Telemetric Blood Pressure Assessment in Angiotensin II-Infused ApoE\u3csup\u3e-/-\u3c/sup\u3e Mice: 28 Day Natural History and Comparison to Tail-Cuff Measurements

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of arterial pulse pressure in anesthetized mice would have sufficient accuracy to enable calculations of aortic distensibility with minimal error. Telemetry devices and osmotic mini-pumps filled with saline or angiotensin-II were surgically implanted in male apolipoprotein-E deficient (ApoE-/-) mice. Blood pressure in the aortic arch was measured continuously via telemetry. In addition, simultaneous blood pressure measurements with a volume/pressure tail-cuff system were performed under anesthesia at specific intervals to assess agreement between techniques. Compared to controls, mice infused with angiotensin-II had an overall statistically significant increase in systolic pressure, with no overall difference in pulse pressure; however, pulse pressure did increase significantly with time. Systolic measurements agreed well between telemetry and tail-cuff (coefficient of variation = 10%), but agreement of pulse pressure was weak (20%). In fact, group-averaged pulse pressure from telemetry was a better predictor of a subject\u27s pulse pressure on a given day than a simultaneous tail-cuff measurement. Furthermore, these approximations introduced acceptable errors (15.1 ± 12.8%) into the calculation of aortic distensibility. Contrary to our hypothesis, we conclude that tail-cuff measures of arterial pulse pressure have limited accuracy. Future studies of aneurysm mechanics using the ApoE-/-/angiotensin-II model would be better in assuming pulse pressure profiles consistent with our telemetry findings instead of attempting to measure pulse pressure in individual mice

SN2013fs and SN2013fr: Exploring the circumstellar-material diversity in Type II supernovae

We present photometry and spectroscopy of SN2013fs and SN2013fr in the first 100 days post-explosion. Both objects showed transient, relatively narrow H$\alpha$ emission lines characteristic of SNeIIn, but later resembled normal SNeII-P or SNeII-L, indicative of fleeting interaction with circumstellar material (CSM). SN2013fs was discovered within 8hr of explosion. Its light curve exhibits a plateau, with spectra revealing strong CSM interaction at early times. It is a less luminous version of the transitional SNIIn PTF11iqb, further demonstrating a continuum of CSM interaction intensity between SNeII-P and IIn. It requires dense CSM within 6.5$\times$10$^{14}$~cm of the progenitor, from a phase of advanced pre-SN mass loss shortly before explosion. Spectropolarimetry of SN2013fs shows little continuum polarization, but noticeable line polarization during the plateau phase. SN2013fr morphed from a SNIIn at early times to a SNII-L. After the first epoch its narrow lines probably arose from host-galaxy emission, but the bright, narrow H$\alpha$ emission at early times may be intrinsic. As for SN2013fs, this would point to a short-lived phase of strong CSM interaction if proven to be intrinsic, suggesting a continuum between SNeIIn and II-L. It is a low-velocity SNII-L, like SN2009kr but more luminous. SN2013fr also developed an IR excess at later times, due to warm CSM dust that require a more sustained phase of strong pre-SN mass loss.Comment: MNRAS accepted. 28 pages, 23 figures, 8 table

Discovery of A New Retrograde Trans-Neptunian Object: Hint of A Common Orbital Plane for Low Semi-Major Axis, High Inclination TNOs and Centaurs

Although the majority of Centaurs are thought to have originated in the scattered disk, with the high-inclination members coming from the Oort cloud, the origin of the high inclination component of trans-Neptunian objects (TNOs) remains uncertain. We report the discovery of a retrograde TNO, which we nickname "Niku", detected by the Pan-STARRS 1 Outer Solar System Survey. Our numerical integrations show that the orbital dynamics of Niku are very similar to that of 2008 KV$_{42}$ (Drac), with a half-life of $\sim 500$ Myr. Comparing similar high inclination TNOs and Centaurs ($q > 10$ AU, $a 60^\circ$), we find that these objects exhibit a surprising clustering of ascending node, and occupy a common orbital plane. This orbital configuration has high statistical significance: 3.8-$\sigma$. An unknown mechanism is required to explain the observed clustering. This discovery may provide a pathway to investigate a possible reservoir of high-inclination objects.Comment: 18 pages, 4 figures, 1 table, accepted for publication in ApJ Letter

Gaussian field theories, random Cantor sets and multifractality

The computation of multifractal scaling properties associated with a critical field theory involves non-local operators and remains an open problem using conventional techniques of field theory. We propose a new description of Gaussian field theories in terms of random Cantor sets and show how universal multifractal scaling exponents can be calculated. We use this approach to characterize the multifractal critical wave function of Dirac fermions interacting with a random vector potential in two spatial dimensions. We show that the multifractal scaling exponents are self-averaging.Comment: Extensive modifications of previous version; exact results replace numerical calculation

Observation of the hyperfine transition in lithium-like Bismuth 209Bi80+^{209}\text{Bi}^{80+}: Towards a test of QED in strong magnetic fields

