337 research outputs found
Swing State Rulings on Restrictive Voting Laws Highlight the Need for Comprehensive Electoral Reform
The right to elect our leaders has been one of the defining features of America\u27s political system from its very beginning. Throughout the two and a half centuries that the United States has existed, that right to vote has gradually been expanded to previously disenfranchised groups, and strengthened through legislation like the Voting Rights Act, Help America Vote Act, and National Voter Registration Act. However, recent elections-such as Florida in 2000 and Ohio in 2004-have shown that the right to vote can still be undermined by incompetent or conflicted officials. Additionally, measures whose purpose is ostensibly to prevent voter fraud, such as voter identification (ID) laws and rules regarding voter registration, can also have a disenfranchising effect. This Comment reviews these recent problems, and proposes that state-by-state administration of Federal elections is no longer adequate to ensure that all eligible voters are enfranchised. Instead, standardized national rules and independent, nonpartisan election commissions should govern Federal elections
Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages.
International audienceFollowing infection, HIV establishes reservoirs within tissues that are inaccessible to optimal levels of antiviral drugs or within cells where HIV lies latent, thus escaping the action of anti-HIV drugs. Macrophages are a persistent reservoir for HIV and may contribute to the rebound viremia observed after antiretroviral treatment is stopped. In this study, we further investigate the potential of poly(lactic-co-glycolic) acid (PLGA)-based nanocarriers as a new strategy to enhance penetration of therapeutic molecules into macrophages. We have prepared stable PLGA nanoparticles (NPs) and evaluated their capacity to transport an active molecule into the human monocyte/macrophage cell line THP-1 using bovine serum albumin (BSA) as a proof-of-concept compound. Intracellular localization of fluorescent BSA molecules encapsulated into PLGA NPs was monitored in live cells using confocal microscopy, and cellular uptake was quantified by flow cytometry. In vitro and in vivo toxicological studies were performed to further determine the safety profile of PLGA NPs including inflammatory effects. The size of the PLGA NPs carrying BSA (PLGA-BSA) in culture medium containing 10% serum was ~126 nm in diameter, and they were negatively charged at their surface (zeta potential =-5.6 mV). Our confocal microscopy studies and flow cytometry data showed that these PLGA-BSA NPs are rapidly and efficiently taken up by THP-1 monocyte-derived macrophages (MDMs) at low doses. We found that PLGA-BSA NPs increased cellular uptake and internalization of the protein in vitro. PLGA NPs were not cytotoxic for THP-1 MDM cells, did not modulate neutrophil apoptosis in vitro, and did not show inflammatory effect in vivo in the murine air pouch model of acute inflammation. In contrast to BSA alone, BSA encapsulated into PLGA NPs increased leukocyte infiltration in vivo, suggesting the in vivo enhanced delivery and protection of the protein by the polymer nanocarrier. We demonstrated that PLGA-based nanopolymer carriers are good candidates to efficiently and safely enhance the transport of active molecules into human MDMs. In addition, we further investigated their inflammatory profile and showed that PLGA NPs have low inflammatory effects in vitro and in vivo. Thus, PLGA nanocarriers are promising as a drug delivery strategy in macrophages for prevention and eradication of intracellular pathogens such as HIV and Mycobacterium tuberculosis
Air pollution in the week prior to delivery and preterm birth in 24 Canadian cities: a time to event analysis.
BACKGROUND: Numerous studies have examined the association between air pollution and preterm birth (< 37 weeks gestation) but findings have been inconsistent. These associations may be more difficult to detect than associations with other adverse birth outcomes because of the different duration of exposure in preterm vs. term births, and the existence of seasonal cycles in incidence of preterm birth. METHODS: We analyzed data pertaining to 1,001,700 singleton births occurring between 1999 and 2008 in 24 Canadian cities where daily air pollution data were available from government monitoring sites. In the first stage, data were analyzed in each city employing Cox proportional hazards models using gestational age in days as the time scale, obtaining city-specific hazard ratios (HRs) with their 95% confidence intervals (CIs) expressed per interquartile range (IQR) of each air pollutant. Effects were examined using distributed lag functions for lags of 0-6 days prior to delivery, as well as cumulative lags from two to six days. We accounted for the potential nonlinear effect of daily mean ambient temperature using a cubic B-spline with three internal knots. In the second stage, we pooled the estimated city-specific hazard ratios using a random effects model. RESULTS: Pooled estimates across 24 cities indicated that an IQR increase in ozone (O3, 13.3 ppb) 0-3 days prior to delivery was associated with a hazard ratio of 1.036 (95% CI 1.005, 1.067) for preterm birth, adjusting for infant sex, maternal age, marital status and country of birth, neighbourhood socioeconomic status (SES) and visible minority, temperature, year and season of birth, and a natural spline function of day of year. There was some evidence of effect modification by gestational age and season. Associations with carbon monoxide, nitrogen dioxide, particulate matter, and sulphur dioxide were inconsistent. CONCLUSIONS: We observed associations between daily O3 in the week before delivery and preterm birth in an analysis of approximately 1 million births in 24 Canadian cities between 1999 and 2008. Our analysis is one of a limited number which have examined these short term associations employing Cox proportional hazards models to account for the different exposure durations of preterm vs. term births
Phenotypic plasticity enables considerable acclimation to heat and drought in a cold-adapted boreal forest tree species
Increasing frequencies of severe heat waves and drought are expected to influence the composition and functioning of ecosystems globally. Our ability to predict and mitigate these impacts depends on our understanding of species- and age-specific responses to these stressors. To assess the adaptive capacity of balsam fir to climate change, a cold-adapted boreal tree species, we conducted a climate-controlled greenhouse experiment with four provenances originating from across the species biogeographic range, 12 temperature treatments ensuring a minimum of +11°C warming, and five drought treatment intensities. We found considerable acclimation to temperature and drought treatments across all provenances, with steady gains in biomass under temperatures well-beyond the “worst-case” (RCP 8.5) climate forcing scenario within the species natural range. Acclimation was supported by high phenotypic plasticity in root:shoot ratio (RSR) and photosynthesis, which were greatly increased with warming, but were not affected by drought. Our results suggest that regardless of the observed provenance variation, drought and heat are not limiting factors of the current-year balsam fir seedling growth, instead, these factors may be more impactful on later stages of regeneration or previously stressed individuals, thus highlighting the necessity of incorporating the factors of ontogeny and provenance origin in future research regarding plant and climate interactions
Near-Infrared Spectroscopy of the Extrasolar Planet HR 8799 b
[Abridged] We present 2.12-2.23 um high contrast integral field spectroscopy
of the extrasolar planet HR 8799 b. Our observations were obtained with OSIRIS
on the Keck II telescope and sample the 2.2 um CH4 feature, which is useful for
spectral classification and as a temperature diagnostic for ultracool objects.
The spectrum of HR 8799 b is relatively featureless, with little or no methane
absorption, and does not exhibit the strong CH4 seen in T dwarfs of similar
absolute magnitudes. Overall, we find that HR 8799 b has a spectral type
consistent with L5-T2, although its SED is atypical compared to most field
objects. We fit the 2.2 um spectrum and the infrared SED using the Hubeny &
Burrows, Burrows et al., and Ames-Dusty model atmosphere grids, which
incorporate nonequilibrium chemistry, non-solar metallicities, and clear and
cloudy variants. No models agree with all of the data, but those with
intermediate clouds produce significantly better fits. The largest discrepancy
occurs in the J-band, which is highly suppressed in HR 8799 b. The best-fitting
effective temperatures range from 1300-1700 K with radii between ~0.3-0.5 RJup.
These values are inconsistent with evolutionary model-derived values of 800-900
K and 1.1-1.3 RJup based on the luminosity of HR 8799 b and the age of HR 8799,
a discrepancy that probably results from imperfect atmospheric models or the
limited range of physical parameters covered by the models. The low temperature
inferred from evolutionary models indicates that HR 8799 b is ~400 K cooler
than field L/T transition objects, providing further evidence that the L/T
transition is gravity-dependent. With an unusually dusty photosphere, an
exceptionally low luminosity for its spectral type, and hints of extreme
secondary physical parameters, HR 8799 b appears to be unlike any class of
field brown dwarf currently known.Comment: 21 pages, 23 figures; accepted by Ap
A Disk Around the Planetary-Mass Companion GSC 06214-00210 b: Clues About the Formation of Gas Giants on Wide Orbits
We present Keck/OSIRIS 1.1-1.8 um adaptive optics integral field spectroscopy
of the planetary-mass companion to GSC 06214-00210, a member of the ~5 Myr
Upper Scorpius OB association. We infer a spectral type of L0+/-1, and our
spectrum exhibits multiple signs of youth. The most notable feature is
exceptionally strong PaBeta emission (EW=-11.4 +/- 0.3 A) which signals the
presence of a circumplanetary accretion disk. The luminosity of GSC 06214-00210
b combined with its age yields a model-dependent mass of 14 +/- 2 MJup, making
it the lowest-mass companion to show evidence of a disk. With a projected
separation of 320 AU, the formation of GSC 06214-00210 b and other very
low-mass companions on similarly wide orbits is unclear. One proposed mechanism
is formation at close separations followed by planet-planet scattering to much
larger orbits. Since that scenario involves a close encounter with another
massive body, which is probably destructive to circumplanetary disks, it is
unlikely that GSC 06214-00210 b underwent a scattering event in the past. This
implies that planet-planet scattering is not solely responsible for the
population of gas giants on wide orbits. More generally, the identification of
disks around young planetary companions on wide orbits offers a novel method to
constrain the formation pathway of these objects, which is otherwise
notoriously difficult to do for individual systems. We also refine the spectral
type of the primary from M1 to K7 and detect a mild (2-sigma) excess at 22 um
using WISE photometry.Comment: 25 pages, 13 figures; Accepted by Ap
POTs: Protective Optimization Technologies
Algorithmic fairness aims to address the economic, moral, social, and
political impact that digital systems have on populations through solutions
that can be applied by service providers. Fairness frameworks do so, in part,
by mapping these problems to a narrow definition and assuming the service
providers can be trusted to deploy countermeasures. Not surprisingly, these
decisions limit fairness frameworks' ability to capture a variety of harms
caused by systems.
We characterize fairness limitations using concepts from requirements
engineering and from social sciences. We show that the focus on algorithms'
inputs and outputs misses harms that arise from systems interacting with the
world; that the focus on bias and discrimination omits broader harms on
populations and their environments; and that relying on service providers
excludes scenarios where they are not cooperative or intentionally adversarial.
We propose Protective Optimization Technologies (POTs). POTs provide means
for affected parties to address the negative impacts of systems in the
environment, expanding avenues for political contestation. POTs intervene from
outside the system, do not require service providers to cooperate, and can
serve to correct, shift, or expose harms that systems impose on populations and
their environments. We illustrate the potential and limitations of POTs in two
case studies: countering road congestion caused by traffic-beating
applications, and recalibrating credit scoring for loan applicants.Comment: Appears in Conference on Fairness, Accountability, and Transparency
(FAT* 2020). Bogdan Kulynych and Rebekah Overdorf contributed equally to this
work. Version v1/v2 by Seda G\"urses, Rebekah Overdorf, and Ero Balsa was
presented at HotPETS 2018 and at PiMLAI 201
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