bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of scheduling, design, and control of multiproduct chemical processes under uncertainty
Authors: Patil Bhushan P. , Maia Eduardo , Ricardez‐Sandoval Luis A.
Published: April 2015

The development of a methodology that addresses the simultaneous design, scheduling, and control of multiproduct processes is focused. The proposed methodology takes into account the influence of disturbances by the identification of their critical frequency, which is used to quantify the worst‐case variability in the controlled variables via frequency response analysis. The uncertainty in the demands of products has also been addressed by creating critical demand scenarios with different probabilities of occurrence, while the nominal stability of the system has been ensured. Two case studies have been developed as applications of the methodology. The first case study focuses on the comparison of classical semisequential approach against the simultaneous methodology developed, while the second case study demonstrates the capability of the methodology in application to a large‐scale nonlinear system. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2456–2470, 2015
Case cluster of pneumoconiosis at a coal slag processing facility
Authors: Fagan Kathleen M. , Cropsey Erin B. , Armstrong Jenna L.
Published: April 2015

Background

During an inspection by the Occupational Safety and Health Administration (OSHA) of a small coal slag processing plant with 12 current workers, four cases of pneumoconiosis were identified among former workers.

Methods

The OSHA investigation consisted of industrial hygiene sampling, a review of medical records, and case interviews.

Results

Some personal sampling measurements exceeded the OSHA Permissible Exposure Limit (PEL) for total dust exposures of 15 mg/m3, and the measured respirable silica exposure of 0.043 mg/m3, although below OSHA's current PEL for respirable dust containing silica, was above the American Conference of Governmental Industrial Hygienists' Threshold Limit Value (TLV). Chest x‐rays for all four workers identified small opacities consistent with pneumoconiosis.

Conclusion

This is the first known report of lung disease in workers processing coal slag and raises concerns for workers exposed to coal slag dust. Am. J. Ind. Med. 58:568–576, 2015. © 2015 Wiley Periodicals, Inc.
Showdown in Newark: The Consumer Financial Protection Bureau Issues a Massive Three‐Year Arbitration Study, Drawing Audience Praise and Industry Scorn
Authors: Bleemer Russ
Published: April 2015

The March 10 unveiling of extensive arbitration research by the Consumer Financial Protection Bureau began a new era in the public policy fight over the use of arbitration in consumer disputes.
Even in the CFPB's Numbers, Arbitration Benefits Consumers
Authors: Kaplinsky Alan S.
Published: April 2015

The following article is adapted from a Ballard Spahr blog post, as well as prepared remarks by the author, who participated in a panel at the Consumer Financial Protection Bureau's March 10, Newark, N.J., “Field Hearing on Arbitration,” which followed the Bureau's release earlier the same day of its report to Congress on arbitration, available at http://1.usa.gov/19cVrvE. The full versions of the blog analysis and the author's remarks are available at www.cfpbmonitor.com.
Biomimetic Total Synthesis of Santalin Y
Authors: Strych Sebastian , Journot Guillaume , Pemberton Ryan P. , Wang Selina C. , Tantillo Dean J. , Trauner Dirk
Published: April 2015

A biomimetic total synthesis of santalin Y, a structurally complex but racemic natural product, is described. The key step is proposed to be a (3+2) cycloaddition of a benzylstyrene to a “vinylogous oxidopyrylium”, which is followed by an intramolecular Friedel–Crafts reaction. This cascade generates the unique oxafenestrane framework of the target molecule and sets its five stereocenters in one operation. Our work provides rapid access to santalin Y and clarifies its biosynthetic relationship with other colorants isolated from red sandalwood.
Influence of fly ash cenospheres on performance of coir fiber‐reinforced recycled high‐density polyethylene biocomposites
Authors: Satapathy Sukanya , Kothapalli Raju V. S.
Published: April 2015

Recycled high‐density polyethylene (RHDPE)/coir fiber (CF)‐reinforced biocomposites were fabricated using melt blending technique in a twin‐screw extruder and the test specimens were prepared in an automatic injection molding machine. Variation in mechanical properties, crystallization behavior, water absorption, and thermal stability with the addition of fly ash cenospheres (FACS) in RHDPE/CF composites were investigated. It was observed that the tensile modulus, flexural strength, flexural modulus, and hardness properties of RHDPE increase with an increase in fiber loading from 10 to 30 wt %. Composites prepared using 30 wt % CF and 1 wt % MA‐g‐HDPE exhibited optimum mechanical performance with an increase in tensile modulus to 217%, flexural strength to 30%, flexural modulus to 97%, and hardness to 27% when compared with the RHDPE matrix. Addition of FACS results in a significant increase in the flexural modulus and hardness of the RHDPE/CF composites. Dynamic mechanical analysis tests of the RHDPE/CF/FACS biocomposites in presence of MA‐g‐HDPE revealed an increase in storage (E′) and loss (E″) modulus with reduction in damping factor (tan δ), confirming a strong influence between the fiber/FACS and MA‐g‐HDPE in the RHDPE matrix. Differential scanning calorimetry, thermogravimetric analysis thermograms also showed improved thermal properties in the composites when compared with RHDPE matrix. The main motivation of this study was to prepare a value added and low‐cost composite material with optimum properties from consumer and industrial wastes as matrix and filler. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42237.
Epoxy functionalized poly(lactide) reactive modifier for blown film applications
Authors: Schneider Jeff , Shi Xiangke , Manjure Shilpa , Gravier Daniel , Narayan Ramani
Published: April 2015

