bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Activity of Josamycin Against Aerobic Gram-Positive Cocci and Anaerobes
Authors: Westerman Eric L. , Williams Temple W. , Moreland Nedra
Published: June 2012

Josamycin, a new macrolide antibiotic, was compared with ampicillin, erythromycin, and clindamycin in vitro against 25 isolates each of pneumococci, enterococci,
Staphylococcus aureus, S. epidermidis
, and nonenterococcal hemolytic streptococci and against 25 anaerobes including 10
Bacteroides fragilis
. Minimal inhibitory concentration and minimal bactericidal concentration data were obtained for the aerobic organisms, using serial twofold tube dilutions in Mueller-Hinton broth. Minimal inhibitory concentrations were determined for the anaerobes by the agar dilution technique. Josamycin was comparable to erythromycin and clindamycin in activity against the pneumococci, streptococci, and staphylococci and was more active than clindamycin against enterococci. It was somewhat less active than ampicillin against enterococci and
S. epidermidis
and showed its greatest in vitro activity against anaerobes, being comparable to clindamycin.
Draft Genome Sequence of Pseudomonas syringae Pathovar Syringae Strain FF5, Causal Agent of Stem Tip Dieback Disease on Ornamental Pear
Authors: Sohn Kee Hoon , Jones Jonathan D. G. , Studholme David J.
Published: June 2012

Pseudomonas syringaeFF5 causes stem tip dieback disease on ornamental pear (Pyrus calleryana). Its genome encodes a complete type III secretion system (T3SS) and HopAC1, HopM1, AvrE1, HopI1, HopAA1, HopJ1, HopAH2, HopAH1, HopAG1, and HopAZ1. Lacking detectable homologues of other T3SS effectors, it may encode novel, undiscovered effectors.
Draft Genome Sequence of Pedobacter agri PB92
T
, Which Belongs to the Family Sphingobacteriaceae
Authors: Lee Myunglip , Roh Seong Woon , Lee Hae-Won , Yim Kyung June , Kim Kil-Nam , Bae Jin-Woo , Choi Kwang-Sik , Jeon You-Jin , Jung Won-Kyo , Kang Heewan , Hyun Chang-Gu , Kim Daekyung
Published: June 2012

Strain PB92
T
of
Pedobacter agri
, which belongs to the family
Sphingobacteriaceae
, was isolated from soil in the Republic of Korea. The draft genome of strain PB92
T
contains 5,141,552 bp, with a G+C content of 38.0%. This is the third genome sequencing project of the type strains among the
Pedobacter
species.
Draft Genome Sequence of Gillisia sp. Strain CBA3202, a Novel Member of the Genus Gillisia, Which Belongs to the Family Flavobacteriaceae
Authors: Nam Young-Do , Lee Hae-Won , Lee Myunglip , Yim Kyung June , Kim Kil-Nam , Roh Seong Woon , Kim Daekyung
Published: June 2012

Gillisia
sp. strain CBA3202, which belongs to the family
Flavobacteriaceae
, was isolated from sand of the seashore on Jeju Island, Republic of Korea. The draft genome of
Gillisia
sp. CBA3202 contains 2,981,404 bp with a G+C content of 34.9%. This is the second genome sequence of the
Gillisia
strains.
Genome Sequence of the Marine Bacterium Marinilabilia salmonicolor JCM 21150
T
Authors: Kumar Shailesh , Subramanian Srikrishna , Raghava Gajendra Pal Singh , Pinnaka Anil Kumar
Published: June 2012

We report the 4.98-Mb genome sequence of
Marinilabilia salmonicolor
JCM 21150
T
, which was isolated from marine mud in the year 1961. The draft genome of strain
Marinilabilia salmonicolor
JCM 21150
T
contains 4,982,627 bp with a G+C content of 41.92% and 4,227 protein coding genes, 52 tRNAs, and 3 rRNAs.
Draft Genome of Streptomyces tsukubaensis NRRL 18488, the Producer of the Clinically Important Immunosuppressant Tacrolimus (FK506)
Authors: Barreiro Carlos , Prieto Carlos , Sola-Landa Alberto , Solera Elena , Martínez-Castro Miriam , Pérez-Redondo Rosario , García-Estrada Carlos , Aparicio Jesús F. , Fernández-Martínez Lorena T. , Santos-Aberturas Javier , Salehi-Najafabadi Zahra , Rodríguez-García Antonio , Tauch Andreas , Martín Juan F.
Published: June 2012

The macrocyclic polyketide tacrolimus (FK506) is a potent immunosuppressant that prevents T-cell proliferation produced solely by
Streptomyces
species. We report here the first draft genome sequence of a true FK506 producer,
Streptomyces tsukubaensis
NRRL 18488, the first tacrolimus-producing strain that was isolated and that contains the full tacrolimus biosynthesis gene cluster.
Dose‐response investigation of oral ketoprofen in pigs challenged with Escherichia coli endotoxin
Authors: Mustonen K. , Banting A. , Raekallio M. , Heinonen M. , Peltoniemi O. A. T. , Vainio O.
Published: June 2012

In order to determine the effective dose, the effects of orally administered ketoprofen were evaluated in pigs following intravenous challenge with Escherichia coli endotoxin. One hour after the challenge, five groups of pigs were treated with either tap water or ketoprofen (0.5 mg/kg, 1 mg/kg, 2 mg/kg or 4 mg/kg). The body temperature was measured and a total clinical score was calculated after assessing the general behaviour, respiratory rate and locomotion of the pigs. Thromboxane B2 and ketoprofen concentrations were analysed from blood samples. Ketoprofen treatment significantly reduced the rectal temperature and total clinical scores, and lowered blood thromboxane B2 concentrations when compared with the control group. Ketoprofen plasma concentrations were lower than previously reported in healthy pigs after similar doses. The appropriate dose of orally administered ketoprofen in pigs in this model is 2 mg/kg, as the higher dose of 4 mg/kg failed to provide an additional benefit.
Gaseous CO2 signal initiates growth of butyric-acid-producing Clostridium butyricum in both pure culture and mixed cultures with Lactobacillus brevis
Authors: Hakalehto Elias , Hänninen Osmo
Published: June 2012

Microbial strains produce numerous volatile substances in the anaerobic conditions of the human intestines. The availability of CO2 is known to be a prerequisite for bacterial growth in general. In experiments with anaerobic Lactobacillus brevis and Clostridium butyricum bacteria in the Portable Microbial Enrichment Unit (PMEU) it was shown that these strains interact; this interaction being mediated by CO2 emission. CO2 promoted clostridial growth in pure cultures and mixed cultures with lactobacilli. The growth of C. butyricum in pure cultures was much delayed or did not start at all without CO2 from outside. Conversely, the onset of growth was provoked by a short (15 min) CO2 burst. In mixed cultures the presence of lactobacilli in equal numbers speeded up the onset of clostridial growth by 10 h. If C. butyricum cultures designated as PMEU 1, 2, and 3 in cultivation syringes were chained by connecting the gas flow thereby allowing the volatiles of the preceding syringe culture to bubble to the next one, the growth started in 20, 10, or 6 h, respectively. This effect of gaseous emissions from other cultures speeding up the bacterial growth initiation was abolished if the gas was passed through sodium hydroxide to remove the CO2. The positive contribution of lactobacilli to the growth of butyric-acid-producing clostridia documented in this simulation experiment with PMEU has in vivo implications and indicates molecular communication between the species. CO2 is a necessary signal for the growth of clostridia, and lactobacilli can promote clostridial growth in mixed cultures where both bacteria grow well with mutual benefit.
Characterization of the complete genome segments from BmCPV-SZ, a novelBombyx moricypovirus 1 isolate
Authors: Cao Guangli , Meng Xiangkun , Xue Renyu , Zhu Yuexiong , Zhang Xiaorong , Pan Zhonghua , Zheng Xiaojian , Gong Chengliang
Published: June 2012

A novel Bombyx mori cypovirus 1 isolated from infected silkworm larvae and tentatively assigned as Bombyx mori cypovirus 1 isolate Suzhou (BmCPV-SZ). The complete nucleotide sequences of genomic segments S1–S10 from BmCPV-SZ were determined. All segments possessed a single open reading frame; however, bioinformatic evidence suggested a short overlapping coding sequence in S1. Each BmCPV-SZ segment possessed the conserved terminal sequences AGUAA and GUUAGCC at the 5′ and 3′ ends, respectively. The conserved A/G at the –3 position in relation to the AUG codon could be found in the BmCPV-SZ genome, and it was postulated that this conserved A/G may be the most important nucleotide for efficient translation initiation in cypoviruses (CPVs). Examination of the putative amino acid sequences encoded by BmCPV-SZ revealed some characteristic motifs. Homology searches showed that viral structural proteins VP1, VP3, and VP4 had localized homologies with proteins of Rice ragged stunt virus , a member of the genus Oryzavirus within the family Reoviridae. A phylogenetic tree based on RNA-dependent RNA polymerase sequences demonstrated that CPV is more closely related to Rice ragged stunt virus and Aedes pseudoscutellaris reovirus than to other members of Reoviridae, suggesting that they may have originated from common ancestors.
SUPPORT VECTOR REGRESSION MODEL FOR DIRECT METHANOL FUEL CELL
Authors: TANG J. L. , CAI C. Z. , XIAO T. T. , HUANG S. J.
Published: June 2012

The purpose of this paper is to establish a direct methanol fuel cell (DMFC) prediction model by using the support vector regression (SVR) approach combined with particle swarm optimization (PSO) algorithm for its parameter selection. Two variables, cell temperature and cell current density were employed as input variables, cell voltage value of DMFC acted as output variable. Using leave-one-out cross-validation (LOOCV) test on 21 samples, the maximum absolute percentage error (APE) yields 5.66%, the mean absolute percentage error (MAPE) is only 0.93% and the correlation coefficient (R2) as high as 0.995. Compared with the result of artificial neural network (ANN) approach, it is shown that the modeling ability of SVR surpasses that of ANN. These suggest that SVR prediction model can be a good predictor to estimate the cell voltage for DMFC system.
ELECTRICAL POWER PREDICTION OF PROTON EXCHANGE MEMBRANE FUEL CELL BY USING SUPPORT VECTOR REGRESSION
Authors: TANG J. L. , CAI C. Z. , ZHAO S.
Published: June 2012

