Search

The growing burden of liver fibrosis and lack of effective antifibrotic therapies highlight the need for identification of pathways and complementary model systems of hepatic fibrosis. A rare, monogenic disorder in which children with mutations in mannose phosphate isomerase (MPI) develop liver fibrosis led us to explore the function of MPI and mannose metabolism in liver development and adult liver diseases. Herein, analyses of transcriptomic data from three human liver cohorts demonstrate that MPI gene expression is down-regulated proportionate to fibrosis in chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis B virus. Depletion of MPI in zebrafish liver in vivo and in human hepatic stellate cell (HSC) lines in culture activates fibrotic responses, indicating that loss of MPI promotes HSC activation. We further demonstrate that mannose supplementation can attenuate HSC activation, leading to reduced fibrogenic activation in zebrafish, culture-activated HSCs, and in ethanol-activated HSCs. Conclusion: These data indicate the prospect that modulation of mannose metabolism pathways could reduce HSC activation and improve hepatic fibrosis.

Impaired formation of the biliary network can lead to congenital cholestatic liver diseases; however, the genes responsible for proper biliary system formation and maintenance have not been fully identified. Combining computational network structure analysis algorithms with a zebrafish forward genetic screen, we identified 24 new zebrafish mutants that display impaired intrahepatic biliary network formation. Complementation tests suggested that these 24 mutants affect 24 different genes. We applied unsupervised clustering algorithms to classify the recovered mutants into three classes unbiasedly. Further computational analyses revealed that each of the recovered mutations in these three classes shows a unique effect on node subtype composition and connection property distribution of the intrahepatic biliary network. Besides, we found that most recovered mutations are viable. In those mutant fish, biliary network phenotypes persist into adulthood, which themselves are good animal models to study chronic cholestatic liver diseases. Altogether, this study provides unique genetic and computational toolsets that advance our understanding of the molecular pathways leading to biliary system malformation and cholestatic liver diseases.

The intrahepatic biliary network is a highly branched three-dimensional network lined by biliary epithelial cells, but how its branching patterns are precisely established is not clear. We designed a new computer-based algorithm that quantitatively computes the structural differences of the three-dimensional networks. Utilizing the algorithm, we showed that inhibition of Cyclin-dependent kinase 5 (Cdk5) led to reduced branching in the intrahepatic biliary network in zebrafish. Further, we identified a previously unappreciated downstream kinase cascade regulated by Cdk5. Pharmacological manipulations of this downstream kinase cascade produced a crowded branching defect in the intrahepatic biliary network and influenced actin dynamics in biliary epithelial cells. We generated larvae carrying a mutation in cdk5 regulatory subunit 1a (cdk5r1a), an essential activator of Cdk5. cdk5r1a mutant larvae show similar branching defects as those observed in Cdk5 inhibitor-treated larvae. A small-molecule compound that interferes with the downstream kinase cascade rescued the mutant phenotype. These results provide new insights into branching morphogenesis of the intrahepatic biliary network.

SummaryAdipose triglyceride lipase (ATGL) and comparative gene identification 58 (CGI-58) are critical regulators of triacylglycerol (TAG) turnover. CGI-58 is thought to regulate TAG mobilization by stimulating the enzymatic activity of ATGL. However, it is not known whether this coactivation function of CGI-58 occurs in vivo. Moreover, the phenotype of human CGI-58 mutations suggests ATGL-independent functions. Through direct comparison of mice with single or double deficiency of CGI-58 and ATGL, we show here that CGI-58 knockdown causes hepatic steatosis in both the presence and absence of ATGL. CGI-58 also regulates hepatic diacylglycerol (DAG) and inflammation in an ATGL-independent manner. Interestingly, ATGL deficiency, but not CGI-58 deficiency, results in suppression of the hepatic and adipose de novo lipogenic program. Collectively, these findings show that CGI-58 regulates hepatic neutral lipid storage and inflammation in the genetic absence of ATGL, demonstrating that mechanisms driving TAG lipolysis in hepatocytes differ significantly from those in adipocytes.

