bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust myocardial T2 and T2* mapping at 3T using image‐based shimming
Authors: Zaman Arshad , Higgins David M. , Motwani Manish , Kidambi Ananth , Kouwenhoven Marc , Kozerke Sebastian , Greenwood John P. , Plein Sven
Published: April 2014

Purpose

Intramyocardial hemorrhage and area at risk are both prognostic markers in acute myocardial infarction (AMI). Myocardial T2 and T2* mapping have been used to detect such tissue changes at 1.5T but these techniques are challenging at 3.0T due to additional susceptibility variation. We studied T2 and T2* myocardial mapping techniques at 3.0T on a system employing B1 shimming and compared two different methods of B0 shimming.

Materials and Methods

Fifteen volunteers and six AMI patients were scanned on a 3T system. Volume and image‐based (IB) B0 shimming techniques were implemented. Single breath‐hold, multiecho gradient, and spin echo sequences were employed from which T2* and T2 maps were calculated.

Results

In volunteers, there was no significant difference in mean values obtained with volume or IB shimming for T2 mapping (39.1 ± 6.0 msec vs. 39.4 ± 6.1 msec; P > 0.05) or for T2* mapping (24.2 ± 6.7 msec vs. 24.1 ± 5.2 msec; P > 0.05). There were no significant regional differences in mean T2 values between septal, anterior, and posterior segments with either shimming technique (all P > 0.05); but there were significant regional differences in mean T2* values using volume shimming (27.8 ± 5.2 msec vs. 28.4 ± 5.8 msec vs. 15.9 ± 8.3 msec; P < 0.05)—but not with IB shimming (25.7 ± 5.4 msec vs. 25.3 ± 5.9 msec vs. 18.7 ± 4.6 msec; P > 0.05).

Conclusion

At 3.0T, cardiac T2 mapping is robust. Although T2* mapping is prone to more regional heterogeneity this can be reduced by using IB instead of conventional volume B0 shimming. J. Magn. Reson. Imaging 2015;41:1013–1020. © 2014 Wiley Periodicals, Inc.
Long‐term fate of grafted hippocampal neural progenitor cells following ischemic injury
Authors: Tsupykov Oleg , Kyryk Vitaliy , Smozhanik Ekaterina , Rybachuk Oksana , Butenko Gennadii , Pivneva Tatyana , Skibo Galina
Published: April 2014

The adult CNS has a very limited capacity to regenerate neurons after insult. To overcome this limitation, the transplantation of neural progenitor cells (NPCs) has developed into a key strategy for neuronal replacement. This study assesses the long‐term survival, migration, differentiation, and functional outcome of NPCs transplanted into the ischemic murine brain. Hippocampal neural progenitors were isolated from FVB‐Cg‐Tg(GFPU)5Nagy/J transgenic mice expressing green fluorescent protein (GFP). Syngeneic GFP‐positive NPCs were stereotactically transplanted into the hippocampus of FVB mice following a transient global cerebral ischemia model. Behavioral tests revealed that ischemia/reperfusion induced spatial learning disturbances in the experimental animals. The NPC transplantation promoted cognitive function recovery after ischemic injury. To study the long‐term fate of grafted GFP‐positive NPCs in a host brain, immunohistochemical approaches were applied. Confocal microscopy revealed that grafted cells survived in the recipient tissue for 90 days following transplantation and differentiated into mature neurons with extensive dendritic trees and apparent spines. Immunoelectron microscopy confirmed the formation of synapses between the transplanted GFP‐positive cells and host neurons that may be one of the factors underlying cognitive function recovery. Repair and functional recovery following brain damage represent a major challenge for current clinical and basic research. Our results provide insight into the therapeutic potential of transplanted hippocampal progenitor cells following ischemic brain injury. © 2014 Wiley Periodicals, Inc.
Bayesian Error Propagation for a Kinetic Model of n‐Propylbenzene Oxidation in a Shock Tube
Authors: Mosbach Sebastian , Hong Je Hyeong , Brownbridge George P. E. , Kraft Markus , Gudiyella Soumya , Brezinsky Kenneth
Published: April 2014

We apply a Bayesian parameter estimation technique to a chemical kinetic mechanism for n‐propylbenzene oxidation in a shock tube to propagate errors in experimental data to errors in Arrhenius parameters and predicted species concentrations. We find that, to apply the methodology successfully, conventional optimization is required as a preliminary step. This is carried out in two stages: First, a quasi‐random global search using a Sobol low‐discrepancy sequence is conducted, followed by a local optimization by means of a hybrid gradient‐descent/Newton iteration method. The concentrations of 37 species at a variety of temperatures, pressures, and equivalence ratios are optimized against a total of 2378 experimental observations. We then apply the Bayesian methodology to study the influence of uncertainties in the experimental measurements on some of the Arrhenius parameters in the model as well as some of the predicted species concentrations. Markov chain Monte Carlo algorithms are employed to sample from the posterior probability densities, making use of polynomial surrogates of higher order fitted to the model responses. We conclude that the methodology provides a useful tool for the analysis of distributions of model parameters and responses, in particular their uncertainties and correlations. Limitations of the method are discussed. For example, we find that using second‐order response surfaces and assuming normal distributions for propagated errors is largely adequate, but not always.
Environment‐Specific Fluorescence Response of Microporous, Conformation‐Variable Conjugated Polymer Film to Water in Organic Solvents: On‐line Real‐Time Monitoring in Fluidic Channels
Authors: Han Dong‐Cheul , Jin Young‐Jae , Lee Joong‐Heon , Kim Shin‐Il , Kim Hyo‐Jin , Song Kyu‐Ho , Kwak Giseop
Published: April 2014