We performed a laser spectroscopic determination of the $2s$ hyperfine splitting (HFS) of Li-like $^{209}\text{Bi}^{80+}$ and repeated the measurement of the $1s$ HFS of H-like $^{209}\text{Bi}^{82+}$. Both ion species were subsequently stored in the Experimental Storage Ring at the GSI Helmholtzzentrum f\"ur Schwerionenforschung Darmstadt and cooled with an electron cooler at a velocity of $\approx 0.71\,c$. Pulsed laser excitation of the $M1$ hyperfine-transition was performed in anticollinear and collinear geometry for $\text{Bi}^{82+}$ and $\text{Bi}^{80+}$, respectively, and observed by fluorescence detection. We obtain $\Delta E^{(1s)}= 5086.3(11)\,\textrm{meV}$ for $\text{Bi}^{82+}$, different from the literature value, and $\Delta E^{(2s)}= 797.50(18)\,\textrm{meV}$ for $\text{Bi}^{80+}$. These values provide experimental evidence that a specific difference between the two splitting energies can be used to test QED calculations in the strongest static magnetic fields available in the laboratory independent of nuclear structure effects. The experimental result is in excellent agreement with the theoretical prediction and confirms the sum of the Dirac term and the relativistic interelectronic-interaction correction at a level of 0.5% confirming the importance of accounting for the Breit interaction.Comment: 5 pages, 2 figure

Neighbor-directed histidine N (τ)-alkylation: A route to imidazolium-containing phosphopeptide macrocycles

Our recently discovered, selective, on-resin route to N(τ)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. Interestingly, these cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Neighbor-directed histidine N(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.National Institutes of Health (U.S.) (Grants ES015339 and GM104047

Effects of cardiomyopathy-linked mutations K15N and R21H in tropomyosin on thin-filament regulation and pointed-end dynamics

Missense mutations K15N and R21H in striated muscle tropomyosin are linked to dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), respectively. Tropomyosin, together with the troponin complex, regulates muscle contraction and, along with tropomodulin and leiomodin, controls the uniform thin-filament lengths crucial for normal sarcomere structure and function. We used Förster resonance energy transfer to study effects of the tropomyosin mutations on the structure and kinetics of the cardiac troponin core domain associated with the Ca2+-dependent regulation of cardiac thin filaments. We found that the K15N mutation desensitizes thin filaments to Ca2+ and slows the kinetics of structural changes in troponin induced by Ca2+ dissociation from troponin, while the R21H mutation has almost no effect on these parameters. Expression of the K15N mutant in cardiomyocytes decreases leiomodin’s thin-filament pointed-end assembly but does not affect tropomodulin’s assembly at the pointed end. Our in vitro assays show that the R21H mutation causes a twofold decrease in tropomyosin’s affinity for F-actin and affects leiomodin’s function. We suggest that the K15N mutation causes DCM by altering Ca2+-dependent thin-filament regulation and that one of the possible HCM-causing mechanisms by the R21H mutation is through alteration of leiomodin’s function

DEFENS - Drug Exposure Feedback and Education for Nurses’ Safety: study protocol for a randomized controlled trial

Abstract Background Three decades of research findings have documented the health effects of handling hazardous drugs. Oncology nurses are vulnerable due to frequent administration of antineoplastics, low adherence to equipment use, reported barriers to use, and perceived low risk of health effects. No interventions have been tested in a controlled, multi-site trial to increase nurses’ use of protective equipment when handling hazardous drugs. The Drug Exposure Feedback and Education for Nurses’ Safety (DEFENS) study will compare the efficacy of education (control) versus an audit and feedback intervention (treatment) on nurses’ self-reported use of personal protective equipment when handling hazardous drugs. The treatment intervention will include tailored messages based on nurses’ reported barriers to protective equipment use. Methods/Design The DEFENS Study is a cluster randomized controlled trial. We are enrolling cancer centers and will recruit nurse participants in April 2015. Eligible cancer centers employ at least 20 eligible registered nurses in the chemotherapy infusion setting and have on-site phlebotomy resources. Eligible participants are nurses who work at least 0.40 full-time equivalent hours in the chemotherapy infusion setting and have not received an antineoplastic drug for a health problem in the past year. An encrypted, user-authenticated website will administer surveys and deliver control and treatment interventions. The primary endpoint is the change in score on nurses’ reports of the Revised Hazardous Drug Handling Questionnaire between baseline and approximately 18 months later. A baseline survey is completed after informed consent and is repeated 18 months later. Nurses in all sites who experience a drug spill will also report incidents as they occur; these reports inform the treatment intervention. Plasma will be obtained at baseline, approximately 18 months later (the primary endpoint), and with drug spill occurrences to measure hazardous drugs levels and to inform the treatment intervention. Potential mediators include knowledge of hazardous drug handling and perceived risk of drug exposure. We will examine whether personal factors and organizational factors moderate the intervention effects. Trial registration Clinicaltrials.gov NCT02283164 , registered 31 October 2014.http://deepblue.lib.umich.edu/bitstream/2027.42/111045/1/13063_2015_Article_674.pd