentrations of clozapine for 48 hr. Quantitative trait measures of cell viability as well as area under the survival curve were used in a linear mixed model for genome‐wide association analyses. The estimated heritability of clozapine‐induced cell viability reduction in these cell lines is h2 = 0.76. No genome‐wide significant association was observed after correction for multiple testing. Two independent loci with nominal evidence of association were observed at 30× clinical clozapine concentration: rs2709505 (P = 1.41 × 10−8) in an intron of MDFIC and rs10457252 (P = 1.79 × 10−8) located in a gene desert at chromosome 6q21. We identified one locus (rs1293970) near PRG4 that was consistently associated for all separate concentration analyses at P < 5 × 10−5. PRG4 encodes hemangiopoietin, a growth stimulator for hematopoietic stem cells. No evidence was observed for involvement of the MHC region. Our results demonstrate that clozapine‐induced viability reduction in lymphoblast cell lines is a heritable, polygenic trait. Thus, in vitro models of CIA might be a useful tool for future discovery of genetic risk factors, although larger sample sizes will be required to unambiguously identify these loci. © 2015 Wiley Periodicals, Inc.
Genetic association of ACSM1 variation with schizophrenia and major depressive disorder in the Han Chinese population
Authors: Li Wenjin , Ji Weidong , Li Zhiqiang , He Kuanjun , Wang Qingzhong , Chen Jianhua , Qiang Yu , Feng Guoyin , Li Xingwang , Shen Jiawei , Wen Zujia , Ji Jue , Shi Yongyong
Published: February 2015

Schizophrenia (SCZ) and major depressive disorder (MDD) are two of the most common and severe mental disorders, the etiologies of which are not yet clearly elucidated. The ACSM1 gene has been identified as a susceptibility gene for SCZ in two previous genome‐wide association studies (GWAS). ACSM1 catalyzes the activation of fatty acids and plays an important role in the metabolic system. Some evidence has suggested that ACSM1 contributes to a genetic risk for MDD. The present study aimed to evaluate the common genetic risk of the ACSM1 gene in these two disorders in the Han Chinese population. In total, 1235 patients with SCZ, 1045 patients with MDD and 1235 control subjects of Chinese origin were recruited. Six single nuclear polymorphisms (SNPs) in ACSM1 were genotyped to test their associations with SCZ and MDD. SNP rs163234 was found to be significantly associated with both SCZ (permutated Pallele = 1.700 × 10−3, OR = 1.350 [95% CI = 1.152–1.581]) and MDD (permutated Pallele = 4.800 × 10−3, OR = 1.329 [95% CI = 1.127–1.567]). SNP rs433598 showed a strong association with SCZ (permutated Pallele = 4.300 × 10−3, OR = 1.303 [95% CI = 1.117–1.520]). Haplotype analysis of the blocks containing the two positive markers also revealed a significant association. This is the first study to assess the possible association of the ACSM1 gene with a genetic susceptibility for MDD. Our data are the first to suggest a positive association of the ACSM1 gene with a genetic susceptibility for SCZ and MDD in the Han Chinese population. © 2015 Wiley Periodicals, Inc.
Connective tissue, Ehlers–Danlos syndrome(s), and head and cervical pain
Authors: Castori Marco , Morlino Silvia , Ghibellini Giulia , Celletti Claudia , Camerota Filippo , Grammatico Paola
Published: February 2015

