bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of human lactoferrin in animal milk1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Goldman I.L. , Georgieva S.G. , Gurskiy Ya.G. , Krasnov A.N. , Deykin A.V. , Popov A.N. , Ermolkevich T.G. , Budzevich A.I. , Chernousov A.D. , Sadchikova E.R.
Published: May 2012

Genetic constructs containing the human lactoferrin (hLf) gene were created within a joint program of Russian and Belorussian scientists. Using these constructs, transgenic mice were bred (the maximum hLf concentration in their milk was 160 g/L), and transgenic goats were also generated (up to 10 g/L hLf in their milk). Experimental goatherds that produced hLf in their milk were also bred, and the recombinant hLf was found to be identical to the natural protein in its physical and chemical properties. These properties included electrophoretic mobility, isoelectric point, recognition by polyclonal and monoclonal antibodies, circular dichroic spectra, interaction with natural ligands (DNA, lipopolysaccharides, and heparin), the binding of iron ions, the sequence of the 7 terminal amino acids, and its biological activity. The latter was assessed by the agglutination of Micrococcus luteus protoplasts, bactericidal activity against Escherichia coli and Listeria monocytogenes , and fungicidal activity against Candida albicans . We also demonstrated a significant increase in the activity of antibiotics when used in combination with Lf.
Lactoferrin: an alternative view of its role in human biological fluids1This article is part of a Special Issue entitled Lactoferrin and has undergone the Journal's usual peer review process.
Authors: Alexander David B. , Iigo Masaaki , Yamauchi Koji , Suzui Masumi , Tsuda Hiroyuki
Published: May 2012

Lactoferrin is a major component of biologically important mucosal fluids and of the specific granules of neutrophils. Understanding its biological function is essential for understanding neutrophil- and mucosal-mediated immunity. In this review, we reevaluate the in vivo functions of human lactoferrin (hLF) emphasizing in vivo studies and in vitro studies performed in biologically relevant fluids. We discuss the evidence in the literature that supports (or does not support) proposed roles for hLF in mucosal immunity and in neutrophil function. We argue that the current literature supports a microbiostatic role, but not a microbicidal role, for hLF in vivo. The literature also supports a role for hLF in inhibiting colonization and infection of epithelial surfaces by microorganisms and in protecting tissues from neutrophil-mediated damage. Using this information, we briefly discuss hLF in the context of the complex biological fluids in which it is found.
GENERALIZED POINT INTERACTION AND TUNNELING TIMES
Authors: KOČINAC S. Lj. S. , MILANOVIĆ V.
Published: May 2012

The scattering properties of four-parameter one-dimensional point interactions also define time aspect of these interactions. In this paper we investigate how different families of point interactions affect the relevant tunneling times. Particular emphasis is given to various interpretations of so called δ' potential.
LIGHTNING IMPULSE BREAKDOWN CHARACTERISTICS AND ELECTRODYNAMIC PROCESS OF INSULATING VEGETABLE OIL-BASED NANOFLUID
Authors: LI JIAN , ZHANG ZHAO-TAO , ZOU PING , DU BIN , LIAO RUI-JIN
Published: May 2012

Insulating vegetable oils are considered environment-friendly and fire-resistant substitutes for insulating mineral oils. This paper presents the lightning impulse breakdown characteristic of insulating vegetable oil and insulating vegetable oil-based nanofluids. It indicates that Fe 3 O 4 nanoparticles can increase the negative lightning impulse breakdown voltages of insulating vegetable oil by 11.8% and positive lightning impulse breakdown voltages by 37.4%. The propagation velocity of streamer is reduced by the presence of nanoparticles. The propagation velocities of streamer to positive and negative lightning impulse breakdown in the insulating vegetable oil-based nanofluids are 21.2% and 14.4% lesser than those in insulating vegetable oils, respectively. The higher electrical breakdown strength and lower streamer velocity is explained by the charging dynamics of nanoparticles in insulating vegetable oil. Space charge build-up and space charge distorted filed in point-sphere gap is also described. The field strength is reduced at the streamer tip due to the low mobility of negative nanoparticles.
NUMERICAL STUDY OF OHMIC-SCHOTTKY CARBON NANOTUBE FIELD EFFECT TRANSISTOR
Authors: YOUSEFI REZA , GHOREYSHI SEYED SALEH
Published: May 2012

MOS-like transistors are one of the transistor topologies based on the carbon nanotubes. Some modified structures have been proposed to improve their electrical characteristics, such as band to band tunneling (BTBT) and switching behavior. Unfortunately, most of them increase the transistor length due to the use of additional regions. In this paper, we propose a structure that improves the OFF state and switching behavior of the transistor without increase in the transistor length. The proposed structure is constructed by a modification of the conventional structure in a way that its drain high-doped extension part is replaced by a lightly linear doped region. Then, the proposed structure has a Schottky contact at the drain side. With a nonequilibrium Green's function (NEGF) formalism, we have studied the characteristics of the proposed device and compared them with those obtained by a conventional structure with the same channel length. The results show that the proposed structure enjoys from better switching characteristics and OFF-state behavior, especially at low currents, in comparison to the main structure and, as a result, can be a good candidate for the low-power applications.
BAYESIAN NETWORK REVISION WITH PROBABILISTIC CONSTRAINTS
Authors: PENG YUN , DING ZHONGLI , ZHANG SHENYONG , PAN RONG
Published: May 2012

