Multiple sclerosis: Benefits of q-space imaging in evaluation of normal-appearing and periplaque white matter

Introduction

Diffusion tensor imaging (DTI) reveals white matter pathology in patients with multiple sclerosis (MS). A recent non-Gaussian diffusion imaging technique, q-space imaging (QSI), may provide several advantages over conventional MRI techniques in regard to in vivo evaluation of the disease process in patients with MS. The purpose of this study is to investigate the use of root mean square displacement (RMSD) derived from QSI data to characterize plaques, periplaque white matter (PWM), and normal-appearing white matter (NAWM) in patients with MS.

Methods

We generated apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps by using conventional DTI data from 21 MS patients; we generated RMSD maps by using QSI data from these patients. We used the Steel–Dwass test to compare the diffusion metrics of regions of interest in plaques, PWM, and NAWM.

Results

ADC differed (P < 0.05) between plaques and PWM and between plaques and NAWM. FA differed (P < 0.05) between plaques and NAWM. RMSD differed (P < 0.05) between plaques and PWM, plaques and NAWM, and PWM and NAWM.

Conclusion

RMSD values from QSI may reflect microstructural changes and white-matter damage in patients with MS with higher sensitivity than do conventional ADC and FA values.     

Novel cycloundecapeptides related to gramicidin S with both high antibiotic activity and low hemolytic activity

To find candidates with high antimicrobial and low hemolytic activities, many gramicidin S (GS) analogs of various ring sizes have been designed and synthesized. However, syntheses of antimicrobially active analogues of GS having a disordered symmetry structure from C(2) have almost never been reported, because the stable, amphiphilic β-sheet structure of GS with C(2) symmetry is considered essential for its strong antibacterial activity. In the present studies, novel thirteen cycloundecapeptides 1-13 related to GS were synthesized and examined. Among them, cyclo(-Va1(1)-Orn(2)-Leu(3)-D-Phe(4)-X(5)-Pro(6)-Val(7)-Orn(8)-Leu(9)-D-Phe(10)-Pro(11)-) (X=Lys (10), Orn (11), Arg (12) and Lys(Lys) (13)) resulted in high antibiotic activity against both Gram-positive and Gram-negative microorganisms tested. In addition, 11 showed low toxicity against sheep blood cells compared with that of GS. Further, circular dichroism (CD) spectra of 10-13 had a curve similar to each other, suggesting that the conformations of these analogues in methanol are similar to each other. However, CD spectra of 10-13 were different from that of GS in the 190-210 nm region. These results suggest that the presences of one added amino acid residue at position 5 of 10-13 might be partially effective through a structural change in the biological activity of 10-13. In addition, the structural modifications at position 5 lower the undesirable hemolytic activity and enhance the desirable antibiotic activity.     

Practical Oxirane Ring Opening with In Situ Prepared LiCN; Synthesis of (2S,3R)-3-(2,4-Difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)-1-butanenitrile

Trisubstituted oxirane 1 was regiospecifically opened with LiCN in situ prepared from acetone cyanohydrin and LiH to provide the corresponding β-hydroxy nitrile 2 in satisfactory yield, enabling us to manufacture a key intermediate for a new antifungal agent on a multi-kg scale. Some applications of this method to the ring opening of other oxiranes and nucleophilic substitution are also described.     

Extensive and subextensive chaos in globally coupled dynamical systems

Using a combination of analytical and numerical techniques, we show that chaos in globally coupled identical dynamical systems, whether dissipative or Hamiltonian, is both extensive and subextensive: their spectrum of Lyapunov exponents is asymptotically flat (thus extensive) at the value λ(0) given by a single unit forced by the mean field, but sandwiched between subextensive bands containing typically O(logN) exponents whose values vary as λ?λ(∞)+c/logN with λ(∞)≠λ(0).     

Correction for phase-shift deviation in a complex Fourier-transform integrated-optic spatial heterodyne spectrometer with an active phase-shift scheme

We report that a spectrum can be retrieved with a planar waveguide spatial heterodyne spectrometer (SHS) incorporating an active phase-shift scheme, where the phase shifts are distributed around π/2. This was confirmed experimentally with an SHS that had 32 interleaved Mach-Zehnder interferometers and whose free spectral range was 625 GHz. The phase shifts ranged from 0.71 to 2.2 rad against the target of π/2 rad.     

