846 research outputs found
Simulations of pion production in the Daedalus targets
DAEDALUS, the Decay At-rest Experiment for DCP at a
Laboratory for Underground Science will look for evidence
of CP-violation in the neutrino sector, an ingredient in theories
that seek to explain the matter/antimatter asymmetry
in our universe. It will make a precision measurement of
the oscillations of muon antineutrinos to electron antineutrinos
using multiple neutrino sources created by low-cost
compact cyclotrons. The experiment utilizes decay-at-rest
neutrino beams produced by 800 MeV protons impinging
a beam target of graphite and copper. Two well established
Monte Carlo codes, MARS and GEANT4, have been used
to optimise the design and the performance of the target. A
study of the results obtained with these two codes is presented
in this paper
Drosophila melanogaster Long Timescale Data 2022
Please see readme file for a full description of this dataset and an orientation to its file structure.This dataset is too large to download directly from this item page. You can access and download the data via Globus at this link: https://app.globus.org/file-manager?destination_id=dc43f461-0ca7-4203-848c-33a9fc00a464&destination_path=%2F1sab-8845%2F (See https://docs.globus.org/how-to/get-started/ for instructions on how to use Globus; sign-in is required).This dataset contains lifetime recordings and associated postural data and ethograms for 47 male Drosophila melanogaster
Unsupervised Quantification of Stereotyped Behavior in Flies and Mice
Recent advances in the study of animal behavior have utilized tools from computer vision and machine learning in order to perform high-throughput behavior quantification. Here, we utilize a behavior analysis paradigm established by Berman et al. (2014). Using a principle component-based approach, raw behavior video data is reduced to a postural time series. A dimensionality reduction approach embeds the dynamics of this time series into a two-dimensional “behavioral map,” and discrete behaviors are identified as peaks in the map's probability density function.
Here, we expand on the work of Berman et al. in two main ways. Firstly, we define a metric for quantifying the stereotypy of a given behavior, based on the variance in a behavior's postural trajectory over many instances of the behavior. We find that most identified behaviors in the fruit fly Drosophila exhibit a high degree of stereotypy, providing support for the view of behavior as a set of discrete states, at least to an approximation.
Additionally, we apply this framework, which was originally developed for Drosophila, to the mouse. The mouse is a prominent model organism in neuroscience research, and we hope that these behavior quantification techniques can be combined with modern neural recording and perturbation techniques in order to understand the mechanisms through which the brain responds to external stimuli and generates complex behaviors. Finally, we utilize proof-of-concept experiments to suggest that our analyses can quantify the behavioral effect of neuropharmacological agents and neural perturbations with optogenetics
Hebrew made easy [electronic resource] : or, a brief introduction to the Hebrew grammar, (upon a new and delightful plan); Whereby our British Gentlemen and Ladies may, in so very short a Time as Twenty-Four Days, learn the most necessary and essential Variations of that incomparable Language, without the Help of the Latin, or the Assistance of a Master. The second edition, with additions. By the author of The great importance of the Hebrew language.
The author of "The great importance of the Hebrew language" = Joshua Kettilby.Kettilby's 'Hebrew made easy' was first published in [1760?] (c.f.t123545). 'The excellency and great importance of the Hebrew language ... by Joshua Kettilby, author of Hebrew made easy' was published in 1762 (c.f.t183663)Electronic reproduction.English Short Title Catalog,Reproduction of original from Bodleian Library (Oxford)
Behavior at High Resolution
The physics of animal behavior is at an exciting time where an explosion of new computational tools and techniques is giving us access to unprecedented amounts of high quality data. With these superior data, we can probe long standing questions in the physics behavior about the temporal structure of behavior, the impact of biological factors on behavior, and how internal state and external context modulate behavior. Here I present two projects that take advantage of the opportunities created by these advances to examine behavior at high resolution.
