1,298 research outputs found

    An Examination of Citizens United: Where We\u27re Going and How We Got There

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    Citizens United v. Federal Elections Commission (2010) has been touted as both champion and destroyer of First Amendment free speech rights. It remains a controversial decision of which we are only beginning to see its true effects. The case brought rise to the Super PACs commonly denounced in the media and the vast amount of money that comes with them. We have seen negative and positive campaign ads that candidates for election don’t have to answer to. In order to truly understand these effects, I examined the Supreme Court’s decision to determine its line of reasoning as well as media reactions to the case results. Many have expressed concern over a corporation’s ability to buy elections by using their monetary resources for political advertisements. Others have taken a more humorous approach to the case outcome in order to explain the new regulations, or lack thereof, to the general public. While it is still too early to tell just how much PACs could affect the election process, it is clear that there has been a large amount of money (over $88 million on the 2012 election cycle alone) spent on media (such as television and radio advertisements) related to candidates for political office. Most of these advertisements have been negative in hopes of dissuading voters from certain candidates. More in-depth research would be required to determine how effective these ads are and ultimately how much of a true effect the extra money has made on the system

    Tuning transcriptional regulation through signaling: A predictive theory of allosteric induction

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    Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response. Our model not only accurately captures the induction profiles of these strains but also enables us to derive analytic expressions for key properties such as the dynamic range and [EC50][EC_{50}]. Finally, we derive an expression for the free energy of allosteric repressors which enables us to collapse our experimental data onto a single master curve that captures the diverse phenomenology of the induction profiles.Comment: Substantial revisions for resubmission (3 new figures, significantly elaborated discussion); added Professor Mitchell Lewis as another author for his continuing contributions to the projec

    The Energetics of Molecular Adaptation in Transcriptional Regulation

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    Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level responses. Here, we present a framework centered on measuring changes in the free energy of the system to link individual mutations in an allosteric transcriptional repressor to the parameters which govern its response. We find the energetic effects of the mutations can be categorized into several classes which have characteristic curves as a function of the inducer concentration. We experimentally test these diagnostic predictions using the well-characterized LacI repressor of Escherichia coli, probing several mutations in the DNA binding and inducer binding domains. We find that the change in gene expression due to a point mutation can be captured by modifying only a subset of the model parameters that describe the respective domain of the wild-type protein. These parameters appear to be insulated, with mutations in the DNA binding domain altering only the DNA affinity and those in the inducer binding domain altering only the allosteric parameters. Changing these subsets of parameters tunes the free energy of the system in a way that is concordant with theoretical expectations. Finally, we show that the induction profiles and resulting free energies associated with pairwise double mutants can be predicted with quantitative accuracy given knowledge of the single mutants, providing an avenue for identifying and quantifying epistatic interactions.Comment: 11 pages, 6 figures, supplemental info. available via http://rpgroup.caltech.edu/mwc_mutant

    Taxonomic Features and Comparison of the Gut Microbiome from Two Edible Fungus-Farming Termites (Macrotermes falciger, M. natalensis) Harvested in the Vhembe District of Limpopo, South Africa

