bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetic and pharmacodynamic analysis of plasma Aβ40 and Aβ42 following single oral doses of the BACE1 inhibitor AZD3839 to healthy volunteers
Authors: Quartino Angelica , Huledal Gunilla , Sparve Erik , Lüttgen Maria , Bueters Tjerk , Karlsson Pär , Olsson Tina , Paraskos Jonathan , Maltby Justine , Claeson‐Bohnstedt Kristina , Lee Chi‐Ming , Alexander Robert , Fälting Johanna , Paulsson Björn 
Published: May 2014

AbstractModulating deposition of Aβ‐containing plaques in the brain may be beneficial in treating Alzheimer's disease. β‐site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors have been shown to reduce Aβ in plasma and CSF in healthy volunteers. In this study safety, pharmacokinetics and pharmacodynamics that is reduction of the plasma biomarkers Aβ40 and Aβ42, of the BACE1 inhibitor AZD3839 were evaluated.Single oral ascending doses (1–300 mg) of AZD3839 were administered to 54 young healthy volunteers in a randomized, double‐blind, placebo‐controlled study. The data was analyzed using non‐linear mixed effects modeling. AZD3839 reduced Aβ40 and Aβ42 in plasma with estimated potencies (EC50) of 46 and 59 nM, respectively, and a maximum effect of approximately 55%. This was in excellent agreement with the concentration–response relationships obtained in mouse and guinea pig. AZD3839 exposure displayed non‐linear kinetics, described by a three‐compartment model with a saturated binding compartment and an increase in bioavailability with dose. AZD3839 was safe, although, a dose‐dependent QTcF prolongation was observed (mean 20 milliseconds at 300 mg).In conclusion, AZD3839 reduced plasma Aβ40 and Aβ42, demonstrating clinical peripheral proof of mechanism. Pre‐clinical models were predictive for the effect of AZD3839 on the human plasma biomarker in a strictly quantitative manner.
iPortal: the swiss grid proteomics portal: Requirements and new features based on experience and usability considerations
Authors: Kunszt Peter , Blum Lorenz , Hullár Béla , Schmid Emanuel , Srebniak Adam , Wolski Witold , Rinn Bernd , Elmer Franz‐Josef , Ramakrishnan Chandrasekhar , Quandt Andreas , Malmström Lars 
Published: May 2014

SummaryDevelopment of workflow and data management systems are challenging because of the need to provide a service for users with varying degrees of expertise from novices to experts with more knowledge than the developers. We have received feedback from users and developers on the functionality and usability of the Swiss Grid Proteomics Portal, now called iPortal, during its first year of operation. Monitoring and interaction with the production system under heavy use have provided further information on how to improve efficiency and stability. In a second, highly upgraded version of iPortal, we have introduced several new concepts based on this feedback. In this paper, we detail the requirements and the improvements we have made, and also give an outlook on future directions. Copyright © 2014 John Wiley & Sons, Ltd.
Artificial bee colony based energy‐aware resource utilization technique for cloud computing
Authors: Kansal Nidhi Jain , Chana Inderveer 
Published: May 2014

SummaryCloud computing is a form of distributed computing, which promises to deliver reliable services through next‐generation data centers that are built on virtualized compute and storage technologies. It is becoming truly ubiquitous and with cloud infrastructures becoming essential components for providing Internet services, there is an increase in energy‐hungry data centers deployed by cloud providers. As cloud providers often rely on large data centers to offer the resources required by the users, the energy consumed by cloud infrastructures has become a key environmental and economical concern. Much energy is wasted in these data centers because of under‐utilized resources hence contributing to global warming. To conserve energy, these under‐utilized resources need to be efficiently utilized and to achieve this, jobs need to be allocated to the cloud resources in such a way so that the resources are used efficiently and there is a gain in performance and energy efficiency. In this paper, a model for energy‐aware resource utilization technique has been proposed to efficiently manage cloud resources and enhance their utilization. It further helps in reducing the energy consumption of clouds by using server consolidation through virtualization without degrading the performance of users’ applications. An artificial bee colony based energy‐aware resource utilization technique corresponding to the model has been designed to allocate jobs to the resources in a cloud environment. The performance of the proposed algorithm has been evaluated with the existing algorithms through the CloudSim toolkit. The experimental results demonstrate that the proposed technique outperforms the existing techniques by minimizing energy consumption and execution time of applications submitted to the cloud. Copyright © 2014 John Wiley & Sons, Ltd.
An architecture‐level graphics processing unit energy model
Authors: Wang Zhuowei , Cheng Lianglun , Zhao Wuqing , Xiong Naixue 
Published: May 2014

