Search

Background The oral, selective Janus kinase inhibitor upadacitinib (UPA) has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Ulcerative Colitis (UC) in a Phase 3 clinical programme comprising two identical induction trials (U-ACHIEVE Induction [NCT02819635] and U-ACCOMPLISH [NCT03653026]) and a maintenance study (U-ACHIEVE Maintenance). This analysis assessed the impact of baseline corticosteroid (CS) use on the efficacy and safety of UPA in patients in these trials. Methods Patients were randomised 2:1 to UPA 45 mg once daily (QD) or placebo (PBO) for 8 weeks. Patients who achieved a clinical response at Week 8 were re-randomised 1:1:1 to UPA 15 mg QD, UPA 30 mg QD or PBO for 52 weeks. Here, we report induction and maintenance endpoints and safety data stratified by baseline CS use. Results Baseline demographics and disease characteristics were generally well balanced across treatment groups, regardless of baseline CS use. Clinical remission rates among patients receiving UPA 45 mg induction therapy did not differ by baseline CS use (Figure 1A). In the induction period, rates of treatment-emergent adverse events of special interest (AESI), including serious and opportunistic infections, were increased in the UPA 45 mg plus baseline CS group compared with the PBO and UPA without baseline CS groups (Table 1). In the maintenance study, CS tapering was mandated. CS-free remission at Week 52 (defined as clinical remission, per Adapted Mayo Score, and CS free for ≥90 days immediately prior to Week 52) was significantly increased with UPA 30 and 15 mg compared with PBO (both p Conclusion This post hoc analysis suggests that, in patients with moderately to severely active UC, UPA is superior to PBO in conferring CS-free remission. Baseline CS use was not associated with any apparent efficacy benefit and carried a potential increased safety risk. These results suggest that achieving early disease control with UPA and without CS use is an optimal treatment strategy for this population.

$\bar K$-nuclear bound systems, kaonic nuclei, have been widely discussed as products of the strongly attractive $\bar K N$ interaction in $I = 0$ channels. Recently, we demonstrated that kaonic nuclei can be produced via in-flight $(K^-,N)$ reactions using the low-momentum DC kaon beam at the J-PARC E15 experiment. We observed the simplest kaonic nuclei, $K^-pp$, having a much deeper binding energy than normal nuclei. For further studies, we have proposed a series of experimental programs for the systematic investigation of light kaonic nuclei, from $\bar K N$ ($\Lambda(1405)$) to $\bar K NNNN$. In the new experiment approved as J-PARC E80, we will measure the $\bar K NNN$ ($A=3$) system as a first step toward a comprehensive study., Comment: 10 pages, 5 figures, proceedings of the 8th Asia-Pacific Conference on Few-Body Problems in Physics (APFB2020), accepted for publication in Fwe-Body Systems

Electron paramagnetic resonance (EPR) spectra of synthetic diamond microcrystals with NV(-) centers have been studied. It is shown that under the conditions of irradiation of the material with the light of a xenon lamp at low temperatures ~100 K, the intensities of the EPR signals corresponding to the “forbidden” (dms=2) and low-field allowed (dms=1) transitions are amplified several times, while the EPR signals from paramagnetic nitrogen and impurity nickel in the charge state -1 practically do not change. This is due to a change in the population of levels of the ground triplet state of the NV(-) center and the optical polarization of spins in the state ms=0 of the triplet level.