This paper deals with an important probabilistic knowledge integration problem: revising a Bayesian network (BN) to satisfy a set of probability constraints representing new or more specific knowledge. We propose to solve this problem by adopting IPFP (iterative proportional fitting procedure) to BN. The resulting algorithm E-IPFP integrates the constraints by only changing the conditional probability tables (CPT) of the given BN while preserving the network structure; and the probability distribution of the revised BN is as close as possible to that of the original BN. Two variations of E-IPFP are also proposed: 1) E-IPFP-SMOOTH which deals with the situation where the probabilistic constraints are inconsistent with each other or with the network structure of the given BN; and 2) D-IPFP which reduces the computational cost by decomposing a global E-IPFP into a set of smaller local E-IPFP problems.
ADAPTIVE FUZZY-BASED TRACKING CONTROL FOR A CLASS OF STRICT-FEEDBACK SISO NONLINEAR TIME-DELAY SYSTEMS WITHOUT BACKSTEPPING
Authors: YOUSEF HASAN A. , HAMDY MOHAMED , SHAFIQ MUHAMMAD
Published: May 2012

In this paper, an adaptive fuzzy tracking control is presented for a class of SISO nonlinear strict feedback systems with unknown time delays. The proposed algorithm does not use the backstepping scheme rather it converts the strict-feedback time-delayed system to the normal form. The Mamdani-type fuzzy system is employed to approximate on-line the lumped uncertain system nonlinearity. The developed controller guarantees uniform ultimate boundedness of all signals in the closed-loop system. The designed control law is independent of the time delays and has a simple form with only one adaptive parameter vector needed to be updated on-line. As a result, the proposed control algorithm is considerably simpler than the previous ones based on backstepping. The Lyapunov stability of the fuzzy system parameters and the filtered tracking error is employed to guarantee semiglobal uniform boundedness for the closed loop system. Simulation results are presented to verify the effectiveness of the proposed approach.
A GOAL PROGRAMMING APPROACH TO GROUP DECISION MAKING WITH INCOMPLETE FUZZY AND INTERVAL PREFERENCE RELATIONS
Authors: JIANG JIANG , LI XUAN , CHEN YINGWU , TANG DAWEI
Published: May 2012

In order to solve group decision making (GDM) problems where the preference relations are provided by decision makers with incomplete fuzzy and interval numbers, this paper develops a GDM approach on the basis of multiple objective optimization and goal programming methods. The proposed approach first analyzes the two types of preference relations and then builds their respective optimization models. Subsequently, an integrated programming model combining the two preference relations is developed to minimize the inconsistency among the decision makers' opinions. By solving the programming model, the ranking of alternatives or selection of the most desirable alternative can be obtained using the intermediate priority vector. Two numerical examples including incomplete fuzzy and interval preference relations are examined to illustrate and show the applicability of the proposed approach.
FEATURE SELECTION AND GRANULARITY LEARNING IN GENETIC FUZZY RULE-BASED CLASSIFICATION SYSTEMS FOR HIGHLY IMBALANCED DATA-SETS
Authors: VILLAR PEDRO , FERNÁNDEZ ALBERTO , CARRASCO RAMÓN A. , HERRERA FRANCISCO
Published: May 2012

This paper proposes a Genetic Algorithm for jointly performing a feature selection and granularity learning for Fuzzy Rule-Based Classification Systems in the scenario of highly imbalanced data-sets. We refer to imbalanced data-sets when the class distribution is not uniform, a situation that it is present in many real application areas. The aim of this work is to get more compact models by selecting the adequate variables and adapting the number of fuzzy labels for each problem, improving the interpretability of the model. The experimental analysis is carried out over a wide range of highly imbalanced data-sets and uses the statistical tests suggested in the specialized literature.
A STOCK MODEL WITH JUMPS FOR UNCERTAIN MARKETS
Authors: YU XICHANG
Published: May 2012

Uncertain differential equation with jumps is a type of differential equation driven by two classes of uncertain processes, namely canonical process and renewal process. Based on uncertain differential equation with jumps, this paper proposes a stock model with jumps for uncertain financial markets. Furthermore, the European call and put option pricing formulas for the stock model are formulated and some mathematical properties of them are studied. Finally, some generalized uncertain stock models with jumps are discussed.
ON SIMILARITY, INCLUSION MEASURE AND ENTROPY BETWEEN TYPE-2 FUZZY SETS
Authors: HWANG CHAO-MING , YANG MIIN-SHEN , HUNG WEN-LIANG
Published: May 2012

In this paper, new similarity, inclusion measure and entropy between type-2 fuzzy sets corresponding to grades of memberships are proposed. We also create the relationships among these measures between type-2 fuzzy sets. Several examples are used to present the calculation of these similarity, inclusion measure and entropy between type-2 fuzzy sets. The comparison results show that the proposed similarity measure presents better than those of Hung and Yang (2004) and Yang and Lin (2009). Moreover, measuring the similarity between type-2 fuzzy sets is important in clustering. We also use the proposed similarity measure as a clustering method for type-2 fuzzy sets.
A NEW RULE-BASED SIR APPROACH TO SUPPLIER SELECTION UNDER INTUITIONISTIC FUZZY ENVIRONMENTS
Authors: CHAI JUNYI , LIU JAMES N.K. , XU ZESHUI
Published: May 2012

