Mitsubishi Heavy Industries (Italy)

PURPOSE: Genomic instability is a hallmark of cancer and targeting DNA damage response (DDR) is emerging as a promising therapeutic strategy in different solid tumors. The effectiveness of targeting DDR in colorectal cancer has not been extensively explored. EXPERIMENTAL DESIGN: We challenged 112 cell models recapitulating the genomic landscape of metastatic colorectal cancer with ATM, ATR, CHK1, WEE1, and DNA-PK inhibitors, in parallel with chemotherapeutic agents. We focused then on ATR inhibitors (ATRi) and, to identify putative biomarkers of response and resistance, we analyzed at multiple levels colorectal cancer models highly sensitive or resistant to these drugs. RESULTS: We found that around 30% of colorectal cancers, including those carrying KRAS and BRAF mutations and unresponsive to targeted agents, are sensitive to at least one DDR inhibitor. By investigating potential biomarkers of response to ATRi, we found that ATRi-sensitive cells displayed reduced phospho-RPA32 foci at basal level, while ATRi-resistant cells showed increased RAD51 foci formation in response to replication stress. Lack of ATM and RAD51C expression was associated with ATRi sensitivity. Analysis of mutational signatures and HRDetect score identified a subgroup of ATRi-sensitive models. Organoids derived from patients with metastatic colorectal cancer recapitulated findings obtained in cell lines. CONCLUSIONS: In conclusion, a subset of colorectal cancers refractory to current therapies could benefit from inhibitors of DDR pathways and replication stress. A composite biomarker involving phospho-RPA32 and RAD51 foci, lack of ATM and RAD51C expression, as well as analysis of mutational signatures could be used to identify colorectal cancers likely to respond to ATRi.

IMPACT is the name of a program and of specific simulation software, which will perform full-scope and detailed calculations of various phenomena in a nuclear power plant for a wide range of event scenarios. The four years of the IMPACT project Phase 1 have been completed, and each analysis module of the prototype version of the severe accident analysis code SAMPSON has been developed and verified by comparison with separate-effect test data. Verification of the integrated code with combinations of up to 11 analysis modules has been conducted, with the Analysis Control Module, to demonstrate the code capability and integrity. A 10-inch cold leg failure Loss of Coolant Accident in the Surry Plant was the assumed initiating event. The system analysis was divided into two cases; one was an in-vessel retention analysis when gap cooling was effective, the other was an analysis of phenomena when the event was extended to ex-vessel due to the reactor pressure vessel failure when gap cooling was not sufficient. Using the Analysis Control Module to select and execute adequate combinations of the various analysis modules dynamically according to the progression of plant phenomena and to control parallel processing, the goal of integrated calculations by SAMPSON with multiple analysis modules executing in parallel was achieved.

Journal Article The use of bradykinin-induced effects in rats as an assay for analgesic drugs Get access G Deffenu, G Deffenu Farmitalia Research Institute. Via dei Gracchi, 35 Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar L Pegrassi, L Pegrassi Farmitalia Research Institute. Via dei Gracchi, 35 Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar B Lumachi B Lumachi Farmitalia Research Institute. Via dei Gracchi, 35 Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 18, Issue 2, February 1966, Page 135, https://doi.org/10.1111/j.2042-7158.1966.tb07838.x Published: 12 April 2011 Article history Received: 14 December 1965 Published: 12 April 2011

Abstract Two types of anionic surfactants and one type of nonionic surfactant were investigated in order to clarify their roles and behaviors in a highly loaded coal–water slurry (CWM) of high coal concentration. Both saturated adsorption of the surfactant on coal particles and its presence in water were found to be necessary to prepare a practical CWM. The adsorption isotherms of the surfactants were described using the “Langmuir” equation. Each surfactant had a characteristic value of saturated adsorption. An estimation method of the required amount of the surfactant to prepare a practical CWM was proposed. The zeta potential of the CWM was found to vary with the coal concentration, and to be controlable using surfactants, thus failing to be a proper measure of the CWM at high coal concentrations.

In relation to thermal-hydraulic design of the solid-target system of a spallation neutron source, heat transfer experiments were performed to obtain experimental data systematically on heat transfer coefficient and critical heat flux (CHF) for vertical upward and horizontal flows in thin rectangular channels simulating a coolant channel of the proposed spallation neutron source.Single phase heat transfer coefficients and CHF data for rectangular channels with 1.0 mm gap (L h /D e =50.2) with mass flux of 10-7,500 kg/m 2 s, single phase and two phase heat transfer coefficients, onset of nucleate boiling (ONB) and CHF data for 1.5 mm gap (L h /D e =33.9) with mass flux of 10-5,000 kg/m 2 s were obtained in the atmospheric pressure with inlet subcooling of 40-80 K. Finally, thermal-hydraulic correlations that could be used for design calculations were proposed based on the obtained data.

BACKGROUND: The traditional assessment tools for dementia, such as the MMSE, have only limited ability to follow subjects with severe dementia because they show a floor effect. Specific observational and performance-based instruments were recently developed. OBJECTIVES: To directly compare an observational scale to a performance-based instrument in moderate to severe dementia. METHODS: We compared a slightly modified version of the performance-based Test for Severe Impairment (mTSI) to the observer-based Bedford Alzheimer Nursing Severity Scale (BANS-S). Both scales were administered, together with the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating scale (CDR), to a nursing-home sample of 130 women suffering from different types of dementia (CDR range:1-4; MMSE range:0-18), defined according to DSM-IV criteria. Mean age was 86.9 +/- 7.3 years and mean education was 2.7 +/- 1.1 years. RESULTS: The BANS-S could be applied to all patients, the mTSI to 87 subjects (66.9%). Mean mTSI score decreased progressively from CDR stage 2 to CDR stage 4, whereas no difference was detectable between CDR stages 1 and 2. By contrast, the BANS-S was not significantly different for CDR stages 1 to 3, and the mean BANS-S score worsened only in CDR stage 4. Results were similar for AD and non AD dementia. Both scales were independent from age and education and their test-retest and inter-rater reliabilities were satisfactory. CONCLUSION: The mTSI looks promising in the moderate-to-severe range, whereas the BANS-S seems more useful in the very late stage of dementia. However, neither scale was optimal and additional instruments should be tested in future studies.

To evaluate barrier protective properties of Rhinosectan® spray, a medical device containing xyloglucan, on nasal epithelial cells (MucilAir). MucilAir-Nasal, a three-dimensional organotypic (with different cell types) airway tissue model, was treated with the medical device Rhinosectan® (30 µL) or with controls (Rhinocort—budesonide—or saline solution). The protective barrier effects of Rhinosectan® were evaluated by: TEER (trans-epithelial electrical resistance) (preservation of tight junctions), Lucifer Yellow assay (preservation of paracellular flux) and confocal immunofluorescence microscopy (localization of tight junction proteins). Exposure of MucilAir with Rhinosectan® protected cell tight junctions (increases in TEER of 13.1% vs −6.3% with saline solution after 1 h of exposure), and preserved the paracellular flux, even after exposure with pro-inflammatory compounds (TNF-α and LPS from Pseudomonas aeruginosa 10). Results of confocal immunofluorescence microscopy demonstrated that, after treatment with the pro-inflammatory mixture, Rhinosectan® produced a slight relocation of zona occludens-1 in the cytosol compartment (while Rhinocort induced expression of zona-occludens-1), maintaining the localization of occludin (similarly to negative control). Results of our study indicates that Rhinosectan® creates a protective physical barrier on nasal epithelial cells in vitro, allowing the avoidance of allergens and triggering factors, thus confirming the utility of this medical device in the management of nasal respiratory diseases, as rhinitis or rhinosinusitis.

An application of novel, highly porous nonswelling resins (Synbeads) for enzymatic catalysis on solid supports is reported. These new resins combine easy handling of the beads, chemical stability, improved accessibility of proteins and higher productivity relative to swelling polymers. The present study demonstrates that the resin porosity greatly affects the efficiency in solid-phase biotransformations and that Synbead resins are valuable alternatives to swelling polymers for solid-phase chemistry and biocatalysis. The present study investigates the influence of key parameters, such as porosity and reactive functional-group density, on the reaction efficiency.

To assess the effects of Rhinosectan® spray, a medical device containing xyloglucan, on nasal ciliary function (in MucilAir™Nasal cells). MucilAir™Nasal, a three-dimensional organotypic airway tissue model (with different cell types), was treated with Rhinosectan® (30 µl) or with a control (saline solution). The effects of Rhinosectan® were evaluated at 15 and 60 min post-exposure by: measurement of the cilia beating frequency (Hz), mucin detection (Enzyme-Linked Lectin Assay—ELLA), mucociliary clearance (µm/s) and phagocytosis assay (fluorescence). Exposure of MucilAir™ to Rhinosectan® did not alter the cilia beating frequency at 15 and 60 min post-exposure (diluted and undiluted). Exposure to Rhinosectan® (undiluted) during 60 min increased mucociliary clearance (93.3 ± 2.1 µm/s vs. 80.9 ± 1.8 µm/s; p < 0.01) and phagocytic activity (1.89-fold increase) in comparison with saline solution. Moreover, a significant decrease in mucin concentration was observed after 15 min of exposure (171.4 ng/ml vs. 306.5 ng/ml; p < 0.01) and at 60 min post-treatment (242.7 ng/ml vs. 339 ng/ml; p < 0.05). The application of Rhinosectan® to nasal epithelial cells does not impair ciliary movement, enhances mucociliary clearance and facilitates phagocytosis while reducing mucin secretion, which are optimal properties for the management of rhinitis and associated conditions.

Abstract The roles and behaviors of an anionic surfactant, such as naphthalenesulfonate-formaldehyde condensate (NSF) and poly(styrenesulfonate) (PSS) in the high-loaded suspensions of the Celejon coal with low mineral content (1.2%), carbon black, kaolinite, and montmorillonite were studied. It was found that it is necessary to prepare a slurry of low-viscosity Celejon coal, carbon black and kaolinite in such a way that the surfactant is present as saturatedly adsorbed on the particles as well as being free in water. In the presence of a surfactant, high-loaded suspensions exhibited non-Newtonian fluidity without yield values in their shear-rate and shear stress relation. In contrast, neither NSF nor PSS showed any adsorption on the bentonite particles. Its suspension exhibited a non-Newtonian fluidity with the yield value, even if its concentration was low. The roles of the bentonite were confirmed by adding bentonite to the CWM of Celejon. The CWM of Taiheiyo coal which carried 4.81% montmorillonite suffered a limited coal concentration due to because of a large yield value. Sodium polycarbonate was found to be effective to reduce the yield value, allowing a high coal concentration in CWM.

Non-oxidative ethane dehydroaromatization to form aromatic hydrocarbons was investigated over various metal supported on H-ZSM-5 catalysts. Co/H-ZSM-5 prepared using an ion-exchange (IE) method exhibited high catalytic performance with a small amount of carbon deposition. Results obtained from temperature-programmed reduction and X-ray absorption fine structure spectroscopy indicate that stable Co2+ cations exist on Co/H-ZSM-5 IE during the reaction. Co2+ cations efficiently activate ethane without coke formation.