Poly[1‐phenyl‐2‐(p‐trimethylsilyl)phenylacetylene] (PTMSDPA) with microporous and intramolecular stack structures in the bulk solid state can be used as a fluorescent water sensor for on‐line real‐time monitoring. A solubility parameter (δ) of PTMSDPA is estimated from the degree of swelling and solvation of the polymer in various organic solvents. When the PTMSDPA film is immersed in organic solvents with a range of δ values, the fluorescence (FL) intensity increases significantly due to swelling, whereas the FL intensity decreases gradually upon the addition of water in the solvents due to deswelling. The FL decreasing ratios are quite different according to the solvents. The hydrogen‐bonding strength of the solvents toward water plays a key role in determining the FL responsivity of the polymer. The FL response is very specific to water in organic solvents. The PTMSDPA film responds quickly to water within several seconds. A fluidic channel of which the inner wall is coated with PTMSDPA is fabricated to demonstrate the on‐line, real‐time monitoring of water in flowing solvents. The development of more facile and convenient devices, such as microfluidic lab‐on‐chip and optode sensors, using PTMSDPA as an active layer will advance practical applications.

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Efficient Synthesis of α,ω‐Divinyl‐Functionalized Polyolefins
Authors: Patil Vishal B. , Saliu Kuburat O. , Jenkins Roxanne M. , Carnahan Edmund M. , Kramer Edward J. , Fredrickson Glenn H. , Bazan Guillermo C.
Published: April 2014

A facile one‐step olefin metathesis‐mediated ethenolysis reaction on polyolefins containing 1,4‐inserted butadiene units yields α,ω‐divinyl telechelic polymers. These reactions can be successfully performed with well‐defined thermally stable ruthenium catalysts to yield essentially complete metathesis of internal double bonds. The reaction progress is monitored by 1H NMR spectroscopy over time, by tracking the disappearance of the signal due to internal unsaturation of 1,4‐butadiene at ca. 5.5 ppm in toluene‐d8 solvent. The reaction conditions are optimized for ethylene pressure, temperature, catalyst loading, and reaction time. Catalyst loading of 45:1 1,4‐butadiene unsaturation to catalyst at 90 °C with 25 psi ethylene pressure is successful in removing internal unsaturation with no detectable isomerization side reactions. High‐temperature gel‐permeation chromatography (GPC) analysis of the depolymerized product correlates to the calculated molecular weight based on the number of internal double bonds observed in the 1H NMR analysis of the starting polyolefin. This method offers a single step, rapid, and clean route toward divinyl‐terminated telechelic polymers based on commodity materials in high yields.

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Product Packaging Metaphors: Effects of Ambiguity and Explanatory Information on Consumer Appreciation and Brand Perception
Authors: van Rompay Thomas J. L. , Veltkamp Martijn
Published: April 2014

Product packaging is an important means for communicating product and brand benefits. Research suggests that visual metaphors may be particularly suited in this context, however, the conditions under which metaphors are effective are not yet well understood. In the research reported herein, effects of metaphor ambiguity and explanatory information on consumer appreciation and brand personality perceptions are tested. Study 1 shows that explicit information explaining the metaphor increases consumer appreciation and positively affects brand perception, but only for ambiguous metaphors. Study 2 shows that drawing consumer attention to packaging design by means of a visual packaging cue may be equally or even more effective for enhancing consumer appreciation and steering brand personality perceptions. In addition, Study 2 shows that effects of explanatory information and information type vary with participants’ readiness to engage in metaphor processing. Together, the results provide greater insight into the effects of metaphors in product design and provide guidelines to packaging designers.
Make it Your Own: How Process Valence and Self‐Construal Affect Evaluation of Self‐Made Products
Authors: Atakan Sukriye Sinem , Bagozzi Richard P. , Yoon Carolyn
Published: April 2014

Self‐production, participation of consumers in the production process of products for their own consumption, leads to consumers’ enhanced evaluations of the self‐made products. Three experimental studies investigate how and why self‐production affects consumers’ product evaluations and reveal that not all production experiences create additional value for all consumers. In particular, Studies 1 and 2, using hypothetical stories and real experiences, show that only positive (vs. negative) production experiences enhance evaluations of self‐made products over products made by others. Positive (but not negative) experiences decrease the psychological distance between the self and the product and strengthen identification with it. Study 3 manipulates self‐construal (independent vs. interdependent) to investigate its role on evaluation of self‐made products and products made with close others as a group (i.e., group‐made). Consumers with independent self‐construal evaluate self‐made (vs. other‐made) products more favorably only if the process is positive. However, consumers with interdependent self‐construal evaluate self‐made products more favorably even if the process is negative. Additionally, consumers with interdependent (vs. independent) self‐construal exhibit more favorable evaluation of group‐made products. Finally, even if consumers know how another person feels while making a product, other people's process emotions do not affect consumers’ product judgments as strongly as their own experienced process emotions.
What can biomarkers tell us about cognition in Parkinson's disease?
Authors: Mollenhauer Brit , Rochester Lynn , Chen‐Plotkin Alice , Brooks David
Published: April 2014

Cognitive decline is common in Parkinson's disease (PD), even in the early motor stage, and this non‐motor feature impacts quality of life and prognosis tremendously. In this article, we discuss marker candidates for cognitive decline in PD from different angles, including functional and structural imaging techniques, biological fluid markers in cerebrospinal fluid, and blood genetic predictors, as well as gait as a surrogate marker of cognitive decline. Specifically, imaging‐based markers of cognitive impairment in PD include cortical atrophy, reduced cortical metabolism, loss of cortical cholinergic and frontal dopaminergic function, as well as an increased cortical amyloid load. Reduced β‐amyloid(1‐42) in cerebrospinal fluid and lower plasma levels of epidermal growth factor are predictors for cognitive decline in PD. In addition, genetic variation in the apolipoprotein E (APOE), catechol‐O‐methyltransferase (COMT), microtubule‐associated protein tau (MAPT), and glucocerebrosidase (GBA) genes may confer risk for cognitive impairment in PD; and gait disturbance may also indicate an increased risk for dementia. Other marker candidates have been proposed and are discussed. All of the current studies are hampered by gaps in our knowledge about the molecular causes of cognitive decline, which will have to be considered in future biomarker studies. © 2014 International Parkinson and Movement Disorder Society
The spectrum of cognitive impairment in Lewy body diseases
Authors: Goldman Jennifer G. , Williams‐Gray Caroline , Barker Roger A. , Duda John E. , Galvin James E.
Published: April 2014

Cognitive impairment represents an important and often defining component of the clinical syndromes of Lewy body disorders: Parkinson's disease and dementia with Lewy bodies. The spectrum of cognitive deficits in these Lewy body diseases encompasses a broad range of clinical features, severity of impairment, and timing of presentation. It is now recognized that cognitive dysfunction occurs not only in more advanced Parkinson's disease but also in early, untreated patients and even in those patients with pre‐motor syndromes, such as rapid eye movement behavior disorder and hyposmia. In recent years, the concept of mild cognitive impairment as a transitional or pre‐dementia state in Parkinson's disease has emerged. This has led to much research regarding the diagnosis, prognosis, and underlying neurobiology of mild cognitive impairment in Parkinson's disease, but has also raised questions regarding the usefulness of this concept and its application in clinical and research settings. In addition, the conundrum of whether Parkinson's disease dementia and dementia with Lewy bodies represent the same or different entities remains unresolved. Although these disorders overlap in many aspects of their presentations and pathophysiology, they differ in other elements, such as timing of cognitive, behavioral, and motor symptoms; medication responses; and neuropathological contributions. This article examines the spectrum and evolution of cognitive impairment in Lewy body disorders and debates these controversial issues in the field using point‐counterpoint approaches. © 2014 International Parkinson and Movement Disorder Society
Regulation of intestinal calcium absorption by luminal calcium content: Role of intestinal alkaline phosphatase
Authors: Brun Lucas R. , Brance María L. , Lombarte Mercedes , Lupo Maela , Di Loreto Verónica E. , Rigalli Alfredo
Published: April 2014

Scope

Intestinal alkaline phosphatase is a brush border enzyme that is stimulated by calcium. Inhibition of intestinal alkaline phosphatase increases intestinal calcium absorption. We hypothesized that intestinal alkaline phosphatase acts as a minute‐to‐minute regulatory mechanism of calcium entry. The aim of this study was to evaluate the mechanism by which intestinal luminal calcium controls intestinal calcium absorption.

Methods and results

We performed kinetic studies with purified intestinal alkaline phosphatase and everted duodenal sacs and showed that intestinal alkaline phosphatase modifies the luminal pH as a function of enzyme concentration and calcium luminal content. A decrease in pH occurred simultaneously with a decrease in calcium absorption. The inhibition of intestinal alkaline phosphatase by l‐phenylalanine caused an increase in calcium absorption. This effect was also confirmed in calcium uptake experiments with isolated duodenal cells.

Conclusion

Changes in luminal pH arising from intestinal alkaline phosphatase activity induced by luminal calcium concentration modulate intestinal calcium absorption.
Dual echo vessel‐encoded ASL for simultaneous BOLD and CBF reactivity assessment in patients with ischemic cerebrovascular disease
Authors: Faraco Carlos C. , Strother Megan K. , Dethrage Lindsey M. , Jordan Lori , Singer Robert , Clemmons Paul F. , Donahue Manus J.
Published: April 2014

Purpose

Blood oxygenation level‐dependent (BOLD)‐weighted and vessel‐encoded arterial spin labeling (VE‐ASL) MRI provide complementary information and can be used in sequence to gauge hemodynamic contributions to cerebrovascular reactivity. Here, cerebrovascular reactivity is assessed using dual echo VE‐ASL MRI to understand how VE labeling preparations influence BOLD and ASL contrast in flow‐limited and healthy perfusion territories.

