bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug‐induced liver injury in rats
Authors: Tonomura Yutaka , Kato Yuki , Hanafusa Hiroyuki , Morikawa Yuji , Matsuyama Keigo , Uehara Takeki , Ueno Motonobu , Torii Mikinori
Published: September 2014

Traditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug‐induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver‐operating characteristic (ROC) curve, using a free‐access database where 142 hepatotoxic or non‐hepatotoxic compounds were administrated to male rats (n = 5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in‐house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI. Copyright © 2014 John Wiley & Sons, Ltd.
mTORC2 Signaling Promotes Skeletal Growth and Bone Formation in Mice
Authors: Chen Jianquan , Holguin Nilsson , Shi Yu , Silva Matthew J. , Long Fanxin
Published: September 2014

Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase controlling many physiological processes in mammals. mTOR functions in two distinct protein complexes, namely mTORC1 and mTORC2. Compared to mTORC1, the specific roles of mTORC2 are less well understood. To investigate the potential contribution of mTORC2 to skeletal development and homeostasis, we have genetically deleted Rictor, an essential component of mTORC2, in the limb skeletogenic mesenchyme of the mouse embryo. Loss of Rictor leads to shorter and narrower skeletal elements in both embryos and postnatal mice. In the embryo, Rictor deletion reduces the width but not the length of the initial cartilage anlage. Subsequently, the embryonic skeletal elements are shortened due to a delay in chondrocyte hypertrophy, with no change in proliferation, apoptosis, cell size, or matrix production. Postnatally, Rictor-deficient mice exhibit impaired bone formation, resulting in thinner cortical bone, but the trabecular bone mass is relatively normal thanks to a concurrent decrease in bone resorption. Moreover, Rictor-deficient bones exhibit a lesser anabolic response to mechanical loading. Thus, mTORC2 signaling is necessary for optimal skeletal growth and bone anabolism. © 2014 American Society for Bone and Mineral Research.
Enzyme Kinetics of an Alternative Splicing Isoform of Mitochondrial 8‐Oxoguanine DNA Glycosylase, OGG1‐1b, and Compared with the Nuclear OGG1‐1a
Authors: Ogawa Akira , Watanabe Takashi , Shoji Sayaka , Furihata Chie
Published: September 2014

Eight alternatively spliced isoforms of human 8‐oxoguanine DNA glycosylase (OGG1) (OGG1‐1a to ‐1c and ‐2a to ‐2e) are registered in the National Center for Biotechnology Information. OGG1(s) in mitochondria have not yet been fully characterized biochemically. In this study, we purified mitochondrial recombinant OGG1‐1b protein and compared its activity with nuclear OGG1‐1a protein. The reaction rate constant (kg) of the 7,8‐dihydro‐8‐oxoguanine (8‐oxoG) glycosylase activity of OGG1‐1b was 8‐oxoG:C >> 8‐oxoG:T >> 8‐oxoG:G > 8‐oxoG:A (7.96, 0.805, 0.070, and 0.015 min−1, respectively) and that of the N‐glycosylase/DNA lyase activity (kgl) of OGG1‐1b was 8‐oxoG:C > 8‐oxoG:T ≃8‐oxoG:G >> 8‐oxoG:A (0.286, 0.079, 0.040, and negligible min−1, respectively). These reaction rate constants were similar to those of OGG1‐1a except for kgl against 8‐oxoG:A. APEX nuclease 1 was required to promote DNA strand breakage by OGG1‐1b. These results suggest that OGG1‐1b is associated with 8‐oxoG cleavage in human mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1‐1a.
Methotrexate‐Induced Bone Marrow Adiposity Is Mitigated by Folinic Acid Supplementation Through the Regulation of Wnt/β‐Catenin Signalling
Authors: Georgiou Kristen R. , Nadhanan Rethi Raghu , Fan Chia‐Ming , Xian Cory J.
Published: September 2014

Antimetabolite Methotrexate (MTX) is commonly used in childhood oncology. As a dihydrofolate reductase inhibitor it exerts its action through the reduction of cellular folate, thus its intensive use is associated with damage to soft tissues, bone marrow, and bone. In the clinic, MTX is administered with folinic acid (FA) supplementation to alleviate some of this soft tissue damage. However, whether and how FA alleviates damage to the bone and bone marrow requires further investigation. As the Wnt/β‐catenin signalling pathway is critical for commitment and differentiation of mesenchymal stem cells down the osteogenic or adipogenic lineage, its deregulation has been found associated with increased marrow adiposity following MTX treatment. In order to elucidate whether FA supplementation prevents MTX‐induced bone marrow adiposity by regulating Wnt/β‐catenin signalling, young rats were given saline or 0.75 mg/kg MTX once daily for 5 days, receiving saline or 0.75 mg/kg FA 6 h after MTX. FA rescue alleviated the MTX‐induced bone marrow adiposity, as well as inducing up‐regulation of Wnt10b mRNA and β‐catenin protein expression in the bone. Furthermore, FA blocked up‐regulation of the secreted Wnt antagonist sFRP‐1 mRNA expression. Moreover, secreted sFRP‐1 protein in the bone marrow and its expression by osteoblasts and adipocytes was found increased following MTX treatment. This potentially indicates that sFRP‐1 is a major regulator of defective Wnt/β‐catenin signalling following MTX treatment. This study provides evidence that folate depletion caused by MTX chemotherapy results in increased bone marrow adiposity, and that FA rescue alleviates these defects by up‐regulating Wnt/β‐catenin signalling in the bone. J. Cell. Physiol. 230: 648–656, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Surgical treatment of intrahepatic cholangiocarcinoma in the USA
Authors: Lubezky Nir , Facciuto Marcelo , Harimoto Norifumi , Schwartz Myron E. , Florman Sander S.
Published: September 2014

