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• Consequence analysis for detecting indoor leak sources with the help of machine learning algorithm. • Generation of the gas leak dataset using CFD and pre-processing method. • Encoding-prediction network development for the spatiotemporal and layout-adaptive prediction of leak gas dispersion. Gas leak accident has been troublesome issues in the chemical industries. Predicting dispersion boundaries are important to make rapid and proper actions. Currently, computational fluid dynamics (CFD) are used to predict the dispersion boundaries. However, when the facility-layout of a workplace is often modified, using CFD is not desirable since it requires large computational expenses. This study proposes an encoding-prediction neural network to learn representations between dispersion of leak gas, velocity field, and facility-layouts. This network predict volume fraction field of leak gas in t + kΔt timestep by observing that data in t ∼ t + (k-1)Δt timestep. Training and test losses are decreased to 1.04 × 10−5 and 1.46 × 10−5, respectively. The network predicts dispersion of leak gas through recursive prediction scheme, the predicted results shows good agreement with ground truth. Methodology to generated various facility-layouts, and preprocessing methods to deal with skewed data are suggested. The methodology and results proposed in this study would be useful for developing the CFD surrogate model. [ABSTRACT FROM AUTHOR]

A novel concept for diesel fuel processing utilizing H 2 O 2 is suggested to obtain the high-purity H 2 required for air-independent propulsion using polymer electrolyte membrane fuel cells for use in submarines and unmanned underwater vehicles. The core components include 1) a diesel-H 2 O 2 autothermal reforming (ATR) reactor to produce H 2 -rich gas, 2) a water-gas shift (WGS) reactor to convert CO to H 2 , and 3) a H 2 separation membrane to separate only high-purity H 2 . Diesel and H 2 O 2 can easily be pressurized as they are liquids. The application of the H 2 separation membrane without a compressor in the middle of the process is thus advantageous. In this paper, the characteristics of pressurized ATR and WGS reactions are investigated according to the operating conditions. In both reactors, the methanation reaction is enhanced as the pressure increases. Then, permeation experiments with a H 2 separation membrane are performed while varying the temperature, pressure difference, and inlet gas composition. In particular, approximately 90% of the H 2 is recovered when the steam-separated rear gas of the WGS reactor is used in the H 2 separation membrane. Finally, based on the experimental results, design points are suggested for maximizing the efficiency of the diesel-H 2 O 2 fuel processor. [ABSTRACT FROM AUTHOR]

A novel technology of a diesel reformer that uses hydrogen peroxide is developed to obtain the hydrogen required for fuel cell air-independent propulsion for underwater applications, such as submarines and unmanned underwater vehicles. Diesel fuel could be a promising hydrogen source for underwater applications due to its high hydrogen density and its globally well-equipped infrastructure. An alternative oxidant, hydrogen peroxide (H 2 O 2 ), is applied to supply not only oxygen but also the water required for diesel autothermal (ATR) reforming. The proposed reformer does not require an additional heating device to supply heat for the vaporization of diesel or oxidant due to the exothermic nature of the ATR reaction and the heat of decomposition of H 2 O 2 . The effects of H 2 O 2 on diesel reforming were confirmed based on operating the engineering-scale (kW e -class) diesel-H 2 O 2 reformer. Undecomposed H 2 O 2 caused an excessively high temperature in the mixing zone and a corrosion effect in the reformer wall. To overcome these phenomena, we introduced a catalytic H 2 O 2 decomposer to fully decompose hydrogen peroxide into steam and oxygen. From this important step, we essentially eliminate side effects from undecomposed H 2 O 2 and retain a high reforming efficiency by utilizing the heat of decomposition of H 2 O 2 . [ABSTRACT FROM AUTHOR]

