Architecture-Dependent Noise Discriminates Functionally Analogous Differentiation Circuits

Gene regulatory circuits with different architectures (patterns of regulatory interactions) can generate similar dynamics. This raises the question of why a particular circuit architecture is selected to implement a given cellular process. To investigate this problem, we compared the Bacillus subtilis circuit that regulates differentiation into the competence state to an engineered circuit with an alternative architecture (SynEx) in silico and in vivo. Time-lapse microscopy measurements showed that SynEx cells generated competence dynamics similar to native cells and reconstituted the physiology of differentiation. However, architectural differences between the circuits altered the dynamic distribution of stochastic fluctuations (noise) during circuit operation. This distinction in noise causes functional differences between the circuits by selectively controlling the timing of competence episodes and response of the system to various DNA concentrations. These results reveal a tradeoff between temporal precision and physiological response range that is controlled by distinct noise characteristics of alternative circuit architectures

Correlated Prompt Fission Data in Transport Simulations

Detailed information on the fission process can be inferred from the observation, modeling and theoretical understanding of prompt fission neutron and $\gamma$-ray~observables. Beyond simple average quantities, the study of distributions and correlations in prompt data, e.g., multiplicity-dependent neutron and \gray~spectra, angular distributions of the emitted particles, $n$-$n$, $n$-$\gamma$, and $\gamma$-$\gamma$~correlations, can place stringent constraints on fission models and parameters that would otherwise be free to be tuned separately to represent individual fission observables. The FREYA~and CGMF~codes have been developed to follow the sequential emissions of prompt neutrons and $\gamma$-rays~from the initial excited fission fragments produced right after scission. Both codes implement Monte Carlo techniques to sample initial fission fragment configurations in mass, charge and kinetic energy and sample probabilities of neutron and $\gamma$~emission at each stage of the decay. This approach naturally leads to using simple but powerful statistical techniques to infer distributions and correlations among many observables and model parameters. The comparison of model calculations with experimental data provides a rich arena for testing various nuclear physics models such as those related to the nuclear structure and level densities of neutron-rich nuclei, the $\gamma$-ray~strength functions of dipole and quadrupole transitions, the mechanism for dividing the excitation energy between the two nascent fragments near scission, and the mechanisms behind the production of angular momentum in the fragments, etc. Beyond the obvious interest from a fundamental physics point of view, such studies are also important for addressing data needs in various nuclear applications. (See text for full abstract.)Comment: 39 pages, 57 figure files, published in Eur. Phys. J. A, reference added this versio

Injury and Skeletal Biomechanics

This book covers many aspects of Injury and Skeletal Biomechanics. As the title represents, the aspects of force, motion, kinetics, kinematics, deformation, stress and strain are examined in a range of topics such as human muscles and skeleton, gait, injury and risk assessment under given situations. Topics range from image processing to articular cartilage biomechanical behavior, gait behavior under different scenarios, and training, to musculoskeletal and injury biomechanics modeling and risk assessment to motion preservation. This book, together with "Human Musculoskeletal Biomechanics", is available for free download to students and instructors who may find it suitable to develop new graduate level courses and undergraduate teaching in biomechanics

TAO Conceptual Design Report: A Precision Measurement of the Reactor Antineutrino Spectrum with Sub-percent Energy Resolution

The Taishan Antineutrino Observatory (TAO, also known as JUNO-TAO) is a satellite experiment of the Jiangmen Underground Neutrino Observatory (JUNO). A ton-level liquid scintillator detector will be placed at about 30 m from a core of the Taishan Nuclear Power Plant. The reactor antineutrino spectrum will be measured with sub-percent energy resolution, to provide a reference spectrum for future reactor neutrino experiments, and to provide a benchmark measurement to test nuclear databases. A spherical acrylic vessel containing 2.8 ton gadolinium-doped liquid scintillator will be viewed by 10 m^2 Silicon Photomultipliers (SiPMs) of >50% photon detection efficiency with almost full coverage. The photoelectron yield is about 4500 per MeV, an order higher than any existing large-scale liquid scintillator detectors. The detector operates at -50 degree C to lower the dark noise of SiPMs to an acceptable level. The detector will measure about 2000 reactor antineutrinos per day, and is designed to be well shielded from cosmogenic backgrounds and ambient radioactivities to have about 10% background-to-signal ratio. The experiment is expected to start operation in 2022