IMPACT is the name of a program and of specific simulation software, which will perform full-scope and detailed calculations of various phenomena in a nuclear power plant for a wide range of event scenarios. The four years of the IMPACT project Phase 1 have been completed, and each analysis module of the prototype version of the severe accident analysis code SAMPSON has been developed and verified by comparison with separate-effect test data. Verification of the integrated code with combinations of up to 11 analysis modules has been conducted, with the Analysis Control Module, to demonstrate the code capability and integrity. A 10-inch cold leg failure Loss of Coolant Accident in the Surry Plant was the assumed initiating event. The system analysis was divided into two cases; one was an in-vessel retention analysis when gap cooling was effective, the other was an analysis of phenomena when the event was extended to ex-vessel due to the reactor pressure vessel failure when gap cooling was not sufficient. Using the Analysis Control Module to select and execute adequate combinations of the various analysis modules dynamically according to the progression of plant phenomena and to control parallel processing, the goal of integrated calculations by SAMPSON with multiple analysis modules executing in parallel was achieved.

To realize the NOx recycle process using the vacuum pressure swing adsorption method reported previously, development experiments were carried out. Among such experiments were the removal of volatile ruthenium tetroxide from the off-gas, 23-month operation of a bench-scale apparatus and 100-day operation of a pilot plant ⅕ the size of the actual scale. After evaluation of the results for operability and durability of components under acidic conditions, this process was concluded applicable to an actual plant. Compared to the conventional NOx production method using chemical reaction, it has the great advantage of reducing largely low-level radioactive and non-radioactive sodium nitrate waste. With this conclusion, the procedure to install the process at the Rokkasho Reprocessing Plant has been commenced.

High-temperature characteristics (especially high-temperature strength and oxidation resistance) of gas pressure sintered Si3N4 ceramics using Yb2O3-SiO2 additives were evaluated. The high temperature characteristic of Si3N4 depended on the Yb2O3/SiO2 molar ratio of additives. High 1500°C bending strength of 395 MPa was obtained for sintered bodies with 10.0 mass% addition of additives with Yb2O3/SiO2 molar ratio of 1.0. Also, small weight change (13.2 g/m2) during oxidation at 1300°C for 300 h was obtained in this sintered body. This is considered to be due to the precipitation of Yb4Si2N2O7 and Yb2Si2O7 phase in the grain boundary glass phase, as induced by a crystallization process.

Abstract The behaviors and roles of anionic surfactants in highly loaded aqueous suspensions of carbon black were investigated in order to clarify how they increase the achievable concentration while maintaining the apparent viscosity of a suspension. In a suspension, organic particles and the water bound to them define the effective volume of the solid particles, which determines the relative viscosity, as formulated by the Brinkman equation. The surfactant was found to be adsorbed on the organic particles, decreasing the amount of bound water, as measured by 1H NMR. The result of the study was that a surfactant in a highly-loaded aqueous suspension plays the following three roles at the same time: (Role-1) The decrease in the bound water due to the surfactant allows an increase in the achievable solid concentration at a fixed viscosity by decreasing the effective volume fraction of solids in a suspension. (Role-2) The adsorption of the surfactant was also found to be necessary to inhibit the aggregation of dispersed particles; if, however, the amount of surfactant is insufficient, aggregation can occur even with mechanical stirring, owing to a hydrophobic interaction among the particles. (Role-3) The surfactant influences the viscosity of the suspension through the “k” factor of the Brinkman equation. Surfactants with larger molecules were found to give a larger k value, thus increasing the viscosity, probably because of their effects on the interactions between the dispersed particles.

