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At least 667 records · Page 37

Therapeutic efficacy of improved α-fetoprotein promoter-mediated tBid delivered by folate-PEI600-cyclodextrin nanopolymer vector in hepatocellular carcinoma

SNPs in human AFP promoter are associated with serum AFP levels in hepatocellular carcinoma (HCC), suggesting that AFP promoter variants may generate better transcriptional activities while retaining high specificity to AFP-producing cells. We sequenced human AFP promoters, cloned 15 different genotype promoters and tested their reporter activities in AFP-producing and non-producing cells. Among various AFP variant fragments tested, EA4D exhibited the highest reporter activity and thus was selected for the further study. EA4D was fused with tBid and coupled with nano-particle vector (H1) to form pGL3-EA4D-tBid/H1. pGL3-EA4D-tBid/H1 could express a high level of tBid while retain the specificity to AFP-producing cells. In a HCC tumor model, application of pGL3-EA4D-tBid/H1 significantly inhibited the growth of AFP-producing-implanted tumors with minimal side-effects, but had no effect on non-AFP-producing tumors. Furthermore, pGL3-EA4D-tBid/H1 could significantly sensitize HCC cells to sorafenib, an approved anti-HCC agent. Collectively, pGL3-EA4D-tBid/H1, a construct with the AFP promoter EA4D and the novel H1 delivery system, can specifically target and effectively suppress the AFP-producing HCC. This new therapeutic tool shows little toxicity in vitro and in vivo and it should thus be safe for further clinical tests. - Highlights: • The nano-particle vector H1 has advantages in mediating gene therapy construct pGL3-EA4D-tBid for HCC treatment. • pGL3-EA4D-tBid/H1, a construct with the AFP promoter EA4D, can specifically target the AFP-producing HCC. • pGL3-EA4D-tBid/H1effectively suppresses the proliferation and growth of AFP-producing HCC. • This novel pGL3-EA4D-tBid/H1 therapeutic tool shows little toxicity in vitro and in vivo.

60 APPLIED LIFE SCIENCES↗

Robust Biaxial Anisotropy and Switchable Néel Vectors in LaFeO 3 Epitaxial Films

Antiferromagnets with highly stable but switchable Néel vectors are desired for antiferromagnetic spintronics with ultrafast speed and terahertz frequencies. Electrical switching of antiferromagnetic insulators has been demonstrated using binary antiferromagnets, while large families of complex antiferromagnets such as perovskites are largely unexplored. Here, we show that epitaxial LaFeO 3 thin films on SrTiO 3 (001) exhibit clear, robust biaxial anisotropy with a spin-flop field of a few tesla. Angular-dependent spin-Hall magnetoresistance (SMR) characterizations of Pt/LaFeO 3 bilayers with the current channel along SrTiO 3 [100] and [110] reveal distinct, intriguing shapes and field dependence. Simulations using a macrospin model accurately describe the main behavior and fine features of the SMR data from which key antiferromagnetic parameters are extracted. Furthermore, remanent SMR measurement confirms the high fidelity of the Néel vector along either easy axis of the biaxial anisotropy, indicating that epitaxial films of LaFeO 3 and potentially other perovskite antiferromagnets offer an attractive platform for antiferromagnetic spintronics.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector

Blood-feeding disease vectors mitigate the negative effects of hemostasis and inflammation through the binding of small-molecule agonists of these processes by salivary proteins. In this study, a lipocalin protein family member (LTBP1) from the saliva of Rhodnius prolixus, a vector of the pathogen Trypanosoma cruzi, is shown to sequester cysteinyl leukotrienes during feeding to inhibit immediate inflammatory responses. Calorimetric binding experiments showed that LTBP1 binds leukotrienes C 4 (LTC 4 ), D 4 (LTD 4 ), and E 4 (LTE 4 ) but not biogenic amines, adenosine diphosphate, or other eicosanoid compounds. Crystal structures of ligand-free LTBP1 and its complexes with LTC 4 and LTD 4 reveal a conformational change during binding that brings Tyr114 into close contact with the ligand. LTC 4 is cleaved in the complex, leaving free glutathione and a C 20 fatty acid. As a result, chromatographic analysis of bound ligands showed only intact LTC 4 , suggesting that cleavage could be radiation-mediated.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

