Showing papers by "Osaka University published in 2001"
TL;DR: Evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.
Abstract: Recognition of pathogens is mediated by a set of germline-encoded receptors that are referred to as pattern-recognition receptors (PRRs). These receptors recognize conserved molecular patterns (pathogen-associated molecular patterns), which are shared by large groups of microorganisms. Toll-like receptors (TLRs) function as the PRRs in mammals and play an essential role in the recognition of microbial components. The TLRs may also recognize endogenous ligands induced during the inflammatory response. Similar cytoplasmic domains allow TLRs to use the same signaling molecules used by the interleukin 1 receptors (IL-1Rs): these include MyD88, IL-1R--associated protein kinase and tumor necrosis factor receptor--activated factor 6. However, evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.
4,686 citations
TL;DR: It is reported that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-κB and stimulates tumour necrosis factor-α production, and the data suggest thatTLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flageLLated bacterial pathogens.
Abstract: The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, but not on the host. Toll-like receptors (TLRs) recognize PAMPs and mediate the production of cytokines necessary for the development of effective immunity. Flagellin, a principal component of bacterial flagella, is a virulence factor that is recognized by the innate immune system in organisms as diverse as flies, plants and mammals. Here we report that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor-alpha production. TLR5-stimulating activity was purified from Listeria monocytogenes culture supernatants and identified as flagellin by tandem mass spectrometry. Expression of L. monocytogenes flagellin in non-flagellated Escherichia coli conferred on the bacterium the ability to activate TLR5, whereas deletion of the flagellin genes from Salmonella typhimurium abrogated TLR5-stimulating activity. All known TLRs signal through the adaptor protein MyD88. Mice challenged with bacterial flagellin rapidly produced systemic interleukin-6, whereas MyD88-null mice did not respond to flagellin. Our data suggest that TLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flagellated bacterial pathogens.
3,575 citations
TL;DR: It is confirmed that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to thedegree of insulin resistance and hyperinsulinemia than to the level of adiposity and glucose intolerance.
Abstract: Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.
3,529 citations
TL;DR: Micromachines can be created with higher resolution using two-photon absorption, and the results can be higher resolution than previously reported using single photon absorption techniques.
Abstract: Micromachines can be created with higher resolution using two-photon absorption.
2,583 citations
TL;DR: In this review, functions of small G proteins and their modes of activation and action are described.
Abstract: Small GTP-binding proteins (G proteins) exist in eukaryotes from yeast to human and constitute a superfamily consisting of more than 100 members. This superfamily is structurally classified into at least five families: the Ras, Rho, Rab, Sar1/Arf, and Ran families. They regulate a wide variety of cell functions as biological timers (biotimers) that initiate and terminate specific cell functions and determine the periods of time for the continuation of the specific cell functions. They furthermore play key roles in not only temporal but also spatial determination of specific cell functions. The Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. Many upstream regulators and downstream effectors of small G proteins have been isolated, and their modes of activation and action have gradually been elucidated. Cascades and cross-talks of small G proteins have also been clarified. In this review, functions of small G proteins and their modes of activation and action are described.
2,520 citations
TL;DR: Thiazolidinediones (TZDs) might prevent atherosclerotic vascular disease in insulin-resistant patients by inducing the production of adiponectin through direct effect on its promoter and antagonizing the effect of TNF-alpha on the adiponECTin promoter.
