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At least 19 records

Dwarf spheroidal J-factor likelihoods for generalized NFW profiles

ABSTRACT Indirect detection strategies of particle dark matter (DM) in Dwarf spheroidal satellite galaxies (dSphs) typically entail searching for annihilation signals above the astrophysical background. To robustly compare model predictions with the observed fluxes of product particles, most analyses of astrophysical data – which are generally frequentist – rely on estimating the abundance of DM by calculating the so-called J factor. This quantity is usually inferred from the kinematic properties of the stellar population of a dSph using the Jeans equation, commonly by means of Bayesian techniques that entail the presence (and additional systematic uncertainty) of prior choice. Here, extending earlier work, we develop a scheme to derive the profile likelihood for J factors of dwarf spheroidals for models with five or more free parameters. We validate our method on a publicly available simulation suite, released by the Gaia Challenge, finding satisfactory statistical properties for bias and probability coverage. We present the profile likelihood function and maximum likelihood estimates for the J-factor of 10 dSphs. As an illustration, we apply these profile likelihoods to recently published analyses of γ-ray data with the Fermi Large Area Telescope to derive new, consistent upper limits on the DM annihilation cross-section. We do this for a subset of systems, generally referred to as classical dwarfs. The implications of these findings for DM searches are discussed, together with future improvements and extensions of this technique.

79 ASTRONOMY AND ASTROPHYSICS↗

The Morphology and Structure of Stellar Populations in the Fornax Dwarf Spheroidal Galaxy from Dark Energy Survey Data

Using deep wide-field photometry 3 yr data (Y3) from the Dark Energy Survey (DES), we introduce a panoramic study of the Fornax dwarf spheroidal galaxy. The data discussed here—a small subset of the full survey—uniformly cover a region of 25 deg 2 centered on the galaxy to a depth of g ~ 23.5. We use these data to study the structural properties of Fornax, overall stellar population, and its member stars in different evolutionary phases. We also search for possible signs of tidal disturbance. Fornax is found to be significantly more spatially extended than what early studies suggested. No statistically significant distortions or signs of tidal disturbances were found down to a surface brightness limit of ~32.1 mag arcsec -2 . Yet, there are hints of shell-like features located ~20'–40' from the center of Fornax that may be stellar debris from past merger events. We also find that intermediate-age and young main-sequence populations show different orientation at the galaxy center and have many substructures. The deep DES Y3 data allow us to characterize the age of those young stellar substructures with great accuracy, both those previously known and those newly identified as possible overdensities in this work, on the basis of their color–magnitude diagram morphology. We find that the youngest overdensities are all found on the eastern side of Fornax, where the Fornax field population itself is slightly younger than in the west. In summary, the high-quality DES Y3 data reveal that Fornax has many rich structures and provide insights into its complex formation history.

79 ASTRONOMY AND ASTROPHYSICS↗

Characterization of Virgin, Re-used, and Oxygen-reduced Copper Powders processed by the Plasma Spheroidization Process

We report that fabrication of parts with high mechanical properties heavily depend on the quality of powder deployed in the fabrication process. Copper powder in three different powder types were spheroidized using radio-frequency inductively coupled plasma (ICP) spheroidization process (TekSphero-15 system). The characterized powders include virgin powder as purchased from the powder manufacturer, powder used in electron beam powder bed fusion (EB-PBF) process, and reconditioned powder, which was used powder that underwent an oxygen-reduction treatment. The goal of spheroidizing these powder types was to evaluate the change in powder morphology, the possibility of enhancing the powder properties back to their as-received conditions, and assess oxygen reduction of the powder lots given their initial oxygen contents. Also, to investigate the impact of re-spheroidization on powder properties, the second round of spheroidization was performed on the already used-spheroidized powder. The impact of powder type on powder sphericity and particle size distribution was evaluated using the image analysis of scanning electron microscope (SEM) micrographs and laser diffraction, respectively. The spheroidized powder showed higher sphericity and more uniform particle size distribution overall. Depending on the powder collection bin, second round of spheroidization affected the powder sphericity differently. The possibility of deploying the plasma spheroidization process as an alternative oxygen-reduction technique was also investigated through tracking the powders’ oxygen content using inert gas fusion method before and after the spheroidization. The plasma spheroidized powder showed less oxygen content than the hydrogen-treated powder. The second round of spheroidization caused no change in oxygen content. The correlation between oxygen-reduction and created cracks was discussed and compared between plasma spheroidization and hydrogen-treatment. The plasma spheroidization process created a powder with higher sphericity, uniform particle size, and less oxygen content.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Integrin α5 mediates intrinsic cisplatin resistance in three-dimensional nasopharyngeal carcinoma spheroids via the inhibition of phosphorylated ERK /caspase-3 induced apoptosis

Highlights: • Highly expressed integrin α5 was observed in in vitro three-dimensional NPC spheroids. • The overexpression of integrin α5 in NPC spheroids demonstrated a correlation with intrinsic cisplatin resistance. • The integrin α5-induced intrinsic cisplatin resistance was mediated by an inactivation of ERK/caspase-3-induced apoptosis. • ATN-161, an integrin α5β1 inhibitor, reduced integrin α5 expression and increased sensitization to cisplatin in NPC spheroids. • ATN-161 reversed the intrinsic cisplatin resistance in NPC spheroids by reactivating ERK/caspase-3-induced apoptosis. Nasopharyngeal carcinoma (NPC) originates in the nasopharynx epithelium. Although concurrent chemoradiation therapy followed by chemotherapy is considered as an effective treatment, there is substantial drug resistance in locally advanced NPC patients. One major contributor to the chemoresistance includes aberrant expression of cell adhesion molecules, such as integrin α and β subunits, giving rise to cell adhesion-mediated drug resistance. Thus, the aim of this study was to investigate the effect of integrin α5 on the development of intrinsic cisplatin resistance in NPC and the associated underlying mechanisms using in vitro three-dimensional (3D) spheroid models, as well as induced cisplatin-resistant NPC (NPCcisR). We demonstrated that established 3D highly- (5-8F) and lowly- (6-10B) metastatic NPC spheroids overexpressed integrin α5 and aggravated their resistance to cisplatin. Besides, enhanced integrin α5 resulted in substantially reduced growth, corresponding to G{sub 0}/G{sub 1} and G{sub 2}/M cell cycle arrest. In addition, 5-8FcisR and 6-10BcisR cells in 3D forms synergistically strengthened endurance of their spheroids to cisplatin treatment as observed by increased resistance index (RI) and decreased apoptosis. Mechanistically, the aberrantly expressed integrin α5 decreased drug susceptibility in NPC spheroids by inactivating ERK and inhibition of caspase-3 inducing apoptosis. Furthermore, the effect of integrin α5 inducing intrinsic resistance was verified via treatment with ATN-161, a peptide inhibitor for integrin α5β1. The results showed dramatic reduction in integrin α5 expression, reversal of ERK phosphorylation and caspase-3 cleavage, together with elevated cisplatin sensitivity, indicating regulation of innate drug resistance via integrin α5. Taken together, our findings suggest that integrin α5 could act as a promising target to enhance the chemotherapeutic sensitivity in NPC.

60 APPLIED LIFE SCIENCES↗

Outgrowth of erlotinib-resistant subpopulations recapitulated in patient-derived lung tumor spheroids and organoids

A model that recapitulates development of acquired therapeutic resistance is needed to improve oncology drug development and patient outcomes. To achieve this end, we established methods for the preparation and growth of spheroids from primary human lung adenocarcinomas, including methods to culture, passage, monitor growth, and evaluate changes in mutational profile over time. Primary lung tumor spheroids were cultured in Matrigel® with varying concentrations of erlotinib, a small molecule kinase inhibitor of epidermal growth factor receptor (EGFR) that is ineffective against KRAS mutant cells. Subtle changes in spheroid size and number were observed within the first two weeks of culture. Spheroids were cultured for up to 24 weeks, during which time interactions between different cell types, movement, and assembly into heterogeneous organoid structures were documented. Allele-specific competitive blocker PCR (ACB-PCR) was used to quantify low frequency BRAF V600E, KRAS G12D, KRAS G12V, and PIK3CA H1047R mutant subpopulations in tumor tissue residue (TR) samples and cultured spheroids. Mutant subpopulations, including multiple mutant subpopulations, were quite prevalent. Twelve examples of mutant enrichment were found in eight of the 14 tumors analyzed, based on the criteria that a statistically-significant increase in mutant fraction was observed relative to both the TR and the no-erlotinib control. Of the mutants quantified in erlotinib-treated cultures, PIK3CA H1047 mutant subpopulations increased most often (5/14 tumors), which is consistent with clinical observations. Thus, this ex vivo lung tumor spheroid model replicates the cellular and mutational tumor heterogeneity of human lung adenocarcinomas and can be used to assess the outgrowth of mutant subpopulations. Spheroid cultures with characterized mutant subpopulations could be used to investigate the efficacy of lung cancer combination therapies.

