First passage times for a tracer particle in single file diffusion and fractional Brownian motion.

PubMed

Sanders, Lloyd P; Ambjörnsson, Tobias

2012-05-07

We investigate the full functional form of the first passage time density (FPTD) of a tracer particle in a single-file diffusion (SFD) system whose population is: (i) homogeneous, i.e., all particles having the same diffusion constant and (ii) heterogeneous, with diffusion constants drawn from a heavy-tailed power-law distribution. In parallel, the full FPTD for fractional Brownian motion [fBm-defined by the Hurst parameter, H ∈ (0, 1)] is studied, of interest here as fBm and SFD systems belong to the same universality class. Extensive stochastic (non-Markovian) SFD and fBm simulations are performed and compared to two analytical Markovian techniques: the method of images approximation (MIA) and the Willemski-Fixman approximation (WFA). We find that the MIA cannot approximate well any temporal scale of the SFD FPTD. Our exact inversion of the Willemski-Fixman integral equation captures the long-time power-law exponent, when H ≥ 1/3, as predicted by Molchan [Commun. Math. Phys. 205, 97 (1999)] for fBm. When H < 1/3, which includes homogeneous SFD (H = 1/4), and heterogeneous SFD (H < 1/4), the WFA fails to agree with any temporal scale of the simulations and Molchan's long-time result. SFD systems are compared to their fBm counter parts; and in the homogeneous system both scaled FPTDs agree on all temporal scales including also, the result by Molchan, thus affirming that SFD and fBm dynamics belong to the same universality class. In the heterogeneous case SFD and fBm results for heterogeneity-averaged FPTDs agree in the asymptotic time limit. The non-averaged heterogeneous SFD systems display a lack of self-averaging. An exponential with a power-law argument, multiplied by a power-law pre-factor is shown to describe well the FPTD for all times for homogeneous SFD and sub-diffusive fBm systems.

Utilization of fluidized bed material as a calcium and sulfur source for apples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korcak, R.F.

1984-01-01

Fluidized bed material (FBM), a dry, high Ca, alkaline waste product which results from combining coal and limestone, was used as a Ca or S source or lime substitute in an established apple orchard (Malus domestica Borkh., cv. York Imperial) over a four year period. Treatment comparisons were made between FBM was applied at one or two times (1x or 2x) the soil lime requirement and CaCO/sub 3/ applied at the lime requirement (1x). Additionally, FBM 1x was compared to a combination treatment consisting of CaCO/sub 3/ plus gypsum to apply similar amounts of Ca and S. All treatments weremore » also compared to an untreated control. No significant treatment comparisons were noted on leaf Ca levels, however, leaf Mg significantly decreased when FBM applied at the 1x or 2x level compared to CaCO/sub 3/ 1x. When FBM was compared with CaCO/sub 3/ plus gypsum there was a significant decrease in leaf Ca with FBM but no difference in leaf Mg. These effects were probably due to either a solubility difference between nutrients or to actual amount of Mg applied by the different sources. Leaf S levels were unaffected by treatments. Yields, fresh fruit weight and the incidence of cork spot were little affected by treatments. Soil extractable Mg, 1N NH/sub 4/Ac, was not a good prediction of leaf Mg content or Mg added to the soil. Only soil Al was significantly reduced, compared to the control, by the treatments among the metals studied (Zn, Mn, Cu, Cd, Pb and Al). FBM applied at twice the lime requirement (wt. basis) resulted in similar soil pH to CaCO/sub 3/ applied at the lime requirement. 14 references, 6 figures, 1 table.« less

Characterization of the initial level and migration of silicone oil lubricant in empty prefilled syringes for biologics using infrared spectroscopy.

PubMed

Bee, Jared S; Frey, Vadim V; Javed, Urooj; Chung, Jonathan; Corcoran, Marta L; Roussel, Paul S; Krause, Stephan O; Cash, Patricia W; Bishop, Steven M; Dimitrova, Mariana N

2014-01-01

Glass prefillable syringes are lubricated with silicone oil to ensure functionality and a consistent injection for the end user. If excessive silicone is applied, droplets could potentially result in aggregation of sensitive biopharmaceuticals or clouding of the solution. Therefore, monitoring and optimization of the applied silicone layer is critical for prefilled syringe development. The hydrophobic properties of silicone oil, the potential for assay interference, and the very small quantities applied to prefilled syringes present a challenge for the development of a suitable assay. In this work we present a rapid and simple Fourier transform infrared (FTIR) spectroscopy method for quantitation of total silicone levels applied to prefilled syringes. Level-dependent silicone oil migration occurred over time for empty prefilled syringes stored tip-up. However, migration from all prefilled syringes with between 0.25 and 0.8 mg of initial silicone oil resulted in a stable limiting minimum level of between 0.15 and 0.26 mg of silicone in the syringe reached after 1 to 4 years of empty tip-up storage. The results of the FTIR assay correlated well with non-destructive reflectometry characterization of the syringes. This assay can provide valuable data for selection of a robust initial silicone oil target and quality control of prefilled syringes intended for biopharmaceuticals. Glass prefillable syringes are lubricated with silicone oil to ensure functionality and a consistent injection for the end user. If excessive silicone is applied, droplets could potentially result in aggregation of sensitive biopharmaceuticals or clouding of the solution. Therefore, monitoring and optimization of the applied silicone layer is critical for prefilled syringe development. The hydrophobic properties of silicone oil, the potential for assay interference, and the very small quantities applied to prefilled syringes present a challenge for the development of a suitable assay. In this work we present a rapid and simple Fourier transform infrared (FTIR) spectroscopy method for quantitation of total silicone levels applied to prefilled syringes. Level-dependent silicone oil migration occurred over time for empty prefilled syringes stored tip-up. However, migration from all prefilled syringes with between 0.25 and 0.8 mg of initial silicone oil resulted in a stable limiting minimum level of between 0.15 and 0.26 mg of silicone in the syringe reached after 1 to 4 years of empty tip-up storage. The results of the FTIR assay correlated well with non-destructive reflectometry characterization of the syringes. This assay can provide valuable data for selection of a robust initial silicone oil target and quality control of prefilled syringes intended for biopharmaceuticals. © PDA, Inc. 2014.

Recombinant LH (lutropin alfa) for the treatment of hypogonadotrophic women with profound LH deficiency: a randomized, double-blind, placebo-controlled, proof-of-efficacy study.

PubMed

Shoham, Z; Smith, H; Yeko, T; O'Brien, F; Hemsey, G; O'Dea, L

2008-09-01

To confirm the safety and efficacy of 75 IU lutropin alfa with concomitant follitropin alfa in inducing follicular development in women with profound gonadotrophin deficiency. Double-blind, randomized, placebo-controlled trial conducted in 25 medical centres in four countries. Thirty-nine patients with LH < 1.2 IU/l and FSH < 5.0 IU/l were treated with concomitant 75 IU lutropin alfa and 150 IU follitropin alfa or concomitant placebo and 150 IU follitropin alfa. Primary efficacy end-point (intent-to-treat): follicular development defined by (i) at least one follicle >or= 17 mm; (ii) serum E(2) level >or= 400 pmol/l on day of hCG administration (DhCG); and (iii) mid-luteal phase progesterone level >or= 25 nmol/l. In the analysis of evaluable patients, 66.7% (16 of 24) of patients given lutropin alfa achieved follicular development compared with 20.0% (2 of 10) of patients receiving placebo (P = 0.023). In the intent-to-treat analysis, follicular development was achieved in 65.4% (17 of 26) of patients receiving lutropin alfa and 15.4% (2 of 13) of patients receiving placebo (P = 0.006). The statistical difference between treatment groups was preserved when over-response leading to cycle cancellation was analysed as a failed response (P = 0.034). Lutropin alfa was well tolerated. Subcutaneous co-administration of 75 IU lutropin alfa with follitropin alfa is safe and effective in inducing follicular development in women with profound gonadotrophin deficiency.

Comparison between volatility return intervals of the S&P 500 index and two common models

NASA Astrophysics Data System (ADS)

Vodenska-Chitkushev, I.; Wang, F. Z.; Weber, P.; Yamasaki, K.; Havlin, S.; Stanley, H. E.

2008-01-01

We analyze the S&P 500 index data for the 13-year period, from January 1, 1984 to December 31, 1996, with one data point every 10 min. For this database, we study the distribution and clustering of volatility return intervals, which are defined as the time intervals between successive volatilities above a certain threshold q. We find that the long memory in the volatility leads to a clustering of above-median as well as below-median return intervals. In addition, it turns out that the short return intervals form larger clusters compared to the long return intervals. When comparing the empirical results to the ARMA-FIGARCH and fBm models for volatility, we find that the fBm model predicts scaling better than the ARMA-FIGARCH model, which is consistent with the argument that both ARMA-FIGARCH and fBm capture the long-term dependence in return intervals to a certain extent, but only fBm accounts for the scaling. We perform the Student's t-test to compare the empirical data with the shuffled records, ARMA-FIGARCH and fBm. We analyze separately the clusters of above-median return intervals and the clusters of below-median return intervals for different thresholds q. We find that the empirical data are statistically different from the shuffled data for all thresholds q. Our results also suggest that the ARMA-FIGARCH model is statistically different from the S&P 500 for intermediate q for both above-median and below-median clusters, while fBm is statistically different from S&P 500 for small and large q for above-median clusters and for small q for below-median clusters. Neither model can fully explain the entire regime of q studied.

Inverse statistics and information content

NASA Astrophysics Data System (ADS)

Ebadi, H.; Bolgorian, Meysam; Jafari, G. R.

2010-12-01

Inverse statistics analysis studies the distribution of investment horizons to achieve a predefined level of return. This distribution provides a maximum investment horizon which determines the most likely horizon for gaining a specific return. There exists a significant difference between inverse statistics of financial market data and a fractional Brownian motion (fBm) as an uncorrelated time-series, which is a suitable criteria to measure information content in financial data. In this paper we perform this analysis for the DJIA and S&P500 as two developed markets and Tehran price index (TEPIX) as an emerging market. We also compare these probability distributions with fBm probability, to detect when the behavior of the stocks are the same as fBm.

The emotional and reconstructive determinants of emotional memories: an experimental approach to flashbulb memory investigation.

PubMed

Lanciano, Tiziana; Curci, Antonietta; Semin, Gun R

2010-07-01

Flashbulb memories (FBMs) are vivid and detailed memories of the reception context of a public emotional event. Brown and Kulik (1977) introduced the label FBM to suggest the idea that individuals are able to preserve knowledge of an event in an indiscriminate way, in analogy with a photograph that preserves all details of a scene. Research work on FBMs has primarily been conducted using a naturalistic approach in order to explore the role of the emotional and reconstructive factors on FBM formation and maintenance. Nevertheless, these studies lack a sufficient control on the factors that might intervene in the process of FBM formation. The contribution of the present studies is addressed to experimentally investigating the role of emotional and reconstructive factors on emotionally charged memories, specifically on FBMs. Paralleling FBM findings, the two studies revealed that simply being in an emotional state allows people to remember all available information, such as irrelevant and unrelated details. Furthermore, the resulting memories are affected by reconstructive processes so that they are not as accurate as their richness of details would suggest.

Analyzing long-term correlated stochastic processes by means of recurrence networks: Potentials and pitfalls

NASA Astrophysics Data System (ADS)

Zou, Yong; Donner, Reik V.; Kurths, Jürgen

2015-02-01

Long-range correlated processes are ubiquitous, ranging from climate variables to financial time series. One paradigmatic example for such processes is fractional Brownian motion (fBm). In this work, we highlight the potentials and conceptual as well as practical limitations when applying the recently proposed recurrence network (RN) approach to fBm and related stochastic processes. In particular, we demonstrate that the results of a previous application of RN analysis to fBm [Liu et al. Phys. Rev. E 89, 032814 (2014), 10.1103/PhysRevE.89.032814] are mainly due to an inappropriate treatment disregarding the intrinsic nonstationarity of such processes. Complementarily, we analyze some RN properties of the closely related stationary fractional Gaussian noise (fGn) processes and find that the resulting network properties are well-defined and behave as one would expect from basic conceptual considerations. Our results demonstrate that RN analysis can indeed provide meaningful results for stationary stochastic processes, given a proper selection of its intrinsic methodological parameters, whereas it is prone to fail to uniquely retrieve RN properties for nonstationary stochastic processes like fBm.

Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: structural elucidation of the sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, E.D.; Baenziger, J.U.

1988-01-05

The authors have elucidated the structures of the anionic asparagine-linked oligosaccharides present on the glycoprotein hormones lutropin (luteinizing hormone), follitropin (follicle-stimulating hormone), and thyrotropin (thyroid-stimulating hormone). Purified hormones, isolated from bovine, ovine, and human pituitaries, were digested with N-glycanase, and the released oligosaccharides were reduced with NaB(/sup 3/H)/sub 4/. The /sup 3/H-labeled oligosaccharides from each hormone were then fractionated by anion-exchange high performance liquid chromatography (HPLC) into populations differing in the number of sulfate and/or sialic acid moieties. The sulfated, sialylated, and sulfated/sialylated structures, which together comprised 67-90% of the asparagine-linked oligosaccharides on the pituitary glycoprotein hormones, were highly heterogeneousmore » and displayed hormone- as well as animal species-specific features. A previously uncharacterized dibranched oligosaccharide, bearing one residue each of sulfate and sialic acid, was found on all of the hormones except bovine lutropin. In this study, they describe the purification and detailed structural characterizations of the sulfated, sialylated, and sulfated/sialylated oligosaccharides found on lutropin, follitropin, and thyrotropin from several animal species.« less

The valuation of currency options by fractional Brownian motion.

PubMed

Shokrollahi, Foad; Kılıçman, Adem

2016-01-01

This research aims to investigate a model for pricing of currency options in which value governed by the fractional Brownian motion model (FBM). The fractional partial differential equation and some Greeks are also obtained. In addition, some properties of our pricing formula and simulation studies are presented, which demonstrate that the FBM model is easy to use.

Anomalous volatility scaling in high frequency financial data

NASA Astrophysics Data System (ADS)

Nava, Noemi; Di Matteo, T.; Aste, Tomaso

2016-04-01

Volatility of intra-day stock market indices computed at various time horizons exhibits a scaling behaviour that differs from what would be expected from fractional Brownian motion (fBm). We investigate this anomalous scaling by using empirical mode decomposition (EMD), a method which separates time series into a set of cyclical components at different time-scales. By applying the EMD to fBm, we retrieve a scaling law that relates the variance of the components to a power law of the oscillating period. In contrast, when analysing 22 different stock market indices, we observe deviations from the fBm and Brownian motion scaling behaviour. We discuss and quantify these deviations, associating them to the characteristics of financial markets, with larger deviations corresponding to less developed markets.

[Economic impact of strategies using ephedrine prefilled syringes].

PubMed

Crégut-Corbaton, J; Malbranche, C; Guignard, M-H; Fagnoni, P

2013-11-01

Ephedrine is an emergency drug available in ampules and syringes need to be prepared in advance according to one of two strategies in our establishment: strategy 1 (S1: 1 ampule per patient) and strategy 2 (S2: 1 ampule per operating room). There are also prefilled syringes. Because of their high cost and conflicting results in the literature, we assessed the economic interest of using prefilled syringes compared with strategies S1 and S2. This was a prospective observational study. The consumption of ephedrine was recorded over two periods of 14 days: P1 with syringes prepared in advance according to S1 or S2 and P2 with the on-demand use of prefilled syringes. The cost of a syringe of ephedrine prepared in advance (nurse time preparation included) was evaluated at €1.65 vs. €3.57 for a prefilled syringe. In operating rooms using S1, the use of prefilled syringes reduced overall the cost per patient about €1.22 and global annual costs by 72% (€2830), while the decrease was about €0.32 for the cost per patient and about 47% (€2760) for global annual costs for operating rooms using S2. The interest of our study is that we investigated different supply strategies for ephedrine within a large number of operating rooms. In our establishment, it was decided to use prefilled syringes in operating rooms that used S1. As well as the economic interest, prefilled syringes contributed to improved safety and saved nursing time. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

PubMed

Fragoulakis, Vassilis; Pescott, Chris P; Smeenk, Jesper M J; van Santbrink, Evert J P; Oosterhuis, G Jur E; Broekmans, Frank J M; Maniadakis, Nikos

2016-12-01

Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F ® ) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur ® ) and urinary follicle-stimulating hormone (uFSH, Fostimon ® )-for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands. A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting. The mean total treatment costs were estimated as €5664 for follitropin alfa (95 % UI €5167-6151), €5990 for hp-HMG (95 % UI €5498-6488) and €5760 for uFSH (95 % UI €5256-6246). The probability of a live birth was estimated at 36.1 % (95 % UI 27.4-44.3 %), 33.9 % (95 % UI 26.2-41.5 %) and 34.1 % (95 % UI 25.9-41.8 %) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5 % that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses. The present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

Structural and temporal requirements of Wnt/PCP protein Vangl2 function for convergence and extension movements and facial branchiomotor neuron migration in zebrafish.

PubMed

Pan, Xiufang; Sittaramane, Vinoth; Gurung, Suman; Chandrasekhar, Anand

2014-02-01

Van gogh-like 2 (Vangl2), a core component of the Wnt/planar cell polarity (PCP) signaling pathway, is a four-pass transmembrane protein with N-terminal and C-terminal domains located in the cytosol, and is structurally conserved from flies to mammals. In vertebrates, Vangl2 plays an essential role in convergence and extension (CE) movements during gastrulation and in facial branchiomotor (FBM) neuron migration in the hindbrain. However, the roles of specific Vangl2 domains, of membrane association, and of specific extracellular and intracellular motifs have not been examined, especially in the context of FBM neuron migration. Through heat shock-inducible expression of various Vangl2 transgenes, we found that membrane associated functions of the N-terminal and C-terminal domains of Vangl2 are involved in regulating FBM neuron migration. Importantly, through temperature shift experiments, we found that the critical period for Vangl2 function coincides with the initial stages of FBM neuron migration out of rhombomere 4. Intriguingly, we have also uncovered a putative nuclear localization motif in the C-terminal domain that may play a role in regulating CE movements. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparison of utilization, cost, adherence, and hypoglycemia in patients with type 2 diabetes initiating rapid-acting insulin analog with prefilled pen versus vial/syringe.

PubMed

Lee, Lauren J; Li, Qian; Reynolds, Matthew W; Pawaskar, Manjiri D; Corrigan, Sheila M

2011-01-01

Studies examining outcomes of different insulin delivery systems are limited. The objective of this study was to compare healthcare utilization, costs, adherence, and hypoglycemia rates in patients with type 2 diabetes mellitus (T2DM) initiating rapid-acting insulin analog (RAIA) using prefilled pen versus vial/syringe. A retrospective analysis was conducted using a US claims database (1/1/2007 to 12/31/2008). Inclusion criteria were: ≥18 years old, with T2DM, ≥12 months of continuous eligibility, and new to RAIA. Difference-in-difference analyses after propensity score matching were conducted to compare changes in outcomes from 6 months prior to and 6 months after initiating RAIA with a prefilled pen versus vial/syringe (Wilcoxon rank-sum test for costs and t-test for other outcomes). Categories of utilization and costs (2009 USD) included total and diabetes-related inpatient, outpatient, and emergency room. Adherence was measured by proportion of days covered (PDC). Hypoglycemia was identified using ICD-9-CM codes. Baseline characteristics were similar between the prefilled pen (n = 239) and vial/syringe (n = 590) cohorts after matching. Adherence to RAIA was greater in the prefilled pen cohort than the vial/syringe cohort (PDC: 54.6 vs. 45.2%, p < 0.001). While the increase in diabetes-related pharmacy costs from before to after initiating RAIA was greater in the prefilled pen cohort than the vial/syringe cohort (+$900 vs. +$607, p < 0.001), the prefilled pen cohort was associated with greater reductions in the total diabetes-related costs (-$235 vs. +$61, p = 0.006) and the utilization of oral anti-hyperglycemic agents (-1.3 vs. -0.7, p = 0.016). There were no significant differences in other outcomes. Claims databases do not provide optimal measures for adherence or T2DM severity, and only capture hypoglycemia events requiring clinical intervention. Initiating RAIA with a prefilled pen was associated with better adherence and greater reduction in total diabetes-related costs than a vial/syringe. There was no significant difference in total healthcare costs.

Depressive symptoms, body composition and bone mass in young adults: a prospective cohort study.

PubMed

Zhu, K; Allen, K; Mountain, J; Lye, S; Pennell, C; Walsh, J P

2017-04-01

An association between depression and obesity is well recognised, but longitudinal studies of depressive symptoms in adolescents as a predictor of body composition are lacking. We examined depressive symptoms at age 14, 17 and 20 years as predictors of lean, fat and bone mass at age 20 years in a birth cohort. In 1161 participants (569 females) in the Western Australia Pregnancy Cohort (Raine) Study, depressive symptoms were assessed using the Beck Depression Inventory for Youth at age 14 and 17 years, and the Depression, Anxiety and Stress Scale 21 at age 20 years. Participants were further classified into two trajectories using latent class analysis: no/transient and persistent/recurrent depression. At age 20 years, lean body mass (LBM), fat body mass (FBM) and total body bone mass were measured by dual-energy X-ray absorptiometry. In females, accounting for age and lifestyle factors, depression scores at age 14 and 20 years were positively associated with body weight, body mass index (BMI), FBM and % FBM (r=0.110-0.184, P<0.05) but negatively correlated with % LBM (r=-0.120, P<0.05) at age 20 years. Females in the persistent/recurrent depression trajectory (n=99) had significantly higher body weight (+5.1 kg), BMI (+1.8 kg m -2 ), FBM (+3.9 kg) and % FBM (+2.2%) and significantly lower % LBM (-2.2%) at age 20 years than those with no/transient depression (n=470; all P<0.05). In males, depression scores at age 17 and 20 years were negatively associated with LBM but not weight or BMI, and depression trajectory was not a predictor of body composition at age 20 years. Depression scores and trajectories did not predict bone mass in either males or females. Depressive symptoms and persistent/recurrent depression in adolescence are predictors of greater adiposity at age 20 years in females, but not males, but do not predict bone mass in either gender.

Shockley-Read-Hall recombination in pre-filled and photo-filled intermediate band solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayani, Maryam Gholami; Reenaas, Turid Worren, E-mail: turid.reenaas@ntnu.no

2014-08-18

In this work, we study how Shockley-Read-Hall (SRH) recombination via energy levels in the bandgap, caused by defects or impurities, affects the performance of both photo-filled and pre-filled intermediate band solar cells (IBSCs). For a pre-filled cell, the IB is half-filled in equilibrium, while it is empty for the photo-filled cell in equilibrium. The energy level, density, and capture cross-sections of the defects/impurities are varied systematically. We find that the photo-filled cells are, in general, less efficient than pre-filled cells, except when the defect level is between the conduction band and the IB. In that case, for a range ofmore » light intensities, the photo-filled cell performs better than the pre-filled. When the defect level is at the same energy as the IB, the efficiency is above 82% of the defect-free case, when less than 50% of the states at the IB lead to SRH recombination. This shows that even if SRH recombination via the IB takes place, high efficiencies can be achieved. We also show that band gap optimization can be used to reduce the SRH recombination.« less

Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

PubMed

Wechowski, Jaroslaw; Connolly, Mark; Schneider, Dirk; McEwan, Philip; Kennedy, Richard

2009-04-01

To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. Fifty-three fertility clinics in 13 European countries and Israel. Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

Prefilled syringes: An innovation in parenteral packaging

PubMed Central

Makwana, Sagar; Basu, Biswajit; Makasana, Yogita; Dharamsi, Abhay

2011-01-01

Parenteral administration of pharmaceutical products is one of the most popular methods used to produce quick onset of action and also 100% bioavailability. Main problem occurs with the parenteral drug delivery is lack of convenience, affordability, accuracy, sterility, safety etc. Such drawbacks with this delivery system makes it less preferable. Hence, all the disadvantages of these systems can be easily overcome by use of prefilled syringes. The objective of this review article is to provide information regarding prefilled syringes; it's method of preparation, direction to use, advantages, its future scope, and development. PMID:23071944

FOLLITROPIN RECEPTORS CONTAIN CRYPTIC LIGAND BINDING SITES1

PubMed Central

Lin, Win; Bernard, Michael P.; Cao, Donghui; Myers, Rebecca V.; Kerrigan, John E.; Moyle, William R.

2007-01-01

Human choriogonadotropin (hCG) and follitropin (hFSH) have been shown to contact different regions of the extracellular domains of G-protein coupled lutropin (LHR) and follitropin (FSHR) receptors. We report here that hCG and hFSH analogs interact with an FSHR/LHR chimera having only two unique LHR residues similar to the manners in which they dock with LHR and FSHR, respectively. This shows that although the FSHR does not normally bind hCG, it contains a cryptic lutropin binding site that has the potential to recognize hCG in a manner similar to the LHR. The presence of this cryptic site may explain why equine lutropins bind many mammalian FSHR and why mutations in the transmembrane domain distant from the extracellular domain enable the FSHR to bind hCG. The leucine-rich repeat domain (LRD) of the FSHR also appears to contain a cryptic FSH binding site that is obscured by other parts of the extracellular domain. This will explain why contacts seen in crystals of hFSH complexed with an LRD fragment of the human FSHR are hard to reconcile with the abilities of FSH analogs to interact with membrane G-protein coupled FSHR. We speculate that cryptic lutropin binding sites in the FSHR, which are also likely to be present in thyrotropin receptors (TSHR), permit the physiological regulation of ligand binding specificity. Cryptic FSH binding sites in the LRD may enable alternate spliced forms of the FSHR to interact with FSH. PMID:17059863

Particulate and microbial contamination in in-use admixed intravenous infusions.

PubMed

Yorioka, Katsuhiro; Oie, Shigeharu; Oomaki, Masafumi; Imamura, Akihisa; Kamiya, Akira

2006-11-01

We compared particulate and microbial contamination in residual solutions of peripheral intravenous admixtures after the termination of drip infusion between intravenous fluids admixed with glass ampoule drugs and those admixed with pre-filled syringe drugs. The mean number of particles>or=1.3 microm in diameter per 1 ml of residual solution was 758.4 for fluids (n=60) admixed with potassium chloride in a glass ampoule (20 ml volume), 158.6 for fluids (n=63) admixed with potassium chloride in a pre-filled syringe (20 ml volume), 736.5 for fluids (n=66) admixed with sodium chloride in a glass ampoule (20 ml volume), 179.2 for fluids (n=15) admixed with sodium chloride in a pre-filled syringe (20 ml volume), 1884.5 in fluids (n=30) admixed with dobutamine hydrochloride in 3 glass ampoules (5 ml volume), and 178.9 (n=10) in diluted dobutamine hydrochloride in pre-filled syringes (50 ml volume: For these samples alone, particulate and microbial contamination were evaluated in sealed products.) Thus, for potassium chloride or sodium chloride for injection, the number of particles>or=1.3 microm in diameter in the residual intravenous solution was significantly higher for fluids admixed with glass ampoule drugs than for those admixed with pre-filled syringe drugs (p<0.0001). For dobutamine hydrochloride for injection, the number of particles>or=1.3 microm in diameter in the residual intravenous solution was estimated to be higher for fluids admixed with its glass ampoule drug than for those admixed with its pre-filled syringe drug. Observation of the residual solutions of fluids admixed with potassium chloride, sodium chloride, or dobutamine hydrochloride in glass ampoules using an electron microscope with an X-ray analyzer showed glass fragments in each residual solution. Therefore, for the prevention of glass particle contamination in peripheral intravenous admixtures, the use of pre-filled syringe drugs may a useful method. No microbial contamination was observed in any of the residual solutions of 5 types of admixture.

Statistical properties of the anomalous scaling exponent estimator based on time-averaged mean-square displacement

NASA Astrophysics Data System (ADS)

Sikora, Grzegorz; Teuerle, Marek; Wyłomańska, Agnieszka; Grebenkov, Denis

2017-08-01

The most common way of estimating the anomalous scaling exponent from single-particle trajectories consists of a linear fit of the dependence of the time-averaged mean-square displacement on the lag time at the log-log scale. We investigate the statistical properties of this estimator in the case of fractional Brownian motion (FBM). We determine the mean value, the variance, and the distribution of the estimator. Our theoretical results are confirmed by Monte Carlo simulations. In the limit of long trajectories, the estimator is shown to be asymptotically unbiased, consistent, and with vanishing variance. These properties ensure an accurate estimation of the scaling exponent even from a single (long enough) trajectory. As a consequence, we prove that the usual way to estimate the diffusion exponent of FBM is correct from the statistical point of view. Moreover, the knowledge of the estimator distribution is the first step toward new statistical tests of FBM and toward a more reliable interpretation of the experimental histograms of scaling exponents in microbiology.

18 CFR 5.29 - Other provisions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... member of the public. (c) Requests for privileged or Critical Energy Infrastructure Information treatment of pre-filing submission. If a potential Applicant requests privileged or critical energy infrastructure information treatment of any information submitted to the Commission during pre-filing...

18 CFR 5.29 - Other provisions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... member of the public. (c) Requests for privileged or Critical Energy Infrastructure Information treatment of pre-filing submission. If a potential Applicant requests privileged or critical energy infrastructure information treatment of any information submitted to the Commission during pre-filing...

18 CFR 50.5 - Pre-filing procedures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ELECTRIC TRANSMISSION FACILITIES § 50.5 Pre-filing procedures. (a) Introduction. Any applicant seeking a... consultations, project engineering, route planning, environmental and engineering contractor engagement... proceeding. This description also must include the identification of the environmental and engineering firms...

Biopharmaceutical formulations for pre-filled delivery devices.

PubMed

Jezek, Jan; Darton, Nicholas J; Derham, Barry K; Royle, Nikki; Simpson, Iain

2013-06-01

Pre-filled syringes are becoming an increasingly popular format for delivering biotherapeutics conveniently and cost effectively. The device design and stable liquid formulations required to enable this pre-filled syringe format are technically challenging. In choosing the materials and process conditions to fabricate the syringe unit, their compatibility with the biotherapeutic needs to be carefully assessed. The biothereaputic stability demanded for the production of syringe-compatible low-viscosity liquid solutions requires critical excipient choices to be made. The purpose of this review is to discuss key issues related to the stability aspects of biotherapeutics in pre-filled devices. This includes effects on both physical and chemical stability due to a number of stress conditions the product is subjected to, as well as interactions with the packaging system. Particular attention is paid to the control of stability by formulation. We anticipate that there will be a significant move towards polymer primary packaging for most drugs in the longer term. The timescales for this will depend on a number of factors and hence will be hard to predict. Formulation will play a critical role in developing successful products in the pre-filled syringe format, particularly with the trend towards concentrated biotherapeutics. Development of novel, smart formulation technologies will, therefore, be increasingly important.

18 CFR 5.20 - Deficient applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of the Office of Energy Projects will notify the applicant if, in the Director's judgment, the... Energy Projects determines that an application patently fails to substantially comply with the prefiling... Energy Projects determines that an application patently fails to comply with the prefiling consultation...

18 CFR 5.20 - Deficient applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of the Office of Energy Projects will notify the applicant if, in the Director's judgment, the... Energy Projects determines that an application patently fails to substantially comply with the prefiling... Energy Projects determines that an application patently fails to comply with the prefiling consultation...

18 CFR 5.20 - Deficient applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... of the Office of Energy Projects will notify the applicant if, in the Director's judgment, the... Energy Projects determines that an application patently fails to substantially comply with the prefiling... Energy Projects determines that an application patently fails to comply with the prefiling consultation...

18 CFR 5.20 - Deficient applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... of the Office of Energy Projects will notify the applicant if, in the Director's judgment, the... Energy Projects determines that an application patently fails to substantially comply with the prefiling... Energy Projects determines that an application patently fails to comply with the prefiling consultation...

18 CFR 5.20 - Deficient applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of the Office of Energy Projects will notify the applicant if, in the Director's judgment, the... Energy Projects determines that an application patently fails to substantially comply with the prefiling... Energy Projects determines that an application patently fails to comply with the prefiling consultation...

Comparison of vials and prefilled pens of a rapid-acting insulin analog on pharmacy budgets in a long-term care setting.

PubMed

Eby, Elizabeth L; Smolen, Lee J; Pitts, Amber C; Krueger, Linda A; Andrews, Jeffrey Scott

2014-12-01

Estimate budgetary impact for skilled nursing facility converting from individual patient supply (IPS) delivery of rapid-acting insulin analog (RAIA) 10-mL vials or 3-mL prefilled pens to 3-mL vials. A budget-impact model used insulin volume purchased and assumptions of length of stay (LOS), daily RAIA dose, and delivery protocol to estimate the cost impact of using 3-mL vials. Skilled nursing facility. Medicare Part A patients. Simulations conducted using 12-month current and future scenarios. Comparisons of RAIA use for 13- and 28-day LOS. RAIA costs and savings, waste reduction. For patients with 13-day LOS using 20 units/day of IPS insulin, the model estimated a 70% reduction in RAIA costs and units purchased and a 95% waste reduction for the 3-mL vial compared with the 10-mL vial. The estimated costs for prefilled pen use were 58% lower than for use of 10-mL vials. The incremental savings associated with 3-mL vial use instead of prefilled pens was 28%, attributable to differences in per-unit cost of insulin in vials versus prefilled pens. Using a more conservative scenario of 28-day LOS at 20 units/day, the model estimated a 40% reduction in RAIA costs and units purchased, resulting in a 91% reduction in RAIA waste for the 3-mL vial, compared with 10-mL vial. Budget-impact analysis of conversion from RAIA 10-mL vials or 3-mL prefilled pens to 3-mL vials estimated reductions in both insulin costs and waste across multiple scenarios of varying LOS and patient daily doses for skilled nursing facility stays.

Adrenaline in cardiac arrest: Prefilled syringes are faster.

PubMed

Helm, Claire; Gillett, Mark

2015-08-01

Standard ampoules and prefilled syringes of adrenaline are widely available in Australasian EDs for use in cardiac arrest. We hypothesise that prefilled syringes can be administered more rapidly and accurately when compared with the two available standard ampoules. This is a triple arm superiority study comparing the time to i.v. administration and accuracy of dosing of three currently available preparations of adrenaline. In their standard packaging, prefilled syringes were on average more than 12 s faster to administer than the 1 mL 1:1000 ampoules and more than 16 s faster than the 10 mL 1:10,000 ampoules (P < 0.01 in both comparisons). With packaging removed, the time to administration was equal for the 1 mL (1:1000) ampoule and the prefilled syringe. Accuracy of dosing was excellent with both the 10 mL (1:10 000) ampoules and prefilled syringes. The 1 mL (1:1000) ampoules delivered a small number of markedly inaccurate doses, but these did not reach statistical significance. The speed of administration of adrenaline utilising a Minijet (CSL Limited, Parkville, Victoria, Australia) is faster than using adrenaline in glass ampoules presented in their plastic packaging. Removing the plastic packaging from the 1 mL (1 mg) ampoule might result in more rapid administration similar to the Minijet. Resuscitation personnel requiring rapid access to adrenaline should consider storing it as either Minijets or ampoules devoid of packaging. These results might be extrapolatable to other clinical scenarios, including pre-hospital and anaesthesia, where other drugs are required for rapid use. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

An assessment of models that predict soil reinforcement by plant roots

NASA Astrophysics Data System (ADS)

Hallett, P. D.; Loades, K. W.; Mickovski, S.; Bengough, A. G.; Bransby, M. F.; Davies, M. C. R.; Sonnenberg, R.

2009-04-01

Predicting soil reinforcement by plant roots is fraught with uncertainty because of spatio-temporal variability, the mechanical complexity of roots and soil, and the limitations of existing models. In this study, the validity of root-reinforcement models was tested with data from numerous controlled laboratory tests of both fibrous and woody root systems. By using pot experiments packed with homogeneous soil, each planted with one plant species and grown in glasshouses with controlled water and temperature regimes, spatio-temporal variability was reduced. After direct shear testing to compare the mechanical behaviour of planted versus unplanted samples, the size distribution of roots crossing the failure surface was measured accurately. Separate tensile tests on a wide range of root sizes for each test series provided information on the scaling of root strength and stiffness, which was fitted using power-law relationships. These data were used to assess four root-reinforcement models: (1) Wu et al.'s (1979) root-reinforcement model, (2) Rip-Root fibre bundle model (FBM) proposed by Pollen & Simon (2005), (3) a stress-based FBM and (4) a strain-based FBM. For both fibrous (barley) and woody (willow) root systems, all of the FBMs provided a better prediction of reinforcement than Wu's root-reinforcement model. As FBMs simulate progressive failure of roots, they reflect reality better than the Wu model which assumes all roots break (and contribute to increased shear strength) simultaneously. However, all of the FBMs contain assumptions about the distribution of the applied load within the bundle of roots and the failure criterion. The stress-based FBM assumes the same stiffness for different sized roots, resulting in progressive failure from the largest to smallest roots. This is not observed in testing where the smallest roots fail first. The Rip-Root FBM predicts failure from smallest to largest roots, but the distribution of load between different sized roots is based on unverified scaling rules (stiffness is inversely proportional to diameter). In the strain-based FBM, both stiffness and strength data are used to evaluate root breakage. As roots stretch across the shear surface, the stress mobilised in individual roots depends on both their individual stiffness and strain. Small roots being stiffer, mobilise more stress for the same strain (or shear displacement) and therefore fail first. The strain based FBM offers promise as a starting point to predict the reinforcement of soil by plant roots using sound mechanical principles. Compared to other models, it provided the best prediction of root reinforcement. Further developments are required to account particularly for the stochastic variability of the mechanical behaviour and spatial distribution of roots and this will be achieved by adapting advanced fibre bundle methods. Pollen, N., and A. Simon. 2005. Estimating the mechanical effects of riparian vegetation on stream bank stability using a fiber bundle model. Water Resour. Res. 41: W07025. Wu T. H., W. P. McKinnell, and D. N. Swanston. 1979. Strength of tree roots and landslides on Prince of Wales Island, Alaska. Can. Geotech. J. 16: 19-33.

Feature-Based Morphometry: Discovering Group-related Anatomical Patterns

PubMed Central

Toews, Matthew; Wells, William; Collins, D. Louis; Arbel, Tal

2015-01-01

This paper presents feature-based morphometry (FBM), a new, fully data-driven technique for discovering patterns of group-related anatomical structure in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between subjects, FBM explicitly aims to identify distinctive anatomical patterns that may only be present in subsets of subjects, due to disease or anatomical variability. The image is modeled as a collage of generic, localized image features that need not be present in all subjects. Scale-space theory is applied to analyze image features at the characteristic scale of underlying anatomical structures, instead of at arbitrary scales such as global or voxel-level. A probabilistic model describes features in terms of their appearance, geometry, and relationship to subject groups, and is automatically learned from a set of subject images and group labels. Features resulting from learning correspond to group-related anatomical structures that can potentially be used as image biomarkers of disease or as a basis for computer-aided diagnosis. The relationship between features and groups is quantified by the likelihood of feature occurrence within a specific group vs. the rest of the population, and feature significance is quantified in terms of the false discovery rate. Experiments validate FBM clinically in the analysis of normal (NC) and Alzheimer's (AD) brain images using the freely available OASIS database. FBM automatically identifies known structural differences between NC and AD subjects in a fully data-driven fashion, and an equal error classification rate of 0.80 is achieved for subjects aged 60-80 years exhibiting mild AD (CDR=1). PMID:19853047

In-use Stability of Ceftaroline Fosamil in Elastomeric Home Infusion Systems and MINI-BAG Plus Containers.

PubMed

Bhattacharya, Sisir; Parekh, Satish; Dedhiya, Mahendra

2015-01-01

The objective of this study was to determine in-use stability of ceftaroline fosamil infusion solution of concentrations up to 12 mg/mL in elastomeric home infusion system prefilled with 0.9% Sodium Chloride Injection USP or 5% Dextrose Injection USP and MINI-BAG Plus Container delivery devices prefilled with 0.9% sodium chloride injection. In-use ceftaroline fosamil infusion solution (12 mg/mL) was prepared for elastomeric home infusion systems (Homepump Eclipse, Baxter Intermate, and AccuRx Elastomeric Pump) pre-filled with either 0.9% sodium chloride injection or 5% dextrose; or Baxter MINI-BAG Plus Containers pre-filled with 0.9% Sodium Chloride Injection USP (4 mg/mL to 12 mg/mL ceftaroline fosamil in final solution). The systems were stored refrigerated for 24 hours followed by up to 6 hours of storage at room temperature. Samples were analyzed at various time points for assay and degradation product by a validated stability-indicating high-performance liquid chromatography method. In-use ceftaroline fosamil infusion solution, ranging from 4-mg/mL to a maximum of 12-mg/mL concentration, in elastomeric home infusion systems prefilled with 0.9% sodium chloride injection or 5% dextrose, and MINI-BAG Plus Containers prefilled with 0.9% sodium chloride injection were chemically stable for up to 24 hours refrigerated at 2°C to 8°C (36°F to 46°F) and up to 6 hours at room temperature and had acceptable compatibility with material used. Ceftaroline fosamil (4 mg/mL to 12 mg/mL) maintains its potency for up to 24 hours refrigerated at 2°C to 8°C (36°F to 46°F) and up to 6 hours of storage at room temperature upon reconstitution in infusion solution with 0.9% sodium chloride or 5% dextrose when used in elastomeric home infusion system and MINI-BAG Plus Containers delivery devices prefilled with 0.9% sodium chloride injection.

In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

PubMed Central

Munier, Mathilde; Grouleff, Julie; Gourdin, Louis; Fauchard, Mathilde; Chantreau, Vanessa; Henrion, Daniel; Coutant, Régis; Schiøtt, Birgit; Chabbert, Marie; Rodien, Patrice

2016-01-01

Background: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p′-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p′-DDT exposure and reproductive abnormalities. Objectives: To investigate the putative effects of p,p′-DDT on the human follitropin receptor (FSHR) function. Methods and Results: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p′-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p′-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p′-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p′-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p′-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p′-DDT was dependent on the FSHR. In addition, p,p′-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p′-DDT and potentiation of the FSHR response to FSH by p,p′-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p′-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p′-DDT and 16a into the FSHR transmembrane bundle. Conclusion: p,p′-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein–coupled receptors are additional targets of endocrine disruptors. Citation: Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016. In vitro effects of the endocrine disruptor p,p′-DDT on human follitropin receptor. Environ Health Perspect 124:991–999; http://dx.doi.org/10.1289/ehp.1510006 PMID:26895433

In Vitro Effects of the Endocrine Disruptor p,p'-DDT on Human Follitropin Receptor.

PubMed

Munier, Mathilde; Grouleff, Julie; Gourdin, Louis; Fauchard, Mathilde; Chantreau, Vanessa; Henrion, Daniel; Coutant, Régis; Schiøtt, Birgit; Chabbert, Marie; Rodien, Patrice

2016-07-01

1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p'-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p'-DDT exposure and reproductive abnormalities. To investigate the putative effects of p,p'-DDT on the human follitropin receptor (FSHR) function. We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p'-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p'-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p'-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p'-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p'-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p'-DDT was dependent on the FSHR. In addition, p,p'-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p'-DDT and potentiation of the FSHR response to FSH by p,p'-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p'-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p'-DDT and 16a into the FSHR transmembrane bundle. p,p'-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptors. Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016. In vitro effects of the endocrine disruptor p,p'-DDT on human follitropin receptor. Environ Health Perspect 124:991-999; http://dx.doi.org/10.1289/ehp.1510006.

Predictions for the top-quark forward-backward asymmetry at high invariant pair mass using the principle of maximum conformality

DOE PAGES

Wang, Sheng -Quan; Wu, Xing -Gang; Si, Zong -Guo; ...

2016-01-07

In this study, the D0 collaboration at FermiLab has recently measured the top-quark pair forward-backward asymmetry inmore » $$\\bar{p}p$$ → $$t\\bar{t}$$X reactions as a function of the $$t\\bar{t}$$ invariant mass M $$t\\bar{t}$$. The D0 result for A FB(M $$t\\bar{t}$$ > 650 GeV) is smaller than A FB(M $$t\\bar{t}$$) obtained for small values of M $$t\\bar{t}$$, which may indicate an “increasing-decreasing” behavior for A FB(M $$t\\bar{t}$$ > M cut). This behavior is not explained using conventional renormalization scale setting, or even by a next-to-next-to-leading order (N 2LO) QCD calculation—one predicts a monotonically increasing behavior. In the conventional scale-setting method, one simply guesses a single renormalization scale μr for the argument of the QCD running coupling and then varies it over an arbitrary range. However, the conventional method has inherent difficulties.« less

Use of polyclonal and monoclonal antibodies to study hCG-receptor interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milius, R.P.

1985-01-01

Although the glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) bind to different receptors, each contains an identical alpha subunit. Specificity is somehow endowed by theta subunits which are distinct for each hormone. Human choriogonadotropin (hCG) is a natural LH analog that contains a beta subunit nearly identical to that of LH. The roles of these subunits in the recognition and high affinity binding of hCG to receptor was examined. Polyclonal and monoclonal antibodies specific for the individual subunits of hCG were used to probe the hormone-receptor interaction. Conformation-specific and sequence-specific antibodies were examined for their abilities to bindmore » Triton X-100-solubilized /sup 125/I-hCG-receptor complex and to inhibit hormone binding to crude rat ovarian membranes containing receptor. Even though the immunoreactive sites are not located on the receptor binding surface of the beta subunit, most, but not all, of these polyclonal and monoclonal antibodies were able to inhibit /sup 125/I-hCG binding to receptor. Although the inhibition of binding may be due to steric interference due to the size of the antibody molecules, a two-step model for hCG binding to receptor is presented that also explains these results. In this model, the beta subunit initially binds with the receptor with a highly specific but low affinity interaction. This activates a site for the high affinity binding of the alpha subunit and stabilization of the complex. This is an attractive model as it may be applied to other glycoprotein hormones sharing an alpha subunit.« less

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

18 CFR 4.38 - Consultation requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Consultation... original license commences first stage pre-filing consultation on or after July 23, 2005 it shall file a... potential applicant for an original license that commences pre-filing consultation on or after July 23, 2005...

77 FR 71587 - Wisconsin Public Service Corporation; Notices of Intent To File License Applications, Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-03

...] Wisconsin Public Service Corporation; Notices of Intent To File License Applications, Filing of Pre-Application Documents (PAD), Commencement of Pre-Filing Processes and Scoping, Request for Comments on the...: Notices of Intent to File License Applications for Two New Licenses and Commencing the Pre-filing Process...

Behaviours, thoughts and perceptions around mealtime insulin usage and wastage among people with type 1 and type 2 diabetes mellitus: A cross-sectional survey study.

PubMed

Van Brunt, Kate; Pedersini, Riccardo; Rooney, Jillian; Corrigan, Sheila M

2017-04-01

People with diabetes who use mealtime insulin (MTI) were surveyed about insulin wastage and injection habits when insufficient insulin remains in a disposable prefilled pen/cartridge to administer a full dose in a single injection. Cross-sectional, online, self-reported survey of MTI usage/wastage behaviour in 400 adults with type 1 (n=120) or type 2 (n=280) diabetes mellitus administering >20units/day of MTI via 100units/ml prefilled pens/cartridges for ⩾1month, conducted in France, Germany, Italy and UK. Participants' mean±standard deviation age was 54.5±12.2years, body mass index was 29.9±7.2kg/m 2 and duration of MTI therapy was 8.6±7.8years. They administered 3.7±5.9 injections/day with meals, using 11.3±18.0 prefilled pens/cartridges per month. Overall, 63.5% split the dose across two prefilled pens/cartridges (i.e. administered two injections to obtain a full dose), 15.0% used just what remained in their current pen (i.e. took a lower-than-prescribed dose) and 36.3% discarded prefilled pens/cartridges still containing insulin (i.e. took full dose with new pen). The latter participants discarded a mean 5.5±8.2 prefilled pens/cartridges monthly still containing insulin, each containing 8.6±8.7 units of insulin. Participants who wasted insulin considered it frustrating, time-consuming and painful to inject twice. Patients taking >20units/day MTI can find transitions between insulin pens challenging. This study highlights the need to identify ways of improving transitions between pens to make transitions easier for insulin users, which could potentially improve adherence to prescribed doses and reduce waste. Copyright © 2016 Eli Lilly and Company. Published by Elsevier B.V. All rights reserved.

Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction.

PubMed

Nawroth, Frank; Tandler-Schneider, Andreas; Bilger, Wilma

2015-01-01

This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI.

Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction

PubMed Central

Nawroth, Frank; Tandler-Schneider, Andreas; Bilger, Wilma

2015-01-01

This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI. PMID:25926755

18 CFR 157.21 - Pre-filing procedures and review process for LNG terminal facilities and other natural gas...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Pre-filing procedures... applications. 157.21 Section 157.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY...) A description of a Public Participation Plan which identifies specific tools and actions to...

18 CFR 157.21 - Pre-filing procedures and review process for LNG terminal facilities and other natural gas...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Pre-filing procedures... applications. 157.21 Section 157.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY...) A description of a Public Participation Plan which identifies specific tools and actions to...

18 CFR 157.21 - Pre-filing procedures and review process for LNG terminal facilities and other natural gas...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Pre-filing procedures... applications. 157.21 Section 157.21 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY...) A description of a Public Participation Plan which identifies specific tools and actions to...

18 CFR 153.12 - Pre-filing procedures for applications for authorization to site, construct, maintain, connect or...

Code of Federal Regulations, 2010 CFR

2010-04-01

... used for the export or import of natural gas. 153.12 Section 153.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT... NATURAL GAS Application Under Section 3 § 153.12 Pre-filing procedures for applications for authorization...

18 CFR 157.21 - Pre-filing procedures and review process for LNG terminal facilities and other natural gas...

Code of Federal Regulations, 2010 CFR

2010-04-01

... the pre-filing review of any pipeline or other natural gas facilities, including facilities not... from the subject LNG terminal facilities to the existing natural gas pipeline infrastructure. (b) Other... and review process for LNG terminal facilities and other natural gas facilities prior to filing of...

18 CFR 153.12 - Pre-filing procedures for applications for authorization to site, construct, maintain, connect or...

Code of Federal Regulations, 2011 CFR

2011-04-01

... used for the export or import of natural gas. 153.12 Section 153.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT... NATURAL GAS Application Under Section 3 § 153.12 Pre-filing procedures for applications for authorization...

77 FR 55210 - Public Service Company of New Hampshire; Notice of Intent To File License Application, Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2457-038] Public Service... (PAD), Commencement of Pre-Filing Process, and Scoping; Request for Comments on the PAD And Scoping... File License Application for a New License and Commencing Pre-filing Process. b. Project No.: 2457-038...

Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial☆, ☆

PubMed Central

Stevens, Allen D.; Hernandez, Caleb; Jones, Seth; Moreira, Maria E.; Blumen, Jason R.; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S.

2016-01-01

Background Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. Methods We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded-syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Results Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28–39) seconds and 42 (95% CI: 36–51) seconds, respectively (difference = 9 [95% CI: 4–14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference = 39%, 95% CI: 13–61%). Conclusions A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. PMID:26247145

Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial.

PubMed

Stevens, Allen D; Hernandez, Caleb; Jones, Seth; Moreira, Maria E; Blumen, Jason R; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S

2015-11-01

Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28-39) seconds and 42 (95% CI: 36-51) seconds, respectively (difference=9 [95% CI: 4-14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference=39%, 95% CI: 13-61%). A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Flashbulb Memories

PubMed Central

Hirst, William; Phelps, Elizabeth A.

2015-01-01

We review and analyze the key theories, debates, findings, and omissions of the existing literature on flashbulb memories (FBMs), including what factors affect their formation, retention, and degree of confidence. We argue that FBMs do not require special memory mechanisms and are best characterized as involving both forgetting and mnemonic distortions, despite a high level of confidence. Factual memories for FBM-inducing events generally follow a similar pattern. Although no necessary and sufficient factors straightforwardly account for FBM retention, media attention particularly shapes memory for the events themselves. FBMs are best characterized in term of repetitions, even of mnemonic distortions, whereas event memories evidence corrections. The bearing of this literature on social identity and traumatic memories is also discussed. PMID:26997762

77 FR 64971 - Lock+ Hydro Friends Fund XLII, LLC; Notice of Waiver, in Part, of Prefiling Consultation Required...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-24

... Friends Fund XLII, LLC; Notice of Waiver, in Part, of Prefiling Consultation Required Under Section 4.38(C... License. b. Project No.: 13739-002. c. Date Filed: September 17, 2012. d. Applicant: Lock+ Hydro Friends.... 791(a)-825(r). h. Applicant Contact: Mr. Mark R. Stover, Lock+\\TM\\ Hydro Friends Fund XLII, c/o Hydro...

Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

PubMed Central

Rinaldi, Leonardo; Selman, Helmy

2016-01-01

A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

Potential Insulin Underdelivery from Prefilled and Reusable Insulin Pens in Cases of Premature Needle Withdrawal: A Laboratory Evaluation.

PubMed

Joubert, Michael; Haddouche, Aini; Morera, Julia; Rod, Anne; Reznik, Yves

2015-10-01

Devices for the treatment of diabetes are not always used as recommended in good practice. Our aim was to evaluate potential insulin underdelivery in cases of premature needle withdrawal after injection with insulin pens, which is a commonly observed misuse, especially in young type 1 diabetes patients. Potential insulin underdelivery was evaluated using five prefilled insulin pens (lispro Kwikpen(®) [Eli Lilly, Indianapolis, IN], aspart Flexpen(®) [Novo Nordisk, Bagsvaerd, Denmark], glulisine Solostar(®) [Sanofi, Paris, France], detemir Flexpen(®) [Novo Nordisk], and glargine Solostar(®) [Sanofi]) and three reusable insulin pens (Humapen(®) Luxura HD with lispro cartridge [Eli Lilly], Novopen(®) Echo with aspart and detemir cartridge [Novo Nordisk], and JuniorSTAR(®) with glulisine and glargine cartridge [Sanofi]) in a laboratory. For each pen and insulin, we simulated premature needle withdrawal 2 and 3 s after an insulin injection of 5 and 10 units, respectively. With prefilled pens, mean potential insulin underdelivery was 0.43±0.30 and 0.44±0.32 units after injection of 5 and 10 units, respectively. With reusable pens, mean potential insulin underdelivery was lower (0.29±0.13 and 0.29±0.12 units after injection of 5 and 10 units, respectively; P<0.001). The results were heterogeneous across pens, ranging from 2.6%/1.6% to 20.2%/8.6% of the selected insulin dose for prefilled/reusable pens, respectively (P<0.001). Potential insulin underdelivery varies across prefilled and reusable insulin pens but may represent up to one-fifth of the total injected dose. Clinicians should be aware of the potential consequences of premature needle withdrawal and should reinforce insulin injection education.

Immunization against exon 1 decapeptides from the lutropin/choriogonadotropin receptor or the follitropin receptor as potential male contraceptive.

PubMed

Remy, J J; Couture, L; Rabesona, H; Haertle, T; Salesse, R

1996-11-01

Pituitary gonadotropin hormones lutropin (LH) and follitropin (FSH) control steroidogenesis and gametogenesis in male and female gonads through interaction with G protein-coupled receptors, LHR and FSHR. In the male, LH acts on leydig cells and is mostly responsible for the acquisition of puberty and the production of androgens while FSH, together with androgens, regulates spermatogenesis within Sertoli cells. We have engineered filamentous phages displaying mouse LHR and human FSHR decapeptides chosen in hormone binding regions. Peptides from both receptors displayed on phages belong either to the receptor specific exon 1 (amino acids 18-27) or to the homologous exon 4 (amino acids 98-107). Vaccination of prepubertal BALB/c male mice with hybrid phages using sub-cutaneous or intraperitoneal injections induced immunity against receptors. Anti-receptor immunization produced agonist or antagonist effects depending only on the circulating levels of the antibodies. Both anti-LHR and anti-FSHR vaccines induced efficient as well as reversible male contraception, through different mechanisms: targeting LH receptors inhibited or hyperstimulated Leydig cell testosterone production while targeting FSH receptors did not affect testosterone levels.

Non-destructive vacuum decay method for pre-filled syringe closure integrity testing compared with dye ingress testing and high-voltage leak detection.

PubMed

Simonetti, Andrea; Amari, Filippo

2015-01-01

In reaction to the limitations of the traditional sterility test methods, in 2008, the U.S. Food and Drug Administration issued the guidance "Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products" encouraging sterile drug manufacturers to use properly validated physical methods, apart from conventional microbial challenge testing, to confirm container closure integrity as part of the stability protocol. The case study presented in this article investigated the capability of four container closure integrity testing methods to detect simulated defects of different sizes and types on glass syringes, prefilled both with drug product intended for parenteral administration and sterile water. The drug product was a flu vaccine (Agrippal, Novartis Vaccines, Siena, Italy). Vacuum decay, pharmacopoeial dye ingress test, Novartis specific dye ingress test, and high-voltage leak detection were, in succession, the methods involved in the comparative studies. The case study execution was preceded by the preparation of two independent sets of reference prefilled syringes, classified, respectively, as examples of conforming to closure integrity requirements (negative controls) and as defective (positive controls). Positive controls were, in turn, split in six groups, three of with holes laser-drilled through the prefilled syringe glass barrel, while the other three with capillary tubes embedded in the prefilled syringe plunger. These reference populations were then investigated by means of validated equipment used for container closure integrity testing of prefilled syringe commercial production; data were collected and analyzed to determine the detection rate and the percentage of false results. Results showed that the vacuum decay method had the highest performance in terms of detection sensitivity and also ensured the best reliability and repeatability of measurements. An innovative technical solution, preventing possible prefilled syringe plunger movement during container closure integrity testing execution, is presented as well. The growing need to meet sterile drug products' regulatory, quality, and safety expectations has progressively driven new developments and improvements both in container closure integrity testing methods and in the respective equipment, over the last years. Indeed, container closure integrity testing establishes the container closure system capability to provide required protection to the drug product and to demonstrate maintenance of product sterility over its shelf life. This article describes the development of four container closure integrity testing approaches for the evaluation of glass prefilled syringe closure integrity, including two destructive (pharmacopoeial and Novartis specific dye ingress test) and two non-destructive (vacuum decay and high-voltage leak detection) methods. The important finding from the validation of comparative studies was that the vacuum decay method resulted in the most effective, reliable and repeatable detection of defective samples, whether the defect was exposed to sterile water, to drug product, or to air. Complete sets of known defects were created for this purpose (5 μm, 10 μm, 20 μm certified leakages by laser drilled holes and capillary tubes). All investigations and studies were conducted at Bonfiglioli Engineering S.r.l. (Vigarano Pieve, Ferrara, Italy) and at Novartis Vaccines (Sovicille, Siena, Italy). © PDA, Inc. 2015.

Aggregation and Particle Formation of Therapeutic Proteins in Contact With a Novel Fluoropolymer Surface Versus Siliconized Surfaces: Effects of Agitation in Vials and in Prefilled Syringes.

PubMed

Teska, Brandon M; Brake, Jeffrey M; Tronto, Gregory S; Carpenter, John F

2016-07-01

We examined the effects of an accelerated agitation protocol on 2 protein therapeutics, intravenous immunoglobulin (IVIG) and Avastin (bevacizumab), in contact with a novel fluoropolymer surface and more typical siliconized surfaces. The fluoropolymer surface provides "solid-phase" lubrication for the syringe plunger-obviating the need for silicone oil lubrication in prefilled syringes. We tested the 2 surfaces in a vial system and in prefilled glass syringes. We also examined the effects of 2 buffers, phosphate-buffered saline (PBS) and 0.2-M glycine, with and without the addition of polysorbate 20, on agitation-induced aggregation of IVIG. Aggregation was monitored by measuring subvisible particle formation and soluble protein loss. In both vials and syringes, protein particle formation was much lower during agitation with the fluoropolymer surface than with the siliconized surface. Also, particle formation was greater in PBS than in glycine buffer, an effect attributed to lower colloidal stability of IVIG in PBS. Polysorbate 20 in the formulation greatly inhibited protein particle formation. Overall, the fluoropolymer plunger surface in an unsiliconized glass barrel was demonstrated to be a viable solution for eliminating silicone oil droplets from prefilled syringe formulations and providing a consistent system for rationale formulation development and simplified particle analysis. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Functionality of a novel follitropin alfa pen injector: results from human factor interactions by patients and nurses.

PubMed

Saunders, Helen; de la Fuente Bitaine, Laura; Eftekhar, Chriss; Howles, Colin M; Glaser, Johanna; Hoja, Tina; Arriagada, Pablo

2018-06-01

The main objective of this user experience testing study was to evaluate the impact of human factors on the use of a disposable pen containing follitropin alfa by patients and nurses with special focus on the convenience, safety and ease of use, in different types of stimulation protocols. Infertile women trying to conceive, and specialist nurses were recruited across 6 European countries. In total 18 patients and 19 nurses took part in the testing, which included both nurse-patient pairings and in-depth interviews. A standardized list of expected and pre-defined critical steps according to the Instructions for Use (IFU), was used to assess the correct handling of the pen. During the user experience testing, no critical errors, related to the use of the pen, which could affect the success of the injection process were identified. In general, both nurses and patients found the pen very easy to learn, use and would be confident using the pen for self-injection. Nurses also found the pen very easy to train the patients. The study provides valuable information on the pen from both patient and nurse perspectives in different simulated scenarios reflecting standard practice.

Quality evaluation of radiographic contrast media in large-volume prefilled syringes and vials.

PubMed

Sendo, T; Hirakawa, M; Yaginuma, M; Aoyama, T; Oishi, R

1998-06-01

The authors compared the particle contaminations of radiographic contrast media packaged in large-volume prefilled syringes and vials. Particle counting was performed for four contrast media packaged in large-volume prefilled syringes (iohexol, ioversol, ioversol for angiography, and ioxaglate) and three contrast media packaged in vials (iohexol, ioversol, and ioxaglate). X-ray emission spectrometry was performed to characterize the individual particles. The amount of silicone oil in the syringe was quantified with infrared spectrophotometry. The particle contamination in syringes containing ioversol was higher than that in syringes containing iohexol or ioxaglate. Particle contamination in the vials was relatively low, except with ioxaglate. X-ray emission spectrometry of the components of the syringe and vial showed that the source of particles was internal material released from the rubber stopper or inner surface. The particle counts for contrast media packaged in syringes and vials varied considerably among the different contrast media and were related to the amount of silicone oil on the inner surface and rubber piston of the syringe.

A comparative analysis of carbon dioxide displacement rates for euthanasia of the ferret.

PubMed

Fitzhugh, Dawn C; Parmer, Amanda; Shelton, Larry J; Sheets, James T

2008-02-01

Though carbon dioxide asphyxiation is a common method of euthanasia for laboratory animals, species-specific guidelines have not been established for this procedure in the domestic ferret (Mustela putorius furo). The authors investigated the efficacy and stress effects of carbon dioxide euthanasia in 24 ferrets that had participated in previous experimental protocols. They euthanized ferrets by placing them in cages that were either prefilled with carbon dioxide or gradually filled at a displacement rate of 10%, 20% or 50% of the cage volume per min. Blinded observers subjectively evaluated ferret distress. Prefilling the cage or filling it at a rate of 50% volume per min resulted in less time to recumbency and to last breath than did filling the cage at a slower displacement rate. Slower carbon dioxide displacement rates also caused an increase in ferret blood glucose concentrations, which may indicate distress. Overall, observers found that prefilling the euthanasia cage caused the least stress to ferrets.

Contributions of arginines-43 and -94 of human choriogonadotropin. beta. to receptor binding and activation as determined by oligonucleotide-based mutagenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang Chen; Puett, D.

1991-10-22

Members of the glycoprotein hormone family contain a common {alpha} subunit and a hormone-specific {beta} subunit. Human choriogonadotropin (hCG) {beta} is a 145 amino acid residue protein glycosylated at 6 positions (2 N-linked and 4 O-linked oligosaccharides). In an effort to elucidate receptor determinants on hCG{beta}, the authors have used site-directed mutagenesis to prepare and express several mutant cDNAs with replacements at arginines-43 and -94. Arg-43 is invariant in all known mammalian CG/lutropin {beta} amino acid sequences, and Arg-94 is conserved in 10 of the 12 sequences. Moreover, various studies involving synthetic peptides and enzymatic digestions of intact {beta} chainsmore » suggest that these residues may be important in hCG receptor binding. Point mutants were made in which these two arginines were replaced with the corresponding residues in human follitropin {beta}, Leu-43 and Asp-94. The wild-type and mutant {beta} chains were expressed in CHO cells containing a stably integrated gene for bovine {alpha}, and heterodimer formation occurred. These heterologous gonadotropins were active in assays using transformed Leydig cells, competitive binding with standard {sup 125}I-hCG, and cAMP and progesterone production, but the potency was considerably less than that associated with the hCG{beta} wild-type-containing gonadotropin. The double-mutant protein Arg-43 to Leu/Arg-94 to Asp also associated with bovine {alpha}, but the resultant heterodimer exhibited only low activity. Replacement but the Lys-43-containing {beta} chain appeared to exhibit a low degree of subunit association or reduced stability relative to the expressed hCG{beta} wild type. These results demonstrate that arginines-43 and -94 contribute to receptor binding through a positive charge.« less

Bacteriological monitoring of water reservoirs in oxygen humidifiers: safety of prolonged and multipatient use of prefilled disposable oxygen humidifier bottles.

PubMed

Kobayashi, Nobuharu; Yamazaki, Tsutomu; Maesaki, Shigefumi

2006-03-01

Bacterial colony counts in water specimens from oxygen humidifiers that used reusable water reservoirs were compared with counts in water specimens from humidifiers that used prefilled disposable reservoir bottles to evaluate the effects of prolonged and multipatient use of humidifiers. Bacteria were detected after 1 week of operation in water specimens collected from many humidifiers with reusable reservoirs, but no bacteria were detected in water specimens from disposable bottles for up to 12 weeks during use of the humidifier by multiple patients.

Evaluation of pharmacokinetics, user handling, and tolerability of peginterferon alfa-2a (40 kDa) delivered via a disposable autoinjector device

PubMed Central

Varunok, Peter; Lawitz, Eric; Beavers, Kimberly L; Matusow, Gary; Leong, Ruby; Lambert, Nathalie; Bernaards, Coen; Solsky, Jonathan; Brennan, Barbara J; Wat, Cynthia; Bertasso, Anne

2011-01-01

Background Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device. Methods In trial 1, 50 healthy adult subjects received one 180 μg dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing) for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 μg peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment. Results In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation), and area under the concentration time curve (0–168 hours) was 1996 ± 613 ng · hour/mL, similar to that reported using a vial/syringe or prefilled syringe. In trial 2, few patients showed handling difficulties with either device. Generally, patients were observed to be more satisfied and confident, followed instructions better, and successfully initiated injection with the autoinjector versus the prefilled syringe. Patients reported the autoinjector to be more convenient and easier to use. No pain or discomfort was experienced using the autoinjector. The autoinjector safety profile was consistent with that known for peginterferon alfa-2a/ribavirin. Conclusion These results indicate that peginterferon alfa-2a can be successfully and safely delivered via the autoinjector and that the device is easy to handle. PMID:22163158

Secukinumab Self-Administration by Prefilled Syringe Maintains Reduction of Plaque Psoriasis Severity Over 52 Weeks: Results of the FEATURE Trial.

PubMed

Gottlieb, Alice B; Blauvelt, Andrew; Prinz, Jörg C; Papanastasiou, Philemon; Pathan, Rashidkhan; Nyirady, Judit; Fox, Todd; Papavassilis, Charis

2016-10-01

Secukinumab, a human monoclonal antibody that selectively targets interleukin-17A, is highly efficacious in the treatment of moderate-to-severe psoriasis, starting at early time points, with a sustained effect and a favorable safety profile. Patients with moderate-to-severe plaque psoriasis were randomized to secukinumab 300 mg, secukinumab 150 mg, or placebo self-administered by prefilled syringe at baseline, weeks 1, 2, and 3, and then every four weeks from week 4 to 48. Efficacy responses (≥ 75/90/100% improvement in Psoriasis Area and Severity Index [PASI 75/90/100] and clear/almost clear skin by Investigator's Global Assessment 2011 modified version [IGA mod 2011 0/1]) were measured to week 52. Patient-reported usability of the prefilled syringe was evaluated by the Self-Injection Assessment Questionnaire to week 48. The efficacy of secukinumab increased to week 16 and was maintained to week 52. With secukinumab 300 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 83.5%/68.0%/47.5% and 71.5% of patients when analyzed by multiple imputation, respectively, and by 75.9%/62.1%/43.1% and 63.8% of patients when analyzed by nonresponder imputation, respectively. With secukinumab 150 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 63.5%/50.3%/31.1% and 43.6% of patients when analyzed by multiple imputation, respectively, and by 61.0%/49.2%/30.5% and 42.4% of patients when analyzed by nonresponder imputation, respectively. Self-reported acceptability of the prefilled syringe was high throughout the study. The incidence of adverse events (AE) was well balanced between groups, with AEs reported in 74.4% of patients receiving secukinumab 300 mg and 77.3% of patients receiving secukinumab 150 mg. Nasopharyngitis was the most common AE across both secukinumab groups. Self-administration of secukinumab by prefilled syringe was associated with robust and sustained efficacy and a favorable safety profile up to week 52.

J Drugs Dermatol. 2016;15(10):1226-1234.

Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells.

PubMed

Wang, Linli; Chen, Yuehua; Guan, Chunyan; Zhao, Zhiju; Li, Qiang; Yang, Jianguo; Mo, Jian; Wang, Bin; Wu, Wei; Yang, Xiaohui; Song, Libing; Li, Jun

2017-11-02

Because the lack of an induced pluripotent stem cell (iPSC) induction system with optimal safety and efficiency limits the application of these cells, development of such a system is important. To create such an induction system, we screened a variety of reprogrammed plasmid combinations and multiple compounds and then verified the system's feasibility using urine cells from different individuals. We also compared large-scale iPSC chromosomal variations and expression of genes associated with genomic stability between this system and the traditional episomal system using karyotype and quantitative reverse transcription polymerase chain reaction analyses. We developed a high-efficiency episomal system, the 6F/BM1-4C system, lacking tumorigenic factors for human urine-derived cell (hUC) reprogramming. This system includes six low-risk factors (6F), Oct4, Glis1, Klf4, Sox2, L-Myc, and the miR-302 cluster. Transfected hUCs were treated with four compounds (4C), inhibitor of lysine-demethylase1, methyl ethyl ketone, glycogen synthase kinase 3 beta, and histone deacetylase, within a short time period. Comparative analysis revealed significantly decreased chromosomal variation in iPSCs and significantly increased Sirt1 expression compared with iPSCs induced using the traditional episomal system. The 6F/BM1-4C system effectively induces reprogramming of urine cells in samples obtained from different individuals. iPSCs induced using the 6F/BM1-4C system are more stable at the cytogenetic level and have potential value for clinical application.

Ensemble Solute Transport in 2-D Operator-Stable Random Fields

NASA Astrophysics Data System (ADS)

Monnig, N. D.; Benson, D. A.

