Particle Computation: Complexity, Algorithms, and Logic

We investigate algorithmic control of a large swarm of mobile particles (such as robots, sensors, or building material) that move in a 2D workspace using a global input signal (such as gravity or a magnetic field). We show that a maze of obstacles to the environment can be used to create complex systems. We provide a wide range of results for a wide range of questions. These can be subdivided into external algorithmic problems, in which particle configurations serve as input for computations that are performed elsewhere, and internal logic problems, in which the particle configurations themselves are used for carrying out computations. For external algorithms, we give both negative and positive results. If we are given a set of stationary obstacles, we prove that it is NP-hard to decide whether a given initial configuration of unit-sized particles can be transformed into a desired target configuration. Moreover, we show that finding a control sequence of minimum length is PSPACE-complete. We also work on the inverse problem, providing constructive algorithms to design workspaces that efficiently implement arbitrary permutations between different configurations. For internal logic, we investigate how arbitrary computations can be implemented. We demonstrate how to encode dual-rail logic to build a universal logic gate that concurrently evaluates and, nand, nor, and or operations. Using many of these gates and appropriate interconnects, we can evaluate any logical expression. However, we establish that simulating the full range of complex interactions present in arbitrary digital circuits encounters a fundamental difficulty: a fan-out gate cannot be generated. We resolve this missing component with the help of 2x1 particles, which can create fan-out gates that produce multiple copies of the inputs. Using these gates we provide rules for replicating arbitrary digital circuits.Comment: 27 pages, 19 figures, full version that combines three previous conference article

Tilt: The Video - Designing Worlds to Control Robot Swarms with Only Global Signals

We present fundamental progress on the computational universality of swarms of micro- or nano-scale robots in complex environments, controlled not by individual navigation, but by a uniform global, external force. More specifically, we consider a 2D grid world, in which all obstacles and robots are unit squares, and for each actuation, robots move maximally until they collide with an obstacle or another robot. The objective is to control robot motion within obstacles, design obstacles in order to achieve desired permutation of robots, and establish controlled interaction that is complex enough to allow arbitrary computations. In this video, we illustrate progress on all these challenges: we demonstrate NP-hardness of parallel navigation, we describe how to construct obstacles that allow arbitrary permutations, and we establish the necessary logic gates for performing arbitrary in-system computations

Scaling laws governing stochastic growth and division of single bacterial cells

Uncovering the quantitative laws that govern the growth and division of single cells remains a major challenge. Using a unique combination of technologies that yields unprecedented statistical precision, we find that the sizes of individual Caulobacter crescentus cells increase exponentially in time. We also establish that they divide upon reaching a critical multiple ($\approx$1.8) of their initial sizes, rather than an absolute size. We show that when the temperature is varied, the growth and division timescales scale proportionally with each other over the physiological temperature range. Strikingly, the cell-size and division-time distributions can both be rescaled by their mean values such that the condition-specific distributions collapse to universal curves. We account for these observations with a minimal stochastic model that is based on an autocatalytic cycle. It predicts the scalings, as well as specific functional forms for the universal curves. Our experimental and theoretical analysis reveals a simple physical principle governing these complex biological processes: a single temperature-dependent scale of cellular time governs the stochastic dynamics of growth and division in balanced growth conditions.Comment: Text+Supplementar

Evolution of coordinated mutagenesis and somatic hypermutation in VH5

The VH5 human antibody gene was analyzed using a computer program (mfg) which simulates transcription, to better understand transcription-driven mutagenesis events that occur during phase 1 of somatic hypermutation. Results show that the great majority of mutations in the non-transcribed strand occur within loops of two predicted high-stability stem-loop structures, termed SLSs 14.9 and 13.9. In fact, 89% of the 2505 mutations reported are within the encoded complementarity-determining region (CDR) and occur in loops of these high-stability structures. In vitro studies were also done and verified the existence of SLS 14.9. Following the formation of SLSs 14.9 and 13.9, a sustained period of transcriptional activity occurs within a window size of 60-70 nucleotides. During this period, the stability of these two SLSs does not change, and may provide the substrate for base exchanges and mutagenesis. The data suggest that many mutable bases are exposed simultaneously at pause sites, allowing for coordinated mutagenesis