• Effectiveness of scrubbers to reduce explosion risk of ZrO 2 ALD by-product was evaluated. • Burn-wet scrubber makes the by-product more thermally stable. • Burn-wet scrubber treatment is to combust the organic residues remaining in the by-product. • Burn-wet scrubber was shown to be more effective at reducing the risk than dry scrubber. In processes of manufacturing semiconductors, reactive by-products (as a form of fine powder, i.e., dust) are deposited in pipes installed on post processing and exhaust systems, potentially involving a considerable explosion risk. In this study, the effectiveness of scrubber methods (e.g., dry scrubber and burn-wet scrubber) to mitigate the risk was evaluated. To this end, three by-products generated from a ZrO 2 atomic layer deposition (ALD) process were collected from semiconductor manufacturers, which were treated with different methods (i.e., no treatment, treatment using dry scrubber, and treatment using burn-wet scrubber), and their characteristics were analyzed and compared. Particle size measurements of the by-products proved that the burn-wet scrubber treatment less decreased their particle size than the dry scrubber treatment. The burn-wet scrubber treatment made the by-product thermally stable, confirmed by thermogravimetric analysis. Fourier-transform infrared spectroscopy of the by-products before and after the scrubber treatments showed that burn-wet scrubbing of the by-product decreases surface functionalities that play a role in explosion. Dust explosion testing proved that robustness of explosion of the untreated by-product is about 7 times higher than the by-product treated with the burn-wet scrubber. Based on the results of this study, it would be suggested that burn-wet scrubber is a useful treatment method to decrease the explosion risks caused by dust by-products generated from ALD in semiconductor manufacturing processes. [ABSTRACT FROM AUTHOR]

Memory streaming operations (i.e., memory-to-memory data transfer with or without simple arithmetic/logical operations) are one of the most important tasks in general embedded/mobile computer systems. In this paper, we propose a technique to accelerate memory streaming operations. The conventional way to accelerate memory streaming operations is employing direct memory access (DMA) with dedicated hardware accelerators for simple arithmetic/logical operations. In our technique, we utilize not only a hardware accelerator with DMA but also a central processing unit (CPU) to perform memory streaming operations, which improves the performance and energy efficiency of the system. We also implemented our prototype in a field-programmable gate array system-on-chip (FPGA-SoC) platform and evaluated our technique in real measurement from our prototype. From our experimental results, our technique improves memory streaming performance by 34.1–73.1% while reducing energy consumption by 29.0–45.5%. When we apply our technique to various real-world applications such as image processing, 1 × 1 convolution operations, and bias addition/scale, performances are improved by 1.1 × –2.4 ×. In addition, our technique reduces energy consumptions when performing image processing, 1 × 1 convolution, and bias addition/scale by 7.9–17.7%, 46.8–57.7%, and 41.7–58.5%, respectively. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase ( ALK ) gene rearrangements invariably develop resistance to 2 nd -generation ALK inhibitors. Lorlatinib (PF-06463922) ( 6 ) is a 3 rd -generation macrocyclic ALK-TKI that demonstrates many advantages over 2 nd -generation ALK inhibitors. Lorlatinib has demonstrated decent kinase selectivity, promising pharmacokinetic profile, selective brain-penetration and strong antiproliferative activity in several ALK/ROS1-driven tumor models. The current review describes the activity spectrum, key events from discovery to clinical applications and the evidences that lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings. [ABSTRACT FROM AUTHOR]

Abstract: It has been recognized that the friction coefficient decreases with decreasing viscosity of lubricant oil in lubrication. In general, as the viscosity of the lubricant decreases, the wear rate increases due to a decrease of load-carrying capacity of the lubricant. It has been proposed that nano particles in oil decrease the friction coefficient and wear rate. The purpose of this study is to apply oil, which has lower viscosity and is mixed with nano particles, to the compressor used in a refrigerator to decrease the friction coefficient with the same or superior load-carrying capacity. Mineral oil of 8mm2/s was used and mixed with fullerene nanoparticles of 0.1vol%. Friction coefficient was evaluated by a disk-on-disk tribotester. As a result, the friction coefficient of the nano-oil decreased by 90% in comparison with raw oil. These results lead us to the conclusion that nano-oil can contribute to improving the efficiency and reliability of the compressor. [Copyright &y& Elsevier]

Abstract: Purpose: We evaluated right atrial (RA) contractility and right ventricular (RV) diastolic function in adult patients with acquired chronic pulmonary hypertension (PH) by pulsed Tissue Doppler Imaging (TDI) and assessed their relationship with serum brain natriuretic peptide (BNP). Materials and methods: Systolic myocardial wave (Sa), early diastolic myocardial wave (Ea), and late diastolic myocardial wave (Aa) at the tricuspid annulus were recorded in 77 consecutive patients with acquired PH. Early (E) RV inflow waves were recorded from 4-chamber views. RV Aa was regarded as the parameter of RA contractility and RV E/Ea was taken as the parameter of RV diastolic function using TDI. Results: All subjects had elevated BNP (mean 188.9±244.0 pg/dl) and pulmonary arterial systolic pressure (PASP) estimated at 62.9±26.7 mm Hg. BNP levels were positively correlated with RV E/Ea, Aa and PASP (r =0.47, p <0.0001 and r =0.35, p <0.01, respectively) but negatively with Aa (r =−0.29, p <0.05). Next, all predictor variables were used in a multiple regression model with serum BNP values as dependent variables, refined to include 3 predictors: RV E/Ea, Aa, and PASP, which were all found to influence serum BNP values (p <0.0001) by the formula Y =34.1X1⁎⁎ −19.11X2⁎⁎ +2.95X3⁎ (⁎⁎ p <0.001, ⁎ p <0.01) where Y =BNP, X1=E/Ea of RV, X2=Aa, and X3=PASP (standard regression coefficients were 0.37, −0.34 and 0.34, respectively). Conclusion: Serum BNP correlates with RA contractility and RV diastolic dysfunction by RV TDI in adults with acquired PH. Increased BNP may be related to decreased RA systolic function and RV diastolic function in these patients. [Copyright &y& Elsevier]

