Expected seismicity and the seismic noise environment of Europa

Seismic data will be a vital geophysical constraint on internal structure of Europa if we land instruments on the surface. Quantifying expected seismic activity on Europa both in terms of large, recognizable signals and ambient background noise is important for understanding dynamics of the moon, as well as interpretation of potential future data. Seismic energy sources will likely include cracking in the ice shell and turbulent motion in the oceans. We define a range of models of seismic activity in Europa's ice shell by assuming each model follows a Gutenberg-Richter relationship with varying parameters. A range of cumulative seismic moment release between $10^{16}$ and $10^{18}$ Nm/yr is defined by scaling tidal dissipation energy to tectonic events on the Earth's moon. Random catalogs are generated and used to create synthetic continuous noise records through numerical wave propagation in thermodynamically self-consistent models of the interior structure of Europa. Spectral characteristics of the noise are calculated by determining probabilistic power spectral densities of the synthetic records. While the range of seismicity models predicts noise levels that vary by 80 dB, we show that most noise estimates are below the self-noise floor of high-frequency geophones, but may be recorded by more sensitive instruments. The largest expected signals exceed background noise by $\sim$50 dB. Noise records may allow for constraints on interior structure through autocorrelation. Models of seismic noise generated by pressure variations at the base of the ice shell due to turbulent motions in the subsurface ocean may also generate observable seismic noise.Comment: 24 pages, 11 figures, Added in supplementary information from revision submission, including 3 audio files with sonification of Europa noise records. To view attachments, please download and extract the gzipped tar source file listed under "Other formats

Human Biodistribution and Dosimetry of 11C-CUMI-101, an Agonist Radioligand for Serotonin-1A Receptors in Brain

As a reported agonist,11C-CUMI-101 is believed to selectively bind the G-protein-coupled state of the serotonin-1A (5-HT1A) receptor, thereby providing a measure of the active subset of all 5-HT1A receptors in brain. Although 11C-CUMI-101 has been successfully used to quantify 5-HT1A receptors in human and monkey brain, its radiation exposure has not previously been reported. The purpose of this study was to calculate the radiation exposure to organs of the body based on serial whole-body imaging with positron emission tomography (PET) in human subjects

Development of a non-radiometric method for measuring the arterial input function of a C-11-labeled PET radiotracer

Positron emission tomography (PET) uses radiotracers to quantify important biochemical parameters in human subjects. A radiotracer arterial input function (AIF) is often essential for converting brain PET data into robust output measures. For radiotracers labeled with carbon-11 (t(1/2)=20.4 min), AIF is routinely determined with radio-HPLC of blood sampled frequently during the PET experiment. There has been no alternative to this logistically demanding method, neither for regular use nor validation. A C-11-labeled tracer is always accompanied by a large excess of non-radioactive tracer known as carrier. In principle, AIF might be obtained by measuring the molar activity (A(m); ratio of radioactivity to total mass; Bq/mol) of a radiotracer dose and the time-course of carrier concentration in plasma after radiotracer injection. Here, we implement this principle in a new method for determining AIF, as shown by using [C-11]PBR28 as a representative tracer. The method uses liquid chromatography-tandem mass spectrometry for measuring radiotracer A(m) and then the carrier in plasma sampled regularly over the course of a PET experiment. A(m) and AIF were determined radiometrically for comparison. The new non-radiometric method is not constrained by the short half-life of carbon-11 and is an attractive alternative to conventional AIF measurement

Seismic Expression of Pleistocene Paleoceanographic Changes in the California Borderland from Digitally Acquired 3.5 Khz Subbottom Profiles and Ocean Drilling Program Leg 167 Drilling

