Optical and mechanical design of a telescope for lunar spectral irradiance measurements from a high-altitude aircraft.

We have designed a non-imaging telescope for measurement of the spectral irradiance of the moon. The telescope was designed to be integrated into a wing pod of a National Aeronautics and Space Administration ER-2 research aircraft to measure lunar spectral irradiance during flight. The telescope and support system were successfully flown in August 2018 at altitudes near 21 km and at speeds of ∼760 km/h. The wing pod in which the telescope is mounted has an opening through which the moon can be observed. The mount exposes the telescope to high winds, low pressures, temperatures near -60 °C, and vibrations both due to flight and due to the motion of the aircraft on the ground. This required a telescope design with high thermal stability and high resistance to shock. The optical design of the telescope is optimized to have high throughput and spatially uniform transmission from 380 nm to 1000 nm over a field of view about three times the angular size of the moon as viewed from the Earth. The final design resulted in a telescope with singlet design incorporating a 139.7 mm lens with an effective focal length of 377 mm and a field of view of 1.6°. The light from the telescope is introduced into an integrating sphere, which destroys the image and the polarization for measurement by a fiber-coupled spectroradiometer. Herein, we present an overview of the instrument and support system with emphasis on the telescope design.

Precise methane absorption measurements in the 1.64 µm spectral region for the MERLIN mission.

In this article we describe a high-precision laboratory measurement targeting the R(6) manifold of the 2ν3 band of 12CH4. Accurate physical models of this absorption spectrum will be required by the Franco-German, Methane Remote Sensing LIDAR (MERLIN) space mission for retrievals of atmospheric methane. The analysis uses the Hartmann-Tran profile for modeling line shape and also includes line-mixing effects. To this end, six high-resolution and high signal-to-noise absorption spectra of air-broadened methane were recorded using a frequency-stabilized cavity ring-down spectroscopy apparatus. Sample conditions corresponded to room temperature and spanned total sample pressures of 40 hPa - 1013 hPa with methane molar fractions between 1 µmol mol-1 and 12 µmol mol-1. All spectroscopic model parameters were simultaneously adjusted in a multispectrum nonlinear least-squares fit to the six measured spectra. Comparison of the fitted model to the measured spectra reveals the ability to calculate the room-temperature, methane absorption coefficient to better than 0.1% at the on-line position of the MERLIN mission. This is the first time that such fidelity has been reached in modeling methane absorption in the investigated spectral region, fulfilling the accuracy requirements of the MERLIN mission. We also found excellent agreement when comparing the present results with measurements obtained over different pressure conditions and using other laboratory techniques. Finally, we also evaluated the impact of these new spectral parameters on atmospheric transmissions spectra calculations.

Multiheterodyne spectroscopy with optical frequency combs generated from a continuous-wave laser.

Dual-drive Mach-Zehnder modulators were utilized to produce power-leveled optical frequency combs (OFCs) from a continuous-wave laser. The resulting OFCs contained up to 50 unique frequency components and spanned more than 200 GHz. Simple changes to the modulation frequency allowed for agile control of the comb spacing. These OFCs were then utilized for broadband, multiheterodyne measurements of CO2 using both a multipass cell and an optical cavity. This technique allows for robust measurements of trace gas species and alleviates much of the cost and complexity associated with the use of femtosecond OFCs produced with mode-locked pulsed lasers.

Toxicity and exposure of an adenovirus containing human interferon alpha-2b following intracystic administration in cynomolgus monkeys.

The safety and toxicokinetics of SCH 721015, an adenovirus encoding the human interferon alpha-2b gene, and Syn3 (SCH 209702), a novel excipient, were assessed in cynomolgus monkeys administered intravesical doses of 2.5 × 10E11 or 1.25 × 10E13 particles SCH 721015 in 25 mg Syn3 or 25 mg Syn3 alone on study days 1 and 91. There was no systemic toxicity. Monkeys dosed with SCH 721015 in Syn3 were positive for SCH 721015-specific DNA in the urine for 2 to 3 days following each dose and had interferon alpha-2b protein in the urine for 1-3 days after a single dose and in fewer animals after a second dose. Intracystic administration was associated with inflammation and focal/multifocal ulceration in the urinary bladder and irritation in the ureters and urethra at necropsy. The physical trauma from catheterization and filling/emptying of the bladder was likely a contributing factor and Syn3 exacerbated the trauma. There was nearly complete resolution of these findings 2 months after the last dose. The trauma to the bladder likely contributed to low, transient systemic exposure to Syn3, SCH 721015 and human interferon protein. The results of this study support the clinical investigation of SCH 721015 in Syn3.

Number fluctuations and energy dissipation in sodium spinor condensates.

We characterize fluctuations in atom number and spin populations in F=1 sodium spinor condensates. We find that the fluctuations enable a quantitative measure of energy dissipation in the condensate. The time evolution of the population fluctuations shows a maximum. We interpret this as evidence of a dissipation-driven separatrix crossing in phase space. For a given initial state, the critical time to the separatrix crossing is found to depend exponentially on the magnetic field and linearly on condensate density. This crossing is confirmed by tracking the energy of the spinor condensate as well as by Faraday rotation spectroscopy. We also introduce a phenomenological model that describes the observed dissipation with a single coefficient.

Quantum phase transitions and continuous observation of spinor dynamics in an antiferromagnetic condensate.

Condensates of spin-1 sodium display rich spin dynamics due to the antiferromagnetic nature of the interactions in this system. We use Faraday rotation spectroscopy to make a continuous and minimally destructive measurement of the dynamics over multiple spin oscillations on a single evolving condensate. This method provides a sharp signature to locate a magnetically tuned separatrix in phase space which depends on the net magnetization. We also observe a phase transition from a two- to a three-component condensate at a low but finite temperature using a Stern-Gerlach imaging technique. This transition should be preserved as a zero-temperature quantum phase transition.

High-flux beam source for cold, slow atoms or molecules.

We demonstrate and characterize a high-flux beam source for cold, slow atoms or molecules. The desired species is vaporized using laser ablation, then cooled by thermalization in a cryogenic cell of buffer gas. The beam is formed by particles exiting a hole in the buffer gas cell. We characterize the properties of the beam (flux, forward velocity, temperature) for both an atom (Na) and a molecule (PbO) under varying buffer gas density, and discuss conditions for optimizing these beam parameters. Our source compares favorably to existing techniques of beam formation, for a variety of applications.

Assessment of a multiple-dose drug interaction between ezetimibe, a novel selective cholesterol absorption inhibitor and gemfibrozil.

OBJECTIVE: Ezetimibe is a novel lipid-lowering drug that prevents intestinal absorption of dietary and biliary cholesterol leading to significant reduction in total-C, LDL-C, Apo B, and TG and increases in HDL-C in patients with hypercholesterolemia. Gemfibrozil, a fibric acid derivative, is an effective lipid-modulating agent that increases serum high-density lipoprotein cholesterol and decreases serum TG. The objective of this study was to evaluate the potential for a pharmacokinetic (PK) interaction between ezetimibe and gemfibrozil. METHODS: This was a randomized, open-label, 3-way crossover, multiple-dose study in 12 healthy adult male volunteers. All subjects received the following 3 treatments orally for 7 days: ezetimibe 10 mg once daily, gemfibrozil 600 mg every 12 hours, and ezetimibe 10 mg once daily plus gemfibrozil 600 mg every 12 hours. A washout period of > or = 7 days separated the 3 treatments. In each treatment, blood samples were collected on day 7 to assess the steady-state PK of ezetimibe and gemfibrozil. The oral bioavailability of ezetimibe coadministered with gemfibrozil relative to each drug administered alone was evaluated with an analysis-of-variance model. RESULTS: Ezetimibe was rapidly absorbed and extensively conjugated to its glucuronide metabolite. Ezetimibe did not alter the bioavailability (based on AUC) of gemfibrozil. The mean AUC0-12 of gemfibrozil was 74.7 and 74.1 microg h/ml with and without ezetimibe coadministration, respectively (log-transformed geometric mean ratio (GMR) = 99.2; 90% confidence interval (CI) = 92 - 107%). Conversely, gemfibrozil significantly (p < 0.05) increased the plasma concentrations of ezetimibe and total ezetimibe (i.e. ezetimibe plus ezetimibe-glucuronide). Exposure to ezetimibe and total ezetimibe was increased approximately 1.4-fold and 1.7-fold, respectively (CI = 109 - 173% for ezetimibe and 142 - 190% for total ezetimibe), however, this increase was not considered to be clinically relevant. Ezetimibe and gemfibrozil administered alone or concomitantly for 7 days was well tolerated. CONCLUSIONS: The coadministration of ezetimibe and gemfibrozil in patients is unlikely to cause a clinically significant drug interaction. The coadministration of these agents is a promising approach for patients with mixed dyslipidemia. Additional clinical studies are warranted.

