Spatial control of irreversible protein aggregation

Liquid cellular compartments spatially segregate from the cytoplasm and can regulate aberrant protein aggregation, a process linked to several medical conditions, including Alzheimer's and Parkinson's diseases. Yet the mechanisms by which these droplet-like compartments affect protein aggregation remain unknown. Here, we combine kinetic theory of protein aggregation and liquid-liquid phase separation to study the spatial control of irreversible protein aggregation in the presence of liquid compartments. We find that, even for weak interactions between the compartment constituents and the aggregating monomers, aggregates are strongly enriched inside the liquid compartment relative to the surrounding cytoplasm. We show that this enrichment is caused by a positive feedback mechanism of aggregate nucleation and growth which is mediated by a flux maintaining the phase equilibrium between the compartment and the cytoplasm. Our model predicts that the compartment volume that maximizes aggregate enrichment in the compartment is determined by the reaction orders of aggregate nucleation. The underlying mechanism of aggregate enrichment could be used to confine cytotoxic protein aggregates inside droplet-like compartments suggesting potential new avenues against aberrant protein aggregation. Our findings could also represent a common mechanism for the spatial control of irreversible chemical reactions in general

Towards population coding principles in the primate premotor and parietal grasping network

As humans, the only way for us to interact with the world around us is by utilizing our highly trained motor system. Therefore, understanding how the brain generates movement is essential to understanding all aspects of human behavior. Despite the importance the motor system, the manner in which the brain prepares and executes movements, especially grasping movements, is still unclear. In this thesis I undertake a number of electrophysiological and computational experiments on macaque monkeys, primates showing similar grasping behavior to humans, to shed light on how grasping movements are planned and executed across distributed brain regions in both parietal and premotor cortices. Through these experiments, I reveal how the use of large-scale electrophysiological recording of hundreds of neurons simultaneously in primates allows the investigation of network computational principles essential for grasping, and I develop a series of analytical techniques for dissecting the large data sets collected from these experiments. In chapter 2.1 I show how large-scale parallel recordings can be leveraged to make behavioral predictions on single trials. The methods used to extract single-trial predictions varied in their performance, but population-based methods provided the most consistent and meaningful interpretation of the data. In addition, the success of these behavioral predictions could be used to make inferences about how areas differ in their contribution to preparation of grasping movements. It was found that while reaction time could be predicted from the population activity of either area, performance was significantly higher using the data from premotor cortex, suggesting that population activity in premotor cortex may have a more direct effect on behavior. In chapter 2.2 I show how preparation and movement intermingle and interact with one another on the continuum between immediate and withheld movement. Our population-based and dimensionality reduction techniques enable interpretation of the data, even when single neuron tuning properties are highly temporally and functionally complex. Activity in parietal cortex stabilizes during the memory period, while it continues to evolve in premotor cortex, revealing a decodable signature of time. Furthermore, activity during movement initiation clusters into two groups, movements initiated as fast as possible and movements from memory, showing how a state shift likely occurs on the border between these two types of actions. In chapter 2.3 I show that the question of how motor cortex controls movement is an ongoing issue in the field. I address crucial details about recent methodology used to extract rotational dynamics in motor cortex. I show how a simple neural network simulation and novel statistical test reveal properties of motor cortex not examined before, showing how models of movement generation can be essential tools in adding perspective to empirical results. Finally, in chapter 2.4 I show how the specificity of hand use can be used as a tool to dissociate levels of abstraction in the visual to motor transformation in parietal and premotor cortex. While preparatory activity is mostly hand-invariant in parietal cortex, activity in premotor cortex dissociates the intended hand use well before movement. Importantly, we show how appropriate dimensionality reduction techniques can disentangle the effects of multiple task parameters and find latent dimensions consistent between areas and animals. Together, the results of my experiments reinforce the importance of seeing the motor system not as a collection of individually tuned neurons, but as a dynamic network of neurons continuously acting together to produce the complex and flexible behavior we observe in all primates

Strategic Concealment: Locating Armed Private Contractors in State Foreign Policy

The global expansion of armed private contractors has led to a revived interest in researching armed private contracting firms, especially investigating how their personnel have functioned as an extension of state foreign policy. However, the literature on the industry contains a confusing diversity of terms when reviewing such firms, whether private military company, private security company, private military security company, or even just mercenary. Using the Singer (2010) ‘tip of the spear’ typology, I analyze the distinctions across armed private contracting firms and discuss the differences between armed private contractors and conventional militaries, armed private contractors and mercenaries, and highlight the differences between private military companies and private security companies. I find several substantive distinctions, including recruitment and retainment, rent-seeking behavior and compliance with international regulations, and expected threat environment, respectively. Armed private contracting firms will continue to influence international security dynamics and necessitate further research and attention