2006-12-01

The heterogeneous velocity field that exists at many scales in an aquifer will typically cause a dissolved solute plume to grow at a rate faster than Fick's Law predicts. Some statistical model must be adopted to account for the aquifer structure that engenders the velocity heterogeneity. A fractional Brownian motion (fBm) model has been shown to create the long-range correlation that can produce continually faster-than-Fickian plume growth. Previous fBm models have assumed isotropic scaling (defined here by a scalar Hurst coefficient). Motivated by field measurements of aquifer hydraulic conductivity, recent techniques were developed to construct random fields with anisotropic scaling with a self-similarity parameter that is defined by a matrix. The growth of ensemble plumes is analyzed for transport through 2-D "operator- stable" fBm hydraulic conductivity (K) fields. Both the longitudinal and transverse Hurst coefficients are important to both plume growth rates and the timing and duration of breakthrough. Smaller Hurst coefficients in the transverse direction lead to more "continuity" or stratification in the direction of transport. The result is continually faster-than-Fickian growth rates, highly non-Gaussian ensemble plumes, and a longer tail early in the breakthrough curve. Contrary to some analytic stochastic theories for monofractal K fields, the plume growth rate never exceeds Mercado's [1967] purely stratified aquifer growth rate of plume apparent dispersivity proportional to mean distance. Apparent super-Mercado growth must be the result of other factors, such as larger plumes corresponding to either a larger initial plume size or greater variance of the ln(K) field.

Conversion of human choriogonadotropin into a follitropin by protein engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, R.K.; Dean-Emig, D.M.; Moyle, W.R.

1991-02-01

Human reproduction is dependent upon the action of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the {alpha} subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their {beta} subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG {beta}-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH{beta} and hFSH{beta} in receptor recognition and activation. Since the {beta} subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region,more » the authors postulated that these residues might contribute to hormone specificity. To test this hypothesis the authors constructed chimeric hCG/hFSH {beta} subunits, coexpressed them with the human {alpha} subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH{beta} residues 33-52 for hCG{beta} residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH{beta} residues 88-108 in place of the carboxyl terminus of hCG{beta} (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG{beta} residues 108-145 or substitution of residues in the determinant loop located between hCD{beta} residues 93 and 100.« less

Pedicle screw cement augmentation. A mechanical pullout study on different cement augmentation techniques.

PubMed

Costa, Francesco; Ortolina, Alessandro; Galbusera, Fabio; Cardia, Andrea; Sala, Giuseppe; Ronchi, Franco; Uccelli, Carlo; Grosso, Rossella; Fornari, Maurizio

2016-02-01

Pedicle screws with polymethyl methacrylate (PMMA) cement augmentation have been shown to significantly improve the fixation strength in a severely osteoporotic spine. However, the efficacy of screw fixation for different cement augmentation techniques remains unknown. This study aimed to determine the difference in pullout strength between different cement augmentation techniques. Uniform synthetic bones simulating severe osteoporosis were used to provide a platform for each augmentation technique. In all cases a polyaxial screw and acrylic cement (PMMA) at medium viscosity were used. Five groups were analyzed: I) only screw without PMMA (control group); II) retrograde cement pre-filling of the tapped area; III) cannulated and fenestrate screw with cement injection through perforation; IV) injection using a standard trocar of PMMA (vertebroplasty) and retrograde pre-filling of the tapped area; V) injection through a fenestrated trocar and retrograde pre-filling of the tapped area. Standard X-rays were taken in order to visualize cement distribution in each group. Pedicle screws at full insertion were then tested for axial pullout failure using a mechanical testing machine. A total of 30 screws were tested. The results of pullout analysis revealed better results of all groups with respect to the control group. In particular the statistical analysis showed a difference of Group V (p = 0.001) with respect to all other groups. These results confirm that the cement augmentation grants better results in pullout axial forces. Moreover they suggest better load resistance to axial forces when the distribution of the PMMA is along all the screw combining fenestration and pre-filling augmentation technique. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Color-Coded Prefilled Medication Syringes Decrease Time to Delivery and Dosing Error in Simulated Emergency Department Pediatric Resuscitations.

PubMed

Moreira, Maria E; Hernandez, Caleb; Stevens, Allen D; Jones, Seth; Sande, Margaret; Blumen, Jason R; Hopkins, Emily; Bakes, Katherine; Haukoos, Jason S

2015-08-01

The Institute of Medicine has called on the US health care system to identify and reduce medical errors. Unfortunately, medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients when dosing requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national health care priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared with conventional medication administration, in simulated pediatric emergency department (ED) resuscitation scenarios. We performed a prospective, block-randomized, crossover study in which 10 emergency physician and nurse teams managed 2 simulated pediatric arrest scenarios in situ, using either prefilled, color-coded syringes (intervention) or conventional drug administration methods (control). The ED resuscitation room and the intravenous medication port were video recorded during the simulations. Data were extracted from video review by blinded, independent reviewers. Median time to delivery of all doses for the conventional and color-coded delivery groups was 47 seconds (95% confidence interval [CI] 40 to 53 seconds) and 19 seconds (95% CI 18 to 20 seconds), respectively (difference=27 seconds; 95% CI 21 to 33 seconds). With the conventional method, 118 doses were administered, with 20 critical dosing errors (17%); with the color-coded method, 123 doses were administered, with 0 critical dosing errors (difference=17%; 95% CI 4% to 30%). A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by emergency physician and nurse teams during simulated pediatric ED resuscitations. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Etanercept (Enbrel®) alternative storage at ambient temperature.

PubMed

Shannon, Edel; Daffy, Joanne; Jones, Heather; Paulson, Andrea; Vicik, Steven M

2017-01-01

Biologic disease-modifying antirheumatic drugs, including tumor necrosis factor inhibitors such as etanercept (Enbrel ® ), have improved outcomes for patients with rheumatic and other inflammatory diseases, with sustained remission being the optimal goal for patients with rheumatoid arthritis. Flexible and convenient treatment options, compatible with modern lifestyle, are important in helping patients maintain treatment and manage their disease. Etanercept drug product (DP) is available in lyophilized powder (Lyo) for solution injection, prefilled syringe, and prefilled pen presentations and is typically stored under refrigerated conditions. We aimed to generate a comprehensive analytical data package from stability testing of key quality attributes, consistent with regulatory requirements, to determine whether the product profile of etanercept is maintained at ambient temperature. Test methods assessing key attributes of purity, quality, potency, and safety were performed over time, following storage of etanercept DP presentations under a range of conditions. Results and statistical analysis from stability testing (based on size exclusion high-performance liquid chromatography, hydrophobic interaction chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis Coomassie) across all etanercept presentations (10 and 25 mg/vial Lyo DP; 25 and 50 mg prefilled syringe DP; 50 mg prefilled pen DP) showed key stability-indicating parameters were within acceptable limits through the alternative storage condition of 25°C±2°C for 1 month. Stability testing performed in line with regulatory requirements supports a single period of storage for etanercept DP at an alternative storage condition of 25°C±2°C for up to 1 month within the approved expiry of the product. This alternative storage condition represents further innovation in the etanercept product lifecycle, providing greater flexibility and enhanced overall convenience for patients.

Protein adsorption and excipient effects on kinetic stability of silicone oil emulsions.

PubMed

Ludwig, D Brett; Carpenter, John F; Hamel, Jean-Bernard; Randolph, Theodore W

2010-04-01

The effect of silicone oil on the stability of therapeutic protein formulations is of concern in the biopharmaceutical industry as more proteins are stored and delivered in prefilled syringes. Prefilled syringes provide convenience for medical professionals and patients, but prolonged exposure of proteins to silicone oil within prefilled syringes may be problematic. In this study, we characterize systems of silicone oil-in-aqueous buffer emulsions and model proteins in formulations containing surfactant, sodium chloride, or sucrose. For each of the formulations studied, silicone oil-induced loss of soluble protein, likely through protein adsorption onto the silicone oil droplet surface. Excipient addition affected both protein adsorption and emulsion stability. Addition of surfactant stabilized emulsions but decreased protein adsorption to silicone oil microdroplets. In contrast, addition of sodium chloride increased protein adsorption and decreased emulsion stability. Silicone oil droplets with adsorbed lysozyme rapidly agglomerated and creamed out of suspension. This decrease in the kinetic stability of the emulsion is ascribed to surface charge neutralization and a bridging flocculation phenomenon and illustrates the need to investigate not only the effects of silicone oil on protein stability, but also the effects of protein formulation variables on emulsion stability. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Silicone-oil-based subvisible particles: their detection, interactions, and regulation in prefilled container closure systems for biopharmaceuticals.

PubMed

Felsovalyi, Flora; Janvier, Sébastien; Jouffray, Sébastien; Soukiassian, Hervé; Mangiagalli, Paolo

2012-12-01

Recent increased regulatory scrutiny concerning subvisible particulates (SbVPs) in parenteral formulations of biologics has led to the publication of numerous articles about the sources, characteristics, implications, and approaches to monitoring and detecting SbVPs. Despite varying opinions on the level of associated risks and method of regulation, nearly all industry scientists and regulators agree on the need for monitoring and reporting visible and subvisible particles. As prefillable drug delivery systems have become a prominent packaging option, silicone oil, a common primary packaging lubricant, may play a role in the appearance of particles. The goal of this article is to complement the current SbVP knowledge base with new insights into the evolution of silicone-oil-related particulates and their interactions with components in prefillable systems. We propose a "toolbox" for improved silicone-oil-related particulate detection and enumeration, and discuss the benefits and limitations of approaches for lowering and controlling silicone oil release in parenterals. Finally, we present surface cross-linking of silicone as the recommended solution for achieving significant SbVP reduction without negatively affecting functional performance. Copyright © 2012 Wiley Periodicals, Inc.

Single-use autoinjector for once-weekly intramuscular injection of IFNβ-1a.

PubMed

Limmroth, Volker; Gerbershagen, Kathrin

2014-12-01

IFNβ products and glatiramer acetate are established treatment first-line options in long-term disease-modifying therapy of multiple sclerosis (MS). These self-injectable medications are used once weekly to once daily. Injection-related issues are common patient-cited reasons for nonadherence. Autoinjectors have been shown to support long-term adherence to injectable medications. The ability to self-inject in MS patients has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patient independence. The recently introduced easy-to-use prefilled once-weekly pen is a safe and effective device for intramuscular (IM) IFNβ-1a application and provides a convenient method for self-injection. We reviewed the available published evidence on the characteristics of this device. The once-weekly pen facilitates self-injection and was preferred over prefilled syringes by patients in a prospective open-label, multicenter Phase IIIb trial in MS patients who had been using IM IFNβ-1a in prefilled syringes. The simple and safe handling, shielded short needle, single-use disposable design and virtually painless injection by the device may contribute to adherence, quality of life and independence in patients using IM IFNβ-1a.

Home delivery of heat-stable vaccines in Indonesia: outreach immunization with a prefilled, single-use injection device.

PubMed Central

Sutanto, A.; Suarnawa, I. M.; Nelson, C. M.; Stewart, T.; Soewarso, T. I.

1999-01-01

Extending immunization coverage to underserved populations will require innovative immunization strategies. This study evaluated one such strategy: the use of a prefilled, single-use injection device for outreach immunization by village midwives. The device, UniJect, is designed to prevent refilling or reuse. Stored at ambient temperatures for up to 1 month in midwives' homes, vaccine-filled UniJect devices were immediately available for outreach. Between July 1995 and April 1996, 110 midwives on the Indonesia islands of Lombok and Bali visited the homes of newborn infants to deliver hepatitis B vaccine to the infants and tetanus toxoid to their mothers. Observations and interviews showed that the midwives used the device properly and safely to administer approximately 10,000 sterile injections in home settings. There were no problems with excessive heat exposure during the storage or delivery of vaccine. Injection recipients and midwives expressed a strong preference for the UniJect device over a standard syringe. Use of the prefilled device outside the cold chain simplified the logistics and facilitated the speed and efficiency of home visits, while the single-dose format minimized vaccine wastage. PMID:10083709

Interlaboratory variability in the quantification of new generation antiepileptic drugs based on external quality assessment data.

PubMed

Williams, John; Bialer, Meir; Johannessen, Svein I; Krämer, Günther; Levy, René; Mattson, Richard H; Perucca, Emilio; Patsalos, Philip N; Wilson, John F

2003-01-01

To assess interlaboratory variability in the determination of serum levels of new antiepileptic drugs (AEDs). Lyophilised serum samples containing clinically relevant concentrations of felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), the monohydroxy derivative of oxcarbazepine (OCBZ; MHD), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were distributed monthly among 70 laboratories participating in the international Heathcontrol External Quality Assessment Scheme (EQAS). Assay results returned over a 15-month period were evaluated for precision and accuracy. The most frequently measured compound was LTG (65), followed by MHD (39), GBP (19), TPM (18), VGB (15), FBM (16), and TGB (8). High-performance liquid chromatography was the most commonly used assay technique for all drugs except for TPM, for which two thirds of laboratories used a commercial immunoassay. For all assay methods combined, precision was <11% for MHD, FBM, TPM, and LTG, close to 15% for GBP and VGB, and as high as 54% for TGB (p < 0.001). Mean accuracy values were <10% for all drugs other than TGB, for which measured values were on average 13.9% higher than spiked values, with a high variability around the mean (45%). No differences in precision and accuracy were found between methods, except for TPM, for which gas chromatography showed poorer accuracy compared with immunoassay and gas chromatography-mass spectrometry. With the notable exception of TGB, interlaboratory variability in the determination of new AEDs was comparable to that reported with older-generation agents. Poor assay performance is related more to individual operators than to the intrinsic characteristics of the method applied. Participation in an EQAS scheme is recommended to ensure adequate control of assay variability in therapeutic drug monitoring.

On the relationship between the Hurst exponent, the ratio of the mean square successive difference to the variance, and the number of turning points

NASA Astrophysics Data System (ADS)

Tarnopolski, Mariusz

2016-11-01

The long range dependence of the fractional Brownian motion (fBm), fractional Gaussian noise (fGn), and differentiated fGn (DfGn) is described by the Hurst exponent H. Considering the realizations of these three processes as time series, they might be described by their statistical features, such as half of the ratio of the mean square successive difference to the variance, A, and the number of turning points, T. This paper investigates the relationships between A and H, and between T and H. It is found numerically that the formulae A(H) = aebH in case of fBm, and A(H) = a + bHc for fGn and DfGn, describe well the A(H) relationship. When T(H) is considered, no simple formula is found, and it is empirically found that among polynomials, the fourth and second order description applies best. The most relevant finding is that when plotted in the space of (A , T) , the three process types form separate branches. Hence, it is examined whether A and T may serve as Hurst exponent indicators. Some real world data (stock market indices, sunspot numbers, chaotic time series) are analyzed for this purpose, and it is found that the H's estimated using the H(A) relations (expressed as inverted A(H) functions) are consistent with the H's extracted with the well known wavelet approach. This allows to efficiently estimate the Hurst exponent based on fast and easy to compute A and T, given that the process type: fBm, fGn or DfGn, is correctly classified beforehand. Finally, it is suggested that the A(H) relation for fGn and DfGn might be an exact (shifted) 3 / 2 power-law.

Dynamic variability of the heading-flowering stages of single rice in China based on field observations and NDVI estimations.

PubMed

Zhang, Zhao; Song, Xiao; Chen, Yi; Wang, Pin; Wei, Xing; Tao, Fulu

2015-05-01

Although many studies have indicated the consistent impact of warming on the natural ecosystem (e.g., an early flowering and prolonged growing period), our knowledge of the impacts on agricultural systems is still poorly understood. In this study, spatiotemporal variability of the heading-flowering stages of single rice was detected and compared at three different scales using field-based methods (FBMs) and satellite-based methods (SBMs). The heading-flowering stages from 2000 to 2009 with a spatial resolution of 1 km were extracted from the SPOT/VGT NDVI time series data using the Savizky-Golay filtering method in the areas in China dominated by single rice of Northeast China (NE), the middle-lower Yangtze River Valley (YZ), the Sichuan Basin (SC), and the Yunnan-Guizhou Plateau (YG). We found that approximately 52.6 and 76.3 % of the estimated heading-flowering stages by a SBM were within ±5 and ±10 days estimation error (a root mean square error (RMSE) of 8.76 days) when compared with those determined by a FBM. Both the FBM data and the SBM data had indicated a similar spatial pattern, with the earliest annual average heading-flowering stages in SC, followed by YG, NE, and YZ, which were inconsistent with the patterns reported in natural ecosystems. Moreover, diverse temporal trends were also detected in the four regions due to different climate conditions and agronomic factors such as cultivar shifts. Nevertheless, there were no significant differences (p > 0.05) between the FBM and the SBM in both the regional average value of the phenological stages and the trends, implying the consistency and rationality of the SBM at three scales.

COMBINED SEWER OVERFLOW - BALANCING FLOW FOR CSO ABATEMENT

EPA Science Inventory

Instead of using conventional storage units, e.g., reinforced concrete tanks and lined earthen basins, which are relatively expensive and require a lot of urban land area, the in-receiving water flow balance method (FBM) facilities use the receiving water body itself for storage ...

Statistical model with two order parameters for ductile and soft fiber bundles in nanoscience and biomaterials.

PubMed

Rinaldi, Antonio

2011-04-01

Traditional fiber bundles models (FBMs) have been an effective tool to understand brittle heterogeneous systems. However, fiber bundles in modern nano- and bioapplications demand a new generation of FBM capturing more complex deformation processes in addition to damage. In the context of loose bundle systems and with reference to time-independent plasticity and soft biomaterials, we formulate a generalized statistical model for ductile fracture and nonlinear elastic problems capable of handling more simultaneous deformation mechanisms by means of two order parameters (as opposed to one). As the first rational FBM for coupled damage problems, it may be the cornerstone for advanced statistical models of heterogeneous systems in nanoscience and materials design, especially to explore hierarchical and bio-inspired concepts in the arena of nanobiotechnology. Applicative examples are provided for illustrative purposes at last, discussing issues in inverse analysis (i.e., nonlinear elastic polymer fiber and ductile Cu submicron bars arrays) and direct design (i.e., strength prediction).

Attitude changes during and after long submarine missions.

PubMed

Weybrew, B B; Molish, H B

1979-01-01

To assess the kind and degree of attitude changes occurring during a 2-month submerged mission, two enlisted crews of one fleet ballistic missile submarine (FBM) (n = 101 each) were administered the Submarine Attitude Questionnaire before and after two 55-day submerged missions interspersed with a rehabilitation period of the same duration. Results showed that time-in-service and pay grade bore a U-shaped relationship to positive attitudes toward the service. During submergence, most attitudes became negative and then reversed polarity during rehabilitation. However, there were no cumulative effects upon attitudes during successive missions. Attitudes pertaining to the realities of the mission (for example, boredom, hazardous aspects) became more negative but recovered faster. On the other hand, attitude changes related to long-range expectancies in terms of goal achievement of the crew members were less likely to recover. Several possible explanations for these attitude changes are discussed in the context of the mission of the FBM submarine. Suggestions for preventing or alleviating untoward attitude changes during long submarine missions are also presented.

The length of time necessary to break even after converting to digital mammography.

PubMed

Hiatt, M D; Carr, J J; Manning, R L

2000-01-01

The cost differences between film-based mammography (FBM) and digital mammography (DM) were estimated after discussions with hospital personnel and industry representatives. Human resource costs were not included. The fixed cost of FBM per machine was estimated to be $50,000 and the variable cost $4.60 per examination. The fixed cost of DM per machine was estimated to be $102,000 and the variable cost $0.10 per examination. The total number of examinations required to break even was therefore 11,556. At a rate of 15 examinations per machine per day and with 251 working days per year, it would take 3.1 years to break even. In the first year after the break-even point had been attained, $16,943 would be saved for every 3765 examinations performed. Extrapolating to the USA as a whole, in which 23 million mammographic examinations are performed each year, suggests that the annual savings from going filmless would be more than $103 million.

Pre-filled syringe - a ready-to-use drug delivery system: a review.

PubMed

Ingle, Rahul G; Agarwal, Aayush S

2014-09-01

Fueled by a growing global expectation of the health and medical fields, billions of dollars/euros/pounds are invested every year in the research of new biological and chemical entities. However, little interest is seen in the development of novel drug delivery systems. One such system, pre-filled syringe (PFS), was invented decades ago but is still a rare mode of delivery in many therapeutic segments. This review comprises properties and effects of extractables, leachables and discuss the characteristics of PFS technology; its composition, glass and polymer types, configuration of PFS, advantages over glass, technical and commercial applicability; its significance against patient, industry, quality, environment and cost; and its business potential. We discuss in brief about PFS used in various major and life-threatening disorders and future prospects. It provides showers of knowledge in the field of PFS drug delivery technology to the reader's, industrialist's and researcher's point of view. The PFS drug delivery system offers a wonderful panorama to lifesaving drugs that are currently only available in conventional vials and ampoules in the market. A novel approach of Form Fill Seal technology can be adopted for this particular ready-to-use dosage form also, which opens the new global doors for budding researchers in the field of pre-filled drug delivery system.

Characteristics of users and usage of different types of electronic cigarettes: findings from an online survey.

PubMed

Etter, Jean-François

2016-04-01

Studying users of e-cigarettes is important to help determine whether these devices aid smoking cessation. Obtaining data in representative samples is difficult, but online surveys of users may begin to build a picture. Therefore, this study aimed, through a large online survey, to describe usage and characteristics of users of e-cigarettes. Cross-sectional internet survey between 2012 and 2014. A total of 2807 current e-cigarette users enrolled via e-cigarette and smoking cessation websites, who lived in France (n = 988), the United States (n = 579), Switzerland (n = 310), the United Kingdom (n = 143) and other countries (n = 787). Type of e-cigarette used: pre-filled cartridges (n = 71), unmodified refillable tanks (n = 758), modified refillable tanks (n = 392), patterns of use, perceived effects. Pre-filled models were perceived to be less effective than unmodified refillable tanks for smoking cessation by former smokers ('definitely helped': 74% vs. 94%, P < 0.001) and by current smokers for smoking reduction ('definitely helped': 37% vs. 78%, P < 0.001). Users modified their e-cigarettes mainly to obtain a better taste ('very true' 60%, 55.5-64.5%). Modified tanks were perceived to make it easier to abstain from smoking than unmodified tanks 95% vs. 89%, P < 0.001); 34% of users of pre-filled cartridges, 60% of users of unmodified tanks and 83% of users of modified tanks were men (P < 0.001). Newer-generation e-cigarettes were perceived to be more satisfactory and more effective for refraining from smoking than older models. Women tended to use pre-filled, unmodified models, which were perceived by participants to be the least effective in terms of abstaining from smoking. © 2015 Society for the Study of Addiction.

Preventable drug waste among anesthesia providers: opportunities for efficiency.

PubMed

Atcheson, Carrie Leigh Hamby; Spivack, John; Williams, Robert; Bryson, Ethan O

2016-05-01

Health care service bundling experiments at the state and regional levels have showed reduced costs by providing a single lump-sum reimbursement for anesthesia services, surgery, and postoperative care. Potential for cost savings related to the provision of anesthesia care has the potential to significantly impact sustainability. This study defines and quantifies routine and preventable anesthetic drug waste and the patient, procedure, and anesthesia provider characteristics associated with increased waste. Over a 12-month period, the type and quantity of clean drugs prepared by the anesthesia team for the first case of the day were recorded. The amount of each drug administered was obtained from the computerized anesthesia record, and data were analyzed to determine the incidence and cost of routine and preventable drug waste. The monthly and yearly cost of preventable waste, including the cost of pharmacy tech labor and materials where applicable, was estimated based on surgical case volume at the study institution. All analyses were performed using SAS software v9.2. Anesthetic drugs prepared for 543 separate surgical cases were observed. Less than 20% of cases generated routine waste. Preventable waste was generated most frequently for ephedrine (59.5% of cases), succinylcholine (33.7%), and lidocaine (25.1%), and least frequently for ondansetron (1.3%), phenylephrine (2.6%), and dexamethasone (2.8%). The estimated yearly cost of preventable anesthetic drug waste was $185,250. Significant potential savings with little impact on clinically significant availability may be achieved through the use of prefilled syringes for some commonly used anesthetic drugs. An intelligently implemented switch to prefilled syringes for select drugs is a potential cost saving measure, but savings might be diminished by disposal of prefilled syringes when they expire, hidden costs in the hospital pharmacy, and inability to supply some medications in prefilled syringes due to stability or manufacturing issues. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility of Using Fluorescence Spectrophotometry to Develop a Sensitive Dye Immersion Method for Container Closure Integrity Testing of Prefilled Syringes.

PubMed

Lu, Xujin; Lloyd, David K; Klohr, Steven E

2016-01-01

A feasibility study was conducted for a sensitive and robust dye immersion method for the measurement of container closure integrity of unopened prefilled syringes using fluorescence spectrophotometry as the detection method. A Varian Cary Eclipse spectrofluorometer was used with a custom-made sample holder to position the intact syringe in the sample compartment for fluorescence measurements. Methylene blue solution was initially evaluated as the fluorophore in a syringe with excitation at 607 nm and emission at 682 nm, which generated a limit of detection of 0.05 μg/mL. Further studies were conducted using rhodamine 123, a dye with stronger fluorescence. Using 480 nm excitation and 525 nm emission, the dye in the syringe could be easily detected at levels as low as 0.001 μg/mL. The relative standard deviation for 10 measurements of a sample of 0.005 μg/mL (with repositioning of the syringe after each measurement) was less than 1.1%. A number of operational parameters were optimized, including the photomultiplier tube voltage, excitation, and emission slit widths. The specificity of the testing was challenged by using marketed drug products and a protein sample, which showed no interference to the rhodamine detection. Results obtained from this study demonstrated that using rhodamine 123 for container closure integrity testing with in-situ (in-syringe) fluorescence measurements significantly enhanced the sensitivity and robustness of the testing and effectively overcame limitations of the traditional methylene blue method with visual or UV-visible absorption detection. Ensuring container closure integrity of injectable pharmaceutical products is necessary to maintain quality throughout the shelf life of a sterile drug product. Container closure integrity testing has routinely been used to evaluate closure integrity during product development and production line qualification of prefilled syringes, vials, and devices. However, container closure integrity testing has recently gained industry attention due to increased regulatory agency scrutiny regarding the analytical rigor of container closure integrity testing methods and expectations to use container closure integrity testing in lieu of sterility tests in stability programs. Methylene blue dye is often used for dye ingress testing of container closure integrity, but we found it unsuitable for reliable detection of small breaches in prefilled syringes of drug product. This work describes the suitability and advantages of using a fluorescent dye and spectroscopic detection for a robust, sensitive, and quality control-friendly container closure integrity testing method for prefilled syringes. © PDA, Inc. 2016.

Variability in syringe components and its impact on functionality of delivery systems.

PubMed

Rathore, Nitin; Pranay, Pratik; Eu, Bruce; Ji, Wenchang; Walls, Ed

2011-01-01

Prefilled syringes and autoinjectors are becoming increasingly common for parenteral drug administration primarily due to the convenience they offer to the patients. Successful commercialization of such delivery systems requires thorough characterization of individual components. Complete understanding of various sources of variability and their ranking is essential for robust device design. In this work, we studied the impact of variability in various primary container and device components on the delivery forces associated with syringe injection. More specifically, the effects of barrel size, needle size, autoinjector spring force, and frictional forces have been evaluated. An analytical model based on underlying physics is developed that can be used to fully characterize the design space for a product delivery system. Use of prefilled syringes (syringes prefilled with active drug) is becoming increasingly common for injectable drugs. Compared to vials, prefilled syringes offer higher dose accuracy and ease of use due to fewer steps required for dosage. Convenience to end users can be further enhanced through the use of prefilled syringes in combination with delivery devices such as autoinjectors. These devices allow patients to self-administer the drug by following simple steps such as pressing a button. These autoinjectors are often spring-loaded and are designed to keep the needle tip shielded prior to injection. Because the needle is not visible to the user, such autoinjectors are perceived to be less invasive than syringes and help the patient overcome the hesitation associated with self-administration. In order to successfully develop and market such delivery devices, we need to perform an in-depth analysis of the components that come into play during the activation of the device and dose delivery. Typically, an autoinjector is activated by the press of a button that releases a compressed spring; the spring relaxes and provides the driving force to push the drug out of the syringe and into the site of administration. Complete understanding of the spring force, syringe barrel dimensions, needle size, and drug product properties is essential for robust device design. It is equally important to estimate the extent of variability that exists in these components and the resulting impact it could have on the performance of the device. In this work, we studied the impact of variability in syringe and device components on the delivery forces associated with syringe injection. More specifically, the effect of barrel size, needle size, autoinjector spring force, and frictional forces has been evaluated. An analytical model based on underlying physics is developed that can be used to predict the functionality of the autoinjector.

Combined assessment of polymorphisms in the LHCGR and FSHR genes predict chance of pregnancy after in vitro fertilization.

PubMed

Lindgren, I; Bååth, M; Uvebrant, K; Dejmek, A; Kjaer, L; Henic, E; Bungum, M; Bungum, L; Cilio, C; Leijonhufvud, I; Skouby, S; Andersen, C Yding; Giwercman, Y Lundberg

2016-03-01

Can gonadotrophin receptor variants separately or in combination, be used for the prediction of pregnancy chances in in vitro fertilization (IVF) trials? The luteinizing hormone/human chorionic gonadotrophin receptor (LHCGR) variant N312S and the follicle-stimulating hormone receptor (FSHR) variant N680S can be utilized for the prediction of pregnancy chances in women undergoing IVF. The FSHR N680S polymorphism has been shown to affect the ovarian response in response to gonadotrophin treatment, while no information is currently available regarding variants of the LHCGR in this context. Cross-sectional study, duration from September 2010 to February 2015. Women undergoing IVF were consecutively enrolled and genetic variants compared between those who became pregnant and those who did not. The study was subsequently replicated in an independent sample. Granulosa cells from a subset of women were investigated regarding functionality of the genetic variants. Women undergoing IVF (n = 384) were enrolled in the study and genotyped. Clinical variables were retrieved from medical records. For replication, an additional group of n = 233 women was utilized. Granulosa cells from n = 135 women were isolated by flow cytometry, stimulated with Follitropin alpha or Menotropin, and the downstream targets 3',5'-cyclic adenosine monophosphate (cAMP) and inositol 1,4,5-trisphosphate (IP3) measured with enzyme-linked immunosorbent assay. Women homozygous for serine (S) in both polymorphisms displayed higher pregnancy rates than women homozygous asparagine (N) (OR = 14.4, 95% CI: [1.65, 126], P = 0.016). Higher pregnancy rates were also evident for women carrying LHCGR S312, regardless of FSHR variant (OR = 1.61, 95% CI: [1.13, 2.29], P = 0.008). These women required higher doses of FSH for follicle recruitment than women homozygous N (161 versus 148 IU, P = 0.030). When combining the study cohort with the replication cohort (n = 606), even stronger associations with pregnancy rates were noted for the combined genotypes (OR = 11.5, 95% CI: [1.86, 71.0], P = 0.009) and for women carrying LHCGR S312 (OR = 1.49, 95% CI: [1.14, 1.96], P = 0.004). A linear significant trend with pregnancy rate and increasing number of G alleles was also evident in the merged study population (OR = 1.34, 95% CI: [1.10, 1.64], P = 0.004). A lower cAMP response in granulosa cells was noted following Follitropin alpha stimulation for women homozygous N in both polymorphisms, compared with women with other genotypes (0.901 pmol cAMP/mg total protein versus 2.19 pmol cAMP/mg total protein, P = 0.035). Due to racial differences in LHCGR genotype distribution, these results may not be applicable for all populations. Despite that >250 000 cycles of gonadotrophin stimulations are performed annually worldwide prior to IVF, it has not been possible to predict neither the pregnancy outcome, nor the response to the hormone with accuracy. If LHCGR and FSHR variants are recognized as biomarkers for chance of pregnancy, more individualized and thereby more efficient treatment modalities can be developed. This work was supported by Interreg IV A, EU (grant 167158) and ALF governments grant (F2014/354). Merck-Serono (Darmstadt, Germany) supported the enrollment of the subjects. The authors declare no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

IN VIVO ASSESSMENT OF THE SOLUBILITY OF TOOTH ENAMEL DURING AN FBM PATROL

DTIC Science & Technology

The solubility of dental enamel is a prime factor in the dental decay process. Conditions which may influence the enamel solubility and the degree of...normal variation of this factor are therefore of interest to the Navy Dental Corps. Enamel solubility was determined in a group of volunteers from

Return Intervals Approach to Financial Fluctuations

NASA Astrophysics Data System (ADS)

Wang, Fengzhong; Yamasaki, Kazuko; Havlin, Shlomo; Stanley, H. Eugene

Financial fluctuations play a key role for financial markets studies. A new approach focusing on properties of return intervals can help to get better understanding of the fluctuations. A return interval is defined as the time between two successive volatilities above a given threshold. We review recent studies and analyze the 1000 most traded stocks in the US stock markets. We find that the distribution of the return intervals has a well approximated scaling over a wide range of thresholds. The scaling is also valid for various time windows from one minute up to one trading day. Moreover, these results are universal for stocks of different countries, commodities, interest rates as well as currencies. Further analysis shows some systematic deviations from a scaling law, which are due to the nonlinear correlations in the volatility sequence. We also examine the memory in return intervals for different time scales, which are related to the long-term correlations in the volatility. Furthermore, we test two popular models, FIGARCH and fractional Brownian motion (fBm). Both models can catch the memory effect but only fBm shows a good scaling in the return interval distribution.

Chromosomal locus tracking with proper accounting of static and dynamic errors

PubMed Central

Backlund, Mikael P.; Joyner, Ryan; Moerner, W. E.

2015-01-01

The mean-squared displacement (MSD) and velocity autocorrelation (VAC) of tracked single particles or molecules are ubiquitous metrics for extracting parameters that describe the object’s motion, but they are both corrupted by experimental errors that hinder the quantitative extraction of underlying parameters. For the simple case of pure Brownian motion, the effects of localization error due to photon statistics (“static error”) and motion blur due to finite exposure time (“dynamic error”) on the MSD and VAC are already routinely treated. However, particles moving through complex environments such as cells, nuclei, or polymers often exhibit anomalous diffusion, for which the effects of these errors are less often sufficiently treated. We present data from tracked chromosomal loci in yeast that demonstrate the necessity of properly accounting for both static and dynamic error in the context of an anomalous diffusion that is consistent with a fractional Brownian motion (FBM). We compare these data to analytical forms of the expected values of the MSD and VAC for a general FBM in the presence of these errors. PMID:26172745

The pricing of credit default swaps under a generalized mixed fractional Brownian motion

NASA Astrophysics Data System (ADS)

He, Xinjiang; Chen, Wenting

2014-06-01

In this paper, we consider the pricing of the CDS (credit default swap) under a GMFBM (generalized mixed fractional Brownian motion) model. As the name suggests, the GMFBM model is indeed a generalization of all the FBM (fractional Brownian motion) models used in the literature, and is proved to be able to effectively capture the long-range dependence of the stock returns. To develop the pricing mechanics of the CDS, we firstly derive a sufficient condition for the market modeled under the GMFBM to be arbitrage free. Then under the risk-neutral assumption, the CDS is fairly priced by investigating the two legs of the cash flow involved. The price we obtained involves elementary functions only, and can be easily implemented for practical purpose. Finally, based on numerical experiments, we analyze quantitatively the impacts of different parameters on the prices of the CDS. Interestingly, in comparison with all the other FBM models documented in the literature, the results produced from the GMFBM model are in a better agreement with those calculated from the classical Black-Scholes model.

Heterogeneous porous media: Fronts and noise

NASA Astrophysics Data System (ADS)

Chaouchel, M.; Rakotomalala, N.; Salin, D.; Xu, B.; Yortsos, Y. C.

Capillary effects can be important in immiscible flows in heterogeneous media, particularly at low capillary numbers (Ca). We present experiments and simulations of slow drainage in 3-D porous media, either homogeneous and in the presence of buoyancy or heterogeneous and in its absence. An acoustic technique allows for an accurate study of the 3-D fronts and the cross-over region. Our results suggest that both cases can be described by invasion percolation in a gradient. Both front tails scale with the corresponding Bond numbers as σft≈B-47 in agreement with the theory. An analogous scaling for viscous effects is also given. The noise of these fronts are found correlated in the form of a fractional Brownian motion (fBm) of a Hurst exponent H≈.5. At higher Ca, experiments performed in 3-D porous media with sharp changes in permeability, exhibit a saturation profile response closely linked to the permeability variations. This viscous response to heterogeneity provides an opportunity to investigate and determine correlated (even at all scales, i.e. fBm), permeability fields.

A New Method for Non-destructive Measurement of Biomass, Growth Rates, Vertical Biomass Distribution and Dry Matter Content Based on Digital Image Analysis

PubMed Central

Tackenberg, Oliver

2007-01-01

Background and Aims Biomass is an important trait in functional ecology and growth analysis. The typical methods for measuring biomass are destructive. Thus, they do not allow the development of individual plants to be followed and they require many individuals to be cultivated for repeated measurements. Non-destructive methods do not have these limitations. Here, a non-destructive method based on digital image analysis is presented, addressing not only above-ground fresh biomass (FBM) and oven-dried biomass (DBM), but also vertical biomass distribution as well as dry matter content (DMC) and growth rates. Methods Scaled digital images of the plants silhouettes were taken for 582 individuals of 27 grass species (Poaceae). Above-ground biomass and DMC were measured using destructive methods. With image analysis software Zeiss KS 300, the projected area and the proportion of greenish pixels were calculated, and generalized linear models (GLMs) were developed with destructively measured parameters as dependent variables and parameters derived from image analysis as independent variables. A bootstrap analysis was performed to assess the number of individuals required for re-calibration of the models. Key Results The results of the developed models showed no systematic errors compared with traditionally measured values and explained most of their variance (R2 ≥ 0·85 for all models). The presented models can be directly applied to herbaceous grasses without further calibration. Applying the models to other growth forms might require a re-calibration which can be based on only 10–20 individuals for FBM or DMC and on 40–50 individuals for DBM. Conclusions The methods presented are time and cost effective compared with traditional methods, especially if development or growth rates are to be measured repeatedly. Hence, they offer an alternative way of determining biomass, especially as they are non-destructive and address not only FBM and DBM, but also vertical biomass distribution and DMC. PMID:17353204

Microbiological contamination in high and low flow oxygen humidifiers: A systematic review.

PubMed

de la Fuente-Sancho, I; Romeu-Bordas, Ó; Fernández-Aedo, I; Vallejo De la Hoz, G; Ballesteros-Peña, S

2017-12-16

To determine the risk of microbiological contamination with hospital use high- and low-flow bubbling humidifiers. A systematic literature review was carried out in 6 databases. Observational or experimental studies published between 1990 and 2016 were selected, written in English or Spanish, and in which microbiological contamination with hospital use high- and low-flow bubbling humidifiers was investigated. A total of 12 articles were included: 4 analyzed the water from reusable humidifiers, 4 analyzed the water from prefilled system humidifiers, and the rest compared samples from both models. Microbial contamination was observed in all studies in which reusable humidifiers were evaluated, usually involving common bacteria from the skin flora, while potential pathogenic species were notified in 2 studies. No microbial contamination was isolated from reusable humidifiers, regardless of whether they had been consecutively used over time by a single patient or by several patients. On one hand, there seems to be a low risk of contamination during the first weeks of use of prefilled humidifiers, which allows multiple use in different patients, without a risk of cross-contamination. On the other hand, it should be underscored that handling reusable humidifiers without correct aseptic measures can increase the risk of contamination; replacing reusable humidifiers with prefilled models therefore could be the safest option. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Impact of malnutrition on gastrointestinal disorders and gross motor abilities in children with cerebral palsy.

PubMed

Campanozzi, Angelo; Capano, Guglielmo; Miele, Erasmo; Romano, Alfonso; Scuccimarra, Goffredo; Del Giudice, Ennio; Strisciuglio, Caterina; Militerni, Roberto; Staiano, Annamaria

2007-01-01

Children with cerebral palsy (CP) often demonstrate abnormal feeding behaviours, leading to reduced food consumption and malnutrition. Moreover, most of them present with gastrointestinal disorders, such as gastroesophageal reflux disease (GERD) and/or chronic constipation (CC), and poor motor function rehabilitation. The aim of our study was to assess the possible relationship between malnutrition and gastrointestinal problems and to evaluate the role of nutrition on their gross motor abilities in a population of children with CP and mental retardation. Twenty-one consecutive children (10 boys; mean age: 5.8+/-4.7 years; range: 1-14 years) with CP and severe mental retardation. Nutritional assessment included the measurement of body mass index (BMI=W/H2), fat body mass (FBM) and fat free mass (FFM). Children with symptoms suggesting GERD underwent prolonged 24h intraesophageal pH monitoring and/or upper GI endoscopy with biopsies before and after a 6 months of pharmaceutical (omeprazole) and nutritional (20% increment of daily caloric intake) treatments. The motor function was evaluated by "The Gross Motor Function Measure" (GMFM) before and after the 6 months on nutritional rehabilitation. BMI for age was or=25 degrees percentile, five of nine (55.5%) patients had persistent GERD when they were taken off the medication. Malnutrition and gastrointestinal disorders are very common in children with cerebral palsy. Improved nutritional status, particularly fat free mass gain, appears to have an impact on motor function in children with CP.

Prefilled certolizumab pegol (Cimzia®) syringes for self-use in the treatment of rheumatoid arthritis

PubMed Central

Rosa, J; Sabelli, M; Soriano, Enrique R

2010-01-01

A new anti-tumor necrosis factor alpha (TNF-α) inhibitor with a novel mechanism of action has entered phase 3 trials in rheumatoid arthritis (RA). Certolizumab pegol (Cimzia®) is a humanized Fab′ antibody fragment against TNF-α with a polyethylene glycol tail that prevents complement-dependent and antibody-dependent cell-mediated cytotoxicity or apoptosis. Four randomized clinical trials have been published so far. Reported results are similar to those published in previous studies with other TNF-α inhibitors, with ACR20, ACR50, and ACR70 responses of around 60%, 40%, and 20%, respectively, when combined with methotrexate and slightly lower when used as monotherapy. Safety was shown to be similar to that seen with TNF-α blockers and some cases of tuberculosis were seen in the trials, stressing the importance of a complete screening in these patients. Although we still need effectiveness and safety data in larger numbers of patients and longer follow-up, this new TNF inhibitor is a welcome addition to our current armamentarium for the treatment of RA. PMID:22915918

Improved biomedical electrode

NASA Technical Reports Server (NTRS)

Frost, J. D., Jr.

1972-01-01

Newly designed electrode is prefilled, disposable, electrolyte-saturated spong. New design permits longe periods of storage without deterioration, and readiness in matter of seconds. Electrodes supply signals for electroencephalogram, electro-oculogram, and electrocardiogram.

Humalog(®) KwikPen™: an insulin-injecting pen designed for ease of use.

PubMed

Schwartz, Sherwyn L; Ignaut, Debra A; Bodie, Jennifer N

2010-11-01

Insulin pens offer significant benefits over vial and syringe injections for patients with diabetes who require insulin therapy. Insulin pens are more discreet, easier for patients to hold and inject, and provide better dosing accuracy than vial and syringe injections. The Humalog(®) KwikPen™ (prefilled insulin lispro [Humalog] pen, Eli Lilly and Company, Indianapolis, IN, USA) is a prefilled insulin pen highly rated by patients for ease of use in injections, and has been preferred by patients to both a comparable insulin pen and to vial and syringe injections in comparator studies. Together with an engineering study demonstrating smoother injections and reduced dosing error versus a comparator pen, recent evidence demonstrates the Humalog KwikPen device is an accurate, easy-to-use, patient-preferred insulin pen.

Reorganizing Freshman Business Mathematics II: Authentic Assessment in Mathematics through Professional Memos

ERIC Educational Resources Information Center

Green, Kris; Emerson, Allen

2008-01-01

The first part of this two-part paper [see EJ787497] described the development of a new freshman business mathematics (FBM) course at our college. In this paper, we discuss our assessment tool, the business memo, as a venue for students to apply mathematical skills, via mathematical modelling, to realistic business problems. These memos have…

Reorganizing Freshman Business Mathematics I: Background and Philosophy

ERIC Educational Resources Information Center

Green, Kris; Emerson, Allen

2008-01-01

This article is the first of the two-part discussion of the development of a new Freshman Business Mathematics (FBM) course at our college. Part I of the article describes the background and history behind the course, and provides a theoretical framework for the design of the course. This design involves students in learning and applying…

Efficacy of Home-use Bleaching Agents Delivered in Customized or Prefilled Disposable Trays: A Randomized Clinical Trial.

PubMed

Carlos, N R; Bridi, E C; Amaral, Flb; França, Fmg; Turssi, C P; Basting, R T

The purpose of this study was to evaluate bleaching methods containing hydrogen peroxide (HP) or carbamide peroxide (CP), dispensed in customized or prefilled trays, in terms of color change, tooth sensitivity, gingival irritation, acceptance, and comfort. Seventy-five volunteers were randomly selected and distributed according to the whitening agent (n=25): 10% HP dispensed in prefilled trays (Opalescence Go 10%) and 9.5% HP (Pola Day) and 10% CP both delivered in customized trays (Opalescence PF 10%). HP was applied for 30 min/d for 14 days (d), and CP for 8 h/d for 14 days. Evaluations were performed at baseline and at 7 days and 14 days of treatment. Color change was measured with Commission internationale de l'éclairage color coordinates (L*, a*, b*), Vita Classical, and 3D Master scales. A visual analog scale was used to assess tooth sensitivity, acceptance of the method and degree of comfort of the tray. Gingival irritation was evaluated as present or absent and localized or generalized. Regarding gingival irritation, tray acceptance, and tooth sensitivity, no differences were observed among the groups at any time (p>0.05). As for degree of comfort, 10% HP showed lower scores (comfortable) than 10% CP, with significant differences (p<0.05) from the other groups (comfortable to very comfortable). In terms of ΔL, Δa, and ΔE, no difference was observed among the groups or between the time periods (p>0.05). The Δb average was higher at 14 days (p<0.05), and there was no difference among the groups (p>0.05). Localized gingival irritation was observed in both tray methods. Mild tooth sensitivity was observed with time, regardless of the bleaching agent concentration or the application time. Color change was similar for all the groups at 7 days and 14 days, but there was a greater reduction in the yellow hue at 14 days. All the bleaching methods were highly accepted and effective in promoting whitening. Although prefilled trays are generally comfortable, they proved less comfortable than customized trays.

18 CFR 50.4 - Stakeholder participation.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., including a local or toll-free phone number, the name of a specific person to contact who is knowledgeable... pre-filing process, the Commission's Internet address, and the telephone number for the Commission's...

18 CFR 50.4 - Stakeholder participation.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., including a local or toll-free phone number, the name of a specific person to contact who is knowledgeable... pre-filing process, the Commission's Internet address, and the telephone number for the Commission's...

18 CFR 50.4 - Stakeholder participation.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., including a local or toll-free phone number, the name of a specific person to contact who is knowledgeable... pre-filing process, the Commission's Internet address, and the telephone number for the Commission's...

18 CFR 50.4 - Stakeholder participation.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., including a local or toll-free phone number, the name of a specific person to contact who is knowledgeable... pre-filing process, the Commission's Internet address, and the telephone number for the Commission's...

18 CFR 50.4 - Stakeholder participation.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., including a local or toll-free phone number, the name of a specific person to contact who is knowledgeable... pre-filing process, the Commission's Internet address, and the telephone number for the Commission's...

A Comparison of Taste and Odor Perception in Pediatric Patients Receiving a 0.9% Sodium Chloride Flush From 2 Different Brands of Prefilled 0.9% Sodium Chloride Syringes.

PubMed

Hamze, Benjamin; Vaillancourt, Régis; Sharp, Diane; Villarreal, Gilda

2016-01-01

The aim of this randomized single-blind study is to compare taste and odor disturbances in patients receiving 0.9% sodium chloride flushes from 2 brands. Seventy-five patients from 6 to 18 years of age received intravenous 0.9% sodium chloride infusions, and 50 healthy volunteers who tasted the 2 brands of 0.9% sodium chloride from prefilled syringes were assessed for taste and/or odor disturbances. Taste or odor disturbances were equally present in patients flushed with MedXL and Becton-Dickinson 0.9% sodium chloride. Disturbances are more frequent when 0.9% sodium chloride is flushed through central venous access devices than through peripheral catheters. No difference between the brands was found when healthy volunteers tasted it orally.

Recent trends and future of pharmaceutical packaging technology

PubMed Central

Zadbuke, Nityanand; Shahi, Sadhana; Gulecha, Bhushan; Padalkar, Abhay; Thube, Mahesh

2013-01-01

The pharmaceutical packaging market is constantly advancing and has experienced annual growth of at least five percent per annum in the past few years. The market is now reckoned to be worth over $20 billion a year. As with most other packaged goods, pharmaceuticals need reliable and speedy packaging solutions that deliver a combination of product protection, quality, tamper evidence, patient comfort and security needs. Constant innovations in the pharmaceuticals themselves such as, blow fill seal (BFS) vials, anti-counterfeit measures, plasma impulse chemical vapor deposition (PICVD) coating technology, snap off ampoules, unit dose vials, two-in-one prefilled vial design, prefilled syringes and child-resistant packs have a direct impact on the packaging. The review details several of the recent pharmaceutical packaging trends that are impacting packaging industry, and offers some predictions for the future. PMID:23833515

Current sheet characteristics of a parallel-plate electromagnetic plasma accelerator operated in gas-prefilled mode

NASA Astrophysics Data System (ADS)

Liu, Shuai; Huang, Yizhi; Guo, Haishan; Lin, Tianyu; Huang, Dong; Yang, Lanjun

2018-05-01

The axial characteristics of a current sheet in a parallel-plate electromagnetic plasma accelerator operated in gas-prefilled mode are reported. The accelerator is powered by a fourteen stage pulse forming network. The capacitor and inductor in each stage are 1.5 μF and 300 nH, respectively, and yield a damped oscillation square wave of current with a pulse width of 20.6 μs. Magnetic probes and photodiodes are placed at various axial positions to measure the behavior of the current sheet. Both magnetic probe and photodiode signals reveal a secondary breakdown when the current reverses the direction. An increase in the discharge current amplitude and a decrease in pressure lead to a decrease in the current shedding factor. The current sheet velocity and thickness are nearly constant during the run-down phase under the first half-period of the current. The current sheet thicknesses are typically in the range of 25 mm to 40 mm. The current sheet velocities are in the range of 10 km/s to 45 km/s when the discharge current is between 10 kA and 55 kA and the gas prefill pressure is between 30 Pa and 800 Pa. The experimental velocities are about 75% to 90% of the theoretical velocities calculated with the current shedding factor. One reason for this could be that the idealized snowplow analysis model ignores the surface drag force.

Particle Characterization for a Protein Drug Product Stored in Pre-Filled Syringes Using Micro-Flow Imaging, Archimedes, and Quartz Crystal Microbalance with Dissipation.

PubMed

Zheng, Songyan; Puri, Aastha; Li, Jinjiang; Jaiswal, Archana; Adams, Monica

2017-01-01

Micro-flow imaging (MFI) has been used for formulation development for analyzing sub-visible particles. Archimedes, a novel technique for analyzing sub-micron particles, has been considered as an orthogonal method to currently existing techniques. This study utilized these two techniques to investigate the effectiveness of polysorbate (PS-80) in mitigating the particle formation of a therapeutic protein formulation stored in silicone oil-coated pre-filled syringes. The results indicated that PS-80 prevented the formation of both protein and silicone oil particles. In the case of protein particles, PS-80 might involve in the interactions with the hydrophobic patches of protein, air bubbles, and the stressed surfaces of silicone oil-coated pre-filled syringes. Such interactions played a role in mitigating the formation of protein particles. Subsequently, quartz crystal microbalance with dissipation (QCM-D) was utilized to characterize the interactions associated with silicone oil, protein, and PS-80 in the solutions. Based on QCM-D results, we proposed that PS-80 likely formed a layer on the interior surfaces of syringes. As a result, the adsorbed PS-80 might block the leakage of silicone oil from the surfaces to solution so that the silicone oil particles were mitigated at the presence of PS-80. Overall, this study demonstrated the necessary of utilizing these three techniques cooperatively in order to better understand the interfacial role of PS-80 in mitigating the formation of protein and silicone oil particles.

Wood used in pallets manufactured in the United States, 1982

Treesearch

D. B. McKeever; D. R. McCurdy; F. H. Kung; J. T. Ewers

This paper reports results of a cooperative study by the USDA Forest Service, Southern Illinois University at Carbondale, and Tuskegee Institute. The study was designed to provide statistically reliable information on national and regional use of wood in pallets, by species and pallet type. An estimated 17 fbm of wood was required to produce a finished pallet; the...

A Case Study on Mathematics Anxiety for Mathematics of Finance Course

ERIC Educational Resources Information Center

Abidin, Rabiatul Alawiyah Zainal; Alwi, Fatimah; Jaafar, Noor Faiza M.

2010-01-01

The DIIA (Diploma in Investment Analysis) students from the FBM (Faculty of Business Management) were required to undertake several MOF (Mathematic of Finance) courses. The passing rates for all of the MOF courses were good except for one course. There are many factors for this low passing rate phenomenon for this particular MOF course. One of the…

Structural Determinants Underlying Constitutive Dimerization of Unoccupied Human Follitropin Receptors

PubMed Central

Guan, Rongbin; Wu, Xueqing; Feng, Xiuyan; Zhang, Meilin; Hébert, Terence E.; Segaloff, Deborah L.

2009-01-01

The human follitropin receptor (hFSHR) is a G protein-coupled receptor (GPCR) central to reproductive physiology that is composed of an extracellular domain (ECD) fused to a serpentine region. Using bioluminescence resonance energy transfer (BRET) in living cells, we show that hFSHR dimers form constitutively during their biosynthesis. Mutations in TM1 and TM4 had no effect on hFSHR dimerization, alone or when combined with mutation of Tyr110 in the ECD, a residue predicted to mediate dimerization of the soluble hormone-binding portion of the ECD complexed with FSH (Q. Fan and W. Hendrickson, Nature 433:269–277, 2005). Expressed individually, the serpentine region and a membrane-anchored form of the hFSHR ECD each exhibited homodimerization, suggesting that both domains contribute to dimerization of the full-length receptor. However, even in the context of only the membrane-anchored ECD, mutation of Tyr110 to alanine did not inhibit dimerization. The full-length hFSHR and the membrane-anchored ECD were then each engineered to introduce a consensus site for N-linked glycosylation at residue 110. Despite experimental validation of the presence of carbohydrate on residue 110, we failed to observe disruption of dimerization of either the full-length hFSHR or membrane-anchored ECD containing the inserted glycan wedge. Taken altogether, our data suggest that both the serpentine region and the ECD contribute to hFSHR dimerization and that the dimerization interface of the unoccupied hFSHR does not involve Tyr110 of the ECD. PMID:19800402

Concentration of floating biogenic material in convergence zones

NASA Astrophysics Data System (ADS)

Dandonneau, Yves; Menkes, Christophe; Duteil, Olaf; Gorgues, Thomas

Some organisms that live just below the sea surface (the neuston) are known more as a matter of curiosity than as critical players in biogeochemical cycles. The hypothesis of this work is that their existence implies that they receive some food from an upward flux of organic matter. The behaviour of these organisms and of the associated organic matter, hereafter mentioned as floating biogenic material (FBM) is explored using a global physical-biogeochemical coupled model, in which its generation is fixed to 1% of primary production, and decay rate is of the order of 1 month. The model shows that the distribution of FBM should depart rapidly from that of primary production, and be more sensitive to circulation patterns than to the distribution of primary production. It is trapped in convergence areas, where it reaches concentrations larger by a factor 10 than in divergences, thus enhancing and inverting the contrast between high and low primary productivity areas. Attention is called on the need to better understand the biogeochemical processes in the first meter of the ocean, as they may impact the distribution of food for fishes, as well as the conditions for air-sea exchange and for the interpretation of sea color.

Characterisation of Plasma Filled Rod Pinch electron beam diode operation

NASA Astrophysics Data System (ADS)

MacDonald, James; Bland, Simon; Chittenden, Jeremy

2016-10-01

The plasma filled rod pinch diode (aka PFRP) offers a small radiographic spot size and a high brightness source. It operates in a very similar to plasma opening switches and dense plasma focus devices - with a plasma prefill, supplied via a number of simple coaxial plasma guns, being snowploughed along a thin rod cathode, before detaching at the end. The aim of this study is to model the PFRP and understand the factors that affect its performance, potentially improving future output. Given the dependence on the PFRP on the prefill, we are making detailed measurements of the density (1015-1018 cm-3), velocity, ionisation and temperature of the plasma emitted from a plasma gun/set of plasma guns. This will then be used to provide initial conditions to the Gorgon 3D MHD code, and the dynamics of the entire rod pinch process studied.

Educational session as a tool to increase patient satisfaction of switching etanercept from the prefilled syringe to the autoinjection pen.

PubMed

Borrás-Blasco, Joaquín; Gracia-Pérez, Antonio; Casterá, M Dolores-Elvira; Rosique-Robles, J Dolores; Abad, Javier

2013-08-01

To assess patients' acceptability of switching etanercept from the prefilled syringe to the autoinjection pen in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis patients. A two-phase cross-sectional study was designed. First phase: consisted of a 2 h information/education session to present the pen and learning its use. At the end of the session, patients completed a self-administered questionnaire regarding the meeting usefulness. Second phase: eight single-use prefilled Enbrel® Pen Myclic were provided. The number of patients included were 104 (rheumatoid arthritis 58, psoriatic arthritis 31, ankylosing spondylitis 15). Attendees showed a high satisfaction degree with the meeting. A high percentage of patients (74.4 - 95.1%) rated the items of the questionnaire as 'very much'. Patients reported > 95% adherence to etanercept autoinjection pen. The percentage of patients self-administering etanercept increased from 66 to 94% and the percentage of those attending primary care for injection decreased from 23 to 2%. It produced important cost savings, in our study represents > 22.000 euros/year. Pain at the injection site was significantly reduced with the use of autoinjection pen. Ninty seven (93%) patients considered that the use of the autoinjection pen was easier than the syringe and 94.2% chose the pen as their preferred delivery system. The autoinjection pen is an advantageous delivery option for etanercept. This study provides further evidence to support that the education strategy is a valid method for switching anti-TNF-α drugs from syringe to pen in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

Randomised clinical trial: a 'nudge' strategy to modify endoscopic sedation practice.

PubMed

Harewood, G C; Clancy, K; Engela, J; Abdulrahim, M; Lohan, K; O'Reilly, C

2011-07-01

In behavioural economics, a 'nudge' describes configuration of a choice to encourage a certain action without taking away freedom of choice. To determine the impact of a 'nudge' strategy - prefilling either 3mL or 5mL syringes with midazolam - on endoscopic sedation practice. Consecutive patients undergoing sedation for EGD or colonoscopy were enrolled. On alternate weeks, midazolam was prefilled in either 3mL or 5mL syringes. Preprocedure sedation was administered by the endoscopist to achieve moderate conscious sedation; dosages were at the discretion of the endoscopist. Meperidine was not prefilled. Overall, 120 patients received sedation for EGD [59 (5mL), 61 (3mL)] and 86 patients were sedated for colonoscopy [38 (5mL), 48 (3mL)]. For EGDs, average midazolam dose was significantly higher in the 5-mL group (5.2mg) vs. 3-mL group (3.3mg), (P<0.0001); for colonoscopies, average midazolam dose was also significantly higher in the 5-mL group (5.1mg) vs. 3-mL group (3.3mg), (P<0.0001). There was no significant difference in mean meperidine dose (42.1mg vs. 42.8mg, P=0.9) administered to both colonoscopy groups. No adverse sedation-related events occurred; no patient required reversal of sedation. These findings demonstrate that 'nudge' strategies may hold promise in modifying endoscopic sedation practice. Further research is required to explore the utility of 'nudges' in impacting other aspects of endoscopic practice. © 2011 Blackwell Publishing Ltd.

Investigating Liquid Leak from Pre-Filled Syringes upon Needle Shield Removal: Effect of Air Bubble Pressure.

PubMed

Chan, Edwin; Maa, Yuh-Fun; Overcashier, David; Hsu, Chung C

2011-01-01

This study is to investigate the effect of headspace air pressure in pre-filled syringes on liquid leak (dripping) from the syringe needle upon needle shield removal. Drip tests to measure drip quantity were performed on syringes manually filled with 0.5 or 1.0 mL of various aqueous solutions. Parameters assessed included temperature (filling and test), bulk storage conditions (tank pressure and the type of the pressurized gas), solution composition (pure water, 0.9% sodium chloride, and a monoclonal antibody formulation), and testing procedures. A headspace pressure analyzer was used to verify the drip test method. Results suggested that leakage is indeed caused by headspace pressure increase, and the temperature effect (ideal gas expansion) is a major, but not the only, factor. The dissolved gases in the liquid bulk prior to or during filling may contribute to leakage, as these gases could be released into the headspace due to solubility changes (in response to test temperature and pressure conditions) and cause pressure increase. Needle shield removal procedures were found to cause dripping, but liquid composition played little role. Overall, paying attention to the processing history (pressure and temperature) of the liquid bulk is the key to minimize leakage. The headspace pressure could be reduced by decreasing liquid bulk storage pressure, filling at a higher temperature, or employing lower solubility gas (e.g., helium) for bulk transfer and storage. Leakage could also be mitigated by simply holding the syringe needle pointing upward during needle shield removal. Substantial advances in pre-filled syringe technology development, particularly in syringe filling accuracy, have been made. However, there are factors, as subtle as how the needle shield (or tip cap) is removed, that may affect dosing accuracy. We recently found that upon removal of the tip cap from a syringe held vertically with needle pointed downwards, a small amount of solution, up to 3-4% of the 1 mL filled volume or higher for filled volume of <1 mL, leaked out from the needle. This paper identified the root causes of this problem and offered solutions from the perspectives of the syringe fill process and the end user procedure. The readers will benefit from this paper by understanding how each process step prior to and during syringe filling may affect delivery performance of the pre-filled syringe device.

Computer-Based Instruction for TRIDENT FBM Training

DTIC Science & Technology

1976-06-01

remote voice feedback to an operator. In this case it is possible to display text which represents the voice messages required during sequential ...provides two main services: (a) the preparation of missiles for sequential launching with self-guidance after launch, and (b) the coordination of...monitor- ing the status of the guidance system in each missile. FCS SWS coordina- tion consists of monitoring systems involved in sequential functions at

18 CFR 50.5 - Pre-filing procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to prepare the environmental documentation for the project and the specifications for the applicant's... showing all major components, including a description of zoning and site availability for any permanent... environmental reviews and authorizations for the project, including contact names and telephone numbers, and a...

Mass Producing Targets for Nuclear Fusion

NASA Technical Reports Server (NTRS)

Wang, T. G.; Elleman, D. D.; Kendall, J. M.

1983-01-01

Metal-encapsulating technique advances prospects of controlling nuclear fusion. Prefilled fusion targets form at nozzle as molten metal such as tin flows through outer channel and pressurized deuterium/tritium gas flows through inner channel. Molten metal completely encloses gas charge as it drops off nozzle.

The increased incidence of pure red cell aplasia with an Eprex formulation in uncoated rubber stopper syringes.

PubMed

Boven, Katia; Stryker, Scott; Knight, John; Thomas, Adrian; van Regenmortel, Marc; Kemeny, David M; Power, David; Rossert, Jerome; Casadevall, Nicole

2005-06-01

The incidence of pure red cell aplasia (PRCA) in chronic kidney disease patients treated with epoetins increased substantially in 1998, was shown to be antibody mediated, and was associated predominantly with subcutaneous administration of Eprex. A technical investigation identified organic compounds leached from uncoated rubber stoppers in prefilled syringes containing polysorbate 80 as the most probable cause of the increased immunogenicity. This study investigated whether the incidence of PRCA was higher for exposure to the product form containing leachates than for leachate-free product forms. Antibody-mediated PRCA cases were classified according to indication, product form, and route of administration. Exposure estimates were obtained by country, indication, route of administration, and product form. For 2001 to 2003, the PRCA incidence rate for patients with subcutaneous exposure to Eprex in prefilled syringes with polysorbate 80 and uncoated rubber stoppers (leachates present) was 4.61/10,000 patient years (95% CI 3.88-5.43) versus 0.26/10,000 patient years (95% CI 0.007-1.44) for syringes with coated stoppers (leachates absent). The rate difference was 4.35/10,000 patient years (95% CI 3.44-5.26; P < 0.0001); the rate ratio was 17 (95% CI 3.14-707). A substantial rate difference remained in sensitivity analyses that adjusted for exposure to multiple product forms. The epidemiologic data, together with the chemical and immunologic data, support the hypothesis that leachates from uncoated rubber syringe stoppers caused the increased incidence of PRCA associated with Eprex. Currently, all Eprex prefilled syringes contain fluoro-resin coated stoppers, which has contributed to decreased incidence of PRCA with continued surveillance.

High concentration biotherapeutic formulation and ultrafiltration: Part 1 pressure limits.

PubMed

Lutz, Herb; Arias, Joshua; Zou, Yu

2017-01-01

High therapeutic dosage requirements and the desire for ease of administration drive the trend to subcutaneous administration using delivery systems such as subcutaneous pumps and prefilled syringes. Because of dosage volume limits, prefilled syringe administration requires higher concentration liquid formulations, limited to about 30 cP or roughly 100-300 g L -1 for mAb's. Ultrafiltration (UF) processes are routinely used to formulate biological therapeutics. This article considers pressure constraints on the UF process that may limit its ability to achieve high final product concentrations. A system hardware analysis shows that the ultrafiltration cassette pressure drop is the major factor limiting UF systems. Additional system design recommendations are also provided. The design and performance of a new cassette with a lower feed channel flow resistance is described along with 3D modeling of feed channel pressure drop. The implications of variations in cassette flow channel resistance for scaling up and setting specifications are considered. A recommendation for a maximum pressure specification is provided. A review of viscosity data and theory shows that molecular engineering, temperature, and the use of viscosity modifying excipients including pH adjustment can be used to achieve higher concentrations. The combined use of a low pressure drop cassette with excipients further increased final concentrations by 35%. Guidance is provided on system operation to control hydraulics during final concentration. These recommendations should allow one to design and operate systems to routinely achieve the 30 cP target final viscosity capable of delivery using a pre-filled syringe. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:113-124, 2017. © 2016 American Institute of Chemical Engineers.

20 CFR 655.120 - Offered wage rate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TEMPORARY EMPLOYMENT OF FOREIGN WORKERS IN THE UNITED STATES Labor Certification Process for Temporary Agricultural Employment in the United States (H-2A Workers) Prefiling Procedures § 655.120 Offered wage rate. (a) To comply with...

77 FR 21977 - Whitestone Power and Communications; Notice Concluding Pre-Filing Process and Approving Process...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-12

...) pontoon and a 34- foot-long, 3-foot-diameter HDPE pontoon; (3) a 100-kilowatt turbine/ generator unit; (4..., 16-foot- diameter Poncelet undershot water wheel; (2) a 34-foot-long, 19- to 24- foot-wide aluminum...

Effect of saliva contamination and artificial aging on different primer/cement systems bonded to zirconia.

PubMed

Pitta, João; Branco, Teresa C; Portugal, Jaime

2018-05-01

Saliva contamination has been shown to decrease bonding to zirconia. Adopting a less contamination-sensitive cement system may be an alternative to decontamination. The purpose of this in vitro study was to assess the ability of different primer/cement systems to promote a durable bond to zirconia after saliva contamination. Zirconia blocks (Lava Plus) (N=320) were airborne-particle abraded (50 μm Al 2 O 3 ) and divided into 32 experimental groups (n=10) according to the variables in the study: saliva contamination; primer/cement system (Panavia SA [PSA]; RelyX Unicem 2 [RU2]; Bifix SE [BSE]; Panavia F2.0 [PF2]; Scotchbond Universal + RelyX Ultimate [SBU+RXU]; Futurabond M+ + Bifix QM [FBM+BQM]; All-Bond Universal + Duo-link [ABU+DL]; Z-Prime Plus + Duo-link [ZPP+DL]; and aging period (72 hours; 30 days with 10 000 thermocycles at 5°C to 55°C). After half of the blocks had been contaminated with fresh human saliva for 10 minutes, rinsed with water, and air-dried, each primer/cement was applied. Polymerized composite resin disks were then placed over the cement, and the resin cement was light-polymerized for 20 seconds each at 2 opposite margins. After the aging time, the specimens were tested in shear (1 mm/min). The failure mode was classified as adhesive, cohesive, or mixed. Statistical analysis of the shear bond strength (SBS) data was performed with ANOVA followed by Tukey honest significant difference post hoc tests. Chi-square tests were used to analyze the failure mode data (α=.05). The mean SBS ranged between 4.2 and 34.5 MPa. Shear bond strength was influenced (P<.001) by all the factors studied (cement system, saliva contamination, aging time). SBU+RXU and FBM+BQM showed a higher mean SBS than those of the other experimental groups (P<.05) and were the only groups not affected by saliva contamination (P>.05). Failure was predominantly classified as adhesive. In general, saliva contamination and aging decreased bonding efficacy. Two systems, combining an application of a universal adhesive and a resin cement (SBU+RXU and FBM+BQM) were not affected by saliva contamination. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

18 CFR 5.29 - Other provisions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... member of the public. (c) Requests for privileged treatment of pre-filing submission. If a potential... there are only insignificant differences between the final applications of an existing licensee and a... licensee for the purpose of the insignificant differences provision of section 15(a)(2) of the Federal...

20 CFR 655.1302 - Required pre-filing activity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... as specified in this section. (c) Retention of documentation. An employer filing an Application for... the certification. There is no record retention requirement for any application (and supporting... steps. An employer filing an application must: (1) Submit a job order to the SWA serving the area of...

Engineering study comparing injection force and dose accuracy between two prefilled insulin injection pens.

PubMed

Ignaut, Debra A; Opincar, Michael R; Clark, Paula E; Palaisa, Melanie K; Lenox, Sheila M

2009-12-01

This study compared injection force (measured by glide force [GF] and glide force variability [GFV]) and dosing accuracy of the Humalog KwikPen * (prefilled insulin lispro [Humalog dagger] pen, Eli Lilly and Company, Indianapolis, IN) and the Next Generation FlexPen double dagger (prefilled insulin aspart [NovoRapid section sign] pen, Novo Nordisk A/S, Bagsvaerd, Denmark). * Humalog KwikPen is a registered trademark of Eli Lilly and Company, Indianapolis, IN, USA. dagger Humalog is a registered trademark of Eli Lilly and Company, Indianapolis, IN, USA. double dagger FlexPen is a registered trademark of Novo Nordisk A/S, Bagsvaerd, Denmark. section sign NovoRapid is a registered trademark of Novo Nordisk A/S, Bagsvaerd, Denmark. A total of 100 prefilled insulin pens (50 insulin lispro pens, 50 insulin aspart pens) were tested using two dose sizes (30 U and 60 U). In all, 50 devices (25 of each type) were tested at 10 U/s dosing speed and 50 were tested at 6.6 U/s. Devices were used per manufacturer instructions. Dose accuracy (represented as absolute dose error %), maximum and average GF, and GFV data were automatically collected by the test system for all datasets (dose size/dosing speed/device type). The test system controlled for potential dosing errors. The insulin lispro pen demonstrated a significantly lower median maximum GF at both dosing speeds: (2.83 vs. 3.92 lbs [30 U] and 3.00 vs. 4.14 lbs [60 U]) at 10 U/s; (1.85 vs. 2.93 lbs [30 U] and 2.14 vs. 3.02 lbs [60 U]) at 6.6 U/s, all p < 0.0001. For all datasets, the median GFV was significantly lower for the insulin lispro pen, p < 0.0001. Median dose error was comparable between device types when tested at 10 U/s dosing speed; however, at 6.6 U/s, the median dose error was significantly lower for insulin lispro pen compared to insulin aspart pen (0.47 vs. 0.67% [30 U] and 0.50 vs. 0.78% [60 U], both p < 0.05). The insulin lispro pen had significantly lower median GF and GFV compared with insulin aspart pen when tested at two dose sizes and two dosing speeds. Median dose error was similar between the device types at the 10 U/s dosing speed, but median dose error was significantly lower for the insulin lispro pen at the 6.6 U/s dosing speed. A limitation of this study was that it was executed as an open label study.

