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ObjectiveThis study aimed to elucidate whether molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea.MethodTwenty patients with mild obstructive sleep apnoea (control group) and 40 patients with moderate to severe obstructive sleep apnoea (obstructive sleep apnoea group) who desired uvulopalatopharyngoplasty were recruited for the study. After uvulopalatopharyngoplasty, surgical specimens of the uvula were subjected to haematoxylin and eosin, Masson's trichrome and immunohistochemical staining. Western blot and reverse transcriptase-polymerase chain reaction were used to evaluate the protein and messenger RNA expressions.ResultsThe obstructive sleep apnoea group showed more severe inflammation, increased collagen deposition and higher immunohistochemical staining intensity for TGF-ß and MMP-9 as well as higher protein and messenger RNA expression of MMP-9, VEGF, TGF-ß, p38 MAPK, SMAD 2/3, AKT and JNK in the uvula than control group.ConclusionPatients with obstructive sleep apnoea demonstrated more severe inflammation, increased airway remodelling, and increased protein and messenger RNA expression of pro-inflammatory and pro-fibrotic cytokines in the uvula than control participants.

By focusing conventional 1-TW 40-fs laser pulses into a dense 450- μm-long nitrogen gas cell, we demonstrate the feasibility of routinely generating electron beams from laser wakefield acceleration (LWFA) with primary energies scaling up to 10 MeV and a high charge in excess of 50 pC. When electron beams are generated with a charge of ≈30 pC and a beam divergence of ≈40 mrad from the nitrogen cell having a peak atom density of [Formula: see text] cm−3, increasing the density inside the cell by 25%—controlled by tuning the backing pressure of fed nitrogen gas—can induce defocusing of the pump pulse that leads to a twofold increase in the output charge but with a trade-off in beam divergence. Therefore, this LWFA scheme has two preferred regimes for acquiring electron beams with either lower divergence or higher beam charge depending on a slight variation of the gas/plasma density inside the cell. Our results identify the high potential for implementing sub-millimeter nitrogen gas cells in the future development of high-repetition-rate LWFA driven by sub-TW or few-TW laser pulses.

Passive detection of special nuclear material (SNM) is challenging due to its inherently low rate of spontaneous emission of penetrating radiation, the relative ease of shielding, and the fluctuating and frequently overwhelming background. Active interrogation, the use of external radiation to increase the emission rate of characteristic radiation from SNM, has long been considered to be a promising method to overcome those challenges. Current active-interrogation systems that incorporate radiography tend to use bremsstrahlung beams, which can deliver high radiation doses. Low-energy ion-driven nuclear reactions that produce multiple monoenergetic photons may be used as an alternative. The ${}^{12}\mathrm{C}(\mathrm{p},{\mathrm{p}}^{\ensuremath{'}}{)}^{12}\mathrm{C}$ reaction is one such reaction that could produce large yields of highly penetrating 4.4- and 15.1-MeV gamma rays. This reaction does not directly produce neutrons below the approximately 19.7 MeV threshold, and the 15.1-MeV gamma-ray line is well matched to the photofission cross section of ${}^{235}\mathrm{U}$ and ${}^{238}\mathrm{U}$. We report the measurements of thick-target gamma-ray yields at 4.4 and 15.1 MeV from the ${}^{12}\mathrm{C}(\mathrm{p},{\mathrm{p}}^{\ensuremath{'}}{)}^{12}\mathrm{C}$ reaction at proton energies of 19.5, 25, and 30 MeV. Measurements are made with two $3$-in. EJ-309 cylindrical liquid scintillation detectors and thermoluminescent dosimeters placed at ${0}^{\ensuremath{\circ}}$ and ${90}^{\ensuremath{\circ}}$, with an additional $1.5$-in. $\mathrm{Na}\mathrm{I}$($\mathrm{Tl}$) cylindrical scintillation detector at ${0}^{\ensuremath{\circ}}$. We estimate the highest yields of the 4.4- and 15.1-MeV gamma rays of $1.65\ifmmode\times\else\texttimes\fi{}{10}^{10}$ and $4.47\ifmmode\times\else\texttimes\fi{}{10}^{8}\phantom{\rule{0.2em}{0ex}}{\mathrm{sr}}^{\ensuremath{-}1}$ $\ensuremath{\mu}{\mathrm{C}}^{\ensuremath{-}1}$ at a proton energy of 30 MeV, respectively. The yields in all experimental configurations are greater than in a comparable deuteron-driven reaction that produces the same gamma-ray energies---${}^{11}\mathrm{B}(\mathrm{d},\mathrm{n}\ensuremath{\gamma}{)}^{12}\mathrm{C}$. However, a significant increase of the neutron radiation dose accompanies the proton energy increase from 19.5 to 30 MeV.