Abstract: Purpose: We evaluated whether right ventricular (RV) diastolic dysfunction assessed by pulsed tissue Doppler imaging (TDI) predicts cardiac events in patients with chronic pulmonary thromboembolism (CPTE). Materials and methods: In 63 consecutive patients with CPTE, early diastolic myocardial velocity (Ea) at the tricuspid annulus by TDI and early diastolic tricuspid inflow (E) by conventional pulsed Doppler were obtained, and E/Ea was calculated as an indicator of RV diastolic dysfunction. Brain natriuretic peptide (BNP) and other echo parameters were also obtained. A cardiac event (rehospitalization caused by congestive heart failure or cardiac death) was the study endpoint. Incidence of cardiac events was determined over a 374±451 day follow-up period. Results: In the follow-up period twelve patients had cardiac events. We divided patients into group A with cardiac events and group B without events. E/Ea was significantly increased in group A as compared with group B (8.3±4.1 vs. 5.7±2.6, p <0.01). BNP was higher in group A than group B (221±191 vs. 121±140 mg/dl, p <0.05), and in addition E/Ea was significantly positively correlated with BNP (r=0.48, p <0.001). A logistic regression model for predicting cardiac events was constructed and E/Ea was associated with an increased incidence of cardiac events (relative risk=1.33, 95% CI 1.00–1.75). Conclusion: Elevated values of E/Ea obtained by TDI may predict cardiac events in patients with CPTE. BNP may also be a significant predictor. [Copyright &y& Elsevier]

Abstract: Purpose: To assess the effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation, we measured coronary flow velocity reserve (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy adult subjects. Materials and methods: The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy men (mean age 29.7±3.9 years, range 23–40 years). Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd, including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) as markers of oxidative stress. Results: Flavonoid-rich dark chocolate consumption significantly improved CFVR (3.38±0.49 before intake, 4.28±0.85 after intake; p <0.01), whereas non-flavonoid white chocolate consumption did not (3.28±0.49 before intake, 3.16±0.49 after intake; p =0.44). All predictor variables were used as dependent variables in a multiple regression model of the incremental change in CFVR after 2 weeks of chocolate intake. Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and heart rate (HR) significantly influenced the change of CFVR after 2 weeks of intake (p <0.01) according to the multiple regression formula: Y =1.01X 1 −0.005X 2 −0.003X 3 −0.017X 4 (Y =change in CFVR after 2 weeks of chocolate intake, X 1 =intake of dark (but not white) chocolate, X 2 =MDA-LDL, X 3 =TG, X 4 =HR). Conclusion: Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects. [Copyright &y& Elsevier]

Abstract: Purpose: It has been reported that mental stress is an independent risk factor for cardiovascular events and impairs coronary circulation. Lavender aromatherapy, one of the most popular complementary treatments, is recognized as a beneficial mental relaxation therapy. However, no study has examined the effect of this therapy on coronary circulation. We aimed to assess the effect of lavender aromatherapy on coronary circulation by measuring coronary flow velocity reserve (CFVR) with noninvasive transthoracic Doppler echocardiography (TTDE). Material and methods: We enrolled 30 young healthy men (mean age 34±4.7 years, range 24–40 years). Coronary flow velocities in the left anterior descending coronary artery were recorded by TTDE at rest and during hyperemia induced with an intravenous infusion of adenosine triphosphate (ATP). CFVR was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. CFVR was assessed at baseline and immediately after lavender aromatherapy (four drops of essential oil diluted with 20 ml of hot water and inhaled for 30 min). Simultaneously, serum cortisol was measured as a marker of stress hormones. To exclude the relaxation effects of rest, the same measurements were repeated in the same volunteers without aromatherapy as a control study. Results: CFVR measurements were obtained in all volunteers (100%). Blood pressure and heart rate responses to ATP infusion were not affected by lavender aromatherapy. Serum cortisol significantly decreased after lavender aromatherapy (8.4±3.6 to 6.3±3.3, p <0.05), but remained unchanged in controls (9.1±3.5 to 8.1±3.9, p =ns). In addition, CFVR significantly increased after lavender aromatherapy (3.8±0.87 to 4.7±0.90, p <0.001), but not in controls (3.9±0.8 to 3.9±0.8, p =ns). Conclusions: Lavender aromatherapy reduced serum cortisol and improved CFVR in healthy men. These findings suggest that lavender aromatherapy has relaxation effects and may have beneficial acute effects on coronary circulation. [Copyright &y& Elsevier]

An intermittently aerated membrane bioreactor (IAMBR) system has been developed to improve the efficiency of nutrient removal, and for the stable treatment of organic matter which is contained as suspended solid (SS) in the influent. The important operating factors of an intermittently aerated bioreactor (IABR) are sludge retention times (SRTs) and carbon/nitrogen (C/N) ratios. Because research on IAMBR is young, this paper explores the effect of SRTs and C/N ratios on these systems. For SRTs of 20, 25, 30, and 40 days, there was little difference in the removal of COD, T–N, and T–P. In comparing C/N ratios of 4.5, 7, and 10, the COD concentration in permeate with a C/N ratio of 10 was most stable, although the concentration of organic matter in the influent was high. The removal efficiencies of T–N and T–P in permeate with a C/N ratio of 10 were the highest at 92.9% and 88.9%, respectively. This implies that a C/N ratio above 10 should be maintained for a nutrient removal efficiency of approximately 90%. [Copyright &y& Elsevier]

The bromodomain and extraterminal domain (BET) family proteins recognize acetyl-lysine (K ac) at the histone tail through two tandem bromodomains, i.e., BD1 and BD2, to regulate gene expression. BET proteins are attractive therapeutic targets in cancer due to their involvement in oncogenic transcriptional activation, and bromodomains have defined K ac -binding pockets. Here, we present DW-71177 , a potent BET inhibitor that selectively interacts with BD1 and exhibits strong antileukemic activity. X-ray crystallography, isothermal titration calorimetry, and molecular dynamic studies have revealed the robust and specific binding of DW-71177 to the K ac -binding pocket of BD1. DW-71177 effectively inhibits oncogenes comparable to the pan-BET inhibitor OTX-015, but with a milder impact on housekeeping genes. It efficiently blocks cancer-associated transcriptional changes by targeting genes that are highly enriched with BRD4 and histone acetylation marks, suggesting that BD1-selective targeting could be an effective and safe therapeutic strategy against leukemia. [Display omitted] • [1,2,4]triazolo[4,3-a]quinoxaline aminophenyl derivatives exhibited potent in vitro inhibitory activity for BET bromodomains. • DW-71177 exhibited a significantly greater binding affinity towards BD1 (bromodomain 1) compared to BD2 (bromodomain 2). • X-ray crystallography and molecular modeling studies elucidated the molecular-level basis of domain selectivity of DW-71177. • DW-71177 effectively reduced tumor growth in an AML xenograft model, comparable to the pan-BET inhibitor. • DW-71177 strongly suppressed oncogenes that are essential for cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Bromodomain and extra-terminal (BET) proteins, a class of epigenetic reader domains has emerged as a promising new target class for small molecule drug discovery for the treatment of cancer, inflammatory, and autoimmune diseases. Starting from in silico screening campaign, herein we report the discovery of novel BET inhibitors based on [1,2,4]triazolo[4,3- a ]quinoxaline scaffold and their biological evaluation. The hit compound was optimized using the medicinal chemistry approach to the lead compound with excellent inhibitory activities against BRD4 in the binding assay. The substantial antiproliferative activities in human cancer cell lines, promising drug-like properties, and the selectivity for the BET family make the lead compound ( 13 ) as a novel BRD4 inhibitor motif for anti-cancer drug discovery. [ABSTRACT FROM AUTHOR]

[Display omitted] Glutamine-addicted cancer metabolism is recently recognized as novel cancer target especially for KRAS and KEAP1 co-occurring mutations. Selective glutaminase1 (GLS1) inhibition was reported using BPTES which has novel mode of allosteric inhibition. However, BPTES is a highly hydrophobic and symmetric molecule with very poor solubility which results in suboptimal pharmacokinetic parameters and hinders its further development. As an ongoing effort to identify more drug-like GLS1 inhibitors via systematic structure − activity relationship (SAR) analysis of BPTES analogs, we disclose our novel macrocycles for GLS1 inhibition with conclusive SAR analysis on the core, core linker, and wing linker, respectively. Selected molecules resulted in reduction in intracellular glutamate levels in LR (LDK378-resistant) cells which is consistent to cell viability result. Finally, compounds 13 selectively reduced the growth of A549 and H460 cells which have co-occurring mutations including KRAS and KEAP1. [ABSTRACT FROM AUTHOR]

DRAK2 is a serine/threonine kinase belonging to the death-associated protein kinase (DAPK) family and has emerged as a promising drug target for the treatment of autoimmune diseases and cancers. To identify small molecule inhibitors for DRAK2, we performed a high throughput screening campaign using in-house chemical library and identified indirubin-3′-monoximes as novel class of DRAK2 inhibitors. Among the compounds tested, compound 16 exhibited the most potent inhibitory activity against DRAK2 (IC 50 = 0.003 μM). We also propose that compound 16 may bind to the ATP-binding site of the enzyme based on enzyme kinetics and molecular docking studies. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines is described and their structure–activity-relationship to anaplastic lymphoma kinase (ALK) is presented. KRCA-0008 is selective and potent to ALK and Ack1, and displays drug-like properties without hERG liability. KRCA-0008 demonstrates in vivo efficacy comparable to Crizotinib in xenograft mice model. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate the efficiency of automated function imaging (AFI) on transthoracic echocardiogram (TTE) for detecting left ventricular (LV) wall motion (LVWM) abnormalities, we compared longitudinal peak systolic strain (LPSS) measurements using AFI with naked eye TTE evaluations by experienced cardiologists and non-experienced residents. Materials and methods: A total of 352 segments of LV myocardium from 22 consecutive subjects with LVWM abnormalities based on American Heart Association classifications (11 male, mean age 58±14years) on previous TTE (Vivid-7, GE) were evaluated. LPSS was measured using stored AFI data. Naked eye evaluation of LVWM was performed by 2 experienced cardiologists and 2 non-experienced residents. Results: AFI successfully tracked 342 (97%) of all segments (mean LPSS −14.8±8.1%). A significant strong negative correlation was observed between LV ejection fraction using method of disks and global LPSS (R=−0.8974). Temporary AFI criteria of LPSS were normal <−12; hypokinesis −12-2; and akinesis >2. Of 342 segments, 239, 87, and 16 segments were diagnosed as normal, hypokinesis, and akinesis, respectively. Level of agreement and kappa coefficients between qualitative evaluation of LVWM by AFI temporary criteria and qualitative evaluation of LVWM by experienced cardiologist 2 (0.784 and 0.479, respectively) were inferior to those comparing experienced cardiologists (0.845 and 0.595) but superior comparing experienced cardiologist with non-experienced resident (0.696 and 0.323), and between the 2 non-experienced-residents (0.682 and 0.347). Conclusion: Qualitative evaluation of LVWM using temporary AFI criteria had a 97% success rate and agreed well with findings of an experienced cardiologist. AFI can be a useful tool for training residents. [Copyright &y& Elsevier]

Abstract: Purpose: To distinguish focal fibrotic and non-fibrotic lesions in left-ventricular myocardium (LVM) in hypertrophic-cardiomyopathy (HCM)-subjects, we compared myocardial regional peak-strain values using two-dimensional speckle-tracking transthoracic-echocardiography (TTE) in multislice computed-tomography (CT)-detected fibrotic, non-fibrotic and normal control lesions. Methods: Twenty subjects (10 consecutive HCM-subjects (8-males, mean 63.4-years), 10 healthy controls (5-males, mean 51.5-years)) underwent speckle-tracking TTE (iE-33), and analysis of regional peak-longitudinal (LS) and radial-strain (RS), and corresponding strain rates in each of 17 LVM segments (American-Heart-Association classification). In HCM-subjects, fibrotic lesions were identified by early-phase defective enhancement and late-phase abnormal enhancement by CT (Light-Speed-Ultra-16). Regional peak LS and RS at basal, mid and apical levels were measured in MSCT-detected fibrotic and non-fibrotic LVM lesions. Results: In 10 HCM subjects, 143 lesions (84.1%) yielded good tracking on TTE. Twenty lesions showed fibrotic changes in 5 subjects by CT. Regional peak-LS and RS absolute values were significantly lower in both fibrotic and non-fibrotic lesions in HCM subjects than in controls at basal, mid, apical levels (all P<0.05). While peak-LS (%) absolute values were significantly lower in fibrotic than non-fibrotic lesions at basal, mid and apical levels (all P<0.05), regional peak-RS absolute values were significantly lower only at mid levels. LS was a more sensitive indicator than the corresponding rate, with better reproducibility. Conclusions: In HCM, regional peak-LS was significantly lower in fibrotic than non-fibrotic lesions in LVM by CT. Regional peak-LS by speckle-tracking provides useful information noninvasively to distinguish fibrotic from non-fibrotic lesions in LVM in HCM and normal LVM in healthy controls. [Copyright &y& Elsevier]