Background AJM300 (INN; carotegrast methyl), an orally active small molecule antagonist of the α4 subunit of α4β1/α4β7 integrins, demonstrated the efficacy and safety in patients with moderately active ulcerative colitis (UC) in a phase 2 study. The phase 3 study (NCT 03531892) of AJM300 as induction therapy was conducted in patients with moderately active UC. Methods Eligible patients were moderately active Japanese UC, defined as total Mayo Clinic scores (MCS) of 6–10, endoscopic subscores (ES) ≥2, and rectal bleeding subscores (RBS) ≥1, who had inadequate response or intolerance to oral 5-ASA. Followed by a 2-week single-blind placebo (PBO) run-in phase, patients were randomized 1:1 to receive AJM300 960 mg or PBO 3 times daily for 8 weeks. Responders or remitters were allowed to receive AJM300 960 mg again at the subsequent relapse (open-label). The primary endpoint was clinical response at week 8, defined as reduction of the MCS of ≥3-pts and ≥30%, reduction in RBS of ≥1-pt or RBS of ≤1, and ES ≤1. Results The randomized 203 patients had moderately active endoscopic evidence at baseline with median UC duration of 6.1 years and MCS of 7.8. For the primary endpoint, 45.1% (46/102) and 20.8% (21/101) of patients in the AJM300 and PBO groups, respectively, achieved clinical response at week 8 (OR=3.30 [95% CI, 1.73–6.29]; p=0.0003). Symptomatic remission, endoscopic improvement and endoscopic remission were also statistically significant for AJM300 vs PBO (Table). In case of episodic AJM300 treatment, AJM300 exhibited similar response to initial treatment. Overall, the incidence of AEs and serious AEs were similar between AJM300 and PBO. There were no deaths or cases of progressive multifocal leukoencephalopathy. Conclusion AJM300 induced clinical response as well as endoscopic remission with good tolerability. AJM300 may become a novel therapeutic option for patients who had inadequate response or intolerance to oral 5-ASA.

The K¯NN bound system, symbolically denoted as “K−pp”, is the simplest K¯-nuclear bound system which has been widely discussed as a consequence of the strongly attractive K¯N interaction in I = 0 channels. Many theoretical works have pointed out the existence of the “K−pp” bound system, but the calculated properties such as the binding energy and the width spread out due to the uncertainty of the K¯N interaction below the K¯+N mass threshold. Experimentally, there are several reports on observation of a “K−pp” candidate with the binding energy of around 100 MeV, however, no definitive evidence was available so far. At J-PARC, we conducted a experimental search for the “K−pp” bound system using K− + 3He reaction at 1.0 GeV/c where the “K−pp” is expected to be directly produced via the (K−, n) reaction. We finally observed a bound state below the K− +p+p mass threshold in the Λpn final state, which can be interpreted as the “K− pp” bound state. The possible existence of the “K− pp” state is discussed from both aspects of production and decay.

The structure of the Λ(1405) hyperon is an important and long-standing issue related to the K-nucleus interaction. The J-PARC E31 experiment has been performed to investigate the Λ(1405) spectrum shape. Because it is hard to form the Λ(1405) directly by a KN scattering in free space, E31 uses the d(K-, n) reaction with an incident kaon momentum of 1 GeV/c. We will identify three final states - ς-π+, ς+π-, ς0π0-so that the isospin structure of hyperon resonance states produced can be decomposed. The first physics run of the E31 experiment was performed in 2016. To enhance the statistics of the data set, we have performed the second physics run in the beginning of 2018. During the second run of E31, around 3.9×1010 kaons impacted on the deuteron target.

In this paper, the results of rock stress recently measured in Japan are discussed. Firstly, the CCBO developed by the authors is described in brief. Then, the case examples of stress measurement for rock slope and underground cavern by the CCBO are demonstrated, then the state of stress in rock slope and the design of underground powerhouse are discussed from the rock engineering viewpoint, based on the measured stress.

The J-PARC E15 experiment will be performed to search for the simplest kaonic nuclear bound state, K ¯ N N , by the in-flight He 3 ( K − , N ) reaction. The exclusive measurement will be performed by a simultaneous measurement of the missing mass using the forward neutron or proton, and the invariant mass via the expected decay, e.g. K − p p → Λ p → p π − p . In this report, an overview of the experiment and an analysis of engineering runs performed in February and June are presented.

The alpha inelastic scattering from 24Mg was measured to obtain the isoscalar natural-parity excitation strengths and to search for the α-condensed states. The multipole decomposition analysis for the measured cross sections was performed. The strength distributions for the \({{\Delta}L=0{-}3}\) were successfully obtained and the possible candidates for the α-condensed states around the 16O core were found.

We constructed a test stand of 20 m-class DC superconducting power transmission cable in Chubu University, in 2006. The cable consisted of thirty-nine Bi-2223 HTS tapes in two layers; nineteen tapes were used in the first layer and twenty tapes were used in the second layer. One of the features of the cable is that each HTS tape in the first layer is electrically isolated. Therefore, we can apply the current to the individual HTS tapes in the first layer. We measured critical current of the one HTS tape in the first layer when current was applied to the other HTS tapes, and compared the result with the magnetic field calculation due to the applied current. The critical current increased by 2 ~ 4% when the current was applied to all other eighteen HTS tapes in the same layer. From the magnetic field calculation, we concluded that the self magnetic field of the measured HTS tape was eliminated at the tape edge by the applied magnetic field from the neighbor HTS tapes, and then the critical current increased.

A test stand of a DC superconducting power transmission cable was finished to construct in October 2006 in Chubu University, Japan, and three cooling cycles were carried out to measure the properties of the cable. Critical current of HTS tapes in the cable was measured at every cooling cycle and shows the similar temperature dependence; conclusively, the HTS tapes suffered no damage after cooling and heating process between the each cycle. Peltier current leads were partly installed in the test stand, and it was measured that the temperatures of the feedthrough near to the liquid nitrogen were decreased in spite of a current feeding.

A new Oil Country Tubular Goods (OCTG) Corrosion Resistant Material (CRA) 17-Chrome (17CR) was introduced in late 2011. The corrosion resistance performance of such material was claimed to be comparable to a higher grade material of duplex stainless steel 22-Chrome (22CR) under a given aggressive corrosion environment. In addition to that, 17CR was expected to be significantly competitive and commands shorter delivery lead time compared to 22CR as it does not require cold-drawing process to achieve the required high yield strength. PCSB had evaluated this new material for one of its massive LNG development projects through a series of qualification testing. These LNG carbonate fields were highly corrosive with CO2 and H2S content up to 22 mol% and 140ppm respectively. Maximum bottom hole temperature anticipated was more than 180 degrees Celsius. Material selection for production tubing was therefore of paramount importance in such severe well condition to ensure that long term well integrity was not compromised with this newly developed material. Through the establishment of a multidisciplinary team, PCSB had established a set of rigorous qualification test procedure, fully aligned with industry standards to ensure that the identified risks were mitigated from both material and connection perspectives. This paper will describe the systematic approach that was used to evaluate the reliability of the new material with a premium connection under the defined worst case conditions; discuss the corresponding results which led to significant cost savings for the mentioned project.

We have searched for the simplest kaonic nuclear state, KNN, using the in-flight 3He (K-, n) reaction at the J-PARC hadron experimental facility. In the semi-inclusive neutron missing-mass spectrum at θnlab=0°, an excess of yield was observed just below the K- pp mass-threshold, which cannot be explained by any elementary reactions [PTEP 2015, 061D01]. To understand the missing-mass spectrum of 3He (K-, n) X, we investigated the elementary (K-, n) reactions using hydrogen and deuterium targets. The p (K-, n) X missing-mass spectrum was well described by the charge-exchange reaction. However, in the d (K-, n) X spectrum, we observed an excess of yield just below the K- p mass-threshold, which was similar to that in the 3He (K-, n) X spectrum. (Less)

Due to the recent developments of the electric power devices and the HTS power cables, DC superconducting power transmission system is considered to be practical. As one of the R & D issues of the DC superconducting power transmission system, we measured the radiation heat of the thermally-isolated stainless steel pipes with different surfaces. As the result, one sheet of aluminum foil pasted on the inner pipe surface reduced the heat radiation to 1.98 m/W between LN2 and the room temperature of 300 K.

Leiomyomas of uterus are common disease in gynecology. It is important to differentiate leiomyoma from leiomyosarcoma at the decision of treatment methods, especially in the case of the conservative treatment for uterine leiomyoma. But the exact diagnosis of benign leiomyoma is often difficult due to the degeneration of myoma by imaging modalities including magnetic resonance imaging. Recently, whole-body positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) has been used for a diagnosis of malignant tumors. There is a growing body of evidence for the use of FDG in differentiating malignant from benign disease. But optimal utilization in gynecology remains unclear. Our case represents increased uptake of FDG in myomatous uterus, which is pathologically confirmed benign leiomyoma by the hysterectomy. Immunohistochemical analysis of glucose transporter-1 showed positive in endometrial tissue and negative in leiomyoma. Our case indicates that myomatous uterus in premenopausal women shows the potential pitfall of a positive result of FDG-PET

Correlated Λp pairs with smaller invariant mass than the K− + 2p threshold were observed by recent experiments with stopped K− absorption in 4He and heavier nuclei, which may be related to the existence of deeply-bound K−pp states. We discuss a possibility to investigate the existence of K−pp states by an exclusive measurement with more simple 3He target.

