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Biomedical subjects

J B Miller

Publications and source records attributed to J B Miller.

At least 19 recordsLinked to original sources

Contribution of anthropogenic and natural sources to atmospheric methane variability.

Methane is an important greenhouse gas, and its atmospheric concentration has nearly tripled since pre-industrial times. The growth rate of atmospheric methane is determined by the balance between surface emissions and photochemical destruction by the hydroxyl radical, the major atmospheric oxidant. Remarkably, this growth rate has decreased markedly since the early 1990s, and the level of methane has remained relatively constant since 1999, leading to a downward revision of its projected influence on global temperatures. Large fluctuations in the growth rate of atmospheric methane are also observed from one year to the next, but their causes remain uncertain. Here we quantify the processes that controlled variations in methane emissions between 1984 and 2003 using an inversion model of atmospheric transport and chemistry. Our results indicate that wetland emissions dominated the inter-annual variability of methane sources, whereas fire emissions played a smaller role, except during the 1997-1998 El Niño event. These top-down estimates of changes in wetland and fire emissions are in good agreement with independent estimates based on remote sensing information and biogeochemical models. On longer timescales, our results show that the decrease in atmospheric methane growth during the 1990s was caused by a decline in anthropogenic emissions. Since 1999, however, they indicate that anthropogenic emissions of methane have risen again. The effect of this increase on the growth rate of atmospheric methane has been masked by a coincident decrease in wetland emissions, but atmospheric methane levels may increase in the near future if wetland emissions return to their mean 1990s levels.

Atmosphere↗

Unexpected changes to the global methane budget over the past 2000 years.

We report a 2000-year Antarctic ice-core record of stable carbon isotope measurements in atmospheric methane (delta13CH4). Large delta13CH4 variations indicate that the methane budget varied unexpectedly during the late preindustrial Holocene (circa 0 to 1700 A.D.). During the first thousand years (0 to 1000 A.D.), delta13CH4 was at least 2 per mil enriched compared to expected values, and during the following 700 years, an about 2 per mil depletion occurred. Our modeled methane source partitioning implies that biomass burning emissions were high from 0 to 1000 A.D. but reduced by almost approximately 40% over the next 700 years. We suggest that both human activities and natural climate change influenced preindustrial biomass burning emissions and that these emissions have been previously understated in late preindustrial Holocene methane budget research.

Journal Article↗

Liver histopathology and liver and serum alanine aminotransferase and alkaline phosphatase activities in epileptic dogs receiving phenobarbital.

Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were obtained from 12 PB-treated dogs without clinical signs of liver disease but with elevated serum ALT and/or AP activities or both. Liver biopsies were obtained from eight healthy control dogs not receiving PB. Biopsies were evaluated histopathologically (all dogs) and liver homogenates were assayed for ALT (all dogs) and AP (six treated dogs, all controls) activities. As a positive control, liver cytochrome P4502B, an enzyme known to be induced by PB, was measured by benzyloxyresorufin-O-dealkylase activity and immunoblotting (five treated dogs, all controls). Serum AP isoenzyme analyses were performed. Results showed that ALT and AP activities in liver homogenates were not increased in treated dogs compared with controls, whereas the positive control for induction, CYP2B, was dramatically increased in treated dogs. Histopathological examination of liver biopsies revealed more severe and frequent abnormalities in treated dogs compared to controls, but similar types of abnormalities were found in both groups. Serum AP isoenzyme analyses in treated dogs demonstrated increased corticosteroid-induced and liver isoenzyme activities compared to controls. Results do not support induction of ALT or AP in the liver as the cause of elevated serum activities of these enzymes due to PB.

Alanine Transaminase↗

Gate-controlled spin-orbit quantum interference effects in lateral transport.

In situ control of spin-orbit coupling in coherent transport using a clean GaAs/AlGaAs two-dimensional electron gas is realized, leading to a gate-tunable crossover from weak localization to antilocalization. The necessary theory of 2D magnetotransport in the presence of spin-orbit coupling beyond the diffusive approximation is developed and used to analyze experimental data. With this theory the Rashba contribution and linear and cubic Dresselhaus contributions to spin-orbit coupling are separately estimated, allowing the angular dependence of spin-orbit precession to be extracted at various gate voltages.

