Home About us Contact
|
Home About us Contact | ||
|
|
||
Proposed Mechanism (proposed + mechanism)
Selected AbstractsA Proposed Mechanism for the Reductive Ring Opening of the Cyclodiphosphate MEcPP, a Crucial Transformation in the New DXP/MEP Pathway to Isoprenoids Based on Modeling Studies and Feeding ExperimentsCHEMBIOCHEM, Issue 3 2004Wolfgang Brandt Dr. Abstract Experimental and theoretical investigations concerning the second-to-last step of the DXP/MEP pathway in isoprenoid biosynthesis in plants are reported. The proposed intrinsic or late intermediates 4-oxo-DMAPP (12) and 4-hydroxy-DMAPP (11) were synthesized in deuterium- or tritium-labeled form according to new protocols especially adapted to work without protection of the diphosphate moiety. When the labeled compounds MEcPP (7), 11, and 12 were applied to chromoplast cultures, aldehyde 12 was not incorporated. This finding is in agreement with a mechanistic and structural model of the responsible enzyme family: a three-dimensional model of the fragment L271,A375 of the enzyme GcpE of Streptomyces coelicolor including NADPH, the Fe4S4cluster, and MEcPP (7) as ligand has been developed based on homology modeling techniques. The model has been accepted by the Protein Data Bank (entry code 1OX2). Supported by this model, semiempirical PM3 calculations were performed to analyze the likely catalysis mechanism of the reductive ring opening of MEcPP (7), hydroxyl abstraction, and formation of HMBPP (8). The mechanism is characterized by a proton transfer (presumably from a conserved arginine 286) to the substrate, accompanied by a ring opening without high energy barriers, followed by the transfer of two electrons delivered from the Fe4S4cluster, and finally proton transfer from a carboxylic acid side chain to the hydroxyl group to be removed from the ligand as water. The proposed mechanism is in agreement with all known experimental findings and the arrangement of the ligand within the enzyme. Thus, a very likely mechanism for the second to last step of the DXP/MEP pathway in isoprenoid biosynthesis in plants is presented. A principally similar mechanism is also expected for the reductive dehydroxylation of HMBPP (8) to IPP (9) and DMAPP (10) in the last step. [source] Proposed mechanism of inactivating Escherichia coli O157:H7 by ultra-high pressure in combination with tert -butylhydroquinoneJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2008A.S. Malone Abstract Aims:, Investigating mechanisms of lethality enhancement when Escherichia coli O157:H7, and selected E. coli mutants, were exposed to tert -butylhydroquinone (TBHQ) during ultra-high pressure (UHP) treatment. Methods and Results:,Escherichia coli O157:H7 EDL-933, and 14 E. coli K12 strains with mutations in selected genes, were treated with dimethyl sulfoxide solution of TBHQ (15,30 ppm), and processed with UHP (400 MPa, 23 ± 2°C for 5 min). Treatment of wild-type E. coli strains with UHP alone inactivated 2·4,3·7 log CFU ml,1, whereas presence of TBHQ increased UHP lethality by 1·1,6·2 log CFU ml,1; TBHQ without pressure was minimally lethal (0,0·6 log reduction). Response of E. coli K12 mutants to these treatments suggests that iron,sulfur cluster-containing proteins ([Fe,S]-proteins), particularly those related to the sulfur mobilization (SUF system), nitrate metabolism, and intracellular redox potential, are critical to the UHP,TBHQ synergy against E. coli. Mutations in genes maintaining redox homeostasis and anaerobic metabolism were associated with UHP,TBHQ resistance. Conclusions:, The redox cycling activity of cellular [Fe,S]-proteins may oxidize TBHQ, potentially leading to the generation of bactericidal reactive oxygen species. Significance and Impact of the Study:, A mechanism is proposed for the enhanced lethality of UHP by TBHQ against E. coli O157:H7. The results may benefit food processors using UHP,based preservation, and biologists interested in piezophilic micro-organisms. [source] Contribution of ROCK in contraction of trabecular meshwork: Proposed mechanism for regulating aqueous outflow in monkey and human eyesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2005Emi Nakajima Abstract Aqueous outflow in the conventional outflow pathway is regulated by the contraction and relaxation of the ciliary muscle (CM) and the trabecular meshwork (TM). Rho-associated coiled coil-forming protein kinase (ROCK) is thought to regulate actomyosin-based contractility in many types of cells by phosphorylation of ROCK substrates. In animal models, ROCK inhibitor Y-39983 relaxed CM and TM and decreased intraocular pressure (IOP). Thus, ROCK is implicated in the regulation of aqueous outflow and IOP. However, the site of action of ROCK in monkey and man is unknown. In the present communication, RT-PCR analysis of monkey tissues showed higher levels of mRNAs for ROCK and ROCK substrates in TM compared to CM. Human TM also showed higher levels of mRNAs for ROCK and ROCK substrates compared to CM. Differences between TM and CM in human were not as high as in monkey. ROCK inhibitor Y-39983 led to a dose-dependent relaxation of carbachol-induced, contracted TM from monkey. In contrast, Y-39983 was only slightly effective in relaxing CM. Our results suggested that TM was one of the major sites for regulating IOP by ROCK. ROCK inhibitor Y-39983 might be a candidate drug for lowering IOP by increasing conventional outflow and producing fewer side effects on accommodation and miosis. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:701,708, 2005 [source] Topical vitamins, minerals and botanical ingredients as modulators of environmental and chronological skin damageBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2003A. Chiu Summary Ageing skin is characterized by fine lines, wrinkles, lentigines, dyspigmentation and increased coarseness. Topical preparations alleged to combat these changes abound in the over-the-counter market. Some of the most popular ingredients used in these products are vitamins, minerals and botanical extracts. Proposed mechanisms for antiageing effects on skin range from antioxidant properties to improved collagen synthesis or protection from collagen breakdown. Despite the media attention and consumer popularity that these ingredients have generated, there have been few scientific studies to support these claims. In this report, we review recent published studies on the most common of these ingredients for the topical photoprotection and the treatment of ageing skin. [source] Protein-Losing Enteropathy after Fontan OperationCONGENITAL HEART DISEASE, Issue 5 2007Jack Rychik MD ABSTRACT Protein-losing enteropathy (PLE) is a poorly understood and enigmatic disease process affecting patients with single ventricle after Fontan operation. In those afflicted, PLE after Fontan operation results in significant morbidity and mortality. The pathophysiology of the disease is unknown; however, a proposed mechanism incorporates a combination of phenomena including: (1) altered hemodynamics, specifically low cardiac output; (2) increased mesenteric vascular resistance; (3) systemic inflammation; and (4) altered enterocyte basal membrane glycosaminoglycan make-up. A paradigm for the clinical management of PLE after Fontan operation is proposed. [source] A proposed mechanism for cell polarization with no external cuesCYTOSKELETON, Issue 2 2004Barbara W. Bernstein First page of article [source] Novel treatments for autistic spectrum disordersDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2005Susan E. Levy Abstract In no area of developmental pediatric practice is there more controversy regarding the choice of treatment than related to children with autistic spectrum disorders (ASD). Complementary and alternative medical therapies (CAM) are often elected because they are perceived as treating the cause of symptoms rather than the symptoms themselves. CAM used for autism can be divided by proposed mechanism: immune modulation, gastrointestinal, supplements that affect neurotransmitter function, and nonbiologic intervention. Secretin as a therapy for autism is discussed as an example of how a clinical observation rapidly grew to a widespread treatment before well-designed studies demonstrated absence of effect. The plausibility for behavioral effect was not substantiated by clinical studies. CAM used for treatment of autism is examined in terms of rationale, evidence of efficacy, side effects, and additional commentary. Families and clinicians need access to well-designed clinical evidence to assist them in choice of therapies. © 2005 Wiley-Liss, Inc. MRDD Research Reviews 2005;11:131,142. [source] A study on video performance of multipoint-to-point video streaming with multiple description coding over ad hoc networksELECTRICAL ENGINEERING IN JAPAN, Issue 4 2010Keisuke Utsu Abstract Supporting multimedia applications over wireless networks has become a very active research topic recently because video applications are forecast to receive high demand in future wireless networks, such as ad hoc networks. However, enabling video transmission over wireless ad hoc networks is more challenging than over other wireless networks due to node mobility, interference, and the absence of a supporting infrastructure. This paper addresses the problem of video transmission over ad hoc networks. We propose to combine Multiple Description Coding (MDC) with multiple source transport (Multipoint-to-Point transfer: MP2P) in order to maintain smooth video streaming over wireless ad hoc networks. In this paper, we describe a comprehensive simulation and test bed experiment designed to show the effect of the proposed MP2P video transfer with MDC for two description cases of video streaming over wireless ad hoc networks. The results show that the proposed mechanism successfully improves video transfer performance in terms of video packet reachability and throughput. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 170(4): 43,50, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20999 [source] Embryonic Arrhythmia by Inhibition of HERG Channels: A Common Hypoxia-related Teratogenic Mechanism for Antiepileptic Drugs?EPILEPSIA, Issue 5 2002Faranak Azarbayjani Summary: ,Purpose: There is evidence that drug-induced embryonic arrhythmia initiates phenytoin (PHT) teratogenicity. The arrhythmia, which links to the potential of PHT to inhibit a specific potassium channel (Ikr), may result in episodes of embryonic ischemia and generation of reactive oxygen species (ROS) at reperfusion. This study sought to determine whether the proposed mechanism might be relevant for the teratogenic antiepileptic drug trimethadione (TMO). Methods: Effects on embryonic heart rhythm during various stages of organogenesis were examined in CD-1 mice after maternal administration (125,1,000 mg/kg) of dimethadione (DMO), the pharmacologically active metabolite of TMO. Palatal development was examined after administration of a teratogenic dose of DMO and after simultaneous treatment with DMO and a ROS-capturing agent (,-phenyl- N -tert-butyl-nitrone; PBN). The Ikr blocking potentials of TMO and DMO were investigated in HERG-transfected cells by using voltage patch-clamping tests. Results: DMO caused stage-specific (gestation days 9,13 only) and dose-dependent embryonic bradycardia and arrhythmia at clinically relevant maternal plasma concentrations (3,11 mM). Hemorrhage in the nasopharyngeal part of the embryonic palate (within 24 h) preceded cleft palate in fetuses at term. Simultaneous treatment with PBN significantly reduced the incidence of DMO-induced cleft palate, from 40 to 13%. Voltage patch-clamping studies showed that particularly DMO (70% inhibition), but also TMO, had Ikr blocking potential at clinically relevant concentrations. Conclusions: TMO teratogenicity, in the same way as previously shown for PHT, was associated with Ikr -mediated episodes of embryonic cardiac arrhythmia and hypoxia/reoxygenation damage. [source] A Novel Approach to 2-Chloro-2-fluorostyrenesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2003Valentine G. Nenajdenko Abstract A new general catalytic olefination reaction (COR) of aromatic and heteroaromatic aldehydes and ketones was applied to synthesise 2-chloro-2-fluorostyrenes. The two-stage procedure includes the transformation of carbonyl compounds into hydrazones followed by treatment with CFCl3 mediated by copper catalysis. Trichlorofluoromethane was used as a chlorofluoromethylene transfer reagent. The reaction proceeds stereoselectively and the target alkenes were obtained in high yield. A proposed mechanism for the reaction is discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Changes in spawning stock structure strengthen the link between climate and recruitment in a heavily fished cod (Gadus morhua) stockFISHERIES OCEANOGRAPHY, Issue 3 2006GEIR OTTERSEN Abstract Atlantic cod (Gadus morhua) is one of the commercially most important fish species in the North Atlantic and plays a central role in several ecosystems. Fishing pressure has been heavy over a prolonged period and the recent decades have shown dramatic decline in abundance of many stocks. The Arcto-Norwegian (or North-east Arctic) cod stock in the Barents Sea is now the largest stock of Atlantic cod. Recruitment to this stock has varied extensively during the last 60 yr. There is evidence for fluctuations in climate, particularly sea temperature, being a main cause for this variability, higher temperatures being favourable for survival throughout the critical early life stages. Our studies of time series present compelling evidence for a strengthening of the climate,cod recruitment link during the last decades. We suggest this is an effect of the age and length composition of the spawning stock having changed distinctly. The age of the average spawner has decreased by more than 3 yr from between 10 