An experiment to search for the $K^-pp$ bound state was performed via the in-flight $^3$He($K^-,n)$ reaction using 5.3 $\times$ $10^9$ kaons at 1 GeV/$c$ at the J-PARC hadron experimental facility. In the semi-inclusive neutron missing-mass spectrum at $\theta_{n}^{lab}=0^\circ$, no significant peak was observed in the region corresponding to $K^-pp$ binding energy larger than 80 MeV, where a bump structure has been reported in the $\Lambda p$ final state in different reactions. Assuming the state to be isotropically decaying into $\Lambda p$, mass-dependent upper limits on the production cross section were determined to be 30--180, 70--250, and 100--270 $\mu$b/sr, for the natural widths of 20, 60, and 100 MeV, respectively, at 95\% confidence level., Comment: 12 pages, 6 figures

During ischemia, large amounts of catecholamine are released to the myocardium from the sympathetic nerve endings in the heart. It has not been clearly shown whether the released catecholamine has detrimental or beneficial effects on postischemic myocardial contractile function. The aim of the present study was to investigate the effect of endogenous catecholamine released during ischemia on myocardial contractile function, using ferret papillary muscles in a stimulated ischemia model. Papillary muscles were excised and mounted in organ baths containing oxygenated physiological salt solution at 37 degrees C. In order to eliminate the effect of endogenous catecholamine, a subset of animals was reserpinized for 2 days prior to the experiments. Muscles were stabilized for 1 h, and stretched to the length at which maximal isometric tension developed. Ischemia was simulated by changing the solution to liquid fluorocarbon bubbled with 95% N2 and 5% CO2. After 20 min of ischemia, the bathing medium was replaced with oxygenated physiological salt solution and developed tension was measured for 60 min. Pharmacologic agents with specific effects on myocardial autonomic pathways were used to investigate the cellular mechanisms of the observed effects. Tension recovery of reserpinized muscles was significantly better than control muscles (65.5 +/- 2.8% vs. 54.9 +/- 5.0%, P < 0.01). Exogenously administered beta-adrenergic antagonists did not attenuate stunning in control muscles; whereas forskolin and carbachol exacerbated stunning. These results indicate that catecholamine released during ischemia exacerbates myocardial stunning and overrides the effect of clinically relevant concentrations of beta-adrenergic antagonists, which may limit their ability to protect myocardium from acute ischemic insult. The effect of endogenous catecholamine was simulated by forskolin, but not attenuated by carbachol, which suggests that changes in the contractile apparatus activated by excess cyclic AMP were relevant to the mechanical dysfunction that developed.

We have collected the first physics data of an experimental search for the simplest kaonic nuclear bound state, “ K − pp”, by the 3He( K − n) reaction at J-PARC. We confirmed that our spectrometer system works as designed and observed clear peak structure composed of the quasi-elastic K − “ n ” → K − n and the charge-exchange K − “ p ” → ¯ K 0 n reactions in the forward neutron spectrum.

In the J-PARC E15 experiment, a K − pp search was performed via the 3 He(K − , n ) reaction at 1.0 GeV/c . A forward-going neutron is detected by a neutron counter with 15 m flight length, and decay particles from K − pp are simultaneously measured by a cylindrical detector system that surrounds a liquid 3 He target system. In March and May, 2013, we carried out the first physics data-taking with 5×109 incident kaons on the 3 He target, and we have obtained a preliminary exclusive analysis result of 3 He(K − , Λp )n reaction.

We evaluated the cardiac effects of the principle pyrolysis product of crack cocaine smoking, methylecgonidine (MEG), in comparison with cocaine. Peak cell shortening and intracellular Ca2+, as detected by the Ca2+ indicator indo 1, were recorded in enzymatically isolated ferret myocytes. Both cocaine and MEG decreased peak cell shortening and peak intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner (10(-8)-10(-4) M). MEG shifted the peak [Ca2+]i-to-peak shortening relationship downward and was more potent than cocaine. Atropine (10(-6) M) upwardly shifted the dose-response curves of MEG, cocaine, and carbachol but not of procaine. The negative inotropic effects of MEG were inhibited by methoctramine, a selective M2 receptor blocker but not by M1 (pirenzepine) or M3 (4-diphenylacetoxy-N-methylpiperidine methiodide) blocking agents. In contrast to cocaine, the effects of large doses of MEG were irreversible over the time course of our experiments, raising the possibility of structural damage. We conclude that MEG acts primarily on M2 cholinergic receptors in the heart to produce acute cardiac intoxication and, in contrast to cocaine, may decrease the myofilament Ca2+ responseness and cause structural damage to myocytes by a direct toxic effect.

Acidosis affects multiple steps in the excitation-contraction coupling pathway of myocardium, producing decreased calcium sensitivity of myofibrils and modification of the function of the sarcoplasmic reticulum. Our aim was to evaluate the effectiveness of three different classes of inotropic agents under acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances cellular cyclic AMP concentrations, 2) elevated extracellular Ca 2+ and 3) endothelin-l, an activator of the inositol triphosphate, diacylglycerol pathway. Ferret papillary muscles were mounted in organ baths containing normal physiological solution (pH = 7.4). After baseline tension was measured, the muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to 40% of the control; subsequently, the muscles were washed with normal physiological solution until they returned to baseline. Each inotropic agent was added to the bathing solution in a concentration sufficient to increase tension by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the continuous presence of that concentration of inotropic agent and the resultant steady-state developed tension measured. The increases in tension induced by each inotropic agent at normal pH were adjusted to be similar; in contrast, the response to each drug in acidosis was significantly different. Under acidotic conditions, endothelin-l was the most effective inotropic agent in restoring the depressed developed tension. This was possibly due to enhancement of the myofilament sensitivity to Ca 2+ , which was more effective than increasing [Ca 2+ ] i through elevating extracellular Ca 2+ or the addition of forskolin which increased [Ca 2+ ] i but desensitized the myofilaments to Ca 2+ .

The Acoustic Radiation Force Impulse (ARFI) is recently used to evaluate tissue elasticity in some organ. When the biological tissue is exposed by ARFI, the damage by greater ultrasonic pulse and combination with contrast agents is still unknown in both mechanical and thermal effects. Thus, concurrent administration of contrast agent for ultrasound imaging with ARFI had not been advocated, the heat and/or cavitation may occur. Purpose: The thermal effect of ARFI on the living animal tissue is evaluated with or without contrast material, Sonazoid™ (perfluorobutane). Material and method: The rabbit (Japan white, BW 3 kg, male) on general anesthesia is examined. The ultrasound wave with ARFI is focused on the rabbit's liver through the skin with the transducer that has central hole for the guide needle and thermocouple to measure the tissue temperature passing through. The focal length is 35 mm. After that Sonazoid™ is administered intravenously bolus fashion and measured temperature repeatedly at the another site of the liver. Mechanical index of ultrasound with ARFI was 3.4 that was measured by the hydrophone and the pulse duration is serially changed from 0.3 to 400 msec. Result: The temperature rise was observed correlated with the pulse duration of the ARFI, maximally 1.4 °C rise from the baseline. The range of the temperature rise had no difference regardless of the use of Sonazoid™, because the presence of Sonazoid may increase the attenuation of ultrasound in the tissue. Conclusion: In the liver of living rabbit, the temperature of the focus site of ARFI rose. Although the existence of Sonazoid™ with ARFI was no influence about the thermal evaluation, the tissue destruction by a cavitation might occur and the challenging problem.

