bluuebunny/crossref_metadata_2025 huggingface dataset:
Animation – Based Legendary Stories Materials from Banjarnegara to Teach Javanese in Junior High School
Authors: Erwinsyah H , Andayani  , Sumarwati
Published: December 2019

The development of technology is increasingly rapid so it requires humans to follow and keep up. Various kinds of technology have been used by humans in everyday life, including in the educational system. This study discusses the use of technology in the form of teaching materials for Banjarnegara legendary stories based on animation for Javanese language learning in junior high schools. Through this animation, it is expected that students will be more interested and not feel bored while attending class learning. This study uses a qualitative descriptive method with data in the form of information on legend stories in Banjarnegara Regency. The results of this study are legend stories of Banjarnegara Regency which are used as teaching materials based on animations. The source of the data comes from sources, historical heritage, and written documents. This research is expected to be able to encourage other researchers to carry out various studies related to legend stories in one place as teaching materials at schools by utilizing existing technology.
Linear regression statistic from accounting information system application for Employee integrity
Authors: Syah L Y , Nafsiah S N , Saddhono K
Published: December 2019

The purpose of this study was to determine the effect of the accounting information systems application on employee performance, whether organizational culture and employee integrity moderated the accounting information systems application influence on employee performance. The research conducted at BankPerkreditan Rakyatin Palembang. The samples of this study were 42 respondents by using purposive sampling. The data collection methods were questionnaire and interview, while the data analysis technique was multiple linear regression analysis. According to the research result by distributing questionnaires to 42 respondents, it could be concluded that the accounting information systems application had a positive and significant effect on employee performance. The organizational culture and employee integrity influenced positively and significantly toward employee performance as well as organizational culture and employee integrity as the accounting information system application moderation showed that employee integrity could moderate the organizational culture.
Thermodynamics of oxygen solutions in the Fe-Co-Cr melts containing silicon, titanium, and aluminum
Authors: Dashevskii V Ya , Aleksandrov A A , Kanevskii A G , Leontev L I
Published: December 2019

Effect of Si, Ti, and Al on the oxygen solubility in the Fe-Co-Cr melts at 1873 K was thermodynamically analyzed. At low Si, Ti, and Al contents, the oxygen concentration increases very slightly. At the higher their contents, when the mechanism of interaction of Si, Ti and Al with oxygen is changed, just these elements determine the oxygen solubility in melt and the oxygen concentration decreases significantly.
Laser formation of thin-film memristor structures based on vanadium dioxide
Authors: Novodvorsky O A , Parshina L S , Khramova O D , Panchenko V Ya
Published: December 2019

The thin films of VO2 and the metal-oxide-metal (MOM)-structures of Au/VO2/VO2-
x/Au based on them, which are promising for the use in neuromorphic electronic devices, have been obtained by the method of pulsed laser drop-free deposition on the c-sapphire substrates at room temperature. Using the cyclic I-V characteristics, a memristive effect has been revealed in the vertical geometry of the Au/VO2/VO2-x/Au MOM-structures. The x value was varied in the course of their growth by changing the pressure of buffer oxygen from 0.1 to 40 mTorr in the vacuum chamber, which provided the needed conductivity in the depleted injection layer. The dependence of memristive properties on the thickness of the semiconductor layer and concentration of the oxygen vacancies has been established. The oxygen pressure in the PLD method has been determined, at which the volatile behavior of the memristor resistive switching starts to appear at an oxide region thickness of 10/30 nm.
Magnetic properties of fired clay (bricks) possibly containing epsilon iron (III) oxide
Authors: Gurylev A , Kharitonskii P , Kosterov A , Berestnev I , Sergienko E
Published: December 2019

We investigated bricks with ages from modern to late 19th century. The experimental and theoretical analysis of hysteresis loops and magnetization (ARM, IRM) acquisition curves show presence of two magnetic phases with high and low coercivity, respectively, which might be related to nanoparticles of oxidized and/or cation-substituted magnetite and epsilon iron (III) oxide. The fired clay (bricks) thus can be viewed as a model system in which epsilon iron (III) oxide forms readily.
Effect of Yb2O3stabilizing impurity on the structure and properties of (ZrO2)0.9-x(Sc2O3)0.1(Yb2O3)xcrystals
Authors: Kulebyakin A V , Agarkov D A , Borik M A , Eliseeva G M , Kolotygin V A , Kuritsyna I E , Lomonova E E , Milovich F O , Myzina V A , Osiko V V , Chislov A S , Tabachkova N Yu
Published: December 2019

The effect of introduction of 0.5 – 2 mol.% Yb2O3additional doping oxide into ZrO2– 10 mol.% Sc2O3solid solutions on the phase composition, structure and electrophysical properties has been studied. ZrO2stabilization due to the joint effect of 10 mol.% Sc2O3and 2 mol.% Yb2O3provides for the formation of transparent homogeneous crystals with a cubic structure having high phase stability. Mechanical grinding of the crystals has not changed their phase composition, the powders retaining the initial fluorite crystalline structure. We show that the high-temperature electrical conductivity of the crystals decreases with an increase in the Yb2O3concentration.
Mechanical properties of SiCf/SiC mini-composites reinforcements for SiCf/SiC composites
Authors: Yang Haitang , Xu Shenwei , Yang Pingping , Chen Yang , Dong Leiting , Guo Zaoyang , Huang Xiaozhong
Published: December 2019

SiCf/SiC mini-composites with single-tow microstructures are typically used as reinforcing materials for larger composites and it is essential to obtain accurate mechanical properties for such mini-composites to understand the fundamental mechanical properties of larger composites. In this paper, the mechanical properties of SiCf/SiC mini-composites fabricated through a precursor infiltration and pyrolysis process, as well as those of their constituents, are analysed. The Young’s moduli, strengths, and ultimate strains of the SiCf/SiC mini-composites and SiC fibres are measured through uniaxial tensile tests. The experimental results reveal that the mechanical performance of the SiC fibres is diminished during the high-temperature manufacturing process. The effects of the PyC interface on the mechanical properties of the SiC fibres and SiCf/SiC mini-composites are also explored. The results demonstrate that the influence of the PyC interface on the mechanical properties of the SiC fibres is negligible, but significantly increases the strength and failure strain of the SiCf/SiC mini-composites. A nanoindentation test is employed to measure the Young’s modulus of the SiC matrix. The relationship between the Young’s moduli of the fibre, matrix, and mini-composite is theoretically characterised and can be reasonably explained by the theory of composite mechanics based on the microstructures of the mini-composites.
Study of the thermal stability of structure and mechanical properties of submicrocrystalline aluminum alloys Al-2.5Mg-Sc-Zr
Authors: Nokhrin A V , Shadrina I S , Chuvil’deev V N , Kopylov V I , Bobrov A A , Gryaznov M Yu , Sysoev A N , Kozlova N A , Chegurov M K , Berendeev N N , Zheleznov A E , Piskunov A V , Pushkova D A , Murashov A A , Revva D A
Published: December 2019

The paper provides the results of experimental studies of the microstructure, mechanical properties, and corrosion resistance of cast and submicrocrystalline (SMC) aluminum alloys Al-2.5Mg-Sc-Zr with different ratios of scandium and zirconium (Sc + Zr = 0.32 wt.%). SMC structure in alloys was formed by methods of severe plastic deformation: equal-channel angular pressing and rotary swaging. In our paper, we demonstrate that the alloys have high thermal stability – the recrystallization point in SMC alloys is 250-275 °C. We prove that the replacing scandium with zirconium leads to an increase in the thermal stability of the solid solution of scandium in cast and SMC aluminum alloys Al-Mg-Sc-Zr.
Investigation of the influence of ultrasonic treatment on the sorption properties of the pyrolysis product of wood waste
Authors: Nasyrov I A , Mavrin G V , Fazullin D D , Shaikhiev I G
Published: December 2019

Annotation

In the article, the object of study is the sorption material obtained by low-temperature pyrolysis from wood waste and treated with ultrasound. Ultrasonic treatment is one of the methods of improving the sorption characteristics of the pyrolysis product by increasing the specific surface area. The adsorption capacity of pyrolysis products was studied by titrimetric method using methylene blue on the UNICO 2800 spectrophotometer and iodine. An increase in sorption activity was found after ultrasonic action on the sorption material: 1,3 times for methylene blue, 3 times for iodine. Sorption properties of the product of wood waste pyrolysis were investigated after ultrasonic treatment in relation to ions of iron, copper, chromium, nickel and zinc under static conditions using atomic emission spectrometry with inductively coupled plasma on the Agilent 720-OES spectrometer. The sorption degree is calculated. The degree of purification from HMI with the use of wood waste pyrolysis product after ultrasonic treatment is: for Fe – 98%, Cu – 93.6%, Cr – 72.2%, Ni – 60.6%, and Zn – 77.9%. The paper shows that the product of pyrolysis of wood waste after ultrasonic treatment is almost equal to the degree the sorption of commercial sorbent BAU with respect to ions of iron, copper and chromium. Ultrasonic treatment to a frequency of 35 kHz for 30 minutes allows to increase the sorption capacity of the product of pyrolysis of wood waste by Fe ions by 8.8 times, Cu – 2.6 times, Cr – 1.1 times.
Application of supercritical fluids for complete decellularization of porcine cartilage
Authors: Sevastianov V I , Nemets E , Lazhko A , Basok Yu , Kirsanova L , Kirillova A
Published: December 2019

Porcine cartilage was ground by cryomill (Retch, Germany) at –196°C. A fraction of cartilage microparticles (CMP) of size 100-250 µm was isolated. CMP was decellularized at room temperature with periodic mixing in 3 shifts of 0.1% sodium dodecyl sulfate buffer solution, containing an increasing concentration (1, 2 and 3%) of Triton X100. CMP treatment in a supercritical CO2 (sc-CO2) atmosphere was carried out at a pressure of 300 bar, T = 35°C, with a flow rate of sc-CO2 of 2.5 ±0.5 ml/min for 8-24 hours using RESS-SAS equipment (Waters Corporation, USA). Ethanol (96%) at a concentration of 10% was used as a polarity modifier. The degree of decellularization of CMP was assessed by histological methods (stained by hematoxylin and eosin) and by detection of the residual amount of DNA in samples using DNA-binding fluorescent dye DAPI. In the case of treatment with the detergents only and detergents after sc-CO2, the required degree of decellularization of CMP was not achieved. Histological analysis of the samples has shown that only a partial release of chondrocytes occurs. CMP treatment by detergents followed by sc-CO2 was more effective. Complete removal of cells can be achieved if the cartilage is first treated with surfactant, and then CO2. When ethanol was added as a polarity modifier, histological studies confirm that non-disrupted cells were almost completely absent and study with the DAPI dye has shown that more than 90% of CMP samples were completely free of DNA or contained only single whole cells.To achieve the highest possible degree of decellularization, the treatment of cartilage microparticles should be carried out first with detergent solutions followed by exposure to sc-CO2. The introduction of a polarity modifier (ethanol) at a concentration of 10% has a positive effect on the degree of decellularization and in combination with lengthy treatment time allows to reach complete decellularization of cartilage tissue.
The effect of buffer sedimentation on the process of biometric deposition of calcium phosphates
Authors: Radkova E A , Teterina A Yu , Baranov O V , Mikheeva P V , Smirnov I V , Fedotov A Yu , Komlev V S
Published: December 2019

