536 research outputs found
Rates of vertical mixing, gas exchange, and new production : estimates from seasonal gas cycles in the upper ocean near Bermuda
Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution June 1989Argon measurements, obtained from three years of monthly detailed vertical profiles near
Bermuda (Station S, 32°N 64°W), show a maximum in argon supersaturation of about 4% in
the seasonal thermocline in late summer. Since the argon supersaturation is 3-4 times smaller
than that of oxygen, most of the oxygen supersaturation is not of physical origin and hence
must result from biological production.
In the winter mixed layer, air injection produces argon supersaturation despite high gas
exchange rates. During spring and summer, radiative heating, air injection, and an upward
argon flux create an even larger supersaturation in the mixed layer. In the seasonal thermocline,
radiative heating creates argon supersaturations that persist in spite of vertical mixing.
The observed seasonal cycles of temperature, argon, helium, and oxygen are simulated with
an upper ocean model. I linearize the model's response to variations in vertical diffusivity, air
injection, gas exchange rate, and new production and then use an inverse technique (singular
value decomposition) to determine the values of these parameters that best fit the data. Results
for the 1985-1987 average are as follows: A vertical turbulent diffusivity of 1.0 ± 0.1 x 10-4 m2
s-1 is consistent with both the thermal history and subsurface argon distribution. The rate of
air injection, determined to ±15%, is similar to previous estimates. The seasonally-averaged
gas exchange rate, determined to ± 11%, is consistent within errors with that predicted by Liss
and Merlivat (1986). I estimate a lower limit to depth-integrated new production below the
mixed layer of 5.0 ± 1.0 moles 0 2 m-2 yr-1 , and obtain an estimate of 6.2 ± 0.9 moles 0 2 m-2
yr-1 if new production in the mixed layer is fixed at zero. The period 1985-1987 appears to
be typical of the climatological mean conditions at Station S and comparable to the 1960-1970
average period analyzed by Jenkins & Goldman (1985) and Musgrave et al. (1988).
I propose that a mesoscale anticyclonic eddy is responsible for excess 3He and nitrate in the
euphotic zone observed at a July, 1986 occupation of the Station S site. Hydrographic profiles
are consistent with a type of eddy observed by Brundage & Dugan (1986), characterized by an
unusually thick lens of subtropical mode (18°C) water. Analysis of the 35 year hydrographic
record suggests that such eddies may arrive at Station S with an average frequency of 2-6 times
per year, mostly during the summer and in years of vigorous 18°C water formation. Their
timing and character suggest that they may be formed during winter convection events in the northeastern Sargasso Sea, advected southwestward by the gyre-scale circulation, and eventually
absorbed by the Gulf Stream. Their magnitude and frequency indicate that they may supply
a significant portion of the 3He and nutrient flux into the euphotic zone near Bermuda, and
suggest a mechanism by which newly formed subtropical mode water is incorporated within the
gyre interior. However, enhanced new production in such eddies could account for only a small
portion of the new production integrated over the Sargasso Sea.This
project has been supported by grant OCE85-01171 from the National Science Foundation
Rates of vertical mixing, gas exchange and new production: Estimates from seasonal gas cycles in the upper ocean near Bermuda
Argon measurements, obtained from one year of monthly detailed vertical profiles near Bermuda (32N 64W), show a maximum in argon supersaturation of about 4% in the seasonal thermocline in late summer. Since the argon supersaturation is 3–4 times smaller than that of oxygen, most of the oxygen supersaturation is not of physical origin and hence must result from biological production. In the winter mixed layer, air injection produces argon supersaturation in spite of high gas exchange rates. During spring and summer, radiative heating, air injection, and an upward argon flux create an even larger supersaturation in the mixed layer. In the seasonal thermocline, radiative heating maintains argon concentrations above solubility equilibrium in spite of vertical mixing. The observed seasonal cycles of temperature, argon, helium, and oxygen are simulated with an upper ocean model. We linearized the model\u27s response to variations in vertical diffusivity, air injection, gas exchange rate, and new production and then used an inverse technique (singular value decomposition) to determine the values of these parameters that best fit the data. A vertical turbulent diffusivity of 0.9 ± 0.1 × 10–4 m2 s–1 is consistent with both the thermal history and subsurface argon distribution. The rate of air injection, determined to ±25%, is similar to previous estimates. The seasonally-averaged gas exchange rate is 17 ± 12% lower than predicted by Liss and Merlivat (1986). We estimate a lower limit to depth-integrated new production below the mixed layer of 4.3 ± 1.7 moles O2 m–2 yr–1 during 1985, and obtain an estimate of 5.6 ± 1.5 moles O2 m–1 yr–1 if new production in the mixed layer is fixed at zero
