Correction: 'Transition mechanism for a periodic bar-and-joint framework with limited degrees of freedom controlled by uniaxial load and internal stiffness' (2018), by Tanaka et al.

[This corrects the article DOI: 10.1098/rsos.180139.][This corrects the article DOI: 10.1098/rsos.180139.].

Creep trajectory transition of a nonstationary viscoelastic model onto a single rate parameter.

A system of three-variable differential equations, which has a nonstationary trajectory transition through the control of a single rate parameter, is formulated. For the nondimensional system, the critical trajectory creeps before a transition in a long-lasting plateau region in which the velocity vector of the system hardly changes and then diverges positively or negatively in finite time. The mathematical model well represents the compressive viscoelasticity of a spring-damper structure simulated by the multibody dynamics analysis. In the simulation, the post-transition behaviors realize a tangent stiffness of the self-contacted structure that is polarized after transition. The mathematical model is reduced not only to concisely express the abnormal compression problem, but also to elucidate the intrinsic mechanism of creep-to-transition trajectories in a general system.

Auxetic vibration behaviours of periodic tetrahedral units with a shared edge.

A very low-frequency mode supported within an auxetic structure is presented. We propose a constrained periodic framework with corner-to-corner and edge-to-edge sharing of tetrahedra and develop a kinematic model incorporating two types of linear springs to calculate the momentum term under infinitesimal transformations. The modal analysis shows that the microstructure with its two degrees of freedom has both low- and high-frequency modes under auxetic transformations. The low-frequency mode approaches zero frequency when the corresponding spring constant tends to zero. With regard to coupled eigenmodes, the stress-strain relationship of the uniaxial forced vibration covers a wide range. When excited, a very slow motion is clearly observed along with a structural expansion for almost zero values of the linear elastic modulus.

Transition mechanism for a periodic bar-and-joint framework with limited degrees of freedom controlled by uniaxial load and internal stiffness.

A specific periodic bar-and-joint framework with limited degrees of freedom is shown to have a transition mechanism when subjected to an external force. The static nonlinear elasticity of this framework under a uniaxial load is modelled with the two angular variables specifying the rotation and distortion of the linked square components. Numerically exploring the equilibrium paths then reveals a transition state of the structure at a critical value of the internal stiffness. A simplified formulation of the model with weak nonlinear terms yields an exact solution of its transition state. Load-displacement behaviour and stability for the two systems with or without approximation are analysed and compared.

Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin.

AIMS/HYPOTHESIS: The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function. METHODS: Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1(-/-)) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells. RESULTS: BetaRac1(-/-) mice showed decreased glucose-stimulated insulin secretion, while there were no apparent differences in islet morphology. Isolated islets from the mice had blunted insulin secretion in response to high glucose levels. In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels, consistent with the phenotype of betaRac1(-/-) mice. Even under high glucose levels, RAC1 knockdown INS-1 cells remained intact with F-actin, which inhibits the recruitment of the insulin granules, resulting in an inhibition of insulin secretion. CONCLUSIONS/INTERPRETATION: In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion.

Chemiluminescence method with potassium permanganate for the determination of organic pollutants in seawater.

A chemiluminescence method with potassium permanganate was developed for use as an indicator of organic pollutants in fresh water. This method could be applied to the determination of organic pollutants in seawater as well. However, the flow chemiluminescence method suffered from the interference of chloride ions at the same concentration of seawater because of the production of manganese dioxide in the oxidation of chloride ions with permanganate. The conditions (concentrations of potassium permanganate and sulfuric acid and sample volume, i.e. flow injection method) were chosen to minimize the interference of chloride ions. The chemiluminescence method shows a good correlation with the chemical oxygen demand method on fresh water added artificial sea salt and seawater samples. Natural seawater was analyzed by the chemiluminescence method. The results obtained were compared with those obtained by chemical oxygen demand under the alkaline condition and total organic carbon methods. The chemiluminescence method has higher sensitivity and reproducibility than the conventional chemical oxygen demand and total organic carbon methods.

Synthesis and metal-ion binding properties of monoazathiacrown ethers.

Synthetic procedures for monoazathiacrown ethers were explored, and monoazatrithia-12-crown-4, monoazatetrathia-15-crown-5, and monoazapentathia-18-crown-6 were obtained in moderate yields by the reaction of bis(2-chloroethyl)amine with the appropriate dithiols in the presence of lithium hydroxide in THF. To evaluate metal-ion binding properties of the monoazathiacrown ethers by solvent extraction, lipophilic dodecyl and dodecanoyl groups were incorporated onto the monoazathiacrown ethers. The solvent extraction experiments suggested that monoazathiacrown ethers have Ag(+) and Hg(2+) selectivities and that the relative selectivity between Ag(+) and Hg(2+) depends on their nitrogen atom properties and numbers of sulfur atoms reflecting the respective affinities of nitrogen and sulfur atoms to Hg(2+) and Ag(+). An interesting ability to bind Mg(2+) was observed in the case of N-dodecyl monoazatrithia-12-crown-4.