In this work was considered the influence of the buffer solutions, modeling biogenic extracellular liquid, including Simulated Body Fluid and also physiological solution for comparison, on microstructure and properties of octacalcium phosphate granules. The research was conducted, according to Russian state standard specification № 10993-14-2001. The correlation of pH - value and concentration of calcium and phosphorus ions in solutions on a degradation kinetics and recrystallization of the surface layer were analyzed.
Submicronic nanostructured spherical zirconium-cerium powders for products of an orthopedic stomatology
Authors: Kolmakov A G , Vinogradov L V , Antipov V I , Baranov E E , Mukhina Yu E
Published: December 2019

The method of the ultrasonic spraying pyrolysis (USP) synthesized submicronic ceramic powders of structure of ZrO2+12 mol.%CeO2 intended for the subsequent manufacture on their basis of ceramic implants in an orthopedic stomatology. It is shown that (URP) allows to receive microspherical powders of zirconium-cerium ceramics, the multiparticle agglomerates having narrow dispersion and not forming in itself difficult the separable. The exemplars baked from new aerosol powders on the level of mechanical characteristics are close similar to characteristics for the ceramics manufactured of ultradispersed powders.
New genetic resources and technologies in development of blast resistant rice forms for greening the rice growing industry
Authors: Korotenko T L , Savenko E G , Mukhina Zh M , Glazyrina V A
Published: December 2019

To accelerate development of competitive new-generation rice varieties adapted for environmentally friendly non-pesticide farming, we used the achievements of modern Russian and Chinese national rice breeding. The article observes the technologies of developing rice initial forms combining economically valuable traits with long-term resistance to biotic stressors (blast) using modern methods of phenotyping and genotyping as well as experimental haploidy with subsequent experimental development of breeding resources.
Prospects for the development of green technologies for producing alternative energy resources
Authors: Gubacheva L , Makarova I , Andreev S , Andreev A , Shevchenko D
Published: December 2019

The transition to “green technology” is caused by the negative action of human life on the environment. “Green technologies” are environmentally friendly for human health. To reduce the negative burden on the environment, it is necessary to decrease the consumption of resources while reducing the growth of production and consumption waste. The negative impact of municipal solid waste (MSW) on the environment leads to climatic change, increases the greenhouse effect and the number of natural hazards. These facts necessitate the search for solutions to reduce harmful emissions into the atmosphere, to increase fuel efficiency, as well as energy efficiency, for example, transport systems, by improving the technology for producing the generator gas as an alternative fuel. The article discusses technologies to reduce the concentration of nitrogen oxides in any device for burning solid, liquid and gaseous fuels in internal combustion engines.
Facile synthesis and characterization of 1-ethyl-3-methylimidazolium fluoride ionic liquid
Authors: Liu Fengguo , Zhong Xiongwei , Xu Junli , Wang Zhaowen , Shi Zhongning
Published: December 2019

1-ethyl-3-methylimidazolium fluoride ([EMIm]F) was synthesized by a facile route via an anion metathesis process. The structure of [EMIm]F was characterized by Fourier transform infrared and Raman spectroscopy, mass spectrometry, as well as nuclear magnetic resonance spectroscopy. The results show that imidazole ring structure is not destructed during the synthesis process, and the disassociated [EMIm]+ and [(EMIm)2F]+ ions are detected in [EMIm]F. It has a potential widow with about 1.80V and shows potential application for reactive metals electrodepostion.
Identification of sex-linked markers in the sexually cryptic coco de mer: are males and females produced in equal proportions?
Authors: Morgan Emma J , Kaiser-Bunbury Christopher N , Edwards Peter J , Scharmann Mathias , Widmer Alex , Fleischer-Dogley Frauke , Kettle Chris J
Published: December 2019

Lodoicea maldivica (coco de mer) is a long-lived dioecious palm in which male and female plants are visually indistinguishable when immature, only becoming sexually dimorphic as adults, which in natural forest can take as much as 50 years. Most adult populations in the Seychelles exhibit biased sex ratios, but it is unknown whether this is due to different proportions of male and female plants being produced or to differential mortality. In this study, we developed sex-linked markers in Lodoicea using ddRAD sequencing, enabling us to reliably determine the gender of immature individuals. We screened 589 immature individuals to explore sex ratios across life stages in Lodoicea. The two sex-specific markers resulted in the amplification of male-specific bands (Lm123977 at 405 bp and Lm435135 at 130 bp). Our study of four sub-populations of Lodoicea on the islands of Praslin and Curieuse revealed that the two sexes were produced in approximately equal numbers, with no significant deviation from a 1:1 ratio before the adult stage. We conclude that sex in Lodoicea is genetically determined, suggesting that Lodoicea has a chromosomal sex determination system in which males are the heterogametic sex (XY) and females are homogametic (XX). We discuss the potential causes for observed biased sex ratios in adult populations, and the implications of our results for the life history, ecology and conservation management of Lodoicea.
PDEparams: parameter fitting toolbox for partial differential equations in python
Authors: Parra-Rojas César , Hernandez-Vargas Esteban A
Published: December 2019

Motivation

Partial differential equations (PDEs) is a well-established and powerful tool to simulate multi-cellular biological systems. However, available free tools for validation against data are on development.

Results

The PDEparams module provides a flexible interface and readily accommodates different parameter analysis tools in PDE models such as computation of likelihood profiles, and parametric bootstrapping, along with direct visualization of the results. To our knowledge, it is the first open, freely available tool for parameter fitting of PDE models.

Availability and implementation

PDEparams is distributed under the MIT license. The source code, usage instructions and examples are freely available on GitHub at github.com/systemsmedicine/PDE_params.

Supplementary information

Supplementary data are available at Bioinformatics online.
A missing touch of Adam Smith in Amartya Sen’s account of public reasoning: the man within for the man without
Authors: Bréban Laurie , Gilardone Muriel
Published: December 2019

Sen claims that his 2009 theory of justice is based in part upon Smith’s idea of the ‘impartial spectator’. His claim has received criticism: some authors have responded that his interpretation of Smith’s concept is unfaithful to the original; others, focussing on internal features of Sen’s analysis, critique his use of the Smithian impartial spectator, arguing that it is a weak point in his comparative theory of justice. In this paper, we address both sets of criticisms. While agreeing with commentators that Sen’s reading of Smith is somewhat unfaithful, we reiterate that his aim in The Idea of Justice is not to provide an exegesis of Smith but rather to build his own comparative theory of justice by ‘extending Adam Smith’s idea of the impartial spectator’ (IJ: 134) to his own project. After clarifying their distinct approaches to the concept of the impartial spectator, we draw upon our account of these differences to evaluate Sen’s own use of the concept. Despite significant divergences, we show that Sen’s version of the impartial spectator is not inconsistent with Smith’s analysis. Though it does not correspond to Smith’s concept, that is to what the Scottish philosopher sometimes calls the ‘man within’, it is reminiscent of another figure from Smith’s moral philosophy: the ‘man without’. Beyond this analogy, there are further connections between Smith’s imaginary figure of the ‘man within’ and Sen’s account of ‘common beliefs’—both notions are ways of representing our beliefs regarding what is moral or just. But whereas Smith’s moral philosophy offers an analysis of the process by which the ‘man without’ influences the ‘man within’, nothing of that kind is to be found in Sen’s conception of public reasoning. And it is here that Smith’s famous concept of ‘sympathy’ can supplement Sen’s theory, in a way that furnishes an answer to Shapiro’s (2011) criticism regarding the possibility of spontaneous change of beliefs towards greater impartiality.
Cell Architecture of the Giant Sulfur Bacterium Achromatium oxaliferum: Extra-cytoplasmic Localization of Calcium Carbonate Bodies
Authors: Schorn Sina , Salman-Carvalho Verena , Littmann Sten , Ionescu Danny , Grossart Hans-Peter , Cypionka Heribert
Published: December 2019

Achromatium oxaliferum is a large sulfur bacterium easily recognized by large intracellular calcium carbonate bodies. Although these bodies often fill major parts of the cells’ volume, their role and specific intracellular location are unclear. In this study, we used various microscopy and staining techniques to identify the cell compartment harboring the calcium carbonate bodies. We observed that Achromatium cells often lost their calcium carbonate bodies, either naturally or induced by treatments with diluted acids, ethanol, sodium bicarbonate and UV radiation which did not visibly affect the overall shape and motility of the cells (except for UV radiation). The water-soluble fluorescent dye fluorescein easily diffused into empty cavities remaining after calcium carbonate loss. Membranes (stained with Nile Red) formed a network stretching throughout the cell and surrounding empty or filled calcium carbonate cavities. The cytoplasm (stained with FITC and SYBR Green for nucleic acids) appeared highly condensed and showed spots of dissolved Ca2+ (stained with Fura-2). From our observations, we conclude that the calcium carbonate bodies are located in the periplasm, in extra-cytoplasmic pockets of the cytoplasmic membrane and are thus kept separate from the cell's cytoplasm. This periplasmic localization of the carbonate bodies might explain their dynamic formation and release upon environmental changes.
Large Fecal Reservoir of Escherichia coli Sequence Type 131-H30 Subclone Strains That Are Shared Within Households and Resemble Clinical ST131-H30 Isolates
Authors: Mohamed Muhanad , Clabots Connie , Porter Stephen B , Bender Tricia , Thuras Paul , Johnson James R
Published: December 2019

Background

Emerging antimicrobial-resistant Escherichia coli represent mainly the nested (fluoroquinolone-resistant [FQR]) H30R and H30Rx subclones within sequence type 131 (ST131). Intestinal colonization and within-household transmission may underlie H30R’s emergence.

Methods

We screened fecal samples from 741 volunteers (383 veterans, 358 household members, including pets) for ST131 and FQR E. coli (FQREC) and used molecular profiling to resolve unique strains. Selected strains underwent PCR-based detection of phylogroups, sequence types (STs), H30, H30Rx, and 53 virulence genes (VGs). Within-household strain sharing was compared with household, host, and bacterial characteristics. Fecal isolates were compared with clinical isolates.

Results

Colonization prevalence was 5.1% for H30R, 8% for ST131 (67% FQREC), and 10% for FQREC (52% ST131). ST131 isolates exhibited more VGs than non-ST131 isolates. Strain sharing (27% of multisubject households, 18% of corresponding subjects) was associated with the elderly, FQREC, H30R, H30Rx, ST73, and specific VGs. Fecal ST131 and FQREC isolates resembled contemporaneous and historical clinical isolates according to all studied traits.

Conclusions

Veterans and their human household members commonly carry and extensively share FQREC, predominantly H30R, thereby likely facilitating the ST131 pandemic. Strain sharing corresponds with multiple bacterial characteristics, including FQ resistance and specific VGs, which may promote intestinal colonization and/or host-to-host transmission.
A stitch in time: narrative review of interventions to reduce preterm births in Malawi
Authors: Batura Rekha , Colbourn Tim
Published: December 2019

Background

The rising rate of preterm births (PTBs) is a global concern, and Malawi has a high rate of PTBs (10.5%). The resulting neonatal and under-5 mortality, morbidity and lifelong disability represent a significant loss of human potential affecting individuals, families and society as a whole. This study aims to review the literature to determine the risk factors for PTB in Malawi and to identify effective interventions to prevent PTBs.

Methods

A literature search yielded 22 studies that were categorized according to risk factors implicated for PTBs and health interventions to reduce the risks.

Results

The study has shown that maternal pregnancy factors, infections, nutrition, anaemia and young maternal age are the main causes and risk factors of PTBs in Malawi. The literature revealed no evidence of community-based interventions for reducing the rates of PTBs in Malawi.

Conclusions

Any successful effort to reduce the rate of PTBs will require a multisector, multilevel strategy targeted at the community, homes and individuals as a package to improve the education, nutrition and reproductive health of girls and women as well as focus on improving the delivery of antenatal services in the community.
HIV MDR is still a relevant issue despite its dramatic drop over the years
Authors: Armenia D , Di Carlo D , Flandre P , Bouba Y , Borghi V , Forbici F , Bertoli A , Gori C , Fabeni L , Gennari W , Pinnetti C , Mondi A , Cicalini S , Gagliardini R , Vergori A , Bellagamba R , Malagnino V , Montella F , Colafigli M , Latini A , Marocco R , Licthner M , Andreoni M , Mussini C , Ceccherini-Silberstein F , Antinori A , Perno C F , Santoro M M
Published: December 2019

Objectives

To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.

Methods

Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).

Results

Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010–18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance.

Conclusions

A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.
On the applicability of a renormalized Born series for seismic wavefield modelling in strongly scattering media
Authors: Huang Xingguo , Jakobsen Morten , Wu Ru-Shan
Published: December 2019

Scattering theory is the basis for various seismic modeling and inversion methods. Conventionally, the Born series suffers from an assumption of a weak scattering and may face a convergence problem. We present an application of a modified Born series, referred to as the convergent Born series (CBS), to frequency-domain seismic wave modeling. The renormalization interpretation of the CBS from the renormalization group prospective is described. Further, we present comparisons of frequency-domain wavefields using the reference full integral equation method with that using the convergent Born series, proving that both of the convergent Born series can converge absolutely in strongly scattering media. Another attractive feature is that the Fast Fourier Transform is employed for efficient implementations of matrix–vector multiplication, which is practical for large-scale seismic problems. By comparing it with the full integral equation method, we have verified that the CBS can provide reliable and accurate results in strongly scattering media.
Identification of Li-ion battery models through monotonic echo serial networks for coarse data
Authors: Álvarez-Caballero Antonio , Blanco Cecilio , Couso Inés , Sánchez Luciano
Published: December 2019

Monotone transformation models are extended to inaccurate data and are combined with recurrent neural networks in a new battery model that is able to ascertain the health of rechargeable batteries for automotive applications. The presented method exploits the information contained in the vehicle’s operational records better than other cutting-edge models and uses a minimum amount of human expert knowledge. The experimental validation of the technique includes a comparative analysis of batteries in different health conditions, comprising first-principles models and different machine learning procedures.
HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial
Authors: Barber Paul R , Weitsman Gregory , Lawler Katherine , Barrett James E , Rowley Mark , Rodriguez-Justo Manuel , Fisher David , Gao Fangfei , Tullis Iain D C , Deng Jinhai , Brown Louise , Kaplan Richard , Hochhauser Daniel , Adams Richard , Maughan Timothy S. , Vojnovic Borivoj , Coolen Anthony C C , Ng Tony
Published: December 2019

Background

The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response.

Methods

HER2-HER3 dimerization was quantified by fluorescence lifetime imaging microscopy in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab. Bayesian latent class analysis and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation, and cetuximab on progression-free survival and overall survival (OS). All statistical tests were two-sided.

Results

Latent class analysis on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS = 1624 days [95% confidence interval [CI] = 1466 to 1816 days] vs 461 days [95% CI = 431 to 504 days]): Class 1 (15.6%) showed a benefit from cetuximab in OS (hazard ratio = 0.43, 95% CI = 0.25 to 0.76, P = .004). Class 2 showed an association of increased HER2-HER3 with better OS (hazard ratio = 0.64, 95% CI = 0.44 to 0.94, P = .02). A class prediction signature was formed and tested on an independent validation cohort (n = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (n = 1630) based on 10 baseline clinicopathological and genetic covariates.

Conclusions

Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment.
Mechanical Circulatory Support
Authors: Joyce David L. , Joyce Lyle D.
Published: December 2019

Mechanical circulatory support (MCS) offers life-saving treatment options for patients with advanced heart failure, cardiogenic shock, and acute cardiopulmonary failure. With the development of short-term, long-term, left-sided, right-sided, biventricular, and cardiopulmonary support options, the complexity surrounding this field has evolved substantially in the past decade. This textbook seeks to provide a logical and systematic framework for managing patients who require MCS therapies. In chapters 2–9, a comprehensive approach to selecting and preparing patients for MCS interventions is described. In chapters 10–23, the range of currently available devices is reviewed with updates on the most up-to-date clinical experiences based on recently published outcomes. Chapters 24–30 describe the current state of the art in perioperative strategies for achieving long-term success. Finally, chapters 31–46 outline the myriad of clinical challenges that often occur in the postoperative period, including some of the frequently encountered adverse events that are unique to the physiology associated with this technology. The fundamental principles included in this textbook will provide a framework for the MCS provider that can serve as a road map amidst the rapidly evolving landscape created by the technology pipeline within this industry.
Structural analysis of disc super star clusters of M82: size and profile shape at intermediate ages
Authors: Cuevas-Otahola B , Mayya Y D , Puerari I , Rosa-González D
Published: December 2019

We present the structural parameters of 99 super star clusters (SSCs) in the disc of M82. Moffat-EFF, King, and Wilson models were fitted using a χ2-minimization method to background-subtracted surface brightness profiles in the F435W (B), F555W (V), and F814W (I) bands of the Advanced Camera for Surveys (ACS) of the Hubble Space Telescope. The majority of the SSC profiles are best fitted by the Moffat-EFF profile. The scale parameter rd and the shape parameter γ in the three filters are identical within the measurement errors. The analysed sample is big enough to allow the characterization of the distributions of core radii Rc and γ. The obtained distribution of Rc follows a lognormal form, with centre and $\sigma \mathrm{ log}\big {(}\frac{R_{\rm c}}{pc}\big {)}$ being 1.73 pc and 0.25, respectively. The γ distribution is also lognormal with centre and σlog(γ) being 2.88 and 0.08, respectively. M82 is well known for the absence of current star formation in its disc, with all disc SSCs older than 50 Myr and hardly any cluster older than ∼300 Myr. The derived distributions compare very well with the distributions for intermediate-age clusters in the Large Magellanic Cloud (LMC), which is also a low-mass late-type galaxy similar to M82. On the other hand, the distributions of Rc in both these galaxies are shifted towards larger values as compared to SSCs of similar age in the giant spiral galaxy M83. M82 and LMC also span a narrower range of γ values as compared to that in M83.
Evolution of giant molecular clouds across cosmic time
Authors: Guszejnov Dávid , Grudić Michael Y , Offner Stella S R , Boylan-Kolchin Michael , Faucher-Gigère Claude-André , Wetzel Andrew , Benincasa Samantha M , Loebman Sarah
Published: December 2019

Giant molecular clouds (GMCs) are well studied in the local Universe, however, exactly how their properties vary during galaxy evolution is poorly understood due to challenging resolution requirements, both observational and computational. We present the first time-dependent analysis of GMCs in a Milky Way-like galaxy and an Large Magellanic Cloud (LMC)-like dwarf galaxy of the FIRE-2 (Feedback In Realistic Environments) simulation suite, which have sufficient resolution to predict the bulk properties of GMCs in cosmological galaxy formation self-consistently. We show explicitly that the majority of star formation outside the galactic centre occurs within self-gravitating gas structures that have properties consistent with observed bound GMCs. We find that the typical cloud bulk properties such as mass and surface density do not vary more than a factor of 2 in any systematic way after the first Gyr of cosmic evolution within a given galaxy from its progenitor. While the median properties are constant, the tails of the distributions can briefly undergo drastic changes, which can produce very massive and dense self-gravitating gas clouds. Once the galaxy forms, we identify only two systematic trends in bulk properties over cosmic time: a steady increase in metallicity produced by previous stellar populations and a weak decrease in bulk cloud temperatures. With the exception of metallicity, we find no significant differences in cloud properties between the Milky Way-like and dwarf galaxies. These results have important implications for cosmological star and star cluster formation and put especially strong constraints on theories relating the stellar initial mass function to cloud properties.
CBMS-03 PHOSPHORYLATION STATE OF OLIG2 REGULATES PROLIFERATION OF GLIOMA STEM CELLS
Authors: Saito Norihiko , Hirai Nozomi , Aoki Kazuya , Sato Sho , Suzuki Ryo , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Sakurai Takatoshi , Iwabuchi Satoshi
Published: December 2019

