Kyoto University of Education

A nonlinear least squares program (MULTI) for microcomputers was developed. The program is written in BASIC programming language. Four algorithms, (1) Gauss-Newton method, (2) damping Gauss-Newton method, (3) modified Marquardt method and (4) simplex method, can be used for nonlinear curve fitting in MULTI. Up to five pharmacokinetic equations, which are voluntarily defined by the user, are simultaneously fitted to observed time courses. The executions of MULTI are demonstrated for time courses of ampicillin and oxacillin in man.

CONTEXT: In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. OBJECTIVE: To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. INTERVENTIONS: Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients). MAIN OUTCOME MEASURES: The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. RESULTS: The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. CONCLUSIONS: Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: C000000412.

It is assumed that people seek positive self-regard; that is, they are motivated to possess, enhance, and maintain positive self-views. The cross-cultural generalizability of such motivations was addressed by examining Japanese culture. Anthropological, sociological, and psychological analyses revealed that many elements of Japanese culture are incongruent with such motivations. Moreover, the empirical literature provides scant evidence for a need for positive self-regard among Japanese and indicates that a self-critical focus is more characteristic of Japanese. It is argued that the need for self-regard must be culturally variant because the constructions of self and regard themselves differ across cultures. The need for positive self-regard, as it is currently conceptualized, is not a universal, but rather is rooted in significant aspects of North American culture. Conventional interpretations of positive self-regard are too narrow to encompass the Japanese experience.

A collective constructionist theory of the self proposes that many psychological processes, including enhancement of the self (pervasive in the United States) and criticism and subsequent improvement of the self (widespread in Japan), result from and support the very ways in which social acts and situations are collectively defined and subjectively experienced in the respective cultural contexts. In support of the theory, 2 studies showed, first, that American situations are relatively conducive to self-enhancement and American people are relatively likely to engage in self-enhancement and, second, that Japanese situations are relatively conducive to self-criticism and Japanese people are relatively likely to engage in self-criticism. Implications are discussed for the collective construction of psychological processes implicated in the self and, more generally, for the mutual constitution of culture and the self.

Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 +/- 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, delta(CS-Ao)BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [delta(AIV-Ao)BNP] was comparable to delta(CS-Ao)BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than alpha-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of alpha-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.

BACKGROUND: B-type or brain natriuretic peptide (BNP) is a novel natriuretic peptide secreted from the heart that forms a peptide family with A-type or atrial natriuretic peptide (ANP), and its plasma level has been shown to be increased in patients with congestive heart failure. This study was designed to examine the sources and mechanisms of the secretion of BNP in comparison with those of ANP in control subjects and in patients with heart failure. METHODS AND RESULTS: We measured the plasma levels of BNP as well as ANP in 16 patients with dilated cardiomyopathy (11 men and 5 women; mean age, 59 years) and 18 control subjects (9 men and 9 women; mean age, 54 years) by sampling blood from the femoral vein, the aortic root, the anterior interventricular vein (AIV), and the coronary sinus using the newly developed immunoradiometric assay systems. In the control subjects, there was no significant difference in the plasma ANP level between the aortic root and the AIV (24.0 +/- 5.2 pg/mL versus 32.2 +/- 17.0 pg/mL), but there was a highly significant step-up of the level between the AIV and the coronary sinus (32.2 +/- 17.0 pg/mL versus 371.4 +/- 111.1 pg/mL, P < .001). In contrast, there was a significant step-up of the plasma BNP level between the aortic root and the AIV (8.6 +/- 6.4 pg/mL versus 19.0 +/- 11.5 pg/mL, P < .01) but not between the AIV and the coronary sinus (19.0 +/- 11.5 pg/mL versus 28.8 +/- 14.0 pg/mL). On the other hand, in patients with dilated cardiomyopathy, there was a significant step-up in the plasma ANP level between the aortic root and the AIV (280.6 +/- 183.7 pg/mL versus 612.3 +/- 431.6 pg/mL, P < .01) and between the AIV and the coronary sinus (612.3 +/- 431.6 pg/mL versus 1229.0 +/- 772.7 pg/mL, P < .01). There was a significant step-up in the plasma BNP level between the aortic root and the AIV (268.4 +/- 293.2 pg/mL versus 511.6 +/- 458.1 pg/mL, P < .01) but not between the AIV and the coronary sinus (511.6 +/- 458.1 pg/mL versus 529.7 +/- 455.3 pg/mL) in patients with dilated cardiomyopathy. The arteriovenous difference at the AIV of the plasma level of BNP had a significant positive correlation with left ventricular end-systolic volume index (r = 0.859, P < .001) and a significant negative correlation with left ventricular ejection fraction (r = -.735, P < .001). CONCLUSIONS: We conclude that (1) BNP is secreted mainly from the left ventricle in normal adult humans as well as in patients with left ventricular dysfunction, whereas ANP is secreted from atria in normal adult humans and also from the left ventricle in patients with left ventricular dysfunction; (2) secretion of BNP as well as ANP from the left ventricle increases in proportion to the severity of the left ventricular dysfunction, suggesting that the secretions of ANP and BNP from the left ventricle are regulated mainly by wall tension of the left ventricle; and (3) the peripheral plasma levels of ANP and BNP reflect the secretion rate of these hormones from the left ventricle and may be used as a marker of the degree of left ventricular dysfunction in patients with left ventricular dysfunction.

