Epidermolysis bullosa:evidence for linkage to genetic markers on chromosome 1 in a family with the autosomal dominant simplex form

DNA from members of a three-generation pedigree of Irish origin, displaying an autosomal dominant simplex form of epidermolysis bullosa of the epidermolytic, simplex, or Koebner variety (EBS2), was analyzed for linkage with a set of markers derived from the long arm of chromosome 1. Two-point analysis revealed positive lod scores for five of these markers, AT3 (Z = 2.107, theta = 0), APOA2 (Z = 1.939, theta = 0.15), D1S66 (Z = 1.204, theta = 0), D1S13 (Z = 1.026, theta = 0.15), and D1S65 (Z = 0.329, theta = 0.15). Multilocus analysis, incorporating the markers D1S19, D1S16, D1S13, APOA2, D1S66, AT3, and D1S65, resulted in a lod score of 3 maximizing at AT3. These data strongly support previous tentative indications of linkage between EBS2 and genetic markers on the long arm of chromosome 1.

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma:analysis of a clinic-based population

Five to ten percent of individuals with melanoma have another affected family member, suggesting familial predisposition. Germ-line mutations in the cyclin-dependent kinase (CDK) inhibitor p16 have been reported in a subset of melanoma pedigrees, but their prevalence is unknown in more common cases of familial melanoma that do not involve large families with multiple affected members. We screened for germ-line mutations in p16 and in two other candidate melanoma genes, p19ARF and CDK4, in 33 consecutive patients treated for melanoma; these patients had at least one affected first or second degree relative (28 independent families). Five independent, definitive p16 mutations were detected (18%, 95% confidence interval: 6%, 37%), including one nonsense, one disease-associated missense, and three small deletions. No mutations were detected in CDK4. Disease-associated mutations in p19ARF, whose transcript is derived in part from an alternative codon reading frame of p16, were only detected in patients who also had mutations inactivating p16. We conclude that germ-line p16 mutations are present in a significant fraction of individuals who have melanoma and a positive family history.

Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt's lymphoma. A cytogenetic and comparative genomic hybridization study.

Comparative genomic hybridization (CGH) studies have demonstrated a high incidence of chromosomal imbalances in non-Hodgkin's lymphoma. However, the information on the genomic imbalances in Burkitt's Lymphoma (BL) is scanty. Conventional cytogenetics was performed in 34 cases, and long-distance PCR for t(8;14) was performed in 18 cases. A total of 170 changes were present with a median of four changes per case (range 1-22). Gains of chromosomal material (143) were more frequent than amplifications (5) or losses (22). The most frequent aberrations were gains on chromosomes 12q (26%), Xq (22%), 22q (20%), 20q (17%) and 9q (15%). Losses predominantly involved chromosomes 13q (17%) and 4q (9%). High-level amplifications were present in the regions 1q23-31 (three cases), 6p12-p25 and 8p22-p23. Upon comparing BL vs Burkitt's cell leukemia (BCL), the latter had more changes (mean 4.3 +/- 2.2) than BL (mean 2.7 +/- 3.2). In addition, BCL cases showed more frequently gains on 8q, 9q, 14q, 20q, and 20q, 9q, 8q and 14q, as well as losses on 13q and 4q. Concerning outcome, the presence of abnormalities on 1q (ascertained either by cytogenetics or by CGH), and imbalances on 7q (P=0.01) were associated with a short survival.

Finite amplitude envelope solitons in pair-ion plasmas

The nonlinear coupling between finite amplitude ion thermal waves (ITWs) and quasistationary density perturbations in a pair-ion plasma is considered. A generalized nonlinear Schrödinger equation is derived for the ITW electric field envelope, accounting for large amplitude quasistationary plasma slow motion describing the ITW ponderomotive force. The present theory accounts for the trapping of ITWs in a large amplitude ion density hole. The small amplitude limit is considered and exact analytical solutions are obtained. Finite amplitude solutions are obtained numerically and their characteristics are discussed.

Comment on the preparation of the ionic liquid 1-ethyl-3-methylimidazolium ethanoate: a unique monomeric, homoleptic pentacoordinate lead ethanoate complex

Atomic absorption spectroscopy of the ionic liquid 1-ethyl-3-methylimidazolium ethanoate ([emim](2)[O2CMe]), prepared according to International Patent WO 96/18459, showed it to contain large amounts of lead impurity: (ca. 0.5 M): [emim](2)[Pb(O2CMe)(4)] was isolated and shown crystallographically to contain the first known example of a monomeric, homoleptic pentacoordinate lead(ii) carboxylate complex, with a stereochemically active lone-pair.

