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The various types of atmospheric pressure plasma jets (APPJs) have been developed as the proto-type of user friend in Plasma-Bio Research Center (PBRC), Korea. According to the power sources the discharge-types are DC & a low frequency AC, RF, and micro-wave. (i) The plasma jet devices of DC-type and DBD-types have been made as the portable hand-carriers using DC-battery installed. (ii) AC-type jets with the frequency of a few tens of kHz have been developed with respect to the miniature and user-friend with the electric-safety using for the applications of human body and biology. In the proto-type device for the biomedicine applications the current is adjustable in the range from the low current of 0.1 mA to the high current of a few mAs. The inert gases or mixed gases are used. Especially, for the applications of semiconductor doping process, the single channel and the multi-channel of jet-doping systems are developed in the current range of a few or several tens of mA. (iii) RF-plasma jet is introduced with the power of 13.56 MHz. The RF power is adjustable in the range less than 100 W. The single channel of the proto-type device is shown with the discharge of inert gas for the biomedicine applications. (iv) Two-types of MW-plasma jets are developed. One is the proto-type MW-jet equipped with the miniature power source of semiconductor circuit which has been developed in this study. The frequency range is several hundreds of MHz and the power is adjustable in the range of several tens of Watt. The harmonic-tuned power amplifier of the oscillator was designed for improving drain efficiency with a single Laterally Diffused Metal Oxide Semiconductor (LDMOS) transistor using a non-linear harmonic balance simulation code. The other is the high power MW-jet system with the commercial MW-power sources. This Microwave plasma was excited at 2.45 GHz frequency and 0.8 W average power with a pulse generating width of 20µs and pulse generating period 2500µs. For the various applications this system is adjustable with respect to the peak power, the duration of pulse generation, and the pulse width of microwave.

Schizophrenia is a highly heritable neuropsychiatric disorder of complex genetic etiology. Previous genome-wide surveys have revealed a greater burden of large, rare CNVs in schizophrenia cases and identified multiple rare recurrent CNVs that increase risk of schizophrenia although with incomplete penetrance and pleiotropic effects. Identification of additional recurrent CNVs and biological pathways enriched for schizophrenia CNVs requires greater sample sizes. We conducted a genome-wide survey for CNVs associated with schizophrenia using a Swedish national sample (4,719 cases and 5,917 controls). High-confidence CNV calls were generated using genotyping array intensity data and their effect on risk of schizophrenia was measured. Our data confirm increased burden of large, rare CNVs in schizophrenia cases as well as significant associations for recurrent 16p11.2 duplications, 22q11.2 deletions and 3q29 deletions. We report a novel association for 17q12 duplications (odds ratio=4.16, P=0.018), previously associated with autism and mental retardation but not schizophrenia. Intriguingly, gene set association analyses implicate biological pathways previously associated with schizophrenia through common variation and exome sequencing (calcium channel signaling and binding partners of the fragile X mental retardation protein). We found significantly increased burden of the largest CNVs (>500Kb) in genes present in the post-synaptic density, in genomic regions implicated via schizophrenia genome-wide association studies, and in gene products localized to mitochondria and cytoplasm. Our findings suggest that multiple lines of genomic inquiry – genome-wide screens for CNVs, common variation, and exonic variation – are converging on similar sets of pathways and/or genes.

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia. ispartof: Nature vol:511 issue:7510 pages:421-7 ispartof: location:England status: published

Current catalogs of brain expression quantitative trait loci (eQTL) are incomplete and the findings do not replicate well across studies. All existing cortical eQTL studies are small and emphasize the need for a meta-analysis. We performed a meta-analysis of 424 brain samples across five studies to identify regulatory variants influencing gene expression in human cortex. We identified 3584 genes in autosomes and chromosome X with false discovery rate q

Genome-wide association studies (GWAS) have strongly implicated MIR137 (the gene encoding the microRNA miR-137) in schizophrenia. A parsimonious hypothesis is that a pathway regulated by miR-137 is important in the etiology of schizophrenia. Full evaluation of this hypothesis requires more definitive knowledge about biological targets of miR-137, which is currently lacking. Our goals were to expand knowledge of the biology of miR-137 by identifying its empirical targets, and to test whether the resulting lists of direct and indirect targets were enriched for genes and pathways involved in risk for schizophrenia. We overexpressed miR-137 in a human neural stem cell line and analyzed gene expression changes at 24 and 48 h using RNA sequencing. Following miR-137 overexpression, 202 and 428 genes were differentially expressed after 24 and 48 h. Genes differentially expressed at 24 h were enriched for transcription factors and cell cycle genes, and differential expression at 48 h affected a wider variety of pathways. Pathways implicated in schizophrenia were upregulated in the 48 h findings (major histocompatibility complex, synapses, FMRP interacting RNAs and calcium channels). Critically, differentially expressed genes at 48 h were enriched for smaller association P-values in the largest published schizophrenia GWAS. This work provides empirical support for a role of miR-137 in the etiology of schizophrenia.

AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

We examined gene expression in the blood of six females with anorexia nervosa (AN) before and after weight restoration using RNAseq. AN cases (aged 19-39) completed clinical assessments and had blood drawn for RNA at hospital admission (T1, < ~75% ideal body weight, IBW) and again at discharge (T2, ≥ ~85% IBW). To examine the relationship between weight restoration and differential gene expression, normalized gene expression levels were analyzed using a paired design. We found 564 genes whose expression was nominally significantly different following weight restoration (p < 0.01, 231 increased and 333 decreased). With a more stringent significance threshold (false discovery rate q < 0.05), 67 genes met criteria for differential expression. Of the top 20 genes, CYP11A1, C16orf11, LINC00235, and CPA3 were down-regulated more than two-fold after weight restoration while multiple olfactory receptor genes (OR52J3, OR51L1, OR51A4, OR51A2) were up-regulated more than two-fold after weight restoration. Pathway analysis revealed up-regulation of two broad pathways with largely overlapping genes, one related to protein secretion and signaling and the other associated with defense response to bacterial regulation. Although results are preliminary secondary to a small sample size, these data provide initial evidence of transcriptional alterations during weight restoration in AN.

