75 research outputs found
Lead identification and structure-activity relationships of heteroarylpyrazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists
A knowledge-based library of aryl 2,3-dichlorophenylsulfonamides was synthesised and screened as human CCR4 antagonists, in order to identify a suitable hit for the start of a lead-optimisation programme. X-ray diffraction studies were used to identify the pyrazole ring as a moiety that could bring about intramolecular hydrogen bonding with the sulfonamide NH and provide a clip or orthogonal conformation that was believed to be the preferred active conformation. Replacement of the core phenyl ring with a pyridine, and replacement of the 2,3-dichlorobenzenesulfonamide with 5- chlorothiophenesulfonamide provided compound 33 which has excellent physicochemical properties and represents a good starting point for a lead optimisation programme. Electronic structure calculations indicated that the preference for the clip or orthogonal conformation found in the small molecule crystal structures of 7 and 14 was in agreement with the order of potency in the biological assay
The road to deterministic matrices with the restricted isometry property
The restricted isometry property (RIP) is a well-known matrix condition that
provides state-of-the-art reconstruction guarantees for compressed sensing.
While random matrices are known to satisfy this property with high probability,
deterministic constructions have found less success. In this paper, we consider
various techniques for demonstrating RIP deterministically, some popular and
some novel, and we evaluate their performance. In evaluating some techniques,
we apply random matrix theory and inadvertently find a simple alternative proof
that certain random matrices are RIP. Later, we propose a particular class of
matrices as candidates for being RIP, namely, equiangular tight frames (ETFs).
Using the known correspondence between real ETFs and strongly regular graphs,
we investigate certain combinatorial implications of a real ETF being RIP.
Specifically, we give probabilistic intuition for a new bound on the clique
number of Paley graphs of prime order, and we conjecture that the corresponding
ETFs are RIP in a manner similar to random matrices.Comment: 24 page
Self-persuasion as marketing technique: the role of consumersâ involvement
Purpose
This paper aims to demonstrate that self-persuasion can be used as a marketing technique to increase consumersâ generosity and that the efficacy of this approach is dependent on consumersâ involvement with target behavior.
Design/methodology/approach
An experimental field-study was conducted to investigate the effects of self-persuasion versus direct persuasion attempts versus no persuasion attempts on consumersâ tipping behavior in a lunchroom. Additionally, in a lab experiment, the moderating role of involvement on self-persuasion versus direct persuasion was tested.
Findings
The results reveal that self-persuasion is more effective than direct persuasion attempts or no persuasive messages in increasing consumersâ generosity. This is moderated by consumersâ involvement with the target behavior. For consumers with high involvement, self-persuasion is more effective than direct persuasion, while no differences were found for consumers with moderate or low involvement.
Practical implications
The scope of self-persuasion is not limited to the inhibition of undesired behavior, but it also extends to the facilitation of desired behavior, which considerably broadens the scope of this technique. Self-persuasion might be used as a marketing technique to influence consumersâ purchase behavior. This might be particularly viable in situations in which consumers feel high involvement with products or behavior.
Originality/value
Recently, research in health psychology demonstrated that self-persuasion is a very effective way of inhibiting undesired, addictive behavior and being more successful than direct persuasion. Yet, insufficient knowledge is available about the efficacy of self-persuasion with regard to promoting other target behaviors. In particular, its potential as a marketing technique to influence consumersâ behavior and its boundary conditions are still understudied
Cytological changes related to Brucella canis variants uptake in vitro
In this study, evidence for in vitro uptake, invasion, and cytopathogonomic effects of normal and variant strains of B. canis on tissue culture, is presented. B. canis L-phase were penicillin-induced and these microorganisms produced revertants on penicillin-free media. Tissue culture (LLC-MK 2 ) cells were divided into different normal and variant-infected groups (IâIV), including controls. Bright-field and electron microscopic observations indicated uptake of all the strains and recognizable host cell damage (CPE) to varying degrees. At 72 h after infection, the extent of damage by L-phase was the least (55.5% CPE). The L-phase-derived revertants resulted in 80% damage; this approximates the adverse effect of normal B. canis (85%). In addition to these gross changes, various structural abnormalities, including pyknosis, nuclear disorganization, vacuolation, and karyorrhexis, were apparent. The implications of these findings and the indirect role of the L-phase in brucellosis due to B. canis are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47529/1/430_2005_Article_BF02123560.pd
Ăndice de positividade da reação imunoenzimĂĄtica (ELISA) para cisticercose no lĂquido cefalorraquidiano (LCR) e no soro de pacientes com epilepsia
ModĂ©lisation des flux dâozone en forĂȘts pour lâĂ©valuation des risques : Ă©tat et perspectives
Does the rate of competing isomerisation during alkene metathesis depend on pre-catalyst initiation rate?
Experimental studies of the ring-closing metathesis reaction of 1,8-nonadiene and the ROMP reaction of cycloheptene show that the rate of isomerisation is not correlated to the initiation rate of the pre-catalyst, and that the absence of phosphine leads to a greatly increased rate of isomerisation. A range of pre-catalysts and solvents were probed and it is proposed that the isomerisation is mediated by a ruthenium hydride complex; our results are consistent with the rate-determining formation of such a species, which might be trapped in situ by tricyclohexylphosphane
A concise route to difluorinated analogues of cyclitols and sugars
Allyl ethers of trifluoroethanol are transformed to difluorinated analogues of deoxysugars via concise sequences involving dehydrofluorination/metallation, [3,3]-Claisen rearrangement, reduction, and RCM, affording cyclohexenediol substrates for dihydroxylation reactions
The interplay of structure and reactivity in a most unusual furan diels-alder reaction
Difluorinated alkenoate ethyl 3,3-difluoro-2-(N,N-diethylcarbamoyloxy)-2-propenoate reacts rapidly and in high yield with furan and a range of substituted furans in the presence of a tin(IV) catalyst. Non-fluorinated congener 2-(N,N-diethylcarbamoyloxy)-2-propenoate fails to react at all under the same conditions. These reactions have been explored using density functional theory (DFT) calculations. They reveal a highly polar transition state, which is stabilized by the Lewis acid catalyst SnCl4 and by polar solvents. In the presence of both catalyst and solvent, a two-step reaction is predicted, corresponding to the stepwise formation of the two new carbonâcarbon bonds via transition states which have similar energies in all cases. Our experimental observations of the lack of reaction of the non-fluorinated dienophile, the stereochemical outcomes, and the rate acceleration accompanying furan methylation are all well predicted by our calculations. The calculated free energy barriers generally correlate well with measured reaction rates, supporting a reaction mechanism in which zwitterionic character is developed strongly. An in situ ring opening reaction of exo-cycloadduct ethyl exo-2-(N,N-diethylcarbamoyloxy)-3,3-difluoro-7-oxabicyclo[2.2.1]hept-5-enyl-2-endo-carboxylate, which results in the formation of cyclic carbonate ethyl 4,4-difluoro-5-hydroxy-2-oxo-5,7a-dihydro-4H-benzo[1,3]dioxole-3a-carboxylate by a CurtinâHammett mechanism, has also been examined. Substantial steric opposition to Lewis acid binding prevents carbonate formation from 2-substituted furans
Synthesis of 4,4-difluoroglycosides using ring-closing metathesis
4-Deoxy-4,4-difluoro-glycosides have been synthesised for the first time via a direct sequence involving ring-closing metathesis and indium-mediated difluoroallylation with 1-bromo-1,1-difluoropropene in water. Two protecting group strategies were explored, one to allow protection of the primary C-6 hydroxyl group throughout the sequence, while the second was intended to allow deprotection after RCM and before dihydroxylation. The benzyl ether could be used in the first role, and pivaloyl is effective in the second. Dihydroxylations were highly stereoselective and controlled by the orientation of the glycosidic C-O bond
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