Phonetic Drift in Fricatives and the Effects of L2 Experience on L1 Phonetic Categories

Previous research has shown that L2 learners immersed in a target language environment exhibit phonetic drift in L1 category boundaries along VOT （Chang, 2002, 2010; Tice & Woodley, 2012） and vowel formant （Guion, 2003） dimensions, which subsides after an extended duration of immersion. This study investigates the articulation of sibilant fricatives in Japanese and in English by three groups of bilinguals – a） late bilinguals who have studied abroad; b） late bilinguals with no experience abroad; c） early （simultaneous） bilinguals – to determine whether they differ from one another in distinguishing post-alveolar sibilants of English, [ʃ], and Japanese, [㷡], and whether there is evidence among late bilinguals of phonetic drift in the alveolar sibilant [s] common to both languages under pressure from the novel English post-alveolar.Participants produced real words containing each of the test segments before a high or a low vowel in four blocks, two in English and two in Japanese both in isolation and embedded within a carrier phrase. Productions were recorded and submitted to acoustic analysis. Measurements of spectral Center of Gravity (Hanulíková and Weber, 2010) revealed differences between the two languages only among late bilinguals with no study abroad experience. Without intensive immersion experience, these participants were expected to exhibit no evidence of phonetic drift; however, the pool from which they were recruited was comprised of Japanese university students majoring in linguistics with coursework in English phonetics. We therefore speculate that phonetic drift may not arise solely from intensive exposure in an immersion environment but from heightened perceptual awareness brought about through acquired metalinguistic knowledge as well. It is surmised that any experience of phonetic drift that the other two groups may have had must already have subsided by the time of testing given the extent of their exposure experience

Cyclooxygenase-2 Overexpression is Common in Serrated and Non-Serrated Colorectal Adenoma, but Uncommon in Hyperplastic Polyp and Sessile Serrated Polyp/Adenoma

Background: Cyclooxygenase-2 (COX-2, PTGS2) plays an important role in colorectal carcinogenesis. COX-2 overexpression in colorectal cancer is inversely associated with microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). Evidence suggests that MSI/CIMP+ colorectal cancer may arise through the serrated tumorigenic pathway through various forms of serrated neoplasias. Therefore, we hypothesized that COX-2 may play a less important role in the serrated pathway. Methods: By immunohistochemistry, we assessed COX-2 expression in 24 hyperplastic polyps, 7 sessile serrated polyp/adenomas (SSA), 5 mixed polyps with SSA and adenoma, 27 traditional serrated adenomas, 515 non-serrated adenomas (tubular adenoma, tubulovillous adenoma and villous adenoma), 33 adenomas with intramucosal carcinomas, 96 adenocarcinomas with serration (corkscrew gland) and 111 adenocarcinomas without serration. Results: Strong (2+) COX-2 overexpression was more common in non-serrated adenomas (28% = 143/515) than in hyperplastic polyps (4.2% = 1/24, p = 0.008) and serrated polyps (7 SSAs and 5 mixed polyps) (0% = 0/12, p = 0.04). Furthermore, any (1+/2+) COX-2 overexpression was more frequent in non-serrated adenomas (60% = 307/515) than in hyperplastic polyps (13% = 3/24, p < 0.0001) and serrated polyps (SSAs and mixed polyps) (25% = 3/12, p = 0.03). Traditional serrated adenomas and non-serrated adenomas showed similar frequencies of COX-2 overexpression. Regardless of serration, COX-2 overexpression was frequent (~85%) in colorectal adenocarcinomas. Tumor location was not significantly correlated with COX-2 overexpression, although there was a trend towards higher frequencies of COX-2 overexpression in distal tumors (than proximal tumors) among hyperplastic polyps, SSAs, mixed polyps, traditional serrated adenomas and adenocarcinomas. Conclusion: COX-2 overexpression is infrequent in hyperplastic polyp, SSA and mixed polyp with SSA and adenoma, compared to non-serrated and serrated adenoma. COX-2 overexpression becomes more frequent as tumors progress to higher grade neoplasias. Our observations suggest that COX-2 may play a less significant role in the serrated pathway of tumorigenesis; however, COX-2 may still play a role in later stage of the serrated pathway

Erythropoietin Receptor Signaling Mitigates Renal Dysfunction-Associated Heart Failure by Mechanisms Unrelated to Relief of Anemia

