bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnic and migrant differences in the use of anti‐asthmatic medication for children: the effect of place of residence
Authors: Cantarero‐Arévalo Lourdes , Ersbøll Annette Kjær , Holstein Bjørn E. , Andersen Anette , Kaae Susanne , Hansen Ebba Holme
Published: October 2013

Background

Ethnic differences in the use of anti‐asthmatic medication have been reported, with ethnic minorities being at a higher risk of suboptimal asthma control. As contextual socioeconomic characteristics may play a role, we analysed whether ethnic differences in the use of anti‐asthmatic medication among children residing in the Capital Region of Denmark varied by place of residence.

Methods

Data were obtained from the Danish Civil Registration System, the Central Taxpayers' Register and the Danish National Prescription Register and were linked at the individual level. Population used was the entire child population in the Capital Region from 0 to 17 years old in 2008 (n = 342 403). Use of anti‐asthma medicine was defined as at least one prescription having been filled in 2008. The analyses included multiple multilevel logistic regression models.

Results

Children living in low‐income places of residence had lower odds of being prescribed preventive anti‐asthmatics compared with children living in higher‐income places of residence [odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.84–0.91]. Immigrant children had the lowest OR of being prescribed anti‐asthmatics medication, both relief (OR = 0.50, 95% CI 0.20–0.77) and preventive (OR = 0.47, 95% CI 0.24–0.82) compared with ethnic Danes. Similar associations were found among descendants of immigrant children (OR for preventive medication = 0.70, 95% CI 0.62–0.78). Place of residence contributed to but did not account for the ethnic differences in the use of anti‐asthmatic medication.

Conclusions

Ethnic differences in the use of anti‐asthmatic medication were documented, and they cannot be explained by socioeconomic characteristics of place of residence. The lower prevalence of anti‐asthmatic medication among ethnic minority children suggests poor asthma management control. Copyright © 2013 John Wiley & Sons, Ltd.
Two birds with one stone: Doing metabolomics with your proteomics kit
Authors: Fischer Roman , Bowness Paul , Kessler Benedikt M.
Published: October 2013

Proteomic research facilities and laboratories are facing increasing demands for the integration of biological data from multiple ‘‐OMICS’ approaches. The aim to fully understand biological processes requires the integrated study of genomes, proteomes and metabolomes. While genomic and proteomic workflows are different, the study of the metabolome overlaps significantly with the latter, both in instrumentation and methodology. However, chemical diversity complicates an easy and direct access to the metabolome by mass spectrometry (MS). The present review provides an introduction into metabolomics workflows from the viewpoint of proteomic researchers. We compare the physicochemical properties of proteins and peptides with metabolites/small molecules to establish principle differences between these analyte classes based on human data. We highlight the implications this may have on sample preparation, separation, ionisation, detection and data analysis. We argue that a typical proteomic workflow (nLC‐MS) can be exploited for the detection of a number of aliphatic and aromatic metabolites, including fatty acids, lipids, prostaglandins, di/tripeptides, steroids and vitamins, thereby providing a straightforward entry point for metabolomics‐based studies. Limitations and requirements are discussed as well as extensions to the LC‐MS workflow to expand the range of detectable molecular classes without investing in dedicated instrumentation such as GC‐MS, CE‐MS or NMR.
Time Efficiency of Point-of-Sale Payment Methods: Empirical Results for Cash, Cards and Mobile Payments
Authors: Polasik Michal , Górka Jakub , Wilczewski Gracjan , Kunkowski Janusz , Przenajkowska Karolina , Tetkowska Natalia
Published: October 2013

We propose a novel approach for the time efficiency study of payment process at Point-Of-Sale (POS). A wide range of payment methods from cash and standard cards to contactless cards, RFID stickers and mobile payments (NFC and remote) was analysed. Transactions were timed by means of digital chronography of video material recorded in the biggest chain of convenience stores in Poland. Our results confirm that cash is a significantly faster payment method than traditional payment card with a magnetic stripe or EMV chip. However, the innovative payment methods, such as contactless cards and NFC mobile payments, are competitive to cash in terms of time efficiency. Contactless cards used in offline mode and without printing paper slips are the first popular electronic payment method in history faster than cash. Our results could be applied to optimise the payment process at POS as well as to develop innovative and efficient payment solutions.
Valproyl‐CoA inhibits the activity of ATP‐ and GTP‐dependent succinate:CoA ligases
Authors: Luís Paula B. M. , Ruiter Jos , IJlst Lodewijk , de Almeida Isabel Tavares , Duran Marinus , Wanders Ronald J. A. , Silva Margarida F. B.
Published: October 2013

Background

Valproic acid (VPA) is an effective antiepileptic drug that may induce progressive microvesicular steatosis. The impairment of mitochondrial function may be an important metabolic effect of VPA treatment with potential adverse consequences.

Objective

To investigate the influence of VPA on the activity of GTP‐ and ATP‐specific succinate:CoA ligases (G‐SUCL and A‐SUCL).

Methods

The GTP‐ and ATP‐specific SUCL activities were measured in human fibroblasts in the reverse direction, i.e. the formation of succinyl‐CoA. These were assessed at different concentrations of succinate in the presence of VPA, valproyl‐CoA and zinc chloride, an established inhibitor of the enzymes. Activities were measured using an optimized HPLC procedure.

