A pilot study evaluating concordance between blood-based and patient-matched tumor molecular testing within pancreatic cancer patients participating in the Know Your Tumor (KYT) initiative

Recent improvements in next-generation sequencing (NGS) technology have enabled detection of biomarkers in cell-free DNA in blood and may ultimately replace invasive tissue biopsies. However, a better understanding of the performance of blood-based NGS assays is needed prior to routine clinical use. As part of an IRBapproved molecular profiling registry trial of pancreatic ductal adenocarcinoma (PDA) patients, we facilitated blood-based NGS testing of 34 patients from multiple community-based and high-volume academic oncology practices. 23 of these patients also underwent traditional tumor tissue-based NGS testing. cfDNA was not detected in 9/34 (26%) patients. Overall concordance between blood and tumor tissue NGS assays was low, with only 25% sensitivity of blood-based NGS for tumor tissue NGS. Mutations in KRAS, the major PDA oncogene, were only detected in 10/34 (29%) blood samples, compared to 20/23 (87%) tumor tissue biopsies. The presence of mutations in circulating DNA was associated with reduced overall survival (54% in mutation-positive versus 90% in mutation-negative). Our results suggest that in the setting of previously treated, advanced PDA, liquid biopsies are not yet an adequate substitute for tissue biopsies. Further refinement in defining the optimal patient population and timing of blood sampling may improve the value of a blood-based test. © Pishvaian et al

The solar eclipse and associated atmospheric variations observed in South Korea on 22 July 2009

A partial solar eclipse occurred in South Korea on 22 July 2009. It started at 09:30 a.m. and lasted until 12:14 LST with coverage of between 76.8% and 93.1% of the sun. The observed atmospheric effects of the eclipse are presented. It was found that from the onset of the eclipse, solar radiation was reduced by as much as 88.1 ∼ 89.9% at the present research centre. Also, during the eclipse, air temperature decreased slightly or remained almost unchanged. After the eclipse, however, it rose by 2.5 to 4.5°C at observed stations. Meanwhile, relative humidity increased and wind speeds were lowered by the eclipse. Ground-level ozone was observed to decrease during the event

The Spectrum of Goldstini and Modulini

When supersymmetry is broken in multiple sectors via independent dynamics, the theory furnishes a corresponding multiplicity of "goldstini" degrees of freedom which may play a substantial role in collider phenomenology and cosmology. In this paper, we explore the tree-level mass spectrum of goldstini arising from a general admixture of F-term, D-term, and almost no-scale supersymmetry breaking, employing non-linear superfields and a novel gauge fixing for supergravity discussed in a companion paper. In theories of F-term and D-term breaking, goldstini acquire a mass which is precisely twice the gravitino mass, while the inclusion of no-scale breaking renders one of these modes, the modulino, massless. We argue that the vanishing modulino mass can be explained in terms of an accidental and spontaneously broken "global" supersymmetry.Comment: 10 pages, 2 figures; v2: typo corrected, references updated; v3: version to appear in JHE

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

The Target Silicon Detector for the FOCUS Spectrometer

We describe a silicon microstrip detector interleaved with segments of a beryllium oxide target which was used in the FOCUS photoproduction experiment at Fermilab. The detector was designed to improve the vertex resolution and to enhance the reconstruction efficiency of short-lived charm particles.Comment: 18 pages, 14 figure

Measurement of the relative branching ratio BR(\Xi_c^+ \to p^+ K^-\pi^+)\BR(\Xi_c^+ \to \Xi^- \pi^+ \pi^+)

We report the observation of the Cabibbo suppressed decay \Xi_c^+ \to p K^-\pi^+ using data collected with the FOCUS spectrometer during the 1996--97 Fermilab fixed target run. We find a \Xi_c^+ signal peak of 202\pm35 events. We have measured the relative branching ratios BR(\Xi^+_c\to p K^-\pi^+)/BR(\Xi^+_c\to\Xi^-\pi^+\pi^+)= 0.234 \pm 0.047 \pm 0.022 and BR(\Xi^+_c\to p \bar{K}^*(892)^0)/BR(\Xi^+_c\to p K^-\pi^+)= 0.54 \pm 0.09 \pm 0.05 .Comment: 9 pages, 4 figure

A measurement of lifetime differences in the neutral D-meson system

Using a high statistics sample of photoproduced charm particles from the FOCUS experiment at Fermilab, we compare the lifetimes of neutral D mesons decaying via D0 to K- pi+ and K- K+ to measure the lifetime differences between CP even and CP odd final states. These measurements bear on the phenomenology of D0 - D0bar mixing. If the D0 to K-pi+ is an equal mixture of CP even and CP odd eigenstates, we measure yCP = 0.0342 \pm 0.0139 \pm 0.0074.Comment: 15 pages, 5 figure

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

Measurements of the Sigma_c^0 and Sigma_c^{++} Mass Splittings

Using a high statistics sample of photoproduced charmed particles from the FOCUS experiment at Fermilab (FNAL-E831), we measure the mass splittings of the charmed baryons Sigma_c^0 and Sigma_c^{++}. We find M(Sigma_c^0 - Lambda_c^+) = 167.38 +/- 0.21 +/- 0.13 MeV/c^2 and M(Sigma_c^++ - Lambda_c^+) = 167.35 +/- 0.19 +/- 0.12 MeV/c^2 with samples of 362 +/- 36 and 461 +/- 39 events, respectively. We measure the isospin mass splitting M(Sigma_c^++ - Sigma_c^0) to be -0.03 +/- 0.28 +/- 0.11 Mev/c^2. The first errors are statistical and the second are systematic.Comment: 10 pages, 2 figure

Simulation of dilated heart failure with continuous flow circulatory support

Lumped parameter models have been employed for decades to simulate important hemodynamic couplings between a left ventricular assist device (LVAD) and the native circulation. However, these studies seldom consider the pathological descending limb of the Frank-Starling response of the overloaded ventricle. This study introduces a dilated heart failure model featuring a unimodal end systolic pressure-volume relationship (ESPVR) to address this critical shortcoming. The resulting hemodynamic response to mechanical circulatory support are illustrated through numerical simulations of a rotodynamic, continuous flow ventricular assist device (cfVAD) coupled to systemic and pulmonary circulations with baroreflex control. The model further incorporated septal interaction to capture the influence of left ventricular (LV) unloading on right ventricular function. Four heart failure conditions were simulated (LV and bi-ventricular failure with/ without pulmonary hypertension) in addition to normal baseline. Several metrics of LV function, including cardiac output and stroke work, exhibited a unimodal response whereby initial unloading improved function, and further unloading depleted preload reserve thereby reducing ventricular output. The concept of extremal loading was introduced to reflect the loading condition in which the intrinsic LV stroke work is maximized. Simulation of bi-ventricular failure with pulmonary hypertension revealed inadequacy of LV support alone. These simulations motivate the implementation of an extremum tracking feedback controller to potentially optimize ventricular recovery. © 2014 Wang et al