Calibration of a high spectral resolution lidar using a Michelson interferometer, with data examples from ORACLES.

The NASA Langley airborne second-generation High Spectral Resolution Lidar (HSRL-2) uses a density-tuned field-widened Michelson interferometer to implement the HSRL technique at 355 nm. The Michelson interferometer optically separates the received backscattered light between two channels, one of which is dominated by molecular backscattering, while the other contains most of the light backscattered by particles. This interferometer achieves high and stable contrast ratio, defined as the ratio of particulate backscatter signal received by the two channels. We show that a high and stable contrast ratio is critical for precise and accurate backscatter and extinction retrievals. Here, we present retrieval equations that take into account the incomplete separation of particulate and molecular backscatter in the measurement channels. We also show how the accuracy of the contrast ratio assessment propagates to error in the optical properties. For both backscattering and extinction, larger errors are produced by underestimates of the contrast ratio (compared to overestimates), more extreme aerosol loading, and-most critically-smaller true contrast ratios. We show example results from HSRL-2 aboard the NASA ER-2 aircraft from the 2016 ORACLES field campaign in the southeast Atlantic, off the coast of Africa, during the biomass burning season. We include a case study where smoke aerosol in two adjacent altitude layers showed opposite differences in extinction- and backscatter-related Ångström exponents and a reversal of the lidar ratio spectral dependence, signatures which are shown to be consistent with a relatively modest difference in smoke particle size.

Simultaneous polarimeter retrievals of microphysical aerosol and ocean color parameters from the "MAPP" algorithm with comparison to high-spectral-resolution lidar aerosol and ocean products.

We present an optimal-estimation-based retrieval framework, the microphysical aerosol properties from polarimetry (MAPP) algorithm, designed for simultaneous retrieval of aerosol microphysical properties and ocean color bio-optical parameters using multi-angular total and polarized radiances. Polarimetric measurements from the airborne NASA Research Scanning Polarimeter (RSP) were inverted by MAPP to produce atmosphere and ocean products. The RSP MAPP results are compared with co-incident lidar measurements made by the NASA High-Spectral-Resolution Lidar HSRL-1 and HSRL-2 instruments. Comparisons are made of the aerosol optical depth (AOD) at 355 and 532 nm, lidar column-averaged measurements of the aerosol lidar ratio and Ångstrøm exponent, and lidar ocean measurements of the particulate hemispherical backscatter coefficient and the diffuse attenuation coefficient. The measurements were collected during the 2012 Two-Column Aerosol Project (TCAP) campaign and the 2014 Ship-Aircraft Bio-Optical Research (SABOR) campaign. For the SABOR campaign, 73% RSP MAPP retrievals fall within ±0.04 AOD at 532 nm as measured by HSRL-1, with an R value of 0.933 and root-mean-square deviation of 0.0372. For the TCAP campaign, 53% of RSP MAPP retrievals are within 0.04 AOD as measured by HSRL-2, with an R value of 0.927 and root-mean-square deviation of 0.0673. Comparisons with HSRL-2 AOD at 355 nm during TCAP result in an R value of 0.959 and a root-mean-square deviation of 0.0694. The RSP retrievals using the MAPP optimal estimation framework represent a key milestone on the path to a combined lidar+polarimeter retrieval using both HSRL and RSP measurements.

Prairie Voles as a Model to Screen Medications for the Treatment of Alcoholism and Addictions.

Most preclinical studies of medications to treat addictions are performed in mice and rats. These two rodent species belong to one phylogenetic subfamily, which narrows the likelihood of identifying potential mechanisms regulating addictions in other species, ie, humans. Expanding the genetic diversity of organisms modeling alcohol and drug abuse enhances our ability to screen for medications to treat addiction. Recently, research laboratories adapted the prairie vole model to study mechanisms of alcohol and drugs of abuse. This development not only expanded the diversity of genotypes used to screen medications, but also enhanced capabilities of such screens. Prairie voles belong to 3-5% of mammalian species exhibiting social monogamy. This unusual trait is reflected in their ability to form lasting long-term affiliations between adult individuals. The prairie vole animal model has high predictive validity for mechanisms regulating human social behaviors. In addition, these animals exhibit high alcohol intake and preference. In laboratory settings, prairie voles are used to model social influences on drug reward and alcohol consumption as well as effects of addictive substances on social bonding. As a result, this species can be adapted to screen medications whose effectiveness could be (a) resistant to social influences promoting excessive drug taking, (b) dependent on the presence of social support, and (c) medications affecting harmful social consequences of alcohol and drug abuse. This report reviews the literature on studies of alcohol and psychostimulants in prairie voles and discusses capabilities of this animal model as a screen for novel medications to treat alcoholism and addictions.

Bacterial safety of reconstituted continuous drip tube feeding.

Chemically defined diets require reconstitution and transfer to a delivery system. When reconstituted High Vivonex was noted in our Medical Center to be bacteriologically contaminated, we instituted a series of control procedures. We then reevaluated bacterial growth in reconstituted High Nitrogen Vivonex and diluted Isocal under ward conditions. The mixtures were prepared with sterile water versus tap water, using a hand washed blender versus a machine washed blender. We also investigated the bacteriological effect of blast freezing reconstituted High Nitrogen Vivonex. All preparations of the nonfrozen High Nitrogen Vivonex showed occasional low level contamination, although quantitative cultures did not show logarithmic growth over eight hours of observation. No growth occurred in the blast frozen High Nitrogen Vivonex or in the Isocal. We conclude that reconstituted High Nitrogen Vivonex and diluted Isocal may be prepared and hung safely for eight hours, and that blast freezing of High Nitrogen Vivonex is bacteriologically safe. As a result of our initial findings of bacteriologic contamination, we believe a program for bacterial monitoring of the tube feeding is desirable.

Intrauterine injection of recombinant ovine interferon-tau extends the interestrous interval in sheep.

The ability of recombinant ovine interferon-tau (roIFNtau) to extend the interestrous interval (IEI) in sheep was studied. Ewes were fitted with bilateral uterine catheters 7 or 8 days post estrus and were assigned to receive either 10 or 20 million antiviral (AV) units/day i.u. ( approximately 100 or 200 ug) of roIFNtau or ovine conceptus secretory proteins containing equivalent AV units of native oIFNtau (noIFNtau; 4 ewes/treatment). Four control ewes received ovine serum proteins (SP). Total protein injected was 6 mg per day, half at 0700 hours and half at 1730 hours. The treatments were administered from Day 11.5 (estrus=Day 0) to Day 16. Blood samples were collected by jugular vienipuncture daily from Day 11 until ewes returned to estrus. Concentrations of progesterone (P) in plasma were determined by RIA. Treatment with either noIFNtau or roIFNtau extended IEI beyond that of SP-treated ewes (19.1 vs 31.2+/-3.4 days P<0.03). Of the ewes receiving 100 mug/day of oIFNtau, 2 of 4 receiving noIFNtau (23.6+/-5.2 days) and 3 of 4 receiving roIFNtau (34.2+/-5.2 days) had an extended IEI. All ewes receiving 200 mug/day of noIFNtau or roIFNtau had an extended IEI (28.8 and 38.5+/-5.2 days. respectively). Ewes receiving roIFNtau had a longer IEI than those receiving noIFNtau (36.7 vs 26.2+/-3.4 days; P=0.07). Ewes with an extended IEI had functional corpora lutea, as assessed by P production. The results demonstrate that 10 or 20 million AV units ( approximately 100 or 200 ug) of roIFNtau extends the IEI and that the length of the IEI is longer for ewes receiving roIFNtau than noIFNtau following injection of equivalent AV units.

Exogenous oxytocin decreases interestrous interval of cyclic gilts.

