Early days of molecular biology in the California Institute of Technology.
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Air quality modeling in the South Coast Air Basin of California: what do the numbers really mean?
This study evaluates air quality model sensitivity to input and to model components. Simulations are performed using the California Institute of Technology (CIT) airshed model. Results show the impacts on ozone (O3) concentration in the South Coast Air Basin (SCAB) of California because of changes in: (1) input data, including meteorological conditions (temperature, UV radiation, mixing height, and wind speed), boundary conditions, and initial conditions (ICs); and (2) model components, including advection solver and chemical mechanism. O3 concentrations are strongly affected by meteorological conditions and, in particular, by temperature. ICs also affect O3 concentrations, especially in the first 2 days of simulation. On the other hand, boundary conditions do not significantly affect the absolute peak O3 concentration, although they do affect concentrations near the inflow boundaries. Moreover, predicted O3 concentrations are impacted considerably by the chemical mechanism. In addition, dispersion of pollutants is affected by the advection routine used to calculate its transport. Comparison among CIT, California Photochemical Grid Model (CALGRID), and Urban Airshed Model air quality models suggests that differences in O3 predictions are mainly caused by the different chemical mechanisms used. Additionally, advection solvers contribute to the differences observed among model predictions. Uncertainty in predicted peak O3 concentration suggests that air quality evaluation should not be based solely on this single value but also on trends predicted by air quality models using a number of chemical mechanisms and with an advection solver that is mass conservative.
Air Pollution↗
Commuting to high altitude. Recent studies of oxygen enrichment.
Further studies have been carried out on the potential value of oxygen enrichment of room air for commuters to high altitude. Novel ways of providing oxygen-enriched spaces for working and sleeping are being tested at the California Institute of Technology where a radiotelescope is being designed for an altitude of 5,000 m in north Chile. The modules are containers such as those used on container ships, and they are fitted out in California and then sealed and transported to the telescope site in Chile. The result is a turnkey facility which shows promise for field studies. The oxygen is provided by oxygen concentrators, and different modules are used for sleeping, living, and laboratory quarters. Two extensive experiments on oxygen enrichment were carried out at the University of California White Mountain Research Station, altitude 3,800 m, in the summer of 1998. The first study was devoted to the mechanism for the increase in arterial oxygen saturation on the day after sleeping in an oxygen-enriched atmosphere compared with sleeping in ambient air (5). Possible mechanisms include less fluid accumulation in the lung associated with acute mountain sickness, or a change in the control of ventilation. A double blind study was therefore carried out of the effects of sleeping in oxygen enrichment on both the ventilatory response to hypoxia and to carbon dioxide. In a related study, subjects who had been at an altitude of 3,800 m for two days, and were therefore partially acclimatized, were studied at a simulated altitude of 5,000 both breathing ambient air and 27% oxygen. The studies were done at 3800 m altitude by enriching the atmosphere of the test room with appropriate amounts of nitrogen or oxygen. An extensive series of neuropsychological tests were carried out with the objective of determining which features of CNS function were improved by oxygen enrichment at an altitude of 5,000 m.
Altitude↗
Calculations of incremental secondary organic aerosol reactivity.
The incremental secondary organic aerosol reactivity (ISOAR) of a species j is defined as the relative incremental change in secondary organic aerosol (SOA) formed per relative incremental change in the amount of species jemitted. The California Institute of Technology three-dimensional air quality model is used in conjunction with the Caltech Atmospheric Chemistry Mechanism (CACM) and the Model to Predict the Multiphase Partitioning of Organics to calculate spatially and temporally averaged ISOAR values for the South Coast Air Basin of California (SoCAB). The base case SOA concentrations are derived for September 9, 1993. The South Coast Air Quality Management District of California provided emission and meteorological data. ISOAR values are calculated for the lumped surrogate compounds considered by CACM: isoprene, low-yield monoterpenes, high-yield monoterpenes, high-yield aromatics, etc. This work presents basin-wide ISOAR values determined through regression analysis. In addition, ISOAR values are reported at individual locations within the SoCAB. Modeled data are compared with ISOAR values calculated using smog chamber data. Results indicate that long-chain alkanes present the highest ISOAR. On the other hand, short-chain organics present the lowest ISOAR.
Aerosols↗
Modeling the oxidative capacity of the atmosphere of the south coast air basin of California. 1. Ozone formation metrics.
Metrics associated with ozone (O3) formation are investigated using the California Institute of Technology (CIT) three-dimensional air-quality model. Variables investigated include the O3 production rate (P(O3)), O3 production efficiency (OPE), and total reactivity (the sum of the reactivity of carbon monoxide (CO) and all organic gases that react with the hydroxyl radical). Calculations are spatially and temporally resolved; surface-level and vertically averaged results are shown for September 9, 1993 for three Southern California locations: Central Los Angeles, Azusa, and Riverside. Predictions indicate increasing surface-level O3 concentrations with distance downwind, in line with observations. Surface-level and vertically averaged P(O3) values peak during midday and are highest downwind; surface P(O3) values are greater than vertically averaged values. Surface OPEs generally are highest downwind and peak during midday in downwind locations. In contrast, peaks occur in early morning and late afternoon in the vertically averaged case. Vertically averaged OPEs tend to be greater than those for the surface. Total reactivities are highest in upwind surface locations and peak during rush hours; vertically averaged reactivities are smaller and tend to be more uniform temporally and spatially. Total reactivity has large contributions from CO, alkanes, alkenes, aldehydes, unsubstituted monoaromatics, and secondary organics. Calculations using estimated emissions for 2010 result in decreases in P(O3) values and reactivities but increases in OPEs.
Air Pollutants↗
Modeling the oxidative capacity of the atmosphere of the south coast air basin of California. 2. HOx radical production.
The production of HOx radicals in the South Coast Air Basin of California is investigated during the smog episode of September 9, 1993 using the California Institute of Technology (CIT) air-quality model. Sources of HOx(hydroxyl, hydroperoxy, and organic peroxy radicals) incorporated into the associated gas-phase chemical mechanism include the combination of excited-state singlet oxygen (formed from ozone (O3) photolysis (hv)) with water, the photolysis of nitrous acid, hydrogen peroxide (H2O2), and carbonyl compounds (formaldehyde (HCHO) or higher aldehydes and ketones), the consumption of aldehydes and alkenes (ALK) by the nitrate radical, and the consumption of alkenes by O3 and the oxygen atom (O). At a given time or location for surface cells and vertical averages, each route of HOx formation may be the greatest contributor to overall formation except HCHO-hv, H2O2-hv, and ALK-O, the latter two of which are insignificant pathways in general. The contribution of the ALK-O3 pathway is dependent on the stoichiometric yield of OH, but this pathway, at least for the studied smog episode, may not be as generally significant as previous research suggests. Future emissions scenarios yield lower total HOx production rates and a shift in the relative importance of individual pathways.
Air Pollutants↗
Isolation and characterization of gap junctions in the osteoblastic MC3T3-E1 cell line.