Cholangiocarcinoma (CC) is a malignancy that arises from the epithelial cells of the biliary system (ductules as well as large ducts, and likely from progenitor cells, as well). Intrahepatic CC (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC), and accounts for 10–15% of primary liver cancers. ICC differs from both extrahepatic and CC and HCC and has unique risk factors, histological features, genetic alterations and clinical outcomes. The natural history and results of surgical intervention are not well described as ICC is a relatively uncommon tumor, especially in the USA. This article reviews the literature relevant to the surgical management and outcome of patients with ICC in the USA.
Guidance on current good radiopharmacy practice for the small‐scale preparation of radiopharmaceuticals using automated modules: a European perspective
Authors: Aerts Joel , Ballinger James R. , Behe Martin , Decristoforo Clemens , Elsinga Philip H. , Faivre‐Chauvet Alain , Mindt Thomas L. , Kolenc Peitl Petra , Todde Sergio C. , Koziorowski Jacek
Published: September 2014

This document is meant to complement Part B of the EANM ‘Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals’ issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small‐scale in‐house preparation of radiopharmaceuticals with automated modules. The aim is to provide more detailed and practice‐oriented guidance to those who are involved in the small‐scale preparation of radiopharmaceuticals, which are not intended for commercial purposes or distribution.
Imatinib preserves blood–brain barrier integrity following experimental subarachnoid hemorrhage in rats
Authors: Zhan Yan , Krafft Paul R. , Lekic Tim , Ma Qingyi , Souvenir Rhonda , Zhang John H. , Tang Jiping
Published: September 2014

Blood–brain barrier (BBB) disruption and consequent edema formation contribute to the development of early brain injury following subarachnoid hemorrhage (SAH). Various cerebrovascular insults result in increased platelet‐derived growth factor receptor (PDGFR)‐α stimulation, which has been linked to BBB breakdown and edema formation. This study examines whether imatinib, a PDGFR inhibitor, can preserve BBB integrity in a rat endovascular perforation SAH model. Imatinib (40 or 120 mg/kg) or a vehicle was administered intraperitoneally at 1 hr after SAH induction. BBB leakage, brain edema, and neurological deficits were evaluated. Total and phosphorylated protein expressions of PDGFR‐α, c‐Src, c‐Jun N‐terminal kinase (JNK), and c‐Jun were measured, and enzymatic activities of matrix metalloproteinase (MMP)−2 and MMP‐9 were determined in the injured brain. Imatinib treatment significantly ameliorated BBB leakage and edema formation 24 hr after SAH, which was paralleled by improved neurological functions. Decreased brain expressions of phosphorylated PDGFR‐α, c‐Src, JNK, and c‐Jun as well as reduced MMP‐9 activities were found in treated animals. PDGFR‐α inhibition preserved BBB integrity following experimental SAH; however, the protective mechanisms remain to be elucidated. Targeting PDGFR‐α signaling might be advantageous to ameliorate early brain injury following SAH. © 2014 Wiley Periodicals, Inc.
Characterization of chemical constituents in Zhi–Zi–Da–Huang decoction by ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry
Authors: Zhu Heyun , Yin Ran , Han Fei , Guan Jiao , Zhang Xiaoshu , Mao Xinjuan , Zhao Longshan , Li Qing , Hou Xiaohong , Bi Kaishun
Published: September 2014

A sensitive and reliable ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry method was established to separate and identify the chemical constituents of Zhi–Zi–Da–Huang decoction, a classic traditional Chinese medicine formula. The chromatographic separation was achieved on a Shim‐pack XR‐ODS C18 column (75  × 3.0 mm, 2.2 μm) using a gradient elution program. The detection was performed on a Waters Xevo G2 Q‐TOF mass spectrometer equipped with electrospray ionization source in both positive and negative modes. With the optimized conditions, a total of 82 compounds were identified or tentatively characterized. Of the 82 compounds, 21 compounds were identified by comparing the retention time and MS data with reference standards, the rest were characterized by analyzing MS data and retrieving the reference literature. In addition, 31 compounds were identified from Gardenia jasminoides Ellis, ten compounds were identified from Rheum palmatum L., 33 compounds were identified from Citrus aurantium L., and eight compounds were identified from Sojae Semen Praeparatum. Results indicated that iridoids, anthraquinones, flavonoids, isoflavonoids, coumarins, glycosides of crocetin, monoterpenoids, and organic acids were major constituents in Zhi–Zi–Da–Huang decoction. It is concluded that the developed ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of Zhi–Zi–Da–Huang decoction, and the analysis provides a helpful chemical basis for further research on Zhi–Zi–Da–Huang decoction.
Improved Thin‐Film Transistor Performance Through a Melt of Poly(para‐phenyleneethynylene)
Authors: Schmid Stefanie , Kast Anne K. , Schröder Rasmus R. , Bunz Uwe H. F. , Melzer Christian
Published: September 2014