To search for an S= -1 di-baryonic state which decays to $\Lambda p$, the $ {\rm{}^3He}(K^-,\Lambda p)n_{missing}$ reaction was studied at 1.0 GeV/$c$. Unobserved neutrons were kinematically identified from the missing mass $M_X$ of the $ {\rm{}^3He}(K^-,\Lambda p)X$ reaction in order to have a large acceptance for the $\Lambda pn$ final state. The observed $\Lambda p n$ events, distributed widely over the kinematically allowed region of the Dalitz plot, establish that the major component comes from a three nucleon absorption process. A concentration of events at a specific neutron kinetic energy was observed in a region of low momentum transfer to the $\Lambda p$. To account for the observed peak structure, the simplest S-wave pole was assumed to exist in the reaction channel, having Breit-Wigner form in energy and with a Gaussian form-factor. A minimum $\chi^2$ method was applied to deduce its mass $M_X\ =$ 2355 $ ^{+ 6}_{ - 8}$ (stat.) $ \pm 12$ (syst.) MeV/c$^2$, and decay-width $\Gamma_X\ = $ 110 $ ^{+ 19}_{ - 17}$ (stat.) $ \pm 27$ (syst.) MeV/c$^2$, respectively. The form factor parameter $Q_X \sim$ 400 MeV/$c$ implies that the range of interaction is about 0.5

We report the clinical course, and neurophysiological and neuroimaging findings of a patient with Guillain-Barré syndrome associated with central nervous system lesions. During a course of intravenous immunoglobulin therapy, she had headache with meningism. Cerebral magnetic resonance imaging showed lesions in both frontal and right occipital lobes. Cerebrospinal fluid showed a raised protein concentration accompanied by mild pleocytosis. Her symptoms resolved within two months. Subsequent magnetic resonance imaging revealed cavity formation in the deep white matter and atrophic changes in the right occipital lobes.

The alpha inelastic scattering from 24Mg was measured to obtain the isoscalar natural-parity excitation strengths and to search for the α-condensed states. The multipole decomposition analysis for the measured cross sections was performed. The strength distributions for the ΔL = 0–3 were successfully obtained and the possible candidates for the α-condensed states around the 16O core were found.

Fluorine-doped silica glasses containing up to 2 wt% were prepared by the vapour-phaseaxial-deposition (VAD) sintering process. The characteristics of these glasses were investigated by Raman spectroscopy, vacuum-ultraviolet-ultraviolet (v.u.v-u.v.) spectroscopy, and viscosity measurements. From the Raman spectroscopic investigation, it has been shown that the Si-F bond structure in the fibres is the same as that in bulk glass and is not affected by codoped additives such as B2O3. From the u.v.-v.u.v, spectroscopic investigation, it has been shown that the absorption band at 7.6 eV in high-purity silica glass is removed with the addition of fluorine. This addition produces a silica glass with most excellent transparency in u.v. and v.u.v. regions. Also it was observed that the optimum addition is around 1 wt%. This fact proves that fluorine incorporation in glass prevents the generation of defects related to optical loss in fibres. From the viscosity study, it was found that the viscosity decreases with an increase of the fluorine content in glass and the activation energy also decreases with increasing fluorine content.

Two novel eudesmane-type sesquiterpenes, dictyophorines A and B, and a known compound, teucrenone, were isolated from the mushroom Dictyophora indusiata. Dictyophorines A and B promoted nerve growth factor (NGF)-synthesis by astroglial cells.

The J-PARC E15 experiment has the aims to search for the simplest kaonic nuclear bound state, K − pp, by the in-flight 3He(K −,n) reaction. The exclusive measurement is performed by a simultaneous measurement of the missing mass using the knocked out neutron and the invariant mass via the expected decay, K − pp → Λ p → pπ− p. In this paper, an overview of the experiment and current data analysis of the engineering runs performed in February and June 2012 are presented.