Studies have shown that numerous operating parameters affecting the proton exchange membrane fuel cell (PEMFC) performance, such as fuel cell operating temperature, operating pressure, anode/cathode humidification temperatures, anode/cathode stoichiometric flow ratios. In order to improve performance of fuel cell systems, it is advantageous to have an accurate model with which one can predict fuel cell behavior at different operating conditions. In this paper, a model using support vector regression (SVR) approach combining with particle swarm optimization (PSO) algorithm for its parameter optimization was developed to modeling and predicting the electrical power of proton exchange membrane fuel cell. The accuracy and reliability of the constructed support vector regression model are validated by leave-one-out cross-validation. Prediction results show that the maximum absolute percentage error does not exceed 5%, the mean absolute percentage error (MAPE) reached 0.68% and the correlation coefficient (R2) as high as 0.998. This implies that one can estimate an available combination of controller parameters by using support vector regression model to get suitable electrical power of proton exchange membrane fuel cell system.
REENTRANT BEHAVIOR IN LANDAU–FERMI LIQUIDS WITH SPIN-SPLIT POMERANCHUK INSTABILITIES
Authors: PONTE P. RODRÍGUEZ , CABRA D. C. , GRANDI N.
Published: June 2012

We study the effects of spin-antisymmetric interactions on the stability of a Landau–Fermi liquid on the square lattice, using the generalized Pomeranchuk method for two-dimensional lattice systems. In particular, we analyze interactions that could induce instabilities of the so-called spin-split type, that is when spin-up and spin-down Fermi surfaces are displaced with respect to each other. The phase space is studied as a function of the strength of the interaction V, the electron chemical potential μ and an external magnetic field h. We find that such interactions produce in general an enhancement of the instability region of the Landau–Fermi liquid. More interestingly, in certain regions of the V–μ phase space, we find a reentrant behavior as a function of the magnetic field h, similar to that found in recent experiments, e.g. in URu 2 Si 2 and Sr 3 Ru 2 O 7.
FINGERPRINT IMAGE SEGMENTATION USING DATA MANIFOLD CHARACTERISTIC FEATURES
Authors: PAIVA ANTÓNIO R. C. , TASDIZEN TOLGA
Published: June 2012

Automatic fingerprint identification systems (AFIS) have been studied extensively and are widely used for biometric identification. Given its importance, many well-engineered methods have been developed for the different stages that encompass those systems. The first stage of any such system is the segmentation of the actual fingerprint region from the background. This is typically achieved by classifying pixels, or blocks of pixels, based on a set of features. In this paper, we describe novel features for fingerprint segmentation that express the underlying manifold topology associated with image patches in a local neighborhood. It is shown that fingerprint patches seen in a high-dimensional space form a simple and highly regular circular manifold. The characterization of the manifold topology suggests a set of optimal features that characterize the local properties of the fingerprint. Thus, fingerprint segmentation can be formulated as a classification problem based on the deviation from the expected topology. This leads to features that are more robust to changes in contrast than mean, variance and coherence. The superior performance of the proposed features for fingerprint segmentation is shown in the eight datasets from the 2002 and 2004 Fingerprint Verification Competitions.
FROM SELF-SIMILAR STRUCTURES TO SELF-SIMILAR GROUPS
Authors: KELLEHER DANIEL J. , STEINHURST BENJAMIN A. , WONG CHUEN-MING M.
Published: June 2012

We explore the relationship between the limit spaces of contracting self-similar groups and self-similar structures. We give the condition on a contracting group such that its limit space admits a self-similar structure, and also the condition such that this self-similar structure is post-critically finite (p.c.f.). We then give necessary and sufficient conditions for a p.c.f. self-similar structure to be the limit space of a contracting self-similar group. When these conditions hold we give a construction of the contracting group. Finally, we illustrate our results with several examples.
A FUNCTIONAL DIFFERENTIAL EQUATION MODEL FOR BIOLOGICAL CELL SORTING DUE TO DIFFERENTIAL ADHESION
Authors: LEMON GREG , KING JOHN R.
Published: June 2012

This paper presents a mathematical model to describe the sorting of two different types of cells, arising from differential adhesion mechanisms within biological tissue. The model is based on a continuum approach that takes into account individual cell behavior including aspects of the cell-migration process, dynamics of the adhesions between contacting cells, and finite cell size. Numerical solutions and bifurcation analyses for the case of a collection of two different cell types show a variety of behaviors observed in experiments, including spatially uniform mixing of cells and the formation of two distinct, containing both types of cells or just one. The mathematical model, which is in the form of a set of functional differential equations, represents a novel approach to continuum modeling of cell sorting and migration within biological tissue.
MULTI-DIMENSIONAL SCALAR CONSERVATION LAWS WITH FLUXES DISCONTINUOUS IN THE UNKNOWN AND THE SPATIAL VARIABLE
Authors: BULÍČEK MIROSLAV , GWIAZDA PIOTR , ŚWIERCZEWSKA-GWIAZDA AGNIESZKA
Published: June 2012

The paper deals with a scalar conservation law in an arbitrary dimension d with a discontinuous flux. The flux is supposed to be a discontinuous function in the spatial variable x and in an unknown function u. Under some additional hypothesis on the structure of possible discontinuities, we formulate an appropriate notion of entropy solution and establish its existence and uniqueness. The framework for proving the existence and uniqueness of entropy weak solutions is provided by the studies on entropy measure-valued solutions and may be viewed as a corollary of the uniqueness theorem for entropy measure-valued solutions.
ON THE MODELING OF MIGRATION PHENOMENA ON SMALL NETWORKS
Authors: KNOPOFF D.
Published: June 2012

This paper deals with the modeling of migration phenomena in a small network of nations, with the aim of investigating the influence that the wealth and the welfare policies have on this phenomena. The modeling approach is based on the kinetic theory of active particles, while individuals over the network are distinguished by a scalar variable (the activity) which expresses their social state. The dynamics is induced both by the communication of individuals over the network and by the welfare policy within each nation, which is expressed in terms of competitive and altruistic interactions. The evolution of the discrete probability distribution over the social state is described by a system of nonlinear ordinary differential equations. The existence and uniqueness of the solution is discussed and some specific case-studies are proposed in order to carry out simulations and to investigate the emerging behaviors.
EDGE-BIPANCYCLICITY OF HYPERCUBES WITH CONDITIONAL FAULTS
Authors: SUN CHAO-MING
Published: June 2012

In this paper, we consider the conditionally faulty graphs G that each vertex of G is incident with at least m fault-free edges, 2 ≤ m ≤ n - 1. We extend the limitation m ≥ 2 in all previous results of edge-bipancyclicity with faulty edges and faulty vertices. Let fe (respectively, fv) denotes the number of faulty edges (respectively, faulty vertices) in an n-dimensional hypercube Qn. For all m, we show that every fault-free edge of Qn lies on a fault-free cycle of every even length from 4 to |V| - 2fv inclusive provided fe + fv ≤ n - 2. This result is not only optimal, but also improves on the previously best known results reported in the literature.
DESIGN OF ROBUST DISTRIBUTION NETWORKS RUN BY THIRD PARTY LOGISTICS SERVICE PROVIDERS
Authors: HENDRIKS M. P. M. , ARMBRUSTER D. , LAUMANNS M. , LEFEBER E. , UDDING J. T.
Published: June 2012

We consider a third party logistics service provider (LSP), who faces the problem of distributing different products from suppliers to consumers having no control on supply and demand. In a third party set-up, the operations of transport and storage are run as a black box for a fixed price. Thus the incentive for an LSP is to reduce its operational costs. The objective of this paper is to find an efficient network topology on a tactical level, which still satisfies the service level agreements on the operational level. We develop an optimization method, which constructs a tactical network topology based on the operational decisions resulting from a given model predictive control (MPC) policy. Experiments suggest that such a topology typically requires only a small fraction of all possible links. As expected, the found topology is sensitive to changes in supply and demand averages. Interestingly, the found topology appears to be robust to changes in second order moments of supply and demand distributions.
TUTORIAL ON DE NOVO PEPTIDE SEQUENCING USING MS/MS MASS SPECTROMETRY
Authors: CHONG KET FAH , LEONG HON WAI
Published: June 2012

This paper is a self-contained introductory tutorial on the problem in proteomics known as peptide sequencing using tandem mass spectrometry. This tutorial deals specifically with de novo sequencing methods (as opposed to database search methods). We first give an introduction to peptide sequencing, its importance and history and some background on proteins. Next we show the relationship between a peptide and the final spectrum produced from a tandem mass spectrometer, together with a description of the various sources of complications that arise during the process of generating the mass spectrum. From there we model the computational problem of de novo peptide sequencing, which is basically the reverse problem of identifying the peptide which produced the spectrum. We then present several major approaches to solve it (including reviewing some of the current algorithms in each approach), and also discuss related problems and post-processing approaches.
Early History and Challenges of Implantable Electronics
Authors: Ko Wen H.
Published: June 2012

Implantable systems for biomedical research and clinical care are now a flourishing field of activities in academia as well as industrial institutions. The broad field includes experimental explorations in electronics, mechanical, chemical, and biological components and systems, and the combination of all these. Today virtually all implants involve both electronic circuits and micro-electro-mechanical-systems (MEMS). This article offers a very brief glance back at the early history of implant electronics in the period from the 1950s to the 1970s, by employing selected examples from the author’s research. This short review also discusses the challenges of implantable electronics at present, and suggests some potentially important trends in the future research and development of implantable microsystems. It is aimed as an introduction of implantable/attached electronic systems to research engineers that are interested in implantable systems as a section of Biomedical Instrumentations.
Nonvolatile Memories as the Data Storage System for Implantable ECG Recorder
Authors: Sun Zhenyu , Chen Xiang , Zhang Yaojun , Li Hai , Chen Yiran
Published: June 2012

In this article, we propose a data storage system with the emerging nonvolatile memory technologies used for the implantable electrocardiography (ECG) recorder. The proposed storage system can record the digitalized real-time ECG waveforms continuously inside the implantable device and export the stored data to external reader periodically to obtain a long-term backup. Spin transfer torque random access memory (STT-RAM) and spintronic memristor are selected as the storage elements for their nonvolatility, high density, high reliability, low power consumption, good scalability, and CMOS technology compatibility. The new read and write schemes of STT-RAM and spintronic memristors are presented and optimized to fit the specific application scenario. The tradeoffs among data accuracy, chip area, and read/write energy for the different technologies are thoroughly analyzed and compared. Our simulation results show the configuration with a data sampling rate (e.g., 128 Hz) and a quantization resolution (e.g., 12 bits) can record 18-hour real-time data within ~ 3.6-mm
2
chip area when the data storage is built with single-level cell (SLC) STT-RAMs. Daily energy consumption is 5.46 mJ. Utilizing the multilevel cell (MLC) STT-RAMs or the spintronic memristors as the storage elements can further reduce the chip area and decrease energy dissipation.
Wegener's Granulomatosis with Extensive Bone Abnormalities Mimicking Fungal Sinusitis
Authors: Kodama Satoru , Nomi Nozomi , Suzuki Masashi
Published: June 2012

