bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced cardiac chemical exchange saturation transfer (cardioCEST) MRI for in vivo cell tracking and metabolic imaging
Authors: Pumphrey Ashley , Yang Zhengshi , Ye Shaojing , Powell David K. , Thalman Scott , Watt David S. , Abdel‐Latif Ahmed , Unrine Jason , Thompson Katherine , Fornwalt Brandon , Ferrauto Giuseppe , Vandsburger Moriel
Published: December 2015

An improved pre‐clinical cardiac chemical exchange saturation transfer (CEST) pulse sequence (cardioCEST) was used to selectively visualize paramagnetic CEST (paraCEST)‐labeled cells following intramyocardial implantation. In addition, cardioCEST was used to examine the effect of diet‐induced obesity upon myocardial creatine CEST contrast. CEST pulse sequences were designed from standard turbo‐spin‐echo and gradient‐echo sequences, and a cardiorespiratory‐gated steady‐state cine gradient‐echo sequence. In vitro validation studies performed in phantoms composed of 20 mM Eu‐HPDO3A, 20 mM Yb‐HPDO3A, or saline demonstrated similar CEST contrast by spin‐echo and gradient‐echo pulse sequences. Skeletal myoblast cells (C2C12) were labeled with either Eu‐HPDO3A or saline using a hypotonic swelling procedure and implanted into the myocardium of C57B6/J mice. Inductively coupled plasma mass spectrometry confirmed cellular levels of Eu of 2.1 × 10−3 ng/cell in Eu‐HPDO3A‐labeled cells and 2.3 × 10−5 ng/cell in saline‐labeled cells. In vivo cardioCEST imaging of labeled cells at ±15 ppm was performed 24 h after implantation and revealed significantly elevated asymmetric magnetization transfer ratio values in regions of Eu‐HPDO3A‐labeled cells when compared with surrounding myocardium or saline‐labeled cells. We further utilized the cardioCEST pulse sequence to examine changes in myocardial creatine in response to diet‐induced obesity by acquiring pairs of cardioCEST images at ±1.8 ppm. While ventricular geometry and function were unchanged between mice fed either a high‐fat diet or a corresponding control low‐fat diet for 14 weeks, myocardial creatine CEST contrast was significantly reduced in mice fed the high‐fat diet. The selective visualization of paraCEST‐labeled cells using cardioCEST imaging can enable investigation of cell fate processes in cardioregenerative medicine, or multiplex imaging of cell survival with imaging of cardiac structure and function and additional imaging of myocardial creatine. Copyright © 2015 John Wiley & Sons, Ltd.
A New Approach to Health Services and Pharmacy in Cuba
Authors: Sánchez Alina M.
Published: December 2015

In December 17, 2014, U.S. President Barack Obama surprised the world by announcing his intention to enter into negotiations aimed at reestablishing diplomatic relations with Cuba. Since then, expectations and interest regarding the health system of that country have increased. This report focuses on the Cuban health and pharmacy systems from a practical and educational standpoint. Pharmaceutical services, strengths, opportunities, and challenges are described. Cuba's new trends toward patient‐centered care are analyzed to provide insights for developing pharmaceutical care practice and implementing policies suitable for practice in all health care settings.
Disopyramide for Hypertrophic Cardiomyopathy: A Pragmatic Reappraisal of an Old Drug
Authors: Verlinden Nathan J. , Coons James C.
Published: December 2015

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by unexplained left ventricular hypertrophy in the absence of other cardiac or systemic etiologies. Approximately two‐thirds of patients with HCM develop left ventricular outflow tract (LVOT) obstruction with or without provocation, whereas nearly half develop heart failure with preserved ejection fraction. Medical management of heart failure with preserved ejection fraction is based on the presence of symptoms and LVOT obstruction and frequently includes β‐blockers or verapamil. Disopyramide is a class Ia antiarrhythmic that historically was used for the treatment of arrhythmias; however, its contemporary use is often reserved for patients with HCM who are persistently symptomatic despite β‐blockers or verapamil and have evidence of LVOT obstruction. The pharmacologic rationale for use of disopyramide is largely based on its strong negative inotropic property. Three clinical studies have showed significant improvements in heart failure symptoms and a reduction in the need for invasive therapy in patients treated with disopyramide. Appropriate dosing and monitoring of disopyramide are important to mitigate the potential for anticholinergic adverse events and proarrhythmias. Disopyramide is a safe and effective medication that reduces heart failure symptoms and LVOT gradient and delays the need for invasive therapy in patients with obstructive HCM.
Comparison of the Safety of Adenosine and Regadenoson in Patients Undergoing Outpatient Cardiac Stress Testing
Authors: Brink Heidi L. , Dickerson Jennifer A. , Stephens Julie A. , Pickworth Kerry K.
Published: December 2015

Study Objective

To compare the adverse effect profiles of adenosine and regadenoson in patients undergoing outpatient cardiac stress testing.

Design

Single‐center retrospective cohort study.

Setting

Two outpatient clinics, both of which are part of a single tertiary academic medical health system; one clinic exclusively used adenosine for cardiac stress testing, and the other clinic exclusively used regadenoson.

