Objectives: To investigate whether the ratio of early transmitral flow velocity (E) to early diastolic mitral annular velocity (E′) predict prognosis in patients with non-valvular atrial ...fibrillation. Methods: 230 patients with non-valvular atrial fibrillation were enrolled and studied. According to E/E′ value, patients were divided into groups with lower (group A with E/E′ ⩽ 15) and higher (group B with E/E′ > 15) E/E′. Results: During follow up (average 245 days), 21 (9.1%) deaths were documented. All cause death (15/90 (16.7%) v 6/140 (4.3%)), cardiac death (10 (11.1%) v 2 (1.4%)) and congestive heart failure (16 (17.8%) v 8 (5.7%)) were more common in group B than in group A (all p < 0.01). A Kaplan–Meier survival curve showed that the cumulative survival rate was significantly lower in group B than in group A (log rank p = 0.0013). By multivariate logistic regression analysis, E/E′ (χ2 = 4.47, odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.11, p = 0.03) and age (χ2 = 6.45, OR 1.06, 95% CI 1.01 to 1.11, p = 0.02) were independent predictors of mortality. Conclusion: The Doppler-derived index of left ventricular filling pressure, E/E′, is a powerful predictor of the clinical outcome of patients with non-valvular atrial fibrillation.
The peptide binding specificities of HLA-DRB1*0401, DRB1*0101, and DRB1*0701 have been analyzed by the use of large collections of synthetic peptides corresponding to naturally occurring sequences. ...The results demonstrated that nearly all peptides binding to these DR molecules bear a motif characterized by a large aromatic or hydrophobic residue in position 1 (Y, F, W, L, I, V, M) and a small, noncharged residue in position 6 (S, T, C, A, P, V, I, L, M). In addition, allele-specific secondary effects and secondary anchors were defined, and these parameters were utilized to derive allele-specific motifs and algorithms. By the combined use of such algorithms, peptides capable of degenerate DRB1*0101, DRB1*0401, and DRB1*0701 binding were identified. Additional experiments utilizing a panel of quantitative assays specific for nine additional common DR molecules identified a large set of DR molecules, which includes at least the DRB1*0101, DRB1*0401, DRB1*0701, DRB5*0101, DRB1*1501, DRB1*0901, and DRB1*1302 allelic products, characterized by overlapping peptide-binding repertoires. These results have implications for understanding the molecular interactions involved in peptide-DR binding, as well as the genetic and structural basis of MHC polymorphism. These results also have potential practical implications for the development of epitope-based prophylactic and therapeutic vaccines.
We report a robust display technology for the screening of disulfide-rich peptides, based on cDNA–protein fusions, by developing a novel and versatile puromycin-linker DNA. This linker comprises four ...major portions: a ‘ligation site’ for T4 RNA ligase, a ‘biotin site’ for solid-phase handling, a ‘reverse transcription primer site’ for the efficient and rapid conversion from an unstable mRNA–protein fusion (mRNA display) to a stable mRNA/cDNA–protein fusion (cDNA display) whose cDNA is covalently linked to its encoded protein and a ‘restriction enzyme site’ for the release of a complex from the solid support. This enables not only stabilizing mRNA–protein fusions but also promoting both protein folding and disulfide shuffling reactions. We evaluated the performance of cDNA display in different model systems and demonstrated an enrichment efficiency of 20-fold per selection round. Selection of a 32-residue random library against interleukin-6 receptor generated novel peptides containing multiple disulfide bonds with a unique linkage for its function. The peptides were found to bind with the target in the low nanomolar range. These results show the suitability of our method for in vitro selections of disulfide-rich proteins and other potential applications.
•We measured the production cross sections for a variety of radioactive isotopes.•They were produced from 124Xe, 48Ca, and 238U beams at 345MeV/nucleon using BigRIPS.•The measured production cross ...sections were compared with the EPAX formulae.•We discovered four new isotopes 85,86Ru and 81,82Mo produced by 124Xe+Be.•103Sb is particle unbound with an upper limit of 49ns for the half-life.
