bluuebunny/crossref_metadata_2025 huggingface dataset:
Scintigraphic evaluation of cheek teeth in clinically sound horses
Authors: Szulakowski Marcin , Mageed Mahmoud , Steinberg Tim , Winter Karsten , Gerlach Kerstin
Published: August 2019

Dental disorders are one of the top‐ranking clinical domains in equine practice. Scintigraphy has emerged as a useful diagnostic imaging modality for equine dental diseases. There is a paucity of the normal scintigraphic uptake and its correlation with age. This prospective, cross‐sectional, descriptive and pilot‐designed study aimed to describe the radioisotope uptake (RU) patterns of the reserved crown and periodontal bone of the maxillary and mandibular cheek teeth (CT) in clinically sound horses and to evaluate the age effect on RU. For this purpose, 60 horses that underwent a bone scintigraphy for reason unrelated to head were included and divided equally into four age groups. Regions of interests (ROIs) were positioned around alveolar and periodontal bone of each maxillary and mandibular CT including their reserve crown, and a reference ROI positioned at the mandibular ramus. The count per pixel of each ROI was measured using a dedicated software and the RU ratio relative to the reference region was calculated. The results showed that the maxillary and mandibular CT had a standard RU pattern, where it increased from rostral to caudal, and peaked in the middle of dental arcades and decreased slightly towards the last CT. The maxillary CT had a higher RU compared with the mandibular CT, and there was no significant difference in the maxillary and mandibular CT uptake between age groups. This information may aid veterinarians evaluating potentially abnormal dental scintigraphy.
Probing the anomaloustqγ couplings through single top production at the future lepton–hadron colliders
Authors: Alici E. , Köksal M.
Published: August 2019

The measurements of the top quark flavor changing neutral current interactions are one of the most important goals of the top quark physics program in the present and the future collider experiments. These measurements provide direct information on nonstandard interactions of the top quark. Within the framework of new physics beyond the Standard Model, these interactions can be defined by an effective Lagrangian. In this study, we have investigated the potential of the future [Formula: see text] colliders on the top quark flavor changing neutral current interactions through the subprocesses [Formula: see text], where [Formula: see text]. These subprocesses have been produced through the main reaction [Formula: see text] at the LHC-[Formula: see text], the FCC-[Formula: see text] and the SPPC-[Formula: see text]. For the main reaction, the total cross-sections have been calculated as a function of the anomalous [Formula: see text] couplings. In addition, sensitivities on [Formula: see text] at 95% Confidence Level have been calculated. We obtain that the best constraints on [Formula: see text] are at the order of [Formula: see text] which is four orders of magnitude better than the LHC’s experimental results.
Collision dynamics of proton to water dimer at 250 eV
Authors: Wang Zhiping , Zhang Fengshou , Xu Xuefeng , Wang Yanbiao , Qian Chaoyi
Published: August 2019

Applying a real-space, real-time implementation of time-dependent density functional theory coupled to molecular dynamics (TDDFT-MD) non-adiabatically, we study the ionization and fragmentation of water dimer in collision with a proton at 250 eV. Four different incident orientations with various impact parameters are employed to account for orientation effects. The reaction channels, electronic density evolution, scattering pattern and energy loss of proton are obtained. We find that proton is scattered away for all impact parameters and the head-on collision effects the energy loss of proton dominantly as well as the scattering angle. The locations of peaks of the scattering angles are similar to those corresponding to the energy loss. The single-electron capture, the double-electron capture as well as the total electron capture cross-sections are obtained. We find that the single-electron capture cross-section contributes most to the total electron capture cross-section and the calculated total electron capture cross-section is in reasonable agreement with experimental and other theoretical results with respect to water gas and liquid water.
Prioritized Process Test: An Alternative to Current Process Testing Strategies
Authors: Bures Miroslav , Ahmed Bestoun S. , Zamli Kamal Z.
Published: August 2019

Testing processes and workflows in information and Internet of Things systems is a major part of the typical software testing effort. Consistent and efficient path-based test cases are desired to support these tests. Because certain parts of software system workflows have a higher business priority than others, this fact has to be involved in the generation of test cases. In this paper, we propose a Prioritized Process Test (PPT), which is a model-based test case generation algorithm that represents an alternative to currently established algorithms that use directed graphs and test requirements to model the system under test. The PPT accepts a directed multigraph as a model to express priorities, and edge weights are used instead of test requirements. To determine the test-coverage level of test cases, a test-depth-level concept is used. We compared the presented PPT with five alternatives (i.e. the Process Cycle Test (PCT), a naive reduction of test set created by the PCT, Brute Force algorithm, Set-covering-Based Solution and Matching-based Prefix Graph Solution) for edge coverage and edge-pair coverage. To assess the optimality of the path-based test cases produced by these strategies, we used 14 metrics based on the properties of these test cases and 59 models that were created for three real-world systems. For all edge coverage, the PPT produced more optimal test cases than the alternatives in terms of the majority of the metrics. For edge-pair coverage, the PPT strategy yielded similar results to those of the alternatives. Thus, the PPT strategy is an applicable alternative as it reflects both the required test coverage level and the business priority in parallel.
Research Notes — Software Process Selection Based Upon Abstract Machines for Slow Intelligence Systems
Authors: Chang Shi-Kuo , Zhou Jinpeng , Yendluri Akhil , Clancy Kadie
Published: August 2019

