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Ciglitazone-a human PPARĪ³ agonist-disrupts dorsoventral patterning in zebrafish.
Peroxisome proliferator-activated receptor Ī³ (PPARĪ³) is a ligand-activated transcription factor that regulates lipid/glucose homeostasis and adipocyte differentiation. While the role of PPARĪ³ in adipogenesis and diabetes has been extensively studied, little is known about PPARĪ³ function during early embryonic development. Within zebrafish, maternally-loaded pparĪ³ transcripts are present within the first 6 h post-fertilization (hpf), and de novo transcription of zygotic pparĪ³ commences at ~48 hpf. Since maternal pparĪ³ transcripts are elevated during a critical window of cell fate specification, the objective of this study was to test the hypothesis that PPARĪ³ regulates gastrulation and dorsoventral patterning during zebrafish embryogenesis. To accomplish this objective, we relied on (1) ciglitazone as a potent PPARĪ³ agonist and (2) a splice-blocking, pparĪ³-specific morpholino to knockdown pparĪ³. We found that initiation of ciglitazone-a potent human PPARĪ³ agonist-exposure by 4 hpf resulted in concentration-dependent effects on dorsoventral patterning in the absence of epiboly defects during gastrulation, leading to ventralized embryos by 24 hpf. Interestingly, ciglitazone-induced ventralization was reversed by co-exposure with dorsomorphin, a bone morphogenetic protein signaling inhibitor that induces strong dorsalization within zebrafish embryos. Moreover, mRNA-sequencing revealed that lipid- and cholesterol-related processes were affected by exposure to ciglitazone. However, pparĪ³ knockdown did not block ciglitazone-induced ventralization, suggesting that PPARĪ³ is not required for dorsoventral patterning nor involved in ciglitazone-induced toxicity within zebrafish embryos. Our findings point to a novel, PPARĪ³-independent mechanism of action and phenotype following ciglitazone exposure during early embryonic development
Poverty in the Aftermath of Katrina: Reimagining Citizen Leadership in t he Context of Federalism
It is a cruel irony that a lead singer with the name Katrina and a back-up band called the Waves performed a pop song in the 1980s with bright lyrics and happy beat. Many years later, a natural disaster bearing the same name, backed by a surge of seawater, consumed the city of New Orleans and the Gulf Coast. In the wake of Hurricane Katrina, America and the rest of the world witnessed the desperate side of the world\u27s wealthiest nation. Many people, who had neither time nor resources to escape the storm\u27s surge, and the destruction that followed, became first-hand witnesses to America\u27s failure to adequately address its poverty problem. The world was shocked to see Americans displaced and immobilized. Chilling reports of the disintegration of the community with rampant plundering and lawlessness punctuated media broadcasts. The ravages of death and deprivation were graphically depicted even as relief providers scrambled to address the massive needs of the displaced and injured. The failed infrastructure and lack of services to help the unfortunates who remained behind to weather the storm resurrected the national debate on poverty-who is responsible for giving willing Americans the tools to remove themselves from poverty to become contributing members of society
Uncertainty handling in surrogate assisted optimisation of games
In this thesis entitled Uncertainty handling in surrogate assisted optimisation of games, we started out with the goal to investigate the uncertainty in game optimisation problems, as well as to identify or develop suitable optimisation algorithms. In order to approach this problem systematically, we first created a benchmark consisting of suitable game optimisation functions (GBEA). The suitability of these functions was determined using a taxonomy that was created based on the results of a literature survey of automatic game evaluation approaches. In order to improve the interpretability of the results, we also implemented an experimental framework that adds several features aiding the analysis of the results, specifically for surrogate-assisted evolutionary algorithms.
After describing potentially suitable algorithms, we proposed a promising algorithm (SAPEO), to be tested on the benchmark alongside state-of-the-art optimisation algorithms. SAPEO is utilising the observation that most evolutionary algorithms only need fitness evaluations for survival selections. However, if the individuals in a population can be distinguished reliably based on predicted values, the number of function evaluations can be reduced. After a theoretical analysis of the performance limits of SAPEO, which produced very promising insights, we conducted several sets of experiments in order to answer the three central hypotheses guiding this thesis. We find that SAPEO performs comparably to state-of-the-art surrogate-assisted algorithms, but all are frequently outperformed by stand-alone evolutionary algorithms. From a more detailed analysis of the behaviour of SAPEO, we identify a few pointers that could help to further improve the performance.
