Showing papers by "University of Tokyo published in 1999"

A Dipole Mode in the Tropical Indian Ocean

Abstract: For the tropical Pacific and Atlantic oceans, internal modes of variability that lead to climatic oscillations have been recognized1,2, but in the Indian Ocean region a similar ocean–atmosphere interaction causing interannual climate variability has not yet been found3. Here we report an analysis of observational data over the past 40 years, showing a dipole mode in the Indian Ocean: a pattern of internal variability with anomalously low sea surface temperatures off Sumatra and high sea surface temperatures in the western Indian Ocean, with accompanying wind and precipitation anomalies. The spatio-temporal links between sea surface temperatures and winds reveal a strong coupling through the precipitation field and ocean dynamics. This air–sea interaction process is unique and inherent in the Indian Ocean, and is shown to be independent of the El Nino/Southern Oscillation. The discovery of this dipole mode that accounts for about 12% of the sea surface temperature variability in the Indian Ocean—and, in its active years, also causes severe rainfall in eastern Africa and droughts in Indonesia—brightens the prospects for a long-term forecast of rainfall anomalies in the affected countries.

A Novel Aqueous Process for Preparation of Crystal Form-Controlled and Highly Crystalline BiVO4 Powder from Layered Vanadates at Room Temperature and Its Photocatalytic and Photophysical Properties

Abstract: BiVO4 photocatalysts for O2 evolution, which work under visible light irradiation, were prepared by an aqueous process. The BiVO4 photocatalysts were obtained by the reaction of layered potassium vanadate powder (KV3O8 and K3V5O14) with Bi(NO3)3 for 3 days in aqueous media at room temperature. Highly crystalline monoclinic and tetragonal BiVO4 were selectively synthesized by changing the ratio of vanadium to bismuth in the starting materials. X-ray diffraction and scanning electron microscopy measurements showed that the monoclinic BiVO4 was formed via a tetragonal BiVO4 intermediate. Tetragonal BiVO4 with a 2.9 eV band gap mainly possessed an ultraviolet absorption band while monoclinic BiVO4 with a 2.4 eV band gap had a characteristic visible light absorption band in addition to the UV band. The UV bands observed in the tetragonal and monoclinic BiVO4 were assigned to the band transition from O2p to V3d whereas the visible light absorption was due to the transition from a valence band formed by Bi6s or ...

Catalytic enantioselective addition to imines.

Abstract: Chiral nitrogen-containing compounds are widely distributed in nature and include many biologically important molecules (Chart 1). In these compounds, the nitrogen-containing units are known to play important roles for their bioactivities. For the synthesis of these chiral nitrogen-containing building blocks, use of imines as electrophiles is the most promising and convenient route.1 While many approaches using chiral imines or chiral nucleophiles have been reported,1 these diastereoselective reactions have some disadvantages. First, the procedures to introduce chiral auxiliaries to substrates and to remove them after the diastereoselective reactions are often tedious. Second, more than stoichiometric amounts of chiral sources are needed to obtain chiral compounds according to these reactions. On the other hand, catalytic enantioselective reactions provide the most efficient methods for the synthesis of chiral compounds,2 because large quantities of chiral compounds are expected to be prepared using small amounts of chiral sources. While much progress has been made recently in catalytic enantioselective reactions of aldehydes and ketones such as aldol,3 allylation,4 Diels-Alder,5 cyanation reactions,6 reduction,1b,2b etc., progress in catalytic enantioselective reactions of imines is rather slow. There are some difficulties in performing catalytic enantioselective reactions of imines. For example, in the cases of chiral Lewis acid promoted asymmetric Shū Kobayashi was born in 1959 in Tokyo, Japan. He studied chemistry at the University of Tokyo and received his Ph.D. in 1988 (Professor T. Mukaiyama). After spending 11 years at Science University of Tokyo (SUT), he moved to Graduate School of Pharmaceutical Sciences, University of Tokyo, in 1998. His research interests include development of new synthetic methods, development of novel catalysts (especially chiral catalysts), organic synthesis in water, solid-phase organic synthesis, total synthesis of biologically interesting compounds, and organometallic chemistry. He received the first Springer Award in Organometallic Chemistry in 1997.