Epoxy functionalized poly(lactide) (EF‐PLA) was synthesized by reacting PLA with a multifunctional epoxy polymer (MEP) using reactive extrusion processing. These polymers can function as a rheology modifier for PLA and a compatibilizer for other biopolyesters in blown film and foam applications. Model compound studies show that the epoxy functional group on the MEP reacts selectively with the carboxylic acid chain‐ends of PLA at processing temperatures below 200°C. An EF‐PLA containing up to 10% MEP was prepared without gel formation and reactively extruded with neat PLA to obtain three different product formulations containing MEP (0.25, 0.5, and 1.0%). These products showed significantly enhanced rheological properties compared to what has been reported by other groups and is currently used in the PLA blown film industry, the blending of MEP with PLA in a single step. These benefits are a result of how the MEP gets distributed in the material, and can lead to improved properties even at lower MEP concentrations. Our new materials showed significant strain hardening rheological behavior demonstrating that they can be readily blown into films and foams. A statistical simulation was developed to provide a fundamental understanding of the reaction as well as provide information on the molecular weight characteristics and reactivity of the EF‐PLA. The EF‐PLA molecule shows good potential for use as a rheology modifier and compatibilizer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42243.
Control of swelling properties of polyvinyl alcohol/hyaluronic acid hydrogels for the encapsulation of chondrocyte cells
Authors: Pirinen Sami , Karvinen Jennika , Tiitu Virpi , Suvanto Mika , Pakkanen Tuula T.
Published: April 2015

Hydrogel scaffolds for tissue engineering are important biomaterials. The target in this study was to prepare polyvinyl alcohol/hyaluronic acid hydrogels for the encapsulation of chondrocyte cells by a simple cross‐linking reaction. Control of the swelling properties and morphology of the hydrogels for cultivation of chondrocytes was studied. The hydrogels were prepared from polyvinyl alcohol and hyaluronic acid derivatives bearing primary amine and aldehyde functionalities, respectively. The formation of the hydrogel upon mixing the aqueous solutions of the polymer derivatives took place at room temperature in a few seconds. The swelling properties of the hydrogels were found to depend on the polymer concentration and degree of substitution of the modified polymers. Scanning electron microscopy studies showed that the hydrogels had a suitable porous morphology for cell encapsulation. Furthermore, in vitro cell viability tests with the hydrogels showed no cytotoxicity for chondrocytes and that the cells grew well in the hydrogel scaffolds. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42272.
A guide to the field of palaeo colour
Authors: Vinther Jakob
Published: April 2015

Melanin, and other pigments have recently been shown to preserve over geologic time scales, and are found in several different organisms. This opens up the possibility of inferring colours and colour patterns ranging from invertebrates to feathered dinosaurs and mammals. An emerging discipline is palaeo colour: colour plays an important role in display and camouflage as well as in integumental strengthening and protection, which makes possible the hitherto difficult task of doing inferences about past ecologies, behaviours, and organismal appearance. Several studies and techniques have been presented in the last couple of years that have described ways to characterize pigment patterns. Here, I will review the available methods and the likely applications to understand past ecologies. A golden age of colourized dinosaurs and other animals is now dawning upon us, which may elucidate the nature of ancient predator prey interactions and display structures.

Also watch the Video Abstract.
The role of electron donors generated from UV photolysis for accelerating pyridine biodegradation
Authors: Tang Yingxia , Zhang Yongming , Yan Ning , Liu Rui , Rittmann Bruce E.
Published: April 2015

Employing an internal circulation baffled biofilm reactor (ICBBR), we evaluated the mechanisms by which photolysis accelerated the biodegradation and mineralization of pyridine (C5H5N), a nitrogen‐containing heterocyclic compound. We tested the hypothesis that pyridine oxidation is accelerated because a key photolysis intermediate, succinate, is as electron donor that promotes the initial mono‐oxygenation of pyridine. Experimentally, longer photolysis time generated more electron‐donor products (succinate), which stimulated faster pyridine biodegradation. This pattern was confirmed by directly adding succinate, and the stimulation effect occurred similarly with addition of the same equivalents of acetate and formate. Succinate, whether generated by UV photolysis or added directly, also accelerated mono‐oxygenation of the first biodegradation intermediate, 2‐hydroxyl pyridine (2HP). 2HP and pyridine were mutually inhibitory in that their mono‐oxygenations competed for internal electron donor; thus, the addition of any readily biodegradable donor accelerated both mono‐oxygenation steps, as well as mineralization. Biotechnol. Bioeng. 2015;112: 1792–1800. © 2015 Wiley Periodicals, Inc.
Expression‐level dependent perturbation of cell proteostasis and nuclear morphology by aggregation‐prone polyglutamine proteins
Authors: Lu Meng , Williamson Neil , Boschetti Chiara , Ellis Tom , Yoshimi Tatsuya , Tunnacliffe Alan
Published: April 2015

