bluuebunny/crossref_metadata_2025 huggingface dataset:
A long‐term study of the effects of antiviral therapy on survival of patients with HBV‐associated hepatocellular carcinoma (HCC) following local tumor ablation
Authors: Hann Hie‐Won , Coben Robert , Brown Daniel , Needleman Laurence , Rosato Ernest , Min Albert , Hann Richard S. , Park Kyong Bin , Dunn Stephen , DiMarino Anthony J.
Published: February 2014

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow‐up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46–66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20–73]) received treatment. Between the two groups, there was no difference in their median tumor size and levels of alpha‐fetoprotein and albumin. However, the survival was significantly different (P = 0.001): the median survival of the untreated was 16 months (3–36 months) while that of the treated was 80 months (15–152 months). Fourteen of 16 treated patients are alive to date with two longest survivors alive for ≥151 months. In conclusion, concomitant antiviral therapy for CHB patients with HCC reduces and prevents new/recurrent tumor and improves survival. This novel treatment strategy offers an alternative to liver transplantation in patients with HBV‐associated HCC.
Life Cycle Cost Analysis as Decision Support Tool in Chemical Process Development
Authors: Sell Ina , Ott Denise , Kralisch Dana
Published: February 2014

Today, it is common sense that environmentally benign chemical production processes are needed as the basis for future competitiveness and long‐term sustainability. Decision support in the development of such processes can be provided by life cycle assessment. New technologies, however, can be established only if they lead to cost‐efficient production processes as well. Life cycle costing analyses provide an appropriate methodological basis linking the cost‐side evaluation of alternative options during the process development with environmental decision criteria. The results of both methods can be combined in an eco‐portfolio. In summary, development of both ecologically and economically efficient processes can thus already be supported in the early design phase of the chemical processes.
CDK1 switches mitotic arrest to apoptosis by phosphorylating Bcl‐2/Bax family proteins during treatment with microtubule interfering agents
Authors: Zhou Lingli , Cai Xiaoling , Han Xueyao , Xu Naihan , Chang Donald C.
Published: February 2014

Microtubule interfering agents (MIAs), that can stabilise or depolymerise microtubules, are an important class of cancer chemotherapeutic drugs. They can lead to mitotic arrest and subsequent apoptosis. We demonstrate that cell cycle‐dependent kinase 1 (CDK1) is important in switching cells from mitotic arrest to apoptosis during MIAs treatment. Overexpression of non‐degradable cyclin B1 sustained CDK1 activation and mitotic arrest, followed by caspase‐3 dependent apoptosis. CDK1 is responsible for the phosphorylation of several pro‐ and anti‐apoptotic Bcl‐2 family proteins during MIAs treatment. CDK1‐mediated Bcl‐2 serine 70 phosphorylation enhances its pro‐apoptotic function, whereas CDK1‐mediated Bad serine 128 phosphorylation promotes apoptosis. Blockage of CDK1 activity with a specific pharmacological inhibitor suppresses Mcl‐1 phosphorylation, degradation and its anti‐apoptotic function. Therefore, the death of cancer cells under MIAs treatment was caused by imbalance between CDK1‐induced alterations in the pro‐apoptotic and anti‐apoptotic functions of phosphorylated Bcl‐2 family proteins.
Transition‐Metal‐Catalyzed CH Bond Functionalizations: Feasible Access to a Diversity‐Oriented β‐Carboline Library
Authors: Wu Ningjie , Song Feijie , Yan Lipeng , Li Juan , You Jingsong
Published: February 2014

Diversification of the β‐carboline skeleton has been demonstrated to assemble a β‐carboline library starting from the tetrahydro‐β‐carboline framework. This strategy affords feasible access to heteroaryl‐, aryl‐, alkenyl‐, or alkynyl‐substituted β‐carbolines at the C1, C3, or C8 position through three categorically different types of transition‐metal‐catalyzed CC bond‐forming reactions, in the presence of multiple potentially reactive positions. These site‐selective functionalizations include; 1) the Cu‐catalyzed C1/C3‐selective decarboxylative CC and CCsp coupling of hexahydro‐β‐carboline‐3‐carboxylic acid with a CH bond of a heteroarene or terminal alkyne; 2) the chelation‐assisted Pd‐catalyzed C1/C8‐selective CH arylation of hexahydro‐β‐carboline with aryl boron reagents; and 3) the chelation‐assisted Pd‐catalyzed C1/C3‐selective oxidative CH/CH cross‐coupling of β‐carboline‐N‐oxide with arenes, heteroarenes, or alkenes. The saturated structural feature of the hexahydro‐β‐carboline framework can increase reactivity and control site selectivity. The robustness of these approaches has been demonstrated through the synthesis of hyrtioerectine analogues and perlolyrine. We believe that these strategies could provide inspiration for late‐stage diversifications of bioactive core scaffolds.
Epigenetic Molecular Recognition: A Biomolecular Modeling Perspective
Authors: Vellore Nadeem A. , Baron Riccardo
Published: February 2014

