Populating 3D Cities: a True Challenge

In this paper, we describe how we can model crowds in real-time using dynamic meshes, static meshes andimpostors. Techniques to introduce variety in crowds including colors, shapes, textures, individualanimation, individualized path-planning, simple and complex accessories are explained. We also present ahybrid architecture to handle the path planning of thousands of pedestrians in real time, while ensuringdynamic collision avoidance. Several behavioral aspects are presented as gaze control, group behaviour, aswell as the specific technique of crowd patches

GPGPU computation and visualization of three-dimensional cellular automata

This paper presents a general-purpose simulation approach integrating a set of technological developments and algorithmic methods in cellular automata (CA) domain. The approach provides a general-purpose computing on graphics processor units (GPGPU) implementation for computing and multiple rendering of any direct-neighbor three-dimensional (3D) CA. The major contributions of this paper are: the CA processing and the visualization of large 3D matrices computed in real time; the proposal of an original method to encode and transmit large CA functions to the graphics processor units in real time; and clarification of the notion of top-down and bottom-up approaches to CA that non-CA experts often confuse. Additionally a practical technique to simplify the finding of CA functions is implemented using a 3D symmetric configuration on an interactive user interface with simultaneous inside and surface visualizations. The interactive user interface allows for testing the system with different project ideas and serves as a test bed for performance evaluation. To illustrate the flexibility of the proposed method, visual outputs from diverse areas are demonstrated. Computational performance data are also provided to demonstrate the method’s efficiency. Results indicate that when large matrices are processed, computations using GPU are two to three hundred times faster than the identical algorithms using CPU

Combining Enzalutamide with Abiraterone, Prednisone, and Androgen Deprivation Therapy in the STAMPEDE Trial

There are compelling reasons to study the addition of both enzalutamide and abiraterone, in combination, to standard-of-care for hormone-naïve prostate cancer. Through a protocol amendment, this will be assessed in the STAMPEDE trial, with overall survival as primary outcome measure. © 2014 European Association of Urology

Identification of Kinases Regulating Prostate Cancer Cell Growth Using an RNAi Phenotypic Screen

As prostate cancer progresses to castration-resistant disease, there is an increase in signal transduction activity. Most castration-resistant prostate tumors continue to express the androgen receptor (AR) as well as androgen-responsive genes, despite the near absence of circulating androgen in these patients. The AR is regulated not only by its cognate steroid hormone, but also by interactions with a constellation of co-regulatory and signaling molecules. Thus, the elevated signaling activity that occurs during progression to castration resistance can affect prostate cancer cell growth either through the AR or independent of the AR. In order to identify signaling pathways that regulate prostate cancer cell growth, we screened a panel of shRNAs targeting 673 human kinases against LNCaP prostate cancer cells grown in the presence and absence of hormone. The screen identified multiple shRNA clones against known and novel gene targets that regulate prostate cancer cell growth. Based on the magnitude of effect on growth, we selected six kinases for further study: MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1. Knockdown of these kinases decreased cell growth in both androgen-dependent and castration-resistant prostate cancer cells. However, these kinases had different effects on basal or androgen-induced transcriptional activity of AR target genes. MAP3K11 knockdown most consistently altered transcription of AR target genes, suggesting that MAP3K11 affected its growth inhibitory effect by modulating the AR transcriptional program. Consistent with MAP3K11 acting on the AR, knockdown of MAP3K11 inhibited AR Ser 650 phosphorylation, further supporting stress kinase regulation of AR phosphorylation. This study demonstrates the applicability of lentiviral-based shRNA for conducting phenotypic screens and identifies MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1 as regulators of prostate cancer cell growth. The thorough evaluation of these kinase targets will pave the way for developing more effective treatments for castration-resistant prostate cancer

Very Low-Mass Stellar and Substellar Companions to Solar-Like Stars from MARVELS I: A Low Mass Ratio Stellar Companion to TYC 4110-01037-1 in a 79-day Orbit

TYC 4110-01037-1 has a low-mass stellar companion, whose small mass ratio and short orbital period are atypical amongst solar-like (Teff ~< 6000 K) binary systems. Our analysis of TYC 4110-01037-1 reveals it to be a moderately aged (~<5 Gyr) solar-like star having a mass of 1.07 +/- 0.08 MSun and radius of 0.99 +/- 0.18 RSun. We analyze 32 radial velocity measurements from the SDSS-III MARVELS survey as well as 6 supporting radial velocity measurements from the SARG spectrograph on the 3.6m TNG telescope obtained over a period of ~2 years. The best Keplerian orbital fit parameters were found to have a period of 78.994 +/- 0.012 days, an eccentricity of 0.1095 +/- 0.0023, and a semi-amplitude of 4199 +/- 11 m/s. We determine the minimum companion mass (if sin i = 1) to be 97.7 +/- 5.8 MJup. The system's companion to host star mass ratio, >0.087 +/- 0.003, places it at the lowest end of observed values for short period stellar companions to solar-like (Teff ~< 6000 K) stars. One possible way to create such a system would be if a triple-component stellar multiple broke up into a short period, low q binary during the cluster dispersal phase of its lifetime. A candidate tertiary body has been identified in the system via single-epoch, high contrast imagery. If this object is confirmed to be co-moving, we estimate it would be a dM4 star. We present these results in the context of our larger-scale effort to constrain the statistics of low mass stellar and brown dwarf companions to FGK-type stars via the MARVELS survey.Comment: 22 pages; accepted in A