Journal Article↗

Spin-orbit coupling, antilocalization, and parallel magnetic fields in quantum dots.

We investigate antilocalization due to spin-orbit coupling in ballistic GaAs quantum dots. Antilocalization that is prominent in large dots is suppressed in small dots, as anticipated theoretically. Parallel magnetic fields suppress both antilocalization and also, at larger fields, weak localization, consistent with random matrix theory results once orbital coupling of the parallel field is included. In situ control of spin-orbit coupling in dots is demonstrated as a gate-controlled crossover from weak localization to antilocalization.

Journal Article↗

Pro- and anti-apoptotic members of the Bcl-2 family in skeletal muscle: a distinct role for Bcl-2 in later stages of myogenesis.

Apoptotic myonuclei appear during myogenesis and in diseased muscles. To investigate cell death regulation in skeletal muscle, we examined how members of the Bcl-2 family of apoptosis regulators are expressed and function in the C2C12 muscle cell line and in primary muscle cells at different stages of development. Both anti-apoptotic (Bcl-W, Bcl-X(L)) and pro-apoptotic (Bad, Bak, Bax) members of the Bcl-2 family were expressed in developing skeletal muscle in vivo. Each was also expressed in embryonic (E11-12), fetal (E15-16), and neonatal muscle stem cells, myoblasts, and myotubes in vitro. In contrast, Bcl-2 expression was limited to a small group of mononucleate, desmin-positive, myogenin-negative muscle cells that were seen in fetal and neonatal, but not embryonic, muscle cell cultures. The cell surface protein Sca-1, which is associated with muscle and blood stem cells, was found on approximately 1/2 of these Bcl-2-positive cells. Loss of Bcl-2 did not affect expression of other family members, because neonatal muscles of wild-type and Bcl-2-null mice had similar amounts of Bcl-X(L), Bcl-W, Bad, Bak, and Bax mRNAs. Loss of Bcl-2 did have functional consequences; however, because neonatal muscles of Bcl-2-null mice had only approximately 2/3 as many fast muscle fibers as muscles in wild-type mice. Thus, Bcl-2 function is required for particular stages of fetal and postnatal myogenesis.

Age Factors↗

Quantitative amino acid analysis using a Beckman system gold HPLC 126AA analyzer.

BACKGROUND: The Beckman 6300/7300 analyzer, which was widely used for amino acid (AA) analysis, is no longer commercially available. METHODS: To set up an affordable AA analysis program, a Beckman system gold HPLC 126AA analyzer and Pickering Laboratories reagents were used. Two quantitative AA analysis programs were developed. One was an 18-min short program quantitating seven AAs from plasma and dried blood spots (DBS) specimens using Lithium eluents Li-365 and Li-375 at 70 degrees C column temperature. The short program could be used for diagnosis and follow-up dietary management for phenylketonuria (PKU), maple syrup urine disease (MSUD), tyrosinemia and homocystinuria patients. The second program was a 118-min long AA screening panel quantitating 40 AAs using Lithium eluents Li-275, Li-365 and Li-375 at 32, 48 and 72 degrees C column temperatures from plasma and urine specimens. RESULTS: The values obtained from DBS specimens were in good agreement with certified results from the Centers for Disease Control and Prevention. The values obtained from plasma and urine samples were in good correlation with those obtained from Beckman 6300 analyzer (0.9076 < or = r < or = 0.999). CONCLUSIONS: Amino acid quantitation from physiological samples using a Beckman 126AA Analyzer and Pickering Laboratories reagents was useful for clinical diagnosis and monitoring of aminoacidopathies.

Amino Acids↗

The effects of payback and loan repayment programs on medical student career plans.

Many states have considered implementing payback programs on state-subsidized medical education to increase the rate of graduates returning to those states to practice. An alternative is for states to offer and expand loan repayment programs to entice medical school graduates from rural states to return to their home states. The goal of this study is to determine and contrast the impact these two types of programs might have on medical school choice and students' intentions to return to their home states. Two hundred twenty-nine medical students were surveyed (response rate 80 percent). The questionnaire collected background information on the students and addressed the possible impact of payback and loan repayment policy proposals on student plans. Forty-seven percent of students reported that they would attend a different medical school if a required payback program were in place. Students who were more competitive at the time of admission to medical school were significantly more likely to say they would attend another medical school than were less competitive students. In contrast, 48 percent of students reported that they would be more likely to return to their home states if expanded loan repayment programs were available for service in areas of need. The findings suggest that payback programs may dissuade more competitive students from entering medical schools with such requirements, compromising the pool of students most likely to return to rural areas. Conversely, medical students appear willing to consider loan repayment programs upon completion of their training.