Nucleosynthesis in Chandrasekhar Mass Models for Type Ia Supernovae and Constraints on Progenitor Systems and Burning-Front Propagation

Abstract: The major uncertainties involved in the Chandrasekhar mass models for Type Ia supernovae (SNe Ia) are related to the companion star of their accreting white dwarf progenitor (which determines the accretion rate and consequently the carbon ignition density) and the flame speed after the carbon ignition. We calculate explosive nucleosynthesis in relatively slow deflagrations with a variety of deflagration speeds and ignition densities to put new constraints on the above key quantities. The abundance of the Fe group, in particular of neutron-rich species like 48Ca,50Ti,54Cr,54,58Fe, and 58Ni, is highly sensitive to the electron captures taking place in the central layers. The yields obtained from such a slow central deflagration, and from a fast deflagration or delayed detonation in the outer layers, are combined and put to comparison with solar isotopic abundances. To avoid excessively large ratios of 54Cr/56Fe and 50Ti/56Fe, the central density of the average white dwarf progenitor at ignition should be as low as 2 ? 109 g cm-3. To avoid the overproduction of 58Ni and 54Fe, either the flame speed should not exceed a few percent of the sound speed in the central low Ye layers or the metallicity of the average progenitors has to be lower than solar. Such low central densities can be realized by a rapid accretion as fast as -->img1.gif 1 ? 10-7 M? yr-1. In order to reproduce the solar abundance of 48Ca, one also needs progenitor systems that undergo ignition at higher densities. Even the smallest laminar flame speeds after the low-density ignitions would not produce sufficient amount of this isotope. We also found that the total amount of 56Ni, the Si-Ca/Fe ratio, and the abundance of some elements like Mn and Cr (originating from incomplete Si burning), depend on the density of the deflagration-detonation transition in delayed detonations. Our nucleosynthesis results favor transition densities slightly below 2.2 ? 107 g cm-3.

Intestinal polyposis in mice with a dominant stable mutation of the β-catenin gene

Abstract: Ectopic expression of certain Wnt genes in mouse mammary tissue is tumorigenic, and mutations that stabilize beta-catenin are found in various human cancers including colorectal cancer. To determine the role of stabilized beta-catenin in intestinal tumorigenesis in mice, we constructed by embryonic stem (ES) cell-mediated homologous recombination, a mutant beta-catenin allele whose exon 3 was sandwiched by loxP sequences. When the germline heterozygotes were crossed with mice expressing Cre recombinase in the intestines, the serines and threonine encoded by exon 3 and to be phosphorylated by glycogen synthase kinase 3beta (GSK3beta) were deleted in the offspring intestines, which caused adenomatous intestinal polyps resembling those in Apc(Delta716) knockout mice. Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors.

Teddy: a sketching interface for 3D freeform design

Abstract: We present a sketching interface for quickly and easily designing freeform models such as stuffed animals and other rotund objects. The user draws several 2D freeform strokes interactively on the screen and the system automatically constructs plausible 3D polygonal surfaces. Our system supports several modeling operations, including the operation to construct a 3D polygonal surface from a 2D silhouette drawn by the user: it inflates the region surrounded by the silhouette making wide areas fat, and narrow areas thin. Teddy, our prototype system, is implemented as a Java™ program, and the mesh construction is done in real-time on a standard PC. Our informal user study showed that a first-time user typically masters the operations within 10 minutes, and can construct interesting 3D models within minutes.

