Mismatch hypothesis

Butcher KS, Parsons M, MacGregor L, Barber PA, Chalk J, Bladin C, Levi C, Kimber T, Schultz D, Fink J, Tress B, Donnan G, Davis S, Investigators E. Refining the perfusion-diffusion mismatch hypothesis. Stroke 2005 36 1153-1159. 

Fig. 3.6. The potential flaws in the mismatch hypothesis. The perfusion lesion probably overestimates truly hypoperfused tissue and includes some benign oligaemic tissue. The DWI lesion may overestimate the infarct core and be partially reversible...

It is important to note that this trial is not using perfusion-diffusion mismatch to select patients, but as a surrogate outcome measure. The rationale for this is that the mismatch hypothesis, whilst strongly supported by much data, remains unproven. Similarly, it is not yet established that patients with nonmismatch do not respond to thrombolysis (as there is at least a theoretical possibility of partial DWI reversal). Should either the mismatch hypothesis and/or the hypothesis that a large acute DWI lesion predicts ICH be proven in this trial, a logical next... 

Butcher KS, Parsons M, MacGregor L et al (2005) Refining the perfusion-diffusion mismatch hypothesis. Stroke 36 1153-1159... 

The second hypothesis, that patients should be selected for thrombolysis depending on whether or not they exhibit a diffusion-perfusion mismatch, may have enormous implications for stroke therapy in the near future, and is one of the most actively investigated and debated subjects in neuroimaging. 

There was still some room for uncertainty on this retention-retention mechanism. The argument was, if the unobserved tt-allyl Mo complex (such as 77 or B in Scheme 2.18) was more highly reactive towards sodium malonate than experimentally observed tt-allyl Mo complexes (such as 71, 74, and 80), the reaction should proceed through inversion (since there is an equilibrium between the two tt-allyl Mo complexes via the o-allyl complex.) If so, when the isolated Mo-complex 71 was subjected to the reaction, 71 must be equilibrated to the enantiomer of 71 via the o-allyl complex prior to reaction with a nucleophile. Therefore, reaction from the Mo complex 71 should proceed with less stereoselectivity than that from a mismatched branched carbonate. This hypothesis was examined, as shown in Scheme 2.26. 

Some experiments outlined the frequency dependence of phonon scattering on surfaces [74]. Thus, Swartz made the hypothesis that a similar phenomenon could take place at the interface between solids and proposed the diffuse mismatch model [72]. The latter model represents the theoretic limit in which all phonons are heavily scattered at the interface, whereas the basic assumption in the acoustic mismatch model is that no scattering phenomenon takes place at the interface of the two materials. In the reality, phonons may be scattered at the interface with a clear reduction of the contact resistance value as calculated by the acoustic model. 

Utilising a reversion assay in Salmonella enterica, Prieto et al reported an increased frequency of point mutations following bile-salt exposure. Mutations were predominantly nucleotide substitutions (GC to AT transitions) and -1 frameshift mutations.The frameshifts were dependent on SOS induction and linked to the activity of DinB polymerase (Pol IV). The authors proposed that the GC to AT transitions stimulated by bile, could have arisen from oxidative processes giving rise to oxidised cytosine residues. Consistent with this hypothesis, the authors demonstrated that strains of S. enterica-lacking enzymes required for base-excision repair (endonuclease III and exonuclease IV) and the removal of oxidised bases, demonstrated increased bile-acid sensitivity compared with competent strains. In another study using E. coli, resistance to the DNA-damaging effects of bile was associated with Dam-directed mismatch repair, a pathway also involved with the repair of oxidative DNA lesions. ... 

The silicate sheet in kaolinite, for example, has an 0-0 repeat distance in the sheet of 0.893 nm, whereas the octahedral or gibbsite sheet repeat is smaller, about 0.862 nm. Mismatch of the 1 1 sheets induces curvature with the smaller dimension sheet on the interior. The octahedral gibbsite layer in clays is postulated to be situated on the inside of the curve. This relationship contrasts with the hypothesis for chrysotile, in which the tetrahedral silicate sheet is smaller and is postulated to be the interior unit in the scrolled serpentine mineral. 

Backtracking from reaction product 129, speculation about the origin of this species led to the initially uncomfortable hypothesis that carbene 126 must have participated in a cycloaddition process with the tosyl unit s aryl ring in preference to C-H insertion. This curious result may be the outcome of a situation where proximity trumps electronics, as the mismatch between the electrophilic carbene and the electron deficient aryl ring would seem, a priori, to dissuade cycloaddition. 

The evolution of the mismatch model of the penumbra has led to a number of studies examining the response of acute DWI/PI patterns to thrombolytic therapy, particularly with respect to treatment beyond 3 h after stroke onset (Jansen et al. 1999 Kidwell et al. 2000 Parsons et al. 2002a Schellinger et al. 2000). These studies supported the mismatch-penumbra hypothesis by demonstrating that thrombolysis rescues mismatch tissue... 

The hairpin-DNA transporter (Table 24.1) was 30 bases long (30-mer) and contained a thiol substituent at the 5 end that allowed it to be covalently attached to the inside walls of the Au nanotubes [6]. The first six bases at each end of this molecule are complimentary to each other and form the stem of the hairpin, and the middle 18 bases form the loop (Table 24.1). The permeating DNA molecules were 18-mers that are either perfectly complementary to the bases in the loop, or contain one or more mismatches with the loop (Table 24.1). A second thiol-terminated DNA transporter was investigated (Table 24.1). This DNA transporter was also a 30-mer, and the 18 bases in the middle of the strand were identical to the 18 bases in the loop of the hairpin-DNA transporter. However, this second DNA transporter does not have the complementary stem-forming bases on either end and thus cannot form a hairpin. This linear-DNA transporter was used to test the hypothesis that the hairpin-DNA... 

An especially important gap in the present knowledge of processes changing the characteristics of water masses within the Southern Ocean centers on the effect of the seasonal cycle, the formation and dissolution of pack ice and its associated biological processes. One aim must be to explain the paradox of the mismatch of dissolved nutrient concentration and the primary production in the pelagic ecosystems (9). One important hypothesis that needs further testing is the possibility of Fe limitation of nutrient uptake (10). 

Three main features of this multiple stereoselection approach are worth mentioning (i) The configuration of the products of the matched and mismatched pairs are predictable on the basis of the results of the simple stereoselective reactions (ii) the efficiency of the stereocontrol seems also predictable (although not in a very precise manner) by simply multiplying (matched pair) or dividing (mismatched pair) the stereoselectivity of the simple stereoselective reactions and (iii) only the combination of enantiomerically pure reactants is productive, as shown by the result of reaction E, in which a racemic dienophile is exposed to the (R)-diene in a process the diastereoselection of which is calculated on the hypothesis that no kinetic resolution is at work. 

---