Results

Valproyl‐CoA (1 mM) inhibited the activity of A‐SUCL and G‐SUCL by 45‐55 % and 25‐50 %, respectively. VPA (1 mM) had no influence on the activity of the two enzymes.

Discussion

Valproyl‐CoA appears to affect the activity of SUCL, especially with the ATP‐specific enzyme. Considering the key role of SUCL in the Krebs cycle, interference with its activity might impair the cellular energy status. Moreover, A‐SUCL is bound to the nucleoside diphosphate kinase (NDPK), which is responsible for the mitochondrial (deoxy)nucleotide synthesis. An inhibition of A‐SUCL might influence the activity of NDPK inducing an imbalance of nucleotides in the mitochondria and eventually mitochondrial DNA depletion. This may account for the potential liver failure associated with valproate therapy, reported in patients with deficiencies within the mitochondrial DNA replicase system such as polymerase gamma 1.
Spectral Decompositions of Multiple Time Series: A Bayesian Non-parametric Approach
Authors: Macaro Christian , Prado Raquel
Published: October 2013

We consider spectral decompositions of multiple time series that arise in studies where the interest lies in assessing the influence of two or more factors. We write the spectral density of each time series as a sum of the spectral densities associated to the different levels of the factors. We then use Whittle’s approximation to the likelihood function and follow a Bayesian non-parametric approach to obtain posterior inference on the spectral densities based on Bernstein–Dirichlet prior distributions. The prior is strategically important as it carries identifiability conditions for the models and allows us to quantify our degree of confidence in such conditions. A Markov chain Monte Carlo (MCMC) algorithm for posterior inference within this class of frequency-domain models is presented.

We illustrate the approach by analyzing simulated and real data via spectral one-way and two-way models. In particular, we present an analysis of functional magnetic resonance imaging (fMRI) brain responses measured in individuals who participated in a designed experiment to study pain perception in humans.
Engine out of the chassis: Cell‐free protein synthesis and its uses
Authors: Rosenblum Gabriel , Cooperman Barry S.
Published: October 2013

The translation machinery is the engine of life. Extracting the cytoplasmic milieu from a cell affords a lysate capable of producing proteins in concentrations reaching to tens of micromolar. Such lysates, derivable from a variety of cells, allow the facile addition and subtraction of components that are directly or indirectly related to the translation machinery and/or the over‐expressed protein. The flexible nature of such cell‐free expression systems, when coupled with high throughput monitoring, can be especially suitable for protein engineering studies, allowing one to bypass multiple steps typically required using conventional in vivo protein expression.
High non-standard employment rates in the Republic of Korea and Japan: Analyzing policy configurations with fuzzy-set/QCA
Authors: Lee Sophia Seung-yoon
Published: October 2013

The paper investigates policy conditions for high rates of non-standard employment in Korea and Japan exploiting fs/QCA (fuzzy-set Qualitative Comparative Analysis). We first review the previous literature on labor market risks and discuss the advantages of taking a configurational approach in investigating policies related to increase of non-standard workers. Secondly, non-standard employment in Korea and Japan are examined more closely in comparison with other OECD countries. In case of Korea, a low level of statutory minimum wage in combination with strict employment protection legislation for permanent workers is suggested as the sufficient condition for high rate of non-standard employment rate. In case of Japan, a low level of statutory minimum wage in combination with weak employment protection legislations for temporary workers is suggested to lead to a high level of non-standard employment rate. We empirically test which policy configurations cause high rate of non-standard employment and discuss (i) the importance of examining multiple policies together and (ii) that there can be different pathways to the same outcome.
Isotope and trace element evolution of the naica aquifer (Chihuahua, Mexico) over the past 60,000 yr revealed by speleothems
Authors: Gázquez Fernando , Calaforra Jos"-Mar"a , Stoll Heather , Sanna Laura , Forti Paolo , Lauritzen Stein-Erik , Delgado Antonio , Rull Fernando , Martínez-Frías Jesús
Published: October 2013

The “espada” speleothems of Cueva de las Espadas (Naica Mine, Chihuahua, Mexico) comprise a high-purity selenite core overlain by successive deposits of calcite, gypsum and aragonite. Gypsum precipitated under water from a hydrothermal solution (~ 58°C) when the water table was above the cave level ca. 57 ka, during the last glaciation, and some intervals during deglaciation and the Holocene. Aragonite was deposited at lower temperatures (~ 26°C) in a perched lake occupying the cave bottom, when the water table dropped below the cave level during brief dry intervals during deglaciation and the early Holocene. The isotopic composition of gypsum water of crystallization shows that the deglaciation–Holocene aquifer water was enriched in deuterium by 12.8–8.7‰ relative to water from the last glaciation. This is attributed to an increased relative moisture contribution from the Gulf of Mexico during deglaciation and the Holocene compared to the last glaciation. This indicates that drier conditions occurred in the Naica area during the Holocene than around 57 ka. Furthermore, trace element analyses of gypsum served to deduce the circulation regime of the Naica aquifer during the past 60,000 yr, and also suggest that higher aquifer recharge occurred during the last glaciation.
Weakly nonlinear instability of planar viscous sheets
Authors: Yang Lijun , Wang Chen , Fu Qingfei , Du Minglong , Tong Mingxi
Published: October 2013

A second-order instability analysis has been performed for sinuous disturbances on two-dimensional planar viscous sheets moving in a stationary gas medium using a perturbation technique. The solutions of second-order interface disturbances have been derived for both temporal instability and spatial instability. It has been found that the second-order interface deformation of the fundamental sinuous wave is varicose or dilational, causing disintegration and resulting in ligaments which are interspaced by half a wavelength. The interface deformation has been presented; the breakup time for temporal instability and breakup length for spatial instability have been calculated. An increase in Weber number and gas-to-liquid density ratio extensively increases both the temporal or spatial growth rate and the second-order initial disturbance amplitude, resulting in a shorter breakup time or length, and a more distorted surface deformation. Under normal conditions, viscosity has a stabilizing effect on the first-order temporal or spatial growth rate, but it plays a dual role in the second-order disturbance amplitude. The overall effect of viscosity is minor and complicated. In the typical condition, in which the Weber number is 400 and the gas-to-liquid density ratio is 0.001, viscosity has a weak stabilizing effect when the Reynolds number is larger than 150 or smaller than 10; when the Reynolds number is between 150 and 10, viscosity has a weak destabilizing effect.
The Beasts at Ephesus and the Cult of Artemis
Authors: Frayer-Griggs Daniel
Published: October 2013

The wordscrux interpretumare frequently invoked over the question Paul poses to his Corinthian acquaintances in 1 Cor 15:32: εἰ κατὰ ἄνθρωπον ἐθηριομάχησα ἐν Ἐφεσῳ, τί μοι τὸ ὄφελος; “If with merely human hopes I fought with beasts at Ephesus, what would I have gained by it?” Three principal questions have occupied interpreters of this enigmatic verse. First, does the verb ἐθηριομάχησα imply a literal fight with wild beasts, does it allude figuratively to a hostile conflict with human adversaries, or does it refer hypothetically to a literal event (an unreal conditional)? Second, if the verb is meant figuratively, as nearly all today conclude, whom does Paul characterize as “wild beasts”? Third, what is meant by the phrase κατὰ ἄνθρωπον?
The effect of dicyandiamide addition to cattle slurry on soil gross nitrogen transformations at a grassland site in Northern Ireland
Authors: McGEOUGH K. L. , MÜLLER C. , LAUGHLIN R. J. , WATSON C. J. , ERNFORS M. , CAHALAN E. , RICHARDS K. G.
Published: October 2013

Many studies have shown the efficacy of the nitrification inhibitor dicyandiamide (DCD) in reducing nitrous oxide (N2O) emissions and nitrate (NO3−) leaching. However, there is no information on the effect of DCD on gross soil N transformations under field conditions, which is key information if it is to be used as a mitigation strategy to reduce N losses. The current field study was conducted to determine the effect of DCD on ten gross nitrogen (N) transformations in soil following cattle slurry (CS) application to grassland in Northern Ireland on three occasions (June 2010, October 2010 and March 2011).

Ammonium (NH4+) oxidation (ONH4) was the dominant process in total NO3−production (ONH4+ONrec(oxidation of recalcitrant organic N to NO3−)) following CS application, accounting for 0·894–0·949. Dicyandiamide inhibited total NO3−production from CS by 0·781, 0·696 and 0·807 in June 2010, October 2010 and March 2011, respectively. The lower inhibition level in October 2010 was thought to be due to the higher rainfall and soil moisture content in that month compared to the other application times. As DCD strongly inhibited NH4+oxidation following CS application, it also decreased the rate of total NO3−consumption, since less NO3−was formed. The rates of mineralization from recalcitrant organic-N (MNrec) were higher than from labile organic-N (MNlab) on all occasions. The DCD significantly increased total mineralization (MNrec+MNlab) following CS application in June 2010 and March 2011, but had no significant effect in October 2010. In contrast, the rate of immobilization of labile organic-N (INH4_Nlab) was higher than from recalcitrant organic-N (INH4_Nrec) on all occasions, accounting for 0·878–0·976 of total NH4+immobilization from CS. The DCD significantly increased total immobilization (INH4_Nrec+INH4_Nlab) when CS was applied in June 2010, but had no significant effect at other times of the year.

Dicyandiamide was shown to be a highly effective inhibitor of ammonium oxidation at this grassland site. Although there was evidence that it increased both NH4+mineralization and immobilization following CS application, its effect on these processes was inconsistent. Further work is required to understand the reason for these inconsistent effects: future improvements in15N tracer models may help.
The nitrogen footprint of food products in the European Union
Authors: LEIP A. , WEISS F. , LESSCHEN J. P. , WESTHOEK H.
Published: October 2013

Nitrogen (N) is an essential element for plants and animals. Due to large inputs of mineral fertilizer, crop yields and livestock production in Europe have increased markedly over the last century, but as a consequence losses of reactive N to air, soil and water have intensified as well. Two different models (CAPRI and MITERRA) were used to quantify the N flows in agriculture in the European Union (EU27), at country-level and for EU27 agriculture as a whole, differentiated into 12 main food categories. The results showed that the N footprint, defined as the total N losses to the environment per unit of product, varies widely between different food categories, with substantially higher values for livestock products and the highest values for beef (c. 500 g N/kg beef), as compared to vegetable products. The lowest N footprint of c. 2 g N/kg product was calculated for sugar beet, fruits and vegetables, and potatoes. The losses of reactive N were dominated by N leaching and run-off, and ammonia volatilization, with 0·83 and 0·88 due to consumption of livestock products. The N investment factors, defined as the quantity of new reactive N required to produce one unit of N in the product varied between 1·2 kg N/kg N in product for pulses to 15–20 kg N for beef.
From Economic Incentives to Dialogic Nudging – The Politics of Change and Inertia in Norwegian Sickness Insurance
Authors: HAGELUND ANNIKEN
Published: October 2013

In 1978, Norway established a sickness insurance with no waiting days and full wage compensation. For the past thirty years, Norwegian authorities have repeatedly attempted to change this incentive structure in order to reduce comparatively high sickness-absence levels, but with little success. Thus, Norway seems to exemplify the retrenchment literature's diagnosis of fiscally unsustainable welfare states whose attempts to reduce costs are blocked by strong interest groups and institutional inertia. However, while changes in the incentive structure have been blocked, policy development has taken other paths.

New structures for monitoring sickness absence and for activating employers and employees have been established. The course of a sickness-absence spell has been regulated, with ‘stop points’ and procedures which must be adhered to. Rather than increasing employers’ and employees’ economic responsibility, these actors have been made responsible for the establishment of individual plans, they are to enter into dialogue at compulsory meetings and aim towards the use of active measures. While this often has been perceived as a sign of inability to reform, it may alternatively be viewed as the silent establishment of new relations of governance.

By analysing this specific case, the paper addresses the wider issue of welfare state change. Through the analysis of incremental, qualitative reforms such as these – often overlooked in comparative social policy research – it throws light upon how social policies may work through restructuring citizen–employer–social partner–state relationships.
AN INCENTIVE THEORY OF MATCHING
Authors: Brown Alessio , Merkl Christian , Snower Dennis
Published: October 2013

This paper presents a theory of the labor market matching process in terms of incentive-based, two-sided search among heterogeneous agents. The matching process is decomposed into its two component stages: the contact stage, in which job searchers make contact with employers, and the selection stage, in which they decide whether to match. We construct a theoretical model explaining two-sided selection through microeconomic incentives. Firms face adjustment costs in responding to heterogeneous variations in the characteristics of workers and jobs. Matches and separations are described through firms' job offer and firing decisions and workers' job acceptance and quit decisions. Our calibrated model for the United States can account for important empirical regularities, such as the large volatilities of labor market variables, that the conventional matching model cannot.
Detail and the devil of on-farm parasite control under climate change
Authors: Morgan Eric R.
Published: October 2013

Levels and seasonal patterns of parasite challenge to livestock are likely to be affected by climate change, through direct effects on life cycle stages outside the definitive host and through alterations in management that affect exposure and susceptibility. Net effects and options for adapting to them will depend very strongly on details of the system under consideration. This short paper is not a comprehensive review of climate change effects on parasites, but rather seeks to identify key areas in which detail is important and arguably under-recognized in supporting farmer adaptation. I argue that useful predictions should take fuller account of system-specific properties that influence disease emergence, and not just the effects of climatic variables on parasite biology. At the same time, excessive complexity is ill-suited to useful farm-level decision support. Dealing effectively with the ‘devil of detail’ in this area will depend on finding the right balance, and will determine our success in applying science to climate change adaptation by farmers.
Things Can Be Told Apart
Authors: Nett Nadine , Frings Christian
Published: October 2013

A recent finding suggests that people use spatial distances of responses to separate nonspatial information in a simple categorization task like the Stroop task. It was suggested that the larger the distance becomes the easier the categorization will get; indeed, with large distances between response keys a smaller Stroop effect was observed by Lakens and colleagues (2011) as compared with small distances. This is a noteworthy finding albeit the published experiments suffer from two confounds which open the door for explanations of the distance effects in terms of spatial mismatch and recoding strategies. We conceptually replicated the results previously observed without these confounds and confirm the main result of Lakens et al. (2011) in that Stroop effects were significantly smaller if the distance between the response keys increased.
In Touch With the Simon Effect *The first two authors contributed equally.
Authors: Salzer Yael , Aisenberg Daniela , Oron-Gilad Tal , Henik Avishai
Published: October 2013

Cognitive control has been extensively studied using the auditory and visual modalities. In the current study, a tactile version of the Simon task was created in order to test control mechanisms in a modality that was less studied, to provide comparative and new information. A significant Simon effect – reaction time gap between congruent (i.e., stimulus and response in the same relative location) and incongruent (i.e., stimulus and response in opposite locations) stimuli – provided grounds to further examine both general and tactile-specific aspects of cognitive control in three experiments. By implementing a neutral condition and conducting sequential and distributional analysis, the present study: (a) supports two different independent mechanisms of cognitive control – reactive control and proactive control; (b) reveals facilitation and interference within the tactile Simon effect; and (c) proposes modality differences in activation and processing of the spatially driven stimulus-response association.
Blood Glutamate Scavenging as a Novel Neuroprotective Treatment for Paraoxon Intoxication
Authors: Ruban Angela , Mohar Boaz , Jona Ghil , Teichberg Vivian I
Published: October 2013

Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.
Phase equilibrium in Mg-Cu-Y
Authors: Mezbahul-Islam Mohammad , Medraj Mamoun
Published: October 2013

Magnesium-based bulk metallic glasses (BMG) have potential in applications ranging from biomedical to sports equipment and the Mg-Cu-Y system offers some of the most promising alloys. Phase relations and ternary solubility of the binary and ternary compounds of this system have been experimentally investigated. The Isothermal section of Mg-Cu-Y system at 673 K for the entire composition range has been constructed. Phase relations in the Cu-rich (>66 at.% Cu) region of the Mg-Cu-Y system has been determined for the first time. The homogeneity range of three ternary compounds has been determined. Solidifications behavior of several key alloys have been discussed based on the differential scanning calorimetry (DSC) experiments and thermodynamic calculations. Extensive analysis of the DSC curves has been carried out to relate them to the corresponding phase transformation reactions and temperatures. Some of the most promising metallic glass forming regions have been analyzed using thermodynamic calculations.
Exploiting the Dependency of Cancer Cells on Molecular Chaperones
Authors: Sharp Swee , Howes Jenny , Workman Paul
Published: October 2013

More widespread acceptance of molecular chaperones as fertile ground for drug discovery came about relatively recently. The original discovery that Hsp90 is a promising molecular target in oncology was made in 1994 with the observation that the natural product geldanamycin reversed transformation by oncogenic v-SRC via binding to Hsp90 and disrupting the stabilizing complex. We now know that Hsp90 inhibitors exert their anticancer effects by destabilizing and depleting many oncogenic client proteins, including amplified and mutated kinases, notably ERBB2, BRAF, EGFR and ALK, and transcription factors, particularly the androgen and estrogen receptor. Recognition that this combinatorial action is highly tumor-selective and could bring significant therapeutic advantages – especially in circumventing drug resistance – helped greatly to overcome initial concerns of unacceptable toxicity. The trail-blazing geldanamycin analogues cleared the pathway to clinical proof-of-concept and showed that significant therapeutic activity could be obtained at well-tolerated doses in cancers where the major driver oncoprotein is also highly dependent on Hsp90, particularly ERBB2 in breast cancer and mutant EGFR and rearranged ALK in non-small-cell lung cancer. More than 20 Hsp90 inhibitors have now entered the clinic, with some progressing to pivotal studies. There is also considerable interest in other chaperone targets and disease indications.
Discovery of NVP-AUY922
Authors: Brough Paul A. , Schoepfer Joseph , Massey Andrew , Jensen Michael Rugaard
Published: October 2013

This chapter covers the identification and characterization of the novel Hsp90 inhibitor NVP-AUY922, which entered clinical trials in July 2007. The program leading to the identification of NVP-AUY922 (VER-52296) used complementary hit ID technologies such as HTS and fragment-based screening, relied heavily on structure-based design and required the design of new assays and probes to drive the compound optimization. In vivo characterization in tumor-bearing animals assisted in compound selection for pre-clinical studies.
Discovery and Selection of NVP-HSP990 as a Clinical Candidate
Authors: Machajewski Timothy D. , Menezes Daniel , Gao Zhenhai
Published: October 2013

This chapter describes the discovery of NVP-Hsp990, a potent, orally bioavailable Hsp90 inhibitor currently in early clinical development. The program strategy for the discovery of Hsp990 is detailed from hit identification to in vivo pre-clinical evaluation. This approach relied heavily on the application of structure-based drug design to rapidly optimize biochemical potency, and identify opportunities for fine-tuning the in vitro and in vivo properties. A significant protein rearrangement is described, which enabled the identification of a highly potent inhibitor series. PK/PD/efficacy relationships are described that guided dose and schedule optimization for the clinical candidate.
Inhibitors of the Hsp90 C-terminus
Authors: Zhao Huiping , Blagg Brian S. J.
Published: October 2013

Hsp90 is a promising therapeutic target for the treatment of cancer and neurodegenerative diseases. While current research focuses on drugging the N-terminal ATP-binding pocket, small molecules that disrupt the Hsp90 C-terminus manifest distinctive properties and may provide additional advantages over N-terminal inhibitors. Structural modifications to novobiocin, the first Hsp90 C-terminal inhibitor identified, have led to a set of analogues that either induce a strong heat shock response or manifest potent anti-proliferative activities. The development of these novobiocin-based analogues and their biological evaluation is summarized in this chapter. Additional small molecules that bind the Hsp90 C-terminus are also discussed.
Molecular Chaperones as Potential Therapeutic Targets for Neurological Disorders
Authors: Delenclos Marion , McLean Pamela J.
Published: October 2013