Multiple Criteria Decision Making (MCDM) aims at giving people a knowledge recommendation concerning a set of objects evaluated from multiple preference-ordered attributes. The Superiority and Inferiority Ranking (SIR) is a generation of the well-known outranking approach-PROMETHEE, which is an efficient approach for MCDM. As the traditional MCDM approach, however, it faces the obstacle in handling uncertainties of real world. We are concerned about the issue on how to extend the traditional MCDM approach for applications in uncertain environments. This paper proposes a new Intuitionistic Fuzzy SIR (IF-SIR for short) approach and focuses on its application to supplier selection which is the important activity in supply chain management. Toward practical applications, two factors are considered here: (1) multiple decision makers and (2) decision information in the form of linguistic terms. We firstly identify these terms via Intuitionistic Fuzzy Set (IFS) which is proven to be a powerful mathematical tool in modeling uncertain information. Then, we provide the IF-SIR approach for group aggregation and decision analysis. Hereinto, a rule-based method is developed for ranking and selection of suppliers. Finally, an illustrative example is used for illustration of the proposed approach.
MICRO-FABRICATION PROCESS FOR AN INTEGRATED BIOSENSOR COMPOSED OF A SPR TRANSDUCER COUPLED TO A MICROCALORIMETRIC SENSOR
Authors: BÉLAND REMY , CHARETTE PAUL G. , AIMEZ VINCENT , CLOAREC JEAN-PIERRE , SOUTEYRAND ELIANE , CHEVOLOT YANN
Published: May 2012

Integrated biosensors with several types of transducers are complex to manufacture. This paper presents the fabrication process for a bimodal biosensor by using silicon microfabrication process. The device is composed of a surface plasmons resonance (SPR) transducer and a microcalorimetric device. The fabrication process has a yield in our academic foundry. The device was functionalized with a simple BSA-biotin adsorption. SPR sensing performance was assessed by neutravidin binding to immobilized biotins.
ELECTRICAL CHARACTERIZATION OF PLANAR SILICON NANOWIRE FIELD-EFFECT TRANSISTORS
Authors: ROSAZ G. , SALEM B. , PAUC N. , GENTILE P. , POTIÉ A. , SOLANKI A. , BASSANI F. , BARON T. , CAGNON L.
Published: May 2012

Silicon nanowires (Si NWs) are promising candidates for field-effect transistor (FET) conduction channel. Planar configuration using a back gate is an easy way to study these devices. We demonstrate the possibility to build high performance FET using a simple silicidation process leading to high effective holes' mobility between 130 cm2⋅V-1⋅s-1 and 200 cm2⋅V-1⋅s-1 and good ION/IOFF ratio up to 105. Moreover we investigated the possibility to passivate the NWs using either a high-k dielectric layer or a thermal oxide shell around the NWs. This leads to a reduction of the hysteretic behavior during the gate voltage sweep from 30 V to 1 V depending on the material and the gate configuration.
IMPACT OF THE AMBIENT HUMIDITY ON THE KINETICS OF FORMATION OF FERROELECTRIC DOMAINS IN MONOCRYSTALLINE LiTaO3
Authors: GAUTIER BRICE , BRUGÈRE ANTOINE , GIDON SERGE
Published: May 2012

In this communication, we study the role of the water layer present on the surface of a ferroelectric layer during the growth of ferroelectric domains in a single crystal of congruent LiTaO 3, by comparing results from atomic force microscopes operating in controlled atmosphere and in air. The overall kinetics of growth of domains is clearly slower under low relative humidity (RH), which suggests that the water layer present at the surface of the ferroelectric film plays an active role in the propagation of the domains. A finite element model is proposed in order to explain the differences, where the electric potential can propagate beyond the area of the tip in a conductive top layer adsorbed on the ferroelectric sample, this propagation being responsible for the switching of the polarization when the field is locally larger than the coercive field. According to this model, which describes fairly well the experimental observations, the growth of the domain can be described not only by a thermally activated process, but also using a purely electrical model, which strongly depends on the electrical properties of the layer covering the ferroelectric material.
THROUGH SILICON VIAS INTEGRABLE WITH THIN-FILM PIEZOELECTRIC STRUCTURES
Authors: MIRSHEKARI GHOLAMREZA , BROUILLETTE MARTIN , FRÉCHETTE LUC G.
Published: May 2012

This paper reports on the design and microfabrication of novel through silicon vias (TSV) that are compatible with high-temperature processing of piezoelectric structures. The present approach uses metal deposition in cavities etched in the SOI handle layer of the wafer and electrically isolated islands in the device layer. This design avoids the shortcomings of previous TSV designs, which either introduce large topologies on the wafer surface, include metals that cannot sustain high-temperature processing or use poor electrical insulators. TSVs microfabricated using this new approach exhibit good performance, specifically small resistance between the front and backside metal pads, isolation from the ground plane and small capacitance between the vias and the ground. These TSVs are eminently suitable for devices requiring high-temperature processing, such as thin-film piezoelectric sensors and actuators.
SELF-ASSEMBLY ARCHITECTURES OF NEW DNA-BASED STRUCTURES IN AIR AND IN LIQUIDS ANALYZED BY ATOMIC FORCE MICROSCOPY
Authors: IAZYKOV M. , SICARD D. , CHEVOLOT Y. , SOUTEYRAND E. , PHANER-GOUTORBE M. , SKRYSHEVSKY V. A. , POURCEAU G. , VASSEUR J. J. , MORVAN F.
Published: May 2012

The architecture of self assembled X shaped DNA structure was studied by AFM on mica. The dimensions and extent of self assembled structures were influenced by mica surface treatment and depended on whether observations were performed in air or in Tris buffer solution. A molecular model is proposed.
CHARACTERIZATION OF A SURFACE-CHARGE MODULATION ELECTROFLUIDIC TRANSISTOR BY HYDRODYNAMIC MEASUREMENTS
Authors: LAFFITE GUILLAUME , ZHENG XU , RENAUD LOUIS , BESSUEILLE FRANÇOIS , CHARLAIX ELISABETH , KLEIMANN PASCAL
Published: May 2012

