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SUMMARY Purpose: Focal brain cooling is effective for suppression of epileptic seizures, but it is unclear if seizures can be suppressed without a substantial influence on normal neurologic function. To address the issue, a thermoelectrically driven cooling system was developed and applied in freemoving rat models of focal seizure and epilepsy. Methods: Focal seizures limited to the unilateral forelimb were induced by local application of a penicillin G solution or cobalt powder to the unilateral sensorimotor cortex. A proportional integration and differentiation (PID)‐controlled, thermoelectrically driven cooling device (weight of11 g)and bipolarelectrodeswere chronically implanted ontheeloquentarea(ontheepilepticfocus)andtheeffects of cooling (20, 15, and 10� C) on electrocorticography, seizurefrequency,andneurologicchangeswereinvestigated. Key Findings: Cooling was associated with a distinct reduction of the epileptic discharges. In both models, cooling of epileptic foci significantly improved both seizure frequency and neurologic functions from 20� C down to 15� C. Cooling to 10� C also suppressed seizures, but with no further improvement in neurologic function. Subsequent investigation of sensorimotor function revealed significant deterioration in foot-fault tests and the receptive field size at 15� C. Significance: Despite the beneficial effects in ictal rats, sensorimotor functions deteriorated at 15� C, thereby suggesting a lower limit for the therapeutic temperature. These results provide important evidence of atherapeutic effect of temperatures from 20 to 15� C using an implantable, hypothermal device for focal epilepsy.

Substitution reactions of acetals with carbon nucleophiles are fundamental and conventional organic reactions. We succeeded in the preparation of an optically active acetal, which reacted with a silyl enol ether smoothly to afford the desired adducts in racemic forms. By comparison of the ees of the products with the ees of the recovered acetals, we concluded that the aldol-type reactions proceeded not via direct displacement (SN2) or contact ion pairs (intimate ion pair) (SN1) but by a free oxocarbenium ion (SN1) mechanism. Next, a study to achieve asymmetric catalysis of the acetal substitution reactions was conducted. After many trials, it was found that a chiral niobium complex prepared from pentamethoxyniobium [Nb(OMe)5] and a tetradentate BINOL derivative could achieve high enantioselectivities. Asymmetric aldol-type reactions of acetals with silyl enol ethers proceeded smoothly to afford the corresponding aldol-type adducts in good yields with high enantioselectivities.

A cobalt-N-heterocyclic carbene catalyst generated from CoBr2 , imidazolium salt, and cyclohexylmagnesium bromide was found to promote the imine-directed C2-alkylation of indoles with nonconjugated arylalkenes through a tandem alkene isomerization-hydroarylation process, affording 1,1-diarylalkanes with exclusive regioselectivity. The feasibility of the tandem catalysis was demonstrated for allyl-, homoallyl-, and bishomoallylbenzene derivatives. The catalytic system is also applicable to a variety of β-substituted styrene derivatives. Mechanistic experiments using deuterium-labeled indole substrate and Grignard reagent provided insight into the cobalt-mediated C-H activation step, which likely involves exchange of the C2-hydrogen atom of the former and the β-hydrogen atoms of the latter.

A cobalt–N-heterocyclic carbene catalytic system promotes pyridine-directed olefinic C–H alkylation reactions using a variety of primary and secondary alkyl chlorides under mild conditions. Radical clock experiments suggest that the reaction involves single-electron transfer from the cobalt intermediate to the alkyl chloride.

An iron–N-heterocyclic carbene catalyst generated from an iron(III) salt, an imidazolinium salt, and a Grignard reagent promotes alkylation and alkenylation reactions at the indole C2-position with vinylarenes and internal alkynes, respectively, via imine-directed C–H activation. The former reaction affords 1,1-diarylalkane derivatives with exclusive regioselectivity. Deuterium-labeling experiments suggest that these reactions involve oxidative addition of the C–H bond to the iron center, insertion of the unsaturated bond into the Fe–H bond, and C–C reductive elimination.

Aryl imines, 2-arylpyridine, and related N-heterocycles are selectively monoalkylated using alkyl halides in the presence of Co/N-heterocyclic carbene catalytic systems.

ortho-Alkenylation of a variety of aromatic aldimines with internal alkynes is developed using a catalyst generated from CoBr2, triarylphosphine and iPrMgBr.

Various polysubstituted dihydropyridine derivatives are synthesized by the title reaction under mild conditions.

Title reactions proceed with complete ortho-selectivity in the presence of an iron—diamine catalyst and dichloro-2-methylpropane as an oxidant under mild conditions within short reaction times.

Substitution reactions of acetals with carbon nucleophiles are fundamental and conventional organic reactions. We succeeded in the preparation of an optically active acetal, which reacted with a silyl enol ether smoothly to afford the desired adducts in racemic forms. By comparison of the ees of the products with the ees of the recovered acetals, we concluded that the aldol-type reactions proceeded not via direct displacement (SN2) or contact ion pairs (intimate ion pair) (SN1) but by a free oxocarbenium ion (SN1) mechanism. Next, a study to achieve asymmetric catalysis of the acetal substitution reactions was conducted. After many trials, it was found that a chiral niobium complex prepared from pentamethoxyniobium [Nb(OMe)5] and a tetradentate BINOL derivative could achieve high enantioselectivities. Asymmetric aldol-type reactions of acetals with silyl enol ethers proceeded smoothly to afford the corresponding aldol-type adducts in good yields with high enantioselectivities.

Introduction: Ca channel Cav1.3 (α1D subtype) is expressed in many excitable cells as well as Cav1.2 (α1C subtype), and is considered to contribute to pacemaking in nodal cells. Cav1.3 has lower affinity to dihydropyridine Ca antagonits compared to Cav1.2, although the mechanism is not studied well. In this study we evaluated whether co-expression of Ca channel beta subunits might modulate the affinity of Cav1.3 to a Ca antagonist nifedipine. Method: cRNA for Cav1.3 or Cav1.2 were injected to Xenopus oocytes and Ba currents through the expressed channel were measured with two-electrode voltage-clamp method. Blocking effects of nifedipine to the channel subtypes and the modulation of the effect by co-expression of Ca channel β subunits (Cavβ1 or Cavβ2a) were investigated. Result: Nifedipine 10 µM inhibited Cav1.3 by 30±8.5% at holding potential of −100 mV, significantly weaker (p

Modern digital computers have great numerical calculation ability, but processing of fuzzy information is poor in terms of effectiveness and cost. Consequently, hardware systems peculiar to fuzzy information processing are anxiously awaited. This paper proposes a basic fuzzy logic circuit formed by using p-MOS current mirror circuits, discusses the zero-error condition and verifies their operations by the semicostom fuzzy logic IC designed in a standard Al-gate p-MOS technology The distinctive features of the proposed fuzzy logic circuits are: 1) any fuzzy logic functions can be implemented with one kind of master slice (Bounded-Difference array); 2) variations of process parameters affect the electrical characteristics of the logic circuits very little; 3) the basic logic cell is accurate; 4) the current mode design facilitates the algebraic sum only by Al-wiring; and 5) these fuzzy logic circuits can be useful in binary logic and multiple-valued logic The basic fuzzy logic cell described here will be a candidate for a logic circuit of Fuzzy Computer in the near future.