We have measured the production rates and production cross sections for a variety of radioactive isotopes which were produced from 124Xe, 48Ca, and 238U beams at an energy of 345MeV/nucleon using the BigRIPS separator at the RIKEN Nishina Center RI Beam Factory (RIBF). Proton-rich isotopes with atomic numbers Z=40–52 and neutron-rich isotopes with Z=5–16 were produced by projectile fragmentation of the 124Xe and 48Ca beam on Be targets, respectively. Neutron-rich isotopes with Z=20–59 were produced by in-flight fission of the 238U beam, in which both Be and Pb were used as production targets. The measured production rates and production cross sections were compared with those of the LISE++ calculations, and overall fairly good agreement has been obtained. Furthermore, in the measurements with the 124Xe beam, we have discovered four new isotopes on the proton-drip line, 85,86Ru and 81,82Mo, and obtained the clear evidence that 103Sb is particle unbound with an upper limit of 49ns for the half-life. The measurements of projectile-fragment momentum distributions have been also performed with the 124Xe beam, in which the low-momentum tails of the distributions have been measured for the first time at the energy of 345MeV/nucleon.
Organic anion-transporting polypeptides (OATPs) encoded by SLCO mediate the cellular uptake of many compounds, including androgens. SLCO1B3 and SLCO2B1 are polymorphic, and single-nucleotide ...polymorphisms of those genes alter androgen transport efficiency. We aimed to investigate the association between genetic variations in SLCOs and the progression to castration-resistant prostate cancer (CRPC).
We studied the progression to CRPC for the SLCO1B3 rs4149117 and SLCO2B1 rs12422149 genotypes in 87 prostate cancer patients who received androgen deprivation therapy (ADT). Data were analyzed using the χ(2) test, Kaplan-Meier survival analysis and Cox proportional hazard model.
SLCO3B1 genotypes were not significantly associated with the time to progression (TTP); however, patients carrying the active androgen transport SLCO2B1 genotype (GG allele) exhibited a median TTP that was 7 months shorter than that of patients with impaired androgen-transporting activity SLCO2B1 polymorphisms (GA/AA alleles) (10.0 vs 17.0 months, P=0.004). Active androgen transport genotypes of SLCO2B1 (GG allele) occurred more frequently in African and Caucasian populations than in Japanese and Han Chinese populations (P<0.001).
These data suggest that SLCO2B1 rs12422149 variants could provide prognostic value for prostate cancer patients treated with ADT and influence ethnic differences in response to ADT. Active androgen import may be one of the underlying mechanisms of resistance to ADT, and androgen-transporting systems could provide novel biomarkers and targets for CRPC treatment.
BACKGROUND AND AIMS: The timing of cambial reactivation plays an important role in the control of both the quantity and the quality of wood. The effect of localized heating on cambial reactivation in ...the main stem of a deciduous hardwood hybrid poplar (Populus sieboldii x P. grandidentata) was investigated. METHODS: Electric heating tape (20-22 °C) was wrapped at one side of the main stem of cloned hybrid poplar trees at breast height in winter. Small blocks were collected from both heated and non-heated control portions of the stem for sequential observations of cambial activity and for studies of the localization of storage starch around the cambium from dormancy to reactivation by light microscopy. KEY RESULTS: Cell division in phloem began earlier than cambial reactivation in locally heated portions of stems. Moreover, the cambial reactivation induced by localized heating occurred earlier than natural cambial reactivation. In heated stems, well-developed secondary xylem was produced that had almost the same structure as the natural xylem. When cambial reactivation was induced by heating, the buds of trees had not yet burst, indicating that there was no close temporal relationship between bud burst and cambial reactivation. In heated stems, the amount of storage starch decreased near the cambium upon reactivation of the cambium. After cambial reactivation, storage starch disappeared completely. Storage starch appeared again, near the cambium, during xylem differentiation in heated stems. CONCLUSIONS: The results suggest that, in deciduous diffuse-porous hardwood poplar growing in a temperate zone, the temperature in the stem is a limiting factor for reactivation of phloem and cambium. An increase in temperature might induce the conversion of storage starch to sucrose for the activation of cambial cell division and secondary xylem. Localized heating in poplar stems provides a useful experimental system for studies of cambial biology.
Pancreatic cystic lesions are increasingly being detected incidentally because of the increased use of cross-sectional imaging. Squamous-lined cysts of the pancreas (lymphoepithelial cyst, epidermoid ...cyst, and dermoid cyst) are rare cystic lesions lined with squamous epithelium. Distinguishing squamous-lined cysts from other cystic lesions of the pancreas is important to avoid unnecessary surgery, because squamous-lined cysts of the pancreas have no malignant potential. The purpose of this review is to describe findings on computed tomography and magnetic resonance imaging and the histopathological characteristics of squamous-lined cysts, and to summarize the key points of differential diagnosis for pancreatic cystic lesions.
