bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure mode investigation and re-design of heavy-duty commercial vehicle bogie bracket
Authors: Thangapazham P. , Kumaraswamidhas L.A. , Muruganandam D.
Published: March 2019

Heavy-duty commercial vehicles play a significant role in commodity logistics. For each of these vehicles, the suspension is the most essential system to support the load and road shock. Bogie type suspension system is employed to safeguard the vehicle from road shock. The bogie bracket is a juncture between the chassis and the axle in the suspension system. The bogie bracket has been identified as a critical part of the suspension system. In the present study, bogie bracket base design and modelling was performed using computer-aided engineering (CAE). The strength of the bogie was tested to identify weaker sections. Design modifications were performed to improve the strength on identified critical sections through reinforcement techniques. A road load data acquisition (RLDA) test was conducted under different road conditions to validate CAE results. Five different rough-road road surfaces were chosen for RLDA testing. Using strain gauges, strain data were acquired during the test. Corresponding stress values were obtained and maximum stress was found in all driving conditions. For the base design bogie bracket, under RLDA test, crack initiation and crack propagation were identified under vertical loads. A reinforced bogie bracket was designed and found to have a higher strength and longer expected life than that of the base design.
Optimization of PIXE quantitative system to assist traceability of pearls
Authors: Murao S. , Sera K. , Goto S. , Takahashi C. , Cartier L. , Nakashima K.
Published: March 2019

Recent rise of social attention towards ethical jewelry has led scientists to a challenge of how to construct analytical systems that can deliver in line with social and supply chain expectations. Of the various kinds of methods, “Proton/Particle-Induced X-ray Emission” (PIXE) seems to be robust and promising in characterizing gemstones because of its capability of trace element analysis without destruction. The authors established a non-standard method to analyze cultured pearls and applied it to test specimens from different places. The results showed that PIXE could detect important elements for pearl study with good accuracy and sensitivity and that pearl chemistry can be useful to differentiate freshwater and marine pearl products.
Berberine Suppresses RANKL-Induced Osteoclast Differentiation by Inhibiting c-Fos and NFATc1 Expression
Authors: Han Sang-Yong , Kim Yun-Kyung
Published: March 2019

Osteoporosis is a common disorder of bone remodeling, marked by excessive osteoclast formation. Recent studies indicated that berberine (BBR) is a potential natural drug for the treatment of various bone diseases. However, it still needs to be further studied for the treatment of osteoporosis. The current study investigated the inhibitory effects of BBR on receptor activator of nuclear factor-[Formula: see text]B ligand (RANKL)-induced osteoclast differentiation in vitro and in vivo. Cell-based assays were performed using osteoclasts generated in cultures of murine bone marrow-derived macrophages (BMMs) treated with RANKL and M-CSF. The effects of BBR on in vivo lipopolysaccharide (LPS)-mediated bone loss were evaluated using ICR mice. BBR significantly inhibited TRAP-positive osteoclast formation induced by RANKL. BBR also inhibited RANKL-induced Akt, p38 and ERK phosphorylation and I[Formula: see text]B degradation, and suppressed RANKL-induced expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which is a key transcription factors for osteoclast formation. BBR reduced the mRNA levels of osteoclast markers, including TRAP, osteoclast-associated receptor (OSCAR), cathepsin K, and ATPase H[Formula: see text] transporting V0 subunit d2 (ATP6v0d2). Moreover, BBR prevented LPS-mediated bone loss in vivo. We suggest BBR as a natural compound that can be a potential therapeutic agent for osteoclast-related bone diseases.
IMMIGRATION, INNOVATION, AND ECONOMIC GROWTH
Authors: BILGIN MEHMET HUSEYIN , GOZGOR GIRAY , RANGAZAS PETER
Published: March 2019

This paper investigates the empirical effects of immigration on economic growth in a panel dataset of 30 Organization for Economic Cooperation and Development (OECD) countries for the period from 1991 to 2015. We find no effect of immigration generally on economic growth. However, a country’s foreign student share has a robust positive association with the country’s economic growth rate. The results, in conjunction with recent evidence of an immigration–innovation connection, suggest that the foreign student share works through new business startups.
Sub-GeV-scale signatures of hidden braneworlds up to the Planck scale in a SO(3,1)-broken bulk
Authors: Stasser Coraline , Sarrazin Michaël
Published: March 2019

Many-brane Universes are at the heart of several cosmological scenarios related to physics beyond the Standard Model. It is then a major concern to constrain these approaches. Two-brane Universes involving [Formula: see text]-broken 5D bulks are among the cosmological models of interest. They also allow considering matter exchange between branes, a possible way to test these scenarios. Neutron disappearance (reappearance) toward (from) the hidden brane is currently tested with high-precision experiments to constrain the coupling constant [Formula: see text] between the visible and hidden neutron sectors. When dealing with the sub-GeV-scale quantum dynamics of fermions, any pair of braneworlds can be described by a noncommutative two-sheeted space–time [Formula: see text] from which [Formula: see text] emerges. Nevertheless, the calculation of the formal link between [Formula: see text] for a neutron and [Formula: see text]-broken 5D bulks remains an open problem until now although necessary to constrain these braneworld scenarios. Thanks to a phenomenological model, we derive [Formula: see text] — for a neutron — between the two braneworlds endowed with their own copy of the Standard Model in an [Formula: see text]-broken 5D bulk. Constraints on interbrane distance and brane energy scale (or brane thickness) are discussed. While brane energy scale below the GUT scale is excluded, energy scale up to the Planck limit allows neutron swapping detection in forthcoming experiments.
First-principles study of the structural and electronic properties of Sr1−xMxSi2 (M=Ca and Ba)
Authors: Jiang N. Q. , Chen Z. J. , Chen T. H.
Published: March 2019