The kinase TAK1 can activate the NIK-IκB as well as the MAP kinase cascade in the IL-1 signalling pathway

Abstract: Interleukin-1 (IL-1) is a proinflammatory cytokine that has several effects in the inflammation process When it binds to its cell-surface receptor, IL-1 initiates a signalling cascade that leads to activation of the transcription factor NF-kappaB and is relayed through the protein TRAF6 and a succession of kinase enzymes, including NF-kappaB-inducing kinase (NIK) and I kappaB kinases (IKKs) However, the molecular mechanism by which NIK is activated is not understood Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1 signalling Stimulation of TAK1 causes activation of NF-kappaB, which is blocked by dominant-negative mutants of NIK, and an inactive TAK1 mutant prevents activation of NF-kappaB that is mediated by IL-1 but not by NIK Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway

Fgf10 is essential for limb and lung formation

Abstract: The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis In particular, Fgf10 is predicted to function as a regulator of brain, lung and limb development on the basis of its spatiotemporal expression pattern in the developing embryo To define the role of Fgf10, we generated Fgf10-deficient mice Fgf10-/- mice died at birth due to the lack of lung development Trachea was formed, but subsequent pulmonary branching morphogenesis was disrupted In addition, mutant mice had complete truncation of the fore- and hindlimbs In Fgf10-/- embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected Analysis of the expression of marker genes in the mutant limb buds indicated that the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) did not form Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation

Interferon Therapy Reduces the Risk for Hepatocellular Carcinoma: National Surveillance Program of Cirrhotic and Noncirrhotic Patients with Chronic Hepatitis C in Japan

Abstract: Among patients with chronic hepatitis C, interferon therapy significantly reduced the risk for hepatocellular carcinoma, especially in persons who showed a virologic or biochemical response.

Reduced complexity iterative decoding of low-density parity check codes based on belief propagation

Abstract: Two simplified versions of the belief propagation algorithm for fast iterative decoding of low-density parity check codes on the additive white Gaussian noise channel are proposed. Both versions are implemented with real additions only, which greatly simplifies the decoding complexity of belief propagation in which products of probabilities have to be computed. Also, these two algorithms do not require any knowledge about the channel characteristics. Both algorithms yield a good performance-complexity trade-off and can be efficiently implemented in software as well as in hardware, with possibly quantized received values.

Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region

Abstract: The cellular target of leptomycin B (LMB), a nuclear export inhibitor, has been identified as CRM1 (exportin 1), an evolutionarily conserved receptor for the nuclear export signal of proteins. However, the mechanism by which LMB inhibits CRM1 still remains unclear. CRM1 in a Schizosaccharomyces pombe mutant showing extremely high resistance to LMB had a single amino acid replacement at Cys-529 with Ser. The mutant gene, named crm1-K1, conferred LMB resistance on wild-type S. pombe, and Crm1-K1 no longer bound biotinylated LMB. 1H NMR analysis showed that LMB bound N-acetyl-l-cysteine methyl ester through a Michael-type addition, consistent with the idea that LMB binds covalently via its α,β-unsaturated δ-lactone to the sulfhydryl group of Cys-529. When HeLa cells were cultured with biotinylated LMB, the only cellular protein bound covalently was CRM1. Inhibition by N-ethylmaleimide (NEM), an alkylating agent, of CRM1-mediated nuclear export probably was caused by covalent binding of the electrophilic structure in NEM to the sulfhydryl group of Cys-529, because the crm1-K1 mutant showed the normal rate for the export of Rev nuclear export signal-bearing proteins in the presence of not only LMB but also NEM. These results show that the single cysteine residue determines LMB sensitivity and is selectively alkylated by LMB, leading to CRM1 inactivation.

STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells

Abstract: Embryonic stem (ES) cells can be maintained in an undifferentiated state in the presence of leukemia inhibitory factor (LIF). LIF acts through a receptor complex composed of a low affinity LIF receptor (LIFRbeta) and gp130. We reported that the intracellular domain of gp130 plays an important role in self-renewal of ES cells. In the present study, we examined the signaling pathway through which gp130 contributes to the self-renewal of ES cells. Mutational analysis of the cytoplasmic domain of gp130 revealed that the tyrosine residue of gp130 responsible for STAT3 activation is necessary for self-renewal of ES cells, while that required for SHP2 and MAP kinase activation was dispensable. Next, we constructed a fusion protein composed of the entire coding region of STAT3 and the ligand binding domain of the estrogen receptor. This construction (STAT3ER) induced expression of junB (one of the targets of STAT3) in ES cells in the presence of the synthetic ligand 4-hydroxytamoxifen (4HT), thereby indicating that STAT3ER is a conditionally active form. ES cells transfected with STAT3ER cultured in the presence of 4HT maintained an undifferentiated state. Taken together, these results strongly suggest that STAT3 activation is required and sufficient to maintain the undifferentiated state of ES cells.