Background
Alcoholic subjects manifest important deficits in frontal executive function, yet maintain cognitive mental status within normal range.
Methods
This study searched for volumetric ...measurements of segmented brain structures obtained from magnetic resonance imaging (MRI) that would predict executive functions and cognitive mental status in alcoholic subjects. The frontal assessment battery (FAB) and the Mini‐Mental State Examination (MMSE) were applied to alcoholic subjects who underwent MRI. Cortical and subcortical segmentation and corrections were performed using FreeSurfer. Multiple linear regressions analyses having volumetric measures of segmented brain structures as predictors for FAB or MMSE scores as dependent measures were conducted. Sixty alcoholic subjects, 52 males, mean age of 47.2 ± SD 10.4 years, with heavy use of alcohol (mean 284.4 ± SD 275.9 g of alcohol/d) over a long time (mean 32.4 ± SD 11.1 years), showed FAB 11.1 ± SD 3.2 and MMSE of 25.2 ± SD 4.1.
Results
Multiple regression analyses having left and right side of each segment as predictors showed that gray matter volumes of rostral middle frontal cortex and cerebellar cortex (p < 0.001), in which only the left side of these structures showed significant partial effects in the full model (p < 0.05), showed to predict FAB performance. They were even more predictive when considered together (p < 0.001), in which both left rostral middle frontal cortex (p < 0.05) and left cerebellar cortex (p < 0.01) predictors had significant partial effects in the full model. None of brain structures was predictive of MMSE performance.
Conclusions
We have concluded that volumetric measurements of left rostral middle frontal and cerebellar cortices seem to be able to predict the frontal executive performance but not the cognitive mental status in alcoholic subjects.
•Large-area Parallel Plate Avalanche Counter (PPAC) developed for position measurement.•A specially developed delay line is utilized to obtain the position information.•Excellent performance in ...sensitivity uniformity as well as position measurement.•Double-PPAC structure enables to obtain high detection efficiency.•A signal transmission system using optical fiber cables has been developed for PPACs.
We have developed a position-sensitive Parallel Plate Avalanche Counter (PPAC), which has been used as a focal plane detector in the BigRIPS fragment separator and the subsequent RI-beam delivery lines at the RIKEN Nishina Center RI Beam Factory. The PPAC detector plays an important role not only in the tuning of the separator and delivery lines but also in the particle identification of rare isotope (RI) beams. The PPAC detector has a sensitive area of 240mm×150mm, and the position information is obtained by a delay-line readout method. Being called double PPAC, it is composed of two full PPACs, each measuring the particle locus in two dimensions. High detection efficiency has been made possible by the twofold measurement using the double PPAC detector. The sensitivity uniformity is also found to be excellent. The root-mean-square position resolution is measured to be 0.25mm using an α source, while the position linearity is as good as ±0.1mm for the detector size of 240mm. Characteristics, operating principles, specifications, performance and issues of the PPAC detector are presented, including its signal transmission system using optical fiber cables.
Transfer of type-1 helper T-conditioned (Th1-conditioned) cells promotes functional recovery with enhanced axonal remodeling after spinal cord injury (SCI). This study explored the molecular ...mechanisms underlying the beneficial effects of pro-inflammatory Th1-conditioned cells after SCI. The effect of Th1-conditioned cells from interferon-γ (ifn-γ) knockout mice (ifn-γ(-/-) Th1 cells) on the recovery after SCI was reduced. Transfer of Th1-conditioned cells led to the activation of microglia (MG) and macrophages (MΦs), with interleukin 10 (IL-10) upregulation. This upregulation of IL-10 was reduced when ifn-γ(-/-) Th1 cells were transferred. Intrathecal neutralization of IL-10 in the spinal cord attenuated the effects of Th1-conditioned cells. Further, IL-10 is robustly secreted from Th1-conditioned cells in an ifn-γ-dependent manner. Th1-conditioned cells from interleukin 10 knockout (il-10(-/-)) mice had no effects on recovery from SCI. These findings demonstrate that ifn-γ-dependent secretion of IL-10 from Th1 cells, as well as native MG/MΦs, is required for the promotion of motor recovery after SCI.
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