The abstract-machine model was developed by Chang to formalize the decision cycles of slow intelligence systems. It turns out that the selection of software process can also be regarded as a slow intelligence system. In this paper, we formalize abstract-machine prototypes for different software process models (SPMs) such as waterfall model, incremental model, spiral model, extreme programming model and scrum model. A Software Process Generator (SPG) was implemented to generate SPMs based upon design considerations. Initial evaluation by undergraduate students using SPG to learn software processes suggests further improvements to make it a useful learning tool.
STRUCTURAL AND MORPHOLOGICAL PROPERTIES OF ANNEALED MoO3 FILMS ON DIFFERENT SUBSTRATES
Authors: RAZA SYED HAMMAD , AFZAL NAVEED , RAFIQUE MOHSIN , IMRAN M. , AHMAD R.
Published: August 2019

Molybdenum oxide (MoO3) films were deposited on glass, Al, Mo and Si substrates at room temperature in Ar-O2 plasma by RF magnetron sputtering system. The as-deposited films were annealed in air at 400∘C and 500∘C. X-ray diffraction (XRD) results revealed that films annealed at 400∘C on all the substrates exhibited diffraction peaks of orthorhombic (α) and monoclinic (β) phases of MoO3. By increasing the annealing temperature to 500∘C, the [Formula: see text]-MoO3 phase on glass became more significant when compared with the [Formula: see text]-MoO3 phase. In contrast, the [Formula: see text]-MoO3 phase was more prominent in the case of film grown on the Mo substrate. The Fourier transform infrared spectroscopy (FTIR) analysis indicated stretching vibrational modes of Mo[Formula: see text]O and transverse optical modes of Mo-O-Mo on all the substrates. The surface morphology of MoO3 films on glass shows a flat surface at 400∘C that was changed into a layered-like structure at 500∘C. In the case of MoO3 films on Al and Si, arbitrary-shaped particles were transformed into needle and rod shapes, respectively, with increase of annealing temperature from 400∘C to 500∘C. The film annealed on Mo substrate at 400∘C revealed corrugated particles that were changed into coarse and elongated particles at 500∘C. The morphological changes in MoO3 film with increase of annealing temperature were associated with tensile strain developed inside MoO3 due to lattice and thermal mismatch between the film and the substrate.
EFFECTS OF THE BORIDING PROCESS AND OF QUENCHING AND TEMPERING AFTER BORIDING ON THE MICROSTRUCTURE, HARDNESS AND WEAR OF AISI 5140 STEEL
Authors: BICAN OSMAN , BAYCA SALIH UGUR , OCAK-ARAZ SULE , YAMANEL BUNYAMIN , TANIS NACI ARDA
Published: August 2019

An investigation was made on the effects of the boriding process and of quenching and tempering after boriding on the microstructure, hardness and wear of AISI 5140 steel. In this study, a new boriding agent (Baybora[Formula: see text]–1) developed for the solid boriding method was used. It was observed that the wear resistance of the borided samples increased by about four times, but the wear resistance of the sample subjected to quenching and tempering after boriding increased by only about two times. Thus, it was determined that quenching and tempering after boriding worsen wear resistance.
Adsorption of Cu2+ and Mg2+ ions on silica gel derived from rice hulls ash: Experimental and theoretical studies
Authors: Marie Asmaa , Atia Asem A. , ELGogary Tarek M. , El-Nahas Ahmed M.
Published: August 2019

Experimental study and quantum chemical calculations have been used to study the adsorption of Cu2+ and Mg2+ on silica gel derived from rice hulls ash. XRD measurements showed that the silica obtained has amorphous structure with BET of 250.1[Formula: see text]m2/g and pzc at pH 2. Adsorption of Cu2+ and Mg2+ on silica at 28[Formula: see text]∘C showed maximum capacities of 0.26 and 0.20[Formula: see text]mmol/g, respectively. In both cases of metal ions, the interaction was explained to proceed via hydrogen bonding through the outer hydration shell. Using density functional theory (DFT), interactions of hydrated metal ions with naked, mono- and di-hydrated silanol have been investigated. Calculations at the used level predict an increase of the entropy upon adsorption interaction with dehydrated silanol. Adsorption of hydrated Cu2+ and hydrated/un-hydrated Mg2+ on silanol is an exothermic process as predicted by B3LYP/6-31+G(d)//HF/6-31+G(d). This, in turn, leads to more negative free energy of reaction compared to experiment, [Formula: see text]59.8 versus [Formula: see text]25.8[Formula: see text]kJ/mol for Cu2+ and [Formula: see text]53.8 versus [Formula: see text]22.6[Formula: see text]kJ/mol for Mg2+. However, the strength of interaction between silica and both ions was reproduced correctly by theory.
Iron complex of a quadruply fused porphyrin: Synthesis, structure and redox properties
Authors: Ishizuka Tomoya , Komamura Keiyu , Saegusa Yuta , Tanaka Shogo , Shiota Yoshihito , Yoshizawa Kazunari , Kojima Takahiko
Published: August 2019

