bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of driving properties of a three-wheeled vehicle with a newly designed steering system
Authors: Dižo Ján , Blatnický Miroslav , Kurčík Pavol
Published: January 2019

This paper presents results of analyses of a three-wheeled vehicle with the newly designed steering system. Our design of steering system is intended to be mounted on a tricycle with the electric drivetrain. The standard steering system of a three-wheeled vehicle has disadvantage, that such a vehicle is unstable, when it is curving a curve mainly at higher speeds. It results to a breach of stability form the overturning point of view. The newly designed steering system of a three-wheeled vehicle contributes to increasing its stability. It means that a three-wheeled vehicle with the newly designed steering system is able to pass a curve with a smaller radius at higher speed. The main objectives of analyses presented in this paper is comparison of driving properties of a three-wheeled vehicle with two wheels on a rear axle with the standard steering system and with the newly designed steering system by means of simulation computations, which were carried out in Simpack package.
Correlation image system 3D DANTEC as a modern system for measuring deformation
Authors: Domański Tomasz
Published: January 2019

The work presents the possibilities created by the multi-camera 3D image correlation system. The experience is based on non-contact measurement of displacements and deformations. The measurement was used basically to estimate the deflection line of the bending beams and values of strains and displacements at various points of the cross-section. The measurement was carried out by tracking the displacements of the prepared surface of the sample. The results of the numerical analysis were also presented, which were compared with the experience carried out on the measurement stand.
Influence of tension layer quality on mechanical properties of timing belts
Authors: Wilczyński Michał , Domek Grzegorz
Published: January 2019

Reinforcement of the tooth belts is the element responsible for the transmission of the torque. Its structure is related to the dynamics of the belt and such important parameters as the stiffness of running stability on pulleys and above all, the pitch stability. The axis of symmetry of the reinforcement in the vertical direction of the belt is the reference point of the belt geometry as well as the neutral axis of stresses caused by bending. On the arc of the contact between belt and pulley, over the reinforcement, the belt is stretched, and below it is compressed. In the tooth belts, there are various solutions of the carrier layer, in terms of the materials used, but also types of fibers, quantity of the fibers, etc. The paper presents the results of analysis of the carrier layer of the most popular tooth belts with T10 and AT10 trapezoidal teeth. The paper shows possible direction of choice of the construction materials of the carrier layer and their importance for the dynamics of the gear with the tooth belt.
Transient analysis of FGM plates bending under thermal loading: comparative study within classical and generalized thermoelasticity
Authors: Sator Ladislav , Sladek Vladimir , Sladek Jan
Published: January 2019

In the classical thermoelasticty, there is coupling between thermal and elastic fields, in general, but the elastic and thermal excitations spread according to physically different laws. In classical thermodynamics, the temperature change propagates according to diffusion law. However, the heat pulses at low temperature propagate evidently with a finite velocity in view of waves similar to spreading of elastic excitations. A great effort has been spent in this matter and there are two main non-classical theories: Lord-Shulman theory and Green-Lindsay theory. In this paper, we compare the response of thin FGM plates under thermal load within the classical and non-classical theories of thermoelasticity. The variable material properties of plate (such as the Young’s modulus, thermal expansion coefficient, etc.) are allowed to be continuous functions of the position. The strong form meshless formulations for solution of considered initial-boundary value problems is developed in combination with Moving Least Squares (MLS) approximation scheme. The response of FGM plates on thermal loading is studied via numerical simulations with focusing on comparison of results obtained within the classical and generalized thermoelasticity. The numerical results concern also the parametric study of influence of gradation of material coefficients on bending of FGM plates
Determination of the laminate strains using discrete damage mechanics
Authors: Žmindák Milan , Kaco Michal , Novák Pavol , Radziszewski Leszek , Soukup Josef
Published: January 2019

In this paper discrete damage mechanics (DDM) is used to predict inter-laminar transverse and shear damage initiation and evolution in terms of the fracture toughness of the laminate. The finite element method (FEM) is one of the most widely and most popular numerical methods for analyzing composite structures, therefore ANSYS commercial software is used for analysis of layered plate composite structure reinforced with long unidirectional fibers with Carbon/Epoxy material. Because ANSYS does not have a built-in capability for calculating crack density, we have to use plugin. A methodology for determination of the fracture toughness is based on fitting DDM model and these data are obtained from literature. Also, prediction of modulus vs. applied strain is contrasted with ply discount results and the effect of in situ correction of strength is highlighted. Evaluation of matrix cracking detected in lamina has been solved using return mapping algorithm.
Mitigating wakeup effect and improving endurance of ferroelectric HfO2-ZrO2 thin films by careful La-doping
Authors: Kozodaev Maxim G. , Chernikova Anna G. , Korostylev Evgeny V. , Park Min Hyuk , Khakimov Roman R. , Hwang Cheol S. , Markeev Andrey M.
Published: January 2019

The crystalline structure and electrical response of La-doped HfO2-ZrO2 thin films of which processing temperature did not exceed 400 °C were examined, where the La-doping concentration was varied from zero to ≈2 mol. %. The film structure and associated properties were found to vary sensitively with the minute variation in the La-concentration, where the ferroelectric response at low La-concentration (<≈1 mol. %) gradually became antiferroelectric-like for La-concentration >≈1 mol. %, which was accompanied by a significant increase in dielectric permittivity. La-doping was found to be very effective in inhibiting the monoclinic phase formation and in decreasing the leakage current. Notably, the high coercive field, which was one of the most significant problems in this material system, could be decreased by ∼35% at the most promising La-concentration of 0.7 mol. %. As a result, a highly promising field cycling endurance up to 1011 cycles could be secured while maintaining a high remnant polarization value (≥25 μC/cm2). This is one of the best results in this field of the authors' knowledge.
Field-free spin-orbit torque switching of a perpendicular ferromagnet with Dzyaloshinskii-Moriya interaction
Authors: Chen BingJin , Lourembam James , Goolaup Sarjoosing , Lim Sze Ter
Published: January 2019

Leveraging on interfacial Dzyaloshinskii-Moriya interaction (DMI) induced intrinsic magnetization tilting in nanostructures, a parametric window enabling field-free spin-orbit torque (SOT) magnetization switching in a perpendicular ferromagnet is established. The critical current density (Jc) bounds for SOT switching are highly dependent on the DMI, producing a distorted diamond-shaped region bounded by the Jc-DMI curves. The widest Jc interval is found for DMI values between 0.5 mJ/m2 and 0.8 mJ/m2. Geometrical modulation, of the ferromagnetic layer, reveals that the circular structure is optimum for minimizing the switching energy while maximizing the parametric window. For all the structures investigated, the SOT induced reversal process is via domain wall nucleation and propagation, and the switching is practical at room temperature.
Band structure and carrier effective masses of boron arsenide: Effects of quasiparticle and spin-orbit coupling corrections
Authors: Bushick Kyle , Mengle Kelsey , Sanders Nocona , Kioupakis Emmanouil
Published: January 2019

We determine the fundamental electronic and optical properties of the high-thermal-conductivity III–V semiconductor boron arsenide (BAs) using density functional and many body perturbation theory including quasiparticle and spin-orbit coupling corrections. We find that the fundamental bandgap is indirect with a value of 2.049 eV, while the minimum direct gap has a value of 4.135 eV. We calculate the carrier effective masses and report smaller values for the holes than the electrons, indicating higher hole mobility and easier p-type doping. The small difference between the static and high frequency dielectric constants indicates that BAs is only weakly ionic. We also observe that the imaginary part of the dielectric function exhibits a strong absorption peak, which corresponds to parallel bands in the band structure. Our estimated exciton binding energy of 43 meV indicates that excitons are relatively stable against thermal dissociation at room temperature. Our work provides theoretical insights into the fundamental electronic properties of BAs to guide experimental characterization and device applications.
Antenna coupled graphene-FET as ultra-sensitive room temperature broadband THz detector
Authors: G K Rama Murali , Deshmukh Prathmesh , Prabhu S. S. , Basu Palash Kumar
Published: January 2019

A high sensitivity, low power (∼1μW to 10 μW), room temperature, antenna coupled, THz (0.8 THz) detector is presented by means field effect transistor (FETs) fabricated on epitaxial-grown graphene on silicon carbide. The contact resistance across the source and drain are made high to study the effect of THz response. It is demonstrated that the energy coupled to the antenna is the important parameter in designing the ultra-sensitive THz detectors rather than the contact resistances and channel conductivity. The realised graphene based detectors shows quite good responsivity (>535 V/W) and noise equivalent power (NEP) (<100pW/Hz0.5). The individual contributions of photo voltage due to plasma wave generation (PWG) and photo thermo-electric effect (PTE) in the effective THz detection is estimated. It is also seen that the temperature of the hot carriers generated in the FET channel due to PTE is varying with the gate bias and not constant as assumed in earlier works. A new method is proposed in this work for calculating the antenna coupling factor which varies with incident THz-radiation power. A comprehensive analytical model is worked out to understand the graphene based detector performance.
Simulating nanoisland layers in THz detectors using a Monte Carlo method
Authors: Gagnon Etienne , Lytle Amy , Jabbour Charles , Zide Joshua M. O.
Published: January 2019

We present a Monte Carlo model that simulates the effects of non-equilibrium carrier-carrier scattering and the presence of layers of ErAs nanoislands in a GaAs terahertz antenna detector. To minimize computing time, we split the model into two simulations on numerical grids with optimized resolutions. First, we calculate the effects of the ErAs nanoislands on carrier lifetime in a high resolution volume of GaAs. We then incorporate those results into a larger, lower resolution, two-dimensional simulation that models the antenna detector. The computational results match experimental data presented by Kadow et al. [Appl. Phys. Lett. 75, 3548–3550 (1999)] and show that the lifetime of the carriers is closely linked to the periodicity of the nanoisland layers. Our results also highlight how the periodicity of the nanoisland layers affects the sensitivity and bandwidth of the terahertz detector, information that can be used to create custom devices with optimal parameters.
Effect of gap width on electron transport through quantum point contact in hBN/graphene/hBN in the quantum Hall regime
Authors: Ahmad Nurul Fariha , Iwasaki Takuya , Komatsu Katsuyoshi , Watanabe Kenji , Taniguchi Takashi , Mizuta Hiroshi , Wakayama Yutaka , Hashim Abdul Manaf , Morita Yoshifumi , Moriyama Satoshi , Nakaharai Shu
Published: January 2019

This study investigates quantized electron transport in high-mobility quantum point contact (QPC) devices in hBN/graphene/hBN in the quantum Hall regime. This study primarily focuses on the effect of the gap width of split gates on edge-channel manipulations, which defines the QPC structure and its electrostatic potential distribution. The quantized conductance is governed by the dynamics of edge channels passing through or backscattered at the QPC, which is controlled by both the top-gate and back-gate biases. The effects of the split-gate gap width and the filling in the QPC on the edge-channel manipulations are experimentally verified. The experimental results are consistent with the theoretical predictions of open/closed configurations of the edge channels around QPC with different gate gap widths.
X-ray absorption spectrum simulations of hexagonal ice
Authors: Zhovtobriukh Iurii , Norman Patrick , Pettersson Lars G. M.
Published: January 2019

We calibrate basis sets and performance of two theoretical approaches to compute X-ray absorption spectra (XAS) of condensed water by comparison to experiments on hexagonal ice Ih. We apply both the transition-potential half-core-hole approach and the complex polarization propagator using four different models of the crystal with increasing oxygen and proton disorder but find poor agreement with experiments. We note that there are large variations in experimental spectra depending on detection mode and how the ice samples were prepared, which leads us to critically investigate what structures were actually prepared and measured in each case. This is done by using a Monte Carlo-based fitting technique which fits the spectra based on a library of precomputed spectra and assigns weights to contributions from different model structures. These are then used to generate O–O and O–H radial distribution functions and tetrahedrality parameters associated with each of the measured spectra. We find that all spectra are associated with sharp peaks at the oxygen positions in the perfect lattice, but with significant disorder around these positions. We suggest that presently available XAS of hexagonal ice are not fully representative of the perfect crystalline lattice, but contain varying amounts of defects and possible contributions from low-density amorphous ice.
Dielectric relaxation behaviors and dissipation characteristics of colloidal nanocarbon (graphene and CNTs) complex fluids
Authors: Chattopadhyay Ankur , Dhar Purbarun
Published: January 2019

The present article reports the dynamic complex dielectric responses of non-polar nanocolloids of graphene (G) and carbon nanotubes (CNTs). The frequency dependent complex relaxation behaviors of G and CNT colloids were determined in the range of 100 Hz to 3 × 105 Hz employing dielectric spectroscopy at a constant temperature. The governing roles of nanostructure concentration, conductivity, frequency, and amplitude variation of the forcing electric field on the dielectric response have been examined. The experimental observations reveal that the presence of G or CNT, as well as their concentrations, significantly governs the overall dielectric responses of the nanocolloids. The dilute and concentrated colloids display grossly distinguishable capacitive and dissipative behaviors, hinting at the major role of concentration regimes on the dielectric behavior of such colloids. In addition, the variation of electric field intensity results in altering the dielectric responses of the colloids, which points at the role of polarization of the nanomaterials on the overall dielectric relaxation. To model the complex dipolar interactions, the classical Havriliak-Negami model is employed and good agreement has been achieved against the experimental observations. It has been observed that increasing nanomaterial concentration and field amplitude has a dominant influence upon the relaxation parameters. Further, the effects of colloidal concentration on the AC and DC conductivity modes have also been analyzed. The conductivity response of the colloids has been explained by appealing to percolation theories. The present article may find strong implications toward the design and development of liquid dielectric based electrical and electronics systems.
Magnetostriction induced by crystallographic orientation and morphological alignment in a TbFe2-based alloy
Authors: Dong Meng , Liu Tie , Guo Xiaoyu , Xiao Yubao , Yuan Yi , Wang Qiang
Published: January 2019

The effect of crystal orientation and grain alignment on the properties of magnetostrictive materials was investigated in TbFe2 alloys prepared via solidification under different high magnetic field conditions. The magnetostrictive property and magnetization behavior of the alloys were studied. The results revealed that the alloys that are oriented along the easy magnetization axis exhibit better magnetostrictive property in the low-field intensity region (than in the high-field intensity region). However, in the high-field intensity region, regular alignment of grains in the magnetization direction is essential for continued improvement in the magnetostrictive property of the alloys. If the magnetic phases of the TbFe2 alloy are oriented along the easy magnetization axis and the grains of the magnetic phases are aligned regularly along the direction of magnetization, the alloy will exhibit excellent magnetostriction property. This study may serve as a reference for the preparation of high performance rare-earth iron-based magnetostrictive materials.
New insights into folding kinetics of α, ω dye-functionalized poly(N - isopropylacrylamide)
Authors: Wang Xiao-yan , Fan Hai-yan , Ye Xiao-dong , Liu Shi-lin , Zhang Guang-zhao
Published: January 2019

Two narrowly-distributed poly(N - isopropylacrylamide) (PNIPAM) samples were prepared via atom transfer radical polymerization (ATRP) with a novel dansyl functionalized initiator. The other end of the PNIPAM was functionalized by dabcyl group via click reaction. From the static fluorescence measurements, the fluorescence intensity of dansyl group and energy transfer efficiency between dansyl and dabcyl groups increased when the temperature increased from 36 °C to 45 °C, indicating that the microenvironment surrounding dansyl became hydrophobic and the distance between dansyl and dabcyl decreased. The kinetics of the conformational change of the dye-labeled PNIPAM was studied by a home-made laser-induced temperature jump device with fluorescent measurement. Our results revealed that the characteristic transition time was 3.8 and 5.8 ms for PNIPAM with degrees of polymerization of 85 and 142, respectively, indicating that the characteristic transition time was related to the chain length. Besides, characteristic transition time for the change of the energy transfer efficiency was 2.9 ms for PNIPAM with the degree of polymerization of 85, suggesting that the energy transfer efficiency change was faster than the fluorescence intensity change of dansyl group.
A facile surface passivation of hematite photoanodes with molybdate overlayers for efficient PEC water oxidation
Authors: Zhang Qi , Wu Quan-ping , Zhang Yue , Yan Ji-tong , Xue Song , Wang Hong-yan
Published: January 2019

α-Fe2O3 thin films have been synthesized and used as photoanodes for photo-electrochemical (PEC) water oxidation. Molybdate was introduced to mediate hematite thin films via two synthesis routes (namely in situ mediation and ex situ modification). Through the in situ mediation process, the morphology and film thickness could be changed significantly due to the addition of MoO42−, while for the ex situ modification, the PEC performance of the hematite has been greatly improved without changing the nanorod morphology. Various characterizations such as UV-Vis absorption, transmission electronic microscopy, scanning electronic microscopy, Mott-Schottky, electrochemical impedance spectroscopy were conducted and the PEC performances were investigated.
Strong current-polarization and negative differential resistance in FeN3-embedded armchair graphene nanoribbons
Authors: Wu Ying-chao , Rao Jia-rui , Li Xiao-fei
Published: January 2019

Motivated by the recent advances of transition-metal-nitrogen-carbon (TM-N-C) materials in catalysis, we investigate the electronic structure and transport properties of FeN3-embedded armchair and zigzag graphene nanoribbons (FeN3@AGNRs, FeN3@ZGNRs) with different widths. The first-principles results indicate that the FeN3 induces significant changes on the band structures of both ZGNRs and AGNRs, making the resultant systems quite different from the pristine ones and own room-temperature stable ferromagnetic (FM) ground states. While only FeN3@AGNRs possess a significant spin-dependent negative differential resistance (NDR) and a striking current polarization (nearly 100%) behaviors, due to that FeN3 introduces two isolated spin-down states, which contribute current with different performances when they couple with different frontier orbits. It is suggested that by embedding FeN3 complexes, AGNRs can be used to build spin devices in spintronics.
Reducing socioeconomic disparities in the STEM pipeline through student emotion regulation
Authors: Rozek Christopher S. , Ramirez Gerardo , Fine Rachel D. , Beilock Sian L.
Published: January 2019

Significance

Increasing access to Science, Technology, Engineering, and Math (STEM) fields can create career opportunities. Yet many students, especially those from lower-income backgrounds, find the high-stakes exams in courses necessary for STEM success to be stressful and anxiety provoking. Such experiences of stress can lead to underperformance and compromise students’ ability to advance in STEM. We show that lower-income students given the opportunity to emotionally regulate their worries and reinterpret their arousal go on to perform better on their high school science exams and endorse a more adaptive interpretation of stress. Critically, emotion regulation interventions cut in half the course failure rate for lower-income students. For many students, success is based on more than STEM knowledge—their ability to regulate emotions is important too.
Long-term effects of institutional rearing, foster care, and brain activity on memory and executive functioning
Authors: Wade Mark , Fox Nathan A. , Zeanah Charles H. , Nelson Charles A.
Published: January 2019

Children experiencing psychosocial deprivation as a result of early institutional rearing demonstrate many difficulties with memory and executive functioning (EF). To date, there is scant evidence that foster care placement remediates these difficulties during childhood. The current study examined longitudinal trajectories of memory and EF from childhood to adolescence in the Bucharest Early Intervention Project, a randomized controlled trial of foster care for institutionally reared children. We demonstrate that both ever- and never-institutionalized children show age-related improvements on several measures of memory and EF from age 8 to 16. Distinct patterns were observed for different domains of functioning: (
i
) Early-emerging disparities in attention and short-term visual memory, as well as spatial planning and problem solving, between ever- and never-institutionalized children persisted through adolescence; (
ii
) the gap in spatial working memory between ever- and never-institutionalized children widened by adolescence; and (
iii
) early difficulties in visual-spatial memory and new learning among children in foster care were mitigated by adolescence. Secondary analyses showed that higher resting EEG alpha power at age 8 predicted better EF outcomes in several domains at age 8, 12, and 16. These results suggest that early institutional rearing has enduring consequences for the development of memory and EF, with the possibility of catch-up among previously institutionalized children who start out with higher levels of problems. Finally, interindividual differences in brain activity relate to memory and EF across ages, thus highlighting one potential biological pathway through which early neglect impacts long-term cognitive functioning.
Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer
Authors: Blando Jorge , Sharma Anu , Higa Maria Gisela , Zhao Hao , Vence Luis , Yadav Shalini S. , Kim Jiseong , Sepulveda Alejandro M. , Sharp Michael , Maitra Anirban , Wargo Jennifer , Tetzlaff Michael , Broaddus Russell , Katz Matthew H. G. , Varadhachary Gauri R. , Overman Michael , Wang Huamin , Yee Cassian , Bernatchez Chantale , Iacobuzio-Donahue Christine , Basu Sreyashi , Allison James P. , Sharma Padmanee
Published: January 2019

Significance

The study demonstrates that V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint that is preferentially expressed at higher levels in pancreatic cancer. The study gives a detailed analysis of immune infiltration in primary and metastatic pancreatic tumors compared with melanoma, which differs in its tumor/stromal distribution. Our data indicate that human pancreatic tumors express CD68
+
macrophages and highlight the inhibitory checkpoint molecule VISTA as a potential immunotherapeutic target in pancreatic cancer.
Gypsy moth genome provides insights into flight capability and virus–host interactions
Authors: Zhang Jing , Cong Qian , Rex Emily A. , Hallwachs Winnie , Janzen Daniel H. , Grishin Nick V. , Gammon Don B.
Published: January 2019

Since its accidental introduction to Massachusetts in the late 1800s, the European gypsy moth (EGM;
Lymantria dispar dispar
) has become a major defoliator in North American forests. However, in part because females are flightless, the spread of the EGM across the United States and Canada has been relatively slow over the past 150 years. In contrast, females of the Asian gypsy moth (AGM;
Lymantria dispar asiatica
) subspecies have fully developed wings and can fly, thereby posing a serious economic threat if populations are established in North America. To explore the genetic determinants of these phenotypic differences, we sequenced and annotated a draft genome of
L. dispar
and used it to identify genetic variation between EGM and AGM populations. The 865-Mb gypsy moth genome is the largest Lepidoptera genome sequenced to date and encodes ∼13,300 proteins. Gene ontology analyses of EGM and AGM samples revealed divergence between these populations in genes enriched for several gene ontology categories related to muscle adaptation, chemosensory communication, detoxification of food plant foliage, and immunity. These genetic differences likely contribute to variations in flight ability, chemical sensing, and pathogen interactions among EGM and AGM populations. Finally, we use our new genomic and transcriptomic tools to provide insights into genome-wide gene-expression changes of the gypsy moth after viral infection. Characterizing the immunological response of gypsy moths to virus infection may aid in the improvement of virus-based bioinsecticides currently used to control larval populations.
Political ideology shapes the amplification of the accomplishments of disadvantaged vs. advantaged group members
Authors: Kteily Nour S. , Rocklage Matthew D. , McClanahan Kaylene , Ho Arnold K.
Published: January 2019

Significance

Inequality prospers when successes of advantaged group members (e.g., men, whites) get more attention than equivalent successes of disadvantaged group members (e.g., women, blacks). What determines whose successes individuals deem worth promoting vs. those they ignore? Using hundreds of thousands of tweets from the 2016 Olympics, we show that liberals are much more likely than conservatives to shine a spotlight on black and female (vs. white and male) US gold medalists. Two further experiments provide evidence that such differential amplification of successful targets is driven by a motivation—higher among liberals—to raise disadvantaged groups’ standing in service of equality. We find that liberals drive differential amplification more than conservatives and establish a behavioral mechanism through which liberals’ egalitarian motives manifest.
Detaching the tether: Remodeling mitochondrial localization during meiosis
Authors: Lacefield Soni
Published: January 2019

During meiosis, many organelles including mitochondria undergo dramatic remodeling to be inherited in gametes. In this issue, new work from Sawyer et al. (2019. J. Cell. Biol. https://doi.org/10.1083/jcb.201807097) demonstrates that the developmentally programmed destruction of a tether releases mitochondria from the cell cortex during meiosis in budding yeast.
3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice
Authors: Lazic Divna , Sagare Abhay P. , Nikolakopoulou Angeliki M. , Griffin John H. , Vassar Robert , Zlokovic Berislav V.
Published: January 2019

3K3A-activated protein C (APC), a cell-signaling analogue of endogenous blood serine protease APC, exerts vasculoprotective, neuroprotective, and anti-inflammatory activities in rodent models of stroke, brain injury, and neurodegenerative disorders. 3K3A-APC is currently in development as a neuroprotectant in patients with ischemic stroke. Here, we report that 3K3A-APC inhibits BACE1 amyloidogenic pathway in a mouse model of Alzheimer’s disease (AD). We show that a 4-mo daily treatment of 3-mo-old 5XFAD mice with murine recombinant 3K3A-APC (100 µg/kg/d i.p.) prevents development of parenchymal and cerebrovascular amyloid-β (Aβ) deposits by 40–50%, which is mediated through NFκB–dependent transcriptional inhibition of BACE1, resulting in blockade of Aβ generation in neurons overexpressing human Aβ-precursor protein. Consistent with reduced Aβ deposition, 3K3A-APC normalized hippocampus-dependent behavioral deficits and cerebral blood flow responses, improved cerebrovascular integrity, and diminished neuroinflammatory responses. Our data suggest that 3K3A-APC holds potential as an effective anti-Aβ prevention therapy for early-stage AD.
Ensuring privacy and security of genomic data and functionalities
Authors: Mohammed Yakubu Abukari , Chen Yi-Ping Phoebe
Published: January 2019

In recent times, the reduced cost of DNA sequencing has resulted in a plethora of genomic data that is being used to advance biomedical research and improve clinical procedures and healthcare delivery. These advances are revolutionizing areas in genome-wide association studies (GWASs), diagnostic testing, personalized medicine and drug discovery. This, however, comes with security and privacy challenges as the human genome is sensitive in nature and uniquely identifies an individual. In this article, we discuss the genome privacy problem and review relevant privacy attacks, classified into identity tracing, attribute disclosure and completion attacks, which have been used to breach the privacy of an individual. We then classify state-of-the-art genomic privacy-preserving solutions based on their application and computational domains (genomic aggregation, GWASs and statistical analysis, sequence comparison and genetic testing) that have been proposed to mitigate these attacks and compare them in terms of their underlining cryptographic primitives, security goals and complexities—computation and transmission overheads. Finally, we identify and discuss the open issues, research challenges and future directions in the field of genomic privacy. We believe this article will provide researchers with the current trends and insights on the importance and challenges of privacy and security issues in the area of genomics.
From patient-specific induced pluripotent stem cells to clinical translation in long QT syndrome Type 2
Authors: Schwartz Peter J , Gnecchi Massimiliano , Dagradi Federica , Castelletti Silvia , Parati Gianfranco , Spazzolini Carla , Sala Luca , Crotti Lia
Published: January 2019

Aims

Having shown that Lumacaftor rescued the hERG trafficking defect in the induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two LQT2 patients, we tested whether the commercial association Lumacaftor + Ivacaftor (LUM + IVA) could shorten the QTc in the same two patients.

Methods and results

After hospital admission and 1 day of baseline recordings, half dose LUM + IVA was administered on Day 1, followed by full dose (LUM 800 mg + IVA 500 mg) for 7 days. A continuous 12-lead Holter ECG allowed a large number of blind QTc measurements. Lumacaftor + Ivacaftor shortened QTc significantly in both patients: in V6 from 551 ± 22 ms to 523 ± 35 ms in Patient 1 (Pt1) and from 472 ± 21 ms to 449 ± 20 ms in Patient 2 (Pt2); in DII from 562 ± 25 ms to 549 ± 35 ms in Pt1 and from 485 ± 32 ms to 452 ± 18 ms in Pt2. In both patients, the percentage of QTc values in the lower tertile increased strikingly: in V6 from 33% to 68% and from 33% to 76%; in DII from 33% to 50% and from 33% to 87%. In the wash-out period a rebound in QTc was observed. On treatment, both patients developed diarrhoea, Pt1 more than Pt2.

Conclusion

This represents the first attempt to validate in patients the in vitro results of a drug repurposing strategy for cardiovascular disorders. Lumacaftor + Ivacaftor shortened significantly the QTc in the two LQT2 patients with a trafficking defect, largely confirming the findings in their iPSC-CMs but with smaller quantitative changes. The findings are encouraging but immediate translation into clinical practice, without validation in more patients, would be premature.
Very Early Initiation of Antiretroviral Therapy During Acute HIV Infection Is Associated With Normalized Levels of Immune Activation Markers in Cerebrospinal Fluid but Not in Plasma
Authors: Hellmuth Joanna , Slike Bonnie M , Sacdalan Carlo , Best John , Kroon Eugene , Phanuphak Nittaya , Fletcher James L K , Prueksakaew Peeriya , Jagodzinski Linda L , Valcour Victor , Robb Merlin , Ananworanich Jintanat , Allen Isabel E , Krebs Shelly J , Spudich Serena
Published: January 2019

Background

Chronic immune activation in the blood and central nervous system is a consequence of human immunodeficiency virus (HIV) infection that contributes to disease morbidity and can occur despite virally suppressive antiretroviral therapy (ART). The trajectory of HIV-related inflammation may vary with the timing of ART initiation. We examined immune activation markers in cerebrospinal fluid (CSF) and blood specimens collected over 96 weeks from participants who initiated ART during acute HIV infection (AHI).