Investigation on diabetic autonomic neuropathy assessed by power spectral analysis of heart rate variability in WBN/Kob rats.

This article investigates the development of cardiovascular autonomic dysfunction caused by diabetes mellitus. We performed power spectral analysis of heart rate variability in WBN/Kob rats as a model of spontaneous diabetes. The heart rate of the rats was measured continuously for 24 hours with an implanted telemetric transmitter, and power spectral analysis of heart rate variability was performed on continuous electrocardiograms. At 4 to 5 months of age, the rats indicated a tendency toward a decrease in plasma insulin concentration without hyperglycemia. At 8 to 9 months of age, they showed remarkable hyperglycemia, loss of the circadian rhythm of the heart rate, and reversion or loss of the circadian rhythm of the blood pressure. By the power spectral analysis of heart rate variability, it became apparent that the circadian rhythm of the low frequency/high frequency ratio was absent even in prediabetic WBN/Kob rats. In addition, the circadian rhythms of the high-frequency power level and low frequency/high frequency ratio were absent in diabetic WBN/Kob rats. These findings indicate that the autonomic nervous system in WBN/Kob rats is progressively damaged from the prediabetic to diabetic state. In conclusion, diabetic autonomic neuropathy may be characterized by the appearance of sympathetic overactivity that precedes the impairment of parasympathetic activity.

Synthesis and photochromism of spirobenzopyran derivatives bearing an oxymethylcrown ether moiety: metal ion-induced switching between positive and negative photochromisms.

Spirobenzopyran derivatives carrying an oxymethylcrown ether moiety were synthesized, and their photochromism was studied in the presence of various metal ions in acetonitrile. The metal ion complexing ability of the crown ether moiety in crowned spirobenzopyrans affects both thermal isomerization and photoisomerization of their spirobenzopyran moiety to a great extent. When the interaction of the crown ether moiety with a metal ion was strong enough to cause thermal isomerization of the spirobenzopyran moiety to its corresponding merocyanine form and to suppress UV-induced isomerization to the merocyanine form, a negative photochromism appears. On the other hand, a relatively weak interaction of the crown ether moiety with a metal ion affords a positive photochromism. This phenomenon enables us to switch the photochromic behavior between positive and negative photochromisms.

Spectral analysis of circadian rhythms in heart rate variability of dogs.

OBJECTIVE: To determine characteristics of power spectral analysis of heart rate variability (HRV) during a 24-hour period in dogs and to evaluate the effects of vagal and sympathetic tone on HRV ANIMALS: 16 healthy adult Beagles. PROCEDURE: Power spectral analysis of HRV was conducted, using 24-hour ambulatory ECG recordings. Circadian rhythms were evaluated in terms of absolute units of low-frequency (LF) and high-frequency (HF) powers, their ratio (LF:HF), and their adjusted (normalized) units (LF[norm] and HF[norm]). Three or 4 dogs were used for simultaneous measurement of heart rate and respiratory waveform as well as to evaluate treatment (propranolol, atropine, or both) administered to cause blockade of the autonomic nervous system. RESULTS: Values for LF and HF powers, LF:HF, LF(norm), and HF(norm) had obvious rhythmicity in clinically normal dogs. The HF power of HRV in dogs was extremely high, compared with that of other species, and HF peaks corresponded to peaks obtained from respiratory waveforms. Blockade of the autonomic nervous system documented that HRV in dogs was mostly attributable to vagal activity. CONCLUSION AND CLINICAL RELEVANCE: We determined characteristics of power spectral analysis of HRV in dogs, including circadian rhythm of the autonomic nervous system. Power spectral analysis of HRV may provide a useful noninvasive technique for assessing the effect of drugs on activity of the autonomic nervous system in dogs.

Human xanthine dehydrogenase cDNA sequence and protein in an atypical case of type I xanthinuria in comparison with normal subjects.

To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency in a patient with atypical type I xanthinuria, as indicated by oxypurine data, a cDNA sequence encoding XDH, XDH/XO immunoblot analysis and a competitive PCR assay were performed, and the results were compared with those of normal subjects. The xanthine dehydrogenase cDNA sequence of the patient was consistent with the controls, while immunologically reactive 150 kD XDH/XO protein was not present in the xanthinuric duodenal mucosa, unlike the control duodenal mucosa. In addition, a decrease in XDH/XO messenger RNA was found by competitive PCR. These results suggest that atypical type I xanthinuria is due to a decrease in messenger RNA of XDH/XO. Furthermore, it was considered that this decrease could explain the normal plasma level and near normal urinary excretion of hypoxanthine seen in this case of xanthinuria, though XDH/XO activity and protein were not detected spectrophotometrically and immunologically, respectively.

Abnormal haemoglobins, Hb Takamatsu and Hb G-Szuhu, detected during the analysis of glycated haemoglobin (HbA1C) by high performance liquid chromatography.

BACKGROUND: During medical checkups of two unrelated female outpatients during their annual health examination and one male inpatient suffering from cardiac failure the glycated haemoglobin (HbA1C) concentrations measured by high performance liquid chromatography (HPLC) were low, in spite of normal fasting plasma glucose concentrations. However, HbA1C concentrations measured by latex immunoagglutination and fructosamine concentrations were within the normal range. METHOD: Investigations were performed to elucidate the reasons for these discrepancies. RESULTS: Abnormal haemoglobins, Hb Takamatsu and Hb G-Szuhu, were found. The HPLC chromatogram showed an additional peak near HbA1a + b, which resulted in falsely low HbA1C concentrations. Isoelectric focusing analysis of the patients' haemoglobin disclosed abnormal haemoglobins, which migrated faster than normal HbA1 in the two female patients and slower in the male patient. The cDNA sequence and amino acid analyses of the haemoglobin alpha-chains and beta-chains indicated the presence of the haemoglobin variant beta 120 Lys-->Gln in the two female patients and beta 80 Asn-->Lys in the male patient; that is, Hb Takamatsu and Hb G-Szuhu. CONCLUSIONS: These cases show how these silent haemoglobin variants can result in falsely low HbA1C concentration readings when using HPLC.

Growth-stimulating effect of dienogest, a synthetic steroid, on rodent, canine, and primate mammary glands.

We observed hyperplasia of the mammary gland in female beagle dogs, but not in female rats and monkeys, in 91-day toxicity studies on dienogest. In order to elucidate a possible mechanism for its development and to account for this species difference, we determined the plasma level of growth hormone (GH) in dogs, rats, and monkeys treated orally with dienogest for 91 days. As a result, dogs with mammary hyperplasia showed a prominent, dose-dependent increase in their GH level; and, contrarily, rats and monkeys without the hyperplasia of this organ failed to show any such increase. These results were supported by evidence from immunohistochemical and morphometric analysis of the pituitary gland. In addition, dienogest and medroxyprogesterone acetate (MPA) stimulated the growth of canine mammary epithelial cells in the presence of estradiol in vitro, but had no effect on rat and human mammary epithelial cells incubated under the same conditions. In conclusion, dienogest with progestational activity caused proliferation of the mammary gland in beagle dogs by increasing the secretion of GH, as do other progestational compounds. This change may be partially dependent on the direct effect of the drug.

[Intrasellar epidermoid cyst].

We report a rare case of intrasellar epidermoid cyst. A 61-year-old man presented with complaints of the disturbance of consciousness and general fatigability. His laboratory data showed panhypopituitarism and MRI revealed the cystic tumor located at the intrasellar region. Tumor was removed by transsphenoidal approach and histological examination of the surgical specimen showed that the cyst wall was composed of the stratified squamous epithelium with keratohyaline granules.

Suicidal insulin overdose in a type 1 diabetic patient: relation of serum insulin concentrations to the duration of hypoglycemia.

We present a case of a 31-year-old Type 1 diabetic woman who self-administered 2400 units of insulin mixture (70% NPH human insulin and 30% Regular human insulin) as a suicidal attempt. The subsequent hypoglycemia was prolonged probably due to delayed absorption of the subcutaneous insulin, but it was not very difficult to control despite the administration of large amounts of insulin. Although the estimated serum insulin level was not well correlated with the severity of hypoglycemia, the hypoglycemia subsided when the serum insulin level returned to the physiological level. Therefore, the study of insulin pharmacokinetics after insulin overdose may be useful to know the necessary duration of exogenous glucose administration required to manage the medical emergency of severe insulin intoxication in future cases.

Long-term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats.

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, on the development of diabetes, insulin resistance, and abnormalities of blood coagulation in male WBN/Kob rats, a model of spontaneous diabetes mellitus. After 8-month oral EPA-E treatment, the incidence of diabetes at a dose of 0.1, 0.3, and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its incidence was suppressed significantly and dose-dependently at a dose of 0.3 g/kg or higher compared with the rate (100%) for the vehicle control. Additionally, EPA-E significantly and dose-dependently decreased the elevation of plasma glucose after an oral glucose load and increased the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test at a dose of 0.1 g/kg or higher compared with the vehicle control. Furthermore, EPA-E significantly and dose-dependently ameliorated coagulation-related parameters, including the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level, and factor II, V, VII, VIII, IX, X, XI, and XII and antithrombin III (AT III) activities, and fibrinolysis-related parameters, including plasminogen, tissue-type plasminogen activator (t-PA), alpha2-plasmin inhibitor (alpha2-PI), and plasminogen activator inhibitor (PAI), and also suppressed ADP- or collagen-induced platelet aggregation and the cholesterol to phospholipid (C/P) molar ratio in platelet membranes at a dose of 0.1 g/kg or higher. These data demonstrate multiple actions of the product in these laboratory animals. These include changes in platelet function, coagulation/fibrinolysis factors, plasma immunoreactive insulin secretion, and plasma glucose/insulin resistance.

Synthesis and Photochromism of Crowned Spirobenzothiapyran: Facilitated Photoisomerization by Cooperative Complexation of Crown Ether and Thiophenolate Moieties with Metal Ions.

Spirobenzothiapyrans bearing monoaza-12-crown-4, -15-crown-5, -18-crown-6, and oligooxyethylene moieties were synthesized, and their photochromism was examined in the presence of cations in acetonitrile. The cation complexation by their crown ether moieties cannot induce thermal isomerization to their corresponding colored merocyanine form, unlike the corresponding spirobenzopyran derivatives. The UV-light-induced isomerization was, however, facilitated by the cation complexation of the crown ether moieties and the affinity of the merocyanine thiophenolate anion to metal ions, especially in the presence of Li(+) and Ag(+). The presence of Ag(+) brought about the most remarkable effect in the facilitation of photoisomerization of the spirobenzothiapyrans and the thermal stability of the colored merocyanine form mainly due to the powerful interaction of the thiophenolate anion with the soft metal ion.

Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats.

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in alpha2-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.

D0870, an antifungal agent, induces reverse use-dependent QT prolongation in dogs.

We previously reported that D0870 induced QT prolongation and sudden death due to torsades de pointes (TdP) in dogs and that catecholamines played an important part in the development of the sudden death. In the present study, we analyzed in detail the ambulatory electrocardiographic recordings obtained from the just-mentioned study to elucidate the mechanism of the onset of TdPs and conducted an in vitro study using isolated canine Purkinje fibers to assess the effect of D0870 on repolarization. The hearts with TdPs observed before the sudden death showed a higher sinus rate for 5 and 10 sec before the onset, a shorter coupling interval, and a higher ventricular tachycardia rate compared with those having the non-sustained TdPs. These findings suggest that D0870-induced fatal TdPs may be provoked by a triggered activity developed from delayed after depolarizations. In contrast, as the pause-dependent, non-sustained TdPs in bradycardia showed a typical "short-long-short" sequence, they may be developed from early afterdepolarization . Moreover, the results of the in vitro study supported our contention that D0870 induced QT prolongation in a reverse use-dependent manner in vivo and suggested that it may inhibit not only rapidly activating delayed rectifier potassium current (Ik(r)) but also L-type Ca current (I(ca-L)).

Influences of catecholamines on the sudden death induced in dogs by an antifungal agent, D0870.

We previously reported the occurrence of QT prolongation and sudden death owing to torsades de pointes (TdP) in dogs treated with D0870, an antifungal agent. In the present study, we evaluated the influences of epinephrine and isoproterenol on the onset of TdP each time D0870 was given to 6 anesthetized open-chest dogs at a dosage of 20 mg/kg, 5 times every 40 minutes, by the simultaneous measurements of surface electrocardiogram and epicardial monophasic action potential (MAP). D0870 alone induced noticeable prolongation of the QT interval and action potential duration (APD), but neither ventricular premature contraction (VPC) nor sudden death. In contrast, the additional administration of the catecholamines induced a greater shortening of APD during the later phase of repolarization than during its earlier one and VPCs in all dogs tested, and sudden deaths owing to TdPs in 4 of the 6 dogs treated with D0870. These results suggest that D0870 alone does not induce TdP but that catecholamines play an important part in the development of sudden death induced by D0870 in dogs.