Gap junctions are channels connecting cells that function in cell-to-cell communication. Gap junctions are abundant in osteoblastic cells. Membranes enriched for gap junction plaques were obtained by differential centrifugation, followed by treatment of the membranes with potassium iodide and sarkosyl before sucrose density gradient centrifugation. Electron microscopy showed that the preparation was enriched for electron-dense membranes consistent with gap junctions. Coomassie Blue staining of SDS-PAGE preparations revealed a prominent band at approximately 41 kD. Western analysis with a site-directed antibody, CT-360 (D. Laird, California Institute of Technology, Pasadena, CA), to the C-terminal portion of the rat heart connexin 43 molecule was positive in the MC3T3-E1 cell line, a phenotypic osteoblastic cell line derived from normal neonatal mouse calvariae. Western analysis using a monoclonal antibody, R5.21C, to rat liver connexin 32 was negative. Additionally, a prominent band at 59 kD was detected by CT-360 in both gap junction-enriched preparations and cell lysates. Treatment of diluted samples of gap junction-enriched preparations with sulfhydryl reducing agents in combination with detergents resulted in the enhancement and diminution of the 41 and 59 kD bands, respectively. Immunoprecipitation following [35S]methionine/[35S]cysteine labeling revealed a significant band detected at 122 kD in addition to the 41 kD band. To demonstrate functional gap junctions, transfer of lucifer yellow dye to surrounding cells was monitored after microinjection of a target cell. Between passages 10 and 25 in culture, functional cell coupling was found in approximately 70% of injected cells. Coupling was detected within 1-2 minutes after injection. Simultaneous microinjection of the CT-360 antibody with lucifer yellow resulted in the decoupling of cells. In conclusion, (1) MC3T3-E1 cells possess a 41 kD protein that is recognized by connexin 43 antibody to rat heart gap junction; (2) multimers of the MC3T3-E1 gap junctions occur in the preparation; and (3) functional coupling demonstrated by dye transfer may be regulated by region(s) in the C terminus of the connexin molecule.
3T3 Cells↗
Human BAC ends quality assessment and sequence analyses.
End sequences from bacterial artificial chromosomes (BACs) provide highly specific sequence markers in large-scale sequencing projects. To date, we have generated >300,000 end sequences from >186,000 human BAC clones with an average read length of >460 bp for a total of 141 Mb covering approximately 4.7% of the genome. Over 60% of the clones have BAC end sequences (BESs) from both ends representing more than fivefold coverage of the human genome by the paired-end clones. Our quality assessments and sequence analyses indicate that BESs from human BAC libraries developed at The California Institute of Technology (CalTech) and Roswell Park Cancer Institute have similar properties. The analyses have highlighted differences in insert size for different segments of the CalTech library. Problems with the fidelity of tracking of sequence data back to physical clones have been observed in some subsets of the overall BES dataset. The annotation results of BESs for the contents of available genomic sequences, sequence tagged sites, expressed sequence tags, protein encoding regions, and repeats indicate that this resource will be valuable in many areas of genome research.
Chromosome Mapping↗
Spontaneous secondary spiking in excitable cells.
Kepler & Marder (1993, Biol. Cybern.68, 209-214) proposed a model describing the electrical activity of a crab neuron in which a train of directly induced action potentials is sometimes followed by one or more spontaneous action potentials, referred to as spontaneous secondary spikes. We reduce their five-dimensional model to three dimensions in two different ways in order to gain insight into the mechanism underlying the spontaneous spikes. We then treat a slowly varying current as a parameter in order to give a qualitative explanation of the phenomenon using phase-plane and bifurcation analysis. We demonstrate that a three-dimensional model, consisting of a two-dimensional excitable system plus a slow inward current, is sufficient to produce the behaviour observed in the original model. The exact dynamics of the excitable system are not important, but the relative time constant and amplitude of the slow inward current are crucial. Using the numerical bifurcation analysis package AUTO (Doedel & Kernevez, 1986, AUTO: Software for Continuation and Bifurcation Problems in Ordinary Differential Equations. California Institute of Technology), we compute bifurcation diagrams using the maximum amplitude of the slow inward current as the bifurcation parameter. The full and reduced models have a stable resting potential for all values of the bifurcation parameter. At a critical value of the bifurcation parameter, a stable tonic firing mode arises via a saddle-node of periodics bifurcation. Whether or not the models can exhibit transient or continuous spontaneous spiking depends on their position in parameter space relative to this saddle-node of periodics.
Action Potentials↗
Karyotype analysis by computer and its application to mutagenicity testing of environmental chemicals.
Large scale population monitoring by cytogenetics would require vast amounts of effort for meaningful results. Computer techniques promise to assume some of this burden and thus render large scale monitoring a more practical alternative than it is now. A system recently developed at the California Institute of Technology, Jet Propulsion Laboratory and the City of Hope Medical Center, contains many of the features required by a large scale population monitoring system. One part of the system is a semi-automated slide preparation assembly which can process up to 576 specimens per day with uniform treatment. The second part of the system consists of a computer-controlled microscope which performs automatic slide search, metaphase location, and karyotype analysis under the interactive supervision of an operator. While the system was developed primarily for clinical cytogenetics, some aspects of our operating experience suggest promising approaches for population cytogenetics.
Chromosome Aberrations↗
Linus Pauling and the scientific debate over fallout hazards.
From 1954 to 1963, numerous scientists engaged in a public debate over the possible hazards from radioactive fallout from nuclear weapons testing. Nobel laureate Linus Pauling, a California Institute of Technology chemist, was one of the most prominent. His scientific papers relating to the fallout debate reveal many of the scientific, social and political issues involved in the controversy. Although the public controversy ended after the signing of the 1963 Limited Test Ban Treaty, many of the scientific questions about the possible hazards of low-level radiation remain under debate within the scientific community. Moreover, the fallout debate was a prototype of current controversies over environmental and public-health hazards.
Environmental Exposure↗
Q & A: Alexander Varshavsky.
Alexander Varshavsky is Smits Professor of Cell Biology at the California Institute of Technology. He moved to Caltech in 1992, after 15 years at the MIT's Department of Biology. He was born and educated in Russia, and was 30 at the time of his emigration to the U.S. in 1977. In Russia, and for a while at MIT, he studied the structure and replication of chromosomes. Over the last 24 years, the work of his laboratory focused on the ubiquitin system and closely related fields. He is a member of the U.S. National Academy of Sciences, and has received the Gairdner Award, the Lasker Award, the General Motors Sloan Prize, the Wolf Prize, the Horwitz Prize, and the Wilson Medal.
Publishing↗
Reliability of optimal control strategies for photochemical air pollution.
This study illustrates how consideration of modeling uncertainties can affect optimal control strategies for urban ozone. Control strategies are investigated for illustrative cases of air parcel trajectories ending at Azusa, CA, and Riverside, CA, on August 28, 1987. The control strategies are designed to achieve a specified air quality target with a given reliability, considering uncertainties in the California Institute of Technology's trajectory model and its inputs, including uncertainties in emissions and in the SAPRC-97 chemical mechanism. A decoupled stochastic optimization scheme is used to solve the chance-constrained programming problem. Least-cost control strategies derived using nominal model inputs and parameter values have low reliability for some target O3 concentrations when uncertainties are taken into account. For the case considered, reducing volatile organic compound (VOC) emissions from motor vehicles is identified as the least-cost approach to meeting O3 targets at Azusa. However, the optimal control strategies for Riverside depend on the target O3 concentrations and the level of reliability required. Consideration of model uncertainty is found to shift the focus from VOC controls to nitrogen oxide controls for the Riverside trajectory.
Air Pollution↗
A lead user of instruments in science: John D. Roberts and the adaptation of nuclear magnetic resonance to organic chemistry, 1955-1975.
During the 1960s organic chemistry underwent a spectacular transformation as a result of the introduction of high-tech instruments. In this process, nuclear magnetic resonance (NMR) became an important analytical technique in organic chemistry. The theme of this essay is the relationship of Varian Associates of Palo Alto, California, the major manufacturer of NMR spectrometers up to the 1970s, with one early and crucial user, the organic chemist John D. Roberts, who was based at the California Institute of Technology in Pasadena. Roberts's research and teaching contributed to the fast and smooth acceptance of NMR in organic chemistry. He embraced the role of mediator between the instrument manufacturer, which had expertise mainly in physics and electrical engineering, and the customers, who were mostly organic chemists. This essay focuses on the tactics used by Roberts and James N. Shoolery at Varian Associates to implement novel types of instrumentation and on the modes of cooperation between instrument manufacturer and academic scientist.