and 11 in the late 1940s to 7,8 in the 1990s, average length from just above 90 cm to around 80 cm. The number of age classes contributing to the spawning stock has also decreased, while the number of length groups present increased slightly. Significant decrease in age of spawners has frequently been described for other heavily fished stocks worldwide. We therefore find it likely that the proposed mechanism of increased influence of climate on recruitment through changes in the spawning stock age and size composition is of a general nature and might be found in other systems. [source] The platelet as a peripheral marker in psychiatric illnessHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2001Helein Plein Abstract The identification of peripheral markers of psychiatric illness is important if an improvement in the diagnosis and treatment of various diseases with overlapping symptomatology is desired. There are many disorders that not only have overlapping symptomatology, but also have similar biological disturbances. The functional capability of the neurons involved in the disease processes may be at the crux of the underlying pathology. The platelet intracellular calcium response to neurotransmitter stimulation has previously been used as a peripheral marker of psychiatric illness. This review discusses evidence in support of the extended use of the platelet as a peripheral marker. The use of the platelet intracellular calcium response to neurotransmitter stimulation as a state or trait marker in major depression, the specificity and selectivity of this response, and the possible use of the platelet as a peripheral marker in psychotic disorders such as schizophrenia, mania and psychotic depression are shown. Finally, a proposed mechanism for the association between certain psychiatric disorders and cardiovascular disease is discussed. Copyright © 2001 John Wiley & Sons, Ltd. [source] CD20-mediated apoptosis: signalling through lipid raftsIMMUNOLOGY, Issue 2 2002Julie P. Deans Summary CD20 is an effective target for therapeutic B-cell depletion with monoclonal antibodies. One proposed mechanism of action is direct cytotoxicity mediated via tyrosine kinase-dependent signalling pathways activated upon CD20 cross-linking. The association of CD20 with membrane microdomains known as lipid rafts, enriched in src-family tyrosine kinases and other signalling effectors, suggests an indirect mechanism of anti-CD20-induced apoptosis in which activation of src-family kinases occurs as a consequence of lipid raft clustering. [source] Kinetics and mechanism of the oxidation of 4-methyl-3-thiosemicarbazide by acidic bromate,INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2002Sreekantha B. Jonnalagadda The oxidation of 4-methyl-3-thiosemicarbazide (MTSC) by bromate and bromine was studied in acidic medium. The stoichiometry of the reaction is extremely complex, and is dependent on the ratio of the initial concentrations of the oxidant to reductant. In excess MTSC and after prolonged standing, the stoichiometry was determined to be H3CN(H)CSN(H)NH2 + 3BrO3, , 2CO2 + NH4+ + SO42, + N2 + 3Br, + H+ (A). An interim stoichiometry is also obtained in which one of the CO2 molecules is replaced by HCOOH with an overall stoichiometry of 3H3CN(H)CSN(H)NH2 + 8BrO3, , CO2 + NH4+ + SO42, + HCOOH + N2 + 3Br, + 3H+ (B). Stoichiometry A and B are not very different, and so mixtures of the two were obtained. Compared to other oxidations of thiourea-based compounds, this reaction is moderately fast and is first order in both bromate and substrate. It is autocatalytic in HOBr. The reaction is characterized by an autocatalytic sigmoidal decay in the consumption of MTSC, while in excess bromate conditions the reaction shows an induction period before autocatalytic formation of bromine. In both cases, oxybromine chemistry, which involves the initial formation of the reactive species HOBr and Br2, is dominant. The reactions of MTSC with both HOBr and Br2 are fast, and so the overall rate of oxidation is dependent upon the rates of formation of these reactive species from bromate. Our proposed mechanism involves the initial cleavage of the CN bond on the azo-side of the molecule to release nitrogen and an activated sulfur species that quickly and rapidly rearranges to give a series of thiourea acids. These thiourea acids are then oxidized to the sulfonic acid before cleavage of the CS bond to give SO42,, CO2, and NH4+. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 237,247, 2002 [source] An adaptive joining mechanism for improving the connection ratio of ZigBee wireless sensor networksINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 2 2010Tien-Wen Sung Abstract Wireless sensor networks (WSNs) are well suited to many applications, including environment surveillance and target tracking. ZigBee is an IEEE 802.15.4-based standard that is considered suitable for WSNs. The functional operations of a ZigBee network rely on self-organized network connections and the proper deployment of sensor devices. However, the devices comprising a ZigBee network may become isolated from the network after the joining phase due to the configuration constraints of the ZigBee standard. This means that some deployed devices cannot join the network even though they can communicate with other joined nodes. These isolated devices reduce the efficiency of network operation and increase deployment costs. This paper proposes a ZigBee-compatible adaptive joining mechanism with connection shifting schemes to improve the connectivity of ZigBee networks, allowing them to operate at the expected efficiency. Simulation results show that the proposed mechanism significantly improves the join ratio of deployed sensor devices in ZigBee WSNs. Copyright © 2009 John Wiley & Sons, Ltd. [source] MLCC: A new hash-chained mechanism for multicast source authenticationINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 9 2009H. Eltaief Abstract Asymmetric cryptography has been widely used to generate a digital signature for message authentication. However, such a strategy cannot be used for packet authentication. Neither the source nor the receiver will be capable of handling the computational cost of asymmetric cryptography. For unicast communication, the solution adopted is based on symmetric cryptography. Solutions based on symmetric cryptography do not scale for multicast communication. Several solutions have been reported to authenticate multicast streams, with the possibility of packet losses. Proposed solutions are based on the concept of signature amortization, where a single signature is amortized on several packets. In this paper we present a new mechanism for multicast data source authentication based on signature amortization. Multi-layers connected chains divides the packet stream into a multi-layer structure, where each layer is a two-dimensional matrix. The hash of a packet is included into a forward chain of packets within the same layer as well as a downward chain of packets across multiple layers. The values of the key parameters that influence the mechanism efficiency as well as its performance are selected following a mathematical analysis. Comparisons of performance results with the well-known efficient multi-chained stream signature scheme as well as a recently reported scheme multiple connected chains model show that the proposed mechanism achieves a stronger resistance to packet losses with low overhead and high authentication probability. Copyright © 2008 John Wiley & Sons, Ltd. [source] Increasing the throughput of HomePNAINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 7 2008Aurelio Amodei Jr Abstract In this paper we propose a new medium access mechanism for HomePNAv2 and HomePNAv3 standards. This mechanism uses a priority aggregation mechanism to avoid collisions, increasing these protocols throughput. Furthermore, this mechanism does not require modifying standards, since it can be implemented over their actual MAC sublayers. Simulation results show that the proposed mechanism is able to increase the throughput up to 44% for HomePNAv2 and 36% for HomePNAv3. Moreover, we also show how this mechanism affects network delay, analyzing average delay and jitter for all protocols presented. Copyright © 2008 John Wiley & Sons, Ltd. [source] Multimedia transmission with adaptive QoS based on real-time protocolsINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 3 2003Ch. Bouras Abstract In this paper, we describe a mechanism for adaptive transmission of multimedia data, which is based on real-time protocols. The proposed mechanism can be used for unicast or multicast transmission of multimedia data over heterogeneous networks, like the Internet, and has the capability to adapt the transmission of the multimedia data to network changes. In addition, the implemented mechanism uses an inter-receiver fairness function in order to treat the group of clients with fairness during the multicast transmission in a heterogeneous environment. The proposed mechanism uses a ,friendly' to the network users congestion control policy to control the transmission of the multimedia data. We implement a prototype application based on the proposed mechanism and we evaluate the proposed