alpha-particle condensation in 16O studied with a full four-body orthogonality condition model calculation.

To explore the four-alpha-particle condensate state in 16O, we solve a full four-body equation of motion based on the four-alpha-particle orthogonality condition model in a large four-alpha-particle model space spanned by Gaussian basis functions. A full spectrum up to the 0_{6};{+} state is reproduced consistently with the lowest six 0;{+} states of the experimental spectrum. The 0_{6};{+} state is obtained at about 2 MeV above the four-alpha-particle breakup threshold and has a dilute density structure, with a radius of about 5 fm.

Electron-beam instability in left-handed media.

We predict that two electron beams can develop an instability when passing through a slab of left-handed media (LHM). This instability, which is inherent only for LHM, originates from the backward Cherenkov radiation and results in a self-modulation of the beams and radiation of electromagnetic waves. These waves leave the sample via the rear surface of the slab (the beam injection plane) and form two shifted bright circles centered at the beams.

Repair of I-SceI induced DSB at a specific site of chromosome in human cells: influence of low-dose, low-dose-rate gamma-rays.

We investigated the influence of low-dose, low-dose-rate gamma-ray irradiation on DNA double strand break (DSB) repair in human lymphoblastoid TK6 cells. A single DSB was introduced at intron 4 of the TK+ allele (chromosome 17) by transfection with the I-SceI expression vector pCBASce. We assessed for DSB repair due to non-homologous end-joining (NHEJ) by determining the generation of TK-deficient mutants in the TK6 derivative TSCE5 (TK +/-) carrying an I-SceI recognition site.

Association study of the C3 gene with adult and childhood asthma.

Bronchial asthma (BA) is a multifactorial disorder, the development of which is affected by both environmental and genetic factors. The complement system plays an important role in immunological response against invading microorganisms. It has been shown that complement-C3-deficient mice have reduced inflammation of asthmatic airways.

Promoter polymorphisms in the IRF3 gene confer protection against systemic lupus erythematosus.

In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and matched with 152 healthy controls using polymerase chain reaction-restriction fragment length polymorphism analysis.

Phosphorylation of Homer3 by calcium/calmodulin-dependent kinase II regulates a coupling state of its target molecules in Purkinje cells.

Homer proteins are components of postsynaptic density (PSD) and play a crucial role in coupling diverse target molecules. However, the regulatory aspect of Homer-mediated coupling has been addressed only about a dominant-negative effect of Homer1a, which requires de novo gene expression. Here, we present evidence that Homer-mediated coupling is regulated by its phosphorylation state.

Förster mechanism of electron-driven proton pumps.

We examine a simple model of proton pumping through the inner membrane of mitochondria in the living cell. We demonstrate that the pumping process can be described using approaches of condensed matter physics. In the framework of this model, we show that the resonant Förster-type energy exchange due to electron-proton Coulomb interaction can provide a unidirectional flow of protons against an electrochemical proton gradient, thereby accomplishing proton pumping.

Supramolecular assemblies of surfactants and lipid derivatives on free-standing hybrid nanofilms.

A large, free-standing hybrid nanofilm (thickness 35 nm) of zirconia and cross-linked acrylate is stably dispersed in aqueous media via assembly with surfactants and lipid derivatives. These amphiphiles showed three different behaviours. Category 1 is represented by single-chain ionic surfactants of SDS and CTAB and by non-ionic surfactant of Triton X100.

Association of genetic polymorphisms in SLCO1B3 and ABCC2 with docetaxel-induced leukopenia.

Despite long-term clinical experience with docetaxel, unpredictable severe adverse reactions remain an important determinant for limiting the use of the drug. To identify a genetic factor(s) determining the risk of docetaxel-induced leukopenia/neutropenia, we selected subjects who received docetaxel chemotherapy from samples recruited at BioBank Japan, and conducted a case-control association study. We genotyped 84 patients, 28 patients with grade 3 or 4 leukopenia/neutropenia, and 56 with no toxicity (patients with grade 1 or 2 were excluded), for a total of 79 single nucleotide polymorphisms (SNPs) in seven genes possibly involved in the metabolism or transport of this drug: CYP3A4, CYP3A5, ABCB1, ABCC2, SLCO1B3, NR1I2, and NR1I3.

Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy.

The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamixifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4-hydroxytamoxifen and endoxifen. We investigated the predictive value of the CYP2D6*10 allele, which decreased CYP2D6 activity, for clinical outcomes of patients that received adjuvant tamoxifen monotherapy after surgical operation on breast cancer. Among 67 patients examined, those homozygous for the CYP2D6*10 alleles revealed a significantly higher incidence of recurrence within 10 years after the operation (P = 0.

Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1.

Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, the Shank family of postsynaptic scaffold proteins are abundant and enriched in the postsynaptic density (PSD) of central excitatory synapses. When expressed in cultured hippocampal neurons, Shank promotes the maturation and enlargement of dendritic spines.

Highly efficient tip-enhanced Raman spectroscopy and microscopy of strained silicon.

We present a versatile tip-enhanced Raman spectroscopy (TERS) system that permits efficient illumination and detection of optical properties in the visible range to obtain high signal-to-noise Raman signals from surfaces and interfaces of materials using an edge filter. The cutoff wavelength of the edge filter is tuned by changing the angle of incident beam to deliver high incident power and effectively collect scattered near-field signals for nanoscopic investigation in depolarized TERS configuration. The dynamic design of the instrument provides a unique combination of features that allows us to perform reflection or transmission mode TERS to cover both opaque and transparent samples.

Semiclassical dynamics of electron wave packet states with phase vortices.

We consider semiclassical higher-order wave packet solutions of the Schrödinger equation with phase vortices. The vortex line is aligned with the propagation direction, and the wave packet carries a well-defined orbital angular momentum (OAM) variant Planck's over 2pil (l is the vortex strength) along its main linear momentum. The probability current coils around the momentum in such OAM states of electrons.

A functional SNP in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus in Japanese population.

Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases with complex genetic components. To identify a gene(s) susceptible to SLE, we performed a case-control association study using genome-wide gene-based single nucleotide polymorphisms (SNPs) in Japanese population. Here we report that an SNP (rs3748079) located in a promoter region of the inositol 1,4,5-triphosphate receptor type 3 (ITPR3) gene on chromosome 6p21 was significantly associated with SLE in two independent Japanese case-control samples [P=0.

Engineering FRET constructs using CFP and YFP.

Fluorescence resonance energy transfer (FRET) technology has been used to develop genetically encoded fluorescent indicators for various cellular functions. Here we discuss how to engineer constructs for FRET between the cyan- and yellow-emitting variants of green fluorescent protein (GFP) from Aequorea victoria (CFP and YFP, respectively). Throughout this chapter, we stress the fact that FRET is highly sensitive to the relative orientation and distance between the donor and the acceptor.

Frequency structure in an electronically tuned Ti:sapphire laser: periodic appearance of static fringes in both homodyne and heterodyne Michelson interferometers.

Static interference fringes were observed repeatedly with changes of path difference in both homodyne and heterodyne Michelson interferometers. This unique coherence property of an electronically tuned Ti:sapphire laser with an intracavity acousto-optic tunable filter (AOTF) has revealed the frequency structure and dynamics of the laser field. The fact that static interference occurred in a heterodyne interferometer with unequal path lengths indicates backscattering of the intracavity laser field, suggesting that Brillouin-enhanced four-wave mixing occurs in the intracavity AOTF.

Identification of a significant association of a single nucleotide polymorphism in TNXB with systemic lupus erythematosus in a Japanese population.

Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases, with complex genetic components. Here, we report on a case-control association study of 178 SLE patients and 899 control subjects, using genome-wide gene-based single nucleotide polymorphism (SNP) markers. An SNP, rs3130342, in a 5' flanking region of the TNXB gene revealed a significant association with SLE [P = 0.

Simulation of propofol anaesthesia for intracranial decompression using brain hypothermia treatment.

Background: Although propofol is commonly used for general anaesthesia of normothermic patients in clinical practice, little information is available in the literature regarding the use of propofol anaesthesia for intracranial decompression using brain hypothermia treatment. A novel propofol anaesthesia scheme is proposed that should promote such clinical application and improve understanding of the principles of using propofol anaesthesia for hypothermic intracranial decompression.

Methods: Theoretical analysis was carried out using a previously-developed integrative model of the thermoregulatory, hemodynamic and pharmacokinetic subsystems.

Interleukin-1 beta up-regulates TACE to enhance alpha-cleavage of APP in neurons: resulting decrease in Abeta production.

The proinflammatory cytokine interleukin (IL)-1beta is up-regulated in microglial cells surrounding amyloid plaques, leading to the hypothesis that IL-1beta is a risk factor for Alzheimer's disease. However, we unexpectedly found that IL-1beta significantly enhanced alpha-cleavage, indicated by increases in sAPPalpha and C83, but reduced beta-cleavage, indicated by decreases in sAPPbeta and Abeta40/42, in human neuroblastoma SK-N-SH cells. IL-1beta did not significantly alter the mRNA levels of BACE1, ADAM-9, and ADAM-10, but up-regulated that of TACE by threefold.

Phosphatidylglucoside: a new marker for lipid rafts.

Lipid rafts are functional microdomains enriched with sphingolipids and cholesterol. The fatty acyl chain composition of sphingolipids is a critical factor in the localization of lipids in lipid rafts. The recent studies suggest that lipid rafts are more heterogeneous than previously thought.

Mutagenic radioadaptation in a human lymphoblastoid cell line.

We investigated the mutagenic radioadaptive response of human lymphoblastoid TK6 cells by pretreating them with a low dose (5 cGy) of X-rays followed by a high (2 Gy) dose 6h later. Pretreatment reduced the 2-Gy-induced mutation frequency (MF) of the thymidine kinase (TK) gene (18.3 x 10(-6)) to 62% of the original level (11.

Citrullination by peptidylarginine deiminase in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex, multifactorial disease with genetic and immunological aspects. Because RA is an autoimmune condition, dysregulation of the immune system is implied. Many linkage and association studies have also indicated that multiple genetic factors are associated with RA.

Multiplex PCR-based real-time invader assay (mPCR-RETINA): a novel SNP-based method for detecting allelic asymmetries within copy number variation regions.

We report the development of a real-time Invader assay combined with multiplex PCR (mPCR-RETINA), an SNP-based approach that can measure the allelic ratio in copy number variation (CNV) regions of a genome. RETINA monitors the real-time fluorescence intensity of each allele during the Invader assay and detects allelic asymmetries caused by genomic duplication/multiplication in heterozygous individuals. By combining mPCR-RETINA and real-time quantitative PCR that detects total copy number, we can estimate the copy number of each allele in CNV regions, which should be useful for investigating the functional significance of allele copy number with disease susceptibilities and drug responses.

Novel mutations affecting axon guidance in zebrafish and a role for plexin signalling in the guidance of trigeminal and facial nerve axons.

In zebrafish embryos, the axons of the posterior trigeminal (Vp) and facial (VII) motoneurons project stereotypically to a small number of target muscles derived from the first and second branchial arches (BA1, BA2). Use of the Islet1 (Isl1)-GFP transgenic line enabled precise real-time observations of the growth cone behaviour of the Vp and VII motoneurons within BA1 and BA2. Screening for N-ethyl-N-nitrosourea-induced mutants identified seven distinct mutations affecting different steps in the axonal pathfinding of these motoneurons.

In vivo Raman study of the living rat esophagus and stomach using a micro-Raman probe under an endoscope.

A small endoscope system equipped with a micro Raman probe is developed for in vivo Raman measurements in living rats. The measurements are done under anesthesia and artificial respiration to minimize the impact on the rats. Raman spectra of living rat esophagus and stomach are successfully measured.