A new approach to evaluate imperfection sensitivity in asymmetric bifurcation buckling analysis

A direct procedure for the evaluation of imperfection sensitivity in bifurcation problems is presented. The problems arise in the context of the general theory of elastic stability for discrete structural systems, in which the energy criterion of stability of structures and the total potential energy formulation are employed. In cases of bifurcation buckling the sensitivity of the critical load with respect to an imperfection parameter e is singular at the state given by epsilon =0, so that, a regular perturbation expansion of the solution is not possible. In this work we describe a direct procedure to obtain the relations between the critical loads, the generalized coordinates at the critical state, the eigenvector, and the amplitude of the imperfection, using singular perturbation analysis. The expansions are assumed in terms of arbitrary powers of the imperfection parameter, so that both exponents and coefficients of the expansion are unknown. The solution of the series exponents is obtained by searching the least degenerate solution. The formulation is here applied to asymmetric bifurcations, for which explicit expressions of the coefficients are obtained. The use of the method is illustrated by a simple example, which allows consideration of the main features of the formulation.

Hippocampal histamine receptors and conflictive exploration in the rat: studies using the elevated asymmetric plus-maze

The possible role of histamine receptors in the hippocampal formation on the exploratory motivation and emotionality of the rat was studied. An elevated asymmetric plus-maze composed of 4 different arms (no walls, single high wall, high and low walls and two high walls) arranged at 90o angles was used. The exploration score, considered to be an index of exploratory motivation, and the permanency score, considered to be an index of emotionality (anxiety), were determined. Histamine was administered locally into the ventral hippocampus at three different doses (9, 45 and 90 nmol). Another group of rats was also microinjected with 45 nmol of pyrilamine (a histamine H1 receptor antagonist) or ranitidine (a histamine H2 receptor antagonist) in addition to 9 nmol of histamine in order to identify the possible type of histamine receptor involved. Histamine administration significantly inhibited the exploration score and increased the permanency score at the doses of 9 and 45 nmol in two of four arms. These effects were completely blocked by the administration of either histamine receptor antagonist. The present results suggest that in the hippocampal formation histamine inhibits exploratory motivation and decreases emotionality by activating both types of histamine receptors. Also, the elevated asymmetric plus-maze appears to be a suitable technique to quantify exploration and possibly" anxiety"

Behavioral profiles displayed by rats in an elevated asymmetric plus-maze: effects of diazepam

When rats are exposed to unknown environments where novelty and fear-inducing characteristics are present (conflictive environments), some specific behaviors are induced and exploration is apparently modulated by fear. In our laboratory, a new type of plus-maze was designed as a model of conflictive exploration. The maze is composed of four arms with different geometrical characteristics, differing from each other by the presence or absence of walls. The degree of asymmetry was as follows: NW, no wall arm; SW, a single high wall present; HL, a low and a high wall present, and HH, two high walls present. The four arms were arranged at 90o angles and the apparatus was called the elevated asymmetric plus-maze (APM). The purpose of the present study was to assess the behavioral profile of rats exposed for a single time to the APM with or without treatment with benzodiazepine. Increasing doses of diazepam were injected intraperitoneally in several groups of male, 90-day-old Holtzman rats. Distilled water was injected in control animals. Thirty minutes after treatment all rats were exposed singly to a 5-min test in the APM. Diazepam induced a biphasic modification of exploration in the NW and SW arms. The increase in the exploration score was evident at low doses of diazepam (0.25-1.0 mg/kg body weight) and the decrease in exploration was found with the higher doses of diazepam (2.0-3.0 mg/kg body weight). Non-exploratory behaviors (permanency) were not affected by benzodiazepine treatment. In the HL arm, exploration was not modified but permanency was increased in a dose-dependent manner. In the HH arm, exploration and permanency were not affected. Results are compatible with the idea that exploration-processing mechanisms in conflictive environments are modulated by fear-processing mechanisms of the brain.

High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

Political economy of preferential trade agreement: the case of bilateral asymmetric negotiation

The purpose of this paper is to analyse the political economy of preferential trade agreements based on a sequential non-cooperative Stackelberg political game between a large economy and a small one, in which the political dispute of rival lobby groups defines the unilateral stance of both governments in the first stage; and the Stackelberg "coalition-proof" equilibrium defines the free trade agreement format in the second stage. Finally, a few modifications in the initial game structure are discussed in order to enhance the small economy's negotiation power. The political economy model is applied to FTAA case.

Effect of loading type on the fatigue strength of symmetric and asymmetric welded joints made of ultra high strength steel

In this study, finite element analyses and experimental tests are carried out in order to investigate the effect of loading type and symmetry on the fatigue strength of three different non-load carrying welded joints. The current codes and recommendations do not give explicit instructions how to consider degree of bending in loading and the effect of symmetry in the fatigue assessment of welded joints. The fatigue assessment is done by using effective notch stress method and linear elastic fracture mechanics. Transverse attachment and cover plate joints are analyzed by using 2D plane strain element models in FEMAP/NxNastran and Franc2D software and longitudinal gusset case is analyzed by using solid element models in Abaqus and Abaqus/XFEM software. By means of the evaluated effective notch stress range and stress intensity factor range, the nominal fatigue strength is assessed. Experimental tests consist of the fatigue tests of transverse attachment joints with total amount of 12 specimens. In the tests, the effect of both loading type and symmetry on the fatigue strength is studied. Finite element analyses showed that the fatigue strength of asymmetric joint is higher in tensile loading and the fatigue strength of symmetric joint is higher in bending loading in terms of nominal and hot spot stress methods. Linear elastic fracture mechanics indicated that bending reduces stress intensity factors when the crack size is relatively large since the normal stress decreases at the crack tip due to the stress gradient. Under tensile loading, experimental tests corresponded with finite element analyzes. Still, the fatigue tested joints subjected to bending showed the bending increased the fatigue strength of non-load carrying welded joints and the fatigue test results did not fully agree with the fatigue assessment. According to the results, it can be concluded that in tensile loading, the symmetry of joint distinctly affects on the fatigue strength. The fatigue life assessment of bending loaded joints is challenging since it depends on whether the crack initiation or propagation is predominant.

Design and synthesis of new monoterpenoid derived ligands for asymmetric catalysis /

The work to be presented herein illustrates several important facts. First, the synthesis of BIBOL (19), a 1,4-diol derived from the monoterpene camphor has allowed us to demonstrate that oxidative dimerizations of enolates can, and do proceed with nearly complete diastereoselectivity under kinetically controlled conditions. The yield of BIBOL is now 50% on average, with a 10% yield of a second diastereomer, which is likely the result of a non-kinetic hydride reduction, thereby affording the epimeric alcohol, 20, coupled on the exo face of camphor. This implies the production of 60% of a single coupling diastereomer. No other diastereomers from the reduction were observed. The utility of BEBOL has been illustrated in early asymmetric additions of diethylzinc to aryl aldehydes, with e.e.'s as high as 25-30%. '^' To further the oxidative coupling work, the same methodology which gave rise to BIBOL was applied to the chiral pool ketone, menthone. Interestingly, this gave an excellent yield of the a-halohydrin (31), which is the result of a chlorination of menthone. This result clearly indicates the high stereoselectivity of the process regardless of the outcome, and has illustrated an interesting dichotomy between camphor and menthone. The utility of the chlorination product as a precursor other chiral ligands is currently being investigated. > ' Finally, a new series of 1,3-diols as well as a new aminoalcohol have successfully been synthesized from highly diastereoselective aldol/mannich reactions. Early studies have indicated their potential in asymmetric catalysis, while employing pi-stack interactions as a means of controlling enantioselective aldol reactions.