mechanism both in unicast and multicast transmission through a number of experiment and a number of simulations in order to examine its fairness to a group of clients and its behaviour against transport protocols (TCP) and UDP data streams. Copyright © 2003 John Wiley & Sons, Ltd. [source] Sonochemical Synthesis of CdSe Hollow Spherical Assemblies Via an In-Situ Template RouteADVANCED MATERIALS, Issue 2 2003J.J. Zhu CdSe hollow spherical assemblies composed of 5 nm nanoparticles have been synthesized sonochemically. During the process, amorphous Cd(OH)2, which acts as the in-situ template, directs the growth of primary CdSe nanoparticles on its surface and their assembly into hollow spherical structures. The Figure is a schematic of the proposed mechanism for the formation of the hollow chalcogenide spheres. [source] Catalytic Dicyanative 5- exo- and 6- endo -Cyclization Triggered by Cyanopalladation of AlkynesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 5 2010Shigeru Arai Abstract A stereoselective dicyanative 5- exo- and 6- endo -cyclization using various enynes has been investigated. The mode of cyclization is critically controlled by the structure of the substrates. For example, N -allyl derivatives prefer 5- exo -cyclization, while methacryloyl amides are transformed to the corresponding lactams with tetra -substituted carbons at the alpha-position via 6- endo -cyclization. Both reactions include syn -cyanopalladation to carboncarbon triple bonds in the initial step, and sequential cyclization followed by reductive elimination in one operation enables the construction of the highly functionalized nitrogen heterocycles. The scope of suitable substrates and a proposed mechanism are also described. [source] The First General and Selective Palladium(II)-Catalyzed Alkoxycarbonylation of Arylboronates: Interplay among Benzoquinone-Ligated Palladium(0) Complex, Organoboron, and Alcohol SolventADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 2-3 2010Yoshihiko Yamamoto Abstract Methoxycarbonylation of aryl- and alkenylboron compounds was performed using the palladium(II) acetate/triphenylphosphine [Pd(OAc)2/PPh3] catalyst with p -benzoquinone as a stoichiometric oxidant in methanol at ambient temperature to obtain the corresponding methyl esters in good yields. A wide variety of functional groups including various carbonyl functionalities, nitrile, nitro, sulfone, and unprotected pyrrole rings were tolerated in the methoxycarbonlation, while the use of higher alcohols except for tert -butanol afforded various p -chlorobenzoates in moderate to high yields. The catalytic alkoxycarbonylation proceeded without any acid or base additive, and an oxidative transmetalation step is proposed to explain the exceptional efficacy of this protocol. DFT and MP2 calculations support the proposed mechanism. [source] Theoretical ab initio study of NO and CO depollution reaction catalyzed by copperINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 6 2001O. Bouhlel Abstract The reaction between NO and CO leading to N2 and CO2 is the most studied depollution process of the former molecules. An ab initio study of a multistage mechanism of this reaction catalyzed by copper was performed at SCF level. Many intermediates intervene in the proposed mechanism, such as CuCO, CuNO, CuO, and NCO. Geometrical parameters, atomic charge, dipole moment, vibrational normal mode wave number, and dissociation energy of intervening molecules were calculated. Thermochemistry parameters (,H, ,G, ,S) were also obtained. Transition state has also been determined and has allowed us to discuss the reaction mechanism. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001 [source] Activation of Elemental Sulfur by Electrogenerated Cyanomethyl Anion: Synthesis of Substituted 2-Aminothiophenes by the Gewald ReactionADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 17 2008Marta Feroci Abstract The activation of elemental sulfur (S8) has been achieved by means of electrogenerated cyanomethyl anion [easily obtained by galvanostatic reduction from acetonitrile/tetraethylammonium hexafluorophosphate (MeCN-Et4NPF6)]. The "activated" sulfur reacted with ylidenemalononitriles to give substituted 2-aminothiophenes in very high yields. This variation of the Gewald reaction has been carried out using only catalytic amounts of electricity and supporting electrolyte. A proposed mechanism for the interaction between S8 and cyanomethyl anion is described. [source] Electrophysiological Basis and Genetics of Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2005AUGUSTUS O. GRANT M.B.Ch.B., Ph.D. Brugada