Abstract: Insulin resistance and its dreaded consequence, type 2 diabetes, are major causes of atherosclerosis. Adiponectin is an adipose-specific plasma protein that possesses anti-atherogenic properties, such as the suppression of adhesion molecule expression in vascular endothelial cells and cytokine production from macrophages. Plasma adiponectin concentrations are decreased in obese and type 2 diabetic subjects with insulin resistance. A regimen that normalizes or increases the plasma adiponectin might prevent atherosclerosis in patients with insulin resistance. In this study, we demonstrate the inducing effects of thiazolidinediones (TZDs), which are synthetic PPARγ ligands, on the expression and secretion of adiponectin in humans and rodents in vivo and in vitro. The administration of TZDs significantly increased the plasma adiponectin concentrations in insulin resistant humans and rodents without affecting their body weight. Adiponectin mRNA expression was normalized or increased by TZDs in the adipose tissues of obese mice. In cultured 3T3-L1 adipocytes, TZD derivatives enhanced the mRNA expression and secretion of adiponectin in a dose- and time-dependent manner. Furthermore, these effects were mediated through the activation of the promoter by the TZDs. On the other hand, TNF-α, which is produced more in an insulin-resistant condition, dose-dependently reduced the expression of adiponectin in adipocytes by suppressing its promoter activity. TZDs restored this inhibitory effect by TNF-α. TZDs might prevent atherosclerotic vascular disease in insulin-resistant patients by inducing the production of adiponectin through direct effect on its promoter and antagonizing the effect of TNF-α on the adiponectin promoter.
1,696 citations
TL;DR: It is shown that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses, suggesting that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.
Abstract: Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-κB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses. These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.
1,416 citations
TL;DR: Results show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears to discriminate between the N-terminal lipoylated structures of MALp-2 and lipopeptides derived from other bacteria.
Abstract: Bacterial lipoproteins (BLP) trigger immune responses via Toll-like receptor 2 (TLR2) and their immunostimulatory properties are attributed to the presence of a lipoylated N-terminus. Most BLP are triacylated at the N-terminus cysteine residue, but mycoplasmal macrophage-activating lipopeptide-2 kD (MALP-2) is only diacylated. Here we show that TLR6-deficient (TLR6 –/– ) cells are unresponsive to MALP-2 but retain their normal responses to lipopeptides of other bacterial origins. Reconstitution experiments in TLR2 –/– TLR6 –/– embryonic fibroblasts reveal that coexpression of TLR2 and TLR6 is absolutely required for MALP-2 responsiveness. Taken together, these results show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears to discriminate between the N-terminal lipoylated structures of MALP-2 and lipopeptides derived from other bacteria.
1,298 citations
TL;DR: The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adip onectin may act as a modulator for macrophages- to-foams cell transformation.
Abstract: Background—Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. Methods and Results—Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class...
1,270 citations
TL;DR: The complete chromosome sequence of an O157:H7 strain isolated from the Sakai outbreak is reported, and the results of genomic comparison with a benign laboratory strain, K-12 MG1655, are identified, which may represent the fundamental backbone of the E. coli chromosome.
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.
1,265 citations
TL;DR: Body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin, despite the reduction of the only tissue of its own synthesis, suggesting that the expression of adip onectin is under feedback inhibition in obesity.
Abstract: Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as atherosclerosis, against which it may confer protection. In this study, we observed the changes of plasma adiponectin levels with body weight reduction among 22 obese patients who received gastric partition surgery. A 46% increase of mean plasma adiponectin level was accompanied by a 21% reduction in mean body mass index. The change in plasma adiponectin levels was significantly correlated with the changes in body mass index (r = -0.5, P = 0.01), waist (r = -0.4, P = 0.04) and hip (r = -0.6, P = 0.0007) circumferences, and steady state plasma glucose levels (r = -0.5, P = 0.04). In multivariate linear regression models, the increase in adiponectin as a dependent variable was significantly related to the decrease in hip circumference (beta = -0.16, P = 0.028), after adjusting body mass index and waist circumference. The change in steady state plasma glucose levels as a dependent variable was related to the increase of adiponectin with a marginal significance (beta = -0.92, P = 0.053), after adjusting body mass index and waist and hip circumferences. In conclusion, body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin. In addition, the increase in plasma adiponectin despite the reduction of the only tissue of its own synthesis suggests that the expression of adiponectin is under feedback inhibition in obesity.
TL;DR: An intense proton beam to achieve fast ignition is proposed, produced by direct laser acceleration and focused onto the pellet from the rear side of an irradiated target and can be integrated into a hohlraum for indirect drive ICF.