A human tumour cell line, designated RMS-YM, was established from a childhood rhabdomyosarcoma. The monolayer cells were polygonal, round or spindle-shaped. The cells became multilayered and formed many focal piles when confluent. RMS-YM became stable with a doubling time of about 30 h and has been maintained for 104 passages to date. Tumourigenicity of the cells was confirmed by heterotransplantation into nude mice. Morphological features were similar to those of the primary tumour, and myofibrils were found by electron microscopy. The expression of desmin and human myoglobin, and high levels of striated muscle system specific enzymes were recognised. Chromosomal analysis revealed possible gene amplification in the form of homogeneously staining regions. Oncogene analysis was performed on the primary tumour and the cell line, but neither N-myc nor N-ras genes were amplified, nor were Ki-ras, Ha-ras or N-ras genes mutated at the 12th, 13th and 61st codons. The RMS-YM cell line may provide a system to identify novel genes which are amplified in rhabdomyosarcoma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5

A cDNA encoding chicken glycine decarboxylase (pCP15b) was isolated using an antibody specific to this protein. Additional cDNAs were cloned with the aid of the genomic fragments obtained by using the pCP15b cDNA probe. No initiator methionine codon is found in the currently elucidated cDNA sequence, and an ATG codon in an exon is assigned to this role. The precursor glycine decarboxylase deduced from the 3514-base pair nucleotide sequence is comprised of 1,004 amino acids (Mr = 111,848). The 1,020 amino acid residues are encoded for the precursor form of human glycine decarboxylase (Mr = 112,869) in the 3,783-base long cDNA sequence of two 1.9-kilobase pair cDNAs with a pentanucleotide overlap. The pyridoxal phosphate binding site lysine and a glycine-rich region, which is suggested to be responsible for the attachment of the phosphate moiety of pyridoxal phosphate, are found in close proximity in both the chicken and human enzymes. This region essential for the enzyme action is suggested to be embedded in a segment rich in beta-turns and random coils and is surrounded by conserved and repetitive amino acid sequences. It is suggested that these structures are involved in the organization of the active site of glycine decarboxylase.

Multilayer insulator (MLI) is a strong tool for use as a radiation heat shield, though the use of MLI has disadvantages in construction and evacuation for a long superconducting power cable. We have proposed the “MLI-free” radiation heat shielding for DC superconducting power cable and have measured the radiation heat transfer for thermally-isolated double-pipes with different surfaces. Here, Zn coating, MLI, and Al-foil sheet were tested. Consequently, from the radiation heat of 9.7 W/m for bare stainless-steel pipe, Zn-coated stainless-steel surface reduced to 2.6 W/m, whereas the use of MLI reduced to 0.2 W/m. It is expected that the simultaneous use of Zn coating and MLI can reduce the number of total MLI sheets to reduce the evacuation time.

Summary One of eight patients with nonketotic hyperglycinemia resulted by the lesion in glycine decarboxylase showed the deletion of 0.6-kb Sac I and 1.5-kb Pst I fragments identified by the cDNA for this protein. A genomic clone, λHGDG10, encodes a 5′ region of this cDNA in an organized structure and can produce these two fragments. The other clone, λHGDG8, carries a processed gene. Southern analysis using a limited segment of this cDNA demonstrated that the 1.7-kb and 1.5-kb Pst I fragments predicted from its recognition sites in both genomic clones occur actually in the human genome, indicating that at least two copies of glycine decarboxylase cDNA exist in the haploid genome, and the patient has the glycine decarboxylase gene deleted at a 5′ region.

The fundamental cause of almost all problems facing humanity is the size of the human population, multiplied by the intense consumption. There will not be technological solutions unless the population and the consumption are reduced, because apparently the capacity of the planet has already been surpassed. In order to enable a sustainable global civilization, some basic concepts regarding human existence need to be recognized or changed: * The Earth is finite in space, resources and capacities of its systems; * Man is adapted to the current equilibrium in the systems of the Earth; * A healthy biosphere is essential for the equilibrium in the habitats for man; * The biosphere is maintained by photosynthesis in plants; * There is a limit to the size of the biosphere; * An increase of human population means a reduction of those of other species; * Perturbations in the biosphere as well as in other systems could break the equilibrium; * In a closed system the effective fertility of each species must be that of replacement; * There cannot be human rights that lead to the collapse of the community; * The concept of community needs to include all humanity and the biosphere; * Ultimately man has to live with renewable resources; * The principles of economy need to be modified; * The meaning of life must be found in something other than procreation or consumption; * All ideals cannot be realized; * Some new rationality needs to be added to the rules of community; * The Earth can support indefinitely an abundant lifestyle in a limited global civilization; * Human population must be reduced.