We investigated the structural and electronic properties of Sr[Formula: see text]M[Formula: see text]Si2 (M[Formula: see text]=[Formula: see text]Ca and Ba) (x[Formula: see text]=[Formula: see text]0, 0.25, 0.5, 0.75 and 1) by the first-principles calculation in the frame work of density-functional theory. It was found that the structure of Sr[Formula: see text]Ca[Formula: see text]Si2 is evidently compressed with increasing the Ca content. On the other hand, the incorporation of Ba cause the swelling crystal structure. A structure transition for Sr[Formula: see text]M[Formula: see text]Si2 (M[Formula: see text]=[Formula: see text]Ca and Ba) from cubic to tetragonal appear when the doping concentration is 0.5. Band structure calculations indicated that the bandgap decrease or even disappear with increasing Ca atoms, which suggesting the transition from the semiconductor to the metal for SrSi2. Whereas, the semiconducting bandgap increases with the incorporation of Ba atoms. Our results imply that the thermoelectric properties of SrSi2-based alloys can be further enhanced by increasing Ca doping content, Ca-doped SrSi2 is a promising thermoelectric material.
Optoelectronic properties of CaxBa1−xX (X=S, Se and Te) alloys: A first principles investigation employing modified Becke–Johnson (mBJ) functional
Authors: Debnath Bimal , Debbarma Manish , Ghosh Debankita , Chanda Sayantika , Bhattacharjee Rahul , Chattopadhyaya Surya
Published: March 2019

Optoelectronic properties of alkaline-earth calcium-barium chalcogenide ternary alloys Ca[Formula: see text]Ba[Formula: see text]S, Ca[Formula: see text]Ba[Formula: see text]Se and Ca[Formula: see text]Ba[Formula: see text]Te have been calculated using first principle-based FP-LAPW methodology employing modified Becke–Johnson (mBJ) exchange-correlation functional. Both the lattice parameter and the bulk modulus vary nonlinearly with dopant concentration in each of these alloy systems. The evolution of a series of thermodynamically stable wide-direct-bandgap ternary alloys as a result of amalgamation of indirect-bandgap homo-chalcogen CaX and BaX at Ca-concentrations [Formula: see text] = 0.25, 0.50 and 0.75 is observed. Bonding between calcium and chalcogen is ionic, while that between barium and chalcogen is covalent in nature. Each of the alloy systems show substantial nonlinearity in the concentration dependence of bandgap and the dominant role is played by the volume deformation effect in total bandgap bowing. It is observed that the chalcogen-p of valence band as initial states and Ca-3d as well as Ba-5d states of conduction band as final states play the dominant role in optical transitions. Nature of nonlinear concentration dependence of each of the static optical constants is opposite and critical point is similar to that of bandgap in each of the alloy systems. Several calculated properties are found to agree well with the corresponding experimental findings.
Native Code Generation as a Service
Authors: Akbulut Akhan , Catal Cagatay , Karadeniz Emre , Turgut Emre
Published: March 2019

With the widespread use of mobile applications in daily life, it has become crucial for enterprise software companies to quickly develop these applications for multiple platforms. Cross-platform mobile application development is one of the most adopted solutions for rapid development. Since most of these solutions do not generate native code for the underlying platform, the artefacts generally do not satisfy the requirements defined at the beginning of the project. This study designed and implemented a native code generation framework called Nativator built as a cloud service. The framework, which is capable of producing native code for iOS and Android platforms using web-based user interfaces, was implemented based on an open source compiler platform called “Roslyn”. Four case studies were performed to analyze the execution performance of the applications built with the proposed framework. The experimental results demonstrated that the execution performance of the applications built with Nativator is comparable with the applications generated via the state-of-the-art mobile application development framework called Xamarin. Because this framework was implemented as a cloud service, it has several advantages over traditional approaches such as access from anywhere, no installation and flexible and more resources from cloud infrastructure.
MEASURING DEFAULT RISK FOR A PORTFOLIO OF EQUITIES
Authors: RODRIGUES MATHEUS PIMENTEL , MAIALY ANDRE CURY
Published: March 2019

This work evaluates some changes proposed by the Basel Committee on Banking Supervision in regulating capital allocation in the trading book for equities following a company default. In the last decade, the committee designed some measures to account for the risk of a company default that the ten-day value-at-risk measure does not capture. The first and more conservative measure designed to capture the effect of defaults was the incremental risk charge. With time, this measure evolved into the default risk charge. We use a Merton model to compute the probability of default and compare this probability to simulated asset returns in order to compute the one-year value-at-risk and capture the risk of a company default. The analysis compares portfolios of Ibovespa companies and S&P 500 companies. Additionally, we propose a method to account for the correlation in the companies and compare the effects of the standard method of capital allocation to those of our models.
The nonlocal mean-field equation on an interval
Authors: DelaTorre Azahara , Hyder Ali , Martinazzi Luca , Sire Yannick
Published: March 2019

We consider the fractional mean-field equation on the interval [Formula: see text] [Formula: see text] subject to Dirichlet boundary conditions, and prove that existence holds if and only if [Formula: see text]. This requires the study of blowing-up sequences of solutions. We provide a series of tools in particular which can be used (and extended) to higher-order mean field equations of nonlocal type.
Predicting Dynamic Behavior of Rotating Mindlin Plate Using Radial Point Interpolation Method
Authors: Du C. F. , Zhang D. G. , Zhang J. S. , Fan J. H.
Published: March 2019

This paper proposes the radial point interpolation method (RPIM) for studying the dynamic behaviors of rotating Mindlin plates. By considering nonlinear coupling deformation, that is, the in-plane longitudinal shortening terms caused by transverse deformation, the first-order approximation coupled (FOAC) dynamic model is established using Lagrange’s equations of the second kind. The effectiveness of RPIM is first demonstrated in some static cases and then extended for dynamic analysis of a rectangular plate subjected to a large overall motion. The simulation results were compared with those obtained with zero-order approximation coupled (ZOAC) dynamic model, and it was observed that results obtained with FOAC dynamic model are more accurate, especially for cases involving high rotating speed. Furthermore, the influence of the radial basis shape parameters is discussed and the optimal parameters for plates are recommended. An approach to overcome the shear locking issue is also provided.
The Poincaré variational principle in the Lagrange–Poincaré reduction of mechanical systems with symmetry
Authors: Storchak S. N.
Published: March 2019

The local Lagrange–Poincaré equations (the reduced Euler–Lagrange equations) for the mechanical system describing the motion of a scalar particle on a finite-dimensional Riemannian manifold with a given free isometric smooth action of a compact semi-simple Lie group are obtained. The equations are written in terms of dependent coordinates which are used to represent the local dynamic given on the orbit space of the principal fiber bundle. The derivation of the equations is performed with the help of the variational principle developed by Poincaré for mechanical systems with symmetry.
Short Note: Some Hints on Fuzzy Logic’s Negation Functions
Authors: Alsina Claudi , Trillas Enric
Published: March 2019

This paper deals with how non-strong linguistic negations can be represented in Fuzzy Logic by means of Negation Functions. Even if the problem is not closed, the impossibility of representing by exhaustive Negation Functions those that are either weak, or intuitionistic, is proved. A hint on how to continue the study is presented.
Statistics for products of traces of high powers of the Frobenius class of hyperelliptic curves in even characteristic
Authors: Bae Sunghan , Jung Hwanyup
Published: March 2019

We study the averages of products of traces of high powers of the Frobenius class of real hyperelliptic curves of genus [Formula: see text] over a fixed finite field [Formula: see text] in both odd and even characteristic cases.
Some evaluations of infinite series involving parametric harmonic numbers
Authors: Xu Ce
Published: March 2019

In this paper, we deduce the asymptotic formulas of parametric digamma function [Formula: see text] at the integers and poles. Then using these identities and residue theorem, we establish a large number of formulas of double series involving parametric harmonic numbers. Some illustrative special cases as well as immediate consequences of the main results are also considered.
Residuation in modular lattices and posets
Authors: Chajda Ivan , Länger Helmut
Published: March 2019

We show that every complemented modular lattice can be converted into a left residuated lattice where the binary operations of multiplication and residuum are term operations. The concept of an operator left residuated poset was introduced by the authors recently. We show that every strongly modular poset with complementation as well as every strictly modular poset with complementation can be organized into an operator left residuated poset in such a way that the corresponding operators [Formula: see text] and [Formula: see text] can be expressed by means of the operators [Formula: see text] and [Formula: see text] in posets. We describe connections between the operator left residuation in these posets and the residuation in their lattice completion. We also present examples of strongly modular and strictly modular posets.
Advances in Surface Plasmon Resonance Imaging and Microscopy and Their Biological Applications
Authors: Bocková Markéta , Slabý Jiří , Špringer Tomáš , Homola Jiří
Published: March 2019

Surface plasmon resonance microscopy and imaging are optical methods that enable observation and quantification of interactions of nano- and microscale objects near a metal surface in a temporally and spatially resolved manner. This review describes the principles of surface plasmon resonance microscopy and imaging and discusses recent advances in these methods, in particular, in optical platforms and functional coatings. In addition, the biological applications of these methods are reviewed. These include the detection of a broad variety of analytes (nucleic acids, proteins, bacteria), the investigation of biological systems (bacteria and cells), and biomolecular interactions (drug–receptor, protein–protein, protein–DNA, protein–cell).
The Dynamics of Cambial Stem Cell Activity
Authors: Fischer Urs , Kucukoglu Melis , Helariutta Ykä , Bhalerao Rishikesh P.
Published: March 2019

Stem cell populations in meristematic tissues at distinct locations in the plant body provide the potency of continuous plant growth. Primary meristems, at the apices of the plant body, contribute mainly to the elongation of the main plant axes, whereas secondary meristems in lateral positions are responsible for the thickening of these axes. The stem cells of the vascular cambium—a secondary lateral meristem—produce the secondary phloem (bast) and secondary xylem (wood). The sites of primary and secondary growth are spatially separated, and mobile signals are expected to coordinate growth rates between apical and lateral stem cell populations. Although the underlying mechanisms have not yet been uncovered, it seems likely that hormones, peptides, and mechanical cues orchestrate primary and secondary growth. In this review, we highlight the current knowledge and recent discoveries of how cambial stem cell activity is regulated, with a focus on mobile signals and the response of cambial activity to environmental and stress factors.
Beneficial effects of mesenchymal stem cell delivery via a novel cardiac bioscaffold on right ventricles of pulmonary arterial hypertensive rats
Authors: Schmuck Eric G. , Hacker Timothy A. , Schreier David A. , Chesler Naomi C. , Wang Zhijie
Published: March 2019

Right ventricular failure (RVF) is a common cause of death in patients suffering from pulmonary arterial hypertension (PAH). The current treatment for PAH only moderately improves symptoms, and RVF ultimately occurs. Therefore, it is necessary to develop new treatment strategies to protect against right ventricle (RV) maladaptation despite PAH progression. In this study, we hypothesize that local mesenchymal stem cell (MSC) delivery via a novel bioscaffold can improve RV function despite persistent PAH. To test our hypothesis, we induced PAH in adult rats with SU5416 and chronic hypoxia exposure; treated with rat MSCs delivered by intravenous injection, intramyocardial injection, or epicardial placement of a bioscaffold; and then examined treatment effectiveness by in vivo pressure-volume measurement, echocardiography, histology, and immunohistochemistry. Our results showed that compared with other treatment groups, only the MSC-seeded bioscaffold group resulted in RV functional improvement, including restored stroke volume, cardiac output, and improved stroke work. Diastolic function indicated by end-diastolic pressure-volume relationship was improved by the local MSC treatments or bioscaffold alone. Cardiomyocyte hypertrophy and RV fibrosis were both reduced, and von Willebrand factor expression was restored by the MSC-seeded bioscaffold treatment. Overall, our study suggests a potential new regenerative therapy to rescue the pressure-overload failing RV with persistent pulmonary vascular disease, which may improve quality of life and/or survival of PAH patients.

NEW & NOTEWORTHY We explored the effects of mesenchymal stem cell-seeded bioscaffold on right ventricles (RVs) of rats with established pulmonary arterial hypertension (PAH). Some beneficial effects were observed despite persistent PAH, suggesting that this may be a new therapy for RV to improve quality of life and/or survival of PAH patients.
Differences in pulmonary arterial flow hemodynamics between children and adults with pulmonary arterial hypertension as assessed by 4D-flow CMR studies
Authors: Schäfer Michal , Ivy D. Dunbar , Abman Steven H. , Stenmark Kurt , Browne Lorna P. , Barker Alex J. , Mitchell Max B. , Morgan Gareth J. , Wilson Neil , Shah Anar , Kollengode Madhukar , Naresh Nivedita , Fonseca Brian , DiMaria Michael , Buckner J. Kern , Hunter Kendall S. , Kheyfets Vitaly , Fenster Brett E. , Truong Uyen
Published: March 2019

Despite different developmental and pathological processes affecting lung vascular remodeling in both patient populations, differences in 4D MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults ( n = 10) and children ( n = 10) with PAH matched by pulmonary vascular resistance index (PVRi) and healthy adult ( n = 10) and pediatric ( n = 10) subjects underwent comprehensive 4D-flow MRI to assess peak systolic wall shear stress (WSSmax) measured in the main (MPA), right (RPA), and left pulmonary arteries (LPA), viscous energy loss (EL) along the MPA-RPA and MPA-LPA tract, and qualitative analysis of secondary flow hemodynamics. WSSmax was decreased in all pulmonary vessels in children with PAH when compared with the same age group (all P < 0.05). Similarly, WSSmax was decreased in all pulmonary vessels in adult PAH patients when compared with healthy adult subjects (all P < 0.01). Average EL was increased in adult patients with PAH when compared with the same age group along both MPA-RPA ( P = 0.020) and MPA-LPA ( P = 0.025) tracts. There were no differences in EL indices between adults and pediatric patients. Children and adult patients with PAH have decreased shear hemodynamic forces. However, pathological flow hemodynamic formations appear to be more consistent in adult patients, whereas flow hemodynamic abnormalities appear to be more variable in children with PAH for comparable severity of PVRi.

NEW & NOTEWORTHY Both children and adult patients with PAH have decreased shear hemodynamic forces inside the pulmonary arteries associated with the degree of vessel dilation and stiffness. These differences also exist between healthy normotensive children and adults. However, pathological flow hemodynamic formations appear to more uniform in adult patients, whereas in children with PAH flow, hemodynamic abnormalities appear to be more variable. Pathological flow formations appear not to have a major effect on viscous energy loss associated with the flow conduction through proximal pulmonary arteries.
A Novel Approach for Fabricating LaMnO3 Thin Films Using Combined Microwave Combustion and Pulsed Electron Deposition Techniques
Authors: Tran Thi Ha , Tang Thi Trung Anh , Pham Nguyen Hai , Bach Thanh Cong , Sai Cong Doanh , Nguyen Quang Hoa , Le Van Vu , Nguyen Hoang Nam , Doan Quoc Khoa , Nguyen Trong Tam , Le Viet Bau , Ho Khac Hieu , Nguyen Viet Tuyen
Published: March 2019

LaMnO3 (LMO) nanopowder was synthesized by the microwave combustion method using glycine and nitrate salts of La and Mn as precursors. The as-prepared LMO powder was pressed at high pressure and annealed at 1000°C for 8 hours to make a target for thin film deposition. The structural and elemental analysis was obtained by X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS). Thin films of LMO were fabricated using pulsed electron deposition (PED) at room temperature. The effects of discharge voltage and oxygen/argon flux ratio on the produced thin films were studied. The study shows that stoichiometry and structure of the target was preserved well in the thin films prepared with a discharge voltage from 14 to 15 kV, while the oxygen/nitrogen flux ratio did not show a clear effect on the quality of thin films.
Hydrops Fetalis and Persistent Pulmonary Hypertension in a Neonate with Anti-E Alloimmunization
Authors: Sharma Amit , Navalkele Pournima , Desai Jagdish , Agarwal Prashant
Published: March 2019

