Caroli's Disease: Current Knowledge of Its Biliary Pathogenesis Obtained from an Orthologous Rat Model

Caroli's disease belongs to a group of hepatic fibropolycystic diseases and is a hepatic manifestation of autosomal recessive polycystic kidney disease (ARPKD). It is a congenital disorder characterized by segmental saccular dilatations of the large intrahepatic bile duct and is frequently associated with congenital hepatic fibrosis (CHF). The most viable theory explaining its pathogenesis suggests that it is related to ductal plate malformation. The development of the polycystic kidney (PCK) rat, an orthologous rodent model of Caroli's disease with CHF as well as ARPKD, has allowed the molecular pathogenesis of the disease and the therapeutic options for its treatment to be examined. The relevance of the findings of studies using PCK rats and/or the cholangiocyte cell line derived from them to the pathogenesis of human Caroli's disease is currently being analyzed. Fibrocystin/polyductin, the gene product responsible for ARPKD, is normally localized to primary cilia, and defects in the fibrocystin from primary cilia are observed in PCK cholangiocytes. Ciliopathies involving PCK cholangiocytes (cholangiociliopathies) appear to be associated with decreased intracellular calcium levels and increased cAMP concentrations, causing cholangiocyte hyperproliferation, abnormal cell matrix interactions, and altered fluid secretion, which ultimately result in bile duct dilatation. This article reviews the current knowledge about the pathogenesis of Caroli's disease with CHF, particularly focusing on studies of the mechanism responsible for the biliary dysgenesis observed in PCK rats

A New Test Statistic Based on Shrunken Sample Variance for Identifying Differentially Expressed Genes in Small Microarray Experiments

Choosing an appropriate statistic and precisely evaluating the false discovery rate (FDR) are both essential for devising an effective method for identifying differentially expressed genes in microarray data. The t-type score proposed by Pan et al. (2003) succeeded in suppressing false positives by controlling the underestimation of variance but left the overestimation uncontrolled. For controlling the overestimation, we devised a new test statistic (variance stabilized t-type score) by placing shrunken sample variances of the James-Stein type in the denominator of the t-type score. Since the relative superiority of the mean and median FDRs was unclear in the widely adopted Significance Analysis of Microarrays (SAM), we conducted simulation studies to examine the performance of the variance stabilized t-type score and the characteristics of the two FDRs. The variance stabilized t-type score was generally better than or at least as good as the t-type score, irrespective of the sample size and proportion of differentially expressed genes. In terms of accuracy, the median FDR was superior to the mean FDR when the proportion of differentially expressed genes was large. The variance stabilized t-type score with the median FDR was applied to actual colorectal cancer data and yielded a reasonable result

Diet of the minimal armhook squid (Berryteuthis anonychus) (Cephalopoda: Gonatidae) in the northeast Pacific during spring

The stomach contents of the minimal armhook squid (Berryteuthis anonychus) were examined for 338 specimens captured in the northeast Pacific during May 1999. The specimens were collected at seven stations between 145−165°W and 39−49°N and ranged in mantle length from 10.3 to 102.2 mm. Their diet comprised seven major prey groups (copepods, chaetognaths, amphipods, euphausiids, ostracods, unidentified fish, and unidentified gelatinous prey) and was dominated by copepods and chaetognaths. Copepod prey comprised four genera, and 86% by number of the copepods were from the genus Neocalanus. Neocalanus cristatus was the most abundant prey taxa, composing 50% by mass and 35% by number of the total diet. Parasagitta elegans (Chaetognatha) occurred in more stomachs (47%) than any other prey taxon. Amphipods occurred in 19% of the stomachs but composed only 5% by number and 3% by mass of the total prey consumed. The four remaining prey groups (euphausiids, ostracods, unidentified fish, and unidentified gelatinous prey) together composed <2% by mass and <1% by number of the diet. There was no major change in the diet through the size range of squid examined and no evidence of cannibalism or predation on other cephalopod species

Image preference estimation with a data-driven approach: A comparative study between gaze and image features

Understanding how humans subjectively look at and evaluate images is an important task for various applications in the field of multimedia interaction. While it has been repeatedly pointed out that eye movements can be used to infer the internal states of humans, not many successes have been reported concerning image understanding. We investigate the possibility of image preference estimation based on a person’s eye movements in a supervised manner in this paper. A dataset of eye movements is collected while the participants are viewing pairs of natural images, and it is used to train image preference label classifiers. The input feature is defined as a combination of various fixation and saccade event statistics, and the use of the random forest algorithm allows us to quantitatively assess how each of the statistics contributes to the classification task. We show that the gaze-based classifier had a higher level of accuracy than metadata-based baseline methods and a simple rule-based classifier throughout the experiments. We also present a quantitative comparison with image-based preference classifiers and discuss the potential and limitations of the gaze-based preference estimator

Estimating the False Discovery Rate Using Mixed Normal Distribution for Identifying Differentially Expressed Genes in Microarray Data Analysis

The recent development of DNA microarray technology allows us to measure simultaneously the expression levels of thousands of genes and to identify truly correlated genes with anticancer drug response (differentially expressed genes) from many candidate genes. Significance Analysis of Microarray (SAM) is often used to estimate the false discovery rate (FDR), which is an index for optimizing the identifiability of differentially expressed genes, while the accuracy of the estimated FDR by SAM is not necessarily confirmed. We propose a new method for estimating the FDR assuming a mixed normal distribution on the test statistic and examine the performance of the proposed method and SAM using simulated data. The simulation results indicate that the accuracy of the estimated FDR by the proposed method and SAM, varied depending on the experimental conditions. We applied both methods to actual data comprised of expression levels of 12,625 genes of 10 responders and 14 non-responders to docetaxel for breast cancer. The proposed method identified 280 differentially expressed genes correlated with docetaxel response using a cut-off value for achieving FDR <0.01 to prevent false-positive genes, although 92 genes were previously thought to be correlated with docetaxel response ones

Detection of a low-eccentricity and super-massive planet to the subgiant HD 38801

We report the detection of a large mass planet orbiting around the K0 metal-rich subgiant HD38801 ($V=8.26$) by precise radial velocity (RV) measurements from the Subaru Telescope and the Keck Telescope. The star has a mass of $1.36M_{\odot}$ and metallicity of [Fe/H]= +0.26. The RV variations are consistent with a circular orbit with a period of 696.0 days and a velocity semiamplitude of 200.0\mps, which yield a minimum-mass for the companion of 10.7\mjup and semimajor axis of 1.71 AU. Such super-massive objects with very low-eccentricities and hundreds of days period are uncommon among the ensemble of known exoplanets