Statistics of natural reverberation enable perceptual separation of sound and space

In everyday listening, sound reaches our ears directly from a source as well as indirectly via reflections known as reverberation. Reverberation profoundly distorts the sound from a source, yet humans can both identify sound sources and distinguish environments from the resulting sound, via mechanisms that remain unclear. The core computational challenge is that the acoustic signatures of the source and environment are combined in a single signal received by the ear. Here we ask whether our recognition of sound sources and spaces reflects an ability to separate their effects and whether any such separation is enabled by statistical regularities of real-world reverberation. To first determine whether such statistical regularities exist, we measured impulse responses (IRs) of 271 spaces sampled from the distribution encountered by humans during daily life. The sampled spaces were diverse, but their IRs were tightly constrained, exhibiting exponential decay at frequency-dependent rates: Mid frequencies reverberated longest whereas higher and lower frequencies decayed more rapidly, presumably due to absorptive properties of materials and air. To test whether humans leverage these regularities, we manipulated IR decay characteristics in simulated reverberant audio. Listeners could discriminate sound sources and environments from these signals, but their abilities degraded when reverberation characteristics deviated from those of real-world environments. Subjectively, atypical IRs were mistaken for sound sources. The results suggest the brain separates sound into contributions from the source and the environment, constrained by a prior on natural reverberation. This separation process may contribute to robust recognition while providing information about spaces around us

Racial Differences in the Effect of Granulocyte Macrophage Colony-Stimulating Factor on Improved Walking Distance in Peripheral Artery Disease: The PROPEL Randomized Clinical Trial.

Background The effects of race on response to medical therapy in people with peripheral artery disease ( PAD ) are unknown. Methods and Results In the PROPEL (Progenitor Cell Release Plus Exercise to Improve Functional Performance in PAD) Trial, PAD participants were randomized to 1 of 4 groups for 6 months: supervised treadmill exercise+granulocyte-macrophage colony-stimulating factor ( GM - CSF ) (Group 1), exercise+placebo (Group 2), attention control+ GM - CSF (Group 3), or attention control+placebo (Group 4). Change in 6-minute walk distance was measured at 12- and 26-week follow-up. In these exploratory analyses, groups receiving GM - CSF (Groups 1 and 3), placebo (Groups 2 and 4), exercise (Groups 1 and 2), and attention control (Groups 2 and 4) were combined, maximizing statistical power for studying the effects of race on response to interventions. Of 210 PAD participants, 141 (67%) were black and 64 (30%) were white. Among whites, GM - CSF improved 6-minute walk distance by +22.0 m (95% CI : -4.5, +48.5, P=0.103) at 12 weeks and +44.4 m (95% CI : +6.9, +82.0, P=0.020) at 26 weeks, compared with placebo. Among black participants, there was no effect of GM - CSF on 6-minute walk distance at 12-week ( P=0.26) or 26-week (-5.0 m [-27.5, +17.5, P=0.66]) follow-up, compared with placebo. There was an interaction of race on the effect of GM - CSF on 6-minute walk change at 26-week follow-up ( P=0.018). Exercise improved 6-minute walk distance in black ( P=0.006) and white ( P=0.034) participants without interaction. Conclusions GM - CSF improved 6-minute walk distance in whites with PAD but had no effect in black participants. Further study is needed to confirm racial differences in GM - CSF efficacy in PAD . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01408901

Agricultural Land Use Planning and Groundwater Quality

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75123/1/j.1468-2257.1983.tb00394.x.pd

Neurodegenerative Disease and the NLRP3 Inflammasome.

The prevalence of neurodegenerative disease has increased significantly in recent years, and with a rapidly aging global population, this trend is expected to continue. These diseases are characterised by a progressive neuronal loss in the brain or peripheral nervous system, and generally involve protein aggregation, as well as metabolic abnormalities and immune dysregulation. Although the vast majority of neurodegeneration is idiopathic, there are many known genetic and environmental triggers. In the past decade, research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease or is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, a crucial component of the innate immune system, is usually activated in response to infection or tissue damage. Dysregulation of the NLRP3 inflammasome has been implicated in the progression of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and prion diseases. This review aims to summarise current literature on the role of the NLRP3 inflammasome in the pathogenesis of neurodegenerative diseases, and recent work investigating NLRP3 inflammasome inhibition as a potential future therapy

Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC

Closing in on Asymmetric Dark Matter I: Model independent limits for interactions with quarks

It is argued that experimental constraints on theories of asymmetric dark matter (ADM) almost certainly require that the DM be part of a richer hidden sector of interacting states of comparable mass or lighter. A general requisite of models of ADM is that the vast majority of the symmetric component of the DM number density must be removed in order to explain the observed relationship $\Omega_B\sim\Omega_{DM}$ via the DM asymmetry. Demanding the efficient annihilation of the symmetric component leads to a tension with experimental limits if the annihilation is directly to Standard Model (SM) degrees of freedom. A comprehensive effective operator analysis of the model independent constraints on ADM from direct detection experiments and LHC monojet searches is presented. Notably, the limits obtained essentially exclude models of ADM with mass 1GeV$\lesssim m_{DM} \lesssim$ 100GeV annihilating to SM quarks via heavy mediator states. This motivates the study of portal interactions between the dark and SM sectors mediated by light states. Resonances and threshold effects involving the new light states are shown to be important for determining the exclusion limits.Comment: 18+6 pages, 18 figures. v2: version accepted for publicatio

Breeding season concerns and response to forest management: can forest management produce more breeding birds?.

Cerulean Warblers (Setophaga cerulea), one of the fastest declining avian species in North America, are associated with heterogeneous canopies in mature hardwood forests. However, the age of most second and third-growth forests in eastern North American is not sufficient for natural tree mortality to maintain structurally diverse canopies. Previous research suggests that forest management through timber harvest also may create conditions suitable as Cerulean Warbler breeding habitat. We conducted a multistate study that examined Cerulean Warbler response to varying degrees of canopy disturbance created by operational timber harvest. Specifically, 3 harvest treatments and an un-harvested reference plot were replicated on 7 study areas in 4 Appalachian states in 2005-2010. We compared pre-harvest and four years post-harvest demographic response of Cerulean Warblers. Over all study areas, Cerulean Warbler territory density remained stable in un-harvested reference plots and increased significantly the first year post-harvest on intermediate harvest plots. By year 3 post-harvest, territory density remained significantly greater for intermediate harvest than reference plots, and marginally greater for light and heavy harvests than reference plots. However, un-harvested reference plots had greater nest survival than most harvest treatments. The one exception was nest survival between reference plots and the intermediate harvest on the northern study areas did not differ. Our results indicate that intermediate harvests likely benefit Cerulean Warblers in some portions of the species’ breeding range. However, additional research is needed to better examine fitness consequences of timber harvests and to estimate population-level implications. In particular, does the greater number of nesting individuals, particularly in intermediate harvests, compensate for lower nesting success? Until researchers provide such insight, we recommend management decisions be based on local conditions, particularly in forests where Cerulean Warbler populations are high

Emulating Natural Disturbances for Declining Late- Successional Species: A Case Study of the Consequences for Cerulean Warblers (Setophaga cerulea)

Forest cover in the eastern United States has increased over the past century and while some late-successional species have benefited from this process as expected, others have experienced population declines. These declines may be in part related to contemporary reductions in small-scale forest interior disturbances such as fire, windthrow, and treefalls. To mitigate the negative impacts of disturbance alteration and suppression on some late-successional species, strategies that emulate natural disturbance regimes are often advocated, but large-scale evaluations of these practices are rare. Here, we assessed the consequences of experimental disturbance (using partial timber harvest) on a severely declining late-successional species, the cerulean warbler (Setophaga cerulea), across the core of its breeding range in the Appalachian Mountains. We measured numerical (density), physiological (body condition), and demographic (age structure and reproduction) responses to three levels of disturbance and explored the potential impacts of disturbance on source-sink dynamics. Breeding densities of warblers increased one to four years after all canopy disturbances (vs. controls) and males occupying territories on treatment plots were in better condition than those on control plots. However, these beneficial effects of disturbance did not correspond to improvements in reproduction; nest success was lower on all treatment plots than on control plots in the southern region and marginally lower on light disturbance plots in the northern region. Our data suggest that only habitats in the southern region acted as sources, and interior disturbances in this region have the potential to create ecological traps at a local scale, but sources when viewed at broader scales. Thus, cerulean warblers would likely benefit from management that strikes a landscape-level balance between emulating natural disturbances in order to attract individuals into areas where current structure is inappropriate, and limiting anthropogenic disturbance in forests that already possess appropriate structural attributes in order to maintain maximum productivity

Emulating Natural Disturbances for Declining Late-Successional Species: A Case Study of the Consequences for Cerulean Warblers (Setophaga cerulea)

Forest cover in the eastern United States has increased over the past century and while some late-successional species have benefited from this process as expected, others have experienced population declines. These declines may be in part related to contemporary reductions in small-scale forest interior disturbances such as fire, windthrow, and treefalls. To mitigate the negative impacts of disturbance alteration and suppression on some late-successional species, strategies that emulate natural disturbance regimes are often advocated, but large-scale evaluations of these practices are rare. Here, we assessed the consequences of experimental disturbance (using partial timber harvest) on a severely declining latesuccessional species, the cerulean warbler (Setophaga cerulea), across the core of its breeding range in the Appalachian Mountains. We measured numerical (density), physiological (body condition), and demographic (age structure and reproduction) responses to three levels of disturbance and explored the potential impacts of disturbance on source-sink dynamics. Breeding densities of warblers increased one to four years after all canopy disturbances (vs. controls) and males occupying territories on treatment plots were in better condition than those on control plots. However, these beneficial effects of disturbance did not correspond to improvements in reproduction; nest success was lower on all treatment plots than on control plots in the southern region and marginally lower on light disturbance plots in the northern region. Our data suggest that only habitats in the southern region acted as sources, and interior disturbances in this region have the potential to create ecological traps at a local scale, but sources when viewed at broader scales. Thus, cerulean warblers would likely benefit from management that strikes a landscape-level balance between emulating natural disturbances in order to attract individuals into areas where current structure is inappropriate, and limiting anthropogenic disturbance in forests that already possess appropriate structural attributes in order to maintain maximum productivity

Cosmological Simulations with Self-Interacting Dark Matter II: Halo Shapes vs. Observations

If dark matter has a large self-interaction scattering cross section, then interactions among dark-matter particles will drive galaxy and cluster halos to become spherical in their centers. Work in the past has used this effect to rule out velocity-independent, elastic cross sections larger than sigma/m ~ 0.02 cm^2/g based on comparisons to the shapes of galaxy cluster lensing potentials and X-ray isophotes. In this paper, we use cosmological simulations to show that these constraints were off by more than an order of magnitude because (a) they did not properly account for the fact that the observed ellipticity gets contributions from the triaxial mass distribution outside the core set by scatterings, (b) the scatter in axis ratios is large and (c) the core region retains more of its triaxial nature than estimated before. Including these effects properly shows that the same observations now allow dark matter self-interaction cross sections at least as large as sigma/m = 0.1 cm^2/g. We show that constraints on self-interacting dark matter from strong-lensing clusters are likely to improve significantly in the near future, but possibly more via central densities and core sizes than halo shapes.Comment: 17 pages, 11 figure