Anti-E alloimmunization is the third most common cause of neonatal hemolytic disease, typically causing mild to moderate hemolytic anemia. We report an unusual case of severe hydrops fetalis and persistent pulmonary hypertension (PPHN) in a neonate with anti-E alloimmunization. Our case emphasizes the importance of close surveillance for development of severe fetal hemolytic anemia and possible need for antenatal intervention. These neonates may also need vigilant monitoring for PPHN.
Pharmacokinetic Study and Tissue Distribution of Lorlatinib in Mouse Serum and Tissue Samples by Liquid Chromatography-Mass Spectrometry
Authors: Chen Wei , Shi Yafei , Qi Shuya , Zhou Haiyan , Li Chunyu , Jin Dujia , Li Guohui
Published: March 2019

In the present study, we developed and validated a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of lorlatinib in mouse serum and tissue samples, and such a method was successfully applied to investigate the pharmacokinetic study and tissue distribution of lorlatinib after oral administration. Samples were processed with methanol to precipitate protein and extract drugs, and Afatinib-d6 was used as the internal standard (IS). For LC-MS/MS analysis, compounds were separated on a C18 column by gradient elution (0.1% of formic acid and methanol) at 0.5 mL/min in the positive-ion mode with m/z 407.28 [M + H]+ for lorlatinib and m/z 492.10 [M + H]+ for IS. Good linearity was observed within the calibration ranges. Selectivity, accuracy (−6.42% to 8.84%), precision (1.69% to 10.98%), recoveries (91.4% to 115.0%), and matrix effect (84.2% to 110.6%) were all within the acceptable ranges. After oral administration, serum concentration of lorlatinib quickly achieved the maximal concentration (2,705.683 ± 539.779 μg/L) at 0.625 ± 0.231 h. The highest concentration was detected in the liver (3,153.93 ng/100 mg), followed by the stomach (2,159.92 ng/100 mg) and the kidney (548.83 ng/100 mg). In conclusion, a simple and rapid detection method was established and validated for determination of lorlatinib in blood and tissue samples of mouse. The pharmacokinetic study and tissue distribution of lorlatinib were successfully investigated using this method.
MUC1-C Integrates Chromatin Remodeling and PARP1 Activity in the DNA Damage Response of Triple-Negative Breast Cancer Cells
Authors: Yamamoto Masaaki , Jin Caining , Hata Tsuyoshi , Yasumizu Yota , Zhang Yan , Hong Deli , Maeda Takahiro , Miyo Masaaki , Hiraki Masayuki , Suzuki Yozo , Hinohara Kunihiko , Rajabi Hasan , Kufe Donald
Published: March 2019

The oncogenic MUC1-C protein is overexpressed in triple-negative breast cancer (TNBC) cells and contributes to their epigenetic reprogramming and chemoresistance. Here we show that targeting MUC1-C genetically or pharmacologically with the GO-203 inhibitor, which blocks MUC1-C nuclear localization, induced DNA double-strand breaks and potentiated cisplatin (CDDP)-induced DNA damage and death. MUC1-C regulated nuclear localization of the polycomb group proteins BMI1 and EZH2, which formed complexes with PARP1 during the DNA damage response. Targeting MUC1-C downregulated BMI1-induced H2A ubiquitylation, EZH2-driven H3K27 trimethylation, and activation of PARP1. As a result, treatment with GO-203 synergistically sensitized both mutant and wild-type BRCA1 TNBC cells to the PARP inhibitor olaparib. These findings uncover a role for MUC1-C in the regulation of PARP1 and identify a therapeutic strategy for enhancing the effectiveness of PARP inhibitors against TNBC.

Significance:

These findings demonstrate that targeting MUC1-C disrupts epigenetics of the PARP1 complex, inhibits PARP1 activity, and is synergistic with olaparib in TNBC cells.
Preclinical Development of a WT1 Oral Cancer Vaccine Using a Bacterial Vector to Treat Castration-Resistant Prostate Cancer
Authors: Kitagawa Koichi , Gonoi Reina , Tatsumi Maho , Kadowaki Masahide , Katayama Takane , Hashii Yoshiko , Fujisawa Masato , Shirakawa Toshiro
Published: March 2019

Previously, we constructed a recombinant Bifidobacterium longum displaying a partial mouse Wilms' tumor 1 (WT1) protein (B. longum 420) as an oral cancer vaccine using a bacterial vector and demonstrated that oral administration of B. longum 420 significantly inhibited tumor growth compared with the Db126 WT1 peptide vaccine in the TRAMP-C2, mouse castration-resistant prostate cancer (CRPC) syngeneic tumor model. The present study demonstrated that oral administration of 1.0×109 colony-forming units of B. longum 420 induced significantly higher cytotoxicity against TRAMP-C2 cells than intraperitoneal injection of 100 μg of Db126, and the in vivo antitumor activity of B. longum 420 in the TRAMP-C2 tumor model could be augmented by intraperitoneal injections of 250 μg of anti–PD-1 antibody. For the clinical development, we produced the B440 pharmaceutical formulation, which is lyophilized powder of inactivated B. longum 440 displaying the partially modified human WT1 protein. We confirmed that B. longum 440 could induce cellular immunity specific to multiple WT1 epitopes. In a preclinical dosage study, B440 significantly inhibited growth of the TRAMP-C2 tumors compared with that of the control groups (PBS and B. longum not expressing WT1) at all dosages (1, 5, and 10 mg/body of B440). These mouse doses were considered to correspond with practical oral administration doses of 0.2, 1, and 2 g/body for humans. Taken together, these results suggest that the B440 WT1 oral cancer vaccine can be developed as a novel oral immuno-oncology drug to treat CRPC as a monotherapy or as an adjunct to immune checkpoint inhibitors.
Metabolism Drives Carcinogenesis and Maintenance of Pancreatic Tumors
Authors: Halbrook Christopher J. , Nelson Barbara S. , Lyssiotis Costas A.
Published: March 2019

In this issue of Cancer Discovery, Carrer and colleagues find that early events in pancreatic tumorigenesis are driven by altered acetyl-CoA metabolism, where targeting this axis in established cancer models impairs tumor growth. This work provides new insights into the roles of acetyl-CoA in pancreatic cancer and underscores the value of studying early events in carcinogenesis to yield new treatment strategies.

See related article by Carrer et al., p. 416.
Computer-Assisted Expressions of the Perspectives of Refugee Children in Resettlement
Authors: Lawrence Jeanette A. , Kaplan Ida , Dodds Agnes E.
Published: March 2019

Understanding the perspectives of refugee children on their lives is important for acknowledging children’s rights, competence, and contributions to practice and policy. Children’s perspectives are the views they construct for framing events, relationships and images, and the meanings they convey in relational coactions with other people and institutions. We demonstrate the usefulness of digital technology in the form of computer-assisted interviews (CAIs) for enabling refugee children to express perspectives on their lives in resettlement. We describe how CAIs constructed by adopting a child’s perspective recognize the children’s agency and enable their expressions of their perspectives. We illustrate the facilities of CAIs with analyses of children’s ratings and open-ended typed comments about their worries and who helps them to feel better. Children’s views revealed the predominance of family members as sources of worry and help. We discuss the implications of using digital technology in research to provide children with ways of contributing to knowledge construction.
Cardioprotective Effect of Rhapontigenin in Isoproterenol-Induced Myocardial Infarction in a Rat Model
Authors: Fan Ying
Published: March 2019

Background/Aims: Rhapontigenin (RPG) is a stilben derivative and is known to bear several effects such as antiallergic, anticoagulative, hypoglycemic, antiangiogenic, and purgative. The investigation was conducted to evaluate the cardioprotective efficacy of RPG in rats having acute myocardial infarction (MI) induced by isoproterenol (ISO). Methods: Animals were divided into 6 groups: group I (control group), group II (ISO-treated), group III (1.0 mg/kg/day RPG and ISO-treated), group IV (2.5 mg/kg/day RPG and ISO-treated), group V (5.0 mg/kg/day RPG and ISO-treated), and group VI (treated with RPG 5.0 mg/kg/day). Various cardiac stress markers, including infarct size and heart/body weight index, were investigated in animals with ISO-induced MI, such as inducible nitric oxide synthase (iNOS), creatinine kinase (CK), lactate dehydrogenase (LD), cardiac troponin-T (CTT), superoxide dismutase (SOD), and malondialdehyde. INOS, p38, caspase-3, and connexin 43 expressions were analyzed in animals. Inflammatory mediators, tissue necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were detected in serum of experimental animals. Results: Group I animals indicated normal levels of biochemical parameters, whereas group II animals indicated high levels of these parameters and successful induction of MI. Pretreatment of animal groups III, IV, and V with RPG revealed amelioration of infarct size, heart/body weight index, CK, LD, CTT in rats, whereas group VI animals were treated only with RPG (5.0 mg/kg/day) and not with ISO. Levels of TNF-α, IL-6, MD, SOD, p38, and iNOS expressions were significantly downregulated by RPG administration (5.0 mg/kg/day). Conclusion: RPG ameliorates MI caused by ISO in rats and provides cardioprotective effect, via anti-inflammatory, antioxidant, and antiapoptotic effect.
Temporal Trends in Incident Mortality in Dialysis Patients: Focus on Sex and Racial Disparities
Authors: Shah Silvi , Leonard Anthony C. , Meganathan Karthikeyan , Christianson Annette L. , Thakar Charuhas V.
Published: March 2019

Background: Racial minorities and women constitute substantial portions of the incident and prevalent end-stage renal disease (ESRD) population in the United States. Although ESRD is characterized by high mortality, temporal trends, and race and sex differences in mortality have not been studied. Methods: We evaluated 944,650 adult patients who initiated dialysis between January 1, 2005 and December 31, 2014, using the United States Renal Data System, for sex-related and race-related trends in mortality. Logistic regression models adjusted for pre-dialysis health status were used to examine associations among the predictors’ sex, race, and year of incident dialysis, and the outcome all-cause mortality at 1-year post ESRD. Results: The mean age was 65 ± 14 years. The 1-year crude mortality rates in incident ESRD patients decreased by 28% from 2004 to 2015. Risk-adjusted 1-year mortality decreased by 3% for each later year of incident ESRD (p < 0.001). In general, from 2005 to 2014, mortality rates decreased across both sexes, and all races. White patients experienced the lowest reduction in adjusted 1-year mortality rates (16%). While women experienced a survival advantage over men in 2005, by 2014 it was reversed to survival advantage for men. Combining all years, the adjusted risk of dying at 1-year after initiating dialysis was lower in women than men (OR 0.98; 95% CI 0.97–0.99), and as compared to whites, was lower in blacks (OR 0.73; 95% CI ­0.72–0.74), Hispanics (OR 0.64; 95% CI 0.63–0.65), Asians (OR 0.55; 95% CI 0.53–0.56), and Native Americans (OR 0.67; 95% CI 0.63–0.71). Conclusion: The 1-year mortality rates among patients with ESRD have decreased steadily during a recent 10-year period across both men and women, and in all 5 races. Women have only a 2% lower risk of dying at 1-year after dialysis initiation than men. White patients had higher mortality as compared to other races. Our results suggest the need for sex, and race-specific treatment strategies in ESRD care.
Adherence to Kidney Disease: Improving Global Outcomes Mineral and Bone Guidelines for Monitoring Biochemical Parameters
Authors: Roetker Nicholas S. , Peng Yi , Ashfaq Akhtar , Gilbertson David T. , Wetmore James B.
Published: March 2019