Patients

A total of 489 patients who underwent an outpatient cardiac stress test between January 1, 2014, and December 31, 2014; of those patients, 254 received adenosine and 235 received regadenoson.

Measurements and Main Results

Baseline characteristics were similar between groups, except for chronic kidney disease (p<0.001), congestive heart failure (p=0.041), and mean age (p=0.004). The primary outcome was the occurrence of adverse effects—arrhythmia, chest pain or tightness, dizziness, dyspnea, flushing, or headache, and use of the rescue agent aminophylline—in the adenosine and regadenoson groups. A significantly higher proportion of patients who were given regadenoson during cardiac stress testing experienced at least one adverse effect compared with patients who underwent an adenosine stress test (79.6% vs 31.5%, p<0.001). The patients given regadenoson experienced a significantly higher occurrence of arrhythmia (30.6% vs 16.1%, p<0.001), dyspnea (66.0% vs 17.7%, p<0.001), and headache (25.1% vs 3.1%, p<0.001), and they had a significantly higher rate of aminophylline rescue use (19.2% vs 0.8%, p<0.001). A secondary objective evaluated the financial impact of each agent, and adenosine exhibited a medication price that was more than $100/patient lower than regadenoson based on the average wholesale price.

Conclusion

Among patients undergoing an outpatient pharmacologic stress test, the use of adenosine was associated with a lower occurrence of adverse effects and lower rate of a rescue agent use and may provide a potential medication cost savings opportunity compared with regadenoson.
Antiretroviral Treatment Efficacy and Safety in Older HIV‐Infected Adults
Authors: Jourjy Jacqueline , Dahl Keelin , Huesgen Emily
Published: December 2015

Highly active antiretroviral therapy (ART) and its widespread availability have revolutionized the landscape of HIV care and patient outcomes, transforming infection with HIV into a manageable chronic condition rather than a life‐limiting disease. This transformation has created an older patient demographic. The effect that older age has on the outcomes of ART is not completely understood. Limited data are available in older individuals due to underrepresentation in clinical trials. To better understand this relationship, we conducted a literature search to assess the impact of older age on the outcomes of ART in the older HIV‐infected population, including immunologic and virologic outcomes, mortality, disease progression, toxicity of ART, and pharmacokinetic considerations. In addition, package inserts of antiretroviral (ARV) medications were reviewed for efficacy, safety, and pharmacokinetic information pertaining to the older population. Most studies in older adults (50 yrs or older) demonstrated slower and blunted CD4 immune recovery but better virologic suppression in response to ART. Higher rates of mortality and faster disease progression have been observed in adults 50 years and older, particularly during the first year after ART initiation. HIV‐infected patients aged 50 years and older appear to be at greater risk for certain ART‐associated toxicities including nephrotoxicity, decline in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction. The available literature suggests that clinicians should consider avoiding agents such as tenofovir disoproxil fumarate (TDF) in older patients with risk factors for renal impairment and/or osteoporosis. If TDF is used in patients aged 50 years or older, more frequent monitoring should be considered. Older age was a significant predictor for higher atazanavir exposure and higher lopinavir trough concentration at 24 weeks. The clinical implications of these findings are unknown. It is imperative that future development of novel ARV drug therapies includes a greater proportion of older subjects in clinical trials.
Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies
Authors: Patel Roshni S. , Scopelliti Emily M. , Savelloni Julie
Published: December 2015

Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated low‐density lipoprotein cholesterol (LDL‐C) concentrations that result from mutations of the LDL receptor, apolipoprotein B (apo B‐100), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Early and aggressive treatment can prevent premature atherosclerotic cardiovascular disease in these high‐risk patients. Given that the cardiovascular consequences of FH are similar to typical hypercholesterolemia, traditional therapies are utilized to decrease LDL‐C levels. Patients with FH should receive statins as first‐line treatment; high‐potency statins at high doses are often required. Despite the use of statins, additional treatments are often necessary to achieve appropriate LDL‐C lowering in this patient population. Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging. Contemporary therapies including mipomersen (Kynamro, Genzyme), an oligonucleotide inhibitor of apo B‐100 synthesis; lomitapide (Juxtapid, Aegerion), a microsomal triglyceride transfer protein inhibitor; and alirocumab (Praluent, Sanofi‐Aventis/Regeneron) and evolocumab (Repatha, Amgen), PCSK9 inhibitors, are currently approved by the U.S. Food and Drug Administration for use in FH. This review highlights traditional as well as emerging contemporary therapies with supporting clinical data to evaluate current recommendations and discuss the future direction of FH management.
The Role of Statin Therapy in Hemorrhagic Stroke
Authors: Sikora Newsome Andrea , Casciere Bryan C. , Jordan J. Dedrick , Rhoney Denise H. , Sullivan Kelly A. , Morbitzer Kathryn A. , Moore Joseph D. , Durr Emily A.
Published: December 2015