We correlate processed 3.5 kHz seismic profiles with physical properties of cores collected during ODP Leg 167 from the Tanner, East Cortes, and San Nicolas Basins through much of the Pleistocene succession. Results indicate that seismic horizons in the unconsolidated Pleistocene sediments (top 50 m) are mainly controlled by density contrasts. Removing of the compaction trend from the density reveals a very interesting relationship between density and composition - the density closely and inversely correlates with organic carbon indicating that large-scale variations in organic carbon are responsible for seismic reflections through their influence on density. This is a significant discovery since there apparently is no other paleoceanographic setting that we know of where such a close linkage between acoustic properties and organic carbon has been established. The variations in organic carbon are mainly marine in origin and derive from variations in primary productivity associated with upwelling and the preservation regime related to oxygenation of water. Pleistocene reflections on 3.5 kHz profiles in the Borderland province thus record regional cyclical fluctuations in the paleoclimatic signals. The close resemblance in the density profiles at the three different basins indicates that the sedimentary regime was similar in those basins through the Pleistocene. These common density patterns produce regional seismic horizons that correlate well among the basins. It is likely these correlated and dated horizons could be extrapolated to other Borderland basins (e.g., San Clemente), where they can potentially be used as time markers for neotectonic studies in the region

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Image-Derived Input Function for Human Brain Using High Resolution PET Imaging with [11C](R)-rolipram and [11C]PBR28

The aim of this study was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution-recovery reconstruction algorithm using two different radioligands with different radiometabolite fractions. Three of the methods required arterial blood samples to scale the image-input, and four were blood-free methods. values was quantified using a scoring system. Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.)-rolipram, which has a lower metabolite fraction. Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.C]PBR28), the more difficult it is to obtain a reliable image-derived input function; and 4) in association with image inputs, graphical analyses should be preferred over compartmental modelling

Neuronal Oscillations Enhance Stimulus Discrimination by Ensuring Action Potential Precision

Although oscillations in membrane potential are a prominent feature of sensory, motor, and cognitive function, their precise role in signal processing remains elusive. Here we show, using a combination of in vivo, in vitro, and theoretical approaches, that both synaptically and intrinsically generated membrane potential oscillations dramatically improve action potential (AP) precision by removing the membrane potential variance associated with jitter-accumulating trains of APs. This increased AP precision occurred irrespective of cell type and—at oscillation frequencies ranging from 3 to 65 Hz—permitted accurate discernment of up to 1,000 different stimuli. At low oscillation frequencies, stimulus discrimination showed a clear phase dependence whereby inputs arriving during the trough and the early rising phase of an oscillation cycle were most robustly discriminated. Thus, by ensuring AP precision, membrane potential oscillations dramatically enhance the discriminatory capabilities of individual neurons and networks of cells and provide one attractive explanation for their abundance in neurophysiological systems

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

PET radiotracers: crossing the blood–brain barrier and surviving metabolism

Photograph of a piece of Jim Powers' Junkyard Art

Regiospecific Syntheses of Functionalized Diaryliodonium Tosylates via [Hydroxy(tosyloxy)iodo]arenes Generated in Situ from (Diacetoxyiodo)arenes

Ready access to ¹⁸F-labeled aryl synthons is required for preparing novel radiotracers for molecular imaging with positron emission tomography. Diaryliodonium salts react with cyclotron-produced no-carrier-added [¹⁸F]­fluoride ion to produce [¹⁸F]­aryl fluorides. We aimed to prepare functionalized diaryliodonium salts to serve as potential precursors for producing useful ¹⁸F-labeled aryl synthons, such as ¹⁸F-labeled halomethylbenzenes, benzaldehydes, and benzoic acid esters. Such salts were designed to have one functionalized aryl ring, one relatively electron-rich ring, such as 4-methoxyphenyl or 2-thienyl, and a nonfluorine containing weakly nucleophilic anion. Generation of a [hydroxy­(tosyloxy)­iodo]­arene from a functionalized (diacetoxyiodo)­arene in situ followed by treatment with an electron-rich arene, such as anisole or thiophene, or with a functionalized arylstannane gave expedient regiospecific access to a wide range of functionally diverse diaryliodonium tosylates in moderate to high yields (44–98%). The described methodology broadens the scope for producing new functionalized diaryliodonium salts for diverse applications