Showing papers by "University of Tokyo published in 2001"

The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity

Abstract: Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.

A comprehensive two-hybrid analysis to explore the yeast protein interactome

Abstract: Protein-protein interactions play crucial roles in the execution of various biological functions. Accordingly, their comprehensive description would contribute considerably to the functional interpretation of fully sequenced genomes, which are flooded with novel genes of unpredictable functions. We previously developed a system to examine two-hybrid interactions in all possible combinations between the approximately 6,000 proteins of the budding yeast Saccharomyces cerevisiae. Here we have completed the comprehensive analysis using this system to identify 4,549 two-hybrid interactions among 3,278 proteins. Unexpectedly, these data do not largely overlap with those obtained by the other project [Uetz, P., et al. (2000) Nature (London) 403, 623-627] and hence have substantially expanded our knowledge on the protein interaction space or interactome of the yeast. Cumulative connection of these binary interactions generates a single huge network linking the vast majority of the proteins. Bioinformatics-aided selection of biologically relevant interactions highlights various intriguing subnetworks. They include, for instance, the one that had successfully foreseen the involvement of a novel protein in spindle pole body function as well as the one that may uncover a hitherto unidentified multiprotein complex potentially participating in the process of vesicular transport. Our data would thus significantly expand and improve the protein interaction map for the exploration of genome functions that eventually leads to thorough understanding of the cell as a molecular system.

Randomized kinodynamic planning

Abstract: This paper presents the first randomized approach to kinodynamic planning (also known as trajectory planning or trajectory design). The task is to determine control inputs to drive a robot from an ...

Topology matching for fully automatic similarity estimation of 3D shapes

Abstract: There is a growing need to be able to accurately and efficiently search visual data sets, and in particular, 3D shape data sets. This paper proposes a novel technique, called Topology Matching, in which similarity between polyhedral models is quickly, accurately, and automatically calculated by comparing Multiresolutional Reeb Graphs (MRGs). The MRG thus operates well as a search key for 3D shape data sets. In particular, the MRG represents the skeletal and topological structure of a 3D shape at various levels of resolution. The MRG is constructed using a continuous function on the 3D shape, which may preferably be a function of geodesic distance because this function is invariant to translation and rotation and is also robust against changes in connectivities caused by a mesh simplification or subdivision. The similarity calculation between 3D shapes is processed using a coarse-to-fine strategy while preserving the consistency of the graph structures, which results in establishing a correspondence between the parts of objects. The similarity calculation is fast and efficient because it is not necessary to determine the particular pose of a 3D shape, such as a rotation, in advance. Topology Matching is particularly useful for interactively searching for a 3D object because the results of the search fit human intuition well.

Composite Quasar Spectra from the Sloan Digital Sky Survey

Abstract: We have created a variety of composite quasar spectra using a homogeneous data set of over 2200 spectra from the Sloan Digital Sky Survey (SDSS). The quasar sample spans a redshift range of 0.044 ≤ z ≤ 4.789 and an absolute r' magnitude range of -18.0 to -26.5. The input spectra cover an observed wavelength range of 3800–9200 A at a resolution of 1800. The median composite covers a rest-wavelength range from 800 to 8555 A and reaches a peak signal-to-noise ratio of over 300 per 1 A resolution element in the rest frame. We have identified over 80 emission-line features in the spectrum. Emission-line shifts relative to nominal laboratory wavelengths are seen for many of the ionic species. Peak shifts of the broad permitted and semiforbidden lines are strongly correlated with ionization energy, as previously suggested, but we find that the narrow forbidden lines are also shifted by amounts that are strongly correlated with ionization energy. The magnitude of the forbidden line shifts is 100 km s-1, compared with shifts of up to 550 km s-1 for some of the permitted and semiforbidden lines. At wavelengths longer than the Lyα emission, the continuum of the geometric mean composite is well fitted by two power laws, with a break at ≈5000 A. The frequency power-law index, αν, is -0.44 from ≈1300 to 5000 A and -2.45 redward of ≈5000 A. The abrupt change in slope can be accounted for partly by host-galaxy contamination at low redshift. Stellar absorption lines, including higher order Balmer lines, seen in the composites suggest that young or intermediate-age stars make a significant contribution to the light of the host galaxies. Most of the spectrum is populated by blended emission lines, especially in the range 1500–3500 A, which can make the estimation of quasar continua highly uncertain unless large ranges in wavelength are observed. An electronic table of the median quasar template is available.