The 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely utilized class of cholesterol‐lowering agents, carrying multiple indications for both primary and secondary cardiovascular risk reduction. Concern was raised by previously published post hoc analyses and observational studies that noted an increased risk of hemorrhagic stroke in patients receiving a statin. Subsequent studies have demonstrated conflicting results regarding the role of statin therapy on hemorrhagic stroke risk and patient outcomes. New evidence suggests that statins taken prior to or continued during admission for intracerebral hemorrhage (ICH) may be associated with positive outcomes. Evidence also suggests deleterious outcomes resulting from the abrupt discontinuation of statins upon hospital admission for multiple disease states including ICH. Conflicting data also exist for the use of statins following aneurysmal subarachnoid hemorrhage (aSAH). Recent evidence suggests statins started during admission for aSAH confer no additional benefit in reducing delayed ischemic neurologic deficits despite initial positive results. Larger scale evaluation of the role of statin therapy following hemorrhagic stroke is warranted. The available literature is reviewed to provide guidance for therapeutic decision making.
Rapid‐Onset Thrombocytopenia Following Piperacillin‐Tazobactam Reexposure
Authors: Nguyen Van Dong , Tourigny Jean‐François , Roy Renaud , Brouillette Denis
Published: December 2015

Drug‐induced thrombocytopenia is a rare but serious adverse event that has been associated with multiple drugs including β‐lactams. Although it mostly occurs with prolonged medication use, some cases of rapid‐onset thrombocytopenia have been reported. We describe the case of a 69‐year‐old man who developed severe and immediate thrombocytopenia following reexposure to piperacillin‐tazobactam in the critical care setting. He received a 6‐day course of piperacillin‐tazobactam for a possible pneumonia immediately after cardiac surgery. During this course of therapy, his platelet count decreased (fluctuating between 69 × 103/mm3 and 104 × 103/mm3) and then progressively increased after completion of the antibiotic to 340 × 103/mm3 on postoperative day 15. Ten days after the antibiotic course was completed (postoperative day 16), the patient developed new signs of infection (fever and neutrophilia), and piperacillin‐tazobactam was restarted. Eight hours after reintroducing the antibiotic, his platelet count dropped from 317 × 103/mm3 to 7 × 103/mm3. After reviewing all the medications administered to the patient as well as other potential causes of thrombocytopenia, and given the chronology of events, piperacillin‐tazobactam was suspected as the most likely offending agent and was therefore replaced by meropenem on postoperative day 17. The patient's platelet count began to rise 2 days after discontinuation of piperacillin‐tazobactam and reached 245 × 103/mm3 by postoperative day 30. No spontaneous bleeding or thrombosis occurred while the patient was thrombocytopenic. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of thrombocytopenia and piperacillin‐tazobactam therapy. This case highlights the severity and swiftness in which drug‐induced thrombocytopenia may present in the context of cardiac surgery.
Synthesis and characterization of PDEAEMA‐based magneto‐nanogels: Preliminary results on the biocompatibility with cells of human peripheral blood
Authors: Pikabea Aintzane , Ramos Jose , Papachristos Nikos , Stamopoulos Dimosthenis , Forcada Jacqueline
Published: December 2015

Nanogels based on biocompatible, dual pH‐ and temperature‐sensitive poly(2‐(diethylamino)ethyl) methacrylate (PDEAEMA) have been successfully used as nanocontainers for the encapsulation of magnetite, Fe3O4 magnetic nanoparticles (MNPs). For this purpose, citric acid‐coated MNPs were encapsulated into previously synthesized PDEAEMA‐based nanogels using a poly(ethyleneglycol)‐based stabilizer. After the encapsulation of the magnetite MNPs, the so‐called magneto‐nanogels (MNGs) were proved to be multiresponsive on temperature, pH, and magnetic field and colloidally stable. Moreover, preliminary studies on the biocompatibility of these MNGs with cells of human peripheral blood were performed and evidenced quite tolerable biocompatibility, thus suggesting potential use in biomedical applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1479–1494
Strikingly improved toughness of nonpolar rubber by incorporating sacrificial network at small fraction
Authors: Zhang Xuhui , Tang Zhenghai , Huang Jing , Lin Tengfei , Guo Baochun
Published: December 2015

It poses a huge challenge to create nonpolar rubber with high fracture toughness. In the present letter, inspired by the concept of sacrificial bonding associated with many biological materials, we propose that a small fraction of additional sacrificial network can strikingly improve the fracture toughness of nonpolar rubbers. As a proof of concept, we created the additional “fragile” epoxidized natural rubber (ENR) network in commercially available SBR rubber in a facile process. With addition of only 10 phr ENR, the SBR/ENR double network (DN) exhibits a fracture energy nearly fourfold higher than that for the neat SBR. The formation of DN formation and the correlation between the high toughness and presence of the second brittle network have been fully discussed. This is the first time sacrificial networks are created in diene‐based rubber towards high toughness elastomers in a facile and efficient way. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 781–786
On the Thermal Stability of Partially Decomposed Ammonium Perchlorate
Authors: Hedman Trevor D. , Gross Matthew L.
Published: December 2015