Methods

RV254/SEARCH010 study participants with AHI underwent CSF (n = 89) and plasma (n = 146) sampling before initiating ART and at weeks 24 and 96 of treatment. A majority participants (64.4%) received a standard ART regimen (hereafter, “standard ART”), with some (34.7%) also receiving maraviroc and raltegravir for the first 24 weeks (hereafter, “ART plus”). We compared neopterin, CXCL10, CCL2, and interleukin 6 (IL-6) levels in the AHI group to those in 18 healthy, uninfected controls.

Results

Following 24 and 96 weeks of treatment, levels of all CSF markers normalized while levels of several plasma markers remained elevated in the AHI group (P < .001). Participants receiving the ART-plus regimen had lower median plasma CCL2 levels at week 24 and lower plasma neopterin levels at week 96.

Conclusions

ART initiation during AHI differentially impacts the brain compartment, with markers of inflammation returning to normal levels in the CSF, where they were sustained at week 96, but not in plasma.
How many life-years have new drugs saved? A three-way fixed-effects analysis of 66 diseases in 27 countries, 2000–2013
Authors: Lichtenberg Frank R
Published: January 2019

Background

We analyzed the role that the launch of new drugs has played in reducing the number of years of life lost (YLL) before three different ages (85, 70 and 55 y) due to 66 diseases in 27 countries.

Methods

We estimated two-way fixed-effects models of the rate of decline of the disease- and country-specific age-standardized YLL rate. The models control for the average decline in the YLL rate in each country and from each disease.

Results

One additional drug launch 0–11 y before year t is estimated to have reduced the pre-age-85 y YLL rate (YLL85) in year t by 3.0%, and one additional drug launch ≥12 y before year t is estimated to have reduced YLL85 by 5.5%. (A drug’s utilization peaks 8–10 y after it is launched.) Controlling for the number of drugs previously launched, YLL rates are unrelated to the number of drug classes previously launched.

Conclusions

The estimates imply that, if no new drugs had been launched after 1981, YLL85 in 2013 would have been 2.16 times as high as it actually was. We estimated that pharmaceutical expenditure per life-year saved before age 85 y in 2013 by post-1981 drugs was $2837. This amount is about 8% of per capita GDP, indicating that post-1981 drugs launched were very cost-effective overall. But the fact that an intervention is cost-effective does not necessarily mean that it is ‘affordable.’
Deoxyribonuclease I Activity, Cell-Free DNA, and Risk of Liver Cancer in a Prospective Cohort
Authors: Golonka Rachel M , Yeoh Beng San , Petrick Jessica L , Weinstein Stephanie J , Albanes Demetrius , Gewirtz Andrew T , McGlynn Katherine A , Vijay-Kumar Matam
Published: January 2019

Background

Circulating cell-free DNA (cfDNA) is a proposed latent biomarker for several cancers, including liver cancer. Deoxyribonucleases (DNases) facilitate the timely and efficient degradation of cfDNA, leading us to hypothesize that DNase I and/or II might be a more sensitive early biomarker than cfDNA. To test this hypothesis, a study was conducted in a large, prospective cohort.

Methods

A nested case-control study (224 liver cancer case patients and 224 matched control subjects) was conducted in a cohort of Finnish male smokers, followed from baseline (1985–1988) to 2014. The associations among DNase I activity, cfDNA, and the risk of liver cancer were assessed using multivariable-adjusted conditional logistic regression.

Results

DNase I activity, whether measured as radius (mm) or as units per milliliter, was statistically significantly associated with increased risk of liver cancer (Ptrend <.01). DNase I activity in the highest quartile was associated with a greater than threefold risk of developing liver cancer (DNase I activity radius >2.7 mm, hazard ratio [HR] = 3.03, 95% confidence interval [CI] = 1.59 to 5.77; DNase I activity >2.72 units/mL, HR = 3.30, 95% CI = 1.64 to 6.65). The strength of this association was not substantially altered by exclusion of cases diagnosed within the first five years of follow-up or those with hepatitis C virus (HCV) infection. In contrast, cfDNA and DNase II was not statistically significantly associated with risk of liver cancer.

Conclusions

DNase I activity was a superior latent biomarker of liver cancer than cfDNA. These findings advance the goal of developing a means to detect liver cancer years well before the development of clinical manifestations.
The origin of galactic metal-rich stellar halo components with highly eccentric orbits
Authors: Fattahi Azadeh , Belokurov Vasily , Deason Alis J , Frenk Carlos S , Gómez Facundo A , Grand Robert J J , Marinacci Federico , Pakmor Rüdiger , Springel Volker
Published: January 2019

Using the astrometry from the ESA’s Gaia mission, previous works have shown that the Milky Way stellar halo is dominated by metal-rich stars on highly eccentric orbits. To shed light on the nature of this prominent halo component, we have analysed 28 Galaxy analogues in the Auriga suite of cosmological hydrodynamics zoom-in simulations. Some three quarters of the Auriga galaxies contain prominent components with high radial velocity anisotropy, β > 0.6. However, only in one third of the hosts do the high-β stars contribute significantly to the accreted stellar halo overall, similar to what is observed in the Milky Way. For this particular subset we reveal the origin of the dominant stellar halo component with high metallicity, [Fe/H] ∼ −1, and high orbital anisotropy, β > 0.8, by tracing their stars back to the epoch of accretion. It appears that, typically, these stars come from a single dwarf galaxy with a stellar mass of the order of $10^9-10^{10}\, {\rm M}_\odot$ that merged around $6-10 \, {\rm Gyr}$ ago, causing a sharp increase in the halo mass. Our study therefore establishes a firm link between the excess of radially anisotropic stellar debris in the halo and an ancient head-on collision between the young Milky Way and a massive dwarf galaxy.
Plato’s Theaetetus
Authors: Lee Mi-Kyoung
Published: January 2019