Historical sampling reveals dramatic demographic changes in western gorilla populations

Background: Today many large mammals live in small, fragmented populations, but it is often unclear whether this subdivision is the result of long-term or recent events. Demographic modeling using genetic data can estimate changes in long-term population sizes while temporal sampling provides a way to compare genetic variation present today with that sampled in the past. In order to better understand the dynamics associated with the divergences of great ape populations, these analytical approaches were applied to western gorillas (Gorilla gorilla) and in particular to the isolated and Critically Endangered Cross River gorilla subspecies (G. g. diehli).Results: We used microsatellite genotypes from museum specimens and contemporary samples of Cross River gorillas to infer both the long-term and recent population history. We find that Cross River gorillas diverged from the ancestral western gorilla population ~17,800 years ago (95% HDI: 760, 63,245 years). However, gene flow ceased only ~420 years ago (95% HDI: 200, 16,256 years), followed by a bottleneck beginning ~320 years ago (95% HDI: 200, 2,825 years) that caused a 60-fold decrease in the effective population size of Cross River gorillas. Direct comparison of heterozygosity estimates from museum and contemporary samples suggests a loss of genetic variation over the last 100 years.Conclusions: The composite history of western gorillas could plausibly be explained by climatic oscillations inducing environmental changes in western equatorial Africa that would have allowed gorilla populations to expand over time but ultimately isolate the Cross River gorillas, which thereafter exhibited a dramatic population size reduction. The recent decrease in the Cross River population is accordingly most likely attributable to increasing anthropogenic pressure over the last several hundred years. Isolation of diverging populations with prolonged concomitant gene flow, but not secondary admixture, appears to be a typical characteristic of the population histories of African great apes, including gorillas, chimpanzees and bonobos

SIRNA-Directed In Vivo Silencing of Androgen Receptor Inhibits the Growth of Castration-Resistant Prostate Carcinomas

BACKGROUND: Prostate carcinomas are initially dependent on androgens, and castration or androgen antagonists inhibit their growth. After some time though, tumors become resistant and recur with a poor prognosis. The majority of resistant tumors still expresses a functional androgen receptor (AR), frequently amplified or mutated. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that AR is not only expressed, but is still a key therapeutic target in advanced carcinomas, we injected siRNA targeting AR into mice bearing exponentially growing castration-resistant tumors. Quantification of siRNA into tumors and mouse tissues demonstrated their efficient uptake. This uptake silenced AR in the prostate, testes and tumors. AR silencing in tumors strongly inhibited their growth, and importantly, also markedly repressed the VEGF production and angiogenesis. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that carcinomas resistant to hormonal manipulations still depend on the expression of the androgen receptor for their development in vivo. The siRNA-directed silencing of AR, which allows targeting overexpressed as well as mutated isoforms, triggers a strong antitumoral and antiangiogenic effect. siRNA-directed silencing of this key gene in advanced and resistant prostate tumors opens promising new therapeutic perspectives and tools

Insights into hominid evolution from the gorilla genome sequence.

Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution

Populations of planets in multiple star systems

Astronomers have discovered that both planets and binaries are abundant throughout the Galaxy. In combination, we know of over 100 planets in binary and higher-order multi-star systems, in both circumbinary and circumstellar configurations. In this chapter we review these findings and some of their implications for the formation of both stars and planets. Most of the planets found have been circumstellar, where there is seemingly a ruinous influence of the second star if sufficiently close (<50 AU). Hosts of hot Jupiters have been a particularly popular target for binary star studies, showing an enhanced rate of stellar multiplicity for moderately wide binaries (>100 AU). This was thought to be a sign of Kozai-Lidov migration, however recent studies have shown this mechanism to be too inefficient to account for the majority of hot Jupiters. A couple of dozen circumbinary planets have been proposed around both main sequence and evolved binaries. Around main sequence binaries there are preliminary indications that the frequency of gas giants is as high as those around single stars. There is however a conspicuous absence of circumbinary planets around the tightest main sequence binaries with periods of just a few days, suggesting a unique, more disruptive formation history of such close stellar pairs.Comment: Invited review chapter, accepted for publication in "Handbook of Exoplanets", ed. H. Deeg & J. A. Belmont