The response of propellants and explosives to thermal stimuli is an important aspect of their behavior, especially for their safe storage and handling. In the case of ammonium perchlorate (AP), the principal oxidizer used in solid composite propellants, exposure to elevated temperatures causes various levels of decomposition and morphological changes. These changes occur in both neat AP particles and AP based propellants. The hazards associated with thermally damaged, or partially decomposed AP are investigated. It is found that AP is more thermally stable after partial low temperature decomposition. Also, it is found that the extent of decomposition of the AP particles is strongly influenced by prior thermal damage. This dependency is attributed to the exhaustion of nucleation sites on certain crystal planes. Specific surface area measurements of the thermally damaged particles show that the particles recrystallize before they can decompose to a further extent in low temperature decomposition. The behavior of partially decomposed AP in the presence of a propellant binder is also examined.
Resolving the ambiguity: Making sense of intrinsic disorder when PDB structures disagree
Authors: DeForte Shelly , Uversky Vladimir N.
Published: December 2015

Missing regions in X‐ray crystal structures in the Protein Data Bank (PDB) have played a foundational role in the study of intrinsically disordered protein regions (IDPRs), especially in the development of in silico predictors of intrinsic disorder. However, a missing region is only a weak indication of intrinsic disorder, and this uncertainty is compounded by the presence of ambiguous regions, where more than one structure of the same protein sequence “disagrees” in terms of the presence or absence of missing residues. The question is this: are these ambiguous regions intrinsically disordered, or are they the result of static disorder that arises from experimental conditions, ensembles of structures, or domain wobbling? A novel way of looking at ambiguous regions in terms of the pattern between multiple PDB structures has been demonstrated. It was found that the propensity for intrinsic disorder increases as the level of ambiguity decreases. However, it is also shown that ambiguity is more likely to occur as the protein region is placed within different environmental conditions, and even the most ambiguous regions as a set display compositional bias that suggests flexibility. The results suggested that ambiguity is a natural result for many IDPRs crystallized under different conditions and that static disorder and wobbling domains are relatively rare. Instead, it is more likely that ambiguity arises because many of these regions were conditionally or partially disordered.
Dimensions, energetics, and denaturant effects of the protein unstructured state
Authors: Li Maodong , Liu Zhirong
Published: December 2015

Determining the energetics of the unfolded state of a protein is essential for understanding the folding mechanics of ordered proteins and the structure–function relation of intrinsically disordered proteins. Here, we adopt a coil‐globule transition theory to develop a general scheme to extract interaction and free energy information from single‐molecule fluorescence resonance energy transfer spectroscopy. By combining protein stability data, we have determined the free energy difference between the native state and the maximally collapsed denatured state in a number of systems, providing insight on the specific/nonspecific interactions in protein folding. Both the transfer and binding models of the denaturant effects are demonstrated to account for the revealed linear dependence of inter‐residue interactions on the denaturant concentration, and are thus compatible under the coil‐globule transition theory to further determine the dimension and free energy of the conformational ensemble of the unfolded state. The scaling behaviors and the effective θ‐state are also discussed.
Nanoparticles in dielectric matrix for electronics and optics: from the fabrication to the devices
Authors: Mascher Peter
Published: December 2015

The discovery of the nanosize‐related effects has led to tremendous efforts, numerous publications, international symposia and patents on the development and study of nanometer scale based structures. The achievements are specific and novel optical, electronic, and magnetic properties are reported that have never been obtained on a macroscopic scale. Among these nanostructured systems, nanoparticles embedded in a dielectric host matrix offer a wide range of applications in electronics and optics from non‐volatile memories to non‐linear optics, from light emitting diodes to enhanced photovoltaic sensors, and from optical amplifiers to plasmonic substrates. This requires a large range of skills in different fields such as chemistry, physics, and material science.

This symposium aimed at gathering scientists and industrial partners from the above fields and involved in the fabrication and the study of such nanostructured systems and related applications. The goal was to share and discuss recent advances in fabrication, doping, optical and/or electrical properties, biosensing, photovoltaics, plasmonics, fundamental mechanisms of growth or excitation, devices that incorporate those properties, and applications of such materials systems. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Robust exchangeability designs for early phase clinical trials with multiple strata
Authors: Neuenschwander Beat , Wandel Simon , Roychoudhury Satrajit , Bailey Stuart
Published: December 2015

Clinical trials with multiple strata are increasingly used in drug development. They may sometimes be the only option to study a new treatment, for example in small populations and rare diseases. In early phase trials, where data are often sparse, good statistical inference and subsequent decision‐making can be challenging. Inferences from simple pooling or stratification are known to be inferior to hierarchical modeling methods, which build on exchangeable strata parameters and allow borrowing information across strata. However, the standard exchangeability (EX) assumption bears the risk of too much shrinkage and excessive borrowing for extreme strata. We propose the exchangeability–nonexchangeability (EXNEX) approach as a robust mixture extension of the standard EX approach. It allows each stratum‐specific parameter to be exchangeable with other similar strata parameters or nonexchangeable with any of them. While EXNEX computations can be performed easily with standard Bayesian software, model specifications and prior distributions are more demanding and require a good understanding of the context. Two case studies from phases I and II (with three and four strata) show promising results for EXNEX. Data scenarios reveal tempered degrees of borrowing for extreme strata, and frequentist operating characteristics perform well for estimation (bias, mean‐squared error) and testing (less type‐I error inflation). Copyright © 2015 John Wiley & Sons, Ltd.
Offshore deep convection initiation and maintenance during the HyMeX IOP 16a heavy precipitation event
Authors: Duffourg F. , Nuissier O. , Ducrocq V. , Flamant C. , Chazette P. , Delanoë J. , Doerenbecher A. , Fourrié N. , Di Girolamo P. , Lac C. , Legain D. , Martinet M. , Saïd F. , Bock O.
Published: December 2015