A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is m_{H}=125.09±0.21 (stat)±0.11 (syst) GeV.

Covalent modification of histone tails is crucial for transcriptional regulation, mitotic chromosomal condensation, and heterochromatin formation. Histone H3 lysine 9 (H3-K9) methylation catalyzed by the Suv39h family proteins is essential for establishing the architecture of pericentric heterochromatin. We recently identified a mammalian histone methyltransferase (HMTase), G9a, which has strong HMTase activity towards H3-K9 in vitro. To investigate the in vivo functions of G9a, we generated G9a-deficient mice and embryonic stem (ES) cells. We found that H3-K9 methylation was drastically decreased in G9a-deficient embryos, which displayed severe growth retardation and early lethality. G9a-deficient ES cells also exhibited reduced H3-K9 methylation compared to wild-type cells, indicating that G9a is a dominant H3-K9 HMTase in vivo. Importantly, the loss of G9a abolished methylated H3-K9 mostly in euchromatic regions. Finally, G9a exerted a transcriptionally suppressive function that depended on its HMTase activity. Our results indicate that euchromatic H3-K9 methylation regulated by G9a is essential for early embryogenesis and is involved in the transcriptional repression of developmental genes.

Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a W or a Z boson or a pair of top quarks, and of the six decay modes H → ZZ, W W , γγ, ττ, bb, and μμ. All results are reported assuming a value of 125.09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton-proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fb$^{−1}$ at $\sqrt{s}$=7 TeV and 20 fb−1 at $\sqrt{s}$=8 TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1.09 ± 0.11. The combined measurements lead to observed significances for the vector boson fusion production process and for the H → ττ decay of 5.4 and 5.5 standard deviations, respectively. The data are consistent with the Standard Model predictions for all parameterisations considered.

In the last decade the study of the human brain and muscle energetics underwent a radical change, thanks to the progressive introduction of noninvasive techniques, including near-infrared (NIR) spectroscopy (NIRS). This review summarizes the most recent literature about the principles, techniques, advantages, limitations, and applications of NIRS in exercise physiology and neuroscience. The main NIRS instrumentations and measurable parameters will be reported. NIR light (700-1000 m) penetrates superficial layers (skin, subcutaneous fat, skull, etc.) and is either absorbed by chromophores (oxy- and deoxyhemoglobin and myoglobin) or scattered within the tissue. NIRS is a noninvasive and relatively low-cost optical technique that is becoming a widely used instrument for measuring tissue O2 saturation, changes in hemoglobin volume and, indirectly, brain/muscle blood flow and muscle O2 consumption. Tissue O2 saturation represents a dynamic balance between O2 supply and O2 consumption in the small vessels such as the capillary, arteriolar, and venular bed. The possibility of measuring the cortical activation in response to different stimuli, and the changes in the cortical cytochrome oxidase redox state upon O2 delivery changes, will also be mentioned.

Background. Although living donor liver transplantation for small pediatric patients is increasingly accepted, its expansion to older/larger patients is still in question because of the lack of sufficient information on the impact of graft size mismatching. Methods. A total of 276 cases of living donor liver transplantation, excluding ABO-incompatible, auxiliary, or secondary transplants, were reviewed from graft size matching. Forty-three cases were highly urgent cases receiving intensive care preoperatively. Cases were categorized into five groups by graft-to-recipient weight ratio (GRWR): extra-small-for-size (XS; GRWR<0.8%, 17 elective and 4 urgent cases), small (S; 0.8≤GRWR<1.0%, 21 and 7), medium (M; 1.0≤GRWR<3.0%, 119 and 19), large (L; 3.0≤GRWR<5.0%, 67 and 10), and extra-large (XL; GRWR≥5.0%, 9 and 3). Results. Smaller-for-size grafts were associated not only with larger and older recipients, but also with rather older donors. Posttransplant bilirubin clearance was delayed and aspartate aminotransferase corected by relative graft size was higher in XS and S. Posttransplant hemorrhage and intestinal perforation were more frequent in XS and S, and vascular complications and acute rejection were more frequent in larger-for-size grafts. Consequently, graft survival in XS (cumulative 58% and actuarial 42% at 1 year) and S (76% and 74%) was significantly lower compared with that in M (93% and 92%) in elective cases. Graft survival in L (83% and 82%) and XL (75% and 71%) did not reach statistical significance. Conclusions. The use of small-for-size grafts (less than 1% of recipient body weight) leads to lower graft survival, probably through enhanced parenchymal cell injury and reduced metabolic and synthetic capacity. Although large-for-size grafts are associated with some anatomical and immunological disadvantages, the negative impact is less pronounced.

Neutrophil gelatinase-associated lipocalin (Ngal), also known as siderocalin, forms a complex with iron-binding siderophores (Ngal:siderophore:Fe). This complex converts renal progenitors into epithelial tubules. In this study, we tested the hypothesis that Ngal:siderophore:Fe protects adult kidney epithelial cells or accelerates their recovery from damage. Using a mouse model of severe renal failure, ischemia-reperfusion injury, we show that a single dose of Ngal (10 microg), introduced during the initial phase of the disease, dramatically protects the kidney and mitigates azotemia. Ngal activity depends on delivery of the protein and its siderophore to the proximal tubule. Iron must also be delivered, since blockade of the siderophore with gallium inhibits the rescue from ischemia. The Ngal:siderophore:Fe complex upregulates heme oxygenase-1, a protective enzyme, preserves proximal tubule N-cadherin, and inhibits cell death. Because mouse urine contains an Ngal-dependent siderophore-like activity, endogenous Ngal might also play a protective role. Indeed, Ngal is highly accumulated in the human kidney cortical tubules and in the blood and urine after nephrotoxic and ischemic injury. We reveal what we believe to be a novel pathway of iron traffic that is activated in human and mouse renal diseases, and it provides a unique method for their treatment.

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today's technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.

Abstract By trapping sediment in reservoirs, dams interrupt the continuity of sediment transport through rivers, resulting in loss of reservoir storage and reduced usable life, and depriving downstream reaches of sediments essential for channel form and aquatic habitats. With the acceleration of new dam construction globally, these impacts are increasingly widespread. There are proven techniques to pass sediment through or around reservoirs, to preserve reservoir capacity and to minimize downstream impacts, but they are not applied in many situations where they would be effective. This paper summarizes collective experience from five continents in managing reservoir sediments and mitigating downstream sediment starvation. Where geometry is favorable it is often possible to bypass sediment around the reservoir, which avoids reservoir sedimentation and supplies sediment to downstream reaches with rates and timing similar to pre‐dam conditions. Sluicing (or drawdown routing) permits sediment to be transported through the reservoir rapidly to avoid sedimentation during high flows; it requires relatively large capacity outlets. Drawdown flushing involves scouring and re‐suspending sediment deposited in the reservoir and transporting it downstream through low‐level gates in the dam; it works best in narrow reservoirs with steep longitudinal gradients and with flow velocities maintained above the threshold to transport sediment. Turbidity currents can often be vented through the dam, with the advantage that the reservoir need not be drawn down to pass sediment. In planning dams, we recommend that these sediment management approaches be utilized where possible to sustain reservoir capacity and minimize environmental impacts of dams.