ObjectivesWe examined the effect of asialoerythropoietin (asialoEPO), a nonerythrogenic derivative of erythropoietin (EPO), on renal dysfunction-associated heart failure.BackgroundAlthough EPO is known to exert beneficial effects on cardiac function, the clinical benefits in patients with chronic kidney disease are controversial. It remains to be addressed whether previously reported outcomes were the result of relief of the anemia, adverse effects of EPO, or direct cardiovascular effects.MethodsMice underwent 5/6 nephrectomy to cause renal dysfunction. Eight weeks later, when renal dysfunction was established, anemia and cardiac dysfunction and remodeling were apparent. Mice were then assigned to receive saline (control), recombinant human erythropoietin (rhEPO) at 5,000 IU (714 pmol)/kg, or asialoEPO at 714 pmol/kg, twice/week for 4 weeks.ResultsAlthough only rhEPO relieved the nephrectomy-induced anemia, both rhEPO and asialoEPO significantly and similarly mitigated left ventricular dilation and dysfunction. The hearts of rhEPO- or asialoEPO-treated mice showed less hypertrophy, reflecting decreases in cardiomyocyte hypertrophy and degenerative subcellular changes, as well as significant attenuation of fibrosis, leukocyte infiltration, and oxidative deoxyribonucleic acid damage. These phenotypes were accompanied by restored expression of GATA-4, sarcomeric proteins, and vascular endothelial growth factor and decreased inflammatory cytokines and lipid peroxidation. Finally, myocardial activation was observed of extracellular signal-regulated protein kinase and signal transducer and activator of transcription pathways in the treated mice.ConclusionsEPO receptor signaling exerts direct cardioprotection in an animal model of renal dysfunction-associated heart failure, probably by mitigating degenerative, pro-fibrosis, inflammatory, and oxidative processes but not through relief of anemia

Oyygen uptake of adriamycin resistant cells of Ehrlich ascites tumor

エールリッヒ腹水癌細胞を用いアドリアマイシンに対する耐性細胞（ADR耐性細胞）を樹立した。電子顕微鏡を用い撮影写真から細胞質当たりのミトコンドリア（MT）の割合を面積比で求めた。親株に比較して1μg/ml ADR耐性細胞では1.32倍、10μg/ml ADR耐性細胞では1.47倍であった。これらの細胞の呼吸を測定した。耐性細胞の内発呼吸は親株に比較して増加していた。1μg/ml ADR耐性細胞では1.45倍、10μg/ml ADR耐性細胞では1.49倍であり、MTの増加量とほぼ同じ割合であった。これらのことから、細胞が耐性になるとエネルギー消費が高まるために細胞内MTが増加し、その結果呼吸（酸素消費）が増加することが推察された。Adriamycin-resistant cells of Ehrlich ascites tumor cells were established in our laboratory. Using electron microscope, the area of mitochondria (MT) per cytoplasm of ADR-resistant cells were measured with planimeter. The values of wild-type cells, 1μg/ml ADR-resistant cells and 10μg/ml ADR-resistant cells were 39.3, 51.8 and 57.7 μ(2) per 1,000 μ(2) of cytoplasm, respectively. Oxygen consumption of 1 μg/ml ADR-resistant cells and 10 μg/ml ADR-resistant cells were 1.45-fold and 1.49-fold compared to that of wild-type cells, respectively. These results indicate that ADR-resistant cells require more energy to work efflux pump than wild-type cells

パルスセイ ジキ ショウシャ ノ カンセツツウ ニ タイスル コウカ ノ ケントウ ( ダイ1ポウ )

本研究では,家庭用機器として販売されているパルス性磁気発生装置:セルパワー®を用いて,慢性関節痛を訴えるヒトを対象に定期的磁場照射を実施し,生理学的指標の変化と効果を主観的･客観的評価指標を用いて検討した。対象は,慢性関節痛を訴える20～65歳の男女18名。同一関節痛部位に対して照射を1日2回(午前･午後),30分間,2週間施行した。同一被験者に磁場発生(-)機器(偽)と磁場発生(+)機器(真)を用いてクロスオーバー試験を行った。毎照射前後に腋窩体温,照射部位皮膚温度,脈拍数,血圧を測定した。開始時から4週間後まで1週間ごとに関節可動域(ROM)および痛みの指標(VAS)を計測した。一部のプロトコールでは,使用前後で照射部位の皮膚温度が軽度に上昇,拡張期血圧が有意に低下した。脈拍数は,全プロトコールにおいて使用後に有意に低下した。腋窩体温,ROM相対値に有意な急性･慢性変化はなかった。2週間の磁場照射によりVASの有意な低下がみられた。セルパワー®は成人の慢性関節痛に対し,生理学的指標に悪影響を及ぼすことなく使用できること,照射による鎮痛効果を有することが示された。Objectives: Magnetic stimulation is known as one of the treatments of arthritis. Magnetic stimulation has been reported to change the molecular structure of water, resulting in an improvement of blood circulation at the affected part. The purpose of this study was to investigate the effects of magnetic therapeutic instrument; CellPower® (3-5 Hz, 800 G) in human with chronic arthralgia.Methods: We recruited 18 volunteers of 20-65 years old with arthralgia. We examined the serial effects of CellPower® using physiological parameters (body temperature: BT, skin temperature of exposure part; ST, pulse rate: PR, blood pressure: BP) , Range of Motion test (ROM) and Visual Analog Score (VAS) score. Magnetic field exposure was done twice a day for 30min for 2w. We performed cross-over trial using real instrument and placebo for 2w each with washout period of over 4w between the two protocols.Results: Concerning about physiological parameters, in protocol A, ST after the exposure at 2w was ignificantly increased compared with that of Ow. In protocol B, diastolic BP after the exposure at 2w was significantly decreased compared with that of Ow. In both protocol, PR after the exposure was significantly decreased compared with that of before the exposure. All alterations were within normal values. There were no significant alterations in BT and systolic BP during the exposure. Also, there was no significant changes of ROM during the study. Interestingly, changes of VAS score showed a significant decrease by magnetic field exposure of CellPower®. Our results indicated that CellPower® had no baneful effects on physiological parameters and might be useful for the treatment of chronic arthralgia in safety

18q loss of heterozygosity in microsatellite stable colorectal cancer is correlated with CpG island methylator phenotype-negative (CIMP-0) and inversely with CIMP-low and CIMP-high

<p>Abstract</p> <p>Background:</p> <p>The CpG island methylator phenotype (CIMP) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer, associated with microsatellite instability-high (MSI-high) and <it>BRAF </it>mutations. 18q loss of heterozygosity (LOH) commonly present in colorectal cancer with chromosomal instability (CIN) is associated with global hypomethylation in tumor cell. A recent study has shown an inverse correlation between CIN and CIMP (determined by MINTs, p16, p14 and <it>MLH1 </it>methylation) in colorectal cancer. However, no study has examined 18q LOH in relation to CIMP-high, CIMP-low (less extensive promoter methylation) and CIMP-0 (CIMP-negative), determined by quantitative DNA methylation analysis.</p> <p>Methods:</p> <p>Utilizing MethyLight technology (real-time PCR), we quantified DNA methylation in 8 CIMP-specific promoters {<it>CACNA1G</it>, <it>CDKN2A </it>(p16), <it>CRABP1, IGF2</it>, <it>MLH1, NEUROG1, RUNX3 </it>and <it>SOCS1</it>} in 758 non-MSI-high colorectal cancers obtained from two large prospective cohorts. Using four 18q microsatellite markers (D18S55, D18S56, D18S67 and D18S487) and stringent criteria for 18q LOH, we selected 374 tumors (236 LOH-positive tumors with ≥ 2 markers showing LOH; and 138 LOH-negative tumors with ≥ 3 informative markers and no LOH).</p> <p>Results:</p> <p>CIMP-0 (0/8 methylated promoters) was significantly more common in 18q LOH-positive tumors (59% = 139/236, p = 0.002) than 18q LOH-negative tumors (44% = 61/138), while CIMP-low/high (1/8–8/8 methylated promoters) was significantly more common (56%) in 18q LOH-negative tumors than 18q LOH-positive tumors (41%). These relations persisted after stratification by sex, location, or the status of MSI, p53 expression (by immunohistochemistry), or <it>KRAS/BRAF </it>mutation.</p> <p>Conclusion:</p> <p>18q LOH is correlated positively with CIMP-0 and inversely with CIMP-low and CIMP-high. Our findings provide supporting evidence for relationship between CIMP-0 and 18q LOH as well as a molecular difference between CIMP-0 and CIMP-low in colorectal cancer.</p

Short lingual osteotomy without fixation: a new strategy for mandibular osteotomy known as “physiological positioning”

We describe the strategy of physiological positioning, which we regard as a new alternative treatment to conventional orthognathic operations, and treated 18 patients with skeletal mandibular prognathism using it. The positions of SNB, FMA, and Me were measured postoperatively to assess skeletal stability, changes in the angle and perpendicular length of the upper and lower central incisors were measured to assess dental stability, and we confirmed that both skeletal and dental stability were excellent. The width to which the jaw could be opened recovered early, and we saw only one case of disorder of the temporomandibular joint. Short lingual osteotomy with physiological positioning is an effective new approach to the treatment of deformities of the mandible