59 BASIC BIOLOGICAL SCIENCES↗

Incompressible fluid ellipsoids in halos. I - The second-harmonic oscillations of the Maclaurin spheroids

The structure and stability of Maclaurin spheroids embedded in rigid uniform-density oblate spheroidal halos are determined by the tensor virial-equation method. These spheroid-halo systems can be thought of as crude fluid analogs of disk galaxies with halos. The halos are assumed to have the same center, the same axis of symmetry, and the same equatorial radius as the Maclaurin spheroids. Only halos with lower eccentricity than the Maclaurin spheroids are considered. The dynamic instability of the toroidal (barlike) modes is suppressed when m, the ratio of the halo mass to Maclaurin spheroid mass, is greater than 3 pi/8 for spherical halos and when m is greater than 1/2 for halos congruent to the Maclaurin spheroids. Intermediate halo flattenings yield intermediate critical m-values. On the other hand, a neutral point of the toroidal modes in the rotating and inertial frames occurs for all m and for all allowed halo flattenings. Growth rates for secular instability beyond the neutral point are calculated, and the eigenfrequencies of all second-harmonic modes are given for select cases. The Ostriker-Peebles (1973) conjecture concerning the stability of disk galaxies against barlike perturbations appears to be incorrect.

Durisen, R. H.↗

Inhibition of TGF-β pathway reverts extracellular matrix remodeling in T. cruzi-infected cardiac spheroids

Highlights: • A model of cardiac spheroids to study fibrosis in pathological processes is proposed. • The study evaluates a TGF-β inhibitor in restoring extracellular matrix balance disrupted by T. cruzi infection. • Inhibition of TGF-β signaling reduces fibrosis and hypertrophy in infected-cardiac spheroids. • The extracellular matrix remodeling is achieved through regulation of MMP-2 activity and TIMP-1 expression. Chagasic cardiomyopathy (CC) is the main manifestation of Chagas Disease (CD). CC is a progressive dysfunctional illness, in which transforming growth factor beta (TGF-β) plays a central role in fibrogenesis and hypertrophy. In the present study, we tested in a three-dimensional (3D) model of cardiac cells culture (named cardiac spheroids), capable of mimicking the aspects of fibrosis and hypertrophy observed in CC, the role of TGF-β pathway inhibition in restoring extracellular matrix (ECM) balance disrupted by T. cruzi infection. Treatment of T. cruzi-infected cardiac spheroids with SB 431542, a selective inhibitor of TGF-β type I receptor, resulted in a reduction in the size of spheroids, which was accompanied by a decrease in parasite load and in fibronectin expression. The inhibition of TGF-β pathway also promoted an increase in the activity of matrix metalloproteinase (MMP)-2 and a decrease in tissue inhibitor of matrix metalloproteinase (TIMP)-1 expression, which may be one of the mechanisms regulating extracellular matrix remodeling. Therefore, our study provides new insights into the molecular mechanisms by which inhibition of TGF-β signaling reverts fibrosis and hypertrophy generated by T. cruzi during CC and also highlights the use of cardiac spheroids as a valuable tool for the study of fibrogenesis and anti-fibrotic compounds.

60 APPLIED LIFE SCIENCES↗

Three-dimensional spheroid culture induces apical-basal polarity and the original characteristics of immortalized human renal proximal tubule epithelial cells

Highlights: • Immortalized proximal tubule cells (HK-2 cells) formed a tubule-like structure. • The 3D spheroid culture enhanced apical-basal polarity of HK-2 cells. • The 3D spheroid culture induced Na transport function of HK-2 cells. • The 3D spheroid culture promoted up-regulation of kidney development-related genes. The proximal tubules, which are part of the kidney, maintain blood homeostasis by absorbing amino acids, glucose, water, and ions such as sodium (Na), potassium, and bicarbonate. Proximal tubule dysfunction is associated with the pathogenesis of many kidney diseases. Renal proximal tubular epithelial cells (RPTECs) are responsible for the main functions of the proximal tubules. Therefore, in vitro experiments using RPTECs would greatly enhance our understanding of nephron physiology and pathobiology. It is preferable to use immortalized cell lines, such as human kidney-2 (HK-2) cells, because they are derived from humans and maintain growth indefinitely. However, tissue-specific RPTEC phenotypes, including apical-basal polarization, are frequently lost in conventional two-dimensional culture methods in part due to microenvironmental deficiencies. To overcome this limitation, we developed a three-dimensional (3D) spheroid culture method for HK-2 cells using an extracellular matrix. HK-2 spheroids in 3D culture formed a tubule-like architecture with cellular polarity and showed markedly restored Na transport function. 3D culture of HK-2 cells also increased expression of kidney development–related genes, including WNT9B. Models of human renal tubules using HK-2 spheroids will greatly improve our understanding of the physiology and pathobiology of the kidney.

60 APPLIED LIFE SCIENCES↗

Sound scattering by rigid oblate spheroids, with implication to pressure gradient microphones

The frequency limit below which sound scattering by a microphone body is sufficiently small to permit accurate pressure gradient measurements was determined. The sound pressure was measured at various points on the surface of a rigid oblate spheroid illuminated by spherical waves generated by a point source at a large distance from the spheroid, insuring an essentially plane sound field. The measurements were made with small pressure microphones flush mounted from the inside of the spheroid model. Numerical solutions were obtained for a variety of spheroid shapes, including that of the experimental model. Very good agreement was achieved between the experimental and theoretical results. It was found that scattering effects are insignificant if the ratio of the major circumference of the spheroid to the wavelength of the incident sound is less than about 0.7, this number being dependent upon the shape of the spheroid. This finding can be utilized in the design of pressure gradient microphones.

Maciulaitis, A.↗

Nucleation and growth characteristics of graphite spheroids in bainite during graphitization annealing of a medium carbon steel

The evolution of microstructure in bainite during graphitization annealing at 680 °C of Jominy-quenched bars of an Al-Si bearing medium carbon (0.4C wt%) steel has been studied and compared with that in martensite by using light, scanning and transmission electron microscopy. The results show that the graphitization process in bainite is different from that in martensite in many aspects such as the initial carbon state, the behavior of cementite, the nucleation-growth feature and kinetics of formation of graphite spheroids during graphitization annealing, and the shape, size and distribution of these graphite spheroids. The fact that the graphitization in bainite can produce more homogeneous graphite spheroids with more spherical shape and finer size in a shorter annealing time without the help of preexisting coring particles implies that bainite should be a better starting structure than martensite for making graphitic steel. - Highlights: • This article presents a microstructural characterization of formation of graphite spheroids in bainite. • Nucleation and growth characteristics of graphite spheroids formed in bainite and martensite are compared. • Bainite should be a better starting structure for making graphitic steel as results show.

36 MATERIALS SCIENCE↗

Isothermal deformation and spheroidization mechanism of (TiB + La2O3)/Ti composites with different initial structures

Highlights: • Different initial microstructures were obtained through designed heat treatment. • Refined lamellar microstructures promoted dynamic recrystallization. • The spheroidization mechanism was attributed to dynamic recrystallization. • The micron TiB and submicron La{sub 2}O{sub 3} impeded dislocation movement. (TiB + La{sub 2}O{sub 3})/Ti composites with different initial structures were obtained through designed heat treatment. The isothermal deformation and spheroidization mechanisms of (TiB + La{sub 2}O{sub 3})/Ti composites with different initial structures were investigated. Initial structures were refined as the heat treatment temperature decreased. Simultaneously, the quenching and reheating resulted in finer α lamella colonies and α interlamellar spacing compared to the furnace cooling. The flow resistance of furnace cooled samples was lower than the quenched and reheated samples in terms of flow stress data. Following the deformation at 920 °C, the furnace cooled samples demonstrated lamellar α phase and partial spheroidized structure. Moreover, the spheroidization mechanism was similar to the boundary splitting model. Recrystallized grains of approximately 1 μm in diameter were obtained in the quenched and reheated sample following deformation at 920 °C. The spheroidization mechanism was attributed to the development of finer needles through quenching and reheating, as well as to subsequent dynamic recrystallization during the hot deformation. Additionally, the dislocation movement was blocked by the reinforcements on account of the composites with micron TiB and submicron La{sub 2}O{sub 3} during the hot deformation. Furthermore, the reinforcements could facilitate the dynamic recrystallization (DRX) of the α phase.