We describe a gene expression system for use in mammalian cells that yields reproducible, inducible gene expression that can be modulated within the physiological range. A synthetic promoter library was generated from which representatives were selected that gave weak, intermediate‐strength or strong promoter activity. Each promoter resulted in a tight expression range when used to drive single‐copy reporter genes integrated at the same genome location in stable cell lines, in contrast to the broad range of expression typical of transiently transfected cells. To test this new expression system in neurodegenerative disease models, we used each promoter type to generate cell lines carrying single‐copy genes encoding polyglutamine‐containing proteins. Expression over a period of up to three months resulted in a proportion of cells developing juxtanuclear aggresomes whose rate of formation, penetrance, and morphology were expression‐level dependent. At the highest expression levels, fibrillar aggregates deposit close to the nuclear envelope, indicating that cell proteostasis is overwhelmed by misfolded protein species. We also observed expression‐level dependent, abnormal nuclear morphology in cells containing aggresomes, with up to ∼80% of cells affected. This system constitutes a valuable tool in gene regulation at different levels and allows the quantitative assessment of gene expression effects when developing disease models or investigating cell function through the introduction of gene constructs. Biotechnol. Bioeng. 2015;112: 1883–1892. © 2015 Wiley Periodicals, Inc.
Assessing microbial competition in a hydrogen‐based membrane biofilm reactor (MBfR) using multidimensional modeling
Authors: Martin Kelly J. , Picioreanu Cristian , Nerenberg Robert
Published: April 2015

The membrane biofilm reactor (MBfR) is a novel technology that safely delivers hydrogen to the base of a denitrifying biofilm via gas‐supplying membranes. While hydrogen is an effective electron donor for denitrifying bacteria (DNB), it also supports sulfate‐reducing bacteria (SRB) and methanogens (MET), which consume hydrogen and create undesirable by‐products. SRB and MET are only competitive for hydrogen when local nitrate concentrations are low, therefore SRB and MET primarily grow near the base of the biofilm. In an MBfR, hydrogen concentrations are greatest at the base of the biofilm, making SRB and MET more likely to proliferate in an MBfR system than a conventional biofilm reactor. Modeling results showed that because of this, control of the hydrogen concentration via the intramembrane pressure was a key tool for limiting SRB and MET development. Another means is biofilm management, which supported both sloughing and erosive detachment. For the conditions simulated, maintaining thinner biofilms promoted higher denitrification fluxes and limited the presence of SRB and MET. The 2‐d modeling showed that periodic biofilm sloughing helped control slow‐growing SRB and MET. Moreover, the rough (non‐flat) membrane assembly in the 2‐d model provided a special niche for SRB and MET that was not represented in the 1‐d model. This study compared 1‐d and 2‐d biofilm model applicability for simulating competition in counter‐diffusional biofilms. Although more computationally expensive, the 2‐d model captured important mechanisms unseen in the 1‐d model. Biotechnol. Bioeng. 2015;112: 1843–1853. © 2015 Wiley Periodicals, Inc.
Analysis of green algal growth via dynamic model simulation and process optimization
Authors: Zhang Dongda , Chanona Ehecatl Antonio Del‐Rio , Vassiliadis Vassilios S , Tamburic Bojan
Published: April 2015

Chlamydomonas reinhardtii is a green microalga with the potential to generate sustainable biofuels for the future. Process simulation models are required to predict the impact of laboratory‐scale growth experiments on future scaled‐up system operation. Two dynamic models were constructed to simulate C. reinhardtii photo‐autotrophic and photo‐mixotrophic growth. A novel parameter estimation methodology was applied to determine the values of key parameters in both models, which were then verified using experimental results. The photo‐mixotrophic model was used to accurately predict C. reinhardtii growth under different light intensities and in different photobioreactor configurations. The optimal dissolved CO2 concentration for C. reinhardtii photo‐autotrophic growth was determined to be 0.0643 g·L−1, and the optimal light intensity for algal growth was 47 W·m−2. Sensitivity analysis revealed that the primary factor limiting C. reinhardtii growth was its intrinsic cell decay rate rather than light attenuation, regardless of the growth mode. The photo‐mixotrophic growth model was also applied to predict the maximum biomass concentration at different flat‐plate photobioreactors scales. A double‐exposure‐surface photobioreactor with a lower light intensity (less than 50 W·m−2) was the best configuration for scaled‐up C. reinhardtii cultivation. Three different short‐term (30‐day) C. reinhardtii photo‐mixotrophic cultivation processes were simulated and optimised. The maximum biomass productivity was 0.053 g·L−1·hr−1, achieved under continuous photobioreactor operation. The continuous stirred‐tank reactor was the best operating mode, as it provides both the highest biomass productivity and lowest electricity cost of pump operation. Biotechnol. Bioeng. 2015;112: 2025–2039. © 2015 Wiley Periodicals, Inc.
Guns, Impulsive Angry Behavior, and Mental Disorders: Results from the National Comorbidity Survey Replication (NCS‐R)
Authors: Swanson Jeffrey W. , Sampson Nancy A. , Petukhova Maria V. , Zaslavsky Alan M. , Appelbaum Paul S. , Swartz Marvin S. , Kessler Ronald C.
Published: April 2015

Analyses from the National Comorbidity Study Replication provide the first nationally representative estimates of the co‐occurrence of impulsive angry behavior and possessing or carrying a gun among adults with and without certain mental disorders and demographic characteristics. The study found that a large number of individuals in the United States self‐report patterns of impulsive angry behavior and also possess firearms at home (8.9%) or carry guns outside the home (1.5%). These data document associations of numerous common mental disorders and combinations of angry behavior with gun access. Because only a small proportion of persons with this risky combination have ever been involuntarily hospitalized for a mental health problem, most will not be subject to existing mental health‐related legal restrictions on firearms resulting from a history of involuntary commitment. Excluding a large proportion of the general population from gun possession is also not likely to be feasible. Behavioral risk‐based approaches to firearms restriction, such as expanding the definition of gun‐prohibited persons to include those with violent misdemeanor convictions and multiple DUI convictions, could be a more effective public health policy to prevent gun violence in the population. Copyright © 2015 John Wiley & Sons, Ltd.
Development of computer programming attitude scale for university students
Authors: Cetin Ibrahim , Ozden M. Yasar
Published: April 2015