An ongoing area of interest in the physics of behavior is the temporal structure of animal behavior. Progress has been limited by the availability of long timescale data sets. We set out to provide a new high resolution \textit{Drosophila melanogaster} data set as a resource to the field of the physics of behavior. We developed a methodology to capture and process high resolution, high frame rate, continuous recordings of freely behaving \textit{Drosophila melanogaster} over the course of 4-7 days of life. Our data captures well known behavior effects, such as habituation to new environments and circadian rhythms of locomotion. This data set will provide a foundation upon which the field can build our next generation of computational and analytical advances.
We also leverage the tools of computational ethology to quantify and study bumblebee social behaviors. We perturbed the early life social environment of \textit{Bombus impatiens} by isolating them from their natal colony during a critical brain development period. We then assayed their behaviors both alone and in pairs. We found that isolation altered behavioral biases in solo social contexts. We also found significant perturbations to social behaviors, including altered reactions to proximity with a social partner and a loss of specificity in antennation behaviors. This, in combination with the neurogenomic effects found by our collaborators, shows that early life social isolation has a significant effect on neurogenomic development and later solo and social behaviors
Multimodal behavioral aging profiles in Drosophila models of human neurodegenerative diseases
Neurodegenerative diseases are highly disruptive, and they play critical roles in end of life
behavior. Much of the literature on neurodegenerative disease focuses on biochemical and
physiological decline with age, but fails to rigorously categorize the vast set of behavioral
changes that occur. In order to gain a more complete understanding of neurodegeneration,
we use a data-driven approach to construct a space that describes the complete set of
behaviors demonstrated by Drosophila melanogaster. By examining differences in the types
of behaviors and rate of aging in three neurodegenerative models, we observe non-monotonic
aging profiles that differ across the mutants. Closer examination of individual behaviors
in these profiles indicates that behaviors do not necessarily covary with age, nor are they
affected by each neurodegenerative disease in the same manner. This finding emphasizes
the importance of studying nuanced behavioral change at a more granular level, since
neurodegeneration gives rise to non-monotonic behavioral aging profiles that show distinct
modular patterns
The mechanical basis of Myxococcus xanthus self-organization and motility: from single cells to collective behavior
Many living organisms exhibit complicated but highly organized collective behaviors. Unlike passive systems whose dynamics are driven by thermal energy, living organisms are often active systems, in which motilities of individuals put the system far away from equilibrium. Naturally living in soil, social bacteria Myxococcus xanthus exhibits a series of fascinating self-organizing behaviors throughout its developmental cycle, including swarming during vegetative growth, forming rippling waves during predation, and aggregating into fruiting bodies when starved. In this thesis, I use M. xanthus as a model system and explore the mechanical basis behind its motility and self-organization. My work emphasizes on the utilization of microscopy, image processing techniques and data-driven analysis in the examination of M. xanthus on different scales. We first study M. xanthus fruiting body formation based on the statistical physics of active populations. We show that the aggregation process in M. xanthus resembles the dynamics of a spinodal decomposition phase separation. Modeling M. xanthus as active brownian particles, we demonstrate that the phase separation can be understood in terms of cell density and the Peclet number that captures the cell motility regarding its speed and reversal frequency. M. xanthus cells actively take advantage of their cellular control of motility to drive large scale aggregation by promoting gliding speed and suppressing reversals to increase motility persistence. Then we characterize the rippling behavior of M. xanthus both on single cell motility level and on population level. We find tracking data of single cells during rippling lacks the evidence to support the cell motion synchronization hypothesis. Using two different image processing techniques, we are able to characterize low density rippling structures by estimating local cell density. We further examine the high density rippling wave structures using a 3D laser microscope. Finally, we study the force generation mechanism of two distinct motility systems in M. xanthus. We find that cells use these motility systems in coordination while in groups. These results not only provided further understandings of the scale of forces M. xanthus experiences and exerts, but also suggests that M. xanthus mainly utilizes gliding motility during group migration
Exploring the dynamic 3D world inside bacteria with advanced optical microscopy
The bacterial cytoplasm is extremely crowded and polydisperse, with biomolecules spanning many orders of magnitude in size and electrical charge. In Chapter 2, we study this environment by reconstructing the 3D motion of size and charge-controlled nanoparticles (GEMs) with nanometer-scale resolution in live Escherichia coli cells. GEMs range in size from 20 to 50 nm and in charge from -2160 to 1800 e, similar to important macromolecules. In collaboration with theorists at Stanford, we show that GEMs spatially segregate by size and charge due to cytoplasmic polydispersity and charge interactions with cellular components.
Using biplane microscopy for 3D tracking, Monte Carlo simulations, and full-cell colloidal simulations by our collaborators, we find that regardless of charge and particle size, the motion in bacterial cells is mostly normally diffusive. However, this motion appears sub-diffusive due to geometrical confinement to the small cellular volume.
We make progress towards understanding the role of chromosome remodeling on particle diffusion in bacterial cells. We show that 50 nm GEMs in exponentially growing cells experience caging, inhibiting the motion of a fraction of the particles. This caging does not occur for smaller GEMs in exponential phase or for 50 nm GEMs in stationary phase cells, suggesting that caging stems from the DNA pore size and active chromosomal re-arrangements.
Most of this thesis focuses on freely diffusing particles. However, there is a wealth of interesting phenomena occurring in tethered systems, where particle localization is determined by the anchoring of the molecule, and both the local environment and the tethering action influence dynamics. This is the case for chromosomal loci. In Chapter 4, I conclude by describing steps we have taken towards studying the physics of the bacterial chromosome and propose experiments to study this system using the techniques developed in Chapter 2.
In Chapter 3, I present our work rebuilding and optimizing a Stimulated Emission Depletion super resolution microscope. This technique enables sub-diffraction limit imaging by using optical patterning to selectively de-activate fluorescent probes during image acquisition. Although modest super-resolution was achieved, the microscope was never used for biological imaging due to its optical and biological limitations
The Role of MreB in E. coli Shape Determination and Whole-Brain Calcium Dynamics in Freely Behaving C. elegans
Bacteria have remarkably robust cell shape control mechanisms, but the mechanisms of self-organization for robust morphological maintenance remain unclear in most systems. Precise regulation of rod shape in Escherichia coli cells requires the MreB actin-like cytoskeleton, but the mechanism by which MreB maintains rod shape and sets the cell diameter is unknown. Here, I study both of these mechanisms using a novel method for extracting the 3D shape of cells using fluorescence image stacks and forward convolution. I then use time-lapse and 3D imaging coupled with computational analysis to map the growth, geometry, and cytoskeletal organization of single bacterial. Our results demonstrate that feedback between cell geometry and MreB localization maintains rod-like cell shape by targeting cell wall growth to regions of negative cell wall curvature.
I also study how MreB sets the diameter of a cell. Here, I perturb MreB by treating cells with the drug A22 or by creating mreb point mutants. These perturbations modify the steady state diameter of cells to between 790±30 nm to 1700±20 nm. I correlated structural characteristics of fluorescently-tagged MreB polymers to cell diameter and show that the helical pitch angle of MreB inversely correlates with the cell diameter of E. coli. These results demonstrate that the physical properties of MreB filaments are important for shape control and support a model in which MreB organizes the cell wall growth machinery to produce a chiral cell wall structure and dictates cell diameter.
After investigating the control of bacterial cell shape, I study an interesting problem in neuroscience. The ability to acquire large-scale recordings of neuronal activity in freely behaving animals is needed to provide new insights into how populations of neurons generate behavior. I present a new instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal's behavior. We observe calcium transients from 89 neurons for nearly four minutes and correlate this activity with the animal's behavior. We show that, across worms, multiple neurons show significant correlations with, backward, and turning locomotion
Statistical Analysis of Transcription Locations in Early Drosophila Development
New technologies have allowed for precise measurements of transcription
locations in living Drosophila embryos. The ability to track transcription
as it happens means that new avenues of exploration become possible.
One of these avenues is tracking the random motion of these transcription
locations. This paper covers the theoretical background behind random
walks and transcription and ultimately analyzes transcription locations in
order to create a model for their movement
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