Nonalcoholic fatty liver disease is the most common liver disease in both adults and children. The earliest stage of this disease is hepatic steatosis, in which triglycerides are deposited as cytoplasmic lipid droplets in hepatocytes. Through a forward genetic approach in zebrafish, we found that guanosine monophosphate (GMP) synthetase mutant larvae develop hepatic steatosis. We further demonstrate that activity of the small GTPase Rac1 and Rac1-mediated production of reactive oxygen species (ROS) are down-regulated in GMP synthetase mutant larvae. Inhibition of Rac1 activity or ROS production in wild-type larvae by small molecule inhibitors was sufficient to induce hepatic steatosis. More conclusively, treating larvae with hydrogen peroxide, a diffusible ROS that has been implicated as a signaling molecule, alleviated hepatic steatosis in both GMP synthetase mutant and Rac1 inhibitor-treated larvae, indicating that homeostatic production of ROS is required to prevent hepatic steatosis. We further found that ROS positively regulate the expression of the triglyceride hydrolase gene, which is responsible for the mobilization of stored triglycerides in hepatocytes. Consistently, inhibition of triglyceride hydrolase activity in wild-type larvae by a small molecule inhibitor was sufficient to induce hepatic steatosis. Conclusion: De novo GMP synthesis influences the activation of the small GTPase Rac1, which controls hepatic lipid dynamics through ROS-mediated regulation of triglyceride hydrolase expression in hepatocytes. (Hepatology 2013;58:1326–1338)

Mitochondria are the site of iron utilization, wherein imported iron is incorporated into heme or iron–sulfur clusters. Previously, we showed that a cytosolic siderophore, which resembles a bacterial siderophore, facilitates mitochondrial iron import in eukaryotes, including zebrafish. An evolutionarily conserved 3-hydroxy butyrate dehydrogenase, 3-hydroxy butyrate dehydrogenase 2 (Bdh2), catalyzes a rate-limiting step in the biogenesis of the eukaryotic siderophore. We found that inactivation of bdh2 in developing zebrafish embryo results in heme deficiency and delays erythroid maturation. The basis for this erythroid maturation defect is not known. Here we show that bdh2 inactivation results in mitochondrial dysfunction and triggers their degradation by mitophagy. Thus, mitochondria are prematurely lost in bdh2-inactivated erythrocytes. Interestingly, bdh2-inactivated erythroid cells also exhibit genomic alterations as indicated by transcriptome analysis. Reestablishment of bdh2 restores mitochondrial function, prevents premature mitochondrial degradation, promotes erythroid development, and reverses altered gene expression. Thus, mitochondrial communication with the nucleus is critical for erythroid development.

We investigate the k z dispersion in the hole Fermi surfaces (FSs) and the superconducting (SC) gaps of BaFe2(As0.65P0.35)2 by employing bulk-sensitive angle-resolved photoemission spectroscopy (ARPES) with low energy photons. We find that this material exhibits a comparable magnitude of SC gaps for three-hole FSs at k z ∼ π . The comparable magnitude of the SC gap is observed also at k z ∼ 0. Since each FS sheet has a distinct orbital character, these observations are an indication of the orbital-independent SC gaps in the hole FSs.

The origin of superconductivity in the iron pnictides has been attributed to antiferromagnetic spin ordering that occurs in close combination with a structural transition, but there are also proposals that link superconductivity to orbital ordering. We used bulk-sensitive laser angle-resolved photoemission spectroscopy on BaFe(2)(As(0.65)P(0.35))(2) and Ba(0.6)K(0.4)Fe(2)As(2) to elucidate the role of orbital degrees of freedom on the electron-pairing mechanism. In strong contrast to previous studies, an orbital-independent superconducting gap magnitude was found for the hole Fermi surfaces. Our result is not expected from the superconductivity associated with spin fluctuations and nesting, but it could be better explained invoking magnetism-induced interorbital pairing, orbital fluctuations, or a combination of orbital and spin fluctuations. Regardless of the interpretation, our results impose severe constraints on theories of iron pnictides.