Summary form only given. For flow in a pipe or tube, the Reynolds number (Re) is generally defined with fluid velocity, tube diameter, and kinematic viscosity. With a certain value of Re, the flow will become unstable and turbulent. This instability occurs with different fluids, usually when Re is over 2000. The laminar flow is stable if Re is less than 2000. In the interval between 2000 and 4000, laminar and turbulent flows are possible and are called "transition" flows, depending on other factors, such as pipe roughness and flow uniformity. In an atmospheric plasma jet of pencil type, a glass tube is used to insert the discharge gas. The property of plasma jet depends on the gas flow velocity which is given by the tube diameter and the volumetric gas flow rate. However, there exists an optimal flow velocity to obtain a stable plasma jet. The dependence of flow velocity on the instability of discharge plasma can be analyzed with Reynolds number which defines the stability of flow such as the stable laminar flow and the turbulent flow in hydro-kinetics. In this report the optimum flow velocity in a glass tube of plasma jet is investigated according to the stability of discharge plasma with the variation of Reynolds number. In the range of stable discharge where the laminar flow is sustained, the length of plasma jet column and plume is increased and the operational discharge voltage is decreased as the flow velocity is increased in the glass tube. However, if the gas flow velocity is increased to be over the critical value of turbulent flow, the length of plasma jet column as well as the plasma current varies unstably. In the conclusion the flow velocity has the limited value to keep the laminar flow inside the glass tube for the stable discharge of plasma jet.

Summary form only given. The plasma bullet has been explained with the model of streamer propagation in many reports. The streamer theory of ionization wave for plasma plume/bullet might not be enough for proper explanation. The streamer discharge is represented in general to be the random channeling behavior in a wide open space where the discharge path is not restricted. For instances, the discharge of transient state or quasi-steady state must be a streamer discharge in the atmospheric discharge with a sharp needle electrode or with a plane electrode like a dielectric barrier discharge (DBD). However, the plasma jet seems to be a steady state when the discharge path is defined by the glass tube through which the discharge gas is blowing. Therefore, the discharge of plasma jet accompanied with the glass tube seems not to be explained only with the streamer discharge but it must be a normal glow, since the discharge of plasma jet is guided by the flow of inert gas as well as by the discharge route of glass tube or other structures. In this study the electrostatic plasma diffusion waves driven by a plasma density gradient are described to verify the propagation of light signals observed in the discharge experiments such as long discharge tubes, plasma jets, and plasma display panels. Plasma diffusion waves, electron waves and ion waves, propagate together with the group velocity of the wave-packet as ug≈cs2/un, with the acoustic velocity cs and the plasma diffusion velocity un. The propagation phenomena are explained in terms of the plasma density gradient associated with discharge parameters such as the plasma scale, the plasma current, and the electric field strength. The evidence of plasma diffusion wave is shown in the observation results of optical signals providing the information of plasma behavior in the atmospheric plasma jet. In a plasma column between a high-voltage electrode and the virtual ground of infinite open air, the velocity is varied at each area as it is about 104 m/s inside the glass tube, it becomes fast as 105 m/s at the plasma plume exiting the glass tube, and it is slow down to the open air. If the variation of optical intensity corresponds to the plasma density, the propagation velocity could be understood with the density gradient of the plasma. In the optical signals observed in the plasma jets, two types of waves are analyzed. One is a traveling wave along the forward direction of plasma density gradient from high voltage side to the ground electrode. The other is a backward wave from the backward direction of plasma density gradient and a reflecting wave from the ground electrode.

Clinical trials of tolvaptan showed it to be a promising candidate for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential for idiosyncratic drug-induced liver injury (DILI) in this patient population. To identify risk factors and mechanisms underlying tolvaptan DILI, 8 mice in each of 45 strains of the genetically diverse Collaborative Cross (CC) mouse population were treated with a single oral dose of either tolvaptan or vehicle. Significant elevations in plasma alanine aminotransferase (ALT) were observed in tolvaptan-treated animals in 3 of the 45 strains. Genetic mapping coupled with transcriptomic analysis in the liver was used to identify several candidate susceptibility genes including epoxide hydrolase 2, interferon regulatory factor 3, and mitochondrial fission factor. Gene pathway analysis revealed that oxidative stress and immune response pathways were activated in response to tolvaptan treatment across all strains, but genes involved in regulation of bile acid homeostasis were most associated with tolvaptan-induced elevations in ALT. Secretory leukocyte peptidase inhibitor (Slpi) mRNA was also induced in the susceptible strains and was associated with increased plasma levels of Slpi protein, suggesting a potential serum marker for DILI susceptibility. In summary, tolvaptan induced signs of oxidative stress, mitochondrial dysfunction, and innate immune response in all strains, but variation in bile acid homeostasis was most associated with susceptibility to the liver response. This CC study has indicated potential mechanisms underlying tolvaptan DILI and biomarkers of susceptibility that may be useful in managing the risk of DILI in ADPKD patients.

Contains fulltext : 128630.pdf (Publisher’s version ) (Open Access) Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 x 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 x 10(-5)) and CPD (P=9.3 x 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Although the association of common genetic variation in the extended MHC region with schizophrenia is the most significant yet discovered, the MHC region is one of the more complex regions of the human genome, with unusually high gene density and long-range linkage disequilibrium. The statistical test on which the MHC association is based is a relatively simple, additive model which uses logistic regression of SNP genotypes to predict case-control status. However, it is plausible that more complex models underlie this association. Using a well-characterized sample of trios, we evaluated more complex models by looking for evidence for: (a) non-random mating for HLA alleles, schizophrenia risk profiles, and ancestry; (b) parent-of-origin effects for HLA alleles; and (c) maternal-fetal genotype incompatibility in the HLA. We found no evidence for non-random mating in the parents of individuals with schizophrenia in terms of MHC genotypes or schizophrenia risk profile scores. However, there was evidence of non-random mating that appeared mostly to be driven by ancestry. We did not detect over-transmission of HLA alleles to affected offspring via the general TDT test (without regard to parent of origin) or preferential transmission via paternal or maternal inheritance. We evaluated the hypothesis that maternal-fetal HLA incompatibility may increase risk for schizophrenia using eight classical HLA loci. The most significant alleles were in HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 but none was significant after accounting for multiple comparisons. We did not find evidence to support more complex models of gene action, but statistical power may have been limiting.