Although the determination of university students' attitudes towards computer programming is a significant issue, the issue has been rarely studied. The purpose of this study was to develop an attitude scale assessing university students' attitudes towards computer programming. In the first phase, the scale was administered to 522 university students. Explanatory factor analysis yielded three dimensions: affection, cognition, and behavior. In the second phase, final version of the 18 item‐scale was administered to 553 university students. Results of confirmatory factor analysis provided evidence for the factorial structure of the scale. The Cronbach alpha coefficients ranged from 0.80 to 0.90. Psychometric properties of Computer Programming Attitude Scale (CPAS) suggest that it is a valid and reliable instrument for measuring university students' attitudes towards computer programming. © 2015 Wiley Periodicals, Inc. Comput. Appl. Eng. Educ. Comput Appl Eng Educ 23:667–672, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21639
Ad hoc communication in teams of mobile robots using zigbee technology
Authors: Fernandes Amadeu , Couceiro Micael S. , Portugal David , Machado Santos João , Rocha Rui P.
Published: April 2015

Mobile robots developed at the Institute of Systems and Robotics (ISR) Coimbra feature ZigBee technology for inter‐robot communication. The main aim of this paper is to implement and validate ad hoc wireless communication functions between robotic teammates using the ZigBee technology, thus integrating and developing the features of the XBee Original Equipment Manufacturer Radio Frequency module via standard Arduino Serial Commands. This work provides a useful instructive tool for research, enabling the interaction and cooperation of a team of mobile robots in areas such as swarm robotics, multi‐robot patrolling, search and rescue, among others. In order to validate the functional requirements, several experiments were performed at the level of peer communication, namely: i) analysis of the Received Signal Strength Indication (RSSI) of messages by peers to estimate inter‐robot distances for localization purposes; ii) analysis of the communication complexity in experiments with large groups of mobile robots using Zigbee communication modules and its application in a real world exploration scenario. © 2015 Wiley Periodicals, Inc. Comput. Appl. Eng. Educ. Comput Appl Eng Educ 23:733–745, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21646
Oxidative Addition of Haloheteroarenes to Palladium(0): Concerted versus SNAr‐Type Mechanism
Authors: Maes Bert U. W. , Verbeeck Stefan , Verhelst Tom , Ekomié Audrey , von Wolff Niklas , Lefèvre Guillaume , Mitchell Emily A. , Jutand Anny
Published: April 2015

The kinetics of the oxidative additions of haloheteroarenes HetX (X=I, Br, Cl) to [Pd0(PPh3)2] (generated from [Pd0(PPh3)4]) have been investigated in THF and DMF and the rate constants have been determined. In contrast to the generally accepted concerted mechanism, Hammett plots obtained for substituted 2‐halopyridines and solvent effects reveal a reaction mechanism dependent on the halide X of HetX: an unprecedented SNAr‐type mechanism for X=Br or Cl and a classical concerted mechanism for X=I. These results are supported by DFT studies.
Manipulating Simple Reactive Chemical Units: Fishing for Alkaloids from Complex Mixtures
Authors: Poupon Erwan , Gravel Edmond
Published: April 2015

This Concept article describes how key C10 molecular scaffolds, too reactive to be obtained through classical multistep synthesis, were targeted in the most simple reaction conditions, reproducing those that may be encountered in living cells. The rationale was that small amounts of these reactive intermediates might be formed in situ from cheap and abundant reactants (i.e., glutaraldehyde and tetrahydropyridine) resulting, upon further rearrangement in “complex mixtures” from which natural substances would arise. From five types of mixtures, at least six full carbon skeletons of known natural substances were formed spontaneously. This work also led to the discovery of new plausible biosynthetic achiral precursors in the Nitraria metabolism.
RBF‐based discrete sliding mode control for robust tracking of uncertain time‐delay systems with input nonlinearity
Authors: Pai Ming‐Chang
Published: April 2015

In this article, a control scheme combining radial basis function neural network and discrete sliding mode control method is proposed for robust tracking and model following of uncertain time‐delay systems with input nonlinearity. The proposed robust tracking controller guarantees the stability of overall closed‐loop system and achieves zero‐tracking error in the presence of input nonlinearity, time‐delays, time‐varying parameter uncertainties, and external disturbances. The salient features of the proposed controller include no requirement of a priori knowledge of the upper bound of uncertainties and the elimination of chattering phenomenon and reaching phase. Simulation results are presented to demonstrate the effectiveness of the proposed scheme. © 2015 Wiley Periodicals, Inc. Complexity 21: 194–201, 2016
Keep all mobile users′ whereabouts secure: a radio frequency identification protocol anti‐tracking in 5G
Authors: Yin Xi , Fang Binxing , Jin Shuyuan , Qiu Meikang , Vasilakos Athanasios V. , Xu Yongjun
Published: April 2015

In the fifth generation mobile networks (in short, 5G), radio frequency identification (RFID) tags are embedded in a growing number of personal items, especially in smartphones. The RFID authentication protocols in 5G should be anti‐scanning and privacy‐enhancing, because RFID tags in smartphones often suffer from leaking private trace of mobile users. However, majorities of existing RFID protocols are vulnerable to location‐tracking threats, and to distributed denial of service (DDoS) attacks on back‐end servers. To eliminate these threats, we propose a hash‐based mutual authentication protocol for smartphones in 5G. This protocol protects individuals' location privacy against malicious hidden scanning in public places. By the authentication of RFID readers via hash values, the proposed protocol is robust against the aforementioned threats. Additionally, our authentication efficiency on the tag side is 2H (two hash calculations), which outperforms most of previously reported solutions based on hash, and the tag stores only two vectors (one is k‐bit and the other j‐bit). Copyright © 2015 John Wiley & Sons, Ltd.
Effect of sleep deprivation on the electrophysiological signature of habituation to noxious laser stimuli
Authors: Schuh‐Hofer S. , Baumgärtner U. , Treede R.‐D.
Published: April 2015