Plato’s Theaetetus is a dialogue devoted to the question of what knowledge (epistêmê) is; the narrators recount a conversation that Socrates had the day before his trial with Theodorus of Cyrene, who teaches geometry at Athens, and his young student, Theaetetus, who would later go on to make some important mathematical discoveries. After some introductory discussion about what Socrates is looking for, Theaetetus proposes three definitions of knowledge, each of which is subjected to critical examination, and then rejected in turn: knowledge is perception (151e–186e), it is true opinion (187a–200d), or it is true opinion accompanied by a logos (200d–210a). The dialogue ends in aporia. The Theaetetus along with the Meno and Republic form the three most important works for understanding Plato’s epistemology and theory of knowledge. Because of its elenctic or dialectical character—in which the candidate definitions are rejected on the basis of problems or refutations based on the cooperative discussion between Socrates and Theaetetus—it is difficult to pronounce confidently what conclusions the reader is meant to draw, and what views, if any, Plato as the author of the dialogue holds. The dialogue is chock full of original ideas and arguments which would go on to have an enormous influence on later philosophers, including, for example, Socrates’ comparing himself as a philosopher-teacher to a midwife, the idea that knowledge is perception, the thesis of relativism, the thesis of radical metaphysical flux, the comparison of the mind to a wax block, etc. It is also a masterpiece of philosophical writing and often thought of along with the Phaedo and Republic as one of Plato’s most brilliant dialogues. For more on Plato, see the separate Oxford Bibliographies in Classics article “Plato.”
Mountain Buddhism in East Asia
Authors: DeWitt Lindsey E.
Published: January 2019

Mountains play a central role in Buddhist cosmology and practice. Scriptural accounts of Mount Sumeru (cosmological center of the Hindu-Buddhist universe) and Vulture Peak in India (favored abode for the Buddha and a panoply of deities and disciples) clearly attest to this, as does the physical and symbolic construction of Buddhist sacred sites in mountainous locales. The varieties of Buddhist activity that developed in East Asia reflect a new valorization of mountains not found in India, however. Diverse forms of Buddhist thought and practice took root at mountain sites throughout present-day China, Korea, and Japan, flourishing in complex and fascinating ways over time through transregional and transcultural exchange—and always in relation to (and sometimes competing with) local concerns and customs. International research on Buddhist mountain spaces, places, and practices has prospered in the late 20th and early 21st centuries, with various monographs, anthologies, and essays presenting information about mountains in Buddhist discourse or Buddhist activity that takes place in mountains. Still, no single work to date investigates mountain Buddhism in East Asia in a comprehensive or comparative manner. This review introduces an eclectic mix of English-language sources, grouped thematically (although with significant overlap), that span all time periods and employ various disciplinary approaches. The slight geographical imbalance present in the list reflects the nascent state of research on Korean religions and the exceptionally well-developed body of work on mountain Buddhism in Japan, especially Shugendō, a combinatory and mountain-centric religious tradition deeply influenced by Buddhist doctrine and ritual.
Philosophy for Children
Authors: Cam Philip
Published: January 2019

Philosophy for Children is an educational movement that was originally associated with the Institute for the Advancement of Philosophy for Children (IAPC) at Montclair State University (formerly Montclair State College) in the United States beginning in the early 1970s. The term was coined by Matthew Lipman, who was primarily responsible for setting up the institute, after moving from Columbia University in New York, where he first began this work. Lipman and his colleague, Ann Margaret Sharp, promoted Philosophy for Children in the United States and then internationally. It has since attracted the attention of philosophers and educationalists in many parts of the world and both it and its offshoots have become widely represented in schools. Philosophy for Children adapts philosophical subject matter and modes of inquiry for use in school education, either as a separate intervention or by way of integration into existing school subjects. Although philosophy has been traditionally restricted to the senior years, Philosophy for Children is to be found throughout all levels of schooling. This reflects the fact that, while not neglecting the intrinsic value of moral, epistemological, metaphysical, and other philosophical subject matter, it has broader educational objectives. Philosophy for Children is committed to the development of active democratic citizens who have an open inquiring outlook and are prepared to arrive at judgments on the basis of reason and evidence. It supports this outcome through collaborative inquiry-based teaching and learning, treating the classroom as an inquiring community, where emphasis is placed on critical, creative, and caring thinking and the development of associated cognitive and social skills, abilities, and dispositions. A wide array of books for teachers and classroom materials have been produced along with a growing body of research and academic publications in monographs, anthologies, and journals.