The abnormal regulation of epigenetic protein families is associated with the onset and progression of various human diseases. However, epigenetic processes remain relatively obscure at the molecular level, thus preventing the rational design of chemical therapeutics. An array of robust computational and modeling approaches can complement experiments to shed light on the complex mechanisms of epigenetic molecular recognition and can guide medicinal chemists in designing selective and potent drug molecules. Herein we present a review of studies focused on epigenetic molecular recognition from a biomolecular modeling viewpoint. Although the known epigenetic targets are numerous, this review focuses on the more limited protein families on which computational modeling has been successfully applied. Therefore, we review three main topics: 1) histone deacetylases, 2) histone demethylases, and 3) histone tail dynamics. A brief review of the biological background and biomedical relevance is presented for each topic, followed by a detailed discussion of the computational studies and their relevance.
Active smoking and the risk of estrogen receptor‐positive and triple‐negative breast cancer among women ages 20 to 44 years
Authors: Kawai Masaaki , Malone Kathleen E. , Tang Mei‐Tzu C. , Li Christopher I.
Published: February 2014

BACKGROUND

Evidence regarding the correlation between smoking and breast cancer among young women is mixed, and previous studies have not assessed whether smoking is associated differentially with risks of the major breast cancer subtypes.

METHODS

This was a population‐based, case‐control study of 778 women with estrogen receptor (ER)‐positive breast cancers and 182 women with ER‐negative, progesterone receptor‐negative, and human epidermal growth factor receptor 2‐negative (triple‐negative [TN]), invasive breast cancers ages 20 to 44 years who were diagnosed from 2004 to 2010 in the Seattle‐Puget Sound metropolitan area. A control group of 938 cancer‐free women also was included. Associations between various aspects of smoking history and the risks of ER‐positive and TN breast cancer were assessed using polytomous logistic regression.

RESULTS

Ever‐smokers had a 1.3‐fold increased risk (95% confidence interval [CI], 1.1‐fold to 1.7‐fold increased risk) of breast cancer overall; and, when stratified by cancer subtype, they had a 1.4‐fold increased risk (95% CI, 1.1‐fold to 1.8‐fold increased risk) of ER‐positive breast cancer, but there was no elevation in their risk of TN disease (odds ratio, 1.1; 95% CI, 0.7‐1.6). Current/recent smokers with a ≥10 pack‐year history of smoking had a 1.6‐fold increased risk (95% CI, 1.1‐fold to 2.4‐fold increased risk) of ER‐positive breast cancer but had no increase in their risk of TN breast cancer (odds ratio, 1.0; 95% CI, 0.5‐1.9).

CONCLUSIONS

The current results suggested that young women who are current/recent smokers with high pack‐year histories may have an increased risk of ER‐positive breast cancer but not TN breast cancer. Although this association was modest, the findings suggest that an increased risk of ER‐positive breast cancer may be another health risk incurred by young women who smoke. Cancer 2014;120:1026–1034. © 2013 American Cancer Society.
Tuning Quantum‐Dot Organization in Liquid Crystals for Robust Photonic Applications
Authors: Rodarte Andrea L. , Nuno Zachary S. , Cao Blessing H. , Pandolfi Ronald J. , Quint Makiko T. , Ghosh Sayantani , Hein Jason E. , Hirst Linda S.
Published: February 2014

Mesogenic ligands have the potential to provide control over the dispersion and stabilization of nanoparticles in liquid crystal (LC) phases. The creation of such hybrid materials is an important goal for the creation of soft tunable photonic devices, such as the LC laser. Herein, we present a comparison of isotropic and mesogenic ligands attached to the surface of CdSe (core‐only) and CdSe/ZnS (core/shell) quantum dots (QDs). The mesogenic ligand′s flexible arm structure enhances ligand alignment, with the local LC director promoting QD dispersion in the isotropic and nematic phases. To characterize QD dispersion on different length scales, we apply fluorescence microscopy, X‐ray scattering, and scanning confocal photoluminescent imaging. These combined techniques demonstrate that the LC‐modified QDs do not aggregate into the dense clusters observed for dots with simple isotropic ligands when dispersed in liquid crystal, but loosely associate in a fluid‐like droplet with an average interparticle spacing >10 nm. Embedding the QDs in a cholesteric cavity, we observe comparable coupling effects to those reported for more closely packed isotropic ligands.
Electrostatic Ion Thrusters ‐ Towards Predictive Modeling
Authors: Kalentev O. , Matyash K. , Duras J. , Lüskow K. F. , Schneider R. , Koch N. , Schirra M.
Published: February 2014

The development of electrostatic ion thrusters so far has mainly been based on empirical and qualitative knowhow, and on evolutionary iteration steps. This resulted in considerable effort regarding prototype design, construction and testing and therefore in significant development and qualification costs and high time demands. For future developments it is anticipated to implement simulation tools which allow for quantitative prediction of ion thruster performance, long‐term behavior and space craft interaction prior to hardware design and construction. Based on integrated numerical models combining self‐consistent kinetic plasma models with plasmawall interaction modules a new quality in the description of electrostatic thrusters can be reached. These open the perspective for predictive modeling in this field. This paper reviews the application of a set of predictive numerical modeling tools on an ion thruster model of the HEMP‐T (High Efficiency Multi‐stage Plasma Thruster) type patented by Thales Electron Devices GmbH. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Plasma‐Based Pollutant Degradation in Gas Streams: Status, Examples and Outlook
Authors: Brandenburg R. , Kovačević V. V. , Schmidt M. , Basner R. , Kettlitz M. , Sretenović G.B. , Obradović B.M. , Kuraica M.M. , Weltmann K.‐D.
Published: February 2014

The status of the research into and the application of non‐thermal plasmas for the pollutant degradation in gases is discussed, including some fundamental topics and engineering issues.

