Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic and inflammatory microenvironment that is formed primarily by activated, myofibroblast-like, stellate cells. Although the stellate cells are thought to contribute to tumorigenesis, metastasis and drug resistance of PDAC, the signaling events involved in activation of the stellate cells are not well defined. Functioning as transcription co-factors, Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) modulate the expression of genes involved in various aspects of cellular functions, such as proliferation and mobility. Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells. In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues. Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice. These findings indicate that YAP and TAZ may play a critical role in modulating pancreatic tissue regeneration, neoplastic transformation, and stellate cell functions in both PDAC and pancreatitis

Radio Properties of Low Redshift Broad Line Active Galactic Nuclei

The question as to whether the distribution of radio-loudness in active galactic nuclei (AGN) is actually bimodal has been discussed extensively in the literature. Futhermore, there have been claims that radio-loudness depends on black hole mass and Eddington ratio. We investigate these claims using the low redshift broad line AGN sample of Greene & Ho (2007), which consists of 8434 objects at z < 0.35 from the Sloan Digital Sky Survey Fourth Data Release (SDSS DR4). We obtained radio fluxes from the Very Large Array Faint Images of the Radio Sky at Twenty-Centimeters (FIRST) survey for the SDSS AGN. Out of the 8434 SDSS AGN, 821 have corresponding observed radio fluxes in the FIRST survey. We calculated the radio-loudness parameter (R) for all objects above the FIRST detection limit (1 mJy), and an upper limit to R for the undetected objects. Using these data, the question of radio bimodality is investigated for different subsets of the total sample. We find no clear demarcation between the radio-loud (RL, R > 10) and radio-quiet (RQ, R < 10) objects, but instead fill in a more radio-intermediate population in a continuous fashion for all subsamples. We find that 4.7% of the AGN in the flux-limited subsample are RL based on core radio emission alone. We calculate the radio-loud fraction (RLF) as both a function of black hole mass and Eddington ratio. The RLF decreases (from 13% to 2%) as Eddington ratio increases over 2.5 order of magnitude. The RLF is nearly constant (~5%) over 4 decades in black hole mass, except for an increase at masses greater than 10^8 solar masses. We find for the FIRST detected subsample that 367 of the RL AGN have black hole masses less than 10^8 solar masses, a large enough number to indicate that RL AGN are not a product of only the most massive black holes in the local universe.Comment: 28 pages, 14 figures, accepted to A

Raising the unification scale in supersymmetry

In the minimal supersymmetric standard model, the three gauge couplings appear to unify at a mass scale near $2 \times 10^{16}$ GeV. We investigate the possibility that intermediate scale particle thresholds modify the running couplings so as to increase the unification scale. By requiring consistency of this scenario, we derive some constraints on the particle content and locations of the intermediate thresholds. There are remarkably few acceptable solutions with a single cleanly defined intermediate scale far below the unification scale.Comment: 22 pages, macros included. One figure, available at ftp://ftp.phys.ufl.edu/incoming/rais.ep

Avoiding Irrational NeuroLaw Exuberance: A Plea for Neuromodesty

In a 2002 editorial published in The Economist, the following warning was given: Genetics may yet threaten privacy, kill autonomy, make society homogeneous and gut the concept of human nature. But neuroscience could do all of these things first. The genome was fully sequenced in 2001, and there has not been one resulting major advance in therapeutic medicine since. Thus, even in its most natural applied domain-medicine-genetics has not had the far-reaching consequences that were envisioned. The same has been true for various other sciences that were predicted to revolutionize the law, including behavioral psychology, sociology, psychodynamic psychology, and others. This will also be true of neuroscience, which is simply the newest science on the block. Neuroscience is not going to do the terrible things The Economist fears, at least not for the foreseeable future. Neuroscience has many things to say but not nearly as much as people would hope, especially in relation to law. At most, in the near to intermediate term, neuroscience may make modest contributions to legal policy and case adjudication. Nonetheless, there has been irrational exuberance about the potential contribution of neuroscience, an issue I have addressed previously and referred to as Brain Overclaim Syndrome. I first consider the law\u27s motivation and the motivation of some advocates to turn to science to solve the very hard normative problems that law addresses. Part III discusses the law\u27s psychology and its concepts of the person and responsibility. The next Part considers the general relation of neuroscience to law, which I characterize as the issue of translation. Part V canvasses various distractions that have bedeviled clear thinking about the relation of scientific, causal accounts of behavior to responsibility. The following Part examines the limits of neurolaw and Part VII considers why neurolaw does not pose a genuinely radical challenge to the law\u27s concepts of the person and responsibility. Part VIII makes a case for cautious optimism about the contribution neuroscience may make to law in the near and intermediate term. A brief conclusion follows..

Development of quantum perspectives in modern physics

Introductory undergraduate courses in classical physics stress a perspective that can be characterized as realist; from this perspective, all physical properties of a classical system can be simultaneously specified and thus determined at all future times. Such a perspective can be problematic for introductory quantum physics students, who must develop new perspectives in order to properly interpret what it means to have knowledge of quantum systems. We document this evolution in student thinking in part through pre- and post-instruction evaluations using the Colorado Learning Attitudes about Science Survey. We further characterize variations in student epistemic and ontological commitments by examining responses to two essay questions, coupled with responses to supplemental quantum attitude statements. We find that, after instruction in modern physics, many students are still exhibiting a realist perspective in contexts where a quantum-mechanical perspective is needed. We further find that this effect can be significantly influenced by instruction, where we observe variations for courses with differing learning goals. We also note that students generally do not employ either a realist or a quantum perspective in a consistent manner.Comment: 18 pages, plus references; 3 figures; 9 tables. PACS: 01.40.Fk, 03.65._

Arene oxidation with malonoyl peroxides

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed

Radio Properties of Low Redshift Broad Line Active Galactic Nuclei Including Extended Radio Sources

We present a study of the extended radio emission in a sample of 8434 low redshift (z < 0.35) broad line active galactic nuclei (AGN) from the Sloan Digital Sky Survey (SDSS). To calculate the jet and lobe contributions to the total radio luminosity, we have taken the 846 radio core sources detected in our previous study of this sample and performed a systematic search in the Faint Images of the Radio Sky at Twenty-centimeters (FIRST) database for extended radio emission that is likely associated with the optical counterparts. We found 51 out of 846 radio core sources have extended emission (> 4" from the optical AGN) that is positively associated with the AGN, and we have identified an additional 12 AGN with extended radio emission but no detectable radio core emission. Among these 63 AGN, we found 6 giant radio galaxies (GRGs), with projected emission exceeding 750 kpc in length, and several other AGN with unusual radio morphologies also seen in higher redshift surveys. The optical spectra of many of the extended sources are similar to that of typical broad line radio galaxy spectra, having broad H$\alpha$ emission lines with boxy profiles and large M_BH. With extended emission taken into account, we find strong evidence for a bimodal distribution in the radio-loudness parameter R, where the lower radio luminosity core-only sources appear as a population separate from the extended sources, with a dividing line at log(R) $\approx 1.75$. This dividing line ensures that these are indeed the most radio-loud AGN, which may have different or extreme physical conditions in their central engines when compared to the more numerous radio quiet AGN.Comment: 25 pages, 6 figures, accepted to A

Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction

BACKGROUND: Insulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF). METHODS: Serum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77). RESULTS: IGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E’ ratio, and NT-proBNP levels (all P ≤ 0.02). CONCLUSION: In conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement