Characterization of Metastatic Tumor Formation by the Colony Size Distribution

Knowledge regarding the kinetics of metastatic tumor formation, as related to the growth of the primary tumor, represents a fundamental issue in cancer biology. Using an in vivo mammalian model, we show here that one can obtain useful information from the frequency distribution of the sizes of metastatic colonies in distant organs after serial sectioning and image reconstruction. To explain the experimental findings, we constructed a biophysical model based on the respective growth patterns of the primary tumor and metastases and a stochastic process of metastatic colony formation. Heterogeneous distributions of various biological parameters were considered. We found that the elementary assumption of exponential forms of growth for the primary tumor and metastatic colonies predicts a linear relation on a log-log plot of a metastatic colony size distribution, which was consistent with the experimental results. Furthermore, the slope of the curve signifies the ratio of growth rates of the primary and the metastases. Non-exponential (Gompertzian and logistic) tumor growth patterns were also incorporated into the theory to explain possible deviation from the log-log linear relation. The observed metastasis-free probability also supported the assumption of a time-dependent Poisson process. With this approach, we determined the mechanistic parameters governing the process of metastatogenesis in the lungs for two murine tumor cell lines (KHT and MCaK). Since biological parameters specified in the model could be obtained in the laboratory, a workable metastatic "assay" may be established for various malignancies and in turn contribute in formulating rational treatment regimens for subclinical metastases.Comment: 14 pages, 6 figure

The first non-mammalian CXCR5 in a teleost fish: molecular cloning and expression analysis in grass carp (Ctenopharyngodon idella)

<p>Abstract</p> <p>Background</p> <p>Chemokines, a group of small and structurally related proteins, mediate chemotaxis of various cell types via chemokine receptors. In mammals, seven different CXC chemokine receptors denoted as CXCR1 to CXCR7 have been reported. However, the chemokine receptor CXCR5 has not been reported in other vertebrates.</p> <p>Results</p> <p>In the present study, the genomic sequence of CXCR5 was isolated from the grass carp <it>Ctenopharyngodon idella</it>. The cDNA sequence of grass carp CXCR5 (gcCXCR5) consists of 1518 bp with a 43 bp 5' untranslated region (UTR) and a 332 bp 3' UTR, with an open reading frame of 1143 bp encoding 381 amino acids which are predicted to have seven transmembrane helices. The characteristic residues (DRYLAIVHA) and conserved cysteine residues are located in the extracellular regions and in the third to seventh transmembrane domains. The deduced amino acid sequence shows 37.6-66.6% identities with CXCR5 of mammals, avian and other fish species. The grass carp gene consists of two exons, with one intervening intron, spaced over 2081 bp of genomic sequence. Phylogenetic analysis clearly demonstrated that the gcCXCR5 is clustered with those in other teleost fish and then in chicken and mammals. Real-time PCR analysis showed that gcCXCR5 was expressed in all tested organs/tissues and its expression level was the highest in trunk kidney, followed by in the spleen. The expression of gcCXCR5 was significantly modulated by immunostimulants such as peptidoglycan (PGN), lipopolysaccharide (LPS), polyinosinic-polycytidylic acid sodium salt (Poly I:C) and phytohaemagglutinin (PHA).</p> <p>Conclusion</p> <p>The cDNA and genomic sequences of CXCR5 have been successfully characterized in a teleost fish, the grass carp. The CXCR5 has in general a constitutive expression in organs/tissues examined, whereas its expression was significantly up-regulated in immune organs and down-regulated in brain, indicating its potential role in immune response and central nervous system.</p

A Universe of ultradiffuse galaxies: theoretical predictions from ΛCDM simulations