During the first special observation period of the HyMeX program dedicated to heavy precipitation over the western Mediterranean, several Mesoscale Convective Systems (MCSs) formed over the sea and produced heavy precipitation over the coastal regions, as for example during IOP (Intensive Operation Period) 16a. On 26 October 2012, back‐building MCSs formed and renewed over the northwestern Mediterranean Sea while producing heavy rain over the French coastal urbanized regions. This paper analyses the storm evolution along with the ambient flow and the initiation and maintenance mechanisms of the offshore deep convection observed during IOP16a. The suites of water vapour lidars, wind profilers, radiosoundings and boundary‐layer drifting balloons over and along the coast of the northwestern Mediterranean offer a unique framework for validating the convective processes over the sea investigated using kilometre‐scale analyses and simulation.

The high‐resolution simulation shows clearly that the convective system is fed during its evolution over the sea by moist and conditionally unstable air carried by a southwesterly to southeasterly low‐level jet. The low‐level wind convergence in this southeasterly to southwesterly flow over the sea is the main triggering mechanism acting to continually initiate and maintain the renewal of convective cells contributing to the back‐building system. The convergence line appears when a secondary pressure low forms in the lee of the Iberian mountains. A sensitivity test turning off the evaporative cooling within the microphysical parametrization shows that the exact location of the main convergence area focusing the heaviest precipitation is determined by small‐scale feedback mechanisms of the convection to the environment.
Energy‐efficient distributed control of large‐scale systems: A switched system approach
Authors: Zhang Dan , Shi Peng , Wang Qing‐Guo
Published: December 2015

This paper is concerned with the sensor‐network‐based distributed control of large‐scale systems with the power constraint. In the underlying system, the measurement is firstly sampled under nonuniform sampling periods, which are varying in a given set. Then, the measurement size reduction technique and communication rate reduction method are used to save the constrained power in sensor networks. Specifically, only one element of sampled measurement is chosen at each sampling time instant, and it is then quantized and transmitted to the neighbouring controllers. Based on the switched system approach, a unified model is presented to capture the nonuniform sampling, the measurement size reduction, the transmission rate reduction and the controller failure phenomenon. A new sufficient condition is obtained such that the filtering error system is exponentially stable in the mean‐square sense with a prescribed H∞ performance level. Based on this condition, the controller gains are designed by using the cone complementarity linearization algorithm. Finally, a simulation study is given to show the effectiveness of the proposed new design technique. Copyright © 2015 John Wiley & Sons, Ltd.
Hierarchical Patterning of Cells with a Microeraser and Electrospun Nanofibers
Authors: Li Yan , Jiang Xueqin , Zhong Huixiang , Dai Wen , Zhou Jianhua , Wu Hongkai
Published: December 2015

For tissue engineering applications, it is important to develop fabrication strategies for building models with controlled cell distributions in defined structures. Here, a simple, flexible approach (named the μ‐eraser strategy) is developed to construct multicell micropatterns. This approach involves pressing a poly(dimethylsiloxane) stamp to erase cells growing on substrates, and seeding other types of cells. The pressing/seeding process can be conducted in any designed pattern at desired time point. In a proof of concept, multicell micropatterns of human lung adenocarcinoma epithelial A549 cells, murine fibroblast (FB) cells and murine osteoblast (OB) cells are achieved on Petri dishes and electrospun sheets. Besides forming multicell micropatterns, the cell orientation can be regulated by microstripes and alignment of nanofibers. On Petri dishes and random fiber sheets, FB and OB cells align along microstripes, while A549 cells do not. However, when growing on aligned fiber sheets, no matter whether solo‐cultured or co‐cultured, all cells in micropatterns orient along the fibers. Based on this technique, a platform is built up to investigate rates of cell migration and interinvasion under solo‐culture and co‐culture systems. It is believed that this μ‐eraser strategy has promise for biological, pharmaceutical, and biomedical applications.
Evolution of Irradiation‐Induced Vacancy Defects in Boron Nitride Nanotubes
Authors: Cheng Guangming , Yao Shanshan , Sang Xiahan , Hao Boyi , Zhang Dongyan , Yap Yoke Khin , Zhu Yong
Published: December 2015

