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Horacio E. Castillo

Horacio E. Castillo contributes to research discovery and scholarly infrastructure.

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Published work

11 published item(s)

preprint2026arXiv

Approaching human parity in the quality of automated organoid image segmentation

Organoids are complex, three dimensional, self-organizing cell cultures which manifest organ-like features and represent a powerful platform for studying human disease and developing treatment options. Organoid development is characterized by dynamic morphological and cellular organization, which mimic some aspects of organ development. To study these rapid changes over the course of organoid development, advanced imaging and analytical tools are critical to accurately monitor the trajectory of organoid growth and investigate disease processes. In this work, we focus on computer vision and machine learning techniques to automatically measure the size and shape of developing spheroids derived from pluripotent stem cells (iPSCs), which are typically the starting material for generating organoid cultures. To facilitate this task, we introduce a composite method that combines the Segment Anything Model (SAM), a general-purpose foundation model, with an existing domain-specific tool. This composite method is evaluated together with several existing tools by testing them on organoid image data and comparing with the results of manual image segmentation. We find that no single existing tool is able to segment the test images with sufficient accuracy across all test conditions, but the newly introduced composite method produces consistent and accurate results for all but a very small fraction of the most challenging images. Finally, we compare the accuracy of this method to the variability between manual segmentations by independent annotators (inter-observer variability) and find that by one measure it performs at the level of inter-observer variability and by others it performs very close to it.

preprint2021arXiv

Single particle fluctuations dominate the long-time dynamic susceptibility in glass-forming liquids

Liquids near the glass transition exhibit dynamical heterogeneity, i.e. correlated regions in the liquid relax at either a much faster rate or a much slower rate than the average. This collective phenomenon has been characterized by measurements of a dynamic susceptibility $χ_4(t)$, which are sometimes interpreted in terms of the size of those relaxing regions and the intensity of the fluctuations. We show that the results of those measurements can be affected not only by the collective fluctuations in the relaxation rate, but also by density fluctuations in the initial state and by single-particle fluctuations. We also show that at very long times the average overlap $C(t)$ probing the similarity between an initial and a final state separated by a time interval $t$ decays as a power law $C(t) \sim t^{-d/2}$. This is much slower than the stretched exponential behavior $C(t) \sim {\rm e}^{-(t/τ)^β}$ previously observed at times within one or two orders of magnitude of the $α$-relaxation time $τ_α$. We find that for times longer than $10-100 τ_α$, the dynamic susceptibility $χ_4(t)$ is dominated by single particle fluctuations, and that $χ_4(t) \approx C(t) \sim t^{-d/2}$. Finally, we introduce a method to extract the collective relaxation contribution to the dynamic susceptibility $χ_4(t)$ by subtracting the effects of single-particle fluctuations and initial state density fluctuations. We apply this method to numerical simulations of two glass forming models: a binary hard sphere system and a Kob-Andersen Lennard-Jones system. This allows us to extend the analysis of numerical data to timescales much longer than previously possible, and opens the door for further future progress in the study of dynamic heterogeneities, including the determination of the exchange time.

preprint2015arXiv

Cellular reprogramming dynamics follow a simple one-dimensional reaction coordinate

Cellular reprogramming, the conversion of one cell type to another, has fundamentally transformed our conception of cell types. Cellular reprogramming induces global changes in gene expression involving hundreds of transcription factors and thousands of genes and understanding how cells globally alter their gene expression profile during reprogramming is an open problem. Here we reanalyze time-series data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple one-dimensional reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of experimental protocol used. Using Monte-Carlo simulations, we show that such a reaction coordinate emerges naturally from epigenetic landscape models of cell identity where cellular reprogramming is viewed as a "barrier-crossing" between the starting and ending cell fates. The model also provides gene-level insight into reprogramming dynamics and resolves a debate in the stem cell field about the different phases of reprogramming dynamics. Overall, our analysis and model suggest that gene expression dynamics during reprogramming follow a canonical trajectory consistent with the idea of an "optimal path" in gene expression space for reprogramming.

