Long-range mechanical force in colony branching and tumor invasion

The most concerned factors for cancer prognosis are tumor invasion and metastasis. The patterns of tumor invasion can be characterized as random infiltration to surrounding extracellular matrix (ECM) or formation of long-range path for collective migration. Recent studies indicate that mechanical force plays an important role in tumor infiltration and collective migration. However, how tumor colonies develop mechanical interactions with each other to initiate various invasion patterns is unclear. Using a micro-patterning technique, we partition cells into clusters to mimic tumor colonies and quantitatively induce colony-ECM interactions. We find that pre-malignant epithelial cells, in response to concentrations of type I collagen in ECM ([COL]), develop various branching patterns resembling those observed in tumor invasion. In contrast with conventional thought, these patterns require long-range (~ 600 μm) transmission of traction force, but not biochemical factors. At low [COL], cell colonies synergistically develop pairwise and directed branching mimicking the formation of long-range path. By contrast, at high [COL] or high colony density, cell colonies develop random branching and scattering patterns independent of each other. Our results suggest that tumor colonies might select different invasive patterns depending on their interactions with each other and with the ECM

Long-range mechanical force enables self-assembly of epithelial tubular patterns

Enabling long-range transport of molecules, tubules are critical for human body homeostasis. One fundamental question in tubule formation is how individual cells coordinate their positioning over long spatial scales, which can be as long as the sizes of tubular organs. Recent studies indicate that type I collagen (COL) is important in the development of epithelial tubules. Nevertheless, how cell–COL interactions contribute to the initiation or the maintenance of long-scale tubular patterns is unclear. Using a two-step process to quantitatively control cell–COL interaction, we show that epithelial cells developed various patterns in response to fine-tuned percentages of COL in ECM. In contrast with conventional thoughts, these patterns were initiated and maintained by traction forces created by cells but not diffusive factors secreted by cells. In particular, COL-dependent transmission of force in the ECM led to long-scale (up to 600 μm) interactions between cells. A mechanical feedback effect was encountered when cells used forces to modify cell positioning and COL distribution and orientations. Such feedback led to a bistability in the formation of linear, tubule-like patterns. Using micro-patterning technique, we further show that the stability of tubule-like patterns depended on the lengths of tubules. Our results suggest a mechanical mechanism that cells can use to initiate and maintain long-scale tubular patterns

Is it time to repair a fairly fast SAAB convertible? Testing an evidence-based mnemonic for the secondary prevention of cardiovascular disease

OBJECTIVES: Optimising secondary prevention of cardiovascular disease has the greatest potential to reduce recurrent events, yet despite major guidelines there are ongoing treatment gaps. FFSAABC (Fish oils, Fibrates, Statins, Aspirin, Angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, Beta blockers and Clopidogrel) is one mnemonic previously adopted to assist clinicians in remembering medications for use in secondary prevention. The aim of this narrative review is to examine the current evidence base for medications recommended for patients with established cardiovascular disease and the current applicability of this, or a revised mnemonic for their use. STUDY DESIGN: Randomised controlled trials and systematic reviews were sought examining Fish oils, Fibrates, Statins, Aspirin, Angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, Beta blockers or Clopidogrel vs placebo in secondary prevention. The emerging evidence base for other contemporary therapies including the P2Y12 inhibitors (ticagrelor and prasugrel) and aldosterone antagonists was also reviewed. RESULTS: Definitive evidence supports the use of statins, aspirin, angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, and P2Y12 antagonists (clopidogrel, ticagrelor or prasugrel) for the secondary prevention of cardiovascular disease. Aldosterone antagonists have strong evidence in the presence of systolic heart failure. There is a weaker evidence base for the routine use of omega-3 fatty acid supplementation although this therapy carries minimal harms. Fenofibrate reduces cardiovascular events in dyslipidaemic patients, with additional benefits in patients with diabetes. CONCLUSIONS: Mnemonic upgrading from a Fairly Fast SAAB Convertible to a Fairly Fast SA2A2B (Fish oils, Fibrate, Statin, Antiplatelets (Aspirin+Other), ACE/ARB, Aldosterone Antagonist, Beta-blocker) may help to ensure patients receive best practice evidence-based pharmacotherapies for the secondary prevention of cardiovascular disease

Characterization of Probability Distributions via Functional Equations of Power-Mixture Type

We study power-mixture type functional equations in terms of Laplace-Stieltjes transforms of probability distributions. These equations arise when studying distributional equations of the type Z = X + TZ, where T is a known random variable, while the variable Z is defined via X, and we want to `find' X. We provide necessary and sufficient conditions for such functional equations to have unique solutions. The uniqueness is equivalent to a characterization property of a probability distribution. We present results which are either new or extend and improve previous results about functional equations of compound-exponential and compound-Poisson types. In particular, we give another affirmative answer to a question posed by J. Pitman and M. Yor in 2003. We provide explicit illustrative examples and deal with related topics.Comment: 28 page