Thermodynamics of One-Dimensional Solvable Models

Abstract: Part I. Thermodynamics of Non-Interacting Systems and Ground States on Interacting Systems: 1. Free energy and correlation functions of XY models 2. Systems with delta-function potential 3. Isotropic Heisenberg model 4. XXZ model 5. XYZ and eight-vertex models 6. Hubbard model Part II. Finite Temperature Integral Equations for Un-Nested Systems: 7. Repulsive delta-function bosons 8. Thermodynamics of the XXX chain 9. Thermodynamics of the XXZ model 10. Thermodynamics of the XYZ model 11. Low-temperature thermodynamics Part III. Finite Temperature Integral Equations for Nested Systems: 12. S=1/2 fermions with repulsive potential in the continuum 13. S=1/2 fermions with an attractive potential 14. Thermodynamics of the Hubbard model Part IV. Quantum Transfer Matrix and Recent Developments: 15. Transfer matrix and correlation length 16. The spin 1/2 XXZ model in a magnetic field 17. The XYZ model with no magnetic field 18. Recent developments and related topics.

The Olfactory Bulb: Coding and Processing of Odor Molecule Information

Abstract: Olfactory sensory neurons detect a large variety of odor molecules and send information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. The axonal connection is precisely organized so that signals from 1000 different types of odorant receptors are sorted out in 1800 glomeruli in the mouse olfactory bulb. Individual glomerular modules presumably represent a single type of receptor and are thus tuned to specific molecular features of odorants. Local neuronal circuits in the bulb mediate lateral inhibition among glomerular modules to sharpen the tuning specificity of output neurons. They also mediate synchronized oscillatory discharges among specific combinations of output neurons and may contribute to the integration of signals from distinct odorant receptors in the olfactory cortex.

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI

Abstract: Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300.

Abstract: The cytokines LIF (leukemia inhibitory factor) and BMP2 (bone morphogenetic protein-2) signal through different receptors and transcription factors, namely STATs (signal transducers and activators of transcription) and Smads. LIF and BMP2 were found to act in synergy on primary fetal neural progenitor cells to induce astrocytes. The transcriptional coactivator p300 interacts physically with STAT3 at its amino terminus in a cytokine stimulation-independent manner, and with Smad1 at its carboxyl terminus in a cytokine stimulation-dependent manner. The formation of a complex between STAT3 and Smad1, bridged by p300, is involved in the cooperative signaling of LIF and BMP2 and the subsequent induction of astrocytes from neural progenitors.

Menstrual cycle alters face preference

Abstract: Women prefer slightly feminized male facial shapes1. Such faces (Fig. 1a) are given positive personality attributions1 that might correlate with actual behaviour2. In contrast, masculine features seem to signal immunological competence3. Heritable benefits can be realized only if conception follows copulation, so women might be more attentive to phenotypic markers indicating immunological competence during the follicular phase of the menstrual cycle when conception is most likely4,5. Consistent with this hypothesis is the observation that women's preference for the odour of men with low fluctuating asymmetry (a correlate of testosterone-facilitated trait size and developmental stability) increases with the probability of conception across the menstrual cycle5.Symmetrical men report more extra-pair copulation partners6, and extra-pair copulation rates peak in midcycle7. Here we show that female preference for secondary sexual traits in male face shapes varies with the probability of conception across the menstrual cycle.

Phase-field model for binary alloys.