Is Washington Ready for Merit Selection of Judges
In 1980, Seattle established a judicial merit selection process for the Seattle Municipal Court, based on an approach used in many other jurisdictions and by the federal government under President Carter. The Seattle plan represents the first time a merit selection commission of lawyers and lay people has been used for nonfederal appointments in Washington. The two individuals subsequently appointed to the Seattle Municipal Court have gone through one of this state\u27s most rigorous judicial selection processes.
In this article, we will review how judges are presently selected in this state, the various methods of choosing judges in other jurisdictions and then discuss Seattle\u27s experience with merit selection. Then we will suggest the extent to which merit selection might be applied to other judgeships in Washington
Edith Abbott Was Right: Designing Fieldwork Experiences for Contemporary Health Care Practice
Successful social work practice in the contemporary, economically driven, health care environment demands unprecedented levels of technical competence, initiative, creativity and conceptual sophistication. Fieldwork plays a critical role in social work education for such demanding practice by providing interns initial opportunities to apply their newly acquired knowledge, skills and abilities. This article discusses the contribution of fieldwork to the preparation of social work practitioners and presents two programs that may serve as alternative models of fieldwork. Observations of the impact of these models, including a summary of two evaluations of one model are presented. We contend that a fieldwork structure using rotations may increase the value of fieldwork for students both academically and in the employment process.
Correct citation for final version of manuscript is:
Spitzer, W., Holden, G., Cuzzi, L. C., Rutter, S., Chernack, P., & Rosenberg, G. (2001). Edith Abbott was right: Designing fieldwork experiences for contemporary health care practice. Journal of Social Work Education, 37, 79-90
Heavenly Bodies RSVP
The purpose of the Heavenly Bodies RSVP project was to design and fabricate planet props, as well as a mechanism by which they could be raised and lowered in California Polytechnic State University’s Pavilion theater. The project team was comprised of four fourth year mechanical engineering students: Allison Turnbaugh, Braden Lockwood, Jack Boulware, and Justin Spitzer. We conducted extensive research to determine the ideal solution for the design problem brought to us by our sponsor. In our analysis, we discovered that the most important aspects of our design were the absolute reliability of the system, fire retardant material selection, and the overall aesthetics of the planets. These criteria along with our past product research allowed us to design a product that aligned with the vision of our sponsor. The system of planets was planned for use by the Music Department for the 25th installment of their annual diverse transmedia series entitled RSVP XXV: Call and Response. Sponsored by Dr. Antonio Barata, the show’s artistic director and producer, and professor in Cal Poly’s Music Department, the project featured design considerations unique to the location and nature of the production. For instance, the project had a hard completion deadline set for May 17, 2020, as stage construction would have been completed in preparation for rehearsals the following week. We determined that approximately 20 planets would be manufactured by the end of the project as well as a system to deploy them. Our objective was to make these planets safe, quiet, aesthetically pleasing, lightweight, and suitably reliable for use in the play. Though our design was unique to the needs of our sponsor, research of patented mechanisms provided inspiration for a system to raise and lower the planets. This information was utilized during ideation, which resulted in the creation of a few viable solutions, discussed later in this document. Working with our sponsor and advisor, the team finalized and tested a design, then created a structural prototype. However, due to the outbreak of COVID-19, the team was forced to forgo construction of a final product, as the production was cancelled. In response, the team devoted its remaining time to creating a set of online instructions to assist others in building and implementing the developed system
Theory of self-resonance after inflation. II. Quantum mechanics and particle-antiparticle asymmetry
We further develop a theory of self-resonance after inflation in a large class of models involving multiple scalar fields. We concentrate on inflaton potentials that carry an internal symmetry, but also analyze weak breaking of this symmetry. This is the second part of a two-part series of papers. Here in Part 2 we develop an understanding of the resonance structure from the underlying many-particle quantum mechanics. We begin with a small-amplitude analysis, which obtains the central resonant wave numbers, and relate it to perturbative processes. We show that the dominant resonance structure is determined by (i) the nonrelativistic scattering of many quantum particles and (ii) the application of Bose-Einstein statistics to the adiabatic and isocurvature modes, as introduced in Part 1 [M. P. Hertzberg et al., Phys. Rev. D 90, 123528 (2014)]. Other resonance structures are understood in terms of annihilations and decays. We set up Bunch-Davies vacuum initial conditions during inflation and track the evolution of modes including Hubble expansion. In the case of a complex inflaton carrying an internal U(1) symmetry, we show that when the isocurvature instability is active, the inflaton fragments into separate regions of ϕ-particles and anti-ϕ-particles. We then introduce a weak breaking of the U(1) symmetry; this can lead to baryogenesis, as shown by some of us recently [M. P. Hertzberg and J. Karouby, Phys. Lett. B 737, 34 (2014); Phys. Rev. D 89, 063523 (2014)]. Then using our results, we compute corrections to the particle-antiparticle asymmetry from this preheating era.Massachusetts Institute of Technology. Center for Theoretical PhysicsMassachusetts Institute of Technology. Undergraduate Research Opportunities ProgramUnited States. Dept. of Energy (Cooperative Research Agreement Contract DE-FG02-05ER41360)Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship
Theory of self-resonance after inflation. I. Adiabatic and isocurvature Goldstone modes
We develop a theory of self-resonance after inflation. We study a large class of models involving multiple scalar fields with an internal symmetry. For illustration, we often specialize to dimension-four potentials, but we derive results for general potentials. This is the first part of a two part series of papers. Here in Part 1 we especially focus on the behavior of long-wavelength modes, which are found to govern most of the important physics. Since the inflaton background spontaneously breaks the time-translation symmetry and the internal symmetry, we obtain Goldstone modes; these are the adiabatic and isocurvature modes. We find general conditions on the potential for when a large instability band exists for these modes at long wavelengths. For the adiabatic mode, this is determined by a sound speed derived from the time-averaged potential, while for the isocurvature mode, this is determined by a speed derived from a time-averaged auxiliary potential. Interestingly, we find that this instability band usually exists for one of these classes of modes, rather than both simultaneously. We focus on backgrounds that evolve radially in field space, as set up by inflation, and also mention circular orbits, as relevant to Q-balls. In Part 2 [M. P. Hertzberg et al., Phys. Rev. D 90, 123529 (2014)] we derive the central behavior from the underlying description of many-particle quantum mechanics, and introduce a weak breaking of the symmetry to study corrections to particle-antiparticle production from preheating.Massachusetts Institute of Technology. Center for Theoretical PhysicsMassachusetts Institute of Technology. Undergraduate Research Opportunities ProgramUnited States. Dept. of Energy (Cooperative Research Agreement Contract DE-FG02-05ER41360)Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship
Sigma-2 receptor agonist derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) induce cell death via mitochondrial superoxide production and caspase activation in pancreatic cancer
Abstract
Background
Despite considerable efforts by scientific research, pancreatic cancer is the fourth leading cause of cancer related mortalities. Sigma-2 receptors, which are overexpressed in several tumors, represent promising targets for triggering selective pancreatic cancer cells death.
Methods
We selected five differently structured high-affinity sigma-2 ligands (PB28, PB183, PB221, F281 and PB282) to study how they affect the viability of diverse pancreatic cancer cells (human cell lines BxPC3, AsPC1, Mia PaCa-2, and Panc1 and mouse Panc-02, KCKO and KP-02) and how this is reflected in vivo in a tumor model.
Results
Important cytotoxicity was shown by the compounds in the aggressive Panc02 cells, where cytotoxic activity was caspase-3 independent for four of the five compounds. However, both cytotoxicity and caspase-3 activation involved generation of Reactive Oxygen Species (ROS), which could be partially reverted by the lipid antioxidant \u3b1-tocopherol, but not by the hydrophilic N-acetylcysteine (NAC) indicating crucial differences in the intracellular sites exposed to oxidative stress induced by sigma-2 receptor ligands. Importantly, all the compounds strongly increased the production of mitochondrial superoxide radicals except for PB282. Despite a poor match between in vitro and the in vivo efficacy, daily treatment of C57BL/6 mice bearing Panc02 tumors resulted in promising effects with PB28 and PB282 which were similar compared to the current standard-of-care chemotherapeutic gemcitabine without showing signs of systemic toxicities.
Conclusions
Overall, this study identified differential sensitivities of pancreatic cancer cells to structurally diverse sigma-2 receptor ligands. Of note, we identified the mitochondrial superoxide pathway as a previously unrecognized sigma-2 receptor-activated process, which encourages further studies on sigma-2 ligand-mediated cancer cell death for the targeted treatment of pancreatic tumors
Lysosomal membrane permeabilization is an early event in sigma-2 receptor ligand mediated cell death in pancreatic cancer
BACKGROUND: Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer. RESULTS: Fluorescently labeled sigma-2 receptor ligands of two classes (derivatives of SW43 and PB282) localize to cell membrane components in Bxpc3 and Aspc1 pancreatic cancer cells and accumulate in lysosomes. We found that interactions in the lysosome are critical for cell death following sigma-2 ligand treatment because selective inhibition of a protective lysosomal membrane glycoprotein, LAMP1, with shRNA greatly reduced the viability of cells following treatment. Sigma-2 ligands induced lysosomal membrane permeabilization (LMP) and protease translocation triggering downstream effectors of apoptosis. Subsequently, cellular oxidative stress was greatly increased following treatment with SW43, and the hydrophilic antioxidant N-acetylcysteine (NAC) gave greater protection against this than a lipophilic antioxidant, α-tocopherol (α-toco). Conversely, PB282-mediated cytotoxicity relied less on cellular oxidation, even though α-toco did provide protection from this ligand. In addition, we found that caspase-3 induction was not as significantly inhibited by cathepsin inhibitors as by antioxidants. Both NAC and α-toco protected against caspase-3 induction following PB282 treatment, while only NAC offered protection following SW43 treatment. The caspase-3 inhibitor DEVD-FMK offered significant protection from PB282, but not SW43. CONCLUSIONS: Sigma-2 ligand SW43 commits pancreatic cancer cells to death by a caspase-independent process involving LMP and oxidative stress which is protected from by NAC. PB282 however undergoes a caspase-dependent death following LMP protected by DEVD-FMK and α-toco, which is also known to stabilize the mitochondrial membrane during apoptotic stimuli. These differences in mechanism are likely dependent on the structural class of the compounds versus the inherent sigma-2 binding affinity. As resistance of pancreatic cancers to specific apoptotic stimuli from chemotherapy is better appreciated, and patient-tailored treatments become more available, ligands with high sigma-2 receptor affinity should be chosen based on sensitivities to apoptotic pathways
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