K2-231 b: A sub-Neptune exoplanet transiting a solar twin in Ruprecht 147

We identify a sub-Neptune exoplanet ($R_p = 2.5 \pm 0.2$ R$_\oplus$) transiting a solar twin in the Ruprecht 147 star cluster (3 Gyr, 300 pc, [Fe/H] = +0.1 dex). The ~81 day light curve for EPIC 219800881 (V = 12.71) from K2 Campaign 7 shows six transits with a period of 13.84 days, a depth of ~0.06%, and a duration of ~4 hours. Based on our analysis of high-resolution MIKE spectra, broadband optical and NIR photometry, the cluster parallax and interstellar reddening, and isochrone models from PARSEC, Dartmouth, and MIST, we estimate the following properties for the host star: $M_\star = 1.01 \pm 0.03$ M$_\odot$, $R_\star= 0.95 \pm 0.03$ R$_\odot$, and $T_{\rm eff} = 5695 \pm 50$ K. This star appears to be single, based on our modeling of the photometry, the low radial velocity variability measured over nearly ten years, and Keck/NIRC2 adaptive optics imaging and aperture-masking interferometry. Applying a probabilistic mass-radius relation, we estimate that the mass of this planet is $M_p = 7 +5 -3$ M$_\oplus$, which would cause a RV semi-amplitude of $K = 2 \pm 1$ m s$^{-1}$ that may be measurable with existing precise RV facilities. After statistically validating this planet with BLENDER, we now designate it K2-231 b, making it the second sub-stellar object to be discovered in Ruprecht 147 and the first planet; it joins the small but growing ranks of 23 other planets found in open clusters.Comment: 24 pages, 7 figures, light curve included as separate fil

The roles of transcription and genotoxins underlying p53 mutagenesis in vivo

Transcription drives supercoiling which forms and stabilizes single-stranded (ss) DNA secondary structures with loops exposing G and C bases that are intrinsically mutable and vulnerable to non-enzymatic hydrolytic reactions. Since many studies in prokaryotes have shown direct correlations between the frequencies of transcription and mutation, we conducted in silico analyses using the computer program, mfg, which simulates transcription and predicts the location of known mutable bases in loops of high-stability secondary structures. Mfg analyses of the p53 tumor suppressor gene predicted the location of mutable bases and mutation frequencies correlated with the extent to which these mutable bases were exposed in secondary structures. In vitro analyses have now confirmed that the 12 most mutable bases in p53 are in fact located in predicted ssDNA loops of these structures. Data show that genotoxins have two independent effects on mutagenesis and the incidence of cancer: Firstly, they activate p53 transcription, which increases the number of exposed mutable bases and also increases mutation frequency. Secondly, genotoxins increase the frequency of G-to-T transversions resulting in a decrease in G-to-A and C mutations. This precise compensatory shift in the \u27fate\u27 of G mutations has no impact on mutation frequency. Moreover, it is consistent with our proposed mechanism of mutagenesis in which the frequency of G exposure in ssDNA via transcription is rate limiting for mutation frequency in vivo

The infrared imaging spectrograph (IRIS) for TMT: the science case

The InfraRed Imaging Spectrograph (IRIS) is a first-light instrument being designed for the Thirty Meter Telescope (TMT). IRIS is a combination of an imager that will cover a 16.4" field of view at the diffraction limit of TMT (4 mas sampling), and an integral field unit spectrograph that will sample objects at 4-50 mas scales. IRIS will open up new areas of observational parameter space, allowing major progress in diverse fields of astronomy. We present the science case and resulting requirements for the performance of IRIS. Ultimately, the spectrograph will enable very well-resolved and sensitive studies of the kinematics and internal chemical abundances of high-redshift galaxies, shedding light on many scenarios for the evolution of galaxies at early times. With unprecedented imaging and spectroscopy of exoplanets, IRIS will allow detailed exploration of a range of planetary systems that are inaccessible with current technology. By revealing details about resolved stellar populations in nearby galaxies, it will directly probe the formation of systems like our own Milky Way. Because it will be possible to directly characterize the stellar initial mass function in many environments and in galaxies outside of the the Milky Way, IRIS will enable a greater understanding of whether stars form differently in diverse conditions. IRIS will reveal detailed kinematics in the centers of low-mass galaxies, allowing a test of black hole formation scenarios. Finally, it will revolutionize the characterization of reionization and the first galaxies to form in the universe.Comment: to appear in Proc. SPIE 773