A particular population of galaxies have drawn much interest recently, which are as faint as typical dwarf galaxies but have the sizes as large as L* galaxies, the so called ultradiffuse galaxies (UDGs). The lack of tidal features of UDGs in dense environments suggests that their host haloes are perhaps as massive as that of the Milky Way. On the other hand, galaxy formation efficiency should be much higher in the haloes of such masses. Here, we use the model galaxy catalogue generated by populating two large simulations: the Millennium-II cosmological simulation and Phoenix simulations of nine big clusters with the semi-analytic galaxy formation model. This model reproduces remarkably well the observed properties of UDGs in the nearby clusters, including the abundance, profile, colour and morphology, etc. We search for UDG candidates using the public data and find two UDG candidates in our Local Group and 23 in our Local Volume, in excellent agreement with the model predictions. We demonstrate that UDGs are genuine dwarf galaxies, formed in the haloes of ∼1010 M⊙. It is the combination of the late formation time and high spins of the host haloes that results in the spatially extended feature of this particular population. The lack of tidal disruption features of UDGs in clusters can also be explained by their late infall-time

Prognostic factors in patients with complete response of the tumour (ypT0) after neoadjuvant chemoradiotherapy and radical resection of rectal cancer

Background There are only a few studies on the prognosis of patients with complete response of the tumour (ypT0) after neoadjuvant chemoradiotherapy (NCRT) and radical resection of rectal cancer. The aim of the study was to identify prognostic factors with regard to oncological outcome in ypT0 patients after NCRT and radical resection. Methods All ypT0 patients with rectal cancer after NCRT and radical resection between January 2010 and June 2019 were included. Cox univariate and multivariate regression analyses were used to determine the prognostic factors of these patients. Results Seventy-six patients with ypT0 rectal cancer were included. In nine patients (11.8%), lymph node metastasis was identified. Age, gender, elevated carcinoembryonic antigen (CEA) and ypN+ were risk factors associated with a worse 5-year disease-free survival (DFS) rate in univariate analysis (P = 0.08, 0.14, 0.007 and 0.003, respectively). In multivariate analysis, ypN+ and elevated CEA before NCRT were independent risk factors for worse 5-year DFS (P = 0.005 and 0.021, respectively). Elevated CEA before NCRT, post-operative chemotherapy and ypN+ were risk factors associated with worse overall survival in univariate analysis (P = 0.14, 0.002 and 0.17, respectively). However, in multivariate analysis, none of these three factors were independent risk factors for worse overall survival (P = 0.20, 0.34 and 0.06, respectively). Conclusion ypN+ and elevated CEA before NCRT were found to be independent risk factors for an unfavourable DFS in ypT0 patients with complete response of the tumour after neoadjuvant chemoradiotherapy for rectal cancer

Plug-and-Play Latent Feature Editing for Orientation-Adaptive Quantitative Susceptibility Mapping Neural Networks

Quantitative susceptibility mapping (QSM) is a post-processing technique for deriving tissue magnetic susceptibility distribution from MRI phase measurements. Deep learning (DL) algorithms hold great potential for solving the ill-posed QSM reconstruction problem. However, a significant challenge facing current DL-QSM approaches is their limited adaptability to magnetic dipole field orientation variations during training and testing. In this work, we propose a novel Orientation-Adaptive Latent Feature Editing (OA-LFE) module to learn the encoding of acquisition orientation vectors and seamlessly integrate them into the latent features of deep networks. Importantly, it can be directly Plug-and-Play (PnP) into various existing DL-QSM architectures, enabling reconstructions of QSM from arbitrary magnetic dipole orientations. Its effectiveness is demonstrated by combining the OA-LFE module into our previously proposed phase-to-susceptibility single-step instant QSM (iQSM) network, which was initially tailored for pure-axial acquisitions. The proposed OA-LFE-empowered iQSM, which we refer to as iQSM+, is trained in a self-supervised manner on a specially-designed simulation brain dataset. Comprehensive experiments are conducted on simulated and in vivo human brain datasets, encompassing subjects ranging from healthy individuals to those with pathological conditions. These experiments involve various MRI platforms (3T and 7T) and aim to compare our proposed iQSM+ against several established QSM reconstruction frameworks, including the original iQSM. The iQSM+ yields QSM images with significantly improved accuracies and mitigates artifacts, surpassing other state-of-the-art DL-QSM algorithms.Comment: 13pages, 9figure