The performance of polymer field‐effect transistors (PFETs) based on short rigid rod semiconducting poly(2,5‐didodecyloxy‐p‐phenyleneethynylene) (D‐OPPE) is highlighted. The controlled heating and cooling of thin films of D‐OPPE allows for a recrystallization from the melt, boosting the performance of D‐OPPE‐based transistors. The improved film properties induced by controlled annealing lead to a hole field‐effect mobility around 0.014 cm2 V−1 s−1, an on/off ratio of 106, a sub‐threshold swing of 3 V dec−1 and a threshold voltage of −35 V, employing a poly(methyl methacrylate) (PMMA) gate dielectric. Thus, PFETs out of D‐OPPE compete now with spin‐coated, polycrystalline poly(3‐hexylthiophene)‐based PFETs.

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Work Recognition and Labor Productivity: Evidence from French Data
Authors: Grolleau Gilles , Mzoughi Naoufel , Pekovic Sanja
Published: September 2014

We empirically investigate whether labor productivity is related to work recognition. Using survey data about a large sample of French firms (N = 5309), we find that firms in which employees think their work is recognized are likely to report higher labor productivity, compared with firms where employees do not feel recognized. Our estimation results also suggest that labor productivity is strongly related to wages. Copyright © 2014 John Wiley & Sons, Ltd.
Automated whole‐brain N‐acetylaspartate proton MRS quantification
Authors: Soher Brian J. , Wu William E. , Tal Assaf , Storey Pippa , Zhang Ke , Babb James S. , Kirov Ivan I. , Lui Yvonne W. , Gonen Oded
Published: September 2014

Concentration of the neuronal marker, N‐acetylaspartate (NAA), a quantitative metric for the health and density of neurons, is currently obtained by integration of the manually defined peak in whole‐head proton (1H)‐MRS. Our goal was to develop a full spectral modeling approach for the automatic estimation of the whole‐brain NAA concentration (WBNAA) and to compare the performance of this approach with a manual frequency‐range peak integration approach previously employed. MRI and whole‐head 1H‐MRS from 18 healthy young adults were examined. Non‐localized, whole‐head 1H‐MRS obtained at 3 T yielded the NAA peak area through both manually defined frequency‐range integration and the new, full spectral simulation. The NAA peak area was converted into an absolute amount with phantom replacement and normalized for brain volume (segmented from T1‐weighted MRI) to yield WBNAA. A paired‐sample t test was used to compare the means of the WBNAA paradigms and a likelihood ratio test used to compare their coefficients of variation. While the between‐subject WBNAA means were nearly identical (12.8 ± 2.5 mm for integration, 12.8 ± 1.4 mm for spectral modeling), the latter's standard deviation was significantly smaller (by ~50%, p = 0.026). The within‐subject variability was 11.7% (±1.3 mm) for integration versus 7.0% (±0.8 mm) for spectral modeling, i.e., a 40% improvement. The (quantifiable) quality of the modeling approach was high, as reflected by Cramer–Rao lower bounds below 0.1% and vanishingly small (experimental ‐ fitted) residuals. Modeling of the whole‐head 1H‐MRS increases WBNAA quantification reliability by reducing its variability, its susceptibility to operator bias and baseline roll, and by providing quality‐control feedback. Together, these enhance the usefulness of the technique for monitoring the diffuse progression and treatment response of neurological disorders. Copyright © 2014 John Wiley & Sons, Ltd.
Injection‐molded parts of polypropylene/multi‐wall carbon nanotubes composites with an electrically conductive tridimensional network
Authors: Torres‐Giner Sergio , Chiva‐Flor Alberto , Feijoo José Luis
Published: September 2014

Polypropylene‐based composites filled with multi‐wall carbon nanotubes (MWCNTs), ranging from 1 to 6 wt%, were obtained by injection molding from a previous masterbatch compounded by twin‐screw extrusion (TSE). Resultant electrical percolation phenomenon was related to the ultrathin structure of the carbon‐based fillers and the high dispersion achieved in the thermoplastic matrix. In particular, conductivity experiments showed a threshold value of 3 wt% (1.3 vol%) of MWCNTs for percolation to occur. Electrical percolation was achieved as a result of the formation of an interconnected three‐dimensional structure compromising a top average inter‐nanotube distance of about 493 nm among isolated nanotubes in polypropylene. The current work is hoped to bear significance toward understanding of the electrical performance for industrial ultrathin carbon black‐based polyolefin composites. POLYM. COMPOS., 37:488–496, 2016. © 2014 Society of Plastics Engineers
Enantiomeric Determination of Four Diastereoisomeric Oxyneolignans from Bambusa tuldoides Munro
Authors: Sun Jia , Yu Jin , Zhang Pei‐Cheng , Yue Yong‐De
Published: September 2014

Introduction

Bambusa tuldoides Munro, a bamboo species, is used as a health food, dietary supplement and folk medicine in China, and produces lignans that can be used to supplement other natural sources.

Objective

To simultaneously separate eight stereoisomers of a particular type of oxyneolignan by chiral chromatography.

Methods

Ninety‐five per cent ethanol extracts of B. tuldoides Munro were analysed using HPLC/UV with a chiral column. The structures and configurations of isolated compounds were elucidated using NMR and circular dichroism (CD).

