Mixed-effects location-scale model based on generalized hyperbolic distribution

Motivated by better modeling of intra-individual variability in longitudinal data, we propose a class of location-scale mixed effects models, in which the data of each individual is modeled by a parameter-varying generalized hyperbolic distribution. We first study the local maximum-likelihood asymptotics and reveal the instability in the numerical optimization of the log-likelihood. Then, we construct an asymptotically efficient estimator based on the Newton-Raphson method based on the original log-likelihood function with the initial estimator being naive least-squares-type. Numerical experiments are conducted to show that the proposed one-step estimator is not only theoretically efficient but also numerically much more stable and much less time-consuming compared with the maximum-likelihood estimator

Effect of Controlled-release Fertilizer and Root-proof Capillary Wick Addition to Root-zone on Tomato Growth and Yield

This study was conducted to investigate the effects of controlled-release fertilizers and wick addition to the root-zone on plant growth and yield of medium-fruit sized tomato up to the 18(th) truss in long-term forcing culture. The set-up consisted of a box partitioned by a board into two halves, named box 1 and box 2. Box 1 contained 2.8 ℓ of growth medium (soil : bark : perlite : peat=2 : 2 : 1 : 1). Plant was grown in box 1 with a capillary wick, and at flowering of the 8(th) truss, the partition was removed and box 2 filled with 2.8 ℓ of the medium. There were two treatments, with or without capillary wick in box 2, namely, single wick (S) and double wicks (D). Plant height was greater in D than S in January, and the difference increased gradually thereafter. Flowering time of 18(th) truss in D was 10 days earlier and decapitated shoot weight was twice that of S. Fruit yield per plant was 8 kg in S and 9 kg in D with similar value of Brix and titratable acidity. There was no difference between S and D in dry root weight (7g/plant) or in xylem exudates (8ml/h), while in S in April plant growth was inferior, leaf color yellow greenish and fruit colour uneven towards the end of growth of plants. Xylem sap analysis showed that NO(3)-N was 10 me/ℓ in S and 6 me/ℓ in D. This concentration is weaker than that of Enshi standard nutrient solution generally used in hydroponics. These results suggest that application of controlled-release fertilizers and wick addition to box 2 with root-zone extended was effective for plant growth performance and fruit yield.中玉トマト18段摘心の長期促成栽培における肥効調節型肥料の適用と生育途中の根域拡張に伴う「紐」適用が生育と果実収量に及ぼす効果を調べた．栽培容器は可動仕切り板で2つに仕切り区画当たり容量は2.8ℓとし，第8段花房開花時に仕切り板をはずして5.6ℓ（1st Box＋2nd Box）とした．試験区は2区で2nd Boxに紐を配置しない1本区と2nd Boxにもう１本を配した2本区である．2本区の草丈は1月以降，1本区に比べ高く推移し第18段花房の開花日が約10日早まり，成長の指標とした摘心時の茎頂部新鮮重も1本区の2倍となった．1株の果実収量は1本区で8kg，2本区で9kgとなり果実の糖度，酸度には両区間に差はなかった．栽培終了時の根の乾物重と茎切断面から採取した木部いっ泌液は両区間に差はなかったが，両区とも栽培終期の4月には生育が衰え葉色は黄緑色で果実の着色も不均一であった．木部いっ泌の成分分析ではNO(3)-N濃度が1本区で10me/ℓ，2本区で6me/ℓであり，これらの濃度は一般に養液栽培に使用される園試標準濃度よりも低かった．以上の結果から，第8段花房開花時に仕切りを開放し新区画への土壌と肥料ならびに紐の新たな適用は，生育安定と収量確保に効果的に作用することが明らかとなった．しかし，紐の有無にかかわらず生育後期の生育が不良となったことから，今後は施肥設計の面から，とくにNO(3)-NとSO(4)-Sの両面から検討する必要があると考察した

circRNA : A New Biomarker and Therapeutic Target for Esophageal Cancer

Circular RNAs (circRNAs) comprise a large class of endogenous non-coding RNA with covalently closed loops and have independent functions as linear transcripts transcribed from identical genes. circRNAs are generated by a “back-splicing” process regulated by regulatory elements in cis and associating proteins in trans. Many studies have shown that circRNAs play important roles in multiple processes, including splicing, transcription, chromatin modification, miRNA sponges, and protein decoys. circRNAs are highly stable because of their closed ring structure, which prevents them from degradation by exonucleases, and are more abundant in terminally differentiated cells, such as brains. Recently, it was demonstrated that numerous circRNAs are differentially expressed in cancer cells, and their dysfunction is involved in tumorigenesis and metastasis. However, the crucial functions of these circRNAs and the dysregulation of circRNAs in cancer are still unknown. In this review, we summarize the recent reports on the biogenesis and biology of circRNAs and then catalog the advances in using circRNAs as biomarkers and therapeutic targets for cancer therapy, particularly esophageal cancer