Irradiation‐induced vacancy defects in multiwalled (MW) boron nitride nanotubes (BNNTs) are investigated via in situ high‐resolution transmission electron microscope operated at 80 kV, with a homogeneous distribution of electron beam intensity. During the irradiation triangle‐shaped vacancy defects are gradually generated in MW BNNTs under a mediate electron current density (30 A cm−2), by knocking the B atoms out. The vacancy defects grow along a well‐defined direction within a wall at the early stage as a result of the curvature induced lattice strain, and then develop wall by wall. The orientation or the growth direction of the vacancy defects can be used to identify the chirality of an individual wall. With increasing electron current density, the shape of the irradiation‐induced vacancy defects changes from regular triangle to irregular polygon.
GISQAF: MapReduce guided spatial query processing and analytics system
Authors: Al‐Naami Khaled Mohammed , Seker Sadi Evren , Khan Latifur
Published: December 2015

The Global Database of Event, Language, and Tone (GDELT) is the only global political georeferenced event dataset with more than 250 million observations covering all countries in the world since January 1, 1979. TABARI and CAMEO are the tools that are used to collect and code events from all international news coverage. To query such big geospatial data, traditional RDBMS can no longer be used, and the need for parallel distributed solutions has become a necessity. MapReduce paradigm has proven to be a scalable platform to process and analyze Big Data in the cloud. Hadoop, as an implementation of MapReduce, is an open‐source application that has been widely used and accepted in academia and industry. However, when dealing with Spatial Data, Hadoop is not equipped well and does not perform efficiently. SpatialHadoop is an extension of Hadoop with the support of spatial data. In this paper, we present Geographic Information System Query and Analytics Framework (GISQAF), which has been built on top of SpatialHadoop. GISQAF focuses on two parts: query processing and data analytics. For the query processing part, we show how this solution outperforms Hadoop query processing by orders of magnitude when applying queries on the GDELT dataset with a size of 60 GB. We show the results for various types of queries. For the data analytics part, we present an approach for finding Spatial co‐occurring events. We show how GISQAF is suitable and efficient to handle data analytics techniques. Copyright © 2015 John Wiley & Sons, Ltd.
Polymorphic bytecode instrumentation
Authors: Binder Walter , Moret Philippe , Tanter Éric , Ansaloni Danilo
Published: December 2015

Bytecode instrumentation is a widely used technique to implement aspect weaving and dynamic analyses in virtual machines such as the Java virtual machine. Aspect weavers and other instrumentations are usually developed independently and combining them often requires significant engineering effort, if at all possible. In this article, we present polymorphic bytecode instrumentation(PBI), a simple but effective technique that allows dynamic dispatch amongst several, possibly independent instrumentations. PBI enables complete bytecode coverage, that is, any method with a bytecode representation can be instrumented. We illustrate further benefits of PBI with three case studies. First, we describe how PBI can be used to implement a comprehensive profiler of inter‐procedural and intra‐procedural control flow. Second, we provide an implementation of execution levels for AspectJ, which avoids infinite regression and unwanted interference between aspects. Third, we present a framework for adaptive dynamic analysis, where the analysis to be performed can be changed at runtime by the user. We assess the overhead introduced by PBI and provide thorough performance evaluations of PBI in all three case studies. We show that pure Java profilers like JP2 can, thanks to PBI, produce accurate execution profiles by covering all code, including the core Java libraries. We then demonstrate that PBI‐based execution levels are much faster than control flow pointcuts to avoid interference between aspects and that their efficient integration in a practical aspect language is possible. Finally, we report that PBI enables adaptive dynamic analysis tools that are more reactive to user inputs than existing tools that rely on dynamic aspect‐oriented programming with runtime weaving. These experiments position PBI as a widely applicable and practical approach for combining bytecode instrumentations. © 2015 The Authors. Software: Practice and Experience Published by John Wiley & Sons Ltd.
A method for rapid estimation of dynamic coupling and spectral responses of connected adjacent structures
Authors: Behnamfar Farhad , Dorafshan Sattar , Taheri Ali , Hosseini Hashemi Behrokh
Published: December 2015

A simple method is presented for estimation of dynamic coupling and maximum seismic responses of structures connected through links. The purpose is preparing a simple measure for distinguishing the cases where two connected structures interfere in the response of each individual structure and incorporating such cases in spectral analysis. First, each structure is analysed independently, and the natural modes with considerable interference with the other structure are identified. Then the spectral responses corresponding to such modes are modified in modal space. It is shown that the proposed method can estimate the spectral responses of adjacent systems with good accuracy. Copyright © 2015 John Wiley & Sons, Ltd.
Performance of RC columns with debonded bars subjected to cyclic lateral loading
Authors: Mitra Damodaran Chitra , Bindhu Kochunaraya Rugmini
Published: December 2015

Concrete columns with light confinement reinforcement subjected to cyclic lateral load exhibit brittle shear failure along with flexural yielding of longitudinal steel reinforcement bars. The present study investigates the effect of debonding of longitudinal bars on the performance of columns under lateral loading. Column specimens were tested under quasi‐static reverse cyclic lateral loading. A comparative study has been carried out on the performance of columns with and without debonding using circular steel tubes of varying lengths. Steel tubes were provided to the longitudinal reinforcement in the potential plastic hinge zone. It is observed that the specimens with debonded reinforcement have significant enhancement in deformation capacity, ductility and energy dissipation capacity than the specimens without it. The congestion of reinforcement at the joints can also be eliminated by reducing the confining reinforcement for these debonded specimens. Copyright © 2015 John Wiley & Sons, Ltd.
Spatial navigation by congenitally blind individuals
Authors: Schinazi Victor R. , Thrash Tyler , Chebat Daniel‐Robert
Published: December 2015