Cell-free translation reconstituted with purified components

Abstract: We have developed a protein-synthesizing system reconstituted from recombinant tagged protein factors purified to homogeneity. The system was able to produce protein at a rate of about 160 μg/ml/h in a batch mode without the need for any supplementary apparatus. The protein products were easily purified within 1 h using affinity chromatography to remove the tagged protein factors. Moreover, omission of a release factor allowed efficient incorporation of an unnatural amino acid using suppressor transfer RNA (tRNA).

Color Separation of Galaxy Types in the Sloan Digital Sky Survey Imaging Data

Abstract: We study the optical colors of 147,920 galaxies brighter than g* = 21, observed in five bands by the Sloan Digital Sky Survey (SDSS) over ~100 deg2 of high Galactic latitude sky along the celestial equator. The distribution of galaxies in the g*-r* versus u*-g* color-color diagram is strongly bimodal, with an optimal color separator of u*-r* = 2.22. We use visual morphology and spectral classification of subsamples of 287 and 500 galaxies, respectively, to show that the two peaks correspond roughly to early- (E, S0, and Sa) and late-type (Sb, Sc, and Irr) galaxies, as expected from their different stellar populations. We also find that the colors of galaxies are correlated with their radial profiles, as measured by the concentration index and by the likelihoods of exponential and de Vaucouleurs' profile fits. While it is well known that late-type galaxies are bluer than early-type galaxies, this is the first detection of a local minimum in their color distribution. In all SDSS bands, the counts versus apparent magnitude relations for the two color types are significantly different and demonstrate that the fraction of blue galaxies increases toward the faint end.

IRF family of transcription factors as regulators of host defense

Abstract: Interferon regulatory factors (IRFs) constitute a family of transcription factors that commonly possess a novel helix-turn-helix DNA-binding motif. Following the initial identification of two structurally related members, IRF-1 and IRF-2, seven additional members have now been reported. In addition, virally encoded IRFs, which may interfere with cellular IRFs, have also been identified. Thus far, intensive functional analyses have been done on IRF-1, revealing a remarkable functional diversity of this transcription factor in the regulation of cellular response in host defense. Indeed, IRF-1 selectively modulates different sets of genes, depending on the cell type and/or the nature of cellular stimuli, in order to evoke appropriate responses in each. More recently, much attention has also been focused on other IRF family members. Their functional roles, through interactions with their own or other members of the family of transcription factors, are becoming clearer in the regulation of host defense, such as innate and adaptive immune responses and oncogenesis.

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Abstract: Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.

A Formulation of a Phase-Independent Wave-Activity Flux for Stationary and Migratory Quasigeostrophic Eddies on a Zonally Varying Basic Flow

Abstract: A new formulation of an approximate conservation relation of wave-activity pseudomomentum is derived, which is applicable for either stationary or migratory quasigeostrophic (QG) eddies on a zonally varying basic flow. The authors utilize a combination of a quantity A that is proportional to wave enstrophy and another quantity E that is proportional to wave energy. Both A and E are approximately related to the wave-activity pseudomomentum. It is shown for QG eddies on a slowly varying, unforced nonzonal flow that a particular linear combination of A and E, namely, M ≡ (A + E)/2, is independent of the wave phase, even if unaveraged, in the limit of a small-amplitude plane wave. In the same limit, a flux of M is also free from an oscillatory component on a scale of one-half wavelength even without any averaging. It is shown that M is conserved under steady, unforced, and nondissipative conditions and the flux of M is parallel to the local three-dimensional group velocity in the WKB limit. The autho...

Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses

Abstract: In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.

Complete Genome Sequence of Enterohemorrhagic Eschelichia coli O157:H7 and Genomic Comparison with a Laboratory Strain K-12

Abstract: Escherichia coli O157:H7 is a major food-borne infectious pathogen that causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Here we report the complete chromosome sequence of an O157:H7 strain isolated from the Sakai outbreak, and the results of genomic comparison with a benign laboratory strain, K-12 MG1655. The chromosome is 5.5 Mb in size, 859 Kb larger than that of K-12. We identified a 4.1-Mb sequence highly conserved between the two strains, which may represent the fundamental backbone of the E. coli chromosome. The remaining 1.4-Mb sequence comprises of O157:H7-specific sequences, most of which are horizontally transferred foreign DNAs. The predominant roles of bacteriophages in the emergence of O157:H7 is evident by the presence of 24 prophages and prophage-like elements that occupy more than half of the O157:H7-specific sequences. The O157:H7 chromosome encodes 1632 proteins and 20 tRNAs that are not present in K-12. Among these, at least 131 proteins are assumed to have virulence-related functions. Genome-wide codon usage analysis suggested that the O157:H7-specific tRNAs are involved in the efficient expression of the strain-specific genes. A complete set of the genes specific to O157:H7 presented here sheds new insight into the pathogenicity and the physiology of O157:H7, and will open a way to fully understand the molecular mechanisms underlying the O157:H7 infection.

Featherweight Java: a minimal core calculus for Java and GJ

Abstract: Several recent studies have introduced lightweight versions of Java: reduced languages in which complex features like threads and reflection are dropped to enable rigorous arguments about key properties such as type safety. We carry this process a step further, omitting almost all features of the full language (including interfaces and even assignment) to obtain a small calculus, Featherweight Java, for which rigorous proofs are not only possible but easy. Featherweight Java bears a similar relation to Java as the lambda-calculus does to languages such as ML and Haskell. It offers a similar computational "feel," providing classes, methods, fields, inheritance, and dynamic typecasts with a semantics closely following Java's. A proof of type safety for Featherweight Java thus illustrates many of the interesting features of a safety proof for the full language, while remaining pleasingly compact. The minimal syntax, typing rules, and operational semantics of Featherweight Java make it a handy tool for studying the consequences of extensions and variations. As an illustration of its utility in this regard, we extend Featherweight Java with generic classes in the style of GJ (Bracha, Odersky, Stoutamire, and Wadler) and give a detailed proof of type safety. The extended system formalizes for the first time some of the key features of GJ.

Spectroscopic Target Selection for the Sloan Digital Sky Survey: The Luminous Red Galaxy Sample

Abstract: We describe the target selection and resulting properties of a spectroscopic sample of luminous red galaxies (LRGs) from the imaging data of the Sloan Digital Sky Survey (SDSS). These galaxies are selected on the basis of color and magnitude to yield a sample of luminous intrinsically red galaxies that extends fainter and farther than the main flux-limited portion of the SDSS galaxy spectroscopic sample. The sample is designed to impose a passively evolving luminosity and rest-frame color cut to a redshift of 0.38. Additional, yet more luminous red galaxies are included to a redshift of ~0.5. Approximately 12 of these galaxies per square degree are targeted for spectroscopy, so the sample will number over 100,000 with the full survey. SDSS commissioning data indicate that the algorithm efficiently selects luminous (M^+_g ≈ -21.4) red galaxies, that the spectroscopic success rate is very high, and that the resulting set of galaxies is approximately volume limited out to z = 0.38. When the SDSS is complete, the LRG spectroscopic sample will fill over 1 h^(-3) Gpc^3 with an approximately homogeneous population of galaxies and will therefore be well suited to studies of large-scale structure and clusters out to z = 0.5.

Evidence for ubiquitous strong electron-phonon coupling in high-temperature superconductors.

Abstract: Coupling between electrons and phonons (lattice vibrations) drives the formation of the electron pairs responsible for conventional superconductivity. The lack of direct evidence for electron-phonon coupling in the electron dynamics of the high-transition-temperature superconductors has driven an intensive search for an alternative mechanism. A coupling of an electron with a phonon would result in an abrupt change of its velocity and scattering rate near the phonon energy. Here we use angle-resolved photoemission spectroscopy to probe electron dynamics-velocity and scattering rate-for three different families of copper oxide superconductors. We see in all of these materials an abrupt change of electron velocity at 50-80 meV, which we cannot explain by any known process other than to invoke coupling with the phonons associated with the movement of the oxygen atoms. This suggests that electron-phonon coupling strongly influences the electron dynamics in the high-temperature superconductors, and must therefore be included in any microscopic theory of superconductivity.

Few-electron quantum dots

Abstract: We review some electron transport experiments on few-electron, vertical quantum dot devices. The measurement of current versus source–drain voltage and gate voltage is used as a spectroscopic tool to investigate the energy characteristics of interacting electrons confined to a small region in a semiconducting material. Three energy scales are distinguished: the single-particle states, which are discrete due to the confinement involved; the direct Coulomb interaction between electron charges on the dot; and the exchange interaction between electrons with parallel spins. To disentangle these energies, a magnetic field is used to reorganize the occupation of electrons over the single-particle states and to induce changes in the spin states. We discuss the interactions between small numbers of electrons (between 1 and 20) using the simplest possible models. Nevertheless, these models consistently describe a large set of experiments. Some of the observations resemble similar phenomena in atomic physics, such as shell structure and periodic table characteristics, Hund’s rule, and spin singlet and triplet states. The experimental control, however, is much larger than for atoms: with one device all the artificial elements can be studied by adding electrons to the quantum dot when changing the gate voltage.

Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene

Abstract: The serine/threonine kinase Akt has been implicated in the control of cell survival and metabolism. Here we report the disruption of the most ubiquitously expressed member of the akt family of genes, akt1, in the mouse. Akt1−/− mice are viable but smaller when compared to wild-type littermates. In addition, the life span of Akt1−/− mice, upon exposure to genotoxic stress, is shorter. However, Akt1−/− mice do not display a diabetic phenotype. Increased spontaneous apoptosis in testes, and attenuation of spermatogenesis is observed in Akt1−/− male mice. Increased spontaneous apoptosis is also observed in the thymi of Akt1−/− mice, and Akt1−/− thymocytes are more sensitive to apoptosis induced by γ-irradiation and dexamethasone. Finally, Akt1−/− mouse embryo fibroblasts (MEFs) are more susceptible to apoptosis induced by TNF, anti-Fas, UV irradiation, and serum withdrawal.

Selective Preparation of Monoclinic and Tetragonal BiVO4 with Scheelite Structure and Their Photocatalytic Properties

Abstract: BiVO4 powder with scheelite structure was obtained by hydrolyzing a nitric acid solution of Bi(NO3)3 and Na3VO4 with bases (Na2CO3 and NaHCO3) at room temperature. Tetragonal BiVO4 of a high-temperature form was obtained after 4.5 h of preparation time while monoclinic BiVO4 was done after 46 h. Although the structure and the band gap of tetragonal BiVO4 with scheelite structure were similar to those of monoclinic BiVO4, the photocatalytic activity of the tetragonal BiVO4 for O2 evolution from an aqueous AgNO3 solution under visible light irradiation was negligible. In contrast, the monoclinic BiVO4 showed high photocatalytic activity. Distortion of a Bi−O polyhedron by a 6s2 lone pair of Bi3+ plays an important role for high photocatalytic activity of the monoclinic BiVO4 under visible light irradiation.

A Survey of z > 5.8 quasars in the Sloan Digital Sky Survey I: Discovery of three new quasars and the spatial density of luminous quasars at z ~ 6

Abstract: We present the results from a survey of i-dropout objects selected from ~1550 deg2 of multicolor imaging data from the Sloan Digital Sky Survey to search for luminous quasars at z 5.8. Objects with i*-z* > 2.2 and z* 0.90. The ARC 3.5 m spectrum of SDSSp J103027.10+052455.0 shows that over a range of ~300 A immediately blueward of the Lyα emission, the average transmitted flux is only 0.003 ± 0.020 times that of the continuum level, consistent with zero flux over a ~300 A range of the Lyα forest region and suggesting a tentative detection of the complete Gunn-Peterson trough. The existence of strong metal lines in the quasar spectra suggests early metal enrichment in the quasar environment. The three new objects, together with the previously published z = 5.8 quasar SDSSp J104433.04-012502.2, form a complete color-selected flux-limited sample at z 5.8. We estimate the selection function of this sample, taking into account the estimated variations in the quasar spectral energy distribution, as well as observational photometric errors. We find that at z = 6, the comoving density of luminous quasars at M1450 < -26.8 (H0 = 50 km s-1 Mpc-1, Ω = 1) is 1.1 × 10-9 Mpc-3. This is a factor of ~2 lower than that at z ~ 5 and is consistent with an extrapolation of the observed quasar evolution at z < 5. Using the current sample, we discuss the constraint on the shape of the quasar luminosity function and the implications for the contribution of quasars to the ionizing background at z ~ 6. The luminous quasars discussed in the paper have central black hole masses of several times 109 M⊙ by the Eddington argument, with likely dark halo masses on the order of 1013 M⊙. Their observed space density provides a sensitive test of models of quasar and galaxy formation at high redshift.

Impact of the Indian Ocean dipole on the relationship between the Indian monsoon rainfall and ENSO

Abstract: The influence of the recently discovered Indian Ocean Dipole (IOD) on the interannual variability of the Indian summer monsoon rainfall (ISMR) has been investigated for the period 1958-1997. The IOD and the El Nino/Southern Oscillation (ENSO) have complementarily affected the ISMR during the last four decades. Whenever the ENSO-ISMR correlation is low (high), the IOD-ISMR correlation is high (low). The IOD plays an important role as a modulator of the Indian monsoon rainfall, and influences the correlation between the ISMR and ENSO. We have discovered that the ENSO-induced anomalous circulation over the Indian region is either countered or supported by the IOD-induced anomalous meridional circulation cell, depending upon the phase and amplitude of the two major tropical phenomena in the Indo-Pacific sector.