Two reactor concepts, both based on dielectric barrier discharges (DBDs), are presented and investigated for various tasks. The DBD‐stack reactor shows a very good scalability and was investigated for the oxidation of NO in combustion gases (shipping diesel engine exhausts). The oxidation processes were significantly enhanced by the admixture of hydrocarbons. Significant NO conversion at low specific energy densities below 100 J/L were achieved in laboratory and test bench studies. The water falling film reactor demonstrated its feasibility for the removal of hydrocarbon pollutants from gases. Undecane, a long‐chain, harmful hydrocarbon, was decomposed. The conversion of non‐soluble compounds into soluble ones (formic acid) is a promising development towards a compact plasma‐assisted scrubbing technology. These approaches are good progress not only in the field of environmental plasma application, but also for indoor air quality, hygiene, and plasma synthesis. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Generation of Large‐Area Highly‐Nonequlibrium Plasma in Pure Hydrogen at Atmospheric Pressure
Authors: Prysiazhnyi V. , Brablec A. , Čech J. , Stupavská M. , Černák M.
Published: February 2014

Diffuse Coplanar Surface Barrier Discharge (DCSBD) is a novel type of atmospheric‐pressure plasma source developed for high‐speed large‐area surface plasma treatments. Basic characteristics of DCSBD operated in pure atmospheric‐pressure hydrogen were measured using optical and emission spectroscopy methods, and its potential for the surface treatment application was demonstrated by hydrogen plasma reduction of Cu2O thin layers. The discharge generates a thin layer of diffuse non‐equilibrium plasma with a high power density of 70 Wcm–3. The mean electron density and electron temperature derived from spectroscopic data were 1.3 x 1016cm–3 and 19 x 103K, and the surface Cu2O layers forming a weak boundary were reduced to metallic copper within several seconds. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Basic Study of Two‐Dimensional Thomson Scattering Measurement by Multiple Reflections and Time‐of‐Flight of Laser Beam
Authors: Ito Shingo , Sakamoto Hisashi , Kotani Raita , Inomoto Michiaki , Ono Yasushi , Narihara Kazumichi
Published: February 2014

A novel two‐dimensional Thomson scattering (TS) measurement system has been developed by adopting the time‐of‐flight (TOF) difference in the signals scattered from three parallel laser beams formed by multiple reflections. New ideas are: (1) a YAG laser beam is reflected by 6 mirrors so that it covers the whole r–z plane of a spherical Tokamak (ST) plasma; (2) the observation position is determined by the time delay of the scattered light, which helps to significantly reduce the necessary numbers of spectrometers and detectors. Using a TS‐4 torus plasma merging device. we successfully measured the electron temperature at nine points, demonstrating the basic theory of this novel TS system.
A Pulse‐Type Hardware Level Difference Detection Model Based on Sound Source Localization Mechanism in the Barn Owl
Authors: Sakurai Tsubasa , Sekine Yoshifumi
Published: February 2014

Auditory information processing is very important in the darkness where vision information is extremely limited. Barn owls have an excellent hearing information processing function. Barn owls can detect a sound source with high accuracy to within less than two degrees in both the vertical and horizontal directions. When they perform sound source localization, barn owls use the interaural time difference for localization in the horizontal plane, and the interaural level difference for localization in the vertical plane. We are constructing a two‐dimensional sound source localization model using pulse‐type hardware neuron models based on sound source the localization mechanism of barn owl for the purpose of engineering application. In this paper we propose a pulse‐type hardware model for level difference detection based on sound source the localization mechanism of the barn owl. First, we discuss the response characteristics of the mathematical model for level difference detection. Next we discuss the response characteristics of the hardware mode. The results show clearly that this proposed model can be used as a sound source localization model for the vertical direction.
Enhancement of Passive Surveillance System for Airport Surface Movement
Authors: Kakubari Yasuyuki , Koga Tadashi , Miyazaki Hiromi , Shimada Hiroki , Nihei Shiro
Published: February 2014

Multilateration is an aircraft surveillance system for airport surface movement utilizing hyperbolic positioning. The system performance is sometimes degraded by multipath signals in airport apron areas. ENRI has proposed an enhanced multilateration system named OCTPASS (Optically Connected Passive Surveillance System), which has interference immunity in a multipath environment. This paper describes evaluation results for OCTPASS prototype equipment.
Automatic Generation of 3D Facial Image Using Artificial Neural Network
Authors: Yamamoto Takuma , Hattori Koosuke , Taguchi Ryo , Hoguro Masahiro , Umezaki Taizo
Published: February 2014