Envelope solitons associated with electromagnetic waves in a magnetized pair plasma

The amplitude modulation of magnetic field-aligned circularly polarized electromagnetic (CPEM) waves in a magnetized pair plasma is reexamined. The nonlinear frequency shifts include the effects of the radiation pressure driven density and compressional magnetic field perturbations as well as relativistic particle mass variations. The dynamics of the modulated CPEM wave packets is governed by a nonlinear Schrodinger equation, which has attractive and repulsive interaction potentials for fast and slow CPEM waves. The modulational stability of a constant amplitude CPEM wave is studied by deriving a nonlinear dispersion from the cubic Schrodinger equation. The fast (slow) CPEM mode is modulationally unstable (stable). Possible stationary amplitude solutions of the modulated fast (slow) CPEM mode can be represented in the form of bright and dark/gray envelope electromagnetic soliton structures. Localized envelope excitations can be associated with the microstructures in pulsar magnetospheres and in laboratory pair magnetoplasmas. (C) 2005 American Institute of Physics.

Modulated electrostatic modes in pair plasmas: Modulational stability profile and envelope excitations

A pair plasma consisting of two types of ions, possessing equal masses and opposite charges, is considered. The nonlinear propagation of modulated electrostatic wave packets is studied by employing a two-fluid plasma model. Considering propagation parallel to the external magnetic field, two distinct electrostatic modes are obtained, namely a quasiacoustic lower moddfe and a Langmuir-like, as optic-type upper one, in agreement with experimental observations and theoretical predictions. Considering small yet weakly nonlinear deviations from equilibrium, and adopting a multiple-scale technique, the basic set of model equations is reduced to a nonlinear Schrodinger equation for the slowly varying electric field perturbation amplitude. The analysis reveals that the lower (acoustic) mode is stable and may propagate in the form of a dark-type envelope soliton (a void) modulating a carrier wave packet, while the upper linear mode is intrinsically unstable, and may favor the formation of bright-type envelope soliton (pulse) modulated wave packets. These results are relevant to recent observations of electrostatic waves in pair-ion (fullerene) plasmas, and also with respect to electron-positron plasma emission in pulsar magnetospheres. (c) 2006 American Institute of Physics.

Oblique modulation of electrostatic modes and envelope excitations in pair-ion and electron-positron plasmas

The nonlinear amplitude modulation of electrostatic waves propagating in a collisionless two-component plasma consisting of negative and positive species of equal mass and absolute charge is investigated. Pair-ion (e.g., fullerene) and electron-positron (e-p) plasmas (neglecting recombination) are covered by this description. Amplitude perturbation oblique to the direction of propagation of the wave has been considered. Two distinct linear electrostatic modes exist, namely an acoustic lower mode and Langmuir-type optic-type upper one. The behavior of each of these modes is examined from the modulational stability point of view. The stability criteria are investigated, depending on the electrostatic carrier wave number, the angle theta between the modulation and propagation directions, and the positron-to-electron temperature ratio sigma. The analysis shows that modulated electrostatic wavepackets associated to the lower (acoustic) mode are unstable, for small values of carrier wave number k (i.e., for large wavelength lambda) and for finite (small) values of the angle theta (yet stable for higher theta), while those related to the upper (optic-like) mode are stable for large values of the angle theta only, in the same limit, yet nearly for all values of sigma. These results are of relevance in astrophysical contexts (e.g., in pulsar environments), where e-p plasmas are encountered, or in pair fullerene-ion plasmas, in laboratory. (c) 2006 American Institute of Physics.

Nonlinear perpendicular propagation of ordinary mode electromagnetic wave packets in pair plasmas and electron-positron-ion plasmas

The nonlinear amplitude modulation of electromagnetic waves propagating in pair plasmas, e.g., electron-positron or fullerene pair-ion plasmas, as well as three-component pair plasmas, e.g., electron-positron-ion plasmas or doped (dusty) fullerene pair-ion plasmas, assuming wave propagation in a direction perpendicular to the ambient magnetic field, obeying the ordinary (O-) mode dispersion characteristics. Adopting a multiple scales (reductive perturbation) technique, a nonlinear Schrodinger-type equation is shown to govern the modulated amplitude of the magnetic field (perturbation). The conditions for modulation instability are investigated, in terms of relevant parameters. It is shown that localized envelope modes (envelope solitons) occur, of the bright- (dark-) type envelope solitons, i.e., envelope pulses (holes, respectively), for frequencies below (above) an explicit threshold. Long wavelength waves with frequency near the effective pair plasma frequency are therefore unstable, and may evolve into bright solitons, while higher frequency (shorter wavelength) waves are stable, and may propagate as envelope holes.(c) 2007 American Institute of Physics.

