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Essence of chicken (EOC), a hot water extract of chicken, is widely consumed in Southeast Asia as a beverage. EOC has an inhibitory effect on the elevation of blood glucose levels and a secretagogue effect on insulin. However, the mechanism by which EOC promotes insulin secretion is unknown. We aimed to verify the postprandial hyperglycemic inhibitory effect and the insulin secretory effect of EOC in healthy adults under appropriate placebo settings. In addition, we aimed to understand the mechanism underlying the insulin secretory effect of EOC.Thirty-four healthy Japanese adults were fed 68 mL of EOC or control food, followed by 200 g of cooked rice. Blood glucose and plasma insulin levels were measured at 30, 45, 60, 90, and 120 min after the participants ate cooked rice. The trial had a randomized, double-blind, crossover, placebo-controlled design.The ingestion of EOC induced an increase in the maximum blood concentration (Cmax) of insulin and shortened the time required to reach the maximum blood concentration following rice consumption. Ingestion of the test beverage resulted in a significantly higher insulinogenic index than that obtained after ingestion of the control beverage. No side effects were observed in this study. Mechanistic experiments revealed that EOC stimulated significant (p0.05) secretion of GLP-1 from NCI-H716 human intestinal L cells at 0.1, 1, and 10 mg/mL.Consuming EOC when eating rice supports pancreatic function. Daily consumption of EOC could elevate the early-phase insulin response; therefore, it could prevent diabetes in Asians with low insulin secretion.

Type I X-ray bursts are thermonuclear explosions on the neutron star (NS) surface caused by mass accretion from a companion star. Observations of X-ray bursts provide valuable information on X-ray binary systems, e.g., binary parameters, the chemical composition of accreted matter, and the nuclear equation of state (EOS) of NSs. There have been several theoretical studies to constrain the physics of X-ray bursters. However, they have mainly focused on the burning layers above the solid crust of the NS, which brings up issues of the treatment of NS gravitation and internal energy. In this study, focusing on the microphysics inside NSs, we calculate a series of X-ray bursts using a general-relativistic stellar-evolution code with several NS EOSs. We compare the X-ray-burst models with the burst parameters of a clocked burster associated with GS 1826-24. We find a monotonic correlation between the NS radius and the light-curve profile. A larger radius shows a higher recurrence time and a large peak luminosity. In contrast, the dependence of light curves on the NS mass becomes more complicated, where the neutrino cooling suppresses the efficiency of nuclear ignition. We also constrain the EOS and mass of GS 1826-24, i.e., stiffer EOSs, corresponding to larger NS radii, are not preferred due to too-high peak luminosity. The EOS and the cooling and heating of NSs are important to discuss the theoretical and observational properties of X-ray bursts., 19 pages, 16 figures, 3 tables, updated to match published version (ApJ)

Currently, preoperative chemotherapy is usually done for advanced esophageal cancer according to guidelines. It is still difficult to predict the effect of chemotherapy before the chemotherapy. If the effect would be poor, the patient may miss the possibility of treatment. We have been examining the possibility of predicting the chemotherapy effect based on test results before and during chemotherapy. In this study we used artificial intelligence to predict the effect of chemotherapy. Methods 80 patients who underwent preoperative chemotherapy for esophageal cancer in our department from 2012 to 2019. We predict the chemotherapy effect according to age, sex, type of chemotherapy (FP/DCF), number of chemotherapy, T, M, N, blood examination results before chemotherapy as WBC, neutrophil count, lymphocyte count, hemoglobin, platelets, total protein, Albumin, CRP, IgG, IgA, IgM, IL6, creatinine, lowest WBC, neutrophil and lymphocyte count, during chemotherapy. The effect of chemotherapy was classified: CR, PR, and PD. Prediction were performed using MatLab R2019b classification learner and Neural Net Pattern Recognition. Results The actual effect was CR/PR/SD/PD = 0/33/42/5 cases. The correct answer rate was 66.3% for the optimized tree model, 66.3% for the optimized Naïve Bayesian model, 67.5% for the optimized SVM model, and 56.3% for the optimized ensemble model. With optimized SVM, the sensitivity to predict PD was 20%, specificity was 94.5%, and AUC was 0.83. Moreover, the sensitivity to predict PR was 75.8%, and the specificity was 76.6%. With Neural Net Pattern Recognition, the correct answer rate was 90%, and the sensitivity to predict PD was 20%, specificity was 94.7%. Conclusion In this study, Neural Net Pattern Recognition as a deep learning model could predict the effect of preoperative chemotherapy more accurately than that of classification learner. The poor prediction of PD was due to the small number of teacher models, and the prediction of PR with many teacher models was more accurate. We will add more teacher models, and establish a prediction model that can be used clinically for both sensitivity and specificity.