Many neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and Polyglutamine disorders are characterized by conformational change in proteins that result in misfolding, aggregation and accumulation of amyloid fibrils. These misfolded species result in toxicity in cells and ultimately lead to the death of specific neuronal populations. The cellular pathways involved in these neurological disorders are still unclear but a large body of evidence suggests that molecular chaperones, regulators of cellular protein quality control, may play a critical role in neurodegeneration. Indeed in patient post-mortem brain, chaperones are found in the hallmark neuronal inclusions. Molecular chaperones are able to inhibit the aggregation of denatured proteins and facilitate refolding of different disease-causing proteins. Experimental approaches in animal and cellular models have shown prevention of protein misfolding and facilitation of clearance mechanisms via up-regulation of molecular chaperones. Therefore manipulating the molecular chaperone system may be a successful strategy to counter the conformational changes occurring in protein misfolding diseases and may offer new therapeutic promise. Here we review the evidence for the involvement of various molecular chaperones in several neurodegenerative disorders and examine the current research investigating the role of the chaperones as novel targets for therapy of these devastating diseases.
Retracted Article: Temperature-regulated polymerization and swelling/collapsing/flocculation properties of hybrid nanospheres with magnetic cores and thermo/pH-sensitive nanogel shells
Authors: Gui Rijun , Jin Hui
Published: October 2013

This article reported the synthesis of Fe3O4/p(NIPAM-co-MAA) nanospheres using a temperature-regulated one-pot copolymerization and studied their unique swelling/collapsing/flocculation behavior.
PCSK9 acts as a chaperone for the LDL receptor in the endoplasmic reticulum
Authors: Strøm Thea Bismo , Tveten Kristian , Leren Trond P.
Published: October 2013

PCSK9 (proprotein convertase subtilisin/kexin type 9) binds to the LDLR (low-density lipoprotein receptor) at the cell surface and disrupts recycling of the LDLR. However, PCSK9 also interacts with the LDLR in the ER (endoplasmic reticulum). In the present study we have investigated the role of PCSK9 for the transport of the LDLR from the ER to the cell membrane. A truncated LDLR consisting of the ectodomain (ED-LDLR) was used for these studies to avoid PCSK9-mediated degradation of the LDLR. The amount of secreted ED-LDLR was used as a measure of the amount of ED-LDLR transported from the ER. From co-transfection experiments of various PCSK9 and ED-LDLR plasmids, PCSK9 increased the amount of WT (wild-type) ED-LDLR in the medium, but not of an ED-LDLR lacking the EGF (epidermal growth factor)-A repeat or of a Class 2a mutant ED-LDLR which fails to exit the ER. Mutant PCSK9s which failed to undergo autocatalytic cleavage or failed to exit the ER, failed to increase the amount of WT-ED-LDLR in the medium. These mutants also reduced the amount of WT-ED-LDLR intracellularly, which could partly be prevented by the proteasome inhibitor lactacystine. WT-ED-LDLR promoted autocatalytic cleavage of pro-PCSK9. The findings of the present study indicate that the binding of WT-ED-LDLR to pro-PCSK9 in the ER promotes autocatalytic cleavage of PCSK9, and autocatalytically cleaved PCSK9 acts as a chaperone to promote the exit of WT-ED-LDLR from the ER.
Multipole expansion of polarised electromagnetic fields
Authors: Naus H.W.L.
Published: October 2013

The multipole expansion of a general plane polarised electromagnetic field is derived. This is accomplished by calculating the coefficients of the dynamical multipole expansion of electromagnetic fields, representing generic solutions of the Maxwell equations in a source‐free region. The analytical results are confirmed by comparing the suitably terminated expansions to the exact fields.
Digital predistortion using modified dynamic deviation reduction‐based Volterra model
Authors: He Zhuohui , Ye Wu , Feng Suili
Published: October 2013

A modified dynamic deviation reduction‐based Volterra (MDDRV) model is presented for digital predistortion of power amplifiers. The MDDRV model is a combination of the memory polynomial model and the DDRV model. The effectiveness of the MDDRV model is validated based on experimental results.
High density QR code with multi‐view scheme
Authors: Chiang Jen‐Shiun , Hsia Chih‐Hsien , Li Hsin‐Ting
Published: October 2013

Since the data storage capacity per unit area of a QR code is very limited, it is restricted in various QR code applications. An approach is proposed based on visual skew to improve the data capacity of the QR code. The proposed method can enhance the capacity of the QR code per unit area by using different angle views to combine several QR codes together. The storage capacity of the proposed mechanism can be increased 1.5 times per unit area more than that of the normal QR code.
Interference covariance matrix reconstruction via steering vectors estimation for robust adaptive beamforming
Authors: Lu Zhenxing , Li Yunjie , Gao Meiguo , Zhang Yangrui
Published: October 2013

In the presence of steering vector model mismatches, a novel robust adaptive beamformer is proposed based on interference‐plus‐noise covariance matrix reconstruction. An interference region is first selected according to the coarsely estimated desired signal direction, and then the interference steering vectors are estimated with the robust Capon beamformer. Finally, the interference‐plus‐noise covariance matrix is reconstructed by integrating the Capon spatial spectrum over the interference region by using the estimated steering vectors.
Sample‐and‐hold circuit with dynamic switch leakage compensation
Authors: Zou L. , Pathrose J. , Chai K.T.C. , Je M. , Xu Y.P.
Published: October 2013

For sample‐and‐hold (S/H) circuits operating at low sampling rate and high temperature, the switch leakage current is one of the major error sources. A S/H circuit with dynamic switch leakage compensation is presented. The proposed leakage current compensation circuit generates switch leakage replicas that track the actual leakages in the sampling switches. A bidirectional current steering circuit allows the switch leakage to be dynamically compensated with the leakage replicas. A prototype S/H circuit is fabricated in a 1 µm silicon‐on‐isolation CMOS technology. Measurement has shown the effectiveness of dynamic leakage current compensation up to 280°C with a maximum 75% leakage reduction.
0.5 V switching current integrator
Authors: Shen D.‐L.
Published: October 2013

A switching current integrator that works in an environment with a low supply voltage is presented. The sampling transistors are all realised using PMOSs, by connecting their body to the ground, in order to lower their threshold voltage. The current sources are constructed using NMOSs by tying their gate to the supply voltage, in order to minimise the voltage required between drain and source. In this type of approach, the proposed switching current integrator works at a supply voltage of 0.5 V, using a sampling frequency of 100 MHz in a 0.18 μm CMOS technology.
Dynamic orientation of receiver arrays using particle swarm optimisation
Authors: Cakir O. , Kaya I. , Yazgan A. , Cakir Ö.
Published: October 2013

Considering a time difference of arrival (TDOA) localisation system, it is well known that the accuracy depends on the transmitter–receiver geometry, time differences estimation error and the selection of the localisation algorithm. Although many studies related to TDOA estimation and emitter location finding can be found in the literature, the effect of transmitter–receiver geometry on positioning accuracy has not been investigated sufficiently. Most of the studies focused on figuring out the optimum receiver arrays by minimising the Cramer‐Rao lower bound (CRLB) or maximising the Fisher information matrix. In this reported work, depending on the target position, the optimum receiver arrays are dynamically oriented. By using particle swarm optimisation (PSO) the target is localised and the offset angle which makes the CRLB minimum is determined. After rotating the receiver array by the offset angle, the target is localised again. At the end of the process, a significant decrement in the positioning error is obtained. To show the effectiveness of the proposed method, a uniform angular array and a cross array are selected as optimum two‐dimensional geometries.
Uniform and linear variable doping ultra‐thin PSOI LDMOS with n‐type buried layer
Authors: Li Yanfei , Qiao Ming , Jiang Yongheng , Zhou Xin , Xu Wan , Zhang Bo
Published: October 2013

A novel ultra‐thin partial silicon‐on‐insulator (PSOI) LDMOS with n‐type buried (n‐buried) layer (NBL PSOI LDMOS) is proposed. The new PSOI LDMOS features an n‐buried layer underneath the n‐type drift (n‐drift) region close to the source side, providing a large conductivity region for majority carriers to significantly improve the self‐heating effect. A combination of uniform and linear variable doping (LVD) profile with highly initial concentration is utilised in the n‐drift region, which alleviates the inherent tradeoff between specific on‐resistance (Ron,sp) and breakdown voltage (BV), as well as achieving low power dissipation. With a 60‐µm n‐drift region length, the NBL PSOI LDMOS obtains a high BV of 940 V with a low maximum temperature (Tmax) of 327 K at a power (P) of 1 mW/μm, which is reduced by around 56 K in comparison to the conventional SOI LDMOS using an LVD profile for the n‐drift region (LVD SOI LDMOS). Moreover, Ron,sp of the NBL PSOI LDMOS is lower than that of the LVD SOI LDMOS for a wide range of BV from 400 to 900 V.
Low‐cost low‐power HV startup circuit with 50 V pJFET and 700 V T‐nJFET
Authors: Mao Kun , Qiao Ming , Li Zhaoji , Zhang Bo
Published: October 2013

An advanced low‐cost and low‐power high‐voltage (HV) startup circuit which uses a 50 V pJFET and a 700 V T‐nJFET (triple RESURF nJFET) is proposed. Compared with traditional technology, a mass of module area is saved. This mainly benefits from: first, with increase of VDS, IOFF (leakage current in off‐state) can be quickly pinched off to a low value by pJFET without a large layout area which is needed for the traditional resistance method. Secondly, T‐nJFET is located at the drain terminal of T‐nLDMOS (triple RESURF LDMOS) with common drain electrode which also saves large area than traditional independent nJFET. Moreover, pJFET brings stable and low IOFF which leads to 4 mW POFF (static power consumption in off‐state) due to its low VP (pinch‐off voltage) and high BVDS.
Anti‐Stokes signal conversion of femtosecond pulses at near‐ultraviolet wavelength in photonic crystal fibre
Authors: Yuan Jinhui , Zhou Guiyao , Liu Hongzhan , Xia Changming , Sang Xinzhu , Wu Qiang , Yu Chongxiu , Wang Kuiru , Yan Binbin , Han Ying , Farrell G. , Hou Lantian
Published: October 2013

Anti‐Stokes signals at the near‐ultraviolet wavelength are efficiently generated based on degenerate four‐wave mixing by coupling the femtosecond pulses into the fundamental mode of a photonic crystal fibre. When the pump pulses with the central wavelength of 840 nm and the average power of 300 mW are used, the conversion efficiency ηs of the anti‐Stokes signal at 432 nm can be up to 40℅, and the pulse width is measured to be 42 fs by the Talbot effect.
Sideband‐suppressed narrow bandpass fibre Fabry‐Pérot filter composed of fibre Bragg grating and dielectric mirror
Authors: Sano Y. , Kobayashi M. , Yoshino T.
Published: October 2013

To suppress the undesirable sideband transmission occurring in the conventional fibre Bragg grating based Fabry‐Pérot filter, a fibre Fabry‐Pérot interferometer that is composed of a single fibre Bragg grating and a broadband high‐reflectance dielectric mirror coated on a fibre end surface is considered and its very narrow transmission bandwidth of 8.8 pm and high sideband suppression ratio of more than 20 is experimentally demonstrated in good conformity with the numerical simulation.
UWB small slot antenna with WLAN frequency band‐stop function
Authors: Ojaroudi N. , Ghadimi N.
Published: October 2013

A new design of a multi‐resonance small slot antenna with variable band‐notched function for ultra‐wideband (UWB) applications is proposed. The proposed slot antenna consists of a square radiating stub and a ground plane with a pair of L‐shaped parasitic structures and an inverted T‐shaped strip protruding inside the rectangular slit, which provides a wide usable fractional bandwidth of more than 135% (2.98–16.73 GHz), while showing the band rejection performance in the frequency band of 5.05–5.9 GHz to avoid any interference from wireless local area network systems. The designed antenna has a small size of 20 × 20 × 0.8 mm3. Simulated and experimental results obtained for this antenna show that it exhibits good radiation behaviour within the UWB frequency range.
Efficient access to extended channel bandwidth in wireless LAN
Authors: Stelter A.
Published: October 2013

The channel bonding technique proposed in the IEEE 802.11ac draft makes it possible to multiply the physical layer data rate of the network. Unfortunately, the medium access control (MAC) protocol in 802.11ac that allocates the entire extended bandwidth to a single user at a time is very inefficient if the transmitted data frames are not sufficiently long. A partial bonding MAC (pbMAC) protocol is proposed that allocates only a part of the available bandwidth to a single user at a time. The simulation results show that the pbMAC gives a better utilisation of extended bandwidth than the MAC protocol in 802.11ac.
Miniaturised rat‐race coupler with second and third harmonic suppression using synthesised transmission lines
Authors: Lai C.‐H. , Ma T.‐G.
Published: October 2013

A miniaturised rat‐race coupler capable of suppressing the second and third harmonics is proposed. The coupler is designed with slow‐wave synthesised transmission lines using two π‐networks in cascade. Each π‐network is formed by a parallel LC tank and two shunt capacitors, and is associated with a transmission zero for harmonic attenuation. The two transmission zeros embedded in the synthesised line can be controlled independently. The proposed rat‐race coupler, centred at 2.4 GHz with an operational bandwidth of 18.8%, and at least 21‐dB suppression at the second and third harmonics, features a compact footprint, which is only 12.9% the size of its conventional counterpart.
Frequency planning for clustered jointly processed cellular multiple access channel
Authors: Majid Muhammad I. , Imran Muhammad A. , Hoshyar Reza
Published: October 2013

Owing to limited resources, it is hard to guarantee minimum service levels to all users in conventional cellular systems. Although global cooperation of access points (APs) is considered promising, practical means of enhancing efficiency of cellular systems is by considering distributed or clustered jointly processed APs. The authors present a novel ‘quality of service (QoS) balancing scheme’ to maximise sum rate as well as achieve cell‐based fairness for clustered jointly processed cellular multiple access channel (referred to as CC‐CMAC). Closed‐form cell level QoS balancing function is derived. Maximisation of this function is proved as an NP hard problem. Hence, using power‐frequency granularity, a modified genetic algorithm (GA) is proposed. For inter site distance (ISD) < 500 m, results show that with no fairness considered, the upper bound of the capacity region is achievable. Applying hard fairness restraints on users transmitting in moderately dense AP system, 20% reduction in sum rate contribution increases fairness by upto 10%. The flexible QoS can be applied on a GA‐based centralised dynamic frequency planner architecture.
Joint and distributed scheduling with dynamic power control in multicell orthogonal frequency division multiple access networks
Authors: Zhang Jia , Yuan Dongfeng , Zhang Haixia , Li Huimin
Published: October 2013

This study addresses the issue of intercell interference coordination in a multicell orthogonal frequency division multiple access network with universal frequency reuse, which aims at improving the network spectral efficiency, especially for the cell edge areas. According to different degrees of information sharing within the engaged network, both a joint and a distributed solution are proposed respectively trying to determine the most appropriate power control strategy along with the user scheduling policy. The joint power control and user scheduling scheme with full access to the network information is capable of gaining considerable enhancement on the network capacity and also a performance improvement for users suffering from strong intercell interferences. The distributed scheme with the same purpose manages to adapt the power control and user scheduling strategy on the basis of dynamic programming with respect to both current and future utility of the network with only local information available. Numerical results have shown the advantages of the proposed schemes in achieving better spectral efficiency under both joint and distributed circumstances.