The face is one of the most important regions for communication with others and for recognition of persons, and consequently face recognition systems are highly desirable. Such systems use images captured by a camera to recognize persons. However, face images are variable because of external factors such as the position of the body, ambient lighting, facial expression, and so on. This variability decreases recognition accuracy, and therefore facial recognition systems must overcome this problem. Recognition with 3D data solves this problem, but 3D measuring systems are expensive. Therefore, we propose a method that estimates 3D face data from 2D images captured by a camera. The method uses artificial neural networks, which learn the relations between 2D facial images and 3D facial data, as measured by a CCD camera and a laser range finder. Then, the artificial neural networks are able to reconstruct 3D facial data from 2D images. The experimental results show that the proposed method is effective.
Design of an Implicit GMV‐PID Controller Using Closed Loop Data
Authors: Wakitani Shin , Hosokawa Kei , Yamamoto Toru
Published: February 2014

In industrial processes, PID control has been applied in many real systems. The control performance strongly depends on the PID parameters. Although some schemes for tuning PID parameters have been proposed, these schemes need system parameters which are estimated by system identification in order to calculate the PID parameters. On the other hand, model‐free controller design schemes represented by virtual reference feedback tuning (VRFT) or FRIT have received much attention in the last few years. These methods can calculate control parameters using closed loop data and are expected to reduce computational costs. In this paper, a type of implicit PID controller using closed loop data is proposed. In the proposed method, the PID parameters are calculated on the basis of the implicit generalized minimum variance control. The control performance can be suitably adjusted by means of only a user‐specified parameter. The effectiveness of the proposed method is numerically and experimentally evaluated.
Isotropic Nd‐Fe‐B Thick‐Film Magnets for Micro‐Rotors Prepared by PLD Method
Authors: Nakano Masaki , Itakura Masaru , Yanai Takeshi , Yamashita Fumitoshi , Fukunaga Hirotoshi
Published: February 2014

The flexibility of magnetization of isotropic thick‐film magnets enabled us to enhance the torque of a millimeter‐size motor comprising a multipolar magnetized rotor compared to the torque of a miniaturized motor using an anisotropic Nd‐Fe‐B sintered magnet. In order to upgrade the torque of the small motor further, an increase in the remanence value of the isotropic films is indispensable. In this study, therefore, we prepared nano‐composite Nd‐Fe‐B thick films by a high‐speed PLD (pulsed laser deposition) method with a deposition rate of approximately 40 μm/h. Resultantly, the use of additive (Zr or Nb) was effective to enhance the coercivity value of Nd‐Fe‐B thick‐film magnets with Nd‐poor composition, however it was difficult to increase the remanence values. In order to apply the thick films to a micro‐rotor, investigation on several experiments related to mechanical property was also carried out.
Position and Rotation Estimation for Mobile Robots in Outside of Recording Path Using Ego‐Motion
Authors: Hagiwara Yoshinobu , Shoji Tatsuya , Imamura Hiroki
Published: February 2014

In this research, estimating the position and rotation of a mobile robot outside of a recording path is realized by applying ego‐motion to view‐based navigation. The ego‐motion is calculated based on the differences in 3D positions of SURF feature points between recording and current images obtained by a Kinect sensor. In conventional view‐based navigation, it is difficult to plan another path when people and objects are found in the recording path. By using the authors’ proposed estimation method, it is possible to realize flexible path planning in actual environments that include people and objects. Based on the results of experiments performed in actual indoor environments, the authors evaluated measurement accuracy for the robot's position and rotation estimated under their method, and confirmed the viability of their method for actual environments including people and objects.
Chromium Complexes Containing Polycyclic Condensed Aromatic Ligands: Mono‐ and Bidirectional Synthesis from Chromium–Carbenes, Molecular Structures, and Rearrangement Reactions
Authors: Hegele Peter , Schnakenburg Gregor , Daniels Jörg , Dötz Karl Heinz
Published: February 2014

Chromium–pyrenylcarbenes accessible from halopyrene precursors undergo benzannulation upon gentle warming with 3‐hexyne to give hydroquinoid benzopyrene–Cr(CO)3 complexes. Kinetic benzannulation product 3 rearranges into thermodynamic haptotropomer 4 at 70 °C in octafluorotoluene under first‐order kinetics. Further complexation of 3 by Cr(NH3)3(CO)3 affords syn and anti dinuclear chromium–benzopyrene complexes. Bidirectional extension of the benzannulation protocol results in the formation of syn and anti dibenzopyrene–dichromium complexes, which are structurally characterized by X‐ray analysis.
Unique Deca‐ and Tetranuclear Halocuprate(I) Clusters of a Clamplike Ligand: Isolation, Structure, and Luminescence Properties
Authors: Li Li , Li Hai‐Yan , Ren Zhi‐Gang , Lang Jian‐Ping
Published: February 2014

Invited for the cover of this issue is the group of Jian‐Ping Lang at Soochow University, P. R. China. The cover image shows the structure containing the decanuclear chlorocuprate(I) cluster in which two stairlike [Cu5Cl5] fragments share two μ6‐Cl and two μ‐Cl atoms to form a unique [Cu10Cl10] cluster framework. In the background is a gate with the motto of the university “Unto a Full Grown Man”.
Asymmetric Iodolactonization: An Evolutionary Account
Authors: Nolsøe Jens M. J. , Hansen Trond V.
Published: February 2014