Albumin and globulin make up the majority of serum proteins and are strongly involved in inflammation. In recent years, reports on cancer and inflammation have been scattered, and there are reports indicating that the albumin / globulin ratio (A/G ratio) may be a predictor of prognosis in patients with cancer. Here, we examined the A/G ratio and clinicopathological factors in curative cases of esophageal cancer. Methods A retrospective study was conducted on 122 patients who underwent radical surgery for esophageal cancer in our department from January 2013 to December 2017. We analyzed the correlation between A/G ratio and blood biochemical test values, and the relationship between postoperative complications and prognosis. With respect to prognosis, the cut-off value was set to 1.6 from the ROC curve, and divided into a high-value group and a low-value group, and comparatively examined. Results There were 106 males and 16 females. The median age at surgery was 69 years. Neoadjuvant chemotherapy was performed in 65 patients. A negative correlation was found between the A/G ratio and inflammatory markers. On the other hand, a positive correlation was observed between the A/G ratio and the value of a marker for nutritional indicators. In the prognostic study, the low-value group had a significantly worse prognosis than the high-value group. The group with an A/G ratio of less than 1.6 after chemotherapy had a poor prognosis. The A/G ratio was lower in the group with pneumonia after surgery. Conclusion The A/G ratio reflects the preoperative inflammatory response and nutritional status, suggesting that it is a useful factor for predicting postoperative complications and prognosis in patients with curative esophageal cancer.

Background. The presence of patent foramen ovale (PFO) has been linked to many illness, including cryptogenic stroke, transient ischemic attack, migraine, platypnea-orthodeoxia syndrome and decompression sickness in scuba divers. Transesophageal echocardiography is the gold standard technique for the visualization of atrial septal anatomy, but it is a secondary level exam, not always available, with additional associated costs and not completely free from procedural risks. Standard transthoracic echocardiography (TTE) has a too low sensitivity for PFO screening. Purpose. The aim of the study was to assess the role of TTE associated with agitated saline contrast injection (contrast-TTE) as a gatekeeper for the identification of PFO in a large cohort of patients undergoing selection for percutaneous closure. Methods. A total of 200 patients undergoing a diagnostic work-up for the identification of PFO was imaged by contrast-TTE at rest and after provocative maneuvers (PM: Valsalva in all cases). Contrast TTE was graded from 0 to 4 on the bases of bubbles counting (0: no bubbles; 1: 30 bubbles; 4: complete LV opacification). PFO closure was performed after a consensual clinical decision by the cardiologist and the neurologist taking into account comprehensive imaging, clinical evaluation and thrombophilia screening. PFO closure was always monitored by intracardiac echocardiography. Results. At baseline contrast TTE was positive (≥2) in 34 patients (17%) while contrast TTE with PM was positive in 94 cases (47%). 27 out of 200 patients (14%) had an interatrial septal aneurysms. PFO closure was performed in 34 cases (17%). All of these had severe right-to-left shunting (≥3) at contrast TTE and 9 cases had also an interatrial septal aneurysms. The procedure was aborted in only 1 patient due to a complex defect anatomy. Conclusion. Contrast TTE with PM may be not only considered an accurate tool for the detection of PFO but may be also inserted in the diagnostic work- up as a primary gatekeeper for percutaneous closure. Severe shunting at contrast TTE influences final decision making in a large cohort of cases undergoing screening for PFO closure.

