Analytical Validation and Capabilities of the Epic CTC Platform: Enrichment-Free Circulating Tumour Cell Detection and Characterization

The Epic Platform was developed for the unbiased detection and molecular characterization of circulating tumour cells (CTCs). Here, we report assay performance data, including accuracy, linearity, specificity and intra/inter-assay precision of CTC enumeration in healthy donor (HD) blood samples spiked with varying concentrations of cancer cell line controls (CLCs). Additionally, we demonstrate clinical feasibility for CTC detection in a small cohort of metastatic castrate-resistant prostate cancer (mCRPC) patients. The Epic Platform demonstrated accuracy, linearity and sensitivity for the enumeration of all CLC concentrations tested. Furthermore, we established the precision between multiple operators and slide staining batches and assay specificity showing zero CTCs detected in 18 healthy donor samples. In a clinical feasibility study, at least one traditional CTC/mL (CK+, CD45-, and intact nuclei) was detected in 89 % of 44 mCRPC samples, whereas 100 % of samples had CTCs enumerated if additional CTC subpopulations (CK-/CD45- and CK+ apoptotic CTCs) were included in the analysis. In addition to presenting Epic Platform’s performance with respect to CTC enumeration, we provide examples of its integrated downstream capabilities, including protein biomarker expression and downstream genomic analyses at single cell resolution

Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls

BACKGROUND: Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). METHODOLOGY/PRINCIPAL FINDINGS: MBF was measured with (15)O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58+/-13 years) and in CAD patients (n = 15, mean age 61+/-9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26+/-0.56 vs. 2.02+/-0.56, P<0.005), remote (2.40+/-0.70 vs. 1.78+/-0.46, P<0.001) and in stenotic segments (1.90+/-0.41 vs. 1.38+/-0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). CONCLUSIONS: We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls

Quisquis: A new design for anonymous cryptocurrencies

Despite their usage of pseudonyms rather than persistent identifiers, most existing cryptocurrencies do not provide users with any meaningful levels of privacy. This has prompted the creation of privacy-enhanced cryptocurrencies such as Monero and Zcash, which are specifically designed to counteract the tracking analysis possible in currencies like Bitcoin. These cryptocurrencies, however, also suffer from some drawbacks: in both Monero and Zcash, the set of potential unspent coins is always growing, which means users cannot store a concise representation of the blockchain. Additionally, Zcash requires a common reference string and the fact that addresses are reused multiple times in Monero has led to attacks to its anonymity. In this paper we propose a new design for anonymous cryptocurrencies, Quisquis, that achieves provably secure notions of anonymity. Quisquis stores a relatively small amount of data, does not require trusted setup, and in Quisquis each address appears on the blockchain at most twice: once when it is generated as output of a transaction, and once when it is spent as input to a transaction. Our result is achieved by combining a DDH-based tool (that we call updatable keys) with efficient zero-knowledge arguments

Experimental Limit to Interstellar 244Pu Abundance

Short-lived nuclides, now extinct in the solar system, are expected to be present in the interstellar medium (ISM). Grains of ISM origin were recently discovered in the inner solar system and at Earth orbit and may accrete onto Earth after ablation in the atmosphere. A favorable matrix for detection of such extraterrestrial material is presented by deep open-sea sediments with very low sedimentation rates (0.8-3 mm/kyr). We report here on the measurement of Pu isotopic abundances in a 1-kg deep-sea dry sediment collected in 1992 in the North Pacific. Our measured value of (3+-3)x10^5 244Pu atoms in the Pu-separated fraction of the sample shows no excess over the expected stratospheric nuclear fallout content and under reasonable assumptions we derive a limit of 2x10^-11 g-244Pu/g-ISM for the abundance of 244Pu in ISM.Comment: 10 p, 1 fig, LateX(AASTeX) Accepted for publication in ApJL, aug 2, 200

A System-Wide Investigation of the Dynamics of Wnt Signaling Reveals Novel Phases of Transcriptional Regulation

Aberrant Wnt signaling has been implicated in a wide variety of cancers and many components of the Wnt signaling network have now been identified. Much less is known, however, about how these proteins are coordinately regulated. Here, a broad, quantitative, and dynamic study of Wnt3a-mediated stimulation of HEK 293 cells revealed two phases of transcriptional regulation: an early phase in which signaling antagonists were downregulated, providing positive feedback, and a later phase in which many of these same antagonists were upregulated, attenuating signaling. The dynamic expression profiles of several response genes, including MYC and CTBP1, correlated significantly with proliferation and migration (P<0.05). Additionally, their levels tracked with the tumorigenicity of colon cancer cell lines and they were significantly overexpressed in colorectal adenocarcinomas (P<0.05). Our data highlight CtBP1 as a transcription factor that contributes to positive feedback during the early phases of Wnt signaling and serves as a novel marker for colorectal cancer progression

Total absorption spectroscopy of the β decay of Zr 101,102 and Tc 109

20 pags., 9 figs., 5 tabs.The β decay of Zr101,102 and Tc109 was studied using the technique of total absorption spectroscopy. The experiment was performed at the National Superconducting Cyclotron Laboratory using the Summing NaI(Tl) (SuN) detector in the first-ever application of total absorption spectroscopy with a fast beam produced via projectile fragmentation. The β-decay feeding intensity and Gamow-Teller transition strength distributions were extracted for these three decays. The extracted distributions were compared to three different quasiparticle random-phase approximation (QRPA) models based on different mean-field potentials. A comparison with calculations from one of the QRPA models was performed to learn about the ground-state shape of the parent nucleus. For Zr101 and Zr102, calculations assuming a pure shape configuration (oblate or prolate) were not able to reproduce the extracted distributions. These results may indicate that some type of mixture between oblate and prolate shapes is necessary to reproduce the extracted distributions. For Tc109, a comparison of the extracted distributions with QRPA calculations suggests a dominant oblate configuration. The other two QRPA models are commonly used to provide β-decay properties in r-process network calculations. This work shows the importance of making comparisons between the experimental and theoretical β-decay distributions, rather than just half-lives and β-delayed neutron emission probabilities, as close to the r-process path as possible.A.A. acknowledges support from the Spanish Ministerio de Economía y Competitividad under Grants No. FPA2011-24553, No. FPA2014-52823-C2-1-P, and No. FPA2017-83946-C2-1-P and the program Severo Ochoa (SEV-2014-0398). P.S. acknowledges support from MCIU/AEI/FEDER,UE (Spain) under Contract No. PGC2018-093636-B-I00. S.V. acknowledges support from Czech Science Foundation Project No. 19-14048 and the Charles University Project No. UNCE/SCI/013. This work was supported by the National Science Foundation under Grants No. PHY 1565546 (NSCL), No. PHY 1430152 (JINA-CEE), and No. PHY 1350234 (CAREER). This material is based upon work supported by the Department of Energy National Nuclear Security Administration through the Nuclear Science and Security Consortium under Awards No. DE-NA0003180 and/or No. DE-NA000097