The development of multiple domains of child and adolescent self-concept: a cohort sequential longitudinal design.

The development of child and adolescent self-concept was examined as a function of the self-concept domain, social/developmental/educational transitions, and gender. In two overlapping age cohorts of public school students (Ns = 936 and 984), five dimensions of self-concept were evaluated every 6 months in a manner that spanned grades 3 through 11 (representing the elementary, middle, and high school years). Domains of self-concept included academic competence, physical appearance, behavioral conduct, social acceptance, and sports competence. Structural equation modeling addressed questions about the stability of individual differences over time. Multilevel modeling addressed questions about mean-level changes in self-concept over time. Significant effects emerged with regard to gender, age, dimension of self-concept, and educational transition.

The proof of the pudding: an illustration of the relative strengths of null hypothesis, meta-analysis, and Bayesian analysis.

Some methodologists have recently suggested that scientific psychology's over-reliance on null hypothesis significance testing (NHST) impedes the progress of the discipline. In response, a number of defenders have maintained that NHST continues to play a vital role in psychological research. Both sides of the argument to date have been presented abstractly. The authors take a different approach to this issue by illustrating the use of NHST along with 2 possible alternatives (meta-analysis as a primary data analysis strategy and Bayesian approaches) in a series of 3 studies. Comparing and contrasting the approaches on actual data brings out the strengths and weaknesses of each approach. The exercise demonstrates that the approaches are not mutually exclusive but instead can be used to complement one another.

Structural differences in parent and child reports of children's symptoms of depression and anxiety.

Two cohorts of public elementary school children and their parents (assessed 3 years apart) completed child and parent forms of the Children's Depression Inventory (CDI) and the Revised Children's Manifest Anxiety Scale (RCMAS). Assessments were conducted twice, once during the fall (N = 562) and again during the spring (N = 630) of the 6th grade. Factor analyses revealed 3 factors for each measure. Two of the 3 parent CDI factors manifested some degree of congruence with their counterparts from the child CDI. Similarly, 2 of the 3 RCMAS factors were somewhat congruent across informant types. Differences between parent and child factor structures suggest that parents' and children's reports focus on somewhat different aspects of child psychopathology, and they can make qualitatively different contributions to the multiaxial assessment of children.

Prenatal maternal predictors of cognitive and emotional delays in children of adolescent mothers.

The present study examined relationships among prenatal characteristics of 121 adolescent mothers-including cognitive readiness for parenting, intelligence, social support, and personal adjustment-and intellectual-linguistic development, social-emotional functioning, and adaptive behavior in their children at three years of age. Only 28% of the children scored within normal ranges on all three types of outcomes. Intellectual and linguistic delays were predicted best by prenatal measures of maternal Performance IQ and social support from extended family. Socioemotional problems were predicted best by maternal internalizing problems and social support from partner and friends. Adaptive behavior was associated with parenting style. Implications for the early identification of high-risk children--and associated intervention programs--are discussed.

Sample size and multiple regression analysis.

Despite the development of procedures for calculating sample size as a function of relevant effect size parameters, rules of thumb tend to persist in designs of multiple regression studies. One explanation for their persistence may be the difficulty in formulating a reasonable a priori value of an effect size to be detected. This article presents methods for calculating effect sizes in multiple regression from a variety of perspectives and also introduces a new method based on an exchangeability structure among predictor variables. No single method is deemed superior, but rather examples show that a combination of methods is likely to be most valuable in many situations. A simulation provides a 2nd explanation for why rules of thumb for choosing sample size have persisted but also shows that the outcome of such underpowered studies will be a literature consisting of seemingly contradictory results.

Cumulative and compensatory effects of competence and incompetence on depressive symptoms in children.

The authors tested 5 hypotheses from a competency-based model of child depression using classification and regression tree analysis. The authors obtained measures of 5 domains of competency (i.e., academic competence, social acceptance, sports competence, physical attractiveness, and behavioral conduct) and depressive symptoms that were derived from parent, teacher, peer, and self-reports on 1,063 3rd- and 6th-grade children. Results suggested that (a) multiple domains of competence related to depressive symptoms, (b) significant others' positive evaluations in multiple domains have a cumulative inverse relation to depressive symptoms, (c) negative evaluations in multiple domains have a cumulative but positive relation to depressive symptoms, (d) positive evaluations in one domain somewhat compensate for negative evaluations in another domain, and (e) negative evaluations in one domain offset positive evaluations in another domain.

COOH-terminal processing of nascent polypeptides by the glycosylphosphatidylinositol transamidase in the presence of hydrazine is governed by the same parameters as glycosylphosphatidylinositol addition.

Proteins anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) moiety are found in all eukaryotes. After NH2-terminal peptide cleavage of the nascent protein by the signal peptidase, a second COOH-terminal signal peptide is cleaved with the concomitant addition of the GPI unit. The proposed mechanism of the GPI transfer is a transamidation reaction that involves the formation of an activated carbonyl intermediate (enzyme-substrate complex) with the ethanolamine moiety of the preassembled GPI unit serving as a nucleophile. Other nucleophilic acceptors like hydrazine (HDZ) and hydroxylamine have been shown to be possible alternate substrates for GPI. Since GPI has yet to be purified, the use of readily available nucleophilic substitutes such as HDZ and hydroxylamine is a viable alternative to study COOH-terminal processing by the putative transamidase. As a first step in developing a soluble system to study this process, we have examined the amino acid requirements at the COOH terminus for the transamidation reaction using HDZ as the nucleophilic acceptor instead of GPI. The hydrazide-forming reaction shows identical amino acid requirement profiles to that of GPI anchor addition. Additionally, we have studied other parameters relating to the kinetics of the transamidation reaction in the context of rough microsomal membranes. The findings with HDZ provide further evidence for the transamidase nature of the enzyme and also provide a starting point for development of a soluble assay.

A defect in glycosylphosphatidylinositol (GPI) transamidase activity in mutant K cells is responsible for their inability to display GPI surface proteins.