Purpose Papillary muscle ischemia (PMI) is caused by micro-vessels' occlusion in the broad endocardium because papillary muscle perfusion is supply from micro-vessels of peripheral coronary arteries and is easy to fail by the increase in peripheral vascular resistance. However, the clinical significant is not understood because PMI could not be detected by existing perfusion imaging such as SPECT and MRI. We propose the detection method of PMI using 13N-ammonia PET (NH3-PET), and investigate the association with the global myocardial flow reserve (Global-MFR) reflecting coronary microvascular dysfunction. Methods Data of adenosine-stress NH3-PET for consecutive 260 patients with coronary artery disease (CAD) or suspected CAD was retrospectively analyzed. Using high-resolution cine imaging derived from NH3-PET, PMI was defined as the absence of the PM accumulation at stress conditions. Myocardial flow was generated from the time activity curve of left ventricle input and myocardial uptake using 3-compartment model and the first 2 minutes' dataset of list mode images. Global-MFR was calculated by stress to rest flow ratio. Summed stress score (SSS) was used as an estimate of the extent of myocardial ischemia. 150 out of 260 patients (58%) with SSS ≥4 or with the past history of coronary artery diseases were classified as ischemic group, and 110 patients (42%) with SSS Results PMI was seen in 68 of 260 patients (26.6%). The frequency of PMI was higher in the ischemic group than the non-ischemic group (37.8% vs. 10.1%, p Typical case of PMI Conclusion High-resolution cine imaging derived from NH3-PET makes it possible to detect PMI in about a quarter of patients with CAD or suspected CAD. PMI associates with reduced Global-MFR regardless of the presence of myocardial ischemia, suggesting that PMI is an important sign of early ischemia confined to the papillary muscle or the broad microvascular injury.

We report the clinical features of a patient with hereditary transthyretin (ATTR) amyloidosis associated with a novel mutation (Y114S, p.Y134S). A 65-year-old Japanese man was admitted to our hospital after a 3-year history of progressive dyspnea on exertion. Five years previously, he presented dysesthesia in both hands caused by carpal tunnel syndrome. A genetic analysis revealed a base pair substitution of adenine to cytosine in the second codon of exon 4, residue 114, in the TTR gene (c.401A>C). The clinical characteristics were progressive cardiomyopathy with a poor vital prognosis, late onset, sporadic case, bilateral carpal tunnel syndrome, hypothyroidism, and small fiber neuropathy.

Alternative oxidase (AOX) catalyzes the four-electron reduction of dioxygen to water as an additional terminal oxidase, and the catalytic reaction is critical for the parasite to survive in its bloodstream form. Recently, the X-ray crystal structure of trypanosome alternative oxidase (TAO) complexed with ferulenol was reported and the molecular structure of the non-heme diiron center was determined. The binding of O2 was a unique side-on type compared to other iron proteins. In order to characterize the O2 binding state of TAO, the O2 binding states were searched at a quantum mechanics/molecular mechanics (QM/MM) theoretical level in the present study. We found that the most stable O2 binding state is the end-on type, and the binding states of the side-on type are higher in energy. Based on the binding energies and electronic structure analyses, O2 binds very weakly to the TAO iron center (ΔE =6.7 kcal mol−1) in the electronic state of Fe(II)…O O, not in the suggested charge transferred state such as the superoxide state (Fe(III) O O· –) as seen in hemerythrin. Coordination of other ligands such as water, Cl−, CN−, CO, N3− and H2O2 was also examined, and H2O2 was found to bind most strongly to the Fe(II) site by ΔE = 14.0 kcal mol−1. This was confirmed experimentally through the measurement of ubiquinol oxidase activity of TAO and Cryptosporidium parvum AOX which was found to be inhibited by H2O2 in a dose-dependent and reversible manner.

Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi). It was originally a Latin American endemic health problem, but now is expanding worldwide as a result of increasing migration. The currently available drugs for Chagas disease, benznidazole and nifurtimox, provoke severe adverse effects, and thus the development of new drugs is urgently required. Ubiquinone (UQ) is essential for respiratory chain and redox balance in trypanosomatid protozoans, therefore we aimed to provide evidence that inhibitors of the UQ biosynthesis have trypanocidal activities. In this study, inhibitors of the human COQ7, a key enzyme of the UQ synthesis, were tested for their trypanocidal activities because they were expected to cross-react and inhibit trypanosomal COQ7 due to their genetic homology. We show the trypanocidal activity of a newly found human COQ7 inhibitor, an oxazinoquinoline derivative. The structurally similar compounds were selected from the commercially available compounds by 2D and 3D ligand-based similarity searches. Among 38 compounds selected, 12 compounds with the oxazinoquinoline structure inhibited significantly the growth of epimastigotes of T. cruzi. The most effective 3 compounds also showed the significant antitrypanosomal activity against the mammalian stage of T. cruzi at lower concentrations than benznidazole, a commonly used drug today. We found that epimastigotes treated with the inhibitor contained reduced levels of UQ9. Further, the growth of epimastigotes treated with the inhibitors was partially rescued by UQ10 supplementation to the culture medium. These results suggest that the antitrypanosomal mechanism of the oxazinoquinoline derivatives results from inhibition of the trypanosomal UQ synthesis leading to a shortage of the UQ pool. Our data indicate that the UQ synthesis pathway of T. cruzi is a promising drug target for Chagas disease.

Introduction V117957 is a recently described investigational oral, potent, and selective nociceptin/orphanin-FQ peptide (NOP) receptor partial agonist which was previously evaluated in ~200 healthy subjects. Its satisfactory safety/tolerability profile has been established with the top doses at 30mg following a single oral administration and 10mg once daily for 2 weeks. V117957 demonstrated favorable drug-like properties for insomnia treatment, including oral bioavailability, fast absorption, and rapid elimination. Methods A total of 52 patients with insomnia disorder have been evaluated in two separate randomized, double-blind, crossover, placebo-controlled sleep studies. Insomnia disorder was confirmed by screening polysomnography (PSG). All subjects received orally, for two consecutive nights, either V117957 10mg or placebo in Study #1 or 0.5, 1, 3, 6mg or placebo in Study #2. Efficacy was measured via PSG for the primary endpoint of sleep efficiency (SE) and secondary endpoints of sleep onset (latency to persistent sleep [LPS]) and maintenance (wakefulness after sleep onset [WASO]). Efficacy also was measured by patient diary (subjective sleep latency [sSL], subjective total sleep time [sTST], sWASO). Pharmacodynamics (PD) on next-day residual effects were also measured, including cognitive, psychomotor and mood effects. Results V117957 showed statistically significant greater sleep efficiency and less WASO in a dose-dependent manner (0.5-10 mg) and a statistically significant reduction in LPS at 10mg, as compared to placebo. V117957 at 0.5mg and 1mg exhibited next-day residual effects similar to placebo. At doses of 3mg or higher, V117957 showed dose-dependent next-day residual effects. V117957 was safe and well-tolerated across all doses tested with no serious adverse events, with somnolence being the most frequent treatment-emergent adverse event. No concerning laboratory findings and no clinically significant findings on vital signs and electrocardiograms have been attributed to V117957 in these subjects. Conclusion V117957 was safe and well-tolerated in patients with insomnia disorder. These results demonstrated that NOP receptors represent a novel mechanistic treatment for insomnia disorder and support continued evaluation of V117957. Support Funded by Shionogi and Imbrium Therapeutics, a subsidiary of Purdue Pharma L.P.

Plasmodium falciparum is an apicomplexan parasite that causes the most severe malaria in humans. Due to a lack of effective vaccines and emerging of drug resistance parasites, development of drugs with novel mechanisms of action and few side effects are imperative. To this end, ideal drug targets are those essential to parasite viability as well as absent in their mammalian hosts. The mitochondrial electron transport chain (ETC) of P. falciparum is one source of such potential targets because enzymes, such as L-malate:quinone oxidoreductase (PfMQO), in this pathway are absent humans. PfMQO catalyzes the oxidation of L-malate to oxaloacetate and the simultaneous reduction of ubiquinone to ubiquinol. It is a membrane protein, involved in three pathways (ETC, the tricarboxylic acid cycle and the fumarate cycle) and has been shown to be essential for parasite survival, at least, in the intra-erythrocytic asexual stage. These findings indicate that PfMQO would be a valuable drug target for development of antimalarial with novel mechanism of action. Up to this point in time, difficulty in producing active recombinant mitochondrial MQO has hampered biochemical characterization and targeted drug discovery with MQO. Here we report for the first time recombinant PfMQO overexpressed in bacterial membrane and the first biochemical study. Furthermore, about 113 compounds, consisting of ubiquinone binding site inhibitors and antiparasitic agents, were screened resulting in the discovery of ferulenol as a potent PfMQO inhibitor. Finally, ferulenol was shown to inhibit parasite growth and showed strong synergism in combination with atovaquone, a well-described anti-malarial and bc1 complex inhibitor.

