bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B virus, hepatitis C virus and other blood-borne infections in healthcare workers: guidelines for prevention and management in industrialised countries
Authors: FitzSimons D , François G , De Carli G , Shouval D , Prüss-Üstün A , Puro V , Williams I , Lavanchy D , De Schryver A , Kopka A , Ncube F , Ippolito G , Van Damme P
Published: June 2008

The Viral Hepatitis Prevention Board (VHPB) convened a meeting of international experts from the public and private sectors in order to review and evaluate the epidemiology of blood-borne infections in healthcare workers, to evaluate the transmission of hepatitis B and C viruses as an occupational risk, to discuss primary and secondary prevention measures and to review recommendations for infected healthcare workers and (para)medical students. This VHPB meeting outlined a number of recommendations for the prevention and control of viral hepatitis in the following domains: application of standard precautions, panels for counselling infected healthcare workers and patients, hepatitis B vaccination, restrictions on the practice of exposure-prone procedures by infected healthcare workers, ethical and legal issues, assessment of risk and costs, priority setting by individual countries and the role of the VHPB. Participants also identified a number of terms that need harmonisation or standardisation in order to facilitate communication between experts.
ECONOMIC ORDER QUANTITY UNDER CONDITIONS OF A ONE-TIME-ONLY EXTENDED PERMISSIBLE DELAY PERIOD IN PAYMENTS
Authors: GOYAL SURESH KUMAR , CHANG CHUN-TAO
Published: June 2008

In today's business environment, a supplier usually offers customers a permissible delay for settling outstanding account balance for the goods supplied. However, a supplier on occasion may allow this permissible delay in payments to be more than the usual during a given specified period. In this paper, we establish an appropriate model for a customer to determine its optimal special order quantity when the supplier offers a special extended permissible delay for one time only during a specified period. We then establish two theorems for a customer to find the optimal special order quantity. Finally, several numerical examples are given to illustrate the theoretical results.
ON SOLVING SHORTEST PATHS WITH A LEAST-SQUARES PRIMAL-DUAL ALGORITHM
Authors: WANG I.-LIN
Published: June 2008

Recently a new least-squares primal-dual (LSPD) algorithm, that is impervious to degeneracy, has effectively been applied to solving linear programming problems by Barnes et al., 2002. In this paper, we show an application of LSPD to shortest path problems with nonnegative arc length is equivalent to the Dijkstra's algorithm. We also compare the LSPD algorithm with the conventional primal-dual algorithm in solving shortest path problems and show their difference due to degeneracy in solving the 1-1 shortest path problems.
BIBLIOMETRIC OVERVIEW OF OPERATIONS RESEARCH/MANAGEMENT SCIENCE RESEARCH IN ASIA
Authors: CHANG PAO-LONG , HSIEH PAO-NUAN
Published: June 2008

This paper evaluates the distribution of papers published by Asian authors in Operations Research and Management Science (OR/MS) journals from 1968 to 2006. The impact of OR/MS research in Asia is compared with that of the United States and the World, and research trends are highlighted through an analysis of keywords. From 1968 to 2006, 89,293 papers were published in 60 OR/MS journals. Of these, 41.4% came from USA and 16.6% came from seven Asian countries/regions. The contribution of different countries/regions is as follows: Japan 3.7%, Taiwan 3.2%, India 2.3%, Hong Kong 2.2%, South Korea 2.1%, People's Republic of China (PRC) 1.9%, and Singapore 1.2%. Among all the articles analyzed, 20% have a single author, and 9% have more than three authors; additionally, 22 papers have been cited more than 100 times and 29% have never been cited. Most articles originating in Japan, Taiwan, India, South Korea, PRC, and Singapore are produced in collaboration with local scholars, followed by authors from the United States. Hong Kong is a notable exception, 73% of articles from Hong Kong are produced in cooperation with the PRC, followed by local scholars. The five most productive institutions are as follows: The Indian Institute of Technology, the Korea Advanced Institute of Science and Technology, the National University of Singapore, The Hong Kong Polytechnic University, and the National Chiao-Tung University (Taiwan).
MINIMIZING A LINEAR OBJECTIVE FUNCTION SUBJECT TO FUZZY RELATION EQUATIONS CONSTRAINTS WITH MAX-HAMACHER PRODUCT COMPOSITION
Authors: MOLAI ALI ABBASI , KHORRAM ESMAILE
Published: June 2008

In this paper, an optimization model with a linear objective function subject to a system of fuzzy relation equations, using max-Hamacher product composition operator, is presented. Since its nonempty feasible solution set is in general a nonconvex set, conventional linear programming methods are not suitable to solve such a problem, so an efficient solution procedure for such problems is necessary. In this paper, the feasible solution set of this problem is studied at first. Then, one efficient algorithm (i.e. tabular method algorithm) is proposed in order to solve the problem. Some procedures are also presented to reduce the original problem. Then, the reduced problem is decomposed (if possible) into several sub-problems with smaller dimensions, so solving them becomes very easier by the algorithm. By combining the algorithm and these procedures, another more efficient algorithm is suggested in order to obtain the optimal solution of the original problem. Some numerical examples are also given to illustrate the algorithms.
SEQUENTIAL LAGRANGE MULTIPLIER CONDITIONS FOR MINIMAX PROGRAMMING PROBLEMS
Authors: DHARA ANULEKHA , MEHRA APARNA
Published: June 2008

In this article, we study nonsmooth convex minimax programming problems with cone constraint and abstract constraint. Our aim is to develop sequential Lagrange multiplier rules for this class of problems in the absence of any constraint qualification. These rules are obtained in terms of ∊-subdifferentials of the functions. As an application of these rules, a sequential dual is proposed and sequential duality results are presented.
AN EXACT APPROACH FOR THE SINGLE MACHINE SCHEDULING PROBLEM WITH LINEAR EARLY AND QUADRATIC TARDY PENALTIES
Authors: VALENTE JORGE M. S.
Published: June 2008

In this paper, we consider the single machine scheduling problem with linear earliness and quadratic tardiness costs, and no machine idle time. We propose a lower bounding procedure based on the relaxation of the jobs' completion times. Optimal branch-and-bound algorithms are then presented. These algorithms incorporate the proposed lower bound, as well as an insertion-based dominance test.

The branch-and-bound procedures are tested on a wide set of randomly generated problems. The computational results show that the branch-and-bound algorithms are capable of optimally solving, within reasonable computation times, instances with up to 20 jobs.
ANALYTICAL APPROXIMATIONS FOR KITTING SYSTEMS WITH MULTIPLE INPUTS
Authors: RAMAKRISHNAN RAM , KRISHNAMURTHY ANANTH
Published: June 2008

This research analyzes a kitting system where multiple components are grouped to form a predefined kit prior to assembly. The kitting system is modeled as a fork/join synchronization station and component supply is assumed to be from fabrication facilities operating under a kanban control policy. Exact analysis of these systems is computationally intensive even under Markovian assumptions. To evaluate the impact of input parameters on kitting system performance, several easily computable bounds on system throughput are first identified. Using these bounds, closed form approximate expressions for system throughput are derived. The throughput estimate is used to compute other performance measures of interest such as mean queue length and mean waiting time in the system. The accuracy of the approximations is validated using numerical experiments and some performance insights are given.
AN EQUIVALENCE OF TWO MASS GENERATION MECHANISMS FOR GAUGE FIELDS
Authors: SEVOSTYANOV ALEXEY
Published: June 2008

Two mass generation mechanisms for gauge theories are studied. It is proved that in the Abelian case the topological mass generation mechanism introduced in Refs. 4, 12 and 15 is equivalent to the mass generation mechanism defined in Refs. 5 and 20 with the help of "localization" of a nonlocal gauge invariant action. In the non-Abelian case the former mechanism is known to generate a unitary renormalizable quantum field theory, describing a massive vector field.
TOPOLOGICALLY MASSIVE ABELIAN GAUGE THEORY
Authors: SAYGILI K.
Published: June 2008

We discuss three mathematical structures which arise in topologically massive Abelian gauge theory. First, the Euclidean topologically massive Abelian gauge theory defines a contact structure on a manifold. We briefly discuss three solutions and the related contact structures on the flat 3-torus, the AdS space, the 3-sphere which respectively correspond to Bianchi type I, VIII, IX spaces. We also present solutions on Bianchi type II, VI and VII spaces. Secondly, we discuss a family of complex (anti-)self-dual solutions of the Euclidean theory in Cartesian coordinates on [Formula: see text] which are given by (anti)holomorpic functions. The orthogonality relation of contact structures which are determined by the real parts of these complex solutions separates them into two classes: the self-dual and the anti-self-dual solutions. Thirdly, we apply the curl transformation to this theory. An arbitrary solution is given by a vector tangent to a sphere whose radius is determined by the topological mass in transform space. Meanwhile a gauge transformation corresponds to a vector normal to this sphere. We discuss the quantization of topological mass in an example.
THE WHITE WALL, A GRAVITATIONAL MIRROR
Authors: GAMBOA SARAVÍ RICARDO E.
Published: June 2008

We describe the exact solution of Einstein's equation corresponding to a static homogenous distribution of matter with plane symmetry lying below z = 0. We study the geodesics in it and we show that this simple space–time exhibits very curious properties. In particular, it has a repelling singular boundary and all geodesics bounce off it.
AN ALTERNATIVE INTERPRETATION FOR THE MODULI FIELDS OF THE COSMOLOGY ASSOCIATED TO TYPE IIB SUPERGRAVITY WITH FLUXES
Authors: MATOS TONATIUH , LUÉVANO JOSÉ-RUBÉN , GARCÍA-COMPEÁN HUGO , VÁZQUEZ J. ALBERTO
Published: June 2008

The aim of this work is to provide a basis to interpret the dilaton as the dark matter of the universe, in the context of a particular cosmological model derived from type IIB supergravity theory with fluxes. In this theory, the dilaton is usually interpreted as a quintessence field. But, with this alternative interpretation we find that (in this supergravity model) the model gives a similar evolution and structure formation of the universe compared with the ΛCDM model in the linear regime of fluctuations of the structure formation. Some free parameters of the theory are fixed using the present cosmological observations. In the nonlinear regime there are some differences between the type IIB supergravity theory with the traditional CDM paradigm. The supergravity theory predicts the formation of galaxies earlier than the CDM and there is no density cusp in the center of galaxies. These differences can distinguish both models and might give a distinctive feature to the phenomenology of the cosmology coming from superstring theory with fluxes.
NONCOMMUTATIVE SPACE AND THE LOW-ENERGY PHYSICS OF QUASICRYSTALS
Authors: MONREAL L. , FERNÁNDEZ DE CÓRDOBA P. , FERRANDO A. , ISIDRO J. M.
Published: June 2008

We prove that the effective low-energy, nonlinear Schrödinger equation for a particle in the presence of a quasiperiodic potential is the potential-free, nonlinear Schrödinger equation on noncommutative space. Thus quasiperiodicity of the potential can be traded for space noncommutativity when describing the envelope wave of the initial quasiperiodic wave.
UMBRAL DEFORMATIONS ON DISCRETE SPACE–TIME
Authors: ZACHOS COSMAS K.
Published: June 2008

Given a minimum measurable length underlying space–time, the latter may be effectively regarded as discrete, at scales of order of the Planck length. A systematic discretization of continuum physics may be effected most efficiently through the umbral deformation. General functionals yielding such deformations at the level of solutions are furnished and illustrated, and broad features of discrete oscillations and wave propagation are outlined.
NEUTRINO OSCILLATION AND THE DAYA BAY θ13 EXPERIMENT
Authors: YOUNG BING-LIN
Published: June 2008

A brief summary of the current status of neutrino oscillations will be given. Then the on-going construction of the Daya Bay Reaction Neutrino Experiment near the Daya Bay nuclear power plant is sketched. The Daya Bay experiment will measure the mixing angle θ13 to the level of sin 2 2θ13 = 0.01.
CORRELATION FUNCTIONS AND INVARIANT MEASURES IN CONTINUOUS CONTACT MODEL
Authors: KONDRATIEV YURI , KUTOVIY OLEKSANDR , PIROGOV SERGEY
Published: June 2008

We study the continuous version of the contact model. Using an analytic approach, we construct the non-equilibrium contact process as a Markov process on configuration space. The construction is based on the analysis of correlation functions evolution. The problem concerning invariant measures as well as asymptotics of correlation functions are also studied.
DYNAMIC QUANTUM BERNOULLI RANDOM WALKS
Authors: GUILLOTIN-PLANTARD NADINE , SCHOTT RENÉ
Published: June 2008

Quantum Bernoulli random walks can be realized as random walks on the dual of SU(2). We use this realization in order to study a model of dynamic quantum Bernoulli random walk with time-dependent transitions. For the corresponding dynamic random walk on the dual of SU(2), we prove several limit theorems (local limit theorem, central limit theorem, law of large numbers, large deviation principle). In addition, we characterize a large class of transient dynamic random walks.
FREE ENTROPY DIMENSION OF PROJECTIONS AND FACTORIALITY OF GENERATED VON NEUMANN ALGEBRAS
Authors: MIYAMOTO TAKUHO
Published: June 2008

We examine the free entropy and free entropy dimension for projections, and obtain a sufficient condition for the factoriality of the von Neumann algebra generated by projections in terms of their free entropy dimension. This corresponds to Voiculescu's result for self-adjoint elements.
NO ZERO DIVISOR FOR WICK PRODUCT IN (S)*
Authors: HASEBE TAKAHIRO , OJIMA IZUMI , SAIGO HAYATO
Published: June 2008

In White Noise Analysis (WNA), various random quantities are analyzed as elements of (S)*, the space of Hida distributions.1 Hida distributions are generalized functions of white noise, which is to be naturally viewed as the derivative of the Brownian motion. On (S)*, the Wick product is defined in terms of the [Formula: see text]-transform. We have found such a remarkable property that the Wick product has no zero divisors among Hida distributions. This result is a WNA version of Titchmarsh's theorem and is expected to play fundamental roles in developing the "operational calculus" in WNA along the line of Mikusiński's version for solving differential equations.
HEAT KERNEL MEASURE ON LOOP AND PATH GROUPS
Authors: CECIL MATTHEW , DRIVER BRUCE K.
Published: June 2008

Diffusions on the pinned loop and pathgroup of a general (non-compact) Lie group are constructed. The laws of the endpoint processes satisfy heat equations related to second order differential operators associated to subspaces of the Cameron–Martin space.
FORWARD INTEGRALS AND AN ITÔ FORMULA FOR FRACTIONAL BROWNIAN MOTION
Authors: BIAGINI FRANCESCA , ØKSENDAL BERNT
Published: June 2008

We consider the forward integral with respect to fractional Brownian motion B(H)(t) and relate this to the Wick–Itô–Skorohod integral by using the M-operator introduced by Ref. 10 and the Malliavin derivative [Formula: see text]. Using this connection we obtain a general Itô formula for the Wick–Itô–Skorohod integralswith respect to B(H)(t), valid for [Formula: see text].
ON THE STRONG UNIQUENESS OF SOME FINITE DIMENSIONAL DIRICHLET OPERATORS
Authors: KOLB MARTIN
Published: June 2008

We prove essential self-adjointness of a class of Dirichlet operators in ℝnusing the hyperbolic equation approach. This method allows one to prove essential self-adjointness under minimal conditions on the logarithmic derivative of the density and a condition of Muckenhoupt type on the density itself.
DECOMPOSITION BASED IMAGING WITH FIBER AND CCD CAMERA DETECTIONS
Authors: CAMPBELL S. D. , GOODIN I. L. , GROBE S. D. , SU Q. , GROBE R.
Published: June 2008

We generalize a previously proposed imaging scheme to situations for which the set of hidden objects embedded in the highly scattering medium can take arbitrary shapes. We compare the accuracy of images obtained from optical detection fibers with those from a ccd camera. The latter approach is more efficient and can be applied to non-contact geometries, but it requires an a priori linearization of the obtained digitized images. We discuss some details of this calibration for the camera and establish its potential as a new tool for decomposition based imaging.
REAL-TIME MONITORING OF MITOCHONDRIAL FUNCTION AND CEREBRAL BLOOD FLOW FOLLOWING FOCAL ISCHEMIA IN RATS
Authors: LIVNAT AMIR , TOLMASOV MICHAEL , BARBIRO-MICHAELY EFRAT , MAYEVSKY AVRAHAM
Published: June 2008

Focal ischemia due to reduction of cerebral blood flow (CBF), creates 2 zones of damage: the core area, which suffers severe damage, and penumbra area, which surrounds the core and suffers intermediate levels of injury. Objectives: A novel method is introduced, which evaluates mitochondrial function in the core and in the penumbra, during focal cerebral ischemia. Methods: Wistar rats underwent focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 60 minutes, followed by 60 minutes of reperfusion. Mitochondrial function was assessed by a unique Multi-Site – Multi-Parametric (MSMP) monitoring system, which measures mitochondrial NADH using fluorometric technique, and CBF using Laser Doppler Flowmetry (LDF). Results: At the onset of occlusion, CBF dropped and NADH increased significantly only in the right hemisphere. CBF levels were significantly lower and NADH significantly higher in the core than in the penumbra. After reperfusion, CBF and NADH recovered correspondingly to the intensity of ischemia. Conclusion: Application of the MSMP system can add significant information for the understanding of the cerebral metabolic state under ischemic conditions, with an emphasis on mitochondrial function.
RECENT DEVELOPMENTS OF TERAHERTZ TECHNOLOGY IN BIOMEDICINE
Authors: PICKWELL-MACPHERSON EMMA , HUANG SHENGYANG , KAN KANIS WAI CHI , SUN YIWEN , ZHANG YUAN TING
Published: June 2008

Terahertz technology is continually evolving and much progress has been made in recent years. Many new applications are being discovered and new ways to implement terahertz imaging investigated. In this review, we limit our discussion to biomedical applications of terahertz imaging such as cancer detection, genetic sensing and molecular spectroscopy. Our discussion of the development of new terahertz techniques is also focused on those that may accelerate the progress of terahertz imaging and spectroscopy in biomedicine.
RAMAN SPECTROSCOPY FOR IN VIVO TISSUE ANALYSIS AND DIAGNOSIS, FROM INSTRUMENT DEVELOPMENT TO CLINICAL APPLICATIONS
Authors: ZENG HAISHAN , ZHAO JIANHUA , SHORT MICHAEL , MCLEAN DAVID I. , LAM STEPHEN , MCWILLIAMS ANNETTE , LUI HARVEY
Published: June 2008

Raman spectroscopy is a noninvasive, nondestructive analytical method capable of determining the biochemical constituents based on molecular vibrations. It does not require sample preparation or pretreatment. However, the use of Raman spectroscopy for in vivo clinical applications will depend on the feasibility of measuring Raman spectra in a relatively short time period (a few seconds). In this work, a fast dispersive-type near-infrared (NIR) Raman spectroscopy system and a skin Raman probe were developed to facilitate real-time, noninvasive, in vivo human skin measurements. Spectrograph image aberration was corrected by a parabolic-line fiber array, permitting complete CCD vertical binning, thereby yielding a 16-fold improvement in signal-to-noise ratio. Good quality in vivo skin NIR Raman spectra free of interference from fiber fluorescence and silica Raman scattering can be acquired within one second, which greatly facilitates practical noninvasive tissue characterization and clinical diagnosis. Currently, we are conducting a large clinical study of various skin diseases in order to develop Raman spectroscopy into a useful tool for non-invasive skin cancer detection. Intermediate data analysis results are presented. Recently, we have also successfully developed a technically more challenging endoscopic Laser-Raman probe for early lung cancer detection. Preliminary in vivo results from endoscopic lung Raman measurements are discussed.
SHEDDING LIGHT ON LIFE: OPTICAL ASSESSMENT OF MITOCHONDRIAL FUNCTION AND TISSUE VITALITY IN BIOLOGY AND MEDICINE
Authors: MAYEVSKY AVRAHAM
Published: June 2008

The involvement of mitochondrial dysfunction in various pathophysiological conditions, developed in experimental and clinical situations, is widely documented. Nevertheless, real time monitoring of mitochondrial function In-vivo is very rare. The pressing question is how the mitochondria of intact tissues behave under In-vivo conditions as compared to isolated mitochondria that had been described by Chance and Williams over 50 years ago. This subject has been recently discussed in detail (Mayevsky and Rogatsky 2007). We reviewed the subject of evaluating mitochondrial function by monitoring NADH fluorescence together with microcirculatory blood flow, Hemoglobin oxygenation and tissue reflectance. These 4 parameters represent the vitality of the tissue and could be monitored in vivo, using optical spectroscopy, in animal models as well as in clinical practice. It is a well known physiological hypothesis that, under emergency conditions, the sympathetic nervous system will give preference to the most vital organs in the body, namely the brain, heart and adrenal glands. The less vital organs, such as the skin, GI-tract, and Urethral wall, will become hypoperfused and their mitochondrial activity will be inhibited. The monitoring of the less vital organs may reveal critical tissue conditions that may manifest an early phase of body deterioration. The aim of the current presentation is to review the experimental and preliminary clinical results accumulated using a new integrated medical device – the "CritiView" which enabled, for the first time, monitoring 4 parameters from the tissue using a single optical probe. The CritiView is a computerized optical device that integrates hardware and software in order to provide real time information on tissue vitality. In preliminary clinical testing, we used a 3-way Foley catheter that includes a bundle of optical fibers enabling the monitoring of the 4 parameters, representing the vitality of the urethral wall (a less vital organ).We found that the exposure of patients to metabolic imbalances in the operation room led to changes in tissue blood flow and inhibition of mitochondrial function in the urethral wall. In conclusion, the new device "CritiView" could provide reliable, real time data on mitochondrial function and tissue vitality in experimental animals as well as in patients.
OPTICAL IMAGING AND SPECTROSCOPY OF SUPERFICIAL TISSUE
Authors: MORGAN S. P. , STOCKFORD I. M. , CROWE J. A. , HAYES-GILL B. R.
Published: June 2008

An overview of three techniques developed by our group for imaging superficial tissue is presented. Firstly, a novel polarized light capillaroscope has been developed for imaging the microcirculation. The capillaroscope has been used to make in vivo measurements of sickle cell disorder sufferers with aim of monitoring the polymerization of sickled red blood cells. Secondly, hyperspectral imaging for measuring oxygen saturation is described. The accuracy of such measurements is affected by the non-linear relationship between scattering and absorption and it is demonstrated that polarization techniques can be used to make the relationship more linear, thus improving accuracy. Finally, the use of smart CMOS optical sensors for laser Doppler blood flowmetry is described. A 32 × 32 pixel imaging array with on-chip processing is described and the potential for full field laser Doppler blood flow imaging is demonstrated through measurement on blood flow of tissue before and after occlusion.
LIVE IMAGING OF XIAO-AI-PING-INDUCED CELL DEATH IN HUMAN LUNG ADENOCARCINOMA CELLS
Authors: WANG XIAO-PING , CHEN TONGSHENG , WANG LONGXIANG , SUN LEI
Published: June 2008

Xiao-Ai-Ping (XAP), a traditional oriental medicinal herb isolated from the stem of Marsdenia tenacissima (Roxb.) Wight et Arn., has been shown to induce tumor cell apoptosis. In this study, we used confocal fluorescence microscopy and fluorescence resonance energy transfer (FRET) techniques to study the molecular mechanism of XAP-induced apoptosis in single living human lung adenocarcinoma (ASTC-a-1) cells. The efficacious apoptosis was observed at 6 h after of 100 μl XAP treatment. Further monitoring the dynamics of caspase-3 activation using FRET imaging in single living ASTC-a-1 cell expressing stably with SCAT3, a FRET probe, showed that XAP activated the caspase-3 at about 2 h after XAP treatment. These data suggest that caspase-3 activation was involved in the XAP-induced apoptosis in ASTC-a-1 cells.
OPTICAL COHERENCE TOMOGRAPHY FOR BLADDER CANCER DIAGNOSIS: FROM ANIMAL STUDY TO CLINICAL DIAGNOSIS
Authors: YUAN ZHIJIA , REN HUGANG , WALTZER WAYNE , KIM JASON , LIU JINGXUAN , JIA KEMIAO , XIE HUIKAI , PAN YINGTIAN
Published: June 2008

This paper summarizes the recent technological development in our lab on cystoscopic optical coherence tomography (COCT) by integrating time-domain OCT (TDOCT) and spectral-domain OCT (SDOCT) with advanced MEMS-mirror technology for endoscopic laser scanning imaging. The COCT catheter can be integrated into the instrument channel of a commercial 22Fr rigid cystoscopic sheath for in vivo imaging of human bladder under the cystosocopic visual guidance; the axial/transverse resolutions of the COCT catheter are roughly 9 μm and 12 μm, respectively, and 2D COCT imaging can be performed with over 110dB dynamic range at 4–8 fps. To examine the utility and potential limitations of OCT for bladder cancer diagnosis, systemic ex vivo rat bladder carcinogenesis studies were performed to follow various morphological changes induced by tumor growth and in vivo porcine study was performed to examine the feasibility of COCT for in vivo imaging. Justified by promising results of the animal studies, preliminary clinical study was conducted on patients scheduled for operating-room cystoscopy for bladder cancers. Double-blind clinical results reveal that COCT can delineate detailed bladder architectures (e.g., urothelium, lamina propria, muscularis) at high resolution and detect bladder cancers based on enhanced urothelial heterogeneity as a result of excessive growing nature of bladder cancers. The diagnostic sensitivity and specificity can be enhanced to 92% and 85%, respectively. Results also suggest that due to reduced imaging depth of COCT in cancerous lesions, staging of bladder cancers may be limited to Ta or T1 for non-outgrowing cancerous lesions.
ACTIVATABLE SMART PROBES FOR MOLECULAR OPTICAL IMAGING AND THERAPY
Authors: LOVELL JONATHAN F. , ZHENG GANG
Published: June 2008

Recent years have seen the design and implementation of many optical activatable smart probes. These probes are activatable because they change their optical properties and are smart because they can identify specific targets. This broad class of detection agents has allowed previously unperformed visualizations, facilitating the study of diverse biomolecules including enzymes, nucleic acids, ions and reactive oxygen species. Designed to be robust in an in vivo environment, these probes have been used in tissue culture cells and in live small animals. An emerging class of smart probes has been designed to harness the potency of singlet oxygen generating photosensitizers. Combining the discrimination of activatable agents with the toxicity of photosensitizers represents a new and powerful approach to disease treatment. This review highlights some applications of activatable smart probes with a focus on developments of the past decade.
SINGLET OXYGEN QUANTUM YIELDS OF PORPHYRIN-BASED PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY
Authors: LI BU-HONG , LIN LI-SHENG , LIN HUI-YUN , XIE SHU-SEN
Published: June 2008

The major cytotoxic agent with most current photosensitizers used in photodynamic therapy (PDT) is widely believed to be singlet oxygen (1O2). Determination of the1O2quantum yields for porphyrin-based photosensitizers, including hematoporphyrin derivative (HiPorfin), hematoporphyrin monomethyl ether (HMME) and photocarcinorin (PsD-007) in air-saturated dimethylformamide (DMF) solutions were performed by the direct measurement of their near-infrared luminescence. In addition,1O2quencher sodium azide was employed to confirm the1O2generation from the investigated photosensitizers. The maximal1O2luminescence occurs at about 1280 nm with full width at half maximum of 30 nm. The1O2quantum yields were found to be 0.61 ± 0.03, 0.60 ± 0.02 and 0.59 ± 0.03 for HiPorfin, HMME and PsD-007, respectively. These results provide that these porphyrin-based photosensitizers produce1O2under irradiation, which is of significance for the study of their photodynamic action in PDT.
Direct evidence of iNOS-mediated in vivo free radical production and protein oxidation in acetone-induced ketosis
Authors: Stadler Krisztian , Bonini Marcelo G. , Dallas Shannon , Duma Danielle , Mason Ronald P. , Kadiiska Maria B.
Published: June 2008

Diabetic patients frequently encounter ketosis that is characterized by the breakdown of lipids with the consequent accumulation of ketone bodies. Several studies have demonstrated that reactive species are likely to induce tissue damage in diabetes, but the role of the ketone bodies in the process has not been fully investigated. In this study, electron paramagnetic resonance (EPR) spectroscopy combined with novel spin-trapping and immunological techniques has been used to investigate in vivo free radical formation in a murine model of acetone-induced ketosis. A six-line EPR spectrum consistent with the α-(4-pyridyl-1-oxide)- N-t-butylnitrone radical adduct of a carbon-centered lipid-derived radical was detected in the liver extracts. To investigate the possible enzymatic source of these radicals, inducible nitric oxide synthase (iNOS) and NADPH oxidase knockout mice were used. Free radical production was unchanged in the NADPH oxidase knockout but much decreased in the iNOS knockout mice, suggesting a role for iNOS in free radical production. Longer-term exposure to acetone revealed iNOS overexpression in the liver together with protein radical formation, which was detected by confocal microscopy and a novel immunospin-trapping method. Immunohistochemical analysis revealed enhanced lipid peroxidation and protein oxidation as a consequence of persistent free radical generation after 21 days of acetone treatment in control and NADPH oxidase knockout but not in iNOS knockout mice. Taken together, our data demonstrate that acetone administration, a model of ketosis, can lead to protein oxidation and lipid peroxidation through a free radical-dependent mechanism driven mainly by iNOS overexpression.
Maternal protein restriction during early lactation induces GLUT4 translocation and mTOR/Akt activation in adipocytes of adult rats
Authors: Garcia-Souza Érica Patrícia , da Silva Simone Vargas , Félix Gisele Barreto , Rodrigues Ananda Lages , de Freitas Marta Sampaio , Moura Aníbal Sanchez , Barja-Fidalgo Christina
Published: June 2008

Epidemiological and experimental studies have demonstrated that early postnatal nutrition has been associated with long-term effects on glucose homeostasis in adulthood. Recently, our group demonstrated that undernutrition during early lactation affects the expression and activation of key proteins of the insulin signaling cascade in rat skeletal muscle during postnatal development. To elucidate the molecular mechanisms by which undernutrition during early life leads to changes in insulin sensitivity in peripheral tissues, we investigated the insulin signaling in adipose tissue. Adipocytes were isolated from epididymal fat pads of adult male rats that were the offspring of dams fed either a normal or a protein-free diet during the first 10 days of lactation. The cells were incubated with 100 nM insulin before the assays for immunoblotting analysis, 2-deoxyglucose uptake, immunocytochemistry for GLUT4, and/or actin filaments. Following insulin stimulation, adipocytes isolated from undernourished rats presented reduced tyrosine phosphorylation of IR and IRS-1 and increased basal phosphorylation of IRS-2, Akt, and mTOR compared with controls. Basal glucose uptake was increased in adipocytes from the undernourished group, and the treatment with LY294002 induced only a partial inhibition both in basal and in insulin-stimulated glucose uptake, suggesting an involvement of phosphoinositide 3-kinase activity. These alterations were accompanied by higher GLUT4 content in the plasma membrane and alterations in the actin cytoskeleton dynamics. These data suggest that early postnatal undernutrition impairs insulin sensitivity in adulthood by promoting changes in critical steps of insulin signaling in adipose tissue, which may contribute to permanent changes in glucose homeostasis.
Failure of adrenal corticosterone production in POMC-deficient mice results from lack of integrated effects of POMC peptides on multiple factors
Authors: Karpac Jason , Czyzewska Katarzyna , Kern Andras , Brush Richard S. , Anderson Robert E. , Hochgeschwender Ute
Published: June 2008

Production of corticosteroids from the adrenal gland is a multistep process in which corticosterone is enzymatically processed from its precursor cholesterol. The main hormone regulating the production of corticosterone is the proopiomelanocortin (POMC)-derived adrenocorticotropic hormone (ACTH). Adrenals of POMC-deficient (POMC−/−) mice do not produce corticosterone either at basal levels or in response to acute stimulation with ACTH. However, pharmacological amounts of ACTH delivered continuously elicit corticosterone production over time. To define the relative effects of ACTH on individual factors involved in corticosterone production, parameters of adrenal cholesterol metabolism and steroidogenesis were examined in POMC−/−mice compared with wild-type and ACTH-treated mutant mice. POMC−/−adrenals lack cholesterol esters (CE); adrenal CE is restored with ACTH treatment. However, discontinuation of ACTH treatment stops corticosterone production despite the presence of adrenal CE. Failure of corticosterone production by POMC−/−adrenals occurs despite the constitutive presence of transcripts of genes required for cholesterol metabolism and steroidogenesis. Levels of key proteins involved in selective cholesterol uptake and steroidogenesis were attenuated; ACTH treatment increased these protein levels, most significantly those of the receptor responsible for selective uptake of CE, scavenger receptor class B, type I (SR-BI). Our studies reveal that failure of corticosterone production of POMC−/−adrenal glands and its pharmacological reconstitution by ACTH are not mediated by any one individual protein, but rather as an integrated effect on multiple factors from import of the substrate cholesterol to its conversion to corticosterone.
Pathogenic role of Fgf23 in Dmp1-null mice
Authors: Liu Shiguang , Zhou Jianping , Tang Wen , Menard Rochelle , Feng Jian Q. , Quarles L. D.
Published: June 2008