Abstract: The concept of fast ignition with inertial confinement fusion (ICF) is a way to reduce the energy required for ignition and burn and to maximize the gain produced by a single implosion. Based on recent experimental findings at the PETAWATT laser at Lawrence Livermore National Laboratory, an intense proton beam to achieve fast ignition is proposed. It is produced by direct laser acceleration and focused onto the pellet from the rear side of an irradiated target and can be integrated into a hohlraum for indirect drive ICF.
TL;DR: Tie2-Cre transgenic mice are a new genetic tool for the analyses of endothelial cell-lineage and endothelialcell-specific gene targeting and lacZ staining in Tie2- Cre;CAG-CAT-Z embryos is consistent with endocardial-mesenchymal transformation in the atrioventricular canal and outflow tract regions.
TL;DR: Reduction in circulating adiponectin may be related to the development of insulin resistance in rhesus monkeys, which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes.
Abstract: Adiponectin is an adipose-specific plasma protein whose plasma concentrations are decreased in obese subjects and type 2 diabetic patients. This protein possesses putative antiatherogenic and anti-inflammatory properties. In the current study, we have analyzed the relationship between adiponectin and insulin resistance in rhesus monkeys (Macaca mulatta), which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes. The plasma levels of adiponectin were decreased in obese and diabetic monkeys as in humans. Prospective longitudinal studies revealed that the plasma levels of adiponectin declined at an early phase of obesity and remained decreased after the development of type 2 diabetes. Hyperinsulinemic-euglycemic clamp studies revealed that the obese monkeys with lower plasma adiponectin showed significantly lower insulin-stimulated peripheral glucose uptake (M rate). The plasma levels of adiponectin were significantly correlated to M rate (r = 0.66, P < 0.001). Longitudinally, the plasma adiponectin decreased in parallel to the progression of insulin resistance. No clear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue. These results suggest that reduction in circulating adiponectin may be related to the development of insulin resistance.
TL;DR: The characterization of the MyD88-independent pathway via TLR4 is reported, a MyD 88-dependent pathway that is critical to the induction of inflammatory cytokines and a Myd88/TNFR-associated factor 6- independent pathway that regulates induction of IP-10.
Abstract: Bacterial lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor (TLR) 4, a member of the TLR family that participates in pathogen recognition. TLRs recruit a cytoplasmic protein, MyD88, upon pathogen recognition, mediating its function for immune responses. Two major pathways for LPS have been suggested in recent studies, which are referred to as MyD88-dependent and -independent pathways. We report in this study the characterization of the MyD88-independent pathway via TLR4. MyD88-deficient cells failed to produce inflammatory cytokines in response to LPS, whereas they responded to LPS by activating IFN-regulatory factor 3 as well as inducing the genes containing IFN-stimulated regulatory elements such as IP-10. In contrast, a lipopeptide that activates TLR2 had no ability to activate IFN-regulatory factor 3. The MyD88-independent pathway was also activated in cells lacking both MyD88 and TNFR-associated factor 6. Thus, TLR4 signaling is composed of at least two distinct pathways, a MyD88-dependent pathway that is critical to the induction of inflammatory cytokines and a MyD88/TNFR-associated factor 6-independent pathway that regulates induction of IP-10.
TL;DR: Cyclodextrins have been used as a cyclic component in the construction of supramolecular architectures, such as rotaxanes and catenanes.
Abstract: Cyclodextrins have been used as a cyclic component in the construction of supramolecular architectures. Recently they have been studied as a component in the construction of rotaxanes and catenanes. A cyclodextrin ring can translocate in some rotaxane and catenane structures. Therefore, much attention has been given to cyclodextrins as a component of molecular shuttles, motors, and machines. Attempts to design and synthesize molecular-level machines using cyclodextrins as a cyclic component are described.
TL;DR: In this paper, the authors showed that the anatase and rutile particles separately form their agglomerates and the average sizes of anatase particles are 85 and 25 nm, respectively.
TL;DR: Evidence is provided that cytokinins can activate CRE1 to initiate phosphorelay signalling, and this work identifies Arabidopsis cre1 (cytokinin response 1) mutants, which exhibited reduced responses to cytokinin responses.
Abstract: Cytokinins are a class of plant hormones that are central to the regulation of cell division and differentiation in plants. It has been proposed that they are detected by a two-component system, because overexpression of the histidine kinase gene CKI1 induces typical cytokinin responses and genes for a set of response regulators of two-component systems can be induced by cytokinins. Two-component systems use a histidine kinase as an environmental sensor and rely on a phosphorelay for signal transduction. They are common in microorganisms, and are also emerging as important signal detection routes in plants. Here we report the identification of a cytokinin receptor. We identified Arabidopsis cre1 (cytokinin response 1) mutants, which exhibited reduced responses to cytokinins. The mutated gene CRE1 encodes a histidine kinase. CRE1 expression conferred a cytokinin-dependent growth phenotype on a yeast mutant that lacked the endogenous histidine kinase SLN1 (ref. 10), providing direct evidence that CRE1 is a cytokinin receptor. We also provide evidence that cytokinins can activate CRE1 to initiate phosphorelay signalling.
University of Tokyo1, Boston University2, Massachusetts Institute of Technology3, Brookhaven National Laboratory4, University of California, Irvine5, California State University, Dominguez Hills6, George Mason University7, Gifu University8, Kobe University9, Kyoto University10, Louisiana State University11, University of Maryland, College Park12, University of Minnesota13, Stony Brook University14, University of Utah15, Niigata University16, Osaka University17, Seoul National University18, Shizuoka University19, Tohoku University20, Tokai University21, Tokyo Institute of Technology22, University of Warsaw23, University of Washington24
TL;DR: Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented and the recoil electron energy spectrum is consistent with no spectral distortion.
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.
Kyoto University1, University of Texas Southwestern Medical Center2, University of Strasbourg3, University of Southern California4, Osaka University5, University of Rochester6, National Institutes of Health7, Weizmann Institute of Science8, University of Texas Medical Branch9, Massachusetts Institute of Technology10, University of Kentucky11
TL;DR: The unrooted phylogenetic tree shown in Figure 1 shows the progression of tree-like structures formed over time in the presence of E.coli and shows the relationships between E. Coli and Tournaisian trees.
TL;DR: This work combines production of compressed matter in a laser-driven implosion with picosecond-fast heating by a laser pulse timed to coincide with the peak compression, allowing efficient compression and heating to be carried out simultaneously, providing a route to efficient fusion energy production.
Abstract: Modern high-power lasers can generate extreme states of matter that are relevant to astrophysics, equation-of-state studies and fusion energy research. Laser-driven implosions of spherical polymer shells have, for example, achieved an increase in density of 1,000 times relative to the solid state. These densities are large enough to enable controlled fusion, but to achieve energy gain a small volume of compressed fuel (known as the 'spark') must be heated to temperatures of about 108 K (corresponding to thermal energies in excess of 10 keV). In the conventional approach to controlled fusion, the spark is both produced and heated by accurately timed shock waves, but this process requires both precise implosion symmetry and a very large drive energy. In principle, these requirements can be significantly relaxed by performing the compression and fast heating separately; however, this 'fast ignitor' approach also suffers drawbacks, such as propagation losses and deflection of the ultra-intense laser pulse by the plasma surrounding the compressed fuel. Here we employ a new compression geometry that eliminates these problems; we combine production of compressed matter in a laser-driven implosion with picosecond-fast heating by a laser pulse timed to coincide with the peak compression. Our approach therefore permits efficient compression and heating to be carried out simultaneously, providing a route to efficient fusion energy production.
TL;DR: It is concluded that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.
Abstract: The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.
TL;DR: Results indicate that TRAF2 plays crucial roles not only in the signaling of the c-Jun N-terminal kinase pathway but also in activation of caspase-12 to transduce signals from IRE1s, providing a missing link in the ER stress-induced apoptosis-signaling pathway.