The diversity entailed by halolactonization makes it a fundamental transformation, enabling the synthetic organic chemist to build up molecular complexity in a way that relates structural elements in a predictable manner. Due to practical aspects and the subsequent flexible manipulation of the installed halogen handle, iodolactonization takes precedence over the other variants. The asymmetry that can be conferred on the products by iodine‐induced cyclization has been the subject of various approaches. For a long time stereoselectivity has been achieved by substrate‐controlled reactions. However, lately, the reagent‐controlled counterpart has surfaced as an alternative based on the action of a catalyst. Despite the fact that the current progress in catalytic asymmetric iodolactonization has happened only in the space of the last three years, a number of conceptually different approaches have already been applied to advance beyond the substrate‐controlled reaction. Herein we describe the various strategies, which have propelled the development of asymmetric iodolactonization to its current state, putting an emphasis on catalysis.
Direct Trifluoromethylthiolation Reactions: The “Renaissance” of an Old Concept
Authors: Toulgoat Fabien , Alazet Sébastien , Billard Thierry
Published: February 2014

Because of its high lipophilicity, the CF3S group has always interested chemists. However, strategies to introduce it into organic molecules have been, for the most part, reserved to specialized “fluorine chemists”. Recent published work has demystified these preconceived ideas by proposing new efficient methods or easy‐to‐handle reagents to enrich the toolbox of chemists. However, all these new concepts arise from the pioneering works of the past! In this review, we will do a “back to the future” by remembering the most significant results of the past and by presenting extensions and novelties of the present and for the future.
The Purpose and Age of Underwater Walls in the Bay of Elaia of Western Turkey: A Multidisciplinary Approach
Authors: Seeliger Martin , Brill Dominik , Feuser Stefan , Bartz Melanie , Erkul Ercan , Kelterbaum Daniel , Vött Andreas , Klein Christina , Pirson Felix , Brückner Helmut
Published: February 2014

Pergamum (modern: Bergama) was operating an important harbour used by military forces and merchants at the city of Elaia during Hellenistic and Roman Imperial times. Harbour‐related facilities such as warehouses, breakwaters and wharfs document the importance of this harbour site not only for the Pergamenians. This paper focuses on the purpose and age of six submerged wall structures situated approximately 1 km south of the ancient closed harbour basin of Elaia. Geoelectric cross‐sections and semi‐aquatic coring near these walls failed to detect any solid basement under the walls which excludes their possible use as breakwaters or wharfs. Instead, the walls were most likely delineating and separating evaporation ponds of salt works, which compares well with similar structures from other periods and places around the Mediterranean. Combined OSL and 14C‐dating determined the construction age of the installation between the 4th and 6th centuries A.D. Subsequent (re‐)uses are likely and are in agreement with findings from archaeological surveys.
A FIM Study to Assess Safety and Exposure of Inhaled Single Doses of AP301—A Specific ENaC Channel Activator for the Treatment of Acute Lung Injury
Authors: Schwameis Richard , Eder Sandra , Pietschmann Helmut , Fischer Bernhard , Mascher Hermann , Tzotzos Susan , Fischer Hendrik , Lucas Rudolf , Zeitlinger Markus , Hermann Robert
Published: February 2014

AP301 is an activator of ENaC‐mediated Na+ uptake for the treatment of pulmonary permeability edema in acute respiratory distress syndrome (ARDS). The purpose of this “first‐in‐man” study was to examine local and systemic safety and systemic exposure of ascending single doses of AP301, when inhaled by healthy male subjects. In a double‐blind, placebo‐controlled study, 48 healthy male subjects were randomized to 6 ascending dose groups (single doses up to 120 mg) of 8 subjects each (3:1 randomization of AP301: placebo). Serial assessments included spirometry, exhaled nitric oxide (eNO), vital signs, ECG, safety laboratory, adverse events (AE), and blood samples for the quantification of AP301 in plasma. Descriptive statistics was applied. All 48 subjects received treatment, and completed the study as per protocol. No serious, local (e.g., hoarseness, cough, bronchospasm), or dose‐limiting AEs were noted. None of the assessments indicated notable dose or time‐related alterations of safety outcomes. Observed AP301 systemic exposure levels were very low, with mean Cmax values of <2.5 ng/mL in the highest dose groups. Inhaled AP301 single doses up to 120 mg were safe and well tolerated by healthy male subjects. Distribution of inhaled AP301 was largely confined to the lung, as indicated by very low AP301 systemic exposure levels.
Plasmid DNA purification using a multimodal chromatography resin
Authors: Matos Tiago , Queiroz João A. , Bülow Leif
Published: February 2014