Stereoselective synthesis of cis-2,3-diphenyl-2-cyanooxirane by reaction of 2-bromodeoxybenzoin with cyanide ion on solid adsorbents

Treatment of 2-bromodeoxybenzoin with cyanide ion in the presence of solid adsorbent (silica gel or alumina) stereoselectively gives cis-2,3-diphenyl-2-cyanooxirane in a good yield. The mechanism is discussed.     

Chemistry of mixed melanogenesis--pivotal roles of dopaquinone

Melanins can be classified into two major groups-insoluble brown to black pigments termed eumelanin and alkali-soluble yellow to reddish-brown pigments termed pheomelanin. Both types of pigment derive from the common precursor dopaquinone (ortho-quinone of 3,4-dihydroxyphenylalanine) which is formed via the oxidation of l-tyrosine by the melanogenic enzyme tyrosinase. Dopaquinone is a highly reactive ortho-quinone that plays pivotal roles in the chemical control of melanogenesis. In the absence of sulfhydryl compounds, dopaquinone undergoes intramolecular cyclization to form cyclodopa, which is then rapidly oxidized by a redox reaction with dopaquinone to give dopachrome (and dopa). Dopachrome then gradually and spontaneously rearranges to form 5,6-dihydroxyindole and to a lesser extent 5,6-dihydroxyindole-2-carboxylic acid, the ratio of which is determined by a distinct melanogenic enzyme termed dopachrome tautomerase (tyrosinase-related protein-2). Oxidation and subsequent polymerization of these dihydroxyindoles leads to the production of eumelanin. However, when cysteine is present, this process gives rise preferentially to the production of cysteinyldopa isomers. Cysteinyldopas are subsequently oxidized through redox reaction with dopaquinone to form cysteinyldopaquinones that eventually lead to the production of pheomelanin. Pulse radiolysis studies of early stages of melanogenesis (involving dopaquinone and cysteine) indicate that mixed melanogenesis proceeds in three distinct stages-the initial production of cysteinyldopas, followed by their oxidation to produce pheomelanin, followed finally by the production of eumelanin. Based on these data, a casing model of mixed melanogenesis is proposed in which a preformed pheomelanic core is covered by a eumelanic surface.     

The switching element for a Leonard pair

Let V denote a vector space with finite positive dimension. We consider a pair of linear transformations A:V→V and A^∗:V→V that satisfy (i) and (ii) below:

(i)

There exists a basis for V with respect to which the matrix representing A is irreducible tridiagonal and the matrix representing A^∗ is diagonal.

(ii)

There exists a basis for V with respect to which the matrix representing A^∗ is irreducible tridiagonal and the matrix representing A is diagonal.

We call such a pair a Leonard pair on V. Let (resp. ) denote a basis for V referred to in (i) (resp. (ii)). We show that there exists a unique linear transformation S:V→V that sends v₀ to a scalar multiple of v_d, fixes w₀, and sends w_i to a scalar multiple of w_i for 1?i?d. We call S the switching element. We describe S from many points of view.     

CH/pi interactions in methane clusters with polycyclic aromatic hydrocarbons

Geometries and interaction energies for methane clusters with naphthalene and pyrene were studied. Estimated CCSD(T) interaction energies for the clusters at the basis set limit were -1.92 and -2.50 kcal mol(-1), respectively. Dispersion is mainly responsible for the attraction. Electrostatic interaction is very small. Although the benzene-methane cluster prefers a monodentate structure, in which a C-H bond of the methane points toward the benzene, the methane clusters with the polycyclic aromatic hydrocarbons do not prefer monodentate structures. In the benzene-methane cluster, the weak electrostatic interaction stabilizes the monodentate structure. On the other hand the dispersion interaction controls the orientation of methane in the naphthalene and pyrene clusters. The dispersion interactions in these clusters are significantly larger than those in the benzene-methane cluster. The methane prefers the orientation which is suitable for stabilization by dispersion. Hydrogen atoms of the methane locate above the centers of hexagonal rings of the polycyclic aromatic hydrocarbons in the stable structures. The structures have a small steric repulsion and this positions them only a short distance from the aromatic plane. The large dispersion contribution to the attraction shows that interactions between carbon atoms are mainly responsible for the attraction, and that hydrogen atoms are not important for the attraction. This shows that the interactions between the methane and polycyclic aromatic hydrocarbons are not pi-hydrogen bonds.