A Turing test for crowds

The accuracy and believability of crowd simulations underpins computational studies of human collective behaviour, with implications for urban design, policing, security and many other areas. Accuracy concerns the closeness of the fit between a simulation and observed data, and believability concerns the human perception of plausibility. In this paper, we address both issues via a so-called ‘Turing test’ for crowds, using movies generated from both accurate simulations and observations of real crowds. The fundamental question we ask is ‘Can human observers distinguish between real and simulated crowds?’ In two studies with student volunteers (n = 384 and n = 156), we find that non-specialist individuals are able to reliably distinguish between real and simulated crowds when they are presented side-by-side, but they are unable to accurately classify them. Classification performance improves slightly when crowds are presented individually, but not enough to out-perform random guessing. We find that untrained individuals have an idealized view of human crowd behaviour which is inconsistent with observations of real crowds. Our results suggest a possible framework for establishing a minimal set of collective behaviours that should be integrated into the next generation of crowd simulation models

Genome-Scale DNA Methylation Analysis in Distinct Pluripotent Stem Cells

Mouse embryonic stem cells (ESCs) and embryonic germ cells (EGCs) are both pluripotent cell types derived from distinct developmental stages. Despite sharing many characteristics, some differences have been reported between the two cell types. For instance, EGCs generally lack of DNA methylation at imprinted regions and they have been suggested to display overall global hypomethylation. These characteristics have always been regarded as reflective of their derivation origin from primordial germ cells (PGCs), whereas ESCs are derived from preimplantation blastocysts. A large set of newly derived, genetically matched ESC and EGC lines has enabled us to clarify several of these observations at genome-wide scale. DNA methylation analysis of ESCs and EGCs, in particular lines derived from both sexes demonstrates that the DNA methylation profiles of female ESCs and EGCs are comparable low, while the male cell lines all share a more hypermethylated genome. The observed hypomethylation is not restricted to promoters but is also evident in many retroelements including the regions often regarded as resistant to demethylation. Mechanistically it appears that the two active X chromosomes in female cells are involved. Specifically, we find that the X-linked gene Dusp9 may play a central role in the regulation of DNA methylation via the inhibition of Erk signaling. Taken together, our results provide novel mechanistic insights as well as clarify that it is not the EGC identity that caused the global hypomethylation in prior studies, but rather the fact that the lines in those experiments happened to be female EGCs

Identification of Lifelike Characteristics of Human Crowds Through a Classification Task

Crowd simulations are used extensively to study the dynamics of human collectives. Such studies are underpinned by specific movement models, which encode rules and assumptions about how people navigate a space and handle interactions with others. These models often give rise to macroscopic simulated crowd behaviours that are statistically valid, but which lack the noisy microscopic behaviours that are the signature of believable “real” crowds. In this paper, we use an existing “Turing test” for crowds to identify “lifelike” features of real crowds that are generally omitted from simulation models. Our previous study using this test established that untrained individuals have difficulty in classifying movies of crowds as “Real” or “Simulated”, and that such people often have an idealised view of how crowds move. In this follow-up study (with new participants) we perform a second trial, which now includes a training phase (showing participants movies of real crowds). We find that classification performance significantly improves after training, confirming the existence of features that allow participants to identify real crowds. High-performing individuals are able to identify the features of real crowds that should be incorporated into future simulations if they are to be considered “lifelike

Crowd-Sourced Identification of Characteristics of Collective Human Motion

Crowd simulations are used extensively to study the dynamics of human collectives. Such studies are underpinned by specific movementmodels, whichencoderules andassumptions about howpeople navigate a space and handle interactions with others. These models often give rise to macroscopic simulated crowd behaviours that are statistically valid, but which lack the noisy microscopic behaviours that are the signature of believable real crowds. In this paper, we use an existing “Turing test” for crowds to identify realistic features of real crowds that are generally omitted from simulation models. Our previous study using this test established that untrained individuals have difficulty in classifying movies of crowds as real or simulated, and that such people often have an idealised view of how crowds move. In this follow-up study (with new participants) we perform a second trial, which now includes a training phase (showing participants movies of real crowds). We find that classification performance significantly improves after training, confirming the existence of features that allow participants to identify real crowds. High-performing individuals are able to identify the features of real crowds that should be incorporated into future simulations if they are to be considered realistic

Mitotic activity of survivin is regulated by acetylation at K129

Survivin is a cancer-associated protein regulated by multiple factors, including acetylation at K129 within its C-terminal alpha-helical tail. Acetylation of survivin is being pursued as a potential prognostic marker in breast cancer. This modification at K129 may cause nuclear accumulation of survivin in interphase cells; however, whether this affects its essential role during mitosis has not been addressed. We posited whether mimicking acetylation of survivin at K129 alters its activity during mitosis. Fluorescence microscopy and time-lapse imaging showed that, mutating this site to an alanine to act as a constitutive acetyl mimetic, K129A, causes defects in chromosome segregation and cytokinesis. As a non-acetylatable version, K129R, also has difficulty during mitotic exit, we conclude that cyclical acetylation and deacetylation is required for fully functional survivin during mitosis