An iron(II) complex of a quadruply ring-fused porphyrin (QFP), Fe-1, in which four mesityl groups were introduced at the periphery to improve the solubility in organic solvents, has been newly synthesized and characterized. In the pyridine solution, two pyridine molecules bind to the low-spin Fe[Formula: see text] center of Fe-1 as axial ligands to make the complex stable even under air. Characterization of Fe-1 was performed using 1H NMR spectroscopy, MALDI-TOF-MS spectrometry and single-crystal X-ray diffraction analysis. The 1H NMR signals of Fe-1 were observed in the diamagnetic region, reflecting the low-spin state of the FeII center. In the differential pulse voltammogram of Fe-1, three oxidation waves and four reduction waves were observed in pyridine; the first oxidation wave at -0.08 V vs. Fc/Fc[Formula: see text] can be ascribed to the oxidation process of the FeII center, FeII/FeIII, and other six waves can be assigned to the redox processes of the QFP ligand. Furthermore, the ESR measurement of 1e[Formula: see text]-reduced Fe-1 upon controlled-potential bulk electrolysis in pyridine exhibited a signal at [Formula: see text] = 2.003 with a well-resolved 45-line hyperfine splitting at room temperature, due to the coupling with four nitrogen nuclei and twelve hydrogen ones of the QFP ligand. This indicates that the ligand radical anion of Fe-1 is stabilized by delocalization of the spin density owing to the peripheral ring fusion and resultant expansion of the [Formula: see text]-conjugation.
Uncertainty principle related to Flensted–Jensen partial differential operators
Authors: Laffi Raoudha , Negzaoui Selma
Published: August 2019

This paper deals with some formulations of the uncertainty principle associated to generalized Fourier transform [Formula: see text] related to Flensted–Jensen partial differential operators. The aim result is to prove the analogue of Bonami–Demange–Jaming’s theorem : A version of Beurling–Hörmander’s theorem which gives more precision in the form of nonzero functions verifying modified-Beurling’s condition. As application, we get analogous of Gelfand–Schilov’s theorem, Cowling–Price’s theorem and Hardy’s theorem for [Formula: see text].
Study of Stokes dynamical system in a thin domain with Fourier and Tresca boundary conditions
Authors: Letoufa Y. , Benseridi H. , Dilmi M.
Published: August 2019

Asymptotic analysis of an incompressible Stokes fluid in a dynamic regime in a three-dimensional thin domain [Formula: see text] with mixed boundary conditions and Tresca friction law is studied in this paper. The problem statement and variational formulation of the problem are reformulated in a fixed domain. In which case, the estimates on velocity and pressure are proved. These estimates will be useful in order to give a specific Reynolds equation associated with variational inequalities and prove the uniqueness.
News from the SIGs
Authors: Walker Ellen , Settle Amber
Published: August 2019

In this issue, Amber Settle, our SIGCSE reporter, writes her final column as SIGCSE Chair. Thanks so much, Amber, for your leadership!
Transgenic expression of carbonic anhydrase III in cardiac muscle demonstrates a mechanism to tolerate acidosis
Authors: Feng Han-Zhong , Jin J.-P.
Published: August 2019

Carbonic anhydrase III (CAIII) is abundant in liver, adipocytes, and skeletal muscles, but not heart. A cytosolic enzyme that catalyzes conversions between CO2 and [Formula: see text] in the regulation of intracellular pH, its physiological role in myocytes is not fully understood. Mouse skeletal muscles lacking CAIII showed lower intracellular pH during fatigue, suggesting its function in stress tolerance. We created transgenic mice expressing CAIII in cardiomyocytes that lack endogenous CAIII. The transgenic mice showed normal cardiac development and life span under nonstress conditions. Studies of ex vivo working hearts under normal and acidotic conditions demonstrated that the transgenic and wild-type mouse hearts had similar pumping functions under normal pH. At acidotic pH, however, CAIII transgenic mouse hearts showed significantly less decrease in cardiac function than that of wild-type control as shown by higher ventricular pressure development, systolic and diastolic velocities, and stroke volume via elongating the time of diastolic ejection. In addition to the effect of introducing CAIII into cardiomyocytes on maintaining homeostasis to counter acidotic stress, the results demonstrate the role of carbonic anhydrases in maintaining intracellular pH in muscle cells as a potential mechanism to treat heart failure.
MicroRNA-221 is overexpressed in the equine asthmatic airway smooth muscle and modulates smooth muscle cell proliferation
Authors: Issouf Mohamed , Vargas Amandine , Boivin Roxane , Lavoie Jean-Pierre
Published: August 2019

Airway wall remodeling, including hyperplasia and hypertrophy of smooth muscle (ASM) cells leading to an increased smooth muscle mass, is considered central to asthma. However, molecular pathways responsible for ASM remodeling remain poorly understood. MicroRNAs (miRNAs) have emerged as key regulators of inflammatory and repair processes affecting the lungs and can downregulate protein expression by inhibiting target mRNA translation. We therefore hypothesized that miRNAs are involved in ASM remodeling in asthma by modulating ASM proliferation. We have analyzed the expression of miRNAs in bronchial smooth muscle from asthmatic horses during disease exacerbation and remission and from controls. Their involvement in ASM cell proliferation was then studied. Our results shown that miR-26a, miR-133, and miR-221 were upregulated in ASM from horses with asthma exacerbation compared with asthma remission and controls. MiR-221 induced cell hyperproliferation and reduced the expression of contractile gene markers in ASM cells. These changes were associated with the decreased mRNA expression of cell cycle regulatory genes ( p53, p21, and p27). In conclusion, we demonstrated for the first time an upregulation of miR-221 in asthmatic airway smooth muscle and confirm the involvement of miR-221 in ASM cell proliferation by regulation of the cell cycle arrest genes. Targeting miR-221 network genes may represent a novel approach for the treatment of ASM remodeling in asthma.
Expression of obesity-related adipokine genes during fasting in a naturally obese marine mammal
Authors: Khudyakov Jane I. , Abdollahi Eileen , Ngo Angela , Sandhu Gureet , Stephan Alicia , Costa Daniel P. , Crocker Daniel E.
Published: August 2019