Multimodal chromatography is widely used for isolation of proteins because it often results in improved selectivity compared to conventional separation resins. The binding potential and chromatographic behavior of plasmid DNA have here been examined on a Capto Adhere resin. Capto Adhere is a recent multimodal chromatography material allowing molecular recognition between the ligand and target molecule, which is based on combined ionic and aromatic interactions. Capto Adhere proved to offer a very strong binding of nucleic acids. This property could be used to isolate plasmid DNA from a crude Escherichia coli extract. Using a stepwise NaCl gradient, pure plasmid DNA could be obtained without protein and endotoxin contaminations. The RNA fraction bound most strongly to the resin and could be eluted only at very high salt concentrations (2.0 M NaCl). The chromatographic separation behavior was very robust between pH values 6 and 9, and the dynamic binding capacity was estimated to 60 µg/ml resin. Copyright © 2014 John Wiley & Sons, Ltd.
Dynamic and geometric analyses of Nudaurelia capensis ω virus maturation reveal the energy landscape of particle transitions
Authors: Tang Jinghua , Kearney Bradley M. , Wang Qiu , Doerschuk Peter C. , Baker Timothy S. , Johnson John E.
Published: February 2014

Quasi‐equivalent viruses that infect animals and bacteria require a maturation process in which particles transition from initially assembled procapsids to infectious virions. Nudaurelia capensis ω virus (NωV) is a T = 4, eukaryotic, single‐stranded ribonucleic acid virus that has proved to be an excellent model system for studying the mechanisms of viral maturation. Structures of NωV procapsids (diameter = 480 Å), a maturation intermediate (410 Å), and the mature virion (410 Å) were determined by electron cryo‐microscopy and three‐dimensional image reconstruction (cryoEM). The cryoEM density for each particle type was analyzed with a recently developed maximum likelihood variance (MLV) method for characterizing microstates occupied in the ensemble of particles used for the reconstructions. The procapsid and the mature capsid had overall low variance (i.e., uniform particle populations) while the maturation intermediate (that had not undergone post‐assembly autocatalytic cleavage) had roughly two to four times the variance of the first two particles. Without maturation cleavage, the particles assume a variety of microstates, as the frustrated subunits cannot reach a minimum energy configuration. Geometric analyses of subunit coordinates provided a quantitative description of the particle reorganization during maturation. Superposition of the four quasi‐equivalent subunits in the procapsid had an average root mean square deviation (RMSD) of 3 Å while the mature particle had an RMSD of 11 Å, showing that the subunits differentiate from near equivalent environments in the procapsid to strikingly non‐equivalent environments during maturation. Autocatalytic cleavage is clearly required for the reorganized mature particle to reach the minimum energy state required for stability and infectivity. Copyright © 2014 John Wiley & Sons, Ltd.
Comparison of interpolation methods for estimating spatial distribution of precipitation in Ontario, Canada
Authors: Wang S. , Huang G. H. , Lin Q. G. , Li Z. , Zhang H. , Fan Y. R.
Published: February 2014

In this study, different interpolation techniques in a geographical information system (GIS) environment are analysed and compared for estimating the spatial distribution of precipitation in the province of Ontario, Canada. A high‐resolution regional climate modelling system [Providing Regional Climates for Impacts Studies (PRECIS)] is used to simulate the present (1961–1990) and future (2071–2100) precipitation events for 12 meteorological stations over Ontario. The results verify that for the present case PRECIS simulates well the precipitation events when compared with observed data. The future precipitation events can be projected after the validation of PRECIS. Six interpolation methods are then used to generate spatial distribution of precipitation based on the projections of future precipitation of 12 meteorological stations; they include inverse distance weighting (IDW), global polynomial interpolation (GPI), local polynomial interpolation (LPI), radial basis functions (RBF), ordinary kriging (OK), and universal kriging (UK). Cross‐validation is applied to evaluate the accuracy of interpolation methods in terms of the root mean square error (RMSE). The results indicate that LPI is the optimal method with the least RMSE for interpolating the PRECIS precipitation. LPI is then used to analyse spatial variations of the average annual precipitation for the period of 2071–2100 over Ontario.
Novel chiral stationary phases based on peptoid combining a quinine/quinidine moiety through a C9‐position carbamate group
Authors: Wu Haibo , Wang Dongqiang , Song Guangjun , Ke Yanxiong , Liang Xinmiao
Published: February 2014

By connecting a quinine or quinidine moiety to the peptoid chain through the C9‐position carbamate group, we synthesized two new chiral selectors. After immobilizing them onto 3‐mercaptopropyl‐modified silica gel, two novel chiral stationary phases were prepared. With neutral, acid, and basic chiral compounds as analytes, we evaluated these two stationary phases and compared their chromatographic performance with chiral columns based on quinine tert‐butyl carbamate and the previous peptoid. From the resolution of neutral and basic analytes under normal‐phase mode, it was found that the new stationary phases exhibited much better enantioselectivity than the quinine tert‐butyl carbamate column; the peptoid moiety played an important role in enantiorecognition, which controlled the elution orders of enantiomers; the assisting role of the cinchona alkaloid moieties was observed in some separations. Under acid polar organic phase mode, it was proved that cinchona alkaloid moieties introduced excellent enantiorecognitions for chiral acid compounds; in some separations, the peptoid moiety affected enantioseparations as well. Overall, chiral moieties with specific enantioselectivity were demonstrated to improve the performance of peptoid chiral stationary phase efficiently.
Cell Adhesion Behavior in 3D Hydrogel Scaffolds Functionalized with D‐ or L‐Aminoacids
Authors: Benson Kathrin , Galla Hans‐Joachim , Kehr Nermin Seda
Published: February 2014

