Effects of WB4101 and chloroethylclonidine on the positive and negative inotropic actions of phenylephrine in rat cardiac muscle

This study was designed to determine if the positive and negative inotropic actions of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium are mediated via different alpha-1-adrenergic receptor (AR) subtypes. Inotropic effects of phenylephrine were examined in isolated left atrial and papillary muscle before and after treatment with prazosin, WB4101 (N-[2-(2,6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine), chloroethylclonidine (CEC) and WB4101 plus CEC. Phenylephrine (10 microM) elicited a monophasic positive inotropic response in left atrial muscle and a triphasic inotropic action in papillary muscle (transient positive, then negative inotropic components preceding a sustained positive inotropic response). CEC, WB4101 and prazosin each antagonized the monophasic response in isolated left atria and the sustained positive inotropic response in papillary muscle. CEC and prazosin each antagonized the transient negative inotropic component in papillary muscle. The transient positive inotropic response was not affected by CEC, WB4101 or CEC plus WB4101, but was antagonized by higher concentrations of prazosin. These data suggest that the sustained positive inotropic effect of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of alpha-1A and alpha-1B ARs, whereas the transient negative inotropic component of the triphasic response in ventricular preparations is mediated via alpha-1B ARs. However, present data do not exclude the possibility that the CEC-sensitive inotropic responses elicited by phenylephrine may be mediated in part by other recently described alpha-1 subtypes. The receptors involved in the transient positive inotropic action cannot be identified by current results.     

A characterization of the stochastic process underlying astochastic Petri net

Stochastic Petri nets (SPN's) with generally distributed firing times can model a large class of systems, but simulation is the only feasible approach for their solution. We explore a hierarchy of SPN classes where modeling power is reduced in exchange for an increasingly efficient solution. Generalized stochastic Petri nets (GSPN's), deterministic and stochastic Petri nets (DSPN's), semi-Markovian stochastic Petri nets (SM-SPN's), timed Petri nets (TPN's), and generalized timed Petri nets (GTPN's) are particular entries in our hierarchy. Additional classes of SPN's for which we show how to compute an analytical solution are obtained by the method of the embedded Markov chain (DSPN's are just one example in this class) and state discretization, which we apply not only to the continuous-time case (PH-type distributions), but also to the discrete case     

The CD40 TRAF family member interacting motif carries the information to rescue WEHI 231 cells from anti-IGM-induced growth arrest

Engagement of the antigen receptor on WEHI 231 murine B lymphoma cells leads to growth arrest and induction of apoptosis. Concomitant signaling through CD40 sustains proliferation and rescues the cells from apoptosis. At the molecular level, CD40 has been shown to activate nuclear factor kappaB (NF-kappaB) and stress-activated protein kinase (SAPK). The aim of our present study was to define the stretch of the CD40 cytoplasmic tail responsible for mediating these effects in WEHI 231 cells. Using recombinant retroviruses with the enhanced green fluorescent protein as selection marker we transduced WEHI 231 cells with chimeric molecules consisting of the extracellular and transmembrane region of human CD40 or rat CD4 and selected portions of the murine CD40 tail. Chimeric molecules with cytoplasmic fragments encompassing the "CD40 tumor necrosis factor-associated factor family member interacting motif" (TIM) were able to sustain growth and to uphold NF-kappaB activity as efficiently as the whole intracellular region of CD40. While the potential of the motif relative to the whole cytoplasmic tail was independent of the heterologous part of the chimeras it was strongly influenced by its distance to the membrane. Placing the 17-amino acid stretch of the motif too close to the membrane, i. e. only two or four amino acids apart, destroyed its capacity to mitigate the anti-IgM effect. Activation of SAPK through the chimeric molecules always correlated with their ability to activate NF-kappaB activity and to rescue the cells from apoptosis induced by antigen receptor ligation. Our data indicate that CD40-TIM carries most if not all of the information needed to deliver the signals responsible for sustaining growth in anti-IgM-stimulated WEHI 231 cells.     

The autonomy-safety-paradox of service robotics in Europe and Japan: a comparative analysis

Service and personal care robots are starting to cross the threshold into the wilderness of everyday life, where they are supposed to interact with inexperienced lay users in a changing environment. In order to function as intended, robots must become independent entities that monitor themselves and improve their own behaviours based on learning outcomes in practice. This poses a great challenge to robotics, which we are calling the “autonomy-safety-paradox” (ASP). The integration of robot applications into society requires the reconciliation of two conflicting aspects: increasing machine autonomy and ensuring safety in end-use. As the level of robot autonomy grows, the risk of accidents will increase, and it will become more and more difficult to identify who is responsible for any damage incurred. However, emphasizing safety impairs the autonomous functioning of the robot. This problem implies the need for a broadened concept of product safety. Our comparative study shows that the institutional framing of the ASP as well as concrete solutions to this problem differs between Europe and Japan in two respects: (1) the understanding of robot agency and (2) the concept of “appropriate” user–robot interaction.     