Ehlers–Danlos syndrome (EDS) is an umbrella term for a growing group of hereditary disorders of the connective tissue mainly manifesting with generalized joint hypermobility, skin hyperextensibility, and vascular and internal organ fragility. In contrast with other well known heritable connective tissue disorders with severe cardiovascular involvement (e.g., Marfan syndrome), most EDS patients share a nearly normal life span, but are severely limited by disabling features, such as pain, fatigue and headache. In this work, pertinent literature is reviewed with focus on prevalence, features and possible pathogenic mechanisms of headache in EDSs. Gathered data are fragmented and generally have a low level of evidence. Headache is reported in no less than 1/3 of the patients. Migraine results the most common type in the hypermobility type of EDS. Other possibly related headache disorders include tension‐type headache, new daily persistent headache, headache attributed to spontaneous cerebrospinal fluid leakage, headache secondary to Chiari malformation, cervicogenic headache and neck–tongue syndrome, whose association still lacks of reliable prevalence studies. The underlying pathogenesis seems complex and variably associated with cardiovascular dysautonomia, cervical spine and temporomandibular joint instability/dysfunction, meningeal fragility, poor sleep quality, pain‐killer drugs overuse and central sensitization. Particular attention is posed on a presumed subclinical cervical spine dysfunction. Standard treatment is always symptomatic and usually unsuccessful. Assessment and management procedures are discussed in order to put some basis for ameliorating the actual patients' needs and nurturing future research. © 2015 Wiley Periodicals, Inc.
Organisch‐anorganische Perowskit‐Dünnfilme für hocheffiziente Solarzellen
Authors: Stranks Samuel D. , Nayak Pabitra K. , Zhang Wei , Stergiopoulos Thomas , Snaith Henry J.
Published: February 2015

Organisch‐anorganische Perowskite sind ein hochaktuelles Thema in der Photovoltaikforschung. Die Wirkungsgrade von Laborzellen auf Perowskit‐Basis konkurrieren mittlerweile mit etablierten Dünnfilmtechnologien. Die größten Fortschritte wurden bislang durch Verbesserungen der Filmqualitäten erreicht, und man kann vermuten, dass die Optimierung von Schichtbildung und Kristallisation der Perowskitfilme von höchster Bedeutung für weitere Effizienzsteigerungen sind. Hier fassen wir die verschiedenen Schichtbildungstechniken zusammen und diskutieren den Einfluss von Lösungsmittel und Ausgangsprodukten im Prozess. Wir besprechen, welche Rolle Chlorid in der Schichtbildung von gemischten Halogenid‐Perowskiten spielt – eine der zentralen Fragen auf dem Gebiet. Des Weiteren betrachten wir die Materialeigenschaften, die für die Funktion von Hochleistungssolarzellen essenziell sind, und identifizieren Wege für die weitere Verbesserung der Morphologien.
Steigerung der Interkombinationseffizienz in Phenothiazinfarbstoffen durch Einlagerung in DNA
Authors: Nogueira Juan J. , Oppel Markus , González Leticia
Published: February 2015

Phenothiazinfarbstoffe werden als Photosensibilisatoren in der photodynamischen Therapie eingesetzt. Ihr Wirkmodus ist eng an die Erzeugung von angeregten Triplettzuständen durch Interkombination geknüpft. Das Verständnis der Faktoren, welche die Interkombination beeinflussen, ist daher essenziell zur Verbesserung der Wirksamkeit der photodynamischen Therapie. Wir setzen eine Kombination aus quantenmechanischen und molekülmechanischen Rechenverfahren ein, um die Effekte einer wässrigen und einer DNA‐Umgebung auf den Mechanismus der Interkombination in Methylenblau zu untersuchen. Dabei stellt sich heraus, dass die Erzeugung von Triplettzuständen stark von der Umgebung beeinflusst wird. Während die Interkombination in Wasser ausschließlich durch vibronische Spin‐Bahn‐Kopplungen ausgelöst wird, findet sich in DNA‐Umgebung ein weiterer, durch elektronische Spin‐Bahn‐Kopplung vermittelter Weg. Konkurrierende, in DNA‐Umgebungen ebenfalls mögliche Ladungstransferprozesse können daher unterdrückt werden, um die Wirksamkeit der photodynamischen Therapie zu erhöhen.
Elektroneninduzierte Hydratisierung eines Alkens: alternative Reaktionswege
Authors: Warneke Jonas , Wang Ziyan , Swiderek Petra , Bredehöft Jan Hendrik
Published: February 2015

Elektroneninduzierte Reaktionen in kondensierten Mischungen aus Ethen und Wasser führen zur Synthese von Ethanol, wie sich anhand von thermischer Desorptionsspektrometrie (TDS) nach Bestrahlung zeigen lässt. Diese Reaktion wird nicht nur durch Elektronenstoß‐Ionisation nahe der Ionisationsschwelle ausgelöst, sondern auch durch Elektronenanlagerung an Ethen und eine nachfolgende Säure‐Base‐Reaktion mit Wasser.
Unexpected Luminescence Behavior of Coinage Metal π‐Diborene Complexes
Authors: Bissinger Philipp , Steffen Andreas , Vargas Alfredo , Dewhurst Rian D. , Damme Alexander , Braunschweig Holger
Published: February 2015