Methods

Patients (n = 12; age = 55 +/– 14 years; 6F/6M) presenting with ischemic steno‐occlusive cerebrovascular disease underwent 3.0T angiographic imaging, T1‐weighted structural, and planning‐free dual echo hypercarbic hyperoxic (i.e., carbogen) VE‐ASL MRI. Vasculopathy extent, timecourses, and cerebrovascular reactivity (signal change and Z‐statistic) for different VE‐ASL images were contrasted across flow territories and Bonferroni‐corrected P‐values reported.

Results

BOLD cerebrovascular reactivity (i.e., long‐TE VE‐ASL) Z‐statistics were similarly sensitive to asymmetric disease (P ≤ 0.002) regardless of labeling scenario. Cerebral blood flow reactivity correlated significantly with BOLD reactivity (Z‐statistic). However, BOLD signal changes did not differ significantly between labeling scenarios (P > 0.003) or across territories (P > 0.002), indicating BOLD signal changes in response to carbogen offer low sensitivity to lateralizing disease.

Conclusion

Dual echo VE‐ASL can provide simultaneous cerebral blood flow and qualitative BOLD contrast consistent with lateralizing disease severity in patients with asymmetric steno‐occlusive disease. The methodological strengths and limitations of composite BOLD and VE‐ASL measurements in the clinic are discussed. Magn Reson Med 73:1579–1592, 2015. © 2014 Wiley Periodicals, Inc.
A Survey of Psychological Support Provision for People with Inflammatory Arthritis in Secondary Care in England
Authors: Dures Emma , Almeida Celia , Caesley Judy , Peterson Alice , Ambler Nicholas , Morris Marianne , Pollock Jon , Hewlett Sarah
Published: April 2014

Objectives

The consequences of inflammatory arthritis can include depression, anxiety and low mood, reducing patients’ quality of life and increasing pressure on the healthcare system. Treatment guidelines recommend psychological support, but data are lacking on the provision available.

Methods

A postal survey concerning psychological support provision was sent to rheumatology units in 143 acute trusts across England. Nurses from 73 rheumatology units (51%) responded.

Results

Overall, 73% rated their unit's psychological support provision as ‘inadequate’ and only 4% rated it as ‘good’. Few units believed that psychological support did not fall within their remit (12%), yet only 8% had a psychologist in the team. Most units (68%) did not routinely screen patients to identify psychological difficulties. Referral to other service providers was reported in 42% of units, with 3% very satisfied with this provision. Within units, services containing elements of psychological support ranged from occupational therapy (81%) to psychology/counselling (14%). Psychological approaches used by team members ranged from shared decision making (77%) to cognitive–behavioural approaches (26%). The current barriers to providing psychological support were lack of clinical time and available training (86% and 74%, respectively), and delivery costs (74%). Future facilitators included management support (74%) and availability of skills training (74%).

Conclusions

Rheumatology units viewed psychological support provision as part of their remit but rated their overall provision as inadequate, despite some team members using psychological skills. To improve provision, clinicians’ training needs must be addressed and organizational support generated, and further research needs to define adequate psychological support provision from the patient perspective. © 2014 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.
Elastic models for nonlinear response of rigid passive piles
Authors: Guo W. D.
Published: April 2014

Recent study indicates that the response of rigid passive piles is dominated by elastic pile–soil interaction and may be estimated using theory for lateral piles. The difference lies in that passive piles normally are associated with a large scatter of the ratio of maximum bending moment over maximum shear force and induce a limiting pressure that is ~1/3 that on laterally loaded piles. This disparity prompts this study.

This paper proposes pressure‐based pile–soil models and develops their associated solutions to capture response of rigid piles subjected to soil movement. The impact of soil movement was encapsulated into a power‐law distributed loading over a sliding depth, and load transfer model was adopted to mimic the pile–soil interaction. The solutions are presented in explicit expressions and can be readily obtained. They are capable of capturing responses of model piles in a sliding soil owing to the impact of sliding depth and relative strength between sliding and stable layer on limiting force prior to ultimate state. In comparison with available solutions for ultimate state, this study reveals the 1/3 limiting pressure (of the active piles) on passive piles was induced by elastic interaction. The current models employing distributed pressure for moving soil are more pertinent to passive piles (rather than plastic soil flow). An example calculation against instrumented model piles is provided, which demonstrates the accuracy of the current solutions for design slope stabilising piles. Copyright © 2014 John Wiley & Sons, Ltd.
Obesity independently influences gonadal function in very long‐term adult male survivors of childhood cancer
Authors: Blijdorp Karin , van Dorp Wendy , Laven Joop S.E. , Pieters Rob , de Jong Frank H. , Pluijm Saskia M.F. , van der Lely Aart Jan , van den Heuvel‐Eibrink Marry M. , Neggers Sebastian J.C.M.M.
Published: April 2014

Objective

Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment.

Methods

Three hundred fifty‐one male CCS were included. Median age at diagnosis was 5.9 years (0‐17.8) and median age at follow‐up 25.6 years (18.0‐45.8). Total and non‐SHBG‐bound testosterone, sex hormone‐binding globulin, inhibin B, and follicle‐stimulating hormone (FSH) were studied. Potential determinants were BMI, waist circumference, waist–hip ratio, and body composition measures (dual energy X‐ray absorptiometry).

Results

Non‐SHBG‐bound testosterone was significantly decreased in survivors with BMI ≥ 30 kg/m2 (adjusted mean 9.1 nmol/L vs. 10.2 nmol/L, P = 0.015), high fat percentage (10.0 vs. 11.2, P = 0.004), and high waist circumference (>102 cm) (9.0 vs. 11.0, P = 0.020). Survivors with high fat percentage (≥25%) had significantly lower inhibin B/FSH ratios (inhibin B/FSH ratio: β −34%, P = 0.041).

Conclusion

Obesity is associated with gonadal dysfunction in male CCS, independent of the irreversible effect of previous cancer treatment. Randomized controlled trials are required to evaluate whether weight normalization could improve gonadal function, especially in obese survivors with potential other mechanisms than lifestyle causing their obesity.
Novel interpenetrating amphiphilic Co‐networks based on compatibilized NBR/SBR‐montmorillonite composites: A study on the oil absorption characteristics
Authors: Essawy Hisham A. , El‐Sabbagh Salwa H. , Tawfik Magda E.
Published: April 2014

This work explores the fabrication of novel amphiphilic interpenetrating co‐network structures that may afford a reasonable solution to the problem of oil spills. It depends upon compatibilization of the binary immiscible rubber blend, containing the polar acrylonitrile–butadiene rubber and the non‐polar styrene–butadiene rubber. The compatibilization process was accomplished successfully using organic‐inorganic hybrid structures based on montmorillonites, priory treated with a hydrophobic cationic agent to different levels so that they acquire wide range of amphiphilicity. With achieving the goal of compatibilization using bi‐polar montmorillonites, the formed amphiphilic interpenetrating network structures are thought to qualify as oil absorbent materials for oils exhibiting a broad spectrum of hydrophilicity/hydrophobicity. For this purpose, toluene, which exhibits both polar and non‐polar characters, was chosen as model to predict the oil absorption and swelling extent as a function of the clay philicity. The capacity of oil uptake showed good correlation to the cross‐linking density. The combination of both polar and non‐polar moieties in polymer structures used as oil absorptive materials provides a good tool to control the properties of the resulting materials supposing that the polarity and/or content of the inserted clay are the key variables: toughness offers buoyancy, stability, and easy recovery of absorbed oils irrespective of their polarity. Furthermore, the recovered oil‐swelled materials are suitable for regular oil‐refining processes (economic, no waste, green approach). The developed materials in this work are additionally advantageous because of cost‐effective concerns with respect to other developed materials in recent years in particular in the presence of the clay as one of the main constituents of these structures. This approach can reduce the environmental impacts from oil spills and help recover one of most precious natural resources. POLYM. COMPOS., 36:1494–1501, 2015. © 2014 Society of Plastics Engineers
Electrochromic enhancement of poly(3,4‐ethylenedioxythiophene) films functionalized with hydroxymethyl and ethylene oxide
Authors: Zhang Shimin , Xu Jingkun , Lu Baoyang , Qin Leiqiang , Zhang Long , Zhen Shijie , Mo Daize
Published: April 2014

2‐((2,3‐Dihydrothieno[3,4‐b]dioxin‐2‐yl)methoxy)methyl oxirane (EDOT‐MO) was successfully synthesized by the reaction of epichlorohydrin with hydroxymethylated‐3,4‐ethylenedioxylthiophene (EDOT‐MeOH), which was synthesized via a simple four‐step sequence. Poly(hydroxymethylated‐3,4‐ethylenedioxylthiophene) (PEDOT‐MeOH) and poly(2‐((2,3‐dihydrothieno[3,4‐b]dioxin‐2‐yl)methoxy)methyl oxirane) (PEDOT‐MO) were electrosynthesized through electropolymerization of EDOT‐MeOH and EDOT‐MO, respectively. Structural, electrochemical, optical, and thermal properties of as‐formed polymers were investigated by FTIR, cyclic voltammetry, UV–vis, and thermogravimetry. Spectroelectrochemistry studies demonstrated that PEDOT‐MeOH and PEDOT‐MO could be reversibly oxidized and reduced accompany with obvious color changes. Further kinetic studies demonstrated that the introduction of hydroxymethyl or ethylene oxide group significantly improved electrochromic properties of 3,4‐ethylenedioxythiophene (PEDOT) and resulted in high contrast ratios (57.3% at 585 nm) and coloration efficiencies (338.5 cm2 C−1), low switching voltages, and fast response time. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1989–1999
Fibrinogen α‐chain‐derived peptide is upregulated in hippocampus of rats exposed to acute morphine injection and spontaneous alternation testing
Authors: Maki Agatha E. , Morris Kenneth A. , Catherman Kasia , Chen Xian , Hatcher Nathan G. , Gold Paul E. , Sweedler Jonathan V.
Published: April 2014

Fibrinogen is a secreted glycoprotein that is synthesized in the liver, although recent in situ hybridization data support its expression in the brain. It is involved in blood clotting and is released in the brain upon injury. Here, we report changes in the extracellular levels of fibrinogen α‐chain‐derived peptides in the brain after injections of saline and morphine. More specifically, in order to assess hippocampus‐related working memory, an approach pairing in vivo microdialysis with mass spectrometry was used to characterize extracellular peptide release from the hippocampus of rats in response to saline or morphine injection coupled with a spontaneous alternation task. Two fibrinopeptide A‐related peptides derived from the fibrinogen α‐chain – fibrinopeptide A (ADTGTTSEFIEAGGDIR) and a fibrinopeptide A‐derived peptide (DTGTTSEFIEAGGDIR) – were shown to be consistently elevated in the hippocampal microdialysate. Fibrinopeptide A was significantly upregulated in rats exposed to morphine and spontaneous alternation testing compared with rats exposed to saline and spontaneous alternation testing (P < 0.001), morphine alone (P < 0.01), or saline alone (P < 0.01), respectively. The increase in fibrinopeptide A in rats subjected to morphine and a memory task suggests that a complex interaction between fibrinogen and morphine takes place in the hippocampus.
Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA
Authors: Eriksson Robert , Aagaard Lise , Jensen Lars Juhl , Borisova Liza , Hørlück Dorte , Brunak Søren , Hansen Ebba Holme
Published: April 2014