The People’s Liberation Army and China in Transition

DTIC Science & Technology

2003-08-01

and long- range land-attack cruise missiles. China currently has just one FBM, the Xia, which may not be opera - ble. Its successor class, the Type...prospects for U.S.- China relations and military-to-military cooperation, and the implications of these developments for U.S. defense planning...A R T I THE PEOPLE’S LIBERATION ARMY AND CHINA IN TRANSITION edited by Stephen J. Flanagan and Michael E. Marti, with contributions from: Richard

Solute-Filled Syringe For Formulating Intravenous Solution

NASA Technical Reports Server (NTRS)

Owens, Jim; Bindokas, AL; Dudar, Tom; Finley, Mike; Scharf, Mike

1993-01-01

Prefilled syringe contains premeasured amount of solute in powder or concentrate form used to deliver solute to sterile interior of large-volume parenteral (LVP) bag. Predetermined amount of sterile water also added to LVP bag through sterilizing filter, and mixed with contents of syringe, yielding sterile intravenous solution of specified concentration.

47 CFR 22.150 - Standard pre-filing technical coordination procedure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... this procedure for specific channels and types of stations are contained in the subparts governing the..., emission type and polarization. (4) Transmitting antenna pattern and maximum gain. (5) Transmitting antenna..., even if no channel usage conflicts are anticipated. If any notified party fails to respond within 30...

Low Leachable Container System Consisting of a Polymer-Based Syringe with Chlorinated Isoprene Isobutene Rubber Plunger Stopper.

PubMed

Kiminami, Hideaki; Takeuchi, Katsuyuki; Nakamura, Koji; Abe, Yoshihiko; Lauwers, Philippe; Dierick, William; Yoshino, Keisuke; Suzuki, Shigeru

2015-01-01

A 36 month leachable study on water for injection in direct contact within a polymer-based prefillable syringe consisting of a cyclo olefin polymer barrel, a chlorinated isoprene isobutene rubber plunger stopper, a polymer label attached on the barrel, and a secondary packaging was conducted at 25 ± 2 °C and 60 ± 5% relative humidity. Through the various comparison studies, no difference in the leachable amounts was observed between this polymer-based prefilled syringe and a glass bottle as a blank sample reference by 36 months. No influence on the leachables study outcome was noted from the printed label and/or label adhesive or from the secondary packaging. In an additional study, no acrylic acid used as the label adhesive leachable was detected by an extended storage for 45 months at 25 ± 2 °C and 60 ± 5% relative humidity as a worst case. To obtain more details, a comparison extractable study was conducted between a cyclo olefin polymer barrel and a glass barrel. In addition, chlorinated isoprene isobutene rubber and bromo isoprene isobutene rubber were compared. As a result, no remarkable difference was found in the organic extractables for syringe barrels. On the other hand, in the case of element extractable analysis, the values for the cyclo olefin polymer barrel were lower than that for the glass barrel. For the plunger stoppers, the chlorinated isoprene isobutene rubber applied in this study was showing a lower extractable profile as compared to the bromo isoprene isobutene rubber, both for organic and element extractables. In conclusion, the proposed polymer-based prefillable syringe system has great potential and represents a novel alternative that can achieve very low level extractable profiles and can bring additional value to the highly sensitive biotech drug market. A 36 month leachable study on water for injection in direct contact within a cyclo olefin polymer barrel and chlorinated isoprene isobutene rubber plunger stopper that has a polymer label attached to the barrel and is wrapped into a secondary packaging was conducted at 25 °C and 60% relative humidity. Through the various comparison studies, no difference in the leachable amounts was observed between polymer-based prefilled syringes and a glass bottle as a blank sample reference by 36 months. No influences on the leachables study outcome were noted from the secondary packaging. To obtain more details, a comparison extractable study was conducted between the cyclo olefin polymer and the glass barrel. In addition, chlorinated isoprene isobutene rubber and bromo isoprene isobutene rubber plunger stoppers were compared as well. As a result, no remarkable difference was found in the organic extractables for barrels. As for element extractable analysis, the values for the cyclo olefin polymer barrel were lower than that for the glass barrel. For the plunger stoppers, the chlorinated isoprene isobutene rubber applied in this study was showing a lower extractable profile as compared to the bromo isoprene isobutene rubber, both for organic and element extractables. In conclusion, the proposed polymer-based prefillable syringe system has great potential and represents a novel alternative that can achieve very low level extractable profiles and can bring additional value to the highly sensitive biotech drug market. © PDA, Inc. 2015.

Fractional Brownian motion and long term clinical trial recruitment

PubMed Central

Zhang, Qiang; Lai, Dejian

2015-01-01

Prediction of recruitment in clinical trials has been a challenging task. Many methods have been studied, including models based on Poisson process and its large sample approximation by Brownian motion (BM), however, when the independent incremental structure is violated for BM model, we could use fractional Brownian motion to model and approximate the underlying Poisson processes with random rates. In this paper, fractional Brownian motion (FBM) is considered for such conditions and compared to BM model with illustrated examples from different trials and simulations. PMID:26347306

Fractional Brownian motion and long term clinical trial recruitment.

PubMed

Zhang, Qiang; Lai, Dejian

2011-05-01

Prediction of recruitment in clinical trials has been a challenging task. Many methods have been studied, including models based on Poisson process and its large sample approximation by Brownian motion (BM), however, when the independent incremental structure is violated for BM model, we could use fractional Brownian motion to model and approximate the underlying Poisson processes with random rates. In this paper, fractional Brownian motion (FBM) is considered for such conditions and compared to BM model with illustrated examples from different trials and simulations.

Continuous tunnel kiln direct-fired with bark to dry 1.75-inch southern pine in 12 hours.

Treesearch

P. Koch; W.L. Wellford

1977-01-01

Length-sorted lumber is surfaced on one side to 1.75-inch thickness, mechanically stacked 5 feet wide and 10 feet high on 1-1/4-inch-thick sticks, and continuously transported through a zone-controlled tunnel kiln at 8 ft./hr. to yield 500,000 fbm of lumber dried to 9 percent average MC per 168-hour week. In the tunnel, the lumber is dried for 8 (possibly 10) hours at...

Continuous tunnel kiln direct-fired with bark to dry 1.75-inch southern pine in 12 hours

Treesearch

Peter Koch; Walker L. Wellford

1976-01-01

Length-sorted lumber is surfaced on one side to 1.75-inch thickness, mechanically stacked 5 feet wide and 10 feet high on 1-1/4-inch-thick sticks, and continuously transported through a zone-controlled tunnel kiln at 8 ft./hr. to yield 500,000 fbm of lumber dried to 9 percent average MC per 168-hour week. In the tunnel, the lumber is dried for 8 (possibly 10) hours of...

Time to dry 2-, 30, and 40inch S4S southern pine at 240°F, as related to board width

Treesearch

Peter Koch

1973-01-01

With 80°F wet-bulb depression and air cross-circulated at 1,000 fbm, southern pine in 2-, 3-, and 4-inch thicknesses attained 10 percent moisture content in 22.4, 35.6, and 45.3 hours. In 3- and 4-inch thicknesses, 4-inch-wide lumber required less time to dry than that 8 or 12 inches wide. Surface checks were absent or moderate in all thicknesses and widths. End-...

12 CFR 516.15 - Must I meet with OTS before I file my application?

Code of Federal Regulations, 2010 CFR

2010-01-01

... with OTS before filing your application. You must submit a draft business plan before this meeting. (2... you to submit a draft business plan or other relevant information before this meeting. (b) Contacting... pre-filing meeting or a draft business plan, the Regional Office will determine whether it will...

20 CFR 655.15 - Required pre-filing recruitment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... all required steps of the recruitment process as specified in this section. (c) Retention of... § 655.10; (2) Submit a job order to the SWA serving the area of intended employment; (3) Publish two... section); and (4) Where the employer is a party to a collective bargaining agreement governing the job...

20 CFR 655.122 - Contents of job offers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Contents of job offers. 655.122 Section 655... Employment in the United States (H-2A Workers) Prefiling Procedures § 655.122 Contents of job offers. (a) Prohibition against preferential treatment of aliens. The employer's job offer must offer to U.S. workers no...

20 CFR 655.121 - Job orders.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Job orders. 655.121 Section 655.121 Employees... United States (H-2A Workers) Prefiling Procedures § 655.121 Job orders. (a) Area of intended employment... job order, Form ETA-790, to the SWA serving the area of intended employment for intrastate clearance...

20 CFR 655.122 - Contents of job offers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Contents of job offers. 655.122 Section 655... Employment in the United States (H-2A Workers) Prefiling Procedures § 655.122 Contents of job offers. (a) Prohibition against preferential treatment of aliens. The employer's job offer must offer to U.S. workers no...

20 CFR 655.121 - Job orders.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Job orders. 655.121 Section 655.121 Employees... United States (H-2A Workers) Prefiling Procedures § 655.121 Job orders. (a) Area of intended employment... job order, Form ETA-790, to the SWA serving the area of intended employment for intrastate clearance...

20 CFR 655.121 - Job orders.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Job orders. 655.121 Section 655.121 Employees... United States (H-2A Workers) Prefiling Procedures § 655.121 Job orders. (a) Area of intended employment... job order, Form ETA-790, to the SWA serving the area of intended employment for intrastate clearance...

20 CFR 655.121 - Job orders.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Job orders. 655.121 Section 655.121 Employees... United States (H-2A Workers) Prefiling Procedures § 655.121 Job orders. (a) Area of intended employment... job order, Form ETA-790, to the SWA serving the area of intended employment for intrastate clearance...

20 CFR 655.122 - Contents of job offers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Contents of job offers. 655.122 Section 655... Employment in the United States (H-2A Workers) Prefiling Procedures § 655.122 Contents of job offers. (a) Prohibition against preferential treatment of aliens. The employer's job offer must offer to U.S. workers no...

20 CFR 655.121 - Job orders.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Job orders. 655.121 Section 655.121 Employees... United States (H-2A Workers) Prefiling Procedures § 655.121 Job orders. (a) Area of intended employment... job order, Form ETA-790, to the SWA serving the area of intended employment for intrastate clearance...

75 FR 2126 - Regulations Governing the Conduct of Open Seasons for Alaska Natural Gas Transportation Projects...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

... Governing the Conduct of Open Seasons for Alaska Natural Gas Transportation Projects; Notice of Alaska Natural Gas Transportation Projects Open Season Pre-Filing Workshop January 5, 2010. On January 12, 2010... and process for commenting upon and holding an open season for an Alaska Natural Gas Transportation...

75 FR 6370 - Regulations Governing the Conduct of Open Seasons for Alaska Natural Gas Transportation Projects...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

... Governing the Conduct of Open Seasons for Alaska Natural Gas Transportation Projects; Notice of Alaska Natural Gas Transportation Projects Open Season Pre-Filing Workshop February 2, 2010. On February 11, 2010... and process for holding and commenting on an open season for an Alaska Natural Gas Transportation...

76 FR 56507 - Availability of Information, Public Observation of Meetings, Procedure, Practice for Hearings...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-13

... to issue orders) with respect to the supervision of SLHCs and their non-depository subsidiaries... notice of intent also advised that the Board would issue an interim final rule to effectuate the... elimination of requirements in OTS rules for prefiling meetings and submission of draft business plans, and...

76 FR 42122 - Ocean Renewable Power Company, LLC; Notice Concluding Pre-Filing Process and Approving Process...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-18

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12711-003] Ocean Renewable.... e. Name of Project: Cobscook Bay Tidal Energy Project. f. Location: In Cobscook Bay, in Washington... a two-phased development approach for the Cobscook Bay Tidal Energy Project. The project would...

Highly purified human-derived follicle-stimulating hormone (Bravelle®) has equivalent efficacy to follitropin-beta (Follistim ®) in infertile women undergoing in vitro fertilization

PubMed Central

Dickey, Richard P; Nichols, John E; Steinkampf, Michael P; Gocial, Benjamin; Thornton, Melvin; Webster, Bobby W; Bello, Sandra M; Crain, Jack; Marshall, Dennis C

2003-01-01

Background These data compare the efficacy and safety of highly purified human-derived follicle-stimulating hormone (Bravelle(R)) and recombinant follitropin-β (Follistim(R)) in women undergoing in vitro fertilization. Methods This report describes the pooled data from two, nearly identical, randomized, controlled, parallel-group, multicenter studies conducted in a total of 19 academic and private IVF-ET centers in the United States. Infertile premenopausal women underwent pituitary down-regulation using leuprolide acetate followed by a maximum of 12 days of subcutaneous Bravelle(R) (n = 120) or Follistim(R) (n = 118), followed by administration of human chorionic gonadotropin, oocyte retrieval and embryo transfer. The primary efficacy measure was the mean number of oocytes retrieved; secondary efficacy measures included the total dose and duration of gonadotropin treatment; peak serum estradion levels; embryo transfer and implantation rates; chemical, clinical and continuing pregnancies; and live birth rates. All adverse events were recorded and injection site pain was recorded daily using a patient, self-assessment diary. Results Similar efficacy responses were observed for all outcome parameters in the two treatment groups. Although patients receiving Bravelle(R) consistently reported a greater number of chemical, clinical and continuing pregnancies, as well as an increased rate of live birth, the data did not attain statistical significance (P > 0.05). The overall incidence of adverse events was similar in both groups, but compared to Follistim(R), injections of Bravelle(R) were reported by patients to be significantly less painful (P < 0.001). Conclusions Bravelle(R) and Follistim(R) had comparable efficacy in controlled ovarian hyperstimulation in women undergoing IVF-ET. There were no differences in the nature or number of adverse events between the treatment groups although Bravelle(R) injections were reported to be significantly less painful. PMID:14609434

A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection

PubMed Central

Esteves, Sandro C; Schertz, Joan C; Verza, Sidney; Schneider, Danielle T; Zabaglia, Silval FC

2009-01-01

Background Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. Methods A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. Results Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. Conclusion Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG. PMID:19828024

Acceptability and Feasibility of Delivering Pentavalent Vaccines in a Compact, Prefilled, Autodisable Device in Vietnam and Senegal

PubMed Central

Guillermet, Elise; Dicko, Hamadou M.; Mai, Le Thi Phuong; N’Diaye, Mamadou; Hane, Fatoumata; Ba, Seydina Ousmane; Gomis, Khadidjatou; Tho, Nguyen Thi Thi; Lien, Nguyen Thi Phuong; Than, Phan Dang; Dinh, Tran Van; Jaillard, Philippe; Gessner, Bradford D.; Colombini, Anais

2015-01-01

Background Prefilled syringes are the standard in developed countries but logistic and financial barriers prevent their widespread use in developing countries. The current study evaluated use of a compact, prefilled, autodisable device (CPAD) to deliver pentavalent vaccine by field actors in Senegal and Vietnam. Methods We conducted a logistic, programmatic, and anthropological study that included a) interviews of immunization staff at different health system levels and parents attending immunization sessions; b) observation of immunization sessions including CPAD use on oranges; and c) document review. Results Respondents perceived that the CPAD would improve safety by being non-reusable and preventing needle and vaccine exposure during preparation. Preparation was considered simple and may reduce immunization time for staff and caretakers. CPAD impact on cold storage requirements depended on the current pentavalent vaccine being used; in both countries, CPAD would reduce the weight and volume of materials and safety boxes thereby potentially improving outreach strategies and waste disposal. CPAD also would reduce stock outages by bundling vaccine and syringes and reduce wastage by using a non-breakable plastic presentation. Respondents also cited potential challenges including ability to distinguish between CPAD and other pharmaceuticals delivered via a similar mechanism (such as contraceptives), safety, and concerns related to design and ease of administration (such as activation, ease of delivery, and needle diameter and length). Conclusions Compared to current pentavalent vaccine presentations in Vietnam and Senegal, CPAD technology will address some of the main barriers to vaccination, such as supply chain issues and safety concerns among health workers and families. Most of the challenges we identified can be addressed with health worker training, minor design modifications, and health messaging targeting parents and communities. Potentially the largest remaining barrier is the marginal increase in pentavalent cost – if any – from CPAD use, which we did not assess in our study. PMID:26186456

Nitrous oxide as a humane method for piglet euthanasia: Behavior and electroencephalography (EEG).

PubMed

Rault, Jean-Loup; Kells, Nikki; Johnson, Craig; Dennis, Rachel; Sutherland, Mhairi; Lay, Donald C

2015-11-01

The search for humane methods to euthanize piglets is critical to address public concern that current methods are not optimal. Blunt force trauma is considered humane but esthetically objectionable. Carbon dioxide (CO2) is used but criticized as aversive. This research sought to: 1) evaluate the aversiveness of inhaling nitrous oxide (N2O; 'laughing gas') using an approach-avoidance test relying on the piglet's perspective, and 2) validate its humaneness to induce loss of consciousness by electroencephalography (EEG). The gas mixtures tested were N2O and air (90%:10%; '90 N'); N2O, oxygen and air (60%:30%:10%; '60 N'); and CO2 and air (90%:10%; '90 C'). Experiment 1 allowed piglets to walk freely between one chamber filled with air and another prefilled with 60 N or 90 N. All piglets exposed to 60 N lasted for the 10 min test duration whereas all piglets exposed to 90 N had to be removed within 5 min because they fell recumbent and unresponsive and then started to flail. Experiment 2 performed the same test except the gas chamber held N2O prefilled at 25%, 50%, or 75% or CO2 prefilled at 7%, 14%, or 21%. The test was terminated more quickly at higher concentrations due to the piglets' responses. Time spent ataxic was greater in the middle concentration gradients. Flailing behavior tended to correlate with increasing concentrations of CO2 but not N2O. Experiment 3, using the minimal anesthesia model, showed that both 90 N and 90 C induced isoelectric EEG, in 71 and 59 s respectively, but not 60 N within 15 min. The EEG results together with the observed behavioral changes reflect differences in the animal's perceptive experience. The implications for animal welfare are that N2O is much less aversive than CO2, and 90% N2O can euthanize piglets. Copyright © 2015 Elsevier Inc. All rights reserved.

Magnocaine: Physical Compatibility and Chemical Stability of Magnesium Sulphate and Lidocaine Hydrochloride in Prefilled Syringes.

PubMed

Houlihan, Sara; Decarie, Diane; Benes, Cindy; Cleve, Richard; Vidler, Marianne; Magee, Laura A; Ensom, Mary H H; von Dadelszen, Peter

2016-10-01

To evaluate the physical compatibility and chemical stability of mixtures of magnesium sulphate and lidocaine in order to determine the feasibility of manufacturing a prefilled syringe combining these two drugs for use as an intramuscular (IM) loading dose for eclampsia prevention and/or treatment. This ready-to-use mixture will provide a more tolerable and accessible route of administration appropriate for widespread use. Physical compatibility (pH, colour, and formation of precipitate) and chemical stability (maintaining > 90% of initial concentrations) of mixtures of MgSO 4 , using both commercially available MgSO 4 (50%) and MgSO 4 reconstituted from salt (61%), with lidocaine hydrochloride (2%) were evaluated every 14 days over six months. The concentration of lidocaine was determined by a stability indicating high performance liquid chromatographic method, while the concentration of magnesium was determined by an automated chemistry analyzer. No changes in pH, color or precipitates were observed for up to 6 months. The 95% confidence interval of the slope of the curve relating concentration to time, determined by linear regression, indicated that only the admixtures of commercially-available magnesium sulfate and lidocaine as well as the 61% magnesium sulfate solution (reconstituted from salt) maintained at least 90% of the initial concentration of both drugs at 25°C and 40°C at 6 months. Commercially available MgSO4 and lidocaine hydrochloride, when combined, are stable in a pre-filled syringe for at least six months in high heat and humidity conditions. This finding represents the first step in improving the administration of magnesium sulphate in the treatment and prevention of eclampsia in under-resourced settings. Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

Change in lean body mass is a major determinant of change in areal bone mineral density of the proximal femur: a 12-year observational study.

PubMed

Liu-Ambrose, T; Kravetsky, L; Bailey, D; Sherar, L; Mundt, C; Baxter-Jones, A; Khan, K M; McKay, H A

2006-09-01

Our objective was to assess the contribution of lean body mass (LBM) and fat body mass (FBM) to areal bone mineral density (aBMD) in women during the years surrounding menopause. We used a 12-year observational design. Participants included 75 Caucasian women who were premenopausal, 53 of whom were available for follow-up. There were two measurement periods: baseline and 12-year follow-up. At both measurement periods, bone mineral content and aBMD of the proximal femur, posterior-anterior lumbar spine, and total body was assessed using dual-energy X-ray absorptiometry (DXA). LBM and FBM were derived from the total-body scans. General health, including current menopausal status, hormone replace therapy use, medication use, and physical activity, was assessed by questionnaires. At the end of the study, 44% of the women were postmenopausal. After controlling for baseline aBMD, current menopausal status, and current hormone replacement therapy, we found that change in LBM was independently associated with change in aBMD of the proximal femur (P = 0.001). The cross-sectional analyses also indicated that LBM was a significant determinant of aBMD of all three DXA-scanned sites at both baseline and follow-up. These novel longitudinal data highlight the important contribution of LBM to the maintenance of proximal femur bone mass at a key time in women's life span, the years surrounding menopause.

12 CFR 516.45 - What is the filing date of my application?

Code of Federal Regulations, 2010 CFR

2010-01-01

... the following requirements. (1) You attend a pre-filing meeting and submit a draft business plan or... required number of copies with that office. (iii) If you file after the close of business established by a Regional Office or OTS Headquarters, you have filed with that office on the next business day. (3) You pay...

75 FR 70224 - New York Tidal Energy Company; Notice Concluding Pre-Filing Process and Approving Process Plan...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 12665-003] New York Tidal... Tidal Energy Company. e. Name of Project: East River Tidal Energy Pilot Project. f. Location: In the.... Filed Pursuant to: 18 CFR 5.3 of the Commission's regulations. h. Applicant Contact: Daniel Power...

76 FR 40628 - Groundfish Fisheries of the EEZ Off Alaska; Pacific Halibut Fisheries; CDQ Program; Bering Sea...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

..., business telephone number, e-mail address, port of landing, operation type (for catcher/processors.../processor, the at-sea operation type is pre-filled automatically. (3) If an SFP and crab delivery is... Registered Crab Receiver record in eLandings the region in which the stationary floating processor is located...

76 FR 41237 - Public Utility District No. 1 of Snohomish County, WA; Notice Concluding Pre-Filing Process and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-13

... monitoring plans; (2) a request for waivers of certain Integrated Licensing Process (ILP) regulations...Hydro Group Ltd., mounted on completely submerged gravity foundations; (2) two 250-meter service cables connected at a subsea junction box or spliced to a 0.5-kilometer subsea transmission cable, connecting to a...

76 FR 40906 - Pacific Gas and Electric Company; Notice of Intent To File License Application, Filing of Pre...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-12

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2678-005] Pacific Gas and... Application for a Subsequent License and Commencing Pre-filing Process. b. Project No.: 2678-005. c. Dated Filed: April 29, 2011. d. Submitted By: Pacific Gas and Electric Company. e. Name of Project: Narrows No...

78 FR 55069 - Whitewater Green Energy, LLC; Notice of Intent to File License Application, Filing of Pre...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-09

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14383-005] Whitewater Green... Application for an Original License and Commencing Pre-filing Process. b. Project No.: 14383-005. c. Dated Filed: July 8, 2013. d. Submitted By: Whitewater Green Energy, LLC. e. Name of Project: Whitewater Creek...

20 CFR 655.1302 - Required pre-filing activity.

Code of Federal Regulations, 2011 CFR

2011-04-01

... in paragraph (g) of this section); (3) Contact former U.S. employees who were employed within the...-2A workers in order to force the hiring of U.S. workers during the 30-day rule under paragraph (f)(3... this section). (h) Contact with former U.S. employees. The employer must contact by mail or other...

20 CFR 655.1302 - Required pre-filing activity.

Code of Federal Regulations, 2012 CFR

2012-04-01

... in paragraph (g) of this section); (3) Contact former U.S. employees who were employed within the...-2A workers in order to force the hiring of U.S. workers during the 30-day rule under paragraph (f)(3... this section). (h) Contact with former U.S. employees. The employer must contact by mail or other...

20 CFR 655.1302 - Required pre-filing activity.

Code of Federal Regulations, 2013 CFR

2013-04-01

... in paragraph (g) of this section); (3) Contact former U.S. employees who were employed within the...-2A workers in order to force the hiring of U.S. workers during the 30-day rule under paragraph (f)(3... this section). (h) Contact with former U.S. employees. The employer must contact by mail or other...

20 CFR 655.1302 - Required pre-filing activity.

Code of Federal Regulations, 2014 CFR

2014-04-01

... in paragraph (g) of this section); (3) Contact former U.S. employees who were employed within the...-2A workers in order to force the hiring of U.S. workers during the 30-day rule under paragraph (f)(3... this section). (h) Contact with former U.S. employees. The employer must contact by mail or other...

18 CFR 157.21 - Pre-filing procedures and review process for LNG terminal facilities and other natural gas...

Code of Federal Regulations, 2011 CFR

2011-04-01

... and review process for LNG terminal facilities and other natural gas facilities prior to filing of... COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER NATURAL GAS ACT APPLICATIONS FOR CERTIFICATES OF PUBLIC CONVENIENCE AND NECESSITY AND FOR ORDERS PERMITTING AND APPROVING ABANDONMENT UNDER SECTION 7 OF THE NATURAL...

77 FR 61585 - FPL Energy Maine Hydro LLC; Notice of Intent To File License Application, Filing of Pre...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-10

... Hydro LLC; Notice of Intent To File License Application, Filing of Pre-Application Document (PAD... Application for a New License and Commencing Pre-filing Process. b. Project No.: 2531-067. c. Dated Filed... Commission a Pre-Application Document (PAD; including a proposed process plan and schedule), pursuant to 18...

Controllability of fractional higher order stochastic integrodifferential systems with fractional Brownian motion.

PubMed

Sathiyaraj, T; Balasubramaniam, P

2017-11-30

This paper presents a new set of sufficient conditions for controllability of fractional higher order stochastic integrodifferential systems with fractional Brownian motion (fBm) in finite dimensional space using fractional calculus, fixed point technique and stochastic analysis approach. In particular, we discuss the complete controllability for nonlinear fractional stochastic integrodifferential systems under the proved result of the corresponding linear fractional system is controllable. Finally, an example is presented to illustrate the efficiency of the obtained theoretical results. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

77 FR 11523 - Bryant Mountain, LLC; Notice of Intent To File License Application, Filing of Pre-Application...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... and Commencing Pre-filing Process. b. Project No.: 13680-001. c. Dated Filed: December 21, 2011. d... Reclamation and private lands. g. Filed Pursuant to: 18 CFR Part 5 of the Commission's Regulations. h..., California, 94505, (925) 634-1550 or email at [email protected] . i. FERC Contact: Ryan Hansen at (202...

77 FR 21758 - Notice of Application Accepted for Filing With The Commission, Intent To Waive Scoping...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-11

... with a total installed capacity of 1,230 kilowatts; (5) a 1,600-foot-long tailrace canal; (6) a 2.2... intends to prepare a single environmental assessment (EA). Commission staff determined that the issues that need to be addressed in its EA have been adequately identified during the pre-filing period, which...

Evaluation of a new syringe presentation of reduced-antigen content diphtheria, tetanus, and acellular pertussis vaccine in healthy adolescents - A single blind randomized trial

PubMed Central

Pavia-Ruz, Noris; Abarca, Katia; Lepetic, Alejandro; Cervantes-Apolinar, Maria Yolanda; Hardt, Karin; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay; de la O, Manuel

2015-01-01

Reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) vaccine, Boostrix™, is indicated for booster vaccination of children, adolescents and adults. The original prefilled disposable dTpa syringe presentation was recently replaced by another prefilled-syringe presentation with latex-free tip-caps and plunger-stoppers. 671 healthy adolescents aged 10–15 years who had previously received 5 or 6 previous DT(P)/dT(pa) vaccine doses, were randomized (1:1) to receive dTpa booster, injected using the new (dTpa-new) or previous syringe (dTpa-previous) presentations. Immunogenicity was assessed before and 1-month post-booster vaccination; safety/reactogenicity were assessed during 31-days post-vaccination. Non-inferiority of dTpa-new versus dTpa-previous was demonstrated for all antigens (ULs 95% CIs for GMC ratios ranged between 1.03-1.13). 1-month post-booster, immune responses were in similar ranges for all antigens with both syringe presentations. dTpa delivered using either syringe presentation was well-tolerated. These clinical results complement the technical data and support the use of the new syringe presentation to deliver the dTpa vaccine. PMID:26075317

Vacuum decay container/closure integrity testing technology. Part 2. Comparison to dye ingress tests.

PubMed

Wolf, Heinz; Stauffer, Tony; Chen, Shu-Chen Y; Lee, Yoojin; Forster, Ronald; Ludzinski, Miron; Kamat, Madhav; Mulhall, Brian; Guazzo, Dana Morton

2009-01-01

Part 1 of this series demonstrated that a container closure integrity test performed according to ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method using a VeriPac 325/LV vacuum decay leak tester by Packaging Technologies & Inspection, LLC (PTI) is capable of detecting leaks > or = 5.0 microm (nominal diameter) in rigid, nonporous package systems, such as prefilled glass syringes. The current study compared USP, Ph.Eur. and ISO dye ingress integrity test methods to PTI's vacuum decay technology for the detection of these same 5-, 10-, and 15-microm laser-drilled hole defects in 1-mL glass prefilled syringes. The study was performed at three test sites using several inspectors and a variety of inspection conditions. No standard dye ingress method was found to reliably identify all holed syringes. Modifications to these standard dye tests' challenge conditions increased the potential for dye ingress, and adjustments to the visual inspection environment improved dye ingress detection. However, the risk of false positive test results with dye ingress tests remained. In contrast, the nondestructive vacuum decay leak test method reliably identified syringes with holes > or = 5.0 microm.

Methods To Determine the Silicone Oil Layer Thickness in Sprayed-On Siliconized Syringes.

PubMed

Loosli, Viviane; Germershaus, Oliver; Steinberg, Henrik; Dreher, Sascha; Grauschopf, Ulla; Funke, Stefanie

2018-01-01

The silicone lubricant layer in prefilled syringes has been investigated with regards to siliconization process performance, prefilled syringe functionality, and drug product attributes, such as subvisible particle levels, in several studies in the past. However, adequate methods to characterize the silicone oil layer thickness and distribution are limited, and systematic evaluation is missing. In this study, white light interferometry was evaluated to close this gap in method understanding. White light interferometry demonstrated a good accuracy of 93-99% for MgF 2 coated, curved standards covering a thickness range of 115-473 nm. Thickness measurements for sprayed-on siliconized prefilled syringes with different representative silicone oil distribution patterns (homogeneous, pronounced siliconization at flange or needle side, respectively) showed high instrument (0.5%) and analyst precision (4.1%). Different white light interferometry instrument parameters (autofocus, protective shield, syringe barrel dimensions input, type of non-siliconized syringe used as base reference) had no significant impact on the measured average layer thickness. The obtained values from white light interferometry applying a fully developed method (12 radial lines, 50 mm measurement distance, 50 measurements points) were in agreement with orthogonal results from combined white and laser interferometry and 3D-laser scanning microscopy. The investigated syringe batches (lot A and B) exhibited comparable longitudinal silicone oil layer thicknesses ranging from 170-190 nm to 90-100 nm from flange to tip and homogeneously distributed silicone layers over the syringe barrel circumference (110- 135 nm). Empty break-loose (4-4.5 N) and gliding forces (2-2.5 N) were comparably low for both analyzed syringe lots. A silicone oil layer thickness of 100-200 nm was thus sufficient for adequate functionality in this particular study. Filling the syringe with a surrogate solution including short-term exposure and emptying did not significantly influence the silicone oil layer at the investigated silicone level. It thus appears reasonable to use this approach to characterize silicone oil layers in filled syringes over time. The developed method characterizes non-destructively the layer thickness and distribution of silicone oil in empty syringes and provides fast access to reliable results. The gained information can be further used to support optimization of siliconization processes and increase the understanding of syringe functionality. LAY ABSTRACT: Silicone oil layers as lubricant are required to ensure functionality of prefilled syringes. Methods evaluating these layers are limited, and systematic evaluation is missing. The aim of this study was to develop and assess white light interferometry as an analytical method to characterize sprayed-on silicone oil layers in 1 mL prefilled syringes. White light interferometry showed a good accuracy (93-99%) as well as instrument and analyst precision (0.5% and 4.1%, respectively). Different applied instrument parameters had no significant impact on the measured layer thickness. The obtained values from white light interferometry applying a fully developed method concurred with orthogonal results from 3D-laser scanning microscopy and combined white light and laser interferometry. The average layer thicknesses in two investigated syringe lots gradually decreased from 170-190 nm at the flange to 100-90 nm at the needle side. The silicone layers were homogeneously distributed over the syringe barrel circumference (110-135 nm) for both lots. Empty break-loose (4-4.5 N) and gliding forces (2-2.5 N) were comparably low for both analyzed syringe lots. Syringe filling with a surrogate solution, including short-term exposure and emptying, did not significantly affect the silicone oil layer. The developed, non-destructive method provided reliable results to characterize the silicone oil layer thickness and distribution in empty siliconized syringes. This information can be further used to support optimization of siliconization processes and increase understanding of syringe functionality. © PDA, Inc. 2018.

THE DEPENDENCE OF PRESTELLAR CORE MASS DISTRIBUTIONS ON THE STRUCTURE OF THE PARENTAL CLOUD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parravano, Antonio; Sanchez, Nestor; Alfaro, Emilio J.

2012-08-01

The mass distribution of prestellar cores is obtained for clouds with arbitrary internal mass distributions using a selection criterion based on the thermal and turbulent Jeans mass and applied hierarchically from small to large scales. We have checked this methodology by comparing our results for a log-normal density probability distribution function with the theoretical core mass function (CMF) derived by Hennebelle and Chabrier, namely a power law at large scales and a log-normal cutoff at low scales, but our method can be applied to any mass distributions representing a star-forming cloud. This methodology enables us to connect the parental cloudmore » structure with the mass distribution of the cores and their spatial distribution, providing an efficient tool for investigating the physical properties of the molecular clouds that give rise to the prestellar core distributions observed. Simulated fractional Brownian motion (fBm) clouds with the Hurst exponent close to the value H = 1/3 give the best agreement with the theoretical CMF derived by Hennebelle and Chabrier and Chabrier's system initial mass function. Likewise, the spatial distribution of the cores derived from our methodology shows a surface density of companions compatible with those observed in Trapezium and Ophiucus star-forming regions. This method also allows us to analyze the properties of the mass distribution of cores for different realizations. We found that the variations in the number of cores formed in different realizations of fBm clouds (with the same Hurst exponent) are much larger than the expected root N statistical fluctuations, increasing with H.« less

Levetiracetam selectively potentiates the acute neurotoxic effects of topiramate and carbamazepine in the rotarod test in mice.

PubMed

Luszczki, Jarogniew J; Andres, Marta M; Czuczwar, Piotr; Cioczek-Czuczwar, Anna; Wojcik-Cwikla, Joanna; Ratnaraj, Neville; Patsalos, Philip N; Czuczwar, Stanislaw J

2005-12-01

The effect of levetiracetam (LEV) on the acute neurotoxic profiles of various antiepileptic drugs (carbamazepine [CBZ], phenytoin [PHT], phenobarbital [PB], valproate [VPA], lamotrigine [LTG], topiramate [TPM], oxcarbazepine [OXC], and felbamate [FBM]) was evaluated in the rotarod test, allowing the determination of median toxic doses (TD50 values) with respect to impairment of motor coordination in mice. The TD50 of LEV administered singly was 1601 mg/kg. Whilst LEV at 150 mg/kg, being its TID50 (a dose increasing the electroconvulsive threshold by 50%), was without effect with regards to motor coordination impairment associated with PHT, PB, VPA, LTG, OXC, and FBM, it significantly enhanced that associated with CBZ and TPM co-administration. Thus LEV (150 mg/kg) significantly decreased the TD50 of CBZ from 53.6 to 37.3 mg/kg (P<0.01) and that of TPM from 423 to 246 mg/kg (P<0.01). In addition LEV (75 mg/kg) significantly decreased the TD50 of TPM from 423 to 278 (P<0.01). That concurrent measurement of total brain LEV, CBZ, and TPM concentrations showed that concentrations were not significantly different when AEDs were administered singly compared to when they were administered in combination would suggest that there is no pharmacokinetic interaction between these AEDs. Thus, the observed potentialization of the acute neurotoxic effects of CBZ and TPM by LEV is the consequence of a pharmacodynamic interaction. These data support both experimental and clinical published data advocating that LEV may interact with some AEDs by pharmacodynamic mechanisms.

Fractal scaling analysis of groundwater dynamics in confined aquifers

NASA Astrophysics Data System (ADS)

Tu, Tongbi; Ercan, Ali; Kavvas, M. Levent

2017-10-01

Groundwater closely interacts with surface water and even climate systems in most hydroclimatic settings. Fractal scaling analysis of groundwater dynamics is of significance in modeling hydrological processes by considering potential temporal long-range dependence and scaling crossovers in the groundwater level fluctuations. In this study, it is demonstrated that the groundwater level fluctuations in confined aquifer wells with long observations exhibit site-specific fractal scaling behavior. Detrended fluctuation analysis (DFA) was utilized to quantify the monofractality, and multifractal detrended fluctuation analysis (MF-DFA) and multiscale multifractal analysis (MMA) were employed to examine the multifractal behavior. The DFA results indicated that fractals exist in groundwater level time series, and it was shown that the estimated Hurst exponent is closely dependent on the length and specific time interval of the time series. The MF-DFA and MMA analyses showed that different levels of multifractality exist, which may be partially due to a broad probability density distribution with infinite moments. Furthermore, it is demonstrated that the underlying distribution of groundwater level fluctuations exhibits either non-Gaussian characteristics, which may be fitted by the Lévy stable distribution, or Gaussian characteristics depending on the site characteristics. However, fractional Brownian motion (fBm), which has been identified as an appropriate model to characterize groundwater level fluctuation, is Gaussian with finite moments. Therefore, fBm may be inadequate for the description of physical processes with infinite moments, such as the groundwater level fluctuations in this study. It is concluded that there is a need for generalized governing equations of groundwater flow processes that can model both the long-memory behavior and the Brownian finite-memory behavior.

The Dependence of Prestellar Core Mass Distributions on the Structure of the Parental Cloud

NASA Astrophysics Data System (ADS)

Parravano, Antonio; Sánchez, Néstor; Alfaro, Emilio J.

2012-08-01

The mass distribution of prestellar cores is obtained for clouds with arbitrary internal mass distributions using a selection criterion based on the thermal and turbulent Jeans mass and applied hierarchically from small to large scales. We have checked this methodology by comparing our results for a log-normal density probability distribution function with the theoretical core mass function (CMF) derived by Hennebelle & Chabrier, namely a power law at large scales and a log-normal cutoff at low scales, but our method can be applied to any mass distributions representing a star-forming cloud. This methodology enables us to connect the parental cloud structure with the mass distribution of the cores and their spatial distribution, providing an efficient tool for investigating the physical properties of the molecular clouds that give rise to the prestellar core distributions observed. Simulated fractional Brownian motion (fBm) clouds with the Hurst exponent close to the value H = 1/3 give the best agreement with the theoretical CMF derived by Hennebelle & Chabrier and Chabrier's system initial mass function. Likewise, the spatial distribution of the cores derived from our methodology shows a surface density of companions compatible with those observed in Trapezium and Ophiucus star-forming regions. This method also allows us to analyze the properties of the mass distribution of cores for different realizations. We found that the variations in the number of cores formed in different realizations of fBm clouds (with the same Hurst exponent) are much larger than the expected root {\\cal N} statistical fluctuations, increasing with H.

Determination of porcine plasma follitropin levels during superovulation treatment in cows.

PubMed

Demoustier, M M; Beckers, J F; Van Der Zwalmen, P; Closset, J; Gillard, J L; Ectors, F

1988-08-01

Porcine follicle stimulating hormone (pFSH) and porcine luteinizing hormone (pLH), are widely used to induce superovulation in cows. An advantage of this treatment is that the LH:FSH ratio can be varied to optimize the growth of the ovarian follicles. However, due to the relatively short half-life of FSH, the superovulatory treatment requires numerous injections. A performant radioimmunoassay system (sensitivity=0.2 ng/ml plasma) was used to determine plasma pFSH levels in cows that were superovulated with 2 daily injections of 4 Armour Units (A.U.) of pFSH for 4 d. From plasma profiles, the half-life and the disappearance of pFSH were estimated at 5 h and at 10 to 12 h, respectively, confirming the necessity of using two daily injections.

Exponential stability of impulsive stochastic genetic regulatory networks with time-varying delays and reaction-diffusion

DOE PAGES

Cao, Boqiang; Zhang, Qimin; Ye, Ming

2016-11-29

We present a mean-square exponential stability analysis for impulsive stochastic genetic regulatory networks (GRNs) with time-varying delays and reaction-diffusion driven by fractional Brownian motion (fBm). By constructing a Lyapunov functional and using linear matrix inequality for stochastic analysis we derive sufficient conditions to guarantee the exponential stability of the stochastic model of impulsive GRNs in the mean-square sense. Meanwhile, the corresponding results are obtained for the GRNs with constant time delays and standard Brownian motion. Finally, an example is presented to illustrate our results of the mean-square exponential stability analysis.

Chronic estrogen deficiency leads to molecular aberrations related to neurodegenerative changes in follitropin receptor knockout female mice.

PubMed

Tam, J; Danilovich, N; Nilsson, K; Sairam, M R; Maysinger, D

2002-01-01

The follitropin receptor knockout (FORKO) mouse undergoes ovarian failure, thereby providing an animal model to investigate the consequences of the depletion of circulating estrogen in females. The estrogen deficiency causes marked defects in the female reproductive system, obesity, and skeletal abnormalities. In light of estrogen's known pleiotropic effects in the nervous system, our study examined the effects of genetically induced estrogen-testosterone imbalance on this system in female FORKO mice. Circulating concentrations of 17-beta-estradiol (E2) in FORKO mice are significantly decreased (FORKO -/-: 1.13+/-0.34 pg/ml; wild-type +/+: 17.6+/-3.5 pg/ml, P<0.0001, n=32-41); in contrast, testosterone levels are increased (-/-: 37.7+/-2.3 pg/ml; wild-type +/+: 3.9+/-1.7 pg/ml, P<0.005, n=25-33). The focus was on the activities of key enzymes in the central cholinergic and peripheral nervous systems, on dorsal root ganglia (DRGs) capacity for neurite outgrowth, and on the phosphorylation state of structural neurofilament (NF) proteins. Choline acetyltransferase activity was decreased in several central cholinergic structures (striatum 50+/-3%, hippocampus 24+/-2%, cortex 12+/-3%) and in DRGs (11+/-6%). Moreover, we observed aberrations in the enzymatic activities of mitogen-activated protein kinases (extracellular-regulated kinase and c-Jun N-terminal kinase) in the hippocampus, DRGs, and sciatic nerves. Hippocampal and sensory ganglia samples from FORKO mice contained hyper-phosphorylated NFs. Finally, explanted ganglia of FORKO mice displayed decreased neurite outgrowth (20-50%) under non-treated conditions and when treated with E2 (10 nM). Our results demonstrate that genetic depletion of circulating estrogen leads to biochemical and morphological changes in central and peripheral neurons, and underlie the importance of estrogen in the normal development and functioning of the nervous system. In particular, the findings suggest that an early and persisting absence of the steroid leads to neurodegenerative changes and identify several key enzymes that may contribute to the process. This model provides a system to explore the consequences of circulating estrogen deprivation and other hormonal imbalances in the nervous system.

Container Closure Integrity Testing of Prefilled Syringes.

PubMed

Peláez, Sarah S; Mahler, Hanns-Christian; Matter, Anja; Koulov, Atanas; Singh, Satish K; Germershaus, Oliver; Mathaes, Roman

2018-04-05

Prefilled syringes (PFSs) are increasingly preferred over vials as container closure systems (CCSs) for injectable drug products when facilitated or self-administration is required. However, PFSs are more complex compared to CCSs consisting of vial, rubber stopper, and crimp cap. Container closure integrity (CCI) assurance and verification has been a specific challenge for PFSs as they feature several sealing areas. A comprehensive understanding of the CCS is necessary for an appropriate CCI assessment as well as for packaging development and qualification. A comprehensive CCI assessment of 6 different PFSs from 3 different manufacturers (including 1 polymeric PFS) was conducted using helium leak testing. PFS components were manipulated to systematically assess the contribution of the different sealing areas to CCI, namely rigid needle shield (RNS)/needle, RNS/tip cone, and the individual ribs of a syringe plunger. The polymeric PFS required an equilibrium measurement for accurate container closure integrity testing. The different sealing areas and a single plunger rib were shown to provide adequate CCI. Acceptable tip cap movement until the point of CCI failure was estimated. The assessment of acceptable tip cap movement demonstrated the importance of considering the RNS/tip cone seal design to ensure CCI of the PFS upon post assembly possesses and shipment. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Field Evaluation of Seepage Meters in the Coastal Marine Environment

NASA Astrophysics Data System (ADS)

Cable, J. E.; Burnett, W. C.; Chanton, J. P.; Corbett, D. R.; Cable, P. H.

1997-09-01

The response of seepage meters was evaluated in a nearshore marine environment where water motion effects are more pronounced than in lake settings, where these meters have been used traditionally. Temporal and spatial variations of seepage, as well as potential artifacts, were evaluated using empty and 1000-ml pre-filled bag measurements. Time-series measurements confirmed earlier observations that anomalously high fluxes occur during the early stages (≤10 min) of collection. As deployment times increased (30-60 min), measured flow rates stabilized at a level thought to represent the actual seepage flux. Pre-filling the plastic measurement bags effectively alleviated this anomalous, short-term influx. Reliable seepage measurements required deployment times sufficient to allow a net volume of at least 150 ml into the collection bag. Control experiments, designed by placing seepage meters inside sand-filled plastic swimming pools, served as indicators of external effects on these measurements, i.e. they served as seepage meter blanks. When winds were under 15 knots, little evidence was found that water motion caused artifacts in the seepage measurements. Tidal cycle influences on seepage rates were negligible in the present study area, but long-term temporal variations (weeks to months) proved substantial. Observed long-term changes in groundwater flux into the Gulf of Mexico correlated with water table elevation at a nearby monitoring well.

The Fluctuating Bond Model, a Glue for Cuprate Superconductivity?

NASA Astrophysics Data System (ADS)

Newns, Dennis

2008-03-01

Twenty years of research have yet to produce a consensus on the origin of high temperature superconductivity (HTS). The mechanism of HTS - which originates in the CuO2 plane, common to all HTS families - can be constrained by some key experimental facts regarding superconducting and pseudogap behaviors. Superconductivity, involving a Tc of order 100 K, exhibits an unusual d-wave superconducting gap, with Fermi liquid nodal excitations, and an anomalous doping- dependent oxygen isotope shift. A ``pseudogap,'' also with d-symmetry, leads to a dip in the density of states below a characteristic temperature scale T^*, which has a negative isotope shift; we associate the pseudogap with the recently observed spatially inhomogeneous (nanometer- scale) C4 symmetry breaking. The isotope shifts and other evidence imply a key role for oxygen vibrations, but conventional BCS single-phonon coupling is essentially forbidden by symmetry and by the on-site Coulomb interaction U. In a novel approach, we introduce a model based on a strong, local, nonlinear interaction between electrons within the Cu-O-Cu bond in the CuO2 plane, and the oxygen vibrational degrees of freedom, termed the Fluctuating Bond Model (FBM) [D.M. Newns and C.C. Tsuei, Nature Physics 3, 184 (2007)]. In mean field the model predicts a phase manifesting broken C4 symmetry, with a d-type pseudogap, and an upper phase boundary in temperature, with a negative isotope shift, which we identify with T^*. An intrinsic d-wave pairing tendency is found, leading to a transition temperature dome and an anomalous isotope shift similar to that found experimentally. The softening in the oxygen vibrational frequency below Tc, seen in Raman and neutron spectra, has a natural explanation in the FBM. Recent ab initio calculations have been implemented which provide microscopic support for the model.

Fractal properties of background noise and target signal enhancement using CSEM data

NASA Astrophysics Data System (ADS)

Benavides, Alfonso; Everett, Mark E.; Pierce, Carl; Nguyen, Cam

2003-09-01

Controlled-source electromagnetic (CSEM) spatial profiles and 2-D conductivity maps were obtained on the Brazos Valley, TX floodplain to study the fractal statistics of geological signals and effects of man-made conductive targets using Geonics EM34, EM31 and EM63. Using target-free areas, a consistent power-law power spectrum (|A(k)| ~ k ^-β) for the profiles was found with β values typical of fractional Brownian motion (fBm). This means that the spatial variation of conductivity does not correspond to Gaussian statistics, where there are spatial correlations at different scales. The presence of targets tends to flatten the power-law power spectrum (PS) at small wavenumbers. Detection and localization of targets can be achieved using short-time Fourier transform (STFT). The presence of targets is enhanced because the signal energy is spread to higher wavenumbers (small scale numbers) in the positions occupied by the targets. In the case of poor spatial sampling or small amount of data, the information available from the power spectrum is not enough to separate spatial correlations from target signatures. Advantages are gained by using the spatial correlations of the fBm in order to reject the background response, and to enhance the signals from highly conductive targets. This approach was tested for the EM31 using a pre-processing step that combines apparent conductivity readings from two perpendicular transmitter-receiver orientations at each station. The response obtained using time-domain CSEM is influence to a lesser degree by geological noise and the target response can be processed to recover target features. The homotopy method is proposed to solve the inverse problem using a set of possible target models and a dynamic library of responses used to optimize the starting model.

How performing a repetitive one-legged stance modifies two-legged postural control.

PubMed

Burdet, Cyril; Vuillerme, Nicolas; Rougier, Patrice R

2011-10-01

The proprioceptive cues in the control of movement is recognized as playing a major role in postural control. However, little is known about its possible increased contribution to postural control consecutive to repetitive muscular activations. To test this, the short-term effects induced by a 1-legged exercise on 2-legged postural control with the eyes closed were assessed in healthy subjects. The center-of-pressure (CP) displacements obtained using a force platform were split into 2 elementary movements: center-of-gravity vertical projection (CGv) and the difference (CP - CGv). These movements assessed the net postural performance and the level of neuromuscular activity, respectively, and were processed afterward (a) through variances, mean velocity, and the average surface covered by the trajectories and (b) a fractional Brownian motion (fBm) modeling. The latter provides further information about how much the subject controls the movements and the spatiotemporal relation between the successive control mechanisms. No difference was found using the classical parameters. In contrast, fBm parameters showed statistically significant changes in postural control after 1-legged exercises: The spatial and temporal coordinates of the transition points for the CG movements along the anteroposterior axis are decreased. Because the body movement control does not rely on visual or vestibular cues, this ability to trigger the corrective process of the CG movements more quickly in the postexercise condition and once a more reduced distance has been covered emphasizes how prior muscular activation improves body movement detection. As a general rule, these data show that the motor systems control body motions better after repetitive stimulation of the sensory cues. These insights should be of interest in physical activities based on a precise muscular length control.

Effect of mechanical processing and fat removal on the nutritive value of cottonseed for lactating dairy cows.

PubMed

Meyer, M J; Shirley, J E; Titgemeyer, E C; Park, A F; VanBaale, M J

2001-11-01

In experiment 1, 24 midlactation, multiparous Holstein cows were used in six 4 x 4 Latin squares to evaluate extruded-expelled cottonseed (EEC) as a source of ruminally undegradable protein (RUP). Diets were formulated to contain: 16% crude protein (CP), 35% RUP (SBM16); 18% CP, 35% RUP (SBM18); 16% CP, 40% RUP using EEC (EC16); and 16% CP, 40% RUP using a fishmeal-blood meal blend (FBM16). Milk yields (37.2 kg/d) and percentages of milk fat, protein, casein, and SNF were similar across diets. Cows fed FBM16 consumed less dry matter (DM) (28.0 kg/d) than those consuming other diets (29.4 kg/d). In experiment 2, 18 midlactation, multiparous Holstein cows were used in six 3 x 3 Latin squares to determine the value of EEC as a replacement for whole cottonseed in lactating cow diets. Diets contained whole cottonseed (CS), EEC plus tallow (ECT), or EEC (EC). Diets were formulated to be similar in energy, N, and RUP. Milk yields (35.5 kg/d), DM intake (27.0 kg/d), and milk fat percent were similar across diets. Percentages of milk protein and SNF were higher for EC than CS or ECT. These production data suggest that EEC can replace whole cottonseed in isocaloric diets and can be partially substituted for soybean meal or a fishmeal-blood meal blend without affecting lactational performance. In situ ruminal degradation and in vitro ammonia N release indicate that processing of EEC was inadequate to protect the protein from ruminal degradation and EEC would not be a source of RUP.

Morphological and semi-quantitative characteristics of diesel soot agglomerates emitted from commercial vehicles and a dynamometer.

PubMed

Luo, Chin-Hsiang; Lee, Whei-May; Liaw, Jiun-Jian

2009-01-01

Diesel soot aggregates emitted from a model dynamometer and 11 on-road vehicles were segregated by a micro-orifice uniform deposit impactor (MOUDI). The elemental contents and morphological parameters of the aggregates were then examined by scanning electron microscopy coupled with an energy dispersive spectrometer (SEM-EDS), and combined with a fractional Brownian motion (fBm) processor. Two mode-size distributions of aggregates collected from diesel vehicles were confirmed. Mean mass concentration of 339 mg/m3 (dC/dlogdp) existed in the dominant mode (180-320 nm). A relatively high proportion of these aggregates appeared in PM1, accentuating the relevance regarding adverse health effects. Furthermore, the fBm processor directly parameterized the SEM images of fractal like aggregates and successfully quantified surface texture to extract Hurst coefficients (H) of the aggregates. For aggregates from vehicles equipped with a universal cylinder number, the H value was independent of engine operational conditions. A small H value existed in emitted aggregates from vehicles with a large number of cylinders. This study found that aggregate fractal dimension related to H was in the range of 1.641-1.775, which is in agreement with values reported by previous TEM-based experiments. According to EDS analysis, carbon content ranged in a high level of 30%-50% by weight for diesel soot aggregates. The presence of Na and Mg elements in these sampled aggregates indicated the likelihood that some engine enhancers composed of biofuel or surfactants were commonly used in on-road vehicles in Taiwan. In particular, the morphological H combined with carbon content detection can be useful for characterizing chain-like or cluster diesel soot aggregates in the atmosphere.

Alkali metal/sulfur battery

DOEpatents

Anand, Joginder N.

1978-01-01

Alkali metal/sulfur batteries in which the electrolyte-separator is a relatively fragile membrane are improved by providing means for separating the molten sulfur/sulfide catholyte from contact with the membrane prior to cooling the cell to temperatures at which the catholyte will solidify. If the catholyte is permitted to solidify while in contact with the membrane, the latter may be damaged. The improvement permits such batteries to be prefilled with catholyte and shipped, at ordinary temperatures.

Ease of use and patient preference injection simulation study comparing two prefilled insulin pens.

PubMed

Clark, Paula E; Valentine, Virginia; Bodie, Jennifer N; Sarwat, Samiha

2010-07-01

To determine patient ease of use and preference for the Humalog KwikPen* (prefilled insulin lispro [Humalog dagger] pen, Eli Lilly and Company, Indianapolis, IN, USA) (insulin lispro pen) versus the Next Generation FlexPen double dagger (prefilled insulin aspart [NovoRapid section sign ] pen, Novo Nordisk A/S, Bagsvaerd, Denmark) (insulin aspart pen). This was a randomized, open-label, 2-period, 8-sequence crossover study in insulin pen-naïve patients with diabetes. Randomized patients (N = 367) received device training, then simulated low- (15 U) and high- (60 U) dose insulin injections with an appliance. Patients rated pens using an ease of use questionnaire and were asked separately for final pen preferences. The Insulin Device 'Ease of Use' Battery is a 10-item questionnaire with a 7-point scale (higher scores reflect greater ease of use). The primary objective was to determine pen preference for 'easy to press to inject my dose' (by comparing composite scores [low- plus high-dose]). Secondary objectives were to determine pen preference on select questionnaire items (from composite scores), final pen preference, and summary responses for all questionnaire items. On the primary endpoint, 'easy to press to inject my dose,' a statistically significant majority of patients with a preference chose the insulin lispro pen over the insulin aspart pen (68.4%, 95% CI = 62.7-73.6%). Statistically significant majorities of patients with a preference also favored the insulin lispro pen on secondary items: 'easy to hold in my hand when I inject' (64.9%, 95% CI = 58.8-70.7%), 'easy to use when I am in a public place' (67.5%, 95% CI = 61.0-73.6%), and 'overall easy to use' (69.9%, 95% CI = 63.9-75.4%). A statistically significant majority of patients had a final preference for the insulin lispro pen (67.3%, 95% CI = 62.2-72.1%). Among pen-naïve patients with diabetes who had a preference, the majority preferred the insulin lispro pen over the insulin aspart pen with regard to ease of use. Study limitations included open-label design and injection simulation, use of an unvalidated questionnaire, and enrollment of mostly insulin-naïve patients.

Protein aggregation and particle formation in prefilled glass syringes.

PubMed

Gerhardt, Alana; Mcgraw, Nicole R; Schwartz, Daniel K; Bee, Jared S; Carpenter, John F; Randolph, Theodore W

2014-06-01

The stability of therapeutic proteins formulated in prefilled syringes (PFS) may be negatively impacted by the exposure of protein molecules to silicone oil-water interfaces and air-water interfaces. In addition, agitation, such as that experienced during transportation, may increase the detrimental effects (i.e., protein aggregation and particle formation) of protein interactions with interfaces. In this study, surfactant-free formulations containing either a monoclonal antibody or lysozyme were incubated in PFS, where they were exposed to silicone oil-water interfaces (siliconized syringe walls), air-water interfaces (air bubbles), and agitation stress (occurring during end-over-end rotation). Using flow microscopy, particles (≥2 μm diameter) were detected under all conditions. The highest particle concentrations were found in agitated, siliconized syringes containing an air bubble. The particles formed in this condition consisted of silicone oil droplets and aggregated protein, as well as agglomerates of protein aggregates and silicone oil. We propose an interfacial mechanism of particle generation in PFS in which capillary forces at the three-phase (silicone oil-water-air) contact line remove silicone oil and gelled protein aggregates from the interface and transport them into the bulk. This mechanism explains the synergistic effects of silicone oil-water interfaces, air-water interfaces, and agitation in the generation of particles in protein formulations. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Cell Communication during Aggregation and Development of the Cellular Slime Mould Distyostelium discoideum.

DTIC Science & Technology

1985-01-01

of actin protein xg relative centrifugal force glorin N-propionyl- Y -L-glutawyl-L-ornithine- S- lactam ethyl ester [3 H]FA [7,9,3’,5 ’-3H]folic acid...solubilize the pellet and radioactivity was measured on a LKB Rack Beta scintillation counter. cAMP Binding to Whole Cells. This assay followed the well...inserts, pre-filled with 4ml of Unisolve I scintillant, and radioactivity measured on a LKB Rack Beta scintillation counter. Controls included: a) no

Transport behaviors of locally fractional coupled Brownian motors with fluctuating interactions

NASA Astrophysics Data System (ADS)

Wang, Huiqi; Ni, Feixiang; Lin, Lifeng; Lv, Wangyong; Zhu, Hongqiang

2018-09-01

In some complex viscoelastic mediums, it is ubiquitous that absorbing and desorbing surrounding Brownian particles randomly occur in coupled systems. The conventional method is to model a variable-mass system driven by both multiplicative and additive noises. In this paper, an improved mathematical model is created based on generalized Langevin equations (GLE) to characterize the random interaction with locally fluctuating number of coupled particles in the elastically coupled factional Brownian motors (FBM). By the numerical simulations, the effect of fluctuating interactions on collective transport behaviors is investigated, and some abnormal phenomena, such as cooperative behaviors, stochastic resonance (SR) and anomalous transport, are observed in the regime of sub-diffusion.

Waste utilization of red snapper (Lutjanus sp.) fish bone to improve phosphorus contents in compost

NASA Astrophysics Data System (ADS)

Ramadhani, S.; Iswanto, B.; Purwaningrum, P.

2018-01-01

The purpose of this research is to get the idea that bone waste will be the P content enhancer in compost so that the compost produced meets the standard P levels specified in SNI 19-7030-2004 which regulating compost quality standard. Nutrient levels were obtained in fish bone meal (FBM) are C (3.35%), N (0.48%), P (30.90%) and K (0.02%). Effects of fish bone meal to the rising levels of P in the compost has been known. P levels of compost B, C, D, and E increased at 428.57; 542.85; 657.14 and 914.28% against the compost A (blank). FBM ideal addition indicated in compost B, as much as 15 gr, with a P content of 0.37% and has been passed according standards (0.10% for P). C/N ratio decreased over the 21 days period of composting, with the greatest decline was compost E with a ratio of 16:1. Highest nitrogen (N) levels recorded respectively in compost B and C with value of 1.09% and the lowest of recorded N content was compost A, D and E (1.08%). N content in all samples of compost were eligible minimum N of 0.40%. Carbon (C) is the highest recorded in compost B; 20.20% and the lowest in the compost E; 17.34%. Highest and lowest C levels on the compost has met the minimum C of 9.80%. Composting is done in a bucket as an aerobic composter (with air holes), compost pile turnover for each sample is controlled as much as once/2 days. Mesophilic period (23-450C) occurs during the 21-day period of composting. Compost B has P content of 0.37%, so it has fulfilled the provisions of SNI 19-7030-2004 about the recommended compost standard.

Statistical physics approaches to financial fluctuations

NASA Astrophysics Data System (ADS)

Wang, Fengzhong

2009-12-01

Complex systems attract many researchers from various scientific fields. Financial markets are one of these widely studied complex systems. Statistical physics, which was originally developed to study large systems, provides novel ideas and powerful methods to analyze financial markets. The study of financial fluctuations characterizes market behavior, and helps to better understand the underlying market mechanism. Our study focuses on volatility, a fundamental quantity to characterize financial fluctuations. We examine equity data of the entire U.S. stock market during 2001 and 2002. To analyze the volatility time series, we develop a new approach, called return interval analysis, which examines the time intervals between two successive volatilities exceeding a given value threshold. We find that the return interval distribution displays scaling over a wide range of thresholds. This scaling is valid for a range of time windows, from one minute up to one day. Moreover, our results are similar for commodities, interest rates, currencies, and for stocks of different countries. Further analysis shows some systematic deviations from a scaling law, which we can attribute to nonlinear correlations in the volatility time series. We also find a memory effect in return intervals for different time scales, which is related to the long-term correlations in the volatility. To further characterize the mechanism of price movement, we simulate the volatility time series using two different models, fractionally integrated generalized autoregressive conditional heteroscedasticity (FIGARCH) and fractional Brownian motion (fBm), and test these models with the return interval analysis. We find that both models can mimic time memory but only fBm shows scaling in the return interval distribution. In addition, we examine the volatility of daily opening to closing and of closing to opening. We find that each volatility distribution has a power law tail. Using the detrended fluctuation analysis (DFA) method, we show long-term auto-correlations in these volatility time series. We also analyze return, the actual price changes of stocks, and find that the returns over the two sessions are often anti-correlated.

Temporal Variation and Scaling of Hydrological Variables in a Typical Watershed

NASA Astrophysics Data System (ADS)

Yang, C.; Zhang, Y. K.; Liang, X.; Liu, J.

2016-12-01

Temporal variations of the main hydrological variables over 16 years were systematically investigated based on the results from an integrated hydrological modeling at the Sagehen Creek Watershed in northern Sierra Nevada. Temporal scaling of these variables and damping effects of the hydrological system as well as its subsystems, i.e., the land surface, unsaturated zone, and saturated zone, were analyzed with spectral analyses. It was found that the hydrological system may act as a cascade of hierarchical fractal filters which sequentially transfer a non-fractal or less correlated fractal hydrological signal to a more correlated fractal signal. Temporal scaling of infiltration (I), actual evapotraspiration (ET), recharge (R), baseflow (BF), streamflow (SF) exist and the temporal autocorrelation of these variables increase as water moves through the system. The degree of the damping effect of the subsystems is different and is strongest in the unsaturated zone compared with that of the land surface and saturated zone. The temporal scaling of the groundwater levels (h) also exists and is strongly affected by the river: the temporal autocorrelation of h near the river is similar to that of the river stage fluctuations and increases away from the river. There is a break in the temporal scaling of h near the river at low frequencies due to the effect of the river. Temporal variations of the soil moisture (θ) is more complicated: the value of the scaling exponent (β) for θ increases with depth as water moves downwards and its high-frequency fluctuations are damped by the unsaturated zone. The temporal fluctuations of precipitation (P) and I are fractional Gauss noise (fGn), those of ET, R, BF, and SF are fractional Brownian motion (fBm), and those of h away from the river are 2nd-order fBm based on the values of β obtained in this study. Keywords: Temporal variations, Scaling, Damping effect, Hydrological system.

Advanced Motor-Controller Development.

DTIC Science & Technology

1983-06-22

OUTPUTS: 16 BIT PROE:UCT IN ACCA , FiCC:B Oi:t2 -* 0011: 0172 B:7 .04E SIFY STA A MCAN:,* SF,-’E MULTIPLICAND 001t4 0175 iF CLF: A INIT RESUI_I_T AOll5...OL-:t41) 04: ELSE ACCA IS UNC:HANGED 0-142 01SF ::,A 0CI CLAMP 0’Fi A #0 TEST SIGN OF A C0It 0l91 E’E: fBM I C.LIPI EBRFNCH IF NEG 01t4 4 : : 001,15 19...ELSE S.:ET ACCA =-ACCB:1B TQJ5. 01 .’ NEG B .ESTOPE ACCE: 01155 C. l1’-9 E -9 PTI RETUR’N Al? I .9~~ _________ . .... ... | |- - - - . . rjOt :E

Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.

PubMed

Gao, Jianjun; Tiwari-Pandey, Rashmi; Samadfam, Rana; Yang, Yinzhi; Miao, Dengshun; Karaplis, Andrew C; Sairam, M Ram; Goltzman, David

2007-06-01

Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth.

PubMed

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth

PubMed Central

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

We present a case with a severe injection error: a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth. PMID:24592042

Optimisation of a two-liquid component pre-filled acrylic bone cement system: a design of experiments approach to optimise cement final properties.

PubMed

Clements, James; Walker, Gavin; Pentlavalli, Sreekanth; Dunne, Nicholas

2014-10-01

The initial composition of acrylic bone cement along with the mixing and delivery technique used can influence its final properties and therefore its clinical success in vivo. The polymerisation of acrylic bone cement is complex with a number of processes happening simultaneously. Acrylic bone cement mixing and delivery systems have undergone several design changes in their advancement, although the cement constituents themselves have remained unchanged since they were first used. This study was conducted to determine the factors that had the greatest effect on the final properties of acrylic bone cement using a pre-filled bone cement mixing and delivery system. A design of experiments (DoE) approach was used to determine the impact of the factors associated with this mixing and delivery method on the final properties of the cement produced. The DoE illustrated that all factors present within this study had a significant impact on the final properties of the cement. An optimum cement composition was hypothesised and tested. This optimum recipe produced cement with final mechanical and thermal properties within the clinical guidelines and stated by ISO 5833 (International Standard Organisation (ISO), International standard 5833: implants for surgery-acrylic resin cements, 2002), however the low setting times observed would not be clinically viable and could result in complications during the surgical technique. As a result further development would be required to improve the setting time of the cement in order for it to be deemed suitable for use in total joint replacement surgery.

In vitro performance of prefilled CO2 absorbers with the Zeus®.

PubMed

Omer, Mohab; Hendrickx, Jan F A; De Ridder, Simon; De Houwer, Alexander; Carette, Rik; De Cooman, Sofie; De Wolf, Andre M

2017-12-13

Low fresh gas flows (FGFs) decrease the use of anesthetic gases, but increase CO 2 absorbent usage. CO 2 absorbent usage remains poorly quantified. The goal of this study is to determine canister life of 8 commercially available CO 2 absorbent prepacks with the Zeus ® . Pre-packed CO 2 canisters of 8 different brands were tested in vitro: Amsorb Plus, Spherasorb, LoFloSorb, LithoLyme, SpiraLith, SpheraSorb, Drägersorb 800+, Drägersorb Free, and CO2ntrol. CO 2 (160 mL min - 1 ) flowed into the tip of a 2 L breathing bag that was ventilated with a tidal volume of 500 mL, a respiratory rate of 10/min, and an I:E ratio of 1:1 using the controlled mechanical ventilation mode of the Zeus ® (Dräger, Lubeck, Germany). In part I, canister life of 5 canisters each of 2 different lots of each brand was determined with a 350 mL min - 1 FGF. Canister life is the time it takes for the inspired CO 2 concentration (F I CO 2 ) to rise to 0.5%. In part II, canister life was measured accross a FGF range of 0.25 to 4 L min - 1 for Drägersorb 800+ (2 lots) and SpiraLith (1 lot). In part III, the calculated canister life per 100 g fresh granule content of the different brands was compared between the Zeus and (previously published data for) the Aisys. In vitro canister life of prefilled CO 2 absorber canisters differed between brands, and depended on the amount of CO 2 absorbent and chemical composition. Canister life expressed as FCU 0.5 (the fraction of the canister used per hour) was proportional to FGF over 0.2-2 L min -1 range only, but was non-linear with higher FGF: FCU 0.5 was larger than expected with FGF > 2 L min -1 , and even with FGF > minute ventilation FCU 0.5 did not become zero, indicating some CO 2 was being absorbed. Canister life on a per weight basis of the same brand is higher with the Zeus than the Aisys. Canister life of prefilled CO 2 absorber canisters differs between brands. The FCU 0.5 -FGF relationship is not linear across the entire FGF range. Canister life of prepacks of the same brand for the Zeus and Aisys differs, the exact etiology of which is probably multifactorial, and may include differences in the absolute amount of absorbent and different rebreathing characteristics of the machines.

Stability of sodium bicarbonate injection 8.4% in syringes over a six-week period in refrigerated temperature.

PubMed

Seki, Jack T; Wang, Tian Q; Yip, Paul M; Mazzulli, Tony; Minden, Mark D

2018-04-01

Background Dysfunctional central venous catheter prohibits the administration of potential life-saving chemotherapy and the delivery of essential supportive care needs to patients. Sodium bicarbonate injection has been shown to impede against fibrin clot formation and prolong prothrombin time and thrombin clotting time. Sodium bicarbonate injection has been tried as a second-line agent with good results in a small number of patients (internal data not published) when alteplase failed. We assessed whether the pre-filled sodium bicarbonate injection in 5 mL syringes would not only preserve sterility and retain its pH and concentration but also amount to the potential cost savings for future use when stored in a refrigerated environment. Methodology Twelve pre-filled 5 mL syringes were prepared aseptically, of which four each were tested for pH, sodium bicarbonate injection concentration and sterility when stored in refrigerated temperature over a six-week period. A standard pH meter, enzymatic carbon dioxide analyzer, and a 14-day incubation for microbial detection were employed for this study. Results Sodium bicarbonate concentration measured in the form of carbon dioxide ranged from 923 mmol/L or (1846 mosol/L) to 1006 mmol/L or (2012 mosmol/L), and pH ranged from (7.88 to 8.05) were reported over the duration of the study period. The 14-day incubation period resulted in no microbial growth. Conclusion Our study results have indicated that the pH and sodium bicarbonate injection concentration values were stable and within range, comparable to those reported by the manufacturer within the study period. The contents of the subdivided sodium bicarbonate injection 5 mL syringes retained sterility over a 14-day incubation period.

[Preference for etanercept pen versus syringe in patients with chronic arthritis. Nurse education workshop].

PubMed

Garcia-Diaz, Silvia; Girabent-Farrés, Montserrat; Roig-Vilaseca, Daniel; Reina, Delia; Cerdà, Dacia; González, Marina; Torrente-Segarra, Vicenç; Fíguls, Ramon; Corominas, Hèctor

2013-01-01

The aims of this study are to evaluate the level of fear of post-injection pain prior to the administration, the difficulty in handling the device, and the level of satisfaction of patients using a pre-filled syringe versus an etanercept pen, as well as to evaluate the usefulness of the training given by nursing staff prior to starting with the pen, and the preferences of patients after using both devices. A prospective study was designed to follow-up a cohort of patients during a 6 months period. The data was collected using questionnaires and analyzed with SPSS 18.00. Rank and McNemar tests were performed. Statistical significance was pre-set at an α level of 0.05. A total of 29 patients were included, of whom 69% female, and with a mean age 52.5±10.9 years. Of these, 48% had rheumatoid arthritis, 28% psoriatic arthritis, 21% ankylosing spondylitis, and 3% undifferentiated spondyloarthropathy. There were no statistically significant differences either with the fear or pain or handling of the device between the syringe and the pen (P=.469; P=.812; P=.169 respectively). At 6 months, 59% of patients referred to being satisfied or very satisfied with the pen. Almost all (93%) found useful or very useful the training given by nursing staff prior to using the pen, and 55% preferred the pen over the pre-filled syringe. The etanercept pen is another subcutaneous device option for patients with chronic arthritis. According to the present study, nursing educational workshops before starting this therapy are recommended. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Clogging in staked-in needle pre-filled syringes (SIN-PFS): Influence of water vapor transmission through the needle shield.

PubMed

De Bardi, M; Müller, R; Grünzweig, C; Mannes, D; Rigollet, M; Bamberg, F; Jung, T A; Yang, K

2018-06-01

Staked-in needle pre-fillable syringes (SIN-PFS) are a convenient delivery system widely established in the growing pharmaceutical market. Under specific storage conditions, the needle of PFS containing high concentration drug product (DP) solution is prone to clogging, which prevents administration of the liquid. The purpose of this study is to clarify the clogging phenomenon of SIN-PFS and to elucidate the role of water vapor transmission via the needle shield. The presence of liquid within needles is a prerequisite condition for clogging and was investigated non-invasively by neutron imaging (NI) to confirm that liquid can migrate into the needle under certain processing conditions. The water vapor transmission rate (WVTR) of different needle shields was measured and the impact of temperature and relative humidity (rH) on the WVTR was investigated on sheets with the same composition as used in commercial needle shields. Our study clearly showed that the partial vapor pressure difference (ΔPP) across the needle shield is the dominant driving factor for water vapor transmission. A linear correlation between ΔPP and WVTR was found and a model to predict the water vapor transmission for PFS under specific storage conditions was developed. The impact of the WVTR on needle clogging was confirmed by clogging tests performed on SIN-PFS stored under different conditions. Thereby, we clearly show that high water loss induced by higher WVTR can be correlated to an increased occurrence of needle clogging. In conclusion, the WVTR of the needle shield plays a key role in needle clogging and the established WVTR model can be employed to assess the clogging risk for product development. Copyright © 2018 Elsevier B.V. All rights reserved.

SureClick® (Darbepoetin alfa) can improve perceived satisfaction and competence for anemia treatment and increase self-administration in non-dialyzed patients with chronic kidney disease.

PubMed

Bonafont, Xavier; Romero, Ramón; Martínez, Isabel; del Pino, María D; Gil, José M; Aranda, Pedro; Roca, Ramón; Claverol, Joana; Cucala, Mercedes

2013-01-01

SureClick® is a prefilled pen for administration of darbepoetin alfa (DA) that is ready-to-use. We explored patient satisfaction with SureClick® compared with prefilled syringes (PFS). Multicenter, prospective, 6-months, observational study in non-dialyzed patients with chronic kidney disease (CKD) treated with DA in PFS who switched to SureClick® at baseline. Main outcomes were: change in Anemia Treatment Satisfaction Questionnaire (ATSQ-S), Perceived Competence for Anemia Scale (PCAS) and self-administration rate. We enrolled 132 patients with a mean(SD) age of 71.3 (14.6) years, 57.6% women. Mean(SD) ATSQ-S scores at baseline and final records were 25.5 (7.9) and 31.6 (4.9) (on a scale from 0 to 36 maximum satisfaction-, mean change: 6.2, 95%CI: 4.6-7.8, p<0.0001). The PCAS also increased significantly (4.3 (2.0) vs 5.6 (1.6), on a scale from 1 to 7 maximum competence, p<0.0001). At baseline 47.7% of patients self-administered DA with PFS, vs 74.2% with SureClick® (p<0.001). No significant changes in hemoglobin were observed (11.4 (0.5) vs 11.6 (1.3) g/dl, p=0.193). Two patients (1.5%) had adverse reactions to SureClick® (pain on application). Our results suggest that the change from PFS to SureClick® could increase patient satisfaction and perceived competence in anemia management in non-dialyzed CKD patients, and could increase the self-administration rate, thereby reducing use of health resources.

Ready-to-use pre-filled syringes of atropine for anaesthesia care in French hospitals - a budget impact analysis.

PubMed

Benhamou, Dan; Piriou, Vincent; De Vaumas, Cyrille; Albaladejo, Pierre; Malinovsky, Jean-Marc; Doz, Marianne; Lafuma, Antoine; Bouaziz, Hervé

2017-04-01

Patient safety is improved by the use of labelled, ready-to-use, pre-filled syringes (PFS) when compared to conventional methods of syringe preparation (CMP) of the same product from an ampoule. However, the PFS presentation costs more than the CMP presentation. To estimate the budget impact for French hospitals of switching from atropine in ampoules to atropine PFS for anaesthesia care. A model was constructed to simulate the financial consequences of the use of atropine PFS in operating theatres, taking into account wastage and medication errors. The model tested different scenarios and a sensitivity analysis was performed. In a reference scenario, the systematic use of atropine PFS rather than atropine CMP yielded a net one-year budget saving of €5,255,304. Medication errors outweighed other cost factors relating to the use of atropine CMP (€9,425,448). Avoidance of wastage in the case of atropine CMP (prepared and unused) was a major source of savings (€1,167,323). Significant savings were made by means of other scenarios examined. The sensitivity analysis suggests that the results obtained are robust and stable for a range of parameter estimates and assumptions. The financial model was based on data obtained from the literature and expert opinions. The budget impact analysis shows that even though atropine PFS is more expensive than atropine CMP, its use would lead to significant cost savings. Savings would mainly be due to fewer medication errors and their associated consequences and the absence of wastage when atropine syringes are prepared in advance. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

[Interest of evaluation of professional practice for the improvement of the management of postoperative pain with patient controlled analgesia (PCA)].

PubMed

Baumann, A; Cuignet-Royer, E; Cornet, C; Trueck, S; Heck, M; Taron, F; Peignier, C; Chastel, A; Gervais, P; Bouaziz, H; Audibert, G; Mertes, P-M

2010-10-01

To evaluate the daily practice of postoperative PCA in Nancy University Hospital, in continuity with a quality program of postoperative pain (POP) care conducted in 2003. A retrospective audit of patient medical records. A review of all the medical records of consecutive surgical patients managed by PCA over a 5-week period in six surgical services. Criteria studied: Evaluation of hospital means (eight criteria) and of medical and nursing staff practice (16 criteria). A second audit was conducted 6 months after the implementation of quality improvement measures. Assessment of the hospital means: temperature chart including pain scores and PCA drug consumption, patient information leaflet, PCA protocol, postoperative pre-filled prescription form (PFPF) for post-anaesthesia care including PCA, and optional training of nurses in postoperative pain management. EVALUATION OF PRACTICES: One hundred and fifty-nine files of a total of 176 patients were analyzed (88%). Improvements noted after 6 months: trace of POP evaluation progressed from 73 to 87%, advance prescription of PCA adjustment increased from 56 to 68% and of the treatment of adverse effects from 54 to 68%, trace of PCA adaptation by attending nurse from 15 to 43%, trace of the administration of the treatment of adverse effects by attending nurse from 24% to 64%, as did the use of PFPF from 59 to 70%. The usefulness of a pre-filled prescription form for post-anaesthesia care including PCA prescription is demonstrated. Quality improvement measures include: poster information and pocket guides on PCA for nurses, training of 3 nurses per service to act as "PCA advisers" who will in turn train their ward colleagues in PCA management and the use of equipment until an acute pain team is established. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

The effects, safety and acceptability of compact, pre-filled, autodisable injection devices when delivered by lay health workers.

PubMed

Glenton, Claire; Khanna, Rajesh; Morgan, Chris; Nilsen, Elin Strømme

2013-08-01

To systematically assess (i) the effects and safety and (ii) the acceptability of using lay health workers (LHWs) to deliver vaccines and medicines to mothers and children through compact pre-filled autodisable devices (CPADs). We searched electronic databases and grey literature. For the systematic review of effects and safety, we sought randomised and non-randomised controlled trials, controlled before-after studies and interrupted time series studies. For the systematic review of acceptability, we sought qualitative studies. Two researchers independently carried out data extraction, study quality assessment and thematic analysis of the qualitative data. No studies met our criteria for the review exploring the effects and safety of using LHWs to deliver CPADs. For the acceptability review, six qualitative studies assessed the acceptability of using LHWs to deliver hepatitis B vaccine, tetanus toxoid vaccine, gentamicin or oxytocin using Uniject™ devices. All studies took place in low- or middle-income countries and explored the perceptions of community members, LHWs, supervisors, health professionals or programme managers. Most of the studies were of low quality. Recipients generally accepted the intervention. Most health professionals were confident that LHWs could deliver the intervention with sufficient training and supervision, but some had problems delivering supervision. The LHWs perceived Uniject™ as effective and important and were motivated by positive responses from the community. However, some LHWs feared the consequences if harm should come to recipients. Evidence of the effects and safety of using CPADs delivered by LHWs is lacking. Evidence regarding acceptability suggests that this intervention may be acceptable although LHWs may feel vulnerable to blame. © 2013 John Wiley & Sons Ltd.

The impact of derivatives on Malaysian stock market

NASA Astrophysics Data System (ADS)

Malim, M. R.; Halim, F. A.; Murad, A.; Maad, H. A.; Annuar, N. F. M.

2017-09-01

The essential of derivatives has been discovered by researchers over recent decade. However, the conclusions made regarding the impact of derivatives on stock market volatility remains debatable. The main objective of this study is to examine the impact of derivatives on Malaysian stock market volatility by exploring FTSE Bursa Malaysia Kuala Lumpur Composite Index Futures (BMD FKLI) using FBM KLCI as the underlying asset. Generalized Autoregressive Conditional Heteroskedasticity (GARCH) (1, 1) model was employed to realize the objective. The results have shown that the introduction of futures trading has decreased the volatility of Malaysian stock market. The volatility increased vigorously during the Asian financial crisis compared to the Global financial crisis. However, the role of futures as a risk transfer is agreed as it could improve the market by decreasing the volatility in the spot market.

[Can we transfer the mechanisms of the generics market to biosimilars?

PubMed

Jacke, Ch O; Wild, F

2016-12-15

Personalized medicines such as biologics and their generic equivalents, biosimilars, are pouring onto the pharmaceutical markets. Data of 16 private health insurance companies were used to describe the market shares of selected biosimilars available in 2014 and 2015. The purpose of this study focuses on the question of whether market access of biosimilars will lead to a price competition of the expense of innovation competition. The results show that prescriptions of biosimilars made up 37% of total prescriptions in 2015 compared to 35% in 2014, and that their share of prescription costs went up from 21% to 23% in the same period. Price competition similar to that found in the generic markets has been established for erythropoietin and filgrastim. The same has not been observed for follitropin alfa and somatropin due to the limited number of competitors and products available at this stage. No definitive conclusions can be drown from the results at this stage. Time will tell whether it will be possible for physicians and individuals with private health insurance to fully leverage the savings potential of biosimilars while safeguarding patient safety.

Note: A pulsed laser ion source for linear induction accelerators

NASA Astrophysics Data System (ADS)

Zhang, H.; Zhang, K.; Shen, Y.; Jiang, X.; Dong, P.; Liu, Y.; Wang, Y.; Chen, D.; Pan, H.; Wang, W.; Jiang, W.; Long, J.; Xia, L.; Shi, J.; Zhang, L.; Deng, J.

2015-01-01

We have developed a high-current laser ion source for induction accelerators. A copper target was irradiated by a frequency-quadrupled Nd:YAG laser (266 nm) with relatively low intensities of 108 W/cm2. The laser-produced plasma supplied a large number of Cu+ ions (˜1012 ions/pulse) during several microseconds. Emission spectra of the plasma were observed and the calculated electron temperature was about 1 eV. An induction voltage adder extracted high-current ion beams over 0.5 A/cm2 from a plasma-prefilled gap. The normalized beam emittance measured by a pepper-pot method was smaller than 1 π mm mrad.

Experimental characterization of active plasma lensing for electron beams

NASA Astrophysics Data System (ADS)

Pompili, R.; Anania, M. P.; Bellaveglia, M.; Biagioni, A.; Bini, S.; Bisesto, F.; Brentegani, E.; Castorina, G.; Chiadroni, E.; Cianchi, A.; Croia, M.; Di Giovenale, D.; Ferrario, M.; Filippi, F.; Giribono, A.; Lollo, V.; Marocchino, A.; Marongiu, M.; Mostacci, A.; Di Pirro, G.; Romeo, S.; Rossi, A. R.; Scifo, J.; Shpakov, V.; Vaccarezza, C.; Villa, F.; Zigler, A.

2017-03-01

The active plasma lens represents a compact and affordable tool with radially symmetric focusing and field gradients up to several kT/m. In order to be used as a focusing device, its effects on the particle beam distribution must be well characterized. Here, we present the experimental results obtained by focusing an high-brightness electron beam by means of a 3 cm-long discharge-capillary pre-filled with Hydrogen gas. We achieved minimum spot sizes of 24 μ m (rms) showing that, during plasma lensing, the beam emittance increases due to nonlinearities in the focusing field. The results have been cross-checked with numerical simulations, showing an excellent agreement.

Hurst Estimation of Scale Invariant Processes with Stationary Increments and Piecewise Linear Drift

NASA Astrophysics Data System (ADS)

Modarresi, N.; Rezakhah, S.

The characteristic feature of the discrete scale invariant (DSI) processes is the invariance of their finite dimensional distributions by dilation for certain scaling factor. DSI process with piecewise linear drift and stationary increments inside prescribed scale intervals is introduced and studied. To identify the structure of the process, first, we determine the scale intervals, their linear drifts and eliminate them. Then, a new method for the estimation of the Hurst parameter of such DSI processes is presented and applied to some period of the Dow Jones indices. This method is based on fixed number equally spaced samples inside successive scale intervals. We also present some efficient method for estimating Hurst parameter of self-similar processes with stationary increments. We compare the performance of this method with the celebrated FA, DFA and DMA on the simulated data of fractional Brownian motion (fBm).

Nozzle Initiative Industry Advisory Committee on Standardization of Carbon-Phenolic Test Methods and Specifications

NASA Technical Reports Server (NTRS)

Bull, William B. (Compiler); Pinoli, Pat C. (Compiler); Upton, Cindy G. (Compiler); Day, Tony (Compiler); Hill, Keith (Compiler); Stone, Frank (Compiler); Hall, William B.

1994-01-01

This report is a compendium of the presentations of the 12th biannual meeting of the Industry Advisory Committee under the Solid Propulsion Integrity Program. A complete transcript of the welcoming talks is provided. Presentation outlines and overheads are included for the other sessions: SPIP Overview, Past, Current and Future Activity; Test Methods Manual and Video Tape Library; Air Force Developed Computer Aided Cure Program and SPC/TQM Experience; Magneto-Optical mapper (MOM), Joint Army/NASA program to assess composite integrity; Permeability Testing; Moisture Effusion Testing by Karl Fischer Analysis; Statistical Analysis of Acceptance Test Data; NMR Phenolic Resin Advancement; Constituent Testing Highlights on the LDC Optimization Program; Carbon Sulfur Study, Performance Related Testing; Current Rayon Specifications and Future Availability; RSRM/SPC Implementation; SRM Test Methods, Delta/Titan/FBM/RSRM; and Open Forum on Performance Based Acceptance Testing -- Industry Experience.

Note: A pulsed laser ion source for linear induction accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, H., E-mail: bamboobbu@hotmail.com; School of Physics, Peking University, Beijing 100871; Zhang, K.

2015-01-15

We have developed a high-current laser ion source for induction accelerators. A copper target was irradiated by a frequency-quadrupled Nd:YAG laser (266 nm) with relatively low intensities of 10{sup 8} W/cm{sup 2}. The laser-produced plasma supplied a large number of Cu{sup +} ions (∼10{sup 12} ions/pulse) during several microseconds. Emission spectra of the plasma were observed and the calculated electron temperature was about 1 eV. An induction voltage adder extracted high-current ion beams over 0.5 A/cm{sup 2} from a plasma-prefilled gap. The normalized beam emittance measured by a pepper-pot method was smaller than 1 π mm mrad.

Sources and characteristics of acoustic emissions from mechanically stressed geologic granular media — A review

NASA Astrophysics Data System (ADS)

Michlmayr, Gernot; Cohen, Denis; Or, Dani

2012-05-01

The formation of cracks and emergence of shearing planes and other modes of rapid macroscopic failure in geologic granular media involve numerous grain scale mechanical interactions often generating high frequency (kHz) elastic waves, referred to as acoustic emissions (AE). These acoustic signals have been used primarily for monitoring and characterizing fatigue and progressive failure in engineered systems, with only a few applications concerning geologic granular media reported in the literature. Similar to the monitoring of seismic events preceding an earthquake, AE may offer a means for non-invasive, in-situ, assessment of mechanical precursors associated with imminent landslides or other types of rapid mass movements (debris flows, rock falls, snow avalanches, glacier stick-slip events). Despite diverse applications and potential usefulness, a systematic description of the AE method and its relevance to mechanical processes in Earth sciences is lacking. This review is aimed at providing a sound foundation for linking observed AE with various micro-mechanical failure events in geologic granular materials, not only for monitoring of triggering events preceding mass mobilization, but also as a non-invasive tool in its own right for probing the rich spectrum of mechanical processes at scales ranging from a single grain to a hillslope. We review first studies reporting use of AE for monitoring of failure in various geologic materials, and describe AE generating source mechanisms in mechanically stressed geologic media (e.g., frictional sliding, micro-crackling, particle collisions, rupture of water bridges, etc.) including AE statistical features, such as frequency content and occurrence probabilities. We summarize available AE sensors and measurement principles. The high sampling rates of advanced AE systems enable detection of numerous discrete failure events within a volume and thus provide access to statistical descriptions of progressive collapse of systems with many interacting mechanical elements such as the fiber bundle model (FBM). We highlight intrinsic links between AE characteristics and established statistical models often used in structural engineering and material sciences, and outline potential applications for failure prediction and early-warning using the AE method in combination with the FBM. The biggest challenge to application of the AE method for field applications is strong signal attenuation. We provide an outlook for overcoming such limitations considering emergence of a class of fiber-optic based distributed AE sensors and deployment of acoustic waveguides as part of monitoring networks.

A Survey of the American Society of Anesthesiologists Regarding Environmental Attitudes, Knowledge, and Organization.

PubMed

Ard, John L; Tobin, Katherine; Huncke, Tessa; Kline, Richard; Ryan, Susan M; Bell, Charlotte

2016-04-01

Our planet is in the midst of an environmental crisis. Government and international agencies such as the Intergovernmental Panel on Climate Change urge radical and transformative change at every level of how we conduct our personal and professional lives. The health care industry contributes to climate change. According to a study from the University of Chicago, the health care sector accounts for 8% of the United States' total greenhouse gas emissions. In an effort to understand the current state of environmental practice, attitudes, and knowledge among anesthesiologists in the United States, we conducted a survey of American anesthesiologists regarding environmental sustainability. The environmental survey was sent out by e-mail to a random sampling of 5200 members of the American Society of Anesthesiologists. This process was repeated a second time. A total of 2189 anesthesiologists of 5200 responded to the survey, a 42% response rate. Of the survey respondents, 80.1% (confidence interval, 78.2%-81.9%) were interested in recycling. Respondents reported recycling in 27.7% of operating rooms where they work. The majority of respondents (67%; confidence interval, 64%-69%) reported there was insufficient information on how to recycle intraoperatively. Respondents supported sustainability practices such as reprocessing equipment, using prefilled syringes, and donating unused equipment and supplies. The affirmative response rate was 48.4% for reprocessing equipment, 56.6% for using prefilled syringes, and 65.1% for donating equipment and supplies to medical missions. Questions about hospital-wide organization of sustainability programs elicited many "I don't know" responses. Eighteen percent of responders indicated the presence of a sustainability or "green" task force. A total of 12.6% of responders indicated the presence of a mandate from hospital leadership to promote sustainability programs. Two important conclusions drawn from the survey data are a lack of hospital-wide organization of sustainability programs and a belief among survey responders that they lack adequate information on recycling and sustainability.

Viscoelastic substance in prefilled syringe as an etiology of Toxic Anterior Segment Syndrome.

PubMed

Althomali, Talal Abdulrahman

2016-09-01

Toxic Anterior Segment Syndrome (TASS) is an acute postoperative inflammatory reaction in which a noninfectious substance enters the anterior segment and induces toxic damage to the intraocular tissues. To present etiologic investigation of two consecutive clusters of TASS. TASS outbreak and investigation: This paper presents two consecutive clusters of TASS in 15 of the 24 uneventful surgeries and the investigation carried out to find the etiology. After the occurrence of first cluster of TASS, sterilization-related etiology was explored; however, we did not find any lacunae in the sterilization and cleaning process in the operating theater (OT). Nevertheless, multiple changes in cleaning process were implemented. Still a second cluster of TASS was encountered in the following session of OT. Several other factors which include preservatives, hand gloves, intraocular lenses, medications/solutions, intraocular penetration of topically administered drugs, and viscoelastics were investigated as the possible etiology of the second consecutive cluster of TASS; however, most of them were ruled out. The newly introduced viscoelastic I-visc® 1.4% sodium hyaluronate (I medical, i-Medical Ophthalmic International GmbH, Heidelberg, Germany) was thought to be the most likely cause and was replaced with previously in use sodium hyaluronate 1.5% and lidocaine hydrochloride 1% (Visthesia, CZ, Germany) in the following session of OT. No further TASS incident was encountered after replacing the viscoelastic. Investigation revealed that 1.4% sodium hyaluronate in prefilled syringe (PFS) (I-visc® 1.4%) was the etiologic factor of two consecutive clusters of TASS. While TASS due to residual denatured ophthalamic viscosurgical devices (OVDs) is a common knowledge, current study brings out that even disposable viscoelastic material supplied in PFSs can be an etiology of TASS. It is important to recognize that contamination of OVDs with endotoxins can occur at the time of manufacturing. Therefore, in the absence of appropriate guidelines for ophthalmic preparations, endotoxin limit for medical preparations (i.e. <0.5 endotoxin units/ml) must be considered during OVD manufacture.

Plasma-gun-assisted field-reversed configuration formation in a conical θ-pinch

NASA Astrophysics Data System (ADS)

Weber, T. E.; Intrator, T. P.; Smith, R. J.

2015-04-01

Injection of plasma via an annular array of coaxial plasma guns during the pre-ionization phase of field-reversed configuration (FRC) formation is shown to catalyze the bulk ionization of a neutral gas prefill in the presence of a strong axial magnetic field and change the character of outward flux flow during field-reversal from a convective process to a much slower resistive diffusion process. This approach has been found to significantly improve FRC formation in a conical θ-pinch, resulting in a ˜350% increase in trapped flux at typical operating conditions, an expansion of accessible formation parameter space to lower densities and higher temperatures, and a reduction or elimination of several deleterious effects associated with the pre-ionization phase.

Application of ground-penetrating radar at McMurdo Station, Antarctica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stefano, J.E.

1992-05-01

Argonne National Laboratory initiated a site investigation program at McMurdo Station, Antarctica, to characterize environmental contamination. The performance and usefulness of ground-penetrating radar (GPR) was evaluated under antarctic conditions during the initial site investigation in January 1991. Preliminary surveys were successful in defining the contact between reworked pyroclastic material and in the prefill, undisturbed pyroclastics and basalts at some sites. Interference from radio traffic at McMurdo Station was not observed, but interference was a problem in work with unshielded antennas near buildings. In general, the results of this field test suggest that high-quality, high-resolution, continuous subsurface profiles can be producedmore » with GPR over most of McMurdo Station.« less

Application of ground-penetrating radar at McMurdo Station, Antarctica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stefano, J.E.

1992-01-01

Argonne National Laboratory initiated a site investigation program at McMurdo Station, Antarctica, to characterize environmental contamination. The performance and usefulness of ground-penetrating radar (GPR) was evaluated under antarctic conditions during the initial site investigation in January 1991. Preliminary surveys were successful in defining the contact between reworked pyroclastic material and in the prefill, undisturbed pyroclastics and basalts at some sites. Interference from radio traffic at McMurdo Station was not observed, but interference was a problem in work with unshielded antennas near buildings. In general, the results of this field test suggest that high-quality, high-resolution, continuous subsurface profiles can be producedmore » with GPR over most of McMurdo Station.« less

Analysis of solid particles falling down and interacting in a channel with sedimentation using fictitious boundary method

NASA Astrophysics Data System (ADS)

Usman, K.; Walayat, K.; Mahmood, R.; Kousar, N.

2018-06-01

We have examined the behavior of solid particles in particulate flows. The interaction of particles with each other and with the fluid is analyzed. Solid particles can move freely through a fixed computational mesh using an Eulerian approach. Fictitious boundary method (FBM) is used for treating the interaction between particles and the fluid. Hydrodynamic forces acting on the particle's surface are calculated using an explicit volume integral approach. A collision model proposed by Glowinski, Singh, Joseph and coauthors is used to handle particle-wall and particle-particle interactions. The particulate flow is computed using multigrid finite element solver FEATFLOW. Numerical experiments are performed considering two particles falling and colliding and sedimentation of many particles while interacting with each other. Results for these experiments are presented and compared with the reference values. Effects of the particle-particle interaction on the motion of the particles and on the physical behavior of the fluid-particle system has been analyzed.

The suitability of monopolar and bipolar ion exchange membranes as separators for biological fuel cells.

PubMed

Harnisch, Falk; Schröder, Uwe; Scholz, Fritz

2008-03-01

A proton exchange (Nafion-117), a cation exchange (Ultrex CMI7000), an anion exchange (Fumasep FAD), and a bipolar (FumasepFBM) membrane have been studied to evaluate the principle suitability of ion exchange membranes as separators between the anode and the cathode compartment of biological fuel cells. The applicability of these membranes is severely affected by the neutral pH, and the usually low ionic strength of the electrolyte solutions. Thus, the ohmic resistance of the monopolar membranes was found to greatly increase at neutral pH and at decreasing electrolyte concentrations. None of the studied membranes can prevent the acidification of the anode and the alkalization of the cathode compartment, which occurs in the course of the fuel cell operation. Bipolar membranes are shown to be least suitable for biofuel cell application since they show the highest polarization without being able to prevent pH splitting between the anode and cathode compartments.

Update on the mechanism of action of antiepileptic drugs.

PubMed

Meldrum, B S

1996-01-01

Novel antiepileptic drugs (AEDs) are thought to act on voltage-sensitive ion channels, on inhibitory neurotransmission or on excitatory neurotransmission. Two successful examples of rational AED design that potentiate GABA-mediated inhibition are vigabatrin (VGB) by irreversible inhibition of GABA-transaminase, and tiagabine (TGB) by blocking GABA uptake. Lamotrigine (LTG) prolongs inactivation of voltage-dependent sodium channels. The anticonvulsant action of remacemide (RCM) is probably largely due to blockade of NMDA receptors and prolonged inactivation of sodium channels induced by its desglycinated metabolite. Felbamate (FBM) apparently blocks NMDA receptors, potentiates GABA-mediated responses, blocks L-type calcium channels, and possibly also prolongs sodium channel inactivation. Similarly, topiramate (TPM) has multiple probable sites of action, including sodium channels, GABA receptors, and glutamate (AMPA) receptors. Gabapentin (GBP) apparently has a completely novel type of action, probably involving potentiation of GABA-mediated inhibition and possibly also inactivation of sodium channels. The therapeutic advantages of the novel AEDs are as yet only partially explained by our present understanding of their mechanisms of action.

Plasma-gun-assisted field-reversed configuration formation in a conical θ-pinch

DOE PAGES

Weber, T. E.; Intrator, T. P.; Smith, R. J.

2015-04-29

We show through injection of plasma via an annular array of coaxial plasma guns, during the pre-ionization phase of field-reversed configuration (FRC) formation how to catalyze the bulk ionization of a neutral gas prefill in the presence of a strong axial magnetic field and change the character of outward flux flow during field-reversal from a convective process to a much slower resistive diffusion process. Our approach has been found to significantly improve FRC formation in a conical θ-pinch, resulting in a ~350% increase in trapped flux at typical operating conditions, an expansion of accessible formation parameter space to lower densitiesmore » and higher temperatures, and a reduction or elimination of several deleterious effects associated with the pre-ionization phase.« less

Plasma-gun-assisted field-reversed configuration formation in a conical θ-pinch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, T. E., E-mail: tweber@lanl.gov; Intrator, T. P.; Smith, R. J.

2015-04-15

Injection of plasma via an annular array of coaxial plasma guns during the pre-ionization phase of field-reversed configuration (FRC) formation is shown to catalyze the bulk ionization of a neutral gas prefill in the presence of a strong axial magnetic field and change the character of outward flux flow during field-reversal from a convective process to a much slower resistive diffusion process. This approach has been found to significantly improve FRC formation in a conical θ-pinch, resulting in a ∼350% increase in trapped flux at typical operating conditions, an expansion of accessible formation parameter space to lower densities and highermore » temperatures, and a reduction or elimination of several deleterious effects associated with the pre-ionization phase.« less

Controlling Catalyst Bulk Reservoir Effects for Monolayer Hexagonal Boron Nitride CVD.

PubMed

Caneva, Sabina; Weatherup, Robert S; Bayer, Bernhard C; Blume, Raoul; Cabrero-Vilatela, Andrea; Braeuninger-Weimer, Philipp; Martin, Marie-Blandine; Wang, Ruizhi; Baehtz, Carsten; Schloegl, Robert; Meyer, Jannik C; Hofmann, Stephan

2016-02-10

Highly controlled Fe-catalyzed growth of monolayer hexagonal boron nitride (h-BN) films is demonstrated by the dissolution of nitrogen into the catalyst bulk via NH3 exposure prior to the actual growth step. This "pre-filling" of the catalyst bulk reservoir allows us to control and limit the uptake of B and N species during borazine exposure and thereby to control the incubation time and h-BN growth kinetics while also limiting the contribution of uncontrolled precipitation-driven h-BN growth during cooling. Using in situ X-ray diffraction and in situ X-ray photoelectron spectroscopy combined with systematic growth calibrations, we develop an understanding and framework for engineering the catalyst bulk reservoir to optimize the growth process, which is also relevant to other 2D materials and their heterostructures.

Can a Compact Pre-Filled Auto-Disable Injection System (cPAD) Save Costs for DTP-HepB-Hib Vaccine as Compared with Single-Dose (SDV) and Multi-Dose Vials (MDV)? Evidence from Cambodia, Ghana, and Peru.

PubMed

Nogier, Cyril; Hanlon, Patrick; Wiedenmayer, Karin; Maire, Nicolas

2015-03-01

A compact pre-filled auto-disable injection (cPAD) presentation is being developed for the fully liquid pentavalent DTP-HepB-Hib vaccine. A cost analysis (CA) to compare this presentation with the presently used single-dose vial (SDV) and multi-dose vial (MDV) was conducted in Cambodia, Ghana, and Peru. The CA included the development of an excel-based costing model and considered the costs of vaccine, safe injection equipment, procurement, storage, transport and distribution, vaccine administration by health staff, medical waste management, start-up activities, as well as coverage, birth cohort, vaccine, and safe injection equipment wastage rates. The outcome was the change in cost per pentavalent fully immunized child (PFIC) for a switch to cPAD. Field visits to health facilities, and interviews with key informants from immunization services and regulatory authorities, were conducted to collect data and to test the costing model in country context. Cost data were also obtained from manufacturers, published price lists, and author estimates. A sensitivity analysis (SA) was conducted to explore possible variations in values of data collected. Based on vaccine price trends estimated for 2016, cPAD is less costly in Ghana [incremental cost per PFIC: $US-0.59 (-6.46 %)] than the current presentation (ten-dose MDV) and in Peru (SDV): $US-0.89 (-7.14 %). In Cambodia, cPAD is more costly than SDV: $US+0.33 (+3.90 %). The most significant cost item per PFIC is the vaccine (reflecting wastage rates) in all presentations. The dominance of the vaccine price per dose and, to a lesser extent, the wastage rates in the incremental cost per PFIC show potential to simplify future analyses. Other relevant considerations at country level for a change of presentation include the potential for improved safety with cPAD, planned introduction of other vaccines, environmental and safety issues, and financial sustainability.

Pullout characteristics of percutaneous pedicle screws with different cement augmentation methods in elderly spines: An in vitro biomechanical study.

PubMed

Charles, Y P; Pelletier, H; Hydier, P; Schuller, S; Garnon, J; Sauleau, E A; Steib, J-P; Clavert, P

2015-05-01

Vertebroplasty prefilling or fenestrated pedicle screw augmentation can be used to enhance pullout resistance in elderly patients. It is not clear which method offers the most reliable fixation strength if axial pullout and a bending moment is applied. The purpose of this study is to validate a new in vitro model aimed to reproduce a cut out mechanism of lumbar pedicle screws, to compare fixation strength in elderly spines with different cement augmentation techniques and to analyze factors that might influence the failure pattern. Six human specimens (82-100 years) were instrumented percutaneously at L2, L3 and L4 by non-augmented screws, vertebroplasty augmentation and fenestrated screws. Cement distribution (2 ml PMMA) was analyzed on CT. Vertebral endplates and the rod were oriented at 45° to the horizontal plane. The vertebral body was held by resin in a cylinder, linked to an unconstrained pivot, on which traction (10 N/s) was applied until rupture. Load-displacement curves were compared to simultaneous video recordings. Median pullout forces were 488.5 N (195-500) for non-augmented screws, 643.5 N (270-1050) for vertebroplasty augmentation and 943.5 N (750-1084) for fenestrated screws. Cement augmentation through fenestrated screws led to significantly higher rupture forces compared to non-augmented screws (P=0.0039). The pullout force after vertebroplasty was variable and linked to cement distribution. A cement bolus around the distal screw tip led to pullout forces similar to non-augmented screws. A proximal cement bolus, as it was observed in fenestrated screws, led to higher pullout resistance. This cement distribution led to vertebral body fractures prior to screw pullout. The experimental setup tended to reproduce a pullout mechanism observed on radiographs, combining axial pullout and a bending moment. Cement augmentation with fenestrated screws increased pullout resistance significantly, whereas the fixation strength with the vertebroplasty prefilling method was linked to the cement distribution. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Diffusion, Dispersion, and Uncertainty in Anisotropic Fractal Porous Media

NASA Astrophysics Data System (ADS)

Monnig, N. D.; Benson, D. A.

2007-12-01

Motivated by field measurements of aquifer hydraulic conductivity (K), recent techniques were developed to construct anisotropic fractal random fields, in which the scaling, or self-similarity parameter, varies with direction and is defined by a matrix. Ensemble numerical results are analyzed for solute transport through these 2-D "operator-scaling" fractional Brownian motion (fBm) ln(K) fields. Contrary to some analytic stochastic theories for monofractal K fields, the plume growth rates never exceed Mercado's (1967) purely stratified aquifer growth rate of plume apparent dispersivity proportional to mean distance. Apparent super-stratified growth must be the result of other demonstrable factors, such as initial plume size. The addition of large local dispersion and diffusion does not significantly change the effective longitudinal dispersivity of the plumes. In the presence of significant local dispersion or diffusion, the concentration coefficient of variation CV={σc}/{\\langle c \\rangle} remains large at the leading edge of the plumes. This indicates that even with considerable mixing due to dispersion or diffusion, there is still substantial uncertainty in the leading edge of a plume moving in fractal porous media.

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2002-05-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole hydrochloride, rosuvastatin calcium; Sevoflurane, sildenafil citrate, simvastatin, somatropin; Tacrolimus, tamoxifen citrate, telmisartan, temozolomide, thiopental sodium, tinzaparin sodium, tirofiban hydrochloride, treosulfan, triamcinolone acetonide; Urokinase; Valsartan, vardenafil, vincristine; Warfarin sodium; Ximelagatran; Zidovudine.

Pulsed electromagnetic gas acceleration. [magnetohydrodynamics, plasma power sources and plasma propulsion

NASA Technical Reports Server (NTRS)

Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

1975-01-01

Terminal voltage measurements with various cathodes and anodes in a high power, quasi-steady magnetoplasmadynamic (MPD) are discussed. The magnitude of the current at the onset of voltage fluctuations is shown to be an increasing function of cathode area and a weaker decreasing function of anode area. Tests with a fluted cathode indicated that the fluctuations originate in the plasma adjacent to the cathode rather than at the cathode surface. Measurements of radiative output from an optical cavity aligned to examine the current-carrying portion of a two-dimensional, 56 kA magnetoplasmadynamic discharge reveal no lasing in that region, consistent with calculations of electron excitation and resonance radiation trapping. A voltage-swept double probe technique allows single-shot determination of electron temperature and electron number density in the recombining MPD exhaust flow. Current distributions within the cavity of MPD hollow cathodes for various static prefills with no injected mass flow are examined.

Clinical Documents: Attribute-Values Entity Representation, Context, Page Layout And Communication

PubMed Central

Lovis, Christian; Lamb, Alexander; Baud, Robert; Rassinoux, Anne-Marie; Fabry, Paul; Geissbühler, Antoine

2003-01-01

This paper presents how acquisition, storage and communication of clinical documents are implemented at the University Hospitals of Geneva. Careful attention has been given to user-interfaces, in order to support complex layouts, spell checking, templates management with automatic prefilling in order to facilitate acquisition. A dual architecture has been developed for storage using an attributes-values entity unified database and a consolidated, patient-centered, layout-respectful files-based storage, providing both representation power and sinsert (peed of accesses. This architecture allows great flexibility to store a continuum of data types from simple type values up to complex clinical reports. Finally, communication is entirely based on HTTP-XML internally and a HL-7 CDA interface V2 is currently studied for external communication. Some of the problem encountered, mostly concerning the typology of documents and the ontology of clinical attributes are evoked. PMID:14728202

Pros and Cons of Clinical Pathway Software Management: A Qualitative Study.

PubMed

Aarnoutse, M F; Brinkkemper, S; de Mul, M; Askari, M

2018-01-01

In this study we aimed to assess the perceived effectiveness of clinical pathway management software for healthcare professionals. A case study on the clinical pathway management software program Check-It was performed in three departments at an academic medical center. Four months after the implementation of the software, interviews were held with healthcare professionals who work with the system. The interview questions were posed in a semi-structured interview format and the participant were asked about the perceived positive or negative effects of Check-It, and whether they thought the software is effective for them. The interviews were recorded and transcribed based on grounded theory, using different coding techniques. Our results showed fewer overlooked tasks, pre-filled orders and letters, better overview, and increased protocol insight as positive aspects of using the software. Being not flexible enough was experienced as a negative aspect.

A Comparison of Glide Force Characteristics Between 2 Prefilled Insulin Lispro Pens

PubMed Central

Lennartz, Amanda H.; Ignaut, Debra A.

2015-01-01

Background: Glide force, average glide force, and glide force variability of the insulin lispro 200 units/mL pen (Eli Lilly and Company, Indianapolis, IN, USA) were compared to the Humalog® KwikPen® 100 units/mL pen (hereafter, KwikPen; Eli Lilly and Company, Indianapolis, IN, USA). Methods: Data were collected on 2 doses, 2 injection speeds, and 2 needle types. Results: Insulin lispro 200 units/mL pen showed significantly lower maximum glide force, average glide force, and glide force variability than the KwikPen across all combinations of dose size, dose speed, and needle type. Conclusions: The lower glide force observed with the insulin lispro 200 units/mL pen offers another treatment option for patients with type 1 or type 2 diabetes who require greater than 20 units of mealtime insulin daily. PMID:25591858

Snap-in compressible biomedical electrode

NASA Technical Reports Server (NTRS)

Frost, J. D., Jr.; Hillman, C. E., Jr. (Inventor)

1977-01-01

A replaceable, prefilled electrode enclosed in a plastic seal and suitably adapted for attachment to a reusable, washable cap having snaps thereon is disclosed. The apparatus is particularly adapted for quick positioning of electrodes to obtain an EEG. The individual electrodes are formed of a sponge body which is filled with a conductive electrolyte gel during manufacture. The sponge body is adjacent to a base formed of a conductive plastic material. The base has at its center a male gripper snap. The cap locates the female snap to enable the electrode to be positioned. The electrode can be stored and used quickly by attaching to the female gripper snap. The snap is correctly positioned and located by mounting it in a stretchable cap. The cap is reusable with new electrodes for each use. The electrolyte gel serves as the contact electrode to achieve a good ohmic contact with the scalp.

Semaglutide: First Global Approval.

PubMed

Dhillon, Sohita

2018-02-01

Novo Nordisk has developed a subcutaneous formulation of semaglutide (Ozempic ® ), a modified human glucagon-like peptide-1 (GLP-1) analogue, for the treatment of type 2 diabetes mellitus. It has been developed using Novo Nordisk's proprietary protein-acylation technology, and is administered using an injection device. Semaglutide lowers blood glucose by stimulating the release of insulin and also lowers body weight. Once-weekly subcutaneous semaglutide has recently been approved in the US, Puerto Rico and Canada, and has received a positive opinion in the EU for the treatment of patients with type 2 diabetes. It will be launched as the Ozempic ® Pen, a pre-filled device. Semaglutide is also under regulatory review in Japan and Switzerland for the treatment of type 2 diabetes. Clinical development for obesity, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease is underway worldwide. This article summarizes the milestones in the development of semaglutide leading to this first approval for type 2 diabetes.

Solubility and Stability of Baclofen 3 mg/mL Intrathecal Formulation and Its Compatibility With Implantable Programmable Intrathecal Infusion Systems.

PubMed

Yue, Baohua; Brendel, Ron; Lukitsch, Amelia; Prentice, Thomas; Doty, Brian

2017-06-01

Commercial baclofen formulations used with infusion pumps are available at therapeutic concentrations of 0.5-2.0 mg/mL. However, patients who receive higher daily doses of baclofen may benefit from products with greater baclofen concentrations since their refill frequency would be reduced (up to a maximum of 180 days). We evaluated baclofen solubility, baclofen 3 mg/mL intrathecal (IT) formulation stability, and chemical and physical compatibility with Medtronic SynchroMed ® II and Codman Medstream ® programmable IT infusion pumps. For solubility evaluations, baclofen powder was dissolved into isotonic saline and tested at 5°C, 25°C, and 40°C. To demonstrate drug product stability, both physical and chemical stability attributes of baclofen 3 mg/mL in prefilled syringes were evaluated over 36 months with storage at 25°C. For a simulated in-use stability (compatibility) study, a 3 mg/mL baclofen IT formulation was placed in SynchroMed II and Codman Medstream pumps at 37ºC for study durations, and evaluated at different flow rates. Pump effluent was collected at various times and analyzed by high-performance liquid chromatography for baclofen content. On completion of the in-use stability study, pumps exposed to baclofen 3 mg/mL were dissected and visually evaluated for signs of deterioration. Baclofen solubility was found to be 3.2 mg/mL at 5°C, 3.6 mg/mL at 25°C, and 3.9 mg/mL at 40°C. During the 36-month stability study of prefilled syringes stored at 25°C, baclofen content remained unchanged and no precipitation was observed. The simulated in-use pump study performed at 37ºC showed that a baclofen 3 mg/mL IT formulation was stable at different flow rates and throughout different expected residence times for both pump models. Components from both pumps exhibited no noticeable deterioration after exposure to the 3 mg/mL formulation. Baclofen 3 mg/mL IT formulation was stable during long-term storage at 25°C and remained stable under conditions matching those encountered in clinical practice (37°C). © 2016 International Neuromodulation Society.

Attachment of composite porous supra-particles to air-water and oil-water interfaces: theory and experiment.

PubMed

Paunov, Vesselin N; Al-Shehri, Hamza; Horozov, Tommy S

2016-09-29

We developed and tested a theoretical model for the attachment of fluid-infused porous supra-particles to a fluid-liquid interface. We considered the wetting behaviour of agglomerated clusters of particles, typical of powdered materials dispersed in a liquid, as well as of the adsorption of liquid-infused colloidosomes at the liquid-fluid interface. The free energy of attachment of a composite spherical porous supra-particle made from much smaller aggregated spherical particles to the oil-water interface was calculated. Two cases were considered: (i) a water-filled porous supra-particle adsorbed at the oil-water interface from the water phase, and, (ii) an oil-filled porous supra-particle adsorbed at the oil-water interface from the oil-phase. We derived equations relating the three-phase contact angle of the smaller "building block" particles and the contact angle of the liquid-infused porous supra-particles. The theory predicts that the porous supra-particle contact angle attached at the liquid interface strongly depends on the type of fluid infused in the particle pores and the fluid phase from which it approaches the liquid interface. We tested the theory by using millimetre-sized porous supra-particles fabricated by evaporation of droplets of polystyrene latex suspension on a pre-heated super-hydrophobic surface, followed by thermal annealing at the glass transition temperature. Such porous particles were initially infused with water or oil and approached to the oil-water interface from the infusing phase. The experiment showed that when attaching at the hexadecane-water interface, the porous supra-particles behaved as hydrophilic when they were pre-filled with water and hydrophobic when they were pre-filled with hexadecane. The results agree with the theoretically predicted contact angles for the porous composite supra-particles based on the values of the contact angles of their building block latex particles measured with the Gel Trapping Technique. The experimental data for the attachment of porous supra particles to the air-water interface from both air and water also agree with the theoretical model. This study gives important insights about how porous particles and particle aggregates attach to the oil-water interface in Pickering emulsions and the air-water surface in particle-stabilised aqueous foams relevant in ore flotation and a range of cosmetic, pharmaceutical, food, home and personal care formulations.

Filling of High-Concentration Monoclonal Antibody Formulations into Pre-filled Syringes: Investigating Formulation-Nozzle Interactions To Minimize Nozzle Clogging.

PubMed

Shieu, Wendy; Stauch, Oliver B; Maa, Yuh-Fun

2015-01-01

Syringe filling of high-concentration/viscosity monoclonal antibody formulations is a complex process that is not fully understood. This study, which builds on a previous investigation that used a bench-top syringe filling unit to examine formulation drying at the filling nozzle tip and subsequent nozzle clogging, further explores the impact of formulation-nozzle material interactions on formulation drying and nozzle clogging. Syringe-filling nozzles made of glass, stainless steel, or plastic (polypropylene, silicone, and Teflon®), which represent a full range of materials with hydrophilic and hydrophobic properties as quantified by contact angle measurements, were used to fill liquids of different viscosity, including a high-concentration monoclonal antibody formulation. Compared with hydrophilic nozzles, hydrophobic nozzles offered two unique features that discouraged formulation drying and nozzle clogging: (1) the liquid formulation is more likely to be withdrawn into the hydrophobic nozzle under the same suck-back conditions, and (2) the residual liquid film left on the nozzle wall when using high suck-back settings settles to form a liquid plug away from the hydrophobic nozzle tip. Making the tip of the nozzle hydrophobic (silicone-coating on glass and Teflon-coating stainless steel) could achieve the same suck-back performance as plastic nozzles. This study demonstrated that using hydrophobic nozzles are most effective in reducing the risk of nozzle clogging by drying of high-concentration monoclonal antibody formulation during extended nozzle idle time in a large-scale filling facility and environment. Syringe filling is a well-established manufacturing process and has been implemented by numerous contract manufacturing organizations and biopharmaceutical companies. However, its technical details and associated critical process parameters are rarely published. Information on high-concentration/viscosity formulation filling is particularly lacking. This study is the continuation of a previous investigation with a focus on understanding the impact of nozzle material on the suck-back function of liquid formulations. The findings identified the most critical parameter-nozzle material hydrophobicity-in alleviating formulation drying at the nozzle tip and eventually limiting the occurrence of nozzle clogging during the filling process. The outcomes of this study will benefit scientists and engineers who develop pre-filled syringe products by providing a better understanding of high-concentration formulation filling principles and challenges. © PDA, Inc. 2015.

Fibre optic gyroscopes for space use

NASA Astrophysics Data System (ADS)

Faussot, Nicolas; Cottreau, Yann; Hardy, Guillaume; Simonpietri, Pascal; Gaiffe, Thierry

2017-11-01

Among the technologies available for gyroscopes usable in space, the Fibre Optic Gyroscope (FOG) technology appears to be the most suitable: no moving parts, very good lifetime, low power consumption, very low random walk, arbitrarily low angular resolution and very good behaviour in radiations and vacuum. Benefiting from more than ten years of experience with this technology, Ixsea (formerly the Navigation Division of Photonetics) is developing space FOG under both CNES and ESA contracts since many years. In the 1996-1998 period, two space FOG demonstrators in the 0,01°/h class were manufactured, including an optical head (optic and optoelectronic part) designed for space use and a standard ground electronics. Beyond the demonstration of the specified FOG performances, the behaviour of the optical head has been validated for use in typical space environment: vibrations, shocks, radiations (up to 50 krad) and thermal vacuum. Since the beginning of 1999, Ixsea is developing a space electronics in order to manufacture two complete space FOG. The first one entered in qualification in October. The second one will be delivered beginning of next year, it will be used in a CNES attitude measurement experiment (MAGI) onboard the FrenchBrazilian Microsatellite (FBM) partly dedicated to technology evaluation.

Long-acting follicle-stimulating hormone analogs containing N-linked glycosylation exhibited increased bioactivity compared with o-linked analogs in female rats.

PubMed

Weenen, C; Peña, J E; Pollak, S V; Klein, J; Lobel, L; Trousdale, R K; Palmer, S; Lustbader, E G; Ogden, R T; Lustbader, J W

2004-10-01

The effects of altering the number and type of additional carbohydrate moieties on the pharmacokinetic and pharmacodynamic properties of FSH were examined in this report. A series of single-chain follitropins, containing variable numbers of additional N- (or O-) linked carbohydrates, were designed and expressed in Chinese hamster ovary cells. Proper folding, efficient receptor binding, and signal transduction were confirmed by in vitro assays. Pharmacokinetic and pharmacodynamic parameters were evaluated in immature female Sprague Dawley rats. Increasing the number of glycosylation sites with either N- (or O-) linked moieties extended the elimination half-life as much as 2-fold compared with recombinant human FSH (rhFSH). However, there was a maximum elimination half-life such that further glycosylation provided no additional lengthening of the half-life. Conversely, biopotency, as assessed by inhibin A levels 74 h post injection, and follicle production were significantly higher for the N-linked analogs. Rats stimulated with the longest acting analogs (either N- or O-linked) showed significantly higher ovarian weights than rats receiving a single injection of rhFSH. The analog containing four additional N-linked sites (rhFSH-N4) had the greatest number of large, preovulatory follicles. Although the half-life of rhFSH-N4 displayed no further enhancement beyond the other longest acting analogs, this analog exhibited significantly increased biopotency in rats. This work provides the basis for the generation of a series of reagents potentially useful for therapeutic applications.

Family Impact of Migraine: Development of the Impact of Migraine on Partners and Adolescent Children (IMPAC) Scale

PubMed Central

Buse, Dawn C.; Adams, Aubrey Manack; Varon, Sepideh F.; Fanning, Kristina M.; Reed, Michael L.

2017-01-01

Objective To describe the development of the Impact of Migraine on Partners and Adolescent Children (IMPAC) scale. Background Although existing data and clinical experience suggest that the impact of migraine is pervasive and extends beyond the individual with migraine, no validated tools exist for assessing the impact of migraine on the family. Methods The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a longitudinal study of people with migraine in the United States. The Family Burden Module (FBM) of the CaMEO Study contained an item pool of 53 questions derived through literature review, clinician input, and patient focus groups pertaining to the following concepts: impact of migraine on family interpersonal relationships, activities, well‐being, finances, and health‐related quality of life. Respondents with migraine (ie, probands) were categorized into 4 groups based on household composition: migraine probands with partners/spouses and children (M‐PC), migraine probands with partners/spouses only (M‐P), migraine probands with child(ren) only (M‐C), and migraine probands without a partner/spouse or child(ren) (M‐O). The IMPAC scale was developed in 3 steps: (1) exploratory factor analysis and item reduction, (2) bifactor analysis, confirmatory factor analysis, and scoring, and (3) reliability and construct validity analyses. Results The analysis of data from 13,064 respondents to the FBM meeting criteria for migraine yielded a 12‐item IMPAC scale, with 4 items applying to all of the groups, 4 more items applying to the groups with partners (M‐P and M‐PC), and 4 additional items to the groups with children (M‐C and M‐PC). Item responses can be summed and converted into a scoring system assessing mild (<0.5 SD below mean; IMPAC scale Grade I), moderate (0.5 SD below to <0.5 SD above mean; Grade II), severe (0.5‐<1.5 SD above mean; Grade III), and very severe (≥0.5 SD above mean; Grade IV) family impact. Test information curves relating to the IMPAC scale for each household type indicated adequate reliability across a large range of family burden severity (from ∼1 SD below to ∼3 SD above mean) and IMPAC scores showed moderate‐to‐large correlations with other validated tools (range, ± 0.38‐0.52), providing support for construct validity. Conclusions We developed a questionnaire to assess family burden attributed to migraine that is brief, robust, and psychometrically sound, with a simple scoring algorithm that can be applied to various household compositions. This questionnaire may be valuable in research settings to provide quantifiable data on the impact of migraine on family dynamics and in clinical settings to facilitate conversations about family burden as a target and a motivation for better treatment. PMID:28185239

Effect of 2 Bedding Materials on Ammonia Levels in Individually Ventilated Cages

PubMed Central

Koontz, Jason M; Kumsher, David M; III, Richard Kelly; Stallings, Jonathan D

2016-01-01

This study sought to identify an optimal rodent bedding and cage-change interval to establish standard procedures for the IVC in our rodent vivarium. Disposable cages were prefilled with either corncob or α-cellulose bedding and were used to house 2 adult Sprague–Dawley rats (experimental condition) or contained no animals (control). Rats were observed and intracage ammonia levels measured daily for 21 d. Intracage ammonia accumulation became significant by day 8 in experimental cages containing α-cellulose bedding, whereas experimental cages containing corncob bedding did not reach detectable levels of ammonia until day 14. In all 3 experimental cages containing α-cellulose, ammonia exceeded 100 ppm (our maximum acceptable limit) by day 11. Two experimental corncob cages required changing at days 16 and 17, whereas the remaining cage containing corncob bedding lasted the entire 21 d without reaching the 100-ppm ammonia threshold. These data suggests that corncob bedding provides nearly twice the service life of α-cellulose bedding in the IVC system. PMID:26817976

Magnetically insulated diode for generating pulsed neutron and gamma ray emissions

DOEpatents

Kuswa, G.W.; Leeper, R.J.

1984-08-16

A magnetically insulated diode employs a permanent magnet to generate a magnetic insulating field between a spaced anode and cathode in a vacuum. An ion source is provided in the vicinity of the anode and used to liberate ions for acceleration toward the cathode. The ions are virtually unaffected by the magnetic field and are accelerated into a target for generating a nuclear reaction. The ions and target material may be selected to generate either neutrons or gamma ray emissions from the reaction of the accelerated ions and the target. In another aspect of the invention, a field coil is employed as part of one of the electrodes. A plasma prefill is provided between the electrodes prior to the application of a pulsating potential to one of the electrodes. The field coil multiplies the applied voltage for high diode voltage applications. The diode may be used to generate a /sup 7/Li(p,..gamma..)/sup 8/Be reaction to produce 16.5 MeV gamma emission.

Activation energies of diffusion of organic migrants in cyclo olefin polymer.

PubMed

Welle, Frank

2014-10-01

Cyclo olefin polymer (COP) is an amorphous polymer with good optical transparency and barrier properties, which is increasingly used for pharmaceutical packaging applications like pre-filled syringes, plastic vials, nutrition bags and blisters as well as for micro-well plates. For regulatory purposes, it is important to know the amount and quantity of compounds which migrate from the polymer into the pharmaceutical product. Within the study, diffusion coefficients of organic (model) compounds in COP at various temperatures were determined and the activation energies of diffusion were calculated according to the Arrhenius approach. Correlations were established between the molecular volume V of the migrating compound and the activation energy of diffusion EA as well as between the pre-exponential factor in the Arrhenius equation D0 and EA. From these correlations a prediction model was established for the migration of organic compounds in COP. This might be a useful tool supporting the evaluation process of COP packed pharmaceutical products. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of 2 Bedding Materials on Ammonia Levels in Individually Ventilated Cages.

PubMed

Koontz, Jason M; Kumsher, David M; Kelly, Richard; Stallings, Jonathan D

2016-01-01

This study sought to identify an optimal rodent bedding and cage-change interval to establish standard procedures for the IVC in our rodent vivarium. Disposable cages were prefilled with either corncob or α-cellulose bedding and were used to house 2 adult Sprague-Dawley rats (experimental condition) or contained no animals (control). Rats were observed and intracage ammonia levels measured daily for 21 d. Intracage ammonia accumulation became significant by day 8 in experimental cages containing α-cellulose bedding, whereas experimental cages containing corncob bedding did not reach detectable levels of ammonia until day 14. In all 3 experimental cages containing α-cellulose, ammonia exceeded 100 ppm (our maximum acceptable limit) by day 11. Two experimental corncob cages required changing at days 16 and 17, whereas the remaining cage containing corncob bedding lasted the entire 21 d without reaching the 100-ppm ammonia threshold. These data suggests that corncob bedding provides nearly twice the service life of α-cellulose bedding in the IVC system.

Quality considerations of paediatric investigation plans for monoclonal antibodies: A regulatory perspective from the MHRA.

PubMed

Hussain, Nasir; Siapkara, Angeliki; Branch, Sarah

2015-08-15

Since the advent of the EU Paediatric Regulation in 2007, 78 of the 1688 Paediatric Investigation Plans (PIPs) have been for monoclonal antibodies (Mabs). Of these, 22 have been assessed by the MHRA. The purpose of this mini-review is to aid those researching and developing this class of drugs to better understand regulatory concerns leading to improved medicinal products for children. Three principal quality issues were identified for PIPs under Article 7 and 8: i) the level of anti-aggregation stabilisers, ii) acceptability and tolerability of administration (i.e. multiple injections, infusion time and volume), and iii) the need to develop new presentational forms (e.g. pre-filled syringe). Overall, two types of concerns were ascertained - those which are potentially avoidable (e.g. through development of new presentational forms) and others which require the evolution of new technologies in the sector (e.g. production of concentrated, stabilised preparations). Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Application of Townsend avalanche theory to tokamak startup by coaxial helicity injection

NASA Astrophysics Data System (ADS)

Hammond, K. C.; Raman, R.; Volpe, F. A.

2018-01-01

The Townsend avalanche theory is employed to model and interpret plasma initiation in NSTX by Ohmic heating and coaxial helicity injection (CHI). The model is informed by spatially resolved vacuum calculations of electric field and magnetic field line connection length in the poloidal cross-section. The model is shown to explain observations of Ohmic startup including the duration and location of breakdown. Adapting the model to discharges initiated by CHI offers insight into the causes of upper divertor (absorber) arcs in cases where the discharge fails to start in the lower divertor gap. Finally, upper and lower limits are established for vessel gas fill based on requirements for breakdown and radiation. It is predicted that CHI experiments on NSTX-U should be able to use as much as four times the amount of prefill gas employed in CHI experiments in NSTX. This should provide greater flexibility for plasma start-up, as the injector flux is projected to be increased in NSTX-U.

Aggregation of a Monoclonal Antibody Induced by Adsorption to Stainless Steel

PubMed Central

Bee, Jared S.; Davis, Michele; Freund, Erwin; Carpenter, John F.; Randolph, Theodore W.

2014-01-01

Stainless steel is a ubiquitous surface in therapeutic protein production equipment and is also present as the needle in some pre-filled syringe biopharmaceutical products. Stainless steel microparticles can cause of aggregation of a monoclonal antibody (mAb). The initial rate of mAb aggregation was second-order in steel surface area and zero-order in mAb concentration, generally consistent with a bimolecular surface aggregation being the rate-limiting step. Polysorbate 20 (PS20) suppressed the aggregation yet was unable to desorb the firmly bound first layer of protein that adsorbs to the stainless steel surface. Also, there was no exchange of mAb from the first adsorbed layer to the bulk phase, suggesting that the aggregation process actually occurs on subsequent adsorption layers. No oxidized Met residues were detected in the mass spectrum of a digest of a highly aggregated mAb, although there was five-fold increase in carbonyl groups due to protein oxidation. PMID:19725039

Magnetically insulated diode for generating pulsed neutron and gamma ray emissions

DOEpatents

Kuswa, Glenn W.; Leeper, Ramon J.

1987-01-01

A magnetically insulated diode employs a permanent magnet to generate a magnetic insulating field between a spaced anode and cathode in a vacuum. An ion source is provided in the vicinity of the anode and used to liberate ions for acceleration toward the cathode. The ions are virtually unaffected by the magnetic field and are accelerated into a target for generating an nuclear reaction. The ions and target material may be selected to generate either neutrons or gamma ray emissions from the reaction of the accelerated ions and the target. In another aspect of the invention, a field coil is employed as part of one of the electrodes. A plasma prefill is provided between the electrodes prior to the application of a pulsating potential to one of the electrodes. The field coil multiplies the applied voltage for high diode voltage applications. The diode may be used to generate a .sup.7 Li(p,.gamma.).sup.8 Be reaction to produce 16.5 MeV gamma emission.

Effects of flow rate and gas mixture on the welfare of weaned and neonate pigs during gas euthanasia.

PubMed

Sadler, L J; Hagen, C D; Wang, C; Widowski, T M; Johnson, A K; Millman, S T

2014-02-01

The objectives of this study were to assess efficacy and welfare implications of gas euthanasia when applied to weaned and neonate pigs. Parameters associated with welfare, which were measured before loss of consciousness, included open-mouth breathing, ataxia, righting response, and escape attempts. Two age groups (weaned and neonate) were assessed in 9 gas treatments arranged in a 2 × 4 factorial design, with 2 gas types (CO2 = 100% CO2 and 50:50 = 50:50 CO2:argon) and 4 flow rates (box volume exchange/min: slow = 20%; medium = 35%; fast = 50%; prefill = prefilled followed by 20%) and a control treatment in which ambient air was passed through the box. Pig pairs (10/treatment) were placed in a modified Euthanex AgPro system (Euthanex Corp., Palmer, PA). Behavioral and physiological responses were observed directly and from video recordings for latency, duration, prevalence (percent of pigs affected), and frequency (number of occurrences/pig). Data were analyzed as linear mixed models or with a Cox proportional hazard model as appropriate. Piglet pair was the experimental unit. For the weaned pig, welfare was superior with CO2 relative to 50:50 within 1 or more flow rates on the basis of reduced duration of open-mouth breathing, duration of ataxia, frequency of escape attempts, and duration and frequency of righting response (P < 0.05). No measured parameters indicated superior welfare with the use of 50:50, whereas latencies to loss of posture and last movement favored CO2 (P < 0.05). Faster flow rates were associated with reduced (P < 0.05) duration or frequency of open-mouth breathing, ataxia, and righting response, as well as superior (P < 0.05) indicators of efficacy, including latencies to loss of posture, gasping, and last movement, relative to slower flow rates. Weaned pigs were more likely to defecate (P < 0.01), display nasal discharge (P < 0.05), and display longer (P < 0.001) latencies to loss of posture and last movement than neonates. Duration of ataxia was the only parameter for which neonates were superior (P < 0.01) to weaned pigs during euthanasia. As such, a 50:50 CO2:argon gas mixture and slower flow rates should be avoided when euthanizing weaned or neonate pigs with gas methods. Neonate pigs succumb to the effects of gas euthanasia quicker than weaned pigs and display fewer signs of distress.

A strategy for the prevention of protein oxidation by drug product in polymer-based syringes.

PubMed

Nakamura, Koji; Abe, Yoshihiko; Kiminami, Hideaki; Yamashita, Arisa; Iwasaki, Kazuhiro; Suzuki, Shigeru; Yoshino, Keisuke; Dierick, William; Constable, Kevin

2015-01-01

Recently, new and advanced ideas have been presented on the value of polymer-based syringes for improved safety, better strength, reduced aggregation, and the prevention of drug degradation. In this report, our findings on drug degradation from protein oxidation will be presented and discussed. Commonly, dissolved oxygen is one of the factors for causing protein degradation. Due to the nature of higher gas permeability in polymer-based syringes, it was thought to be difficult to control the oxygen level during storage. However, this report demonstrates the appropriateness of combining the use of an oxygen absorber within the secondary packaging as a deoxygenated packaging system. In addition, this report suggests that another factor to enhance protein oxidization is related to radicals on the syringe barrel from sterilization by irradiation. We demonstrate that steam sterilization can minimize protein oxidization, as the protein filled in steam sterilized syringe is much more stable. In conclusion, the main oxidation pathway of a protein has been identified as dissolved oxygen and radical generation within a polymer container. Possible solutions are herewith presented for controlling oxidation by means of applying a deoxygenated packaging system as well as utilizing steam sterilization as a method of sterilization for prefillable polymer syringes. There have been many presentations and discussions about the risks associated with glass prefilled syringes. Advanced ideas are being presented on the value of polymer-based syringes for improved safety, better strength, reduced protein aggregation, and the prevention of drug degradation. Drug degradation based on protein oxidation is discussed in this report. Identification of the main factors causing this degradation and possible solutions available by using polymer-based syringes will be presented. The causes of protein oxidation have been identified as dissolved oxygen and radicals generated by the applied method of sterilization. The oxidation reaction created by dissolved oxygen within the drug product can be effectively inhibited by controlling the removal of the oxygen through the use of a deoxygenated packaging system. This packaging system can control the level or complete removal of oxygen from the primary container and the secondary packaging system. Protein oxidation induced by the formation of radicals from sterilization by irradiation is another critical aspect where it was thought that various sterilization methods were acceptable without loosing drug product quality. However, this report is first to demonstrate that gamma sterilized polymer-based syringes accelerated protein oxidation by radical generation; this effect can be prevented by means of steam sterilization. © PDA, Inc. 2015.

Protein delivery with infusion pumps.

PubMed

Bremer, U; Horres, C R; Francoeur, M L

1997-01-01

When a therapeutic effect is optimized by precise control of specific temporal patterns of plasma levels, infusion offers distinct advantages over oral administration, bolus injection, or depot delivery of polypeptides. The limitations of oral delivery are well known, and although research is under way into development of carrier systems that prevent degradation of labile agents, it is unlikely that the variances in absorption will meet the need for precise control. Depot delivery from subcutaneous or intramuscular implants presents a difficult situation when local tissue reactions to the agent sometimes occur. Removal of a depot system in the event of adverse reactions presents additional difficulties. Bolus injections are unable to sustain constant plasma levels unless the drug half-life is long or the injections are frequently administered. Insulin injections, for example, would be required every 30-60 minutes to approximate the plasma levels provided by a continuous infusion; such frequent injections would not be practical on a 24-hour basis. For the developer of new polypeptides, parenteral administration offers the most direct route to the marketplace. The step from periodic injections to tightly controlled infusion is a logical progression as compared with modification of the molecules or vehicles to obtain equivalent profiles. In Table II several different types of devices that can be used for infusion of proteins are compared. Microelectronics have played a major role in the miniaturization of infusion devices and undoubtedly will continue to do so. Micromachining, a spin-off technology of integrated circuit manufacture, will also find application in small infusion devices. In the future, we will have cost-effective disposable devices (Saaman et al., 1994) built on this technology that are programmable and thus can be adapted to meet each individual therapeutic need (Horres, 1994). We can also expect to see more closed-loop drug delivery systems where biosensors and infusion devices are combined to optimize a particular therapy. Recent positive results obtained in diabetics by a decade on tight glucose control may forecast a resurgence of popularity of insulin pumps. At the other end of the spectrum, low-cost, small, and simple-to-use osmotically powered systems are close to being marketed; these systems will make infusion almost as convenient as transdermal patches. We will also see major advances in how drugs and devices are interfaced. Prefilled and ready-to-use drug cartridges have proven to be efficient in surgical and emergency medicine and can greatly improve most infusion applications. It is anticipated that coded, prefilled cartridges or pouches will be automatically, recognized by preprogrammed pumps to reduce operator labor and entry error.

Automatic orientation and 3D modelling from markerless rock art imagery

NASA Astrophysics Data System (ADS)

Lerma, J. L.; Navarro, S.; Cabrelles, M.; Seguí, A. E.; Hernández, D.

2013-02-01

This paper investigates the use of two detectors and descriptors on image pyramids for automatic image orientation and generation of 3D models. The detectors and descriptors replace manual measurements and are used to detect, extract and match features across multiple imagery. The Scale-Invariant Feature Transform (SIFT) and the Speeded Up Robust Features (SURF) will be assessed based on speed, number of features, matched features, and precision in image and object space depending on the adopted hierarchical matching scheme. The influence of applying in addition Area Based Matching (ABM) with normalised cross-correlation (NCC) and least squares matching (LSM) is also investigated. The pipeline makes use of photogrammetric and computer vision algorithms aiming minimum interaction and maximum accuracy from a calibrated camera. Both the exterior orientation parameters and the 3D coordinates in object space are sequentially estimated combining relative orientation, single space resection and bundle adjustment. The fully automatic image-based pipeline presented herein to automate the image orientation step of a sequence of terrestrial markerless imagery is compared with manual bundle block adjustment and terrestrial laser scanning (TLS) which serves as ground truth. The benefits of applying ABM after FBM will be assessed both in image and object space for the 3D modelling of a complex rock art shelter.

Fractal analysis of the short time series in a visibility graph method

NASA Astrophysics Data System (ADS)

Li, Ruixue; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Chen, Yingyuan

2016-05-01

The aim of this study is to evaluate the performance of the visibility graph (VG) method on short fractal time series. In this paper, the time series of Fractional Brownian motions (fBm), characterized by different Hurst exponent H, are simulated and then mapped into a scale-free visibility graph, of which the degree distributions show the power-law form. The maximum likelihood estimation (MLE) is applied to estimate power-law indexes of degree distribution, and in this progress, the Kolmogorov-Smirnov (KS) statistic is used to test the performance of estimation of power-law index, aiming to avoid the influence of droop head and heavy tail in degree distribution. As a result, we find that the MLE gives an optimal estimation of power-law index when KS statistic reaches its first local minimum. Based on the results from KS statistic, the relationship between the power-law index and the Hurst exponent is reexamined and then amended to meet short time series. Thus, a method combining VG, MLE and KS statistics is proposed to estimate Hurst exponents from short time series. Lastly, this paper also offers an exemplification to verify the effectiveness of the combined method. In addition, the corresponding results show that the VG can provide a reliable estimation of Hurst exponents.