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    Background Termites are an important food resource for many human populations around the world, and are a good supply of nutrients. The fungus-farming ‘higher’ termite members of Macrotermitinae are also consumed by modern great apes and are implicated as critical dietary resources for early hominins. While the chemical nutritional composition of edible termites is well known, their microbiomes are unexplored in the context of human health. Here we sequenced the V4 region of the 16S rRNA gene of gut microbiota extracted from the whole intestinal tract of two Macrotermes sp. soldiers collected from the Limpopo region of South Africa. Results Major and minor soldier subcastes of M. falciger exhibit consistent differences in taxonomic representation, and are variable in microbial presence and abundance patterns when compared to another edible but less preferred species, M. natalensis. Subcaste differences include alternate patterns in sulfate-reducing bacteria and methanogenic Euryarchaeota abundance, and differences in abundance between Alistipes and Ruminococcaceae. M. falciger minor soldiers and M. natalensissoldiers have similar microbial profiles, likely from close proximity to the termite worker castes, particularly during foraging and fungus garden cultivation. Compared with previously published termite and cockroach gut microbiome data, the taxonomic representation was generally split between termites that directly digest lignocellulose and humic substrates and those that consume a more distilled form of nutrition as with the omnivorous cockroaches and fungus-farming termites. Lastly, to determine if edible termites may point to a shared reservoir for rare bacterial taxa found in the gut microbiome of humans, we focused on the genus Treponema. The majority of Treponemasequences from edible termite gut microbiota most closely relate to species recovered from other termites or from environmental samples, except for one novel OTU strain, which clustered separately with Treponema found in hunter-gatherer human groups. Conclusions Macrotermes consumed by humans display special gut microbial arrangements that are atypical for a lignocellulose digesting invertebrate, but are instead suited to the simplified nutrition in the fungus-farmer diet. Our work brings to light the particular termite microbiome features that should be explored further as avenues in human health, agricultural sustainability, and evolutionary research

    SIG-DB: leveraging homomorphic encryption to Securely Interrogate privately held Genomic DataBases

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    Genomic data are becoming increasingly valuable as we develop methods to utilize the information at scale and gain a greater understanding of how genetic information relates to biological function. Advances in synthetic biology and the decreased cost of sequencing are increasing the amount of privately held genomic data. As the quantity and value of private genomic data grows, so does the incentive to acquire and protect such data, which creates a need to store and process these data securely. We present an algorithm for the Secure Interrogation of Genomic DataBases (SIG-DB). The SIG-DB algorithm enables databases of genomic sequences to be searched with an encrypted query sequence without revealing the query sequence to the Database Owner or any of the database sequences to the Querier. SIG-DB is the first application of its kind to take advantage of locality-sensitive hashing and homomorphic encryption to allow generalized sequence-to-sequence comparisons of genomic data.Comment: 38 pages, 3 figures, 4 tables, 1 supplemental table, 7 supplemental figure

    Test-Retest Reliability and Minimum Detectable Change for Various Frontal Plane Projection Angles during Dynamic Tasks

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    Objective: Establish between-day test-retest reliability metrics for 2-dimensional frontal plane projection angles (FPPAs) during the lateral step-down (LSD), single-limb squat (SLS), single-limb landing (SLL), and drop vertical jump (DVJ). Design: Test-retest reliability study Setting: University laboratory Participants: 20 healthy adults (12 female, age = 23.60±1.93 years old, body mass index = 24.26±2.54 kg/m2) were tested on 2 separate occasions 7-14 days apart. Main Outcome Measures: Intraclass correlation coefficients (ICC), standard errors of the measurement (SEM), and minimal detectable change (MDC) values across the LSD, SLS, SLL, and DVJ for the following body region variables: trunk, trunk on pelvis, pelvis, hip, thigh to vertical, knee, and shank to vertical. Results: There was moderate-to-substantial between-day test-retest reliability for nearly all body regions across all tasks (ICC = 0.65-0.96). SEM values varied across body regions and tasks (0.9-3.5 degrees). MDCs were variable (2.3-9.8 degrees). Of the body regions, MDCs were largest for the knee and hip. By task, MDCs were lowest for the LSD. Conclusions: This study identified between-day test-retest reliability metrics for 2-dimensional FPPAs across a variety of body regions during commonly assessed clinical tasks. These data allow clinicians and researchers to more confidently assess true change between assessments or over time

    The development of strain typical defensive patterns in the play fighting of laboratory rats