The final step in the pathway that provides for glycosylphosphatidylinositol (GPI) anchoring of cell-surface proteins occurs in the lumen of the endoplasmic reticulum and consists of a transamidation reaction in which fully assembled GPI anchor donors are substituted for specific COOH-terminal signal peptide sequences contained in nascent polypeptides. In previous studies we described a human K562 cell mutant line, designated class K, which assembles all the known intermediates of the GPI pathway but fails to display GPI-anchored proteins on its surface membrane. In the present study, we used mRNA encoding miniPLAP, a truncated form of placental alkaline phosphatase (PLAP), in in vitro assays with rough microsomal membranes (RM) of mutant K cells to further characterize the biosynthetic defect in this line. We found that RM from mutant K cells supported NH2-terminal processing of the nascent translational product, preprominiPLAP, but failed to show any detectable COOH-terminal processing of the resulting prominiPLAP to GPI-anchored miniPLAP. Proteinase K protection assays verified that NH2-terminal processed prominiPLAP was appropriately translocated into the endoplasmic reticulum lumen. The addition of hydrazine or hydroxylamine, which can substitute for GPI donors, to RM from wild-type or mutant cells defective in various intermediate biosynthetic steps in the GPI pathway produced large amounts of the hydrazide or hydroxamate of miniPLAP. In contrast, the addition of these nucleophiles to RM of class K cells yielded neither of these products. These data, taken together, lead us to conclude that mutant K cells are defective in part of the GPI transamidase machinery.

An active carbonyl formed during glycosylphosphatidylinositol addition to a protein is evidence of catalysis by a transamidase.

Glycosylphosphatidylinositol (GPI) substitution is now recognized to be a ubiquitous method of anchoring a protein to membranes in eukaryotes. The structure of GPI and its biosynthetic pathways are known and the signals in a nascent protein for GPI addition have been elucidated. The enzyme(s) responsible for GPI addition with release of a COOH-terminal signal peptide has been considered to be a transamidase but has yet to be isolated, and evidence that it is a transamidase is indirect. The experiments reported here show that hydrazine and hydroxylamine, in the presence of rough microsomal membranes, catalyze the conversion of the pro form of the engineered protein miniplacental alkaline phosphatase (prominiPLAP) to mature forms from which the COOH-terminal signal peptide has been cleaved, apparently at the same site but without the addition of GPI. The products, presumable the hydrazide or hydroxamate of miniPLAP, have yet to be characterized definitively. However, our demonstration of enzyme-catalyzed cleavage of the signal peptide in the presence of the small nucleophiles, even in the absence of an energy source, is evidence of an activated carbonyl intermediate which is the hallmark of a transamidase.

Cleavage without anchor addition accompanies the processing of a nascent protein to its glycosylphosphatidylinositol-anchored form.

Rough microsomal membranes from most mammalian cells, in the presence of a translation system, process nascent proteins with appropriate COOH-terminal signal peptides to their mature glycosylphosphatidylinositol (GPI)-linked forms. The present study, using preprominiplacental alkaline phosphatase as substrate, shows that as much as 10% of the mature product is cleaved correctly but is not linked to GPI. Some of the factors that influence the relative proportions of GPI linked to free mini-placental alkaline phosphatase are the amounts of GPI in the cells and the amino acid substituent at the omega site of the nascent protein. A mechanism for explaining cleavage both with and without GPI addition is presented, which supports a transamidase type of enzyme as the catalyst.

Personal adjustment during pregnancy and adolescent parenting.

This study examined "naturally occurring differences" in personal adjustment (social competence, behavior problems, and problem-solving skills) among representative groups of pregnant and nonpregnant adolescents and pregnant adults. Differences in parenting stress and parenting style were also assessed among a subsample of adolescent and adult mothers. Finally, the relationship between prenatally assessed personal adjustment and parenting was evaluated in the adolescent mother group. The contributions of important demographic characteristics (socioeconomic status and race) to both between- and within-group relationships were examined. Results suggested that pregnant adolescents were less socially competent and less proficient in their problem solving than their nonpregnant peers and that they exhibited more behavioral problems than a pregnant adult comparison group. Adolescent mothers displayed higher levels of parenting stress and were less responsive and sensitive in interactions with their infants than adult mothers. Support for the hypothesized link between prenatally assessed personal adjustment and adolescent parenting stress was found, whereas no relationship between socioeconomic status and race and parenting stress was established. These results suggest that intervention with young mothers identified during pregnancy as having personal problems might forestall parenting problems that arise during early child rearing.