SUMMARYUsing a newly developed rapid test, an outbreak of human metapneumovirus (HMPV) infection in a long-term care facility was detected within only 2 days after the onset of symptoms in a putative index case. The outbreak was almost under control within 8 days mainly by zoning patients, with the exception of two cases of HMPV that were diagnosed 16 and 17 days after the onset of the outbreak. According to an immunological diagnosis as well as the rapid test, it was eventually proven that 18 patients had HMPV infections. We suspected that even asymptomatic residents, who had not been completely separated from the facility population, were a source of infection. That suggested that all asymptomatic residents should be tested and that the separation of the infected patients should be absolute, if an outbreak of HMPV infection is suspected in such a facility.

To calculate the iron loss in an electric machine accurately, the anomalous eddy current loss generated by domain wall motion should be considered. A simple numeric modeling of anomalous eddy current loss by modifying the conductivity of steel plates is sometimes used. However, investigation on this method in detail has not been carried out. In this paper, this method is investigated in two iron-loss models neglecting and including the skin effect and then applied to the loss calculation of various kinds of nonoriented and oriented silicon steel plates. Then, the dependence of the modified conductivity on the amplitude and frequency of the induction magnetic field for each material is obtained and the appropriate iron-loss model and method for modifying the conductivity are proposed for the nonoriented and oriented silicon steel plates. The calculated iron losses using the appropriate iron-loss model with modified conductivity are compared with the measured data. It is clarified that for nonoriented materials, the iron-loss model including the skin effect with constant modified conductivity shows good agreement. And for oriented materials, the model neglecting the skin effect with the modified conductivity depending on frequency is better.

The Coulomb dissociation of the proton-rich nuclei 31 Cl was studied experimentally using 31 Cl beams at 58 MeV/nucleon with a lead target. The relative energy between the reaction products, 30 S and proton, was obtained. The first excited state in 31 Cl was observed which is relevant to the resonant capture of stellar 30 S (p,γ)31 Cl reaction.

Ultrahigh-definition television (UHDTV) is the next-generation ultrahigh-resolution video system with more than 4000 lines, and 7680 horizontal pixels × 4320 vertical lines at 60 f/s (frames per second) in video format. We propose a method of converting high-quality UHDTV video to digital cinema video that is 3840 horizontal pixels × 2160 vertical lines at 24 f/s. Here, it is important to detect motion vectors extremely accurately to convert the frame rate. We introduced two new algorithms to increase the accuracy of detecting motion vectors. First, we introduced a method of interpolation frames using 1/2 block-shift bi-directional motion estimation by expanding the time axis. The experimental results revealed that our new method produced higher quality video images than conventional methods of video conversion using forward-directional and overlapped block bi-directional motion estimation. Next, we focused on Bayer pattern sampling in existing UHDTV, and introduced a motion-compensated method of interpolation where the first algorithm utilizes the high-frequency components from green signals. The experimental results demonstrated that our proposed method achieves higher quality video conversions than conventional methods using only the first algorithm for motion-compensated interpolation, linear interpolation, and 5:2 frame skipping.

FMS-like tyrosine kinase-3 (FLT3) is a new therapeutic target for acute myelocytic leukemia (AML), because FLT3 mutations are the most common genetic alterations in AML and are directly related to leukemogenesis. We studied cytotoxic interactions of a FLT3 inhibitor, PKC412, with eight conventional antileukemic agents (cytarabine, doxorubicin, idarubicin, mitoxantrone, etoposide, 4-hydroperoxy-cyclophosphamide, methotrexate and vincristine) using three leukemia cell lines carrying FLT3 mutations (MOLM13, MOLM14 and MV4-11) and five leukemia cell lines without FLT3 mutations (KOPB-26, THP-1, BALL-1, KG-1 and U937). PKC412 showed synergistic effects with all agents studied except methotrexate for FLT3-mutated cell lines in isobologram analysis. In contrast, PKC412 was rather antagonistic to most drugs, except for 4-hydroperoxy-cyclophosphamide and vincristine, in leukemia cell lines without FLT3 mutations. Cell-cycle analysis revealed that PKC412 induced G1 arrest in leukemia cell lines carrying FLT3 mutations, whereas it arrested cells in G2/M phase in the absence of FLT3 mutations, which may underlie the divergent cytotoxic interactions. These results suggest that the simultaneous administration of PKC412 and other agents except methotrexate is clinically effective against FLT3 mutation-positive leukemias, whereas it would be of little benefit for FLT3 mutation-negative leukemias. Our findings may be of help for the design of PKC412-based combination chemotherapy.

The present paper carried out the numerical simulation and experimental study of the thermofluid fields induced by a pen-like atmospheric nonthermal plasma torch, which is a very simple device to produce atmospheric plasma and has been successfully applied for surface treatment to improve the hydrophilic properties of plastic film and polyethylene. The device consists of a small cylindrical stainless steel pipe with 6.5 mm diameter and 170 mm length inserted into a ceramic tube as the inner electrode. A ring outer electrode made of stainless steel is fixed at near the edge of the ceramic. The 13.56 MHz RF power was applied between the two electrodes to produce a surface discharge. The power into the torch is 60 W. The driving gas is argon and the flow rate varies in the range of 3–12 L min −1 . Fundamental research results describing the major features of the flow fields induced by the plasma torch are provided in the present study. The stress is laid on the investigation of the influence of gas flow rate, which is one of important operation conditions, on the flow fields excited by the plasma torch. The principal results show that as the power input is fixed the increase of the gas flow rate will reduce the plasma temperature. The plasma penetration length stretching toward the atmospheric surroundings is also found to be closely related with the gas flow rate. Experimental confirmation by measuring the rotational temperature using optical spectroscopic method has been carried out, and a reasonable agreement between calculation and experiment has been obtained. These results provide fundamental understanding of the thermofluid fields induced by a pen-like atmospheric plasma torch, and also build up a basic predictive capability by numerical simulations to perform the further detailed investigation for practical applications in future.

Summary 1 Although metabolic resource losses are maintained at low rates during diapause, the accumulation of losses over a long period negatively affects organisms with prolonged diapause usually extending beyond 1 year. The seed-predatory weevil Exechesops leucopis (Jordan) (Coleoptera: Anthribidae) enters winter diapause at the final-instar larval stage within seeds of Styrax japonica Sieb. et Zucc. (Styracaceae) at a density of one larva per seed. After diapause, larvae pupate within the seeds and then emerge as adults. 2 The adult emergence pattern of a single cohort of E. leucopis was monitored for 5 years under seminatural conditions in the laboratory. The duration of diapause varied from 1 year (single winter) to 4 years (four winters). Adults that emerged after 1 year were smaller than those that emerged after 2 years or more. When temperature was not decreased experimentally in winter, no adults emerged in the following season. 3 Metabolic resource losses during diapause were examined by comparing adult body sizes between controls and groups in which emergence was delayed by 1 year under manipulated winter temperature regimes. Adults that emerged after an additional year in the larval stage were smaller than those in the control group. Moreover, the rates of reduction in body size as a consequence of diapause being extended experimentally were greater in smaller individuals. Thus smaller individuals have disadvantages in longer diapause, suggesting that weevils may vary the duration of diapause depending on individual body size. 4 Exechesops leucopis shows sexual dimorphism in the degree of eye protrusion. Eyestalk length affects male fitness through intrasexual selection. The duration of diapause affected the length of the eyestalks: when an additional year was spent in diapause, eyestalk length was nearly maintained in larger males but was greatly decreased in smaller males. In all females eyestalk length decreased according to the duration of diapause.

We developed a new float polishing technique for use as a non-contact polishing tool utilizing a magnetic compound fluid (MCF). MCF has been developed by one of the present authors for the purpose of magnetically and hydrodynamically improving intelligent or smart fluid. The float polishing succeeded experimentally during wide clearance range between the polishing tool and the polished material surface of 0.1–0.3 mm. The polishing effect changes according to the magnetic field strength. The cause is due to the possibility of polishing a material using magnetic clusters involved in MCF as a polishing tool. It is also useful to substitute the buffer material for the polishing pad in the case of MCF float polishing.

Human leukemia-lymphoma (LL) cell lines represent an extremely important resource for research in a variety of fields and disciplines. As the cell lines are used as in vitro model systems in lieu of primary cell material, it is crucial that the cells in the culture flasks faithfully correspond to the purported objects of study. Obviously, proper authentication of cell line derivation and precise characterization are indispensable requirements to use as model systems. A number of studies has shown an unacceptable level of LL cell lines to be false. We present here the results of authenticating a comprehensively large sample (n = 550) of LL cell lines mainly by DNA fingerprinting and cytogenetic evaluation. Surprisingly, near-identical incidences (ca 15%) of false cell lines were observed among cell lines obtained directly from original investigators (59/395: 14.9%) and from secondary sources (23/155: 14.8%) implying that most cross-contamination is perpetrated by originators, presumably during establishment. By comparing our data with those published, we were further able to subclassify the false cell lines as (1) virtual: cross-contaminated with and unretrievably overgrown by other cell lines during initiation, never enjoying independent existence; (2) misidentified: cross-contaminated subsequent to establishment so that an original prototype may still exist; or (3) misclassified: unwittingly established from an unintended (often normal) cell type. Prolific classic leukemia cell lines were found to account for the majority of cross-contaminations, eg CCRF-CEM, HL-60, JURKAT, K-562 and U-937. We discuss the impact of cross-contaminations on scientific research, the reluctance of scientists to address the problem, and consider possible solutions. These findings provide a rationale for mandating the procurement of reputably sourced LL cell lines and their regular authentication thereafter.

From MnZn ferrite ("6H20" of FDK production), cores having grain size of about 8/spl sim/10 /spl mu/m were produced by controlling the calcination temperature, after-calcination milling time, and sintering conditions. The ferrite powder production conditions and core microstructure were examined to determine their effects on the magnetic properties and mechanical strength of MnZn ferrite cores. A tendency of core loss to decline with a decrease in grain size was confirmed. Strength increased also with a decrease in grain size. Thus, a relation similar to that between strength and fracture toughness in the equation of Griffith-Irwin was noted. By these findings, it has become possible to produce MnZn ferrite cores with lower loss and greater strength.

We present the establishment of a natural killer (NK) leukemia cell line, designated KHYG-1, from the blood of a patient with aggressive NK leukemia, which both possessed the same p53 point mutation. The immunophenotype of the primary leukemia cells was CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16+, CD56+, CD57+ and HLA-DR+. A new cell line (KHYG-1) was established by culturing peripheral leukemia cells with 100 units of recombinant interleukin (IL)-2. The KHYG-1 cells showed LGL morphology with a large nucleus, coarse chromatin, conspicuous nucleoli, and abundant basophilic cytoplasm with many azurophilic granules. The immunophenotype of KHYG-1 cells was CD1-, CD2+, surface CD3-, cytoplasmic CD3epsilon+, CD7+, CD8alphaalpha+, CD16-, CD25-, CD33+, CD34-, CD56+, CD57-, CD122+, CD132+, and TdT-. Southern blot analysis of these cells revealed a normal germline configuration for the beta, delta, and gamma chains of the T cell receptor and the immunoglobulin heavy-chain genes. Moreover, the KHYG-1 cells displayed NK cell activity and IL-2-dependent proliferation in vitro, suggesting that they are of NK cell origin. Epstein-Barr virus (EBV) DNA was not detected in KHYG-1 cells by Southern blot analysis with a terminal repeat probe from an EBV genome. A point mutation in exon 7 of the p53 gene was detected in the KHYG-1 cells by PCR/SSCP analysis, and direct sequencing revealed the conversion of C to T at nucleotide 877 in codon 248. The primary leukemia cells also carried the same point mutation. Although the precise role of the p53 point mutation in leukemogenesis remains to be clarified, the establishment of an NK leukemia cell line with a p53 point mutation could be valuable in the study of leukemogenesis.

