bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of a non‐peptidic PET tracer designed for α5β1 integrin receptor
Authors: Monaco Alessandra , Michelin Olivier , Prior John , Rüegg Curzio , Scapozza Leonardo , Seimbille Yann
Published: March 2014

Arginine–glycine–aspartic acid (RGD)‐containing peptides have been traditionally used as PET probes to noninvasively image angiogenesis, but recently, small selective molecules for α5β1 integrin receptor have been developed with promising results. Sixty‐one antagonists were screened, and tert‐butyl (S)‐3‐(2‐((3R,5S)‐1‐(3‐(1‐(2‐fluoroethyl)‐1H‐1,2,3‐triazol‐4‐yl)propanoyl)‐5‐((pyridin‐2‐ylamino)methyl)pyrrolidin‐3‐yloxy)acetamido)‐2‐(2,4,6‐trimethylbenzamido)propanoate (FPMt) was selected for the development of a PET tracer to image the expression of α5β1 integrin receptors. An alkynyl precursor (PMt) was initially synthesized in six steps, and its radiolabeling was performed according to the azide–alkyne copper(II)‐catalyzed Huisgen's cycloaddition by using 1‐azido‐2‐[18F]fluoroethane ([18F]12). Different reaction conditions between PMt and [18F]12 were investigated, but all of them afforded [18F]FPMt in 15 min with similar radiochemical yields (80–83%, decay corrected). Overall, the final radiopharmaceutical ([18F]FPMt) was obtained after a synthesis time of 60–70 min in 42–44% decay‐corrected radiochemical yield. Copyright © 2014 John Wiley & Sons, Ltd.
Race/ethnicity, nativity and trends in BMI among U.S. adults
Authors: Krueger Patrick M. , Coleman‐Minahan Kate , Rooks Ronica N.
Published: March 2014

Objective

The average BMI is rising even as the U.S. population grows increasingly diverse. Prior research by examining BMI trends in diverse groups including whites, blacks, Chinese, Filipinos, Asian Indians, Mexicans, Puerto Ricans, and Cubans who are U.S. born, recent immigrants, or long‐term immigrants was extended.

Methods

Cross‐sectional data from the 1989 to 2011 waves of the National Health Interview Survey (N = 989,273) have been pooled and linear regression models to examine trends in BMI among U.S. adults have been used.

Results

Annual increases in BMI are greatest among U.S.‐born Puerto Ricans and Mexicans and slowest among foreign born Chinese. Among the U.S. born in 2011, Chinese adults have an average BMI below the threshold for overweight, whereas blacks, Mexicans, and Puerto Ricans have average BMIs in the obese range. Foreign‐born adults average lower BMIs than U.S. born adults in most race/ethnic groups, and nativity disparities generally widen over time. BMI increases across calendar periods rather than birth cohorts.

Conclusion

Our results suggest that calendar period interventions may be particularly useful in reversing rising BMIs in the United States. However, interventions must be tailored to different race/ethnic and nativity groups in order to reduce disparities in body mass.
Perceptions of body mass index (BMI) in pediatric cancer survivors and their providers
Authors: Elchuri Swati V. , Patterson Briana C. , Wasilewski‐Masker Karen , Mertens Ann C. , Record Elizabeth , Meacham Lillian R.
Published: March 2014

Background

Abnormalities in BMI are well documented in childhood cancer survivors. Perceptions of BMI status in cancer survivors have been understudied. This study determines the accuracy of parent/survivor and provider reporting of BMI status in a cancer survivor program.

Procedure

This is a retrospective study. Parent/survivor assessment of BMI status was obtained from a baseline questionnaire of subjects enrolled in Children's Healthcare of Atlanta‐Childhood, Adolescent, and Young Adult Cancer Survivor Study (CHOA‐CAYACSS). Provider reporting of BMI was obtained from a clinic visit close in date to completion of the survey. Perceptions of BMI were compared to actual BMI status calculated from clinic visits and categorized based on the Centers for Disease Control and Prevention (CDC) BMI guidelines.

Results

Perceptions of BMI were collected from 290 survivors of pediatric cancer or their parents (range, 4.3–22.9 years). Nearly 5% of survivors were underweight, 19.7% overweight and 16.2% obese. High BMI was the BMI state least likely to be correctly identified by parents, survivors, and providers. Among survivors with high BMI, parents, survivors, and providers failed to identify the problem 49.4%, 66.7%, and 26.9% of the time, respectively. Providers were less likely to correctly identify overweight compared to obese status (P < 0.0001). Accuracy of BMI recognition was independent of gender of survivor, ethnicity, or primary cancer diagnosis.

Conclusion

Abnormal BMI states, especially overweight, are frequently not correctly perceived by parents/survivors or providers. Assessment of BMI status and discussion about steps to normalize BMI is needed to prevent weight related morbidities in this population. Pediatr Blood Cancer 2014; 61:1445–1450. © 2014 Wiley Periodicals, Inc.
Secondary malignant neoplasms after high‐dose chemotherapy and autologous stem cell rescue for high‐risk neuroblastoma
Authors: Martin Alissa , Schneiderman Jennifer , Helenowski Irene B. , Morgan Elaine , Dilley Kimberley , Danner‐Koptik Karina , Hatahet Mohamad , Shimada Hiroyuki , Cohn Susan L. , Kletzel Morris , Hijiya Nobuko
Published: March 2014

Background

Outcomes for high‐risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long‐term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing.

Methods

We retrospectively reviewed data from 87 patients with high‐risk neuroblastoma who were treated with intensive induction chemotherapy followed by ASCR between January 1991 and July 2011 following one of two institutional protocols: Chicago Pilot 1 (CP1; n = 12) and Chicago Pilot 2 (CP2; n = 75).

Results

The 15‐year overall survival rate for all 87 patients was 33.9% (95% confidence interval [CI], 23.1–45.0%). The 10‐ and 15‐year cumulative incidence of SMN was 16.5% (95%CI, 7.2–38.0%) and 34.2% (95%CI, 18.6–63.1%), respectively, without evidence of a plateau at 15 years. Six of the 10 patients (n = 2 in CP1 and n = 8 in CP2) who developed SMN had hematologic malignancies including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Solid tumors included thyroid papillary carcinoma, chondrosarcoma, hepatocellular carcinoma, and biliary adenocarcinoma.

Conclusion

A significantly higher incidence of SMN, especially hematological malignancies, was observed in this cohort compared to older neuroblastoma studies, potentially due to exposure to epipodophyllotoxins and a high cumulative dose of alkylating agents these patients received. The risk of developing an SMN continued to increase with survival time and did not reach the plateau at 15 years. Although the number of the patients is relatively small, our study emphasizes the need for life‐long follow‐up of survivors who were treated using modern therapy. Pediatr Blood Cancer 2014; 61:1350–1356. © 2014 Wiley Periodicals, Inc.
Ultrasonic properties of epoxy resin/marble waste powder composites
Authors: Oral Imran
Published: March 2014

Non‐destructive techniques are suitable alternatives for characterization of composites. The aim of this study is to analyze the composites of epoxy resin (ER)/marble waste powder (MWP) by ultrasonic method. The effects of marble powder, coagulant type, and dosage on the ultrasonic properties of ER/MWP composites were investigated. The ultrasonic wave velocities of composites were measured with the pulse–echo method at room temperature by a flaw detector. The values of the acoustic impedance, Poisson's ratio, and elastic constants of the samples were calculated by the measured values of the densities and both longitudinal and shear ultrasonic wave velocities. According to the results, the ER/MWP composite using sepiolite coagulant in dosages of 4 g/500 mL has showed the highest values of elastic constants. POLYM. COMPOS. 36:584–590, 2015. © 2014 Society of Plastics Engineers
Calibrating short‐range ensemble forecasts using estimated model error variances
Authors: Boisserie M. , Descamps L. , Arbogast P.
Published: March 2014

This study investigates the impact of a calibration technique using estimated global model error variances on the performance of short‐range ensemble forecasts. The calibration technique is rather simple as it consists of adding a random white noise of zero mean and variance equal to estimated model error variances. Two calibrated ensemble forecasts are generated, one using a homogeneous calibration factor and another one using a heterogeneous calibration factor. Based on probabilistic scores, the qualities of these two ensemble forecasts are evaluated against a non‐calibrated ensemble and the operational ensemble prediction system of Météo‐France. The results show that this calibration technique significantly improves the reliability and, to a less extent, the resolution of ensemble forecasts. Better reliability results are found using a spatially heterogeneous calibration factor instead of using the homogeneous calibration factor at forecast ranges beyond 48 and 72 h.
On the geometry of bifurcation currents for quadratic rational maps
Authors: BERTELOOT FRANÇOIS , GAUTHIER THOMAS
Published: March 2014

We describe the behaviour at infinity of the bifurcation current in the moduli space of quadratic rational maps. To this purpose, we extend it to some closed, positive $(1,1)$-current on a two-dimensional complex projective space and then compute the Lelong numbers and the self-intersection of the extended current.
Constructing a place for critical practice in China: the history and outlook of the journal Time + Architecture
Authors: Ding Guanghui , Hale Jonathan , Parnell Steve
Published: March 2014

This paper investigates the history and programme of the Chinese architectural journal Time + Architecture (Shidai Jianzhu). As one of the newly established architectural periodicals in post-Mao China, the journal was launched in 1984 by academics Luo Xiaowei, Wang Shaozhou and their colleagues at the Department of Architecture in Tongji University, Shanghai. The journal's close association with academic institutions and commercial design firms shaped its dual nature; that is, both scholarly and professional. At the turn of the millennium, the journal's substantial reform of editorial policy redefined its character from a ‘presenter’ of received materials to a ‘producer’ of selected collaborative work, and enabled it to maintain editorial distinctiveness in the Chinese architectural publishing scene.

This paper argues that Time + Architecture constructed a significant place for critical practice in contemporary China through the presentation of critical architecture and architectural criticism. Over the past few decades, the journal, under the editorship of Zhi Wenjun, published a number of special issues on the work of emerging independent architects such as Yung Ho Chang, Wang Shu, Liu Jiakun and others. The thematic topics, projects and criticisms presented by the journal exemplified an editorial agenda to publish innovative and exploratory work and demonstrated the editors' and contributors' collective endeavours to develop a critical discourse that confronted the dominant ideology of architecture.
The beauty of production: module and its social significance
Authors: Blagojević Ljiljana , Milinković Marija
Published: March 2014

