Perceptual Pluralism

Perceptual systems respond to proximal stimuli by forming mental representations of distal stimuli. A central goal for the philosophy of perception is to characterize the representations delivered by perceptual systems. It may be that all perceptual representations are in some way proprietarily perceptual and differ from the representational format of thought (Dretske 1981; Carey 2009; Burge 2010; Block ms.). Or it may instead be that perception and cognition always trade in the same code (Prinz 2002; Pylyshyn 2003). This paper rejects both approaches in favor of perceptual pluralism, the thesis that perception delivers a multiplicity of representational formats, some proprietary and some shared with cognition. The argument for perceptual pluralism marshals a wide array of empirical evidence in favor of iconic (i.e., image-like, analog) representations in perception as well as discursive (i.e., language-like, digital) perceptual object representations

Estrogen metabolism and mammographic density in postmenopausal women : a cross-sectional study

Background: Prospective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD. Methods: Postmenopausal women without breast cancer (n = 194), ages 48 to 82 years, and reporting no current menopausal hormone therapy use were enrolled at a clinic in Western NY in 2005. Urinary estrogens and estrogen metabolites were measured using mass spectrometry. Percent MD and dense area (cm2) were measured using computer-assisted analyses of digitized films. Linear regression models were used to estimate associations of log-transformed estrogen measures with MD while adjusting for age, body mass index (BMI), parity, and past hormone therapy use. Results: Urinary concentrations of most individual estrogens and metabolites were not associated with MD; however, across the interdecile range of the ratio of parent estrogens (estrone and estradiol) to their metabolites, MD increased by 6.8 percentage points (P = 0.02) and dense area increased by 10.3 cm2 (P = 0.03). Across the interdecile ranges of the ratios of 2-, 4-, and 16-hydroxylation pathways to the parent estrogens, MD declined by 6.2 (P = 0.03), 6.4 (P = 0.04), and 5.7 (P = 0.05) percentage points, respectively. All associations remained apparent in models without adjustment for BMI. Conclusion: In this study of postmenopausal women, less extensive hydroxylation of parent estrogens was associated with higher MD. Impact: Hydroxylation of estrogens may modulate postmenopausal breast cancer risk through a pathway involving MD

Robust statistics towards detection of the 21 cm signal from the Epoch of Reionization

© 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. We explore methods for robust estimation of the 21 cm signal from the Epoch of Reionization (EoR). A Kernel Density Estimator (KDE) is introduced for measuring the spatial temperature fluctuation power spectrum from the EoR. The KDE estimates the underlying probability distribution function of fluctuations as a function of spatial scale, and contains different systematic biases and errors to the typical approach to estimating the fluctuation power spectrum. Extraction of histograms of visibilities allows moments analysis to be used to discriminate foregrounds from 21 cm signal and thermal noise. We use the information available in the histograms, along with the statistical dis-similarity of foregrounds from two independent observing fields, to robustly separate foregrounds from cosmological signal, while making no assumptions about the Gaussianity of the signal. Using two independent observing fields to robustly discriminate signal from foregrounds is crucial for the analysis presented in this paper. We apply the techniques to 13 h of Murchison Widefield Array EoR data over two observing fields. We compare the output to that obtained with a comparative power spectrum estimation method, and demonstrate the reduced foreground contamination using this approach. Using the second moment obtained directly from the KDE distribution functions yields a factor of 2-3 improvement in power for k < 0.3 h Mpc-1 compared with a matched delay space power estimator, while weighting data by additional statistics does not offer significant improvement beyond that available for thermal noise-only weights

The Origin, Early Evolution and Predictability of Solar Eruptions

Coronal mass ejections (CMEs) were discovered in the early 1970s when space-borne coronagraphs revealed that eruptions of plasma are ejected from the Sun. Today, it is known that the Sun produces eruptive flares, filament eruptions, coronal mass ejections and failed eruptions; all thought to be due to a release of energy stored in the coronal magnetic field during its drastic reconfiguration. This review discusses the observations and physical mechanisms behind this eruptive activity, with a view to making an assessment of the current capability of forecasting these events for space weather risk and impact mitigation. Whilst a wealth of observations exist, and detailed models have been developed, there still exists a need to draw these approaches together. In particular more realistic models are encouraged in order to asses the full range of complexity of the solar atmosphere and the criteria for which an eruption is formed. From the observational side, a more detailed understanding of the role of photospheric flows and reconnection is needed in order to identify the evolutionary path that ultimately means a magnetic structure will erupt

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)–microdystrophin (μDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 1013 vector genomes per kilogram (vg/kg), 1 × 1014 vg/kg, and 2 × 1014 vg/kg; n = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day-7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; μDys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD

The Physical Processes of CME/ICME Evolution

As observed in Thomson-scattered white light, coronal mass ejections (CMEs) are manifest as large-scale expulsions of plasma magnetically driven from the corona in the most energetic eruptions from the Sun. It remains a tantalizing mystery as to how these erupting magnetic fields evolve to form the complex structures we observe in the solar wind at Earth. Here, we strive to provide a fresh perspective on the post-eruption and interplanetary evolution of CMEs, focusing on the physical processes that define the many complex interactions of the ejected plasma with its surroundings as it departs the corona and propagates through the heliosphere. We summarize the ways CMEs and their interplanetary CMEs (ICMEs) are rotated, reconfigured, deformed, deflected, decelerated and disguised during their journey through the solar wind. This study then leads to consideration of how structures originating in coronal eruptions can be connected to their far removed interplanetary counterparts. Given that ICMEs are the drivers of most geomagnetic storms (and the sole driver of extreme storms), this work provides a guide to the processes that must be considered in making space weather forecasts from remote observations of the corona.Peer reviewe