Northern elephant seals ( Mirounga angustirostris) are exceptional among fasting-adapted animals in coupling prolonged fasting with energetically costly activities, relying on oxidation of fat stores accrued during foraging to power metabolic demands of reproduction and molting. We hypothesized that high rates of energy expenditure, insulin resistance, and immune responses to colonial breeding in fasting seals are mediated by adipokines, or signaling molecules secreted by adipose tissue that are associated with obesity and inflammation in humans. We measured mRNA expression of 10 adipokine genes in blubber tissue of adult female elephant seals sampled early and late during their lactation and molting fasts and correlated gene expression with adiposity and circulating levels of corticosteroid and immune markers. Expression of adiponectin ( ADIPOQ) and its receptor ADIPOR2, leptin receptor ( LEPR), resistin ( RETN), retinol binding protein 4 ( RBP4), and visfatin/nicotinamide phosphoribosyltransferase ( NAMPT) was increased, whereas that of fat mass and obesity-associated protein ( FTO) was decreased in late-fasted compared with early-fasted groups. Abundance of adipokine transcripts that increased in late fasting was negatively associated with body mass and positively associated with cortisol, suggesting that they may mediate local metabolic effects of cortisol in blubber during fasting. Expression of several adipokines was correlated with the immune markers IL-6, haptoglobin, IgM, and IgE, suggesting a potential role in modulating immune responses to colonial breeding and molting. Since many of these adipokines have not been measured in other wild animals, this study provides preliminary insights into their local regulation in fat tissue and targeted assays for future studies.
Differences in acidosis-stimulated renal ammonia metabolism in the male and female kidney
Authors: Harris Autumn N. , Lee Hyun-Wook , Fang Lijuan , Verlander Jill W. , Weiner I. David
Published: August 2019

Renal ammonia excretion is a critical component of acid-base homeostasis, and changes in ammonia excretion are the predominant component of increased net acid excretion in response to metabolic acidosis. We recently reported substantial sex-dependent differences in basal ammonia metabolism that correlate with sex-dependent differences in renal structure and expression of key proteins involved in ammonia metabolism. The purpose of the present study was to investigate the effect of sex on the renal ammonia response to an exogenous acid load. We studied 4-mo-old C57BL/6 mice. Ammonia excretion, which was less in male mice under basal conditions, increased in response to acid loading to a greater extent in male mice, such that maximal ammonia excretion did not differ between the sexes. Fundamental structural sex differences in the nonacid-loaded kidney persisted after acid loading, with less cortical proximal tubule volume density in the female kidney than in the male kidney, whereas collecting duct volume density was greater in the female kidney. To further investigate sex-dependent differences in the response to acid loading, we examined the expression of proteins involved in ammonia metabolism. The change in expression of phosphoenolpyruvate carboxykinase and Rh family B glycoprotein with acid loading was greater in male mice than in female mice, whereas Na+-K+-2Cl–cotransporter and inner stripe of the outer medulla intercalated cell Rh family C glycoprotein expression were significantly greater in female mice than in male mice. There was no significant sex difference in glutamine synthetase, Na+/H+exchanger isoform 3, or electrogenic Na+-bicarbonate cotransporter 1 variant A protein expression in response to acid loading. We conclude that substantial sex-dependent differences in the renal ammonia response to acid loading enable a similar maximum ammonia excretion response.
Sphingosine-1-phosphate signaling in blood pressure regulation
Authors: Intapad Suttira
Published: August 2019

Sphingolipids were originally believed to play a role only as a backbone of mammalian cell membranes. However, sphingolipid metabolites, especially sphingosine-1-phosphate (S1P), are now recognized as new bioactive signaling molecules that are critically involved in numerous cellular functions of multiple systems including the immune system, central nervous system, and cardiovascular system. S1P research has accelerated in the last decade as new therapeutic drugs have emerged that target the S1P signaling axis to treat diseases of the immune and central nervous systems. There is limited knowledge of the specific effects on cardiovascular disease. This review discusses the current state of knowledge regarding the role of S1P on the regulation of blood pressure, vascular tone, and renal functions.
Practice induces a qualitative change in the memory representation for visuomotor learning
Authors: Huberdeau David M. , Krakauer John W. , Haith Adrian M.
Published: August 2019

Adaptation of our movements to changes in the environment is known to be supported by multiple learning processes that operate in parallel. One is an implicit recalibration process driven by sensory-prediction errors; the other process counters the perturbation through more deliberate compensation. Prior experience is known to enable adaptation to occur more rapidly, a phenomenon known as “savings,” but exactly how experience alters each underlying learning process remains unclear. We measured the relative contributions of implicit recalibration and deliberate compensation to savings across 2 days of practice adapting to a visuomotor rotation. The rate of implicit recalibration showed no improvement with repeated practice. Instead, practice led to deliberate compensation being expressed even when preparation time was very limited. This qualitative change is consistent with the proposal that practice establishes a cached association linking target locations to appropriate motor output, facilitating a transition from deliberate to automatic action selection.

NEW & NOTEWORTHY Recent research has shown that savings for visuomotor adaptation is attributable to retrieval of intentional, strategic compensation. This does not seem consistent with the implicit nature of memory for motor skills and calls into question the validity of visuomotor adaptation of reaching movements as a model for motor skill learning. Our findings suggest a solution: that additional practice adapting to a visuomotor perturbation leads to the caching of the initially explicit strategy for countering it.
YDJC Induces Epithelial-Mesenchymal Transition via Escaping from Interaction with CDC16 through Ubiquitination of PP2A
Authors: Kim Eun Ji , Park Mi Kyung , Kang Gyeoung-Jin , Byun Hyun Jung , Kim Hyun Ji , Yu Lu , Kim Boram , Chae Hee-Sung , Chin Young-Won , Shim Jae Gal , Lee Ho , Lee Chang Hoon
Published: August 2019

Lung cancer is the number 1 cause of cancer-related casualties in the world. Appropriate diagnostic markers and novel targets for lung cancer are needed. Chitooligosaccharide deacetylase homolog (YDJC) catalyzes the deacetylation of acetylated carbohydrates; however, the role of YDJC in lung cancer progression has yet to be studied. A549 lung cancer orthotopic mouse model was used for mice experiments. We found that YDJC overexpression contributes to lung cancer progression in an orthotopic mouse model. Long-term treatment (48 h) induces YDJC expression in sphingosylphosphorylcholine (SPC)-induced epithelial-mesenchymal transition (EMT). Gene silencing of YDJC (siYDJC) reduced N-cadherin expression and increased E-cadherin expression in SPC-induced EMT. Overexpression of YDJC reverses them but overexpression of the deacetylase deficient mutant YDJCD13A could not. Interestingly, overexpression of CDC16, a YDJC binding partner, suppressed EMT. ERK2 is activated in siCDC16-induced EMT. YDJC overexpression reduces expression of protein phosphatase 2A (PP2A), whereas CDC16 overexpression induces PP2A expression. YDJC overexpression induced ubiquitination of PP2A but YDJCD13A could not. CDC16 overexpression increased the ubiquitination of YDJC. These results suggest that YDJC contributes to the progression of lung cancer via enhancing EMT by inducing the ubiquitination of PP2A. Therefore, YDJC might be a new target for antitumor therapy against lung cancer.
Mixing Dyadic and Deliberative Opinion Dynamics in an Agent‐Based Model of Group Decision‐Making
Authors: Butler George , Pigozzi Gabriella , Rouchier Juliette
Published: August 2019

In this article, we propose an agent‐based model of opinion diffusion and voting where influence among individuals and deliberation in a group are mixed. The model is inspired from social modeling, as it describes an iterative process of collective decision‐making that repeats a series of interindividual influences and collective deliberation steps, and studies the evolution of opinions and decisions in a group. It also aims at founding a comprehensive model to describe collective decision‐making as a combination of two different paradigms: argumentation theory and ABM‐influence models, which are not obvious to combine as a formal link between them is required. In our model, we find that deliberation, through the exchange of arguments, reduces the variance of opinions and the proportion of extremists in a population as long as not too much deliberation takes place in the decision processes. Additionally, if we define the correct collective decisions in the system in terms of the arguments that should be accepted, allowing for more deliberation favors convergence towards the correct decisions.
Prospective Cohort Study on Refractive Changes after Trabeculectomy
Authors: Iwasaki Kentaro , Takamura Yoshihiro , Arimura Shogo , Tsuji Takahiro , Matsumura Takehiro , Gozawa Makoto , Inatani Masaru
Published: August 2019

We prospectively evaluated refractive changes in the eyes of 97 patients who underwent trabeculectomy at Fukui University Hospital, Fukui, Japan. The primary outcome measure was the refractive change after trabeculectomy. Secondary outcome measures included postoperative complications and prognostic factors for refractive change. We observed a progressive and significant mean refractive myopic shift of −0.80 D at 12 months after surgery. In phakic eyes, the mean myopic refractive shifts progressed significantly by −0.46 D at 3 months after surgery (P=0.003), by −0.52 D at 6 months (P=0.012), and by −1.31 D at 12 months (P<0.001). In the pseudophakic eyes, we found no significant refraction progression at any of the postsurgery follow-up visits. Our multivariable analyses showed that lens nuclear color grade change was a significant prognostic factor for refractive myopic progression (P<0.001). Trabeculectomy causes refractive myopic progression in phakic eyes. Nuclear sclerotic cataract progression is associated with refractive myopic shift after trabeculectomy. This trail is registered with UMIN000007813.
A Two-Fluid Conditional Averaging Paradigm for the Theory and Modeling of Turbulent Premixed Combustion
Authors: Zimont Vladimir L.
Published: August 2019