Background: Chronic myeloid leukemia (CML) risks may equal the number of hematopoietic stem cells (HSC) per person N multiplied by the risk per HSC. If N is regulated to increase only if below a threshold needed to sustain a functional hematopoietic system, N would then lie in a dead-band of acceptable values [Radiat Res157 106-109 (2002)] that may have evolved to be not too high to avoid hematologic malignancy risks and not too low to have sufficient reserves in times of severe needs. This view is consistent with broad variation in N across individuals, low N after marrow transplants, and N varying across races and cities. If N can be manipulated, perhaps via TET2 activity, monitoring and controlling N could become an important public health objective. Our goal is to estimate N by combining CML incidence data with BCR and ABL data. Methods: Using intron and genome sizes we estimated N by analyzing CML incidence and translocations as functions of radiation dose [Math Biosci162, 85-101 (1999)] and age [Radiat Environ Biophys38, 201-206 (1999)]. As CML risk is fixed by epidemiological data, increases in risks per cell due to BCR-to-ABL tethering [Chromosoma108, 426-435 (1999)] imply lower estimates of N [Radiat Environ Biophys40, 1-9 (2001)]. Assuming such tethering, and sex differences in CML incidence being due to N rather than latency [Radiat Environ Biophys53, 55-63 (2014)], fitting Eq. (1) to A-bomb survivor data yields, via Eqs. (2) and (3), city- and sex specific A-bomb survivor estimates of N (Table 1). In Eq. (1), the first term is the background incidence, the second the probability of radiation forming BCR-ABL in any of N HSC per person and observing CML t years later, and the third the probability of HSC survival; consistent with a dead-band this probability also multiplies the background incidence. Eqs. (2) and (3) show how fitted parameters of the radiation induced term and an external estimate of the risk per cell r were merged to estimate N. To identify chemotherapy-associated reductions in radiation-induced CML risks in Surveillance, Epidemiology, and End Results (SEER) data (Figure 1) we used our R package SEERaBomb [Leukemia30, 285-94 (2016)]. Results: A-bomb survivor data yields estimates of N that are lower in females and lower in Nagasaki (Table 1). Perhaps related to low Nagasaki rates, in SEER patients irradiated for a previous cancer, CML risks are lower in those also treated with chemotherapy (Figure 1). Discussion: It is not known why CML incidence is lower in Nagasaki. Environmental exposures in Nagasaki not present in Hiroshima may have lowered N within the HSC dead-band, either via direct HSC killing or via HSC exhaustion as a result of high downstream cell turnover. For HSC killing as the mechanism, as most HSC are quiescent and thus in G0/G1 wherein error-prone non-homologous end-joining DNA double strand break repair is dominant, suspects include agents that cause cell-lethal DNA double-strand break misrejoinings, such as large deletions and dicentrics. Nagasaki survivors had greater gamma vs. neutron exposures due to plutonium vs. uranium bomb differences, and for a fixed dose, this decreases the probability of killing a struck HSC while increasing the probability of an HSC being struck. Neutron doses were, however, a small fraction of total doses. Another option is a chemical exposure. Chemotherapy reducing radiation-induced CML in Figure 1 suggests that differences in city industries should be considered. For HSC exhaustion as a mechanism of lowering N, if pregnancies reduce breast cancer risks by consuming target cells, a chronic infection could in principle also shift N down in the dead-band. HTLV in Nagasaki but not Hiroshima is not suspected, but perhaps it should be. Radiation does not induce adult T-cell leukemia (ATL), but HTLV lowering N in most people infected might be independent of it causing ATL in a few, and N stopping at the dead-band threshold implies that HTLV is not expected to cause anemia, and it does not. If values of N in the dead-band evolved to be high to survive young adult ages in a more violent non-hygienic world, lowering N, as Nagasaki survivors may have proven is possible, may be a worthwhile goal. CML incidence could be a reporter of N and thus a means of monitoring it. If the target cells of chronic lymphocytic leukemia (CLL) are also HSC, and lower rates of CLL in Nagasaki survivors reflect lower N, lowering N could become an important means of preventing chronic leukemias. Disclosures Maciejewski: Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharmaceuticals, Inc: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Apellis Pharmaceuticals: Consultancy.

Recently, destruction and disturbance of marine ecosystem have been caused by adventive aquatic organisms. To solve the problems, water treatment technique is necessary to remove aquatic organisms efficiently. In this study, magnetic separation system for continuous removal of the aquatic organisms using superconducting magnet which generates strong magnetic field was developed. The jar tests to remove aquatic organisms using permanent magnet showed that nearly 100% of separation efficiency was achieved by aggregation of aquatic organisms using ferromagnetic particles and flocculants. Cost and waste reduction by lowering agent dosages was examined for practical application of magnetic separation system, and continuous processing equipment was designed by simulation and experiment using superconducting magnet.

Recently, destruction and disturbance of marine ecosystem have been caused by changes in global environment and transplants of farmed fishes and shellfishes. To solve the problems, water treatment techniques to kill or to remove aquatic organisms are necessary. In this study, application of magnetic separation for removal of the aquatic organisms was examined in order to establish the process with high-speed, compact device and low environmental load. Techniques of magnetic seeding and magnetic separation using superconducting magnet are important for high-speed processing of aquatic organisms. Magnetic seeding is to adhere separating object to the surface of ferromagnetic particles, and magnetic separation is to remove aquatic organisms with magnetic force. First, we confirmed the possibility of magnetic seeding of aquatic organisms, and then interaction between aquatic organisms and ferromagnetic particles was examined. Next, for practical application of magnetic separation system using superconducting magnet for removal of aquatic organisms, particle trajectories were simulated and magnetic separation experiment using superconducting magnet was performed in order to design magnetic separation system to achieve high separation efficiency.

Notch and fibroblast growth factor (FGF) signaling pathways have been implicated in the establishment of proper periodicity of vertebrate somites. Here, we show evidence that a Hes6-related hairy/Enhancer of split-related gene, her13.2, links FGF signaling to the Notch-regulated oscillation machinery in zebrafish. Expression of her13.2 is induced by FGF-soaked beads and decreased by an FGF signaling inhibitor. her13.2 is required for periodic repression of the Notch-regulated genes her1 and her7, and for proper somite segmentation. Furthermore, Her13.2 augments autorepression of her1 in association with Her1 protein. Therefore, FGF signaling appears to maintain the oscillation machinery by supplying a binding partner, Her13.2, for Her1.

Vertebrate endoderm development has recently become the focus of intense investigation. We have identified a novel sox gene, 226D7, which is important in zebrafish endoderm development. 226D7 was isolated by an in situ hybridization screening for genes expressed in the yolk syncytial layer (YSL) at the blastula stage. 226D7 is expressed mainly in the YSL at this stage and, during gastrulation, its expression is also detected in the forerunner cells and endodermal precursor cells. The expression of 226D7 is positively regulated by Nodal signaling. The knockdown of 226D7 using morpholino antisense oligonucleotides results in a lack of sox17-expressing endodermal precursor cells during gastrulation, and, consequently, lacks endodermal derivatives such as gut tissue. The effect is strictly restricted to the endodermal lineage, while the mesoderm is normally formed, a phenotype that is nearly identical to that of the casanova mutant (Dev. Biol. 215 (1999) 343). We further demonstrate that overexpression of 226D7 increases the number of sox17-expressing endodermal progenitor cells without upregulating the expression of the Nodal genes, cyclops and squint. Region-specific knockdown and overexpression of 226D7 by injection into the YSL suggest that 226D7 in the YSL is not involved in endoderm formation and 226D7 in the endoderm progenitor cells is important for endoderm development. Taken together, our data demonstrate that 226D7 is a downstream target of Nodal signal and a critical transcriptional regulator of early endoderm formation.

We examined the ultrafast response of the metallic high-temperature phase in the conducting charge transfer complex (EDO-TTF)2PF6. A large reflectivity change of approximately 10% was observed when the intra-molecular band was excited by a weak 3.1 eV ultraviolet light pulse. The lifetimes of the photo-induced states were 0.2 and 0.7 ps in the Drude-like band and the intra-molecular band, respectively. Measurement of the photo-induced spectrum just after photo-excitation and simulation using the Drude model revealed that the electronically excited EDO-TTF molecules shortened the relaxation time of conduction electrons and reduced the reflectivity of the Drude-like band.

Nonalcoholic fatty liver disease is the most common liver disease in both adults and children. The earliest stage of this disease is hepatic steatosis, in which triglycerides are deposited as cytoplasmic lipid droplets in hepatocytes. Through a forward genetic approach in zebrafish, we found that guanosine monophosphate (GMP) synthetase mutant larvae develop hepatic steatosis. We further demonstrate that activity of the small GTPase Rac1 and Rac1-mediated production of reactive oxygen species (ROS) are down-regulated in GMP synthetase mutant larvae. Inhibition of Rac1 activity or ROS production in wild-type larvae by small molecule inhibitors was sufficient to induce hepatic steatosis. More conclusively, treating larvae with hydrogen peroxide, a diffusible ROS that has been implicated as a signaling molecule, alleviated hepatic steatosis in both GMP synthetase mutant and Rac1 inhibitor-treated larvae, indicating that homeostatic production of ROS is required to prevent hepatic steatosis. We further found that ROS positively regulate the expression of the triglyceride hydrolase gene, which is responsible for the mobilization of stored triglycerides in hepatocytes. Consistently, inhibition of triglyceride hydrolase activity in wild-type larvae by a small molecule inhibitor was sufficient to induce hepatic steatosis.De novo GMP synthesis influences the activation of the small GTPase Rac1, which controls hepatic lipid dynamics through ROS-mediated regulation of triglyceride hydrolase expression in hepatocytes.