四塩化珪素とアンモニアとの気相反応による窒化珪素合成反応を, 1050°-1500℃で行ない, 生成物の構造を, X線回折, 赤外吸収スペクトル, 化学分析, 電子顕微鏡により調べ, つぎの結果を得た.(1) 気相反応の生成物は, Si(NH)2, Si3N4H3, (SiN)2-NHのような組成をもち, 過剩のNとHとを含む非晶質物質である. 過剩のNとHの含有量は, 反応温度が高くなると小さくなる.(2) 生成物は, ほぼ球形で, 粒径が10-100mμの微粒子であった.(3) 約1400℃での加熱処理により, 生成物はNH3を放出してα-Si3N4へ結晶化する. しかし過剩のNとHの分解は非常に遅く, NH結合は熱的にかなり安定である. これに対して, 低温生成物のSi(NH2)4は, 熱処理によって比較的容易に窒化珪素へ変化する. 高温気相反応生成物の窒化珪素への変化が遅いのは, その構造の不規則性に関係していると推定される.(4) Si(CH3)4とアンモニアの反応生成物も, 四塩化珪素の場合と同様に非晶質物質であった. しかし, この場合には加熱処理により, α相に加えてβ相の窒化珪素の生成が認められた.

Neutron activation cross sections between 30 and 70 MeV were measured by the activation method using a semi-monoenergetic neutron field settled at the AVF cyclotron of the Cyclotron and Radioisotope Center(CYRIC), Tohoku University. Natural samples of N, O, Si, Na, Ca and Mg which are the major elements of water, air and soil were irradiated in this neutron field generated through the 7Li(p,n)7Be reaction by 30, 35,40, 50,60 and 70 MeV protons on thin Li target. Neutron yields were measured with the time-of-flight method using a calibrated NE213 organic liquid scintillator. From the induced activities measured with the HPGe detectors, we estimated the excitation functions of 15 cross sections.

The diffusion-theory-based nodal method is widely used in PWR core designs for reason of its high computing speed in three-dimensional calculations.The baffle/reflector (B/R) constants used in nodal calculations are usually calculated based on a one-dimensional transport calculation.However, to achieve high accuracy of assembly power prediction, two-dimensional model is needed.For this reason, the method for calculating transport equivalent diffusion constants of reflector material was developed so that the neutron currents on the material boundaries could be calculated exactly in diffusion calculations.Two-dimensional B/R constants were calculated using the transport equivalent diffusion constants in the two-dimensional diffusion calculation whose geometry reflected the actual material configuration in the reflector region.The two-dimensional B/R constants enabled us to predict assembly power within an error of 1.5% at hot full power conditions.

Abstract The roles and behaviors of two kinds of anionic surfactants were investigated in order to clarify their influence on the properties of a highly loaded coal water slurry (CWM) prepared from six kinds of coals. It was confirmed that the adsorbed surfactants on coal particles and their presence in water were both required for preparing practical CWMs of every type of coal. The ion concentrations of alkaline earth metals and protons derived from coal increased the adsorption of surfactants; the amounts of the adsorbed surfactants varied from coal to coal. A surfactant of molecular weight around 5000 was found to be preferentially adsorbed, and thus the most effective for controlling the properties of the CWM.

In order to develop and validate a procedure of creep rupture tests using miniature specimens in estimating the remaining life of fossil power plant parts, a method to make the miniature specimens was investigated first. Then the accelerated stress-rupture tests were performed on the miniature specimens to predict the remaining creep life of Cr-Mo-V, 21/4Cr-Mo and 11/4-1/2Mo steels.The results obtained are summarized as follows:(1) The miniature specimens could be produced by either only machining, or welding the grips at the ends of specimen and then machining them. The miniature specimen sized into 2mm dia.×30mm was suitable as a reduced size specimen.(2) The creep curve and rupture life of the miniature specimens tested in argon were similar to those of the conventional size specimens in air. The fracture mode of the miniature specimens was also consistent with that of the conventional size specimens.(3) On a graph of temperature vs. logtr, the creep rupture data of Cr-Mo-V, 21/4Cr-Mo and 11/4Cr-Mo steels were represented with an iso-stress line, respectively. Each iso-stress line moved parallel with the stress level. It was found that the miniature specimens could be used in the short time iso-stress creep line extrapolation method to predict the remaining creep life.(4) The present method was found to be applicable to the parts subjected to long-term service. It is considered that the creep life evaluation based on this method is very useful because of its convenience and reliability.