Before running experiments on the developed benchmark, we first verify its suitability using a second set of experiments. We find that GBEA is practical and contains interesting and challenging functions. However, we also discover that, in order to produce interpretable result with the benchmark, a set of baseline results is required. Due to this issue, we are not able to produce meaningful results with the GBEA at the time of writing. However, after more experiments are conducted with the benchmark, we will be able to interpret our results in the future. The insights developed will most likely not only be able to provide an assessment of optimisation algorithms, but can also be used to gain a deeper understanding of the characteristics of game optimisation problems
Tools for Landscape Analysis of Optimisation Problems in Procedural Content Generation for Games
The term Procedural Content Generation (PCG) refers to the (semi-)automatic
generation of game content by algorithmic means, and its methods are becoming
increasingly popular in game-oriented research and industry. A special class of
these methods, which is commonly known as search-based PCG, treats the given
task as an optimisation problem. Such problems are predominantly tackled by
evolutionary algorithms.
We will demonstrate in this paper that obtaining more information about the
defined optimisation problem can substantially improve our understanding of how
to approach the generation of content. To do so, we present and discuss three
efficient analysis tools, namely diagonal walks, the estimation of high-level
properties, as well as problem similarity measures. We discuss the purpose of
each of the considered methods in the context of PCG and provide guidelines for
the interpretation of the results received. This way we aim to provide methods
for the comparison of PCG approaches and eventually, increase the quality and
practicality of generated content in industry.Comment: 30 pages, 8 figures, accepted for publication in Applied Soft
Computin
MCTS/EA hybrid GVGAI players and game difficulty estimation
In the General Video Game Playing competitions of the last years, Monte-Carlo tree search as well as Evolutionary Algorithm based controllers have been successful. However, both approaches have certain weaknesses, suggesting that certain hybrids could outperform both. We envision and experimentally compare several types of hybrids of two basic approaches, as well as some possible extensions. In order to achieve a better understanding of the games in the competition and the strength and weaknesses of different controllers, we also propose and apply a novel game difficulty estimation scheme based on several observable game characteristics
Mental imagery-induced attention modulates pain perception and cortical excitability
Background Mental imagery is a powerful method of altering brain activity and
behavioral outcomes, such as performance of cognition and motor skills.
Further, attention and distraction can modulate pain-related neuronal networks
and the perception of pain. This exploratory study examined the effects of
mental imagery-induced attention on pressure pain threshold and cortical
plasticity using transcranial magnetic stimulation (TMS). This blinded,
randomized, and parallel-design trial comprised 30 healthy right-handed male
subjects. Exploratory statistical analyses were performed using ANOVA and
t-tests for pain and TMS assessments. Pearsonās correlation was used to
analyze the association between changes in pain threshold and cortical
excitability. Results In the analysis of pain outcomes, there was no
significant interaction effect on pain between group versus time. In an
exploratory analysis, we only observed a significant effect of group for the
targeted left hand (ANOVA with pain threshold as the dependent variable and
time and group as independent variables). Although there was only a within-
group effect of mental imagery on pain, further analyses showed a significant
positive correlation of changes in pain threshold and cortical excitability
(motor-evoked potentials via TMS). Conclusions Mental imagery has a minor
effect on pain modulation in healthy subjects. Its effects appear to differ
compared with chronic pain, leading to a small decrease in pain threshold.
Assessments of cortical excitability confirmed that these effects are related
to the modulation of pain-related cortical circuits. These exploratory
findings suggest that neuronal plasticity is influenced by pain and that the
mental imagery effects on pain depend on the state of central sensitization
Coating versus Doping: Understanding the Enhanced Performance of HighāVoltage Batteries by the Coating of Spinel LiNiMnO with LiLaTiO
LiLaTiO (LLTO) coated spinel LiNiMnO (LNMO) as cathode material is fabricated by a new method using hydrogen-peroxide as activating agent. The structure of the obtained active materials is investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), and the electrochemical properties of the prepared cathodes are probed by the chargeādischarge studies. The morphology of the coating material on the surface and the degree of coverage of the coated particles is investigated by the SEM, which shows a fully dense and homogeneous coating (thickness ā 7 nm, determined by TEM) on the surface of active material. XRD studies of the coated active materials treated at different temperatures (between 300 Ā°C and 1000 Ā°C) reveal expansion or contraction of the unit cell in dependence of the coating concentration and degree of Ti diffusion. It is concluded, that for the LNMO particles calcined at low temperatures, the LLTO coating layer is still intact and protects the active material from the interaction with the electrolyte. However, for the coated particles treated at high temperatures, Ti ions migrate into the structure of LNMO during the modification process between 500 Ā°C and 800 Ā°C, resulting in ānakedā and unprotected particles
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