The article examines the post-WW2 expanded understanding of the concept of Mediterraneità or Mediterranean-ness in the South Adriatic coastal region of Montenegro in the former Yugoslavia, primarily as a modernist recourse against the demand for productivity and tenets of socialist realism and socialist aestheticism. The discussion of Mediterraneità refers to recent research of Italian architecture by Michelangelo Sabatino (2010), arguing that over the period of thirty years in its wider resonance across the Adriatic littoral, the original notion was adapted to different regional, cultural and socio-political contexts. This article specifically analyses the theory of modular coordination of the architect Milan Zloković (Trieste, 1898 – Belgrade, 1965), professor of architectural composition and design at the University of Belgrade, and its application in the tourist colony Hotel Mediterranean in the city of Ulcinj in Montenegro, which he realised in co-authorship with his son, architect and engineer Đorđe Zloković (1927, Trieste) and daughter, architect Milica Mojović (1932, Belgrade), in the early 1960s. In order to achieve meaningful if economically highly restrained design and efficient construction for developing mass tourism of the Montenegro littoral, the architects argued for the usefulness of modular coordination not only from the rational but also from the compositional point of view. The article explores a specific understanding of modern Mediterraneità in the Ulcinj colony which combines scientific means of modular coordination and the spirit of vernacular building in stone. The methodology combines historical and theoretical interpretation with geometric and proportional analysis of typology and modular coordination. The original graphic geometric methods are derived from the theory of the architect Milan Zloković through comparative analysis of Le Corbusier's Modulor, Alexander Klein's method of successive increments and Richard Padovan's interpretation of proportional systems correspondences. The article brings previously unpublished photographic documentation from the period.
Pseudo-graft polymer based on adamantyl-terminated poly(oligo(ethylene glycol) methacrylate) and homopolymer with cyclodextrin as pendant: its thermoresponsivity through polymeric self-assembly and host–guest inclusion complexation
Authors: Li Yinwen , Guo Huilong , Zhang Yunfei , Zheng Jian , Gan Jianqun , Guan Xiaoxiao , Lu Mangeng
Published: March 2014

Thermoresponsivity and self-assembly of a pseudo-graft polymer based on Ad-terminated poly(oligo(ethylene glycol) methacrylate) and homopolymer with CD pendants.
Diastereo- and enantioselective reductive amination of cycloaliphatic ketones by preformed chiral palladium complexes
Authors: Cabrera Armando , Sharma Pankaj , Pérez-Flores F. Javier , Velasco Luis , Arias J. Luis , Rubio-Pérez Laura
Published: March 2014

Chiral cycloaliphatic amines were obtained from the direct asymmetric reductive amination of cycloaliphatic ketones using a preformed chiral palladium catalyst.
A facile one-step approach for the synthesis of uniform spherical Cu/Cu2O nano- and microparticles with high catalytic activity in the Buchwald–Hartwig amination reaction
Authors: Bhosale Manohar A. , Bhanage Bhalchandra M.
Published: March 2014

An efficient, rapid, and additive-free protocol for synthesis of uniform spherical Cu/Cu2O nano/microparticles and application in Buchwald–Hartwig amination reaction.
A light harvesting mononuclear manganese(ii) complex: synthesis, characterization, DFT and TDDFT calculations and photophysical profile
Authors: Ghosh Debalina , Saha Urmila , Mukherjea Kalyan K.
Published: March 2014

A new manganese(ii) [MnII(DEMP)(NCS)(H2O)] (DEMP = Schiff base derived from salicylaldehyde and 2-diethylaminoethylamine) complex has been synthesized and characterized. The complex absorbs light ranging from 200–850 nm. Thus, the molecule is capable of harvesting the entire range of sunlight falling on earth.
Deformation and dynamics of red blood cells in flow through cylindrical microchannels
Authors: Fedosov Dmitry A. , Peltomäki Matti , Gompper Gerhard
Published: March 2014

The behavior of red blood cells (RBCs) in microvessels plays an important role in blood flow resistance and in the cell partitioning within a microcirculatory network. We employ mesoscopic hydrodynamic simulations to study the behavior and deformation of single RBCs in microchannels yielding the construction of diagrams of RBC shapes for a wide range of flow conditions.
Synthesis and aggregation-induced emissions of thienyl substituted cyclobutene derivatives
Authors: Zhang Xiaotao , Lu Xiuqiang , Zhen Yonggang , Liu Jie , Dong Huanli , Zhao Guangyao , He Ping , Wang Zongrui , Jiang Lang , Hu Wenping
Published: March 2014

Thienyl substituted cyclobutenes with aggregation induced emission behaviour have been synthesized for the first time in good selectivity, opening the possibility of cyclobutenes for application in light emitting diodes.
Mitochondrial thiol oxidase Erv1: both shuttle cysteine residues are required for its function with distinct roles
Authors: Ang Swee Kim , Zhang Mengqi , Lodi Tiziana , Lu Hui
Published: March 2014

Erv1 (essential for respiration and viability 1), is an essential component of the MIA (mitochondrial import and assembly) pathway, playing an important role in the oxidative folding of mitochondrial intermembrane space proteins. In the MIA pathway, Mia40, a thiol oxidoreductase with a CPC motif at its active site, oxidizes newly imported substrate proteins. Erv1 a FAD-dependent thiol oxidase, in turn reoxidizes Mia40 via its N-terminal Cys30–Cys33 shuttle disulfide. However, it is unclear how the two shuttle cysteine residues of Erv1 relay electrons from the Mia40 CPC motif to the Erv1 active-site Cys130–Cys133 disulfide. In the present study, using yeast genetic approaches we showed that both shuttle cysteine residues of Erv1 are required for cell growth. In organelle and in vitro studies confirmed that both shuttle cysteine residues were indeed required for import of MIA pathway substrates and Erv1 enzyme function to oxidize Mia40. Furthermore, our results revealed that the two shuttle cysteine residues of Erv1 are functionally distinct. Although Cys33 is essential for forming the intermediate disulfide Cys33–Cys130′ and transferring electrons to the redox active-site directly, Cys30 plays two important roles: (i) dominantly interacts and receives electrons from the Mia40 CPC motif; and (ii) resolves the Erv1 Cys33–Cys130 intermediate disulfide. Taken together, we conclude that both shuttle cysteine residues are required for Erv1 function, and play complementary, but distinct, roles to ensure rapid turnover of active Erv1.
The influence of laser clipped by the laser entrance hole on hohlraum radiation measurement on Shenguang-III prototype
Authors: Yang Dong , Li Zhichao , Guo Liang , Li Sanwei , Yi Rongqing , Song Tianming , Zhang Huan , Wang Zhebin , Jiang Xiaohua , Jiang Shaoen , Ding Yongkun
Published: March 2014

Measuring the x-ray flux exiting the target's laser entrance hole (LEH) is the most common diagnostic that quantifies the x-ray intensity inside the laser-driven hohlraum. However, this signal accounts for only a small portion of the incident laser power and thus is likely to be affected by unwanted x-ray background from non-target area, leading to an overestimation of the hohlraum drive. Unwanted emission might be produced when the laser light is clipped by the LEH (LEH clipping) because of a lack of clearance for laser spot, or with a laser spot comprising of discrete structure, or even with a poor pointing accuracy. Its influence on the hohlraum radiation diagnostic is investigated on Shenguang-III prototype laser facility with the typical 1 ns square pulse. The experiment employed three types of targets to excite the unwanted x-ray background from LEH clipping, unconverted light, and both effects, respectively. This work gives an absolute evaluation of x-ray produced by the LEH clipping, which is measured by flat-response x-ray detectors (FXRD) at multiple view angles. The result indicates that there is little variation in measured emission to various view angles, because the unwanted x-rays are mainly generated at the side face of the LEH lip when laser is obliquely incident. Therefore, the LEH clipping brings more overestimation in hohlraum radiation measurement at larger view angle since the hohlraum LEH as an emitting source viewed by FXRD is decreased as the view angle increases. In our condition, the LEH clipping contributes 2%–3.5% overestimation to the hohlraum flux measurement.
Near-flat self-biased magnetoelectric response in geometry gradient composite
Authors: Zhou Yuan , Priya Shashank
Published: March 2014

We demonstrate a near-flat self-biased magnetoelectric (ME) effect in geometry gradient magnetostrictive-piezoelectric laminates. The near-flat behavior was characterized by a stable ME response over a wide range of magnetic DC bias. By adjusting the configuration of the magnetostrictive layer, we were able to control the magnitude of the self-biased magnetoelectric coefficient. The ME response was found to be almost independent of the applied DC bias in the range of 0∼260 Oe. This bandwidth was almost 650%∼3800% higher than that of the conventional ME composites. This significant advancement opens great potential towards the development of high stability/sensitivity magnetic field sensors and energy harvesters.
Oxygen-assisted multipass cutting of carbon fiber reinforced plastics with ultra-short laser pulses
Authors: Kononenko T. V. , Freitag C. , Komlenok M. S. , Onuseit V. , Weber R. , Graf T. , Konov V. I.
Published: March 2014

Deep multipass cutting of bidirectional and unidirectional carbon fiber reinforced plastics (CFRP) with picosecond laser pulses was investigated in different static atmospheres as well as with the assistance of an oxygen or nitrogen gas flow. The ablation rate was determined as a function of the kerf depth and the resulting heat affected zone was measured. An assisting oxygen gas flow is found to significantly increase the cutting productivity, but only in deep kerfs where the diminished evaporative ablation due to the reduced laser fluence reaching the bottom of the kerf does not dominate the contribution of reactive etching anymore. Oxygen-supported cutting was shown to also solve the problem that occurs when cutting the CFRP parallel to the fiber orientation where a strong deformation and widening of the kerf, which temporarily slows down the process speed, is revealed to be typical for processing in standard air atmospheres.
Establishing IMMULITE® 2000 cut‐off values for serum allergen‐specific immunoglobulin and exploring their relationship to exhaled nitric oxide
Authors: Evjenth Bjørg , Hansen Tonje E. , Brekke Ole‐Lars , Holt Jan
Published: March 2014

Aim

Paediatric cut‐off values for serum allergen‐specific IgE (sIgE) using the Siemens IMMULITE® 2000 system to diagnose allergic rhinoconjunctivitis have not been established. We aimed to determine cut‐off levels for sIgE for 10 common inhalant allergens and to study the relationship between sIgE, total IgE and fractional exhaled nitric oxide (FENO).

Methods

We enrolled 243 schoolchildren, including 164 with allergic rhinoconjunctivitis. Parental interviews, skin prick tests, sIgE, total IgE, FENO measurements, spirometry and exercise tests were performed.

Results

Cut‐off values with the best combined sensitivity and specificity were above the detection limit of the assay for seven of the ten allergens (0.23–1.1 kU/L). The overall accuracy of the IMMULITE® in detecting allergic rhinoconjunctivitis was good. sIgE was superior to total IgE and FENO in predicting allergic rhinoconjunctivitis to timothy, birch, mugwort, cat, dog and house dust mite. FENO was elevated in children with allergic rhinoconjunctivitis, irrespective of asthma.

Conclusion

Cut‐off values for sIgE were dependent on the allergic phenotype and were above the IMMULITE® detection limit for seven of ten inhalant allergens. Consequently, using the detection limit for sIgE as the decision point would result in over‐diagnosing allergic rhinoconjunctivitis. When measuring elevated FENO in children, allergic rhinoconjunctivitis should be suspected.
Implementing newer agents for the management of castrate‐resistant prostate cancer: what is known and what is needed?
Authors: Mottet Nicolas , Clarke Noel , De Santis Maria , Zattoni Filiberto , Morote Juan , Joniau Steven
Published: March 2014

Men receiving androgen‐deprivation therapy will in time develop metastatic castrate‐resistant prostate cancer (mCRPC). Whilst effective treatment options for mCRPC have traditionally been limited, new agents are becoming available. Since 2010, the number and class of agents available to treat mCRPC has increased dramatically. As such, there is a need for clear guidance on the optimum treatment and sequence of treatments for mCRPC before and after chemotherapy. This evidence‐based statement, reflecting the views of the authors, provides suggestions on the continued relevance of conventional approaches to first‐ and second‐line treatment in mCRPC, the potential role of novel treatments, and factors that may influence the choice of hormonal agents and/or chemotherapy.
Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations
Authors: McLatchie L M , Young J S , Fry C H
Published: March 2014

Background and Purpose

The aim of this study was to quantify and characterize the mechanism of non‐neuronal ACh release from bladder urothelial cells and to determine if urothelial cells could be a site of action of anti‐muscarinic drugs.

Experimental Approach

A novel technique was developed whereby ACh could be measured from freshly isolated guinea pig urothelial cells in suspension following mechanical stimulation. Various agents were used to manipulate possible ACh release pathways in turn and to study the effects of muscarinic receptor activation and inhibition on urothelial ATP release.

Key Results

Minimal mechanical stimulus achieved full ACh release, indicating a small dynamic range and possible all‐or‐none signal. ACh release involved a mechanism dependent on the anion channel CFTR and intracellular calcium concentration, but was independent of extracellular calcium, vesicular trafficking, connexins or pannexins, organic cation transporters and was not affected by botulinum‐A toxin. Stimulating ACh receptors increased ATP production and antagonizing them reduced ATP release, suggesting a link between ACh and ATP release.

Conclusions and Implications

These results suggest that release of non‐neuronal ACh from the urothelium is large enough and well located to act as a modulator of ATP release. It is hypothesized that this pathway may contribute to the actions of anti‐muscarinic drugs in reducing the symptoms of lower urinary tract syndromes. Additionally the involvement of CFTR in ACh release suggests an exciting new direction for the treatment of these conditions.
Cardiac responses to β‐adrenoceptor stimulation is partly dependent on mitochondrial calcium uniporter activity
Authors: Fernández‐Sada E , Silva‐Platas C , Villegas C A , Rivero S L , Willis B C , García N , Garza J R , Oropeza‐Almazán Y , Valverde C A , Mazzocchi G , Zazueta C , Torre‐Amione G , García‐Rivas G
Published: March 2014

Background and Purpose

Despite the importance of mitochondrial Ca2+ to metabolic regulation and cell physiology, little is known about the mechanisms that regulate Ca2+ entry into the mitochondria. Accordingly, we established a system to determine the role of the mitochondrial Ca2+ uniporter in an isolated heart model, at baseline and during increased workload following β‐adrenoceptor stimulation.

Experimental Approach

Cardiac contractility, oxygen consumption and intracellular Ca2+ transients were measured in ex vivo perfused murine hearts. Ru360 and spermine were used to modify mitochondrial Ca2+ uniporter activity. Changes in mitochondrial Ca2+ content and energetic phosphate metabolite levels were determined.

Key Results

The addition of Ru360, a selective inhibitor of the mitochondrial Ca2+ uniporter, induced progressively and sustained negative inotropic effects that were dose‐dependent with an EC50 of 7 μM. Treatment with spermine, a uniporter agonist, showed a positive inotropic effect that was blocked by Ru360. Inotropic stimulation with isoprenaline elevated oxygen consumption (2.7‐fold), Ca2+‐dependent activation of pyruvate dehydrogenase (5‐fold) and mitochondrial Ca2+ content (2.5‐fold). However, in Ru360‐treated hearts, this parameter was attenuated. In addition, β‐adrenoceptor stimulation in the presence of Ru360 did not affect intracellular Ca2+ handling, PKA or Ca2+/calmodulin‐dependent PK signalling.

Conclusions and Implications

Inhibition of the mitochondrial Ca2+ uniporter decreases β‐adrenoceptor response, uncoupling between workload and production of energetic metabolites. Our results support the hypothesis that the coupling of workload and energy supply is partly dependent on mitochondrial Ca2+ uniporter activity.
Effects of arginine 10 to lysine substitution on ω‐conotoxin CVIE and CVIF block of Cav2.2 channels
Authors: Berecki G , Daly N L , Huang Y H , Vink S , Craik D J , Alewood P F , Adams D J
Published: March 2014

Background and Purpose

ω‐Conotoxins CVIE and CVIF (CVIE&F) selectively inhibit Cav2.2 channels and are lead molecules in the development of novel analgesics. At physiological membrane potentials, CVIE&F block of Cav2.2 channels is weakly reversible. To improve reversibility, we designed and synthesized arginine CVIE&F analogues in which arginine was substituted for lysine at position 10 ([R10K]CVIE&F), and investigated their serum stability and pharmacological actions on voltage‐gated calcium channels (VGCCs).

Experimental Approach

Changes in peptide structure due to R10K substitution were assessed by NMR. Peptide stability in human serum was analysed by reversed‐phase HPLC and MS over a 24 h period. Two‐electrode voltage‐clamp and whole‐cell patch clamp techniques were used to study [R10K]CVIE&F effects on VGCC currents in Xenopus oocytes and rat dorsal root ganglion neurons respectively.

Key Results

R10K substitution did not change the conserved ω‐conotoxin backbone conformations of CVIE&F nor the ω‐conotoxin selectivity for recombinant or native Cav2.2 channels, although the inhibitory potency of [R10K]CVIF was better than that of CVIF. At −80 mV, the R10K chemical modification significantly affected ω‐conotoxin−channel interaction, resulting in faster onset kinetics than those of CVIE&F. Heterologous and native Cav2.2 channels recovered better from [R10K]CVIE&F block than CVIE&F. In human serum, the ω‐conotoxin half‐lives were 6−10 h. CVIE&F and [R10K]CVIE&F were more stable than CVID.

Conclusions and Implications

R10K substitution in CVIE&F significantly alters the kinetics of ω‐conotoxin action and improves reversibility without diminishing conotoxin potency and specificity for the Cav2.2 channel and without diminishing the serum stability. These results may help generate ω‐conotoxins with optimized kinetic profiles for target binding.
Influence of Abutment Design on Stiffness, Strength, and Failure of Implant‐Supported Monolithic Resin Nano Ceramic (RNC) Crowns
Authors: Joda Tim , Huber Samuel , Bürki Alexander , Zysset Philippe , Brägger Urs
Published: March 2014

Background

Recent technical development allows the digital manufacturing of monolithic reconstructions with high‐performance materials. For implant‐supported crowns, the fixation requires an abutment design onto which the reconstruction can be bonded.

Purpose

The aim of this laboratory investigation was to analyze stiffness, strength, and failure modes of implant‐supported, computer‐assisted design and computer‐aided manufacturing (CAD/CAM)‐generated resin nano ceramic (RNC) crowns bonded to three different titanium abutments.

Materials and Methods

Eighteen monolithic RNC crowns were produced and loaded in a universal testing machine under quasi‐static condition according to DIN ISO 14801. With regard to the type of titanium abutment, three groups were defined: (1) prefabricated cementable standard; (2) CAD/CAM‐constructed individualized; and (3) novel prefabricated bonding base. Stiffness and strength were measured and analyzed statistically with Wilcoxon rank sum test. Sections of the specimens were examined microscopically.

Results

Stiffness demonstrated high stability for all specimens loaded in the physiological loading range with means and standard deviations of 1,579 ± 120 N/mm (group A), 1,733 ± 89 N/mm (group B), and 1,704 ± 162 N/mm (group C). Mean strength of the novel prefabricated bonding base (group C) was 17% lower than of the two other groups. Plastic deformations were detectable for all implant‐abutment crown connections.

Conclusions

Monolithic implant crowns made of RNC seem to represent a feasible and stable prosthetic construction under laboratory testing conditions with strength higher than the average occlusal force, independent of the different abutment designs used in this investigation.
p‐Phenylenediamine and other allergens in hair dye products in the United States: a consumer exposure study
Authors: Hamann Dathan , Yazar Kerem , Hamann Carsten R. , Thyssen Jacob P. , Lidén Carola
Published: March 2014

Background

Hair dye products constitute an important source of allergen exposure, and contribute importantly to allergic contact dermatitis in consumers and hairdressers.

Objectives

To evaluate the presence of potent contact sensitizers in oxidative hair dye products intended for home use on the US market.

Methods

Ingredient labels of 107 hair dyes from 10 major brands were examined and used to assess the prevalence of hair dye substances known to be potent contact sensitizers.

Results

One hundred and six of 107 (99%) products contained at least one potent sensitizer, and the average product contained six (range 0–11). p‐Phenylenediamine (PPD) was found in 83 products (78%), but resorcinol (89%), m‐aminophenol (75%), p‐aminophenol (60%) and toluene‐2,5‐diamine (21%) were also frequently identified.

Conclusions

Potent contact sensitizers were almost universally included in the hair dyes investigated in the United States. Although PPD is a common allergen, resorcinol and m‐aminophenol were found more frequently. In total, 30 potent sensitizers were found. Clinicians should consider other allergens in addition to PPD when evaluating patients with suspected hair dye allergy.
Hepatic artery complications following liver transplantation. Does preoperative chemoembolization impact the postoperative course?
Authors: Panaro Fabrizio , Ramos Jeanne , Gallix Benoit , Mercier Grégoire , Herrero Astrid , Niampa Halidou , Pageaux Georges‐Philippe , Navarro Francis
Published: March 2014

Background

Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) may cause damage to the hepatic artery (HA) and impact the postoperative course of the liver transplantation (LT). We aim to describe the relationship between preoperative TACE and the occurrence of histological and radiological hepatic artery complications (HAC).

Methods

All cirrhotic patients with HCC undergoing LT between January 2009 and October 2012 were included and divided in two groups: TACE (group 1) and No TACE (group 2). HA histological complications were reviewed and compared.

Results

Sixty‐seven patients were reviewed, 32 in group 1 and 35 in group 2. Both groups were similar in gender, age, cirrhosis origin, and American Society of Anesthesiology (ASA) score. After a mean follow‐up of 17 months, 10 radiological HAC occurred: seven in group 1 and three in group 2 (p = 0.02). There was one thrombosis in each group: six non‐thrombotic complications in group 1 and two in group 2. Histological screening showed 12 HA injuries in group 1 (three HA wall edemas, five fibrosis, one edema + fibrosis, one hemorragic necrosis + thrombosis, two thrombosis) and three in group 2 (two HA wall edemas, one fibrosis) (p = 0.01). All these injuries were found at the proper HA and at the right/left HA bifurcation level.

Conclusions

Despite the limits of our study, we found a higher incidence of radiological and histological injury in patients underwent TACE.
Combined melanocytic and sweat gland neoplasm: cell subsets harbor an identical HRAS mutation in phacomatosis pigmentokeratotica
Authors: Li Janet Y. , Berger Michael F. , Marghoob Ashfaq , Bhanot Umesh K. , Toyohara Jennifer P. , Pulitzer Melissa P.
Published: March 2014

Phacomatosis pigmentokeratotica (PPK) is characterized by the co‐existence of epidermal nevi and large segmental speckled lentiginous nevi of the papulosa type. PPK, previously explained as ‘twin spot’ mosaicism due to the postzygotic crossing‐over of two homozygous recessive mutations, has recently been shown to derive from one postzygotic activating RAS mutation. Epidermal nevi, including those in PPK, are known to give rise to neoplasms such as trichoblastoma and basal cell carcinoma. Within speckled lentiginous nevi, Spitz nevi and melanoma have been well documented. We report a case of PPK with a combined melanocytic and adnexal neoplasm presenting where the nevi conjoined. Using next‐generation sequencing techniques, we were able to identify the same HRAS G13R mutation within both components of the tumor, and to show the absence of additional mutated modifier genes in a panel of 300 cancer‐related genes. Given the genetic findings in this rare tumor‐type, we suggest that this case may be used as a model for understanding the development of biphenotypic neoplasia or intratumoral heterogeneity in some cases.
Study of the impacts of patient‐educators on the course of basic sciences in dental studies
Authors: Renard E. , Alliot‐Licht B. , Gross O. , Roger‐Leroi V. , Marchand C.
Published: March 2014

Ever since 2006, Nantes University dental educators have started organising lectures led by the mother of a young patient suffering from ectodermic dysplasia (patient‐educator) to help second‐year students to better understand how important it is for their future dental work to better understand basic sciences. In this study, we have analysed this training experience on students' motivation. For this purpose, students were asked to complete questionnaires 10 days after the patient‐educator's lecture (early assessment; n = 193) and 4 years later, during the last year of their dental studies (delayed assessment; n = 47). Moreover, 3 years after the first lecture, we analysed the ability of students to diagnose a mother carrying the ectodermic dysplasia genetic disorder, using a case‐based learning exercise with a patient showing dental features similar to those exposed by the patient‐educator (measure of knowledge; n = 42). Ten days after the lecture, the early assessment shows that all the students were interested in the lecture and 59% of the students declared being motivated to find out more about genetics whilst 54% declared the same thing about embryology courses. Moreover, 4 years later, 67% of the students remembered the patient‐educator's lecture a little or very well. Three years after the course, 83% of the students diagnosed ectodermal dysplasia whilst studying the case‐based example that listed typical dental phenotypes. In conclusion, this study shows that this original educational approach enhances dental students' motivation in learning basic sciences and that patient‐educators could offer many benefits for students and patients.
Genetic effects on information processing speed are moderated by age – converging results from three samples
Authors: Ising M. , Mather K. A. , Zimmermann P. , Brückl T. , Höhne N. , Heck A. , Schenk L. A. , Rujescu D. , Armstrong N. J. , Sachdev P. S. , Reppermund S.
Published: March 2014

Information processing is a cognitive trait forming the basis of complex abilities like executive function. The Trail Making Test (TMT) is a well‐established test of information processing with moderate to high heritability. Age of the individual also plays an important role. A number of genetic association studies with the TMT have been performed, which, however, did not consider age as a moderating factor. We report the results of genome‐wide association studies (GWASs) on age‐independent and age‐dependent TMT performance in two population‐representative community samples (Munich Antidepressant Response Signature, MARS: N1 = 540; Ludwig Maximilians University, LMU: N2 = 350). Age‐dependent genome‐wide findings were then evaluated in a third sample of healthy elderly subjects (Sydney Memory and Ageing Study, Sydney MAS: N3 = 448). While a meta‐analysis on the GWAS findings did not reveal age‐independent TMT associations withstanding correction for multiple testing, we found a genome‐wide significant age‐moderated effect between variants in the DSG1 gene region and TMT‐A performance predominantly reflecting visual processing speed (rs2199301, Pmeta‐analysis = 1.3 × 10−7). The direction of the interaction suggests for the minor allele a beneficial effect in younger adults turning into a detrimental effect in older adults. The detrimental effect of the missense single nucleotide polymorphism rs1426310 within the same DSG1 gene region could be replicated in Sydney MAS participants aged 70–79, but not in those aged 80 years and older, presumably a result of survivor bias. Our findings demonstrate opposing effects of DSG1 variants on information processing speed depending on age, which might be related to the complex processes that DSG1 is involved with, including cell adhesion and apoptosis.
Disparities in prevalence and risk indicators of loneliness between rural empty nest and non‐empty nest older adults in Chizhou, China
Authors: Cheng Pan , Jin Yu , Sun Hongmin , Tang Zhenhai , Zhang Chi , Chen Yuanjing , Zhang Qian , Zhang Qinghe , Huang Fen
Published: March 2014

Aim

The goal of the present study was to determine the disparities in prevalence and risk factors of loneliness between rural empty nest and non‐empty nest older adults in Chizhou, China.

Methods

A sample of 730 participants (381 empty nest older adults and 349 non‐empty nest older adults) were surveyed using the University of California at Los Angeles‐Loneliness Scale, the 30‐item Geriatric Depression Scale (GDS‐30), the Pittsburgh Sleep Quality Index, the Social Support Rate Scale, the Perceived Social Support from Family Scale and the World Health Organization Quality of Life questionnaire abbreviated version.

Results

The present study showed that the mean level of loneliness did significantly differ between empty nest older adults and non‐empty nest older adults (41.52 ± 6.98 vs 39.46 ± 7.38). Empty nesters had significantly higher GDS scores; by contrast, they received lower objective, subjective and family support. Family support, objective support and social interaction were associated significantly with loneliness, which was more pronounced in empty nest older adults, excluding subjective support and psychological domain. The GDS scores (β = 0.237, P < 0.001) and age (β = −0.114, P = 0.002) showed stronger significant associations with loneliness in empty nest older adults.

Conclusions

Loneliness obviously prevails among empty nest older adults than non‐empty nest older adults. Depressive symptoms showed a stronger risk of empty nest older adults being lonely. Family support was suggested as a protective factor for loneliness in both groups. These findings should be considered when developing intervention strategies to reduce loneliness. Geriatr Gerontol Int 2015; 15: 356–364.
Molecular mechanisms regulating CD13‐mediated adhesion
Authors: Ghosh Mallika , Gerber Claire , Rahman M. Mamunur , Vernier Kaitlyn M. , Pereira Flavia E. , Subramani Jaganathan , Caromile Leslie A. , Shapiro Linda H.
Published: March 2014

CD13/Aminopeptidase N is a transmembrane metalloproteinase that is expressed in many tissues where it regulates various cellular functions. In inflammation, CD13 is expressed on myeloid cells, is up‐regulated on endothelial cells at sites of inflammation and mediates monocyte/endothelial adhesion by homotypic interactions. In animal models the lack of CD13 alters the profiles of infiltrating inflammatory cells at sites of ischaemic injury. Here, we found that CD13 expression is enriched specifically on the pro‐inflammatory subset of monocytes, suggesting that CD13 may regulate trafficking and function of specific subsets of immune cells. To further dissect the mechanisms regulating CD13‐dependent trafficking we used the murine model of thioglycollate‐induced sterile peritonitis. Peritoneal monocytes, macrophages and dendritic cells were significantly decreased in inflammatory exudates from global CD13KO animals when compared with wild‐type controls. Furthermore, adoptive transfer of wild‐type and CD13KO primary myeloid cells, or wild‐type myeloid cells pre‐treated with CD13‐blocking antibodies into thioglycollate‐challenged wild‐type recipients demonstrated fewer CD13KO or treated cells in the lavage, suggesting that CD13 expression confers a competitive advantage in trafficking. Similarly, both wild‐type and CD13KO cells were reduced in infiltrates in CD13KO recipients, confirming that both monocytic and endothelial CD13 contribute to trafficking. Finally, murine monocyte cell lines expressing mouse/human chimeric CD13 molecules demonstrated that the C‐terminal domain of the protein mediates CD13 adhesion. Therefore, this work verifies that the altered inflammatory trafficking in CD13KO mice is the result of aberrant myeloid cell subset trafficking and further defines the molecular mechanisms underlying this regulation.
Multiple Job Holding, Skill Diversification, and Mobility
Authors: Panos Georgios A. , Pouliakas Konstantinos , Zangelidis Alexandros
Published: March 2014

In this article, we investigate the interrelated dynamics of dual jobholding, human capital, occupational choice, and mobility, using a panel sample (1991–2005) of UK employees from the British Household Panel Survey. The evidence suggests that individuals may be using multiple jobholding as a conduit for obtaining new skills and expertise and as a stepping‐stone to new careers, also involving self‐employment. Individuals doing a different secondary job than their primary occupation are more likely to switch to a new primary job in the next year, and a job that is different than their current primary employment. The results show that there are human capital spillover effects between primary and secondary employment.
Works Councils, Collective Bargaining, and Apprenticeship Training – Evidence From German Firms
Authors: Kriechel Ben , Muehlemann Samuel , Pfeifer Harald , Schütte Miriam
Published: March 2014

In this paper, we investigate the effects of works councils on apprenticeship training in Germany. The German law attributes works councils substantial information and co‐determination rights to training‐related issues. Thus, works councils may also have an impact on the cost‐benefit relation of workplace training. Using detailed firm‐level data containing information on the costs and benefits of apprenticeship training, we find that firms with works councils make a significantly higher net investment in training compared to firms without such an institution. We also find that the fraction of former trainees still employed with the same firm 5 years after training is significantly higher in the presence of works councils, thus enabling firms to recoup training investments over a longer time horizon. Furthermore, all works council effects are much more pronounced for firms covered by collective bargaining agreements.
Durability of Blended Cement Pastes Containing Ceramic Waste as a Pozzolanic Addition
Authors: Sánchez de Rojas María Isabel , Frías Moisés , Rodríguez Olga , Rivera Julián
Published: March 2014

Durability is one of the focal points of recent research on the behavior of new blended cement matrices in aggressive environments. The material selected for this study was ceramic waste (CW) rejected by Spanish manufacturers, primarily for reasons such as unsuitable kiln temperature or dimensional or mechanical failure. The resistance of CW‐containing cement pastes to three aggressive environments (SO42−, Cl−, and substitute seawater) was tested using the Koch–Steinegger method in this in‐depth analysis of the effect of CW on the chemical resistance of new blended matrices. The samples were also tested for performance in freeze–thaw cycles. The reaction mechanism was analyzed using X‐ray diffraction (XRD), pore‐size distribution, scanning electron microscopy (SEM), and backscattered electron images (BSE) with energy‐dispersive X‐ray (EDX) techniques. The results showed that CW contributed to cement resistance to such media; this enhancement of its mechanical properties was the result of the pozzolanic reaction induced by the addition of CW.