An exothermic neutron capture reaction can be used to uniquely identify neutrons in particle detectors. With the use of a capture-gated coincidence technique, the sequence of scatter events that lead to neutron thermalization prior to the neutron capture can also be used to measure neutron energy. We report on the measurement of thermalization light yield via a time-of-flight technique in a polyvinyl toluene-based scintillator EJ-290 within a heterogeneous composite detector that also includes 6 Li-doped glass scintillator. The thermalization light output exhibits a strong correlation with neutron energy because of the preference for near-complete energy deposition prior to the 6 Li(n,t) 4 He neutron capture reaction. The nonproportionality of the light yield from nuclear recoils contributes to the observed broadening of the distribution of thermalization light output. The nonproportional dependence of the scintillation light output in the EJ-290 scintillator as a function of proton recoil energy has been characterized in the range of 0.3–14.1 MeV via the Birks parametrization through a combination of time-of-flight measurement and previously conducted measurements with monoenergetic neutron sources.

We report a near-field study of the excitation and propagation of surface plasmon on ordered Ag elliptical hole arrays with a scattering-type scanning near-field optical microscope. Strong dipole-like local plasmon is identified at each individual hole from near-field optical intensity and phase images. The excitation of the local plasmon at the elliptical hole is found to follow polarization excitation constraint. The coherent superposition of these local plasmon waves to form an extended surface plasmon wave propagating to an adjacent hole array is observed directly. The near-field results are consistent with the results obtained from far-field extraordinary transmission measurements.

Although genetics analyses have identified the HLA-Cw6 allele to be the major risk allele for psoriasis vulgaris (PV) in many racial groups, it has been proposed that other putative genes near the HLA-C locus are involved in PV susceptibility and that the association of Cw6 is a result of linkage disequilibrium. The SPR1 gene, a predicted gene located 128 kb telomeric to the HLA-C locus, is considered to be one potential candidate gene of PV. Until now, no association study of the SPR1 gene has been conducted on psoriasis patients. We investigated the SPR1 gene for disease association by direct sequencing of the SPR1 gene in 116 Chinese patients with PV and 116 normal subjects. Genotyping for HLA-Cw6 was also carried out using polymerase chain reaction/restriction fragment length polymorphism. Significant increase of the HLA-Cw6 allele was found in psoriasis patients (32.8% vs. 13.8%, P = 0.001). We found that the SPR1 gene is a highly polymorphic gene containing 13 single nucleotide polymorphisms (SNPs), two of which have not been previously reported, and four SNPs cause amino acid change. No significantly different allelic distribution of 13 SPR1 SNPs could be found between the patients with PV and controls after correction for multiple testing. If the frequencies of SPR1 SNPs were compared between the early onset psoriatics and control subjects, early onset patients were more likely to have G allele at position 988 (60% vs. 35.3%, P = 0.001). However, the significance disappeared upon stratification for the Cw6 status. Haplotype-based association analysis showed two susceptibility haplotypes (types 8 and 19) in early onset psoriasis patients. Nonetheless, the significance also disappeared after stratification of the Cw6 status. Our results suggest that HLA-Cw6 remains the major risk allele in Chinese psoriatics, and that the SPR1 gene might not play an important role in the causation of PV.

Pemphigus vulgaris (PV) is a rare autoimmune blistering condition. Treatment typically combines corticosteroids with another immunosuppressive agent, such as azathioprine, mycophenolate mofetil (MMF) or rituximab.This study aims to compare these second agents for their clinical efficacy and steroid-sparing effect.This was a single-centre, retrospective observational cohort study of 21 patients with oral PV over a 6-year period, 18 of whom were newly diagnosed. Of the latter, the first 13 were initially given azathioprine, progressing to MMF and then rituximab on treatment failure, while the next five patients started directly on MMF.Of the 13 newly diagnosed patients, 2/13 were intolerant of azathioprine, and only 1/11 was controlled, with a median time to treatment failure (MTTF) of 254 days. MMF was given to 17 patients, either de novo (5) or after azathioprine (12), and was significantly more effective, controlling activity in 4/17 patients, and for a significantly longer time (MTTF 395 days, P = 0.019). All 13 patients failing MMF received rituximab, seven required a second dose, and three, a third dose. All patients responded, with 11/13 able to cease steroids. Control was maintained for a similar time to MMF (MTTF 364 days, P = NS). Rituximab also had the best steroid-sparing effect followed by MMF, then azathioprine. Side-effects were common with azathioprine, while the other two agents were well tolerated.Rituximab was the most effective of the three immunosuppressives for PV, although repeat dosing was frequently required. These observations have significant implications for the choice of drugs for this condition.