Alginate hydrogels functionalized with D‐, or L‐penicillamine (D‐, L‐PEN‐Alg) are used as new 3D scaffolds for cell adhesion studies. The cells recognize and show different adhesion properties in the respective 3D hydrogel scaffolds. C‐6‐glioma and endothelial cells show higher affinity to the D‐PEN than to the L‐PEN functionalized 3D alginate hydrogel scaffold. The cultivated cells are harvested from the hydrogel and are reused, for example, for cell growth experiments on 2D surfaces to prove their viability as well.
13th Latest Advances in Psychiatry: Biopsychosocial Approaches to Psychiatry
Authors: Laight Katherine
Published: February 2014

The 13th Latest Advances in Psychiatry Symposium, which will be held on the 12th March 2014 at the Royal College of Physicians in London, promises an impressive line‐up of speakers. Copyright © 2014 John Wiley & Sons
Optical selection rules and scattering processes in rocksalt wide band gap ZnO
Authors: Kunert H. W. , Govender M. , Machatine A. G. J. , Mwakikunga B. W. , Niyongabo P.
Published: February 2014

At sufficiently high pressures, wurtzite structure zinc oxide (W‐ZnO) can be transformed to the cubic rocksalt (R‐ZnO) structure. The R‐ZnO exhibits semiconductor behavior with an indirect wide band gap of . The maximum valence band is found far away from the center of the Brillouin zone (BZ) at high symmetry point L and line Σ, depending on the pressure. The unusual electronic band structure (EBS) of the R‐ZnO leads to several direct and indirect optical transitions which find applications in ultraviolet optoelectronic devices. We have investigated radiative and non‐radiative symmetry restricted selection rules, as well as inter‐ and intra‐valley scattering processes.
The ‘Democratisation’ of Statistics: Parastatisticians in Manufacturing
Authors: Sheil John , Hale Dermot
Published: February 2014

The statistics profession is faced with opportunities and challenges that arise from the widespread use of methodology and software, by non‐specialists. These practitioners, or so‐called ‘parastatisticians’, are generally isolated from the wider statistics community. Because of the widespread adoption of Six Sigma and an increasingly regulated marketplace, this phenomenon is particularly prevalent in the manufacturing sector.The paper discusses findings from a survey of parastatisticians in manufacturing, which was designed to quantify practice and attitudes in their companies, from their own perspectives. These findings are discussed in the context of a review of the literature pertaining to what the mainstream statistics profession sees as its future. It then goes on to suggest how the profession might go about supporting and creating linkages to this group of practitioners. Copyright © 2012 John Wiley & Sons, Ltd.
Statistical Methods in Kansei Engineering: a Case of Statistical Engineering
Authors: Marco‐Almagro Lluís , Tort‐Martorell Xavier
Published: February 2014

Kansei engineering (KE) is a methodology used to incorporate emotions in products and services design. Its basic purpose is discovering in which way some properties of a product or a service convey certain emotions in its users. Data are typically collected using questionnaires. KE studies follow a model with three main steps: (i) defining the elicited emotions (semantic space); (ii) deciding on the factors that might affect the responses (space of properties); and (iii) modeling how each factor affects each response (synthesis phase). The procedure resembles that of an experimental design in an industrial context. However, practitioners of KE are hardly ever statisticians. Statistical techniques in KE are sometimes misused, and the discipline could benefit from a more extensive use of statistical methods. KE is thus a good area of application of statistical engineering: focusing not in advancement of statistics but on how current techniques can be best used in a new area.

The aim of this paper is twofold: (i) to present the fundamentals of KE while giving an easy to understand example to illustrate the procedure; and (ii) to explain why KE is a good example of statistical engineering by proposing improvements that emanate from the adequate use of statistical techniques. Copyright © 2012 John Wiley & Sons, Ltd.
Improved Phase I Control Charts for Monitoring Times Between Events
Authors: Kumar N. , Chakraborti S.
Published: February 2014

In many situations, the times between certain events are observed and monitored instead of the number of events particularly when the events occur rarely. In this case, it is common to assume that the times between events follow an exponential distribution. Control charts are one of the main tools of statistical process control and monitoring. Control charts are used in phase I to assist operating personnel in bringing the process into a state of statistical control. In this paper, phase I control charts are considered for the observations from an exponential distribution with an unknown mean. A simulation study is carried out to compare the in‐control robustness and out‐of‐control performance of the proposed chart. It is seen that the proposed charts are considerably more in‐control robust than two competing charts and have comparable out‐of‐control properties. Copyright © 2014 John Wiley & Sons, Ltd.
Microfluidic Blood Cell Sorting: Now and Beyond
Authors: Yu Zeta Tak For , Aw Yong Koh Meng , Fu Jianping
Published: February 2014