This paper extends a recent theoretical study that was previously presented in the form of a brief communication (Zimont, C&F, 192, 2018, 221-223), in which we proposed a simple splitting method for the derivation of two-fluid conditionally averaged equations of turbulent premixed combustion in the flamelet regime, formulated more conveniently for applications involving unclosed equations without surface-averaged unknowns. This two-fluid conditional averaging paradigm avoids the challenge in the Favre averaging paradigm of modeling the countergradient scalar transport phenomenon and the unusually large velocity fluctuations in a turbulent premixed flame. It is a more suitable conceptual framework that is likely to be more convenient in the long run than the traditional Favre averaging method. In this article, we further develop this paradigm and pay particular attention to the problem of modeling turbulent premixed combustion in the context of a two-fluid approach. We formulate and analyze the unclosed differential equations in terms of the conditions of the Reynolds stressesτij,u,τij,band the mean chemical sourceρW¯, which are the only modeling unknowns required in our alternative conditionally averaged equations. These equations are necessary for the development of model differential equations for the Reynolds stresses and the chemical source in the advanced modeling and simulation of turbulent premixed combustion. We propose a simpler approach to modeling the conditional Reynolds stresses based on the use of the two-fluid conditional equations of the standard “k-ε” turbulence model, which we formulate using the splitting method. The main problem arising here is the appearance in these equations of unknown terms describing the exchange of the turbulent energykand dissipation rateεin the unburned and burned gases. We propose an approximate way to avoid this problem. We formulate a simple algebraic expression for the mean chemical source that follows from our previous theoretical analysis of the transient turbulent premixed flame in the intermediate asymptotic stage, in which small-scale wrinkles in the instantaneous flame surface reach statistical equilibrium, while the large-scale wrinkles remain in statistical nonequilibrium.
Tire-Pavement Contact Stress Characteristics and Critical Slip Ratio at Multiple Working Conditions
Authors: Guo Minrui , Zhou Xinglin
Published: August 2019

The contact stress distribution of tire-pavement is generally assumed to be uniformly distributed in circles or rectangles in the pavement design. This simplification can solve some common engineering problems, but it neglects two factors including magnitude and direction of the contact stress. The main purpose of this paper is to analyze the contact stress distribution between the bus tire and the pavement under different driving conditions and pinpoint and compare the critical slip ratio during braking and acceleration. First, a tire-pavement simulated contact model is constructed by ABAQUS. Next, we compare, respectively, contact stresses in the vertical, longitudinal, and transverse directions at various rolling conditions and analyze the longitudinal forces at different slip ratios during braking and acceleration. It is observed that the magnitude, direction, and nonuniform distribution of contact stress are affected by the multiple working conditions while the bus is working. Meanwhile, in the braking and acceleration conditions, the longitudinal force grows rapidly as the slip ratio increases, and then grows slowly and at last decreases when the critical slip ratio is reached. However, the critical slip ratio at the time of braking differs from that at the time of acceleration, and the former is smaller than the latter.
Aortic Arch Calcification Is a Strong Predictor of the Severity of Coronary Artery Disease in Patients with Acute Coronary Syndrome
Authors: Ma Xiaoteng , Hou Fangjie , Tian Jing , Zhou Zhen , Ma Yue , Cheng Yujing , Du Yu , Shen Hua , Hu Bin , Wang Zhijian , Liu Yuyang , Zhao Yingxin , Zhou Yujie
Published: August 2019

Background. The purpose of this study was to investigate the correlation of the extent of aortic arch calcification (AAC) detectable on chest X-rays with the severity of coronary artery disease (CAD) as evaluated by the SYNTAX score (SS) in patients with acute coronary syndrome (ACS). Methods. A total of 1,418 patients (344 women; 59 ± 10 years) who underwent coronary angiography for ACS and were treated with coronary revascularization were included in the present study; chest X-rays were performed on admission. The AAC extent was divided into four grades (0–3). SS was calculated based on each patient’s coronary angiographic findings. The relationship between the AAC extent and SS was assessed. Results. The AAC extent was positively correlated with SS (ρ = 0.639, P < 0.001). In the multivariate analysis, compared with grade 0, odds ratios (ORs) of AAC grades 1, 2, and 3 in predicting SS >22 were 12.95 (95% CI, 7.85–21.36), 191.76 (95% CI, 103.17–356.43), and 527.81 (95% CI, 198.24–1405.28), respectively. Receiver operating characteristic curve analysis yielded a strong predictive ability of the AAC extent for SS >22 (area under curve = 0.840, P < 0.001). Absence of AAC had a sensitivity, specificity, positive prognostic value, negative prognostic value, and accuracy of 46.7%, 95.9%, 94.1%, 56.4%, and 67.3%, respectively, for SS ≤22. AAC grades ≥2 had a sensitivity of 66.3%, specificity of 89.2%, positive prognostic value of 81.5%, negative prognostic value of 78.6%, and accuracy of 79.6% for the correct identification of SS >22. Conclusions. The extent of AAC detectable on chest X-rays might provide valuable information in predicting CAD severity in ACS patients.
Abstract 100: Novel selective PI3Kγ inhibitor AZD3458 promotes anti-tumor immune responses and reverts resistance to immunotherapy in checkpoint blockade refractory preclinical models
Authors: Carnevalli Larissa S. , Carrol Danielle , Moschetta Michele , Gutierrez Pablo Morentin , Gardelli Cristina , Taylor Molly A. , Montoya Antonio , Hughes Adina , King Matthew , Klinowska Teresa , Barry Simon T.
Published: August 2019

The PI3Kγ isoform is a key regulator of immune cell proliferation, survival, migration and activation. PI3Kγ inhibitors have the potential to treat a variety of diseases including respiratory, inflammatory, metabolic disorders and cancer. In the context of cancer PI3Kγ inhibition re-polarizes macrophages to an immuno-stimulatory phenotype activating a T-cell mediated tumor immune response. Selective PI3Kγ inhibitors have potential as monotherapy and in combination with checkpoint inhibition to overcome resistance and to enhance efficacy of checkpoint inhibitors. AZD3458 is a highly selective PI3Kγ clinical candidate kinase inhibitor with a cellular IC50 of 8nM with a 100-fold selectivity over PI3Kδ. In vitro, AZD3458 inhibits pAKTS308/S473 in human macrophages and mouse CD11b activation at 32nM and 30nM free IC50, respectively. At these concentrations AZD3458 reverses macrophage polarization increasing IL12/IL-10 ratio and does not impact T cell proliferation and function analysed by gene expression profiling, cytokine quantification and flow cytometry. Oral administration of AZD3458 (20mg/Kg BID) remodeled the tumor microenvironment in 4T1 orthotopic breast tumor model. AZD3458 decreased tumor associated macrophages by 20% compared to vehicle and reduced overall protein expression of immunosuppressive markers CD206 and PD-L1 measured by flow cytometry. In addition, AZD3458 reduced MDSC/neutrophil activation and promoted cytotoxic T-cell activation in vivo, measured by GzmB and Perforin mRNA and protein expression. Consistent to the observed tumor remodeling, combination with checkpoint inhibitors α-PD-1 or α-PD-L1 antibodies (10mg/kg 3x week) had greater anti-tumor effects than checkpoint inhibitor alone in 4T1, LLC, CT-26 and MC-38 mouse syngeneic models. These data demonstrate that AZD3458 can reverse myeloid suppressive tumor microenvironment and revert tumor resistance to immunotherapy in myeloid-enriched immunosuppressive tumor types.

Citation Format: Larissa S. Carnevalli, Danielle Carrol, Michele Moschetta, Pablo Morentin Gutierrez, Cristina Gardelli, Molly A. Taylor, Antonio Montoya, Adina Hughes, Matthew King, Teresa Klinowska, Simon T. Barry. Novel selective PI3Kγ inhibitor AZD3458 promotes anti-tumor immune responses and reverts resistance to immunotherapy in checkpoint blockade refractory preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 100.
Abstract 1003: Modulating estrogen related receptors (ERRs) activity in breast cancer using endogenous ligands
Authors: Ghanbari Faegheh , Mader Sylvie , Philip Anie
Published: August 2019

Estrogen-receptor related receptors which consists of ERRα, ERRβ and ERRγ belong to the orphan nuclear receptor subfamily of NR3B (nuclear receptor subfamily 3, group B). The ERRs have been shown to actively modulate estrogenic responses, and to play an essential role in pregnancy, and are implicated in breast cancer progression. Despite intensive efforts, no endogenous ligand has been identified for ERRs so far. The discovery of ligands that bind these orphan receptors will allow the manipulation of this pathway and may lead to novel strategies for the treatment of cancer and other diseases. In this study we show two endogenous ligands of ERRs: 1) estradienolone (ED), a novel endogenous steroid during pregnancy which acts as an inverse agonist of ERRs, 2) cholesterol as an agonist of ERRs. Our recent results show that ED acts as an inverse agonist of ERRα and ERRγ by directly interacting with these receptors, and inhibiting their transcriptional activity. We also demonstrate that ED has strong anti-mitogenic properties. ED inhibits the growth of both estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cells in a dose dependent manner, while of displaying a little effect on normal epithelial breast cells. In addition, we show that the effect of cholesterol or lovastatin (a drug known to inhibit cholesterol synthesis) in triple negative breast cancer (MDA-MB 231) requires ERRα. These data suggest that both ED-ERR and cholesterol-ERR interactions may represent novel physiologically relevant ERR pathways in the human.

Citation Format: Faegheh Ghanbari, Sylvie Mader, Anie Philip. Modulating estrogen related receptors (ERRs) activity in breast cancer using endogenous ligands [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1003.
Abstract 1005: Tamoxifen treatment induces the epigenetic changes in breast cancer stem cells
Authors: Palaniyandi Kanagarj , Gnasampandapandian Dhanavathy , Ramachandran Ilangovan , Sambandam Yuvaraj , Chandrakesan Parthasarathy
Published: August 2019

Purpose: Breast cancer is diagnosed in younger women population and is the leading cause of cancer-related deaths in India. Tamoxifen (TOM) is one of the most effective and widely used first-line endocrine therapy for ER+ breast cancer. However, breast cancer patients often develop TOM resistance and enhanced with caner stem cell (CSC)-like phenotypes. These TOM-resistance (TR) breast cancer phenotypes are highly aggressive and they do not respond to most of the chemotherapies. It is therefore essential to understand the mechanism that resulted in the development of TR in breast cancer. The current study was designed to investigate the epigenetic changes associated mechanism that induces the development of hormone-resistance in breast CSCs.

Experimental Procedure: In this study, we used ALDEFLOUR assay, flow cytometry, mammosphere culture, western blot, Chromatin-immunoprecipitation, and RT-PCR analyses.

Results: Our study showed that breast CSC-like population possesses higher TR cancer cell phenotypes than non-CSCs. We generated MCF7-derived mammospheres (CSCs) utilizing MammoCult media. However, when treated with TOM (1µM)-we observed an increased number of mammospheres (CSCs) than vehicle control. We found a strong interplay between TR and epigenetic changes, in particular, the changes observed in histone demethylase, which is believed to be one of the crucial links that involved in the development of therapy resistance and enhanced CSC population. Furthermore, TR breast CSCs derived from MCF7 cells display an increased expression of the NOTCH-1 protein. Induced overexpression of NOTCH in MCF7 cells increased the number of mammosphere formation ability than control cells. Finally, overexpression of NOTCH-1 also led to transcriptional up-regulation of cyclin genes A, B, and D.