Abnormalities of the underlying bone of the paranasal sinuses have sometimes been shown in Wegener’s granulomatosis (WG). We describe an interesting case of WG with extensive bone abnormalities in the sinuses mimicking fungal sinusitis. A 30-year-old woman presented with intermittent unilateral epistaxis. Biopsy was performed for the granulation tissue in the right nasal cavity, and she was diagnosed as having WG. Computed tomography (CT) revealed a ring-like calcification, mimicking a fungus ball, in the right maxillary sinus. Endoscopic sinus surgery was performed to confirm the diagnosis. A spherical bony structure, surrounded by granulation tissue, was identified in the maxillary sinus. The wall of the “bony ball” was fragile, like an egg shell. No fungus was found in the sinus. Thus, the extensive bone abnormalities were due to WG.
Developing a Dynamic Microsimulation Model of the Australian Health System: A Means to Explore Impacts of Obesity over the Next 50 Years
Authors: Lymer Sharyn , Brown Laurie
Published: June 2012

Health of the ageing population has the potential to place considerable pressure on future government spending. Further, the impacts of the obesity epidemic have the potential to place additional pressure on government health budgets. In response to such fiscal concerns in Australia, a dynamic microsimulation model, APPSIM, has been developed at the National Centre for Social and Economic Modelling (NATSEM). The health module was developed to allow consideration of health behaviours within the context of an ageing population and the resultant health profile of the population. Also included in the modelling is the associated use of health services and their costs. All health variables used were imputed onto the 2001 basefile derived from the 1 percent unit record file of the 2001 Australian census. Transition equations of these variables were estimated to allow projections over time. In this paper, the model has been used to look at the impacts of obesity on the Australian population health profile and associated health expenditure. In the scenario, removal of obesity from the population leads to a simulated population with a better health profile but showed only marginal changes in relative health expenditure.
PCR Amplification and Transcription for Site-Specific Labeling of Large RNA Molecules by a Two-Unnatural-Base-Pair System
Authors: Kimoto Michiko , Yamashige Rie , Yokoyama Shigeyuki , Hirao Ichiro
Published: June 2012

For the site-specific labeling and modification of RNA by genetic alphabet expansion, we developed a PCR and transcription system using two hydrophobic unnatural base pairs: 7-(2-thienyl)-imidazo[4,5-b]pyridine (Ds) and 2-nitro-4-propynylpyrrole (Px) as a third pair for PCR amplification andDsand pyrrole-2-carbaldehyde (Pa) for the incorporation of functional components as modifiedPabases into RNA by T7 transcription. To prepareDs-containing DNA templates with long chains, theDs-Pxpair was utilized in a fusion PCR method, by which we demonstrated the synthesis of 282-bp DNA templates containingDsat specific positions. Using theseDs-containing DNA templates and a biotin-linkedPasubstrate (Biotin-PaTP) as a modifiedPabase, 260-mer RNA transcripts containing Biotin-Paat a specific position were generated by T7 RNA polymerase. This two-unnatural-base-pair system, combining theDs-PxandDs-Papairs with modifiedPasubstrates, provides a powerful tool for the site-specific labeling and modification of desired positions in large RNA molecules.
Particle Size Effect on TL Emission of ZnS Nanoparticles and Determination of Its Kinetic Parameters
Authors: Singh L. Robindro , Singh S. Dorendrajit
Published: June 2012

Nanoparticles have large surface area, and most of the ions are lying on its surface. Could these surface ions be contributed in thermoluminescence emission or enhanced nonradiative transition? In view of this, we have prepared small sizes of ZnS nanoparticles at low temperature and made two samples, one as‐prepared (size ~3 nm) and the other heat‐treated at 1073 K (size ~32 nm). Characterization of the samples shows that the prepared phosphors are pure. Thermoluminescence (TL) glow curves could not be recorded in both samples without irradiation. Even for higher dose of γ‐radiation the as‐prepared samples could not show TL signal, but 1073 K heat‐treated sample shows the TL signal. This may be due to the fact that smaller particles have large surface area compared to bigger particles, the surface ions may produce the nonradiative transitions. The kinetic parameters of the TL glow curves are evaluated by the conventional methods and compared with curve fitting computerised glow curve deconvolution (CGCD) technique. The variations in both techniques are found only ±0.02. The shape factor of all the glow curves ~0.48, and these TL glow curves could be fitted with order of kinetics 1.5.
Risk-Adaptive Volumetric Modulated Arc Therapy Using Biological Objective Functions for Subvolume Boosting in Radiotherapy
Authors: Hardcastle Nicholas , Tome Wolfgang A.
Published: June 2012

Objectives. Simultaneous integrated boost (SIB) for prostate cancer allows increases in tumor control probability while respecting normal tissue dose constraints. Biological optimization functions that optimize based on treatment outcome can be used to create SIB prostate plans. This study investigates the feasibility of biologically optimized volumetric modulated arc therapy (VMAT) for SIB prostate radiotherapy.Methods. Five prostate cancer patients with diffusion-weighted MR images were selected for analysis. A two-step VMAT optimization was performed, which consisted of an initial biological optimization of a static gantry angle delivery followed by conversion of the static delivery to a single arc VMAT plan. A dosimetric analysis was performed on the resulting plans.Results. The VMAT plans resulted in a ΔEUD between the prostate and the boost volume of between 15.1 Gy and 20.3 Gy. Rectal volumes receiving 75.6 Gy ranged from 4.5 to 9.9%. Expected rectal normal tissue complication probabilities were between 8.6% and 21.4%. Maximum bladder doses ranged from 73.6 Gy to 75.8 Gy. Estimated treatment time was 120 s or less.Conclusions. The presented biological optimization method resulted in deliverable VMAT plans that achieved sufficient modulation for SIB without violating rectal and bladder dose constraints.Advances in knowledge. This study presents a method for creating simultaneous integrated boost VMAT treatments using biological outcome objective functions.
Observed Human Actions, and Not Mechanical Actions, Induce Searching Errors in Infants
Authors: Moriguchi Yusuke , Matsunaka Reiko , Itakura Shoji , Hiraki Kazuo
Published: June 2012

Recent neurophysiological studies have shown that several human brain regions involved in executing actions are activated by merely observing such actions via a human, and not by a mechanical hand. At a behavioral level, observing a human’s movements, but not those of a robot, significantly interferes with ongoing executed movements. However, it is unclear whether the biological tuning in the observation/execution matching system are functional during infancy. The present study examines whether a human’s actions, and not a mechanical action, influence infants’ execution of the same actions due to the observation/execution matching system. Twelve-month-old infants were given a searching task. In the tasks, infants observed an object hidden at location A, after which either a human hand (human condition) or a mechanical one (mechanical condition) searched the object correctly. Next, the object was hidden at location B and infants were allowed to search the object. We examined whether infants searched the object at location B correctly. The results revealed that infants in the human condition were more likely to search location A than those in the mechanical condition. Moreover, the results suggested that infants’ searching behaviors were affected by their observations of the same actions by a human, but not a mechanical hand. Thus, it may be concluded that the observation/execution matching system may be biologically tuned during infancy.
Visual and Chemical Prey Cues as Complementary Predator Attractants in a Tropical Stream Fish Assemblage
Authors: Elvidge Chris K. , Brown Grant E.
Published: June 2012

To date, little attention has been devoted to possible complementary effects of multiple forms of public information similar information on the foraging behaviour of predators. In order to examine how predators may incorporate multiple information sources, we conducted a series of predator attraction trials in the Lower Aripo River, Trinidad. Four combinations of visual (present or absent) and chemical cues (present or absent) from each of two prey species were presented. The occurrences of three locally abundant predatory species present within a 1 m radius of cue introduction sites were recorded. The relative attractiveness of cue type to each predator was directly related to their primary foraging modes, with visual ambush predators demonstrating an attraction to visual cues, benthivores to chemical cues, and active social foragers demonstrating complementary responses to paired cues. Predator species-pair counts were greatest in response to cues from the more abundant prey species, indicating that individuals may adopt riskier foraging strategies when presented with more familiar prey cues. These differences in predator attraction patterns demonstrate complementary effects of multiple sensory cues on the short-term habitat use and foraging behaviour of predators under fully natural conditions.
What They Want and What They Get: Self-Reported Motives, Perceived Competence, and Relatedness in Adolescent Leisure Activities
Authors: Leversen Ingrid , Danielsen Anne G. , Wold Bente , Samdal Oddrun
Published: June 2012

This study explored the extent to which adolescents’ motives for leisure activity participation are related to their perceptions of competence and relatedness in different kinds of activities and aimed to provide new insight into boys’ and girls’ leisure experiences and their motivational orientations for activity participation. These proposed associations were based on previous empirical work and the theoretical frameworks of motive disposition approach and were tested in a nationally representative sample of Norwegian adolescents (N=3273) aged 15 and 16 years (51.8% boys) from the World Health Organization’s cross-sectional survey, Health Behaviour in School-Aged Children 2005/06. The findings in the current study supported the hypothesis regarding matched correlations between specific motives and specific outcomes in that the adolescents seem to get (perceived competence and relatedness) what they want (competence and social motives) within leisure activities. Furthermore, the analysis using structural equation modeling indicated different motivational orientations in types of leisure activity participation between girls and boys, although the mediating effects of leisure activity participation in different types of activities were not significant.
Impairment and Differential Expression of PR3 and MPO on Peripheral Myelomonocytic Cells with Endothelial Properties in Granulomatosis with Polyangiitis
Authors: Patschan Susann , Patschan Daniel , Henze Elvira , Blaschke Sabine , Wessels Johannes T. , Müller Gerhard Anton
Published: June 2012