Blood plays an important role in homeostatic regulation with each of its cellular components having important therapeutic and diagnostic uses. Therefore, separation and sorting of blood cells hasa been of a great interest to clinicians and researchers. However, while conventional methods of processing blood have been successful in generating relatively pure fractions, they are time consuming, labor intensive, and are not optimal for processing small volume blood samples. In recent years, microfluidics has garnered great interest from clinicians and researchers as a powerful technology for separating blood into different cell fractions. As microfluidics involves fluid manipulation at the microscale level, it has the potential for achieving high‐resolution separation and sorting of blood cells down to a single‐cell level, with an added benefit of integrating physical and biological methods for blood cell separation and analysis on the same single chip platform. This paper will first review the conventional methods of processing and sorting blood cells, followed by a discussion on how microfluidics is emerging as an efficient tool to rapidly change the field of blood cell sorting for blood‐based therapeutic and diagnostic applications.
Simplified finite element analyses for fire design of slabs including membrane action
Authors: Stadler Martin , Mensinger Martin
Published: February 2014

Simplifications to finite element models are the subject of this article. These simplifications form part of a new method for the fire design of concrete and composite slab systems with partly unprotected secondary steel beams, taking into account tensile membrane action. Internal forces can be determined with the simplified model and cross‐section design procedures can be applied to calculate the required reinforcement amount equivalent to ambient temperature. The FE model is simplified by replacing the thermal analysis with a substitute thermal loading. Non‐linear material behaviour is taken into account via a reduced model stiffness, which allows an efficient linear elastic calculation. The new method presented therefore enables the simple and efficient design of slab systems for fire.
Between geometry and craft: the setting‐out of the NiGRES Tower
Authors: Nozhova Ekaterina
Published: February 2014

In 1899 Vladimir Shuchov (1853–1939), the polymath Russian engineer, was awarded a patent covering the principles he had devised for hyperbolic lattice towers. These hyperbolic towers are constructed from an assembly of straight elements connected together with complex three‐dimensional joints. However, their full geometry is difficult to discern from the (orthogonal) drawings still available. Until now, little was known about the technological advances that made these complex designs feasible. This paper presents an investigation into the mathematical principles and operational practices that may have been used for determining the actual geometry of individual elements for setting out and constructing the metal lattices, thus illuminating the conjunction of geometry and craft.
Orthotropic steel bridges in Germany
Authors: Friedrich Heinz
Published: February 2014

This document describes the development and state of the art of orthotropic steel bridges in Germany. Following a short historical review of the performance of orthotropic bridge decks over the last decades, the present traffic loads are described and related to the resistance of the existing structures. Based on four different hazard categories, this paper describes different retrofitting methods. Although several promising strengthening techniques are introduced and evaluated, it appears that further research is urgently required in order to improve these techniques.
Engineering in a computational design environment – New Terminal 3 at Shenzhen Bao’an International Airport, China
Authors: Helbig Thorsten , Scheible Florian , Kamp Florian , Schieber Roman
Published: February 2014

Shenzhen Airport’s Terminal 3 is one of the largest buildings in the world designed with parametrically controlled digital tools. These tools enabled the teams from Fuksas and Knippers Helbig to develop the free‐form, perforated, double‐skin building envelope into which a space truss structure is integrated. The inherent optimization potential of the iterative process not only facilitated the geometrical definition of a large number of unique, non‐repetitive components, but also resulted in a successive performance improvement for the integrated structural system.

In a close collaboration with the architects, specific solutions were developed to provide sufficient structural integrity for the space structure, which is clad by the façade layers. These design interventions enable the mega‐structure to withstand all impacting loads, such as high winds and seismic loads, without disrupting the transparency of the architects’ intended honeycomb‐shaped perforations.

The design process of the new Terminal 3 clearly demonstrates how parametrically controlled design tools can offer the means to design new structures and envelopes that go beyond existing typologies.
Differential and linear insertion of atrioventricular valves: a useful tool?
Authors: Adriaanse B. M. E. , Bartelings M. M. , van Vugt J. M. G. , Chaoui R. , Gittenberger‐de Groot A. C. , Haak M. C.
Published: February 2014

Objective

The differential insertion of the atrioventricular valves is the ultrasonographic representation of the more apical attachment of the tricuspid valve to the septum with respect to the mitral valve. A linear insertion is present when both valves form a linear continuum and has been suggested as a marker for atrioventricular septal defects (AVSDs). The objective of this study was to evaluate the anatomical substratum of differential and linear insertions of the atrioventricular valves in normal fetal hearts and fetal hearts with an AVSD.

Methods

The extent and position of the fibrous skeleton and attachment of the atrioventricular valves to the septum were studied in histological sections of 17 normal hearts and four hearts with an AVSD from 10 + 0 weeks' gestation to 3 days postpartum with various immunohistochemical tissue markers. In addition, spatiotemporal image correlation (STIC) volumes of 10 normal hearts and STIC volumes of eight hearts with an AVSD at 13 + 6 to 35 + 5 weeks' gestation were examined.

Results

The differential insertion of the atrioventricular valves was visible in normal hearts in the four‐chamber plane immediately beneath the aorta, but nearer the diaphragm a linear insertion was found. In hearts with an AVSD, a linear appearance was observed in the four‐chamber plane immediately beneath the aorta. Towards the diaphragm, however, first a differential insertion and, more caudally, a linear insertion was found.

Conclusions

Both differential and linear insertions can be found in normal fetal hearts and fetal hearts with AVSD, depending on the plane in which the four‐chamber view is visualized. Therefore, measurement of the differential insertion is likely to be useful only in experienced hands. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.