Background: Mineral and bone disorder (MBD) is common in patients with chronic kidney disease (CKD), and is associated with risk of fractures, cardiovascular disease, and death. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend monitoring CKD-MBD biochemical markers, including parathyroid hormone (PTH), phosphorus, 25-hydroxyvitamin D (25D), calcium, and alkaline phosphatase (ALP), in patients with moderate-to-severe CKD. Methods: To determine guideline adherence, we used administrative claims records from the 20% sample of Medicare beneficiaries with Parts A, B, and D coverage, 2007 to 2015, and identified cohorts of patients with nondialysis stage 3, 4, or 5 CKD. Testing for biochemical markers during follow-up was defined based on laboratory procedure codes. Baseline factors associated with laboratory testing were determined using logistic regression. All analyses were performed separately by CKD stage. Results: A total of 640,946 stage 3, 136,278 stage 4, and 22,076 stage 5 CKD patients, 50.2–52.9% women, mean age 74.4–78.0 years, were followed for a mean of 2.5, 1.3, and 0.7 years respectively. The frequency of testing was low for PTH (35.2–48.2%), phosphorus (46.6–62.0%), and 25D (29.3–46.7%). Testing was somewhat higher for calcium (88.1–95.4%) and ALP (63.5–88.1%); most tests were features of larger panels (e.g., basic metabolic panel). Older age, most comorbid conditions, and lack of prior nephrology care were associated with lower likelihood of testing. Conclusions: In fee-for-service Medicare beneficiaries, laboratory testing for CKD-MBD biochemical markers appears to be suboptimal in relation to KDIGO guidelines. Competing priories, such as management of comorbid disease and preparation for renal replacement therapy, may distract from CKD-MBD monitoring.
The Jameson Raid: An American Imperial Plot?
Authors: Rotberg Robert I.
Published: March 2019

South Africa’s Jameson Raid ultimately betrayed African rights by transferring power to white Afrikaner nationalists after helping to precipitate the Anglo-Boer War (1899–1902). The Raid also removed Cecil Rhodes from the premiership of the Cape Colony; strengthened Afrikaner control of the South African Republic (the Transvaal) and its world-supplying gold mines; and motivated the Afrikaner-controlled consolidation of segregation in the Union of South Africa, and thence apartheid. Perceptively, Charles van Onselen’s The Cowboy Capitalist links what happened on the goldfields of South Africa to earlier labor unrest in Idaho’s silver mines. Americans helped to originate the Raid and all of the events in its wake.
Learning Typed Entailment Graphs with Global Soft Constraints
Authors: Javad Hosseini Mohammad , Chambers Nathanael , Reddy Siva , Holt Xavier R. , Cohen Shay B. , Johnson Mark , Steedman Mark
Published: March 2019

This paper presents a new method for learning typed entailment graphs from text. We extract predicate-argument structures from multiple-source news corpora, and compute local distributional similarity scores to learn entailments between predicates with typed arguments (e.g., person contracted disease). Previous work has used transitivity constraints to improve local decisions, but these constraints are intractable on large graphs. We instead propose a scalable method that learns globally consistent similarity scores based on new soft constraints that consider both the structures across typed entailment graphs and inside each graph. Learning takes only a few hours to run over 100K predicates and our results show large improvements over local similarity scores on two entailment data sets. We further show improvements over paraphrases and entailments from the Paraphrase Database, and prior state-of-the-art entailment graphs. We show that the entailment graphs improve performance in a downstream task.
“A Very Dangerous Talent”: Wit for Women in Hannah Webster Foster's The Boarding School
Authors: Piggush Yvette R.
Published: March 2019

Hannah Webster Foster's eighteenth-century novel The Boarding School shows how conduct literature and the republican culture of politeness create gender expectations for women's humor in the early United States. Foster teaches readers about the social effects of wit and guides them in using satire and irony to influence public opinion.
DNA barcoding reveals andropolymorphism in Aclerogamasus species (Acari: Parasitidae) MIROSŁAWA DABERT, AGATA BIGOŚ & WOJCIECH WITALIŃSKI (Poland)
Authors: DABERT MIROSŁAWA , BIGOŚ AGATA , WITALIŃSKI WOJCIECH
Published: March 2019

Andropolymorphism, defined as discontinuous morphological variability in males, can lead to taxonomic confusion when different male morphs are determined and described as separate species. This study addresses this issue in two occasionally sympatric mite species Aclerogamasus similis (Willmann, 1953) and A. holzmannae (Micherdziński, 1969) collected in Poland. The females of these two taxa are morphologically indistinguishable but males are quite different, and could be either separate species or one species with two male morphs. We address this question by performing molecular assays, testing variation in a fragment of the mtDNA COI gene and the D2 region of 28S rDNA. Molecular analysis of populations revealed very low variation in the studied gene fragments. All sequences of the D2 region of 28S rDNA (size 375 bp) were identical. Only two COI haplotypes were found, differing by two out of 644 nucleotide positions (0.3% K2P distance). The variant haplotype was found in one A. similis male, and probably represents intraspecific variability. The results strongly suggest that all studied females and males belong to only one species with dimorphic males. This finding confirms some earlier opinions on synonymy of both species. Therefore, Aclerogamasus holzmannae (Micherdziński, 1969) should be regarded as a junior synonym of Aclerogamasus similis (Willmann, 1953). As andropolymorphism has been rarely observed in gamasid mites, we briefly discuss its possible origins and consequences.
A new group of species of Edessa Fabricius, 1803 (Hemiptera: Heteroptera: Pentatomidae)
Authors: FERNANDES JOSÉ ANTÔNIO MARIN , CAMPOS LOURIVAL DIAS
Published: March 2019

Three new species of Edessa (E. metallica sp. nov., E. preclara sp. nov., E. splendens sp. nov.) are described which form a distinct species group. The metallica group is characterized by a metallic blue or green dorsal color. Edessa preclara sp. nov. and E. splendens sp. nov. have an Andean distribution, having been collected above 1000 meters in Ecuador and Colombia respectively. Edessa metallica sp. nov. has been collected in Panama. Illustrations of the metasternal process and male and female external genitalia, photographs of the habitus, and descriptions are provided.
Quill mites (Acari: Syringophilidae) from mimid birds (Aves: Mimidae)
Authors: SIKORA BOZENA , FAJFER MONIKA , SKORACKI MACIEJ
Published: March 2019

Two new species of syringophilid mites parasitizing birds from the family Mimidae are described: Syringophilopsis mimidus sp. nov. ex Margarops fuscatus (Vieillot) from Central America and Rafapicobia toxostoma sp. nov. ex Toxostoma curvirostre (Swainson) from USA. Additionally, Torotrogla mima Kethley, 1970 is redescribed based on the material ex Mimus triurus (Vieillot) from Argentina and M. patagonicus (Lafresnaye and Orbigny) from South Africa.
Gender Gaps in Perceived Start-up Ease: Implications of Sex-based Labor Market Segregation for Entrepreneurship across 22 European Countries
Authors: Tonoyan Vartuhi , Strohmeyer Robert , Jennings Jennifer E.
Published: March 2019

Although scholars have long recognized the consequences of sex-based labor market segregation for gendered outcomes in conventional wage-and-salary employment, comparatively little is known about the implications for entrepreneurship. We call attention to implications stemming from manifestations at distinct levels of analysis, specifically to the differential structural positions that men and women are likely to occupy as employees and to the degree of sex-based labor market segregation in a country overall. We hypothesize that the gendering of labor market positions will have the first-order effect of reducing women’s likelihood of acquiring entrepreneurship-relevant resources, experiencing entrepreneurial career previews, and being exposed to industry opportunity spaces for launching new firms, which will have the second-order effect of lowering their start-up ease perceptions relative to men’s. We further suggest that this gender gap will widen in societies with more highly sex-segregated labor markets. Data from 15,742 employees in 22 European countries provide strong support for these claims. By demonstrating how pre-entry assessments of entrepreneurship are influenced by gendered employment experiences at the individual level and gendered labor market regimes at the country level, this study lays a foundation for further multilevel research on the relationship between institutionalized labor market practices and entrepreneurial activity.
Gendering Resistance to Right-Wing Populism: Black Protest and a New Wave of Feminist Activism in Poland?
Authors: Hall Bogumila
Published: March 2019

The rise to power of the populist Law and Justice Party (PiS) in 2015, and its growing authoritarianism, has politicized thousands of Poles and brought large-scale protests back to Polish streets. Women have been at the forefront of these struggles, aligning the previously unpopular quest for reproductive rights and bodily autonomy with the larger resistance to the ruling party. In particular, the proposal to restrict the abortion law sparked mass mobilization in 2016, with Black Protests turning into a formative experience for many of the previously nonactive participants. This article sheds light on this most recent wave of feminist activism in Poland and its forms of action, from a generational perspective. It scrutinizes in detail the narrative of a “new generation of activists,” who claim to change the contours of Polish feminism, making it more inclusive, more creative and bolder. It reports on the shift, unfolding slowly since the 2000s, from the institutionalized feminism of nongovernmental organizations to less formal, grassroots forms of engagement that combine online activism with organizing on the ground. However, while the latter is often assumed to be skeptical toward the European Union’s “gender equality” framework, the article reveals how, within the context of growing authoritarianism, the youngest cohorts in particular return to the liberal strand of feminism, characterized by the language of human rights and an uncritical gaze toward the European Union. The article ends with a reflection on the proclaimed ‘newness’ of feminism in Poland, as articulated by the new generation of activists. The absence of intergenerational dialogue and transmission of knowledge, it is argued, render past feminist struggles in Poland invisible and forgotten and strikingly leaves unquestioned the legacy of previous neoliberal and patriarchal governments that led to the erosion of women’s rights in postsocialist Poland.