SummaryWith the continued development of hardware and software, graphics processing unit (GPU) has been used in general purpose computational fields, while accelerating applications for CPUs. To achieve high computing performance, a GPU typically includes hundreds of computing units. The high density of computing resource on‐chip incurs high power consumption as well as engendering high performance. The power consumption problem has become one of the most important problems for the development of GPUs. Focusing on a CPU‐GPU heterogeneous parallel system, this research proposed an architecture‐level GPU energy model, with the aim of reducing system energy demand and improving system efficiency. Taking the influences of memory and temperature on GPU energy demand into account, a dynamic energy model based on division of computation and memory and a static energy model based on real‐time temperature perception were established. Validation, through the evaluation and comparative analysis of nine typical GPU programmes, demonstrated that these models could reduce chip energy demand under the performance constraint conditions imposed. Copyright © 2014 John Wiley & Sons, Ltd.
Survival and growth patterns of white spruce (Picea glauca [Moench] Voss) rangewide provenances and their implications for climate change adaptation
Authors: Lu Pengxin , Parker William H. , Cherry Marilyn , Colombo Steve , Parker William C. , Man Rongzhou , Roubal Ngaire 
Published: May 2014

AbstractIntraspecific assisted migration (ISAM) through seed transfer during artificial forest regeneration has been suggested as an adaptation strategy to enhance forest resilience and productivity under future climate. In this study, we assessed the risks and benefits of ISAM in white spruce based on long‐term and multilocation, rangewide provenance test data. Our results indicate that the adaptive capacity and growth potential of white spruce varied considerably among 245 range‐wide provenances sampled across North America; however, the results revealed that local populations could be outperformed by nonlocal ones. Provenances originating from south‐central Ontario and southwestern Québec, Canada, close to the southern edge of the species' natural distribution, demonstrated superior growth in more northerly environments compared with local populations and performed much better than populations from western Canada and Alaska, United States. During the 19–28 years between planting and measurement, the southern provenances have not been more susceptible to freezing damage compared with local populations, indicating they have the potential to be used now for the reforestation of more northerly planting sites; based on changing temperature, these seed sources potentially could maintain or increase white spruce productivity at or above historical levels at northern sites. A universal response function (URF), which uses climatic variables to predict provenance performance across field trials, indicated a relatively weak relationship between provenance performance and the climate at provenance origin. Consequently, the URF from this study did not provide information useful to ISAM. The ecological and economic importance of conserving white spruce genetic resources in south‐central Ontario and southwestern Québec for use in ISAM is discussed.
Development of a Nonlinear Soft Sensor Using a GMDH Network for a Refinery Crude Distillation Tower
Authors: Fujii Kenzo , Yamamoto Toru 
Published: May 2014

SUMMARYIn atmospheric distillation processes, stabilization of processes is required in order to optimize the crude‐oil composition that corresponds to product market conditions. However, the process control systems sometimes fall into unstable states in the case where unexpected disturbances are introduced, and these unusual phenomena have had an undesirable effect on certain products. Furthermore, a useful chemical engineering model has not yet been established for these phenomena. This remains a serious problem in atmospheric distillation processes. This paper describes a new modeling scheme to predict unusual phenomena in the atmospheric distillation process using a GMDH (Group Method of Data Handling) network, which is a type of network model. According to the GMDH network, the model structure can be determined systematically. However, the method of least squares has been commonly utilized in determining weight coefficients (model parameters). Estimation accuracy is not entirely essential, because the sum of the squared errors between the measured values and estimates is evaluated. Therefore, instead of evaluating the sum of the squared errors, the sum of the absolute values of the errors is introduced and the Levenberg–Marquardt method is employed in order to determine the model parameters. The effectiveness of the proposed method is evaluated by foaming prediction in the crude oil switching operation in the atmospheric distillation process.
Modeling of Nonlinear Magnetizing Characteristics of Pole Transformer for Analyzing Islanding Prevention of Photovoltaic System
Authors: Yoshida Yoshiaki , Suzuki Hirokazu , Fujiwara Koji , Ishihara Yoshiyuki 
Published: May 2014