Pharmaceutical product information (PI) supplied by the regulatory authorities serves as a source of information on safe and effective use of drugs. The objectives of this study were to qualitatively and quantitatively compare PIs for selected drugs marketed in both Denmark and the USA with respect to consistency and discrepancy of listed adverse drug reaction (ADR) information. We compared individual ADRs listed in PIs from Denmark and the USA with respect to type and frequency. Consistency was defined as match of ADRs and of ADR frequency or match could not be ruled out. Discrepancies were defined as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n = 1874; 47%) showed consistency. Discrepancies (n = 2129; 53%) were split into ADRs listed only in the USA (n = 1558; 39%), ADRs listed only in Denmark (n = 325; 8%) and ADRs listed with different frequencies (n = 246; 6%). The majority of listed ADRs were of the type “gastrointestinal disorders” and “nervous system disorders”. Our results show great differences in PIs for drugs approved in both Denmark and the USA illuminating concerns about the credibility of the publicly available PIs. The results also represent an argument for further harmonization across borders to improve consistency between authority‐supplied information.
Perivascular adipose tissue contains functional catecholamines
Authors: Ayala‐Lopez Nadia , Martini Marisa , Jackson William F. , Darios Emma , Burnett Robert , Seitz Bridget , Fink Gregory D. , Watts Stephanie W.
Published: April 2014

The sympathetic nervous system and its neurotransmitter effectors are undeniably important to blood pressure control. We made the novel discovery that perivascular adipose tissue (PVAT) contains significant concentrations of catecholamines. We hypothesized thatPVATcontains sufficient releasable catecholamines to affect vascular function. High‐pressure liquid chromatography, isometric contractility, immunohistochemistry, whole animal approaches, and pharmacology were used to test this hypothesis. In normal rat thoracic aorta and superior mesenteric artery, the indirect sympathomimetic tyramine caused a concentration‐dependent contraction that was dependent on the presence ofPVAT. Tyramine stimulated release of norepinephrine (NA), dopamine (DA) and the tryptamine serotonin (5‐hydroxytryptamine [5‐HT]) fromPVATisolated from both arteries. In both arteries, tyramine‐induced concentration‐dependent contraction was rightward‐shifted and reduced by the noradrenaline transporter inhibitor nisoxetine (1 μmol/L), the vesicular monoamine transporter inhibitor tetrabenazine (10 μmol/L), and abolished by theαadrenoreceptor antagonist prazosin (100 nmol/L). Inhibitors of theDAand 5‐HTtransporter did not alter tyramine‐induced,PVAT‐dependent contraction. Removal of the celiac ganglion as a neuronal source of catecholamines for superior mesenteric arteryPVATdid not significantly reduce the maximum or shift the concentration‐dependent contraction to tyramine. Electrical field stimulation of the isolated aorta was not affected by the presence ofPVAT. These data suggest thatPVATcomponents that are independent of sympathetic nerves can releaseNAin a tyramine‐sensitive manner to result in arterial contraction. BecausePVATis intimately apposed to the artery, this raises the possibility of local control of arterial function byPVATcatecholamines.
VS‐501: a novel, nonabsorbed, calcium‐ and aluminum‐free, highly effective phosphate binder derived from natural plant polymer
Authors: Wu‐Wong J. Ruth , Chen Yung‐wu , Gaffin Robert , Hall Andy , Wong Jonathan T. , Xiong Joseph , Wessale Jerry L.
Published: April 2014

Inadequate control of serum phosphate in chronic kidney disease can lead to pathologies of clinical importance. Effectiveness of on‐market phosphate binders is limited by safety concerns and low compliance due to high pill size/burden and gastrointestinal (GI) discomfort. VS‐501 is a nonabsorbed, calcium‐ and aluminum‐free, chemically modified, plant‐derived polymer. In vitro studies show that VS‐501 has a high density and a low swell volume when exposed to simulated gastric fluid (vs. sevelamer). When male Sprague–Dawley (SD) rats on normal diet were treated with VS‐501 or sevelamer, serum phosphate was not significantly altered, but urinary phosphate levels decreased by >90%. VS‐501 had no effect on serum calcium (Ca) or urinary Ca, while 3% sevelamer significantly increased serum and urine Ca. In 5/6 nephrectomized (NX) uremic SD rats on high‐phosphate diet, increasing dietary phosphate led to an increase in serum and urine phosphate, which was prevented in rats treated with VS‐501 or sevelamer (0.2–5% in food). High‐phosphate diet also increased serum fibroblast growth factor‐23 and parathyroid hormone in 5/6 NX rats that was prevented by VS‐501 or sevelamer. VS‐501 or sevelamer increased fecal phosphate in a dose‐dependent manner. More aortic calcification was observed in 5/6 NX rats treated with 5% sevelamer, while VS‐501 and sevelamer did not show significant effects on cardiac parameters, fibrosis, intestine histology, and intestinal sodium‐dependent phosphate cotransporter gene expression. These results suggest that VS‐501 is effective in binding phosphate with no effects on calcium homeostasis, and may have improved pill burden and GI side effects.
NL‐103, a novel dual‐targeted inhibitor of histone deacetylases and hedgehog pathway, effectively overcomes vismodegib resistance conferred by Smo mutations
Authors: Zhao Jie , Quan Haitian , Xie Chengying , Lou Liguang
Published: April 2014