Conclusion: We observed a crucial interplay between TR and breast CSCs. TR associated epigenetic alteration enhanced the expression of NOTCH1, which resulted in increased mitotic signals in the tumor cells including CSCs. Thus, these new phenotypes of breast CSCs with TR characteristics need more understanding for the development of effective combinatorial and adjuvant therapies.

Note: This abstract was not presented at the meeting.

Citation Format: Kanagarj Palaniyandi, Dhanavathy Gnasampandapandian, Ilangovan Ramachandran, Yuvaraj Sambandam, Parthasarathy Chandrakesan. Tamoxifen treatment induces the epigenetic changes in breast cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1005.
Abstract 1010: Extracellular matrix signaling modulates estrogen receptor activity in breast cancer
Authors: DiGiacomo Josh W. , Godet Inês , Rodriguez Michael Trautmann , Ye I Chae , Gilkes Daniele M.
Published: August 2019

The tumor microenvironment plays a crucial role in cancer progression. In breast cancer, the extracellular matrix (ECM) is especially important as it contributes to mammographic breast density. Women with higher mammographic breast densities are at a greater risk for the development of breast cancer. Despite this, much knowledge of the ECM’s effects on breast cancer progression remains elusive. To better understand how ECM signaling affects breast cancer, we utilize fibroblast-deposited, decellularized ECM scaffolds. Scaffolds are produced for in vitro use by culturing a confluent layer of fibroblast cells over six days followed by decellularization with a detergent solution. RNA sequencing analysis of MCF7 human breast cancer cells cultured on ECM scaffolds versus uncoated dishes revealed differential expression of hundreds of genes. Most notably, genes within hallmark sets for early and late responses to estrogen were significantly enriched when cells were cultured on ECM. We confirm the expression of estrogen-responsive genes in breast cancer cells cultured on ECM even in the complete absence of estrogen, and also note that the estrogen receptor (ER) itself is downregulated at both the RNA and protein-level, consistent with results of estrogen stimulation. Treatment of breast cancer cells with ER inhibitors hydroxytamoxifen and fulvestrant reduces ECM-induced expression of estrogen-responsive genes. Likewise, culturing breast cancer cells on ECM enhances phosphorylation of Erk. Inhibition of phospho-Erk also reduces the expression of the same estrogen-responsive genes in cells cultured on ECM. Through luciferase, conditioned media, and estrogen-starvation assays, we demonstrate that ECM signaling activates estrogen receptor signaling in an estrogen-independent, nonclassical mechanism. In addition, we show that ER positive cells cultured on ECM are more resistant to ER-targeted therapeutics, but not other chemotherapeutic agents like paclitaxel or doxorubicin. Ultimately, we describe a pathway in which ECM can induce estrogen-independent activation of the ER as well as resistance to estrogen-targeted therapies in breast cancer. Clinical research into the effects of mammographic breast density beyond breast cancer predisposition is sparse, and this work provides incentive for investigators to better understand the relationship between breast fibrosis and clinical outcome.

Citation Format: Josh W. DiGiacomo, Inês Godet, Michael Trautmann Rodriguez, I Chae Ye, Daniele M. Gilkes. Extracellular matrix signaling modulates estrogen receptor activity in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1010.
Abstract 1036: WISP-1 promotes epithelial-mesenchymal transition in oral squamous cell carcinoma via the miR-153-3p/Snail axis
Authors: Chang An-Chen , Tang Chih-Hsin
Published: August 2019

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy and approximately 50% of patients with OSCC present with regional regional lymph node metastasis. The first step in the ‘invasion-metastasis cascade’ is the phenomenon of epithelial-to-mesenchymal transition (EMT), whereby epithelial cells of the primary tumor lose their apical-basal polarity and transition to a mesenchymal phenotype, gaining the ability to migrate and invade basement membrane and blood vessels. WNT1-inducible signaling pathway protein-1 (WISP-1/CCN4) is an extracellular matrix-related protein that belongs to the CCN family, capable of stimulating bone remodeling and tumor progression. Our previous research showed that WISP-1 promotes cell migration and VEGF-C-dependent lymphangiogenesis in OSCC cells. This investigation further examined the role of WISP-1 in regulating EMT. First, we analyzed data from the cancer genome atlas (TCGA) database, to determine the clinical importance of WISP-1 in oral cancer. We found that WISP-1 expression was significantly associated with clinical disease stage and regional lymph node metastasis. Moreover, we found higher levels of WISP-1 expression in serum samples obtained from 62 patients with OSCC compared with samples from healthy controls. Treatment of the OSCC cell line SCC4 with WISP-1 increased EMT by downregulating expression of the epithelial marker E-cadherin and upregulating the mesenchymal marker Snail. We also observed that WISP-1 regulated the expression of EMT markers via the FAK, ILK and AKT signal transduction pathways. Computational analysis confirmed that microRNA (miR)-29c directly targets the 3′ untranslated region (3′ UTR) of Snail. Treatment of SCC4 cells with WISP-1 inhibited miR-29c expression, while miR-29c mimic prevented WISP-1-induced enhancement of Snail expression, revealing an inverse correlation between miR-29c and Snail expression during WISP-1 treatment. Our findings provide insight into WISP-1-mediated regulation of EMT in OSCC.

Citation Format: An-Chen Chang, Chih-Hsin Tang. WISP-1 promotes epithelial-mesenchymal transition in oral squamous cell carcinoma via the miR-153-3p/Snail axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1036.