Evidence for reionization at z ∼ 6: Detection of a gunn-peterson trough in a z = 6.28 quasar

Abstract: We present moderate-resolution Keck spectroscopy of quasars at z = 5.82, 5.99, and 6.28, discovered by the Sloan Digital Sky Survey (SDSS). We find that the Ly? absorption in the spectra of these quasars evolves strongly with redshift. To z ~ 5.7, the Ly? absorption evolves as expected from an extrapolation from lower redshifts. However, in the highest-redshift object, SDSSp J103027.10+052455.0 (z = 6.28), the average transmitted flux is 0.0038 ? 0.0026 times that of the continuum level over 8450 ? 20, on the optical depth to Ly? absorption at z = 6. This is a clear detection of a complete Gunn-Peterson trough, caused by neutral hydrogen in the intergalactic medium. Even a small neutral hydrogen fraction in the intergalactic medium would result in an undetectable flux in the Ly? forest region. Therefore, the existence of the Gunn-Peterson trough by itself does not indicate that the quasar is observed prior to the reionization epoch. However, the fast evolution of the mean absorption in these high-redshift quasars suggests that the mean ionizing background along the line of sight to this quasar has declined significantly from z ~ 5 to 6, and the universe is approaching the reionization epoch at z ~ 6.

Solar 8B and hep Neutrino Measurements from 1258 Days of Super-Kamiokande Data

Abstract: Solar neutrino measurements from 1258days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0{endash}20.0MeV. The measured solar neutrino flux is 2.32{+-}0.03(stat){sup +0.08}{sub {minus}0.07}(syst){times}10{sup 6} cm{sup {minus}2}s{sup {minus}1} , which is 45.1{+-}0.5(stat ){sup +1.6}{sub {minus}1.4}(syst) % of that predicted by the BP2000 SSM. The day vs night flux asymmetry ({Phi}{sub n}{minus}{Phi}{sub d})/ {Phi}{sub average} is 0.033{+-}0.022(stat){sup +0.013}{sub {minus}0.012}(syst) . The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L.upper limit of 40{times}10{sup 3} cm{sup {minus}2}s{sup {minus}1} , which is 4.3times the BP2000 SSM prediction.

Suppression of hadrons with large transverse momentum in central Au + Au collisions at √sNN = 130 GeV

Abstract: Transverse momentum spectra for charged hadrons and for neutral pions in the range 1 Gev/c < P-T < 5 GeV/c have been measured by the PHENIX experiment at RHIC in Au + Au collisions at rootS(NN) = 130 GeV. At high p(T) the spectra from peripheral nuclear collisions are consistent with scaling the spectra from p + p collisions by the average number of binary nucleon-nucleon collisions. The spectra from central collisions are significantly suppressed when compared to the binary-scaled p + p expectation, and also when compared to similarly binary-scaled peripheral collisions, indicating a novel nuclear-medium effect in central nuclear collisions at RHIC energies.

Genome sequence of an industrial microorganism Streptomyces avermitilis: Deducing the ability of producing secondary metabolites

Abstract: Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest in this genus Streptomyces is the diversity of its production of secondary metabolites as an industrial microorganism. A major factor in its prominence as a producer of the variety of secondary metabolites is its possession of several metabolic pathways for biosynthesis. Here we report sequence analysis of S. avermitilis, covering 99% of its genome. At least 8.7 million base pairs exist in the linear chromosome; this is the largest bacterial genome sequence, and it provides insights into the intrinsic diversity of the production of the secondary metabolites of Streptomyces. Twenty-five kinds of secondary metabolite gene clusters were found in the genome of S. avermitilis. Four of them are concerned with the biosyntheses of melanin pigments, in which two clusters encode tyrosinase and its cofactor, another two encode an ochronotic pigment derived from homogentiginic acid, and another polyketide-derived melanin. The gene clusters for carotenoid and siderophore biosyntheses are composed of seven and five genes, respectively. There are eight kinds of gene clusters for type-I polyketide compound biosyntheses, and two clusters are involved in the biosyntheses of type-II polyketide-derived compounds. Furthermore, a polyketide synthase that resembles phloroglucinol synthase was detected. Eight clusters are involved in the biosyntheses of peptide compounds that are synthesized by nonribosomal peptide synthetases. These secondary metabolite clusters are widely located in the genome but half of them are near both ends of the genome. The total length of these clusters occupies about 6.4% of the genome.

Rotation Curves of Spiral Galaxies

Abstract: ▪ Abstract Rotation curves of spiral galaxies are the major tool for determining the distribution of mass in spiral galaxies. They provide fundamental information for understanding the dynamics, ev...