Misregulation of hedgehog (Hh) signaling has been implicated in the pathogenesis of basal cell carcinoma (BCC) and medulloblastoma. Vismodegib, an orally bioavailable Hh signal pathway inhibitor targeting Smo, has been approved for the treatment of advanced BCC. However, acquired drug resistance to vismodegib induced by point mutation in Smo is emerging as a major problem to vismodegib treatment. In this study, we designed and synthesized a novel chimeric compound NL‐103, which comprises structural elements of Hh pathway inhibitor vismodegib, and histone deacetylase (HDAC) inhibitor vorinostat. NL‐103 simultaneously and significantly inhibited both HDACs and Hh pathway. Importantly, NL‐103, as well as vorinostat, effectively overcame vismodegib resistance induced by Smoothened point mutations. Moreover, NL‐103 and vorinostat, but not vismodegib, significantly downregulated the expression of Gli2 which plays an important role in Hh pathway. These results indicate that HDAC inhibitory activity is essential for NL‐103 to overcome vismodegib resistance and that dual inhibition of HDAC and Hh signaling pathway may be a rational strategy for overcoming vismodegib resistance. Our findings suggest that NL‐103 may be a promising compound for clinical development as a more effective Hh pathway inhibitor.
Dexmedetomidine preconditioning ameliorates kidney ischemia‐reperfusion injury
Authors: Lempiäinen Juha , Finckenberg Piet , Mervaala Elina E. , Storvik Markus , Kaivola Juha , Lindstedt Ken , Levijoki Jouko , Mervaala Eero M.
Published: April 2014

Kidney ischemia‐reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2‐AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham‐operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2‐AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen‐activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury‐induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre‐ nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R‐induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid‐derived 2)‐like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38‐CD44‐pathway and possibly also through ischemic preconditioning.
Causes and recommended management of acute diarrhoea
Authors: Ede Roland
Published: April 2014

Acute diarrhoea is usually the result of a self‐limiting infection and can often be self‐managed; however, hospital admission is indicated for severe cases. In our Drug review, the author discusses the causes and types of acute diarrhoea and the available management options, followed by a review of the prescription data and sources of further information.
Raman imaging for surface characterisation of annealed electrical steel surfaces
Authors: Hambrock Carina , Vincze‐Minya Krisztina , Hild Sabine , Hassel Achim Walter
Published: April 2014

Raman spectroscopy is a powerful tool in the determination of biological and polymeric samples. However, also the use of Raman spectroscopy for inorganic applications like for the determination of different iron oxides after specific corrosion experiments or meteorite compositions is common. In this work, the method of Raman imaging has been used for surface characterisation of high temperature long‐term annealed steel samples as a function of the dew point of the annealing atmosphere. The investigation revealed that at a high dew point, oxides (Al2O3, SiO2), silicates (Fe2SiO4) and spinel phases (Fe2SiO4‐spinel) could be identified by Raman imaging whereas at a low dew point the reactivity of aluminium with nitrogen and oxygen was preferred and the phase of aluminium nitride (AlN) as well as some aluminium oxide (Al2O3) could be detected. The Raman imaging was supported by EDX mapping to obtain the elemental composition of the surface and by XPS measurements to get an insight into the bonding states of the elements which both confirmed the results obtained via Raman imaging.
Toward multi‐analyte bioarray sensors: LAPS‐based on‐chip determination of a Michaelis–Menten‐like kinetics for cell culturing
Authors: Takenaga S. , Herrera C. , Werner C. F. , Biselli M. , Thönnessen V. , Schnitzler Th. , Öhlschläger P. , Almajhdi F. N. , Wagner T. , Schöning M. J.
Published: April 2014

The metabolic activity of Chinese hamster ovary (CHO) cells was observed using a light‐addressable potentiometric sensor (LAPS). The dependency toward different glucose concentrations (17–200 mM) follows a Michaelis–Menten kinetics trajectory with Km = 32.8 mM, and the obtained Km value in this experiment was compared with that found in literature. In addition, the pH shift induced by glucose metabolism of tumor cells transfected with the HPV‐16 genome (C3 cells) was successfully observed. These results indicate the possibility to determine the tumor cells metabolism with a LAPS‐based measurement device.
Synthesis of silicon nanowires from carbothermic reduction of silica fume in RF thermal plasma
Authors: Lamontagne Pascal , Soucy Gervais , Veilleux Jocelyn , Quesnel François , Hovington Pierre , Zhu Wen , Zaghib Karim
Published: April 2014

Silica fume, which is a by‐product of metallurgical‐grade silicon production, is a low cost material with high SiO2 concentration and small particle size (<1 µm). These properties make it a good candidate for radio‐frequency (RF) thermal plasma processing. In this article, the use of silica fume as a reactant is promoted for the RF thermal plasma synthesis of high‐charge capacity, high cyclability anode materials for lithium‐ion batteries. In order to obtain these materials, the carboreduction of silica fume is followed by an in‐flight growth of silicon nanowires in the plasma reactor. The impact of the addition of catalysts and the use of different plasma gases on the yield and the properties of the product has been investigated by X‐ray diffractometry (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy dispersion spectrometry (EDS), and transmission electron microscopy (TEM). It is found that the addition of metal catalysts has a significant effect on the synthesis. It not only promoted the formation of silicon nanowires, but also improved the yield of the reaction upwards of 300%. An insight on the mechanisms leading to the silicon nanowires formation is also discussed in the results section.
Physics‐based modeling and microwave characterization of graphene co‐planar waveguides
Authors: Heo Keun , Cho Kyung‐Sang , Lee Jae Hyun , Jang Yamujin , Kim Sangsig , Hwang Sung Woo , Whang Dongmok
Published: April 2014

In this study, large area mono‐, bi‐, and multi‐layer graphenes (MLG) were synthesized using low pressure chemical vapor deposition (LPCVD) process and co‐planar waveguides (CPW) with graphenes being fabricated using conventional photolithography. The intrinsic room temperature radio frequency (RF) characteristics were measured via direct contact to the graphene surface with a probe–tip in the range of 0.1 GHz to 40 GHz without using metal electrodes. The device characteristics were also evaluated by physics‐based RLC equivalent circuit simulation. The proposed equivalent circuit model reproduced all of the measured characteristics within 3% of RMSE and we numerically extracted the set of component values which minimize the error between the measured data and the simulation results over the measured regime. Our findings demonstrate that MLG is an effective candidate in RF interconnect device applications. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Self‐catalysed growth of InAs nanowires on bare Si substrates by droplet epitaxy
Authors: Anyebe E. A. , Zhuang Q. , Sanchez A. M. , Lawson S. , Robson A. J. , Ponomarenko L. , Zhukov A. , Kolosov O.
Published: April 2014

We demonstrate the self‐catalyst growth of vertically aligned InAs nanowires on bare Si(111) by droplet epitaxy. The growth conditions of indium droplets suitable for nucleation and growth of nanowires have been identified. We have then realized vertically aligned and non‐tapered InAs nanowires on bare Si(111) substrates through optimal indium droplets. It was found that the lateral dimensions and density of nano‐wires are defined by the indium droplets. This technique unravels a controllable, cost‐effective and time‐efficient route to fabricating functional monolithic hybrid structures of InAs nanowires on silicon.

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(© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electronic quantum trajectories in a quantum dot
Authors: Yang Ciann‐Dong , Huang Shih‐Ming
Published: April 2014

This article gives a quantum‐trajectory demonstration of the observed electric, magnetic, and thermal effects on a quantum dot with circular or elliptic shape. By applying quantum trajectory method to a quantum dot, we reveal the quantum‐mechanical meanings of the classical concepts of backscattering and commensurability, which were used in the literature to explain the peak locations of the magnetoresistance curve. Under the quantum commensurability condition, electronic quantum trajectories in a circular quantum dot are shown to be stationary like a standing wave, whose presence increases the electrical resistance. A hidden quantum effect called magnetic stagnation is discovered and shown to be the main cause of the observed jumps of the magnetoresistance curve. Quantum trajectories in an elliptic quantum dot are found to be chaotic and an index of chaos called Lyapunov exponent is proposed to measure the irregularity of the various quantum trajectories. It is shown that the response of the Lyapunov exponent to the applied magnetic field captures the main features of the experimental magnetoresistance curve. © 2014 Wiley Periodicals, Inc.
Assessing the goodness of fit of personal risk models
Authors: Gong Gail , Quante Anne S. , Terry Mary Beth , Whittemore Alice S.
Published: April 2014

We describe a flexible family of tests for evaluating the goodness of fit (calibration) of a pre‐specified personal risk model to the outcomes observed in a longitudinal cohort. Such evaluation involves using the risk model to assign each subject an absolute risk of developing the outcome within a given time from cohort entry and comparing subjects’ assigned risks with their observed outcomes. This comparison involves several issues. For example, subjects followed only for part of the risk period have unknown outcomes. Moreover, existing tests do not reveal the reasons for poor model fit when it occurs, which can reflect misspecification of the model's hazards for the competing risks of outcome development and death. To address these issues, we extend the model‐specified hazards for outcome and death, and use score statistics to test the null hypothesis that the extensions are unnecessary. Simulated cohort data applied to risk models whose outcome and mortality hazards agreed and disagreed with those generating the data show that the tests are sensitive to poor model fit, provide insight into the reasons for poor fit, and accommodate a wide range of model misspecification. We illustrate the methods by examining the calibration of two breast cancer risk models as applied to a cohort of participants in the Breast Cancer Family Registry. The methods can be implemented using the Risk Model Assessment Program, an R package freely available athttp://stanford.edu/~ggong/rmap/. Copyright © 2014 John Wiley & Sons, Ltd.