A number of unprecedented photophysical phenomena were observed in the study of luminescent π‐diborene complexes of Cu and Ag. These observations included unusually high fluorescence quantum yields (up to 100%) in solution for complexes of these metals. This result indicates that very little or no intersystem crossing between S1 and Tn occurs in the complexes, despite the strong spin–orbit coupling of the metal atoms. The replacement of carbon with boron thus yields luminescent isolobal analogues of otherwise non‐emissive olefin complexes of Cu and Ag.
Building of a sulfonyl‐group‐functionalized monomer whose polymer is able to catalyze biodiesel formation
Authors: Gomez Cesar G. , Anníbali German N. , Strumia Miriam C.
Published: February 2015

A linear polymer containing sulfonyl groups was synthesized from a vinyl monomer to use its acid group as a catalyst of the esterification of oleic acid to form biodiesel. First, synthesis optimization of the monomer was carried out in an aqueous system. This molecule was obtained in an excellent yield, where the pH and reaction time were decisive factors in the synthesis performance. The vinyl monomer was then polymerized, and the catalytic activity of the sulfonic acid could be demonstrated in the esterification of oleic acid with short‐chain alcohols. The increase in the catalyst content resulted in a higher concentration of the carbonyl group activated, and this was followed by faster esterification kinetics. The highest yield (98 mol %) was reached after 20 min when a 10 mol‐% of catalyst was used. A larger size alcohol led to slower esterification kinetics because its ability as a nucleophile was decreased by steric impediment. The sulfonyl group in polymer 4, an aryl sulfonic acid polymer, proved to be an acid almost as efficient as sulfuric acid, although the former worked in a heterogeneous system. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41957.
Preparation and application of aluminum‐doped zinc oxide powders via precipitation and plasma processing method
Authors: Wang Xianjun , Zhang Ping , Hong Ruoyu
Published: February 2015

Aluminum‐doped zinc oxide (AZO) conductive powders were successfully obtained through an attractive method based on the pyrolysis of coprecipitated precursors in arc plasma processing. The as‐prepared powders were characterized by the x‐ray diffraction (XRD), transmission electron microscopy (TEM), and UV‐vis spectrum. The results reveal that Al atoms are doped into ZnO lattice successfully and all the samples are polycrystalline with a hexagonal wurtzite structure. Moreover, the particle size of aluminum doped zinc oxide prepared from the plasma pyrolysis was smaller than conventional thermal calcination. Afterward, the synthesized powders were reinforced into polypropylene (PP) matrix and the dispersion of the AZO filler in the PP matrix was observed by SEM. In addition, the effect of AZO concentrations on the electrical and mechanical properties of PP composites was investigated via resistance measurement, tensile and impact tests, respectively. The results show that the electrical and mechanical properties depend on the concentration and dispersion of AZO nanoparticles in the matrix. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41990.
A Facile and Universal Method to Prepare Hydrophilic Molecularly Imprinted Microspheres by Encapsulating a Polymer in Hollow Mesoporous Silica Microspheres
Authors: Yang Shun , Li Najun , Xing Qingjian , Chen Dongyun , Xu Qingfeng , Li Hua , Lu Jianmei
Published: February 2015