The role of 245 phase in alkaline iron selenide superconductors revealed by high pressure studies

Here we show that a pressure of about 8 GPa suppresses both the vacancy order and the insulating phase, and a further increase of the pressure to about 18 GPa induces a second transition or crossover. No superconductivity has been found in compressed insulating 245 phase. The metallic phase in the intermediate pressure range has a distinct behavior in the transport property, which is also observed in the superconducting sample. We interpret this intermediate metal as an orbital selective Mott phase (OSMP). Our results suggest that the OSMP provides the physical pathway connecting the insulating and superconducting phases of these iron selenide materials.Comment: 32 pages, 4 figure

Persistence, extinction and spatio-temporal synchronization of SIRS cellular automata models

Spatially explicit models have been widely used in today's mathematical ecology and epidemiology to study persistence and extinction of populations as well as their spatial patterns. Here we extend the earlier work--static dispersal between neighbouring individuals to mobility of individuals as well as multi-patches environment. As is commonly found, the basic reproductive ratio is maximized for the evolutionary stable strategy (ESS) on diseases' persistence in mean-field theory. This has important implications, as it implies that for a wide range of parameters that infection rate will tend maximum. This is opposite with present results obtained in spatial explicit models that infection rate is limited by upper bound. We observe the emergence of trade-offs of extinction and persistence on the parameters of the infection period and infection rate and show the extinction time having a linear relationship with respect to system size. We further find that the higher mobility can pronouncedly promote the persistence of spread of epidemics, i.e., the phase transition occurs from extinction domain to persistence domain, and the spirals' wavelength increases as the mobility increasing and ultimately, it will saturate at a certain value. Furthermore, for multi-patches case, we find that the lower coupling strength leads to anti-phase oscillation of infected fraction, while higher coupling strength corresponds to in-phase oscillation.Comment: 12page

The Magnetic Field Structure of Mercury’s Magnetotail

In this study, we use the magnetic field data measured by MErcury Surface, Space ENvironment, GEochemistry, and Ranging from 2011 to 2015 to investigate the average magnetic field morphology of Mercury’s magnetotail in the down tail 0–3 RM (RM = 2,440 km, Mercury’s radius). It is found that Mercury has a terrestrial‐like magnetotail; the magnetic field structure beyond 1.5 RM down tail is stretched significantly with typical lobe field 50 nT. A cross‐tail current sheet separating the antiparallel field lines of lobes is present in the equatorial plane. The magnetotail width in north‐south direction is about 5 RM, while the transverse width is about 4 RM. Thus, the magnetotail shows elongation along the north‐south direction. At the cross‐tail current sheet center, the normal component of magnetic field (10–20 nT) is much larger than the cross‐tail component. The lobe‐field‐aligned component of magnetic field over current sheet can be well fitted by Harris sheet model. The curvature radius of field lines at sheet center usually reaches a minimum around midnight (100–200 km) with stronger current density (40–50 nA/m2), while the curvature radius increases toward both flanks (400–600 km) with the decreased current density (about 20 nA/m2). The half‐thickness of current sheet around midnight is about 0.25 RM or 600 km, and the inner edge of current sheet is located at the down tail about 1.5 RM. Our results about the field structure in the near Mercury’s tail show an evident dawn‐dusk asymmetry as that found in the Earth’s magnetotail, but reasons should be different. Possible reasons are discussed.Key PointsThe magnetic field distribution, configuration, and current density in Mercury’s magnetotail are quantitatively addressedMercury’s magnetotail is elongated along the south‐north direction, which is probably due to the effect of the dipole offset or the induction effect of coreThe magnetic structure of tail current sheet shows a clear dawn‐dusk asymmetry with smaller Bz and less flaring field on the dusksidePeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142544/1/jgra54041.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142544/2/jgra54041_am.pd