SUMMARYWith increasing penetration of distributed generators such as photovoltaic (PV) systems in distribution systems, it is very important to quickly detect islanding caused by power system faults in order to assure electrical safety. We have developed a nonlinear magnetizing characteristics model of pole transformers for use in analyzing islanding prevention in PV systems. Basic experiments on the islanding detection were performed for verification of the proposed model. Analytical results obtained by the proposed model agreed well with experimental results.
Impact of a stepwise protocol for treating pain on pain intensity in nursing home patients with dementia: A cluster randomized trial
Authors: Sandvik R.K. , Selbaek G. , Seifert R. , Aarsland D. , Ballard C. , Corbett A. , Husebo B.S. 
Published: May 2014

AbstractBackgroundPain is frequent and distressing in people with dementia, but no randomized controlled trials have evaluated the effect of analgesic treatment on pain intensity as a key outcome.MethodsThree hundred fifty‐two people with dementia and significant agitation from 60 nursing home units were included in this study. These units, representing 18 nursing homes in western Norway, were randomized to a stepwise protocol of treating pain (SPTP) or usual care. The SPTP group received acetaminophen, morphine, buprenorphine transdermal patch and pregabalin for 8 weeks, with a 4‐week washout period. Medications were governed by the SPTP and each participant's existing prescriptions. We obtained pain intensity scores from 327 patients (intervention n = 164, control n = 163) at five time points assessed by the primary outcome measure, Mobilization‐Observation‐Behaviour‐Intensity‐Dementia‐2 (MOBID‐2) Pain Scale. The secondary outcome was activities of daily living (ADL). We used a linear intercept mixed model in a two‐way repeated measures configuration to assess change over time and between groups.ResultsThe SPTP conferred significant benefit in MOBID‐2 scores compared with the control group [average treatment effect (ATE) −1.388; p < 0.001] at week 8, and MOBID‐2 scores worsened during the washout period (ATE = −0.701; p = 0.022). Examining different analgesic treatments, benefit was conferred to patients receiving acetaminophen compared with the controls at week 2 (ATE = −0.663; p = 0.010), continuing to increase until week 8 (ATE = −1.297; p < 0.001). Although there were no overall improvements in ADL, an increase was seen in the group receiving acetaminophen (ATE = +1.0; p = 0.022).ConclusionPain medication significantly improved pain in the intervention group, with indications that acetaminophen also improved ADL function.
Hypoactivation in right inferior frontal cortex is specifically associated with motor response inhibition in adult ADHD
Authors: Morein‐Zamir Sharon , Dodds Chris , van Hartevelt Tim J. , Schwarzkopf Wolfgang , Sahakian Barbara , Müller Ulrich , Robbins Trevor 
Published: May 2014

AbstractAdult ADHD has been linked to impaired motor response inhibition and reduced associated activation in the right inferior frontal cortex (IFC). However, it is unclear whether abnormal inferior frontal activation in adult ADHD is specifically related to a response inhibition deficit or reflects a more general deficit in attentional processing. Using functional magnetic resonance imaging, we tested a group of 19 ADHD patients with no comorbidities and a group of 19 healthy control volunteers on a modified go/no‐go task that has been shown previously to distinguish between cortical responses related to response inhibition and attentional shifting. Relative to the healthy controls, ADHD patients showed increased commission errors and reduced activation in inferior frontal cortex during response inhibition. Crucially, this reduced activation was observed when controlling for attentional processing, suggesting that hypoactivation in right IFC in ADHD is specifically related to impaired response inhibition. The results are consistent with the notion of a selective neurocognitive deficit in response inhibition in adult ADHD associated with abnormal functional activation in the prefrontal cortex, whilst ruling out likely group differences in attentional orienting, arousal and motivation. Hum Brain Mapp 35:5141–5152, 2014. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.
Coarse‐Grained and Atomistic MD Simulations of RNA and DNA Folding
Authors: Leuchter Jessica D. , Green Adam T. , Gilyard Julian , Rambarat Cecilia G. , Cho Samuel S. 
Published: May 2014