Oxytocin (OT) stimulates pulsatile secretion of uterine PGF2 alpha in ruminants, but the role of OT in regulation of the estrous cycle of pigs is not clear. four experiments were performed to examine the effect of exogenous OT on interestrous interval of intact cyclic and hysterectomized gilts. In Exp. 1, i.v. injections of 20 USP units (equivalent to 20 IU) of OT, once/day via an ear vein on d 10, 12, 14, and 16 after estrus, decreased (P < .01) interestrous interval (19.9 +/- .2 d) compared with vehicle-injected control gilts (20.8 +/- .2 d), without affecting ovulation rate (12.1 vs. 12.0 +/- .7 corpora lutea; OT vs control gilts) at subsequent estrus. In Exp. 2, i.v. infusions of 20 USP units of OT, twice/day via an indwelling jugular catheter on d 10 to 16 after estrus, did not alter interestrous interval (20.6 +/- .3 d) compared with control gilts (20.4 +/- .3 d). Concentrations of progesterone in jugular vein plasma did not differ between treatment groups on d 9 to 21 after estrus. In Exp. 3, i.m. injections of 20 USP units of OT, twice/day on d 10 to 16 after estrus, decreased (P < .05) interestrous interval (20.6 +/- .4 d) compared with control gilts (22.3 +/- .4 d). In Exp. 4, i.m. injections of 20 USP units of OT, twice/day on d 10 to 16 after estrus, decreased (P < .05) interestrous interval (20.7 +/- .3 d) compared with control injections in uterine-intact gilts (21.8 +/- .3 d). None of the gilts hysterectomized on d 7 and treated on d 10 to 16 after estrus with either OT or control injections returned to estrus by d 28, and all had increased plasma progesterone on d 21 to 27. Mean weight of individual corpora lutea (502 vs 449 +/- 28 mg; OT vs control gilts) and total weight of corpora lutea (5,758 vs. 5,126 +/- 298 mg; OT vs control gilts) of hysterectomized gilts did not differ between treatment groups at ovariectomy on d 28. These results indicate that 1) exogenous OT administered on d 10 to 16 shortened the interestrous interval of intact cyclic gilts and 2) the effect of OT was uterine-dependent.

Maternal selenium deficiency increases hydrogen peroxide and total lipid peroxides in porcine fetal liver.

To investigate the role of selenium (Se) in the developing porcine fetus, prepubertal gilts (n = 42) were randomly assigned to either Se-adequate (0.39 ppm Se) or Se-deficient (0.05 ppm Se) gestation diets 6 wk prior to breeding. Maternal and fetal liver was collected at d 30, 45, 70, 90, and 114 of pregnancy. Concentrations of Se in maternal liver decreased during gestation in gilts fed the low-Se diet. The activity of cellular glutathione peroxidase (GPx) was decreased at d 30 and 45 of gestation in liver of gilts fed the low-Se diet. Concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2) were greater in liver homogenates from gilts fed the low-Se diet. Within the fetuses, liver Se decreased in those fetuses of gilts fed the low-Se diet. Although the activity of GPx in fetal liver was not affected by the maternal diet, concentrations of H2O2 and MDA in fetal liver were greater in fetuses from gilts fed the low-Se diet. Maternal liver GPx activity was approx 12-fold greater than fetal liver GPx activity regardless of dietary treatment. These results indicate that maternal dietary Se intake affects fetal liver Se concentration and feeding a low-Se diet during gestation increases oxidative stress to the fetus, as measured by fetal liver H2O2 and MDA.

Gestational changes in concentrations of selenium and zinc in the porcine fetus and the effects of maternal intake of selenium.

The effect of maternal dietary selenium (Se) and gestation on the concentrations of Se and zinc (Zn) in the porcine fetus were determined. Mature gilts were randomly assigned to treatments of either adequate (0.39 ppm Se) or low (0.05 ppm Se) dietary Se. Gilts were bred and fetuses were collected throughout gestation. Concentrations of Se in maternal whole blood and liver decreased during gestation in sows fed the low-Se diet compared to sows fed the Se-supplemented diet. Maternal intake of Se did not affect the concentration of Se in the whole fetus; however, the concentration of Se in fetal liver was decreased in fetuses of sows fed the low-Se diet. Although fetal liver Se decreased in both treatments as gestation progressed, the decrease was greater in liver of fetuses from sows fed the low- Se diet. Dietary Se did not affect concentrations of Zn in maternal whole blood or liver or in the whole fetus and fetal liver. The concentration of Se in fetal liver was lower but the concentration of Zn was greater than in maternal liver when sows were fed the adequate Se diet. These results indicate that maternal intake of Se affects fetal liver Se and newborn piglets have lower liver Se concentrations compared to their dams, regardless of the Se intake of sows during gestation. Thus, the piglet is more susceptible Se deficiency than the sow.

DeltaFosB is increased in the nucleus accumbens by amphetamine but not social housing or isolation in the prairie vole.

The nucleus accumbens is a key region that mediates aspects of immediate and long-term adaptations to various stimuli. For example, both repeated amphetamine and pair-bonding increase dopamine D1 receptor binding in the nucleus accumbens of the monogamous prairie vole (Microtus ochrogaster). This upregulation has significant and stimulus-dependent behavioral consequences. A promising candidate for these and other adaptations is the transcription factor ΔfosB. ΔfosB is a highly stable protein that persists in the brain over long periods of time, leading to increasing and accumulating levels with repeated or continuous exposure to specific stimuli. Within the nucleus accumbens, ΔfosB is specifically increased in medium spiny neurons containing D1 receptors. To explore whether ΔfosB is altered by drug and social experience in prairie voles, we performed three separate experiments. In the first experiment, animals were treated with repeated injections of amphetamine and then brain tissue was analyzed for ΔfosB expression. As expected, 4 days of amphetamine treatment increased ΔfosB in the nucleus accumbens, consistent with previous findings in other laboratory species. In the second experiment, animals were housed for 10 days with one of three social partners: a familiar same-sex sibling, an unfamiliar same-sex partner, or an unfamiliar opposite-sex partner. Here, we predicted that 10 days of housing with an opposite-sex partner would act as a "social reward," leading to upregulation of ΔfosB expression in the nucleus accumbens. In a third experiment, we also investigated whether 10 days of social isolation would result in altered ΔfosB activity. We hypothesized that isolation would lead to decreased levels of nucleus accumbens ΔfosB, as seen in other studies. However, neither opposite-sex cohabitation nor social isolation affected ΔfosB expression in the nucleus accumbens. These findings suggest that social stimuli, in contrast to drugs of abuse, are not mediators of ΔfosB in this region in prairie voles.

Effect of selenium intake and fetal age on mRNA levels of two selenoproteins in porcine fetal and maternal liver.

The objective of this study was to determine if levels of mRNA encoding cytosolic glutathione peroxidase (cGPx) and thioredoxin reductase (TrxR-1) change during fetal development, and if maternal Se intake during gestation affects the mRNA levels of these proteins. Prepubertal gilts (n = 24) were randomly assigned to either Se-adequate (0.39 ppm of Se; n = 12) or Se-deficient (0.05 ppm of Se; n = 12) diets, 6 wk before breeding. Maternal liver was collected at d 10, 45, 70, and 114 of pregnancy, and fetal liver samples were collected at the same times except d 10. Complementary DNA sequences encoding cGPx and TrxR-1 were cloned and sequenced. Quantitative real-time PCR analysis indicated that levels of mRNA for cGPx in fetal liver decreased more than 3-fold between d 45 and 114 of gestation. Although the gilts were only marginally deficient in Se, and maternal Se intake did not affect cGPx mRNA levels in fetal liver, the low-Se diet tended (P = 0.1) to reduce fetal TrxR-1 mRNA levels. In the liver of the dams, the low Se intake did not affect mRNA levels for either cGPx or TrxR-1. Compared with the liver of the dams, mRNA levels for cGPx were about 3.5 times lower in fetal liver. Results of this study support the hypothesis that neonatal pigs are born with reduced cGPx corresponding to reduced cGPx mRNA levels during late gestation.

Dear Hillary....

As Hillary Clinton worked on the reforms of the US health system, three University of Minnesota fellows, Meeta Pherwani, Craig Hostetler and Sarah Miller, offered her some advice based on their experience with the NHS.

Comparison of three rapid methods for detection of antibodies to streptolysin O and DNase B.

Three commercial systems were compared for ability to detect antibodies to streptolysin O (ASO) and DNase B (ADB). Streptozyme (Wampole Laboratories, Cranbury, N.J.) exhibited high sensitivity (100%) for detecting ASO but low sensitivity for ADB (22.2%). The LeapStrep (Organon Teknika, Malvern, Pa.) and Check-Spectra (Diagnostic Technology, Hauppauge, N.Y.) tests had low sensitivities for detecting ASO (35.3 and 21.4%, respectively) and ADB (22.2 and 33.3%, respectively).

An accurate prediction of the pH change due to degradation: correction for a "produced" secondary buffering system.

Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxyester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a "secondary buffer" and minimizes the change in pH due to degradation. Equations are presented to calculate the change in the pH when the primary degradation product acts as a secondary buffer. This information can be used in the development of a parenteral product to predict, a priori, the concentration of buffer necessary for optimal pH maintenance. This knowledge can reduce the number of formulation screens required to determine the necessary buffer capacity for optimal drug stability.

Detection of functional oxytocin receptors on endometrium of pigs.