Results

Four diastereoisomers were characterised and given the names oxyneolignans A, B, C and D. Furthermore, each oxyneolignan occurred as a pair of enantiomers. The oxyneolignans A–D consisted of the erythro‐diastereoisomer of oxyneolignan at C7 and C8.

Conclusion

The chiral chromatography combined with the analysis techniques of NMR and CD reported here were reliable methods for discovering and separating the enantiomers. Copyright © 2014 John Wiley & Sons, Ltd.
The relationship between expressed emotion and wellbeing for families and carers of a relative with Borderline Personality Disorder
Authors: Bailey Rachel C. , Grenyer Brin F.S.
Published: September 2014

Background

Previous research has found that family environments high in expressed emotion, in particular emotional overinvolvement, are beneficial to the clinical outcome of patients with Borderline Personality Disorder (BPD).

Aim

This study aims to investigate the relationship between expressed emotion, carer burden and carer wellbeing.

Method

A total of 280 carers of a relative with BPD were administered the McLean Screening Instrument for BPD – Carer Version, The Family Questionnaire, Burden Assessment Scale and Mental Health Inventory.

Results

Carers reported family environments high in expressed emotion, particularly criticism (82.9% of carers) and emotional overinvolvement (69.6%). Elevated emotional overinvolvement was correlated with higher burden and mental health problems.

Conclusions

Elevated criticism and emotional overinvolvement in family environments represent a dynamic involving high conflict, anxious concern, overprotection and emotional closeness. The findings suggest that carers may benefit from intervention and support options considering the challenged interpersonal dynamic, burden and impaired carer wellbeing reported in this study. Copyright © 2014 John Wiley & Sons, Ltd.
Susceptibility to Bt proteins is not required for Agrotis ipsilon aversion to Bt maize
Authors: Binning Rachel R , Coats Joel , Kong Xiaoxiao , Hellmich Richard L
Published: September 2014

BACKGROUND

Although Bacillus thuringiensis (Bt) maize has been widely adopted in diverse regions around the world, relatively little is known about the susceptibility and behavioral response of certain insect pests to Bt maize in countries where this maize is not currently cultivated. These are important factors to consider as management plans are developed. These factors were investigated for Agrotis ipsilon, a global pest of maize, with Cry1F and Cry34Ab1/Cry35Ab1 maize.

RESULTS

Agrotis ipsilon demonstrated an initial, post‐ingestive aversive response to Cry1F maize. Development and mortality were also affected – survival on Cry1F maize tissue was 40% and weight gain of survivors of Cry1F exposure was significantly reduced. A post‐ingestive aversive response was also seen for Cry34Ab1/Cry35Ab1 maize; however, longer‐term feeding, weight gain and survival were not affected.

CONCLUSION

Agrotis ipsilon showed aversion to both Bt treatments. Aversion to Cry34Ab1/Cry35Ab1 maize was unexpected because these proteins have no known insecticidal effect against Lepidoptera; however, results confirm that this aversion was temporary and did not affect growth or development. The Cry1F results suggest that A. ipsilon will abandon Cry1F maize in the field before any selection for resistance. These data support the use of refuge to delay Cry1F resistance development in A. ipsilon populations. © 2014 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
A spirometric journey following lung transplantation
Authors: Fuller Jeremy , Paraskeva Miranda , Thompson Bruce , Snell Greg , Westall Glen
Published: September 2014

Spirometry is regarded as the primary tool for the evaluation of lung function in lung transplant (LTx) recipients. Spirometry is crucial in detecting the various phenotypes of chronic lung allograft dysfunction (CLAD), including restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS) – note that these phenotypes potentially have different etiologies and therapies. Following LTx for idiopathic pulmonary fibrosis, a 60‐year‐old male recipient's lung function began to gradually improve, peaking at 5 months post‐LTx. Subsequently, with increasing impairment of graft function, the diagnosis of BOS was made. A second LTx was performed and lung function subsequently began to increase again. Unfortunately, another year on, lung function deteriorated again – this time due to the development of RAS, antibody‐mediated rejection was implicated as the possible underlying cause. This case report highlights the importance of spirometry in assessing the patterns of CLAD following LTx.
Early detection and rejection probability‐based congestion control scheme for deep space networks
Authors: Jiang Guoxing , Shen Yanqing , Chen Jun
Published: September 2014

Deep Space Networks (DSNs) are a class of DTNs. In such networks, owing to limited radio range and node mobility, end‐to‐end paths between source and destination nodes are not available. Messages are relayed by store‐and‐forward strategy and may be buffered for long periods before being forwarded to the next hop. Therefore, the buffer of message carriers may overflow, and congestion follows. To address this issue, this paper proposes an early detection and rejection probability‐based congestion control algorithm, named ERBA, in which every intermediate node estimates rejection probability when a new message arrives and refuses to receive the message with the rejection probability, so as to avoid congestion. To validate its effectiveness, ERBA is merged into static routing (SR) and dynamic routing (DR). SR and DR are classical routing algorithms for DSNs. The simulation results show that when working with ERBA, the routing overhead of SR and DR decreases rapidly. However, the message delivery ratio also decreases. To deal with this problem, we propose a buffer‐compensation mechanism that effectively reduces the routing overhead for SR and DR without causing the reduction of the message delivery ratio.Copyright © 2014 John Wiley & Sons, Ltd.
The estimation of branching curves in the presence of subject‐specific random effects
Authors: Elmi Angelo , Ratcliffe Sarah J. , Guo Wensheng
Published: September 2014