Physical chemical properties of solutions of bis-quaternary ammonium bromides

The physical chemical properties of a series of bisalkyldimethyldi-ammonium polyoxyethylene bromides were studied by measuring the critical micelle concentrations as function of their molecular structure. The conductivity vs. concentration plots revealed the existence of two distinct discontinuities which were labeled CMC1 and CMC2. The CMC1 was always lower than the CMC2. The conventional surface tension vs. log concentration curve showed the classical sharp break which coincided with either the CMC1 or the CMC2, but failed to reveal the presence of both critical micelle concentrations in the same experiment. The existence of two CMC2 was attributed to the presence of the two charges localized in separated atoms. The CMC1 and CMC2 appear to follow an expression of the type CMC=A —Bn, where A and B are constants and n the number of carbon atoms present in the hydrocarbon long chain attached to the quaternary ammonium nitrogen. The CMCs appear to increase with the increasing number of oxyethylene residues up to a certain length of the polyoxyethylene chain. For most compounds there was a substantial drop in surface tension with the increasing concentration of the salt. However, some compounds containing only one oxyethylene residue showed practically no surface tension dependence on concentration although the critical micelle concentrations were apparent in the conductivity vs. concentration curve. The energy to transfer one methylene group from the aqueous to the micellar phase was found to vary from −0.57 kT to −0.84 kT. The alkylene oxylated bisquaternary bromides studied appear to have unusual physical chemical properties.     

Male Pheromones Influence the Mating Behavior of <Emphasis Type="Italic">Echinothrips americanus</Emphasis>

Two dibasic esters, the dimethyl ester of hexanedioic acid (dimethyl adipate, DBE-6) and the dimethyl ester of pentanedioic acid (dimethyl glutarate, DBE-5) were found in head-thorax extracts of male Echinothrips americanus. DBE-5 induced abdomen wagging and raising in males and females, which is typically exhibited when encountering a male. DBE-6 was avoided by males and was detected on mated, but not on virgin, females. Both substances applied to virgin females lead to females being ignored by males. The role of both substances is discussed with regard to the male mating system.     

组合营销 德国玩具销售新趋势

德国不仅是欧洲重要的国家,在世界经济体系中也举足轻重,纽伦堡玩具展就是世界最大的玩具展。德国的玩具市场和厂商的玩具营销都是很成熟的。由当地从事玩具市场推广战略研究的Lindemann先生撰写的文章,可以说是最新的资讯和分析,这对了解和借鉴德国现代的玩具营销,繁荣玩具内销市场很有益处。     

Insight into the decomposition pathway of the complex hydride Al3Li4(BH4)13

The decomposition pathway of the complex hydride Al₃Li₄(BH₄)₁₃ is in the focus of this study. Initially the compound attracted great interest due to its high H₂ capacity (17.2 wt.%) and desorption at moderate temperatures (<100 °C). This work sheds light on its decomposition reaction by a unique experimental setup of thermogravimetry combined with spectroscopic gas phase analysis (FT-IR and MS) at ambient conditions. It is observed that the compound itself is metastable and decomposes immediately into its components, solid LiBH₄ and Al(BH₄)₃ which is monitored in the gas phase. Carbon addition decreases the observed mass loss and the spectroscopic gas phase analysis is used to learn about the impact of carbon addition.     

Aminoglycoside 3'‐phosphotransferase II (APH(3')II): Review of its safety and use in the production of genetically engineered plants

Calgene conducted a thorough review and analysis of the use of the kan^r gene and gene product, aminoglycoside 3'‐phosphotransferase II (APH(3')II), for use as a selectable marker in FLAVR SAVR? tomatoes, in BXN? cotton and oil‐modified rapeseed. The data generated support the conclusions that APH(3')II is not a toxin or allergen, that the kan ^r gene is highly unlikely to move from the plant genome into microorganisms via horizontal gene transfer, that if such transfer could occur the impact would be minimal, and that APH(3')II in transgenic plants will not compromise antibiotic use in humans or animals.

At FDA's Food Advisory Committee meeting on April 6–8, 1994, the FDA Center for Food Safety and Applied Nutrition (CFSAN) concluded that the FLAVR SAVR tomato was as safe and nutritious as other commonly consumed tomatoes and “that the use of the kan^r gene and APH(3')II will not have a significant impact on the environment and that an environmental impact statement is not required.”; On May 18, 1994, the FDA finished its safety review of the FLAVR SAVR tomato and APH(3')II. The FDA concluded that “FLAVR SAVR? tomatoes have not been significantly altered when compared to varieties of tomatoes with a history of safe use”; (Federal Register 59: 26646) and “that the use of aminoglycoside 3'‐phosphotransferase II is safe for use as a processing aid in the development of new varieties of tomato, oilseed rape, and cotton intended for food use”; (Federal Register 59: 26700).