Spatial navigation in the absence of vision has been investigated from a variety of perspectives and disciplines. These different approaches have progressed our understanding of spatial knowledge acquisition by blind individuals, including their abilities, strategies, and corresponding mental representations. In this review, we propose a framework for investigating differences in spatial knowledge acquisition by blind and sighted people consisting of three longitudinal models (i.e., convergent, cumulative, and persistent). Recent advances in neuroscience and technological devices have provided novel insights into the different neural mechanisms underlying spatial navigation by blind and sighted people and the potential for functional reorganization. Despite these advances, there is still a lack of consensus regarding the extent to which locomotion and wayfinding depend on amodal spatial representations. This challenge largely stems from methodological limitations such as heterogeneity in the blind population and terminological ambiguity related to the concept of cognitive maps. Coupled with an over‐reliance on potential technological solutions, the field has diffused into theoretical and applied branches that do not always communicate. Here, we review research on navigation by congenitally blind individuals with an emphasis on behavioral and neuroscientific evidence, as well as the potential of technological assistance. Throughout the article, we emphasize the need to disentangle strategy choice and performance when discussing the navigation abilities of the blind population.WIREs Cogn Sci2016, 7:37–58. doi: 10.1002/wcs.1375

This article is categorized under:

Psychology > Learning

Neuroscience > Cognition

Neuroscience > Plasticity
Words, rules, and mechanisms of language acquisition
Authors: Endress Ansgar D. , Bonatti Luca L.
Published: December 2015

We review recent artificial language learning studies, especially those following Endress and Bonatti (Endress AD, Bonatti LL. Rapid learning of syllable classes from a perceptually continuous speech stream. Cognition 2007, 105:247–299), suggesting that humans can deploy a variety of learning mechanisms to acquire artificial languages. Several experiments provide evidence for multiple learning mechanisms that can be deployed in fluent speech: one mechanism encodes the positions of syllables within words and can be used to extract generalization, while the other registers co‐occurrence statistics of syllables and can be used to break a continuum into its components. We review dissociations between these mechanisms and their potential role in language acquisition. We then turn to recent criticisms of the multiple mechanisms hypothesis and show that they are inconsistent with the available data. Our results suggest that artificial and natural language learning is best understood by dissecting the underlying specialized learning abilities, and that these data provide a rare opportunity to link important language phenomena to basic psychological mechanisms. WIREs Cogn Sci 2016, 7:19–35. doi: 10.1002/wcs.1376

This article is categorized under:

Psychology > Language

Psychology > Theory and Methods

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Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose‐limited chemostat culture
Authors: Shah Mihir V. , van Mastrigt Oscar , Heijnen Joseph J. , van Gulik Walter M.
Published: December 2015

Currently, research is being focused on the industrial‐scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial‐scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose‐limited chemostat cultures at a cultivation pH of 3.0 (pH < pK). Steady states were achieved with different extracellular levels of fumaric acid, obtained by adding different amounts of fumaric acid to the feed medium. The experiments were carried out with the wild‐type S. cerevisiae CEN.PK 113‐7D and an engineered S. cerevisiae ADIS 244 expressing a heterologous dicarboxylic acid transporter (DCT‐02) from Aspergillus niger, to examine whether it would be capable of exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two‐thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial‐scale production of fumaric acid are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
A phase I trial of ANG1/2-Tie2 inhibitor trebaninib (AMG386) and temsirolimus in advanced solid tumors (PJC008/NCI♯9041)
Authors: Chiu Joanne W. , Hotte Sebastien J. , Kollmannsberger Christian K. , Renouf Daniel J. , Cescon David W. , Hedley David , Chow Sue , Moscow Jeffrey , Chen Zhuo , Perry Meghan , Diaz-Padilla Ivan , Tan David , Hirte Hal , McWhirter Elaine , Chen Helen , Siu Lillian L. , Bedard Philippe L.
Published: December 2015

Background There is crosstalk between the ANG-Tie2 and the PI3K/Akt/mTOR pathways. Combined ANG1/2 and mTOR blockade may have additive anti-cancer activity. The combination of trebananib, an inhibitor of ANG1/2-Tie2 interaction, with temsirolimus was evaluated in patients with advanced solid tumors to determine tolerability, maximum tolerated dose (MTD), and preliminary antitumor activity. Methods Patients were enrolled using 3 + 3 design, and were given intravenous trebananib and temsirolimus on Day 1, 8, 15 and 22 of a 28-day cycle. Dose limiting toxicities (DLTs) were evaluated during cycle 1. Peripheral blood was collected for evaluation of Tie2-expressing monocytes (TEMs) and thymidine phosphorylase (TP). Sparse pharmacokinetic (PK) sampling for trebananib drug levels was performed on Day 1 and 8 of cycle 2. Results Twenty-one patients were enrolled, 6 at dose level (DL) 1, 7 at DL −1, and 8 at DL −2. No effect of temsirolimus on trebananib PK was observed. The most common treatment-related adverse events (AEs) were: fatigue (81 %), edema (62 %), anorexia (57 %), nausea (52 %), rash (43 %) and mucositis (43 %). The most common grade ≥ 3 AEs included lymphopenia (28 %) and fatigue (28 %). The MTD was exceeded at DL-2. Of 18 response evaluable patients, 1 partial response was observed (ER+/HER2−/PIK3CA mutant breast cancer) and 4 patients had prolonged SD ≥ 24 weeks. No correlation with clinical benefit was observed with change in number TEMs or TP expression in TEMs with treatment. Conclusions The MTD was exceeded at trebananib 10 mg/kg weekly and temsirolimus 20 mg weekly, with frequent overlapping toxicities including fatigue, edema, and anorexia.
Prior, translational semantics, and the Barcan formula
Authors: Copeland B. Jack
Published: December 2015

The revolution in semantics in the late 1960s and 1970s overturned an earlier competing paradigm, ‘translational’ semantics. I revive and defend Prior’s translational semantics for modals and tense-modals. I also show how to extend Prior’s propositional modal semantics to quantificational modal logic, and use the resulting semantics to formalize Prior’s own counterexample to the Barcan Formula.
Structure and properties of indium-doped ZnO films prepared by RF magnetron sputtering under different pressures
Authors: Peng Li-Ping , He A-Ling , Fang Liang , Yang Xiao-Fei
Published: December 2015

High conductive and transparent In-doped ZnO thin films were deposited on glass substrates by radio-frequency (RF) magnetron sputtering at 250 °C. Argon gas was used as the sputtering gas, and its pressure varies from 0.1 to 4.0 Pa. The influences of deposition pressure on the structural, electrical and optical properties of the films were investigated by means of X-ray diffraction (XRD), scanning electron microscope (SEM) and Hall and transmittance measurements. The optical constant of the films was estimated from transmittance data using a nonlinear programming method. It is found that the deposition pressure affects the properties of the films significantly. The film deposited at 2.0 Pa shows the optimal crystal quality with a high transmittance of 85 % in the visible range and a low resistivity of 2.4 × 10−3 Ω·cm and can thus be used as a transparent electrode.
Valuación de opciones simples y complejas contenidas en arrendamientos financieros
Authors: Silverio Milanesi Gastón
Published: December 2015

El valor de los contratos de arrendamiento es una función del valor presente de los cánones más las opciones reales operativas. Sin embargo, el método del préstamo equivalente (MPE), con amplia aplicación en la valuación de arrendamientos, falla porque no incorpora las opciones contenidas en el contrato. De esta forma, el presente trabajo propone un modelo de valuación combinando el MPE y el enfoque binomial para valuar opciones reales. Para lograr lo anterior, se realiza el planteamiento matemático y su aplicación para opciones simples (compra, cancelación anticipada, renovación) y compuestas (venture leasing, leasing a porcentaje, pago diferido, pago diferido y compra), demostrando la habilidad del modelo para calcular el valor actual expandido del contrato, como la suma del valor actual de pagos y opciones operativas.
Why has therapy development for dementia failed in the last two decades?
Authors: Gauthier Serge , Albert Marilyn , Fox Nick , Goedert Michel , Kivipelto Miia , Mestre‐Ferrandiz Jorge , Middleton Lefkos T.
Published: December 2015

The success rate of the pharmaceutical research and development (R&D) for dementia drugs has been abysmally low, in the last two decades. Also low has been the number of pipeline drugs in development, compared to other therapy areas. However, the rationale of early terminations has not been reported in the majority of trials. These are key findings of the recently published pharmaceutical pipeline analysis by the UK‐based Office of Health Economics (OHE). Our understanding of main challenges include (1) the significant gaps of knowledge in the nosology and complexity of the underpinning biological mechanisms of the commonest, not familial, forms of late onset dementias; (2) low signal‐to‐noise ratio, notwithstanding the lack of validated biomarkers as entry and/or end‐point criteria; (3) recruitment and retention, particularly in the asymptomatic and early disease stages. A number of current and future strategies aimed at ameliorating drug development are outlined and discussed.
Delayering the global production network into congruent subnetworks
Authors: Ferdows Kasra , Vereecke Ann , De Meyer Arnoud
Published: December 2015

The literature in operations management has not kept up with the growing complexity of and opportunities offered by global production networks. Managers need new tools to cope with this complexity. We propose one that is based on a model that delayers the global plant network into a set of subnetworks on the basis of complexity and proprietary information in the products they produce and production processes they use to produce them. This allows examining whether each subnetwork iscongruent—i.e., has an appropriate manufacturing mission and the competencies that it would need to carry it out. We apply this tool to analyze the global production networks of five companies and illustrate its usefulness in performing periodic audit of the global production network and identifying potential strategic anomalies that deserve attention.