Adult↗

Coding sequence, chromosomal localization, and expression pattern of Nrf1: the mouse homolog of Drosophila erect wing.

In Drosophila, the erect wing (ewg) protein is required for proper development of the central nervous system and the indirect flight muscles. The fly ewg gene encodes a novel DNA-binding domain that is also found in four genes previously identified in sea urchin, chicken, zebrafish, and human. To identify mouse ewg homologs, we designed degenerate primers to the conserved DNA-binding domain. The RT-PCR product obtained from mRNA of the mouse muscle cell line C2C12 was used to screen cDNA libraries; a single gene was identified which encodes a predicted 503 amino acid protein. The mouse ewg homolog, termed Nrf1, was mapped to proximal Chr 6. By RT-PCR and Northern analysis, Nrf1 was expressed in all tissues examined, and Northern analysis on adult tissues revealed a complex banding pattern suggesting extensive alternative splicing. Nrf1 hybridized to mRNA transcripts at approximately 2.2 kb, 4.0 kb, 4.4 kb, and 5.0 kb, with additional tissue-specific transcripts at 1.5 kb in testis, 1.9 kb in lung, and 3.7 kb in skeletal muscle. In situ hybridization on whole-mount E9-10.5 embryos showed a broad pattern of expression, with the highest levels of expression in the central nervous system, somites, first branchial arch, optic vesicle, and otic vesicle.

Amino Acid Sequence↗

Changes in serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year.

A multicentric prospective study was conducted to monitor the effect of phenobarbital on serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in epileptic dogs. Serum T4 concentrations were determined for 22 epileptic dogs prior to initiation of phenobarbital therapy (time 0), and 3 weeks, 6 months, and 12 months after the start of phenobarbital. Median T4 concentration was significantly lower at 3 weeks and 6 months compared to time 0. Thirty-two percent of dogs had T4 concentrations below the reference range at 6 and 12 months. Nineteen of the 22 dogs had serum TSH concentrations determined at all sampling times. A significant upward trend in median TSH concentration was found. No associations were found between T4 concentration, dose of phenobarbital, or serum phenobarbital concentration. No signs of overt hypothyroidism were evident in dogs with low T4, with one exception. TSH stimulation tests were performed on six of seven dogs with low T4 concentrations at 12 months, and all but one had normal responses. In conclusion, phenobarbital therapy decreased serum T4 concentration but did not appear to cause clinical signs of hypothyroidism. Serum TSH concentrations and TSH stimulation tests suggest that the hypothalamic-pituitary-thyroid axis is functioning appropriately.

Analysis of Variance↗

Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets.

Both anthropologists and nutritionists have long recognized that the diets of modern-day hunter-gatherers may represent a reference standard for modern human nutrition and a model for defense against certain diseases of affluence. Because the hunter-gatherer way of life is now probably extinct in its purely un-Westernized form, nutritionists and anthropologists must rely on indirect procedures to reconstruct the traditional diet of preagricultural humans. In this analysis, we incorporate the most recent ethnographic compilation of plant-to-animal economic subsistence patterns of hunter-gatherers to estimate likely dietary macronutrient intakes (% of energy) for environmentally diverse hunter-gatherer populations. Furthermore, we show how differences in the percentage of body fat in prey animals would alter protein intakes in hunter-gatherers and how a maximal protein ceiling influences the selection of other macronutrients. Our analysis showed that whenever and wherever it was ecologically possible, hunter-gatherers consumed high amounts (45-65% of energy) of animal food. Most (73%) of the worldwide hunter-gatherer societies derived >50% (> or =56-65% of energy) of their subsistence from animal foods, whereas only 14% of these societies derived >50% (> or =56-65% of energy) of their subsistence from gathered plant foods. This high reliance on animal-based foods coupled with the relatively low carbohydrate content of wild plant foods produces universally characteristic macronutrient consumption ratios in which protein is elevated (19-35% of energy) at the expense of carbohydrates (22-40% of energy).

Agriculture↗