Abstract: A series of hydroxybenzoxazole derivatives was synthesized, and their c-Met kinase inhibitory activity was evaluated. Described herein is a potent c-Met inhibitor by structural modification of the parent benzoxazole scaffold, with particular focus on the hydroxyl substituent of the benzoxazole moiety. [Copyright &y& Elsevier]

Abstract: A series of 3-(4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-2-yl)-1H-quinolin-2-ones have been identified as a new class of VEGFR-2 kinase inhibitors. A variety of (4,5,6,7-tetrahydro-imidazo[5,4-c]pyridin-2-yl)-acetic acid ethyl esters were synthesized, and their VEGFR-2 inhibitory activity was evaluated. Described herein are the preparation of the series and the effects of the compounds on VEGFR-2 kinase activity. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate efficacy and reproducibility of 320-slice computed tomography (CT) for measuring left atrial (LA) maximum (LAVmax) and minimum volume (LAVmin) during the cardiac cycle, we compared CT with three- and two-dimensional (3D and 2D) transthoracic echocardiogram (TTE). Materials and methods: LAVmax and LAVmin (ml), and LA ejection fraction (LAEF) (%) were assessed in 22 consecutive subjects (15 males, 59.5±15.1years) using retrospective electrocardiogram gated 320-slice CT (Aquilion One, Toshiba Medical) and 3D-TTE (IE-33, Phillips). LAVmax and LAVmin were selected from the time volume curve. LAEF was calculated as (LAVmax−LAVmin)/LAVmax×100(%). Results: Mean±standard deviation (SD) of LAVmax and LAV min were significantly larger by CT than 3D-TTE or 2D-TTE (both P<0.01). LAEF was 25.3±13.1% by CT, 30.2±6.8% by 3D-TTE (P=NS) and 33.9±8.9% by 2D-TTE (P<0.05). The correlation coefficients (CCs) between CT and 3D-TTE in LAVmax, LAmin, and LAEF were 0.64, 0.68 and 0.57, respectively. Mean difference±1.96SD of LAVmax, LAVmin and LAEF by Bland and Altman analysis calculated from CT minus 3D-TTE were 48.8±59.1ml, 41.1±63.2ml, and −4.9±21.1%, respectively. The CCs and mean difference±1.96SD between CT and 2D-TTE had similar tendencies. The CCs of interobserver variation were (for CT, 3D-TTE, 2D-TTE, respectively): 0.90, 0.95 and 0.94 (LAVmax), 0.97 and 0.97 and 0.93 (LAVmin), and 0.64, 0.77 and 0.34 (LAEF). Conclusions: 320-slice CT enables direct LAV measurements and has high reproducibility and positive correlation with 3D and 2D TTE. Absolute value of LAV by CT was larger than that by 3D and 2D TTE. [Copyright &y& Elsevier]

Abstract: Purpose: To differentiate pseudodyskinesis (PD) of the inferior left ventricular (LV) wall from inferior myocardial infarction (IMI) noninvasively, we performed focal site evaluation using two-dimensional speckle tracking transthoracic echocardiography (TTE). Materials and methods: Speckle tracking TTE was carried out in 57 patients, with 19 subjects in each of three groups (Group A, suspected PD; Group B, LV IMI; and Group C, controls). Inferior wall PD was defined as follows: compression of the inferior LV wall by the diaphragm in the LV short axis view with a normal electrocardiogram and no evidence of previous ischemic events. Results: Respective values in Groups A–C for LV ejection fraction (EF) were 63.6±4.2%, 52.3±7.6%, and 61.5±3.8%, for inferior wall speckle tracking focal site evaluation peak radial strain of 30.0±14.3%, 7.5±7.1%, and 42.1±22.9%, for peak circumferential strain of 23.1±6.0%, 16.8±8.4%, and 22.7±7.1%, and for longitudinal strain in the mid-inferior wall of 18.4±3.4%, 11.4±4.0% and 15.8±5.9%. LVEF values were significantly lower in Group B than Groups A and C (P<0.001), as were those of radial, circumferential, and longitudinal strains (P<0.05). In receiver-operating characteristic analysis the optimal cut-off values with corresponding sensitivities and specificities for differentiation of PD from IMI were >19% with 84.2% and 94.7% for radial, >15% with 89.4% and 52.6% for circumferential, and >15% with 73.6% and 100% for longitudinal strain, respectively. Conclusions: Determination of regional strain from speckle tracking TTE, especially radial and longitudinal strains, can provide focal and quantitative noninvasive evaluation for distinguishing PD of the inferior wall from IMI. [Copyright &y& Elsevier]