The ACS Virgo Cluster Survey XV. The Formation Efficiencies of Globular Clusters in Early-Type Galaxies: The Effects of Mass and Environment

The fraction of stellar mass contained in globular clusters (GCs), also measured by number as the specific frequency, is a fundamental quantity that reflects both a galaxy's early star formation and its entire merging history. We present specific frequencies, luminosities, and mass fractions for the globular cluster systems of 100 early-type galaxies in the ACS Virgo Cluster Survey, the largest homogeneous catalog of its kind. We find that 1) GC mass fractions can be high in both giants and dwarfs, but are universally low in galaxies with intermediate luminosities. 2) The behavior of specific frequency across galaxy mass is dominated by the blue GCs. 3) The GC fractions of low-mass galaxies exhibit a dependence on environment. Nearly all dwarf galaxies with high GC fractions are within 1 Mpc of the cD galaxy M87, presenting the first strong evidence that GC formation in dwarfs is biased toward dense environments. 4) GC formation in central dwarfs is biased because their stars form earliest and most intensely. Comparisons to the Millennium Simulation show that central dwarfs have older stellar populations and form more stars at higher star formation rates (SFRs) and SFR surface densities. The SFR surface density in simulated dwarfs peaks before the total SFR, naturally producing GC populations that are older and more metal-poor than the field stars. 5) Dwarfs within ~40 kpc of the giant ellipticals M87 and M49 are red and have few or no GCs, suggesting that they have been tidally stripped and have contributed their GCs to the halos of their giant neighbors. The central dwarfs with high GC mass fractions are thus likely to be the survivors most similar to the protogalaxies that assembled the rich M87 globular cluster system.(Abridged)Comment: 27 pages, 21 figures, 7 tables. Accepted for publication in the Astrophysical Journa

The ACS Fornax Cluster Survey. II. The Central Brightness Profiles of Early-Type Galaxies: A Characteristic Radius on Nuclear Scales and the Transition from Central Luminosity Deficit to Excess

We analyse HST surface brightness profiles for 143 early-type galaxies in the Virgo and Fornax Clusters. Sersic models provide accurate descriptions of the global profiles with a notable exception: the observed profiles deviate systematically inside a characteristic "break" radius of R_b ~ 0.02R_e where R_e is the effective radius of the galaxy. The sense of the deviation is such that bright galaxies (M_B < -20) typically show central light deficits with respect to the inward extrapolation of the Sersic model, while the great majority of low- and intermediate-luminosity galaxies (-19.5 < M_B < -15) show central light excesses; galaxies occupying a narrow range of intermediate luminosities (-20 < M_B < -19.5) are usually well fitted by Sersic models over all radii. The slopes of the central surface brightness profiles, when measured at fixed fractions of R_e, vary smoothly as a function of galaxy luminosity in a manner that depends sensitively on the choice of measurement radius. We show that a recent claim of strong bimodality in slope is likely an artifact of the galaxy selection function used in that study. To provide a more robust characterization of the inner regions of galaxies, we introduce a parameter that describes the central luminosity deficit or excess relative to the inward extrapolation of the outer Sersic model. We find that this parameter varies smoothly over the range of ~ 720 in blue luminosity spanned by the Virgo and Fornax sample galaxies, with no evidence for a dichotomy. We argue that the central light excesses (nuclei) in M_B > -19 galaxies may be the analogs of the dense central cores that are predicted by some numerical simulations to form via gas inflows. (ABRIDGED)Comment: To appear in the Astrophysical Journal, December 2007. Full resolution paper available at http://www.cfa.harvard.edu/~ajordan/ACSFCS/Home.htm

Characterization of Probability Distributions via Functional Equations of Power-Mixture Type

We study power-mixture type functional equations in terms of Laplace–Stieltjes transforms of probability distributions on the right half-line [0,∞). These equations arise when studying distributional equations of the type Z=dX+TZ, where the random variable T≥0 has known distribution, while the distribution of the random variable Z≥0 is a transformation of that of X≥0, and we want to find the distribution of X. We provide necessary and sufficient conditions for such functional equations to have unique solutions. The uniqueness is equivalent to a characterization property of a probability distribution. We present results that are either new or extend and improve previous results about functional equations of compound-exponential and compound-Poisson types. In particular, we give another affirmative answer to a question posed by J. Pitman and M. Yor in 2003. We provide explicit illustrative examples and deal with related topics