IMPORTANCE OF VISUAL INFORMATION AT CHANGE IN MOTION DIRECTION ON DEPTH PERCEPTION

This paper demonstrates the importance of visual information on depth perception from monocular motion parallax presented at the time of change in the motion direction of head and stimulus movements. In head-tracking systems, a longer delay time between the head and stimulus movements degrades the depth perception from monocular motion parallax. Because this delay is noticeable at this time, we hypothesized that the visual information given at the time of the direction change plays a critical role in the depth perception from motion parallax. We evaluated depth perception from monocular motion parallax with and without a visual stimulus at the time of the motion direction change to confirm our hypothesis, and clarified that stable and unambiguous depth can be perceived by presenting the change of the stimulus motion direction. We also demonstrated that it is the change in motion direction itself that is important rather than the temporal stop between deceleration and acceleration of the stimulus motion

Cyp3a5 genotype as a potential pharmacodynamic biomarker for tacrolimus therapy in ulcerative colitis in japanese patients

Tacrolimus has been used to induce remission in patients with steroid-refractory ulcerative colitis. It poses a problem of large individual differences in dosage necessary to attain target blood concentration and, often, this leads to drug inefficacy. We examined the difference in mRNA expression levels of ATP binding cassette transporter B1 (ABCB1) between inflamed and non-inflamed tissues, and the influence of CYP3A5 genotype on tacrolimus therapy. The mRNA expression of CYP3A4 in colonic mucosa and that of cytochrome p450 3A5 (CYP3A5) and ABCB1 in inflamed and non-inflamed areas were examined in 14 subjects. The mRNA expression levels of CYP3A5 were higher than that of CYP3A4. The mRNA expression of ABCB1 was lower in the inflamed than in the non-inflamed mucosa, despite that of CYP3A5 mRNA level being not significantly changed. Hence, the deterioration of the disease is related to the reduction of the barrier in the inflamed mucosa. The relationship between CYP3A5 genotype and blood concentration, dose, and concentration/dose (C/D) ratio of tacrolimus in 15 subjects was studied. The tacrolimus dose to maintain equivalent blood concentrations was lower in CYP3A5*3/*3 than in CYP3A5*1 carriers, and the C/D ratio was significantly higher in the latter. Thus, CYP3A5 polymorphism information played a role in determining the initial dose of tacrolimus. Furthermore, since the effect of tacrolimus appears earlier in CYP3A5*3/*3 than in CYP3A5*1/*1 and *1/*3, it seems necessary to change the evaluation time of therapeutic effect by CYP3A5 genotype. Additionally, the relationship between CYP3A5 genotype and C/D ratio of tacrolimus in colonic mucosa was investigated in 10 subjects. Tacrolimus concentration in the mucosa was two-fold higher in CYP3A5*3/*3 than in CYP3A5*1 carriers, although no significant difference in tacrolimus-blood levels was observed. Therefore, the local concentration of tacrolimus affected by CYP3A5 polymorphism might be related to its therapeutic effect

Increase of GADD34 expression in skeletal muscle by ATRA

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of GADD34 gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p-38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type

Workplace reform with changing management through the user participation workshop : the case study of Seiyo City Office / Ikumi Egawa

The research explains about workplace reform, aimed at improving productivity of General Affairs and Policy Planning department of Seiyo officeby changing management through the user participation workshop at 4th floor of Seiyo city office and on the changes of workplace reform. The purpose of this research is to find the changes that are worker's behaviour and worker’s awareness of workplace through workplace reform. The researchers surveyed changes, worker's behaviour and worker's awareness of workplace using workplace reform at 4th floor of Seiyo office as case study. In workplace reform, in order to create a place where new work style can be practiced, the researchers conducted the user participation workshops with workers a total of 6 times. Through the workshops, concept of work style and plan of renovation were proposed. In addition, the researchers did a survey using two methods which were a set of questionnaire and 3 observationsthat is before the workplace renovation, 3 months after the renovation, and 1 year and 3 months after the renovation. The findings obtained from the questionnaire in the first three months after the renovation showed that the opinions of the workers were divided between pros and cons against workplace reform. However, the survey of 1 year and three months after the renovation showed that almost all workers are satisfied with the new environment. In addition, the researchers found that a positive correlation exist between participation rate of workshops and the satisfaction level. The findings suggest the worth of workshops for workplace reform. In the Observation Survey, the workers needed to select a place freely where they can work comfortably after the workplace reform. For example, they chose to work in refresh space. In addition, the findings from the survey showed that the floor became livelier when the participation rate increses at that workplace. Additionally, the participants became more conscious of the work style such as features of work style, after workplace renovation; they are able to clearly differentiate between short intermittent works separated by conversation and phone and personal work on concentration