Hydrophilic molecularly imprinted microspheres (MIP@SiO2) for the adsorption of water‐soluble molecules in real aqueous samples were successfully synthesized. In this strategy, a molecular imprinted polymer (MIP) was encapsulated in the hollow core of hollow mesoporous silica (HMS) particles via a ‘ship‐in‐a‐bottle’ process. As the HMS shell contains plenty of Si‐OH groups, the as‐prepared microspheres proved to be hydrophilic and could be well dispersed in water. On the other hand, the MIP encapsulated in the HMS could specifically recognize small molecules with good binding efficiency through the mesoporous silica shell. Binding experiments in real aqueous solutions showed that the MIP@SiO2 composites have excellent recognition ability for specific molecules. Thus, MIP@SiO2 are highly promising alternatives to biological receptors with great potential for many analytical applications, such as environmental, food, and clinical analyses and other areas.
Photofunctional Platinum Complexes Featuring N‐heterocyclic Carbene‐Based Pincer Ligands
Authors: Lin Wan‐Jung , Naziruddin Abbas Raja , Chen Yu‐Hsuan , Sun Bian‐Jian , Chang A. Hsiu Hwa , Wang Wen‐Jwu , Hwang Wen‐Shu
Published: February 2015

Photoactive platinum complexes of stoichiometry [Pt(RCCCR)L]0/+ (R=Me, nBu and L=CN, C≡CPh, N≡CCH3, Py, CO) featuring pincer‐type bis N‐heterocyclic carbene (NHC) ligands (RCCCR) were synthesized. Organometallic syntheses of these complexes are facile and achievable through standard laboratory procedures. Control of intermolecular Pt⋅⋅⋅Pt interaction, π–π stacking, and emission tuning is achieved through suitable choice of the NHC‐wingtip substituent (R) and the auxiliary ligand (L). Exposure to specific volatile organic compounds (VOCs) or mechanical grinding triggers changes in emission colors, which render these complexes photofunctional. Solid‐state structures and photoluminescence results are described herein.
Synthesis of Indole Terpenoid Mimics through a Functionality‐Tolerated Eu(fod)3‐Catalyzed Conjugate Addition
Authors: Xiong Xiaochun , Zhang Deliang , Li Jian , Sun Yu , Zhou Shupeng , Yang Ming , Shao Huawu , Li Ang
Published: February 2015

The chemical synthesis of indole terpenoids of structural and biological interests has attracted remarkable attention. Here we report an Eu(fod)3‐catalyzed indole conjugate addition reaction, which tolerates various acid‐sensitive functional groups. A collection of indole terpenoid mimics have been prepared from natural product‐derived α,β‐unsaturated enones on the basis of this reaction. The further conversion of the indole adducts into more complex natural product‐like molecules has also been demonstrated.
Moisture sources of an extreme precipitation event in Sichuan, China, based on the Lagrangian method
Authors: Huang Yongjie , Cui Xiaopeng
Published: February 2015

In July 2013, an extreme precipitation event occurred in Sichuan, China, causing severe flooding, debris flows, and substantial losses. Moisture sources and transport of this event and quantification of the contribution from moisture sources were studied using the Lagrangian method. The results show that the vast majority of particles influencing this event originated from the relatively lower troposphere south of the precipitation region and can be traced back to the Arabian Sea. Moreover, the total moisture from the source regions accounts for more than 80% of the precipitation; moisture originating from the India Peninsula–Bay of Bengal–Indo‐China Peninsula region had the highest contribution.
CRISPR genome engineering and viral gene delivery: A case of mutual attraction
Authors: Schmidt Florian , Grimm Dirk
Published: February 2015

The adaptation of the CRISPR/Cas9 DNA engineering machinery for mammalian cells has revolutionized our approaches to low‐ or high‐throughput genome annotation and paved the way for conceptually novel therapeutic strategies. A large part of the attraction of CRISPR stems from the small size of its two core components – Cas9 and gRNA – and hence its compatibility with virtually any available viral vector delivery system. As a result, over the past two years, four major classes of viral vectors have already been engineered and applied as CRISPR delivery tools – retroviruses, lentiviruses, adenoviruses, and adeno‐associated viruses (AAVs). The juxtaposition of these two technologies reflects a case of tremendous mutual attraction and holds unprecedented promises for biology and medicine. Here, we provide an overview of the state‐of‐the‐art of this rapidly emerging field, from a comparative description of the principal vector designs, to a synopsis of some of the most exciting applications that were reported to date, including the use of viral CRISPR vectors for genome‐wide loss‐of‐function screens, multiplexed gene editing or disease modeling in animals. Once specificity and safety have been improved further, viral vector‐mediated in vitro/in vivo CRISPR delivery and expression promise to radically transform basic and applied biomedical research.
Impact of 4‐hydroxynonenal on matrix metalloproteinase‐9 regulation in lipopolysaccharide‐stimulated RAW 264.7 cells
Authors: Schrimpe‐Rutledge Alexandra C. , Fong Kim Y. , Wright David W.
Published: February 2015