Background

Sleep deprivation induces hyperalgesia. However, this pronociceptive effect is not reflected at the electrophysiological level, since sleep restricted subjects show amplitude reduction of Laser‐evoked Potentials (LEP). We aimed to explore the contribution of habituation to this paradoxical LEP amplitude decline.

Methods

We compared LEP's of 12 healthy students (23.2 ± 1.1 years) after habitual sleep (HS) and a night of total sleep deprivation (TSD). Twelve repetitive laser stimulus blocks (each comprising twenty stimuli) were applied under three attention conditions (‘focusing’ – ‘neutral’ – ‘distraction’ condition). Stimulus blocks were split in part 1 (stimulus 1–10) and part 2 (stimulus 11–20). The contribution of habituation to the TSD‐induced LEP amplitude decline was studied by calculating the percentage amplitude reduction of part 2 as compared to part 1. Individual sleepiness levels were correlated with (1) averaged LEP's and (2) the degree of habituation.

Results

TSD induced hyperalgesia to laser stimuli (p < 0.001). In contrast, depending on the attention condition, the P2 amplitude of the N2P2‐complex was significantly reduced (‘focusing’: p = 0.004; ‘neutral’: p = 0.017; distraction: p = 0.71). Habituation of the P2 amplitude to radiant heat was increased after TSD (‘focusing’: p = 0.04; ‘neutral’: p < 0.001; distraction: p = 0.88). TSD had no significant effect on N1 amplitudes (p > 0.05). Individual sleepiness correlated negatively with averaged P2 amplitudes (p = 0.02), but not with the degree of habituation (p = 0.14).

Conclusion

TSD induces hyperalgesia and results in attention‐dependent enhanced habituation of the P2 component. Increased habituation may – to a substantial degree – explain the TSD‐induced LEP‐amplitude decline.

For this article, a commentary is available at the Wiley Online Library.
Monitoring intracellular protein degradation in antibody‐producing Chinese hamster ovary cells
Authors: Rimbon Jérémy , Sánchez‐Kopper Andrés , Wahl Andreas , Takors Ralf
Published: April 2015

Intracellular proteolysis in mammalian cells is a native cellular strategy to recycle proteins and peptides. Whether or not this mechanism may hamper monoclonal antibody (mAb) formation in Chinese hamster ovary (CHO) cells was the key driver for this study. Exponentially growing, anti‐interleukin (IL)‐8 producing CHO cells were fed with 13C‐labeled L‐lysine. The fate of the labeling signal was tracked in intracellular peptides, which were the proteolytic fragments of the mAb. Signal analysis was performed in samples after cell disruption, anion exchange SPE and Q‐ToF mass detection. Four degradation peptides were found, with HYTQKSLSLSPGK and HYTQKSLSLSPG containing two and one L‐lysine unit (K), respectively. Labeling dynamics were used for model‐based identification of the degradation rate in four biological replicates. Degradation rates of 22–25 pmol/108cells/h were estimated, representing about 3% of the net mAb production. Hence, intracellular mAb degradation occurs even under the rather smooth production conditions installed.
Sensor systems for bioprocess monitoring
Authors: Biechele Philipp , Busse Christoph , Solle Dörte , Scheper Thomas , Reardon Kenneth
Published: April 2015

The ability to measure all process variables is of great importance in the field of bioprocess monitoring and control, and continuous, real‐time measurements are highly desired. The more complete and real‐time the measurements are, the more stable, reproducible, and efficient the process can be, leading to reproducibly high‐quality products. This additional information allows the operator to better document the entire process. The process analytical technologies initiative of the US Food and Drug Administration is strongly related to the analysis and control of biopharmaceutical processes. The aim of the initiative is to create processes, generating products of ensured quality by measuring quality‐related process variables. The quality of the product is enhanced by a deep understanding of the process, which is enabled by an effective and suitable sensor system. The aim of this review is to provide an overview of current and emerging sensors for bioprocess monitoring. Sensors directly interfaced to bioreactors for measuring important variables from the gas phase, such as oxygen and carbon dioxide concentration, are discussed, as well as sensors for the monitoring of the biomass concentration and morphology and of the changing medium composition. Furthermore, sensor systems are discussed. These involve sensors (especially biosensors) that are not implemented directly inside the bioreactor but rather are used in conjunction with sample‐taking systems such as flow injection analysis. A major focus is given to spectroscopic sensors, which are noninvasive and offer interesting options for a simultaneous analysis of various compounds. Since data handling is extremely important for this kind of sensor, chemometrics are also included. Soft sensors are discussed as technology that allows a user to incorporate more process data as it become available. Finally, the current state of disposable sensor technology is presented. These sensors are needed for the growing area of disposable and continuous biomanufacturing.
Towards High‐Throughput Coating and Printing of Light‐Emitting Electrochemical Cells: A Review and Cost Analysis of Current and Future Methods
Authors: Sandström Andreas , Edman Ludvig
Published: April 2015