Bruton's Tyrosine Kinase Is Required For Lipopolysaccharide-induced Tumor Necrosis Factor α Production

Lipopolysaccharide (LPS), a product of Gram-negative bacteria, is potent mediator of tumor necrosis factor (TNF)α production by myeloid/macrophage cells. Inhibitors capable of blocking the signaling events that result in TNFα production could provide useful therapeutics for treating septic shock and other inflammatory diseases. Broad spectrum tyrosine inhibitors are known to inhibit TNFα production, however, no particular family of tyrosine kinases has been shown to be essential for this process. Here we show that the Bruton's tyrosine kinase (Btk)-deficient mononuclear cells from X-linked agammaglobulinemia patients have impaired LPS-induced TNFα production and that LPS rapidly induces Btk kinase activity in normal monocytes. In addition, adenoviral overexpression of Btk in normal human monocytes enhanced TNFα production. We examined the role of Btk in TNFα production using luciferase reporter adenoviral constructs and have established that overexpression of Btk results in the stabilization of TNFα mRNA via the 3′ untranslated region. Stimulation with LPS also induced the activation of related tyrosine kinase, Tec, suggesting that the Tec family kinases are important components for LPS-induced TNFα production. This study provides the first clear evidence that tyrosine kinases of the Tec family, in particular Btk, are key elements of LPS-induced TNFα production and consequently may provide valuable therapeutic targets for intervention in inflammatory conditions

Detection of Crab Giant Pulses Using the Mileura Widefield Array Low Frequency Demonstrator Field Prototype System

We report on the detection of giant pulses from the Crab Nebula pulsar at a frequency of 200 MHz using the field deployment system designed for the Mileura Widefield Array's Low Frequency Demonstrator (MWA-LFD). Our observations are among the first high-quality detections at such low frequencies. The measured pulse shapes are deconvolved for interstellar pulse broadening, yielding a pulse-broadening time of 670$\pm$100 $\mu$s, and the implied strength of scattering (scattering measure) is the lowest that is estimated towards the Crab nebula from observations made so far. The sensitivity of the system is largely dictated by the sky background, and our simple equipment is capable of detecting pulses that are brighter than $\sim$9 kJy in amplitude. The brightest giant pulse detected in our data has a peak amplitude of $\sim$50 kJy, and the implied brightness temperature is $10^{31.6}$ K. We discuss the giant pulse detection prospects with the full MWA-LFD system. With a sensitivity over two orders of magnitude larger than the prototype equipment, the full system will be capable of detecting such bright giant pulses out to a wide range of Galactic distances; from $\sim$8 to $\sim$30 kpc depending on the frequency. The MWA-LFD will thus be a highly promising instrument for the studies of giant pulses and other fast radio transients at low frequencies.Comment: 10 pages, 6 figures, Accepted for publication in the Astrophysical Journa

Pharmacogenetic Testing for Clopidogrel Using the Rapid INFINITI Analyzer A Dose-Escalation Study

ObjectivesOur aim was to assess whether a higher clopidogrel maintenance dose has a greater antiplatelet effect in CYP2C19*2 allele carriers compared with noncarriers.BackgroundClopidogrel is a prodrug that is biotransformed by the cytochrome P450 enzymes CYP2C19, 2C9, and 3A4, 2B6, 1A2. The CYPC219*2 loss of function variant has been associated with a reduced antiplatelet response to clopidogrel and a 3-fold risk of stent thrombosis.MethodsForty patients on standard maintenance dosage clopidogrel (75 mg), for 9.4 ± 9.2 weeks, were enrolled into a dose escalation study. Platelet function was assessed at baseline and after 1 week of 150 mg once daily using the VerifyNow platelet function analyzer (Accumetrics Ltd., San Diego, California). Genomic DNA was hybridized to a BioFilmChip microarray on the INFINITI analyzer (AutoGenomics Inc., Carlsbad, California) and analyzed for the CYP19*2, *4, *17, and CYP2C9*2, *3 polymorphisms.ResultsPlatelet inhibition increased over 1 week, mean +8.6 ± 13.5% (p = 0.0003). Carriers of the CYP2C19*2 allele had significantly reduced platelet inhibition at baseline (median 18%, range 0% to 72%) compared with wildtype (wt) (median 59%, range 11% to 95%, p = 0.01) and at 1 week (p = 0.03). CYP2C19*2 allele carriers had an increase in platelet inhibition of (mean +9 ± 11%, p = 0.03) and reduction in platelet reactivity (mean −26 ± 38 platelet response unit, p = 0.04) with a higher dose. Together CYP2C19*2 and CYP2C9*3 loss of function carriers had a greater change in platelet inhibition with 150 mg daily than wt/wt (+10.9% vs. +0.7%, p = 0.04).ConclusionsIncreasing the dose of clopidogrel in patients with nonresponder polymorphisms can increase antiplatelet response. Personalizing clopidogrel dosing using pharmacogenomics may be an effective method of optimizing treatment