BTG/tob family proteins are thought to be a potential tumor suppressor due to their anti-proliferative activity. We cloned zebrafish btg-b, a member of the BTG1/2 subfamily, using in situ hybridization screening. The tissue-specific expression of btg-b is first observed in the organizer region at the early gastrula stage. Later in development, the forebrain, the hindbrain, the polster and the paraxial mesoderm transiently express btg-b. Recently, mouse Btg1 and Btg2 have been shown to be a cofactor for Hoxb9. Double in situ hybridization with zebrafish btg-b and hoxb9a indicates that the expression domains of these two genes overlap in the posterior paraxial mesoderm.

The bispectral analysis for detecting the nonlinear quadratic mode-mode couplings in fluid and plasma turbulences is developed in a numerical technique with respect to the three-wave vector electro-magnetic wave scattering observation using the coherent signal detection technique. The autoregressive method of Raghuveer-Nikias is extended to a three-channel complex diagonal form by taking into account the sum rule of wave vectors for nonzero bispectrum of stationary homogeneous fluctuations. Some results of simulation and experiment are presented.

The roles of extra-embryonic tissues in early vertebrate body patterning have been extensively studied, yet we know little about their function during later developmental events. Here, we analyze the function of the zebrafish extra-embryonic yolk syncytial layer (YSL) specific transcription factor,Mtx1, and find that it plays an essential role in myocardial migration. Downregulating the function of Mtx1 in the YSL leads to cardia bifida, a phenotype in which the myocardial cells fail to migrate to the midline. Mtx1 in the extra-embryonic YSL appears to regulate the embryonic expression of fibronectin, a gene previously implicated in myocardial migration. We further show dosage-sensitive genetic interactions between mtx1 and fibronectin. Based on these data, we propose that the extra-embryonic YSL regulates myocardial migration, at least in part by influencing fibronectin expression and subsequent assembly of the extracellular matrix in embryonic tissues.

A composite linear model is proposed, which converts from non-Gaussian i.i.d. processes into a nOnGaussian stationary stochastic processes with given third-order cumulant spectrum and with white power spectrum. The design for the model is based on the fact that a type of finite-impulse-response linear system with non-Gaussian i.i.d. input process makes an output process whose third order autocorrelations exist only for special time lags. Arbitrary third order autocorrelation function can be obtained by some superposition of independent output processes of this type. Results of numerical experiments confirm this fact. This model requires at most 2L2+4L+1 input i.i.d. processes independent of one another, for the third order autocorrelation function with the largest time lag L. With sufficient large L, a process with desired bispectrum can be made by this model.

The medaka is becoming an attractive model organism for the study of vertebrate early development and organogenesis and large-scale mutagenesis projects that are aimed at creating developmentally defective mutants are now being conducted by several groups in Japan. To strengthen the study of medaka developmental genetics, we have conducted a large-scale isolation of ESTs from medaka embryos and developed tools that facilitate mutant analysis. In this study, we have characterized a total of 132,082 sequences from both ends of cloned insert cDNAs from libraries generated at different stages of medaka embryo development. Clustering analysis with 3-prime sequences finally identified a total of 12,429 clusters. As a pilot analysis, 924 clusters were subjected to in situ hybridization to determine the spatial localization of their transcripts. Using EST sequence data generated in the present study, a 60-mer oligonucleotide microarray with 8,091 unigenes (Medaka Microarray 8K) was constructed and tested for its usefulness in expression profiling. Furthermore, we have developed a rapid and reliable mutant mapping system using a set of mapped EST markers (M-marker 2003) that covers the entire medaka genome. These resources will accelerate medaka mutant analyses and make an important contribution to the medaka genome project.