Studies of Protein-Protein and Protein-Water Interactions by Small Angle X-Ray Scattering, Terahertz Spectroscopy, ASMOS, And Computer Simulation

The protein folding problem has been one of the most challenging subjects in biological physics due to its complexity. Energy landscape theory based on statistical mechanics provides a thermodynamic interpretation of the protein folding process. We have been working to answer fundamental questions about protein-protein and protein-water interactions, which are very important for describing the energy landscape surface of proteins correctly. At first, we present a new method for computing protein-protein interaction potentials of solvated proteins directly from SAXS data. An ensemble of proteins was modeled by Metropolis Monte Carlo and Molecular Dynamics simulations, and the global X-ray scattering of the whole model ensemble was computed at each snapshot of the simulation. The interaction potential model was optimized and iterated by a Levenberg-Marquardt algorithm. Secondly, we report that terahertz spectroscopy directly probes hydration dynamics around proteins and determines the size of the dynamical hydration shell. We also present the sequence and pH-dependence of the hydration shell and the effect of the hydrophobicity. On the other hand, kinetic terahertz absorption (KITA) spectroscopy is introduced to study the refolding kinetics of ubiquitin and its mutants. KITA results are compared to small angle X-ray scattering, tryptophan fluorescence, and circular dichroism results. We propose that KITA monitors the rearrangement of hydrogen bonding during secondary structure formation. Finally, we present development of the automated single molecule operating system (ASMOS) for a high throughput single molecule detector, which levitates a single protein molecule in a 10 µm diameter droplet by the laser guidance. I also have performed supporting calculations and simulations with my own program codes

Measurements, Models, Systems and Design

531 s.

MECHANISTIC MODELS OF INTERACTIONS WITHIN AND BETWEEN MAPK PATHWAYS

Cells use signaling pathways to receive and process information about their environment. Understanding signaling pathways is of particular interest because pathway dysregulation of these pathways is implicated in many human diseases including many types of cancer. In this dissertation, I specifically address understanding interactions that govern response complex dynamics and heterogeneity within and between signaling pathways. In particular, I focus on two well-characterized MAPK pathways with homology to human signaling pathways implicated in cancer, the mating response pathway (homologous to ERK) and the high osmolarity glycerol (HOG) response pathway (homologous to p38) of S. cerevisiae (yeast). Although much is known about the molecular components of these pathways, less is known about how these components function as a dynamical system and regulate heterogeneity in the pathway responses. To address this gap in knowledge, we developed experimental techniques that allow for quantification of response dynamics and variability (Chapter 2). These methods were then applied to develop a predictive, mechanistic model of the dynamics of the mating response pathway (Chapter 3) that elucidates how various signaling motifs contribute to the overall dynamics. Additionally, these methods were used to provide insight into the mechanisms that drive heterogeneity in mating response alone (Chapter 4) and increase heterogeneity in the mating response when the HOG pathway is also active (Chapter 5). Together, the work included in this dissertation reveal how quantitative experimental methods and mathematical models can be integrated to understand aspects of signaling pathway response that could not have otherwise been studied.Doctor of Philosoph

FIRST experiment: measurements of differential cross sections in 12C fragmentation for hadron-therapy and space applications