Overload of pancreatic beta cells in conditions such as hyperglycemia, obesity, and long-term treatment with sulfonylureas leads to beta cell exhaustion and type 2 diabetes. Because beta cell mass declines under these conditions, apparently as a result of apoptosis, we speculated that overload kills beta cells as a result of endoplasmic reticulum (ER) stress. The Akita mouse, which carries a conformation-altering missense mutation (Cys96Tyr) in Insulin 2, likewise exhibits hyperglycemia and a reduced beta cell mass. In the development of diabetes in Akita mice, mRNAs for the ER chaperone Bip and the ER stress-associated apoptosis factor Chop were induced in the pancreas. Overexpression of the mutant insulin in mouse MIN6 beta cells induced Chop expression and led to apoptosis. Targeted disruption of the Chop gene delayed the onset of diabetes in heterozygous Akita mice by 8-10 weeks. We conclude that ER overload in beta cells causes ER stress and leads to apoptosis via Chop induction. Our findings suggest a new therapeutic approach for preventing the onset of diabetes by inhibiting Chop induction or by increasing chaperone capacity in the ER.

Partial substitution of Pb for Bi in the Bi-Sr-Ca-Cu-O system has been found to sharply increase the volume fraction of the high- T c phase when both the starting material (coprecipitated oxalate being used in the present study) and the heating process are appropriate. The sharp powder X-ray diffraction pattern obtained from well-grown particles, 5∼10 µm wide and 0.5 µm thick typically, was assigned to an orthorhombic cell with a =0.537 nm, b =2.682 nm, and c =3.726 nm. The electrical resistance dropped to zero at 107 K within the experimental limit of 10 -6 Ω. A large diamagnetic response in the ac susceptibility due to the Meissner effect was seen below 120 K. The dominance of the high- T c phase over the low- T c phase was roughly estimated at 9/1 in volume.

Chronic itch is a common and distressing symptom that arises from a variety of skin conditions and systemic diseases. Despite this, there is no clinically based classification of pruritic diseases to assist in the diagnosis and cost-effective medical care of patients with pruritus. The proposed classification focuses on clinical signs and distinguishes between diseases with and without primary or secondary skin lesions. Three groups of conditions are proposed: pruritus on diseased (inflamed) skin (group I), pruritus on non-diseased (non-inflamed) skin (group II), and pruritus presenting with severe chronic secondary scratch lesions, such as prurigo nodularis (group III). The next part classifies the underlying diseases according to different categories: dermatological diseases, systemic diseases including diseases of pregnancy and drug-induced pruritus, neurological and psychiatric diseases. In some patients more than one cause may account for pruritus (category "mixed") while in others no underlying disease can be identified (category "others"). This is the first version of a clinical classification worked out by the members of the International Forum for the Study of Itch. It is intended to serve as a diagnostic route for better evaluation of patients with chronic pruritus and aims to improve patients' care.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimple and selective method for aldehydes (RCHO) .fwdarw. (E)-haloalkenes (RCH:CHX) conversion by means of a haloform-chromous chloride systemK. Takai, K. Nitta, and K. UtimotoCite this: J. Am. Chem. Soc. 1986, 108, 23, 7408–7410Publication Date (Print):November 1, 1986Publication History Published online1 May 2002Published inissue 1 November 1986https://pubs.acs.org/doi/10.1021/ja00283a046https://doi.org/10.1021/ja00283a046research-articleACS PublicationsRequest reuse permissionsArticle Views9474Altmetric-Citations689LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

During 2015 the ATLAS experiment recorded [Formula: see text] of proton-proton collision data at a centre-of-mass energy of [Formula: see text]. The ATLAS trigger system is a crucial component of the experiment, responsible for selecting events of interest at a recording rate of approximately 1 kHz from up to 40 MHz of collisions. This paper presents a short overview of the changes to the trigger and data acquisition systems during the first long shutdown of the LHC and shows the performance of the trigger system and its components based on the 2015 proton-proton collision data.

By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.