Background. Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune-mediated diseases characterized by vasculitic inflammation of respiratory tract and kidneys. Clinical observations indicated a strong association between disease activity and serum levels of certain types of autoantibodies (antineutrophil cytoplasm antibodies with cytoplasmic [cANCA in GPA] or perinuclear [pAN CA in MPA] immunofluorescence). Pathologically, both diseases are characterized by severe microvascular endothelial cell damage. Early endothelial outgrowth cells (eEOCs) have been shown to be critically involved in neovascularization under both physiological and pathological condition.Objectives. The principal aims of our study were (i) to analyze the regenerative activity of the eEOC system and (ii) to determine mPR3 and MPO expression in myelo monocytic cells with endothelial characteristics in GPA and MPA patients.Methods. In 27 GPA and 10 MPA patients, regenerative activity blood-derived eEOCs were analyzed using a culture-forming assay. Flk-1+, CD133+/Flk-1+, mPR3+, and Flk-1+/mPR3+myelomonocytic cells were quantified by FACS analysis. Serum levels of Angiopoietin-1 and TNF-αwere measured by ELISA.Results. We found reduced eEOC regeneration, accompanied by lower serum levels of Angiopoietin-1 in GPA patients as compared to healthy controls. In addition, the total numbers of Flk-1+myelomonocytic cells in the peripheral circulation were decreased. Membrane PR3 expression was significantly higher in total as well as in Flk-1+myelomonocytic cells. Expression of MPO was not different between the groups.Conclusions. These data suggest impairment of the eEOC system and a possible role for PR3 in this process in patients suffering from GPA.
Endothelin-1 and Norepinephrine Overflow from Cardiac Sympathetic Nerve Endings in Myocardial Ischemia
Authors: Tawa Masashi , Yamamoto Satoshi , Ohkita Mamoru , Matsumura Yasuo
Published: June 2012

In protracted myocardial ischemia, sympathetic activation with carrier-mediated excessive norepinephrine (NE) release from its nerve endings due to reversal of NE transporter in an outward direction is a prominent cause of arrhythmias and cardiac dysfunction. Endothelin-1 (ET-1) and its receptors are intimately involved in the regulation of this carrier-mediated NE overflow in protracted myocardial ischemia. The ET-1 system is often complex, sometimes involving opposing actions depending on which receptor subtype is activated, which cells are affected, and whether stimuli are endogenously generated or exogenously applied. Therefore, a detailed understanding of the ET-1 system is important for applying drugs acting on this system in clinical settings for the treatment of ischemic cardiac disease. This article provides a detailed analysis of how the ET-1 system is involved in the regulation of carrier-mediated NE release from sympathetic nerve endings in protracted myocardial ischemia.
The Dopamine Receptor D4 Gene 7-Repeat Allele Interacts with Parenting Quality to Predict Effortful Control in Four-Year-Old Children
Authors: Sheese Brad E. , Rothbart Mary K. , Voelker Pascale M. , Posner Michael I.
Published: June 2012

The dopamine receptor D4 gene (DRD4) 7-repeat allele has been found to interact with environmental factors such as parenting in children and peer attitudes in adults to influence aspects of behavior such as risk taking. We previously found that in toddlers, lower-quality parenting in combination with the 7-repeat allele of the DRD4 gene was associated with greater parent-reported Sensation Seeking (SS), but was unrelated to Effortful Control (EC). We now report findings from a followup assessment with the same sample of children showing that parenting quality interacts with the presence of the 7-repeat allele to predict EC in 3- to 4-year-old children. The change in these patterns of results may reflect the increased role of the executive attention network in older children and adults. However, due to the small sample size (N=52) and the novelty of the results, these findings should be treated with caution and considered preliminary until they are replicated in an independent sample.
P1-12-07: Pharmacokinetics (PK) of Trastuzumab Emtansine and Paclitaxel or Docetaxel in Patients with HER2−Positive MBC Previously Treated with a Trastuzumab-Containing Regimen.
Authors: Lu D , Modi S , Elias AD , Agarwal P , Yi J-H , Guardino AE , Althaus BL , Girish S
Published: June 2012

Background: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab, DM1 (a potent cytotoxic tubulin polymerization inhibitor), and the stable MCC linker. Based on in vitro and preclinical data suggesting synergy in tumor cell cytotoxicity with T-DM1 + taxanes, these combinations are being tested in phase Ib studies. The assessment of risk for PK-based drug interaction (PK-DI) with these combinations is important. T-DM1 is expected to undergo proteolytic degradation with no significant involvement of cytochrome P450 isoenzymes (CYPs), and DM1 is metabolized mainly by CYP3A4 (and to a lesser extent by CYP3A5). Paclitaxel (P) and docetaxel (D) are metabolized primarily by CYP2C8 and CYP3A4, respectively. None of these drugs inhibits or induces CYPs at clinically relevant concentrations. Since DM1 and D are both metabolized by CYP3A4, PK-DI may occur. This is less likely with DM1 and P since they are primarily metabolized by different CYPs.

Methods: The tolerability, PK, and dose-limiting toxicities of T-DM1 + P or D were investigated in 2 studies (TDM4652g and BP22572) of patients with HER2−positive MBC previously treated with a trastuzumab-containing regimen. For PK-DI analysis, both studies used a staggered dosing design in the first cycle, with same-day dosing in subsequent cycles. Study BP22572 was later amended to give both drugs on the same day in all cycles. Either P (65 mg/m2, n=11; 80 mg/m2, n=6) or D (60 mg/m2, n=12; 75 mg/m2, n=6) was combined with T-DM1 at various doses (2 mg/kg or 2.4 mg/kg q3w or 1.2 mg/kg qw for TDM4652g; 2.4 mg/kg or 3.6 mg/kg q3w for BP22572). PK of T-DM1, total trastuzumab (conjugated + unconjugated trastuzumab), DM1, P, and D were evaluated and compared with historical singleagent data and across cycles within the study, using population analysis and/or noncompartmental analysis (NCA), as data allowed. Preliminary safety and efficacy data for the historical T-DM1 singleagent studies were reported previously (Krop JCO 2010; Burris JCO 2010; Krop ESMO 2010).

Results: The PK of P and D were similar from cycle 1 to cycle 2 for maximum concentration (Cmax), area under the concentration-time curve, halflife, clearance (CL) and steady-state volume of distribution, and were also similar to historical single-agent data. The Cmax of DM1 was <8 ng/mL in both studies, and the average Cmax values were similar to historical single-agent data. T-DM1 PK parameters for the combination studies are within the range of historical single-agent data (Table). Data from additional patients and doses in the combination studies will be presented.

Conclusion: The risk of clinically relevant PK-DI between T-DM1 and P or D appears to be low.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-07.
P2-17-09: A Prospective Assessment of Loss of Grip Strength by Baseline BMI in Breast Cancer Patients Receiving Adjuvant Aromatase Inhibitors or Tamoxifen.
Authors: Lintermans A , Dieudonné A-S , Vanderhaegen J , Henry NL , Laenen A , Wildiers H , Paridaens R , Christiaens M-R , Smeets A , Leunen K , Amant F , Vergote I , Neven P
Published: June 2012

Background The 3rd generation aromatase inhibitors (AIs) induce or enhance musculoskeletal problems. Underlying mechanisms are probably multiple, but remain unknown. We have previously reported that loss of grip strength together with tenosynovial abnormalities are more important in AI- than in tamoxifen-users (Morales et al, JCO 2008) and that musculoskeletal changes in AI-users are more pronounced in women with extremes in baseline BMI (Lintermans et al, Ann Oncol 2011) We here report preliminary results from a larger population and plan to validate findings in patients from University of Michigan.

Patients and methods In this prospective observational study, postmenopausal early breast cancer patients scheduled to start adjuvant hormonal therapy with any of the third generation AIs or tamoxifen were recruited. After providing informed consent, a functional assessment test of grip strength was performed with a modified sphygmomanometer. Re-evaluation was done after 3, 6 and 12 months of therapy. BMI and waist to hip ratio (WHR) were assessed and a rheumatological questionnaire was completed at each visit.

Results Ninety-four (79 AI; 15 tamoxifen) of the planned 200 patients were included in this preliminary study. 18% of AI-users discontinued their treatment due to musculoskeletal symptoms compared with none of the tamoxifen-users. 62% of patients on AI and 35% of tamoxifen patients complained of new or worsened joint pain. Table 1 shows the proportion of patients that attribute their complaints to their endocrine therapy. Grip strength significantly decreased over time (p=0.03), with patients under AI treatment having a larger loss of grip strength than patients under tamoxifen treatment (p=0.04). We confirm our previously reported results on the shape of the curve “BMI AI-induced loss of grip strength”. Years past menopause and age showed a significant effect on grip strength (p<0.001 and p=0.0007, respectively), whereas no significant relationship was found between WHR with grip strength or joint pain. Detailed results will be presented.

Conclusion Our preliminary results confirm that a majority of patients treated with an AI experience musculoskeletal problems, which are considered due to the therapy by most patients. Grip strength decreased over time, with a significantly larger loss of grip strength in the AI-users compared with the tamoxifen-users. AI-induced loss of grip strength and baseline BMI showed an inverted U-shaped association, although differences between quartiles were small. Further results should be awaited as this is only a preliminary analysis.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-17-09.
P3-16-17: The Identification of Novel Microtubule Stabilizing Taccalonolides.
Authors: Risinger AL , Li J , Peng J , Chen Z , Mooberry SL
Published: June 2012

Microtubule stabilizing agents, including the taxanes and epothilones, are some of the most important drugs used in the treatment of cancer. All of the microtubule stabilizers used clinically bind within the taxane site on microtubules and work through a similar mechanism of action. We have identified a new class of microtubule stabilizers, the taccalonolides, from plants of the genus Tacca. The most abundant taccalonolides, A and E, are classified as microtubule stabilizers due to their ability to disrupt both interphase and mitotic cellular microtubules, leading to mitotic arrest and apoptosis. However, they are unique from all other microtubule stabilizers in that they do not bind directly to microtubules or stimulate the polymerization of tubulin in biochemical preparations. The taccalonolide structure is characterized by a highly acetylated pentacyclic steroidal skeleton, which is also structurally distinct from all other microtubule targeted agents. The unique structure and mechanism of action of the taccalonolides, together with their ability to circumvent clinically relevant forms of taxane resistance, prompted our efforts to explore the structure-activity relationship of this class of molecules. We have isolated several novel taccalonolides, designated Z, AA, AB, AC, AF and AG, as well as multiple known taccalonolides. Each of these taccalonolides exhibited cellular microtubule stabilizing activity and antiproliferative actions against breast cancer cells. However, profound differences in potencies were noted with IC50 values ranging from 32 nM to 13 μM. These studies demonstrate that microtubule stabilizing activity is a shared trait among this class of molecules and that significant structure-activity relationships exist. Additionally, in vivo antitumor evaluations of taccalonolides A, E and N demonstrate that each of these molecules has activity in vivo and that taccalonolide A is the most effective against a syngeneic mammary model of breast cancer.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-17.