Hastings-Levitov aggregation in the small-particle limit

We establish some scaling limits for a model of planar aggregation. The model is described by the composition of a sequence of independent and identically distributed random conformal maps, each corresponding to the addition of one particle. We study the limit of small particle size and rapid aggregation. The process of growing clusters converges, in the sense of Caratheodory, to an inflating disc. A more refined analysis reveals, within the cluster, a tree structure of branching fingers, whose radial component increases deterministically with time. The arguments of any finite sample of fingers, tracked inwards, perform coalescing Brownian motions. The arguments of any finite sample of gaps between the fingers, tracked outwards, also perform coalescing Brownian motions. These properties are closely related to the evolution of harmonic measure on the boundary of the cluster, which is shown to converge to the Brownian web

Halo Star Streams in the Solar Neighborhood

We have assembled a sample of halo stars in the solar neighborhood to look for halo substructure in velocity and angular momentum space. Our sample includes red giants, RR Lyrae, and red horizontal branch stars within 2.5 kpc of the Sun with [Fe/H] less than -1.0. It was chosen to include stars with accurate distances, space velocities, and metallicities as well as well-quantified errors. We confirm the existence of the streams found by Helmi and coworkers, which we refer to as the H99 streams. These streams have a double-peaked velocity distribution in the z direction. We use the results of modeling of the H99 streams by Helmi and collaborators to test how one might use v_z velocity information and radial velocity information to detect kinematic substructure in the halo. We find that detecting the H99 streams with radial velocities alone would require a large sample. We use the velocity distribution of the H99 streams to estimate their age. From our model of the progenitor of the H99 streams, we determine that it was accreted between 6 and 9 Gyr ago. The H99 streams have [alpha/Fe] abundances similar to other halo stars in the solar neighborhood, suggesting that the gas that formed these stars were enriched mostly by Type II SNe. We have also discovered in angular momentum space two other possible substructures, which we refer to as the retrograde and prograde outliers. The retrograde outliers are likely to be halo substructure, but the prograde outliers are most likely part of the smooth halo. The retrograde outliers have significant structure in the v_phi direction and show a range of [alpha/Fe]. The methods presented in this paper can be used to exploit the kinematic information present in future large databases like RAVE, SDSSII/SEGUE, and Gaia.Comment: 46 pages, 13 figures, and 9 tables. Minor changes to text to match proofed version of the paper. Low resolution figures. High resolution version at http://www.astro.wisc.edu/~kepley/solar_streams.p

Fashionably Late? Building up the Milky Way's Inner Halo

Using a sample of 248 metal-poor stars (RR Lyraes, red giants and RHB stars) which is remarkable for the accuracy of its 6-D kinematical data, we find a new component for the local halo which has an axial ratio c/a ~ 0.2, a similar flattening to the thick disk. It has a small prograde rotation but is supported by velocity anisotropy, and contains more intermediate-metallicity stars (with -1.5 < [Fe/H] < -1.0) than the rest of our sample. We suggest that this component was formed quite late, during or after the formation of the disk. It formed either from the gas that was accreted by the last major mergers experienced by the Galaxy, or by dynamical friction of massive infalling satellite(s) with the halo and possibly the stellar disk or thick disk. The remainder of the stars in our sample exhibit a clumpy distribution in energy and angular momentum, suggesting that the early, chaotic conditions under which the inner halo formed were not violent enough to erase the record of their origins. The clumpy structure suggests that a relatively small number of progenitors were responsible for building up the inner halo, in line with theoretical expectations. We find a difference in mean binding energy between the RR Lyrae variables and the red giants in our sample, suggesting that more of the RR Lyraes in the sample belong to the outer halo, and that the outer halo may be somewhat younger, as first suggested by Searle and Zinn (1978). We also find that the RR Lyrae mean rotation is more negative than the red giants, which is consistent with the recent result of Carollo et al.(2007) that the outer halo has a retrograde rotation and with the difference in kinematics seen between RR Lyraes and BHB stars by Kinman et al.(2007).Comment: 16 pages, 10 figures, this version accepted by Ap

