Origins of choice-related activity in mouse somatosensory cortex.

During perceptual decisions about faint or ambiguous sensory stimuli, even identical stimuli can produce different choices. Spike trains from sensory cortex neurons can predict trial-to-trial variability in choice. Choice-related spiking is widely studied as a way to link cortical activity to perception, but its origins remain unclear. Using imaging and electrophysiology, we found that mouse primary somatosensory cortex neurons showed robust choice-related activity during a tactile detection task. Spike trains from primary mechanoreceptive neurons did not predict choices about identical stimuli. Spike trains from thalamic relay neurons showed highly transient, weak choice-related activity. Intracellular recordings in cortex revealed a prolonged choice-related depolarization in most neurons that was not accounted for by feed-forward thalamic input. Top-down axons projecting from secondary to primary somatosensory cortex signaled choice. An intracellular measure of stimulus sensitivity determined which neurons converted choice-related depolarization into spiking. Our results reveal how choice-related spiking emerges across neural circuits and within single neurons

Almost perfect nonlinear power functions with exponents expressed as fractions

Let $F$ be a finite field, let $f$ be a function from $F$ to $F$, and let $a$ be a nonzero element of $F$. The discrete derivative of $f$ in direction $a$ is $\Delta_a f \colon F \to F$ with $(\Delta_a f)(x)=f(x+a)-f(x)$. The differential spectrum of $f$ is the multiset of cardinalities of all the fibers of all the derivatives $\Delta_a f$ as $a$ runs through $F^*$. The function $f$ is almost perfect nonlinear (APN) if the largest cardinality in the differential spectrum is $2$. Almost perfect nonlinear functions are of interest as cryptographic primitives. If $d$ is a positive integer, the power function over $F$ with exponent $d$ is the function $f \colon F \to F$ with $f(x)=x^d$ for every $x \in F$. There is a small number of known infinite families of APN power functions. In this paper, we re-express the exponents for one such family in a more convenient form. This enables us to give the differential spectrum and, even more, to determine the sizes of individual fibers of derivatives.Comment: 30 page

Evaluating Approaches to Measuring Ocular Pain in Bovine Calves with Corneal Scarification and IBK-Associated Corneal Ulcerations

The objective of this experiment was to describe the magnitude and variation of measures of ocular pain in cattle experiencing corneal scarification and corneal ulcerations associated with experimentally induced IBK. In our study, pressure algometry may be appropriate to quantify ocular pain in calves. This information will enable appropriate design of studies for assessing the extent of ocular pain associated with ophthalmic abnormalities in cattle and efficacy of pain mitigation strategies

Quantification of global myocardial oxygenation in humans: initial experience

<p>Abstract</p> <p>Purpose</p> <p>To assess the feasibility of our newly developed cardiovascular magnetic resonance (CMR) methods to quantify global and/or regional myocardial oxygen consumption rate (MVO₂) at rest and during pharmacologically-induced vasodilation in normal volunteers.</p> <p>Methods</p> <p>A breath-hold T₂quantification method is developed to calculate oxygen extraction fraction (OEF) and MVO₂rate at rest and/or during hyperemia, using a two-compartment model. A previously reported T₂quantification method using turbo-spin-echo sequence was also applied for comparison. CMR scans were performed in 6 normal volunteers. Each imaging session consisted of imaging at rest and during adenosine-induced vasodilation. The new T₂quantification method was applied to calculate T₂in the coronary sinus (CS), as well as in myocardial tissue. Resting CS OEF, representing resting global myocardial OEF, and myocardial OEF during adenosine vasodilation were then calculated by the model. Myocardial blood flow (MBF) was also obtained to calculate MVO₂, by using a first-pass perfusion imaging approach.</p> <p>Results</p> <p>The T₂quantification method yielded a hyperemic OEF of 0.37 ± 0.05 and a hyperemic MVO₂of 9.2 ± 2.4 μmol/g/min. The corresponding resting values were 0.73 ± 0.05 and 5.2 ± 1.7 μmol/g/min respectively, which agreed well with published literature values. The MVO₂rose proportionally with rate-pressure product from the rest condition. The T₂sensitivity is approximately 95% higher with the new T₂method than turbo-spin-echo method.</p> <p>Conclusion</p> <p>The CMR oxygenation method demonstrates the potential for non-invasive estimation of myocardial oxygenation, and should be explored in patients with altered myocardial oxygenation.</p

Deus Ex Machina: A Cautionary Tale for Naturalists

In this paper we critically examine and seek to extend Philip Kitcher’s Ethical Project to weave together a distinctive naturalistic conception of how ethics came to occupy the place it does in our lives and how the existing ethical project should be revised and extended into the future. Although we endorse his insight that ethical progress is better conceived of as the improvement of an existing state than an incremental approach towards a fixed endpoint, we nonetheless go on to argue that the metaethical apparatus Kitcher constructs around this creative metaethical proposal simply cannot do the work that he demands of it. The prospect of fundamental conflict between different functions of the ethical project requires Kitcher to appeal to a particular normative stance in order to judge specific changes in the ethical project to be genuinely progressive, and we argue that the virtues of continuity and coherence to which he appeals can only specify rather than justify the normative stance he favors. We conclude by suggesting an alternative approach for ethical naturalists that seems to us ultimately more promising than Kitcher’s ow

Alcohol Affects the P3 Component of an Adaptive Stop Signal Task ERP

BACKGROUND The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduces P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST). METHODS One hundred and forty eight nondependent moderate to heavy social drinkers, age 21 to 27, participated in 2 single-blind, alcohol or placebo, counterbalanced sessions approximately one week apart. During each session, subjects performed an adaptive stop signal task (aSST) at (1) baseline, (2) upon reaching the target 60 mg/dL breath alcohol concentration or at the equivalent time during the placebo session, and (3) approximately 135 minutes later while the breath alcohol concentration was clamped. Here, we report on differences between baseline and first subsequent measurements across the experimental sessions. During each aSST run, the stop signal delay (SSD, the time between stop and go signals) adjusted trial-by-trial based on the subject’s performance. RESULTS The aSST reliably generated a STOP P3 component that did not change significantly with repeated task performance. The pre-infusion SSD distribution was bimodal, with mean values several hundred msec apart (FAST: 153 msec and SLOW: 390 msec). This suggested different response strategies: FAST SSD favoring “going” over “stopping,” and SLOW SSD favoring “stopping” over “going”. Exposure to alcohol at 60 mg/dL differentially affected the amplitude and latency of the STOP P3 according to SSD group. Alcohol significantly reduced P3 amplitude in the SLOW SSD compared to FAST SSD group, but significantly increased P3 latency in the FAST SSD compared to SLOW SSD group. CONCLUSIONS The aSST is a robust and sensitive task for detecting alcohol induced changes in inhibition behavior as measured by the P3 component in a within subject design. Alcohol was associated with P3 component changes which varied by SSD group, suggesting a differential effect as a function of task strategy. Overall, the data support the potential utility of the aSST in the detection of alcohol response related AUD risk

Iterative methods for Navier-Stokes inverse problems

Even when the partial differential equation underlying a physical process can be evolved forward in time, the retrospective (backward in time) inverse problem often has its own challenges and applications. Direct adjoint looping (DAL) is the defacto approach for solving retrospective inverse problems, but it has not been applied to deterministic retrospective Navier–Stokes inverse problems in 2D or 3D. In this paper, we demonstrate that DAL is ill-suited for solving retrospective 2D Navier–Stokes inverse problems. Alongside DAL, we study two other iterative methods: simple backward integration (SBI) and the quasireversible method (QRM). As far as we know, our iterative SBI approach is novel, while iterative QRM has previously been used. Using these three iterative methods, we solve two retrospective inverse problems: 1D Korteweg–de Vries–Burgers (decaying nonlinear wave) and 2D Navier–Stokes (unstratified Kelvin–Helmholtz vortex). In both cases, SBI and QRM reproduce the target final states more accurately and in fewer iterations than DAL. We attribute this performance gap to additional terms present in SBI and QRM's respective backward integrations which are absent in DAL

A Gravitationally Lensed Supernova with an Observable Two-Decade Time Delay

When the light from a distant object passes very near to a foreground galaxy or cluster, gravitational lensing can cause it to appear as multiple images on the sky. If the source is variable, it can be used to constrain the cosmic expansion rate and dark energy models. Achieving these cosmological goals requires many lensed transients with precise time delay measurements. Lensed supernovae (SN) are attractive for this purpose because they have relatively simple photometric behavior, with well-understood light curve shapes and colours $-$ in contrast to the stochastic variation of quasars. Here we report the discovery of a multiply-imaged supernova, AT2016jka ("SN Requiem"). It appeared in an evolved galaxy at $z=1.95$, gravitationally lensed by a foreground galaxy cluster. It is likely a Type Ia supernova $-$ the explosion of a low-mass stellar remnant, whose light curve can be used to measure cosmic distances. In archival Hubble Space Telescope imaging, three lensed images of the supernova are detected with relative time delays of $<$200 days. We predict a fourth image will appear close to the cluster core in the year 2037$\pm$2. Observation of the fourth image could provide a time delay precision of $\approx$7 days, $<1\%$ of the extraordinary 20 year baseline. The SN classification and the predicted reappearance time could be improved with further lens modelling and a comprehensive analysis of systematic uncertainties.Comment: Accepted for publication in a peer-reviewed journal. Main text = 6 pages, 3 figures, 1 table; Full document = 28 pages, 12 figures with Methods, Supplemental Info and references. v2: reformatted; minor corrections in S

An open‐label, single‐arm, phase 2 study of single‐agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93582/1/bjh9232.pd