syndrome is a primary arrhythmic syndrome arising in the structurally normal heart. Any proposed mechanism should account for the major features of the syndrome: localization of the ST segment and T-wave changes to the right precordial leads, association of conduction slowing at several levels, precipitation or aggravation of the major ECG changes by sodium channel-blocking drugs and the occurrence of ventricular fibrillation. Heterogeneity of repolarization across the ventricle wall plays a major role. Any agency that shifts the net current gradient during phase I outward would exaggerate the normal heterogeneity of repolarization and result in the ST segment and T-wave changes characteristic of the syndrome. When the outward current shift is marked, premature repolarization may occur in epicardial zone and the resulting gradient may precipitate reentry. The syndrome is inherited as an autosomal dominant. However, 75% of clinically affected individuals are males. In 20% of cases, the syndrome is associated with mutations of the cardiac sodium channel gene SCN5A. The mutations result in a loss-of-function as a result of the synthesis of a non-functional protein, altered protein trafficking, or change in gating. Agencies that reduce the sodium current may precipitate the characteristic ECG changes, for example, sodium channel blockers and membrane depolarization by hyperkalemia. Sympathetic stimulation may reverse the ECG changes and reduce arrhythmia recurrence. By its nonspecific potassium channel blocking action, quinidine may also reduce arrhythmia recurrence. We still do not know the basis for defect in the majority of patients with Brugada syndrome. [source] Design and Control of a Four-Wheeled Omnidirectional Mobile Robot with Steerable Omnidirectional WheelsJOURNAL OF FIELD ROBOTICS (FORMERLY JOURNAL OF ROBOTIC SYSTEMS), Issue 4 2004Jae-Bok Song Omnidirectional mobile robots are capable of arbitrary motion in an arbitrary direction without changing the direction of wheels, because they can perform 3 degree-of-freedom (DOF) motion on a two-dimensional plane. In this research, a new class of omnidirectional mobile robot is proposed. Since it has synchronously steerable omnidirectional wheels, it is called an omnidirectional mobile robot with steerable omnidirectional wheels (OMR-SOW). It has 3 DOFs in motion and one DOF in steering. One steering DOF can function as a continuously variable transmission (CVT). CVT of the OMR-SOW increases the range of velocity ratio from the wheel velocities to robot velocity, which may improve performance of the mobile robot. The OMR-SOW with four omnidirectional wheels has been developed in this research. Kinematics and dynamics of this robot will be analyzed in detail. Various tests have been conducted to demonstrate the validity and feasibility of the proposed mechanism and control algorithm. © 2004 Wiley Periodicals, Inc. [source] Do anticoagulants improve survival in patients presenting with venous thromboembolism?JOURNAL OF INTERNAL MEDICINE, Issue 6 2003J. Kelly Abstract. Anticoagulants have been available since around 1940 and have become the standard of treatment for venous thromboembolism (VTE) for over four decades. However, as with other treatments which became established before the evidence-based era, there is a paucity of evidence from randomized controlled trials validating their effectiveness in preventing the most feared complication of VTE, recurrent fatal pulmonary embolism (PE). Only two such trials have been performed, the results of which conflict. The bulk of data supporting their use are derived from three sources. First, studies of thromboprophylaxis, and comparisons of shorter and longer courses of anticoagulants in high-risk patients with established VTE have clearly demonstrated their effectiveness in primary and late secondary prevention. Given that heparin has an immediate onset of action, anticoagulants should therefore also be effective in early secondary prevention, the proposed mechanism of action in the acute treatment of VTE. Secondly, studies of inadequately treated patients have consistently shown higher recurrence rates than in those adequately treated. Finally, comparisons of outcomes in untreated and treated historical series, and of untreated historical series to treated series in the modern era have shown substantially lower rates of fatal PE in anticoagulated patients. Because these differences are so marked, harmonize with our current understanding of the mechanism of action of anticoagulants and are supported by other evidence, it is much more likely that they at least partly reflect the