978 research outputs found

    Northerners\u27 Perspectives on American Emancipation and the End of Russian Serfdom

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    This thesis explores the various perspectives that Northern Americans had on Russian serfdom and its emancipation. This era was significant to both Russia and the United States because each country experienced tremendous reforms including the abolitions of their unfree labor institutions. Generally, Northern Americans viewed serfdom as a milder form of forced labor and suspected that it would be eradicated soon. Abolitionists used rumors of Russian emancipation to advocate for the end of American slavery. Diminishing the realities of serfdom in the American media was a way for abolitionists to condemn the brutality of American slavery by comparison. After the Civil War ended, Reconstruction era politics shaped the way political party-endorsing newspapers would report on the progress of emancipation and reforms in Russia. This thesis will also analyze the frequency of American reports on Russian serfdom and the progress of its emancipation during the Antebellum era while considering the political affiliation of the news sources when possible. Overall, this thesis provides a much-needed examination of the transnational effect of Russian Emancipation on Northern Americans, the Union effort, and the movement to abolish slavery in America

    Comparative analysis of metazoan chromatin organization

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    Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal ‘arms’, and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.National Science Foundation (U.S.) (1122374

    Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo

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    RNA has a dual role as an informational molecule and a direct effector of biological tasks. The latter function is enabled by RNA’s ability to adopt complex secondary and tertiary folds and thus has motivated extensive computational and experimental efforts for determining RNA structures. Existing approaches for evaluating RNA structure have been largely limited to in vitro systems, yet the thermodynamic forces which drive RNA folding in vitro may not be sufficient to predict stable RNA structures in vivo. Indeed, the presence of RNA-binding proteins and ATP-dependent helicases can influence which structures are present inside cells. Here we present an approach for globally monitoring RNA structure in native conditions in vivo with single-nucleotide precision. This method is based on in vivo modification with dimethyl sulphate (DMS), which reacts with unpaired adenine and cytosine residues, followed by deep sequencing to monitor modifications. Our data from yeast and mammalian cells are in excellent agreement with known messenger RNA structures and with the high-resolution crystal structure of the Saccharomyces cerevisiae ribosome. Comparison between in vivo and in vitro data reveals that in rapidly dividing cells there are vastly fewer structured mRNA regions in vivo than in vitro. Even thermostable RNA structures are often denatured in cells, highlighting the importance of cellular processes in regulating RNA structure. Indeed, analysis of mRNA structure under ATP-depleted conditions in yeast shows that energy-dependent processes strongly contribute to the predominantly unfolded state of mRNAs inside cells. Our studies broadly enable the functional analysis of physiological RNA structures and reveal that, in contrast to the Anfinsen view of protein folding whereby the structure formed is the most thermodynamically favourable, thermodynamics have an incomplete role in determining mRNA structure in vivo

    EFFECTS OF A 10 WEEK TRAINING PROGRAM ON PHYSICAL CONDITIONING AND INSTEP KICK KINEMATICS IN SOCCER

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    The instep kick is the kick of choice in soccer scoring and passing over medium to long distances. Its success depends on many factors including the strength of the muscles responsible for the actions of the (kicking lower) extremity, the rate of muscle force production, the synchronization and energy transfer between lower extremity segments (Plagenhoef, 1971), the linear approach velocity (Opavsky, 1988) and approach angle (Isokawa and Less, 1988), and the ability of muscle to utilize effectively the stretch/shorten cycle (BOhrle, 1985). Ultimately, on a given kick, the velocity of the kicking foot and the point of (foot) force application on the ball determine the trajectory characteristics of the ball. Other factors such as flexibility and aerobic/anaerobic capacities also determine the ability of players to successfully perform in a game. The purpose of this study was to study the effects of a 10 week training program on selected physical conditioning and instep kick kinematic parameters in soccer

    Utility and lower limits of frequency detection in surface electrode stimulation for somatosensory brain-computer interface in humans

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    Objective: Stimulation of the primary somatosensory cortex (S1) has been successful in evoking artificial somatosensation in both humans and animals, but much is unknown about the optimal stimulation parameters needed to generate robust percepts of somatosensation. In this study, the authors investigated frequency as an adjustable stimulation parameter for artificial somatosensation in a closed-loop brain-computer interface (BCI) system. Methods: Three epilepsy patients with subdural mini-electrocorticography grids over the hand area of S1 were asked to compare the percepts elicited with different stimulation frequencies. Amplitude, pulse width, and duration were held constant across all trials. In each trial, subjects experienced 2 stimuli and reported which they thought was given at a higher stimulation frequency. Two paradigms were used: first, 50 versus 100 Hz to establish the utility of comparing frequencies, and then 2, 5, 10, 20, 50, or 100 Hz were pseudorandomly compared. Results: As the magnitude of the stimulation frequency was increased, subjects described percepts that were “more intense” or “faster.” Cumulatively, the participants achieved 98.0% accuracy when comparing stimulation at 50 and 100 Hz. In the second paradigm, the corresponding overall accuracy was 73.3%. If both tested frequencies were less than or equal to 10 Hz, accuracy was 41.7% and increased to 79.4% when one frequency was greater than 10 Hz (p = 0.01). When both stimulation frequencies were 20 Hz or less, accuracy was 40.7% compared with 91.7% when one frequency was greater than 20 Hz (p < 0.001). Accuracy was 85% in trials in which 50 Hz was the higher stimulation frequency. Therefore, the lower limit of detection occurred at 20 Hz, and accuracy decreased significantly when lower frequencies were tested. In trials testing 10 Hz versus 20 Hz, accuracy was 16.7% compared with 85.7% in trials testing 20 Hz versus 50 Hz (p < 0.05). Accuracy was greater than chance at frequency differences greater than or equal to 30 Hz. Conclusions: Frequencies greater than 20 Hz may be used as an adjustable parameter to elicit distinguishable percepts. These findings may be useful in informing the settings and the degrees of freedom achievable in future BCI systems