Abstract: We present a phase-field model (PFM) for solidification in binary alloys, which is found from the phase-field model for a pure material by direct comparison of the variables for a pure material solidification and alloy solidification. The model appears to be equivalent with the Wheeler-Boettinger-McFadden (WBM) model [A.A. Wheeler, W. J. Boettinger, and G. B. McFadden, Phys. Rev. A 45, 7424 (1992)], but has a different definition of the free energy density for interfacial region. An extra potential originated from the free energy density definition in the WBM model disappears in this model. At a dilute solution limit, the model is reduced to the Tiaden et al. model [Physica D 115, 73 (1998)] for a binary alloy. A relationship between the phase-field mobility and the interface kinetics coefficient is derived at a thin-interface limit condition under an assumption of negligible diffusivity in the solid phase. For a dilute alloy, a steady-state solution of the concentration profile across the diffuse interface is obtained as a function of the interface velocity and the resultant partition coefficient is compared with the previous solute trapping model. For one dimensional steady-state solidification, where the classical sharp-interface model is exactly soluble, we perform numerical simulations of the phase-field model: At low interface velocity, the simulated results from the thin-interface PFM are in excellent agreement with the exact solutions. As the partition coefficient becomes close to unit at high interface velocities, whereas, the sharp-interface PFM yields the correct answer.

Remote Sensing of Tropospheric Aerosols from Space: Past, Present, and Future.

Abstract: Aerosol particles originate from man-made sources such as urban/industrial activities,rurning associated with land use processes, wind-blown dust, and natural sources. Their interaction with sunlight and their effect on cloud microphysics forms a major uncertainty in predicting climate change. Furthermore, the lifetime of only a few days causes high spatial variability in aerosol optical and radiative properties that requires global observations from space. Remote sensing of aerosol properties from space is reviewed both for present and planned national and international satellite sensors. Techniques that are being used to enhance our ability to characterize the global distribution of aerosol properties include well-calibrated multispectral radiometers, multispectral polarimeters, and multi-angle spectroradiometers. Though most of these sensor systems rely primarily on visible to mid-infrared spectral channels, the availability of of thermal channels to aid in cloud screening is an important additional piece of information that is not always incorporated into the sensor design. In this paper we describe the various satellite sensor systems being developed by Europe, Japan, and the U.S., and highlight the advantages and disadvantages of each of these systems for aerosol applications. An important underlying theme is that the remote sensing of aerosol properties, especially aerosol size distribution and single scattering albedo, is exceedingly difficult. As a consequence, no one sensor system is capable of providing totally unambiguous information, and hence a careful intercomparison of derived products from different sensors, together with a comprehensive network of ground-based sun-photometer and sky radiometer systems, are required to advance our quantitative understanding of global aerosol characteristics.

Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53

Abstract: We have demonstrated previously that the oncoprotein Mdm2 has a ubiquitin ligase activity for the tumor suppressor p53 protein. In the present study, we characterize this ubiquitin ligase activity of Mdm2. We first demonstrate the ubiquitination of several p53 point mutants and deletion mutants by Mdm2. The point mutants, which cannot bind to Mdm2, are not ubiquitinated by Mdm2. The ubiquitination of the C-terminal deletion mutants, which contain so-called Mdm2-binding sites, is markedly decreased, compared with that of wild-type p53. The binding of Mdm2 to p53 is essential for ubiquitination, but p53's tertiary structure and/or C-terminal region may also be important for this reaction. DNA-dependent protein kinase is known to phosphorylate p53 on Mdm2-binding sites, where DNA damage induces phosphorylation, and p53 phosphorylated by this kinase is not a good substrate for Mdm2. This suggests that DNA damage-induced phosphorylation stabilizes p53 by inhibiting its ubiquitination by Mdm2. We further investigated whether the tumor suppressor p19(ARF) affects the ubiquitin ligase activity of Mdm2 for p53. The activity of p19(ARF)-bound Mdm2 was found to be lower than that of free Mdm2, suggesting that p19(ARF) promotes the stabilization of p53 by inactivating Mdm2.

Global and fine information coded by single neurons in the temporal visual cortex.