Previous studies have reported temporal and spectral modification of acoustic signals of speech according to varying speaking modes (i.e. clear, loud speech) in several languages (Krause & Braida, 2004; Lam & Tjaden, 2015). Interestingly, some acoustic characteristics such as vowel contrasts, inferred from the size of the corner vowel space, have been discussed to exhibit common, equivalent change between languages despite the different inventory sizes (Smiljanic & Bradlow, 2005). The current study, as an expansion of this line of research, seeks to examine the effect of native language on selected acoustic measures when speakers voluntarily switch speaking modes among conversational, clear, and slow speech. 24 female adults (12 English-speaking, 12 Korean-speaking) were asked to read CVCV structures in the three aforementioned conditions. English and Korean were chosen mainly because of their differences in vowel and stop inventories. Vowel duration, formant structure (F1-F2), and VOT were measured from ...

Bipolar disorder (BIP) is a highly heritable disorder with complex patterns of genetic inheritance, and recent genetic findings highlight the role of numerous common variants each with subtle effects.1 The existence of Mendelian subtypes of BIP (rare variants of very strong effects) has been postulated, particularly as such variants could prove to be more tractable for subsequent biological investigation.2 One way to evaluate this hypothesis is via the study of pedigrees densely affected with BIP in which a genetic variant of strong effect inherited from a common ancestor may be more likely. With the advent of high-throughput technologies, we can now search densely-affected pedigrees for specific variants that may contribute to risk for BIP. We therefore evaluated a Spanish multi-generational pedigree with an exceptional prevalence of BIP using multiple complementary genomic techniques (Table S1). This pedigree contains 18 cases with BIP (including a sibship with six of 11 affected) and seven individuals with recurrent major depressive disorder (Figure 1a). The lifetime prevalence of mood disorders in this large pedigree (6 generations; 120 individuals, 30 with known mood disorders, 42 with DNA) makes it a strong candidate for identifying genetic risk factors of near-Mendelian effects. Our search strategy is depicted in Figure 1b. All protocols were IRB approved and all subjects provided written informed consent. Figure 1 (a) The pedigree was ascertained in Spain, and has a high prevalence of mood disorders, particularly bipolar disorder (type 1) and recurrent major depressive disorder. First, we used genome-wide linkage analysis and an affecteds-only approach to identify genomic regions sharing identity-by-descent. Linkage analysis was performed using microsatellite data from 13 individuals.3 We used data from Illumina HumanOmni Quad genotyping arrays to identify shared segments using Beagle,4 Germline,5 PedIBD,6 and runs of identity-by-state.7 Regions identified by linkage or with two sharing methods were considered candidate regions (Table S2, six regions totaling 93.7Mb). Second, we hypothesized that one of these regions contained a novel, rare functional single nucleotide variant (SNV) of high penetrance. We attempted to identify novel SNVs in these six genomic regions shared by BIP cases using exome sequencing (five BIP cases) and whole genome sequencing (three BIP cases). Whole genome sequence data was screened to identify high-quality homozygous or heterozygous SNVs that were within the candidate regions, novel, of predicted functional consequence, and present in all three BIP cases. This procedure identified 26 SNVs in three olfactory receptors (OR4C3, OR9G9, and OR4C45). Because multiple variants were present in each gene, given the existence of other highly similar members of the large olfactory gene family, and manual review of alignment patterns, we believed all to be due to misalignment. We repeated this process for the exome sequencing data, and identified 21 SNVs (17 were also identified by whole genome sequencing), and all were in olfactory genes (OR4C3, OR9G9, and OR8U8/OR8U1), and likely due to incorrect alignment. We next evaluated CNVs in these regions. Using PennCNV8 calls from Illumina arrays, no novel CNVs were identified in these candidate regions that were >1kb, present in ≥8 of 11 BIP cases, and confirmed via whole genome sequencing. Therefore, we were unable to identify any potential SNVs or CNVs within these candidate regions that were promising for follow-up. Third, we then extended our analysis genome-wide. From the whole genome sequencing of three individuals, we identified novel SNVs of predicted functionality that were present in all three BIP cases (Table S3). We excluded SNVs in olfactory receptors, with questionable alignments, or that were not confirmed in exome sequencing of five BIP cases. This resulted in eight SNVs that we sequenced in 11 affected individuals using Sanger sequencing. Five SNVs verified and had plausible inheritance patterns, and were then genotyped in 42 individuals in the pedigree. Two SNVs were potentially interesting (chr12:52452495 C>T in NR4A1 and chr18:47793974 G>C in MBD1). Neither exhibited unequivocal Mendelian inheritance (Figures S2–S3). The NR4A1 (nerve growth factor IB, NGFIB or Nur77) SNV is novel but common in this pedigree (homozygous or heterozygous in 30/34 individuals descended from the founders, excluding married-in individuals) and did not clearly segregate in BIP cases as the SNV was found in 92% of BIP cases and 86% of subjects without a mood disorder (although the number of unaffecteds is small). The MBD1 (methyl-CpG-binding domain protein 1) SNV tracked with BIP (66%), other mood disorders (88%), and less so in unaffecteds (21%). However, this SNV was recently identified by the 1000 Genomes Project in subjects from the United Kingdom. Therefore, this variant is not completely novel, but has an interesting pattern of segregation. Both variants warrant additional follow-up in a larger case-control samples although neither appears to be a strong novel Mendelian variant. Genome-wide expansion of the CNV search identified no novel CNVs that were present in ≥8 BIP cases, >1kb in size, overlapped an exon, and verified by whole genome sequencing. Fourth, given the absence of compelling results in support of a near-Mendelian variant, we evaluated the contribution of common variation in this pedigree. The presence of many common variant risk alleles in a pedigree is a potential explanation for a dense pedigree.9 This can be due to or exacerbated by assortative mating (in which mental illness in the family of a spouse is more likely to be tolerated if one has it in one’s own family) and result in an accumulation of common risk alleles. We therefore calculated risk profile scores, which are the weighted number of BIP risk alleles in each subject. Based on results from the Psychiatric GWAS Consortium10 (7,481 BIP cases and 9,250 controls), risk profile scores were computed for the GAIN BIP cases (N=1080) and controls (N=1058),11 and the 11 BIP cases in the densely-affected pedigree (Figure 1c). As anticipated, the GAIN BIP cases had significantly higher risk profile scores than the GAIN controls (p < 0.001). Risk profile scores for 11 BIP cases from the Spanish pedigree were also significantly greater than controls (p < 0.001) but not significantly different from GAIN BIP cases (p = 0.19). It is particularly notable that the BIP pedigree cases did not have markedly lower risk profile scores (e.g., low common variant profiles might be consistent with the present of a strong mutation). Rather, the BIP pedigree cases appeared to have common variant risk profile scores similar to European-American BIP cases ascertained clinically without regard to family history. In conclusion, we systematically assessed this large pedigree dense with BIP for genetic variants of strong effect. This comprehensive analysis did not conclusively identify any SNVs or CNVs of near-Mendelian effect. However, we cannot exclude the presence of risk variants with more complex inheritance patterns, variants with more cryptic functional effects, or variants missed due to coverage or individuals sequenced. However, the common variant risk profiles of BIP cases in this pedigree are similar to those of BIP cases ascertained without regard to family history. Therefore, it is possible that the etiology of BIP in this pedigree is more related to multiple common risk variants rather than one or a few variants of extremely strong effect.