Synthesis of chiral homoallylic alcohols and phthalans through the asymmetric allylation of carbonyl compounds /

The implementation of chiral centres within biologically active compounds has been a perplexing yet motivational force in chemistry. This work presents the attempted formation of a concurrent or sequential tandem catalyzed methodology of enantioselective nucleophilic addition and electrophilic cyclization. The 2'- arylalkynyl- aldehyde, ketone, and imine substrates used within were adeptly chosen with a dually activated structure; 1) for nucleophilic addition to the electrophilic substituents; and 2) for carbophilic activation of the alkyne substituent to undergo cyclization. To accomplish the nucleophilic addition, two distinct allylation methodologies were pursued: (/?)-BINOL catalyzed-allylboration and (5)- BINAP-AgF catalyzed-allylsilylation. BINAP catalyzed enantioselective allylation of 2'-arylalkynyl-aldehydes, to form chiral homoallylic alcohols, was successful. Homoallylic alcohols were isolated with high enantio-purity (>80%), which then underwent sequential cyclization to form chiral allylic phthalans, in moderate yields. An application of this methodology towards the construction of biologically active compounds was included with the partial synthesis of the natural product and H. pylori inhibitor, (+)-Spirolaxine methyl ether.

Attemped asymmetric dehydration with chiral carbodiimides /|nMin-jen Shiao. -- 260 0 St. Catharines [Ont. : s. n.],

This research work has been planned with the intention of synthesizing optically active bicyclo[3,l,0]-hexan-2-one using chiral carbodiimides. Several carbodiimides have been prepared for practice and for attempts at asymmetric induction. The total synthesis of dibenzo[e,g]- (l:3)diazonine and the partial synthesis of l:13-dimethyldibenzo[e,g]- (l:3)diazonine are reported. Attempts to resolve 6,6f-dimethyl-2,2t-diphenic acid were not successful. The NMR spectra of carbodiimides and the related thioureas are compared. The reaction transition state of the 4-hydroxycyclohexanone with optically pure R,R(+)-di(a-phenylethyl)-carbodiimide has been considered. The ORD application to chiral cyclohexanones is discussed.

Attempted asymmetric synthesis of Lactobacillic acid / |nFawzy F. Z. Georges. -- 260 St. Catharines, Ont. : [s. n.],

This research work has been planned with the intention of proving the absolute configuration of lactobacillc acid. During the course of this work, attempts have been made to synthesize cis-2-carboxycyclopropane- l-.acetic acid as,v,a suitable resolvable material. As the results were not satisfactory, the synthesis of ci,s-2-carboxycyclopropane-l-propionic acid has been alternatively attempted by ring opening of bicyclo- [4.1.~-heptan-2-onewithout much success. Attempts to resolve or prepare bicyclo[ 4.1.~-hePtan-2-one optically active are also reported. On the other hand, a complete scheme is described for the possible synthesis of optically active lactobacillic acid. If only bicyclo- ~.1.~ -heptan-2-one can be resolved or prepared optically active, this described scheme can be applied smoothly to the synthesis of enant~omeric lactobacillic acid.

Asymmetric cyclopropanation via catalysts incorporating the 1,4-diol ligands and the newly designed dioxaborolane /

The development of new methodology for the asymmetric synthesis of chiral organic compounds is a major focus in modem organic chemistry. The use of chiral catalysts is replacing chiral auxiliaries as a new tool for synthetic chemists. An efficient chiral catalyst allows for large quantities of optically active product to be obtained on use of relatively small amount of enantiopure material, without the need for the removal and recovery of a chiral auxiliary. Furthermore, the most practical catalytic methods utilize an inexpensive and readily available chiral ligand that can provide high and predictable enantioselectivity across a wide range of substrates. In our project, two type of versatile, upgraded chiral ligands have been designed and synthesized. Their application in Simmons-Smith type cyclopropanation is investigated, and the pleasing results suggest that they are the potential catalytic enantioselective candidates to build C-C bonds.

Asymmetric hydrogenation of alkenes with cationic iridium(I) complexes of 2-phosphino-1-aminoferrocene ligands

Iridium complexes with bidentate P,N ligands represent a class of catalysts that significantly expand the application range of asymmetric hydrogenation. New substrate classes, for which there have previously been no suitable catalysts, can now be efficiently hydrogenated in high conversion and enantioselectivity. These substrates are often of synthetic importance, thus iridium catalysis represents a significant advance in the field of asymmetric catalysis. Planar chiral ferrocenyl aminophosphine ligands in which both heteroatoms were directly bound to the cyclopentadienyl ring were prepared by BF3-activated lithiationsubstitution in the presence of a chiral diamine in 49-59% yield and 75-85% enantiomeric excess. Some of these ligands were recrystallized to enantiomeric purity via ammonium fluoroborate salt formation of the phosphine sulfide. A crystal structure of one of these compounds was obtained and features an intramolecular hydrogen bond between the nitrogen, hydrogen, and sulfur atoms. Neutralization, followed by desulfurization, provided the free ligands in enantiomeric purity. Iridium complexes with these ligands were formed via reaction with [Ir(COD)Clh followed by anion exchange with NaBArF. These complexes were successfully applied in homogeneous hydrogenation of several prochiral substrates, providing products in up to 92% enantiomeric excess. Variation of the dimethyl amino group to a pyrrolidine group had a negative effect on the selectivity of hydrogenation. Variation of the substituents on phosphorus to bulkier ortho-tolyl groups had a positive effect, while variation to the more electron rich dicyclohexyl phosphine had a negative effect on selectivity.

Understanding the Origin of Selectivity in the Asymmetric Lithiation Reaction of N-Heterocycles: A Theoretical Study

The natural abundance of the N-heterocycle containing compounds has pushed the synthetic community toward the invention of new synthetic methods that result in the structural diversity of N-heterocycles. Among this, is the efficient and highly selective diamine mediated asymmetric lithiation process. Amongst the diamine chiral ligands, (-)-sparterine, which is a naturally occurring alkaloid proved to be an efficient one. Many successful, good yielding and highly selective lithiation reactions have been accomplished with the mediation by this chiral diamine base. Although, there are some examples of experimental and theoretical mechanistic studies in the literature, there is a lack of detailed understanding as to how it exactly induces the chirality. In this thesis is described a systematic investigation of how (-)-sparteine influences the stereoselectivity in the course of asymmetric lithiation reaction. This led us to the establishment of the function of A-ring’s β-CH2 effect and D-ring effect. Consequently, the importance of the A-ring and D-ring portions of (-)-sparteine in the stereoselectivity is unraveled. Another part of this thesis deals with the asymmetric lithiation of BF3-activated N,N- dimethylaminoferrocene in the presence of (1R, 2R)-N1,N2-bis(3,3-dimethylbutyl)-N1,N2-dimethylcyclohexane-1,2-diamine ( a (R,R)-TMCDA surrogate) with i-PrLi. Computational findings were in full accord with the experimental observations. Subsequently, the theoretically provided insights into the mechanism of the reaction were exploited in computational design of a new ligand. Unfortunately, the outcome of this design was not experimentally robust and an updated approach towards a successful design was explained.

Experimental and Computational Studies on Copper and Hydrobenzoin Derivatives in Catalytic Asymmetric Reactions

The use of theory to understand and facilitate catalytic enantioselective organic transformations involving copper and hydrobenzoin derivatives is reported. Section A details the use of theory to predict, facilitate, and understand a copper promoted amino oxygenation reaction reported by Chemler et al. Using Density Functional Theory (DFT), employing the hybrid B3LYP functional and a LanL2DZ/6-31G(d) basis set, the mechanistic details were studied on a N-tosyl-o-allylaniline and a [alpha]-methyl-[gamma]-alkenyl sulfonamide substrate. The results suggest the N-C bond formation proceeds via a cisaminocupration, and not through a radical-type mechanism. Additionally, the origin of diastereoselection observed with [alpha]-methyl-[gamma]-alkenyl sulfonamide arises from avoidance of unfavourable steric interactions between the methyl substituent and the N -protecting group. Section B details the computationally guided, experimental investigation of two hydrobenzoin derivatives as ligands/ catalysts, as well as the attempted synthesis of a third hydrobenzoin derivative. The bis-boronic acid derived from hydrobenzoin was successful as a Lewis acid catalyst in the Bignielli reaction and the Conia ene reaction, but provided only racemic products. The chiral diol derived from hydrobenzoin successfully increased the rate of the addition of diethyl zinc to benzaldehyde in the presence of titanium tetraisopropoxide, however poor enantioinduction was obseverved. Notably, the observed reactivity was successfully predicted by theoretical calculations.