CRISPR/Cas9 as an antiviral against Orthopoxviruses using an AAV vector

A vaccine for smallpox is no longer administered to the general public, and there is no proven, safe treatment specific to poxvirus infections, leaving people susceptible to infections by smallpox and other zoonotic Orthopoxviruses such as monkeypox. Using vaccinia virus (VACV) as a model organism for other Orthopoxviruses, CRISPR–Cas9 technology was used to target three essential genes that are conserved across the genus, including A17L, E3L, and I2L. Three individual single guide RNAs (sgRNAs) were designed per gene to facilitate redundancy in rendering the genes inactive, thereby reducing the reproduction of the virus. The efficacy of the CRISPR targets was tested by transfecting human embryonic kidney (HEK293) cells with plasmids encoding both SaCas9 and an individual sgRNA. This resulted in a reduction of VACV titer by up to 93.19% per target. Following the verification of CRISPR targets, safe and targeted delivery of the VACV CRISPR antivirals was tested using adeno-associated virus (AAV) as a packaging vector for both SaCas9 and sgRNA. Similarly, AAV delivery of the CRISPR antivirals resulted in a reduction of viral titer by up to 92.97% for an individual target. Overall, we have identified highly specific CRISPR targets that significantly reduce VACV titer as well as an appropriate vector for delivering these CRISPR antiviral components to host cells in vitro.

60 APPLIED LIFE SCIENCES↗

Predicting distribution of malaria vector larval habitats in Ethiopia by integrating distributed hydrologic modeling with remotely sensed data

Abstract Larval source management has gained renewed interest as a malaria control strategy in Africa but the widespread and transient nature of larval breeding sites poses a challenge to its implementation. To address this problem, we propose combining an integrated high resolution (50 m) distributed hydrological model and remotely sensed data to simulate potential malaria vector aquatic habitats. The novelty of our approach lies in its consideration of irrigation practices and its ability to resolve complex ponding processes that contribute to potential larval habitats. The simulation was performed for the year of 2018 using ParFlow-Common Land Model (CLM) in a sugarcane plantation in the Oromia region, Ethiopia to examine the effects of rainfall and irrigation. The model was calibrated using field observations of larval habitats to successfully predict ponding at all surveyed locations from the validation dataset. Results show that without irrigation, at least half of the area inside the farms had a 40% probability of potential larval habitat occurrence. With irrigation, the probability increased to 56%. Irrigation dampened the seasonality of the potential larval habitats such that the peak larval habitat occurrence window during the rainy season was extended into the dry season. Furthermore, the stability of the habitats was prolonged, with a significant shift from semi-permanent to permanent habitats. Our study provides a hydrological perspective on the impact of environmental modification on malaria vector ecology, which can potentially inform malaria control strategies through better water management.

59 BASIC BIOLOGICAL SCIENCES↗

Photoproduction of vector mesons in ultra-peripheral p–Pb and Pb–Pb collisions at the LHC with the ALICE experiment

Vector mesons are copiously produced in ultra-peripheral collisions. In these collisions, the impact parameter is larger than the sum of the radii of the two projectiles, implying that electromagnetic processes become dominant. The cross section of production of vector mesons is expected to be sensitive to the gluon distribution and can therefore probe nuclear gluon shadowing (Pb–Pb) and the gluon structure function in the nucleon (p-Pb). The ALICE Collaboration has performed the first measurements of the production of ρ{sup 0}, J/ψ and ψ/(2S) in Pb–Pb ultra-peripheral collision as well as the cross section for exclusive J/ψ photoproduction off protons in ultra-peripheral proton-lead collisions at the LHC. The results are compared to the STARLIGHT Monte Carlo and to QCD based models.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Design and simulation of MEMS vector hydrophone with reduced cross section based meander beams

MEMS based vector hydrophone is being one of the key device in the underwater communications. In this paper, we presented a bio-inspired MEMS vector hydrophone. The hydrophone structure consists of a proof mass suspended by four meander type beams with reduced cross-section. Modal patterns of the structure were studied. First three modal frequencies of the hydrophone structure were found to be 420 Hz, 420 Hz and 1646 Hz respectively. The deflection and stress of the hydrophone is found have linear behavior in the 1 µPa – 1Pa pressure range.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Complete Stokes vector analysis with a compact, portable rotating waveplate polarimeter

Accurate calibration of polarization dependent optical elements is often necessary in optical experiments. A versatile polarimeter device to measure the polarization state of light is a valuable tool in these experiments. Here we report a rotating waveplate-based polarimeter capable of complete Stokes vector analysis of collimated light. Calibration of the device allows accurate measurements over a range of wavelengths, with a bandwidth of >30 nm in this implementation. A photo-interrupter trigger system supplies the phase information necessary for full determination of the Stokes vector. An Arduino microcontroller performs rapid analysis and displays the results on a liquid crystal display. The polarimeter is compact and can be placed anywhere on an optical table on a single standard post. The components to construct the device are only a fraction of the cost of commercially available devices while the accuracy and precision of the measurements are of the same order of magnitude.

47 OTHER INSTRUMENTATION↗

Theory and application of the vector pair correlation function for real-space crystallographic analysis of order/disorder correlations from STEM images

Deviations of local structure and chemistry from the average crystalline unit cell are increasingly recognized to have a significant influence on the properties of many technologically important materials. Here, we present the vector pair correlation function (vPCF) as a new real-space crystallographic analysis method, which can be applied to atomic-resolution scanning transmission electron microscopy (STEM) images to quantify and analyze structural order/disorder correlations. Our STEM-based vPCFs have several advantages over radial PCFs and/or 3D pair distribution functions from x-ray total scattering: vPCFs explicitly retain crystallographic orientation information, are spatially resolved, can be applied directly on a sublattice basis, and are suitable for any material that can be imaged with STEM. To show the utility of our approach, we measure partial vPCFs in Ba 5 SmSn 3 Nb 7 O 30 (BSSN), a tetragonal tungsten bronze (TTB) structured complex oxide. Many TTBs are known to be classical or relaxor ferroelectrics, and these properties have been correlated with the presence of superlattice ordering. BSSN, specifically, exhibits relaxor behavior and an incommensurate structural modulation. From the vPCF data, we observe that, of the cation sites, only the Ba (A2) sublattice is structurally modulated. We then infer the local modulation vector and reveal a marked anisotropy in its correlation length. Finally, short-range correlated polar displacements on the B2 cation sites are observed. This work introduces the vPCF as a powerful real-space crystallography technique, which enables direct, robust quantification of short-to-long range order on a sublattice-specific basis and is applicable to a wide range of complex material types.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

A comprehensive method of estimating electric fields from vector magnetic field and Doppler measurements

Photospheric electric fields, estimated from sequences of vector magnetic field and Doppler measurements, can be used to estimate the flux of magnetic energy (the Poynting flux) into the corona and as time-dependent boundary conditions for dynamic models of the coronal magnetic field. We have modified and extended an existing method to estimate photospheric electric fields that combines a poloidal-toroidal decomposition (PTD) of the evolving magnetic field vector with Doppler and horizontal plasma velocities. Our current, more comprehensive method, which we dub the 'PTD-Doppler-FLCT Ideal' (PDFI) technique, can now incorporate Doppler velocities from non-normal viewing angles. It uses the FISHPACK software package to solve several two-dimensional Poisson equations, a faster and more robust approach than our previous implementations. Here, we describe systematic, quantitative tests of the accuracy and robustness of the PDFI technique using synthetic data from anelastic MHD (ANMHD) simulations, which have been used in similar tests in the past. We find that the PDFI method has less than 1% error in the total Poynting flux and a 10% error in the helicity flux rate at a normal viewing angle (θ = 0) and less than 25% and 10% errors, respectively, at large viewing angles (θ < 60°). We compare our results with other inversion methods at zero viewing angle and find that our method's estimates of the fluxes of magnetic energy and helicity are comparable to or more accurate than other methods. We also discuss the limitations of the PDFI method and its uncertainties.