Summary form only given. The hand-held plasma surgical-tools were introduced for immediate cauterization and incision1. It achieves fast coagulation with minimal tissue damage. The plasma surgery may offer a few advantages over both electro-surgery and argon-enhanced coagulation. However, the plasma surgery at the moment is used restrictively with a fine jet of pure plasma for coagulation and for tissue cutting by exposure to plasma.

Summary form only given. The plasma propagations are observed in various discharge plasmas such as the long discharge tubes, the plasma jet devices, and the plasma display panels. Using the optical fiber amplifiers in the long discharge tubes of fluorescent lamps, the lighting signals are measured to propagate with the velocity of 105∼106 m/s.1 In the plasma jet devices measured with the ICCD camera and the optical fiber amplifiers, the plasma propagation as the form of plasma bullet is observed to be the speed of 104∼105 m/s.2 In the plasma display panels of micro discharge with ICCD camera, the plasma is observed to be expanding with the velocity of 103 m/s on the coplanar electrode surface.3 The propagation speed of plasmas is dependent of the plasma scale, where the speed increases as the plasma scale increases. Therefore, the speed of micro-discharge plasmas in plasma display panel is relatively slow, while the plasma propagation speed of the plasma jet devices with a few centimeter scales increases considerably. Moreover, the plasma propagation speed of the plasma column of long discharge tube having the scale of several tens of centimeters is much faster. The propagation phenomena are described with the electrostatic plasma waves including the plasma diffusion due to the plasma density gradient. The diffusion velocity is solved to be dependent of plasma scales which are related to the plasma diffusion waves in each plasma devices.

Summary form only given. In the application of biomedicine plasma, the blood coagulation is investigated to verify the interaction between plasma and blood1. The plasma is irradiated to the blood with various conditions of plasma jet such as the dose of plasma current and the exposure time of various kinds of plasmas. The response of blood coagulation is also observed.

In 2005, we selected 10 genes for which there was reasonable evidence for involvement in the etiology of schizophrenia (COMT, DAOA, DISC1, DRD2, DRD3, DTNBP1, HTR2A, NRG1, SLC6A3, SLC6A4, Table S1)1. Although these genes have not received support from far larger and comprehensive subsequent studies, and may not contain etiological common variation2, it is possible that they contain uncommon variation of etiological importance. To test this hypothesis, we conducted a multistage resequencing study. In Stage 1, we used Sanger methods to sequence the exons, 5′ and 3′ UTRs, splice sites, promoters and conserved intronic regions of these 10 genes in 727 cases with schizophrenia from CATIE3 and 733 controls of European (EUR) and African (AFR) ancestry. In Stage 2, we validated single nucleotide variants (SNVs) using Roche 454 sequencing in the same samples. In Stage 3, we genotyped prioritized SNVs in independent samples (Supplemental Material and Figure S1). In Stage 1, Sanger sequencing identified 782 variants, including 587 novel SNVs not found in dbSNP132 (Tables S2–S4). As expected, the number of novel variants discovered per individual was higher in those of AFR (1.46) than EUR ancestry (0.95) but cases and controls did not differ (EUR cases/controls: 0.920/0.980; AFR cases/controls: 1.492/1.430). The numbers of SNVs per gene were also similar although DISC1 showed a non-significant excess in cases (EUR cases/controls: 0.138/0.119; AFR cases/controls: 0.243/0.167) mostly due to novel variants in AFR subjects (cases/controls: 0.173/0.099). Three unrelated cases, but zero controls, were found to each have a single novel nonsense mutation: two for DISC1 (truncating only the “Es” splice variants) and one for SLC6A4 (Tables S2–S4). The ratio of nonsynonymous to synonomous variants was similar in cases and controls (1.25 vs 1.16). In Stage 2, we prioritized 254 of the 782 variants for technical replication since they met at least one of the following criteria: 1) novel nonsense, missense or splice site variant, 2) novel intronic variant in ≥1 EUR case, 3) novel variant with an odds ratio >2 in the EUR cohort, 4) dbSNP nonsense, missense or splice site variant in ≥1 EUR case. Validation sequencing by Roche 454 revealed 225 true variants and 29 false positives (accuracy rate of 89%, Figure S2). In Stage 3, we selected 92 of the 225 SNVs (Table S5) from Stage 2 for genotyping in an independent sample of 2,191 cases and 2,659 controls (EUR and AFR). We included: 1) all novel nonsense, missense or splice site variants seen in ≥1 case, 2) all variants seen in >1 case, 3) three nonsense variants observed in one case each. After genotyping 92 SNVs in the replication samples, 29 were monomorphic (22 of these were seen in only one case in Stage 1), six had low quality genotypes, and 57 SNVs were tested for association with schizophrenia (logistic regression, separately for EUR and AFR subjects). Table 1 lists the SNVs with the smallest p-value in each gene (complete results in Table S6). No gene contained a SNV reaching criteria for genome-wide significance (p < 5 × 10−8). We then tested the aggregate effects of uncommon variants within a gene for 35 non-intronic SNVs with MAF 99% power to detect genotypic relative risk of 2.9 in the EUR cohort and 4.6 in the AFR cohort. The Stage 1 and 2 results hinted that DISC1 might contain an excess of uncommon variants, and DISC1 was thus the main focus in Stage 3 replication. However, there was no evidence in our results to support the hypothesis that DISC1 contains uncommon variants of relevance to schizophrenia as no single-SNV or aggregate test approach was even of nominal significance. Although DISC1 nonsense variants were present in two Stage 1 cases and 0 controls, no additional cases or controls in the larger Stage 3 sample had those particular nonsense mutations. DISC1 has been the focus of dozens of genetic studies4. However, a recent comprehensive meta-analysis of common variation did not support its role in schizophrenia susceptibility5. To our knowledge, four groups have sequenced DISC1 in cases with schizophrenia6–9, and all had discovery samples far smaller than reported here (34, 90, 198 and 288 cases). Of the association results in these studies, none met criteria for genome-wide significance. Only one study had a replication component, and the initial finding did not replicate9. Therefore, despite employing a replication sample three times the size of the discovery sample, DISC1 was not found to contain common or uncommon variants individually or in aggregate associated with schizophrenia. The results of this study suggest that classical schizophrenia candidate genes do not harbor uncommon coding region variation of etiological importance.