AbstractAlthough the main features of the protein folding problem are coming into clearer focus, the microscopic viewpoint of nucleic acid folding mechanisms is only just beginning to be addressed. Experiments, theory, and simulations are pointing to complex thermodynamic and kinetic mechanisms. As is the case for proteins, molecular dynamics (MD) simulations continue to be indispensable tools for providing a molecular basis for nucleic acid folding mechanisms. In this review, we provide an overview of biomolecular folding mechanisms focusing on nucleic acids. We outline the important interactions that are likely to be the main determinants of nucleic acid folding energy landscapes. We discuss recent MD simulation studies of empirical force field and Go‐type MD simulations of RNA and DNA folding mechanisms to outline recent successes and the theoretical and computational challenges that lie ahead.
Effective release of a broad spectrum antibiotic from elastin‐like polypeptide‐collagen composite
Authors: Anderson Tiffany R. , Marquart Mary E. , Janorkar Amol V. 
Published: May 2014

ABSTRACTPreparation of hydrogels that possess an effective antibiotic release profile and better mechanical properties compared to the traditionally used collagen hydrogels has the potential to minimize post‐surgical infections and support wound healing. Toward this goal, we prepared elastin‐like polypeptide (ELP)‐collagen composite hydrogels that displayed a significantly higher elastic modulus compared to the collagen hydrogels. We then characterized the release behavior of the collagen and ELP‐collagen hydrogels loaded with varying dosages (1–5% w/w) of a commonly used broad spectrum antibiotic, doxycycline hyclate. Both collagen and ELP‐collagen hydrogels showed a gradual time dependent doxycycline release over a period of 5 days. The ELP‐collagen hydrogels, in general, showed a slower release of the doxycycline compared to the collagen hydrogels. The released doxycycline was found to be effective against four bacterial strains (Escherichia coli,Pseudomonas aeruginosa,Streptococcus sanguinis, andmethicillin‐resistant Staphylococcus aureus) in a dose dependent manner. Combined with their improved mechanical properties, the gradual and effective drug release from the biocompatible ELP‐collagen hydrogels shown here may be beneficial for drug delivery and tissue engineering applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 782–790, 2015.
Investigating the solubility and cytocompatibility of CaO–Na2O–SiO2/TiO2 bioactive glasses
Authors: Wren Anthony W. , Coughlan Aisling , Smith Courtney M. , Hudson Sarah P. , Laffir Fathima R. , Towler Mark R. 
Published: May 2014

AbstractThis study aims to investigate the solubility of a series of titanium (TiO2)‐containing bioactive glasses and their subsequent effect on cell viability. Five glasses were synthesized in the composition range SiO2–Na2O–CaO with 5 mol % of increments TiO2 substituted for SiO2. Glass solubility was investigated with respect to (1) exposed surface area, (2) particle size, (3) incubation time, and (4) compositional effects. Ion release profiles showed that sodium (Na+) presented high release rates after 1 day and were unchanged between 7 and 14 days. Calcium (Ca2+) release presented a significant change at each time period and was also composition dependent, where a reduction in Ca2+ release is observed with an increase in TiO2 concentration. Silica (Si4+) release did not present any clear trends while no titanium (Ti4+) was released. Cell numbers were found to increase up to 44%, compared to the growing control population, with a reduction in particle size and with the inclusion of TiO2 in the glass composition. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 709–720, 2015.
Morphology effect of bioglass‐reinforced hydroxyapatite (Bonelike®) on osteoregeneration
Authors: Atayde L. M. , Cortez P. P. , Afonso A. , Santos M. , Maurício A. C. , Santos J. D. 
Published: May 2014

AbstractIn the last decades, the well‐known disadvantages of autografts and allografts have driven to the development of synthetic bone grafts for bone regeneration. Bonelike®, a glass‐reinforced hydroxyapatite (HA) composite was developed and registered for bone grafting. This biomaterial is composed by a modified HA matrix, with α‐ and β‐tricalcium phosphate secondary phases. Aiming to improve the biological characteristics of Bonelike®, new spherical pelleted granules, of different shape and size, were developed with controlled micro and macrostructure. In the present study, it was compared the physicochemical properties and in vivo performance of different Bonelike® granule presentations—Bonelike® polygonal (500–1000 µm size) and Bonelike spherical (250–500 µm; 500–1000 µm size). For the in vivo study, Bonelike® was implanted on sheep femurs, with various implantation times (30 days, 60 days, 120 days, and 180 days). X‐ray diffraction analysis revealed that the phase composition of different granules presentations was similar. Bonelike® spherical 500–1000 µm was the most porous material (global porosity and intraporosity) and Bonelike® polygonal 500–1000 µm the less porous. Considering the in vivo study, both polygonal and spherical granules presented osteoconductive proprieties. The spherical granules showed several advantages, including easier medical application through syringe and improved osteointegration, osteoconduction, and degradation, by the presence of larger pores, controlled micro‐ and macrosctructure and suitable particle format that adapts to bone growth. Bonelike® spherical 500–1000 µm showed improved new bone invasion throughout the material's structure and Bonelike® spherical 250–500 µm appeared to induce faster bone regeneration, presenting less unfilled areas and less lacunae in the histological analysis. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 292–304, 2015.
Bioactivity evolution of the surface functionalized bioactive glasses
Authors: Magyari Klára , Baia Lucian , Vulpoi Adriana , Simon Simion , Popescu Octavian , Simon Viorica 
Published: May 2014

AbstractThe formation of a calcium phosphate layer on the surface of the SiO2–CaO–P2O5 glasses after immersion in simulated body fluid (SBF) generally demonstrates the bioactivity of these materials. Grafting of the surface by chemical bonding can minimize the structural changes in protein adsorbed on the surface. Therefore, in this study our interest was to evaluate the bioactivity and blood biocompatibility of the SiO2–CaO–P2O5 glasses after their surface modification by functionalization with aminopropyl‐triethoxysilane and/or by fibrinogen. It is shown that the fibrinogen adsorbed on the glass surfaces induces a growing of the apatite‐like layer. It is also evidenced that the protein content from SBF influences the growth of the apatite‐like layer. Furthermore, the good blood compatibility of the materials after fibrinogen and bovine serum albumin adsorption is proved from the assessment of the β‐sheet–β‐turn ratio. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 261–272, 2015.
Long-Term Proton Pump Inhibitor Therapy and Falls and Fractures in Elderly Women: A Prospective Cohort Study
Authors: Lewis Joshua R , Barre Deka , Zhu Kun , Ivey Kerry L , Lim EE Mun , Hughes Jeff , Prince Richard L 
Published: May 2014

ABSTRACT

Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance-related function in a post hoc analysis of a longitudinal population-based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25–3.77; p = 0.006 and 1.95; 95% CI, 1.20–3.16; p = 0.007, respectively. In the replication study, long-term PPI use was associated with an increased risk of self-reported falling; AOR, 1.51; 95% CI, 1.00–2.27; p = 0.049. No association of long-term PPI therapy with bone structure was observed; however, questionnaire-assessed falls-associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p &lt; 0.001) and numbness of feet (p = 0.017) and objective clinical measurement such as Timed Up and Go (p = 0.002) and Romberg eyes closed (p = 0.025) tests were all significantly impaired in long-term PPI users. Long-term PPI users were also more likely to have low vitamin B12 levels than non-users (50% versus 21%, p = 0.003). In conclusion, similar to previous studies, we identified an increased fracture risk in subjects on long-term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy. © 2014 American Society for Bone and Mineral Research.