CARMA CO(J = 2 - 1) Observations of the Circumstellar Envelope of Betelgeuse

We report radio interferometric observations of the 12C16O 1.3 mm J = 2-1 emission line in the circumstellar envelope of the M supergiant Alpha Ori and have detected and separated both the S1 and S2 flow components for the first time. Observations were made with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) interferometer in the C, D, and E antenna configurations. We obtain good u-v coverage (5-280 klambda) by combining data from all three configurations allowing us to trace spatial scales as small as 0.9\arcsec over a 32\arcsec field of view. The high spectral and spatial resolution C configuration line profile shows that the inner S1 flow has slightly asymmetric outflow velocities ranging from -9.0 km s-1 to +10.6 km s-1 with respect to the stellar rest frame. We find little evidence for the outer S2 flow in this configuration because the majority of this emission has been spatially-filtered (resolved out) by the array. We also report a SOFIA-GREAT CO(J= 12-11) emission line profile which we associate with this inner higher excitation S1 flow. The outer S2 flow appears in the D and E configuration maps and its outflow velocity is found to be in good agreement with high resolution optical spectroscopy of K I obtained at the McDonald Observatory. We image both S1 and S2 in the multi-configuration maps and see a gradual change in the angular size of the emission in the high absolute velocity maps. We assign an outer radius of 4\arcsec to S1 and propose that S2 extends beyond CARMA's field of view (32\arcsec at 1.3 mm) out to a radius of 17\arcsec which is larger than recent single-dish observations have indicated. When azimuthally averaged, the intensity fall-off for both flows is found to be proportional to R^{-1}, where R is the projected radius, indicating optically thin winds with \rho \propto R^{-2}.Comment: 11 pages, 8 figures To be published in the Astronomical Journal (Received 2012 February 10; accepted 2012 May 25

An Efficient Framework for Global Non-Convex Polynomial Optimization over the Hypercube

We present a novel efficient theoretical and numerical framework for solving global non-convex polynomial optimization problems. We analytically demonstrate that such problems can be efficiently reformulated using a non-linear objective over a convex set; further, these reformulated problems possess no spurious local minima (i.e., every local minimum is a global minimum). We introduce an algorithm for solving these resulting problems using the augmented Lagrangian and the method of Burer and Monteiro. We show through numerical experiments that polynomial scaling in dimension and degree is achievable for computing the optimal value and location of previously intractable global polynomial optimization problems in high dimension

Valuing flexibility in product platforms : an analytical framework

Thesis (S.M. in Engineering and Management)--Massachusetts Institute of Technology, Engineering Systems Division, System Design and Management Program, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 81-83)."The intuitive mind is a sacred gift and the rational mind is a faithful servant. We have created a society that honours the servant and has forgotten the gift." - Einstein. "Whatever you can do, or dream you can, begin it. Boldness has genius, power, and magic in it." - Goethe. It is only with considerable help that I have traversed the steps that culminated in my signature on the cover of this document. I'd like to thank my advisor, Richard de Neufville, for his insightful guidance in completing this work. This document is more compelling, more cohesive, and more comprehensive than it could ever have been without his help. To the many wonderful professors, instructors and lecturers who I have learned from during my time at MIT, I thank you for sharing your wisdom with me. In particular, to Michael Davies and Tom Steenburgh - thank you for leading me to discover that it is neither the courses, the research, nor the degree that make this journey worthwhile; rather, that the greatest gift of my time here will be a lifetime of intellectual curiosity and the boldness to take on incredible projects. To Jim Utterback - thank you for leading me to appreciate that intellectual, technological and managerial practice are, at their core, humanistic pursuits. Finally, thank you to Pat Hale and the SDM staff for the incredible job you do in pulling together the phenomenal System Design and Management Fellows program. To the friends that I've made at MIT, thanks for continuously pushing me to learn more, work harder, and be smarter; I look forward to hearing about, and sharing in, the incredible exploits that await you in years to come. To my friends in Vancouver and scattered around the world, know that I draw strength from your existence, and that I look forward to seeing you again soon. Finally and most importantly: To my family. Thank you for your unwavering support as I have pursued my studies at MIT. In many ways, I embarked on this journey on your behalf; I hope that my experience here will, in the end, enrich all of our lives together.by Matthew A. M. Harper.S.M.in Engineering and Managemen

Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes

Abstract: Tissue factor (TF) plays a central role in haemostasis and thrombosis. Following vascular damage, vessel wall TF initiates the extrinsic coagulation cascade. TF can also be exposed by monocytes. Inflammatory or infectious stimuli trigger synthesis of new TF protein by monocytes over the course of hours. It has also been suggested that monocytes can expose TF within minutes when stimulated by activated platelets. Here, we have confirmed that monocytes rapidly expose TF in whole blood and further demonstrate that platelet P-selectin exposure is necessary and sufficient. Monocyte TF exposure increased within five minutes in response to platelet activation by PAR1-AP, PAR4-AP or CRP-XL. PAR1-AP did not trigger TF exposure on isolated monocytes unless platelets were also present. In whole blood, PAR1-AP-triggered TF exposure required P-selectin and PGSL-1. In isolated monocytes, although soluble recombinant P-selectin had no effect, P-selectin coupled to 2 µm beads triggered TF exposure. Cycloheximide did not affect rapid TF exposure, indicating that de novo protein synthesis was not required. These data show that P-selectin on activated platelets rapidly triggers TF exposure on monocytes. This may represent a mechanism by which platelets and monocytes rapidly contribute to intravascular coagulation

Genetic analysis of the role of protein kinase Ctheta in platelet function and thrombus formation.

BACKGROUND: PKCtheta is a novel protein kinase C isozyme, predominately expressed in T cells and platelets. PKCtheta(-/-) T cells exhibit reduced activation and PKCtheta(-/-) mice are resistant to autoimmune disease, making PKCtheta an attractive therapeutic target for immune modulation. Collagen is a major agonist for platelets, operating through an immunoreceptor-like signalling pathway from its receptor GPVI. Although it has recently been shown that PKCtheta positively regulates outside-in signalling through integrin alpha(IIb)beta(3) in platelets, the role of PKCtheta in GPVI-dependent signalling and functional activation of platelets has not been assessed. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we assessed static adhesion, cell spreading, granule secretion, integrin alpha(IIb)beta(3) activation and platelet aggregation in washed mouse platelets lacking PKCtheta. Thrombus formation on a collagen-coated surface was assessed in vitro under flow. PKCtheta(-/-) platelets exhibited reduced static adhesion and filopodia generation on fibrinogen, suggesting that PKCtheta positively regulates outside-in signalling, in agreement with a previous report. In contrast, PKCtheta(-/-) platelets also exhibited markedly enhanced GPVI-dependent alpha-granule secretion, although dense granule secretion was unaffected, suggesting that PKCtheta differentially regulates these two granules. Inside-out regulation of alpha(IIb)beta(3) activation was also enhanced downstream of GPVI stimulation. Although this did not result in increased aggregation, importantly thrombus formation on collagen under high shear (1000 s(-1)) was enhanced. CONCLUSIONS/SIGNIFICANCE: These data suggest that PKCtheta is an important negative regulator of thrombus formation on collagen, potentially mediated by alpha-granule secretion and alpha(IIb)beta(3) activation. PKCtheta therefore may act to restrict thrombus growth, a finding that has important implications for the development and safe clinical use of PKCtheta inhibitors

Monitoring Glacier Surface Seismicity in Time and Space Using Rayleigh Waves

Sliding glaciers and brittle ice failure generate seismic body and surface wave energy characteristic to the source mechanism. Here we analyze continuous seismic recordings from an array of nine short-period passive seismometers located on Bench Glacier, Alaska (USA) (61.033°N, 145.687°W). We focus on the arrival-time and amplitude information of the dominant Rayleigh wave phase. Over a 46-hour period we detect thousands of events using a cross-correlation based event identification method. Travel-time inversion of a subset of events (7% of the total) defines an active crevasse, propagating more than 200 meters in three hours. From the Rayleigh wave amplitudes, we estimate the amount of volumetric opening along the crevasse as well as an average bulk attenuation ( Q ¯ = 42) for the ice in this part of the glacier. With the remaining icequake signals we establish a diurnal periodicity in seismicity, indicating that surface run-off and subglacial water pressure changes likely control the triggering of these surface events. Furthermore, we find that these events are too weak (i.e., too noisy) to locate individually. However, stacking individual events increases the signal-to-noise ratio of the waveforms, implying that these periodic sources are effectively stationary during the recording period

Syntaxin 8 regulates platelet dense granule secretion, aggregation, and thrombus stability.

Platelet secretion not only drives thrombosis and hemostasis, but also mediates a variety of other physiological and pathological processes. The ubiquitous SNARE machinery and a number of accessory proteins have been implicated in regulating secretion in platelet. Although several platelet SNAREs have been identified, further members of the SNARE family may be needed to fine-tune platelet secretion. In this study we identified expression of the t-SNARE syntaxin 8 (STX8) (Qc SNARE) in mouse and human platelets. In mouse studies, whereas STX8 was not essential for α-granule or lysosome secretion, Stx8(-/-) platelets showed a significant defect in dense granule secretion in response to thrombin and CRP. This was most pronounced at intermediate concentrations of agonists. They also showed an aggregation defect that could be rescued with exogenous ADP and increased embolization in Stx8(-/-) mice in vivo consistent with an important autocrine and paracrine role for ADP in aggregation and thrombus stabilization. STX8 therefore specifically contributes to dense granule secretion and represents another member of a growing family of genes that play distinct roles in regulating granule release from platelets and thus platelet function in thrombosis and hemostasis

Enhanced attention in rats following blast-induced traumatic brain injury

Purpose To evaluate visuo-cognitive sequelae following blast-induced traumatic brain injury in a rat model. Methods Rats were randomly assigned to one of four groups depending on the intensity/quantity of a blast received in a blast chamber: sham (no blast), low intensity (22 psi), medium intensity (26 psi), or three medium intensity blasts (26 psi × 3). After recovery, all subjects were given visual discrimination tasks of increasing complexity, until mastery. After behavioral training, visual function was assessed via spectral-domain optical coherence tomography and pattern electroretinogram, and the extent of retinal damage was quantified via immunohistochemistry of retinal ganglion cells. Results None of the measures assessing visual function revealed significant differences as a function of blast intensity/quantity. Behavioral training did not disclose short-term effects of blast in general motivation or the development of anticipatory responding. No differences in general learning ability and the number of perseverative errors were observed. However, behavioral training found effects of blast in attentional function; relative to controls, subjects that received blasts were faster in learning to attend to informative (over non-informative) cues in the most difficult visual discrimination task. Conclusion Blast exposure in rats resulted in increased attention following blast, with no appreciable deficits in visual function. These results are contrary to what is often reported for human clinical populations; as such, more research bridging methodological differences is necessary

Loss of the insulin receptor in murine megakaryocytes/platelets causes thrombocytosis and alterations in IGF signalling.

AIMS: Patients with conditions that are associated with insulin resistance such as obesity, type 2 diabetes mellitus, and polycystic ovary syndrome have an increased risk of thrombosis and a concurrent hyperactive platelet phenotype. Our aim was to determine whether insulin resistance of megakaryocytes/platelets promotes platelet hyperactivation. METHODS AND RESULTS: We generated a conditional mouse model where the insulin receptor (IR) was specifically knocked out in megakaryocytes/platelets and performed ex vivo platelet activation studies in wild-type (WT) and IR-deficient platelets by measuring aggregation, integrin αIIbβ3 activation, and dense and α-granule secretion. Deletion of IR resulted in an increase in platelet count and volume, and blocked the action of insulin on platelet signalling and function. Platelet aggregation, granule secretion, and integrin αIIbβ3 activation in response to the glycoprotein VI (GPVI) agonist collagen-related peptide (CRP) were significantly reduced in platelets lacking IR. This was accompanied by a reduction in the phosphorylation of effectors downstream of GPVI. Interestingly, loss of IR also resulted in a reduction in insulin-like growth factor-1 (IGF-1)- and insulin-like growth factor-2 (IGF-2)-mediated phosphorylation of IRS-1, Akt, and GSK3β and priming of CRP-mediated platelet activation. Pharmacological inhibition of IR and the IGF-1 receptor in WT platelets recapitulated the platelet phenotype of IR-deficient platelets. CONCLUSIONS: Deletion of IR (i) increases platelet count and volume, (ii) does not cause platelet hyperactivity, and (iii) reduces GPVI-mediated platelet function and platelet priming by IGF-1 and IGF-2