Branching curves are a technique for modeling curves that change trajectory at a change (branching) point. Currently, the estimation framework is limited to independent data, and smoothing splines are used for estimation. This article aims to extend the branching curve framework to the longitudinal data setting where the branching point varies by subject. If the branching point is modeled as a random effect, then the longitudinal branching curve framework is a semiparametric nonlinear mixed effects model. Given existing issues with using random effects within a smoothing spline, we express the model as a B‐spline based semiparametric nonlinear mixed effects model. Simple, clever smoothness constraints are enforced on the B‐splines at the change point. The method is applied to Women's Health data where we model the shape of the labor curve (cervical dilation measured longitudinally) before and after treatment with oxytocin (a labor stimulant). Copyright © 2014 John Wiley & Sons, Ltd.
In‐situ Observations of Nanoscale Effects in Germanium Nanowire Growth with Ternary Eutectic Alloys
Authors: Biswas Subhajit , O'Regan Colm , Morris Michael A. , Holmes Justin D.
Published: September 2014

Vapour‐liquid‐solid (VLS) techniques are popular routes for the scalable synthesis of semiconductor nanowires. In this article, in‐situ electron microscopy is used to correlate the equilibrium content of ternary (Au0.75Ag0.25–Ge and Au0.65Ag0.35–Ge) metastable alloys with the kinetics, thermodynamics and diameter of Ge nanowires grown via a VLS mechanism. The shape and geometry of the heterogeneous interfaces between the liquid eutectic and solid Ge nanowires varies as a function of nanowire diameter and eutectic alloy composition. The behaviour of the faceted heterogeneous liquid–solid interface correlates with the growth kinetics of the nanowires, where the main growth facet at the solid nanowire–liquid catalyst drop contact line lengthens for faster nanowire growth kinetics. Pronounced diameter dependent growth kinetics, as inferred from liquid–solid interfacial behaviour, is apparent for the synthesised nanowires. Direct in‐situ microscopy observations facilitates the comparison between the nanowire growth behaviour from ternary (Au–Ag–Ge) and binary (Au–Ge) eutectic systems.
Automated test case generation for FBD programs implementing reactor protection system software
Authors: Jee Eunkyoung , Shin Donghwan , Cha Sungdeok , Lee Jang‐Soo , Bae Doo‐Hwan
Published: September 2014

Automated and effective testing for function block diagram (FBD) programs has become an important issue, as FBD is increasingly used in implementing safety‐critical systems. This work describes an automated test case generation technique for FBD programs and its associated tool—FBDTester. Given an FBD program and desired test coverage criteria, FBDTester generates test requirements and invokes the Satisfiability Modulo Theories solver iteratively to derive a set of test cases. An industrial case study using reactor protection system software shows that the automatically generated test suites detected at least 82% of the known faults, whereas manually generated test cases only detected approximately 35%. Mutation analysis revealed that the automatically generated test suites substantially outperformed manually generated ones. Although test sequence generation requires some manual effort in the current FBDTester, it is apparent that the proposed approach significantly improves the efficiency and the reliability of FBD testing. Copyright © 2014 John Wiley & Sons, Ltd.
Thin‐walled shell structures made of textile‐reinforced concrete
Authors: Scholzen Alexander , Chudoba Rostislav , Hegger Josef
Published: September 2014

At RWTH Aachen University recently, a pavilion was constructed with a roof shell made of textile‐reinforced concrete (TRC), a composite material consisting of a fine‐grained concrete and high‐strength, non‐corroding textile reinforcement in the form of carbon fibres. The thin‐walled TRC shell structure demonstrates impressively the loadbearing capacity of this innovative composite material. The present paper discusses the practical issues concerning the construction, such as the fabrication of the TRC shells using shotcrete, the concepts developed for the arrangement of the textile reinforcement and the erection of the shells on top of the precast concrete columns. The issues concerning the design, assessment and numerical simulation of the loadbearing behaviour of TRC shells are presented in the companion paper (Part II).
Five‐spring model for complete shear behaviour of deep beams
Authors: Mihaylov Boyan
Published: September 2014

This paper presents a five‐spring model capable of predicting the complete pre‐ and post‐peak shear behaviour of deep beams. The model stems from a two‐parameter kinematic theory (2PKT) for the shear strength and displacement capacity of deep beams under single curvature. Four of the springs of the model represent the shear resistance mechanisms of the beam, while the fifth spring models the flexural behaviour. The model predicts not only the load‐displacement response, but also the deformation patterns of the beam and how these patterns change with increasing load. Validation studies are performed by using 28 tests from the literature, showing excellent results. The model is used to interpret the tests and to draw conclusions about the behaviour of deep beams. It is shown that shear strength variations of up to 60 % between nominally identical specimens can be caused by variations in the path of the critical shear cracks. It is also demonstrated that loss of bond of large reinforcing bars increases the shear capacity of deep beams. Finally, the five‐spring model is shown to predict the post‐peak shear behaviour effectively, which is important for the analysis of structures under extreme loading.
Characterization of the novel GlyT1 PET tracer [18F]MK‐6577 in humans
Authors: Joshi Aniket D. , Sanabria‐Bohórquez Sandra M. , Bormans Guy , Koole Michel , De Hoon Jan , Van Hecken Anne , Depre Marleen , De Lepeleire Inge , Van Laere Koen , Sur Cyrille , Hamill Terence G.
Published: September 2014

Decreased glutamatergic neurotransmission is hypothesized to be involved in the pathophysiology of schizophrenia. Inhibition of glycine transporter Type‐1 (GlyT1) reuptake is expected to increase the glutamatergic neurotransmission and may serve as treatment for cognitive and negative symptoms of schizophrenia. In this article, we present human data from a novel GlyT1 PET tracer, [18F]MK‐6577. In the process of developing a GlyT1 inhibitor therapeutic, a PET tracer can assist in determining the dose with a high probability of sufficiently testing the mechanism of action. This article reports the human PET studies with [18F]MK‐6577 for measuring GlyT1 receptor availability at baseline in normal human subjects and occupancy with a GlyT1 inhibitor, MK‐2637. Studies were also performed to measure radiation burden and the baseline test‐retest (T‐RT) variability of the tracer. The effective dose from sequential whole‐body dosimetry scans in three male subjects was estimated to be 24.5 ± 2.9 µSV/MBq (mean ± SD). The time–activity curves from T‐RT scans modeled satisfactorily using a two tissue compartmental model. The tracer uptake was highest in the pons (VT = 6.7 ± 0.9, BPND = 4.1 ± 0.43) and lowest in the cortex (VT = 2.1 ± 0.5, BPND = 0.60 ± 0.23). VT T‐RT variability measured in three subjects was <12% on average. The occupancy scans performed in a cohort of 15 subjects indicated absence of a reference region. The in vivo potency (Occ50) of MK‐2637 was determined using two methods: A: Lassen plot with a population input function (Occ50 = 106 nM, SE = 20 nM) and B: pseudo reference tissue model using cortex as the pseudo reference region (Occ50 = 141 nM, SE = 21 nM). Synapse 69:33–40, 2015. © 2014 Wiley Periodicals, Inc.
TOPOFOLD, the designed modular biomolecular folds: polypeptide‐based molecular origami nanostructures following the footsteps of DNA
Authors: Kočar Vid , Božič Abram Sabina , Doles Tibor , Bašić Nino , Gradišar Helena , Pisanski Tomaž , Jerala Roman
Published: September 2014

Biopolymers, the essential components of life, are able to form many complex nanostructures, and proteins in particular are the material of choice for most cellular processes. Owing to numerous cooperative interactions, rational design of new protein folds remains extremely challenging. An alternative strategy is to design topofolds—nanostructures built from polypeptide arrays of interacting modules that define their topology. Over the course of the last several decades DNA has successfully been repurposed from its native role of information storage to a smart nanomaterial used for nanostructure self‐assembly of almost any shape, which is largely because of its programmable nature. Unfortunately, polypeptides do not possess the straightforward complementarity as do nucleic acids. However, a modular approach can nevertheless be used to assemble polypeptide nanostructures, as was recently demonstrated on a single‐chain polypeptide tetrahedron. This review focuses on the current state‐of‐the‐art in the field of topological polypeptide folds. It starts with a brief overview of the field of structural DNA and RNA nanotechnology, from which it draws parallels and possible directions of development for the emerging field of polypeptide‐based nanotechnology. The principles of topofold strategy and unique properties of such polypeptide nanostructures in comparison to native protein folds are discussed. Reasons for the apparent absence of such folds in nature are also examined. Physicochemical versatility of amino acid residues and cost‐effective production makes polypeptides an attractive platform for designed functional bionanomaterials. WIREs Nanomed Nanobiotechnol 2015, 7:218–237. doi: 10.1002/wnan.1289

This article is categorized under:

Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
Development and applications of radioactive nanoparticles for imaging of biological systems
Authors: Lewis Michael R. , Kannan Raghuraman
Published: September 2014

Radioactive nanoparticles possess the ability to carry high payloads of radionuclides for noninvasive imaging of regions of interest inside the body. In this way, they can be used for nuclear imaging of systems such as normal physiology and disease states. Various methods have been developed to label nanoparticles using both radiometals and radiohalogens, for single‐photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging in laboratory animals. The use of imaging to develop radioactive nanoparticles with long circulation times and minimal reticuloendothelial uptakes led to the design of nanoparticle constructs for imaging animal models of chronic illnesses, such as cancer and cardiovascular disease. Further improvements in targeting were made by modifying these constructs with vectors having high affinity and specificity for diseased tissue. In addition, constructs containing more than one type of imaging material afforded nanoparticles with multimodal properties, such as those designed for nuclear, magnetic resonance, and/or optical detection. Given the close relationship between diagnosis and therapy, theranostic nanoparticles have also been developed both to deliver radiotherapy and monitor response by imaging. In this article, we review the use of radionuclides to label nanoparticles for development and applications involving noninvasive detection of normal and abnormal biological functions. WIREs Nanomed Nanobiotechnol 2014, 6:628–640. doi: 10.1002/wnan.1292

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Quantitative determination of mineral phase effects observed in APXS analyses of geochemical reference materials
Authors: Perrett Glynis M. , Campbell John L. , Glasauer Susan , Pardo Renato
Published: September 2014