Objective: This study examined the effect of intensity level of presentation on scaling of speech intelligibility in speakers with and without dysarthria. Patients and Methods: A total of 50 utterances produced by speakers with dysarthria and healthy speakers were played to 60 listeners in four conditions, which consisted of two different presentation levels (‘high’ vs. ‘low’) and equalization of levels across utterances (‘adjusted’ vs. ‘unadjusted’). Speech intelligibility was scaled by using a direct magnitude estimation technique with and without modulus. Results: A significant decrease in speech intelligibility was indicated when the stimuli were adjusted to have fixed intensity on the most intense vocalic nuclei of each word, while no significant change was found between ‘high’ and ‘low’ presentation level conditions. Conclusion: The findings suggest that an increase in presentation level alone does not result in significant improvement in speech intelligibility ratings. The results are discussed by considering clinical implications in conducting speech therapy with emphasis on intensity variation.

BackgroundCandidate gene studies have been a key approach to the genetics of schizophrenia (SCZ). However, the results of these studies are confusing and no genes have been unequivocally implicated. The hypothesis-driven candidate gene literature can be appraised by comparison with the results of genome-wide association studies (GWAS).MethodWe describe the characteristics of hypothesis-driven candidate gene studies from the SZGene database, and use pathway analysis to compare hypothesis-driven candidate genes with GWAS results from the International Schizophrenia Consortium (ISC).ResultsSZGene contained 732 autosomal genes evaluated in 1374 studies. These genes had poor statistical power to detect genetic effects typical for human diseases, assessed only 3.7% of genes in the genome, and had low marker densities per gene. Most genes were assessed once or twice (76.9%), providing minimal ability to evaluate consensus across studies. The ISC studies had 89% power to detect a genetic effect typical for common human diseases and assessed 79% of known autosomal common genetic variation. Pathway analyses did not reveal enrichment of smaller ISCpvalues in hypothesis-driven candidate genes, nor did a comprehensive evaluation of meta-hypotheses driving candidate gene selection (SCZ as a disease of the synapse or neurodevelopment). The most studied hypothesis-driven candidate genes (COMT,DRD3,DRD2,HTR2A,NRG1,BDNF,DTNBP1andSLC6A4) had no notable ISC results.ConclusionsWe did not find support for the idea that the hypothesis-driven candidate genes studied in the literature are enriched for the common genetic variation involved in the etiology of SCZ. Larger samples are required to evaluate this conclusion definitively.

Indole-3-carbinol (I3C) is a compound found in high concentrations in Brassica family vegetables, including broccoli, cauliflower and cabbage, and is regarded as a promising chemopreventive agent against various cancers. This study assesses the protective effect of I3C against diet-induced obesity in mice. Mice were randomly grouped to receive either a normal diet, high-fat (40% energy as fat) diet (HFD) or I3C-supplemented diet (1 g/kg diet) for 10 weeks. I3C supplementation significantly ameliorated HFD-induced increases in body weight gain, visceral fat pad weights and plasma lipid levels. The visceral adipose tissue mRNA levels of uncoupling proteins 1 and 3, crucial factors of thermogenesis, and their regulators such as sirtuin 1, peroxisome proliferator-activated receptor (PPAR) α and PPARγ coactivator 1α, which were down-regulated by HFD, were normalized by supplementation with I3C. In contrast, I3C supplementation significantly decreased expression levels of a key adipogenic transcription factor, PPARγ2, and its target genes, such as leptin and adipocyte protein 2, in the visceral adipose tissue of mice maintained on the HFD. Furthermore, HFD-induced up-regulation in mRNA levels of inflammatory cytokines (tumor necrosis factor α, interferon β and interleukin 6) was significantly ameliorated by I3C. These findings suggest that I3C has a potential benefit in preventing obesity and metabolic disorders, and the action for I3C in vivo may involve multiple mechanisms including decreased adipogenesis and inflammation, along with activated thermogenesis.

Plasma plume of atmospheric pressure discharge has been observed as ‘plasma bullet’ whose speed is about 104∼105 m/s. To explain the high velocity of bullet propagation, Lu and Laroussi have suggested a photo-ionization based model1. However, the fundamentals of propagation mechanism are not yet well understood. In this report, more precise observations of plasma plume are conducted with the equipments as ICCD (intensified charge coupled device) camera and a photo sensor amplifier combined with optical fiber.

The plasma diffusion has been investigated with respect to the atmospheric-pressure plasma jets (APPJ). The ambi-polar diffusion equation is solved in the radial and axial directions. To explain the plasma diffusion process, the plasma diffusion equation is derived with the charged particle motion and the plasma fluid continuity equation1. Supposing the initial plasma density n(t=0, r, z), the plasma flux Γ D =−D a ∇n and the diffusion velocity u D =−D a (∇n)/n are calculated.

Purpose This study examined acoustic predictors of speech intelligibility in speakers with several types of dysarthria secondary to different diseases and conducted classification analysis solely by acoustic measures according to 3 variables (disease, speech severity, and dysarthria type). Method Speech recordings from 107 speakers with dysarthria due to Parkinson’s disease, stroke, traumatic brain injury, and multiple system atrophy were used for acoustic analysis and for perceptual judgment of speech intelligibility. Acoustic analysis included 8 segmental/suprasegmental features: 2nd formant frequency slope, articulation rate, voiceless interval duration, 1st moment analysis for fricatives, vowel space, F0, intensity range, and Pairwise Variability Index. Results The results showed that (a) acoustic predictors of speech intelligibility differed slightly across diseases and (b) classification accuracy by dysarthria type was typically worse than by disease type or severity. Conclusions These findings were discussed with respect to (a) the relationship between acoustic characteristics and speech intelligibility and (b) dysarthria classification.

