Nitric oxide donation lowers blood pressure in adrenocorticotrophic hormone-induced hypertensive rats.

Adrenocorticotrophic hormone (ACTH) elevates systolic blood pressure (SBP) and lowers plasma reactive nitrogen intermediates in rats. We assessed the ability of NO donation from isosorbide dinitrate (ISDN) to prevent or reverse the hypertension caused by ACTH. In the prevention study, male Sprague Dawley rats were treated with ACTH (0.2 mg/kg/day) or saline control for 8 days, with either concurrent ISDN (100 mg/kg/day) via the drinking water or water alone. Animals receiving ISDN via the drinking water were provided with nitrate-free water for 8 hours every day. In the reversal study ISDN (100 mg/kg) or vehicle was given as a single oral dose on day 8. SBP was measured daily by the indirect tail-cuff method in conscious, restrained rats. ACTH caused a significant increase in SBP compared with saline (P < 0.0015). In the prevention study, chronic administration of ISDN (100 mg/kg/day) did not affect the SBP in either group. In the reversal study, ISDN significantly lowered SBP in ACTH-treated rats at 1 and 2.5 hours (132 +/- 3 mmHg (1 h) and 131 +/- 2 mmHg (2.5 h) versus 143 +/- 3 mmHg (0 h), P < 0.002), but not to control levels. It had no effect in control (saline treated) rats. In conclusion, the lowering of SBP by NO donation is consistent with the notion that ACTH-induced hypertension involves an impaired bioavailability or action of NO in vivo

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

Performance of Scheduling Policies in Adversarial Networks with Non-synchronized Clocks

In this paper we generalize the Continuous Adversarial Queuing Theory (CAQT) model (Blesa et al. in MFCS, Lecture Notes in Computer Science, vol. 3618, pp. 144–155, 2005) by considering the possibility that the router clocks in the network are not synchronized. We name the new model Non Synchronized CAQT (NSCAQT). Clearly, this new extension to the model only affects those scheduling policies that use some form of timing. In a first approach we consider the case in which although not synchronized, all clocks run at the same speed, maintaining constant differences. In this case we show that all universally stable policies in CAQT that use the injection time and the remaining path to schedule packets remain universally stable. These policies include, for instance, Shortest in System (SIS) and Longest in System (LIS). Then, we study the case in which clock differences can vary over time, but the maximum difference is bounded. In this model we show the universal stability of two families of policies related to SIS and LIS respectively (the priority of a packet in these policies depends on the arrival time and a function of the path traversed). The bounds we obtain in this case depend on the maximum difference between clocks. This is a necessary requirement, since we also show that LIS is not universally stable in systems without bounded clock difference. We then present a new policy that we call Longest in Queues (LIQ), which gives priority to the packet that has been waiting the longest in edge queues. This policy is universally stable and, if clocks maintain constant differences, the bounds we prove do not depend on them. To finish, we provide with simulation results that compare the behavior of some of these policies in a network with stochastic injection of packets

Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma. Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507. Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached. Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted

The Influence of Molecular Adsorption on Elongating Gold Nanowires

Using molecular dynamics simulations, we study the impact of physisorbing adsorbates on the structural and mechanical evolution of gold nanowires (AuNWs) undergoing elongation. We used various adsorbate models in our simulations, with each model giving rise to a different surface coverage and mobility of the adsorbed phase. We find that the local structure and mobility of the adsorbed phase remains relatively uniform across all segments of an elongating AuNW, except for the thinning region of the wire where the high mobility of Au atoms disrupts the monolayer structure, giving rise to higher solvent mobility. We analyzed the AuNW trajectories by measuring the ductile elongation of the wires and detecting the presence of characteristic structural motifs that appeared during elongation. Our findings indicate that adsorbates facilitate the formation of high-energy structural motifs and lead to significantly higher ductile elongations. In particular, our simulations result in a large number of monatomic chains and helical structures possessing mechanical stability in excess of what we observe in vacuum. Conversely, we find that a molecular species that interacts weakly (i.e., does not adsorb) with AuNWs worsens the mechanical stability of monatomic chains.Comment: To appear in Journal of Physical Chemistry

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Rope trauma, sedation, disentanglement, and monitoring-tag associated lesions in a terminally entangled North Atlantic right whale (Eubalaena glacialis)

Author Posting. © Society for Marine Mammalogy, 2012. Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms. The definitive version was published in Marine Mammal Science 29 (2013): E98–E113, doi:10.1111/j.1748-7692.2012.00591.x.A chronically entangled North Atlantic right whale, with consequent emaciation was sedated, disentangled to the extent possible, administered antibiotics, and satellite tag tracked for six subsequent days. It was found dead 11 d after the tag ceased transmission. Chronic constrictive deep rope lacerations and emaciation were found to be the proximate cause of death, which may have ultimately involved shark predation. A broadhead cutter and a spring-loaded knife used for disentanglement were found to induce moderate wounds to the skin and blubber. The telemetry tag, with two barbed shafts partially penetrating the blubber was shed, leaving barbs embedded with localized histological reaction. One of four darts administered shed the barrel, but the needle was found postmortem in the whale with an 80º bend at the blubber-muscle interface. This bend occurred due to epaxial muscle movement relative to the overlying blubber, with resultant necrosis and cavitation of underlying muscle. This suggests that rigid, implanted devices that span the cetacean blubber muscle interface, where the muscle moves relative to the blubber, could have secondary health impacts. Thus we encourage efforts to develop new tag telemetry systems that do not penetrate the subdermal sheath, but still remain attached for many months.Funding from NOAA Cooperative Agreement NA09OAR4320129, PO EA133F09SE4792, M. S. Worthington Foundation, North Pond Foundation, Sloan and Hardwick Simmons, and Woods Hole Oceanographic Institution Marine Mammal Center

Possible origins of macroscopic left-right asymmetry in organisms

I consider the microscopic mechanisms by which a particular left-right (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states driven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handedness such as the emergence of handedness in neurons, in eukaryote cell motility, and in non-flagellated bacteria.Comment: 42 pages, 6 figures, resubmitted to J. Stat. Phys. special issue. Major rewrite, rearranged sections/subsections, new Fig 3 + 6, new physics in Sec 2.4 and 3.4.1, added Sec 5 and subsections of Sec

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr