To determine the role of cyclooxygenase (COX)-2 in anthracycline-induced cardiac toxicity, we administered doxorubicin (Dox) to mice with genetic disruption of COX-2 (COX-2 super(-/-)). After ...treatment with Dox, COX-2 super(-/-) mice had increased cardiac dysfunction and cardiac cell apoptosis compared with Dox-treated wild-type mice. The expression of the death-associated protein kinase-related apoptosis-inducing protein kinase-2 was also increased in Dox-treated COX-2 super(-/-) animals. The altered gene expression, cardiac injury, and dysfunction after Dox treatment in COX-2 super(-/-) mice was attenuated by a stable prostacyclin analog, iloprost. Wild-type mice treated with Dox developed cardiac fibrosis that was absent in COX-2 super(-/-) mice and unaffected by iloprost. These results suggest that genetic disruption of COX-2 increases the cardiac dysfunction after treatment with Dox by an increase in cardiac cell apoptosis. This Dox-induced cardiotoxicity in COX-2 super(-/-) mice was attenuated by a prostacyclin analog, suggesting a protective role for prostaglandins in this setting.
We report the first molecular image of melanin using a novel extension of OCT, pump-probe OCT. Melanin, an abundant endogenous chromophore, could provide general contrast in OCT imaging and means to ...diagnose and/or monitor melanomas.
Integrins are cysteine-rich heterodimeric cell-surface adhesion molecules that alter their affinity for ligands in response
to cellular activation. The molecular mechanisms involved in this ...activation of integrins are not understood. Treatment with
the thiol-reducing agent, dithiothreitol, can induce an activation-like state in many integrins suggesting that cysteine-cysteine
dithiol bonds are important for the receptor's tertiary structure and may be involved in activation-induced conformational
changes. Here we demonstrate that the platelet-specific integrin, α IIb β 3 , contains an endogenous thiol isomerase activity, predicted from the presence of the tetrapeptide motif, C XX C, in each of the cysteine-rich repeats of the β 3 polypeptide. This motif comprises the active site in enzymes involved in disulfide exchange reactions, including protein-disulfide
isomerase (EC 5.3.4.1 ) and thioredoxin. Intrinsic thiol isomerase activity is also observed in the related integrin, α v β 3 , which shares a common β-subunit. Thiol isomerase activity within α IIb β 3 is time-dependent and saturable, and is inhibited by the protein-disulfide isomerase inhibitor, bacitracin. Furthermore,
this activity is calcium-sensitive and is regulated in the EDTA-stabilized conformation of the integrin. This novel demonstration
of an enzymatic activity associated with an integrin subunit suggests that altered thiol bonding within the integrin or its
substrates may be locally modified during α IIb β 3 activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Integrins are cysteine-rich heterodimeric cell-surface adhesion molecules that alter their affinity for ligands in response to cellular activation. The molecular mechanisms involved in this ...activation of integrins are not understood. Treatment with the thiol-reducing agent, dithiothreitol, can induce an activation-like state in many integrins suggesting that cysteine-cysteine dithiol bonds are important for the receptor's tertiary structure and may be involved in activation-induced conformational changes. Here we demonstrate that the platelet-specific integrin, αIIbβ3, contains an endogenous thiol isomerase activity, predicted from the presence of the tetrapeptide motif, CXXC, in each of the cysteine-rich repeats of the β3 polypeptide. This motif comprises the active site in enzymes involved in disulfide exchange reactions, including protein-disulfide isomerase (EC 5.3.4.1) and thioredoxin. Intrinsic thiol isomerase activity is also observed in the related integrin, αvβ3, which shares a common β-subunit. Thiol isomerase activity within αIIbβ3 is time-dependent and saturable, and is inhibited by the protein-disulfide isomerase inhibitor, bacitracin. Furthermore, this activity is calcium-sensitive and is regulated in the EDTA-stabilized conformation of the integrin. This novel demonstration of an enzymatic activity associated with an integrin subunit suggests that altered thiol bonding within the integrin or its substrates may be locally modified during αIIbβ3 activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The PHENIX online control system is responsible for the configuration, control and monitoring of the PHENIX detector data acquisition system and ancillary control hardware, and the collection and ...archiving of the event data. The detector consists of 11 distinct subsystems, which are distributed physically and partitioned logically while ultimately being combined into a single operating unit. The online system consists of a large number of embedded commercial and custom processors as well as custom software processes which are involved in the collection, monitoring and control of the detector and the event data. These processing elements are distributed over a diverse set of computing platforms including VME based Power PC controllers, Pentium based NT systems, and SUN Solaris SPARC processors. CORBA has been adopted as the standard communication mechanism for PHENIX online system. This paper will describe the design, implementation and use of CORBA to achieve a uniform and platform independent control environment while providing for the access, control and monitoring of the online detector elements over the distributed and diverse control environment. Synchronous and asynchronous communication issues will be discussed as well as the development of CORBA compliant components which were developed to achieve client/server isolation and deterministic system behavior. The use and interaction between JAVA based clients and C++ based CORBA servers to further achieve a platform neutral environment will be presented.
We demonstrate the advantage of combining high-resolution Fourier domain optical coherence tomography (OCT) with wide-field time-gated fluorescence lifetime imaging microscopy (FLIM) for a ...comprehensive morphological and biochemical characterization of atherosclerotic vulnerable plaques (VP).
Men are significantly more susceptible to non-melanoma skin cancers than women, and the androgen receptor (AR) is widely distributed in the skin, suggesting a ro\le for androgens acting via AR. ...Therefore, we explored the role of androgen action via AR in susceptibility to experimental 7,12-dimethylbenzaanthracene (DMBA)-induced skin carcinogenesis and in skin structural development of male and female mice. We demonstrate that both the male gender and androgen action via AR modify the susceptibility to carcinogen-induced skin cancer, but the effect depends on the carcinogenesis model used. Following systemic DMBA exposure, males were significantly (
p
< 0.05) more susceptible to DMBA-induced experimental skin cancer than females and AR inactivation significantly delayed cancer detection in both male (median time to palpable tumours 19 vs. >35 weeks (wild-type WT vs. AR knockout ARKO,
p
< 0.001) and female (27 vs. >35 weeks,
p
= 0.008)) mice. In contrast, following DMBA/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced multistage local skin carcinogenesis, AR inactivation protected against formation of DMBA-induced skin cancers in both male and female mice. The skin structure was also affected by gender effect as well as the AR inactivation and could at least partly explain the different responses between the carcinogenesis models (systemic vs. topical). In addition, AR inactivation modified
Cox-1
and
Cox-2
expression in the skin, suggesting possible molecular mechanism for the AR effect on skin. Finally, some gender differences are observed also in ARKO mice insensitive to androgens, suggesting that factors other than androgens also play a role in gender-dependent skin carcinogenesis.
The PHENIX online computing system Purschke, M.L.; Adler, S.; Desmond, E. ...
IEEE transactions on nuclear science,
04/2000, Volume:
47, Issue:
2
Journal Article
Peer reviewed
The Online Computing System (ONCS) is responsible for the overall configuration and control of the PHENIX detector system. The experiment is made up of 4 spectrometer arms with a total number of 11 ...subdetectors, which need to be operated by a single control and monitoring system. This includes the configuration of the individual components of the readout system, as well as the control of the state of the detector's data flow. Furthermore, the ONCS system sets up the environment for the online monitoring of the detectors. The slow control of high voltages and other ancillary devices is also part of the system. The ONCS system is designed around a distributed computing model which relies on CORBA object oriented technology, the ROOT system as the backbone of the online monitoring, and EPICS for the control of the High Voltage systems. Issues regarding the use and implementation of these technologies in the ONCS system are discussed, as well as the methods used to control the state and health of the PHENIX detector.
The work presented here is part of an overall voltammetric design system with a silicon based disposable component for the determination of copper, cadmium, lead and zinc. Voltammetric (the ...measurement of current as a function of potential) methods of analysis are attractive for determinations of trace metals. They offer a combination of simple low cost instrumentation with excellent sensitivity and detection limits, comparable to those obtainable with instruments costing orders of magnitude greater. The system consists of electrodes, an application specific integrated circuit (ASIC) and software control. Screen-printed silver/silver chloride and carbon electrodes are used in the preparation of mercury film electrodes on which anodic stripping voltammetry is performed for the detection of the four heavy metals listed above. Work has also been carried out to investigate calibration problems caused by the formation of intermetallic complexes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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