The Cancer Genome Atlas project described a robust gene expression-based molecular classification of glioblastoma with the functional and biological significance of the subclasses yet to be determined. Here, we show that a comprehensive analysis of a panel of glioma initiating cell (GIC) lines can identify a group of stem cells with high OLIGg2 expression as in Proneural-like GBM subtype. In vitro differentiation studies showed that proneural GIC lines possess the potential to differentiate into astrocytic, neuronal, and oligodendrocytic lineages, whereas mesenchymal GICs exhibited limited potential for neural lineage differentiation following retinoic acid induction. A considerable decline of OLIG2 in proneural GIC lines was observed following retinoic acid treatment. We also showed that OLIG2 is a functional marker associated with cell proliferation in Olig2-high GIC lines. In addition, OLIG2 inhibition disrupted cell-cycle control mechanism by decreasing CDK2 and CDK4 and elevating apoptosis-related molecules. Mechanistic investigations revealed molecular interactions between CDK2/CDK4 and OLIG2. Inhibition of CDK2/CDK4 activity disrupted OLIG2-CDK2/CDK4 interactions and attenuated OLIG2 protein stability. Further investigation on these mechanisms may lead to novel targeted therapy on GBMs with high OLIG2 expression.
SPDR-05 PARP INHIBITORS RESTORE TEMOZOLOMIDE SENSITIVITY IN MSH6-DEFICIENT TEMOZOLOMIDE-RESISTANT GLIOBLASTOMA CELLS
Authors: Higuchi Fumi , Nagashima Hiroaki , Wakimoto Hiroaki , Daniel P Cahill
Published: December 2019

INTRODUCTION

Mismatch repair (MMR) deficiency through MSH6 inactivation has been identified in approximately 25% of recurrent gliomas. This MMR deficiency represents a key molecular mechanism of acquired resistance to the alkylating chemotherapeutic agent temozolomide (TMZ). Potentiation of TMZ-induced cytotoxicity by PARP inhibitors (PARPi) has been reported in several cancers including gliomas. However, mechanisms that underlie the PARPi-mediated chemo-potentiation and biomarkers that predict benefit from this combination treatment have not been identified in gliomas. We investigated whether PARPis could restore TMZ sensitivity of MSH6-deficient chemoresistant gliomas and assessed the role of the base excision repair (BER) DNA damage repair pathway in PARPi-mediated effects.

METHODS

We engineered glioblastoma cell lines and patient-derived glioblastoma neurosphere lines to knockdown MSH6 expression, resulting in acquired MMR-deficient resistance to TMZ. We treated these isogenic pairs of MSH6 wild type and MSH6-inactivated cells with TMZ, PARPi Veriparib or Olaparib, and combination. Using MSH6-deficient glioma xenografts, we tested the in vivo efficacy of veliparib in combination with TMZ. We used genetic and pharmacological approaches to assess the role of BER pathway in PARPi-mediated effects.

RESULTS

We found that combination with PARPi restored TMZ sensitivity in MSH6-inactivated TMZ resistant cells whereas only subtle combination effects were seen in control MMR-proficient cells at the same PARPi concentrations. In vivo, combination treatment of TMZ with Veliparib demonstrated potent suppression of tumor growth of MSH6-inactivated orthotopic and flank xenografts, compared with TMZ monotherapy. Unlike PARPi, genetic and pharmacological blockage of BER pathway did not re-sensitize MSH6-inactivated cells to TMZ.

CONCLUSION

PARPis restore TMZ sensitivity in MSH6-deficient glioblastoma cells. This combination treatment is a promising strategy to target acquired chemoresistance caused by MMR deficiency.
SPDR-09 CHANGES IN CELL CYCLE-RELATED GENE EXPRESSIONS OF GLIOBLASTOMAS BEFORE AND IMMEDIATELY AFTER CHEMO-RADIATION THERAPY
Authors: Iuchi Toshihiko , Hara Ryusuke , Kageyama Hajime , Sugiyama Takahiro , Togasaki Gentaro , Higuchi Akio , Hosono Junji , Setoguchi Taiki , Hasegawa Yuzo , Sakaida Tsukasa , Itami Makiko
Published: December 2019

PURPOSE/OBJECTIVE

The molecular responses of glioblastomas (GBMs) to hypofractionated IMRT/TMZ were investigated to elucidate the molecular targets included in the resistance of these tumors to chemo-radiation therapy.

MATERIALS /METHODS

Phase I study of neo-adjuvant IMRT (72Gy/12Fx.)/TMZ for the treatment of patients with GBMs had been performed previously in our institution. In this trial, stereotactic biopsy of the tumor to confirm the pathological diagnosis prior to treatment was required, and tumor removal was scheduled within 10 days after completion of IMRT/TMZ. Therefore, both the tumor samples before and immediately after IMRT/TMZ were available. By comparing the gene expression profiles before and after IMRT/TMZ using the total mRNA sequencing (RNAseq) analysis, molecular responses of GBMs against IMRT/TMZ were investigated. More than two-fold change of expression levels was defined as significant.