effectiveness of anticoagulants as opposed to being explicable purely in terms of accumulated biases and a changing distribution of disease severity. [source] Plasma serotonin levels and the platelet serotonin transporterJOURNAL OF NEUROCHEMISTRY, Issue 1 2007B. Brenner Abstract Serotonin (5HT) is a platelet-stored vasoconstrictor. Altered concentrations of circulating 5HT are implicated in several pathologic conditions, including hypertension. The actions of 5HT are mediated by different types of receptors and terminated by a single 5HT transporter (SERT). Therefore, SERT is a major mechanism that regulates plasma 5HT levels to prevent vasoconstriction and thereby secure a stable blood flow. In this study, the response of platelet SERT to the plasma 5HT levels was examined within two models: (i) in subjects with chronic hypertension or normotension; (ii) on platelets isolated from normotensive subjects and pretreated with 5HT at various concentrations. The platelet 5HT uptake rates were lower during hypertension due to a decrease in Vmax with a similar Km; also, the decrease in Vmax was primarily due to a decrease in the density of SERT on the platelet membrane, with no change in whole cell expression. Additionally, while the platelet 5HT content decreased 33%, the plasma 5HT content increased 33%. Furthermore, exogenous 5HT altered the 5HT uptake rates by changing the density of SERT molecules on the plasma membrane in a biphasic manner. Therefore, we hypothesize that in a hypertensive state, the elevated plasma 5HT levels induces a loss in 5HT uptake function in platelets via a decrease in the density of SERT molecules on the plasma membrane. Through the feedback effect of this proposed mechanism, plasma 5HT controls its own concentration levels by modulating the uptake properties of platelet SERT. [source] Innovations in oligonucleotide drug deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2003Melanie A. Lysik Abstract Oligonucleotides (ONs) are a new class of therapeutic compounds under investigation for the treatment of a variety of disease states, such as cancer and HIV, and for FDA approval of an anti-CMV retinitis antisense molecule (VitraveneÔ, Isis Pharmaceuticals). However, these molecules are limited not only by poor cellular uptake, but also by a general lack of understanding regarding the mechanism(s) of ON cellular uptake. As a result, various delivery vehicles have been developed that circumvent the proposed mechanism of uptake, endocytosis, while improving target specific delivery and/or drug stability. This review describes various traditional and novel delivery mechanisms that have been employed to improve ON cellular delivery, cost effectiveness, and therapeutic efficacy. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1559,1573, 2003 [source] Evidence for extended ,,n-participation in solvolysis of some benzyl chloridesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 12 2003Sandra Juri Abstract Chlorides 3 (1-aryl-1-chloro-4-methyl-7-methoxy-4-heptene) and 4 (1-aryl-1-chloro-4-methyl-4-hexene) with various phenyl substituents were prepared (Y=p -OCH3, p -CH3, H and m -Br) and the solvolysis rates were measured in 80% (v/v) aqueous ethanol. The rate constants of 3 correlate well with ,+, and the ,+ value obtained is ,1.45±0.15, whereas with 4 breakdown of the Hammett plot occurs, and the ,+ value without the p -anisyl group is ,2.55±0.20, indicating extended ,,n-participation in 3 and simple ,-participation in 4. The drastically smaller activation parameters obtained with 3 than with 4 are consistent with the proposed mechanism in which the high degree of order required in the transition state (large negative ,S,) is overcompensated by a small ,H,. Copyright © 2003 John Wiley & Sons, Ltd. [source] Polymerization of n -phenyl maleimide by lanthanide complexesJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 17 2005Bei Zhao Abstract N -Phenyl maleimide (N -PMI) was successfully polymerized by divalent rare-earth complexes (ArO)2Sm(THF)4 (ArO = 2,6-di- tert -butyl-4-methyl phenoxo-; THF = tetrahydrofuran) and (Ar,O)2Ln(THF)3 (Ar,O = 2,6-di- tert -butyl phenoxo-; Ln = Sm, Yb, or Eu). The central metals greatly affected the reactivity, and the reactivity order was Sm(II) > Yb(II) > Eu(II). The activity of (Ar,O)2Sm(THF)3 was higher than that of (ArO)2Sm(THF)4. The polymerization yields were higher in THF than in other solvents, and the maximum yields were obtained around 25 °C. A proposed mechanism is discussed. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3966,3972, 2005 [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||