Abstract: Purpose: To examine the usefulness of plasma atrial (ANP) and brain natriuretic peptide (BNP) levels and transthoracic echocardiogram (TTE) findings in predicting left ventricular (LV) dysfunction in muscular dystrophies (MD). Materials and methods: 135 MD subjects (83 Duchenne MD (DMD), all males, mean age 22±7years, 20 Becker MD (BMD), all males, 45±16years, 21 limb-girdle MD (LGMD), 14 males, 52±13years, and 11 facioscapulohumeral MD (FSHD), all males, 58±13years) underwent TTE and measurement of BNP and ANP. Results: In DMD, TTE revealed asynergy of the LV posterior-wall (72%), interventricular septum (IVS) (29%) and LV apex-wall (24%); in BMD subjects: TTE revealed asynergy of LV posterior-wall (50%) and IVS (25%); in LGMD and FSHD subjects: TTE revealed asynergy of LV posterior-wall (33 and 27%, respectively). LV end-diastolic (LVDdI) and end-systolic diameter index (LVDsI) were significantly larger in DMD than FSHD, and LV ejection fraction (LVEF) was significantly lower in DMD than LGMD and FSHD. In DMD, when LVEF was >=35%, BNP and ANP levels remained low, but when LVEF<35%, BNP and ANP levels showed steep increase. Relationship between LVEF and BNP or ANP levels was curvilinear (R 2 =0.69 and 0.55, respectively, p <0.001) using following equation: BNP=673491×EF−2.897, ANP=5716.6×EF−1.422, respectively. When LVDdI>=40mm/m2 or LVDsI>=35mm/m2, LVEF<=35%, plasma BNP and ANP levels increased steeply and the relationship between LVDdI, LVDsI, or LVEF and plasma BNP or ANP levels was curvilinear. Conclusion: In DMD, LVEF was significantly lower, asynergy of LV posterior-wall was more frequent and BNP and ANP levels were dramatically higher when LVDdI>=40mm/m2, LVDsI>=35mm/m2 or LVEF<35%. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the influence of the osmotic pressure of solutions used for reconstituting the ultrasound contrast agent “Levovist” on the degree of video intensity of the enhancement and video intensity decay in contrast echocardiogram, we used 6 solutions with different osmotic pressures in both vitro and in vivo experiments. Materials and methods: In the in vitro experiments, Levovist was reconstituted with 6 kinds of solutions with different osmotic pressures (Lactate Ringer''s solution, 2.5%, 5%, 7.5%, and 20% glucose and distilled water) and peak video intensities and video intensity decay were measured. In the in vivo experiments, contrast echocardiography was performed in 7 adult volunteers, following the intravenous injections of Levovist, previously reconstituted with one of 2 solutions (5% glucose or distilled water). Results: In vitro, at peak time, Levovist reconstituted with either Lactate Ringer''s solution, 2.5% glucose, 5% glucose, or distilled water had good peak video intensities. At 30 s after peak time, Levovist reconstituted with Lactate Ringer''s solution had greater enhancement and less decay than the other 5 solutions (P <0.001). In vivo, at 180 heart beats after peak time, the video intensity decay with 5% glucose was greater than that with distilled water (150±13 dB, 123±25 dB, respectively, P <0.05). Conclusion: In this study, among various (2.5–20%) glucose solutions, the stability of the microbubbles differed, depending on the degree of osmotic pressure of the respective solutions; 5% glucose was the best. However, overall, the most suitable solution for reconstituting Levovist, was Lactate Ringer''s solution. These findings could lead to effective strategies for better contrast echocardiography using Levovist by changing the current solution of choice to Lactate Ringer''s solution or 5% glucose. [Copyright &y& Elsevier]