    Parietal neural prosthetic control of a computer cursor in a graphical-user-interface task

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    Objective. To date, the majority of Brain–Machine Interfaces have been used to perform simple tasks with sequences of individual targets in otherwise blank environments. In this study we developed a more practical and clinically relevant task that approximated modern computers and graphical user interfaces (GUIs). This task could be problematic given the known sensitivity of areas typically used for BMIs to visual stimuli, eye movements, decision-making, and attentional control. Consequently, we sought to assess the effect of a complex, GUI-like task on the quality of neural decoding. Approach. A male rhesus macaque monkey was implanted with two 96-channel electrode arrays in area 5d of the superior parietal lobule. The animal was trained to perform a GUI-like 'Face in a Crowd' task on a computer screen that required selecting one cued, icon-like, face image from a group of alternatives (the 'Crowd') using a neurally controlled cursor. We assessed whether the crowd affected decodes of intended cursor movements by comparing it to a 'Crowd Off' condition in which only the matching target appeared without alternatives. We also examined if training a neural decoder with the Crowd On rather than Off had any effect on subsequent decode quality. Main results. Despite the additional demands of working with the Crowd On, the animal was able to robustly perform the task under Brain Control. The presence of the crowd did not itself affect decode quality. Training the decoder with the Crowd On relative to Off had no negative influence on subsequent decoding performance. Additionally, the subject was able to gaze around freely without influencing cursor position. Significance. Our results demonstrate that area 5d recordings can be used for decoding in a complex, GUI-like task with free gaze. Thus, this area is a promising source of signals for neural prosthetics that utilize computing devices with GUI interfaces, e.g. personal computers, mobile devices, and tablet computers

    Pareto-optimal phylogenetic tree reconciliation

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    Motivation: Phylogenetic tree reconciliation is a widely used method for reconstructing the evolutionary histories of gene families and species, hosts and parasites and other dependent pairs of entities. Reconciliation is typically performed using maximum parsimony, in which each evolutionary event type is assigned a cost and the objective is to find a reconciliation of minimum total cost. It is generally understood that reconciliations are sensitive to event costs, but little is understood about the relationship between event costs and solutions. Moreover, choosing appropriate event costs is a notoriously difficult problem. Results: We address this problem by giving an efficient algorithm for computing Pareto-optimal sets of reconciliations, thus providing the first systematic method for understanding the relationship between event costs and reconciliations. This, in turn, results in new techniques for computing event support values and, for cophylogenetic analyses, performing robust statistical tests. We provide new software tools and demonstrate their use on a number of datasets from evolutionary genomic and cophylogenetic studies.National Science Foundation (U.S.) (CAREER award 0644282)University of Connecticut (Startup funds)Harvey Mudd College (R. Michael Shanahan Endowment

    Position specific variation in the rate of evolution in transcription factor binding sites

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    BACKGROUND: The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. RESULTS: Here we analyse the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikatae to study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artefacts of computational motif finding algorithms. CONCLUSION: As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative sequence data in the identification of transcription factor binding sites and is an important step toward understanding the evolution of functional non-coding DNA

    Primary somatosensory cortex organization for engineering artificial somatosensation

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    \ua9 2024 The Authors. Somatosensory deficits from stroke, spinal cord injury, or other neurologic damage can lead to a significant degree of functional impairment. The primary (SI) and secondary (SII) somatosensory cortices encode information in a medial to lateral organization. SI is generally organized topographically, with more discrete cortical representations of specific body regions. SII regions corresponding to anatomical areas are less discrete and may represent a more functional rather than topographic organization. Human somatosensory research continues to map cortical areas of sensory processing with efforts primarily focused on hand and upper extremity information in SI. However, research into SII and other body regions is lacking. In this review, we synthesize the current state of knowledge regarding the cortical organization of human somatosensation and discuss potential applications for brain computer interface. In addition to accurate individualized mapping of cortical somatosensation, further research is required to uncover the neurophysiological mechanisms of how somatosensory information is encoded in the cortex
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