The aim of the present work is to describe some preliminary results obtained within the experiment FIRST (Fragmentation of Ions Relevant for Space and Therapy). This experiment main goal is to measure the differential cross-sections in energy and angle of nuclear fragmentation processes, in a wide energy range (between 100 and 1000 MeV/n). The knowledge of these cross sections will be useful for cancer therapy and space radiation protection. This experiment was carried out because there is a strong need of high-quality experimental data concerning 12 C, 16 O and 56 Fe fragmentation on different targets. The first data taking has been performed at SIS (Heavy Ion Synchrotron) accelerator of GSI Laboratory in Darmstadt (Germany) during August 2011. Different sets of data have been collected using a 400 MeV/n carbon beam impinging on carbon and gold targets. Experimental data of single and double-differential cross sections for C-ions at energies less or equal to 400 MeV/n are needed to improve treatment plannings in particle-therapy. In particular accurate measurements of cross sections of light ions are urgently needed for improving transport codes to be used in cancer therapy. Algorithms that deal with the transport of charged particle in matter are essential for accurate treatment plannings, in order to evaluate possible long term side effects of dose released in healthy tissue. Unfortunately, the production of light fragments and their angular distribu- tions are affected by large uncertainties and various Monte Carlo codes may differ up to one order of magnitude in their predictions. Moreover, codes used for space radiation transport in shielding materials need more information on the fragmentation effects. Recently, NASA completed a large database of these measurements and observed that there are ion species and kinetic energy ranges not yet evaluated. The FIRST experiment aims to contribute to the knowledge of these nu- clear processes and to investigate the secondary effects on human tissues of hadron’s irradiation. In fact, most of the measurements carried out in the past are limited to fragment yields and to total fragmentation cross-sections, while the required measurements of single or double-differential cross-sections are deficient

An automated growth enclosure for metabolic labeling of Arabidopsis thaliana with 13C-carbon dioxide - an in vivo labeling system for proteomics and metabolomics research

<p>Abstract</p> <p>Background</p> <p>Labeling whole <it>Arabidopsis (Arabidopsis thaliana) </it>plants to high enrichment with ¹³C for proteomics and metabolomics applications would facilitate experimental approaches not possible by conventional methods. Such a system would use the plant's native capacity for carbon fixation to ubiquitously incorporate ¹³C from ¹³CO₂gas. Because of the high cost of ¹³CO₂it is critical that the design conserve the labeled gas.</p> <p>Results</p> <p>A fully enclosed automated plant growth enclosure has been designed and assembled where the system simultaneously monitors humidity, temperature, pressure and ¹³CO₂concentration with continuous adjustment of humidity, pressure and ¹³CO₂levels controlled by a computer running LabView software. The enclosure is mounted on a movable cart for mobility among growth environments. <it>Arabidopsis </it>was grown in the enclosure for up to 8 weeks and obtained on average >95 atom% enrichment for small metabolites, such as amino acids and >91 atom% for large metabolites, including proteins and peptides.</p> <p>Conclusion</p> <p>The capability of this labeling system for isotope dilution experiments was demonstrated by evaluation of amino acid turnover using GC-MS as well as protein turnover using LC-MS/MS. Because this 'open source' <it>Arabidopsis </it>¹³C-labeling growth environment was built using readily available materials and software, it can be adapted easily to accommodate many different experimental designs.</p

Modeling the Representation of Medial Axis Structure in Human Ventral Pathway Cortex

Computational modeling of the human brain has long been an important goal of scientific research. The visual system is of particular interest because it is one of the primary modalities by which we understand the world. One integral aspect of vision is object representation, which plays an important role in machine perception as well.In the human brain, object recognition is a part of the functionality of the ventral pathway. In this work, we have developed a computational and statistical techniques to characterize object representation among this pathway. The understanding of how the brain represents objects is essential to developing models of computer vision that are truer to how humans perceive the world. In the ventral pathway, the lateral occipital complex (LOC) is known to respond to images of objects. Neural recording studies in monkeys have shown that the homologue for LOC represents objects as configurations of medial axis and surface components. In this work, we designed and implemented novel experiment paradigms and developed algorithms to test whether the human LOC represents medial axis structure as in the monkey models. We developed a data-driven iterative sparse regression model guided by neuroscience principles in order to estimate the response pattern of LOC voxels. For each voxel, we modeled the response pattern as a linear combination of partial medial axis configurations that appeared as fragments across multiple stimuli. We used this model to demonstrate evidence of structural object coding in the LOC. Finally, we developed an algorithm to reconstruct images of stimuli being viewed by subjects based on their brain images. As a whole, we apply computational techniques to present the first significant evidence that the LOC carries information about the medial axis structure of objects, and further characterize its response properties