The RESOLVE and ECO Gas in Galaxy Groups Initiative: The Group Finder and the Group HI–Halo Mass Relation

We present a four-step group-finding algorithm for the Gas in Galaxy Groups (G3) initiative, a spin-off of the z ∼ 0 REsolved Spectroscopy Of a Local VolumE (RESOLVE) and Environmental COntext (ECO) surveys. In preparation for future comparisons to intermediate redshift (e.g., the LADUMA survey), we design the group finder to adapt to incomplete, shallow, or nonuniform data. We use mock catalogs to optimize the group finder’s performance. Compared to friends-of-friends (with false-pair splitting), the G3 algorithm offers improved completeness and halo-mass recovery with minimal loss of purity. Combining it with the volume-limited H I census data for RESOLVE and ECO, we examine the H I content of galaxy groups as a function of group halo mass. Group-integrated H I mass M rises monotonically over halo masses M ∼ 10–10 M, pivoting in slope at M ∼ 10M, the gas-richness threshold scale. We present the first measurement of the scatter in this relation, which has a median of ∼0.3 dex and is asymmetric toward lower M I,grp. We discuss interesting tensions with theoretical predictions and prior measurements of the M–M relation. In an appendix, we release RESOLVE DR4 and ECO DR3, including updates to survey redshifts, photometry, and group catalogs, as well as a major expansion of the ECO H I inventory with value-added data products. © 2023. The Author(s). Published by the American Astronomical SocietyWe are grateful to the anonymous referee, whose feedback has improved the quality of this work. We also thank Adrienne Erickcek, Andrew Mann, Mugdha Polimera, Matthew Bershady, Joshua Oppor, Jeremy Darling, Hayley Roberts, and Amir Kazemi-Moridani for valuable feedback at varying stages of the project. Z.L.H., S.J.K., and E.R.C. acknowledge support for this research from National Science Foundation (NSF) grant AST-1814486. Z.L.H. and D.S.C. are also supported through a North Carolina Space Grant Graduate Research Fellowship. S.J.K. and D.S.C. acknowledge support from NSF grant AST-2007351. A.J.B. acknowledges support from NSF grant AST-1814421. K.M.H. acknowledges financial support from the State Agency for Research of the Spanish Ministry of Science, Innovation and Universities through the "Center of Excellence Severo Ocho" awarded to the Instituto de Astrofisica de Andalucia (SEV-2017-0709), via participation in SKA-SPAIN, funded by the Ministry of Science and Innovation (MCIN), and financial support from grant RTI2018-096228-B-C31 (MCIU/AEI/FEDER,UE)

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

&lt;b&gt;Objective&lt;/b&gt; &lt;i&gt;ABCB1&lt;/i&gt; encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; The best candidates from fine-mapping analysis of 21 &lt;i&gt;ABCB1&lt;/i&gt; SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt; Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, &lt;i&gt;ABCB1&lt;/i&gt; expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; Our study represents the largest analysis of &lt;i&gt;ABCB1&lt;/i&gt; SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.&lt;p&gt;&lt;/p&gt

Linking compact dwarf starburst galaxies in the resolve survey to downsized blue nuggets

Abstract We identify and characterize compact dwarf starburst (CDS) galaxies in the RESOLVE survey, a volume-limited census of galaxies in the local universe, to probe whether this population contains any residual “blue nuggets,” a class of intensely star-forming compact galaxies first identified at high redshift z. Our 50 low-z CDS galaxies are defined by dwarf masses (stellar mass M* &amp;lt; 109.5 M⊙), compact bulged-disk or spheroid-dominated morphologies (using a quantitative criterion, \mu _\Delta &gt; 8.6), and specific star formation rates above the defining threshold for high-z blue nuggets (log SSFR [Gyr−1] &amp;gt; −0.5). Across redshifts, blue nuggets exhibit three defining properties: compactness relative to contemporaneous galaxies, abundant cold gas, and formation via compaction in mergers or colliding streams. Those with halo mass below Mhalo ∼ 1011.5 M⊙ may in theory evade permanent quenching and cyclically refuel until the present day. Selected only for compactness and starburst activity, our CDS galaxies generally have Mhalo ≲ 1011.5 M⊙ and gas-to-stellar mass ratio ≳1. Moreover, analysis of archival DECaLS photometry and new 3D spectroscopic observations for CDS galaxies reveals a high rate of photometric and kinematic disturbances suggestive of dwarf mergers. The SSFRs, surface mass densities, and number counts of CDS galaxies are compatible with theoretical and observational expectations for redshift evolution in blue nuggets. We argue that CDS galaxies represent a maximally-starbursting subset of traditional compact dwarf classes such as blue compact dwarfs and blue E/S0s. We conclude that CDS galaxies represent a low-z tail of the blue nugget phenomenon formed via a moderated compaction channel that leaves open the possibility of disk regrowth and evolution into normal disk galaxies