Border crossings in northern New York are important to international trade and tourism. How traffic operations at these crossings can be made more efficient has been a concern to the New York State Department of Transportation and the agencies that operate bridges, toll plazas, and customs and immigration plazas. Very little, however, is known about the characteristics of vehicle-processing time and delay at these crossings. This lack of understanding makes it difficult to evaluate the potential impact of changes in operating policies and physical plants. To alleviate this problem, this study identifies the processing time characteristics at three northern New York border crossings and proposes a delay model for planning applications.

Reorganization of the actin cytoskeleton is essential for cell motility and chemotaxis. Actin-binding proteins (ABPs) and membrane lipids, especially phosphoinositides PI(4,5)P2 and PI(3,4,5)P3 are involved in the regulation of this reorganization. At least 15 ABPs have been reported to interact with, or regulated by phosphoinositides (PIPs) whose synthesis is regulated by extracellular signals. Recent studies have uncovered several parallel intracellular signalling pathways that crosstalk in chemotaxing cells. Here, we review the roles of ABPs and phosphoinositides in chemotaxis and cell migration.This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24.

Direct laser acceleration (DLA) of electrons can be achieved by utilizing the axial field of a well-guided, radially polarized laser pulse in a density-modulated plasma waveguide. When a laser pulse of a few terawatt (TW) peak power is applied, however, the laser ponderomotive force perturbs plasma electrons to concentrate in the center, such that the generated electrostatic fields can significantly defocus the externally injected electron witness bunch and considerably deteriorate the acceleration efficiency. To improve the performance of DLA, a leading electron bunch, which acts as a precursor, can be introduced in DLA to effectively confine the witness bunch. Three-dimensional particle-in-cell simulations have been conducted to demonstrate that the transverse properties of the witness bunch can be significantly improved when a precursor bunch is used. Selected bunch transverse sizes, bunch charges, and axial separation from the witness bunch have been assigned to the precursor in a series of DLA simula...

Carnitine is involved in fatty acid metabolism in mammals and is widely used as a nutritional supplement; carnitine orotate is a more absorbable form of carnitine. We investigated the effects of carnitine and carnitine orotate on mouse prolactin-releasing peptide (PrRP) mRNA expression. Twenty-four female mice were randomly divided into four groups of six; control mice were orally drenched with physiological saline solution (250 mg/kg body weight) and treatment mice were orally drenched with carnitine (250 mg/kg) or carnitine orotate (250 or 750 mg/kg), once a day, for 20 days from parturition. The carnitine or carnitine orotate was dissolved in saline solution before administration. The hypothalamus, pituitary and ovary were sampled on day 21 after parturition, and PrRP mRNA levels in these tissues were measured by semi-quantitative PCR, with glyceraldehyde 3-phosphate dehydrogenase as a control. Expression of PrRP in mice treated with carnitine and carnitine orotate was significantly increased in the ovary and significantly reduced in the pituitary gland. Compared with the control, hypothalamus PrRP mRNA increased significantly in the carnitine and low-dose carnitine orotate groups and decreased significantly in the high-dose carnitine orotate group. We conclude that carnitine and carnitine orotate regulate expression of PrRP in the pituitary gland and ovaries.

Alopecia areata (AA) may be related to stress and has been reported to be associated with psychiatric disorders. Nevertheless, a nationwide study of the relationship between AA and comorbid psychiatric diseases has not been conducted, and the effect of onset age has rarely been reported.To analyse the associations between AA and various psychiatric disorders using a nationwide database in Taiwan.Data were obtained from the National Health Insurance Research Database of Taiwan from 2000 to 2009. In total, 5117 patients with AA and 20 468 age- and gender-matched controls were enrolled.Patients with AA tended to have more coexisting anxiety and less comorbid schizophrenia. Differences in ages of onset revealed differences in comorbidities. An increased risk of depression [odds ratio (OR) 2·23; 95% confidence interval (CI) 1·09-4·54] was found in patients with AA aged20years. An increased rate of anxiety (OR 1·43; CI 1·15-1·77) was observed with AA onset between the ages of 20 and 39years. The highest odds of obsessive-compulsive disorder (OR 3·00; CI 1·11-8·12) and anxiety (OR 2·05; CI 1·56-2·68) were observed in patients with AA aged 40-59years. Moreover, about 50% of psychiatric disorders occurred earlier than AA.AA is related to various psychiatric disorders. Onset age of AA is an important factor in the association with different comorbid psychiatric diseases. In addition to cosmetic impact, which may bring about anxiety or depression, stress neuroendocrine immunology may play an important role in the pathogenesis of both AA and psychiatric disorders.

IgG4-related systemic disease (IgG4-RSD) is a systemic inflammatory disease distinguished by tissue infiltrates of IgG4(+) plasma cells and elevated serum IgG4 levels. While IgG4-RSD often involves the pancreas, extra-pancreatic organs are also frequently affected. Here, we review the presentation and management of patients with extra-pancreatic IgG4-RSD.A retrospective analysis was performed on patients diagnosed with extra-pancreatic IgG4-RSD identified from a single centre.Six patients with extra-pancreatic IgG4-RSD were identified. The median age of the patients was 64 years. The range of involved organs included lymph nodes (three patients), ocular adnexa, lung, kidneys, meninges and exocrine glands. The median delay in diagnosis was 13.5 months (4-60 months). Four patients had elevated serum IgG4 levels at diagnosis. Five symptomatic patients were commenced on combination immunosuppression, which included corticosteroids. Maintenance therapy with azathioprine was used in one patient, methotrexate and mycophenolate were each used in two patients, and cyclophosphamide in one patient. Four treated patients went into remission, while two patients had persistent radiological disease. One patient experienced two relapses.IgG4-RSD can manifest in a variety of organs. Lack of awareness regarding this entity may delay diagnosis. Combination treatment of corticosteroids and conventional immunosuppression is effective.

Bullous pemphigoid (BP) has been associated with neurological and psychiatric diseases; however, large-scale population-based study of different comorbid diseases in patients with BP is quite limited.We sought to analyse the prevalence of neurological, psychiatric, autoimmune and inflammatory skin diseases prior to the diagnosis of BP and their associations with BP among patients with BP from a nationwide database in Taiwan.A total of 3485 patients with BP and 17,425 matching controls were identified from the National Health Insurance Database in Taiwan from 1997 to 2008. Conditional logistic regression analyses for a nested case-control study were performed to examine the prevalence of comorbidities prior to the diagnosis of BP between these two groups.Overall, our results showed that stroke [odds ratio (OR) 3·30; 95% confidence interval (95% CI) 3·03-3·60], dementia (OR 4·81; 95% CI 4·26-5·42), Parkinson disease (OR 3·49; 95% CI 3·05-3·98), epilepsy (OR 3·97; 95% CI 3·28-4·81), schizophrenia (OR 2·56; 95% CI 1·52-4·30) and psoriasis (OR 2·02; 95% CI 1·54-2·66) were significantly associated with BP. Among them, the association with schizophrenia and psoriasis was predominant in female and male patients, respectively, with BP. It remains for all these comorbid diseases to be independently associated with BP by multivariate analysis.Patients with BP are more likely to have various neurological diseases, schizophrenia and psoriasis prior to the diagnosis of BP, supporting associations found in other studies. Further research is required to elucidate the tentative causal association with BP.

Generation of intense mid-infrared pulses by laser-plasma interaction in the bubble regime is demonstrated experimentally. Nonlinear phase modulation is shown to be the conversion mechanism by theoretical analysis and numerical simulation.

As an intense laser pulse propagates through an underdense plasma, the strong ponderomotive force pushes away the electrons and produces a trailing plasma bubble. In the meantime the pulse itself undergoes extreme nonlinear evolution that results in strong spectral broadening toward the long-wavelength side. By experiment we demonstrate that this process can be utilized to generate ultrashort midinfrared pulses with an energy three orders of magnitude larger than that produced by crystal-based nonlinear optics. The infrared pulse is encapsulated in the bubble before exiting the plasma, hence is not absorbed by the plasma. The process is analyzed experimentally with laser-plasma tomographic measurements and numerically with three-dimensional particle-in-cell simulation. Good agreement is found between theoretical estimation, numerical simulation, and experimental results.

Objective Clonidine is an α 2 -adrenoceptor agonist which, by coupling with G-protein, has been proposed as an alternative treatment for refractory ascites of patients with cirrhosis for several years. Genetic polymorphisms of β-adrenoceptor and angiotensin II type 1 receptor blockers have been reported to affect drug response in patients with cirrhosis. This study evaluated the clonidine–diuretic response rate, favourable predictors and genetic components of the clonidine–diuretic response in patients with cirrhosis with refractory ascites. Methods 270 patients with cirrhosis with refractory ascites were randomised equally into two treatment groups to receive diuretics alone or the clonidine–diuretics association. The primary end point was clonidine–diuretic response rate. Secondary end points were mean daily dose of diuretics, times of paracentesis, ascites-related readmission and 1-year survival rate. Results Good clonidine responders had better natriuresis and diuresis as well as a significant decrease in abdominal circumference, plasma renin, aldosterone and norepinephrine levels. The overall clonidine–diuretics response rate was 55–60%. In patients with cirrhosis, the prevalence of ARDA 2 C WD/DD and GNB3 CT/TT genotypes was 71% and 77%, respectively. Among the responders, 71% of patients with cirrhosis had the ARDA 2 C WD/DD genotype and 67% has the GNB3 CT/TT genotype. Besides higher baseline norepinephrine levels, the presence of both ARDA 2 C WD/DD and GNB3 CT/TT genotypes showed a positive predictive value of 82% and a negative predictive value of 79% for good clonidine response. Conclusions These results suggest that neurohormonal and genetic testing may be used as predictive factors for the additive effects of clonidine on the diuresis and natriuresis effects of diuretics in patients with cirrhosis with refractory ascites.

Summary Background: Prehypertension, a new category of blood pressure (BP) classification introduced by The Seven Report of the Joint National Commission (JNC-7) on High BP for individuals with systolic BP in the range of 120–139 mmHg or diastolic BP between 80 and 89 mmHg, is a strong predictor for the development of hypertension. Insulin resistance (IR) has been proposed to be a key feature of metabolic abnormalities of hypertension and may precede the elevation of BP. Aim: The purpose of the study is to evaluate whether prehypertension is associated with IR. Design: This is a cross-sectional study. Methods: Anthropometric and BP measurements were performed in 83 prehypertensive subjects and 192 normotensives. All subjects received a 75-g oral glucose tolerance test (OGTT) for the measurements of IR. Results: The prehypertensive subjects were more obese and had higher levels of fasting triglycerides and 2-h insulin than the normotensives. The subjects with prehypertension were more insulin resistant than the counterparts, indicated by lower insulin sensitivity index, ISI0,120, values. While there was no difference between the two groups in insulin response of OGTT after adjustments for confounders, the prehypertension group maintained significant between-group differences in glucose response even when the incremental insulin levels were added to covariates for adjustments. Discussion: Our data show that prehypertension is associated with IR. The subjects with prehypertension have clinical characteristics of the IR syndrome. It seems that the prehypertension group cannot handle oral glucose challenge as well as the normotension, probably a consequence of IR in prehypertension.

Backward Raman amplification of a short laser pulse in a plasma waveguide is demonstrated. With a guided seed pulse of 0.8-microJ energy and a pump pulse of 345-mJ energy in a 9-mm-long optically preformed plasma waveguide, 910-fold energy amplification is achieved. Heating of the plasma by the long pump pulse is identified to be a key issue for plasma-waveguide-based backward Raman amplifiers.

DPI 201-107 (DPI), a diphenylpiperazinylindole derivative, was reported to be a cardio-selective modifier of voltage-gated Na+ channels. It remains unclear whether DPI has any effects on ion currents. The effects of DPI on ion currents and membrane potential in pituitary tumor (GH3) cells were investigated in this study. DPI (1-100 microM) suppressed the amplitude of delayed-rectifier K+ current (I(K(DR))) in a concentration-dependent manner with an IC(50) value of 9.4 microM. The presence of DPI also enhanced the rate and extent of I(K(DR)) inactivation. Recovery from block by DPI (10 microM) was fitted by a single exponential. Crossover of tail currents during the exposure to DPI was also observed. Under current-clamp recordings, DPI prolonged action potential duration in GH3 cells. With a minimal binding scheme, DPI-induced block of I(K(DR))) was quantitatively provided. The exposure to DPI also blocked I(K(DR))) with a concomitant increase in current inactivation in NG108-15 neuronal cells. Taken together, the results imply that DPI acts as an open-channel blocker of delayed-rectifier K+ channels in these cells. The widening of action potentials induced by DPI in these cells may be explained mainly by its block of I(K(DR))) in a state-dependent manner.

This report presents an overview of our recent near-field investigation of both local and surface plasmon resonance (SPR) with a scattering-type scanning near-field optical microscope (s-SNOM) which has sub-10 nanometer resolution. With the ability to perform near-field optical experiments at multiple excitation wavelengths simultaneously, this instrument has recorded near-field intensity and phase images of a wide range of subwavelength plasmonic structures: single nanohole and nanoslit, circular and elliptical hole arrays, etc. The near-field results obtained with different excitation wavelengths were confirmed by numerical calculation and were made direct correspondence with far-field observations by comprehensive models. The multi-wavelength s-SNOM proves to be an essential tool to unravel many interesting plasmonic phenomena in nanometer scale. This work investigates the nature of subwavelength plasmon optics which potentially will play an important role in the development of many innovative highly efficient optoelectronic devices (light-emitting devices and solar cells) and highly sensitive sensors based on SPR and surfaceenhanced Raman scattering.

Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder in South America and Southeast Asia. Most cases of PCA are sporadic but familial aggregation has been reported from South America and Taiwan. The different susceptibility among ethnic groups suggests that genetic factors may play an important role in its pathogenesis.We aimed to perform a genome-wide scan by linkage analysis across 15 families with familial primary cutaneous amyloidosis (FPCA) to map the disease gene(s) for FPCA.A total of 15 FPCA families including 50 individuals affected with PCA were recruited. Throughout the 22 autosomes, 369 polymorphic microsatellite markers were used initially. Regions showing a LOD score1 identified in the initial scan were further analysed with additional markers. Two-point and multipoint linkage analysis were performed by using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program.A maximum two-point LOD score of 4.76 for the marker D5S1490 (theta = 0.10, alpha = 0.60) and a multipoint LOD score of 4.50 between D5S822 and D5S623 (alpha = 0.60) were obtained under the assumption of heterogeneity. A peak NPL score of 5.23 (P value = 0.000007) was found from D5S1490 to D5S2076. Further analysis focusing on two major families identifies a common haplotype shared by all affected individuals between D5S1490 and D5S623. To our knowledge, this is the first report of genome-wide analysis of a large number of FPCA pedigrees.Our study provides evidence for significant linkage to chromosome 5p13.1-q11.2 in a subset of FPCA families.

Besides the HLA-Cw*0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus. The -79C, -26C and +246A alleles of the PSORS1C3 gene, the CDSN*971T allele, CDSN*TTC (619T-1236T-1243C) and CDSN*5 (619T-1240G-1243C) are strongly associated with psoriasis in the caucasian population. Until now, no haplotype study of the PSORS1C3 and CDSN genes has been documented in Chinese patients with psoriasis vulgaris.We aimed to determine whether genetic polymorphisms of the PSORS1C3 and CDSN genes were associated with an increased risk of psoriasis vulgaris in Chinese patients in Taiwan.We investigated the PSORS1C3 and CDSN genes for disease association by direct sequencing in 178 patients with psoriasis vulgaris and 203 control subjects. Genotyping for HLA-Cw*0602, alpha-helix coiled-coil rod homologue (HCR) gene and single nucleotide polymorphism (SNP) n.9 was also carried out using a sequence-based typing method.The PSORS1C3*582A allele, an SNP in the 3'-untranslated region of the PSORS1C3 gene, was a major psoriasis vulgaris susceptibility allele in the Chinese population, and the association was much stronger in patients with early-onset psoriasis vulgaris (22.3% vs. 6.9%, odds ratio = 3.87, P(c) =0.0000072). The frequencies of CDSN*TTC and CDSN*971T were also significantly increased in patients with early-onset psoriasis vulgaris. Moreover, PSORS1C3*582A, SNP n.9*C, Cw*0602 and HCR*WWCC were in near complete linkage disequilibrium (LD) with each other; in contrast, the LD with the CDSN gene was not so strong. SNP n.9*C-Cw*0602-PSORS1C3*582A-HCR*WWCC was a major susceptibility haplotype in patients with early-onset psoriasis vulgaris (P10(-7)) and this risk haplotype also carried CDSN*TTC and CDSN*971T.The PSORS1C3 and CDSN genes are important psoriasis susceptibility genes in Chinese patients with psoriasis vulgaris.

Enhancement of relativistic third-harmonic generation by using an optically preformed periodic plasma waveguide was achieved. Resonant dependence of harmonic intensity on plasma density and density modulation parameters was observed, which is a distinct characteristic of quasi-phase-matching. The results demonstrate the potential of a modulated plasma waveguide in high-field applications.

Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP.We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP.DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and IFN-gamma genes.Although the BP patients were more likely to carry the -511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene. In female patients with BP, the associations with IL-1beta (-511T) and (-31C) alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed.The IL-1beta (-511) and (-31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.

Validating DSP circuits modeled in VHDL involves generating test data, creating VHDL test benches and simulating the models. This is a laborious and time-consuming process. Therefore, it is desired to develop a high-level approach to automating and planning these tasks. This paper summarizes a high-level test planning system for functional validation of DSP circuits modeled in VHDL. Test data are generated bp VHDL test benches which are created using high-level tools and configured by test plans. The test plans use goal trees to partition the system requirements into partially constrained test groups. The test spaces of the test groups are reduced and so economical tests can be derived. Software tools have been developed based on this approach.

A CMP-free process by electropolishing (EP) the planar contact plating (CP) Cu film and TaN dry etching which eliminate the stress induced peeling during CMP was demonstrated. Nanometer smoothness and a highly texture of Cu can be achieved by optimizing the EP process. A 4-level Cu/low-k interconnect with CMP-less process was demonstrated with excellent yield. This process improves the throughput on ECP and CMP by two and has less dishing.

Long QT syndrome (LQT) is a cardiovascular disorder causing syncope and sudden death from arrhythmias. Mutations in KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A genes encoding cardiac potassium and sodium ion channels cause LQT. Two Taiwanese LQT families were screened for mutations in these ion channel genes. In family H87, the diagnosis was made in the 25-year-old female proband and six family members based on recurrent syncope and/or a prolonged QT interval. Genotyping revealed a novel nonsense mutation, R744X (C to T transition in codon 744), in the KCNH2 potassium channel gene, resulting in truncation of the putative cyclic nucleotide-binding domain and C-terminal region of the HERG K(+)-channel in all affected family members. The mutation was confirmed by DdeI endonuclease digestion of the DNA from each family member. The 26-year-old female proband in family L89 developed repeated syncope with QTc of 0.61 seconds. After linkage and mutation analysis, the syndrome in this family was associated with a novel KCNQ1 missense mutation, T309I, causing the substitution of a threonine residue at position 309, in the pore region of the KvLQT1 K(+)-channel, with an isoleucine. By Tsp45I restriction analysis, the mutation was noted in the proband and the proband's asymptomatic brother, but was not detected in 100 unrelated normal individuals. Identification of a mutation has clinical implications for presymptomatic diagnosis and therapy.

Numerous applications in fundamental and applied research, security, and industry require robust, compact sources of x-rays, with a particular recent interest in monochromatic, spatially coherent, and ultrafast x-ray pulses in well-collimated beams. Such x-ray sources usually require production of high-quality electron beams from compact accelerators. Guiding a radially polarized laser pulse in a plasma waveguide has been proposed for realizing direct laser acceleration (DLA), where the electrons are accelerated by the axial electric field of a co-propagating laser pulse (Serafim et al 2000 IEEE Trans. Plasma Sci. 28 1190). A moderate laser peak power is required for DLA when compared to laser wakefield acceleration, thus offering the prospect for high repetition rate operation. By using a density-modulated plasma waveguide for DLA, the acceleration distance can be extended with pulse guiding, while the density-modulation with proper axial structure can realize the quasi-phase matching between the laser pulses and electrons for a net gain accumulation (York et al 2008 Phys. Rev. Lett. 100 195001; York et al 2008 J. Opt. Soc. Am. B 25 B137; Palastro et al 2008 Phys. Rev. E 77 036405). We describe the development and application of a test particle model and particle-in-cell model for DLA. Experimental setups designed for fabrication of optically tailored plasma waveguides via the ignitor-heater scheme, and for generation and characterization of radially polarized short pulses used to drive DLA, are presented.

Quasi-phase matched direct laser acceleration (DLA) of electrons can be realized with guided, radially polarized laser pulses in density-modulated plasma waveguides. A 3-D particle-in-cell model has been developed to describe the interactions among the laser field, injected electrons, and the background plasma in the DLA process. Simulations have been conducted to study the scheme in which seed electron bunches with moderate energies are injected into a plasma waveguide and the DLA is performed by use of relatively low-power (0.5-2 TW) laser pulses. Selected bunch injection delays with respect to the laser pulse, bunch lengths, and bunch transverse sizes have been studied in a series of simulations of DLA in a plasma waveguide. The results show that the injection delay is important for controlling the final transverse properties of short electron bunches, but it also affects the final energy gain. With a long injected bunch length, the enhanced ion-focusing force helps to collimate the electrons and a relatively small final emittance can be obtained. DLA efficiency is reduced when a bunch with a greater transverse size is injected; in addition, micro-bunching is clearly observed due to the focusing and defocusing of electrons by the radially directed Lorentz force. DLA should be performed with a moderate laser power to maintain favorable bunch transverse properties, while the waveguide length can be extended to obtain a higher maximum energy gain, with the commensurate increase of laser pulse duration and energy.

Lifting capacities greater than 41 N/cm2 (60 psi) at 77 K have been achieved using a combination of permanent magnets and high quality melt‐textured YBa2Cu3O7−δ (YBCO). The key concept of this hybrid superconducting magnetic bearing (HSMB) is the use of strong magnetic repulsion and attraction from permanent magnets to support high loads in conjunction with flux pinning in a type II superconductor to counteract instabilities in a system consisting of magnets only. To illustrate this concept, radial and axial forces between magnet/superconductor, magnet/magnet, and magnet/superconductor/magnet, were measured and compared for the thrust and journal bearing configurations on a bearing prototype.

Previous studies have indicated possible linkage of schizophrenia with chromosome 6p21-24. In an attempt to replicate these findings, we studied the linkage of schizophrenia with nine markers on chromosome 6p21-24 in 39 Taiwanese schizophrenic nuclear families with at least two affected siblings. Two diagnostic models (narrow: Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other nonaffective psychotic disorders) were used to define the disease phenotypes. With the broad and narrow diagnostic models, the marker D6S296 produced maximum two-point lod scores of 1.46 (straight theta = 0.2) and 1.35 (straight theta = 0. 2), respectively, in the recessive inheritance model. Assuming locus heterogeneity, a multipoint lod score of 0.85 was obtained between markers D6S296 and D6S277 under the narrow/recessive model. Maximum nonparametric lod scores of 1.25 ( p= 0.09) and 1.36 (p = 0.08) were observed, but still not statistically significant, at D6S296 in the narrow and broad diagnostic models, respectively. Both two-point analysis of the dominant model (lod score 0.85) and nonparametric analysis (lod score 1.25) showed a mild peak lod score appeared at marker D6S 285 as well. The results add some support to the suggestive linkage of schizophrenia with markers in the regions of chromosome 6p22 and 6p24 in an ethnically distinct Taiwanese sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:74-78, 2000.

The effect of chloroform on Ca(2+) mobilization in Madin-Darby canine kidney cells was examined by using Fura-2 as a Ca(2+) probe. Chloroform (24-248 mM) concentration dependently increased intracellular Ca(2+) concentration ([Ca(2+)](i)). Ca(2+) removal inhibited the Ca(2+) signals evoked by 93 to 248 mM chloroform by reducing both the initial rise and the sustained phase. In Ca(2+)-free medium, pretreatment with 93 mM chloroform abolished the Ca(2+) release induced by 1 microM thapsigargin, an endoplasmic reticulum Ca(2+) pump inhibitor, and partially reduced the Ca(2+) release induced by 2 microM carbonylcyanide m-chlorophenylhydrazone, a mitochondrial uncoupler. Pretreatment with carbonylcyanide m-chlorophenylhydrazone and thapsigargin to deplete the Ca(2+) stores in mitochondria and the endoplasmic reticulum, respectively, only partially inhibited chloroform-induced Ca(2+) release. This suggests that chloroform released Ca(2+) from multiple internal pools. The addition of 3 mM Ca(2+) increased [Ca(2+)](i) after pretreatment with 93 mM chloroform in Ca(2+)-free medium. La(3+) (1 mM) partially inhibited the [Ca(2+)](i) increase induced by 93 mM chloroform. Chloroform (93 mM)-induced Ca(2+) release was not altered when the formation of inositol-1,4,5-trisphosphate was abolished by U73122 (2 microM), a phospholipase C inhibitor, but was inhibited by 90% by inhibition of phospholipase A(2) with 40 microM aristolochic acid. Collectively, we found that 93 mM chloroform increased [Ca(2+)](i) in Madin-Darby canine kidney cells by releasing Ca(2+) from multiple stores in a manner independent of the formation of inositol-1,4,5-trisphosphate, followed by Ca(2+) entry from external medium. Other solvents, such as ethanol, methanol, and DMSO, did not affect the resting [Ca(2+)](i) at a concentration of 248 mM.

A study of the levitation forces related to superconducting bearing design was conducted on free‐sintered and melt‐textured Y1Ba2Cu3O7−δ(YBCO) materials. Comparisons were made between free sintered, variously oriented, and randomly oriented melt‐textured materials. Magnetic force measurements were also conducted on oriented YBCO before and after neutron irradiation. A magnetic bearing of new design utilizing the phenomenon of flux pinning was then fabricated using melt‐textured YBCO with permanent magnets and a speed of 135 000 rpm was achieved. Rotational dissipation and magnetic stiffness measurements were performed on the bearing prototype.

Direct laser acceleration (DLA) of electrons by the use of the intense axial electric field of an ultrafast radially polarized laser pulse is a promising technique for future compact accelerators. Density-modulated plasma waveguides can be implemented for guiding the propagation of the laser pulse to extend the acceleration distance and for the quasi-phase-matching between the accelerated electrons and the laser pulse. A test particle model is developed to study the optimal axial density modulation structure of plasma waveguides for laser pulses to efficiently accelerate co-propagating electrons. A simple analytical approach is also presented, which can be used to estimate the energy gain in DLA. The analytical model is validated by the test particle simulation. The effect of injection phase and acceleration of electrons injected at various radial positions are studied. The results indicate that a positively chirped density modulation of the waveguide structure is required to accelerate electron with low initial energies, and can be effectively optimized. A wider tolerance on the injection phase and radial distance from the waveguide axis exists for electrons injected with a higher initial energy.

Two types of double-sided nanostructure, one possessing a slit aperture with parallel grooves and the other possessing a circular aperture with concentric grooves, were fabricated to examine the similarities and differences of their diffraction behavior in one-dimensional (1-D) and two-dimensional (2-D) nanostructures. Based on the projection-slice theory, we conjecture that the surface plasmons in these two different nano-scale grooves possess similar modes. A localized surface plasmon (LSP) was used to examine the transmission characteristics induced by the apertures. The transmission characteristics of the slitted nanostructure and the circular nanostructure aperture were then measured. We coupled the transmission spectra measured from these two apertures with a 1-D parallel groove transmission curve simulated by a 1-D rigorous coupled wave analysis. Measured spectra results show reasonable agreement with the simulated data. We propose that the apparent blueshift observed in the peak frequency of a 2-D nanostructure is due to the difference in the shape of the aperture and the spot transmission characteristics of 1-D and 2-D systems as induced by a LSP.