preprint2015arXiv

Fluctuating Phases and Fluctuating Relaxation Times in Glass Forming Liquids

The presence of fluctuating local relaxation times, $τ_r(t)$ has been used for some time as a conceptual tool to describe dynamical heterogeneities in glass-forming systems. However, until now no general method is known to extract the full space and time dependent $τ_r(t)$ from experimental or numerical data. Here we report on a new method for determining the local phase field, $ϕ_r(t) = \int^{t} dt'/τ_r(t')$ from snapshots $\{r(t_i)\}_{i=1...M}$ of the positions of the particles in a system, and we apply it to extract $ϕ_r(t)$ and $τ_r(t)$ from numerical simulations. By studying how the phase field depends on the number of snapshots, we find that it is a well defined quantity. By studying fluctuations of the phase field, we find that they describe heterogeneities well at long distance scales.

preprint2014arXiv

Strong Dynamical Heterogeneity and Universal Scaling in Driven Granular Fluids

Large scale simulations of two-dimensional bidisperse granular fluids allow us to determine spatial correlations of slow particles via the four-point structure factor $S_4(q,t)$. Both cases, elastic ($\varepsilon=1$) as well as inelastic ($\varepsilon < 1$) collisions, are studied. As the fluid approaches structural arrest, i.e. for packing fractions in the range $0.6 \le ϕ\le 0.805$, scaling is shown to hold: $S_4(q,t)/χ_4(t)=s(qξ(t))$. Both the dynamic susceptibility, $χ_4(τ_α)$, as well as the dynamic correlation length, $ξ(τ_α)$, evaluated at the $α$ relaxation time, $τ_α$, can be fitted to a power law divergence at a critical packing fraction. The measured $ξ(τ_α)$ widely exceeds the largest one previously observed for hard sphere 3d fluids. The number of particles in a slow cluster and the correlation length are related by a robust power law, $χ_4(τ_α) \approxξ^{d-p}(τ_α)$, with an exponent $d-p\approx 1.6$. This scaling is remarkably independent of $\varepsilon$, even though the strength of the dynamical heterogeneity increases dramatically as $\varepsilon$ grows.

preprint2013arXiv

Fluctuations in the Time Variable and Dynamical Heterogeneity in Glass-Forming Systems

We test a hypothesis for the origin of dynamical heterogeneity in slowly relaxing systems, namely that it emerges from soft (Goldstone) modes associated with a broken continuous symmetry under time reparametrizations. We do this by constructing coarse grained observables and decomposing the fluctuations of these observables into transverse components, which are associated with the postulated time-fluctuation soft modes, and a longitudinal component, which represents the rest of the fluctuations. Our test is performed on data obtained in simulations of four models of structural glasses. As the hypothesis predicts, we find that the time reparametrization fluctuations become increasingly dominant as temperature is lowered and timescales are increased. More specifically, the ratio between the strengths of the transverse fluctuations and the longitudinal fluctuations grows as a function of the dynamical susceptibility, χ4, which represents the strength of the dynamical heterogeneity; and the correlation volumes for the transverse fluctuations are approximately proportional to those for the dynamical heterogeneity, while the correlation volumes for the longitudinal fluctuations remain small and approximately constant.

preprint2011arXiv

Mapping dynamical heterogeneity in structural glasses to correlated fluctuations of the time variables

Dynamical heterogeneities -- strong fluctuations near the glass transition -- are believed to be crucial to explain much of the glass transition phenomenology. One possible hypothesis for their origin is that they emerge from soft (Goldstone) modes associated with a broken continuous symmetry under time reparametrizations. To test this hypothesis, we use numerical simulation data from four glass-forming models to construct coarse grained observables that probe the dynamical heterogeneity, and decompose the fluctuations of these observables into two transverse components associated with the postulated time-fluctuation soft modes and a longitudinal component unrelated to them. We find that as temperature is lowered and timescales are increased, the time reparametrization fluctuations become increasingly dominant, and that their correlation volumes grow together with the correlation volumes of the dynamical heterogeneities, while the correlation volumes for longitudinal fluctuations remain small.

preprint2011arXiv

Time reparametrization invariance in arbitrary range p-spin models: symmetric versus non-symmetric dynamics

We explore the existence of time reparametrization symmetry in p-spin models. Using the Martin-Siggia-Rose generating functional, we analytically probe the long-time dynamics. We perform a renormalization group analysis where we systematically integrate over short timescale fluctuations. We find three families of stable fixed points and study the symmetry of those fixed points with respect to time reparametrizations. One of those families is composed entirely of symmetric fixed points, which are associated with the low temperature dynamics. The other two families are composed entirely of non-symmetric fixed points. One of these two non-symmetric families corresponds to the high temperature dynamics. Time reparametrization symmetry is a continuous symmetry that is spontaneously broken in the glass state and we argue that this gives rise to the presence of Goldstone modes. We expect the Goldstone modes to determine the properties of fluctuations in the glass state, in particular predicting the presence of dynamical heterogeneity.

preprint2008arXiv

Equilibrium and non-equilibrium fluctuations in a glass-forming liquid

Glass-forming liquids display strong fluctuations -- dynamical heterogeneities -- near their glass transition. By numerically simulating a binary Weeks-Chandler-Andersen liquid and varying both temperature and timescale, we investigate the probability distributions of two kinds of local fluctuations in the non-equilibrium (aging) regime and in the equilibrium regime; and find them to be very similar in the two regimes and across temperatures. We also observe that, when appropriately rescaled, the integrated dynamic susceptibility is very weakly dependent on temperature and very similar in both regimes.

preprint2006arXiv

Local fluctuations in the aging of a simple glass

The presence of dynamical heterogeneities, i.e. nanometer-scale regions containing molecules rearranging cooperatively at very different rates compared to the bulk, is increasingly being recognized as crucial in our understanding of the glass transition, from the non-exponential nature of relaxation, to the divergence of the relaxation times. Recently, dynamical heterogeneities have been directly observed experimentally. However a clear physical picture for the origin of these heterogeneities is still lacking. Here we investigate a possible physical mechanism for the origin of dynamical heterogeneities in the non-equilibrium dynamics of structural glasses. We test the predictions regarding universal scaling of fluctuations derived from this mechanism against simulation results in a simple binary Lennard-Jones glass model, and find that to a first approximation they are satisfied. We also propose to apply the same kind of analysis to experimental data from confocal microscopy in colloidal glasses.

preprint1996arXiv

Randomly Crosslinked Macromolecular Systems: Vulcanisation Transition to and Properties of the Amorphous Solid State

As Charles Goodyear discovered in 1839, when he first vulcanised rubber, a macromolecular liquid is transformed into a solid when a sufficient density of permanent crosslinks is introduced at random. At this continuous equi- librium phase transition, the liquid state, in which all macromolecules are delocalised, is transformed into a solid state, in which a nonzero fraction of macromolecules have spontaneously become localised. This solid state is a most unusual one: localisation occurs about mean positions that are distributed homogeneously and randomly, and to an extent that varies randomly from monomer to monomer. Thus, the solid state emerging at the vulcanisation transition is an equilibrium amorphous solid state: it is properly viewed as a solid state that bears the same relationship to the liquid and crystalline states as the spin glass state of certain magnetic systems bears to the paramagnetic and ferromagnetic states, in the sense that, like the spin glass state, it is diagnosed by a subtle order parameter. In this review we give a detailed exposition of a theoretical approach to the physical properties of systems of randomly, permanently crosslinked macromolecules. Our primary focus is on the equilibrium properties of such systems, especially in the regime of Goodyear&#39;s vulcanisation transition.