Application of multiplexed ion mobility spectrometry towards the identification of host protein signatures of treatment effect in pulmonary tuberculosis.

RationaleThe monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment.ObjectiveWe utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and at 8 weeks of rifamycin-based treatment. We sought to identify treatment specific signatures within patients as well as correlate the proteome signatures to various clinical markers of treatment efficacy.MethodsSerum samples were collected from 289 subjects enrolled in CDC TB Trials Consortium Study 29 at time of enrollment and at the end of the intensive phase (after 40 doses of TB treatment). Serum proteins were immunoaffinity-depleted of high abundant components, digested to peptides and analyzed for data acquisition utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS). Linear mixed models were utilized to identify serum protein changes in the host response to antibiotic treatment as well as correlations with culture status end points.ResultsA total of 10,137 peptides corresponding to 872 proteins were identified, quantified, and used for statistical analysis across the longitudinal patient cohort. In response to TB treatment, 244 proteins were significantly altered. Pathway/network comparisons helped visualize the interconnected proteins, identifying up regulated (lipid transport, coagulation cascade, endopeptidase activity) and down regulated (acute phase) processes and pathways in addition to other cross regulated networks (inflammation, cell adhesion, extracellular matrix). Detection of possible lung injury serum proteins such as HPSE, significantly downregulated upon treatment. Analyses of microbiologic data over time identified a core set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2) which change in response to treatment and also strongly correlate with culture status. A similar set of proteins at baseline were found to be predictive of week 6 and 8 culture status.ConclusionA comprehensive host serum protein dataset reflective of TB treatment effect is defined. A repeating set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2, among others) were found to change significantly in response to treatment, to strongly correlate with culture status, and at baseline to be predictive of future culture conversion. If validated in cohorts with long term follow-up to capture failure and relapse of TB, these protein markers could be developed for monitoring of treatment in clinical trials and in patient care

Following the status of visual cortex over time in patients with macular degeneration reveals atrophy of visually deprived brain regions

Purpose: Previous research has shown atrophy of visual cortex can occur in retinotopic representations of retinal lesions resulting from eye disease. However, the time course of atrophy cannot be established from these cross-sectional studies, which included patients with long-standing disease of varying severity. Our aim therefore was to measure visual cortical structure over time in participants after onset of unilateral visual loss resulting from age-related macular degeneration (AMD). Methods: Inclusion criteria were onset of acute unilateral neovascular AMD with bilateral dry-AMD based on clinical examination. Therefore, substantial loss of unilateral visual input to cortex was relatively well-defined in time. Changes in cortical anatomy were assessed in the occipital lobe as a whole, and in cortical representations of the lesion and intact retina, the lesion and intact projection zones, respectively. Whole brain, T1-weighted MRI was taken at diagnosis (before anti-angiogenic treatment to stabilise the retina), during the 3-4-month initial treatment period, with a long-term follow-up ~5 (range 3.8 – 6.1 years) years later. Results: Significant cortical atrophy was detected at long-term follow-up only, with a reduction in mean cortical volume across the whole occipital lobe. Importantly, this reduction was explained by cortical thinning of the lesion projection zone, which suggests additional changes to those associated with normal ageing. Over the period of study, anti-angiogenic treatment stabilised visual acuity and central retinal thickness, suggesting that the atrophy detected was most likely governed by long-term decreased visual input. Conclusions: Our results indicate that consequences of eye disease on visual cortex are atrophic and retinotopic. Our work also raises the potential to follow the status of visual cortex in individuals over time to inform on how best to treat patients, particularly with restorative techniques