We present an experimental study on the electrofluidic transistor in this paper. A novel and easy way to integrate the transistor into a microchannel is developed. The performances of the insulating layer, especially the leakage current under gate voltage, are carefully characterized. The change of surface charge on silica surface by gate polarization is measured, however, by measuring the streaming current, the gating effect on zeta potential has not been observed. This result should imply new assumption in the understanding of the charge regulation in the electrical double layer under gate polarization.
THE DS/AHP METHOD UNDER PARTIAL INFORMATION ABOUT CRITERIA AND ALTERNATIVES BY SEVERAL LEVELS OF CRITERIA
Authors: UTKIN LEV V. , SIMANOVA NATALIA V.
Published: May 2012

An extension of the DS/AHP method is proposed in the paper. It takes into account the fact that the multi-criteria decision problem might have several levels of criteria. Moreover, it is assumed that expert judgments concerning the criteria are imprecise and incomplete. The proposed extension also uses groups of experts or decision makers for comparing decision alternatives and criteria. However, it does not require assigning favorability values for groups of decision alternatives and criteria. The computation procedure for processing and aggregating the incomplete information about criteria and decision alternatives is reduced to solving a finite set of linear programming problems. Numerical examples explain in detail and illustrate the proposed approach.
INTERACTIVE ROBUST CONE CONTRACTION METHOD FOR MULTIPLE OBJECTIVE OPTIMIZATION PROBLEMS
Authors: KADZIŃSKI MIŁOSZ , SŁOWIŃSKI ROMAN
Published: May 2012

We introduce a new interactive procedure for multiple objective optimization problems. The identification of the most preferred solution is achieved by means of a systematic dialogue with the decision maker (DM) during which (s)he specifies pairwise comparisons of nondominated solutions from a current sample. We represent this preference information by a compatible form of the achievement scalarizing function, i.e., we are searching for weights of objectives which ensure that the reference solutions are compared by the function in the same way as by the DM. Directions of the isoquants of all compatible achievement scalarizing functions create a cone in the evaluation space, with the origin in a reference point. In successive iterations, each new pairwise comparison of solutions contracts the cone which is zooming on a subregion of nondominated points of greatest interest for the DM. The procedure ends when at least one satisfactory solution is selected or when the DM comes to conclusion that there is no such solution for the current problem setting.
MACBETH
Authors: BANA E COSTA CARLOS A. , DE CORTE JEAN-MARIE , VANSNICK JEAN-CLAUDE
Published: May 2012

This paper presents an up-to-date comprehensive overview of the MACBETH approach to multicriteria decision-aid. It requires only qualitative judgements about differences of attractiveness to help a decision maker, or a decision-advisory group, quantify the relative value of options. The approach, based on the additive value model, aims to support interactive learning about evaluation problems and the elaboration of recommendations to prioritize and select options in individual or group decision making processes. A case study based on a real-world application of MACBETH for multicriteria value measurement of IT solutions is presented. It shows how the M-MACBETH decision support system can be used in practice to construct an additive evaluation model. The paper addresses key issues related to structuring the model, building value scales, weighting criteria and sensitivity and robustness analyzes. Reference is also made to applications of MACBETH reported in the scientific literature.
KNOWLEDGE INTEGRATION IN COLLABORATIVE INNOVATION AND A SELF-ORGANIZING MODEL
Authors: WANG ZHONGTUO
Published: May 2012

The collaborative innovation of industry, academia, and government is an effective way to enhance the innovative task and Triple helix approach can be used for its investigation. Bilateral relations can be expanded into triadic relationships and the complex dynamic process will produce a wide range of possible evolutionary trajectories. The essential feature of innovation is knowledge integration and creation. From different dimensions the knowledge will be integrated at knowledge-flow level and organizational level. In this paper, a self-organizing model of knowledge integration in collaborative innovation and its working processes including the nucleation and autopoiesis processes are introduced. Problem about degree of knowledge integration in collaborative innovation is discussed and a new comprehensive categorization method is suggested. Finally a case study is described.
EMPOWER MCDM BY HABITUAL DOMAINS TO SOLVE CHALLENGING PROBLEMS IN CHANGEABLE SPACES
Authors: CHEN YEN-CHU , HUANG HUNG-SHUN , YU PO-LUNG
Published: May 2012

Challenging decision problems in changeable spaces are characterized by existence of complex decision parameters that are changing with time and situations, including criteria and alternatives. Some of these parameters may be critical for their effective solutions, but hidden in the depth of potential domains. In this rapidly changing world, including technology and attitude, without paying attention to the problems in changeable spaces, we could easily commit serious mistakes due to decision blinds, decision traps and/or decision shocks. The article starts with a brief description of the evolution of MCDM toward challenging problems in changeable spaces. Then it briefly sketches a dynamic human behavior mechanism and habitual domain theory which provide an effective list for us to search relevant decision parameters and pave the way for latter discussion. Competence set analysis, derived from habitual domain, is then introduced to exemplify decision blinds, decision traps and decision shocks in challenging decision problems. Checking lists and methods for discovering blinds and traps and for dealing with shocks are also provided. Innovation dynamics, a systematic network of thoughts, is introduced to further look out relevant key parameters in dynamic challenging problems. The related academic subjects in each link of the innovation dynamics are also explained, which allow us to see the complexity and interconnectivities among different challenging problems in changeable spaces. Finally we introduce three habitual domain tool boxes to empower ourselves to expand and enrich our thoughts into the depth of the potential domains of the challenging problems, which allows us to more effectively identify hidden parameters, problems and competence sets to reduce decision blinds, avoid decision traps and solve the problems, or dissolve the problems before they occur.
DATABASE KEYWORD SEARCH: BEYOND ITS CURRENT LANDSCAPE
Authors: CHEN ZHENGXIN
Published: May 2012

As an active research field, database keyword search (KWS) has put much emphasis on the performance issues, due to its high computational cost. However, a closer examination on KWS reveals that there are some other interesting aspects worth noting. In this paper, we examine KWS from a broader perspective, analyzing its profound implications. Freed from syntax-related considerations, KWS users now have better opportunities to explore the data in the way as they wish, and such exploration may reveal useful hindsight for understanding the hidden nature of the data, thus benefiting the exploitation on the use of the data. In particular, we examine the potential of KWS to data mining from the behavior mining perspective. This examination also leads us to a discussion of viewing KWS in the "web of life" context. We further discuss connections of KWS with other related concepts, including dataspace. Based on our findings and critical examination, we also provide a brief overview of an integrated environment which facilitates the interplay of KWS and data mining.
MULTIPLE CRITERIA DECISION SUPPORT SYSTEM FOR ASSESSMENT OF PROJECTS MANAGERS IN CONSTRUCTION
Authors: ZAVADSKAS EDMUNDAS KAZIMIERAS , VAINIŪNAS POVILAS , TURSKIS ZENONAS , TAMOŠAITIENĖ JOLANTA
Published: May 2012

Construction processes planning and effective management are extremely important for success in construction business. Head of a design must be well experienced in initiating, planning, and executing of construction projects. Therefore, proper assessment of design projects' managers is a vital part of construction process. The paper deals with an effective methodology that might serve as a decision support aid in assessing project managers. Project managers' different characteristics are considered to be more or less important for the effective management of the project. Qualifying of managers is based on laws in force and sustainability of project management involving determination of attributes value and weights by applying analytic hierarchy process (AHP) and expert judgement methods. For managers' assessment and decision supporting is used additive ratio assessment method (ARAS). The model, presented in this study, shows that the three different methods combined (ARAS method aggregated together with the AHP method and the expert judgement method) is an effective tool for multiple criteria decision aiding. As a tool for the assessment of the developed model, was developed multiple criteria decision support system (MCDSS) weighting and assessment of ratios (WEAR) software. The solution results show that the created model, selected methods and MCDSS WEAR can be applied in practice as an effective decision aid.
Development and Characterization of a Novel CD19CherryLuciferase (CD19CL) Transgenic Mouse for the Preclinical Study of B-Cell Lymphomas
Authors: Scotto Luigi , Kruithof-de Julio Marianna , Paoluzzi Luca , Kalac Matko , Marchi Enrica , Buitrago Jairo Baquero , Amengual Jennifer , Shen Michael M. , O'Connor Owen A.
Published: May 2012

Purpose: To generate a transgenic mouse that when crossed with spontaneous mouse models of lymphoma will allow for quantitative in vivo measurement of tumor burden over the entire spectrum of the disease and or response to therapy in a “disease” or lymphoma subtype-specific manner.

Experimental Design: We developed a novel genetically engineered transgenic mouse using a CherryLuciferase fusion gene targeted to the CD19 locus to achieve B-cell–restricted fluorescent bioluminescent emission in transgenic mouse models of living mice. The use of a dual function protein enables one to link the in vivo analysis via bioluminescence imaging to cell discriminating ex vivo analyses via fluorescence emission.

Results: The spatiotemporal tracking of B-cell lymphoma growth and the response of an established B-cell lymphoma to a drug known to induce remission was evaluated in a double transgenic animal obtained by crossing the CD19CherryLuciferase transgenic mouse to a mouse model of an aggressive B-cell lymphoma. The observations validated the use of the CD19CherryLuciferase transgenic mouse in the assessment of an active drug routinely used in the treatment of lymphoproliferative malignancies.

Conclusions: The transgenic mouse described here is the first of its kind, intended to be used to hasten translational studies of novel agents in lymphoma, with the intent that understanding the relevant pharmacology before clinical study will accelerate successful development in clinical studies. Clin Cancer Res; 18(14); 3803–11. ©2012 AACR.
Serum Sex Steroids Depict a Nonlinear U-Shaped Association with High-Risk Prostate Cancer at Radical Prostatectomy
Authors: Salonia Andrea , Abdollah Firas , Capitanio Umberto , Suardi Nazareno , Briganti Alberto , Gallina Andrea , Colombo Renzo , Ferrari Matteo , Castagna Giulia , Rigatti Patrizio , Montorsi Francesco
Published: May 2012

Purpose: To assess the association between preoperative serum total testosterone (tT), 17β-estradiol (E2), sex hormone–binding globulin (SHBG), and tT–E2 ratio values with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network practice guidelines) at radical prostatectomy.

Experimental Design: Serum E2, tT, and SHBG were dosed the day before surgery (7:00–11:00 am) in a cohort of 724 candidates to radical prostatectomy. Restricted cubic spline functions tested the association between predictors (i.e., model 1: age, body mass index, and serum tT, E2, and SHBG levels; model 2: tT–E2 values instead of tT and E2 levels) and high-risk prostate cancer.

Results: Low-, intermediate-, or high-risk prostate cancer was found in 251 (34.7%), 318 (43.9%), and 155 (21.4%) patients, respectively. Patients in the high-risk class showed the lowest tT, E2, and tT–E2 ratio values (all P ≤ 0.02). At univariate analysis, only age, tT, E2, and tT–E2 ratio values were significantly associated with high-risk prostate cancer (all P ≤ 0.006). At multivariate analyses considering model 1 variables, age (P = 0.03), serum tT (all P < 0.001), and E2 (all P ≤ 0.01) were associated with high-risk prostate cancer; only tT–E2 ratios achieved independent predictor status for high-risk prostate cancer (all P < 0.001) when considering model 2. Both the lowest and the highest tT, E2, and tT–E2 values depicted a nonlinear U-shaped significant association with high-risk prostate cancer.

Conclusions: These data showed that preoperative serum sex steroids are independent predictors of high-risk prostate cancer, depicting a nonlinear U-shaped association. Clin Cancer Res; 18(13); 3648–57. ©2012 AACR.
Rupture of the Device Landing Zone During Transcatheter Aortic Valve Implantation
Authors: Pasic Miralem , Unbehaun Axel , Dreysse Stephan , Buz Semih , Drews Thorsten , Kukucka Marian , D'Ancona Giuseppe , Seifert Burkhardt , Hetzer Roland
Published: May 2012

Background—

Iatrogenic damage of different structures of the aortic root, in the region of the so-called “device landing zone,” may occur during transcatheter aortic valve implantation (TAVI). It is mostly considered difficult to treat or even untreatable.

Methods and Results—

We performed a retrospective analysis of the occurrence, clinical presentation, treatment, and outcome of iatrogenic rupture in the device landing zone in a series of 618 consecutive patients who underwent TAVI at our institution between April 2008 and October 2011. The incidence of rupture was 1% (6 patients). The correct diagnosis was established during TAVI procedures in 4 and postmortem in 2 patients. The major sign of the aortic rupture was apparent bleeding in 4 patients and failure of myocardial recovery after valve implantation in 1; it was asymptomatic in 1 patient. The iatrogenic rupture in the region of the device landing zone was treated surgically in 5 patients and only conservatively in the patient without symptoms. When the diagnosis was established correctly during TAVI, only 1 of 4 patients died (25%). The overall mortality rate was 50% (3 of 6 patients died).

Conclusions—

Rupture of different structures in the device landing zone during TAVI is a life-threatening complication that can be treated successfully if it is immediately recognized and adequately managed.
Prevalence and the Long-term Coronary Risks of Patients With Kawasaki Disease in a General Population <40 Years
Authors: Wu Mei-Hwan , Chen Hui-Chi , Yeh Shu-Jen , Lin Min-Tai , Huang Shin-Chung , Huang San-Kuei
Published: May 2012

Background—

Patients with Kawasaki disease (kDa) may develop coronary arterial lesions and subsequent coronary events. The first reported case in Taiwan was in 1976, and the annual incidence from 2003 to 2006 was 69/100 000 children < 5 years. A population study from Taiwan, a country with a high incidence of kDa, national health insurance, and easily accessible medical care, would adequately reflect the long-term risk.

Methods and Results—

We retrieved the data of kDa patients from a national health insurance 2000 to 2010 database of Taiwan, a country with a child health index similar to those in the United States. The occurrence of coronary complications and interventions was identified by the respective
International Classification of Diseases, Ninth Revision,
codes. The prevalence of kDa in the population < 40 years was 34.9/100 000 (male/female ratio, 1.47). Coronary complications occurred in 1254 patients (5.37%; male/female ratio, 2.19), with an average annual risk of 2.4% (2.7% for males and 2.0% for females). An acute myocardial infarction occurred in 19 patients (0.08%; 18 males and 1 female), of whom one third were aged between 10 and 15 years (median, 15.7 years; range, 0.7–36.7 years). A coronary intervention was performed by catheterization in 18 patients (all males) at a median age of 24.5 years and by surgery in 10 patients (male/female ratio, 4.0) at a median age of 21.7 years, with mortality at discharge being 0% and 25%, respectively.

Conclusions—

This study estimated the overall prevalence of kDa (≈1/2940) in a population < 40 years. They, particularly the males, carry long-term coronary risks from a young age. Risk stratification for a timely coronary intervention and risk modification are mandatory.
Racial and Ethnic Differences in Wait-List Outcomes in Patients Listed for Heart Transplantation in the United States
Authors: Singh Tajinder P. , Almond Christopher S. , Taylor David O. , Milliren Carly E. , Graham Dionne A.
Published: May 2012

Background—

Racial differences in long-term survival after heart transplant (HT) are well known. We sought to assess racial/ethnic differences in wait-list outcomes among patients listed for HT in the United States in the current era.

Methods and Results—

We compared wait-list and posttransplant in-hospital mortality among white, black, and Hispanic patients ≥18 years of age listed for their primary HT in the United States between July 2006 and September 2010. Of 10 377 patients analyzed, 71% were white, 21% were black, and 8% were Hispanic. Black and Hispanic patients were more likely to be listed with higher urgency (listing status 1A/1B) in comparison with white patients (
P
<0.001). Overall, 10.5% of white, 11.6% of black, and 13.4% of Hispanic candidates died on the wait-list or became too sick for a transplant within 1 year of listing. After adjusting for baseline risk factors, Hispanic patients were at higher risk of wait-list mortality (hazard ratio 1.51, 95% CI 1.23, 1.85) in comparison with white patients, but not black patients (hazard ratio 1.13, 95% CI 0.97, 1.31). In comparison with white HT recipients, posttransplant in-hospital mortality was higher in black recipients (odds ratio 1.53, 95% CI 1.15, 2.03) but was not different in Hispanic recipients (odds ratio 0.78, 95% CI 0.48, 1.29).