An improved non-Markovian degradation model with long-term dependency and item-to-item uncertainty

NASA Astrophysics Data System (ADS)

Xi, Xiaopeng; Chen, Maoyin; Zhang, Hanwen; Zhou, Donghua

2018-05-01

It is widely noted in the literature that the degradation should be simplified into a memoryless Markovian process for the purpose of predicting the remaining useful life (RUL). However, there actually exists the long-term dependency in the degradation processes of some industrial systems, including electromechanical equipments, oil tankers, and large blast furnaces. This implies the new degradation state depends not only on the current state, but also on the historical states. Such dynamic systems cannot be accurately described by traditional Markovian models. Here we present an improved non-Markovian degradation model with both the long-term dependency and the item-to-item uncertainty. As a typical non-stationary process with dependent increments, fractional Brownian motion (FBM) is utilized to simulate the fractal diffusion of practical degradations. The uncertainty among multiple items can be represented by a random variable of the drift. Based on this model, the unknown parameters are estimated through the maximum likelihood (ML) algorithm, while a closed-form solution to the RUL distribution is further derived using a weak convergence theorem. The practicability of the proposed model is fully verified by two real-world examples. The results demonstrate that the proposed method can effectively reduce the prediction error.

Image informative maps for component-wise estimating parameters of signal-dependent noise

NASA Astrophysics Data System (ADS)

Uss, Mykhail L.; Vozel, Benoit; Lukin, Vladimir V.; Chehdi, Kacem

2013-01-01

We deal with the problem of blind parameter estimation of signal-dependent noise from mono-component image data. Multispectral or color images can be processed in a component-wise manner. The main results obtained rest on the assumption that the image texture and noise parameters estimation problems are interdependent. A two-dimensional fractal Brownian motion (fBm) model is used for locally describing image texture. A polynomial model is assumed for the purpose of describing the signal-dependent noise variance dependence on image intensity. Using the maximum likelihood approach, estimates of both fBm-model and noise parameters are obtained. It is demonstrated that Fisher information (FI) on noise parameters contained in an image is distributed nonuniformly over intensity coordinates (an image intensity range). It is also shown how to find the most informative intensities and the corresponding image areas for a given noisy image. The proposed estimator benefits from these detected areas to improve the estimation accuracy of signal-dependent noise parameters. Finally, the potential estimation accuracy (Cramér-Rao Lower Bound, or CRLB) of noise parameters is derived, providing confidence intervals of these estimates for a given image. In the experiment, the proposed and existing state-of-the-art noise variance estimators are compared for a large image database using CRLB-based statistical efficiency criteria.

Kennedy Space Center Fixation Tube (KFT)

NASA Technical Reports Server (NTRS)

Richards, Stephanie E.; Levine, Howard G.; Romero, Vergel

2016-01-01

Experiments performed on the International Space Station (ISS) frequently require the experimental organisms to be preserved until they can be returned to earth for analysis in the appropriate laboratory facility. The Kennedy Fixation Tube (KFT) was developed to allow astronauts to apply fixative, chemical compounds that are often toxic, to biological samples without the use of a glovebox while maintaining three levels of containment (Fig. 1). KFTs have been used over 200 times on-orbit with no leaks of chemical fixative. The KFT is composed of the following elements: a polycarbonate main tube where the fixative is loaded preflight, the sample tube where the plant or other biological specimens is placed during operations, the expansion plug, actuator, and base plug that provides fixative containment (Fig. 2). The main tube is pre-filled with 25 mL of fixative solution prior to flight. When actuated, the specimen contained within the sample tube is immersed with approximately 22 mL (+/- 2 mL) of the fixative solution. The KFT has been demonstrated to maintain its containment at ambient temperatures, 4degC refrigeration and -100 C freezing conditions.

Role of pharmacists in reducing occupational exposure to HIV.

PubMed

Morris, S N

1989-12-01

The role of pharmacists in reducing the occupational hazard of human immunodeficiency virus (HIV) transmission via needle-stick injuries is described. Some 40% of all pharmaceuticals used in hospitals are now administered by injection, and sales of large-volume injectable drug products continue to grow. Most needle-stick injuries in which health-care workers are exposed to HIV-contaminated blood occur during recapping of used needles, picking up and carrying the needle, or placing it in a receptacle. Pharmacists are responsible not only for the purchase, storage, dispensing, and use of drug products but also for providing information about their administration and safe disposal. Single-use vials, ampuls, and prefilled syringes must all be evaluated for availability, ease of use, and disposal. A major factor in drug-purchasing decisions must be the safety of nurses. Syringes that have been redesigned to eliminate the need for recapping offer a major safety advantage. Needle disposal units should be made more conveniently accessible. Pharmacists can help prevent the transmission of HIV to health-care workers by using their influence as educators and decision makers to reduce the risk of needle-stick injury.

Birth of a hydraulic jump

NASA Astrophysics Data System (ADS)

Duchesne, Alexis; Bohr, Tomas; Andersen, Anders

2017-11-01

The hydraulic jump, i.e., the sharp transition between a supercritical and a subcritical free-surface flow, has been extensively studied in the past centuries. However, ever since Leonardo da Vinci asked it for the first time, an important question has been left unanswered: How does a hydraulic jump form? We present an experimental and theoretical study of the formation of stationary hydraulic jumps in centimeter wide channels. Two starting situations are considered: The channel is, respectively, empty or filled with liquid, the liquid level being fixed by the wetting properties and the boundary conditions. We then change the flow-rate abruptly from zero to a constant value. In an empty channel, we observe the formation of a stationary hydraulic jump in a two-stage process: First, the channel fills by the advancing liquid front, which undergoes a transition from supercritical to subcritical at some position in the channel. Later the influence of the downstream boundary conditions makes the jump move slowly upstream to its final position. In the pre-filled channel, the hydraulic jump forms at the injector edge and then moves downstream to its final position.

Fractional Brownian motion time-changed by gamma and inverse gamma process

NASA Astrophysics Data System (ADS)

Kumar, A.; Wyłomańska, A.; Połoczański, R.; Sundar, S.

2017-02-01

Many real time-series exhibit behavior adequate to long range dependent data. Additionally very often these time-series have constant time periods and also have characteristics similar to Gaussian processes although they are not Gaussian. Therefore there is need to consider new classes of systems to model these kinds of empirical behavior. Motivated by this fact in this paper we analyze two processes which exhibit long range dependence property and have additional interesting characteristics which may be observed in real phenomena. Both of them are constructed as the superposition of fractional Brownian motion (FBM) and other process. In the first case the internal process, which plays role of the time, is the gamma process while in the second case the internal process is its inverse. We present in detail their main properties paying main attention to the long range dependence property. Moreover, we show how to simulate these processes and estimate their parameters. We propose to use a novel method based on rescaled modified cumulative distribution function for estimation of parameters of the second considered process. This method is very useful in description of rounded data, like waiting times of subordinated processes delayed by inverse subordinators. By using the Monte Carlo method we show the effectiveness of proposed estimation procedures. Finally, we present the applications of proposed models to real time series.

Characterization of the APLF FHA–XRCC1 phosphopeptide interaction and its structural and functional implications

PubMed Central

Kim, Kyungmin; Pedersen, Lars C.; Kirby, Thomas W.; DeRose, Eugene F.

2017-01-01

Abstract Aprataxin and PNKP-like factor (APLF) is a DNA repair factor containing a forkhead-associated (FHA) domain that supports binding to the phosphorylated FHA domain binding motifs (FBMs) in XRCC1 and XRCC4. We have characterized the interaction of the APLF FHA domain with phosphorylated XRCC1 peptides using crystallographic, NMR, and fluorescence polarization studies. The FHA–FBM interactions exhibit significant pH dependence in the physiological range as a consequence of the atypically high pK values of the phosphoserine and phosphothreonine residues and the preference for a dianionic charge state of FHA-bound pThr. These high pK values are characteristic of the polyanionic peptides typically produced by CK2 phosphorylation. Binding affinity is greatly enhanced by residues flanking the crystallographically-defined recognition motif, apparently as a consequence of non-specific electrostatic interactions, supporting the role of XRCC1 in nuclear cotransport of APLF. The FHA domain-dependent interaction of XRCC1 with APLF joins repair scaffolds that support single-strand break repair and non-homologous end joining (NHEJ). It is suggested that for double-strand DNA breaks that have initially formed a complex with PARP1 and its binding partner XRCC1, this interaction acts as a backup attempt to intercept the more error-prone alternative NHEJ repair pathway by recruiting Ku and associated NHEJ factors. PMID:29059378

Log-correlated random-energy models with extensive free-energy fluctuations: Pathologies caused by rare events as signatures of phase transitions

NASA Astrophysics Data System (ADS)

Cao, Xiangyu; Fyodorov, Yan V.; Le Doussal, Pierre

2018-02-01

We address systematically an apparent nonphysical behavior of the free-energy moment generating function for several instances of the logarithmically correlated models: the fractional Brownian motion with Hurst index H =0 (fBm0) (and its bridge version), a one-dimensional model appearing in decaying Burgers turbulence with log-correlated initial conditions and, finally, the two-dimensional log-correlated random-energy model (logREM) introduced in Cao et al. [Phys. Rev. Lett. 118, 090601 (2017), 10.1103/PhysRevLett.118.090601] based on the two-dimensional Gaussian free field with background charges and directly related to the Liouville field theory. All these models share anomalously large fluctuations of the associated free energy, with a variance proportional to the log of the system size. We argue that a seemingly nonphysical vanishing of the moment generating function for some values of parameters is related to the termination point transition (i.e., prefreezing). We study the associated universal log corrections in the frozen phase, both for logREMs and for the standard REM, filling a gap in the literature. For the above mentioned integrable instances of logREMs, we predict the nontrivial free-energy cumulants describing non-Gaussian fluctuations on the top of the Gaussian with extensive variance. Some of the predictions are tested numerically.

Influence of final baking technologies in partially baked frozen gluten-free bread quality.

PubMed

Aguilar, Núria; Albanell, Elena; Miñarro, Begoña; Gallardo, Joan; Capellas, Marta

2015-03-01

The effect of final baking in convection oven (FBC), microwave oven (FBM), and microwave oven with susceptor packaging material (FBMS) on partially baked (PB) frozen gluten-free bread characteristics was investigated. Specific volume and crust color of loaves were measured at day 0. Bread moisture, water activity, and crumb and crust texture (at 15, 45, and 90 min after baking) were analyzed at day 0 and after 28 d of frozen storage (-18 °C). Volatile compounds from breads baked in convection oven or microwave oven with susceptor packaging material were also evaluated. Bread finally baked in convection oven or in microwave oven with susceptor packaging increased crust browning. Crumb and roll hardness increased with time after final baking (measured at 15, 45, 90 min) and after 28 d of frozen storage. Bread finally baked in microwave oven was the hardest, due to high water losses. At day 0, bread finally baked in convection oven had softer crumb than bread finally baked in microwave oven with susceptor packaging but, after 28 d of frozen storage, there were no differences between them. Moreover, FBC and FBMS rendered gluten-free breads that could not be distinguished in a triangular test and had the same volatile compounds profile. In conclusion, FBMS could be an alternative to FBC. © 2015 Institute of Food Technologists®

Linking a pharmaceutical claims database with a birth defects registry to investigate birth defect rates of suspected teratogens.

PubMed

Colvin, Lyn; Slack-Smith, Linda; Stanley, Fiona J; Bower, Carol

2010-11-01

Data linkage of population administrative data is being investigated as a tool for pharmacovigilance in pregnancy in Australia. Records of prescriptions of known or suspected teratogens dispensed to pregnant women have been linked to a birth defects registry to determine if defects associated with medicine exposure can be detected. The Pharmaceutical Benefits Scheme is a national claims database that has been linked with population-based data to extract linkages for women with a pregnancy event in Western Australia from 2002 to 2005 (n = 106 074). Records of births to the women who were dispensed medicines in categories D or X of the Australian ADEC pregnancy risk category were linked to the Birth Defects Registry of Western Australia. Population rates of registered birth defects per 1000 births were calculated for each medicine. There were 47 medicines dispensed at least once during pregnancy with 23 associated with a registered birth defect to a woman dispensed the medicine. When the birth defect rate for each medicine was compared with the rate for all other women not dispensed that medicine, most medicines showed an increased risk. Medicines with the higher risks were medroxyprogesterone acetate (OR: 1.8; 95%CI: 1.4-2.3), follitropin alfa (OR: 2.5; 95%CI: 1.2-5.0), carbamazepine (OR: 3.1; 95%CI: 1.7-5.6) and enalapril maleate (OR: 8.1; 95%CI: 1.6-41.7). Many known associations between medicines and birth defects were identified, suggesting that linked administrative data could be an important means of pharmacovigilance in pregnancy in Australia. Copyright © 2010 John Wiley & Sons, Ltd.

Prevalence of -alpha(3.7) and alpha alpha alpha(anti3.7) alleles in sickle cell trait and beta-thalassemia patients in Mexico.

PubMed

Nava, María Paulina; Ibarra, Bertha; Magaña, María Teresa; de la Luz Chávez, María; Perea, F Javier

2006-01-01

The aim of this study was to determine the frequency of alpha-globin gene mutations in three groups of Mexican unrelated individuals. The first two groups were normal and sickle cell trait individuals from the Costa Chica region, a place with a 12.8% frequency of HbS carriers, and the third group comprised of Mexican mestizo patients with beta-thalassemia. We searched for -alpha(3.7) and -alpha(4.2) alpha(+)-thalassemia deletion alleles, as well as the alpha alpha alpha(anti3.7) triplication through long-gap PCR. The alleles -alpha(3.7) and alpha alpha alpha(anti3.7) were found in the heterozygote state only; 19% of the normal subjects had the -alpha(3.7) allele, and 2% showed the alpha alpha alpha(anti3.7) allele. In individuals with the sickle cell trait, 17% had the -alpha(3.7) deletion, and the alpha alpha alpha(anti3.7) triplication was observed in 3% of these individuals. We revealed that 16% of the subjects with beta-thalassemia showed the -alpha(3.7) deletion and 28% the alpha alpha alpha(anti3.7) triplication. The -alpha(4.2) deletion was not detected in any individual. The frequency of the -alpha(3.7) allele was roughly the same in the three groups studied; this can be explained by the fact that the three groups have common genes from Africa and the Mediterranean, where a high prevalence of alpha(+)-thalassemia has been observed. To our knowledge, the frequency of alpha alpha alpha(anti3.7) triplication observed in the Mexican beta-thalassemia patients is the highest reported. As the -alpha(3.7) and alpha alpha alpha(anti3.7) alleles are very common in our selected populations, we believe that there is a need to investigate systematically the alpha-globin gene mutations in all hemoglobinopathies in the Mexican population.

Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum.

PubMed

Porcu, Patrizia; O'Buckley, Todd K; Alward, Sarah E; Marx, Christine E; Shampine, Lawrence J; Girdler, Susan S; Morrow, A Leslie

2009-01-01

The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity, sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3alpha,5alpha-THP (+1488%, p<0.001), (3alpha,5alpha)-3,21-dihydroxypregnan-20-one (3alpha,5alpha-THDOC, +205%, p<0.01), (3alpha,5alpha)-3-hydroxyandrostan-17-one (3alpha,5alpha-A, +216%, p<0.001), (3alpha,5alpha,17beta)-androstane-3,17-diol (3alpha,5alpha-A-diol, +190%, p<0.01). (3alpha,5beta)-3-hydroxypregnan-20-one (3alpha,5beta-THP) and (3alpha,5beta)-3-hydroxyandrostan-17-one (3alpha,5beta-A) were not altered, while (3alpha,5beta)-3,21-dihydroxypregnan-20-one (3alpha,5beta-THDOC) and (3alpha,5beta,17beta)-androstane-3,17-diol (3alpha,5beta-A-diol) were increased from undetectable levels to 271+/-100 and 2.4+/-0.9 pg+/-SEM, respectively (5/8 rats). Progesterone administration increased serum levels of 3alpha,5alpha-THP (+1806%, p<0.0001), 3alpha,5beta-THP (+575%, p<0.001), 3alpha,5alpha-THDOC (+309%, p<0.001). 3alpha,5beta-THDOC levels were increased by 307%, although this increase was not significant because this steroid was detected only in 3/16 control subjects. Levels of 3alpha,5alpha-A, 3alpha,5beta-A and pregnenolone were not altered. This method can be used to investigate the physiological and pathological role of neuroactive steroids and to develop biomarkers and new therapeutics for neurological and psychiatric disorders.

Stereospecific 1,4-addition to an alpha,beta-unsaturated steroidal epoxide: syntheses of new 15-oxygenated sterols.

PubMed

Parish, E J; Tsuda, M; Schroepfer, G J

1988-11-01

3 beta-Benzoyloxy-14 alpha,15 alpha-epoxy-5 alpha-cholest-7-ene (1) is a key intermediate in the synthesis of C-7 and C-15 oxygenated sterols. Treatment of 1 with benzoyl chloride resulted in the formation of 3 beta,15 alpha-bis-benzoyloxy-7 alpha-chloro-5 alpha-cholest-8(14)-ene (2). Reaction of 2 with LiAlH4 or LiAlD4 resulted in the formation of 5 alpha-cholest-7-ene-3 beta,15 alpha-diol (3a) or [14 alpha-2H]5 alpha-cholest-7-ene-3 beta,15 alpha-diol (3b). Diol 3b was selectively oxidized by Ag2CO3/celite to [14 alpha-2H]5 alpha-cholest-7-en-15 alpha-ol-3-one (4). Treatment of 1 with MeMgI/CuI gave 7 alpha-methyl-5 alpha-cholest-8(14)-ene-3 beta,15 alpha-diol (5). Selective oxidation of 5 with pyridinium chlorochromate (PCC)/pyridine or oxidation with PCC resulted in the formation of 7 alpha-methyl-5 alpha-cholest-8(14)-en-3 beta-ol-15-one (6) and 7 alpha-methyl-5 alpha-cholest-8(14)-ene-3,15-dione, respectively. Reduction of 6 with LiAlH4 yielded 5 and 7 alpha-methyl-5 alpha-cholest-8(14)-ene-3 beta,15 beta-diol (6). Reaction of 1 with benzoic acid/pyridine gave 3 beta,7 alpha-bis-benzoyloxy-5 alpha-cholest-8(14)-en-15 alpha-ol (9). Treatment of 9 with LiAlH4 or ethanolic KOH resulted in the formation of 5 alpha-cholest-8(14)-ene-3 beta,7 alpha,15 alpha-triol (10). Dibenzoate 9, upon brief treatment with mineral acid, gave 3 beta-benzoyloxy-5 alpha-cholest-8(14)-ene-15-one (11). Oxidation of 9 with PCC yielded 3 beta,7 alpha-bis-benzoyloxy-5 alpha-cholest-8(14)-ene-15-one (12). Ketone 12 was also prepared by the selective hydride reduction of 5 alpha-cholest-8(14)-en-7 alpha-ol-3,15-dione (13) to give 5 alpha-cholest-8(14)-ene-3 beta,7 alpha-diol-15-one (14), which was then treated with benzoyl chloride to produce 12.

Chondrocyte heterogeneity: immunohistologically defined variation of integrin expression at different sites in human fetal knees.

PubMed

Salter, D M; Godolphin, J L; Gourlay, M S

1995-04-01

During development and at maturity different forms of cartilage vary in morphology and macromolecular content. This reflects heterogeneity of chondrocyte activity, in part involving differential interactions with the adjacent extracellular matrix via specialized cell surface receptors such as integrins. We undertook an immunohistological study on a series of human fetal knee joints to assess variation in the expression of integrins by chondrocytes and potential matrix ligands in articular, epiphyseal, growth plate, and meniscal cartilage. The results show that articular chondrocytes (beta 1+, beta 5 alpha V+, alpha 1+, alpha 2+/-, alpha 5+, weakly alpha 6+, alpha V+) differed from epiphyseal (beta 1+, beta 5 alpha V+, alpha 1+/-, alpha 2+/-, alpha 5+, alpha 6+, alpha V+) growth plate (beta 1+, beta 5 alpha V+, alpha 1-, alpha 2-, alpha 5+, alpha 6+, alpha V+), and meniscal cells (beta 1+, beta 5 alpha V+, alpha 1+, strongly alpha 2+, alpha 5+, alpha 6+, alpha V+ in expression of integrin subunits. There was no expression of beta 3, beta 4, beta 6, or alpha 3 by chondrocytes. These results differ from previous reports on the expression of integrins by adult articular cartilage, where alpha 2 and alpha 6 are not seen. Variation in distribution of matrix ligands was also seen. Fibronectin, laminin and Type VI collagen were expressed in all cartilages but there was restricted expression of tenascin, ED-A and ED-B fibronectin isoforms (articular cartilage and meniscus), and vitronectin (absent from growth plate cartilage). Regulated expression of integrins by chondrocytes, associated with changes in the pericellular matrix composition, is of potential importance in control of cartilage differentiation and function in health and disease.

A practical extension of hydrodynamic theory of porous transport for hydrophilic solutes.

PubMed

Bassingthwaighte, James B

2006-03-01

The equations for transport of hydrophilic solutes through aqueous pores provide a fundamental basis for examining capillary-tissue exchange and water and solute flux through transmembrane channels, but the theory remains incomplete for ratios, alpha, of sphere diameters to pore diameters greater than 0.4. Values for permeabilities, P, and reflection coefficients, sigma, from Lewellen, working with Lightfoot et al., at alpha = 0.5 and 0.95, were combined with earlier values for alpha < 0.4, and the physically required values at alpha = 1.0, to provide accurate expressions over the whole range of 0 < alpha < 1. The "data" were the long-accepted theory for alpha < 0.2 and the computational results from Lewellen and Lightfoot et al. on hard spheres (of 5 different alpha's) moving by convection and diffusion through a tight cylindrical pore, accounting for molecular exclusion, viscous forces, pressure drop, torque and rotation of spheres off the center line (averaging across all accessible radial positions), and the asymptotic values at alpha = 1.0. Coefficients for frictional hindrance to diffusion, F(alpha), and drag, G(alpha), and functions for sigma(alpha) and P(alpha), were represented by power law functions and the parameters optimized to give best fits to the combined "data." The reflection coefficient sigma = {1 - [1 - (1 - phi)2]G'(alpha)} + 2alpha2 phi F'(alpha), and the relative permeability P/Pmax = phi F '(alpha)[1 + 9alpha5.5 x (1.0 - alpha5)0.02], where phi is the partition coefficient or volume fraction of the pore available to solute. The new expression for the diffusive hindrance is F'(alpha) = (1 - alpha2)(3/2) phi/[1 + 0.2 x alpha2 x (1 - alpha2)16], and for the drag factor is G'(alpha) = (1 - 2alpha(2)/3 - 0.20217 alpha5)/(1 - 0.75851 alpha5) - 0.0431[1 - (1 - alpha10)]. All of these converge monotonically to the correct limits at alpha = 1. These are the first expressions providing hydrodynamically based estimates of sigma(alpha) and P(alpha) over 0 < alpha < 1 They should be accurate to within 1-2%.

ScreenCube: A 3D Printed System for Rapid and Cost-Effective Chemical Screening in Adult Zebrafish.

PubMed

Monstad-Rios, Adrian T; Watson, Claire J; Kwon, Ronald Y

2018-02-01

Phenotype-based small molecule screens in zebrafish embryos and larvae have been successful in accelerating pathway and therapeutic discovery for diverse biological processes. Yet, the application of chemical screens to adult physiologies has been relatively limited due to additional demands on cost, space, and labor associated with screens in adult animals. In this study, we present a 3D printed system and methods for intermittent drug dosing that enable rapid and cost-effective chemical administration in adult zebrafish. Using prefilled screening plates, the system enables dosing of 96 fish in ∼3 min, with a 10-fold reduction in drug quantity compared to that used in previous chemical screens in adult zebrafish. We characterize water quality kinetics during immersion in the system and use these kinetics to rationally design intermittent dosing regimens that result in 100% fish survival. As a demonstration of system fidelity, we show the potential to identify two known chemical inhibitors of adult tail fin regeneration, cyclopamine and dorsomorphin. By developing methods for rapid and cost-effective chemical administration in adult zebrafish, this study expands the potential for small molecule discovery in postembryonic models of development, disease, and regeneration.

Precipitation of a monoclonal antibody by soluble tungsten.

PubMed

Bee, Jared S; Nelson, Stephanie A; Freund, Erwin; Carpenter, John F; Randolph, Theodore W

2009-09-01

Tungsten microparticles may be introduced into some pre-filled syringes during the creation of the needle hole. In turn, these microcontaminants may interact with protein therapeutics to produce visible particles. We found that soluble tungsten polyanions formed in acidic buffer below pH 6.0 can precipitate a monoclonal antibody within seconds. Soluble tungsten in pH 5.0 buffer at about 3 ppm was enough to cause precipitation of a mAb formulated at 0.02 mg/mL. The secondary structure of the protein was near-native in the collected precipitate. Our observations are consistent with the coagulation of a monoclonal antibody by tungsten polyanions. Tungsten-induced precipitation should only be a concern for proteins formulated below about pH 6.0 since tungsten polyanions are not formed at higher pHs. We speculate that the heterogenous nature of particle contamination within the poorly mixed syringe tip volume could mean that a specification for tungsten contamination based on the entire syringe volume is not appropriate. The potential potency of tungsten metal contamination is highlighted by the small number of particles that would be required to generate soluble tungsten levels needed to coagulate this antibody at pH 5.0.

Precipitation of a Monoclonal Antibody by Soluble Tungsten

PubMed Central

Bee, Jared S.; Nelson, Stephanie A.; Freund, Erwin; Carpenter, John F.; Randolph, Theodore W.

2009-01-01

Tungsten microparticles may be introduced into some pre-filled syringes during the creation of the needle hole. In turn, these microcontaminants may interact with protein therapeutics to produce visible particles. We found that soluble tungsten polyanions formed in acidic buffer below pH 6.0 can precipitate a monoclonal antibody within seconds. Soluble tungsten in pH 5.0 buffer at about 3 ppm was enough to cause precipitation of a mAb formulated at 0.02 mg/mL. The secondary structure of the protein was near-native in the collected precipitate. Our observations are consistent with the coagulation of a monoclonal antibody by tungsten polyanions. Tungsten-induced precipitation should only be a concern for proteins formulated below about pH 6.0 since tungsten polyanions are not formed at higher pHs. We speculate that the heterogenous nature of particle contamination within the poorly mixed syringe tip volume could mean that a specification for tungsten contamination based on the entire syringe volume is not appropriate. The potential potency of tungsten metal contamination is highlighted by the small number of particles that would be required to generate soluble tungsten levels needed to coagulate this antibody at pH 5.0. PMID:19230018

Integrated multi sensors and camera video sequence application for performance monitoring in archery

NASA Astrophysics Data System (ADS)

Taha, Zahari; Arif Mat-Jizat, Jessnor; Amirul Abdullah, Muhammad; Muazu Musa, Rabiu; Razali Abdullah, Mohamad; Fauzi Ibrahim, Mohamad; Hanafiah Shaharudin, Mohd Ali

2018-03-01

This paper explains the development of a comprehensive archery performance monitoring software which consisted of three camera views and five body sensors. The five body sensors evaluate biomechanical related variables of flexor and extensor muscle activity, heart rate, postural sway and bow movement during archery performance. The three camera views with the five body sensors are integrated into a single computer application which enables the user to view all the data in a single user interface. The five body sensors’ data are displayed in a numerical and graphical form in real-time. The information transmitted by the body sensors are computed with an embedded algorithm that automatically transforms the summary of the athlete’s biomechanical performance and displays in the application interface. This performance will be later compared to the pre-computed psycho-fitness performance from the prefilled data into the application. All the data; camera views, body sensors; performance-computations; are recorded for further analysis by a sports scientist. Our developed application serves as a powerful tool for assisting the coach and athletes to observe and identify any wrong technique employ during training which gives room for correction and re-evaluation to improve overall performance in the sport of archery.

Evaluation of Different Gases and Gas Combinations for On-Farm Euthanasia of Pre-Weaned Pigs.

PubMed

Kells, Nikki; Beausoleil, Ngaio; Johnson, Craig; Sutherland, Mhairi

2018-03-16

The aim of this research was to evaluate the welfare of pre-weaned piglets euthanised using three different gas treatments: 100% carbon dioxide (CO₂), 100% argon (Ar) or a mixture of 60% Ar/40% carbon dioxide (Ar/CO₂). Two studies (n = 5 piglets/treatment/study) were conducted: (1) behavioural and physiological data were collected from conscious piglets during exposure to test gases via immersion in a pre-filled chamber and (2) electrophysiological data were collected from lightly anaesthetised, intubated and mechanically ventilated piglets exposed to the same test gases. Based on the duration of escape attempts and laboured breathing, piglets exposed to 100% CO₂ experienced more stress than piglets exposed to 100% Ar prior to loss of consciousness, but there appeared to be no advantage of mixing Ar with CO₂ on indices of animal welfare. However, spectral analysis of the electroencephalogram revealed no changes consistent with nociception during exposure to any of the three gas treatments. Based on the behavioural response to gas exposure, all gases tested caused signs of stress prior to piglets losing consciousness and hence alternative methods of euthanasia need to be evaluated.

Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents.

PubMed

Aggarwal, Arpit; Gopalakrishna, Ganesh; Lauriello, John

2016-01-01

Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation.

Uniject as a delivery system for the once-a-month injectable contraceptive Cyclofem in Brazil.

PubMed

Bahamondes, L; Marchi, N M; de Lourdes Cristofoletti, M; Nakagava, H M; Pellini, E; Araujo, F; Rubin, J

1996-02-01

This study assessed the administration of Cyclofem using prefilled Uniject devices. A total of 480 injections were administered divided equally between standard syringes and Uniject. The majority of women (82%) reported that they felt anxious prior to receiving the injection with Uniject. After injection, more than 80% expressed no anxiety about the appearance of Uniject or about the technique of injection. A total of 96.3% of the participants reported slight to no pain with Uniject. In comparison to the standard syringe, 5.6% expressed having had more pain with Uniject. Ninety percent of the service providers reported that Uniject was easy to activate and inject and that it was reassuring for users to know that the syringe and needle had never been used previously. Only two service providers demonstrated difficulties in activating the device. No accidental punctures occurred during the manipulation, and incomplete emptying of the Uniject was not observed. In conclusion, Uniject is a good device for the administration of the injectable contraceptive Cyclofem. It is likely to be appropriate for the delivery of other injectable contraceptives after the necessary stability tests have been performed.

Flood-conditioned place aversion as a novel non-pharmacological aversive learning procedure in mice.

PubMed

Goltseker, Koral; Barak, Segev

2018-05-08

The place conditioning paradigm is an efficient, widely-used method to study mechanisms that underlie appetitive or aversive learning and memory processes. However, pharmacological agents used to induce conditioned place preference (CPP) or aversion (CPA) can per se interfere with learning and memory processing, hence confounding the results. Therefore, non-pharmacological place conditioning procedures are of high importance. Here, we introduce a novel procedure for induction of CPA in mice, by water flooding. We found that pairing a context with immersion in moderately cold shallow water resulted in aversion and avoidance of that context during a place preference test. Importantly, place aversion emerged only when mice experienced the onset of flood during conditioning training, but not when mice were placed in a compartment pre-filled with water. We also found that warm water was not sufficiently aversive to induce CPA. Moreover, CPA was observed after two or three context-flood pairings but not after one or four pairings, suggesting that moderate conditioning intensity produces optimal CPA expression. Thus, flood-induced CPA is a simple, cheap, and efficient procedure to form and measure place aversion memories in mice, using an ethologically-relevant threat.

Modulation of gene expression by alpha-tocopherol and alpha-tocopheryl phosphate in thp-1 monocytes

USDA-ARS?s Scientific Manuscript database

The naturally occurring vitamin E analogue, alpha-tocopheryl phosphate (alphaTP), has been reported to be more potent than the un-phosphorylated alpha alpha-tocopherol (alphaT). We have now measured plasma levels of alphaTP and compared the cellular effects of alphaTP and gamma-tocopheryl phosphate ...

THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayes, Matthew; Oestlin, Goeran; Duval, Florent

2013-03-10

We report on new imaging observations of the Lyman alpha emission line (Ly{alpha}), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Ly{alpha}, H{alpha}, and the far ultraviolet continuum. We show that Ly{alpha} is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20% radius, R{sub P20}, Ly{alpha} radii are larger than those of H{alpha} by factors ranging from 1 to 3.6, with an average ofmore » 2.4. The average ratio of Ly{alpha}-to-FUV radii is 2.9. This suggests that much of the Ly{alpha} light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Ly{alpha} compared to H{alpha}, {xi}{sub Ly{alpha}} = R {sup Ly{alpha}}{sub P20}/R {sup H{alpha}}{sub P20}, we find {xi}{sub Ly{alpha}} to be uncorrelated with total Ly{alpha} luminosity. However, {xi}{sub Ly{alpha}} is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Ly{alpha} photons throughout the interstellar medium and drive a large extended Ly{alpha} halo.« less

Integrin expression and integrin-mediated adhesion in vitro of human multipotent stromal cells (MSCs) to endothelial cells from various blood vessels.

PubMed

Semon, Julie A; Nagy, Lauren H; Llamas, Claire B; Tucker, H Alan; Lee, Ryang Hwa; Prockop, Darwin J

2010-07-01

Multipotent mesenchymal stromal cells (MSCs) home to damaged tissue by processes partly regulated by integrins. Integrin subunits expressed by MSCs were identified by flow cytometry (FC), immunocytochemistry (IC), and a panel of integrin-binding antibodies. In subconfluent cultures, over 80% of MSCs expressed integrin subunits beta1, beta2, and alpha3, 20%-55% expressed alpha1, alpha2, alpha4, alpha5, alpha6, and alphaV, and about 10% expressed beta3 when assayed by FC. None of the cells expressed significant levels of 13 other integrins as assayed by FC, but seven of the 13 integrins were detected by IC: beta5, alpha7, alpha8, alpha9, alpha11, alphaX, and alphaD. Expression of some integrins changed with MSC confluency: integrins beta3, alpha1, alpha3, alpha5, and alphaV increased, and alpha6 decreased. Furthermore, alpha4 was the only integrin to vary among preparations of MSCs from different donors. The results resolved some discrepancies in the literature concerning integrin expression by MSCs. We also investigated the role of specific integrins in MSC adhesion to endothelial cells (ECs) from the pulmonary artery (HPAEC), cardiac-derived microvasculature (HMVEC-C), and umbilical veins (HUVEC). In experiments with blocking antibodies to beta integrins, anti-beta5 reduced MSC adhesion to all types of ECs, anti-beta1 to both HUVEC and HPAEC, anti-beta3 to HUVEC, and anti-beta2 to HMVEC-C. With blocking antibodies to alpha integrins, anti-alphaX reduced adhesion to HPAEC and HMVEC-C, anti-alphaV to HPAEC, and both anti-alpha7 and anti-alphaD to HMVEC-C. Thus, MSCs use diverse integrins to adhere to EC from various blood vessels in vitro.

Role of the C-terminal extensions of alpha-crystallins. Swapping the C-terminal extension of alpha-crystallin to alphaB-crystallin results in enhanced chaperone activity.

PubMed

Pasta, Saloni Yatin; Raman, Bakthisaran; Ramakrishna, Tangirala; Rao, Ch Mohan

2002-11-29

Several small heat shock proteins contain a well conserved alpha-crystallin domain, flanked by an N-terminal domain and a C-terminal extension, both of which vary in length and sequence. The structural and functional role of the C-terminal extension of small heat shock proteins, particularly of alphaA- and alphaB-crystallins, is not well understood. We have swapped the C-terminal extensions between alphaA- and alphaB-crystallins and generated two novel chimeric proteins, alphaABc and alphaBAc. We have investigated the domain-swapped chimeras for structural and functional alterations. We have used thermal and non-thermal models of protein aggregation and found that the chimeric alphaB with the C-terminal extension of alphaA-crystallin, alphaBAc, exhibits dramatically enhanced chaperone-like activity. Interestingly, however, the chimeric alphaA with the C-terminal extension of alphaB-crystallin, alphaABc, has almost lost its activity. Pyrene solubilization and bis-1-anilino-8-naphthalenesulfonate binding studies show that alphaBAc exhibits more solvent-exposed hydrophobic pockets than alphaA, alphaB, or alphaABc. Significant tertiary structural changes are revealed by tryptophan fluorescence and near-UV CD studies upon swapping the C-terminal extensions. The far-UV CD spectrum of alphaBAc differs from that of alphaB-crystallin whereas that of alphaABc overlaps with that of alphaA-crystallin. Gel filtration chromatography shows alteration in the size of the proteins upon swapping the C-terminal extensions. Our study demonstrates that the unstructured C-terminal extensions play a crucial role in the structure and chaperone activity, in addition to generally believed electrostatic "solubilizer" function.

Synthesis of 3 alpha,7 alpha,12 alpha,25-tetrahydroxy-5 beta-cholestan-24-one, an intermediate in the 25-hydroxylation pathway of cholic acid biosynthesis from cholesterol.

PubMed

Dayal, B; Tint, G S; Batta, A K; Shefer, S; Salen, G; Bose, A K; Pramanik, B N

1983-02-01

This paper describes the chemical synthesis of 3 alpha,7 alpha,12 alpha,25-tetrahydroxy-5 beta-cholestan-24-one via selective oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha, 24 xi,25-pentol with silver carbonate on celite. The structure of this 24-keto bile alcohol was confirmed by gas-liquid chromatography and mass spectrometry. Synthesis of this compound via pyridinium chlorochromate oxidation of the triacetoxy derivative of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 xi,25-pentol followed by saponification further established its structure. 3 alpha,7 alpha,12 alpha,25-Tetrahydroxy-5 beta-cholestan-24-one was required for the in vivo and in vitro studies of side-chain oxidation and cleavage in the 25-hydroxylation pathway of cholic acid biosynthesis.

Involvement of 20alpha-hydroxysteroid dehydrogenase in the maintenance of pregnancy in mice.

PubMed

Choi, Jae-hyek; Ishida, Maho; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

2008-12-01

The enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) catabolizes progesterone into a biologically inactive steroid, 20alpha-dihydroprogesterone (20alpha-OHP). In the corpora lutea of rats and mice, 20alpha-HSD is considered to be involved in functional luteolysis. It is also distributed in other tissues including the placenta, endometrial epithelia and fetal skin, although the roles it plays in these tissues remain to be elucidated. In the present study, we investigated the role of 20alpha-HSD in the maintenance of pregnancy using mice with targeted disruption of the 20alpha-HSD gene. We first confirmed that the number of pups was significantly smaller in 20alpha-HSD-/- pairs than in 20alpha-HSD+/+ pairs. We then mated 20alpha-HSD+/- males and females so that each pregnant female produced 20alpha-HSD+/+, 20alpha-HSD+/- and 20alpha-HSD-/- offspring. The genotype ratio of the offspring did not match the Mendel's law of inheritance, and the numbers of 20alpha-HSD+/- and 20alpha-HSD-/- offspring were smaller than expected values. Although the genotype ratio of fetuses on days 13, 15 and 18 of pregnancy matched the Mendel's law, the total number of fetuses on day 18 was significantly smaller than that on day 13, suggesting that fetal loss occurred during late pregnancy. Next, we transferred 20alpha-HSD+/+ embryos to 20alpha-HSD+/+ or 20alpha-HSD-/- females and found that the number of offspring was significantly smaller in 20alpha-HSD-/- dams than in 20alpha-HSD+/+ dams. Expression of 20alpha-HSD mRNA in the fetus, placenta and uterus progressively increased from day 11 to 18 of pregnancy. In addition, concentrations of progesterone were significantly higher in the 20alpha-HSD-/- fetuses than in the 20alpha-HSD+/+ fetuses, while those of 20alpha-OHP were lower in the 20alpha-HSD-/- fetuses than in the 20alpha-HSD+/+ fetuses. These results suggest that both maternal and fetal 20alpha-HSD play a role in maintaining normal pregnancy at least partially by reducing progesterone concentrations in fetuses.

Blood and tissue tocopherol levels in rats following intraperitoneally administered alpha-tocopheryl acetate.

PubMed

McGee, C D; Greenwood, C E; Jeejeebhoy, K N

1990-01-01

The correction or maintenance of blood and tissue alpha-tocopherol (alpha-Toc) levels by intraperitoneally administered all-rac-alpha-tocopheryl acetate (alpha-Tac) was compared with RRR- alpha-tocopherol (alpha-Toc) in vitamin E-depleted and control rats. Rats received 1.3 TE vitamin E daily for 7 days. alpha-Tac was detected in plasma of one-third of alpha-Tac-treated rats 24 hr after the first treatment, although not in subsequent samplings. Both alpha-Tac and alpha-Toc increased tocopherol levels in plasma and liver of E-deprived rats, while little or no change was observed in adipose tissue and brain. Similarly, control rats treated with alpha-Tac or alpha-Toc had significantly greater (p less than 0.05) plasma and liver alpha-Toc levels at day 3 and day 7 than did saline-treated rats. There was no significant difference in adipose alpha-Toc levels among treatment groups of control rats. The results of this study suggest that alpha-Tac is rapidly hydrolyzed to its biologically active alcohol form and results in similar effects to that of intraperitoneally administered alpha-Toc.

Chemical conversion of corticosteroids to 3 alpha,5 alpha-tetrahydro derivatives. Synthesis of 5 alpha-cortol 3-glucuronides and 5 alpha-cortolone 3-glucuronides.

PubMed

Hosoda, H; Osanai, K; Nambara, T

1991-12-01

The synthesis of the 3-glucuronides of 5 alpha-cortol-20 alpha, 5 alpha-cortolone-20 alpha and their 20 beta-epimers is described. The 5 alpha-cortol 20,21-diacetates (12, 17) and 5 alpha-cortolone 20,21-diacetates (14, 19) were the key intermediates. Sodium borohydride reduction of the carbonyl group at C-20 in 5 alpha-tetrahydrocortisol 3-tert-butyldimethylsilyl ether 17,21-acetonide (8) gave the 20 alpha-hydroxy-acetonide (9). Selective removal of the acetonide ring was successful when the 20 alpha-acetoxy-17 alpha,21-acetonide (10) was treated with 50% acetic acid. Subsequent acetylation with acetic anhydride in pyridine, followed by removal of the protecting group at C-3 in the silyl ether-acetate (11) gave the desired 20 alpha-intermediate (12). The 11-ketone (14) was prepared from 11 by oxidation with pyridinium chlorochromate, followed by desilylation. The 20 beta-acetates (17, 19) were synthesized from 21-acetoxy-3 alpha,11 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one 3-tert-butyldimethylsilyl ether (15). Introduction of the glucuronyl residue at C-3 was carried out by means of the Koenigs-Knorr reaction.

alpha-Adrenergic-mediated activation of human reconstituted fibrinogen receptor (integrin alphaIIbbeta3) in Chinese hamster ovary cells.

PubMed

Butta, Nora; Larrucea, Susana; Gonzalez-Manchon, Consuelo; Alonso, Sonia; Parrilla, Roberto

2004-12-01

This work reports the functional studies of CHO cells coexpressing alpha-adrenergic (alphaAR) and human fibrinogen (Fg) receptors (integrin alphaIIbbeta3). Stimulation of these cells with alpha-agonists produced a transient rise in the free cytosolic calcium (Ca(++)) accompanied by enhanced binding to soluble Fg, and these effects were prevented by specific alphaAR antagonists. The alpha-adrenergic-induced activation of alphaIIbbeta3 in CHO-alphaIIbbeta3-alphaAR increased the rate of adhesion and extension of cells onto Fg coated plates, and also induced a soluble Fg- and alphaIIbbeta3-dependent formation of cell aggregates, whereas no effects were observed by the stimulation of CHO-alphaIIbbeta3 cells. alpha-Adrenergic antagonists, the ligand mimetic peptide RGDS, pertussis toxin (PTX), or EDTA, they all prevented the alpha-adrenergic stimulation of adhesion and aggregation. However, inhibition of PKC prevented the alpha-adrenergic stimulation of cell adherence, whereas blocking the intracellular Ca(++) mobilization impeded the stimulation of cell aggregation. The alpha-adrenergic activation was associated with phosphorylation of a protein of approximately 100 kDa and proteins of the MAPK family. The former was selectively phosphorylated by alpha-adrenergic stimulation whereas the latter were phosphorylated by the binding of cells to Fg and markedly intensified by alpha-adrenergic stimulation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popp, R.A.; Lalley, P.A.; Whitney, J.B.

A genetic polymorphism for a Bgl I endonuclease site near the ..cap alpha..-globin-like pseudogene ..cap alpha..-4 of C57BL/6 and C3H/HeN mice was used to show that ..cap alpha..-4 was not affected by three independent mutations in which the adult globin genes ..cap alpha..-1 and ..cap alpha..-2 were deleted. These results indicated that ..cap alpha..-4 might not be located adjacent to the adult ..cap alpha..-globin genes on chromosome 11. Restriction endonuclease analysis of DNA of a primary clone of a Chinese hamster-mouse somatic cell hybrid that had lost mouse chromosomes 11 and 18 showed that this clone lacked the adult murinemore » globin genes ..cap alpha..-1 and ..cap alpha..-2 but it did contain the ..cap alpha..-globin-like pseudogenes ..cap alpha..-3 and ..cap alpha..-4. These results indicated that the adult ..cap alpha..-globin genes and ..cap alpha..-globin-like pseudogenes are not located on the same chromosome. Similar analyses of several other Chinese hamster-mouse somatic cell hybrids that had segregated other mouse chromosomes indicated that the ..cap alpha..-globin-like pseudogenes ..cap alpha..-3 and ..cap alpha..-4 are located on mouse chromosomes 15 and 17, respectively. These data explain why ..cap alpha..-3 and ..cap alpha..-4 were not affected by the three independently induced deletion-type mutations that cause ..cap alpha..-thalassemia in the mouse.« less

Urokinase plasminogen activator mRNA is induced by IL-1alpha and TNF-alpha in in vitro acantholysis.

PubMed

Feliciani, Claudio; Toto, Paola; Wang, Binghe; Sauder, Daniel N; Amerio, Pierluigi; Tulli, Antonio

2003-08-01

The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1alpha and TNF-alpha are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1alpha and TNF-alpha are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1alpha, TNF-alpha and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1alpha, TNF-alpha and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1alpha/TNF-alpha mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1alpha, TNF-alpha and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-1alpha, anti-TNF-alpha and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1alpha and anti-TNF-alpha antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1alpha/TNF-alpha mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction.

Distribution of alpha3, alpha5 and alpha(v) integrin subunits in mature and immature human oocytes.

PubMed

Capmany, G; Mart, M; Santaló, J; Bolton, V N

1998-10-01

The distribution of three integrin subunits, alpha3, alpha5 and alpha(v), in immature and mature human oocytes has been examined using immunofluorescence and confocal microscopy. The results demonstrate that both alpha5 and alpha(v) are present at the germinal vesicle stage, while alpha3 was only detected in oocytes after germinal vesicle breakdown, in metaphase I and II stage oocytes. The cortical concentration of integrin subunits alpha3 and alpha5 is consistent with their localization in the oolemma. In contrast, the homogeneous distribution of alpha(v) throughout the oocyte suggests the existence of cytoplasmic reservoirs of this protein in the oocyte.

Solution conformation of a neuronal nicotinic acetylcholine receptor antagonist {alpha}-conotoxin OmIA that discriminates {alpha}3 vs. {alpha}6 nAChR subtypes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Seung-Wook; Kim, Do-Hyoung; Olivera, Baldomero M.

2006-06-23

{alpha}-Conotoxin OmIA from Conus omaria is the only {alpha}-conotoxin that shows a {approx}20-fold higher affinity to the {alpha}3{beta}2 over the {alpha}6{beta}2 subtype of nicotinic acetylcholine receptor. We have determined a three-dimensional structure of {alpha}-conotoxin OmIA by nuclear magnetic resonance spectroscopy. {alpha}-Conotoxin OmIA has an '{omega}-shaped' overall topology with His{sup 5}-Asn{sup 12} forming an {alpha}-helix. Structural features of {alpha}-conotoxin OmIA responsible for its selectivity are suggested by comparing its surface characteristics with other functionally related {alpha}4/7 subfamily conotoxins. Reduced size of the hydrophilic area in {alpha}-conotoxin OmIA seems to be associated with the reduced affinity towards the {alpha}6{beta}2 nAChR subtype.

DNA-binding activity of TNF-{alpha} inducing protein from Helicobacter pylori

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuzuhara, T.; Suganuma, M.; Oka, K.

2007-11-03

Tumor necrosis factor-{alpha} (TNF-{alpha}) inducing protein (Tip{alpha}) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-{alpha} and chemokine genes and activation of nuclear factor-{kappa}B. Since Tip{alpha} enters gastric cancer cells, the Tip{alpha} binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip{alpha} was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip{alpha} and DNA, revealed that the affinity of Tip{alpha} for (dGdC)10 is 2400 times stronger than that of del-Tip{alpha}, an inactive Tip{alpha}. This suggestsmore » a strong correlation between DNA-binding activity and carcinogenic activity of Tip{alpha}. And the DNA-binding activity of Tip{alpha} was first demonstrated with a molecule secreted from H. pylori.« less

Interconversion of the Specificities of Human Lysosomal Enzymes Associated with Fabry and Schindler Diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomasic, Ivan B.; Metcalf, Matthew C.; Guce, Abigail I.

2010-09-03

The human lysosomal enzymes {alpha}-galactosidase ({alpha}-GAL, EC 3.2.1.22) and {alpha}-N-acetylgalactosaminidase ({alpha}-NAGAL, EC 3.2.1.49) share 46% amino acid sequence identity and have similar folds. The active sites of the two enzymes share 11 of 13 amino acids, differing only where they interact with the 2-position of the substrates. Using a rational protein engineering approach, we interconverted the enzymatic specificity of {alpha}-GAL and {alpha}-NAGAL. The engineered {alpha}-GAL (which we call {alpha}-GALSA) retains the antigenicity of {alpha}-GAL but has acquired the enzymatic specificity of {alpha}-NAGAL. Conversely, the engineered {alpha}-NAGAL (which we call {alpha}-NAGAL{sup EL}) retains the antigenicity of {alpha}-NAGAL but has acquired themore » enzymatic specificity of the {alpha}-GAL enzyme. Comparison of the crystal structures of the designed enzyme {alpha}-GAL{sup SA} to the wild-type enzymes shows that active sites of {alpha}-GAL{sup SA} and {alpha}-NAGAL superimpose well, indicating success of the rational design. The designed enzymes might be useful as non-immunogenic alternatives in enzyme replacement therapy for treatment of lysosomal storage disorders such as Fabry disease.« less

Hippocampal 3alpha,5alpha-THP may alter depressive behavior of pregnant and lactating rats.

PubMed

Frye, Cheryl A; Walf, Alicia A

2004-07-01

The 5alpha-reduced metabolite of progesterone (P), 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), may mediate progestins' effects to reduce depressive behavior of female rats in part through actions in the hippocampus. To investigate, forced swim test behavior and plasma and hippocampal progestin levels were assessed in groups of rats expected to differ in their 3alpha,5alpha-THP levels due to endogenous differences (pregnant and postpartum), administration of a 5alpha-reductase inhibitor (finasteride; 50 mg/kg sc), and/or gestational stress [prenatal stress (PNS)], an animal model of depression. Pregnant rats had higher plasma and hippocampal 3alpha,5alpha-THP levels and less depressive behavior (decreased immobility, increased struggling and swimming) in the forced swim test than did postpartum rats. Finasteride, compared to vehicle-administration, reduced plasma and hippocampal 3alpha,5alpha-THP levels and increased depressive behavior (increased immobility, decreased struggling and swimming). PNS was associated with lower hippocampal, but not plasma, 3alpha,5alpha-THP levels and increased swimming compared to that observed in control rats. Together, these data suggest that 3alpha,5alpha-THP in the hippocampus may mediate antidepressive behavior of female rats.

Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans.

PubMed

Lockhart, Shawn R; Wu, Wei; Radke, Joshua B; Zhao, Rui; Soll, David R

2005-04-01

The majority of Candida albicans strains in nature are a/alpha and must undergo homozygosis to a/a or alpha/alpha to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/alpha strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/alpha strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/alpha and offspring a/a or alpha/alpha cells were co-injected, a/alpha always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha2 strain and its isogenic a/a parent strain were co-injected, the a/a/alpha2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/alpha genotype that conserves the mating system of C. albicans in nature.

Progesterone's 5 alpha-reduced metabolite, 3 alpha,5 alpha-THP, mediates lateral displacement of hamsters.

PubMed

Frye, Cheryl A; Rhodes, Madeline E

2005-03-15

5 alpha-Pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), progesterone (P4)'s 5 alpha-reduced, 3 alpha-hydroxysteroid oxidoreduced product, facilitates lordosis of rodents in part via agonist-like actions at GABA(A)/benzodiazepine receptor complexes in the ventral tegmental area (VTA). Whether 3 alpha,5 alpha-THP influences another reproductively-relevant behavior, lateral displacement, of hamsters was investigated. Lateral displacement is the movement that female hamsters make with their perineum towards male-like tactile stimulation. This behavior facilitates, and is essential for, successful mating. Hamsters in behavioral estrus had greater lateral displacement responses when endogenous progestin levels were elevated compared to when progestin levels were lower. Administration of P4, a prohormone for 3 alpha,5 alpha-THP, dose-dependently (500 > 200 > 100, 50, or 0 microg) enhanced lateral displacement of ovariectomized hamsters that had been primed with SC estradiol benzoate (5 or 10 microg). Inhibiting P4's metabolism to 3 alpha,5 alpha-THP by co-administering finasteride, a 5 alpha-reductase inhibitor, or indomethacin, a 3 alpha-hydroxysteroid oxidoreductase inhibitor, either systemically or to the VTA, significantly decreased lateral displacement and midbrain progestin levels of naturally receptive or hormone-primed hamsters compared to controls. These data suggest that lateral displacement is progestin-sensitive and requires the formation of 3 alpha,5 alpha-THP in the midbrain VTA.

Alpha1- and alpha2-containing GABAA receptor modulation is not necessary for benzodiazepine-induced hyperphagia.

PubMed

Morris, H V; Nilsson, S; Dixon, C I; Stephens, D N; Clifton, P G

2009-06-01

Benzodiazepines increase food intake, an effect attributed to their ability to enhance palatability. We investigated which GABA(A) receptor subtypes may be involved in mediating benzodiazepine-induced hyperphagia. The role of the alpha2 subtype was investigated by observing the effects of midazolam, on the behavioural satiety sequence in mice with targeted deletion of the alpha2 gene (alpha2 knockout). Midazolam (0.125, 0.25 and 0.5mg/kg) increased food intake and the amount of time spent feeding in alpha2 knockout mice, suggesting that BZ-induced hyperphagia does not involve alpha2-containing GABA(A) receptors. We further investigated the roles of alpha1- and alpha3-containing GABA(A) receptors in mediating BZ-induced hyperphagia. We treated alpha2(H101R) mice, in which alpha2-containing receptors are rendered benzodiazepine insensitive, with L-838417, a compound which acts as a partial agonist at alpha2-, alpha3- and alpha5-receptors but is inactive at alpha1-containing receptors. L-838417 (10 and 30 mg/kg) increased food intake and the time spent feeding in both wildtype and alpha2(H101R) mice, demonstrating that benzodiazepine-induced hyperphagia does not require alpha1- and alpha2-containing GABA(A) receptors. These observations, together with evidence against the involvement of alpha5-containing GABA(A) receptors, suggest that alpha3-containing receptors mediate BZ-induced hyperphagia in the mouse.

Effect of alpha-tocopherol on bovine in vitro fertilization.

PubMed

Marques, A; Santos, P; Antunes, G; Chaveiro, A; Moreira da Silva, F

2010-02-01

The objectives of this work are to determine if exogenous supplementation with alpha-tocopherol increases the in vitro fertilization (IVF) rate of bovine oocytes and improves viability of selected spermatozoa after 'swim-up'. The percentage of fertilized oocytes was significantly but negatively correlated (r = -0.941, p < 0.01) with the concentration of alpha-tocopherol. The control resulted in 95% of fertilized oocytes, which decreased as follows: 25 microM alpha-tocopherol (alpha25) 86%, 50 microM alpha-tocopherol (alpha50) 74%, 100 microM alpha-tocopherol (alpha100) 66% and 200 microM alpha-tocopherol (alpha200) 56%. Relatively to sperm viability after 'swim-up' with alpha-tocopherol supplementation, this antioxidant proved to have a beneficial effect as its concentration increased up to alpha50, decreasing for the concentrations of alpha100 and alpha200. Control resulted in 83% of live cells and 16% of dead cells; alpha25 resulted in 88% of live cells and 12% of dead cells; alpha50 resulted in 91% of live cells and 9% of dead cells; alpha100 resulted in 67% of live cells and 33% of dead cells; and finally alpha200 resulted in 57% of live cells and 42% of dead cells. In summary, the present study allows to conclude that, in our conditions, supplementation with the antioxidant alpha-tocopherol in IVF of bovine oocytes has a detrimental effect on fertilization rates. Nevertheless, exogenous supplementation with alpha-tocopherol at a concentration of 50 mM in the sperm-TALP media during the 'swim-up' technique has a significant beneficial effect on the selected spermatozoa viability.

Regulation of neurosteroid allopregnanolone biosynthesis in the rat spinal cord by glycine and the alkaloidal analogs strychnine and gelsemine.

PubMed

Venard, C; Boujedaini, N; Belon, P; Mensah-Nyagan, A G; Patte-Mensah, C

2008-04-22

The neurosteroid allopregnanolone (3alpha,5alpha-THP) is well characterized as a potentially therapeutic molecule which exerts important neurobiological actions including neuroprotective, antidepressant, anxiolytic, anesthetic and analgesic effects. We have recently observed that neurons and glial cells of the rat spinal cord (SC) contain various key steroidogenic enzymes such as 5alpha-reductase and 3alpha-hydroxysteroid oxido-reductase which are crucial for 3alpha,5alpha-THP biosynthesis. Furthermore, we demonstrated that the rat SC actively produces 3alpha,5alpha-THP. As the key factors regulating neurosteroid production by nerve cells are unknown and because glycine is one of the pivotal inhibitory neurotransmitters in the SC, we investigated glycine effects on 3alpha,5alpha-THP biosynthesis in the rat SC. Glycine markedly stimulated [(3)H]-progesterone conversion into [(3)H]3alpha,5alpha-THP by SC slices. The alkaloid strychnine, well-known as a glycine receptor (Gly-R) antagonist, blocked glycine stimulatory effect on 3alpha,5alpha-THP formation. Gelsemine, another alkaloid containing the same functional groups as strychnine, increased 3alpha,5alpha-THP synthesis. The stimulatory effects of glycine and gelsemine on 3alpha,5alpha-THP production were additive when the two drugs were combined. These results demonstrate that glycine and gelsemine, acting via Gly-R, upregulate 3alpha,5alpha-THP biosynthesis in the SC. The data also revealed a structure-activity relationship of the analogs strychnine and gelsemine on neurosteroidogenesis. Possibilities are opened for glycinergic agents and gelsemine utilization to stimulate selectively 3alpha,5alpha-THP biosynthetic pathways in diseases evoked by a decreased neurosteroidogenic activity of nerve cells.

The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one affects dopamine-mediated behavior in rodents.

PubMed

Khisti, Rahul T; Deshpande, Laxmikant S; Chopde, Chandrabhan T

2002-05-01

The neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) has been previously shown to induce catalepsy in mice that is modified by GABAergic, dopaminergic, adenosinergic and serotonergic agents. In light of the interaction of this endogenous neurosteroid with GABAergic and dopaminergic transmission, there is potential interest in the possible role of 3alpha,5alpha-THP in psychotic disorders. This study assessed the effect of 3alpha,5alpha-THP in certain dopamine-mediated behavioral paradigms that are widely used to predict antipsychotic-like activity. 3alpha,5alpha-THP (1-8 microg per animal, i.c.v.), the classic neuroleptic (dopamine receptor antagonist) haloperidol (0.25 mg/kg, i.p.), and the benzodiazepine diazepam (7 mg/kg, i.p.) were injected into different groups of animals, and their behavior was screened using the following animal tests: conditioned avoidance response, apomorphine-induced climbing, and amphetamine-induced motor hyperactivity. Separate groups of mice that received 3alpha,5alpha-THP (1-8 microg per animal, i.c.v.) were screened for catalepsy. Furthermore, the effect of a sub-cataleptic dose (0.1 microg per mouse, i.c.v.) of 3alpha,5alpha-THP, either alone or in combination with the GABA(A) receptor antagonist picrotoxin (0.8 mg/kg, i.p.) was measured on haloperidol-induced catalepsy. 3alpha,5alpha-THP like haloperidol reduced conditioned avoidance, apomorphine-induced cage climbing and amphetamine-induced motor hyperactivity. Diazepam only affected conditioned avoidance. 3alpha,5alpha-THP also induced dose-dependent catalepsy. Furthermore, sub-cataleptic doses of 3alpha,5alpha-THP potentiated haloperidol-induced catalepsy. This potentiation was blocked by prior treatment with the GABA(A) receptor antagonist picrotoxin. These findings suggest that 3alpha,5alpha-THP, by its action at the GABA(A) receptors, increases GABAergic tone leading to a behavioral profile similar to that of dopamine receptor antagonists.

78 FR 53189 - Dorel Juvenile Group, Denial of Petition for Decision of Inconsequential Noncompliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... Omega Elite 22187REM Alpha Omega Elite 22187REMA Alpha Omega Elite 22187SAR Alpha Omega Elite 22187SARA Alpha Omega Elite 22465FSM Alpha Omega Elite 22790CGT Deluxe 3 in 1 CC033BMT Alpha Omega Elite CC043ANK Alpha Omega Elite CC043ANL Alpha Omega Elite CC043AQS Alpha Omega Elite CC046AAI Deluxe 3 in 1 CC046AAU...

[Reproductive effort, fattening index and yield of Arca zebra (Filibranchia: Arcidae) by length and its association with environmental variables, Sucre, Venezuela].

PubMed

Lista, María; Velásquez, Carlos; Prieto, Antulio; Longart, Yelipza

2016-06-01

Arca zebra is a mollusk of commercial value and a major socioeconomic fishery in Northeastern Venezuela. The present study aimed to evaluate the reproductive effort (RE), fattening index (FI) and yield (Y) in different size groups of A. zebra from the morro Chacopata, Venezuela. For this, monthly samplings from June 2008 and June 2009, were undertaken, and the bivalves obtained were distributed in three length groups: I (30.1 to 50.0 mm), II (50.1 to 70.0 mm) and III (> 70.0 mm). Monthly RE, FI and Y were determined based on bivalve changes in volume of fresh meat (VFM), intervalvar volume (IV), dry gonad biomass (DW), dry biomass of the organism without gonad (DWs), fresh biomass of meat (FBM) and total biomass including shell (TBIS). Besides, environmental variables such as temperature, salinity, dissolved oxygen, total organic and inorganic seston and chlorophyll a were measured monthly. There was great variation in the DW between length groups (relevant for II and III): increased from June until late September 2008, was followed by a marked decrease in October 2008, recovered in the following months, and decreased in January 2009, with a slight increase until May 2009; these changes were associated with variations in sea temperature. The weight of the gonad (DW) influenced the RE, FI and Y, as these reached their peaks in the months where there was higher gonadal production, indicating the influence of temperature on A. zebra reproduction.

Characterization of the APLF FHA-XRCC1 phosphopeptide interaction and its structural and functional implications.

PubMed

Kim, Kyungmin; Pedersen, Lars C; Kirby, Thomas W; DeRose, Eugene F; London, Robert E

2017-12-01

Aprataxin and PNKP-like factor (APLF) is a DNA repair factor containing a forkhead-associated (FHA) domain that supports binding to the phosphorylated FHA domain binding motifs (FBMs) in XRCC1 and XRCC4. We have characterized the interaction of the APLF FHA domain with phosphorylated XRCC1 peptides using crystallographic, NMR, and fluorescence polarization studies. The FHA-FBM interactions exhibit significant pH dependence in the physiological range as a consequence of the atypically high pK values of the phosphoserine and phosphothreonine residues and the preference for a dianionic charge state of FHA-bound pThr. These high pK values are characteristic of the polyanionic peptides typically produced by CK2 phosphorylation. Binding affinity is greatly enhanced by residues flanking the crystallographically-defined recognition motif, apparently as a consequence of non-specific electrostatic interactions, supporting the role of XRCC1 in nuclear cotransport of APLF. The FHA domain-dependent interaction of XRCC1 with APLF joins repair scaffolds that support single-strand break repair and non-homologous end joining (NHEJ). It is suggested that for double-strand DNA breaks that have initially formed a complex with PARP1 and its binding partner XRCC1, this interaction acts as a backup attempt to intercept the more error-prone alternative NHEJ repair pathway by recruiting Ku and associated NHEJ factors. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

Contribution of alpha3(IV)alpha4(IV)alpha5(IV) Collagen IV to the Mechanical Properties of the Glomerular Basement Membrane

NASA Astrophysics Data System (ADS)

Gyoneva, Lazarina

The glomerular basement membrane (GBM) is a vital part of the blood-urine filtration barrier in the kidneys. In healthy GBMs, the main tension-resisting component is alpha3(IV)alpha4(IV)alpha5(IV) type IV collagen, but in some diseases it is replaced by other collagen IV isoforms. As a result, the GBM becomes leaky and disorganized, ultimately resulting in kidney failure. Our goal is to understanding the biomechanical aspects of the alpha3(IV)alpha4(IV)alpha5(IV) chains and how their absence could be responsible for (1) the initial injury to the GBM and (2) progression to kidney failure. A combination of experiments and computational models were designed for that purpose. A model basement membrane was used to compare experimentally the distensibility of tissues with the alpha3(IV)alpha4(IV)alpha5(IV) chains present and missing. The experiments showed basement membranes containing alpha3(IV)alpha4(IV)alpha5(IV) chains were less distensible. It has been postulated that the higher level of lateral cross-linking (supercoiling) in the alpha3(IV)alpha4(IV)alpha5(IV) networks contributes additional strength/stability to basement membranes. In a computational model of supercoiled networks, we found that supercoiling greatly increased the stiffness of collagen IV networks but only minimally decreased the permeability, which is well suited for the needs of the GBM. It is also known that the alpha3(IV)alpha4(IV)alpha5(IV) networks are more protected from enzymatic degradation, and we explored their significance in GBM remodeling. Our simulations showed that the more protected network was needed to prevent the system from entering a dangerous feedback cycle due to autoregulation mechanisms in the kidneys. Overall, the work adds to the evidence of biomechanical differences between the alpha3(IV)alpha4(IV)alpha5(IV) networks and other collagen IV networks, points to supercoiling as the main source of biomechanical differences, discusses the suitability of alpha3(IV)alpha4(IV)alpha5(IV) networks to meet the mechanics and permeability needs of the GBM, and explores the role of biomechanics and enzymatic digestion in GBM remodeling.

Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.

PubMed

Tan, J; Tay, J S; Wong, Y C; Kham, S K; Bte Abd Aziz, N; Teo, S H; Wong, H B

1995-01-01

Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.

Synthesis of methyl 3-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 3-O-alpha-D-talopyranosyl-alpha-D-talopyranoside.

PubMed

Dubey, R; Jain, R K; Abbas, S A; Matta, K L

1987-08-01

Methyl 2-O-benzyl-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha- D-mannopyranoside (4) and methyl 2-O-benzyl-3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (6) were prepared from a common intermediate, namely, methyl 2-O-benzyl-4,6-O-benzylidene-3-O-(2,3,4,6-tetra-O-acetyl-alpha-D- mannopyranosyl)-alpha-D-mannopyranoside. On treatment with tert-butylchlorodiphenylsilane, in N,N-dimethylformamide in the presence of imidazole, 4 and 6 afforded methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (7), and methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(6-O-tert- butyldiphenylsilyl-alpha-D-mannopyranosyl)-alpha-D-mannopyranoside (8), respectively. Compound 8 was converted into its 2,3-O-isopropylidene derivative (9), and oxidation of 7 and 9 with pyridinium chlorochromate, and reduction of the resulting carbonyl intermediates gave methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-talopyranoside and methyl 2-O-benzyl-6-O-tert-butyldiphenylsilyl-3-O-(6-O-tert-butyldiphe nylsilyl- 2,3-O-isopropylidene-alpha-D-talopyranosyl)-alpha-D-talopyranoside , respectively. Removal of the protecting groups furnished the title disaccharides.

Jellyfish mesogloea collagen. Characterization of molecules as alpha 1 alpha 2 alpha 3 heterotrimers.

PubMed

Miura, S; Kimura, S

1985-12-05

The mesogloea collagen of a primitive animal, the jellyfish Stomolophus nomurai, belonging to the class Scyphozoa in the Coelenterata, was studied with respect to its chain structure. Most of the mesogloea collagen was solubilized by limited digestion with pepsin and isolated by selective precipitation at 0.9 m NaCl in 0.5 M acetic acid. Upon denaturation, the pepsin-solubilized collagen produced three distinct alpha chains, alpha 1, alpha 2, and alpha 3, in comparable amounts which were separable by CM-cellulose chromatography. The nonidentity of these alpha chains was confirmed by amino acid and carbohydrate analyses and peptide mapping. Furthermore, the introduction of intramolecular cross-links into native molecules by formaldehyde yielded a large proportion of gamma 123 chain with chain structure alpha 1 alpha 2 alpha 3, as judged by chromatographic behavior and peptide maps. We concluded that mesogloea collagen is comprised of alpha 1 alpha 2 alpha 3 heterotrimers and is chemically like vertebrate Type V collagen. On the other hand, sea anemone mesogloea collagen from the class Anthozoa was previously reported to comprise (alpha)3 homotrimers (Katzman, R. L., and Kang, A. H. (1972) J. Biol. Chem. 247, 5486-5489). On the basis of these findings, we assume that alpha 1 alpha 2 alpha 3 heterotrimers arose in evolution with the divergence of Scyphozoa and Anthozoa.