Autosomal recessive hypophosphatemic rickets (ARHR), which is characterized by renal phosphate wasting, aberrant regulation of 1α-hydroxylase activity, and rickets/osteomalacia, is caused by inactivating mutations of dentin matrix protein 1 ( DMP1). ARHR resembles autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH), hereditary disorders respectively caused by cleavage-resistant mutations of the phosphaturic factor FGF23 and inactivating mutations of PHEX that lead to increased production of FGF23 by osteocytes in bone. Circulating levels of FGF23 are increased in ARHR and its Dmp1-null mouse homologue. To determine the causal role of FGF23 in ARHR, we transferred Fgf23 deficient/enhanced green fluorescent protein (eGFP) reporter mice onto Dmp1-null mice to create mice lacking both Fgf23 and Dmp1. Dmp1−/− mice displayed decreased serum phosphate concentrations, inappropriately normal 1,25(OH)2D levels, severe rickets, and a diffuse form of osteomalacia in association with elevated Fgf23 serum levels and expression in osteocytes. In contrast, Fgf23−/− mice had undetectable serum Fgf23 and elevated serum phosphate and 1,25(OH)2D levels along with severe growth retardation and focal form of osteomalacia. In combined Dmp1−/−/Fgf23−/−, circulating Fgf23 levels were also undetectable, and the serum levels of phosphate and 1,25(OH)2D levels were identical to Fgf23−/− mice. Rickets and diffuse osteomalacia in Dmp1-null mice were transformed to severe growth retardation and focal osteomalacia characteristic of Fgf23-null mice. These data suggest that the regulation of extracellular matrix mineralization by DMP1 is coupled to renal phosphate handling and vitamin D metabolism through a DMP1-dependent regulation of FGF23 production by osteocytes.
Exercise-induced lipid mobilization in subcutaneous adipose tissue is mainly related to natriuretic peptides in overweight men
Authors: Moro Cedric , Pillard Fabien , de Glisezinski Isabelle , Klimcakova Eva , Crampes Francois , Thalamas Claire , Harant Isabelle , Marques Marie-Adeline , Lafontan Max , Berlan Michel
Published: June 2008

Involvement of sympathetic nervous system and natriuretic peptides in the control of exercise-induced lipid mobilization was compared in overweight and lean men. Lipid mobilization was determined using local microdialysis during exercise. Subjects performed 35-min exercise bouts at 60% of their maximal oxygen consumption under placebo or after oral tertatolol [a β-adrenergic receptor (AR) antagonist]. Under placebo, exercise increased dialysate glycerol concentration (DGC) in both groups. Phentolamine (α-AR antagonist) potentiated exercise-induced lipolysis in overweight but not in lean subjects; the α2-antilipolytic effect was only functional in overweight men. After tertatolol administration, the DGC increased similarly during exercise no matter which was used probe in both groups. Compared with the control probe under placebo, lipolysis was reduced in lean but not in overweight men treated with the β-AR blocker. Tertatolol reduced plasma nonesterified fatty acids and insulin concentration in both groups at rest. Under placebo or tertatolol, the exercise-induced changes in plasma nonesterified fatty acids, glycerol, and insulin concentrations were similar in both groups. Exercise promoted a higher increase in catecholamine and ANP plasma levels after tertatolol administration. In conclusion, the major finding of our study is that in overweight men, in addition to an increased α2-antilipolytic effect, the lipid mobilization in subcutaneous adipose tissue that persists during exercise under β-blockade is not dependent on catecholamine action. On the basis of correlation findings, it seems to be related to a concomitant exercise-induced rise in plasma ANP when exercise is performed under tertatolol intake and a decrease in plasma insulin.
Fetal growth restriction triggered by polycyclic aromatic hydrocarbons is associated with altered placental vasculature and AhR-dependent changes in cell death
Authors: Detmar Jacqui , Rennie Monique Y. , Whiteley Kathie J. , Qu Dawei , Taniuchi Yoshinari , Shang Xueyuan , Casper Robert F. , Adamson S. Lee , Sled John G. , Jurisicova Andrea
Published: June 2008

Maternal cigarette smoking is considered an important risk factor associated with fetal intrauterine growth restriction (IUGR). Polycyclic aromatic hydrocarbons (PAHs) are well-known constituents of cigarette smoke, and the effects of acute exposure to these chemicals at different gestational stages have been well established in a variety of laboratory animals. In addition, many PAHs are known ligands of the aryl hydrocarbon receptor (AhR), a cellular xenobiotic sensor responsible for activating the metabolic machinery. In this study, we have applied a chronic, low-dose regimen of PAH exposure to C57Bl/6 female mice before conception. This treatment caused IUGR in day 15.5 post coitum (d15.5) fetuses and yielded abnormalities in the placental vasculature, resulting in significantly reduced arterial surface area and volume of the fetal arterial vasculature of the placenta. However, examination of the small vasculature within the placental labyrinth of PAH-exposed dams revealed extensive branching and enlargement of these vessels, indicating a possible compensatory mechanism. These alterations in vascularization were accompanied by reduced placental cell death rates, increased expression levels of antiapoptotic Xiap, and decreased expression of proapoptotic Bax, cleaved poly(ADP-ribose) polymerase-1, and active caspase-3. AhR-deficient fetuses were rescued from PAH-induced growth restriction and exhibited no changes in the labyrinthine cell death rate. The results of this investigation suggest that chronic exposure to PAHs is a contributing factor to the development of IUGR in human smokers and that the AhR pathway is involved.
Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury
Authors: Harrison Ewen M. , Sharpe Eva , Bellamy Christopher O. , McNally Stephen J. , Devey Luke , Garden O. James , Ross James A. , Wigmore Stephen J.
Published: June 2008

Heat shock proteins (Hsps) are protective in models of transplantation, yet practical strategies to upregulate them remain elusive. The heat shock protein 90-binding agent (HBA) geldanamycin and its analogs (17-AAG and 17-DMAG) are known to upregulate Hsps and confer cellular protection but have not been investigated in a model relevant to transplantation. We examined the ability of HBAs to upregulate Hsp expression and confer protection in renal adenocarcinoma (ACHN) cells in vitro and in a mouse model of kidney ischemia-reperfusion (I/R) injury. Hsp70 gene expression was increased 30-40 times in ACHN cells treated with HBAs, and trimerization and DNA binding of heat shock transcription factor-1 (HSF1) were demonstrated. A three- and twofold increase in Hsp70 and Hsp27 protein expression, respectively, was found in ACHN cells treated with HBAs. HBAs protected ACHN cells from an H2O2-mediated oxidative stress, and HSF1 short interfering RNA was found to abrogate HBA-mediated Hsp induction and protection. In vivo, Hsp70 was upregulated in the kidneys, liver, lungs, and heart of HBA-treated mice. This was associated with a functional and morphological renal protection from I/R injury. Therefore, HBAs mediate upregulation of protective Hsps in mouse kidneys which are associated with reduced I/R injury and may be useful in reducing transplant-associated kidney injury.
Effects of cholesterol-tagged small interfering RNAs targeting 12/15-lipoxygenase on parameters of diabetic nephropathy in a mouse model of type 1 diabetes
Authors: Yuan Hang , Lanting Linda , Xu Zhong-Gao , Li Shu-Lian , Swiderski Piotr , Putta Sumanth , Jonnalagadda Mahesh , Kato Mitsuo , Natarajan Rama
Published: June 2008

We previously showed that the 12/15-lipoxygenase (12/15-LO) pathway of arachidonate acid metabolism is involved in multiple events related to diabetic nephropathy (DN), including glomerular hypertrophy and extracellular matrix deposition (Kang SW, Adler SG, Nast CC, LaPage J, Gu JL, Nadler JL, Natarajan R. Kidney Int 59: 1354–1362, 2001; Kang SW, Natarajan R, Shahed A, Nast CC, LaPage J, Mundel P, Kashtan C, Adler SG. J Am Soc Nephrol 14: 3178–3187, 2003; Kim YS, Lanting L, Adler SG, Natarajan R. Kindney Int 64: 1702–1714, 2003; Reddy MA, Adler SG, Kim YS, Lanting L, Rossi JJ, Kang SW, Nadler JL, Shahed A, Natarajan R. Am J Physiol Renal Physiol 283: F985–F994, 2002). In this study, we investigated whether in vivo delivery of small interfering RNAs (siRNAs) targeting 12/15-LO can ameliorate renal injury and DN in a streptozotocin-injected mouse model of type 1 diabetes. To achieve greater in vivo access and siRNA expression in the kidney, we used double-stranded 12/15-LO siRNA oligonucleotides conjugated with cholesterol. Diabetic DBA/2J mice were injected subcutaneously with either cholesterol-tagged 12/15-LO siRNA, mismatched control siRNA, or vehicle alone, twice weekly for 7 wk. Relative to controls, mice that received 12/15-LO siRNA showed significant reduction in albuminuria, kidney-to-body weight ratios, glomerular mesangial matrix expansion, renal structural damage, and monocyte/macrophage infiltration. These effects were associated with lower renal cortical or glomerular levels of profibrotic markers transforming growth factor-β, connective tissue growth factor, type I and type IV collagens, plasminogen activator inhibitor 1, and fibronectin. The diabetes-induced increase in glomerular cyclin-dependent kinase inhibitors that are associated with hypertrophy was also prevented by siRNA administration. Our results show for the first time that systemic delivery of cholesterol-tagged siRNAs targeting 12/15-LO has renoprotective effects under diabetic conditions and therefore could be a novel therapeutic approach for DN.
Superior Colliculus Control of Vibrissa Movements
Authors: Hemelt Marie E. , Keller Asaf
Published: June 2008

This study tested the role of the superior colliculus in generating movements of the mystacial vibrissae—whisking. First, we compared the kinematics of whisking generated by the superior colliculus with those generated by the motor cortex. We found that in anesthetized rats, microstimulation of the colliculus evoked a sustained vibrissa protraction, whereas stimulation of motor cortex produced rhythmic protractions. Movements generated by the superior colliculus are independent of motor cortex and can be evoked at lower thresholds and shorter latencies than those generated by the motor cortex. Next we tested the hypothesis that the colliculus is acting as a simple reflex loop with the neurons that drive vibrissa movement receiving sensory input evoked by vibrissa contacts. We found that most tecto-facial neurons do not receive sensory input. Not only did these neurons not spike in response to sensory stimulation, but field potential analysis revealed that subthreshold sensory inputs do not overlap spatially with tecto-facial neurons. Together these findings suggest that the superior colliculus plays a pivotal role in vibrissa movement—regulating vibrissa set point and whisk amplitude—but does not function as a simple reflex loop. With the motor cortex controlling the whisking frequency, the superior colliculus control of set point and amplitude would account for the main parameters of voluntary whisking.