Genetics and physiology of motility by Photorhabdus spp

Photorhabdus is a bacterial symbiont of soil nematodes and a lethal pathogen of insects. Many pathogenic or symbiotic bacteria utilize various methods of motility to reach favorable conditions, colonize a host, or have motility genes that also regulate virulence expression. It is not known how motility is regulated, or how it may confer an advantage, in the complex life cycle of Photorhabdus.. We characterized motility in Photorhabdus and found that the bacterium was motile both by swimming (movement in liquid) and swarming (movement on surfaces) under appropriate conditions. Both types of motility utilized the same peritrichous flagella and shared genetic components. However, unlike swimming, swarming behavior was a social form of movement in which the cells coordinately formed intricate channels that covered a surface. The optimal conditions for motility were established including a Na + or K+ requirement. Interestingly, microarray experiments imply that NaCl and KCl regulate motility posttranscriptionally and not at the gene expression level. This ionic salt posttranscriptional regulation of motility has not been observed in other bacteria. We suggest that this form of regulation may be beneficial for an organism that must adapt quickly to changing environments. To identify the genes involved in motility, P. temperata mutants with altered motility behavior were generated with random transposon mutagenesis. An rssB mutant that displayed a hyperswarming phenotype was isolated, suggesting that RssB acts as a negative regulator of swarming behavior. A yidA mutant, whose function remains unknown, had inhibited swimming behavior and dramatically attenuated virulence. A plu3723 mutant (a luxR homolog) was isolated, that unlike the wild-type, was able to swim without NaCl or KCl. All together 86 motility mutants were isolated and physiologically characterized. Since many of the motility mutants had concomitant changes in expression of antibiotics, hemolysins, proteases, and insect virulence, expression of motility genes may be co-regulated with expression of virulence enzymes in Photorhabdus. The mutants isolated in this study will be useful long-term tools for additional experiments. The ability of Photorhabdus to swarm could provide a rapid and coordinated colonization of either nematode or insect host, or in traveling from one host to another. The nematode environment is low in nutrients, ionic salts, and amino acids, while the insect hemocoel is high in these solutes. When the nematodes release their bacterial symbionts into the insect hemocoel, the bacteria are exposed to the ionic salts that would induce the flagella regulon. Ecologically, it would be beneficial for the bacteria to be motile upon entering the insect to rapidly colonize the hemocoel. If aspects of virulence expression are co-regulated with motility genes as this research suggests, expression of virulence factors would also be induced upon exposure to the insect. The data presented in this study are the first steps for elucidating a model of motility in the life cycle of this insect pathogen and nematode symbiont

Design, development and prototype fabrication of an area hydrogen detector summary report, 5 apr. 1963 - 4 apr. 1964

Area hydrogen detector for unpressurized environments - palladium film sensor elemen

Engineering Electromagnetic Properties of Periodic Nanostructures Using Electrostatic Resonances

Electromagnetic properties of periodic two-dimensional sub-wavelength structures consisting of closely-packed inclusions of materials with negative dielectric permittivity $\epsilon$ in a dielectric host with positive $\epsilon_h$ can be engineered using the concept of multiple electrostatic resonances. Fully electromagnetic solutions of Maxwell's equations reveal multiple wave propagation bands, with the wavelengths much longer than the nanostructure period. It is shown that some of these bands are described using the quasi-static theory of the effective dielectric permittivity $\epsilon_{qs}$, and are independent of the nanostructure period. Those bands exhibit multiple cutoffs and resonances which are found to be related to each other through a duality condition. An additional propagation band characterized by a negative magnetic permeability develops when a magnetic moment is induced in a given nano-particle by its neighbors. Imaging with sub-wavelength resolution in that band is demonstrated

Overview of Venus geology: Preliminary description of terrain units for Venus global geological mapping

Venus terrain units can be categorized on the basis of morphology, reflectivity, backscatter, roughness, and emissivity. Morphology can be inferred from Magellan left-looking nominal incidence angle image mosaics, right-looking coverage, and more limited left-looking stereo. The typical resolution is about 300 m down to about 120 m near periapsis in the cycle one nominal coverage. The scale of geologic mapping governs definition of mappable terrain units. Initial global mapping is being compiled at a scale of 1:50 million. At this scale, the smallest individual features that can be mapped are about 125 km. The categories of terrain types are plains, complex ridge terrain, features with morphology suggesting volcanic or volcano-tectonic origin, features interpreted to be tectonic in origin, crater units, and surficial units such as splotches and streaks. Brief descriptions of terrain units are provided