Solution structure of {alpha}-conotoxin PIA, a novel antagonist of {alpha}6 subunit containing nicotinic acetylcholine receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Seung-Wook; Lee, Si-Hyung; Kim, Do-Hyoung

2005-12-30

{alpha}-Conotoxin PIA is a novel nicotinic acetylcholine receptor (nAChR) antagonist isolated from Conus purpurascens that targets nAChR subtypes containing {alpha}6 and {alpha}3 subunits. {alpha}-conotoxin PIA displays 75-fold higher affinity for rat {alpha}6/{alpha}3{beta}2{beta}3 nAChRs than for rat {alpha}3{beta}2 nAChRs. We have determined the three-dimensional structure of {alpha}-conotoxin PIA by nuclear magnetic resonance spectroscopy. The {alpha}-conotoxin PIA has an '{omega}-shaped' overall topology as other {alpha}4/7 subfamily conotoxins. Yet, unlike other neuronally targeted {alpha}4/7-conotoxins, its N-terminal tail Arg{sup 1}-Asp{sup 2}-Pro{sup 3} protrudes out of its main molecular body because Asp{sup 2}-Pro{sup 3}-Cys{sup 4}-Cys{sup 5} forms a stable type I {beta}-turn. In addition, amore » kink introduced by Pro{sup 15} in the second loop of this toxin provides a distinct steric and electrostatic environment from those in {alpha}-conotoxins MII and GIC. By comparing the structure of {alpha}-conotoxin PIA with other functionally related {alpha}-conotoxins we suggest structural features in {alpha}-conotoxin PIA that may be associated with its unique receptor recognition profile.« less

Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rangwala, Shamina M.; Li, Xiaoyan; Lindsley, Loren

2007-05-25

Estrogen-related receptor {alpha} (ERR{alpha}) is an important mediator of mitochondrial biogenesis and function. To investigate the transcriptional network controlling these phenomena, we investigated mitochondrial gene expression in embryonic fibroblasts isolated from ERR{alpha} null mice. Peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) stimulated mitochondrial gene expression program in control cells, but not in the ERR{alpha} null cells. Interestingly, the induction of levels of mitochondrial oxidative stress protection genes in response to increased PGC-1{alpha} levels was dependent on ERR{alpha}. Furthermore, we found that the PGC-1{alpha}-mediated induction of estrogen-related receptor {gamma} and nuclear respiratory factor 2 (NRF-2), was dependent on the presence of ERR{alpha}.more » Basal levels of NRF-2 were decreased in the absence of ERR{alpha}. The absence of ERR{alpha} resulted in a decrease in citrate synthase enzyme activity in response to PGC-1{alpha} overexpression. Our results indicate an essential role for ERR{alpha} as a key regulator of oxidative metabolism.« less

Toxicity of trichlorotoluene isomers: a 28-day feeding study in the rat.

PubMed

Chu, I; Shen, S Y; Villeneuve, D C; Secours, V E; Valli, V E

1984-03-01

Groups of 10 male and 10 female rats were fed alpha,alpha,alpha-, alpha,2,6- or 2,3,6- trichlorotoluene (TCT) in their diet at 0, 0.5, 5.0, 50 or 500 ppm for 28 days. Growth rate and food consumption were not affected by treatment. No deaths occurred. Significant increases in liver weights were observed in male rats fed 5.0 and 500 ppm 2,3,6-TCT. Mild serum biochemical changes occurred in male rats. These included increased SDH activities in the groups fed 5.0 and 50 ppm alpha, alpha, alpha-TCT, and 5.0 ppm 2,3,6-TCT. Alpha, alpha, alpha-TCT at 500 ppm caused elevated LDH activities in male rats. Hepatic microsomal aminopyrine N-demethylase activities were increased in male rats fed 500 ppm alpha,2,6-TCT. Hematological parameters were not affected by treatment. Mild histological changes were seen in the liver, kidney and thyroid of treated rats. Data presented here suggest that alpha, alpha, alpha-, alpha,2,6- and 2,3,6-TCT possess a low order of oral toxicity in the rat.

Improved synthesis of 3 alpha, 7 alpha, 12 alpha, 24 = xi-tetrahydroxy-5 beta-cholestan-26-oic acid.

PubMed

Batta, A K; Tint, G S; Dayal, B; Shefer, S; Salen, G

1982-06-01

This paper describes three simple and short methods for the conversion of cholic acid into cholylaldehyde with protected hydroxyl groups. The first method involves lithium aluminum hydride reduction of the tetrahydropyranyl ether of methyl cholate and oxidation of the resulting primary alcohol with pyridinium chlorochromate. The second method employs diborane for the reduction of the -COOH group to the -CH2OH group, while the third method involves the reduction of 3 alpha, 7 alpha, 12 alpha-triformyloxy-5 beta-cholan-24-oic acid (as the acid chloride) directly into 3 alpha, 7 alpha, 12 alpha-triformyloxy-5 beta-cholan-24-al with TMA-ferride (tetramethylammonium hydridoirontetracarbonyl). The aldehyde obtained by any of the above methods underwent smooth Reformatsky reaction with ethyl alpha-bromopropionate to yield 3 alpha, 7 alpha, 12 alpha, 24 xi-tetrahydroxy-5 beta-cholestan-26-oic acid.

The effects of SB 216469, an antagonist which discriminates between the alpha 1A-adrenoceptor and the human prostatic alpha 1-adrenoceptor.

PubMed Central

Chess-Williams, R.; Chapple, C. R.; Verfurth, F.; Noble, A. J.; Couldwell, C. J.; Michel, M. C.

1996-01-01

1. The affinity of the alpha 1-adrenoceptor antagonist SB 216469 (also known as REC 15/2739) has been determined at native and cloned alpha 1-adrenoceptor subtypes by radioligand binding and at functional alpha 1-adrenoceptor subtypes in isolated tissues. 2. In radioligand binding studies with [3H]-prazosin, SB 216469 had a high affinity at the alpha 1A-adrenoceptors of the rat cerebral cortex and kidney (9.5-9.8) but a lower affinity at the alpha 1B-adrenoceptors of the rat spleen and liver (7.7-8.2). 3. At cloned rat alpha 1-adrenoceptor subtypes transiently expressed in COS-1 cells and also at cloned human alpha 1-adrenoceptor subtypes stably transfected in Rat-1 cells, SB 216469 exhibited a high affinity at the alpha 1a-adrenoceptors (9.6-10.4) with a significantly lower affinity at the alpha 1b-adrenoceptor (8.0-8.4) and an intermediate affinity at the alpha 1d-adrenoceptor (8.7-9.2). 4. At functional alpha 1-adrenoceptors, SB 216469 had a similar pharmacological profile, with a high affinity at the alpha 1A-adrenoceptors of the rat vas deferens and anococcygeus muscle (pA2 = 9.5-10.0), a low affinity at the alpha 1B-adrenoceptors of the rat spleen (6.7) and guinea-pig aorta (8.0), and an intermediate affinity at the alpha 1D-adrenoceptors of the rat aorta (8.8). 5. Several recent studies have concluded that the alpha 1-adrenoceptor present in the human prostate has the pharmacological characteristics of the alpha 1A-adrenoceptor subtype. However, the affinity of SB 216469 at human prostatic alpha 1-adrenoceptors (pA2 = 8.1) determined in isolated tissue strips, was significantly lower than the values obtained at either the cloned alpha 1a-adrenoceptors (human, rat, bovine) or the native alpha 1A-adrenoceptors in radioligand binding and functional studies in the rat. 6. Our results with SB 216469, therefore, suggest that the alpha 1-adrenoceptor mediating contractile responses of the human prostate has properties which distinguish it from the cloned alpha 1a-adrenoceptor or native alpha 1A-adrenoceptor. Since it has previously been shown that the receptor is not the alpha 1B- or alpha 1D-adrenoceptor, the functional alpha 1-adrenoceptor of the human prostate may represent a novel receptor with properties which differ from any of the alpha 1-adrenoceptors currently defined by pharmacological means. PMID:8937710

Clinical evaluation of glass ionomer for pit and fissure sealing of fully erupted molars.

PubMed

Sly, Edith G; Kaplan, Andrea E; Missana, Liliana

2010-01-01

The aim of this study was to evaluate the clinical behavior of two conventional glass ionomers used for pit and fissure sealing in terms of retention, marginal adaptation, caries recurrence and cracking. Eighty-three fully erupted first permanent molars were sealed, in a group of children aged 5 to 8 years. A double-blind, single operator, paired design was used. Materials applied were Fuji IX and VII. Retention (R), presence of caries (PC), marginal discoloration (MD), marginal adaptation (MA) and cracking (C) were evaluated at 6 and 12 months using Ryge's criteria. Data registered 6 months after treatment were: Fuji IX: R: Alpha 37, Bravo 2, Charlie: 4; PC: Alpha 43, Bravo: 0; MA: Alpha 38, Bravo: 1; MD: Alpha 39, Bravo: 0, Charlie: 0; C: Alpha 39, Bravo: 0. Fuji VII: R: Alpha 29, Bravo 4, Charlie: 7; PC: Alpha 40, Bravo: 0; MA: Alpha: 34, Bravo: 0; MD: Alpha: 34, Bravo: 0, Charlie: 0; C: Alpha 33, Bravo: 0. Results after one year were: Fuji IX: R: Alpha 33, Bravo: 3, Charlie: 9; PC: Alpha 44, Bravo: 1; MA: Alpha 33, Bravo: 1; MD: Alpha: 34, Bravo: 0, Charlie: 0; C: Alpha: 34, Bravo: 0. Fuji VII: R: Alpha 22, Bravo 4, Charlie: 13, PC: Alpha 40, Bravo: 0; MA: Alpha 23, Bravo: 1; MD: Alpha 23, Bravo: 1, Charlie: 0; C: Alpha 23, Bravo: 1. Statistical analysis using Fisher test showed no significant difference (p > 0.05) for R, and MA. For PC, MD and C, values are not reported because both materials showed the same results. The second control showed no significant difference (p > 0.05) for R, MA, PC, MD and C. Results suggest no difference between Fuji IX and Fuji VII as sealants in fully erupted permanent molars.

Cloning, expression, and mapping of allergenic determinants of alphaS1-casein, a major cow's milk allergen.

PubMed

Schulmeister, Ulrike; Hochwallner, Heidrun; Swoboda, Ines; Focke-Tejkl, Margarete; Geller, Beate; Nystrand, Mats; Härlin, Annika; Thalhamer, Josef; Scheiblhofer, Sandra; Keller, Walter; Niggemann, Bodo; Quirce, Santiago; Ebner, Christoph; Mari, Adriano; Pauli, Gabrielle; Herz, Udo; Valenta, Rudolf; Spitzauer, Susanne

2009-06-01

Milk is one of the first components introduced into human diet. It also represents one of the first allergen sources, which induces IgE-mediated allergies in childhood ranging from gastrointestinal, skin, and respiratory manifestations to severe life-threatening manifestations, such as anaphylaxis. Here we isolated a cDNA coding for a major cow's milk allergen, alphaS1-casein, from a bovine mammary gland cDNA library with allergic patients' IgE Abs. Recombinant alphaS1-casein was expressed in Escherichia coli, purified, and characterized by circular dichroism as a folded protein. IgE epitopes of alphaS1-casein were determined with recombinant fragments and synthetic peptides spanning the alphaS1-casein sequence using microarrayed components and sera from 66 cow's milk-sensitized patients. The allergenic activity of ralphaS1-casein and the alphaS1-casein-derived peptides was determined using rat basophil leukemia cells transfected with human FcepsilonRI, which had been loaded with the patients' serum IgE. Our results demonstrate that ralphaS1-casein as well as alphaS1-casein-derived peptides exhibit IgE reactivity, but mainly the intact ralphaS1-casein induced strong basophil degranulation. These results suggest that primarily intact alphaS1-casein or larger IgE-reactive portions thereof are responsible for IgE-mediated symptoms of food allergy. Recombinant alphaS1-casein as well as alphaS1-casein-derived peptides may be used in clinical studies to further explore pathomechanisms of food allergy as well as for the development of new diagnostic and therapeutic strategies for milk allergy.

Involvement of the Clock Gene Rev-erb alpha in the Regulation of Glucagon Secretion in Pancreatic Alpha-Cells

PubMed Central

Vieira, Elaine; Marroquí, Laura; Figueroa, Ana Lucia C.; Merino, Beatriz; Fernandez-Ruiz, Rebeca; Nadal, Angel; Burris, Thomas P.; Gomis, Ramon; Quesada, Ivan

2013-01-01

Disruption of pancreatic clock genes impairs pancreatic beta-cell function, leading to the onset of diabetes. Despite the importance of pancreatic alpha-cells in the regulation of glucose homeostasis and in diabetes pathophysiology, nothing is known about the role of clock genes in these cells. Here, we identify the clock gene Rev-erb alpha as a new intracellular regulator of glucagon secretion. Rev-erb alpha down-regulation by siRNA (60–70% inhibition) in alphaTC1-9 cells inhibited low-glucose induced glucagon secretion (p<0.05) and led to a decrease in key genes of the exocytotic machinery. The Rev-erb alpha agonist GSK4112 increased glucagon secretion (1.6 fold) and intracellular calcium signals in alphaTC1-9 cells and mouse primary alpha-cells, whereas the Rev-erb alpha antagonist SR8278 produced the opposite effect. At 0.5 mM glucose, alphaTC1-9 cells exhibited intrinsic circadian Rev-erb alpha expression oscillations that were inhibited by 11 mM glucose. In mouse primary alpha-cells, glucose induced similar effects (p<0.001). High glucose inhibited key genes controlled by AMPK such as Nampt, Sirt1 and PGC-1 alpha in alphaTC1-9 cells (p<0.05). AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha. Nampt inhibition decreased Sirt1, PGC-1 alpha and Rev-erb alpha mRNA expression (p<0.01) and glucagon release (p<0.05). These findings identify Rev-erb alpha as a new intracellular regulator of glucagon secretion via AMPK/Nampt/Sirt1 pathway. PMID:23936124

Morphological characterization of the AlphaA- and AlphaB-crystallin double knockout mouse lens

PubMed Central

Boyle, Daniel L; Takemoto, Larry; Brady, James P; Wawrousek, Eric F

2003-01-01

Background One approach to resolving some of the in vivo functions of alpha-crystallin is to generate animal models where one or both of the alpha-crystallin gene products have been eliminated. In the single alpha-crystallin knockout mice, the remaining alpha-crystallin may fully or partially compensate for some of the functions of the missing protein, especially in the lens, where both alphaA and alphaB are normally expressed at high levels. The purpose of this study was to characterize gross lenticular morphology in normal mice and mice with the targeted disruption of alphaA- and alphaB-crystallin genes (alphaA/BKO). Methods Lenses from 129SvEvTac mice and alphaA/BKO mice were examined by standard scanning electron microscopy and confocal microscopy methodologies. Results Equatorial and axial (sagittal) dimensions of lenses for alphaA/BKO mice were significantly smaller than age-matched wild type lenses. No posterior sutures or fiber cells extending to the posterior capsule of the lens were found in alphaA/BKO lenses. Ectopical nucleic acid staining was observed in the posterior subcapsular region of 5 wk and anterior subcapsular cortex of 54 wk alphaA/BKO lenses. Gross morphological differences were also observed in the equatorial/bow, posterior and anterior regions of lenses from alphaA/BKO mice as compared to wild mice. Conclusion These results indicated that both alphaA- and alphaB-crystallin are necessary for proper fiber cell formation, and that the absence of alpha-crystallin can lead to cataract formation. PMID:12546709

The effects of infusions of ring-A-reduced derivatives of aldosterone on the antinatriuretic and kaliuretic actions of aldosterone.

PubMed

Morris, D J; Souness, G W; Saccoccio, N A; Harnik, M

1989-01-01

Infusion of Ring-A-reduced metabolites of aldosterone in adrenalectomized male rats for 4 days revealed that 5 alpha-Ring-A-reduced derivatives, 5 alpha-dihydroaldosterone (5 alpha-DHAldo; 2.5-5.0 micrograms/day), 3 alpha,5 alpha-tetrahydroaldosterone (3 alpha,5 alpha-THAldo; 5-25 micrograms/day), and 3 beta,5 alpha-THAldo (50-175 micrograms/day) possessed intrinsic Na+-retaining activity. The same infusions of 5 alpha-DHAldo, 3 alpha,5 alpha-THAldo, and 3 beta,5 alpha-THAldo, also lowered the urinary excretion of potassium. The 5 beta-Ring-A-reduced derivative 3 alpha,5 beta-THAldo did not demonstrate either of these biological properties. In another set of experiments, on the fourth day of infusion, aldosterone (0.1 microgram/rat) was administered acutely subcutaneously; none of the Ring-A-reduced derivatives altered the Na+-retaining activity of aldosterone. However, in a dose-dependent manner, both 3 alpha,5 alpha-THAldo and 3 beta,5 alpha-THAldo blunted the urinary K+-secretory effect of aldosterone; low dosages of 5 alpha-DHAldo and larger dosages of 3 alpha,5 beta-THAldo did not. Thus, the 5 alpha-reduced derivatives of aldosterone not only lowered urinary Na+ and K+ excretion in their own right, but two of them blunted the kaliuretic response of the parent mineralocorticoid, aldosterone. Further experiments will be required to determine whether these aldosterone metabolites are further metabolized or interconverted during the expression of the regulatory properties described here and whether these properties are physiologically relevant.

Reverse-phase HPLC analysis of human alpha crystallin.

PubMed

Swamy, M S; Abraham, E C

1991-03-01

A rapid and highly sensitive reverse-phase HPLC (RP-HPLC) method was used to separate crystallin subunits from human alpha crystallin. Three distinct peaks were separated; by electrophoretic and immunological analyses the first and second peaks were identified as alpha B and alpha A respectively. On the other hand, peak 3 appeared to be a modified form of alpha crystallin. The ratio of alpha A and alpha B proteins was 3:1 in 1 day old lenses which gradually changed to 2:1 in 17 year old lenses and to 1:1 in the 50 and 82 year old whole lenses and 82 year old lens cortex, with a concomitant increase in the modified alpha, suggesting that alpha A subunits are relatively more involved in aggregation. Analysis of the 82 year old lens nucleus also supported this conclusion. The RP-HPLC analysis of the HMW aggregate fraction showed substantial enrichment of the modified alpha. The alpha A and alpha B subunits independently reassociated to form polymeric alpha crystallin whereas the modified alpha reassociated to form HMW aggregates as shown by molecular sieve HPLC. Hence it appears that the HMW aggregate peak was constituted by modified alpha crystallin. Only in the peak 3 material the 280 nm absorbance was about 2-fold higher than what was expected from the actual protein content. The data suggest that the changes induced by post-translational modifications may have some role in the formation of modified alpha. The present RP-HPLC method is useful in separating these modified alpha from the unmodified alpha A and alpha B subunits.

Myofilament mechanical performance is enhanced by R403Q myosin in mouse myocardium independent of sex.

PubMed

Palmer, Bradley M; Wang, Yuan; Teekakirikul, Polakit; Hinson, J Travis; Fatkin, Diane; Strouse, Stacy; Vanburen, Peter; Seidman, Christine E; Seidman, J G; Maughan, David W

2008-04-01

Male but not female mice carrying a single R403Q missense allele for cardiac alpha-myosin heavy chain (M-alphaMHC(R403Q/+) and F-alphaMHC(R403Q/+), respectively) develop significant hypertrophic cardiomyopathy (HCM) compared with male and female wild-type mice (M-alphaMHC(+/+) and F-alphaMHC(+/+), respectively) after approximately 30 wk of age. We tested the hypothesis that myofilament mechanical performance differs between M-alphaMHC(R403Q/+) and F-alphaMHC(R403Q/+) at younger ages (10-20 wk) and could account for sex differences in HCM development. The sensitivity of chemically skinned myocardial strips to Ca(2+) activation (pCa(50)) was significantly (P < 0.05) enhanced in male mice independent of genotype (M-alphaMHC(R403Q/+): 5.70 +/- 0.06, M-alphaMHC(+/+): 5.63 +/- 0.05, F-alphaMHC(R403Q/+): 5.57 +/- 0.03, F-alphaMHC(+/+): 5.54 +/- 0.04) by two-way ANOVA, whereas maximum developed tension was significantly enhanced in alpha-MHC(R403Q/+) independent of sex (M-alphaMHC(R403Q/+): 29.3 +/- 2.3, M-alphaMHC(+/+): 26.0 +/- 1.4, F-alphaMHC(R403Q/+): 30.2 +/- 2.1, F-alphaMHC(+/+): 26.2 +/- 1.2 mN/mm(2)). The frequency of maximum work generated by sinusoidal length perturbation was significantly higher in alphaMHC(R403Q/+) mice than in sex-matched controls (M-alphaMHC(R403Q/+): 2.26 +/- 0.47, M-alphaMHC(+/+): 1.29 +/- 0.18, F-alphaMHC(R403Q/+): 3.21 +/- 0.33, F-alphaMHC(+/+): 2.52 +/- 0.36 Hz). Unloaded shortening velocity was significantly enhanced in alphaMHC(R403Q/+) and in female mice (M-alphaMHC(R403Q/+): 2.26 +/- 0.47, M-alphaMHC(+/+): 1.29 +/- 0.18, F-alphaMHC(R403Q/+): 3.21 +/- 0.33, F-alphaMHC(+/+): 2.52 +/- 0.36 muscle lengths/s), and normalized mechanical power, calculated from the tension-velocity relationship, was significantly enhanced in alphaMHC(R403Q/+) independent of sex (M-alphaMHC(R403Q/+): 60 +/- 2 10(-3), M-alphaMHC(+/+): 37 +/- 3 10(-3), F-alphaMHC(R403Q/+): 57 +/- 3 10(-3), F-alphaMHC(+/+) 25 +/- 3 10(-3) muscle lengths/s x normalized tension). We did not find a statistically significant sex x mutation interaction for any measure of myofilament performance. Therefore, sarcomeric incorporation of the R403Q myosin similarly enhanced left ventricular myofilament mechanical performance in both male and female mice. The sex-dependent development of HCM due to the R403Q myosin may then be inhibited by female sex hormones, which may additionally underlie the observed sex differences for pCa(50) and unloaded shortening velocity.

Expression of G(alpha)(s) proteins and TSH receptor signalling in hyperfunctioning thyroid nodules with TSH receptor mutations.

PubMed

Holzapfel, Hans-Peter; Bergner, Beate; Wonerow, Peter; Paschke, Ralf

2002-07-01

Constitutively activating mutations of the thyrotrophin receptor (TSHR) are the main molecular cause of hyperfunctioning thyroid nodules (HTNs). The G protein coupling is an important and critical step in the TSHR signalling which mainly includes G(alpha)(s), G(alpha)(i) and G(alpha)(q)/11 proteins. We investigated the in vitro consequences of overexpressing G(alpha) proteins on signalling of the wild-type (WT) or mutated TSHR. Moreover, we investigated whether changes in G(alpha) protein expression are pathophysiologically relevant in HTNs or cold thyroid nodules (CTNs). Wild-type TSH receptor and mutated TSH receptors were coexpressed with G(alpha)(s), G(alpha)(i) or G(alpha)(q)/11, and cAMP and inositol phosphate (IP) production was measured after stimulation with TSH. The expression of G(alpha)(s), G(alpha)(i) and G(alpha)(q)/11 proteins was examined by Western blotting in 28 HTNs and 14 CTNs. Coexpression of G(alpha)(s) with the WT TSH receptor in COS 7 cells significantly increased the basal and TSH-stimulated cAMP accumulation while coexpression of the G(alpha)(q) or G(alpha)11 protein significantly increased the production of cAMP and inositol triphosphate (IP(3)). The coexpression of the TSH receptor mutants (I486F, DEL613-621), known to couple constitutively to G(alpha)(s) and G(alpha)(q) with G(alpha)(s) and G(alpha)(q)/11, significantly increased the basal and stimulated cAMP and IP(3) accumulation. Coexpression of the TSH receptor mutant V556F with G(alpha)(s) only increased the basal and stimulated cAMP production while its coexpression with G(alpha)(q)/11 increased the basal and stimulated IP(3) signalling. The expression of G(alpha)(s) protein subunits determined by Western blotting was significantly decreased in 14 HTNs with a constitutively activating TSH receptor mutation in comparison with the corresponding surrounding tissue, while in 14 HTNs without TSH receptor or G(alpha)(s) protein mutation and in 14 CTNs the expression of G(alpha)(s) protein was not different compared with the surrounding tissue. The expression of G(alpha)(i) and G(alpha)(q)/11 proteins in HTNs or CTNs was not significantly different compared with the surrounding tissue. The reduced expression of G(alpha)(s) protein subunits in HTNs with TSHR mutations could act as a feedback mechanism to desensitise the chronically stimulated cAMP cascade. As G(alpha) protein expression was not significantly increased in the majority of CTNs and HTNs an influence of G(alpha) overexpression on TSH signalling could be excluded in these nodules.

Bile alcohol metabolism in man. Conversion of 5beta-cholestane-3alpha, 7alpha,12alpha, 25-tetrol to cholic acid.

PubMed Central

Salen, G; Shefer, S; Setoguchi, T; Mosbach, E H

1975-01-01

To study the role of C25-HYDROXY BILE ALCOHOLS AS PRECURSORS OF CHOlic acid, [G-3-H]5beta-cholestane-3alpha,7alpha12alpha,25-tetrol was administered intravenously to two subjects with cerebrotendinous xanthomatosis (CTX) and two normal individuals. One day after pulse labeling, radioactivity was present in the cholic acid isolated from the bile and feces of the subjects with CTX and the bile of the normal individuals. In the two normal subjects, the sp act decay curves of [G-3-H]-cholic acid were exponential, and no traces of [G-3-H]-5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol were detected. In contrast, appreciable quantities of labeled 5beta-cholestane-3alpha,-7aopha,12alpha,25-tetrol were present in the bile and feces of the CTX subjects. The sp act vs. time curves of fecal [G-3-H]5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol and [G-3-H]-cholic acid showed a precursor-product relationship. Although these results suggest that 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol may be a precursor of cholic acid in man, the possibility that C26-hydroxy intermediates represent the normal pathway can not be excluded. PMID:1141434

Synthesis of methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside.

PubMed

Jain, R K; Dubey, R; Abbas, S A; Matta, K L

1987-03-15

Treatment of methyl 3-O-benzyl-2-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha-D- mannopyranoside (1) with tert-butyldiphenylsilyl chloride in N,N-dimethylformamide afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (2). Oxidation of 2 with pyridinium chlorochromate, followed by reduction of the carbonyl group, and subsequent O-deacetylation afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-alpha-D-mannopyranosyl- alpha-D- talopyranoside (5). Cleavage of the tert-butyldiphenylsilyl group of 5 with tetrabutylammonium fluoride in oxolane, followed by hydrogenolysis, gave methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside (7). O-Deacetylation of 1 gave methyl 3-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (8). Treatment of 8 with tert-butyldiphenylsilyl chloride afforded a 6,6'-disilyl derivative, which was converted into a 2',3'-O-isopropylidene derivative, and then further oxidized with pyridinium chlorochromate. The resulting diketone was reduced and removal of the protecting groups gave methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside (15). The structures of both 7 and 15 were established by 13C-n.m.r. spectroscopy.

Altered expression of extracellular matrix molecules and their receptors in chronic pancreatitis and pancreatic adenocarcinoma in comparison with normal pancreas.

PubMed

Shimoyama, S; Gansauge, F; Gansauge, S; Oohara, T; Beger, H G

1995-12-01

The aim of this study was to elucidate the expression and distribution patterns of both integrins and extracellular matrix (ECM) molecules in chronic pancreatitis (CP) and pancreatic adenocarcinoma (PC) compared with normal pancreas (NP). Expression of nine alpha-subunits (alpha 2-alpha 6, alpha V, alpha L, alpha M, and alpha X), four beta-subunits (beta 1, beta 3-beta 5), and four ECM molecules (type IV collagen, laminin, fibronectin, and vitronectin) was investigated immunohistochemically. In CP, all integrins except alpha V showed nearly the same staining patterns compared with NP. Some acinar cells in CP expressed alpha V. Whereas alpha 2, alpha 3, and alpha 6 expression was stronger and diffuse, no alpha 5 expression was seen in PC. Basement membrane (BM) showed continuous staining in CP, whereas it showed discontinuous/absent staining in PC with antitype IV collagen, laminin, and vitronectin antibodies. Some carcinoma cells showed reverse correlation between alpha 2, alpha 3, and alpha 6 expression and type IV collagen and laminin expression. Fibronectin showed diffuse stromal expression in CP and PC. Some acinar cells or duct cells in CP carcinoma cells in PC showed intracellular VN expression. These results suggest that these integrins and ECM molecules are involved in inflammatory and malignant processes in pancreas.

Five-Body Cluster Structure of the Double-{Lambda} Hypernucleus {sub {Lambda}{Lambda}}{sup 11}Be

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiyama, E.; Kamimura, M.; Yamamoto, Y.

2010-05-28

Energy levels of the double {Lambda} hypernucleus, {sub {Lambda}{Lambda}}{sup 11}Be are calculated within the framework of a {alpha}{alpha}n{Lambda}{Lambda} five-body model. Interactions between constituent particles are determined so as to reproduce reasonably the observed low-energy properties of the {alpha}{alpha}, {alpha}{alpha}n nuclei and the existing data for {Lambda}-binding energies of the {alpha}{Lambda}, {alpha}{alpha}{Lambda}, {alpha}n{Lambda}, and {alpha}{alpha}n{Lambda} systems. An effective {Lambda}{Lambda} interaction is constructed so as to reproduce, within the {alpha}{Lambda}{Lambda} three-body model, the B{sub {Lambda}{Lambda}}of {sub {Lambda}{Lambda}}{sup 6}He, which was extracted from the emulsion experiment, the NAGARA event. With no adjustable parameters for the {alpha}{alpha}n{Lambda}{Lambda} system, B{sub {Lambda}{Lambda}}of the ground and boundmore » excited states of {sub {Lambda}{Lambda}}{sup 11}Be are calculated with the Gaussian expansion method. The Hida event, recently observed at KEK-E373 experiment, is interpreted as an observation of the ground state of the {sub {Lambda}{Lambda}}{sup 11}Be.« less

40 CFR 180.356 - Norflurazon; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... residues of the herbicide norflurazon (4-chloro-5-(methylamino)-2-(alpha, alpha, alpha-trifluoro-m-tolyl)-3-(2H)-pyridazinone) and its desmethyl metabolite 4-chloro-5-(amino)-2-alpha, alpha, alpha-trifluoro-m...

40 CFR 180.356 - Norflurazon; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... residues of the herbicide norflurazon (4-chloro-5-(methylamino)-2-(alpha, alpha, alpha-trifluoro-m-tolyl)-3-(2H)-pyridazinone) and its desmethyl metabolite 4-chloro-5-(amino)-2-alpha, alpha, alpha-trifluoro-m...

40 CFR 180.356 - Norflurazon; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... residues of the herbicide norflurazon (4-chloro-5-(methylamino)-2-(alpha, alpha, alpha-trifluoro-m-tolyl)-3-(2H)-pyridazinone) and its desmethyl metabolite 4-chloro-5-(amino)-2-alpha, alpha, alpha-trifluoro-m...

Differential regulation of the cell cycle by alpha1-adrenergic receptor subtypes.

PubMed

Gonzalez-Cabrera, Pedro J; Shi, Ting; Yun, June; McCune, Dan F; Rorabaugh, Boyd R; Perez, Dianne M

2004-11-01

Alpha(1)-Adrenergic receptors have been implicated in growth-promoting pathways. A microarray study of individual alpha(1)-adrenergic receptor subtypes (alpha(1A), alpha(1B), and alpha(1D)) expressed in Rat-1 fibroblasts revealed that epinephrine altered the transcription of several cell cycle regulatory genes in a direction consistent with the alpha(1A)- and alpha(1D)-adrenergic receptors mediating G(1)-S cell cycle arrest and the alpha(1B-)mediating cell-cycle progression. A time course indicated that in alpha(1A) cells, epinephrine stimulated a G(1)-S arrest, which began after 8 h of stimulation and maximized at 16 h, at which point was completely blocked with cycloheximide. The alpha(1B)-adrenergic receptor profile also showed unchecked cell cycle progression, even under low serum conditions and induced foci formation. The G(1)-S arrest induced by alpha(1A)- and alpha(1D)-adrenergic receptors was associated with decreased cyclin-dependent kinase-6 and cyclin E-associated kinase activities and increased expression of the cyclin-dependent kinase inhibitor p27(Kip1), all of which were blocked by prazosin. There were no differences in kinase activities and/or expression of p27(Kip1) in epinephrine alpha(1B)-AR fibroblasts, although the microarray did indicate differences in p27(Kip1) RNA levels. Cell counts proved the antimitotic effect of epinephrine in alpha(1A) and alpha(1D) cells and indicated that alpha(1B)-adrenergic receptor subtype expression was sufficient to cause proliferation of Rat-1 fibroblasts independent of agonist stimulation. Analysis in transfected PC12 cells also confirmed the alpha(1A)- and alpha(1B)-adrenergic receptor effect. The alpha(1B)-subtype native to DDT1-MF2 cells, a smooth muscle cell line, caused progression of the cell cycle. These results indicate that the alpha(1A)- and alpha(1D)-adrenergic receptors mediate G(1)-S cell-cycle arrest, whereas alpha(1B)-adrenergic receptor expression causes a cell cycle progression and may induce transformation in sensitive cell lines.

Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma.

PubMed

Lewis, Michael J; Wiebe, John P; Heathcote, J Godfrey

2004-06-22

Recent evidence suggests that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that tumorous tissues have higher 5alpha-reductase (5alphaR) and lower 3alpha-hydroxysteroid oxidoreductase (3alpha-HSO) and 20alpha-HSO activities. The resulting higher levels of 5alpha-reduced progesterone metabolites such as 5alpha-pregnane-3,20-dione (5alphaP) in tumorous tissue promote cell proliferation and detachment, whereas the 4-pregnene metabolites, 4-pregnen-3alpha-ol-20-one (3alphaHP) and 4-pregnen-20alpha-ol-3-one (20alphaDHP), more prominent in normal tissue, have the opposite (anti-cancer-like) effects. The aim of this study was to determine if the differences in enzyme activities between tumorous and nontumorous breast tissues are associated with differences in progesterone metabolizing enzyme gene expression. Semi-quantitative RT-PCR was used to compare relative expression (as a ratio of 18S rRNA) of 5alphaR type 1 (SRD5A1), 5alphaR type 2 (SRD5A2), 3alpha-HSO type 2 (AKR1C3), 3alpha-HSO type 3 (AKR1C2) and 20alpha-HSO (AKR1C1) mRNAs in paired (tumorous and nontumorous) breast tissues from 11 patients, and unpaired tumor tissues from 17 patients and normal tissues from 10 reduction mammoplasty samples. Expression of 5alphaR1 and 5alphaR2 in 11/11 patients was higher (mean of 4.9- and 3.5-fold, respectively; p < 0.001) in the tumor as compared to the paired normal tissues. Conversely, expression of 3alpha-HSO2, 3alpha-HSO3 and 20alpha-HSO was higher (2.8-, 3.9- and 4.4-fold, respectively; p < 0.001) in normal than in tumor sample. The mean tumor:normal expression ratios for 5alphaR1 and 5alphaR2 were about 35-85-fold higher than the tumor:normal expression ratios for the HSOs. Similarly, in the unmatched samples, the tumor:normal ratios for 5alphaR were significantly higher than the ratios for the HSOs. The study shows changes in progesterone metabolizing enzyme gene expression in human breast carcinoma. Expression of SRD5A1 (5alphaR1) and SRD5A2 (5alphaR2) is elevated, and expression of AKR1C1 (20alpha-HSO), AKR1C2 (3alpha-HSO3) and AKR1C3 (3alpha-HSO2) is reduced in tumorous as compared to normal breast tissue. The changes in progesterone metabolizing enzyme expression levels help to explain the increases in mitogen/metastasis inducing 5alphaP and decreases in mitogen/metastasis inhibiting 3alphaHP progesterone metabolites found in breast tumor tissues. Understanding what causes these changes in expression could help in designing protocols to prevent or reverse the changes in progesterone metabolism associated with breast cancer.

Near-complete teleportation of a superposed coherent state

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheong, Yong Wook; Kim, Hyunjae; Lee, Hai-Woong

2004-09-01

The four Bell-type entangled coherent states, {alpha}>-{alpha}>{+-}-{alpha}>{alpha}> and {alpha}>{alpha}>{+-}-{alpha}>-{alpha}>, can be discriminated with a high probability using only linear optical means, as long as {alpha} is not too small. Based on this observation, we propose a simple scheme to almost completely teleport a superposed coherent state. The nonunitary transformation that is required to complete the teleportation can be achieved by embedding the receiver's field state in a larger Hilbert space consisting of the field and a single atom and performing a unitary transformation on this Hilbert space00.

Increased alpha 2-macroglobulin in diabetes: a hyperglycemia related phenomenon associated with reduced antithrombin III activity.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Stante, A; Dello Russo, P; Torella, R

1989-01-01

Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.

15 beta-hydroxysteroids (Part IV). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one and its A/B-ring configurational isomers.

PubMed

Reeder, A Y; Joannou, G E

1995-12-01

In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.

Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development

PubMed Central

1982-01-01

Na+- and CA2+-sensitive microelectrodes were used to measure intracellular Na+ and Ca2+ activities (alpha iCa) of sheep ventricular muscle and Purkinje strands to study the interrelationship between Na+ and Ca2+ electrochemical gradients (delta muNa and delta muCa) under various conditions. In ventricular muscle, alpha iNa was 6.4 +/- 1.2 mM and alpha iCa was 87 +/- 20 nM ([Ca/+] = 272 nM). A graded decrease of external Na+ activity (alpha oNa) resulted in decrease of alpha iNa, and increase of alpha iCa. There was increase of twitch tension in low- alpha oNa solutions, and occasional increase of resting tension in 40% alpha oNa. Increase of external Ca2+ (alpha oCa) resulted in increase of alpha iCa and decrease of alpha iNa. Decrease of alpha oCa resulted in decrease of alpha iCa and increase of alpha iNa. The apparent resting Na-Ca energy ratio (delta muCa/delta muNa) was between 2.43 and 2.63. When the membrane potential (Vm) was depolarized by 50 mM K+ in ventricular muscle, Vm depolarized by 50 mV, alpha iNa decreased, and alpha iCa increased, with the development of a contracture. The apparent energy coupling ratio did not change with depolarization. 5 x 10(-6) M ouabain induced a large increase in alpha iNa ad alpha iCa, accompanied by an increase in twitch and resting tension. Under the conditions we have studied, delta muNa and delta muCa appeared to be coupled and n was nearly constant at 2.5, as would be expected if the Na-Ca exchange system was able to set the steady level of alpha iCa. Tension threshold was about 230 nM alpha iCa. The magnitude of twitch tension was directly related to alpha iCa. PMID:6292328

Partial agonist clonidine mediates alpha(2)-AR subtypes specific regulation of cAMP accumulation in adenylyl cyclase II transfected DDT1-MF2 cells.

PubMed

Limon-Boulez, I; Bouet-Alard, R; Gettys, T W; Lanier, S M; Maltier, J P; Legrand, C

2001-02-01

alpha2-Adrenergic receptor (alpha(2)-AR) activation in the pregnant rat myometrium at midterm potentiates beta(2)-AR stimulation of adenylyl cyclase (AC) via Gbetagamma regulation of the type II isoform of adenylyl cyclase. However, at term, alpha(2)-AR activation inhibits beta(2)-AR stimulation of AC. This phenomenon is associated with changes in alpha(2)-AR subtype expression (midterm alpha(2A/D)-AR > alpha(2B)-AR; term alpha(2B) >or =alpha(2A/D)-AR), without any change in ACII mRNA, suggesting that alpha(2A/D)- and alpha(2B)-AR differentially regulate beta(2)-cAMP production. To address this issue, we have stably expressed the same density of alpha(2A/D)- or alpha(2B)-AR with AC II in DDT1-MF2 cells. Clonidine (partial agonist) increased beta(2)-AR-stimulated cAMP production in alpha(2A/D)-AR-ACII transfectants but inhibited it in alpha(2B)-AR-ACII transfectants. In contrast, epinephrine (full agonist) enhanced beta(2)-stimulated ACII in both alpha(2A)- and alpha(2B)-ACII clonal cell lines. 4-Azidoanilido-[alpha-(32)P]GTP-labeling of activated G proteins indicated that, in alpha(2B)-AR transfectants, clonidine activated only Gi(2), whereas epinephrine, the full agonist, effectively coupled to Gi(2) and Gi(3). Thus, partial and full agonists selectively activate G proteins that lead to drug specific effects on effectors. Moreover, these data indicate that Gi(3) activation is required for potentiation of beta(2)-AR stimulation of AC by alpha(2A/D) and alpha(2B)-AR in DDT1-MF2 cells. This may reflect an issue of the amount of Gbetagamma released upon receptor activation and/or betagamma composition of Gi(3) versus Gi(2).

Identification of two novel mammalian genes establishes a subfamily of KH-domain RNA-binding proteins.

PubMed

Makeyev, A V; Liebhaber, S A

2000-08-01

We have identified two novel human genes encoding proteins with a high level of sequence identity to two previously characterized RNA-binding proteins, alphaCP-1 and alphaCP-2. Both of these novel genes, alphaCP-3 and alphaCP-4, are predicted to encode proteins with triplicated KH domains. The number and organization of the KH domains, their sequences, and the sequences of the contiguous regions are conserved among all four alphaCP proteins. The common evolutionary origin of these proteins is substantiated by conservation of exon-intron organization in the corresponding genes. The map positions of alphaCP-1 and alphaCP-2 (previously reported) and those of alphaCP-3 and alphaCP-4 (present report) reveal that the four alphaCP loci are dispersed in the human genome; alphaCP-3 and alphaCP-4 mapped to 21q22.3 and 3p21, and the respective mouse orthologues mapped to syntenic regions of the mouse genome, 10B5 and 9F1-F2, respectively. Two additional loci in the human genome were identified as alphaCP-2 processed pseudogenes (PCBP2P1, 21q22.3, and PCBP2P2, 8q21-q22). Although the overall levels of alphaCP-3 and alphaCP-4 mRNAs are substantially lower than those of alphaCP-1 and alphaCP-2, transcripts of alphaCP-3 and alphaCP-4 were found in all mouse tissues tested. These data establish a new subfamily of genes predicted to encode closely related KH-containing RNA-binding proteins with potential functions in posttranscriptional controls. Copyright 2000 Academic Press.

Functional coupling of rat myometrial alpha 1-adrenergic receptors to Gh alpha/tissue transglutaminase 2 during pregnancy.

PubMed

Dupuis, Morgan; Lévy, Arlette; Mhaouty-Kodja, Sakina

2004-04-30

Gh alpha protein, which exhibits both transglutaminase and GTPase activities, represents a new class of GTP-binding proteins. In the present study, we characterized Gh alpha in rat uterine smooth muscle (myometrium) and followed its expression during pregnancy by reverse transcription-PCR and Western blot. We also measured transglutaminase and GTP binding functions and used a smooth muscle cell line to evaluate the role of Gh alpha in cell proliferation. The results show that pregnancy is associated with an up-regulation of Gh alpha expression at both the mRNA and protein level. Gh alpha induced during pregnancy is preferentially localized to the plasma membrane. This was found associated with an increased ability of plasma membrane preparations to catalyze Ca(2+)-dependent incorporation of [(3)H]putrescine into casein in vitro. In the cytosol, significant changes in the level of immunodetected Gh alpha and transglutaminase activity were seen only at term. Activation of alpha1-adrenergic receptors (alpha1-AR) enhanced photoaffinity labeling of plasma membrane Gh alpha. Moreover, the level of alpha1-AR-coupled Gh alpha increased progressively with pregnancy, which parallels the active period of myometrial cell proliferation. Overexpression of wild type Gh alpha in smooth muscle cell line DDT1-MF2 increased alpha1-AR-induced [(3)H]thymidine incorporation. A similar response was obtained in cells expressing the transglutaminase inactive mutant (C277S) of Gh alpha. Together, these findings underscore the role of Gh alpha as signal transducer of alpha1-AR-induced smooth muscle cell proliferation. In this context, pregnant rat myometrium provides an interesting physiological model to study the mechanisms underlying the regulation of the GTPase function of Gh alpha

Ultrasonographic and endocrine evaluation of three regimes for oestrus and ovulation synchronization for sheep in the subtropics.

PubMed

Ali, A; Hayder, M; Saifelnaser, E O H

2009-12-01

This study aimed to evaluate three regimes for oestrus and ovulation synchronization in Farafra ewes in the subtropics. During autumn, 43 ewes were assigned to (i) controlled internal drug releasing (CIDR)-eCG group, treated with CIDR for 12 days and eCG at insert withdrawal, n=13; (ii) PGF2alpha-PGF2alpha group, treated with two PGF2alpha injections at 11 days interval, n=14; and (iii) GnRH-PGF2alpha-GnRH group, treated with GnRH, followed 5 days later with PGF2alpha and 24 h later with a second GnRH, n=16. Oestrus-mating detection was carried out at 4 h intervals starting on day 0 [the day of CIDR withdrawal (CIDR-eCG group), the day of second PGF2alpha treatment (PGF2alpha-PGF2alpha group) and the day of PGF2alpha treatment (GnRH-PGF2alpha-GnRH group)]. Ovarian dynamics was monitored by ultrasound every 12 h beginning on day 0 and continued for 4 days. Blood samples were obtained daily for progesterone (P4) and oestradiol 17beta (E2) estimation starting on day 0 and continued for 4 days. The obtained results showed that, oestrus expression, ovulation and conception were greater (p<0.05) in CIDR-eCG and PGF2alpha-PGF2alpha groups than in GnRH-PGF2alpha-GnRH group. All ewes of PGF2alpha-PGF2alpha group presented, on day of second PGF2alpha injection with mature CL (P4>2.0 ng/ml), compared to 42.9% in GnRH-PGF2alpha-GnRH group (p=0.01). The peak of oestrus occurred 32-52, 48-60 and 28-96 h after the end of treatment in CIDR-eCG, PGF2alpha-PGF2alpha and GnRH-PGF2alpha-GnRH groups, respectively. Ovulation started 48 h after treatment in all groups and extended for 24, 36 and 48 h for CIDR-eCG, PGF2alpha-PGF2alpha and GnRH-PGF2alpha-GnRH groups, respectively. Results demonstrated that oestrus and ovulation synchronization could be efficiently achieved in Farafra ewes using either CIDR-eCG or PGF2alpha-PGF2alpha regimes; however, the GnRH-PGF2alpha-GnRH treatment induced a more spread oestrus and ovulation that may make the protocol inadequate for timed artificial insemination.

Ultrastructural studies of human and rabbit alpha-M-globulins.

PubMed

Bloth, B; Chesebro, B; Svehag, S E

1968-04-01

Electron micrographs of isolated human alpha(2)M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the alpha(2)M particles were 170 A and 100 A, respectively. Purified rabbit alphamacroglobulins contained about 80% alpha(1)M- and 20% alpha(2)M-globulins. The isolated rabbit alpha(1)M- and alpha(2)M-molecules were morphologically indistinguishable from one another and from human alpha(2)M-molecules. Preliminary immunoprecipitation studies demonstrated that the two rabbit alphaM-globulins were antigenically different. Sedimentation constant determinations gave s(20, w) values of 18.8 and 18.2 for rabbit alpha(1)M and alpha(2)M, respectively.

Seasonal changes in testicular steroidogenesis in the toad Bufo arenarum H.

PubMed

Canosa, L F; Ceballos, N R

2002-02-15

The biosynthesis of androgens in Bufo arenarum takes place through the 5-ene pathway that includes 5-androstane-3beta,17beta-diol as intermediate in testosterone biosynthesis. Besides testosterone and 5alpha-dihydrotestosterone, testes are able to synthesize 5alpha-pregnan-3,20-dione and several 3alpha- and 20alpha-reduced derivatives. Steroid biosynthesis changes during the breeding period (spring and early summer), turning from androgen to C21 steroid production. During the reproductive season, the production of progesterone, 5alpha-pregnan-3alpha,20alpha-diol, 3alpha-hydroxy-5alpha-pregnan-20-one, and 5alpha-pregnan-3,20-dione increases significantly. The function of most of these steroids in amphibians remains unknown. However, 5alpha-androstan-3alpha,17beta-diol and 3alpha-hydroxy-5alpha-pregnan-20-one were shown to be neuroactive in mammals, modulating sexual behavior. Thus, 5alpha/3alpha-reduced steroids could be involved in the regulation of the reproductive behavior in B. arenarum, a species with a dissociated reproductive pattern. Percentage contribution of each enzymes to the total metabolism reveals that neither 3beta-hydroxysteroid dehydrogenase/isomerase nor 5alpha-reductase change throughout the reproductive cycle. However, a strong reduction in 17-hydroxylase-C(17-20) lyase activity occurs in the reproductive season, suggesting that this enzyme could represent a key enzyme in the regulation of the seasonal change of steroidogenesis. Also, 3alpha-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase activities increase during the reproductive period, implying that steroid metabolism is clearly focused on C21-reduced steroids. (C)2002 Elsevier Science (USA).

Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer.

PubMed

Palan, Prabhudas R; Woodall, Angela L; Anderson, Patrick S; Mikhail, Magdy S

2004-05-01

alpha-Tocopherol is a potent antioxidant that protects cell membranes against oxidative damage. Red blood cell alpha-tocopherol levels reflect membrane alpha-tocopherol concentrations, and altered levels may suggest membrane damage. The objective of this study was to determine the levels of alpha-tocopherol and alpha-tocopheryl quinone, the oxidized product of alpha-tocopherol, in plasma and red blood cells that were obtained from control subjects and patients with cervical intraepithelial neoplasia and cervical cancer. In this cross-sectional study, 72 women, (32 African American and 40 Hispanic) were recruited. Among these subjects, 37 women had cervical intraepithelial neoplasia; 14 women had cervical cancer, and 21 women were considered control subjects, who had normal Papanicolaou test results. alpha-Tocopherol and alpha-tocopheryl quinone levels were determined in red blood cell and plasma by high-pressure liquid chromatography. Plasma levels of alpha-tocopherol and alpha-tocopheryl quinone were decreased significantly (P=.012 and=.005, respectively, by Kruskal-Wallis test) in study groups compared with the control group; red blood cell levels of alpha-tocopherol and alpha-tocopheryl quinone were not altered significantly. The lower alpha-tocopherol level that was observed in this study is consistent with our previous reports of decreased antioxidant concentrations and increased oxidative stress in women with cervical intraepithelial neoplasia. Unaltered red blood cell alpha-tocopherol and alpha-tocopheryl quinone levels suggest undamaged cell membrane. Further studies are needed to investigate the potential role of oxidative stress in cervical intraepithelial neoplasia.

cap alpha. /sub i/-3 cDNA encodes the. cap alpha. subunit of G/sub k/, the stimulatory G protein of receptor-regulated K/sup +/ channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Codina, J.; Olate, J.; Abramowitz, J.

1988-05-15

cDNA cloning has identified the presence in the human genome of three genes encoding ..cap alpha.. subunits of pertussis toxin substrates, generically called G/sub i/. They are named ..cap alpha../sub i/-1, ..cap alpha../sub i/-2 and ..cap alpha../sub i/-3. However, none of these genes has been functionally identified with any of the ..cap alpha.. subunits of several possible G proteins, including pertussis toxin-sensitive G/sub p/'s, stimulatory to phospholipase C or A/sub 2/, G/sub i/, inhibitory to adenylyl cyclase, or G/sub k/, stimulatory to a type of K/sup +/ channels. The authors now report the nucleotide sequence and the complete predicted aminomore » acid sequence of human liver ..cap alpha../sub i/-3 and the partial amino acid sequence of proteolytic fragments of the ..cap alpha.. subunit of human erythrocyte G/sub k/. The amino acid sequence of the proteolytic fragment is uniquely encoded by the cDNA of ..cap alpha../sub i/-3, thus identifying it as ..cap alpha../sub k/. The probable identity of ..cap alpha../sub i/-1 with ..cap alpha../sub p/ and possible roles for ..cap alpha../sub i/-2, as well as additional roles for ..cap alpha../sub i/-1 and ..cap alpha../sub i/-3 (..cap alpha../sub k/) are discussed.« less

Localization of type IV collagen a 1 to a 6 chains in basement membrane during mouse molar germ development.

PubMed

Nagai, N; Nakano, K; Sado, Y; Naito, I; Gunduz, M; Tsujigiwa, H; Nagatsuka, H; Ninomiya, Y; Siar, C H

2001-10-01

The dental basement membrane (BM) putatively mediates epithelial-mesenchymal interactions during tooth morphogenesis and cytodifferentiation. Type IV collagen alpha chains, a major network-forming protein of the dental BM, was studied and results disclosed distinct expression patterns at different stages of mouse molar germ development. At the dental placode and bud stage, the BM of the oral epithelium expressed alpha 1, alpha 2, alpha 5 and alpha 6 chains while the gubernaculum dentis, in addition to the above four chains, also expressed a 4 chain. An asymmetrical expression for alpha 4, alpha 5 and alpha 6 chains was observed at the bud stage. At the early bell stage, the BM associated with the inner enamel epithelium (IEE) of molar germ expressed alpha 1, alpha 2 and alpha 4 chains while the BM of the outer enamel epithelium (OEE) expressed only alpha 1 and a 2 chains. With the onset of dentinogenesis, the collagen a chain profile of the IEE BM gradually disappeared. Howeverfrom the early to late bell stage, the gubernaculum dentis consistently expressed alpha 1, alpha 2, alpha 5 and a 6 chains resembling fetal oral mucosa. These findings suggest that stage- and position-specific distribution of type IV collagen alpha subunits occur during molar germ development and that these changes are essential for molar morphogenesis and cytodifferentiation.

Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys.

PubMed

Grant, Kathleen A; Helms, Christa M; Rogers, Laura S M; Purdy, Robert H

2008-07-01

Positive modulation of GABA(A) and antagonism of N-methyl-D-aspartate receptors mediate the discriminative stimulus effects of ethanol. Endogenous neuroactive steroids produce effects similar to ethanol, suggesting that these steroids may modulate ethanol addiction. The four isomers of the functional esters at C-3 of the 3-hydroxy metabolites of 4-pregnene-3,20-dione (progesterone) [allopregnanolone (3alpha,5alpha-P), pregnanolone (3alpha,5beta-P), epiallopregnanolone (3beta,5alpha-P), and epipregnanolone (3beta,5beta-P)], a synthetic analog of steroids modified by endogenous sulfation [pregnanolone hemisuccinate (3alpha,5beta-P HS)], and a structurally similar, adrenally derived steroid [3alpha-hydroxy-5-androstan-17-one (3alpha,5alpha-A, androsterone)] were assessed for ethanol-like discriminative stimulus effects at 30 or 60 min after administration in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) with a 30-min pretreatment interval. The 3alpha-hydroxysteroids completely substituted for ethanol (80% of cases), whereas the 3beta-hydroxysteroids and 3alpha,5beta-P HS rarely substituted for ethanol (6% of cases). There were no sex differences. Compared with monkeys trained to discriminate 2.0 g/kg ethanol, 3alpha,5beta-P and 3alpha,5alpha-A substituted more potently in monkeys trained to discriminate 1.0 g/kg ethanol. Compared with the 5beta-reduced isomer (3alpha,5beta-P), the 5alpha isomer of pregnanolone (3alpha,5alpha-P) substituted for ethanol with 3 to 40-fold greater potency but was least efficacious in female monkeys trained to discriminate 2.0 g/kg ethanol. The data suggest that the discriminative stimulus effects of lower doses (1.0 g/kg) of ethanol are mediated to a greater extent by 3alpha,5beta-P- and 3alpha,5alpha-A-sensitive receptors compared with higher doses (2.0 g/kg). Furthermore, the discriminative stimulus effects of ethanol appear to be mediated by activity at binding sites that are particularly sensitive to 3alpha,5alpha-P.

The molecular chaperone alphaA-crystallin enhances lens epithelial cell growth and resistance to UVA stress.

PubMed

Andley, U P; Song, Z; Wawrousek, E F; Bassnett, S

1998-11-20

alphaA-Crystallin (alphaA) is a member of the small heat shock protein (sHSP) family and has the ability to prevent denatured proteins from aggregating in vitro. Lens epithelial cells express relatively low levels of alphaA, but in differentiated fiber cells, alphaA is the most abundant soluble protein. The lenses of alphaA-knock-out mice develop opacities at an early age, implying a critical role for alphaA in the maintenance of fiber cell transparency. However, the function of alpha-crystallin in the lens epithelium is unknown. To investigate the physiological function of alphaA in lens epithelial cells, we used the following two systems: alphaA knock-out (alphaA(-/-)) mouse lens epithelial cells and human lens epithelial cells that overexpress alphaA. The growth rate of alphaA(-/-) mouse lens epithelial cells was reduced by 50% compared with wild type cells. Cell cycle kinetics, measured by fluorescence-activated cell sorter analysis of propidium iodide-stained cells, indicated a relative deficiency of alphaA(-/-) cells in the G2/M phases. Exposure of mouse lens epithelial cells to physiological levels of UVA resulted in an increase in the number of apoptotic cells in the cultures. Four hours after irradiation the fraction of apoptotic cells in the alphaA(-/-) cultures was increased 40-fold over wild type. In cells lacking alphaA, UVA exposure modified F-actin, but actin was protected in cells expressing alphaA. Stably transfected cell lines overexpressing human alphaA were generated by transfecting extended life span human lens epithelial cells with the mammalian expression vector construct pCI-neoalphaA. Cells overexpressing alphaA were resistant to UVA stress, as determined by clonogenic survival. alphaA remained cytoplasmic after exposure to either UVA or thermal stress indicating that, unlike other sHSPs, the protective effect of alphaA was not associated with its relocalization to the nucleus. These results indicate that alphaA has important cellular functions in the lens over and above its well characterized role in refraction.

Mode of alpha-amylase production by the shochu koji mold Aspergillus kawachii.

PubMed

Nagamine, Kazuki; Murashima, Kenji; Kato, Taku; Shimoi, Hitoshi; Ito, Kiyoshi

2003-10-01

Aspergillus kawachii produces two kinds of alpha-amylase, one is an acid-unstable alpha-amylase and the other is an acid-stable alpha-amylase. Because the quality of the shochu depends strongly on the activities of the alpha-amylases, the culture conditions under which these alpha-amylases are produced were examined. In liquid culture, acid-unstable alpha-amylase was produced abundantly, but, acid-stable alpha-amylase was not produced. The acid-unstable alpha-amylase was produced significantly when glycerol or glucose was used as a carbon source, similarly to the use of inducers such as starch or maltose. In liquid culture, A. kawachii assimilated starch at pH 3.0, but no alpha-amylase activity was recognized in the medium. Instead, the alpha-amylase was found to be trapped in the cell wall. The trapped form was identified as acid-unstable alpha-amylase. Usually, acid-unstable alpha-amylase is unstable at pH 3.0, so its stability appeared to be due to its immobilization in the cell wall. In solid-state culture, both kinds of alpha-amylase were produced. The production of acid-stable alpha-amylase seems to be solid-state culture-specific and was affected by the moisture content in the solid medium.

Anticonvulsant properties of alpha, gamma, and alpha, gamma-substituted gamma-butyrolactones.

PubMed

Klunk, W E; Covey, D F; Ferrendelli, J A

1982-09-01

Derivatives of gamma-butyrolactone (GBL) substituted on the alpha- and/or gamma-positions were synthesized and tested for their effects on behavior in mice, on the electroencephalographs and blood pressure of paralyzed-ventilated guinea pigs, and on electrical activity of incubated hippocampal slices. Several compounds, including alpha-ethyl-alpha-methyl GBL (alpha-EMGBL), alpha, alpha-dimethyl GBL, alpha, gamma-diethyl-alpha, gamma-dimethyl GBL, and gamma-ethyl-gamma-methyl GBL, prevented seizures induced by pentylenetetrazol, beta-ethyl-beta-methyl-gamma-butyrolactone (beta-EMGBL), picrotoxin, or all three compounds in mice and guinea pigs but had no effect on seizures induced by maximal electroshock or bicuculline. Neither gamma-hydroxybutyrate (GHB) nor alpha-isopropylidine GBL had any anticonvulsant activity. The anticonvulsant alpha-substituted compounds had a potent hypotensive effect and antagonized the hypertensive effect of beta-EMGBL, alpha-EMGBL was tested in incubated hippocampal slices and was found to depress basal activity and antagonize excitation induced by beta-EMGBL. These results demonstrate that alpha-alkyl-substituted GBL and, to a lesser extent, gamma-substituted derivatives are anticonvulsant agents and that their effects are strikingly different from those of GHB or beta-alkyl-substituted GBLs, which are epileptogenic. Possibly beta- and alpha-substituted GBLs act at the same site as agonists and antagonists, respectively.

Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.

PubMed

Sanna-Cherchi, Simone; Carnevali, Maria Luisa; Martorana, Davide; Cravedi, Paolo; Maggiore, Umberto; Alinovi, Rossella; Bovino, Achiropita; Mattei, Silvia; Orlandini, Guido; Gatti, Rita; Savi, Mario; Sado, Yoshikazu; Neri, Tauro M; Allegri, Landino

2007-01-01

Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all]. Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury. Copyright 2007 S. Karger AG, Basel.

5Alpha-Reduced Steroids Are Major Metabolites in the Early Equine Embryo Proper and Its Membranes.

PubMed

Raeside, James I; Christie, Heather L; Betteridge, Keith J

2015-09-01

Steroid production and metabolism by early conceptuses are very important for the establishment and maintenance of pregnancy in horses. Our earlier work suggested the possible formation of 5alpha-reduced steroids in equine conceptuses. We have now demonstrated the formation of 5alpha-reduced metabolites of androstenedione, testosterone, and progesterone by the embryo and its membranes. A total of 44 conceptuses were collected from 26 mares between 20 and 31 days of pregnancy. Tissues from the embryo proper and from the separated components of the conceptus (bilaminar and trilaminar trophoblast, allantois) were incubated with tritium-labeled substrates. 5Alpha-reduced metabolites (5alpha-dihydro- and 3beta,5alpha-tetrahydro- steroids) as radiolabeled products were identified from a series of chromatographic steps using four solvent systems for high-performance liquid chromatography. Use of a 5alpha-reductase inhibitor confirmed the metabolites were indeed 5alpha-reduced steroids. For the embryo, the only products from androstenedione were 5alpha-dihydroandrostenedione and 3beta,5alpha-tetrahydroandrostenedione, with no evidence of more polar metabolites; there was some 3beta,5alpha-tetrahydrotestosterone but no 5alpha-dihydrotestosterone from testosterone, and formation of androstenedione was followed by the production of 5alpha-dihydroandrostenedione and 3beta,5alpha-tetrahydroandrostenedione. The major 5alpha-reduced product from progesterone was 3beta,5alpha-tetrahydroprogesterone, with lesser amounts of 5alpha-dihydroprogesterone. For the membranes, reductions to tetrahydro, 5alpha-reduced steroids were prominent in most instances, but also present were considerable amounts of products more polar than the substrates. The well-recognized activity of some 5alpha-reduced steroids--for example, 5alpha-dihydrotestosterone in male sexual differentiation--provokes interest in their even earlier appearance, as seen in this study, and suggests a possible role for them in early embryonic development in horses and, more generally, in other species. © 2015 by the Society for the Study of Reproduction, Inc.

Ovine cardiac Na,K-ATPase: isolation by means of selective solubilization in Lubrol and the effect of 1 alpha,2 alpha-epoxyscillirosidin on this enzyme.

PubMed

Venter, P A; Naudé, R J; Oelofsen, W; Swan, G E

1997-01-01

The inhibition of cardiac Na,K-ATPase by 1 alpha,2 alpha-epoxyscillirosidin is the principal cause of poisoning of cattle by the tulip, Homeria pallida. The ultimate goals of this study were to study the interaction between 1 alpha,2 alpha-epoxyscillirosidin and ovine Na,K-ATPase by means of inhibition and displacement binding studies. Ovine cardiac Na,K-ATPase was isolated in membrane-bound form by means of deoxycholate treatment, high-speed ultracentrifugation, NaI treatment and selective solubilization in Lubrol. The inhibition of ovine cardiac and commercial porcine cerebral cortex Na,K-ATPase by 1 alpha,2 alpha-epoxyscilirosidin and ouabain was studied using a discontinuous Na,K-ATPase assay. The binding of 1 alpha,2 alpha-epoxyscillirosidin, ouabain and digoxin to the above enzymes was compared using a displacement binding assay with [3H] oubain. The Lubrol-solubilized ovine cardiac Na,K-ATPase showed a specific activity of 0.3 U/mg with no ouabain insensitive activity. I50 values of 2.1 x 10(-8) and 2.7 x 10(-8) were obtained for the inhibition of this enzyme by 1 alpha,2 alpha-epoxyscillirosidin and ouabain, respectively. 1 alpha,2 alpha-Epoxyscillirosidin has a much higher KD value (1.5 x 10(-7) M), however, than ouabain (9.5 x 10(-9) M) and digoxin (1.7 x 10(-8) M) in displacement binding studies with [3H]ouabain. 1 alpha,2 alpha-Epoxyscillirosidin is a potent inhibitor of ovine cardiac Na,K-ATPase and is a slightly stronger inhibitor of the enzyme than ouabain. The anomalous result for the displacement of 1 alpha,2 alpha-epoxyscillirosidin from its receptor is either a result of different affinities that K+ has for the enzyme ouabain and enzyme-1 alpha,2 alpha-epoxyscillirosidin complexes or because of different complex stabilities of these complexes.

The glycoinositol-phospholipids of Phytomonas.

PubMed

Redman, C A; Schneider, P; Mehlert, A; Ferguson, M A

1995-10-15

The Phytomonas spp. are trypanosomatid parasites of plants. A polar glycolipid fraction of a Phytomonas sp., isolated from the plant Euphorbia characias and grown in culture, was fractionated into four major glycolipid species (Phy 1-4). The glycolipids were analysed by chemical and enzymic modifications, composition and methylation analyses, electrospray mass spectrometry and microsequencing after HNO2 deamination and NaB3H4 reduction. The water-soluble headgroup of the Phy2 glycolipid was also analysed by 1H NMR. All four glycolipids were shown to be glycoinositol-phospholipids (GIPLs) with phosphatidylinositol (PI) moieties containing the fully saturated alkylacylglycerol lipids 1-O-hexadecyl-2-O-palmitoylglycerol and 1-O-hexadecyl-2-O-stearoylglycerol. The structures of the Phy 1-4 GIPLs are: Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6PI, Glc alpha 1-2(NH2-CH2CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6PI, [formula: see text] Glc alpha 1-2(NH2CH2CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4(NH2-CH2CH2-HPO4-)GlcN alpha 1-6PI [formula: see text] and Glc alpha 1-2Glc alpha 1-2(NH2CH2-CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4(NH2CH2CH2-HPO4-)-GlcN alpha 1-6PI. [formula: see text] The Phytomonas GIPLs represent a novel series of structures. This is the first description of the chemical structure of cell-surface molecules of this plant pathogen. The Phytomonas GIPLs are compared with those of other trypanosomatid parasites and are discussed with respect to trypanosomatid phylogenetic relationships.

The glycoinositol-phospholipids of Phytomonas.

PubMed Central

Redman, C A; Schneider, P; Mehlert, A; Ferguson, M A

1995-01-01

The Phytomonas spp. are trypanosomatid parasites of plants. A polar glycolipid fraction of a Phytomonas sp., isolated from the plant Euphorbia characias and grown in culture, was fractionated into four major glycolipid species (Phy 1-4). The glycolipids were analysed by chemical and enzymic modifications, composition and methylation analyses, electrospray mass spectrometry and microsequencing after HNO2 deamination and NaB3H4 reduction. The water-soluble headgroup of the Phy2 glycolipid was also analysed by 1H NMR. All four glycolipids were shown to be glycoinositol-phospholipids (GIPLs) with phosphatidylinositol (PI) moieties containing the fully saturated alkylacylglycerol lipids 1-O-hexadecyl-2-O-palmitoylglycerol and 1-O-hexadecyl-2-O-stearoylglycerol. The structures of the Phy 1-4 GIPLs are: Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6PI, Glc alpha 1-2(NH2-CH2CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6PI, [formula: see text] Glc alpha 1-2(NH2CH2CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4(NH2-CH2CH2-HPO4-)GlcN alpha 1-6PI [formula: see text] and Glc alpha 1-2Glc alpha 1-2(NH2CH2-CH2-HPO4-)Man alpha 1-2Man alpha 1-6Man alpha 1-4(NH2CH2CH2-HPO4-)-GlcN alpha 1-6PI. [formula: see text] The Phytomonas GIPLs represent a novel series of structures. This is the first description of the chemical structure of cell-surface molecules of this plant pathogen. The Phytomonas GIPLs are compared with those of other trypanosomatid parasites and are discussed with respect to trypanosomatid phylogenetic relationships. Images Figure 1 Figure 2 Figure 3 Figure 6 Figure 7 PMID:7487886

Radiocurability by Targeting Tumor Necrosis Factor-{alpha} Using a Bispecific Antibody in Carcinoembryonic Antigen Transgenic Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larbouret, Christel; Robert, Bruno; Linard, Christine

2007-11-15

Purpose: Tumor necrosis factor-{alpha} (TNF-{alpha}) enhances radiotherapy (RT) killing of tumor cells in vitro and in vivo. To overcome systemic side effects, we used a bispecific antibody (BsAb) directed against carcinoembryonic antigen (CEA) and TNF-{alpha} to target this cytokine in a CEA-expressing colon carcinoma. We report the evaluation of this strategy in immunocompetent CEA-transgenic mice. Methods and Materials: The murine CEA-transfected colon carcinoma MC-38 was used for all experiments. In vitro, clonogenic assays were performed after RT alone, TNF-{alpha} alone, and RT plus TNF-{alpha}. In vivo, the mice were randomly assigned to treatment groups: control, TNF-{alpha}, BsAb, BsAb plus TNF-{alpha},more » RT, RT plus TNF-{alpha}, and RT plus BsAb plus TNF-{alpha}. Measurements of endogenous TNF-{alpha} mRNA levels and evaluation of necrosis (histologic evaluation) were assessed per treatment group. Results: In vitro, combined RT plus TNF-{alpha} resulted in a significant decrease in the survival fraction at 2 Gy compared with RT alone (p < 0.00001). In vivo, we observed a complete response in 5 (50%) of 10, 2 (20%) of 10, 2 (18.2%) of 11, and 0 (0%) of 12 treated mice in the RT plus BsAb plus TNF-{alpha}, RT plus TNF-{alpha}, RT alone, and control groups, respectively. This difference was statistically significant when TNF-{alpha} was targeted with the BsAb (p = 0.03). The addition of exogenous TNF-{alpha} to RT significantly increased the endogenous TNF-{alpha} mRNA level, particularly when TNF-{alpha} was targeted with BsAb (p < 0.01). The percentages of necrotic area were significantly augmented in the RT plus BsAb plus TNF-{alpha} group. Conclusion: These results suggest that targeting TNF-{alpha} with the BsAb provokes RT curability in a CEA-expressing digestive tumor syngenic model and could be considered as a solid rationale for clinical trials.« less

Induction of VEGF expression by alpha-tocopherol and alpha-tocopheryl phosphate via PI3Kgamma/PKB and hTAP1/SEC14L2-mediated lipid exchange

USDA-ARS?s Scientific Manuscript database

In several studies, vitamin E has been observed to influence angiogenesis and vasculogenesis. We recently showed that the phosphorylated form of alpha-tocopherol (alphaT), alpha-tocopheryl phosphate (alphaTP), increases the expression of the vascular endothelial growth factor (VEGF). Thus, alphaTP m...

The mongoose acetylcholine receptor alpha-subunit: analysis of glycosylation and alpha-bungarotoxin binding.

PubMed

Asher, O; Jensen, B S; Lupu-Meiri, M; Oron, Y; Fuchs, S

1998-04-17

The mongoose AChR alpha-subunit has been cloned and shown to be highly homologous to other AChR alpha-subunits, with only six differences in amino acid residues at positions that are conserved in animal species that bind alpha-bungarotoxin (alpha-BTX). Four of these six substitutions cluster in the ligand binding site, and one of them, Asn-187, forms a consensus N-glycosylation site. The mongoose glycosylated alpha-subunit has a higher apparent molecular mass than that of the rat glycosylated alpha-subunit, probably resulting from the additional glycosylation at Asn-187 of the mongoose subunit. The in vitro translated mongoose alpha-subunit, in a glycosylated or non-glycosylated form, does not bind alpha-BTX, indicating that lack of alpha-BTX binding can be achieved also in the absence of glycosylation.

alpha-Mannosidosis in the guinea pig: cloning of the lysosomal alpha-mannosidase cDNA and identification of a missense mutation causing alpha-mannosidosis.

PubMed

Berg, Thomas; Hopwood, John J

2002-03-16

alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity of the lysosomal alpha-mannosidase. We report here the sequencing and expression of the lysosomal alpha-mannosidase cDNA from normal and alpha-mannosidosis guinea pigs. The amino acid sequence of the guinea pig enzyme displayed 82-85% identity to the lysosomal alpha-mannosidase in other mammals. The cDNA of the alpha-mannosidosis guinea pig contained a missense mutation, 679C>T, leading to substitution of arginine by tryptophan at amino acid position 227 (R227W). The R227W allele segregated with the alpha-mannosidosis genotype in the guinea pig colony and introduction of R227W into the wild-type sequence eliminated the production of recombinant alpha-mannosidase activity in heterologous expression studies. Furthermore, the guinea pig mutation has been found in human patients. Our results strongly indicate that the 679C>T mutation causes alpha-mannosidosis and suggest that the guinea pig will be an excellent model for investigation of pathogenesis and evaluation of therapeutic strategies for human alpha-mannosidosis.

Molecular cloning and expression analysis of sea bass (Dicentrarchus labrax L.) tumor necrosis factor-alpha (TNF-alpha).

PubMed

Nascimento, Diana S; Pereira, Pedro J B; Reis, Marta I R; do Vale, Ana; Zou, Jun; Silva, Manuel T; Secombes, Christopher J; dos Santos, Nuno M S

2007-09-01

In the search for pro-inflammatory genes in sea bass a TNF-alpha gene was cloned and sequenced. The sea bass TNF-alpha (sbTNF-alpha) putative protein conserves the TNF-alpha family signature, as well as the two cysteines usually involved in the formation of a disulfide bond. The mouse TNF-alpha Thr-Leu cleavage sequence and a potential transmembrane domain were also found, suggesting that sbTNF-alpha exists as two forms: a approximately 28 kDa membrane-bound form and a approximately 18.4 kDa soluble protein. The single copy sbTNF-alpha gene contains a four exon-three intron structure similar to other known TNF-alpha genes. Homology modeling of sbTNF-alpha is compatible with the trimeric quaternary architecture of its mammalian counterparts. SbTNF-alpha is constitutively expressed in several unstimulated tissues, and was not up-regulated in the spleen and head-kidney, in response to UV-killed Photobacterium damselae subsp. piscicida. However, an increase of sbTNF-alpha expression was detected in the head-kidney during an experimental infection using the same pathogen.

Function of Several Critical Amino Acids in Human Pyruvate Dehydrogenase Revealed by Its Structure

NASA Technical Reports Server (NTRS)

Korotchkina, Lioubov G.; Ciszak, E.; Patel, M.

2004-01-01

Pyruvate dehydrogenase (E1), an alpha 2 beta 2 tetramer, catalyzes the oxidative decarboxylation of pyruvate and reductive acetylation of lipoyl moieties of the dihydrolipoamide acetyltransferase. The roles of beta W135, alpha P188, alpha M181, alpha H15 and alpha R349 of E1 determined by kinetic analysis were reassessed by analyzing the three-dimensional structure of human E1. The residues identified above are found to play a structural role rather than being directly involved in catalysis: beta W135 is the center residue in the hydrophobic interaction between beta and beta' subunits; alpha P188 and alpha M181 are critical for the conformation of the TPP-binding motif and interaction between alpha and beta subunits; alpha H15, is necessary for the organization of the N-terminus of alpha and alpha'; subunits and alpha R349 supports the interaction of the C-terminus of the alpha subunits with the beta subunits. Analysis of several critical E1 residues confirms the importance of residues distant from the active site for subunit interactions and enzyme function.

Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes.

PubMed

Peng, X; Katz, M; Gerzanich, V; Anand, R; Lindstrom, J

1994-03-01

The alpha-bungarotoxin-binding acetylcholine receptors from the human neuroblastoma cell line SH-SY5Y were found to cross-react with some monoclonal antibodies to alpha 7 subunits of nicotinic acetylcholine receptors from chicken brain. The human alpha 7 subunit cDNA from SH-SY5Y was cloned, revealing 94% amino acid sequence identity to rat alpha 7 subunits and 92% identity to chicken alpha 7 subunits. Native human alpha 7 receptors showed affinities for some ligands similar to those previously observed with native chicken alpha 7 receptors, but for other ligands there were large species-specific differences in binding affinity. These results paralleled properties of alpha 7 homomers expressed in Xenopus oocytes. Human alpha 7 homomers exhibited rapidly desensitizing, inwardly rectifying, agonist-induced, cation currents that triggered Ca(2+)-sensitive Cl- channels in the oocytes. A change in efficacy from partial agonist for chicken alpha 7 homomers to full agonist for human alpha 7 homomers was exhibited by 1,1-dimethyl-4-phenylpiperazinium. This result reveals a large species-specific pharmacological difference, despite small differences in alpha 7 sequences. This is important for understanding the effects of these drugs in humans and for identifying amino acids that may contribute to the acetylcholine binding site, for analysis by in vitro mutagenesis. These results also characterize properties of native alpha 7 receptors and alpha 7 homomers that will provide criteria for functional properties expected of structural subunits, when these can be identified, cloned, and coexpressed with alpha 7 subunits.

Assembly of the stator in Escherichia coli ATP synthase. Complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha

PubMed Central

Senior, Alan E.; Muharemagi, Alma; Wilke-Mounts, Susan

2008-01-01

Alpha subunit of Escherichia coli ATP synthase was expressed with a C-terminal 6-His tag and purified. Pure alpha was monomeric, competent in nucleotide binding, and had normal N-terminal sequence. In F1-subunit dissociation/reassociation experiments it supported full reconstitution of ATPase, and reassociated complexes were able to bind to F1-depleted membranes with restoration of ATP-driven proton pumping. Therefore interaction between the stator delta subunit and the N-terminal residue 1-22 region of alpha occurred normally when pure alpha was complexed with other F1 subunits. On the other hand, three different types of experiment showed that no interaction occurred between pure delta and isolated alpha subunit. Unlike in F1, the N-terminal region of isolated alpha was not susceptible to trypsin cleavage. Therefore, during assembly of ATP synthase, complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha. We suggest that the N-terminal 1-22 residues of alpha are sequestered in isolated alpha until released by binding of beta to alpha subunit. This prevents 1/1 delta/alpha complexes from forming, and provides a satisfactory explanation of the stoichiometry of one delta per three alpha seen in the F1 sector of ATP synthase, assuming that steric hindrance prevents binding of more than one delta to the alpha3/beta3 hexagon. The cytoplasmic fragment of the b subunit (bsol) did not bind to isolated alpha. It might also be that complexation of alpha with beta subunits is prerequisite for direct binding of stator b subunit to the F1-sector. PMID:17176112

Liposomal formulation of {alpha}-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turanek, Jaroslav; Wang Xiufang; Knoetigova, Pavlina

2009-06-15

The vitamin E analogue {alpha}-tocopheryl succinate ({alpha}-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of {alpha}-tocopheryl maleamide ({alpha}-TAM), an esterase-resistant analogue of {alpha}-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of {alpha}-TAM towards cancer cells (MCF-7, B16F10) compared to {alpha}-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that {alpha}-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both {alpha}-TOS and {alpha}-TAM to solve the problem with cytotoxicity of free {alpha}-TAM (neurotoxicity and anaphylaxis), as well as the low solubilitymore » of both drugs. Remarkably, neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal {alpha}-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of {alpha}-TAM and {alpha}-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of {alpha}-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of {alpha}-TOS. Thus, the liposomal formulation of {alpha}-TAM preserved its strong anti-cancer efficacy while eliminating the in vivo toxicity found of the free drug applied in DMSO. Liposome-based targeted delivery systems for analogues of vitamin E are of interest for further development of efficient and safe drug formulations for clinical trials.« less

Orthopositronium Lifetime: Analytic Results in O({alpha}) and O({alpha}{sup 3}ln{alpha})

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kniehl, Bernd A.; Kotikov, Anatoly V.; Veretin, Oleg L.

2008-11-07

We present the O({alpha}) and O({alpha}{sup 3}ln{alpha}) corrections to the total decay width of orthopositronium in closed analytic form, in terms of basic irrational numbers, which can be evaluated numerically to arbitrary precision.

Synthesis of methyl 2-O- and 3-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside.

PubMed

Rana, S S; Matta, K L

1986-09-01

Methyl 3,4,6-tri-O-benzyl-2-O-[6-O-(tert-butyldiphenylsilyl)-alpha-D- mannopyranosyl]-alpha-D-mannopyranoside (2) was synthesized by treatment of methyl 3,4,6-tri-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside with tert-butylchlorodiphenylsilane in the presence of imidazole. Isopropylidenation, followed by oxidation with pyridinium chlorochromate, and stereoselective reduction with sodium borohydride, converted 2 into methyl 3,4,6-tri-O-benzyl-2-O-[6-O-(tert-butyldiphenylsilyl)-2,3-O-isopro pylidene- alpha-D-talopyranosyl]-alpha-D-mannopyranoside (5). Treatment of 5 with a molar solution of tetrabutylammonium fluoride in dry oxolane produced a diol which, on O-de-isopropylidenation followed by catalytic hydrogenolysis, afforded the disaccharide glycoside methyl 2-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside. Synthesis of methyl 3-O-alpha-D-talopyranosyl-alpha-D-mannopyranoside was accomplished by a similar reaction-sequence. The structures of the final disaccharides, and of various other intermediates, were established by 1H- and 13C-n.m.r. spectroscopy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng,L.; Gell, D.; Zhou, S.

Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP boundmore » alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.« less

Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersson, G.; Lundgren, E.; Ekre, H.P.

Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition ofmore » the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity.« less

Specific antibodies against Go isoforms reveal the early expression of the Go2 alpha subunit and appearance of Go1 alpha during neuronal differentiation.

PubMed

Rouot, B; Charpentier, N; Chabbert, C; Carrette, J; Zumbihl, R; Bockaert, J; Homburger, V

1992-02-01

We have previously identified two isoforms of Go alpha in membranes of N1E-115 neuroblastoma cells, using an antibody raised against the purified Go alpha subunit; one isoform of the Go alpha subunit (pI 5.80) is present in undifferentiated cells, whereas a more acidic isoform (pI 5.55) appears during differentiation [J. Neurochem. 54:1310-1320 (1990)]. Recently, the Go alpha gene has been shown to encode, by alternative splicing, two polypeptides, Go1 alpha and Go2 alpha, which differ only in their carboxyl-terminal part. To determine unambiguously whether the two Go alpha subunits detected in neuroblastoma cells were actually the products of different mRNAs, rabbit polyclonal antibodies were generated against synthetic peptides (amino acids 291-302) of both sequences. Specificity of the two affinity-purified antipeptide antibodies was assessed on Western blots by comparing their immunoreactivities with those of other G alpha antibodies. On a blotted mixture of purified brain guanine nucleotide-binding proteins, the anti-alpha o1 and anti-alpha o2 peptide antibodies only recognized the 39-kDa Go alpha subunit. Furthermore, the immunological recognition of brain membranes from 15-day-old mouse fetuses by antipeptide antibodies could be specifically blocked by addition of the corresponding antigen. When membrane proteins from differentiated neuroblastoma cells and mouse fetus brain were blotted after two-dimensional gel electrophoresis, the anti-alpha o1 and anti-alpha o2 peptide antibodies labeled a 39-kDa subunit focused at a pI value of 5.55 or 5.80, respectively. Study of the ontogenesis of both Go alpha subunits revealed the predominance of Go2 alpha in the frontal cortex at day 15 of gestation. Thereafter, there was a progressive decline of the Go2 alpha polypeptide to a very low level, concomitant with an increase in the Go1 alpha protein, which plateaued about 15 days after birth to a level 8 times higher than at gestational day 15. Similarly, on neuroblastoma cells, the Go2 alpha subunit was almost exclusively present in undifferentiated cells, and differentiation induced the appearance of the Go1 alpha subunit, with a reduction in the amount of Go2 alpha polypeptide. Thus, the evolution of the two Go alpha subunits during cell differentiation, unambiguously identified with specific antibodies, suggests that neuronal differentiation is responsible for the on/off switch of the expression of the Go alpha isoforms and indicates that Go1 alpha, rather than Go2 alpha, is involved in neurotransmission.

Identification of a novel bile acid in swans, tree ducks, and geese: 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid.

PubMed

Kakiyama, Genta; Iida, Takashi; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Nambara, Toshio; Hagey, Lee R; Schteingart, Claudio D; Hofmann, Alan F

2006-07-01

By HPLC, a taurine-conjugated bile acid with a retention time different from that of taurocholate was found to be present in the bile of the black-necked swan, Cygnus melanocoryphus. The bile acid was isolated and its structure, established by (1)H and (13)C NMR and mass spectrometry, was that of the taurine N-acyl amidate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid. The compound was shown to have chromatographic and spectroscopic properties that were identical to those of the taurine conjugate of authentic 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid, previously synthesized by us from ursodeoxycholic acid. By HPLC, the taurine conjugate of 3alpha,7alpha,15alpha-trihydroxy-5beta-cholan-24-oic acid was found to be present in 6 of 6 species in the subfamily Dendrocygninae (tree ducks) and in 10 of 13 species in the subfamily Anserinae (swans and geese) but not in other subfamilies in the Anatidae family. It was also not present in species from the other two families of the order Anseriformes. 3alpha,7alpha,15alpha-Trihydroxy-5beta-cholan-24-oic acid is a new primary bile acid that is present in the biliary bile acids of swans, tree ducks, and geese and may be termed 15alpha-hydroxy-chenodeoxycholic acid.

[Age-related change in the alpha-tocopherolquinone/alpha-tocopherol ratio in the rat erythrocyte membrane].

PubMed

Yanagawa, K; Takeda, H; Matsumiya, T; Takasaki, M

1999-05-01

alpha-Tocopherol (alpha-Toc), a lipophilic phenolic antioxidant that is localized mainly in the biomembrane, protects cells against oxidation-associated cytotoxicity by prevention of membrane lipid peroxidation, maintenance of the redox balance intracellular thiols and stabilization of the membrane structure. We investigated the age-related changes in redox dynamics of alpha-Toc in plasma and erythrocyte membrane of an elderly (66 weeks old) and young group (10 weeks old). Total, alpha-, beta + gamma-, delta-Toc and alpha-tocopherolquinone (alpha-TocQ) in plasma and erythrocyte membrane were determined by high-performance liquid chromatography (HPLC) with a series of multiple coulometric working electrodes (CWE). Rat venous blood sample was divided into plasma and erythrocyte layers by centrifugation, and then erythrocyte membrane sample was prepared according to the method of Dodge et al. under a stream of nitrogen. In plasma, total and alpha-Toc concentrations were increased, and beta + gamma-, delta-Toc and alpha-TocQ concentrations were decreased age-dependently. In the erythrocyte membrane, total, alpha-TocQ concentrations and three fractions of tocopherols decreased age-dependently. Also, a decrease in the alpha-TocQ/alpha-Toc ratio in erythrocyte membrane was observed in the elderly group. These findings suggest that the alpha-Toc uptake in erythrocyte membrane and utilization rate of alpha-Toc in erythrocyte membrane decline age-dependently. This decline may promote membrane lipid peroxidation. alpha-Toc redox dynamics in erythrocyte membrane were useful to investigate the pathophysiology of aging mechanisms related to oxidative stress.

Contribution of HIF-1alpha or HIF-2alpha to erythropoietin expression: in vivo evidence based on chromatin immunoprecipitation.

PubMed

Yeo, Eun-Jin; Cho, Young-Suk; Kim, Myung-Suk; Park, Jong-Wan

2008-01-01

Circulating erythropoietin (EPO) is mainly produced by the kidneys and mediates erythrogenesis in bone marrow and nonhematopoietic cell survival. EPO is also produced in other tissues where it functions as a paracrine. Moreover, the hypoxic induction of EPO is known to be mediated by HIF-1alpha and HIF-2alpha, but it remains obscure as to which of these two mediators mainly contributes to EPO expression. Thus, we designed in vivo experiments to evaluate the contributions made by HIF-1alpha and HIF-2alpha to EPO expression. In mice exposed to mild whole body hypoxia, HIF-1alpha and HIF-2alpha were both induced in all tissues examined. However, EPO mRNA was expressed in kidney and brain, but not in liver and lung. Likewise, chromatin immunoprecipitation (CHIP) analyses demonstrated that HIF-1alpha or HIF-2alpha binding to the EPO gene increased under hypoxic conditions only in kidney and brain. A comparison of CHIP data and EPO mRNA levels suggested that, during mild hypoxia, renal EPO transcription is induced equally by HIF-1alpha and HIF-2alpha, but that brain EPO is mainly induced during hypoxia by HIF-2alpha. Thus, HIF-1alpha and HIF-2alpha appear to contribute to EPO expression tissue specifically.

{sup 110,116}Cd({alpha},{alpha}){sup 110,116}Cd elastic scattering and systematic investigation of elastic {alpha} scattering cross sections along the Z=48 isotopic and N=62 isotonic chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiss, G. G.; Fueloep, Zs.; Gyuerky, Gy.

2011-06-15

The elastic scattering cross sections for the reactions {sup 110,116}Cd({alpha},{alpha}){sup 110,116}Cd at energies above and below the Coulomb barrier are presented to provide a sensitive test for the {alpha}-nucleus optical potential parameter sets. Additional constraints for the optical potential are taken from the analysis of elastic scattering excitation functions at backward angles which are available in literature. Moreover, the variation of the elastic {alpha} scattering cross sections along the Z=48 isotopic and N=62 isotonic chain is investigated by the study of the ratios of the {sup 106,110,116}Cd({alpha},{alpha}){sup 106,110,116}Cd scattering cross sections at E{sub cm{approx_equal}}15.6and18.8 MeV and the ratio of themore » {sup 110}Cd({alpha},{alpha}){sup 110}Cd and {sup 112}Sn({alpha},{alpha}){sup 112}Sn reaction cross sections at E{sub cm{approx_equal}}18.8 MeV, respectively. These ratios are sensitive probes for the {alpha}-nucleus optical potential parametrizations. The potentials under study are a basic prerequisite for the prediction of {alpha}-induced reaction cross sections (e.g., for the calculation of stellar reaction rates in the astrophysical p or {gamma} process).« less

Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Meisheng; Tran, V.T.; Fong, H.K.W.

1991-05-01

The expression of GTP-binding regulatory proteins (G proteins) in retinal pigment epithelial (RPE) cells was analyzed by RNA blot hybridization and cDNA amplification. Both adult and fetal human RPE cells contain mRNA for multiple G protein {alpha} subunits (G{alpha}) including G{sub s}{alpha}, G{sub i-1}{alpha}, G{sub i-2}{alpha}, G{sub i-3}{alpha}, and G{sub z}{alpha} (or G{sub x}{alpha}), where G{sub s} and G{sub i} are proteins that stimulate or inhibit adenylyl cyclase, respectively, and G{sub z} is a protein that may mediate pertussis toxin-insensitive events. Other G{alpha}-related mRNA transcripts were detected in fetal RPE cells by low-stringency hybridization to G{sub i-2}{alpha} and G{sub s}{alpha}more » protein-coding cDNA probes. The diversity of G proteins in RPE cells was further studied by cDNA amplification with reverse transcriptase and the polymerase chain reaction. This approach revealed that, besides the above mentioned members of the G{alpha} gene family, at least two other G{alpha} subunits are expressed in RPE cells. Human retinal cDNA clones that encode one of the additional G{alpha} subunits were isolated and characterized. The results indicate that this G{alpha} subunit belongs to a separate subfamily of G proteins that may be insensitive to inhibition by pertussis toxin.« less

21 CFR 866.5420 - Alpha-1-glycoproteins immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-glycoproteins immunological test system....5420 Alpha-1-glycoproteins immunological test system. (a) Identification. An alpha-1-glycoproteins... alpha-1-glycoproteins (a group of plasma proteins found in the alpha-1 group when subjected to...

21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-1-antichymotrypsin immunological test system....5080 Alpha-1-antichymotrypsin immunological test system. (a) Identification. An alpha-1... immunochemical techniques alpha-1-antichymotrypsin (a protein) in serum, other body fluids, and tissues. Alpha-1...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha-2-macroglobulin immunological test system....5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... the alpha-2-macroglobulin (a serum protein) in plasma. Measurement of alpha-2-macroglobulin may aid in...

21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-1-antichymotrypsin immunological test system....5080 Alpha-1-antichymotrypsin immunological test system. (a) Identification. An alpha-1... immunochemical techniques alpha-1-antichymotrypsin (a protein) in serum, other body fluids, and tissues. Alpha-1...

21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-1-antichymotrypsin immunological test system....5080 Alpha-1-antichymotrypsin immunological test system. (a) Identification. An alpha-1... immunochemical techniques alpha-1-antichymotrypsin (a protein) in serum, other body fluids, and tissues. Alpha-1...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-2-macroglobulin immunological test system....5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... the alpha-2-macroglobulin (a serum protein) in plasma. Measurement of alpha-2-macroglobulin may aid in...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-2-macroglobulin immunological test system....5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... the alpha-2-macroglobulin (a serum protein) in plasma. Measurement of alpha-2-macroglobulin may aid in...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. 721.10300 Section 721.10300 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10300 Benzeneacetic acid, .alpha.-chloro-.alpha...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. 721.10300 Section 721.10300 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10300 Benzeneacetic acid, .alpha.-chloro-.alpha...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-2-macroglobulin immunological test system....5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... the alpha-2-macroglobulin (a serum protein) in plasma. Measurement of alpha-2-macroglobulin may aid in...

40 CFR 721.10300 - Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzeneacetic acid, .alpha.-chloro-.alpha.-phenyl-, ethyl ester. 721.10300 Section 721.10300 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10300 Benzeneacetic acid, .alpha.-chloro-.alpha...

Binding of actin to lens alpha crystallins

NASA Technical Reports Server (NTRS)

Gopalakrishnan, S.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

1992-01-01

Actin has been coupled to a cyanogen bromide-activated Sepharose 4B column, then tested for binding to alpha, beta, and gamma crystallin preparations from the bovine lens. Alpha, but not beta or gamma, crystallins bound to the actin affinity column in a time dependent and saturable manner. Subfractionation of the alpha crystallin preparation into the alpha-A and alpha-B species, followed by incubation with the affinity column, demonstrated that both species bound approximately the same. Together, these studies demonstrate a specific and saturable binding of lens alpha-A and alpha-B with actin.

Structure of the glycosyl-phosphatidylinositol membrane anchor of acetylcholinesterase from the electric organ of the electric-fish, Torpedo californica.

PubMed Central

Mehlert, A; Varon, L; Silman, I; Homans, S W; Ferguson, M A

1993-01-01

The structure of the glycan moiety of the glycosyl-phosphatidylinositol (GPI) membrane anchor from Torpedo californica (electric fish) electric-organ acetylcholinesterase was solved using n.m.r., methylation analysis and chemical and enzymic micro-sequencing. Two structures were found to be present: Glc alpha 1-2Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol and Glc alpha 1-2Man alpha 1-2Man alpha 1-6(GalNAc beta 1-4)Man alpha 1-4GlcN alpha 1-6myo-inositol. The presence of glucose in this GPI anchor structure is a novel feature. The anchor was also shown to contain 2.3 residues of ethanolamine per molecule. PMID:8257440

[Alpha power voluntary increasing training for cognition enhancement study].

PubMed

Alekseeva, M V; Balioz, N V; Muravleva, K B; Sapina, E V; Bazanova, O M

2012-01-01

With the aim simultaneous alpha EEG stimulating and EMG decreasing biofeedback training impact on the alpha-activity and cognitive functions 27 healthy male subjects (18-34 years) were investigated in pre- and post 10 training sessions of the voluntary increasing alpha power in individual upper alpha range. The accuracy of conceptual span task, fluency and flexibility in alternatives use task performance and alpha-activity indices were compared in real (14 participants) and sham (13 participants) biofeedback groups for the discrimination of the feedback role in training. The follow up effect oftrainings was studied through month over the training sessions. Results showed that alpha biofeedback training enhanced the fluency and accuracy in cognitive performance, increased resting frequency, width and power in individual upper alpha range only in participants with low baseline alpha frequency. While mock biofeedback increased resting alpha power only in participants with high baseline resting alpha frequency and did not change the cognitive performance. Biofeedback training eliminated the alpha power decrease in response to arithmetic task in both with high and low alpha frequency participants and this effect was followed up over the month. Mock biofeedback training has no such effect. It could be concluded that alpha-EEG-EMG biofeedback has application not only for cognition enhancement, but also in prognostic aims in clinical practice and brain-computer interface technology.

Cloning and characterization of the mouse alpha1C/A-adrenergic receptor gene and analysis of an alpha1C promoter in cardiac myocytes: role of an MCAT element that binds transcriptional enhancer factor-1 (TEF-1).

PubMed

O'Connell, T D; Rokosh, D G; Simpson, P C

2001-05-01

alpha1-Adrenergic receptor (AR) subtypes in the heart are expressed by myocytes but not by fibroblasts, a feature that distinguishes alpha1-ARs from beta-ARs. Here we studied myocyte-specific expression of alpha1-ARs, focusing on the subtype alpha1C (also called alpha1A), a subtype implicated in cardiac hypertrophic signaling in rat models. We first cloned the mouse alpha1C-AR gene, which consisted of two exons with an 18 kb intron, similar to the alpha1B-AR gene. The receptor coding sequence was >90% homologous to that of rat and human. alpha1C-AR transcription in mouse heart was initiated from a single Inr consensus sequence at -588 from the ATG; this and a putative polyadenylation sequence 8.5 kb 3' could account for the predominant 11 kb alpha1C mRNA in mouse heart. A 5'-nontranscribed fragment of 4.4 kb was active as a promoter in cardiac myocytes but not in fibroblasts. Promoter activity in myocytes required a single muscle CAT (MCAT) element, and this MCAT bound in vitro to recombinant and endogenous transcriptional enhancer factor-1. Thus, alpha1C-AR transcription in cardiac myocytes shares MCAT dependence with other cardiac-specific genes, including the alpha- and beta-myosin heavy chains, skeletal alpha-actin, and brain natriuretic peptide. However, the mouse alpha1C gene was not transcribed in the neonatal heart and was not activated by alpha1-AR and other hypertrophic agonists in rat myocytes, and thus differed from other MCAT-dependent genes and the rat alpha1C gene.

Tumor necrosis factor-alpha-independent downregulation of hepatic cholesterol 7alpha-hydroxylase gene in mice treated with lead nitrate.

PubMed

Kojima, Misaki; Sekikawa, Kenji; Nemoto, Kiyomitsu; Degawa, Masakuni

2005-10-01

We previously reported that lead nitrate (LN), an inducer of hepatic tumor necrosis factor-alpha (TNF-alpha), downregulated gene expression of cholesterol 7alpha-hydroxylase. Herein, to clarify the role of TNF-alpha in LN-induced downregulation of cholesterol 7alpha-hydroxylase, effects of LN on gene expression of hepatic cholesterol 7alpha-hydroxylase (Cyp7a1) in TNF-alpha-knockout (KO) and TNF-alpha-wild-type (WT) mice were comparatively examined. Gene expression of hepatic Cyp7a1 in both WT and KO mice decreased to less than 5% of the corresponding controls at 6-12 h after treatment with LN (100 mumol/kg body weight, iv). Levels of hepatic TNF-alpha protein in either WT or KO mice were below the detection limit, although expression levels of the TNF-alpha gene markedly increased at 6 h in WT mice by LN treatment, but not in KO mice. In contrast, in both WT and KO mice, levels of hepatic IL-1beta protein, which is known to be a suppressor of the cholesterol 7alpha-hydroxylase gene in hamsters, were significantly increased 3-6 h after LN treatment. Furthermore, LN-induced downregulation of the Cyp7a1 gene did not necessarily result from altered gene expression of hepatic transcription factors, including positive regulators (liver X receptor alpha, retinoid X receptor alpha, fetoprotein transcription factor, and hepatocyte nuclear factor 4alpha) and a negative regulator small heterodimer partner responsible for expression of the Cyp7a1 gene. The present findings indicated that LN-induced downregulation of the Cyp7a1 gene in mice did not necessarily occur through a TNF-alpha-dependent pathway and might occur mainly through an IL-1beta-dependent pathway.

Identification and quantification of metabolites common to 17alpha-methyltestosterone and mestanolone in horse urine.

PubMed

Yamada, Masayuki; Aramaki, Sugako; Okayasu, Toshimasa; Hosoe, Tomoo; Kurosawa, Masahiko; Kijima-Suda, Isao; Saito, Koichi; Nakazawa, Hiroyuki

2007-09-21

Anabolic steroids with the 17alpha-methyl,17beta-hydroxyl group, which were developed as oral formulations for therapeutic purposes, have been abused in the field of human sports. These anabolic steroids are also used to enhance racing performance in racehorses. In humans, structurally related 17alpha-methyltestosterone (MTS) and mestanolone (MSL), which are anabolic steroids with the 17alpha-methyl,17beta-hydroxyl group, have metabolites in common. The purpose of this study was to determine metabolites common to these two steroids in horses, which may serve as readily available screening targets for the doping test of these steroids in racehorses. Urine sample collected after administering MTS and MSL to horses was treated to obtain unconjugated steroid, glucuronide, and sulfate fractions. The fractions were subjected to gas chromatography/mass spectrometry (GC/MS), and 17alpha-methyl-5alpha-androstan-3beta,17beta-diol, 17alpha-hydroxymethyl-5alpha-androstan-3beta,17beta-diol, 17alpha-methyl-5alpha-androstan-3beta,16beta,17beta-triol, and 17alpha-methyl-5alpha-androstan-3beta,16alpha,17beta-triol were detected as the common metabolites by comparison with synthesized reference standards. The urinary concentrations of these metabolites after dosing were determined by GC/MS. 17Alpha-methyl-5alpha-androstan-3beta,16beta,17beta-triol was mainly detected in the sulfate fractions of urine samples after administration. This compound was consistently detected for the longest time in the urine samples after dosing with both steroids. The results suggest that 17alpha-methyl-5alpha-androstan-3beta,16beta,17beta-triol is a very useful screening target for the doping test of MTS and MSL in racehorses.

Islets of Langerhans in the parakeet, Psittacula krameri.

PubMed

Gupta, Y K; Kumar, S

1980-01-01

The pancreatic gland of Psittacula krameri is divisible into 4 lobes i.e. dorsal, ventral, third and splenic. The endocrine part is composed of alpha 1-, alpha 2- and beta-cells. The islets are of 4 kinds viz., alpha islets (having alpha 1- and alpha 2-cells), beta islets (having beta- and alpha 1-cells), pure beta islets (consisting of beta-cells exclusively) and mixed islets (with beta-, alpha 1- and alpha 2-cells). The distribution of alpha islets is mostly restricted to the splenic and third lobes whereas the beta islets are found in all 4 lobes. Though the alpha islets are only few in the dorsal lobe, their size is best developed in the third and dorsal lobes. Sometimes beta and alpha islets are present in very close proximity but their cells never mingle. An interesting feature was the complete absence of alpha islets from the ventral lobe.A relative abundance of alpha 2- cells in this bird seems to be associated with its comparatively higher blood glucose level and frugivorous habit. Tinctorial reactions suggest that the insulin content of the endocrine pancreas is low. There were no seasonal changes in the islet tissue of P. krameri.

Peroxisome proliferator-activated receptor {alpha}-independent peroxisome proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Xiuguo; Tanaka, Naoki; Nakajima, Takero

2006-08-11

Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPAR{alpha}-independent peroxisome proliferation, fenofibrate treatment was used, which was expected to significantly enhance PPAR{alpha} dependence in the assay system. Surprisingly, a novel type of PPAR{alpha}-independent peroxisome proliferation and enlargement was uncovered in PPAR{alpha}-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11{alpha}, might be associated with the PPAR{alpha}-independent peroxisome proliferation at least in part.

Hepatocyte nuclear factor-4alpha is a central transactivator of the mouse Ntcp gene.

PubMed

Geier, Andreas; Martin, Ina V; Dietrich, Christoph G; Balasubramaniyan, Natarajan; Strauch, Sonja; Suchy, Frederick J; Gartung, Carsten; Trautwein, Christian; Ananthanarayanan, Meenakshisundaram

2008-08-01

Sodium taurocholate cotransporting polypeptide (Ntcp) is the major uptake system for conjugated bile acids. Deletions of hepatocyte nuclear factor (HNF)-1alpha and retinoid X receptor-alpha:retinoic acid receptor-alpha binding sites in the mouse 5'-flanking region corresponding to putatively central regulatory elements of rat Ntcp do not significantly reduce promoter activity. We hypothesized that HNF-4alpha, which is increasingly recognized as a central regulator of hepatocyte function, may directly transactivate mouse (mNtcp). A 1.1-kb 5'-upstream region including the mouse Ntcp promoter was cloned and compared with the rat promoter. In contrast to a moderate 3.5-fold activation of mNtcp by HNF-1alpha, HNF-4alpha cotransfection led to a robust 20-fold activation. Deletion analysis of mouse and rat Ntcp promoters mapped a conserved HNF-4alpha consensus site at -345/-326 and -335/-316 bp, respectively. p-475bpmNtcpLUC is not transactivated by HNF-1alpha but shows a 50-fold enhanced activity upon cotransfection with HNF-4alpha. Gel mobility shift assays demonstrated a complex of the HNF-4alpha-element formed with liver nuclear extracts that was blocked by an HNF-4alpha specific antibody. HNF-4alpha binding was confirmed by chromatin immunoprecipitation. Using Hepa 1-6 cells, HNF-4alpha-knockdown resulted in a significant 95% reduction in NTCP mRNA. In conclusion, mouse Ntcp is regulated by HNF-4alpha via a conserved distal cis-element independently of HNF-1alpha.

Mapping High-Velocity H-alpha and Lyman-alpha Emission from Supernova 1987A

NASA Technical Reports Server (NTRS)

France, Kevin; McCray, Richard; Fransson, Claes; Larsson, Josefin; Frank, Kari A.; Burrows, David N.; Challis, Peter; Kirshner, Robert P.; Chevalier, Roger A.; Garnavich, Peter;

P alpha-chiral phosphorothioate analogues of bis(5'-adenosyl)tetraphosphate (Ap4A); their enzymatic synthesis and degradation.

PubMed Central

Lazewska, D; Guranowski, A

1990-01-01

Synthesis of Sp and Rp diastereomers of Ap4A alpha S has been characterized in two enzymatic systems, the lysyl-tRNA synthetase from Escherichia coli and the Ap4A alpha, beta-phosphorylase from Saccharomyces cerevisiae. The synthetase was able to use both (Sp)ATP alpha S and (Rp)ATP alpha S as acceptors of adenylate thus yielding corresponding monothioanalogues of Ap4A,(Sp) Ap4A alpha S and (Rp)Ap4A alpha S. No dithiophosphate analogue was formed. Relative synthetase velocities of the formation of Ap4A,(Sp) Ap4A alpha S and (Rp)Ap4A alpha S were 1:0.38:0.15, and the computed Km values for (Sp)ATP alpha S and (Rp)ATP alpha S were 0.48 and 1.34 mM, respectively. The yeast Ap4A phosphorylase synthesized (Sp)Ap4A alpha S and (Rp)Ap4A alpha S using adenosine 5'-phosphosulfate (APS) as source of adenylate. The adenylate was accepted by corresponding thioanalogues of ATP. In that system, relative velocities of Ap4A, (Sp)Ap4A alpha S and (Rp)Ap4A alpha S formation were 1:0.15:0.60. The two isomeric phosphorothioate analogues of Ap4A were tested as substrates for the following specific Ap4A-degrading enzymes: (asymmetrical) Ap4A hydrolase (EC 3.6.1.17) from yellow lupin (Lupinus luteus) seeds hydrolyzed each of the analogues to AMP and the corresponding isomer of ATP alpha S; (symmetrical) Ap4A hydrolase (EC 3.6.1.41) from E. coli produced ADP and the corresponding diastereomer of ADP alpha S; and Ap4A phosphorylase (EC 2.7.7.53) from S. cerevisiae cleaved the Rp isomer only at the unmodified end yielding ADP and (Rp)ATP alpha S whereas the Sp isomer was degraded non-specifically yielding a mixture of ADP, (Sp)ADP alpha S, ATP and (Sp)ATP alpha S. For all the Ap4A-degrading enzymes, the Rp isomer of Ap4A alpha S appeared to be a better substrate than its Sp counterpart; stereoselectivity of the three enzymes for the Ap4A alpha S diastereomers is 51, 6 and 2.5, respectively. Basic kinetic parameters of the degradation reactions are presented and structural requirements of the Ap4A-metabolizing enzymes with respect to the potential substrates modified at the Ap4A-P alpha are discussed. PMID:2172926

Evaluation of GABAergic neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one as a neurobiological substrate for the anti-anxiety effect of ethanol in rats.

PubMed

Hirani, Khemraj; Sharma, Ajay N; Jain, Nishant S; Ugale, Rajesh R; Chopde, Chandrabhan T

2005-07-01

Acute systemic ethanol administration is known to elevate plasma and cerebral levels of neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha, 5alpha-THP; allopregnanolone) to a concentration sufficient to potentiate GABA(A) receptors. We have earlier demonstrated that 3alpha, 5alpha-THP mediates the antidepressant-like effect of ethanol in Porsolt forced swim test. The aim of the present study is to explain the relationship between endogenous GABAergic neurosteroids and anxiolytic effect of ethanol in Sprague-Dawley rats. The mediation of 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol was assessed by pharmacological interactions of ethanol with various endogenous neurosteroidal modulators and using simulated physiological conditions of altered neurosteroid content in elevated plus maze (EPM) test. Pretreatment of 3alpha, 5alpha-THP (0.5-2.5 mug/rat, i.c.v.) or neurosteroidogenic agents such as 3alpha, 5alpha-THP precursor progesterone (5 or 10 mg/kg, i.p.), 11-beta hydroxylase inhibitor metyrapone (50 or 100 mg/kg, i.p.) or the GABA(A) receptor agonist muscimol (25 ng/rat, i.c.v.) significantly potentiated the anti-anxiety effect of ethanol (1 g/kg, i.p.). On the other hand, the GABAergic antagonistic neurosteroid dehydroepiandrosterone sulphate (DHEAS) (1 mg/kg, i.p.), the GABA(A) receptor blocker bicuculline (1 mg/kg, i.p.), the 5alpha-reductase inhibitor finasteride (50 x 2 mg/kg, s.c.) or the mitochondrial diazepam binding inhibitory receptor antagonist PK11195 (1 mg/kg, i.p.) reduced ethanol-induced preference of time spent and number of entries into open arms. Anti-anxiety effect of ethanol was abolished in adrenalectomized (ADX) rats as compared to sham-operated control. This ADX-induced blockade was restored by prior systemic injection of progesterone, signifying the contribution of peripheral steroidogenesis in ethanol anxiolysis. Socially isolated animals known to exhibit decreased brain 3alpha, 5alpha-THP and GABA(A) receptor functions displayed reduced sensitivity to the effects of ethanol and 3alpha, 5alpha-THP in EPM test. Our results demonstrated the contributory role of neuroactive steroid 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol. It is speculated that ethanol-induced modulation of endogenous GABAergic neurosteroids, especially 3alpha, 5alpha-THP, might be crucial pertinent to the etiology of 'trait' anxiety (tension reduction) and ethanol abuse.

Terpenoids from Tripterygium doianum (Celastraceae).

PubMed

Tanaka, Naonobu; Duan, Hongquan; Takaishi, Yoshihisa; Kawazoe, Kazuyoshi; Goto, Satoru

2002-09-01

The extract of Tripterygium doianum (Celastraceae) afforded three triterpenoids [3beta-acetoxy-11-ursen-13alpha,30-olide, 25-chloro-24-hydroxytirucall-7-en-3-one and tirucall-7-en-3,24-dione], two sesquiterpenoids [5alpha-acetoxy-1beta,8alpha-bis-cinnamoyl-4alpha-hydroxydihydroagarofuran and 5alpha-acetoxy-1beta-benzoyl-8alpha-cinnamoyl-4alpha-hydroxydihydroagarofuran] and nine known triterpenoids. Their structures were established based on spectroscopic studies. Copyright 2002 Elsevier Science Ltd.

Blood-brain barrier transport of the alpha-keto acid analogs of amino acids.

PubMed

Steele, R D

1986-06-01

A number of alpha-keto acid analogs of amino acids have been found to penetrate the blood-brain barrier (BBB). Pyruvate, alpha-ketobutyrate, alpha-ketoisocaproate, and alpha-keto-gamma-methiolbutyrate all cross the BBB by a carrier-mediated process and by simple diffusion. Under normal physiological conditions, diffusion accounts for roughly 15% or less of total transport. Aromatic alpha-keto acids, phenylpyruvate, and p-hydroxyphenylpyruvate do not penetrate the BBB, nor do they inhibit the transport of other alpha-keto acids. Evidence based primarily on inhibition studies indicates that the carrier-mediated transport of alpha-keto acids occurs via the same carrier demonstrated previously for propionate, acetoacetate, and beta-hydroxybutyrate transport, commonly referred to as the monocarboxylate carrier. As a group, the alpha-keto acid analogs of the amino acids have the highest affinity for the carrier, followed by propionate and beta-hydroxybutyrate. Starvation for 4 days induces transport of alpha-keto acids, but transport is suppressed in rats fed commercial laboratory rations and subjected to portacaval shunts. The mitochondrial pyruvate translocator inhibitor alpha-cyanocinnamate has no effect on the BBB transport of alpha-keto acids.

Isolation of a new anti-inflammatory 20, 21, 22, 23, 24, 25, 26, 27-octanorcucurbitacin-type triterpene from Ibervillea sonorae.

PubMed

Jardón-Delgado, Angel; Magos-Guerrero, Gil Alfonso; Martínez-Vázquez, Mariano

2014-01-01

A new cucurbitane-type triterpene, 20, 21, 22, 23, 24, 25, 26, 27-octanorcucurbita-5-ene-3, 11, 16-trione (1), named kinoin D, was isolated from the roots of the medicinal plant Ibervillea sonorae, (wereque). The structure of 1 was established on the basis of extensive NMR and MS studies. In addition, the known kinoins B (3) and C (5) were isolated, as were 16alpha-20,25-trihydroxy-3alpha-(2-O-alpha-L-rhamnopyranosiyl-D-glucopyranosyloxy)-(10alpha)-cucurbit-5-en-11,22-dione (6), (22S)-16alpha,22-diacetoxy-20,25-dihydroxy-3alpha-[3,4,6-tri-O-acetyl-2-O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl)-beta-glucopyranosyl]-(10alpha)-cucurbita-5,23t-dien-11-one (7) and 16alpha-acetoxy-20,25-dihydroxy-3alpha-[3,4,6-tri-O-acetyl-2-O-(2,3,4,-tri-O-acetyl-alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-(10alpha)-cucurbita-5-ene-11,22-dione (8). Compound 1 exhibited anti-inflammatory activity in TPA-induced edema in mice.

Immunostimulatory effects of natural human interferon-alpha (huIFN-alpha) on carps Cyprinus carpio L.

PubMed

Watanuki, Hironobu; Chakraborty, Gunimala; Korenaga, Hiroki; Kono, Tomoya; Shivappa, R B; Sakai, Masahiro

2009-10-15

Human interferon-alpha (huIFN-alpha) is an important immunomodulatory substance used in the treatment and prevention of numerous infectious and immune-related diseases in animals. However, the immunostimulatory effects of huIFN-alpha in fish remain to be investigated. In the current study, the immune responses of the carp species Cyprinus carpio L. to treatment with huIFN-alpha were analyzed via measurement of superoxide anion production, phagocytic activity and the expression of cytokine genes including interleukin-1beta, tumor necrosis factor-alpha and interleukin 10. Low doses of huIFN-alpha were administered orally once a day for 3 days, and sampling was carried out at 1, 3 and 5 days post-treatment. Our results indicate that a low dose of huIFN-alpha significantly increased phagocytic activity and superoxide anion production in the carp kidney. The huIFN-alpha-treated fish also displayed a significant upregulation in cytokine gene expression. The current study demonstrates the stimulatory effects of huIFN-alpha on the carp immune system and highlights the immunomodulatory role of huIFN-alpha in fish.

Plasma binding of an alpha-blocking agent, nicergoline--affinity for serum albumin and native and modified alpha 1-acid glycoprotein.

PubMed

Robert, L; Migne, J; Santonja, R; Zini, R; Schmid, K; Tillement, J P

1983-06-01

The binding of nicergoline, an alpha-blocking drug, by human plasma proteins was studied using gel filtration, polyacrylamide gel electrophoresis, and equilibrium dialysis techniques. 3H-labeled nicergoline added to plasma was eluted together with two major protein fractions, one containing mainly serum albumin, the other glycoproteins such as alpha 1-acid glycoprotein (alpha 1-AG). Equilibrium dialysis experiments with pure human serum albumin and alpha 1-AG as well as with its chemically modified forms, desialylated, carboxymethylated, and both desialylated and carboxymethylated alpha 1-AG gave the following results: nicergoline has about a 4-fold higher affinity for alpha 1-AG than for serum albumin. There are two binding sites per molecule on serum albumin and one on alpha 1-AG. The binding parameters of alpha 1-AG were not significantly modified by desialylation or carboxymethylation. Only desialylated and carboxymethylated alpha 1-AG showed a decreased binding for nicergoline, suggesting conformational modifications induced by these combined treatments. The fact that desialylated alpha 1-AG keeps its affinity for nicergoline suggests the possibility of a selective introduction of this drug in cells possessing the Ashwell-type specific receptor for desialylated alpha 1-AG, for instance hepatocytes. Increased serum alpha 1-AG concentration induced by inflammatory reactions will also modify the distribution of bound nicergoline between serum albumin and alpha 1-AG and as a consequence its half-life and cell distribution.

Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi

2011-04-22

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a humanmore » adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected effects of PPAR{alpha} activation are very valuable for managing diabetic conditions accompanied by obesity, because PPAR{gamma} agonists, usually used as antidiabetic drugs, induce excessive lipid accumulation in adipocytes in addition to improvement of insulin resistance.« less

Bioequivalence of a Liquid Formulation of Alpha1-Proteinase Inhibitor Compared with Prolastin®-C (Lyophilized Alpha1-PI) in Alpha1-Antitrypsin Deficiency.

PubMed

Barker, Alan F; Campos, Michael A; Brantly, Mark L; Stocks, James M; Sandhaus, Robert A; Lee, Douglas; Steinmann, Kimberly; Lin, Jiang; Sorrells, Susan

2017-12-01

This study evaluated the bioequivalence, safety, and immunogenicity of a new liquid formulation of human plasma-derived alpha 1 -proteinase inhibitor, Liquid Alpha 1 -PI, compared with the Lyophilized Alpha 1 -PI formulation (Prolastin®-C), for augmentation therapy in patients with alpha 1 -antitrypsin deficiency (AATD). In this double-blind, randomized, 20-week crossover study, 32 subjects with AATD were randomized to receive 8 weekly infusions of 60 mg/kg of Liquid Alpha 1 -PI or Lyophilized Alpha 1 -PI. Serial blood samples were drawn for 7 days after the last dose followed by 8 weeks of the alternative treatment. The primary endpoint was bioequivalence at steady state, as measured by area under the concentration versus time curve from 0 to 7 days (AUC 0-7 days ) postdose using an antigenic content assay. Bioequivalence was defined as 90% confidence interval (CI) for the ratio of the geometric least squares (LS) mean of AUC 0-7 days for both products within the limits of 0.80 and 1.25. Safety and immunogenicity were assessed. Mean alpha 1 -PI concentration versus time curves for both formulations were superimposable. Mean AUC 0-7 days was 20 320 versus 19 838 mg × h/dl for Liquid Alpha 1 -PI and Lyophilized Alpha 1 -PI, respectively. The LS mean ratio of AUC 0-7 days (90% CI) for Liquid Alpha 1 -PI versus Lyophilized Alpha 1 -PI was 1.05 (1.03-1.08), indicating bioequivalence. Liquid Alpha 1 -PI was well tolerated and adverse events were consistent with Lyophilized Alpha 1 -PI. Immunogenicity to either product was not detected. In conclusion, Liquid Alpha 1 -PI is bioequivalent to Lyophilized Alpha 1 -PI, with a similar safety profile. The liquid formulation would eliminate the need for reconstitution and shorten preparation time for patients receiving augmentation therapy for AATD.

Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors.

PubMed

Lin, Shi-Ming; Lin, Chun-Jung; Hsu, Chao-Wei; Tai, Dar-In; Sheen, I-Shyan; Lin, Deng-Yn; Liaw, Yun-Fan

2004-01-15

Hepatocellular carcinoma (HCC) recurrence after ablation therapy for primary tumors is common. To evaluate the effectiveness of interferon-alpha (IFN-alpha) in preventing HCC recurrence, 30 eligible patients were randomized into three groups: 11 patients treated with three mega units (MU) of IFN-alpha three times weekly for 24 months (IFN-alpha-continuous group), 9 patients treated with 3 MU of IFN-alpha daily for 10 days every month for 6 months followed by 3 MU of IFN-alpha daily for 10 days every 3 months for a further 18 months (IFN-alpha-intermittent group), and 10 patients who received no IFN-alpha therapy (control group). The three groups were comparable in terms of etiology, demographics, and laboratory data at entry and HCC characteristics. After a median follow-up of 27 months (range 4-53 months), 9 patients (90%) in the control group and 9 patients (45%) in 2 treatment groups (6 patients in the IFN-alpha-continuous group and 3 patients in the IFN-alpha-intermittent group) developed an HCC recurrence (P = 0.021). Cumulative HCC recurrence rates in the IFN-alpha-intermittent, IFN-alpha-continuous, and control groups were 22.2%, 27.3%, and 40% at the end of 1 year and 33.3%, 54.6%, and 90% at the end of 4 years (P = 0.0375), respectively (control vs. IFN-alpha-intermittent group, P = 0.0123; vs. IFN-alpha-continuous group, P = 0.0822). If both IFN-alpha groups were combined, the cumulative HCC recurrence rate of the patients treated with IFN-alpha and the control group was 25% and 40% at the end of 1 year and 47% and 90% at the end of 4 years, respectively (P = 0.0135). The data suggested that IFN-alpha therapy may reduce HCC recurrence after medical ablation therapy for primary tumors. Copyright 2003 American Cancer Society.

Expression of alpha-AR subtypes in T lymphocytes and role of the alpha-ARs in mediating modulation of T cell function.

PubMed

Bao, Jing-Yin; Huang, Yan; Wang, Feng; Peng, Yu-Ping; Qiu, Yi-Hua

2007-01-01

Previous work in our laboratory has shown that alpha-adrenoreceptors (alpha-ARs) and beta-ARs exist on lymphocytes from functional profile, and that the receptors mediate the regulation of lymphocyte function by catecholamines. In the present study, we directly examined the expression of alpha-AR subtypes, alpha(1)-AR and alpha(2)-AR mRNAs, in T lymphocytes and explored the roles of the alpha-AR subtypes and intracellular signal transduction mechanisms linked to the receptors in mediating the modulation of T lymphocyte function. T lymphocytes from mesenteric lymph nodes of rats were purified by using a nylon wool column. Reverse transcription polymerase chain reaction was used to detect the expression of alpha(1)-AR and alpha(2)-AR mRNAs in the freshly isolated T cells and the mitogen concanavalin A (Con A)-activated lymphocytes. Colorimetric methylthiazoletetrazolium assay was employed to measure lymphocyte proliferation induced by Con A. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in the Con A-stimulated lymphocyte culture supernatants were examined by enzyme-linked immunosorbent assay. T cells expressed both alpha(1)-AR and alpha(2)-AR mRNAs. The expression of both alpha(1)-AR and alpha(2)-AR mRNAs was significantly higher in the Con A-activated lymphocytes than in the resting lymphocytes. Phenylephrine, a selective alpha(1)-AR agonist, had no evident effect on lymphocyte proliferation nor on IFN-gamma and IL-4 production induced by Con A. However, the selective alpha(2)-AR agonist clonidine attenuated Con A-induced lymphocyte proliferation as well as IFN-gamma and IL-4 production. The inhibited lymphocyte proliferation and IFN-gamma and IL-4 production by clonidine were blocked by yohimbine, an alpha(2)-AR antagonist. Either phospholipase C inhibitor U-73122 or protein kinase C inhibitor chelerythrine partially prevented the suppressive effect of clonidine on Con A-stimulated lymphocyte proliferation and IL-4 production. T lymphocytes express both alpha(1)-ARs and alpha(2)-ARs, but only the alpha(2)-ARs participate in the suppressive modulation of lymphocyte proliferation and cytokine production in vitro. The inhibitory effect of alpha(2)-AR stimulation on lymphocyte function is partially mediated via the phospholipase C-protein kinase C pathway. (c) 2008 S. Karger AG, Basel.

The electrophoretically 'slow' and 'fast' forms of the alpha 2-macroglobulin molecule.

PubMed Central

Barrett, A J; Brown, M A; Sayers, C A

1979-01-01

alpha 2-Macroglobulin (alpha 2M) was isolated from human plasma by a four-step procedure: poly(ethylene glyco) fractionation, gel chromatography, euglobulin precipitation and immunoadsorption. No contaminants were detected in the final preparations by electrophoresis or immunoprecipitation. The protein ran as a single slow band in gel electrophoresis, and was designated 'S-alpha 2M'. S-alpha 2M bound about 2 mol of trypsin/mol. Treatment of S-alpha 2M with a proteinase or ammonium salts produced a form of the molecule more mobile in electrophoresis, and lacking proteinase-binding activity (F-alpha 2M). The electrophoretic mobility of the F-alpha 2M resulting from reaction with NH4+ salts was identical with that of proteinase complexes. We attribute the change in electrophoretic mobility of the alpha 2M to a conformation change, but there was no evidence of a change in pI or Strokes radius. Electrophoresis of S-alpha 2M in the presence of sodium dodecylsulphate gave results consistent with the view that the alpha 2M molecule is a tetramer of identical subunits, assembled as a non-covalent pair of disulphide-linked dimers. Some of the subunits seemed to be 'nicked' into two-thires-length and one-third-length chains, however. This was not apparent with F-alpha 2M produced by ammonium salts. F-alpha 2M produced by trypsin showed two new bands attributable to cleavage of the subunit polypeptide chain near the middle. Immunoassays of F-alpha 2M gave 'rockets' 12-29% lower than those with S-alpha 2M. The nature of the interactions between subunits in S-alpha 2M and F-alpha 2M was investigated by treating each form with glutaraldehyde before electrophoresis in the presence of sodium dodecyl sulphate. A much greater degree of cross-linking was observed with the F-alpha 2M, indicating that the subunits interact most closely in this form of the molecule. Exposure of S-alpha 2M to 3 M-urea or pH3 resulted in dissociation to the disulphide-bonded half-molecules; these did not show the proteinase-binding activity characteristic of the intact alpha 2M. F-alpha 2M was less easily dissociated than was S-alpha 2M. S-alpha 2M was readily dissociated to the quarter-subunits by mild reduction, with the formation of 3-4 new thiol groups per subunit. Inact reactive alpha 2M could then be regenerated in high yield by reoxidation of the subunits. F-alpha 2M formed by reaction with a proteinase or ammonium salts was not dissociated under the same conditions, although the interchain disulphide bonds were reduced. If the thiol groups of the quarter-subunits of S-alpha 2M were blocked by carboxymethylation, oxidative reassociation did not occur. Nevertheless treatment of these subunits with methylammonium salts or a proteinase caused the reassembly of half-molecules and intact (F-) tetramers. It is emphasized that F-alpha 2M does not have the properties of a denatured form of the protein... Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:91367

Addition products of alpha-tocopherol with lipid-derived free radicals.

PubMed

Yamauchi, Ryo

2007-01-01

The addition products of alpha-tocopherol with lipid-derived free radicals have been reviewed. Free radical scavenging reactions of alpha-tocopherol take place via the alpha-tocopheroxyl radical as an intermediate. If a suitable free radical is present, an addition product can be formed from the coupling of the free radical with the alpha-tocopheroxyl radical. The addition products of alpha-tocopherol with lipid-peroxyl radicals are 8a-(lipid-dioxy)-alpha-tocopherones, which are hydrolyzed to alpha-tocopherylquinone. On the other hand, the carbon-centered radicals of lipids prefer to react with the phenoxyl radical of alpha-tocopherol to form 6-O-lipid-alpha-tocopherol under anaerobic conditions. The addition products of alpha-tocopherol with peroxyl radicals (epoxylinoleoyl-peroxyl radicals) produced from cholesteryl ester and phosphatidylcholine were detected in the peroxidized human plasma using a high-sensitive HPLC procedure with postcolumn reduction and electrochemical detection. Thus, the formation of these addition products provides us with much information on the antioxidant function of vitamin E in biological systems.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popp, R.A.; Enlow, M.K.

The clinical hematologic change in 2 groups of progeny from mice carrying radiation-induced strain SEC ..cap alpha..-chain deficiencies was found to be similar to the hematologic alterations in persons with ..cap alpha..-thalassemia. The heterozygous deletion or inactivation of the ..cap alpha..-chain gene in mice caused an anemia similar to ..cap alpha..-thalassemina minor in persons. The ..cap alpha..-chain deficiency in mice created an erythrocytosis, reticulocytosis, and microcytic, hypochromic anemia comparable with the changes in human ..cap alpha..-thalassemia minor resulting from deletion of the ..cap alpha..-chain gene. These mouse mutants are the only known animal models of human thalassemia. A comparison ofmore » hematologic values obtained from progeny possessing an ..cap alpha..-chain gene deficiency and from progeny possessing a ..beta..-chain duplication suggested that the deficiency of ..cap alpha..-chain synthesis, rather than a simple imbalance between the amounts of ..cap alpha..- and ..beta..-chains produced, was primarily responsible for the altered hematologic characteristics in these ..cap alpha..-thalassemic mice.« less

Circulating neuroactive C21- and C19-steroids in young men before and after ejaculation.

PubMed

Stárka, L; Hill, M; Havlíková, H; Kancheva, L; Sobotka, V

2006-01-01

Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), 3beta-hydroxy-pregn-5-en-20-one (pregnenolone), 7alpha-hydroxy-DHEA, and 7beta-hydroxy-DHEA were measured using the GC-MS system in young men before and after ejaculation provoked by masturbation. The circulating level of 17alpha-hydroxypregnenolone increased significantly, whereas the other circulating steroids were not changed at all. This fact speaks against the hypothesis that a drop in the level of neuroactive steroids, e.g. allopregnanolone may trigger the orgasm-related increase of oxytocin, reported by other authors.

Long-acting injectable antipsychotics update: lengthening the dosing interval and expanding the diagnostic indications.

PubMed

Citrome, Leslie

2017-10-01

Long-acting injectable (LAI) antipsychotics are a useful but underutilized option in the management of schizophrenia. Areas covered: This is a narrative review of newer LAI antipsychotics approved by the US Food and Drug Administration and is an update to a previously published review from 2013. Emphasized are new indications and new dosing intervals. Expert commentary: Ensuring that persons receiving oral antipsychotics are aware that LAI antipsychotics are available is important. The use of LAI antipsychotics can decrease the risk of relapse in both first-episode and chronic schizophrenia. Available treatments differ in terms of specific indications, approved injection sites, needle gauge, injection volume, injection interval, requirements for oral supplementation, availability of pre-filled syringes, storage needs, and post-injection observation period, as well as potential drug-drug interactions and commonly encountered adverse reactions. Approved indications have expanded beyond schizophrenia to also include bipolar maintenance (risperidone microspheres and aripiprazole monohydrate) and schizoaffective disorder (paliperidone palmitate monthly). Intervals between injections can be longer than one month (six-week or two-month aripiprazole lauroxil, and three-month paliperidone palmitate). After a review of the evidence-base, guidance is offered on the appropriate selection among the LAI formulations of both first and second-generation antipsychotics.

Analysis of thin baked-on silicone layers by FTIR and 3D-Laser Scanning Microscopy.

PubMed

Funke, Stefanie; Matilainen, Julia; Nalenz, Heiko; Bechtold-Peters, Karoline; Mahler, Hanns-Christian; Friess, Wolfgang

2015-10-01

Pre-filled syringes (PFS) and auto-injection devices with cartridges are increasingly used for parenteral administration. To assure functionality, silicone oil is applied to the inner surface of the glass barrel. Silicone oil migration into the product can be minimized by applying a thin but sufficient layer of silicone oil emulsion followed by thermal bake-on versus spraying-on silicone oil. Silicone layers thicker than 100nm resulting from regular spray-on siliconization can be characterized using interferometric profilometers. However, the analysis of thin silicone layers generated by bake-on siliconization is more challenging. In this paper, we have evaluated Fourier transform infrared (FTIR) spectroscopy after solvent extraction and a new 3D-Laser Scanning Microscopy (3D-LSM) to overcome this challenge. A multi-step solvent extraction and subsequent FTIR spectroscopy enabled to quantify baked-on silicone levels as low as 21-325μg per 5mL cartridge. 3D-LSM was successfully established to visualize and measure baked-on silicone layers as thin as 10nm. 3D-LSM was additionally used to analyze the silicone oil distribution within cartridges at such low levels. Both methods provided new, highly valuable insights to characterize the siliconization after processing, in order to achieve functionality. Copyright © 2015 Elsevier B.V. All rights reserved.

The digital pen and paper technology: implementation and use in an existing clinical information system.

PubMed

Despont-Gros, Christelle; Bœuf, Christophe; Geissbuhler, Antoine; Lovis, Christian

2005-01-01

Evaluation of the technical feasibility of tight integration of the digital pen and paper technology in an existing computerized patient record.Technology: The digital pen is a normal pen able to record all actions of the user and to analyze a micro pattern printed on the paper. The digital paper is a normal paper printed with an almost invisible micro pattern of small dots encoding information such as position and identifiers. We report our experience in the implementation and the use of this technology in an existing large clinical information system for acquiring clinical information. It is possible to print uniquely identified forms using the digital paper technology. These forms can be pre-filled with clinical readable information about the patient. When care providers complete these forms using the digital pen, it is possible to acquire the data in a structured computerized patient record. The technology is easy to integrate in a component-based architecture based on Web Services. The digital pen and paper is a cost-effective technology that can be integrated in an existing clinical information system and allows fast and easy bedside clinical information acquisition without the need for an expensive infrastructure based on traditional portable devices or wireless devices.

Determination of filter pore size for use in HB line phase II production of plutonium oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shehee, T.; Crowder, M.; Rudisill, T.

2014-08-01

H-Canyon and HB-Line are tasked with the production of plutonium oxide (PuO 2) from a feed of plutonium (Pu) metal. The PuO 2 will provide feed material for the Mixed Oxide (MOX) Fuel Fabrication Facility. After dissolution of the Pu metal in H-Canyon, plans are to transfer the solution to HB-Line for purification by anion exchange. Anion exchange will be followed by plutonium(IV) oxalate precipitation, filtration, and calcination to form PuO 2. The filtrate solutions, remaining after precipitation, contain low levels of Pu ions, oxalate ions, and may include solids. These solutions are transferred to H-Canyon for disposition. To mitigatemore » the criticality concern of Pu solids in a Canyon tank, past processes have used oxalate destruction or have pre-filled the Canyon tank with a neutron poison. The installation of a filter on the process lines from the HB-Line filtrate tanks to H-Canyon Tank 9.6 is proposed to remove plutonium oxalate solids. This report describes SRNL’s efforts to determine the appropriate pore size for the filters needed to perform this function. Information provided in this report aids in developing the control strategies for solids in the process.« less

Stability of total nutrient admixtures in reference to ambient temperatures.

PubMed

Lee, Myung Duk; Yoon, Jeung-Ei; Kim, Sang-In; Kim, In-Chul

2003-10-01

To evaluate the stability of emulsions under different temperatures simulating clinical conditions of storage and exposure during infusion, five total nutrient admixture formulas in this institution were analyzed: adult, patients with hepatic failure, infants, stressed patients, and patients with renal failure. Each mixture was allocated in a sterile 100-mL glass bottle, which was prefilled and refilled with nitrogen gas. Bottles were stored at 4 degrees C for 0 d, 3 d, and 7 d and then exposed to three different temperatures: usual room temperature (18 degrees C to 25 degrees C), high (>28 degrees C) in a water bath, or storage (4 degrees C) for 24 and 48 h. The gross inspection of the emulsions and parallel measurements of pH, particle sizes, divalent ions, peroxide levels, and microbial cultures were performed. Every lot was stable near 18 degrees C, but 8 of 10 lots stored for 7 d (25 degrees C and >28 degrees C) and 15 of 20 lots stored for 3 and 7 d (25 degrees C and >28 degrees C) showed coalescence. The overall coalescence incidences by storage, exposure, and heat were statistically significant (P < 0.005). For the safety of total nutrient admixtures, special attention is required to keep the ambient temperature below 28 degrees C and completely exclude air from the container.

[Pathological form in breast cancer: setting and evaluation of a professional pratice].

PubMed

Barré, Maxime; Classe, Jean-Marc; Dravet, François; Dupré, Pierre-François; Loussouarn, Delphine; Toquet, Claire; Sagan, Christine

2009-06-01

According to national recommendations, the surgical oncologic specimens addressed to a pathology department must have the required clinical information. The objectives of this study are to evaluate the quality of filling out a pathology form used in breast pathology, to specify the nonconformity consequences on breast management, on histology report and to define modes of action in order to obtain an increase in the number of correct pathology forms. It is a prospective study on pathology forms transmitted with tumorectomy for cancers or microcalcifications filled out by three surgeons from the 1st October, 2004 to the 31st April, 2005. Two hundred and fifty-nine pathology forms were analyzed. There were not correctly filled out in a third of the cases. Nonconformity concerns only one preset information in 69% of pathology forms and is variable according to the surgeons (14 to 31%). The chapters least informed are "lesion" and "type of surgery". These nonconformities involve additional work for the pathologist either because the missing information must be found or because the specimen management must be modified. The prefilled pathology form is a guarantee of quality control. In our study, in 70% of cases, they are accurate. To improve this conformity rate, quality improvement plans must be implemented.

Friability Testing as a New Stress-Stability Assay for Biopharmaceuticals.

PubMed

Torisu, Tetsuo; Maruno, Takahiro; Yoneda, Saki; Hamaji, Yoshinori; Honda, Shinya; Ohkubo, Tadayasu; Uchiyama, Susumu

2017-10-01

A cycle of dropping and shaking a vial containing antibody solution was reported to induce aggregation. In this study, antibody solutions in glass prefillable syringes with or without silicone oil lubrication were subjected to the combined stresses of dropping and shaking, using a friability testing apparatus. Larger numbers of subvisible particles were generated, regardless of silicone oil lubrication, upon combination stress exposure than that with shaking stress alone. Nucleation of antibody molecules upon perturbation by an impact of dropping and adsorption of antibody molecules to the syringe surface followed by film formation and antibody film desorption were considered key steps in the particle formation promoted by combination stress. A larger number of silicone oil droplets was released when silicone oil-lubricated glass syringes containing phosphate buffer saline were exposed to combination stress than that observed with shaking stress alone. Polysorbate 20, a non-ionic surfactant, effectively reduced the number of protein particles, but failed to prevent silicone oil release upon combination stress exposure. This study indicates that stress-stability assays using the friability testing apparatus are effective for assessing the stability of biopharmaceuticals under the combined stresses of dropping and shaking, which have not been tested in conventional stress-stability assays. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

On the breakdown modes and parameter space of Ohmic Tokamak startup

NASA Astrophysics Data System (ADS)

Peng, Yanli; Jiang, Wei; Zhang, Ya; Hu, Xiwei; Zhuang, Ge; Innocenti, Maria; Lapenta, Giovanni

2017-10-01

Tokamak plasma has to be hot. The process of turning the initial dilute neutral hydrogen gas at room temperature into fully ionized plasma is called tokamak startup. Even with over 40 years of research, the parameter ranges for the successful startup still aren't determined by numerical simulations but by trial and errors. However, in recent years it has drawn much attention due to one of the challenges faced by ITER: the maximum electric field for startup can't exceed 0.3 V/m, which makes the parameter range for successful startup narrower. Besides, this physical mechanism is far from being understood either theoretically or numerically. In this work, we have simulated the plasma breakdown phase driven by pure Ohmic heating using a particle-in-cell/Monte Carlo code, with the aim of giving a predictive parameter range for most tokamaks, even for ITER. We have found three situations during the discharge, as a function of the initial parameters: no breakdown, breakdown and runaway. Moreover, breakdown delay and volt-second consumption under different initial conditions are evaluated. In addition, we have simulated breakdown on ITER and confirmed that when the electric field is 0.3 V/m, the optimal pre-filling pressure is 0.001 Pa, which is in good agreement with ITER's design.

Silicone Migration From Baked-on Silicone Layers. Particle Characterization in Placebo and Protein Solutions.

PubMed

Funke, Stefanie; Matilainen, Julia; Nalenz, Heiko; Bechtold-Peters, Karoline; Mahler, Hanns-Christian; Friess, Wolfgang

2016-12-01

A significant number of therapeutic proteins are marketed as pre-filled syringes or other drug/device combination products and have been safely used in these formats for years. Silicone oil, which is used as lubricant, can migrate into the drug product and may interact with therapeutic proteins. In this study, particles in the size range of 0.2-5 μm and ≥1 μm as determined by resonant mass measurement and micro-flow imaging/light obscuration, respectively, resulted from silicone sloughing off the container barrel after agitation. The degree of droplet formation correlated well with the applied baked-on silicone levels of 13 μg and 94 μg per cartridge. Silicone migration was comparable in placebo, 2 mg/mL and 33 mg/mL IgG1 formulations containing 0.04% (w/v) polysorbate 20. Headspace substantially increased the formation of silicone droplets during agitation. The highest particle concentrations reached, however, were still very low compared to numbers described for spray-on siliconized containers. When applying adequate baked-on silicone levels below 100 μg, bake-on siliconization efficiently limits silicone migration into the drug product without compromising device functionality. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Elastic contact mechanics: percolation of the contact area and fluid squeeze-out.

PubMed

Persson, B N J; Prodanov, N; Krick, B A; Rodriguez, N; Mulakaluri, N; Sawyer, W G; Mangiagalli, P

2012-01-01

The dynamics of fluid flow at the interface between elastic solids with rough surfaces depends sensitively on the area of real contact, in particular close to the percolation threshold, where an irregular network of narrow flow channels prevails. In this paper, numerical simulation and experimental results for the contact between elastic solids with isotropic and anisotropic surface roughness are compared with the predictions of a theory based on the Persson contact mechanics theory and the Bruggeman effective medium theory. The theory predictions are in good agreement with the experimental and numerical simulation results and the (small) deviation can be understood as a finite-size effect. The fluid squeeze-out at the interface between elastic solids with randomly rough surfaces is studied. We present results for such high contact pressures that the area of real contact percolates, giving rise to sealed-off domains with pressurized fluid at the interface. The theoretical predictions are compared to experimental data for a simple model system (a rubber block squeezed against a flat glass plate), and for prefilled syringes, where the rubber plunger stopper is lubricated by a high-viscosity silicon oil to ensure functionality of the delivery device. For the latter system we compare the breakloose (or static) friction, as a function of the time of stationary contact, to the theory prediction.

An industry update: the latest developments in therapeutic delivery.

PubMed

Simpson, Iain

2017-02-01

This Industry Update covers the period from 1 October through to 31 October 2016, and is based on information sourced from company press releases, scientific literature, patents and various news websites. The month saw several news items covering drug-delivery devices, including a new sensor to monitor and support the use of inhalers; launch in the UK of a new autoinjector for Cimzia ® , UCB's rheumatoid arthritis drug; and approval of Roche's Lucentis ® in a prefilled syringe. Research was also published to show the value of continuous blood pressure monitoring in dementia management. Astellas announced the acquisition of German pharmaceutical company Ganymed while Sunovion completed its purchase of Cynapsus. A new EU-funded collaboration was announced looking at the value of PET-based biomarkers in Alzheimer's disease. GSK gained USA approval for its shingles vaccine, but Novo Nordisk and Sanofi received complete response letters from the US FDA, requiring further information before regulatory review of their drug submissions can be completed. The UK's NICE concluded that a drug marketed by BMS to treat a common type of lung cancer was not cost-effective and Cornell University announced results showing that its nanoparticle technology, originally developed as a tumor biomarker, could be effective in directly treating the disease.

Upgrades toward high-heat flux, liquid lithium plasma-facing components in the NSTX-U

DOE PAGES

Jaworski, M. A.; Brooks, A.; Kaita, R.; ...

2016-08-08

Liquid metal plasma-facing components (PFCs) provide numerous potential advantages over solid-material components. One critique of the approach is the relatively less developed technologies associated with deploying these components in a fusion plasma-experiment. Exploration of the temperature limits of liquid lithium PFCs in a tokamak divertor and the corresponding consequences on core operation are a high priority informing the possibilities for future liquid lithium PFCs. An all-metal NSTX-U is envisioned to make direct comparison between all high-Z wall operation and liquid lithium PFCs in a single device. By executing the all-metal upgrades incrementally, scientific productivity will be maintained while enabling physicsmore » and engineering-science studies to further develop the solid- and liquid-metal components. Six major elements of a flowing liquid-metal divertor system are described and a three-step program for implementing this system is laid out. The upgrade steps involve the first high-Z divertor target upgrade in NSTX-U, pre-filled liquid metal targets and finally, an integrated, flowing liquid metal divertor target. As a result, two example issues are described where the engineering and physics experiments are shown to be closely related in examining the prospects for future liquid metal PFCs.« less

Women's preferences for vaginal antimicrobial contraceptives. III. Choice of a formulation, applicator, and packaging.

PubMed

Hardy, E; Jiménez, A L; de Pádua, K S; Zaneveld, L J

1998-10-01

Novel vaginal formulations are under development to combat the increasing incidence of sexually transmitted diseases, including AIDS, and also unplanned pregnancies. A study was performed to determine women's preferences for different dosage forms (gel, cream, ovule/suppository, film, foam, tablet), width, length, and color of an applicator, and various types of packages. The study was conducted in Campinas, Brazil. A total of 635 women were interviewed, including both adolescents and adults and low and middle-high socioeconomic groups. The large majority of the women preferred a gel over a cream; both were preferred over the other methods. When asked which method they would not use, the film was most frequently identified, followed by the tablet and ovule. The primary reasons for selecting a particular dosage form were ease of use, absence of odor or the presence of a pleasant one, absence of color, and insertion with an applicator. The major reasons for not using a method were discomfort, "plastic" appearance, distrust of effectiveness, difficulty with insertion, messiness, and rigidity/hardness. The majority of the women liked the applicator shown. The prefilled single dose applicator was by far the preferred packaging. This information should aid in the development of consumer-friendly, vaginal formulations.

Electron density and plasma dynamics of a colliding plasma experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiechula, J., E-mail: wiechula@physik.uni-frankfurt.de; Schönlein, A.; Iberler, M.

2016-07-15

We present experimental results of two head-on colliding plasma sheaths accelerated by pulsed-power-driven coaxial plasma accelerators. The measurements have been performed in a small vacuum chamber with a neutral-gas prefill of ArH{sub 2} at gas pressures between 17 Pa and 400 Pa and load voltages between 4 kV and 9 kV. As the plasma sheaths collide, the electron density is significantly increased. The electron density reaches maximum values of ≈8 ⋅ 10{sup 15} cm{sup −3} for a single accelerated plasma and a maximum value of ≈2.6 ⋅ 10{sup 16} cm{sup −3} for the plasma collision. Overall a raise of the plasma density by a factor ofmore » 1.3 to 3.8 has been achieved. A scaling behavior has been derived from the values of the electron density which shows a disproportionately high increase of the electron density of the collisional case for higher applied voltages in comparison to a single accelerated plasma. Sequences of the plasma collision have been taken, using a fast framing camera to study the plasma dynamics. These sequences indicate a maximum collision velocity of 34 km/s.« less

Vasodilating effect of norethisterone and its 5 alpha metabolites: a novel nongenomic action.

PubMed

Perusquía, Mercedes; Villalón, Carlos M; Navarrete, Erika; García, Gustavo A; Pérez-Palacios, Gregorio; Lemus, Ana E

2003-08-15

Estrogens are generally administered in hormone replacement therapy in combination with synthetic progestins. Studies of cardiovascular risk factors in postmenopausal women have shown a variety of responses according to the molecular structure of the progestin used in hormone replacement therapy schemes. The present study sets out to determine the vasoactive effects of norethisterone and its 5alpha-dihydro (5alpha-norethisterone) and -tetrahydro (3alpha,5alpha-norethisterone and 3beta,5alpha-norethisterone) metabolites in isolated precontracted rat thoracic aorta. The addition of norethisterone and 3alpha,5alpha-norethisterone in rat aorta exhibited a potent, concentration-response inhibition of noradrenaline-induced contraction, while 5alpha- and 3beta,5alpha-norethisterone had very little, if any, vasorelaxing effect. Relaxation to norethisterone and 3alpha,5alpha-norethisterone had very rapid time-courses and it was neither affected by the absence of endothelium nor by the inhibitor of nitric oxide synthase, Nomega-nitro-L-arginine methyl ester (L-NAME). The addition of specific anti-androgen, anti-progestin and anti-estrogen compounds and protein synthesis inhibitors did not preclude the vasorelaxing effect of norethisterone and its 3alpha,5alpha-reduced metabolite. The results strongly suggest that these effects are not mediated by nuclear sex steroid hormone receptors. The overall data document a novel nongenomic endothelium-independent vasorelaxing action of a 19-nor synthetic progestin and one of its A-ring-reduced derivatives.

Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

PubMed

Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

2007-09-01

Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

Proline-catalysed asymmetric amination of alpha,alpha-disubstituted aldehydes: synthesis of configurationally stable enantioenriched alpha-aminoaldehydes.

PubMed

Vogt, Henning; Vanderheiden, Sylvia; Bräse, Stefan

2003-10-07

Proline-catalysed amination of alpha,alpha-disubstituted racemic aldehydes with azodicarboxylates proceeds smoothly to give configurationally stable scalemic aldehydes and oxazolidinones in up to 86% ee.

[Voluntary alpha-power increasing training impact on the heart rate variability].

PubMed

Bazanova, O M; Balioz, N V; Muravleva, K B; Skoraia, M V

2013-01-01

In order to study the effect of the alpha EEG power increasing training at heart rate variability (HRV) as the index of the autonomic regulation of cognitive functions there were follow tasks: (1) to figure out the impact of biofeedback in the voluntary increasing the power in the individual high-frequency alpha-band effect on heart rate variability and related characteristics of cognitive and emotional spheres, (2) to determine the nature of the relationship between alpha activity indices and heart rate variability, depending on the alpha-frequency EEG pattern at rest (3) to examine how the individual alpha frequency EEG pattern is reflected in changes HRV as a result of biofeedback training. Psychometric indicators of cognitive performance, the characteristics of the alpha-EEG activity and heart rate variability (HRV) as LF/HF and pNN50 were recorded in 27 healthy men aged 18-34 years, before, during, and after 10 sessions of training of voluntary increase in alpha power in the individual high-frequency alpha band with eyes closed. To determine the biofeedback effect on the alpha power increasing training, data subjects are compared in 2 groups: experimental (14) with the real and the control group (13 people)--with mock biofeedback. The follow up effect of trainings was studied through month over the 10 training sessions. Results showed that alpha biofeedback training enhanced the fluency and accuracy in cognitive performance, decreased anxiety and frontal EMG, increased resting frequency, width and power in individual upper alpha range only in participants with low baseline alpha frequency. While mock biofeedback increased resting alpha power only in participants with high baseline resting alpha frequency and did change neither cognitive performance, nor HRV indices. Biofeedback training eliminated the alpha power decrease in response to arithmetic task in both with high and low alpha frequency participants and this effect was followed up over the month. Mock biofeedback training has no such effect. The positive correlation between the alpha-peak frequency and pNN50 in patients with initially low, but negative--those with high baseline alpha frequency explains the multidirectional biofeedback effects on HRV in low and high alpha frequency subjects. The individual alpha-frequency EEG pattern determines the effectiveness of the alpha EEG biofeedback training in changing heart rate variability, which provides a basis for predicting the results and develop individual approaches to the biofeedback technology implementation that can be used in clinical practice for treatment and rehabilitation of psychosomatic syndromes and in educational training.

Progressive accumulation of ubiquitin and disappearance of alpha-synuclein epitope in multiple system atrophy-associated glial cytoplasmic inclusions: triple fluorescence study combined with Gallyas-Braak method.

PubMed

Sakamoto, Masaki; Uchihara, Toshiki; Nakamura, Ayako; Mizutani, Toshio; Mizusawa, Hidehiro

2005-10-01

Alpha-synuclein (alphaS) and ubiquitin (Ub) are shared constituents of glial cytoplasmic inclusions (GCIs) and Lewy bodies (LBs), both composed of fibrillary structures. Staining profiles of GCIs were investigated with triple immunofluorescence involving immunostaining for alphaS and Ub, both amplified with catalyzed reporter deposition, and a fluorochrome, thiazin red (TR) that has an affinity to fibrillary structures. After observation for the triple-fluorescent images, the sections were subsequently stained with the Gallyas-Braak method. Sections of putamen, cerebellar white matter and motor cortex from patients suffering from multiple system atrophy (MSA) with varying duration of the disease (4-15 years) were quantified for these staining profiles of Gallyas-positive GCIs. Although most of GCIs were positive for Ub and variably positive for alphaS, they were consistently negative for TR. The result was opposite in LBs in Lewy body disease with variable affinity to TR, suggesting that the construction of GCIs is different from that of LBs. These four staining features (alphaS, Ub, TR and Gallyas) alone failed to exhibit apparent correlation with disease duration, lesion site or severity of degeneration as reported previously. The fraction of alphaS-negative and Ub-positive GCIs, however, linearly increased along the disease progression, while that of alphaS-positive and Ub-negative GCIs decreased in contrast. This reciprocal change suggests that alphaS immunoreactivity in GCIs is being replaced by Ub immunoreactivity during the disease progression, which resulted in the ultimate predominance of alphaS-negative and Ub-positive GCIs in the most advanced case. Interestingly, this predominance of alphaS-negative and Ub-positive GCIs was a feature of motor cortex, where degeneration usually remains mild in spite of robust appearance of Gallyas-positive GCIs. Another fraction, alphaS-positive and Ub-positive GCIs were frequent in cerebellar white matter, suggesting that GCI evolution is heterogeneous and dependent also on area examined. Progressive accumulation of Ub with concomitant disappearance of alphaS epitope and their colocalization, partly shared with LBs, may represent a process of GCI formation, possibly linked to an aspect of degeneration in MSA.

alpha2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells.

PubMed

Hall, C; Michael, G J; Cann, N; Ferrari, G; Teo, M; Jacobs, T; Monfries, C; Lim, L

2001-07-15

Neuronal differentiation involves Rac and Cdc42 GTPases. alpha-Chimaerin, a Rac/Cdc42 regulator, occurs as alpha1- and alternatively spliced Src homology 2 (SH2) domain-containing alpha2-isoforms. alpha2-chimaerin mRNA was highly expressed in the rat embryonic nervous system, especially in early postmitotic neurons. alpha1-chimaerin mRNA was undetectable before embryonic day 16.5. Adult alpha2-chimaerin mRNA was restricted to neurons within specific brain regions, with highest expression in the entorhinal cortex. alpha2-chimaerin protein localized to neuronal perikarya, dendrites, and axons. The overall pattern of alpha2-chimaerin mRNA expression resembles that of cyclin-dependent kinase regulator p35 (CDK5/p35) which participates in neuronal differentiation and with which chimaerin interacts. To determine whether alpha2-chimaerin may have a role in neuronal differentiation and the relevance of the SH2 domain, the morphological effects of both chimaerin isoforms were investigated in N1E-115 neuroblastoma cells. When plated on poly-lysine, transient alpha2-chimaerin but not alpha1-chimaerin transfectants formed neurites. Permanent alpha2-chimaerin transfectants generated neurites whether or not they were stimulated by serum starvation, and many cells were enlarged. Permanent alpha1-chimaerin transfectants displayed numerous microspikes and contained F-actin clusters, a Cdc42-phenotype, but generated few neurites. In neuroblastoma cells, alpha2-chimaerin was predominantly soluble with some being membrane-associated, whereas alpha1-chimaerin was absent from the cytosol, being membrane- and cytoskeleton-associated, paralleling their subcellular distribution in brain. Transient transfection with alpha2-chimaerin mutated in the SH2 domain (N94H) generated an alpha1-chimaerin-like phenotype, protein partitioned in the particulate fraction, and in NGF-stimulated pheochromocytoma cell line 12 (PC12) cells, neurite formation was inhibited. These results indicate a role for alpha2-chimaerin in morphological differentiation for which its SH2 domain is vital.

Integrin alpha 3 beta 1 participates in the phagocytosis of extracellular matrix molecules by human breast cancer cells.

PubMed

Coopman, P J; Thomas, D M; Gehlsen, K R; Mueller, S C

1996-11-01

The mechanisms and receptors involved in phagocytosis by nonhematopoietic cells are not well understood. The involvement of the alpha 3 beta 1 integrin in phagocytosis of the extracellular matrix by human breast cancer cells was studied. The possible role of this integrin was suggested since alpha 3 and beta 1 but not alpha 2 subunits are concentrated at membrane sites where local degradation of fluorescently labeled gelatin occurs. Strikingly, anti-alpha 3 integrin monoclonal antibodies (mAbs) stimulate the phagocytosis of fluorescently labeled gelatin films, gelatin beads, and Matrigel films in a quantitative phagocytosis assay. Stimulation of the gelatin uptake by the anti-alpha 3 mAb is dose responsive, saturable, and time dependent. Antibodies against other integrin subunits have a lower stimulatory effect (anti-beta 1) or no significant effect (anti-alpha 2, -alpha 5, -alpha 6, and -alpha v) on gelatin phagocytosis. The synthetic HGD-6 human laminin peptide that binds specifically the alpha 3 beta 1 integrin, but not the scrambled HSGD-6 control peptide, also markedly stimulates gelatin uptake in a dose-responsive way. Furthermore, the stimulatory effects of the HGD-6 peptide and the anti-alpha 3 mAb are additive, suggesting that they might promote phagocytosis in different ways. Other laminin (YIGSR, IKVAV) and fibronectin (GRGDS) peptides have no effect on gelatin phagocytosis. Immunofluorescence shows that the alpha 3 and the beta 1, but not the alpha 2 integrin subunit, concentrate into patches on the cell surface after treatment with their respective mAbs. And, both gelatin and the alpha 3 beta 1 but not the alpha 2 beta 1 integrin are cointernalized and routed to acidic vesicles such as lysosomes. In conclusion, we demonstrate that human breast cancer cells locally degrade and phagocytose the extracellular matrix and show for the first time that the alpha 3 beta 1 integrin participates in this phagocytosis. We hypothesize that the anti-alpha 3 antibodies and the laminin peptide HGD-6 activate the alpha 3 beta 1 integrin, which results in a downstream signaling cascade stimulating phagocytosis.

Lens proteome map and alpha-crystallin profile of the catfish Rita rita.

PubMed

Mohanty, Bimal Prasanna; Bhattacharjee, Soma; Das, Manas Kumar

2011-02-01

Crystallins are a diverse group of proteins that constitute nearly 90% of the total soluble proteins of the vertebrate eye lens and these tightly packed crystallins are responsible for transparency of the lens. These proteins have been studied in different model and non-model species for understanding the modifications they undergo with ageing that lead to cataract, a disease of protein aggregation. In the present investigation, we studied the lens crystallin profile of the tropical freshwater catfish Rita rita. Profiles of lens crystallins were analyzed and crystallin proteome maps of Rita rita were generated for the first time. alphaA-crystallins, member of the alpha-crystallin family, which are molecular chaperons and play crucial role in maintaining lens transparency were identified by 1- and 2-D immunoblot analysis with anti-alphaA-crystallin antibody. Two protein bands of 19-20 kDa were identified as alphaA-crystallins on 1-D immunoblots and these bands separated into 10 discrete spots on 2-D immunoblot. However, anti-alphaB-crystallin and antiphospho-alphaB-crystallin antibodies were not able to detect any immunoreactive bands on 1- and 2-D immunoblots, indicating alphaB-crystallin was either absent or present in extremely low concentration in Rita rita lens. Thus, Rita rita alpha-crystallins are more like that of the catfish Clarias batrachus and the mammal kangaroo in its alphaA- and alphaB-crystallin content (contain low amount from 5-9% of alphaB-crystallin) and unlike the dogfish, zebrafish, human, bovine and mouse alpha-crystallins (contain higher amount of alphaB-crystallin from 25% in mouse and bovine to 85% in dogfish). Results of the present study can be the baseline information for stimulating further investigation on Rita rita lens crystallins for comparative lens proteomics. Comparing and contrasting the alpha-crystallins of the dogfish and Rita rita may provide valuable information on the functional attributes of alphaA- and alphaB-isoforms, as they are at the two extremes in terms of alphaA-and alphaB-crystallin content.

Both alpha(1A)- and alpha(1B)-adrenergic receptors crosstalk to down regulate beta(1)-ARs in mouse heart: coupling to differential PTX-sensitive pathways.

PubMed

Rorabaugh, Boyd R; Gaivin, Robert J; Papay, Robert S; Shi, Ting; Simpson, Paul C; Perez, Dianne M

2005-11-01

Adrenergic receptors (ARs) play an important role in the regulation of cardiac function. Cardiac inotropy is primarily regulated by beta(1)-ARs. However, alpha(1)-ARs may play an important role in inotropy during heart failure. Previous work has suggested that the alpha(1B)-AR modulates beta(1)-AR function in the heart. The potential role of the alpha(1A)-AR has not been previously studied. We used transgenic mice that express constitutively active mutant (CAM) forms of the alpha(1A)-AR or alpha(1B)-AR regulated by their endogenous promoters. Expression of the CAM alpha(1A)-AR or CAM alpha(1B)-AR had no effect on basal cardiac function (developed pressure, +dP/dT, -dP/dT, heart rate, flow rate). However, both alpha(1)-AR subtypes significantly decreased isoproterenol-stimulated +dP/dT. Pertussis toxin had no effect on +dP/dT in CAM alpha(1A)-AR hearts but restored +dP/dT to non-transgenic values in CAM alpha(1B)-AR hearts. Radioligand binding indicated a selective decrease in the density of beta(1)-ARs in both CAM mice. However, G-proteins, cAMP, or the percentage of high and low affinity states were unchanged in either transgenic compared with control. These data demonstrate that CAM alpha(1A)- and alpha(1B)-ARs both down regulate beta(1)-AR-mediated inotropy in the mouse heart. However, alpha(1)-AR subtypes are coupled to different beta-AR mediated signaling pathways with the alpha(1B)-AR being pertussis toxin sensitive.

Anticipation and consumption of food each increase the concentration of neuroactive steroids in rat brain and plasma.

PubMed

Pisu, Maria Giuseppina; Floris, Ivan; Maciocco, Elisabetta; Serra, Mariangela; Biggio, Giovanni

2006-09-01

Stressful stimuli and anxiogenic drugs increase the plasma and brain concentrations of neuroactive steroids. Moreover, in rats trained to consume their daily meal during a fixed period, the anticipation of food is associated with changes in the function of various neurotransmitter systems. We have now evaluated the effects of anticipation and consumption of food in such trained rats on the plasma and brain concentrations of 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG) and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH DOC), two potent endogenous positive modulators of type A receptors for gamma-aminobutyric acid (GABA). The abundance of these neuroactive steroids was increased in both the cerebral cortex and plasma of the rats during both food anticipation and consumption. In contrast, the concentration of their precursor, progesterone, was increased in the brain only during food consumption, whereas it was increased in plasma only during food anticipation. Intraperitoneal administration of the selective agonist abecarnil (0.1 mg/kg) 40 min before food presentation prevented the increase in the brain levels of 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC during food anticipation but not that associated with consumption. The change in emotional state associated with food anticipation may thus result in an increase in the plasma and brain levels of 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC in a manner sensitive to the activation of GABA(A) receptor-mediated neurotransmission. A different mechanism, insensitive to activation of such transmission, may underlie the changes in the concentrations of these neuroactive steroids during food consumption.

Activity and subcellular compartmentalization of peroxisome proliferator-activated receptor alpha are altered by the centrosome-associated protein CAP350.

PubMed

Patel, Hansa; Truant, Ray; Rachubinski, Richard A; Capone, John P

2005-01-01

Peroxisome proliferator-activated nuclear hormone receptors (PPAR) are ligand-activated transcription factors that play pivotal roles in governing metabolic homeostasis and cell growth. PPARs are primarily in the nucleus but, under certain circumstances, can be found in the cytoplasm. We show here that PPAR(alpha) interacts with the centrosome-associated protein CAP350. CAP350 also interacts with PPAR(delta), PPAR(gamma) and liver-X-receptor alpha, but not with the 9-cis retinoic acid receptor, RXR(alpha). Immunofluorescence analysis indicated that PPAR(alpha) is diffusely distributed in the nucleus and excluded from the cytoplasm. However, in the presence of coexpressed CAP350, PPAR(alpha) colocalizes with CAP350 to discrete nuclear foci and to the centrosome, perinuclear region and intermediate filaments. In contrast, the subcellular distribution of RXR(alpha) or of thyroid hormone receptor alpha was not altered by coexpression of CAP350. An amino-terminal fragment of CAP350 was localized exclusively to nuclear foci and was sufficient to recruit PPAR(alpha) to these sites. Mutation of the single putative nuclear hormone receptor interacting signature motif LXXLL present in this fragment had no effect on its subnuclear localization but abrogated recruitment of PPAR(alpha) to nuclear foci. Surprisingly, mutation of the LXXLL motif in this CAP350 subfragment did not prevent its binding to PPAR(alpha) in vitro, suggesting that this motif serves some function other than PPAR(alpha) binding in recruiting PPAR(alpha) to nuclear spots. CAP350 inhibited PPAR(alpha)-mediated transactivation in an LXXLL-dependent manner, suggesting that CAP350 represses PPAR(alpha) function. Our findings implicate CAP350 in a dynamic process that recruits PPAR(alpha) to discrete nuclear and cytoplasmic compartments and suggest that altered intracellular compartmentalization represents a regulatory process that modulates PPAR function.

Dynamics of alpha control: Preparatory suppression of posterior alpha oscillations by frontal modulators revealed with combined EEG and event-related optical signal (EROS)

PubMed Central

Mathewson, Kyle E.; Beck, Diane M.; Ro, Tony; Maclin, Edward L.; Low, Kathy A.; Fabiani, Monica; Gratton, Gabriele

2015-01-01

We investigated the dynamics of brain processes facilitating conscious experience of external stimuli. Previously we proposed that alpha (8-12 Hz) oscillations, which fluctuate with both sustained and directed attention, represent a pulsed inhibition of ongoing sensory brain activity. Here we tested the prediction that inhibitory alpha oscillations in visual cortex are modulated by top-down signals from frontoparietal attention networks. We measured modulations in phase-coherent alpha oscillations from superficial frontal, parietal, and occipital cortices using the event-related optical signal (EROS), a measure of neuronal activity affording high spatiotemporal resolution, along with concurrently-recorded electroencephalogram (EEG), while subjects performed a visual target-detection task. The pre-target alpha oscillations measured with EEG and EROS from posterior areas were larger for subsequently undetected targets, supporting alpha's inhibitory role. Using EROS, we localized brain correlates of these awareness-related alpha oscillations measured at the scalp to the cuneus and precuneus. Crucially, EROS alpha suppression correlated with posterior EEG alpha power across subjects. Sorting the EROS data based on EEG alpha power quartiles to investigate alpha modulators revealed that suppression of posterior alpha was preceded by increased activity in regions of the dorsal attention network, and decreased activity in regions of the cingulo-opercular network. Cross-correlations revealed the temporal dynamics of activity within these preparatory networks prior to posterior alpha modulation. The novel combination of EEG and EROS afforded localization of the sources and correlates of alpha oscillations and their temporal relationships, supporting our proposal that top-down control from attention networks modulates both posterior alpha and awareness of visual stimuli. PMID:24702458

Bio-discrimination of alpha-tocopherol stereoisomers in rearing and veal calves fed milk replacer supplemented with all-rac-alpha-tocopheryl acetate.

PubMed

Dersjant-Li, Y; Jensen, S K; Bos, L W; Peisker, M R

2009-07-01

This study evaluated the biological discrimination of different alpha-tocopherol stereoisomers (i. e. RRR-, RRS-, RSR-, RSS- and the four 2S-alpha-tocopherols) from all-rac-alpha-tocopheryl acetate supplementation in milk replacer for rearing and veal calves respectively, in practical farming conditions. Two experiments were conducted. In experiment 1, six rearing calves were fed milk replacer supplemented with 80 mg/kg all-rac-alpha-tocopheryl acetate for a period of 9 weeks. The calves were supplied calf starter concentrate from 1 to 12 weeks. In experiment 2, six veal calves were fed milk replacer supplemented with 80 mg/kg all-rac-alpha-tocopheryl acetate for a period of 24 weeks. Blood samples were taken at the start and every 4 weeks until 12 weeks for rearing calves in experiment 1, and until slaughter (24 weeks) for veal calves in experiment 2. Liver, adipose, muscle, and brain samples were taken at slaughter of the six veal calves in experiment 2. The distribution of different alpha-tocopherol stereoisomers in feed, plasma, and tissues was analyzed. In both experiments, it was observed that RRR-alpha-tocopherol was the dominant stereoisomer in plasma and tissues. The average percentage of the RRR-alpha-tocopherol stereoisomer was 64 %, and 39 % of the total alpha-tocopherol in plasma for rearing and veal calves, respectively. The higher RRR-alpha-tocopherol stereoisomer proportion as percentage of the total alpha-tocopherol in rearing calves was related to higher dietary natural vitamin E intake. Other 2R-alpha-tocopherol stereoisomers had lower utilization efficiency than RRR-alpha-tocopherol stereoisomer. 2S-alpha-tocopherol stereoisomers were basically not utilized by calves.

Glutathione regulation of redox-sensitive signals in tumor necrosis factor-{alpha}-induced vascular endothelial dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsou, T.-C.; Yeh, S.C.; Tsai, F.-Y.

2007-06-01

We investigated the regulatory role of glutathione in tumor necrosis factor-alpha (TNF-{alpha})-induced vascular endothelial dysfunction as evaluated by using vascular endothelial adhesion molecule expression and monocyte-endothelial monolayer binding. Since TNF-{alpha} induces various biological effects on vascular cells, TNF-{alpha} dosage could be a determinant factor directing vascular cells into different biological fates. Based on the adhesion molecule expression patterns responding to different TNF-{alpha} concentrations, we adopted the lower TNF-{alpha} (0.2 ng/ml) to rule out the possible involvement of other TNF-{alpha}-induced biological effects. Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO) resulted in down-regulations of the TNF-{alpha}-induced adhesion molecule expression and monocyte-endothelial monolayermore » binding. BSO attenuated the TNF-{alpha}-induced nuclear factor-kappaB (NF-{kappa}B) activation, however, with no detectable effect on AP-1 and its related mitogen-activated protein kinases (MAPKs). Deletion of an AP-1 binding site in intercellular adhesion molecule-1 (ICAM-1) promoter totally abolished its constitutive promoter activity and its responsiveness to TNF-{alpha}. Inhibition of ERK, JNK, or NF-{kappa}B attenuates TNF-{alpha}-induced ICAM-1 promoter activation and monocyte-endothelial monolayer binding. Our study indicates that TNF-{alpha} induces adhesion molecule expression and monocyte-endothelial monolayer binding mainly via activation of NF-{kappa}B in a glutathione-sensitive manner. We also demonstrated that intracellular glutathione does not modulate the activation of MAPKs and/or their downstream AP-1 induced by lower TNF-{alpha}. Although AP-1 activation by the lower TNF-{alpha} was not detected in our systems, we could not rule out the possible involvement of transiently activated MAPKs/AP-1 in the regulation of TNF-{alpha}-induced adhesion molecule expression.« less

ON THE ORIGINS OF THE DIFFUSE H{alpha} EMISSION: IONIZED GAS OR DUST-SCATTERED H{alpha} HALOS?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seon, Kwang-Il; Witt, Adolf N., E-mail: kiseon@kasi.re.kr

2012-10-20

It is known that the diffuse H{alpha} emission outside of bright H II regions not only are very extended, but also can occur in distinct patches or filaments far from H II regions, and the line ratios of [S II] {lambda}6716/H{alpha} and [N II] {lambda}6583/H{alpha} observed far from bright H II regions are generally higher than those in the H II regions. These observations have been regarded as evidence against the dust-scattering origin of the diffuse H{alpha} emission (including other optical lines), and the effect of dust scattering has been neglected in studies on the diffuse H{alpha} emission. In thismore » paper, we reexamine the arguments against dust scattering and find that the dust-scattering origin of the diffuse H{alpha} emission cannot be ruled out. As opposed to the previous contention, the expected dust-scattered H{alpha} halos surrounding H II regions are, in fact, in good agreement with the observed H{alpha} morphology. We calculate an extensive set of photoionization models by varying elemental abundances, ionizing stellar types, and clumpiness of the interstellar medium (ISM) and find that the observed line ratios of [S II]/H{alpha}, [N II]/H{alpha}, and He I {lambda}5876/H{alpha} in the diffuse ISM accord well with the dust-scattered halos around H II regions, which are photoionized by late O- and/or early B-type stars. We also demonstrate that the H{alpha} absorption feature in the underlying continuum from the dust-scattered starlight ({sup d}iffuse galactic light{sup )} and unresolved stars is able to substantially increase the [S II]/H{alpha} and [N II]/H{alpha} line ratios in the diffuse ISM.« less

Relative changes in the abundance of branchial Na(+)/K(+)-ATPase alpha-isoform-like proteins in marine euryhaline milkfish (Chanos chanos) acclimated to environments of different salinities.

PubMed

Tang, Cheng-Hao; Chiu, Yu-Huei; Tsai, Shu-Chuan; Lee, Tsung-Han

2009-08-01

Previous studies revealed that upon salinity challenge, milkfish (Chanos chanos), the euryhaline teleost, exhibited adaptive changes in branchial Na(+)/K(+)-ATPase (NKA) activity with different Na(+) and K(+) affinities. Since alteration of activity and ion-affinity may be influenced by changes in different isoforms of NKA alpha-subunit (i.e., the catalytic subunit), it is, thus, intriguing to compare the patterns of protein abundance of three major NKA alpha-isoform-like proteins (i.e., alpha1, alpha2, and alpha3) in the gills of euryhaline milkfish following salinity challenge. The protein abundance of three NKA alpha-isoform-like proteins in gills of milkfish reared in seawater (SW), fresh water (FW), as well as hypersaline water (HSW, 60 per thousand) were analyzed by immunoblotting. In the acclimation experiments, the SW group revealed significantly higher levels of NKA alpha1- and alpha3-like proteins than the FW or HSW group. Time-course experiments on milkfish that were transferred from SW to HSW revealed the abundance of branchial NKA alpha1-like and alpha3-like proteins decreased significantly after 96 and 12 hr, respectively, and no significant difference was found in NKA alpha2-like protein. Furthermore, when fish were transferred from SW to FW, the amounts of NKA alpha1- and alpha3-like proteins was significantly decreased after 96 hr. Taken together, acute and chronic changes in the abundance of branchial NKA alpha1- and alpha3-like proteins may fulfill the requirements of altering NKA activity with different Na(+) or K(+) affinity for euryhaline milkfish acclimated to environments of various salinities. 2009 Wiley-Liss, Inc.

Evaluation of the alpha-1 and alpha-2 adrenoceptor-mediated effects of a series of dimethoxy-substituted tolazoline derivatives in the cardiovascular system of the pithed rat.

PubMed

Ruffolo, R R; Messick, K

1985-01-01

The alpha-1 and alpha-2 adrenoceptor-mediated effects of a series of dimethoxy-substituted tolazoline derivatives were investigated in the cardiovascular system of the pithed rat. The 2,5- and 3,5-dimethoxy-substituted tolazoline derivatives produced vasopressor responses that were inhibited by the alpha-1 adrenoceptor antagonist, prazosin (0.1 mg/kg i.v.), and were not affected by the alpha-2 adrenoceptor antagonist, yohimbine (1 mg/kg i.v.), suggesting that these derivatives selectively activate postsynaptic vascular alpha-1 adrenoceptors. The 2,5- and 3,5-dimethoxy-substituted derivatives of tolazoline did not produce an alpha-2 adrenoceptor-mediated inhibition of neurogenic tachycardia in cord-stimulated pithed rats and were therefore presumed to be devoid of alpha-2 adrenoceptor agonist activity. In contrast, 2,3-dimethoxytolazoline produced a vasopressor effect that was inhibited by yohimbine but not by prazosin, suggesting selective activation of postsynaptic vascular alpha-2 adrenoceptors. Consistent with this observation is the fact that 2,3-dimethoxytolazoline elicited a dose-dependent, alpha-2 adrenoceptor-mediated inhibition of neurogenic tachycardia in cord-stimulated pithed rat. 3,4-Dimethoxytolazoline was a weak alpha-1 adrenoceptor agonist in the vasculature of the pithed rat and was devoid of agonist activity at alpha-2 adrenoceptors. However, 3,4-dimethoxytolazoline was found to be an alpha-2 adrenoceptor antagonist of similar potency as yohimbine. The results of the present study indicate that dimethoxy-substituted derivatives of tolazoline possess different activities and selectivities at alpha-1 and alpha-2 adrenoceptors depending upon the positions of substitution.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple alpha subunits of integrin are involved in cell-mediated responses of the Manduca immune system.

PubMed

Zhuang, Shufei; Kelo, Lisha; Nardi, James B; Kanost, Michael R

2008-01-01

The cell-mediated responses of the insect innate immune system-phagocytosis, nodulation, encapsulation-involve multiple cell adhesion molecules of hemocyte surfaces. A hemocyte-specific (HS) integrin and a member of the immunoglobulin (Ig) superfamily (neuroglian) are involved in the encapsulation response of hemocytes in Manduca sexta. In addition, two new integrin alpha (alpha) subunits have been found on these hemocytes. The alpha2 subunit is mainly expressed in epidermis and Malphigian tubules, whereas the alpha3 subunit is primarily expressed on hemocytes and fat body cells. Of the three known alpha subunits, the alpha1 subunit found in HS integrin is the predominant subunit of hemocytes. Cell adhesion assays indicate that alpha2 belongs to the integrin family with RGD-binding motifs, confirming the phylogenetic analysis of alpha subunits based on the amino-acid sequence alignment of different alpha subunits. Double-stranded RNAs (dsRNAs) targeting each of these three integrin alpha subunits not only specifically decreased transcript expression of each alpha subunit in hemocytes, but also abolished the cell-mediated encapsulation response of hemocytes to foreign surfaces. The individual alpha subunits of M. sexta integrins, like their integrin counterparts in mammalian immune systems, have critical, individual roles in cell-substrate and cell-cell interactions during immune responses.

[Interferon alpha-2b modified with polyethylene glycol].

PubMed

Wu, Yingxin; Zhai, Yanqin; Lei, Jiandu; Ma, Guanghui; Su, Zhiguo

2008-09-01

In order to obtain a more stable PEGylated interferon alpha-2b, and prolong its half life, interferon alpha-2b (IFN alpha-2b) was modified with monomethoxy polyethylene glycol propionaldehyde (mPEG-ALD) 20000. It was found that the optimized reaction condition for the maximum bioactivity and highest PEGylation degree of the mono PEGylated interferon alpha-2b was as follows: in 20 mmol/L, pH 6.5, citric acid and sodium dihydrogen phosphate buffer, the concentration of IFN alpha-2b was 4 mg/mL, and the molar ratio of PEG/IFN alpha-2b was 8:1, and the reaction time was 20 h at 4 degrees C. Under the optimized reaction condition, the mono PEGylation degree reached to 55%. Ion exchange chromatography was used to separate and purify mono PEGylated interferon alpha-2b from the reaction mixture. The purity of mono PEGylated interferon alpha-2b was higher than 97% characterized by HPLC. The bioactivity of the mono PEGylated interferon alpha-2b was 13.4% of the native IFN alpha-2b, while its half life in SD rat is much longer than the native IFN alpha-2b. The mono PEGylated interferon alpha-2b is also stable in aqueous.

Studying Lyman-alpha escape and reionization in Green Pea galaxies

NASA Astrophysics Data System (ADS)

Yang, Huan; Malhotra, Sangeeta; Rhoads, James E.; Gronke, Max; Leitherer, Claus; Wofford, Aida; Dijkstra, Mark

2017-01-01

Green Pea galaxies are low-redshift galaxies with extreme [OIII]5007 emission line. We built the first statistical sample of Green Peas observed by HST/COS and used them as analogs of high-z Lyman-alpha emitters to study Ly-alpha escape and Ly-alpha sizes. Using the HST/COS 2D spectra, we found that Ly-alpha sizes of Green Peas are larger than the UV continuum sizes. We found many correlations between Ly-alpha escape fraction and galactic properties -- dust extinction, Ly-alpha kinematic features, [OIII]/[OII] ratio, and gas outflow velocities. We fit an empirical relation to predict Ly-alpha escape fraction from dust extinction and Ly-alpha red-peak velocity. In the JWST era, we can use this relation to derive the IGM HI column density along the line of sight of each high-z Ly-alpha emitter and probe the reionization process.

Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruick, Richard K.; Caldwell, Charles G.; Frantz, Doug E.

2017-09-12

Provided is a method of inhibiting heterodimerization of HIF-2.alpha. to HIF1.beta. (ARNT) comprising binding certain small molecules to the HIF-2.alpha. PAS-B domain cavity but not to HIF1.alpha. and inhibiting HIF-2.alpha. heterodimerization to HIF1.beta. (ARNT) but not inhibiting HIF1.alpha. heterodimerization to HIF1.beta. (ARNT). Those certain small molecules are also referenced synonymously as HIF2-HDI and HIF2.alpha. heterodimerization inhibitors and also simply as certain small molecules.

IgE reactivity to alpha1 and alpha2 chains of bovine type 1 collagen in children with bovine gelatin allergy.

PubMed

Sakaguchi, M; Hori, H; Hattori, S; Irie, S; Imai, A; Yanagida, M; Miyazawa, H; Toda, M; Inouye, S

1999-09-01

Anaphylactic reactions to measles, mumps, and rubella vaccines, including gelatin as a stabilizer, have been reported. It had been found that most of these reactions to live vaccines are caused by the bovine gelatin included in these vaccines. Gelatin mainly includes denatured type I collagen, which consists of alpha1 and alpha2 chains. The current study was designed to investigate the IgE reactivity to alpha1 and alpha2 chains of bovine type I collagen in gelatin-sensitive children. Serum samples were taken from 10 children who had anaphylaxis to the vaccines and high levels of specific IgE to bovine gelatin. Bovine type I collagen was isolated from bovine skin and then separated to alpha1 and alpha2 chains by column chromatography. IgE reactivity to denatured type I collagen and its alpha1 and alpha2 chains was analyzed by immunoblotting, ELISA, and histamine release from the mast cells passive sensitized with IgE antibodies in pooled serum of the children. All children had specific IgE to bovine type I collagen. Furthermore, IgE antibodies in their sera reacted with the alpha;2 chain but not with the alpha1 chain. Similarly, the mast cells sensitized with pooled sera in the children showed alpha2 chain-specific histamine release but not alpha1 chain-specific histamine release. In gelatin allergy denatured bovine type I collagen is a major allergen and IgE-binding sites exist in the alpha2 chain of type I collagen.

{alpha}+{sup 6,8}He resonant scattering and exotic structures in {sup 10,12}Be

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ito, Makoto; Itagaki, Naoyuki

2008-05-21

The {alpha}+{sup 6}He low-energy reactions and the structural changes of {sup 10}Be in the microscopic {alpha}+{alpha}+2N model are studied by the generalized two-center cluster model with the Kohn-Hulthen-Kato variation method. It is found that, in the inelastic scattering to the {alpha}+{sup 6}He(2{sub 1}{sup +}) channel, characteristic enhancements are expected as the results of the parity-dependent non-adiabatic dynamics. The similar method is applied to the resonant scattering of {alpha}+{sup 8}He, and the coupling with the compound configurations of {alpha}+{alpha}+4N are discussed.

Involvement of the N-terminal region in alpha-crystallin-lens membrane recognition

NASA Technical Reports Server (NTRS)

Ifeanyi, F.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

1991-01-01

Previous studies have demonstrated that alpha-crystallin binds specifically, in a saturable manner, to lens membrane. To determine the region of the alpha-crystallin molecule that might be involved in this binding, native alpha-crystallin from the bovine lens has been treated by limited digestion with trypsin, to produce alpha-A molecules with an intact C-terminal region, and a nicked N-terminal region. Compared to intact alpha-crystallin, trypsin-treated alpha-crystallin binds less avidly to lens membrane, suggesting that the N-terminal region of the alpha-A molecule may play a key role in the recognition between lens membrane and crystallin.

The region of CQQQKPQRRP of PGC-1{alpha} interacts with the DNA-binding complex of FXR/RXR{alpha}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanaya, Eiko; Jingami, Hisato

2006-04-14

PGC-1{alpha} co-activates transcription by several nuclear receptors. To study the interaction among PGC-1{alpha}, RXR{alpha}/FXR, and DNA, we performed electrophoresis mobility shift assays. The RXR{alpha}/FXR proteins specifically bound to DNA containing the IR-1 sequence in the absence of ligand. When the fusion protein of GST-PGC-1{alpha} was added to the mixture of RXR{alpha}/FXR/DNA, the ligand-influenced retardation of the mobility was observed. The ligand for RXR{alpha} (9-cis-retinoic acid) was necessary for this retardation, whereas, the ligand for FXR, chenodeoxycholic acid, barely had an effect. The results obtained using truncated PGC-1{alpha} proteins suggested that two regions are necessary for PGC-1{alpha} to interact with themore » DNA-binding complex of RXR{alpha}/FXR. One is the region of the second leucine-rich motif, and the other is that of the amino acid sequence CQQQKPQRRP, present between the second and third leucine-rich motifs. The results obtained with the SPQSS mutation for KPQRR suggested that the basic amino acids are important for the interaction.« less

alpha-DNA II. Synthesis of unnatural alpha-anomeric oligodeoxyribonucleotides containing the four usual bases and study of their substrate activities for nucleases.

PubMed Central

Morvan, F; Rayner, B; Imbach, J L; Thenet, S; Bertrand, J R; Paoletti, J; Malvy, C; Paoletti, C

1987-01-01

This paper describes for the first time the synthesis of alpha-oligonucleotides containing the four usual bases. Two unnatural hexadeoxyribonucleotides: alpha-[d(CpApTpGpCpG)] and alpha-[d(CpGpCpApTpG)], consisting only of alpha-anomeric nucleotide units, were obtained by an improved phosphotriester method, in solution. Starting material was the four base-protected alpha-deoxyribonucleosides 3a-d. Pyrimidine alpha-deoxynucleosides 3a and 3b were prepared by self-anomerization reactions followed by selective deprotection of sugar hydroxyles, while the two purine alpha-deoxynucleosides 3c and 3d were prepared by glycosylation reactions. In the case of guanine alpha-nucleoside derivative a supplementary base-protecting group: N,N-diphenylcarbamoyl was introduced on O6-position in order to avoid side-reactions during oligonucleotide assembling. The hexadeoxynucleotide alpha-[d(CpApTpGpCpG)] was tested as substrate of selected endo- and exonucleases. In conditions where the natural corresponding beta-hexamer was completely degradated by nuclease S1 and calf spleen phosphodiesterase, the alpha-oligonucleotide remained almost intact. PMID:3575096

Crystal structure of IscA, an iron-sulfur cluster assembly protein from Escherichia coli.

PubMed

Cupp-Vickery, Jill R; Silberg, Jonathan J; Ta, Dennis T; Vickery, Larry E

2004-04-16

IscA, an 11 kDa member of the hesB family of proteins, binds iron and [2Fe-2S] clusters, and participates in the biosynthesis of iron-sulfur proteins. We report the crystal structure of the apo-protein form of IscA from Escherichia coli to a resolution of 2.3A. The crystals belong to the space group P3(2)21 and have unit cell dimensions a=b=66.104 A, c=150.167 A (alpha=beta=90 degrees, gamma=120 degrees ). The structure was solved using single-wavelength anomalous dispersion (SAD) phasing of a selenomethionyl derivative, and the IscA model was refined to R=21.4% (Rfree=25.4%). IscA exists as an (alpha1alpha2)2 homotetramer with the (alpha1alpha2) dimer comprising the asymmetric unit. Cys35, implicated in Fe-S cluster assembly, is located in a central cavity formed at the tetramer interface with the gamma-sulfur atoms of residues from the alpha1 and alpha2' monomers (and alpha1'alpha2) positioned close to one another (approximately equal 7 A). C-terminal residues 99-107 are disordered, and the exact positions of Cys99 and Cys101 could not be determined. However, computer modeling of C-terminal residues in the tetramer suggests that Cys99 and Cys101 in the alpha1 monomer and those of the alpha1' monomer (or alpha2 and alpha2') are positioned sufficiently close to coordinate [2Fe-2S] clusters between the two dimers, whereas this is not possible within the (alpha1alpha2) or (alpha1'alpha2') dimer. This symmetrical arrangement allows for binding of two [2Fe-2S] clusters on opposite sides of the tetramer. Modeling further reveals that Cys101 is positioned sufficiently close to Cys35 to allow Cys35 to participate in cluster assembly, formation, or transfer.

Platypus globin genes and flanking loci suggest a new insertional model for beta-globin evolution in birds and mammals.

PubMed

Patel, Vidushi S; Cooper, Steven J B; Deakin, Janine E; Fulton, Bob; Graves, Tina; Warren, Wesley C; Wilson, Richard K; Graves, Jennifer A M

2008-07-25

Vertebrate alpha (alpha)- and beta (beta)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the alpha- and beta-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil beta-globin gene (omega) in the marsupial alpha-cluster, however, suggested that duplication of the alpha-beta cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous alpha- and beta-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. The platypus alpha-globin cluster (chromosome 21) contains embryonic and adult alpha- globin genes, a beta-like omega-globin gene, and the GBY globin gene with homology to cytoglobin, arranged as 5'-zeta-zeta'-alphaD-alpha3-alpha2-alpha1-omega-GBY-3'. The platypus beta-globin cluster (chromosome 2) contains single embryonic and adult globin genes arranged as 5'-epsilon-beta-3'. Surprisingly, all of these globin genes were expressed in some adult tissues. Comparison of flanking sequences revealed that all jawed vertebrate alpha-globin clusters are flanked by MPG-C16orf35 and LUC7L, whereas all bird and mammal beta-globin clusters are embedded in olfactory genes. Thus, the mammalian alpha- and beta-globin clusters are orthologous to the bird alpha- and beta-globin clusters respectively. We propose that alpha- and beta-globin clusters evolved from an ancient MPG-C16orf35-alpha-beta-GBY-LUC7L arrangement 410 million years ago. A copy of the original beta (represented by omega in marsupials and monotremes) was inserted into an array of olfactory genes before the amniote radiation (>315 million years ago), then duplicated and diverged to form orthologous clusters of beta-globin genes with different expression profiles in different lineages.

Bimatoprost and prostaglandin F(2 alpha) selectively stimulate intracellular calcium signaling in different cat iris sphincter cells.

PubMed

Spada, Clayton S; Krauss, Achim H-P; Woodward, David F; Chen, June; Protzman, Charles E; Nieves, Amelia L; Wheeler, Larry A; Scott, David F; Sachs, George

2005-01-01

Bimatoprost is a synthetic analog of prostaglandin F(2 alpha) ethanolamide (prostamide F(2 alpha)), and shares a pharmacological profile consistent with that of the prostamides. Like prostaglandin F(2 alpha) carboxylic acid, bimatoprost potently lowers intraocular pressure in dogs, primates and humans. In order to distinguish its mechanism of action from prostaglandin F(2 alpha), fluorescence confocal microscopy was used to examine the effects of bimatoprost, prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) on calcium signaling in resident cells of digested cat iris sphincter, a tissue which exhibits contractile responses to both agonists. Constant superfusion conditions obviated effective conversion of bimatoprost. Serial challenge with 100 nM bimatoprost and prostaglandin F(2 alpha) consistently evoked responses in different cells within the same tissue preparation, whereas prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) elicited signaling responses in the same cells. Bimatoprost-sensitive cells were consistently re-stimulated with bimatoprost only, and prostaglandin F(2 alpha) sensitive cells could only be re-stimulated with prostaglandin F(2 alpha). The selective stimulation of different cells in the same cat iris sphincter preparation by bimatoprost and prostaglandin F(2 alpha), along with the complete absence of observed instances in which the same cells respond to both agonists, strongly suggests the involvement of distinct receptors for prostaglandin F(2 alpha) and bimatoprost. Further, prostaglandin F(2 alpha) but not bimatoprost potently stimulated calcium signaling in isolated human embryonic kidney cells stably transfected with the feline- and human-prostaglandin F(2 alpha) FP-receptor and in human dermal fibroblast cells, and only prostaglandin F(2 alpha) competed with radioligand binding in HEK-feFP cells. These studies provide further evidence for the existence of a bimatoprost-sensitive receptor that is distinct from any of the known prostaglandin receptor types.

A stereochemical examination of the equine metabolism of 17alpha-methyltestosterone.

PubMed

McKinney, Andrew R; Suann, Craig J; Stenhouse, Allen M

2007-01-09

An investigation was conducted into the stereochemistry of the equine urinary metabolites of 17alpha-methyltestosterone observed after oral administration. Standards of the complete range of C3/C5/C16 stereoisomeric 17alpha-methylandrostane-3,17beta-diols, 17alpha-methylandrostane-3,16,17beta-triols and 17alpha-hydroxymethylandrostane-3,17beta-diols were purchased or synthesised, and were used to unequivocally identify the absolute structures of the metabolites. Phase I metabolism was found to involve combinations of Delta(4)-3-ketone reduction with both 5alpha,3beta- and 5beta,3alpha-stereochemistry, hydroxylation at C16 with both 16alpha- and 16beta-stereochemistry and hydroxylation of the 17alpha-methyl substituent. Phase II metabolism involved mainly sulfation with a lesser degree of beta-glucuronidation.

Study on molecular epidemiology of the alpha-thalassemias in Liuzhou City, Guangxi Autonomous Region, China.

PubMed

Cai, Ren; Liu, Jingzhong; Wang, Lirong; Liang, Xin; Xiao, Bai; Su, Liu; Zhou, Yan; Pan, Lizhen

2004-01-01

Guangxi is one of the provinces of Southern China with the highest incidence of alpha-thalassemia (thal). Liuzhou is the second biggest city in Guangxi. To find out the incidence of the various alpha-thal genotypes, and their distribution in the Liuzhou area, an F820 Blood Cell Analysis System was used to measure the parameters of red blood cells. A SPIFE Rapid Auto-Electrophoresis System was used to analyze the normal and abnormal hemoglobins (Hbs). Multiplex polymerase chain reaction (mPCR) was used to detect the alpha-globin genotypes. Thirty-two (2.05%) out of 7805 young couples undergoing pre-marriage counseling, were diagnosed as having an Hb H (beta4) disease. The study of 1228 cord blood samples revealed 138 newborn children carrying an alpha-thal determinant with nine different genotypes, thus making the total incidence of alpha-thal 11.24%. Among 185 cases of Hb H, 119 (64.1%) were confirmed as being deletional, and 66 cases (35.7%) nondeletional types. The severity of the Hb H diseases could be classified in the following order: alphaCSalpha/--SEA (alphaConstant (Spring)alpha/--Southeast Asia); alpha(-4.2)/--SEA; alpha(-3.7)/--SEA. Ten cases of alpha-thal determinants were found in combination with beta-thal. The mPCR technique can detect all kinds of combinations of the three common large deletions (--SEA, alpha(-4.2) and alpha(-3.7)) accurately and conveniently.

Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

PubMed

Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

2015-01-01

The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

Molecular characterization of the new defective P(brescia) alpha1-antitrypsin allele.

PubMed

Medicina, Daniela; Montani, Nadia; Fra, Anna M; Tiberio, Laura; Corda, Luciano; Miranda, Elena; Pezzini, Alessandro; Bonetti, Fausta; Ingrassia, Rosaria; Scabini, Roberta; Facchetti, Fabio; Schiaffonati, Luisa

2009-08-01

Alpha1-antitrypsin (alpha(1)AT) deficiency is a hereditary disorder associated with reduced alpha(1)AT serum level, predisposing adults to pulmonary emphysema. Among the known mutations of the alpha(1)AT gene (SERPINA1) causing alpha(1)AT deficiency, a few alleles, particularly the Z allele, may also predispose adults to liver disease. We have characterized a new defective alpha(1)AT allele (c.745G>C) coding for a mutant alpha(1)AT (Gly225Arg), named P(brescia). The P(brescia) alpha(1)AT allele was first identified in combination with the rare defective M(würzburg) allele in an 11-year-old boy showing significantly reduced serum alpha(1)AT level. Subsequently, the P(brescia) allele was found in the heterozygous state with the normal M or the defective Z allele in nine and three adults respectively. In cellular models of the disease, we show that the P(brescia) mutant is retained in the endoplasmic reticulum as ordered polymers and is secreted more slowly than the normal M alpha(1)AT. This behaviour recapitulates the abnormal cellular handling and fate of the Z alpha(1)AT and suggests that the mutation present in the P(brescia) alpha(1)AT causes a conformational change of the protein which, by favouring polymer formation, is etiologic to both severe alpha(1)AT deficiency in the plasma and toxic protein-overload in the liver.

Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: progesterone metabolism and the effect of androgens.

PubMed

Nimrod, A

1977-09-01

Metabolic transformations of progesterone in cultures of granulosa cells from immature hypophysectomized rats treated with diethylstilbestrol were studied in relation to the synergistic action of exogenous androgen and FSH on progestin (progesterone and 20alpha-dihydroprogesterone) accumulation. Androstenedione (Ad; 10 ng/ml) enhanced the sensitivity of rat granulosa cells to this steroidogenic action of FSH, lowering the threshold of the response from greater than 4 ng/ml (FSH alone) to 0.8 ng/ml in the presence of Ad. A synergistic effect with FSH was also shown by various 5alpha-androstane derivatives. They were, however, less effective than the parent delta4-3 keto androstenes. Progesterone underwent extensive 5alpha-reduction during culture, leading to accumulation of endogenous 5alpha-pregnane compounds, and to transformation of labelled progesterone into 5 alpha-reduced radiometabolites. These compounds corresponded in gas-liquid and thin-layer chromatographic behaviour to 3alpha-hydroxy-5alpha-pregnan-20-one, 20alpha-hydroxy-5alpha-pregnan-3-one and 5alpha-pregnane-3alpha,20alpha-diol. The rate of 5alpha-reduction of progestins was not affected by the presence of exogenous Ad (1 microgram/ml), ruling out the possibility that the effect of androgen on progestin accumulation depends on competitive inhibition of 5alpha-reductase. An involvement of androgen of thecal origin in the enhancement of the sensitivity of the FSH-responsive mechanism in granulosa cells is suggested.

DIFFUSE Ly{alpha} EMITTING HALOS: A GENERIC PROPERTY OF HIGH-REDSHIFT STAR-FORMING GALAXIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steidel, Charles C.; Bogosavljevic, Milan; Shapley, Alice E.

2011-08-01

Using a sample of 92 UV continuum-selected, spectroscopically identified galaxies with (z) = 2.65, all of which have been imaged in the Ly{alpha} line with extremely deep narrow-band imaging, we examine galaxy Ly{alpha} emission profiles to very faint surface brightness limits. The galaxy sample is representative of spectroscopic samples of Lyman break galaxies (LBGs) at similar redshifts in terms of apparent magnitude, UV luminosity, inferred extinction, and star formation rate and was assembled without regard to Ly{alpha} emission properties. Approximately 45% (55%) of the galaxy spectra have Ly{alpha} appearing in net absorption (emission), with {approx_equal} 20% satisfying commonly used criteriamore » for the identification of 'Ly{alpha} emitters' (LAEs; W{sub 0}(Ly{alpha}) {>=} 20 A). We use extremely deep stacks of rest-UV continuum and continuum-subtracted Ly{alpha} images to show that all sub-samples exhibit diffuse Ly{alpha} emission to radii of at least 10'' ({approx}80 physical kpc). The characteristic exponential scale lengths for Ly{alpha} line emission exceed that of the {lambda}{sub 0} = 1220 A UV continuum light by factors of {approx}5-10. The surface brightness profiles of Ly{alpha} emission are strongly suppressed relative to the UV continuum light in the inner few kpc, by amounts that are tightly correlated with the galaxies' observed spectral morphology; however, all galaxy sub-subsamples, including that of galaxies for which Ly{alpha} appears in net absorption in the spectra, exhibit qualitatively similar diffuse Ly{alpha} emission halos. Accounting for the extended Ly{alpha} emission halos, which generally would not be detected in the slit spectra of individual objects or with typical narrow-band Ly{alpha} imaging, increases the total Ly{alpha} flux (and rest equivalent width W{sub 0}(Ly{alpha})) by an average factor of {approx}5, and by a much larger factor for the 80% of LBGs not classified as LAEs. We argue that most, if not all, of the observed Ly{alpha} emission in the diffuse halos originates in the galaxy H II regions but is scattered in our direction by H I gas in the galaxy's circum-galactic medium. The overall intensity of Ly{alpha} halos, but not the surface brightness distribution, is strongly correlated with the emission observed in the central {approx}1''-more luminous halos are observed for galaxies with stronger central Ly{alpha} emission. We show that whether or not a galaxy is classified as a giant 'Ly{alpha} blob' (LAB) depends sensitively on the Ly{alpha} surface brightness threshold reached by an observation. Accounting for diffuse Ly{alpha} halos, all LBGs would be LABs if surveys were sensitive to 10 times lower Ly{alpha} surface brightness thresholds; similarly, essentially all LBGs would qualify as LAEs.« less

75 FR 36681 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... (7439). I Acetorphine (9319) I Acetyl-alpha-methylfentanyl (9815)......... I Acetyldihydrocodeine (9051... (9603). Alpha-ethyltryptamine (7249) I Alphameprodine (9604) I Alphamethadol (9605) I Alpha-methylfentanyl (9814) I Alpha-methylthiofentanyl (9832) I Alpha-methyltryptamine (7432) I Aminorex (1585) I...

The role of macrophages in the regulation of erythroid colony growth in vitro.

PubMed

Wang, C Q; Udupa, K B; Lipschitz, D A

1992-10-01

Depletion of macrophages from murine marrow by the use of a monoclonal anti-macrophage antibody resulted in a significant increase in the number of erythroid burst forming units (BFU-E). This increase could be neutralized by the addition back to culture of macrophages or macrophage conditioned medium indicating that the suppression was mediated by soluble factors. To further characterize this effect, the addition to culture, either alone or in combination, of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the growth of BFU-E and the colony-forming unit granulocyte-macrophage (CFU-GM) was examined in macrophage-containing and macrophage-depleted cultures. The addition of IL-1 alpha to culture stimulated the release of both TNF alpha and GM-CSF and acted synergistically with both cytokines, resulting in a dose-dependent suppression of BFU-E and stimulation of CFU-GM growth. The increase in CFU-GM caused by the addition of IL-1 alpha was mediated by GM-CSF but not by TNF alpha as the increase was prevented by the addition of a monoclonal anti-GM-CSF antibody but not by anti-TNF alpha. When either TNF alpha or GM-CSF was neutralized by monoclonal antibodies the addition of IL-1 alpha resulted in a significant increase in BFU-E growth. The addition of GM-CSF to culture caused a dose-dependent suppression of BFU-E that was mediated by TNF alpha, as colony number was not reduced when GM-CSF and a monoclonal anti-TNF alpha antibody were simultaneously added to culture. TNF alpha-induced suppression of BFU-E only occurred in the presence of macrophages. In macrophage-depleted cultures, a dose-dependent suppression of BFU-E could be induced if subinhibitory concentrations of IL-1 alpha or GM-CSF were simultaneously added with increasing concentrations of TNF alpha. The effects of IL-1 alpha or GM-CSF and TNF alpha were markedly synergistic so that the doses required to induce suppression when added simultaneously was only 10% of that required when either were added to culture alone. Suppression of BFU-E by GM-CSF or the combined addition of GM-CSF and TNF alpha did not require IL-1 alpha because inhibition was not neutralized by the addition of anti-IL-1 alpha antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Cloning and expression of a novel UDP-GlcNAc:alpha-D-mannoside beta1,2-N-acetylglucosaminyltransferase homologous to UDP-GlcNAc:alpha-3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I.

PubMed Central

Zhang, Wenli; Betel, Doron; Schachter, Harry

2002-01-01

A TBLASTN search with human UDP-GlcNAc:alpha-3-d-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT I; EC 2.4.1.101) as a probe identified human and mouse Unigenes encoding a protein similar to human GnT I (34% identity over 340 amino acids). The recombinant protein converted Man(alpha1-6)[Man(alpha1-3)]Man(beta1-)O-octyl to Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-)O-octyl, the reaction catalysed by GnT I. The enzyme also added GlcNAc to Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-)O-octyl (the substrate for beta-1,2-N-acetylglucosaminyltransferase II), Man(alpha1-)O-benzyl [with K(m) values of approximately 0.3 and >30 mM for UDP-GlcNAc and Man(alpha1-)O-benzyl respectively] and the glycopeptide CYA[Man(alpha1-)O-T]AV (K(m) approximately 12 mM). The product formed with Man(alpha1-)O-benzyl was identified as GlcNAc(beta1-2)Man(alpha1-)O-benzyl by proton NMR spectroscopy. The enzyme was named UDP-GlcNAc:alpha-d-mannoside beta-1,2-N-acetylglucosaminyltransferase I.2 (GnT I.2). The human gene mapped to chromosome 1. Northern-blot analysis showed a 3.3 kb message with a wide tissue distribution. The cDNA has a 1980 bp open reading frame encoding a 660 amino acid protein with a type-2 domain structure typical of glycosyltransferases. Man(beta1-)O-octyl, Man(beta1-)O-p-nitrophenyl and GlcNAc(beta1-2)Man(alpha1-6)[GlcNAc(beta1-2)Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc(beta1-)O-Asn were not acceptors, indicating that GnT I.2 is specific for alpha-linked terminal Man and does not have N-acetylglucosaminyltransferase III, IV, V, VII or VIII activities. CYA[Man(alpha1-)O-T]AV was between three and seven times more effective as an acceptor than the other substrates, suggesting that GnT I.2 may be responsible for the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins. PMID:11742540

In vitro biodegradation of steranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chosson, P.; Connan, J.

1989-03-01

The purpose of this paper is to report reproducible results on the in vitro biodegradation of steranes in various crude oils. 73 pure strains including Pseudomonadacea (33) and Actinomycetaceae (40) have been screened in order to test their capability to degrade steranes contained in total alkanes isolated from various crudes. Biodegradation of steranes has been observed with 7 strains belonging to Nocardia and Arthrobacter genera. 5{alpha}(H), 14{alpha}(H), 17{alpha}(H) and 5{alpha}(H), 14{beta}(H), 17{beta}(H) Steranes with the 20R configuration were degraded under reproducible laboratory conditions. Biodegradation of the sterane mixtures isolated from crude oils followed W. Seiferts rules established on the basismore » of geological observations. 5{alpha}(H), 14{alpha}(H), 17{alpha}(H) C{sub 27}-Steranes with the 20R configuration are degraded first and ends with the 5{alpha}(H), 14{alpha}(H), 17{alpha}(H) C{sub 29}steranes. Then 5{alpha}9h0, 14{beta}(H), and 17{beta}(H) steranes are attacked starting with the 20R configuration. Limited alteration of Tm and Ts terpane has also been observed.« less

Stereoselective Synthesis of [alpha, alpha][superscript ']-Biprolines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vartak, Ashish P.; Young, Jr., Victor G.; Johnson, Rodney L.

2010-11-10

A means to induce dehydrodimerization of Seebach's oxazolidinone (5), the stereochemical outcome of which is entirely temperature dependent, is described. The resultant dimers 3 and 4 are precursors to (R,R)-alpha,alpha'-biproline (1) and meso-alpha,alpha'-biproline (2), respectively. An organohypobromite and an iminium halide are proposed to serve as electrophiles in the reaction with the enolate of 5 to give 3 and 4, respectively.

Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?

PubMed Central

Janecek, S.

1996-01-01

The question of parallel (alpha/beta)8-barrel fold evolution remains unclear, owing mainly to the lack of sequence homology throughout the amino acid sequences of (alpha/beta)8-barrel enzymes. The "classical" approaches used in the search for homologies among (alpha/beta)8-barrels (e.g., production of structurally based alignments) have yielded alignments perfect from the structural point of view, but the approaches have been unable to reveal the homologies. These are proposed to be "hidden" in (alpha/beta)8-barrel enzymes. The term "hidden homology" means that the alignment of sequence stretches proposed to be homologous need not be structurally fully satisfactory. This is due to the very long evolutionary history of all (alpha/beta)8-barrels. This work identifies so-called hidden homology around the strand beta 2 that is flanked by loops containing invariant glycines and prolines in 17 different (alpha/beta)8-barrel enzymes, i.e., roughly in half of all currently known (alpha/beta)8-barrel proteins. The search was based on the idea that a conserved sequence region of an (alpha/beta)8-barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif, given their mutual evolutionary relatedness. For this purpose, the sequence region around the well-conserved second beta-strand of alpha-amylase flanked by the invariant glycine and proline (56_GFTAIWITP, Aspergillus oryzae alpha-amylase numbering), was used as the sequence-structural template. The proposal that the second beta-strand of (alpha/beta)8-barrel fold is important from the evolutionary point of view is strongly supported by the increasing trend of the observed beta 2-strand structural similarity for the pairs of (alpha/beta)8-barrel enzymes: alpha-amylase and the alpha-subunit of tryptophan synthase, alpha-amylase and mandelate racemase, and alpha-amylase and cyclodextrin glycosyltransferase. This trend is also in agreement with the existing evolutionary division of the entire family of (alpha/beta)8-barrel proteins. PMID:8762144

Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?

PubMed

Janecek, S

1996-06-01

The question of parallel (alpha/beta)8-barrel fold evolution remains unclear, owing mainly to the lack of sequence homology throughout the amino acid sequences of (alpha/beta)8-barrel enzymes. The "classical" approaches used in the search for homologies among (alpha/beta)8-barrels (e.g., production of structurally based alignments) have yielded alignments perfect from the structural point of view, but the approaches have been unable to reveal the homologies. These are proposed to be "hidden" in (alpha/beta)8-barrel enzymes. The term "hidden homology" means that the alignment of sequence stretches proposed to be homologous need not be structurally fully satisfactory. This is due to the very long evolutionary history of all (alpha/beta)8-barrels. This work identifies so-called hidden homology around the strand beta 2 that is flanked by loops containing invariant glycines and prolines in 17 different (alpha/beta)8-barrel enzymes, i.e., roughly in half of all currently known (alpha/beta)8-barrel proteins. The search was based on the idea that a conserved sequence region of an (alpha/beta)8-barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif, given their mutual evolutionary relatedness. For this purpose, the sequence region around the well-conserved second beta-strand of alpha-amylase flanked by the invariant glycine and proline (56_GFTAIWITP, Aspergillus oryzae alpha-amylase numbering), was used as the sequence-structural template. The proposal that the second beta-strand of (alpha/beta)8-barrel fold is important from the evolutionary point of view is strongly supported by the increasing trend of the observed beta 2-strand structural similarity for the pairs of (alpha/beta)8-barrel enzymes: alpha-amylase and the alpha-subunit of tryptophan synthase, alpha-amylase and mandelate racemase, and alpha-amylase and cyclodextrin glycosyltransferase. This trend is also in agreement with the existing evolutionary division of the entire family of (alpha/beta)8-barrel proteins.

Stromal laminin chain distribution in normal, hyperplastic and malignant oral mucosa: relation to myofibroblast occurrence and vessel formation.

PubMed

Franz, Marcus; Wolheim, Anke; Richter, Petra; Umbreit, Claudia; Dahse, Regine; Driemel, Oliver; Hyckel, Peter; Virtanen, Ismo; Kosmehl, Hartwig; Berndt, Alexander

2010-04-01

The contribution of stromal laminin chain expression to malignant potential, tumour stroma reorganization and vessel formation in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the expression of the laminin chains alpha2, alpha3, alpha4, alpha5 and gamma2 in the stromal compartment/vascular structures in OSCC was analysed. Frozen tissue of OSCC (9x G1, 24x G2, 8x G3) and normal (2x)/hyperplastic (11x) oral mucosa was subjected to laminin chain and alpha-smooth muscle actin (ASMA) immunohistochemistry. Results were correlated to tumour grade. The relation of laminin chain positive vessels to total vessel number was assessed by immunofluorescence double labelling with CD31. Stromal laminin alpha2 chain significantly decreases and alpha3, alpha4, alpha5 and gamma2 chains and also ASMA significantly increase with rising grade. The amount of stromal alpha3, alpha4 and gamma2 chains significantly increased with rising ASMA positivity. There is a significant decrease in alpha3 chain positive vessels with neoplastic transformation. Mediated by myofibroblasts, OSCC development is associated with a stromal up-regulation of laminin isoforms possibly contributing to a migration promoting microenvironment. A vascular basement membrane reorganization concerning alpha3 and gamma2 chain laminins during tumour angioneogenesis is suggested.

Identification of the antigenic determinants of factors 8, 9, and 34 of genus Candida.

PubMed

Kobayashi, H; Oyamada, H; Suzuki, A; Shibata, N; Suzuki, S; Okawa, Y

1996-10-21

We investigated the antigenic determinants of factors 8, 9, and 34 of the genus Candida among pathogenic yeasts by enzyme-linked immunosorbent assay (ELISA) using mannans of Saccharomyces cerevisiae wild type and mutant types, mnn 1-mnn 4 and mnn 2. Results of ELISA including antisera against the antigenic factors of genus Candida (Candida Check, latron; FAbs) indicated that these three types of mannan distinctly react with FAbs 34, 8 and 9, respectively. To identify the recognition sites of these FAbs, we compared the ability of various oligosaccharides to inhibit the binding of the mannans to FAbs. The results indicated that FAb 34 preferentially recognizes linear side chains containing a non-reducing terminal alpha-1,3-linked mannose residue, Man(alpha)1 --> 3Man(alpha)1 --> (2Man(alpha)1 --> )n(2Man) (n > or = 0), and that one of the recognition sites of FAb 9 is linear alpha-1,6-linked oligomannosyl series, Man(alpha)1 --> (6Man(alpha)1 --> )n(6Man) (n > or = 2). On the other hand, the recognition site of FAb 8 apparently consisted of two alpha-1,2-linked oligomannosyl side chains and an alpha-1,6-linked mannose residue that originated from the mannan backbone, Man(alpha)1 --> 2Man(alpha)1 --> 2(Man(alpha)1 -->2Man(alpha)1 --> 6)Man.