Abstract: When we see a person's face, we can easily recognize their species, individual identity and emotional state. How does the brain represent such complex information? A substantial number of neurons in the macaque temporal cortex respond to faces1,2,3,4,5,6,7,8,9,10,11,12. However, the neuronal mechanisms underlying the processing ofcomplex information are not yet clear. Here we recorded the activity of single neurons in the temporal cortex of macaque monkeys while presenting visual stimuli consisting of geometric shapes, and monkey and human faces with various expressions. Information theory was used to investigate how well the neuronal responses could categorize the stimuli. We found that single neurons conveyed two different scales of facial information intheir firing patterns, starting at different latencies. Global information, categorizing stimuli as monkey faces, human faces or shapes, was conveyed in the earliest part of the responses. Fineinformation about identity or expression was conveyed later,beginning on average 51 ms after global information. We speculate that global information could be used as a ‘header’ to prepare destination areas for receiving more detailed information.

Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling.

Abstract: Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling in vertebrates. The question remains unanswered, however, as to how these Gli proteins participate in the Shh signaling pathway. In this study, regulatory activities associated with the Gli2 protein were investigated in relation to the Shh signaling. Although Gli2 acts as a weak transcriptional activator, it is in fact a composite of positive and negative regulatory domains. In cultured cells, truncation of the activation domain in the C-terminal half results in a protein with repressor activity, while removal of the repression domain at the N terminus converts Gli2 into a strong activator. In transgenic mouse embryos, N-terminally truncated Gli2, unlike the full length protein, activates a Shh target gene, HNF3beta, in the dorsal neural tube, thus mimicking the effect of Shh signal. This suggests that unmasking of the strong activation potential of Gli2 through modulation of the N-terminal repression domain is one of the key mechanisms of the Shh signaling. A similar regulatory mechanism involving the N-terminal region was also found for Gli3, but not for Gli1. When the Shh signal derived from the notochord is received by the neural plate, the widely expressed Gli2 and Gli3 proteins are presumably converted to their active forms in the ventral cells, leading to activation of transcription of their target genes, including Gli1.

Tailored Porous Materials

Abstract: Tailoring of porous materials involves not only chemical synthetic techniques for tailoring microscopic properties such as pore size, pore shape, pore connectivity, and pore surface reactivity, but also materials processing techniques for tailoring the meso- and the macroscopic properties of bulk materials in the form of fibers, thin films, and monoliths. These issues are addressed in the context of five specific classes of porous materials: oxide molecular sieves, porous coordination solids, porous carbons, sol−gel-derived oxides, and porous heteropolyanion salts. Reviews of these specific areas are preceded by a presentation of background material and review of current theoretical approaches to adsorption phenomena. A concluding section outlines current research needs and opportunities.

Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors

Abstract: The 41-kDa and 43-kDa mitogen-activated protein (MAP) kinases play a pivotal role in the mitogenic signal transduction pathway and are essential components of the MAP kinase cascade, which includes MAP kinase kinase (MEK) and Raf-1. As aberrant activation of signal transducing molecules such as Ras and Raf-1 has been linked with cancer, we examined whether constitutive activation of the 41-/43-kDa MAP kinases is associated with the neoplastic phenotype of 138 tumor cell lines and 102 primary tumors derived from various human organs. Constitutive activation of the MAP kinases was observed in 50 tumor cell lines (36.2%) in a rather tissue-specific manner: cell lines derived from pancreas, colon, lung, ovary and kidney showed especially high frequencies with a high degree of MAP kinase activation, while those derived from brain, esophagus, stomach, liver and of hematopoietic origin showed low frequencies with a limited degree of MAP kinase activation. We also detected constitutive activation of the 41-/43-kDa MAP kinases in a relatively large number of primary human tumors derived from kidney, colon and lung tissues but not from liver tissue. Many tumor cells, in which point mutations of ras genes were detected, showed constitutive activation of MAP kinases, however, there were also many exceptions to this observation. In contrast, the activation of the 41-/43-kDa MAP kinases was accompanied by the activation of Raf-1 in the majority of tumor cells and was completely associated with the activation of MEK and p90rsk in all the tumor cells examined. These results suggest that the constitutive activation of 41-/43-kDa MAP kinases in tumor cells is not due to the disorder of MAP kinases themselves, but is due to the disorder of Raf-1, Ras, or some other signaling molecules upstream of Ras.