36 MATERIALS SCIENCE↗

Sedimentation and shear-induced dynamics of spheroids in fluids with spatial viscosity variations

A generalized reciprocal theorem is used to relate the force and torque induced on a particle in an inertia-less fluid with small variation in viscosity to integrals involving Stokes flow fields and the spatial dependence of viscosity. These resistivity expressions are analytically evaluated using spheroidal harmonics and then used to obtain the mobility of the spheroid during sedimentation, and in linear flows, of a fluid with linear viscosity stratification. The coupling between the rotational and translational motion induced by stratification rotates the spheroid’s centerline, creating a variety of rotational and translational dynamics dependent upon the particle’s aspect ratio, κ, and the component of the stratification unit vector in the gravity direction, d g . Spheroids with 0.55 ⪅ κ ⪅ 2.0 exhibit the largest variety of settling behaviors. Interestingly, this range covers most microplastics and typical microorganisms. One of the modes include a stable orientation dependent only on κ and d g , but independent of initial orientation, thus allowing for the potential control of settling angles and sedimentation rates. In a simple shear flow, cross-streamline migration occurs due to the stratification-induced force generated on the particle. Similarly, a particle no longer stays at the stagnation point of a uniaxial extensional flow. While fully analytical results are obtained for spheroids, numerical simulations provide a source of validation. These simulations also provide additional insights into the stratification-induced force- and torque-producing mechanisms through the stratification-induced stress, which is not accessed in the reciprocal theorem-based analytical calculations.

Geophysical and Geological Flows: Stratified flows↗

Evaluation of an in vitro three-dimensional HepaRG spheroid model for genotoxicity testing using the high-throughput CometChip platform

Three-dimensional (3D) culture systems are increasingly being used for genotoxicity studies due to improved cell-to-cell interactions and tissue-like structures that are limited or lacking in 2D cultures. The present study optimized a 3D culture system using metabolically competent HepaRG cells for in vitro genotoxicity testing. 3D HepaRG spheroids, formed in 96- or 384-well ultra-low attachment plates, were exposed to various concentrations of 34 test articles, including 8 direct-acting and 11 indirect-acting genotoxicants/carcinogens as well as 15 compounds that show different genotoxic responses in vitro and in vivo. DNA damage was evaluated using the high-throughput CometChip assay with concurrent cytotoxicity assessment by the ATP assay in both 2D and 3D cultures. 3D HepaRG spheroids maintained a stable phenotype for up to 30 days with higher levels of albumin secretion, cytochrome P450 gene expression, and enzyme activities compared to 2D cultures. 3D spheroids also demonstrated a higher sensitivity than 2D cultures for detecting both direct- and indirect-acting genotoxicants/carcinogens, indicating a better prediction of in vivo genotoxicity responses. When DNA damage dose-response data were quantified using PROAST software, 3D spheroids generally had lower or similar benchmark dose values compared to 2D HepaRG cells and were more comparable with primary human hepatocytes. These results demonstrate that 3D models can be adapted to the CometChip technology for high-throughput genotoxicity testing and that 3D HepaRG spheroids may be used as a reliable and pragmatic in vitro approach to better support the hazard identification and risk assessment of potential human genotoxic carcinogens.

60 APPLIED LIFE SCIENCES↗

Light scattering by randomly oriented spheroidal particles

A study of the light scattering properties of randomly oriented, identical spheroidal particles is presented. A computation method was developed to integrate the Asano and Yamomoto solution (1975) for scattering from a homogeneous spheroid over all particle orientations; the extinction and scattering cross-sections, the asymmetry factor, and scattering matrix elements are calculated for randomly oriented prolate and oblate spheroids and compared with the calculations for spheres and laboratory measurements. The angular scattering behavior of spheroids is found to be different from that of the spheres for side scattering to backscattering directions, and prolate and oblate spheroids of the same shape parameter have similar angular scattering patterns.

Asano, S.↗

Some constraints on the color-magnitude diagram of giants in the galactic spheroid

The color-magnitude diagram of giants in the Galactic spheroid is shown to be important in determining the number-color histogram of stars brighter than B = 19 mag. This result is demonstrated by comparing a standard Galaxy model with observations of 391 stars in a field in the direction of Aquarius (l = 36.5 deg, b = -51.1 deg). More than 80 percent of the spheroid stars and 40 percent of all stars in this magnitude range and direction are predicted to be giants. At most, a few percent of the spheroid stars in the current sample can lie on the main sequence bluer than the turn-off onto the giant branch near B - V approximately 0.4. The available observations suggest that the blue tip of the horizontal branch of the spheroid must be sparsely populated about a factor of 10 less than would be expected if the color-magnitude diagram of the spheroid were the same as diagrams for any of the globular clusters M3, M13, or M92. The total dispersion in colors (measurement errors and intrinsic dispersion) has a standard deviation in B - V color that is less than 0.2 mag.

Bahcall, J. N.↗