A revolution is ongoing in the field of artificial light emission, with two prime examples being the quickly growing application of the energy‐efficient light‐emitting diode (LED) in illumination and the introduction of the high‐contrast organic LED (OLED) display in various handheld appliances. It is anticipated that the next big breakthrough will constitute the emergence of a true low‐cost technology, which features novel and attractive form factors such as flexibility, light‐weight, and large‐area emission. To realize this challenging vision, it is mandatory to identify an emissive technology that can be fabricated in a low‐energy and material‐conservative manner. In this context, recent demonstrations of a roll‐to‐roll (R2R) compatible coating and printing of thin‐film light‐emitting electrochemical cells (LECs) on flexible substrates are highly interesting. Here, we review these achievements, and perform a first analysis of the merits of different LEC fabrication methods with regard to material consumption, capital investment, running cost, and throughput. Among our findings we mention a fault‐tolerant, small‐volume batch fabrication of LEC devices using spray sintering, which can be executed at a low installment cost of 100 000 €, but where the large‐area devices currently carry a fabrication cost tag of 14 000 € m−2. The true appeal of the technology is, therefore, better visualized in the high‐volume R2R‐coating scenario, for which the installment cost is 20 times higher, but where the projected price tag is much more attractive (11 € per m2). If such flexible and light‐weight (and potentially metal‐free) sheets are driven at a luminance of 1000 cd m−2, the cost per lumen is a mere 0.0036 € lm−1, which is one order of magnitude lower than the projected future costs for LEDs and OLEDs.
Effect of electroconvulsive seizures on pattern separation
Authors: Svensson Maria , Grahm Matilda , Ekstrand Joakim , Movahed‐Rad Pouya , Johansson Mikael , Tingström Anders
Published: April 2015

Strategies employing different techniques to inhibit or stimulate neurogenesis have implicated a role for adult‐born neurons in the therapeutic effect of antidepressant drugs, as well as a role in memory formation. Electroconvulsive seizures (ECS), an animal model of electroconvulsive therapy, robustly stimulate hippocampal neurogenesis, but it is not known how this relates to either therapeutic efficacy or unwanted cognitive side effects. We hypothesized that the ECS‐derived increase in adult‐born neurons would manifest in improved pattern separation ability, a memory function that is believed to be both hippocampus‐dependent and coupled to neurogenesis. To test this hypothesis, we stimulated neurogenesis in adult rats by treating them with a series of ECS and compared their performances in a trial‐unique delayed nonmatching‐to‐location task (TUNL) to a control group. TUNL performance was analyzed over a 12‐week period, during which newly formed neurons differentiate and become functionally integrated in the hippocampal neurocircuitry. Task difficulty was manipulated by modifying the delay between sample and choice, and by varying the spatial similarity between target and distracter location. Although animals learned the task and improved the number of correct responses over time, ECS did not influence spatial pattern separation ability. © 2015 Wiley Periodicals, Inc.
Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations
Authors: Mancikova Veronika , Cruz Raquel , Inglada‐Pérez Lucía , Fernández‐Rozadilla Ceres , Landa Iñigo , Cameselle‐Teijeiro José , Celeiro Catuxa , Pastor Susana , Velázquez Antonia , Marcos Ricard , Andía Victor , Álvarez‐Escolá Cristina , Meoro Amparo , Schiavi Francesca , Opocher Giuseppe , Quintela Inés , Ansede‐Bermejo Juan , Ruiz‐Ponte Clara , Santisteban Pilar , Robledo Mercedes , Carracedo Angel
Published: April 2015

Thyroid cancer is the most heritable cancer of all those not displaying typical Mendelian inheritance. However, most of the genetic factors that would explain the high heritability remain unknown. Our aim was to identify additional common genetic variants associated with susceptibility to this disease. In order to do so, we performed a genome‐wide association study in a series of 398 cases and 502 controls from Spain, followed by a replication in four well‐defined Southern European case‐control collections contributing a total of 1,422 cases and 1,908 controls. The association between the variation at the 9q22 locus near FOXE1 and thyroid cancer risk was consistent across all series, with several SNPs identified (rs7028661: OR = 1.64, p = 1.0 × 10−22, rs7037324: OR = 1.54, p = 1.2 × 10−17). Moreover, the rare alleles of three SNPs (rs2997312, rs10788123 and rs1254167) at 10q26.12 showed suggestive evidence of association with higher risk of the disease (OR = 1.35, p = 1.2 × 10−04, OR = 1.26, p = 5.2 × 10−04 and OR = 1.38, p = 5.9 × 10−05, respectively). Finally, the rare allele of rs4075570 at 6q14.1 conferred protection in the series studied (OR = 0.82, p = 2.0 × 10−04). This study suggests that heterogeneity in genetic susceptibility between populations is a key feature to take into account when exploring genetic risk factors related to this disease.
What Is Life?
Authors: Kauffman Stuart
Published: April 2015

Some standard ideas about the origin of life based on classical physics and chemistry are described. The subject of the quantum world and growing evidence for quantum biology is broached, and the apparently real Poised Realm, hovering reversibly between quantum and “classical” worlds, is discussed.
HLA‐A, HLA‐B, and HLA‐DRB1 Allele and Haplotype Frequencies in Renal Transplant Candidates in a Population in Southern Brazil
Authors: Saito Patrícia Keiko , Yamakawa Roger Haruki , Noguti Erika Noda , Bedendo Gustavo Borelli , Júnior Waldir Veríssimo da Silva , Yamada Sérgio Seiji , Borelli Sueli Donizete
Published: April 2015

Background

Very few studies have examined the diversity of human leukocyte antigens (HLA) in the Brazilian renal transplant candidates.

Methods

The frequencies of the HLA‐A, HLA‐B, and HLA‐DRB1 alleles, haplotypes and phenotypes were studied in 522 patients with chronic renal failure, renal transplant candidates, registered at the Transplant Centers in north/northwestern Paraná State, southern Brazil. Patients were classified according to the ethnic group (319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans, Africans, and Amerindians; browns or “pardos”] and 69 blacks). The HLA typing was performed by the polymerase chain reaction sequence‐specific oligonucleotide method (PCR‐SSO), combined with Luminex technology.

Results

In the analysis of the total samples, 20 HLA‐A, 32 HLA‐B, and 13 HLA‐DRB1 allele groups were identified. The most frequent allele groups for each HLA locus were HLA‐A*02 (25.4%), HLA‐B*44 (10.9%), and HLA‐DRB1*13 (13.9%). The most frequent haplotypes were HLA‐A*01‐B*08‐DRB1*03 (2.3%), A*02‐B*44‐DRB1*07 (1.2%), and A*03‐B*07‐DRB1*11 (1.0%). Significant differences (P < 0.05) were observed in the HLA‐A*68, B*08, and B*58 allele frequencies among ethnic groups.

Conclusions

This study provides the first data on the HLA‐A, HLA‐B, and HLA‐DRB1 allele, phenotype and haplotype frequencies of renal transplant candidates in a population in southern Brazil.
Comparison of the pharmacokinetics of an oral extended‐release capsule formulation of carbidopa‐levodopa (IPX066) with immediate‐release carbidopa‐levodopa (Sinemet®), sustained‐release carbidopa‐levodopa (Sinemet® CR), and carbidopa‐levodopa‐entacapone (Stalevo®)
Authors: Hsu Ann , Yao Hsuan‐Ming , Gupta Suneel , Modi Nishit B.
Published: April 2015

IPX066 (extended‐release carbidopa‐levodopa [ER CD‐LD]) is an oral extended‐release capsule formulation of carbidopa and levodopa. The single‐dose pharmacokinetics of ER CD‐LD (as 2 capsules; total dose, 97.5 mg‐390 mg CD‐LD) versus immediate‐release (IR) CD‐LD (25 mg‐100 mg), sustained‐release (CR) CD‐LD (25 mg‐100 mg), and CD‐LD‐entacapone (25 mg‐100 mg‐200 mg) was evaluated in healthy subjects. Following IR dosing, LD reached peak concentrations (Cmax) at 1 hour; LD concentrations then decreased rapidly and were less than 10% of peak by 5 hours. With CR CD‐LD and CD‐LD‐entacapone, LD Cmax occurred at 1.5 hours, and concentrations were less than 10% of peak by 6.3 and 7.5 hours, respectively. The initial increase in LD concentration was similar between ER CD‐LD and IR CD‐LD and faster than for CR CD‐LD and CD‐LD‐entacapone. LD concentrations from ER CD­­‐LD were sustained for approximately 5 hours and did not decrease to 10% of peak until 10.1 hours. Dose‐normalized LD Cmax values for ER CD‐LD were significantly lower (P< .05) than for the other CD‐LD products. Bioavailability of LD from ER CD‐LD was 83.5%, 78.3%, and 58.8% relative to IR CD‐LD, CR CD‐LD, and CD‐LD‐entacapone, respectively.
The highest utilizers of care: Individualized care plans to coordinate care, improve healthcare service utilization, and reduce costs at an academic tertiary care center
Authors: Mercer Tim , Bae Jon , Kipnes Joanna , Velazquez Maureen , Thomas Samantha , Setji Noppon
Published: April 2015

BACKGROUND

High utilizers are medically and psychosocially complex, have high rates of emergency department (ED) visits and hospital admissions, and contribute to rising healthcare costs.

OBJECTIVE

Develop individualized care plans to reduce unnecessary healthcare service utilization and hospital costs for complex, high utilizers of inpatient and ED care.

DESIGN

Quality‐improvement intervention with a retrospective pre/post intervention analysis.

SETTING

Nine hundred twenty‐four–bed tertiary academic medical center.

PATIENTS

Twenty‐four medically and psychosocially complex patients with the highest rates of inpatient admissions and ED visits from August 1, 2012 to August 31, 2013.

INTERVENTION

A multidisciplinary team developed individualized care plans integrated into our electronic medical record (EMR) that summarize patient histories, utilization patterns, and management strategies.

MEASUREMENTS

Primary outcomes included inpatient admissions, ED visits, and corresponding variable direct costs 6 and 12 months after care‐plan implementation. Secondary outcomes include inpatient length of stay (LOS) and 30‐day readmissions.

RESULTS

Hospital admissions decreased by 56% (P < 0.001) and 50.5% (P = 0.003), 6 and 12 months after care‐plan implementation. Thirty‐day readmissions decreased by 66% (P < 0.001) and 51.5% (P = 0.002), 6 and 12 months after care‐plan implementation. ED visits, ED costs, and inpatient LOS did not significantly change. Inpatient variable direct costs were reduced by 47.7% (P = 0.001) and 35.8% (P = 0.052), 6 and 12 months after care‐plan implementation.