Nonlinear Dynamics of Rotating Multi-Component Pair Plasmas and e-p-i Plasmas

The propagation of small amplitude stationary profile nonlinear electrostatic excitations in a pair plasma is investigated, mainly drawing inspiration from experiments on fullerene pair-ion plasmas. Two distinct pair ion species are considered of opposite polarity and same mass, in addition to a massive charged background species, which is assumed to be stationary, given the frequency scale of interest. In the pair-ion context, the third species is thought of as a background defect (e.g. charged dust) component. On the other hand, the model also applies formally to electron-positron-ion (e-p-i) plasmas, if one neglects electron-positron annihilation. A two-fluid plasma model is employed, incorporating both Lorentz and Coriolis forces, thus taking into account the interplay between the gyroscopic (Larmor) frequency ?c and the (intrinsic) plasma rotation frequency O0. By employing a multi-dimensional reductive perturbation technique, a Zakharov-Kuznetsov (ZK) type equation is derived for the evolution of the electric potential perturbation. Assuming an arbitrary direction of propagation, with respect to the magnetic field, we derive the exact form of nonlinear solutions, and study their characteristics. A parametric analysis is carried out, as regards the effect of the dusty plasma composition (background number density), species temperature(s) and the relative strength of rotation to Larmor frequencies. It is shown that the Larmor and mechanical rotation affect the pulse dynamics via a parallel-to-transverse mode coupling diffusion term, which in fact diverges at ?c ? ±2O0. Pulses collapse at this limit, as nonlinearity fails to balance dispersion. The analysis is complemented by investigating critical plasma compositions, in fact near-symmetric (T- ˜ T+) “pure” (n- ˜ n+) pair plasmas, i.e. when the concentration of the 3rd background species is negligible, case in which the (quadratic) nonlinearity vanishes, so one needs to resort to higher order nonlinear theory. A modified ZK equation is derived and analyzed. Our results are of relevance in pair-ion (fullerene) experiments and also potentially in astrophysical environments, e.g. in pulsars.

WASP-26b: a 1-Jupiter-mass planet around an early-G-type star

We report the discovery of WASP-26b, a moderately over-sized Jupiter-mass exoplanet transiting its 11.3-mag early-G-type host star (1SWASP J001824.70-151602.3; TYC 5839-876-1) every 2.7566 days. A simultaneous fit to transit photometry and radial-velocity measurements yields a planetary mass of 1.02 ± 0.03 MJup and radius of 1.32 ± 0.08 RJup. The host star, WASP-26, has a mass of 1.12 ± 0.03 M? and a radius of 1.34 ± 0.06 R? and is in a visual double with a fainter K-type star. The two stars are at least a common-proper motion pair with a common distance of around 250 ± 15 pc and an age of 6 ± 2 Gy.

Binding modes of diketo-acid inhibitors of HIV-1 integrase: A comparative molecular dynamics simulation study

HIV-1 integrase (IN) has become an attractive target since drug resistance against HIV-1 reverse transcriptase (RT) and protease (PR) has appeared. Diketo acid (DKA) inhibitors are potent and selective inhibitors of HIV-1 IN: however the action mechanism is not well understood. Here, to study the inhibition mechanism of DKAs we performed 10 ns comparative molecular dynamics simulations on HIV-1 IN bound with three most representative DMA inhibitors: Shionogi inhibitor, S-1360 and two Merck inhibitors L-731,988 and L-708,906. Our simulations show that the acidic part of S-1360 formed salt bridge and cation-pi interactions with Lys159. In addition, the catalytic Glu152 in S-1360 was pushed away from the active site to form an ion-pair interaction with Arg199. The Merck inhibitors can maintain either one or both of these ion-pair interaction features. The difference in potencies of the DMA inhibitors is thus attributed to the different binding modes at the catalytic site. Such structural information at atomic level, not only demonstrates the action modes of DMA inhibitors but also provides a novel starting point for structural-based design of HIV-1 IN inhibitors.