RESULTS

Tumor sample sets from five patients with GBMs were investigated. Among the 17,532 genes evaluated, 35 genes were found to show significant changes in gene expression in all cases, and 450 genes in more than half of the cases. Among the DNA repair related genes, DDB2 was the only gene that showed significant up-regulation in all cases. On the other hand, among the cell cycle checkpoint related genes, gene expressions of CKD1/CCNB were decreased in all cases. Although the expression of TP53 was not changed, the expressions of CDKN1A/GADD45/Reprimo/SFN were also reduced. Moreover, although the expression change of CHK1 was not found, the expressions of CDC25/PLK1/AURKA were decreased in more than half of the cases. From these results, it was considered that GBM arrested the cell cycle at the G2/M checkpoint without regulation of TP53 or CHK1 after IMRT/TMZ.

CONCLUSIONS

Our results suggested that cell cycle arrest in G2/M plays a significant role in survival of GBM cells after IMRT/TMZ.
ET-04 MOLECULAR TARGETED THERAPY AGAINST (PRO)RENIN RECEPTOR FOR GLIOBLASTOMA
Authors: Fujimori Takeshi , Ogawa Daisuke , Suzuki Kenta , Kochi Masaaki , Shibayama Yuki , Okada Masaki , Miyake Keisuke , Nishiyama Akira , Tamiya Takashi
Published: December 2019

INTRODUCTION

(Pro)renin receptor(PRR) is part of the Wnt receptor complex. Wnt/β-catenin signaling pathway (Wnt signaling) plays important role in pathogenesis and self-renewal of glioblastoma (GBM), or differentiation of glioma stem cell. We previously reported that PRR activate Wnt signaling, PRR expression correlated with malignancy of glioma, and treatment with PRR siRNA reduced the proliferative capacity. This time, we have developed monoclonal antibodies against PRR and examined their effects in GBM.

MATERIAL AND METHODS

We used GBM cell line (U251MG and U87MG) and primary human glioma stem cell line (MGG23). Glioma stem-like cells were cultured and isolated by neurosphere method from U251MG and U87MG. PRR antibody was made targeting the extracellular domain of the PRR with rat lymph node method. WST-1 assay or MTT assay were performed to determine the cell proliferation. Apoptosis was examined by FITC labeled annexin V and propidium iodide with flow cytometry. We analyzed molecules of Wnt signaling and stem cell markers with qRT-PCR.

RESULTS

We observed that PRR antibody significantly reduced cell proliferation, decreased sphere formation. Antibody suppressed cell adherent in stem-like cell. Flow cytometry showed that antibody induced apoptosis. Antibody inhibited Wnt signaling and stem cell markers.

CONCLUSIONS

PRR antibody reduced cell proliferation and induced apoptosis through Wnt signaling. PRR antibody also suppressed stemness. Our results demonstrated that PRR was a potential target for future glioma therapy.
ET-09 ACQUIRED MALIGNANT BEHAVIORS OF NPE6-PDT-SURVIVED GLIOBLASTOMA CELLS ARE SUPPRESSED BY USING MEK1/2 INHIBITOR TRAMETINIB
Authors: Kobayashi Tatsuya , Muragaki Yoshihiro , Takahashi Masamichi , Wada Kojiro , Mori Kentaro , Kawamata Takakazu , Ichimura Koichi , Tomiyama Arata
Published: December 2019

INTRODUCTION

In this study, we tried to investigate alteration of oncogenic properties and their molecular regulatory mechanism of talaporfin sodium (NPe6)-mediated photodynamic therapy (NPe6-PDT)-survived glioblastoma (GBM) cells.

METHODS

As the in-vitro NPe6-PDT model, human GBM cell lines (T98G, U87MG, U343), and patient derived GBM stem cells (GSY03, GSC23, MGG152) were pretreated with 0-30ug/ml NPe6 for 4 hours followed by laser irradiation (wave length 664 nm, laser-power 33 mW/cm2, total amount of irradiation 10 J/cm2) using a semiconductor laser irradiator (Panasonic Healthcare Co., Ltd., Tokyo, Japan). Cell death after PDT was evaluated by vital dye exclusion assay using Hoechst3342 and propidium iodide or CellTiter-Glo. Survived cells after NPe6-PDT (PDT-R cells) were repropagated, and alteration of intracellular molecular signaling or migration/invasion capability were analyzed by immunoblotting or Boyden chamber assay.

RESULTS

In both human GBM cell lines and patient derived GBM cells, cellular viability after NPe6-PDT was decreased with dose-dependent manner of pretreated NPe6. PDT-R cells showed not only resistance against NPe6-PDT-induced cell death but also higher invasiveness and migration capability compared with pre-PDT treated cells (PDT-Con cells), and immunoblot analysis demonstrated upregulation of ERK1/2 phosphorylation in PDT-R cells in comparison with PDT-Con cells. Furthermore, these acquired malignant behavior of PDT-R cells were repressed by concomitant use of MEK1/2 inhibitor Trametinib with NPe6-PDT.

CONCLUSION

We discovered PDT-R cells demonstrated higher malignant phenotypes via ERK1/2-dependent machinery compared with parent pre-PDT-treated cells. It was also suggested concomitant treatment with MEK1/2 inhibitor during PDT therapy in GBM cases would contribute to better outcome.