Oleuropein, an active constituent of olive leaf, has a variety of pharmacological activities associated with its capacity to scavenge reactive oxygen species. Oleuropein is also reported to have protective effects against non-alcoholic fatty liver disease (NAFLD) in vivo. In this study, gene expression profiling of hepatic tissues was examined, and transcription factors (TFs) with target genes that were modulated by oleuropein were identified to gain insights into the molecular mechanisms for the hepatoprotective action of this compound. C57BL/6N mice were fed either a high-fat diet (HFD) or 0.03% oleuropein-supplemented HFD for 10 weeks, after which their livers were subjected to oligo DNA microarray analysis. The oleuropein with which the HFD was supplemented reduced the hepatic mRNA level of the genes that encoded the key regulators of the hepatic fatty acid uptake and transport. In addition, the oleuropein reduced the expression of a number of hepatic genes involved in the oxidative stress responses and detoxification of lipid peroxidation products and proinflammatory cytokine genes. The (putative) candidate TFs that bound to the promoters of the genes regulated at least threefold (both up and down) by oleuropein were implicated in the lipogenesis, inflammation, insulin resistance, fibrosis, and cell proliferation and differentiation, which implies that the mechanisms that underlie the beneficial effects of oleuropein on NAFLD may be multifactorial.

Caveolin-1 (Cav-1) is a membrane scaffolding protein, which functions to regulate intracellular compartmentalization of various signaling molecules. In the present studies, transgenic mice with a targeted disruption of the Cav-1 gene (Cav-1(-/-)) were used to assess the role of Cav-1 in acetaminophen-induced hepatotoxicity. Treatment of wild-type mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis and increases in serum transaminases. This was correlated with decreased expression of Cav-1 in the liver. Acetaminophen-induced hepatotoxicity was significantly attenuated in Cav-1(-/-) mice, an effect that was independent of acetaminophen metabolism. Acetaminophen administration resulted in increased hepatic expression of the oxidative stress marker, lipocalin 24p3, as well as hemeoxygenase-1, but decreased glutathione and superoxide dismutase-1; no differences were noted between the genotypes suggesting that reduced toxicity in Cav-1(-/-) mice is not due to alterations in antioxidant defense. In wild-type mice, acetaminophen increased mRNA expression of the pro-inflammatory cytokines, interleukin-1beta, and monocyte chemoattractant protein-1 (MCP-1), as well as cyclooxygenase-2, while 15-lipoxygenase (15-LOX), which generates anti-inflammatory lipoxins, decreased. Acetaminophen-induced changes in MCP-1 and 15-LOX expression were greater in Cav-1(-/-) mice. Although expression of tumor necrosis factor-alpha, a potent hepatocyte mitogen, was up-regulated in the liver of Cav-1(-/-) mice after acetaminophen, expression of proliferating cell nuclear antigen and survivin, markers of cellular proliferation, were delayed, which may reflect the reduced need for tissue repair. Taken together, these data demonstrate that Cav-1 plays a role in promoting inflammation and toxicity during the pathogenesis of acetaminophen-induced injury.

A map of the background levels of disequilibrium between nearby markers can be useful for association mapping studies. In order to assess the background levels of linkage disequilibrium (LD), multilocus LD measures are more advantageous than pairwise LD measures because the combined analysis of pairwise LD measures is not adequate to detect simultaneous allele associations among multiple markers. Various multilocus LD measures based on haplotypes have been proposed. However, most of these measures provide a single index of association among multiple markers and does not reveal the complex patterns and different levels of LD structure. In this paper, we employ non-homogeneous, multiple order Markov Chain models as a statistical framework to measure and partition the LD among multiple markers into components due to different orders of marker associations. Using a sliding window of multiple markers on phased haplotype data, we compute corresponding likelihoods for different Markov Chain (MC) orders in each window. The log-likelihood difference between the lowest MC order model (MC0) and the highest MC order model in each window is used as a measure of the total LD or the overall deviation from the gametic equilibrium for the window. Then, we partition the total LD into lower order disequilibria and estimate the effects from two-, three-, and higher order disequilibria. The relationship between different orders of LD and the log-likelihood difference involving two different orders of MC models are explored. By applying our method to the phased haplotype data in the ENCODE regions of the HapMap project, we are able to identify high/low multilocus LD regions. Our results reveal that the most LD in the HapMap data is attributed to the LD between adjacent pairs of markers across the whole region. LD between adjacent pairs of markers appears to be more significant in high multilocus LD regions than in low multilocus LD regions. We also find that as the multilocus total LD increases, the effects of high-order LD tends to get weaker due to the lack of observed multilocus haplotypes. The overall estimates of first, second, third, and fourth order LD across the ENCODE regions are 64, 23, 9, and 3%.

The electrical probe diagnostics are very hard to be applied to atmospheric plasmas due to severe perturbation by the electrical probes. To overcome this, the probe for measuring electron temperature and ion current density is indirectly contacted with an atmospheric jet source. The plasma parameters are obtained by using floating harmonic analysis. The probe is mounted on the quartz tube that surrounds plasma. When a sinusoidal voltage is applied to a probe contacting on a quartz tube, the electrons near the sheath at dielectric tube are collected and the probe current has harmonic components due to probe sheath nonlinearity. From the relation of the harmonic currents and amplitude of the sheath voltage, the electron temperature near the wall can be obtained with collisional sheath model. The electron temperatures and ion current densities measured at the discharge region are in the ranges of 2.7–3.4 eV and 1.7–5.2 mA/cm2 at various flow rates and input powers.

Nat. Genet. 47, 353–360 (2015); published online 2 March 2015; corrected after print 16 April 2015 In the version of this article initially published, an accession number was not provided for RNA-seq data sets. The RNA-seq data sets that passed quality control are available at the Sequence Read Archive (SRA) under accession SRP056236.

Summary form only given, as follows. In this study a new model is presented for a direct lighting backlight arrayed with multi-lamps of the cold cathode fluorescent lamps (CCFLs) and the external electrode fluorescent lamps (EEFLs). Avoiding the non-uniformity of luminance and the high voltage operation in a conventional direct lighting backlight driven by a single inverter power system for large area panels of LCD TVs, the auxiliary electrodes are placed under the reflection sheet in the backlight, of new model These electrodes lead to an auxiliary discharge at the center of the tube and also sustain the uniform field strength along the discharge tube inside of the longitudinal direction. These auxiliary discharges provide the luminance uniformity in each lamps and the low driving voltage.

To characterize the Helicobacter pylori gastritis-associated epithelial change, we analyzed 251 randomly selected gastric biopsies. The "malgun" (clear) cell change of the gastric epithelium was noted in 229 biopsies (91.2%). Malgun cells were characterized by large, pale nuclei with a euchromatin pattern, enlarged nucleoli, and clear cytoplasm. In the proliferative zone, individual malgun cells and small clusters were often in close contact with infiltrating neutrophils, suggesting that they had developed individually in the background of acute foveolitis. Mitotic figures of malgun cells were not infrequent, including atypical ones. In the surface epithelium, most malgun cells were in clusters that were often large enough to occupy wide epithelial segments. With Warthin-Starry triple staining, they were distinguished by the absence of silver impregnation, while other cells showed staining of the heterochromatin. They displayed prominent immunostaining for low molecular weight cytokeratin (No. 8). Most malgun cells were PCNA-positive in both surface and proliferative zones, whereas Ki67-positive cells were found only in the proliferative zone. It was suggested that a population of malgun cells, which were positive for PCNA only, were in the process of active DNA repair. The malgun cell change may represent a "cellular pattern of activation" in a population which had significant DNA damage, but somehow escaped the detection by the apoptosis system. The notion of "damage at the genetic level" was supported by the observation that these cells remained at least for 8 weeks after eradication of the H. pylori infection.

We analyzed national data collected by the Health Insurance Review and Assessment Service in Korea from 2007 to 2011; 1) to document procedural numbers and procedural rate of bipolar hemiarthroplasty (BH), primary and revision total hip arthroplasties (THAs), 2) to stratify the prevalence of each procedure by age, gender, and hospital type, and quantified, 3) to estimate the revision burden and evaluate whether the burden is changed over time. Our final study population included 60,230 BHs, 40,760 primary THAs, and 10,341 revision THAs. From 2007 to 2011, both the number and the rate of BHs, primary THAs increased steadily, whereas there was no significant change in revision THAs. Over the 5 yr, the rate of BHs and primary THAs per 100,000 persons significantly increased by 33.2% and 21.4%, respectively. The number of revision THAs was consistent over time. The overall annual revision burden for THA decreased from 22.1% in 2007 to 18.9% in 2011. In contrast to western data, there were no changes in the number and rate of revision THAs, and the rates of primary and revision THAs were higher for men than those for women. Although 5 yr is a short time to determine a change in the revision burden, there have been significant decreases in some age groups. Graphical Abstract Keywords: Epidemiology, Hip, Arthroplasty, Prevalence INTRODUCTION Total hip arthroplasty (THA) has promising outcomes in the treatment of end stage hip disease, which had led to its increased popularity in most western countries over the past decade (1, 2, 3, 4, 5, 6, 7, 8). Some previous studies also showed a steady increase in the annual incidence of revision THA, despite continual development in implant design, bearing couples, and surgical technique (1, 2, 4, 8). Conversely, results from the Norwegian Arthroplasty Register reported a decreased THA revision risk (9). These population-based epidemiological studies can provide important information about national trends of hip replacements as well as public health costs, which are needed to establish healthcare policies. Western epidemiological data cannot be directly applied to Asian countries. Some studies have shown disparities in the rate of THA based on ethnicity (10, 11). There are two previous epidemiological studies from Asian countries (12, 13). One performed in Korea reported a relatively low rate of THA compared to western countries and increased annual incidence of THA from 2002 to 2006 (13). However, the study was limited to primary THA for patients with osteoarthritis and did not determine the prevalence and trends of revision THA. The other study performed in Taiwan reported on the use of partial hip replacement, primary, and revision THAs; different epidemiology of hip disease was evident between Han Chinese and Caucasians (12). This study was based on a national health insurance research database over the 9-yr period; however, trends by age and gender as well as revision burden were not documented. The purpose of this study was to analyze national data collected by the Health Insurance Review and Assessment Service (HIRA) in South Korea from 2007 to 2011 and to document procedural numbers and the procedural rate of primary and revision THA stratified by age, gender, and hospital type. We also quantified the revision burden and evaluated whether the burden changed over time. Data of bipolar hemiarthropalsty (BH) use was also analyzed by same methods because the utilization of BH has recently increased to treat the increased number of patients with hip fractures in Korea (14, 15), and some portion of revision THA may be attributed to failed BHs. We therefore determined 1) whether the use of hip replacements (BH, primary, and revision THAs) and revision burden stratified by gender and age have increased over time, and 2) whether the epidemiological findings in Korea are different from data in western countries. We also determined 3) whether an increasing proportion of procedures had been performed with time by higher volume hospitals, such as tertiary and general hospitals.

The electrical potential of plasma generated from an atmospheric plasma jet device with Ar or He gas is measured with a high voltage probe in a plasma column inside a tube as well as in the plasma ejected through the open end of the tube. When the double plasma jet devices with Ar-gas are operated by the opposite polarities of an ac voltage with a few kV at both ends of a glass tube, the electrical potential of plasma column is high at both ends of the column, while the electrical potential in the middle of the plasma column is a few tens of volts. When the plasma column is formulated with the double plasma jets of a high voltage electrode at one end of the glass tube and a grounded electrode at the other end of the tube, the plasma column potential decreases linearly from a high voltage to a very low value, as the measurement position moves from the side of high voltage to the grounded location. In the double plasma jets of He-gas operated by high voltages in opposite polarities, the ejected plasma jets are attractive to each other at the intersection, merging together and having the electrical potential of a few tens of volts. On the other hand, if the two plasma jet columns are operated by high voltages of same polarity the ejected plasma jets are repulsive to each other at the intersection, having the electrical potential of a few hundreds of volts and causing an electrical shock.