CONCLUSIONS

Individualized care plans developed by a multidisciplinary team and integrated with the existing healthcare workforce and EMR reduce hospital admissions, 30‐day readmissions, and hospital costs for complex, high‐utilizing patients. Journal of Hospital Medicine 2015;10:419–424. © 2015 Society of Hospital Medicine
Can People Recollect Well and Change Their Source Memory Bias of “Aha!” Experiences?
Authors: Du Xiumin , Zhang Ke , Wang Jiali , Luo Junlong , Luo Jing
Published: April 2015

Although many scientific discoveries were frequently reported as kinds of insightful breakthrough that suddenly illuminated in one's mind, we can never exactly know whether these afterward reports were reliable or not. In this study, subjects were asked to solve a list of Remote Associate Test problems and got both subsets of the insightfully and routinely solved items. Then, this study examined whether people can recollect their “Aha!” experiences as well as “non‐Aha” ones. It was found that subjects were more accurate in recollecting their Aha! experiences relative to the routine ones. The study further examined if the report bias of Aha! or non‐Aha problem solving experiences could be changed by the afterward‐suggestive information that indicated the discovery is unique (rare) or not. It was found that the tendency for participants to falsely recollect their routine problem solving experience as Aha! ones if they were told the item they had solved was very rare, and the tendency to falsely recollect the Aha! problem solving experiences as routine ones if the item were said to be common.
Farmed and wild sea bass (Dicentrarchus labrax) volatile metabolites: a comparative study by SPME‐GC/MS
Authors: Vidal Natalia P , Manzanos María J , Goicoechea Encarnación , Guillén María D
Published: April 2015

BACKGROUND

Farmed and wild European sea bass (Dicentrarchus labrax) could be distinguished by its volatile metabolites, an issue not addressed until now. The aim of this work was to study these metabolites by solid‐phase microextraction followed by gas chromatography/mass spectrometry (SPME‐GC/MS).

RESULTS

Both farmed and wild sea bass have a great number of volatile metabolites, most of them being in low concentrations. These include alcohols, aldehydes, ketones, alkylfurans, acids, aliphatic and aromatic hydrocarbons, terpenes, sulfur and nitrogen derivatives, 2,6‐di‐tert‐butyl‐4‐methylphenol and one derived compound, as well as 2,4,7,9‐tetramethyl‐5‐decyne‐4,7‐diol, this latter compound presumably resulting from environmental contamination. Important differences have been detected between both types of sea bass, and also among individuals inside each group. Farmed specimens are richer in volatile metabolites than the wild counterparts; however, these latter, in general, contain a high number and abundance of metabolites resulting from microbial and enzymatic non‐oxidative activity than the former.

CONCLUSIONS

Clear differences in the volatile metabolites of wild and farmed sea bass have been found. A great deal of valuable information on sea bass volatile metabolites has been obtained, which can be useful in understanding certain aspects of the quality and safety of raw and processed sea bass. © 2015 Society of Chemical Industry
The Role of Place Image Dimensions in Residents' Support for Tourism Development
Authors: Stylidis Dimitrios
Published: April 2015

Understanding residents' perceptions of tourism impacts and their level of support for its development is considered vital for the sustainable development of tourism. Despite the plethora of factors examined as determinants of residents' attitudes toward tourism, the role of residents' place image has been under‐examined. This study developed a model examining the relationships between residents' place image dimensions, perceived tourism impacts and support for development. Findings suggest that two (physical appearance, social environment) out of the four place image dimensions identified in this study exercise a significant effect on residents' attitudes toward tourism. The theoretical and practical implications to the formation of planning and development programs for tourism are discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Technical options for outflow reconstruction in domino liver transplantation: A single European center experience
Authors: De la Serna Sofía , Llado Laura , Ramos Emilio , Fabregat Joan , Baliellas Carme , Busquets Juli , Secanella Lluis , Pelaez Nuria , Torras Jaume , Rafecas Antoni
Published: April 2015

Venous outflow is critical to the success of liver transplantation (LT). In domino liver transplantation (DLT), the venous cuffs should be shared between the donor and the recipient, and the length can be compromised. The aim of this study was to describe and compare the technical options for outflow reconstruction used at our institution. This was a retrospective analysis of 39 consecutive DLT recipients between January 1997 and May 2013. Twenty‐seven men and 12 women (mean age, 61.8 ± 4.3 years) underwent LT and consented to receive a liver from a donor with familial amyloid polyneuropathy (FAP). The main indications were hepatocellular carcinoma and hepatitis C virus cirrhosis. All recipients underwent transplantation by a piggyback technique. Liver procurement in the FAP donors was performed with the classic technique in 22 patients and with the piggyback technique in the last 17. In these latter cases, for vascular outflow reconstruction, a cadaveric venous graft was interposed between the hepatic vein (HV) stump of the FAP liver and the recipient HV in 11 cases (28%). Since 2011, we have employed arterial grafts to be interposed between the vessels stumps: a tailored arterial graft in 5 patients and an aortic graft in 1 case. There was no postoperative mortality. Arterial and portal complications presented in 2 (5.1) and 4 patients (10.3), respectively. Postoperative outflow complications (post‐LT subacute Budd‐Chiari syndrome) occurred in 4 patients, and all of them had received a venous interposed graft for reconstruction. The incidence of outflow complications tended to be higher among patients with venous grafts than those with arterial graft interposition. Overall patient survival at 1, 3, 5, and 10 years was 97%, 79%, respectively. Arterial grafts constitute a feasible and safe option for vascular outflow reconstruction in DLT because they are associated with a relatively low incidence of complications. The recently proposed Bellvitge arterial graft technique should be added to the current range of available surgical modalities. Liver Transpl 21:1051‐1055, 2015. © 2015 AASLD.