If a super-large core with a groove is molded with an axial molding press replacing the conventional die set, uneven density distribution occurs in the core because the molding pressure considerably converges on the groove of the core. Since this induces the residual stress in the groove to be released during the sintering process, it is difficult with the conventional die set to obtain the necessary dimensional precision and satisfactory magnetic characteristics. We devised a die mechanism capable of solving these problems through the reduction of converging pressure on the groove. This new die mechanism improves the moldability and magnetic characteristics of super-large ferrite cores through the uniform distribution of density and magnetic characteristics.

To contribute to the size reduction of electromagnetic devices, a multipole magnetizing method for Nd-Fe-B isotropic bonded magnets using a heating system without any magnetizing power supply was examined. After rapidly heating above their Curie temperature, the magnets are magnetized during cooling in the presence of a magnetic field generated by a set of Sm-Co permanent magnets. The level of magnetization can be tailored by variation of the final temperature to which the magnets are cooled in the presence of the magnetic field. Due to the heating process, the magnets show excellent thermal stability.

The microstructure of Mn-Zn ferrite on MoO3 addition was studied. It was found that although MoO3 addition expanded the diameters of crystalline grains, it also promoted porosity, thereby impeding grain growth. When the amount of MoO3 was increased, the grain diameter expanded, peaked, and then gradually declined under the influence of the porosity. It is important to note that it forms a fine microstructure that has large grains and a low level of porosity. We studied the effect of the sintering parameters−sintering time, heating rate, and oxygen partial pressure−on the microstructure of the ferrite. As a result, we obtained a high-initial-permeability Mn-Zn ferrite with μiac = 24,400.

We describe two new human leukemia cell lines, MOLM-13 and MOLM-14, established from the peripheral blood of a patient at relapse of acute monocytic leukemia, FAB M5a, which had evolved from myelodysplastic syndrome (MDS). Both cell lines express monocyte-specific esterase (MSE) and MLL-AF9 fusion mRNA. Gene fusion is associated with a minute chromosomal insertion, ins(11;9)(q23;p22p23). MOLM-13 and MOLM-14 are the first cell lines with, and represent the third reported case of, MLL gene rearrangement arising via chromosomal insertion. Both cell lines carry trisomy 8 which was also present during the MDS phase, as well as the most frequent trisomies associated with t(9;11), ie, +6, +13, +19 variously present in different subclones. Despite having these features in common, differences in antigen expression were noted between the two cell lines: that of MOLM-13 being CD34+, CD13-, CD14-, CD15+, CD33+; whereas MOLM-14 was CD4+, CD13+, CD14+, CD15+, CD33+. Differentiation to macrophage-like morphology could be induced in both cell lines after stimulation with INF-gamma alone, or in combination with TNF-alpha, which treatment also induced or upregulated, expression of certain myelomonocyte-associated antigens, including CD13, CD14, CD15, CD64, CD65 and CD87. Together, these data confirm that both cell lines are likely to be novel in vitro models for studying monocytic differentiation and leukemogenesis.

The PotD protein from Escherichia coli is one of the components of the polyamine transport system present in the periplasm. This component specifically binds either spermidine or putrescine. The crystal structure of the E. coli PotD protein complexed with spermidine was solved at 1.8 A resolution and revealed the detailed substrate-binding mechanism. The structure provided the detailed conformation of the bound spermidine. Furthermore, a water molecule was clearly identified in the binding site lying between the amino-terminal domain and carboxyl-terminal domain. Through this water molecule, the bound spermidine molecule forms two hydrogen bonds with Thr 35 and Ser 211. Another periplasmic component of polyamine transport, the PotF protein, exhibits 35% sequence identity with the PotD protein, and it binds only putrescine, not spermidine. To understand these different substrate specificities, model building of the PotF protein was performed on the basis of the PotD crystal structure. The hypothetical structure suggests that the side chain of Lys 349 in PotF inhibits spermidine binding because of the repulsive forces between its positive charge and spermidine. On the other hand, putrescine could be accommodated into the binding site without any steric hindrance because its molecular size is much smaller than that of spermidine, and the positively charged amino group is relatively distant from Lys 349.