Abstract: Purpose: Chronic pulmonary arterial thromboembolism (CPATE) often causes right ventricular (RV) pressure overload but the relationship between the degrees of CPATE and RV pressure overload is not clear. To quantify the degrees of CPATE and RV pressure overload, we performed multislice computed tomography (CT) and Tissue Doppler Imaging (TDI) and compared the two modalities. Materials and methods: Sixteen consecutive subjects (4 men, 12 women; age 27–72 with proven CPATE underwent CT. The right vascular obstruction index (VOI), the left VOI, and the total VOI (TVOI) were determined using the scoring system of Qanadli. The early systolic myocardial velocity (Sw) and diastole myocardial velocity (Ew) at the tricuspid annulus and the early diastolic tricuspid inflow (E) were obtained by TDI in the apical four chamber view; RV systolic pressure (RVSP) was estimated by pressure gradient of tricuspid valve regurgitation. E/Ew was calculated as the parameter of RV diastolic function. Results: The right VOI was 23±10%, the left VOI was 18±10%, and TVOI was 41±14%. The means with ranges of Sw, Ew, E/Ew, RVSP, and brain natriuretic peptide (BNP) were 10.7 (range 7.7–14.6) cm/s, 7.7 (range 4.2–10.6) cm/s, 5.0 (range 2.2–8.1), 55 (range 26–90) mm Hg, and 50.3 (range 12.2–165) pg/ml, respectively. The correlation coefficients between Sw, Ew, E/Ew, RVSP, and BNP and either larger of right or left side (LVOI) and TVOI were 0.041, −0.163 (Sw vs. LVOI, TVOI), −0.153, −0.232 (Ew vs. LVOI, TVOI), 0.145, 0.241 (E/Ew vs. LVOI, TVOI), 0.255, 0.401 (RVSP vs. LVOI, TVOI), and 0.192, 0.170 (BNP vs. LVOI, TVOI), respectively. The correlation coefficient between RVSP and BNP was 0.390. Conclusions: TVOI was better correlated with RVSP (R =0.401) than the other parameters (Sw, Ew, E/Ew, and BNP), and this was similar to the degree that BNP was correlated with RVSP (R =0.390). TVOI can be a better indicator of RVSP than LVOI. CT VOI may be a useful parameter to assess CPATE morphologically. [Copyright &y& Elsevier]

Abstract: Cardiac amyloidosis is generally a progressive disease with a poor prognosis, so early diagnosis and appropriate treatments are important. Although cardiac amyloidosis can be diagnosed definitively by endomyocardial biopsy, non-invasive methods of diagnosis are desired because of a great risk in biopsy. In ECG-gated enhanced multislice computed tomography, not only clear images of the cardiac morphology but also the character of myocardium indicating fibrosis can be identified. We demonstrate two patients with cardiac amyloidosis who showed marked thickening of left ventricular wall with partial fibrotic changes by enhanced multislice computed tomography. [Copyright &y& Elsevier]

Abstract: We report here a 75-year-old male with hypertrophic obstructive cardiomyopathy of de novo sustained monomorphic ventricular tachycardia (VT) after successful percutaneous transluminal alcohol septal myocardial ablation (PTSMA). In this case history, the necrotic induced by the PTSMA procedure might represent a region of slow conduction that is a circuit of re-entry and therefore stimulation might be spread around. Therefore, the basis of the sustained monomorphic VT was thought to be the presence of a focal necrotic area, itself a complication arising from the PTSMA procedures. In conclusion, the PTSMA procedure may have caused a de novo episode of ventricular arrhythmia. [Copyright &y& Elsevier]

SHP2, a non-receptor protein tyrosine phosphatase encoded by PTPN11 gene, plays an important role in the cell growth and proliferation. Activating mutations of SHP2 have been reported as a cause of various human diseases such as solid tumors, leukemia, and Noonan syndrome. The discovery of SHP2 inhibitor can be a potent candidate for the treatment of cancers and SHP2 related human diseases. Several reports on a small molecule targeting SHP2 have published, however, there are limitations on the discovery of SHP2 phosphatase inhibitors due to the polar catalytic site environment. Allosteric inhibitor can be an alternative to catalytic site inhibitors. 3,4,6-Trihydroxy-5-oxo-5 H -benzo[7]annulene 1 was obtained as an initial hit with a 0.097 μM of IC 50 from high-throughput screening (HTS) study. After the structure-activity relationship (SAR) study, compound 1 still showed the most potent activity against SHP2. Moreover, compound 1 exerted good potency against SHP2 expressing 2D and 3D MDA-MB-468. [ABSTRACT FROM AUTHOR]