Chemistry, Organic↗
Human BAC ends.
The Human BAC Ends database includes all non-redundant human BAC end sequences (BESs) generated by The Institute for Genomic Research (TIGR), the University of Washington (UW) and California Institute of Technology (CalTech). It incorporates the available BAC mapping data from different genome centers and the annotation results of each end sequence for the contents of repeats, ESTs and STS markers. For each BAC end the database integrates the sequence, the phred quality scores, the map and the annotation, and provides links to sites of the library information, the reports of GenBank, dbGSS and GDB, and other relevant data. The database is freely accessible via the web and supports sequence or clone searches and anonymous FTP. The relevant sites and resources are described at http://www.tigr.org/ tdb/humgen/bac_end_search/bac_end_intro.html
Chromosome Mapping↗
Building the TeraGrid.
On 1 October 2004, the most ambitious high-performance Grid project in the United States-the TeraGrid-became fully operational. Resources at nine sites--the San Diego Supercomputer Center, the California Institute of Technology, the National Center for Supercomputing Applications, the University of Chicago/Argonne National Laboratory, Pittsburgh Supercomputing Center, Texas Advanced Computing Center, Purdue University, Indiana University and Oak Ridge National Laboratory-were joined via an ultra-fast optical network, unified policies and security procedures and a sophisticated distributed computing software environment. Funded by the National Science Foundation, the TeraGrid enables scientists and engineers to combine distributed, multiple data sources with computation at any of the sites or link massively parallel computer simulations to extreme-resolution visualizations at remote sites. A single shared utility lets multiple resources be easily leveraged and provides improved access to advanced computational capabilities. One of the demonstrations of this new model for using distributed resources, Teragyroid, linked the infrastructure of the TeraGrid with computing resources in the United Kingdom via a transatlantic data fibre link. Once connected, the software framework of the RealityGrid project was used to successfully explore lattice-Boltzmann simulations involving lattices of over one billion sites.
Computer Security↗
Comparison of WKB and finite difference calculations for a two-dimensional cochlear model.
There are many points of uncertainty in the subject of cochlear models. In this paper only the question of efficient computing methods is addressed. For the cochlear model with a one-dimensional approximation for the fluid motion, Zweig, Lipes, and Pierce [J. Acoust. Soc. Am. 59, 975-982 (1976)] have shown that the WKB method agrees well with a direct numerical integration. For the two-dimensional fluid model, Neely [E.D. thesis, California Institute of Technology, Pasadena, CA (1977)] has shown that a direct finite difference solution is an order of magnitude faster than the integral equation approach used by Allen [J. Acoust. Soc. Am 61, 110-119 (1977)]. In the present work, a formal WKB solution is derived following Whitham [Linear and Nonlinear Waves (Wiley, New York, 1974)]. The advantage of this formulation is simplicity, but the disadvantage is that no error estimate is available. We find that the numerical results from the WKB solution agree well with those of Neely (1977), while the computer time is reduced by another order of magnitude. Thus, the WKB method seems to offer the satisfactory accuracy, efficiency, and flexibility for treating the more realistic cochlear models.
Cochlea↗
An improved WKB calculation for a two-dimensional cochlear model.
The finite difference calculations of Neely [E.D. thesis, California Institute of Technology, Pasadena, CA (1977)] and the WKB solution of Steele and Taber [J. Acoust. Soc. Am. 65, 1001-1006 (1979)] generally agree, except in the "phase plateau" region, where both are irregular. In the present work, an improvement in the accuracy of the WKB procedure is gained by using a closed-form integral which gives the phase and damping functions in the short wavelength region. The present results agree qualitatively with the preceding but show a smooth variation with frequency and distance along the cochlea.
Cochlea↗