TL;DR: It may be possible to construct a laser interferometer gravitational wave antenna in space with h(rms) approximately 10(-27) at f approximately 0.1 Hz and the formula for phase shift due to accelerating motion might be applied for binary sources of LISA.
Abstract: It may be possible to construct a laser interferometer gravitational wave antenna in space with h(rms) approximately 10(-27) at f approximately 0.1 Hz in this century. Using this antenna, (1) typically 10(5) chirp signals of coalescing binary neutron stars per year may be detected with S/N approximately 10(4); (2) we can directly measure the acceleration of the universe by a 10 yr observation of binary neutron stars; and (3) the stochastic gravitational waves of Omega(GW) > or similar to 10(-20) predicted by the inflation may be detected by correlation analysis. Our formula for phase shift due to accelerating motion might be applied for binary sources of LISA.
TL;DR: Cortical activation patterns of human gait were visualized by measuring relative changes in local hemoglobin oxygenation using a recently developed near-infrared spectroscopic (NIRS) topography technique to provide new insight into cortical control of human locomotion.
National Institute of Genetics1, Nippon Telegraph and Telephone2, Osaka University3, Novartis4, University of Iowa5, Rockefeller University6, University of Milan7, Keio University8, University of Maryland, Baltimore9, University of California, Berkeley10, Tokai University11, J. Craig Venter Institute12, National Institutes of Health13, Stanford University14, Lawrence Berkeley National Laboratory15, University of Tokyo16, Harvard University17, University of Queensland18, University of Cambridge19, AREA Science Park20, University of Pennsylvania21, Roswell Park Cancer Institute22, National Cancer Research Institute23, University of Tsukuba24, University of California, San Diego25, Massachusetts Institute of Technology26, Wellcome Trust27
TL;DR: The first RIKEN clone collection is described, which is one of the largest described for any organism and analysis of these cDNAs extends known gene families and identifies new ones.
Abstract: The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.
TL;DR: It is suggested that interference in O-mannosyl glycosylation is a new pathomechanism for muscular dystrophy as well as neuronal migration disorder.
TL;DR: In this paper, phase diagrams of lead-free alloy systems have been intensively examined by using careful thermal and microstructural analysis combined with the thermodynamic calculation such as the CLAPHAD method.
Abstract: Lead-free soldering has emerged as one of the key technologies for assembling in environmental-conscious electronics. Among several candidate alloys, the Sn–Ag–Cu alloy family is believed to be the first choice with the combination of other alloys such as Sn–Zn–Bi, Sn–Cu and Sn–Bi–Ag. Phase diagrams of lead-free alloy systems have been intensively examined by using careful thermal and microstructural analysis combined with the thermodynamic calculation such as the CLAPHAD method. The Cu6Sn5/Cu3Sn layers are formed at most lead-free solder alloy/Cu interfaces, while Cu–Zn compound layers are formed in the Sn–Zn/Cu system. Growth kinetics of intermetallic layers both in solid-state and in soldering are also discussed. Creep and fatigue phenomena are also reviewed. In many aspects of lead-free soldering, much more work is required to establish a sound scientific basis to promote their applications.
TL;DR: This paper presents a combinatorial polynomial-time algorithm for minimizing submodular functions, answering an open question posed in 1981 by Grötschel, Lovász, and Schrijver.
Abstract: This paper presents a combinatorial polynomial-time algorithm for minimizing submodular functions, answering an open question posed in 1981 by Grotschel, Lovasz, and Schrijver. The algorithm employs a scaling scheme that uses a flow in the complete directed graph on the underlying set with each arc capacity equal to the scaled parameter. The resulting algorithm runs in time bounded by a polynomial in the size of the underlying set and the length of the largest absolute function value. The paper also presents a strongly polynomial version in which the number of steps is bounded by a polynomial in the size of the underlying set, independent of the function values.
TL;DR: It is found that leptin increases ROS generation in BAEC in a dose-dependent manner and that its effects are additive with those of glucose, which may play an important role in the progression of atherosclerosis in insulin-resistant obese diabetic patients.