Conclusions—

Hispanic patients listed for HT in the United States appear to be at higher risk of dying on the wait-list or becoming too sick for a transplant in comparison with white patients. Black patients are not at higher risk of wait-list mortality, but they have higher early posttransplant mortality.
Upregulation of Cyclooxygenase-2 (COX-2) and Microsomal Prostaglandin E
2
Synthase-1 (mPGES-1) in Wall of Ruptured Human Cerebral Aneurysms
Authors: Hasan David , Hashimoto Tomoki , Kung David , Macdonald R. Loch , Winn H. Richard , Heistad Donald
Published: May 2012

Background and Purpose—

Cyclooxygenase-2 (COX-2) and Microsomal Prostaglandin E
2
Synthase-1 (mPGES-1) catalyze isomerization of the cyclooxygenase product PGH
2
into PGE
2
. Deletion of COX-2/mPGES-1 suppresses carotid artery atherogenesis and angiotensin II-induced aortic aneurysms formation, and attenuates neointimal hyperplasia after vascular injury in mice. The upregulation of COX-2/mPGES-1 in the wall of ruptured human cerebral aneurysms is not known.

Methods—

Ten patients with intracranial aneurysms (5 ruptured and 5 nonruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for COX-1, COX-2, and mPGES-1. A segment of the superficial temporal artery was also removed and immunostained with monoclonal antibodies for COX-1, COX-2, and mPGES-1.

Results—

All 10 aneurysm tissues stained positive for mPGES-1 monoclonal antibody. Expression of mPGES-1 was more abundant in ruptured aneurysm tissue than in nonruptured aneurysms, based on a semiquantitative grading. None of the superficial temporal artery specimens expressed mPGES-1. COX-2 was upregulated in the same distribution as was mPGES-1. COX-1 was present constitutively in all tissues.

Conclusions—

COX-2/mPGES-1 are expressed in the wall of human cerebral aneurysms and more abundantly so in ruptured aneurysms than in nonruptured. We speculate that the protective effect of aspirin against rupture of cerebral aneurysms may be mediated in part by inhibition of COX-2/mPGES-1.
Differentiation of Transverse Sinus Thrombosis From Congenitally Atretic Cerebral Transverse Sinus With CT
Authors: Chik Yolanda , Gottesman Rebecca F. , Zeiler Steven R. , Rosenberg Jason , Llinas Rafael H.
Published: May 2012

Background and Purpose—

Transverse sinus thrombosis can have nonspecific clinical and radiographic signs. We hypothesized that the novel “sigmoid notch sign” (on head CT) can help differentiate transverse sinus thrombosis from a congenitally atretic sinus among individuals with absent signal in 1 transverse sinus by MR venography.

Methods—

We retrospectively evaluated 53 subjects with a unilaterally absent transverse sinus signal on MR venography. Eleven had true transverse sinus thrombosis and 42 had an atretic transverse sinus. Reviewers were trained in the sigmoid notch sign: “positive” if 1 of the sigmoid notches was asymmetrically smaller than the other, consistent with a congenitally absent transverse sinus on that side. This sign was scored on CT scans by 2 blinded reviewers to determine if signal dropout was clot or atretic sinus. A consensus rating was reached when the reviewers disagreed. Characteristics of the sigmoid notch sign as a diagnostic test were compared with a gold standard of full chart review by an independent reviewer.

Results—

Each reviewer had a sensitivity of 91% (detecting 10 of 11 clots based on a negative sigmoid notch sign) and specificity of 71% to 81%; consensus specificity increased to 86% (36 of 42 individuals with an atretic sinus had a positive notch sign, detecting atretic sinuses based on presence of the sign).

Conclusion—

Asymmetries of the sigmoid notches on noncontrast brain CT is a very sensitive and specific measure of differentiating transverse sinus thrombosis from an atretic transverse sinus when absence of transverse sinus flow is visualized on MR venography.
Interannual Variations of Wind Regimes off the Subtropical Western Australia Coast during Austral Winter and Spring
Authors: Weller Evan , Feng Ming , Hendon Harry , Ma Jian , Xie Shang-Ping , Caputi Nick
Published: May 2012

Off the Western Australia coast, interannual variations of wind regime during the austral winter and spring are significantly correlated with the Indian Ocean dipole (IOD) and the southern annular mode (SAM) variability. Atmospheric general circulation model experiments forced by an idealized IOD sea surface temperature anomaly field suggest that the IOD-generated deep atmospheric convection anomalies trigger a Rossby wave train in the upper troposphere that propagates into the southern extratropics and induces positive geopotential height anomalies over southern Australia, independent of the SAM. The positive geopotential height anomalies extended from the upper troposphere to the surface, south of the Australian continent, resulting in easterly wind anomalies off the Western Australia coast and a reduction of the high-frequency synoptic storm events that deliver the majority of southwest Australia rainfall during austral winter and spring. In the marine environment, the wind anomalies and reduction of storm events may hamper the western rock lobster recruitment process.
Mean Climate Controls on the Simulated Response of ENSO to Increasing Greenhouse Gases
Authors: DiNezio Pedro N. , Kirtman Ben P. , Clement Amy C. , Lee Sang-Ki , Vecchi Gabriel A. , Wittenberg Andrew
Published: May 2012