Oxytocin (OT) stimulates phosphoinositide (PI) hydrolysis and prostaglandin (PG) F2 alpha secretion from the endometrium of cyclic pigs, but the presence of specific endometrial receptors for OT has not been demonstrated in this species. Two experiments were performed to detect the presence of functional OT receptors on endometrium collected 15 days post estrus from cyclic gilts. OT receptor density and Kd were determined by receptor assay and Scatchard analysis. Hydrolysis of PI (i.e., incorporation of [3H]inositol into total inositol phosphates) and PGF2 alpha secretion were studied with use of incubations of endometrial explants. Concentrations of PGF2 alpha were log-transformed for analysis of variance and are expressed as means +/- standard error of log-transformed data. In experiment 1, mean density and mean Kd of OT receptors on endometrium of gilts were 29.2 +/- 5.54 fmol/mg protein and 1.59 +/- 0.23 nM, respectively. OT receptor density was significantly correlated with the ability of 100 nM OT to stimulate PI hydrolysis (r = 0.83, p < 0.05) and PGF2 alpha secretion (r = 0.87, p < 0.10), but was not highly correlated with receptor Kd (r = -0.08, p = 0.85). In contrast, OT receptor Kd was not highly correlated with OT-stimulated PI hydrolysis (r = -0.19, p = 0.68) or OT-stimulated PGF2 alpha secretion (r = 0.14, p = 0.86). OT-stimulated PI hydrolysis was also significantly correlated (r = 0.80, p < 0.05) with OT-stimulated PGF2 alpha secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma zinc and vitamin A in human squamous carcinoma of the esophagus.

Zinc deficiency enhances experimental esophageal tumor induction. Vitamin A supplementation inhibits carcinogenesis in animals. Plasma zinc and plasma vitamin A levels are reduced in several human squamous cancers, but have not been studied in a US population with esophageal cancer. Therefore, we measured plasma zinc and vitamin A in patients with newly diagnosed esophageal cancer. In addition, we assessed hepatic and nutritional status and attempted to control for other factors known to influence plasma zinc and vitamin A levels. Plasma zinc and vitamin A were both significantly less in esophageal carcinoma than in age-matched healthy controls (plasma zinc 65.7 +/- 3.3 micrograms/dl [mean +/- SEM] in esophageal cancer versus 80.5 +/- 2.4 micrograms/dl in controls, P less than 0.01; plasma vitamin A 32.6 +/- 3.4 micrograms/dl in esophageal cancer versus 60.2 +/- 4.2 in controls, P less than 0.001). Overall, 15 of 17 patients with esophageal cancer had decreased plasma zinc and/or decreased plasma vitamin A. Our findings are compatible with a hypothesis that zinc or vitamin A deficiency may be co-factors in the induction of human esophageal carcinoma.

Distribution of Ly-6C on lymphocyte subsets: I. Influence of allotype on T lymphocyte expression.

The expression patterns of the Ly-6C Ag were examined on splenic and thymic lymphocyte subsets of Ly-6.1 and Ly-6.2 strains of mice using the rat mAb 15.1. Ly-6C is expressed on subsets of CD4+ and CD8+ splenocytes, and a portion of NK cells. Within the splenic and lymph node CD4+ T cell compartment, Ly-6C expression is restricted to Ly-6.2 strains of mice, and is present on a subset of naive cells. Ly-6C is expressed on the majority of peripheral CD8+ T cells in both Ly-6.1 and Ly-6.2 strains, and is found primarily on the Ag-experienced subset. In the thymus, Ly-6C is present on subpopulations of CD4- CD8+, CD4- CD8-, and CD4+ CD8- cells. Ly-6C+ CD4- CD8+ thymocytes show a mature phenotype, while Ly-6C+ CD4- CD8- and Ly-6C+ CD4+ CD8- thymocytes appear to be part of the recently described NK1.1+ alphabeta TCR+ population. On account of the marked differences in Ly-6C expression on peripheral CD4+ T cells from Ly-6.1 and Ly-6.2 strains of mice, additional experiments were undertaken to assess Ly-6C expression in parental and Ly-6.1 x Ly-6.2 F1 mice. Neither phenotype dominated in the F1 offspring, with frequencies of Ly-6C+ CD4+ splenocytes falling in the intermediate range. Further experiments compared the staining patterns of the rat anti-pan Ly-6C (Ly-6.1 and Ly-6.2) Ab with a mouse anti-Ly-6.2 allotype specific Ab, with emphasis on both Ly-6.2 and Ly-6.1 x Ly-6.2 F1 mice. The results demonstrate the presence of lymphocytes that express the pan form of Ly-6C but not the form recognized by the alloantibody. This latter finding suggests the presence of more than one form of the Ly-6C Ag.