Tissue degradation and leukocyte extravasation suggest proteolytic destruction of the extracellular matrix (ECM) during severe malaria. Matrix metalloproteinases (MMPs) play an established role in ECM turnover, and increased MMP‐9 protein abundance is correlated with malarial infection. The malaria pigment hemozoin (Hz) is a heme detoxification biomineral that is produced during infection and associated with biologically active lipid peroxidation products such as 4‐hydroxynonenal (HNE) adsorbed to its surface. Hz has innate immunomodulatory activity, and many of its effects can be reproduced by exogenously added HNE. Hz phagocytosis enhances MMP‐9 expression in monocytes; thus, this study was designed to examine the ability of HNE to alter MMP‐9 regulation in activated cells of macrophage lineage. Data show that treatment of lipopolysaccharide‐stimulated RAW 264.7 cells with HNE increased MMP‐9 secretion and activity. HNE treatment abolished the cognate tissue inhibitor of metalloproteinase‐1 protein levels, further decreasing MMP‐9 regulation. Phosphorylation of both p38 mitogen‐activated protein kinase (MAPK) and c‐Jun NH2‐terminal kinase was induced by HNE, but only p38 MAPK inhibition lessened MMP‐9 secretion. These results demonstrate the in vitro ability of HNE to cause MMP‐9 dysregulation in an activated cell model. The findings may extend to myriad pathologies associated with lipid peroxidation and elevated MMP‐9 levels leading to tissue damage. Copyright © 2015 John Wiley & Sons, Ltd.
A Peptide‐Functionalized Polymer as a Minimal Scaffold Protein To Enhance Cluster Formation in Early T Cell Signal Transduction
Authors: Witsenburg J. Joris , Sinzinger Michael D. , Stoevesandt Oda , Ruttekolk Ivo R. , Roth Günter , Adjobo‐Hermans Merel J. W. , Brock Roland
Published: February 2015

In cellular signal transduction, scaffold proteins provide binding sites to organize signaling proteins into supramolecular complexes and act as nodes in the signaling network. Furthermore, multivalent interactions between the scaffold and other signaling proteins contribute to the formation of protein microclusters. Such microclusters are prominent in early T cell signaling. Here, we explored the minimal structural requirement for a scaffold protein by coupling multiple copies of a proline‐rich peptide corresponding to an interaction motif for the SH3 domain of the adaptor protein GADS to an N‐(2‐hydroxypropyl)methacrylamide polymer backbone. When added to GADS‐containing cell lysates, these scaffolds (but not individual peptides) promoted the binding of GADS to peptide microarrays. This can be explained by the cross‐linking of GADS into larger complexes. Furthermore, following import into Jurkat T cell leukemia cells, this synthetic scaffold enhanced the formation of microclusters of signaling proteins.
Rapid Parallel Synthesis of Bioactive Folded Cyclotides by Using a Tea‐Bag Approach
Authors: Aboye Teshome , Kuang Yuting , Neamati Nouri , Camarero Julio A.
Published: February 2015

We report here the first rapid parallel production of bioactive folded cyclotides by using Fmoc‐based solid‐phase peptide synthesis in combination with a “tea‐bag” approach. Using this approach, we efficiently synthesized 15 analogues of the CXCR4 antagonist cyclotide MCo‐CVX‐5c. Cyclotides were synthesized in a single‐pot, cyclization/folding reaction in the presence of reduced glutathione. Natively folded cyclotides were quickly purified from the cyclization/folding crude mixture by activated thiol Sepharose‐based chromatography. The different folded cyclotide analogues were then tested for their ability to inhibit the CXCR4 receptor in a cell‐based assay. The results indicated that this approach can be used for the efficient chemical synthesis of libraries of cyclotides with improved biological properties that can be easily interfaced with solution or cell‐based assays for rapid screening.