Climate model experiments are analyzed to elucidate if and how the changes in mean climate in response to doubling of atmospheric CO2 (2xCO2) influence ENSO. The processes involved the development, transition, and decay of simulated ENSO events are quantified through a multimodel heat budget analysis. The simulated changes in ENSO amplitude in response to 2xCO2 are directly related to changes in the anomalous ocean heat flux convergence during the development, transition, and decay of ENSO events. The weakening of the Walker circulation and the increased thermal stratification, both robust features of the mean climate response to 2xCO2, play opposing roles in ENSO–mean climate interactions. Weaker upwelling in response to a weaker Walker circulation drives a reduction in thermocline-driven ocean heat flux convergence (i.e., thermocline feedback) and, thus, reduces the ENSO amplitude. Conversely, a stronger zonal subsurface temperature gradient, associated with the increased thermal stratification, drives an increase in zonal-current-induced ocean heat flux convergence (i.e., zonal advection feedback) and, thus, increases the ENSO amplitude. These opposing processes explain the lack of model agreement in whether ENSO is going to weaken or strengthen in response to increasing greenhouse gases, but also why ENSO appears to be relatively insensitive to 2xCO2 in most models.
Energetics of the Tropical Atlantic Zonal Mode
Authors: Burls N. J. , Reason C. J. C , Penven P. , Philander S. G.
Published: May 2012

Sea surface temperature in the central-eastern equatorial Atlantic has a seasonal cycle far bigger than that of the Pacific, but interannual anomalies smaller than those of the Pacific. Given the amplitude of seasonal SST variability, one wonders whether the seasonal cycle in the Atlantic is so dominant that it is able to strongly influence the evolution of its interannual variability. In this study, interannual upper-ocean variability within the tropical Atlantic is viewed from an energetics perspective, and the role of ocean dynamics, in particular the role of ocean memory, within zonal mode events is investigated. Unlike in the Pacific where seasonal and interannual variability involve distinctly different processes, the results suggest that the latter is a modulation of the former in the Atlantic, whose seasonal cycle has similarities with El Niño and La Niña in the Pacific. The ocean memory mechanism associated with the zonal mode appears to operate on much shorter time scales than that associated with the El Niño–Southern Oscillation, largely being associated with interannual modulations of a seasonally active delayed negative feedback response. Differences between the El Niño–Southern Oscillation and the zonal mode can then be accounted for in terms of these distinctions. Anomalous wind power over the tropical Atlantic is shown to be a potential predictor for zonal mode events. However, because zonal mode events are due to a modulation of seasonally active coupled processes, and not independent processes operating on interannual time scales as seen in the Pacific, the lead time of this potential predictability is limited.
Nested Mesoscale Large-Eddy Simulations with WRF: Performance in Real Test Cases
Authors: Talbot Charles , Bou-Zeid Elie , Smith Jim
Published: May 2012

This paper assesses the performance of the Weather Research and Forecasting Model (WRF) as a tool for multiscale atmospheric simulations. Tests are performed in real and idealized cases with multiple configurations and with resolutions ranging from the mesoscale (gridcell size ~10 km) for the real cases to local scales (gridcell size ~50 m) for both real and idealized cases. All idealized simulations and the finest real-case simulations use the turbulence-resolving large-eddy simulation mode of WRF (WRF-LES). Tests in neutral conditions and with idealized forcing are first performed to assess the model’s sensitivity to grid resolutions and subgrid-scale parameterizations and to optimize the setup of the real cases. An increase in horizontal model resolution is found to be more beneficial than an increase in vertical resolution. WRF-LES is then tested, using extensive observational data, in real-world cases over complex terrain through nested simulations in which the mesoscale domains drive the LES domains. Analysis of the mesoscale simulations indicates that the data needed to force the largest simulated domain and to initialize surface parameters have the strongest influence on the results. Similarly, LES model fields are primarily influenced by their mesoscale meteorological forcing. As a result, the nesting of LES models down to a 50-m resolution does not improve all aspects of hydrometeorological predictions. Advantages of using fine-resolution LES are noted at nighttime (under stable conditions) and over heterogeneous surfaces when local properties are required or when resolving small-scale surface features is desirable.
Impacts of Typhoon Track and Island Topography on the Heavy Rainfalls in Taiwan Associated with Morakot (2009)
Authors: Xie Baoguo , Zhang Fuqing
Published: May 2012

Cloud-resolving ensemble simulations and sensitivity experiments utilizing the Weather Research and Forecasting model (WRF) are performed to investigate the dynamics and predictability of the record-breaking rainfall and flooding event in Taiwan induced by Typhoon Morakot (2009). It is found that a good rainfall forecast foremost requires a good track forecast during Morakot’s landfall. Given a good track forecast, interaction of the typhoon circulation with complex topography in southern Taiwan plays a dominant role in producing the observed heavy rainfalls. The terrain slope, strength of the horizontal winds, and mid–lower-tropospheric moisture content in the southwesterly upslope flow are the primary factors that determine the rainfall location and intensity, as elucidated by the idealized one-dimensional precipitation-rate forecast model. The typhoon circulation and the southwesterly monsoon flow transport abundant moisture into southern Taiwan, which produces the heavy rainfall through interactions with the complex high terrain in the area. In the meantime, as part of the south China monsoon, the southwesterly flow may be substantially enhanced by the typhoon circulation.