Involving dynamic and coordinated cell movements that cause drastic changes in embryo shape, gastrulation is one of the most important processes of early development. Gastrulation proceeds by various types of cell movements, including convergence and extension, during which polarized axial mesodermal cells intercalate in radial and mediolateral directions and thus elongate the dorsal marginal zone along the anterior-posterior axis [1, 2]. Recently, it was reported that a noncanonical Wnt signaling pathway, which is known to regulate planar cell polarity (PCP) in Drosophila[3, 4], participates in the regulation of convergent extension movements in Xenopus as well as in the zebrafish embryo [5–8]. The Wnt5a/Wnt11 signal is mediated by members of the seven-pass transmembrane receptor Frizzled (Fz) and the signal transducer Dishevelled (Dsh) through the Dsh domains that are required for the PCP signal [6–8]. It has also been shown that the relocalization of Dsh to the cell membrane is required for convergent extension movements in Xenopus gastrulae. Although it appears that signaling via these components leads to the activation of JNK [9, 10] and rearrangement of microtubules, the precise interplay among these intercellular components is largely unknown. In this study, we show that Xenopus prickle (Xpk), a Xenopus homolog of a Drosophila PCP gene [11–13], is an essential component for gastrulation cell movement. Both gain-of-function and loss-of-function of Xpk severely perturbed gastrulation and caused spina bifida embryos without affecting mesodermal differentiation. We also demonstrate that XPK binds to Xenopus Dsh as well as to JNK. This suggests that XPK plays a pivotal role in connecting Dsh function to JNK activation.

The author discusses the systems of the eigenvectors of the operator Q-ikP/sup -1/. The system constitutes an over-complete wavelet system, where the eigenvector associated with a nonreal eigenvalue is transformed to the eigenvalue associated with another nonreal eigenvalue by the affine transform. The author shows this fact in terms of the operator algebra. The eigenfunctions in position coordinate representation are simple rational functions and have a localized 'wavelet-like' shape. They satisfy the 'admissibility condition'. It has been proved that in a limit the eigenvector gradually approaches a sequence of squeezed-state vectors with respect to // ///sub 2/ as k to infinity . >

The eigenfunction system of a kind of operator is identical to the over-complete Cauchy wavelet system, as has been shown previously. In this presentation, the re-ordering problem among this operator and its adjoint is investigated. Then, an application of this re-ordering problem to the pseudo-diagonalization problem of the autocorrelation function of a stochastic process is proposed.

A larger class of systems of almost localized wavepackets is proposed. This class contains the Cauchy wavelet system and the coherent state system as special cases. The wavepacket systems in this class are the eigenfunction systems of a kind of linear operators, and they are invariant under the time-shift. Moreover, we show that they are 'pseudoorthogonal' over-complete systems in L/sup 2/. An application of them to the diagonalization problem of the autocorrelation functions of stochastic processes via overcomplete wavepacket systems is also proposed.

If the covariance function of a random signal can be written in a diagonal form via the wavelet basis, this random signal can be regarded as a superposition of the wavelets which arise randomly. However, it is known that, in general, such an expression is not possible. In this paper, in place of a perfect diagonalization, an optimal approximate diagonalization in the sense of the relative entropy is investigated theoretically. Especially, it is shown that when a set of wavelets forming complete orthonormal sets expressed in a vector form as {/spl phi//sub i/} is used as the basis, an optimal diagonal approximation of the covariance matrix /spl Gamma/ is not the diagonal form /spl Sigma//sub h/(/spl phi/~/sub h//sup /spl tau///spl Gamma//spl phi//sub h/)/spl phi//sub h//spl phi/~/sub h//sup /spl tau// using the so-called 'wavelet spectrum' but /spl Sigma//sub h/(/spl phi/~/sub h//sup /spl tau///spl Gamma//sup -1//spl phi//sub h/)/sup -1//spl phi//sub h//spl phi/~/sub h//sup /spl tau//. Further, several examples are given where Haar wavelets are used.

It is well known that the over-complete Cauchy wavelet system with continuous parameters is the eigenfunction system of the operator T+kJ (T:multiplication by t, J:integral op.). This is quite parallel to the well-known relation between the coherent state system and the boson annihilation operator used in quantum mechanics, in which the annihilation operator is the step-down operator of the number states. In this paper, for the Cauchy wavelet system, we show a similar relation to this on the step-up/down operator of a kind of orthogonal function system. The operator T+kJ itself is not the step-down operator but a kind of rational function of this operator,and is the step-down operator of a kind of orthogonal wavepacket system which is the eigenfunction system of the analogue of 'number' operator.

Zebrafish develop in a typical manner of teleosts (for review, see Driever 1995). The animal/vegetal axis is specified during oogenesis and sperm can enter the egg through a single entry site (micropyle) located at the animal pole. When eggs are laid, yolk and cytoplasm are intermixed. After fertilization, cytoplasm streams to the animal pole as it segregates from the yolk. About 30 min after fertilization, the cytoplasm forms the blastodisc at the animal pole and surrounds the vegetal yolk mass as a thin cytoplasmic layer (Fig. 1A,B). The cleavages take place atop a large yolk mass. During mid-blastula transition, activation of zygotic transcription (10th cleavage in zebrafish) coincides with the generation of the first three separate lineages of the embryo (Fig. 1C,D). Two of these lineages are extra-embryonic, the enveloping layer (EVL) forming the outer surface of the blastoderm, and the yolk syncytial layer (YSL) that covers the animal part of the yolk cell, respectively. The third lineage, termed the deep cell layer, will form the embryo proper.

Non-alcoholic fatty liver disease (NAFLD) is a widespread condition of growing concern. It affects up to 25% of people in the United States, and is caused by the buildup of lipids in the liver. NAFLD may lead to hepatocellular carcinoma, the 5th most common cancer in the world, and the 3rd most common cause of death from cancer. Steatosis is the earliest stage in the progression of NAFLD. It is characterized by the deposition of triglycerides as lipid droplets in the cytoplasm of hepatocytes. Although not usually lethal alone, it may develop into nonalcoholic steatohepatitis, and develop further into cirrhosis and ultimately hepatocellular carcinoma. A mutation in zebrafish is created that completely obstructs the guanine monophosphate synthase. The mutants show a phenotype of steatosis. We hypothesize that genes involved in de novo lipogenesis, lipid oxidation, or lipid transportation are altered in the mutants. To test our hypothesis, we conducted gene expression analysis using qPCR. The data indicates that the genes involved in de novo lipogenesis had no significant change. However, the genes involved in lipid oxidation were all significantly downregulated. This downregulation indicates that inadequate lipid metabolism is responsible for the buildup of lipids and steatosis. The genes involved in lipid transportation showed a downregulation trend. It might be a result of steatosis as the liver takes in less fat. Overall, the data suggests that the mutant cell is unable to metabolize enough lipids through oxidation, causing lipid buildup in the liver. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2111A. doi:1538-7445.AM2012-2111A

When we observe only the sum of two independent stationary time series generated from non-Gaussian white noises, we consider how to separate its spectrum nonparametrically into two respective spectra. For this we propose a simple method which utilizes the nonnegativity of power spectra and uses a part of the fourth-order spectrum estimated from the periodograms. Theoretically, the spectrum is uniquely separated when the spectra of the two time series have different zeros. The simulation results show that our method is successful. The asymptotic property of the method is also investigated.

Laser therapy for bile duct stones, such as the non-contact beam treatment using continuous wave of Nd:YAG laser or contact beam treatment using ceramics rod, has been done in our institution from 1980. As a result, the ratio of complete lithotomy has been increased from 31/47 (66%) to 66/71 (93%). Recently, we had a opportunity to use the Lasertripter by Candera Corp., which was devised for urinary stones. It beams pulse wave to crush stones. The effectiveness of this new laser lithotripsy is different according to the kind of the stones, but it is better than that of conventional YAG laser. Furthermore, as this method can be used with thin fiberscope, this method is more effective to peripheral intrahepatic stones than YAG laser.

In order to elucidate upon the interrelationships among the different structures in and around the nasal cavity, the noses of 95 adults without severe rhinitis, paranasal sinusitis, cysts or tumors were examined by means of X-ray tomography. The results indicate a close correlation between the width of the nasal cavity and 1) the width of the maxillary sinus, 2) the size, form and height of the inferior turbinate, 3) the size of the middle turbinate or 4) the nasal septal deviation; between the height of the nasal cavity and the length and height of the inferior turbinate or the length of the middle turbinate, and also between the degree of septal deviation and the width of the nasal cavity, the nasal meatus or olfactory slit or the form of the inferior turbinate. In conclusion, it is recognized that correction of the abnormal interrelationships among the different structures is important for functional nasal surgery.