Calibration of the Curiosity Rover's alpha particle X‐ray spectrometer (APXS) was accomplished using geochemical reference materials and a fundamental parameters treatment of the X‐ray fluorescence and particle‐induced X‐ray emission (PIXE) excitation processes. For most major and minor elements the influence of different rock types was not significant. For the three light elements, Na, Mg, and Al, which are excited almost entirely by PIXE, systematic differences among felsic and mafic rocks were observed. A qualitative explanation is found in the very shallow interrogation depth (a few microns), which suggests that the X‐rays of these elements must emerge from a single mineral rather than an assumed average over the various minerals present. A quantitative explanation was sought by determining the mineralogy of several reference materials and computing their expected PIXE X‐ray yields with an adaptation of the yield prediction sub‐routine GUYLS in the Guelph PIXE software package GUPIX. The complexity of assigning the certified overall element mass fractions to specific minerals limited this exercise to cases with only a few minerals present. Good agreement was found between the X‐ray yields determined in the calibration exercise and those predicted in this new approach. It is expected that automation of the computational approach may enable examination of mineralogically more complex reference materials. This might also offer a means of coupling results from the X‐ray diffraction and APXS instruments on Mars. Copyright © 2014 John Wiley & Sons, Ltd.
Syntheses, Crystal Structures, and Properties of Two‐dimensional Complexes Coordinated by Mixed Flexible Bis(pyridylmethyl)amine and Rigid Aromatic Multicarboxylate Ligands
Authors: Yan Mei‐Jing , Wang Si‐Si , Gao Dong‐Zhao , Wang Xiu‐Guang , Sun Ya‐Qiu , Zhang Guo‐Ying , Xu Yan‐Yan
Published: September 2014

Three two‐dimensional coordination polymers {[Zn(H‐3, 3‐bpma)(1, 2,4‐btc)]·H2O}n (1), {[Cu2(H‐3, 3‐bpma)2(1, 2,4‐btc)(H‐1, 2,4‐btc)(H2O)2]·ClO4·7.75H2O}n (2), and {[Cd4(H‐3, 3‐bpma)2(1, 3,5‐btc)3Cl(H2O)7]·12.75H2O}n (3) [3, 3‐bpma = N,N′‐bis(3‐pyridylmethyl)amine, H3‐1, 2,4‐btc = 1, 2,4‐benzenetricarboxylic acid, and H3‐1, 3,5‐btc = 1, 3,5‐benzenetricarboxylic acid] were synthesized and characterized by X‐ray crystallography. The complexes are all two‐dimensional layer networks with diverse topologies bridged by mixed flexible bis(pyridylmethyl)amine and auxiliary rigid aromatic multicarboxylate ligands. The H‐3, 3‐bpma ligands adopt different conformations, whereas the aromatic multicarboxylates show various binding modes in the complexes. The magnetic, photoluminescence and thermal properties for complexes 1 and 2 were investigated.
Surgical Needs of Nepal: Pilot Study of Population Based Survey in Pokhara, Nepal
Authors: Gupta Shailvi , Ranjit Anju , Shrestha Ritesh , Wong Evan G. , Robinson William C. , Shrestha Sunil , Nwomeh Benedict C. , Groen Reinou S. , Kushner Adam L.
Published: September 2014

Background

The Surgeons OverSeas assessment of surgical need (SOSAS) tool, a population‐based survey on surgical conditions in low‐ and middle‐income countries (LMICs), was performed in Sierra Leone and Rwanda. This pilot study in Nepal is the initial implementation of the SOSAS survey in South Asia.

Methods

A pilot study of SOSAS, modified for Nepal’s needs and reprogrammed using mobile data collection software, was undertaken in Pokhara in January 2014. Cluster randomized sampling was utilized to interview 100 individuals in 50 households within two wards of Pokhara, one rural and one urban. The first portion of the survey retrieved demographic data, including household members and time to nearest health facilities. The second portion interviewed two randomly selected individuals from each household, inquiring about surgical conditions covering six anatomical regions.

Results

The pilot SOSAS in Nepal was easily completed over 3 days, including training of 18 Nepali interns over 2 days. The response rate was 100 %. A total of 13 respondents had a current surgical need (face 4, chest 1, back 1, abdomen 1, groin 3, extremity 3), although eight reported there was no need for surgical care. Five respondents (5 %) had a current unmet surgical need.

Conclusion

The SOSAS pilot study in Nepal was successfully conducted, demonstrating the feasibility of performing SOSAS in South Asia. The estimated 5 % current unmet surgical need will be used for sample size calculation for the full country survey. Utilizing and improving on the SOSAS tool to measure the prevalence of surgical conditions in Nepal will help enumerate the global surgical burden of disease.
Evaluation of a meal replacement-based weight management program in primary care settings according to the actual European Clinical Practice Guidelines for the Management of Obesity in Adults
Authors: Kruschitz Renate , Wallner-Liebmann Sandra Johanna , Lothaller Harald , Luger Maria , Schindler Karin , Hoppichler Friedrich , Ludvik Bernhard
Published: September 2014

Introduction

The purpose of this study was the evaluation of a weight loss program in primary care settings with respect to the European Clinical Practice Guidelines for the Management of Obesity in Adults with regard to the long-term success of changes in body weight and composition.

Methods

Overweight and obese patients (n = 1167) who underwent a standardized meal replacement-based weight loss program (myLINE®, AENGUS, Austria) in primary care settings were included in this evaluation. Body composition was measured by conventional anthropometry and bioelectrical impedance analysis (AKERN BIA101®, BIACORPUS RX4000®, SoftwareBodycomp Version 8.4 Professional). Data of patients who participated at least 12 months in the program were analyzed retrospectively and compared with their baseline data.

Results

After 12 months, a weight loss of 8.6 ± 7.5 kg (mean ± standard deviation) or 8.2 ± 7.8 % from baseline was seen (p < 0.001). In all, 71.9 % of all patients achieved a minimal weight loss of 5 %, and 18.8 % lost 15 % of their initial weight. In comparison with the baseline (35.7 ± 11.5 kg), body fat decreased to 29.6 ± 10.7 kg, which is 83.7 ± 18.9 % from baseline (100 %; p < 0.001). Body cell mass showed an absolute reduction of − 1.4 ± 2.2 kg (p < 0.001), although a relative increase of 1.5 ± 2.5 % (p < 0.001). There were no significant differences between male and female subjects regarding changes in weight, body fat, and body cell mass.

Conclusion

The evaluated program complies with the European Clinical Practice Guidelines for Management of Obesity in Adults (2008), which recommend a weight reduction of 5–15 % from initial weight within 6 months. Furthermore, the data showed a significant reduction of body fat and a relative increase of body cell mass.
“She Came out of mum's Tummy the Wrong way” (Mis) Conceptions Among Siblings of Children with Rare Disorders
Authors: Vatne Torun M. , Helmen Ingerid Østborg , Bahr David , Kanavin Øivind , Nyhus Livø
Published: September 2014

Misconceptions or uncertainty about the rare disorder of a sibling may cause adjustment problems among children. New knowledge about their misconceptions may enable genetic counselors to provide targeted information and increase siblings’ knowledge. This study aims to describe misconceptions and uncertainties of siblings of children with rare disorders. Content analysis was applied to videotapes of 11 support group sessions with 56 children aged 6 to 17. First, children's statements about the disorder (turns) were categorized into the categories “identity,” “cause,” “cure,” “timeline,” and “consequences” and then coded as medically “correct,” “misunderstood,” or “uncertain.” Next, turns categorized as “misunderstood” or “uncertain” were analyzed to explore prominent trends. Associations between sibling age, type of disorder, and frequency of misconceptions or uncertainties were analyzed statistically. Approximately 16 % of the children's turns were found to involve misconceptions or uncertainty about the disorder, most commonly about the identity or cause of the disorder. Misconceptions seemed to originate from information available in everyday family life, generalization of lay beliefs, or through difficulties understanding abstract medical concepts. Children expressed uncertainty about the reasons for everyday experiences (e.g. the abnormal behavior they observed). A lack of available information was described as causing uncertainty. Misconceptions and uncertainties were unrelated to child age or type of disorder. The information needs of siblings should always be addressed during genetic counseling, and advice and support offered to parents when needed. Information provided to siblings should be based on an exploration of their daily experiences and thoughts about the rare disorder.
Quality Assurance in Legal Translation: Evaluating Process, Competence and Product in the Pursuit of Adequacy
Authors: Prieto Ramos Fernando
Published: September 2014

Building on a functionalist framework for decision-making in legal translation, a holistic approach to quality is presented in order to respond to the specificities of this field and overcome the shortcomings of general models of translation quality evaluation. The proposed approach connects legal, contextual, macrotextual and microtextual variables for the definition of the translation adequacy strategy, which guides problem-solving and the rest of the translationprocess. The same parameters remain traceable between the translation brief and the translationproductboth in pre-delivery (self-)revision and in post-delivery assessment. They are the yardstick for identifying predictable evaluative criteria andcompetencerequirements for translators and quality controllers. The implications of the approach on quality assessment (including training contexts) and quality management practices are also discussed. Overall, the model illustrates the potential benefits of enhancing predictability and reducing subjectivity on the basis of specific legal translation methodologies. It supports the need for legal translation expertise in quality evaluation and the relevance of Legal Translation Studies to raising standards in professional practice.
Existing data sets to support studies of dementia or significant cognitive impairment and comorbid chronic conditions
Authors: Bell Janice F. , Fitzpatrick Annette L. , Copeland Catherine , Chi Gloria , Steinman Lesley , Whitney Robin L. , Atkins David C. , Bryant Lucinda L. , Grodstein Francine , Larson Eric , Logsdon Rebecca , Snowden Mark
Published: September 2014

Background

Dementia or other significant cognitive impairment (SCI) are often comorbid with other chronic diseases. To promote collaborative research on the intersection of these conditions, we compiled a systematic inventory of major data resources.

Methods

Large data sets measuring dementia and/or cognition and chronic conditions in adults were included in the inventory. Key features of the resources were abstracted including region, participant sociodemographic characteristics, study design, sample size, accessibility, and available measures of dementia and/or cognition and comorbidities.

Results

117 study data sets were identified; 53% included clinical diagnoses of dementia along with valid and reliable measures of cognition. Most (79%) used longitudinal cohort designs and 41% had sample sizes greater than 5000. Approximately 47% were European‐based, 40% were US‐based, and 11% were based in other countries.

Conclusions

Many high‐quality data sets exist to support collaborative studies of the effects of dementia or SCI on chronic conditions and to inform the development of evidence‐based disease management programs.