Despite frequent clinical observations of improved speech intelligibility following high vocal intensity training in speakers with dysarthria, the mechanism by which loud speech results in increased speech intelligibility is little understood. Prior research has reported conflicting acoustic results of articulatory modifications in loud speech conditions such as changes in vowel durations, acoustic vowel space, and F2 transition duration/extent. More interestingly, the impact of an overall increase in amplitude of speech signals on perceptual judgment of speech intelligibility is unclear, especially when the entire speech signal is amplified as compared to the amplification of selected phonetic events (see Kim and Kuo, in press). This presentation focuses on the change of relative contrastivity within utterances that were produced at both conversational and loud levels to better understand the underlying mechanism of enhanced speech intelligibility secondary to greater vocal intensity. In this presentation, data on the ratio of vowel durations (long versus short), formant structures of vowels (tense versus lax), as well as the ratio of syllable intensity (stressed vs unstressed) will be compared between conversational and loud speech conditions produced by young adult speakers.

This study aims to provide preliminary data on prosodic characteristics of speakers with schizophrenia as the first phase of a larger study that explores acoustic vocal markers of schizophrenia for the ultimate purpose of differential diagnosis of this disorder. Only a few studies have reported acoustic characteristics of individuals with schizophrenia including flattened intonation [Covington et al. (2005)] and an increase in pause duration [Rapcan et al. (2010)] compared to healthy speakers. For this presentation, 100‐s‐long spontaneous speech samples produced by three female speakers with schizophrenia were analyzed and results were compared to three female speakers with bipolar disorder as a psychiatric control group. Speech recordings were first segmented into a total of 165 breath groups, and then from each breath group, acoustic measures were made including (1) mean and range of fundamental frequency contour, (2) mean and range of intensity contour, (3) duration and frequency of pauses, and (4) speaking/articulation rate. It is expected that the results from these preliminary data will further motivate investigations of negative symptoms of speakers with schizophrenia and the development of automated tools for differential diagnosis of schizophrenia from other psychological conditions known to exhibit symptoms similar to those in schizophrenia such as depression and anxiety.

Although large variability in acoustic characteristics “across” speakers with dysarthria has been reported in previous studies in the process of describing characteristics of dysarthrias and identifying speech severity, relatively less attention has been paid to acoustic variability “within” speakers with dysarthria [Kim et al., JSLHR (in press)]. This is a theoretically and clinically important question regarding validity and reliability of acoustic parameters as markers of speech disorders or severity, especially given the difficulty in data collection due to the physical condition of speakers and the relatively small number of subjects and trials (repetitions of given items) in previous literature. As a follow‐up analysis of Kim et al. (in press), this study aims to examine the degree to which speakers with dysarthria exhibit consistency in repeated articulatory behaviors by measuring variability of selected acoustic measures on word repetition tasks. Acoustic measures include F2 slope for vocalic nuclei and moment analysis for fricatives /s/ and /∫/ produced by 108 speakers with dysarthria and ten healthy controls. These results will be interpreted in terms of dysarthria in general and the different types of dysarthria that are said to be associated with different types of neurological disease.

Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], Β = 1.03, standard error (s.e.) = 0.053, P = 2.8 × 10 73). Two 10q25 SNPs (rs1329650[G], Β = 0.367, s.e. = 0.059, P = 5.7 × 10 10; and rs1028936[A], Β = 0.446, s.e. = 0.074, P = 1.3 × 10 9) and one 9q13 SNP in EGLN2 (rs3733829[G], Β = 0.333, s.e. = 0.058, P = 1.0 × 10 8) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 × 10 8). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 × 10 8) was significantly associated with smoking cessation. © 2010 Nature America, Inc. All rights reserved.

One of the most well‐known treatment techniques to improve speech intelligibility of speakers with dysarthria involves the reduction of speaking rate (Duffy, 1995). The theory of this strategy is that a slower rate provides more time to attain articulatory targets. However, the underlying mechanism of enhanced speech intelligibility at slow speaking rate is not yet clear. In other words, it has not been directly examined whether this strategy causes measurable articulatory improvements or simply provides listeners with greater time to process impaired speech. This is an important question especially in clinical practice, related to establishing a treatment target, and furthermore, an overall treatment plan for the client. In this presentation, we will report some articulatory and acoustic indices of articulatory characteristics of speakers with Parkinson’s Disease and healthy controls, producing the same utterances at three different speaking rates. [Work supported by internal funds from LSU.]

In two previous reports [Weismer, Kuo, & Chung, J. Acoust. Soc. Am. 121, 3135 (2007); Kuo and Weismer, J. Acoust. Soc. Am. 124, 2558 (2008)] the transition characteristics of speakers with dysarthria, secondary to Parkinson disease and amyotrophic lateral sclerosis (ALS), were compared to transition characteristics of healthy controls. The previous reports described the characteristics of obstruent‐vowel [Weismer >etal/> (2007)] and diphthong [Kuo and Weismer (2008)] transitions extracted from an extended passage reading. Our hypothesis was that distributional analyses would show the CV, obstruent‐vowel transitions to be less affected by the neurological disease as compared to diphthong transitions. The hypothesis was not supported by the data, which showed both types of transitions to be slower and less extensive than in healthy controls. The present report completes this analysis with documentation of transition characteristics of liquids and glides. Our expectation is that liquid and glide transition t...

This study seeks to examine the effect of level of presentation on scaling of speech intelligibility of speakers with dysarthria. Previous data [Kim et al. (2007)] reported the somewhat surprising result that different presentation levels do not cause a significant change in speech intelligibility scores of speakers with dysarthria, but do for healthy speakers. The current study reports further data using the same speech stimuli, however, with a main focus on the across‐conditions effect of presentation level, since the previous data were limited to within‐conditions effects. Four conditions of level of presentation were generated by varying absolute level of presentation (high and low) and normalizing each utterance for peak vowel intensity (adjusted and nonadjusted). In this presentation, we will report how scaled speech intelligibility is affected by the level of presentation of speech samples produced by speakers with various types and severity of dysarthria and by healthy speakers. The results of thi...

Using the ionization rates of each atom species in a mixture gas of Ne(95%) + Ar(5%) + Hg(∼mg), the minimum quantity of mercury in the glow plasma discharge of CCFLs and EEFLs for a large area LCD backlight, is calculated to be 0.05 ∼ 0.36 mg without considering the mercury consumption.

External electrode fluorescent lamps of aluminosilicate glass with high dielectric constant, a low dielectric loss and a lowest sodium composition were compared with the conventional EEFLs of borosilicate and soda-lime glasses. The luminance efficiency increases by 15∼25 %, the pinhole stability improves remarkably, and the blackening of Hg-consumption is not observed.