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    Open access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesDuring play fighting, rats attack and defend the nape, which if contacted is nuzzled with the snout. While all strains of rats use the same suite of defensive tactics to protect the nape, different strains use some tactics more frequently. This study tests two hypotheses for this strain difference: (1) each strain has a preference for using particular tactics and (2) strain differences in defense are a byproduct of strain differences in patterns of nape attack. Juvenile Long-Evans (LE) and Sprague-Dawley (SD) males, raised in same strain quads from shortly after weaning to the early juvenile period (i.e., 24-31 days), were tested with unfamiliar same-strain and different-strain partners (Experiment 1) and LE and SD males raised in mixed LE-SD quads were tested with both familiar (Experiment 2) and unfamiliar same-strain and different-strain partners. If hypothesis (1) were true, they would maintain strain-typical defense patterns irrespective of the strain of the attacking partner, whereas if hypothesis (2) were true, it would vary with the strain of the attacking partner. Hypothesis (1) was supported in the first experiment; all the rats maintained their strain-typical patterns regardless of the partner’s strain. However, Experiments 2 and 3 supported neither hypothesis, as each animal displayed strain-divergent behavior when playing with partners of either strain. Given that in Experiments 2 and 3, subjects were reared in mixed-strain groups, it is possible that, during the early juvenile period, play fighting experiences shape strain-typical patterns of use of defensive tactics.Ye

    The Relation Between Galaxy ISM and Circumgalactic OVI Gas Kinematics Derived from Observations and Λ\LambdaCDM Simulations

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    We present the first galaxy-OVI absorption kinematic study for 20 absorption systems (EW>0.1~{\AA}) associated with isolated galaxies (0.15<z<<z<0.55) that have accurate redshifts and rotation curves obtained using Keck/ESI. Our sample is split into two azimuthal angle bins: major axis (Ί<25∘\Phi<25^{\circ}) and minor axis (Ί>33∘\Phi>33^{\circ}). OVI absorption along the galaxy major axis is not correlated with galaxy rotation kinematics, with only 1/10 systems that could be explained with rotation/accretion models. This is in contrast to co-rotation commonly observed for MgII absorption. OVI along the minor axis could be modeled by accelerating outflows but only for small opening angles, while the majority of the OVI is decelerating. Along both axes, stacked OVI profiles reside at the galaxy systemic velocity with the absorption kinematics spanning the entire dynamical range of their galaxies. The OVI found in AMR cosmological simulations exists within filaments and in halos of ~50 kpc surrounding galaxies. Simulations show that major axis OVI gas inflows along filaments and decelerates as it approaches the galaxy while increasing in its level of co-rotation. Minor axis outflows in the simulations are effective within 50-75 kpc beyond that they decelerate and fall back onto the galaxy. Although the simulations show clear OVI kinematic signatures they are not directly comparable to observations. When we compare kinematic signatures integrated through the entire simulated galaxy halo we find that these signatures are washed out due to full velocity distribution of OVI throughout the halo. We conclude that OVI alone does not serve as a useful kinematic indicator of gas accretion, outflows or star-formation and likely best probes the halo virial temperature.Comment: 24 pages, 21 figures, 4 tables. Accepted to ApJ on November 14, 201

    A Quantitative Meta-Analysis of Functional Imaging Studies of Social Rejection

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    Early neuroimaging studies using Cyberball suggested that social rejection activated the pain matrix, as identified in studies of physical pain. However, these early studies were characterized by small sample sizes. Our statistical multi-level kernel density analysis (MKDA) of Cyberball neuroimaging studies with 244 participants fails to support the claim that social rejection operates on the same pain matrix as nociceptive stimuli, questioning whether social pain is more figurative or literal. We also performed an MKDA of the neuroimaging studies of reliving a romantic rejection to test whether the pain matrix was activated if the rejection were more meaningful. Results again failed to support the notion that rejection activates the neural matrix identified in studies of physical pain. Reliving an unwanted rejection by a romantic partner was significantly characterized by activation within and beyond the “Cyberball” brain network, suggesting that the neural correlates of social pain are more complex than previously thought
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