79 ASTRONOMY AND ASTROPHYSICS↗

Vector interaction enhanced bag model for astrophysical applications

For quark matter studies in astrophysics the thermodynamic bag model (tdBAG) has been widely used. Despite its success it fails to account for various phenomena expected from QCD. We suggest a straightforward extension of tdBAG in order to take the dynamical breaking of chiral symmetry and the influence of vector interactions explicitly into account. As for tdBAG the model mimics confinement in a phenomenological approach. It is based on an analysis of the Nambu–Jona-Lasinio (NJL) model at finite density. Furthermore, we demonstrate how NJL and bag models in this regime follow from the more general and QCD-based framework of the Dyson–Schwinger equations in a medium by assuming simple gluon contact interaction. Based on our simple and novel model, we construct quark hadron hybrid equations of state and systematically study chiral and deconfinement phase transitions, the appearance of s-quarks, and the role of vector interaction. We further study these aspects for matter in β-equilibrium at zero temperature, with particular focus on the current ∼2 M{sub ⊙} maximum mass constraint for neutron stars. Our approach indicates that the currently only theoretical evidence for the hypothesis of stable strange matter is an artifact of tdBAG and results from neglecting the dynamical breaking of chiral symmetry.

79 ASTRONOMY AND ASTROPHYSICS↗

PREDICTION OF SOLAR FLARE SIZE AND TIME-TO-FLARE USING SUPPORT VECTOR MACHINE REGRESSION

We study the prediction of solar flare size and time-to-flare using 38 features describing magnetic complexity of the photospheric magnetic field. This work uses support vector regression to formulate a mapping from the 38-dimensional feature space to a continuous-valued label vector representing flare size or time-to-flare. When we consider flaring regions only, we find an average error in estimating flare size of approximately half a geostationary operational environmental satellite (GOES) class. When we additionally consider non-flaring regions, we find an increased average error of approximately three-fourths a GOES class. We also consider thresholding the regressed flare size for the experiment containing both flaring and non-flaring regions and find a true positive rate of 0.69 and a true negative rate of 0.86 for flare prediction. The results for both of these size regression experiments are consistent across a wide range of predictive time windows, indicating that the magnetic complexity features may be persistent in appearance long before flare activity. This is supported by our larger error rates of some 40 hr in the time-to-flare regression problem. The 38 magnetic complexity features considered here appear to have discriminative potential for flare size, but their persistence in time makes them less discriminative for the time-to-flare problem.

79 ASTRONOMY AND ASTROPHYSICS↗

Decaying vector dark matter as an explanation for the 3.5 keV line from galaxy clusters

We present a Vector Dark Matter (VDM) model that explains the 3.5 keV line recently observed in the XMM-Newton observatory data from galaxy clusters. In this model, dark matter is composed of two vector bosons, V and V', which couple to the photon through an effective generalized Chern-Simons coupling, g{sub V}. V' is slightly heavier than V with a mass splitting m{sub V'} – m{sub V} ≅ 3.5 keV. The decay of V' to V and a photon gives rise to the 3.5 keV line. The production of V and V' takes place in the early universe within the freeze-in framework through the effective g{sub V} coupling when m{sub V'} < T < Λ, Λ being the cut-off above which the effective g{sub V} coupling is not valid. We introduce a high energy model that gives rise to the g{sub V} coupling at low energies. To do this, V and V' are promoted to gauge bosons of spontaneously broken new U(1){sub V} and U(1){sub V'} gauge symmetries, respectively. The high energy sector includes milli-charged chiral fermions that lead to the g{sub V} coupling at low energy via triangle diagrams.

79 ASTRONOMY AND ASTROPHYSICS↗

Precision vector control of a superconducting RF cavity driven by an injection locked magnetron

The technique presented in this paper enables the regulation of both radio frequency amplitude and phase in narrow band devices such as a Superconducting RF (SRF) cavity driven by constant power output devices i.e. magnetrons [1]. The ability to use low cost high efficiency magnetrons for accelerator RF power systems, with tight vector regulation, presents a substantial cost savings in both construction and operating costs - compared to current RF power system technology. An operating CW system at 2.45 GHz has been experimentally developed. Vector control of an injection locked magnetron has been extensively tested and characterized with a SRF cavity as the load. Amplitude dynamic range of 30 dB, amplitude stability of 0.3% r.m.s, and phase stability of 0.26 degrees r.m.s. has been demonstrated.

43 PARTICLE ACCELERATORS↗

HEIGHT VARIATION OF THE VECTOR MAGNETIC FIELD IN SOLAR SPICULES

Proving the magnetic configuration of solar spicules has hitherto been difficult due to the lack of spatial resolution and image stability during off-limb ground-based observations. We report spectropolarimetric observations of spicules taken in the He i 1083 nm spectral region with the Tenerife Infrared Polarimeter II at the German Vacuum Tower Telescope of the Observatorio del Teide (Tenerife, Canary Islands, Spain). The data provide the variation with geometrical height of the Stokes I, Q, U, and V profiles, whose encoded information allows the determination of the magnetic field vector by means of the HAZEL inversion code. The inferred results show that the average magnetic field strength at the base of solar spicules is about 80 gauss, and then it decreases rapidly with height to about 30 gauss at a height of 3000 km above the visible solar surface. Moreover, the magnetic field vector is close to vertical at the base of the chromosphere and has mid-inclinations (about 50°) above 2 Mm height.

79 ASTRONOMY AND ASTROPHYSICS↗

Generalized Korn’s inequalities for piecewise $H¹$ and $H²$ vector fields

The purpose of this paper is to construct a new class of discrete generalized Korn’s inequalities for piecewise $H^1$ vector fields and piecewise $H^2$ vector fields in three-dimensional space. The resulting Korn’s inequalities are different from the standard Korn’s inequalities, as they involve the trace-free symmetric gradient operator, in place of the usual symmetric gradient operator. Furthermore, it is anticipated that the new generalized Korn’s inequalities will be useful for the analysis of a broad range of finite element methods, including mixed finite element methods and discontinuous Galerkin methods.

97 MATHEMATICS AND COMPUTING↗

Improved annotation of the insect vector of citrus greening disease: biocuration by a diverse genomics community

The Asian citrus psyllid ( Diaphorina citri Kuwayama) is the insect vector of the bacterium Candidatus Liberibacter asiaticus (CLas), the pathogen associated with citrus Huanglongbing (HLB, citrus greening). HLB threatens citrus production worldwide. Suppression or reduction of the insect vector using chemical insecticides has been the primary method to inhibit the spread of citrus greening disease. Accurate structural and functional annotation of the Asian citrus psyllid genome, as well as a clear understanding of the interactions between the insect and CLas, are required for development of new molecular-based HLB control methods. A draft assembly of the D. citri genome has been generated and annotated with automated pipelines. However, knowledge transfer from well-curated reference genomes such as that of Drosophila melanogaster to newly sequenced ones is challenging due to the complexity and diversity of insect genomes. To identify and improve gene models as potential targets for pest control, we manually curated several gene families with a focus on genes that have key functional roles in D. citri biology and CLas interactions. This community effort produced 530 manually curated gene models across developmental, physiological, RNAi regulatory and immunity-related pathways. As previously shown in the pea aphid, RNAi machinery genes putatively involved in the microRNA pathway have been specifically duplicated. A comprehensive transcriptome enabled us to identify a number of gene families that are either missing or misassembled in the draft genome. In order to develop biocuration as a training experience, we included undergraduate and graduate students from multiple institutions, as well as experienced annotators from the insect genomics research community. The resulting gene set (OGS v1.0) combines both automatically predicted and manually curated gene models.

59 BASIC BIOLOGICAL SCIENCES↗

Sensitivity to longitudinal vector boson scattering and doubly charged Higgs boson production in $W^± W^± jj$ at future hadron colliders

We study the sensitivity to longitudinal vector boson scattering at a 27-, 50-, and 100-TeV pp collider using events containing two leptonically decaying same-electric-charge 𝑊 bosons produced in association with two jets. The baseline FCC-hh detector parametrization within the D ELPHES framework is used under the assumption of fully efficient pileup mitigation. A tightly constrained phase space with a dijet mass greater than 2 TeV is considered in order to suppress the impact of potential instrumental backgrounds. Based on this setup, the expected sensitivity to the production of longitudinally polarized same-sign 𝑊 boson pairs is evaluated. Additionally, expected limits are set on doubly charged Higgs bosons produced via vector boson fusion processes and decaying to same-sign 𝑊 boson pairs.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