ABCC Multidrug Transporters in Childhood Neuroblastoma: Clinical and Biological Effects Independent of Cytotoxic Drug Efflux

Background Although the prognostic value of the ATP-binding cassette, subfamily C (ABCC) transporters in childhood neuroblastoma is usually attributed to their role in cytotoxic drug efflux, certain observations have suggested that these multidrug transporters might contribute to the malignant phenotype independent of cytotoxic drug efflux. Methods A v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN)-driven transgenic mouse neuroblastoma model was crossed with an Abcc1-deficient mouse strain (658 hMYCN1/−, 205 hMYCN+/1 mice) or, alternatively, treated with the ABCC1 inhibitor, Reversan (n = 20). ABCC genes were suppressed using short interfering RNA or overexpressed by stable transfection in neuroblastoma cell lines BE(2)-C, SH-EP, and SH-SY5Y, which were then assessed for wound closure ability, clonogenic capacity, morphological differentiation, and cell growth. Real-time quantitative polymerase chain reaction was used to examine the clinical significance of ABCC family gene expression in a large prospectively accrued cohort of patients (n = 209) with primary neuroblastomas. Kaplan-Meier survival analysis and Cox regression were used to test for associations with event-free and overall survival. Except where noted, all statistical tests were two-sided. Results Inhibition of ABCC1 statistically significantly inhibited neuroblastoma development in hMYCN transgenic mice (mean age for palpable tumor: treated mice, 47.2 days; control mice, 41.9 days; hazard ratio [HR] = 9.3, 95% confidence interval [CI] = 2.65 to 32; P < .001). Suppression of ABCC1 in vitro inhibited wound closure (P < .001) and clonogenicity (P = .006); suppression of ABCC4 enhanced morphological differentiation (P < .001) and inhibited cell growth (P < .001). Analysis of 209 neuroblastoma patient tumors revealed that, in contrast with ABCC1 and ABCC4, low rather than high ABCC3 expression was associated with reduced event-free survival (HR of recurrence or death = 2.4, 95% CI = 1.4 to 4.2; P = .001), with 23 of 53 patients with low ABCC3 expression experiencing recurrence or death compared with 31 of 155 patients with high ABCC3. Moreover, overexpression of ABCC3 in vitro inhibited neuroblastoma cell migration (P < .001) and clonogenicity (P = .03). The combined expression of ABCC1, ABCC3, and ABCC4 was associated with patients having an adverse event, such that of the 12 patients with the "poor prognosis” expression pattern, 10 experienced recurrence or death (HR of recurrence or death = 12.3, 95% CI = 6 to 27; P < .001). Conclusion ABCC transporters can affect neuroblastoma biology independently of their role in chemotherapeutic drug efflux, enhancing their potential as targets for therapeutic interventio

The RESOLVE and ECO Gas in Galaxy Groups Initiative: The Group Finder and the Group H i –Halo Mass Relation

We present a four-step group-finding algorithm for the Gas in Galaxy Groups (G3) initiative, a spin-off of the z ∼ 0 REsolved Spectroscopy Of a Local VolumE (RESOLVE) and Environmental COntext (ECO) surveys. In preparation for future comparisons to intermediate redshift (e.g., the LADUMA survey), we design the group finder to adapt to incomplete, shallow, or nonuniform data. We use mock catalogs to optimize the group finder’s performance. Compared to friends-of-friends (with false-pair splitting), the G3 algorithm offers improved completeness and halo-mass recovery with minimal loss of purity. Combining it with the volume-limited H i census data for RESOLVE and ECO, we examine the H i content of galaxy groups as a function of group halo mass. Group-integrated H i mass M H I,grp rises monotonically over halo masses M halo ∼ 1011–1014.5 M ⊙, pivoting in slope at M halo ∼ 1011.4 M ⊙, the gas-richness threshold scale. We present the first measurement of the scatter in this relation, which has a median of ∼0.3 dex and is asymmetric toward lower M H I,grp. We discuss interesting tensions with theoretical predictions and prior measurements of the M H I,grp–M halo relation. In an appendix, we release RESOLVE DR4 and ECO DR3, including updates to survey redshifts, photometry, and group catalogs, as well as a major expansion of the ECO H i inventory with value-added data products

Integrating data types to estimate spatial patterns of avian migration across the Western Hemisphere

For many avian species, spatial migration patterns remain largely undescribed, especially across hemispheric extents. Recent advancements in tracking technologies and high-resolution species distribution models (i.e., eBird Status and Trends products) provide new insights into migratory bird movements and offer a promising opportunity for integrating independent data sources to describe avian migration. Here, we present a three-stage modeling framework for estimating spatial patterns of avian migration. First, we integrate tracking and band re-encounter data to quantify migratory connectivity, defined as the relative proportions of individuals migrating between breeding and nonbreeding regions. Next, we use estimated connectivity proportions along with eBird occurrence probabilities to produce probabilistic least-cost path (LCP) indices. In a final step, we use generalized additive mixed models (GAMMs) both to evaluate the ability of LCP indices to accurately predict (i.e., as a covariate) observed locations derived from tracking and band re-encounter data sets versus pseudo-absence locations during migratory periods and to create a fully integrated (i.e., eBird occurrence, LCP, and tracking/band re-encounter data) spatial prediction index for mapping species-specific seasonal migrations. To illustrate this approach, we apply this framework to describe seasonal migrations of 12 bird species across the Western Hemisphere during pre- and postbreeding migratory periods (i.e., spring and fall, respectively). We found that including LCP indices with eBird occurrence in GAMMs generally improved the ability to accurately predict observed migratory locations compared to models with eBird occurrence alone. Using three performance metrics, the eBird + LCP model demonstrated equivalent or superior fit relative to the eBird-only model for 22 of 24 species–season GAMMs. In particular, the integrated index filled in spatial gaps for species with over-water movements and those that migrated over land where there were few eBird sightings and, thus, low predictive ability of eBird occurrence probabilities (e.g., Amazonian rainforest in South America). This methodology of combining individual-based seasonal movement data with temporally dynamic species distribution models provides a comprehensive approach to integrating multiple data types to describe broad-scale spatial patterns of animal movement. Further development and customization of this approach will continue to advance knowledge about the full annual cycle and conservation of migratory birds

A G316A polymorphism in the ornithine decarboxylase gene promoter modulates MYCN-driven childhood neuroblastoma

Simple Summary Neuroblastoma is a devasting childhood cancer in which multiple copies (amplification) of the cancer-causing gene MYCN strongly predict poor outcome. Neuroblastomas are reliant on high levels of cellular components called polyamines for their growth and malignant behavior, and the gene regulating polyamine synthesis is called ODC1. ODC1 is often coamplified with MYCN, and in fact is regulated by MYCN, and like MYCN is prognostic of poor outcome. Here we studied a naturally occurring genetic variant or polymorphism that occurs in the ODC1 gene, and used gene editing to demonstrate the functional importance of this variant in terms of ODC1 levels and growth of neuroblastoma cells. We showed that this variant impacts the ability of MYCN to regulate ODC1, and that it also influences outcome in neuroblastoma, with the rarer variant associated with a better survival. This study addresses the important topic of genetic polymorphisms in cancer. Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein