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

An open-label, multicenter study to evaluate the safe and effective use of the single-use autoinjector with an Avonex® prefilled syringe in multiple sclerosis subjects

PubMed Central

2011-01-01

Background The ability to self-inject in patients with multiple sclerosis (MS) has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patients' independence. However, injection anxiety, needle phobia and disease-related disability are major barriers to a patient's ability to self-administer treatment. Use of an autoinjector may improve patients' ability to self-inject. This study evaluated the safe and effective use of Avonex Pen™ (prefilled pen), a single use autoinjector, for intramuscular delivery of interferon beta-1a (IM IFNβ-1a, Avonex) in MS patients. Methods This was a Phase IIIb, open-label, single-country, multicenter trial in MS patients currently using IM IFNβ-1a prefilled syringes. Patients received weekly 30 mcg IM IFNβ-1a treatment over 4 weeks. On Day 1, patients self-administered IM IFNβ-1a using a prefilled syringe at the clinic. On Day 8, patients received training on the prefilled pen and self-administered IM IFNβ-1a using the device. On Day 15, patients self-administered IM IFNβ-1a at home using the prefilled pen. A final injection occurred at the clinic on Day 22 when patients self-administered IM IFNβ-1a using the prefilled pen while clinic staff observed and completed a detailed questionnaire documenting patients' ability to self-inject with the device. Serum neopterin levels were evaluated pre and post-injection on Days 1 and 8. Adverse events were monitored throughout. Results Seventy-one (96%) patients completed the study. The overall success rate in safely and effectively using the prefilled pen was 89%. No device malfunctions occurred. One unsuccessful administration occurred at Day 22 due to patient error; no patient injury resulted. Patients gave the prefilled pen high ratings (8.7-9.3) on a 10-point scale for ease of use (0 = extremely difficult, 10 = extremely easy). Ninety-four percent of patients preferred the prefilled pen over the prefilled syringe. Induction of

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

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

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.

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.

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.

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

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.

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.

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

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

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 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...

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 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...

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.

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

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...

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.

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

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

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

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.

Recombinant follicle-stimulating hormone: new biotechnology for infertility.

PubMed

Prevost, R R

1998-01-01

The frequency of infertility in developed countries is approximately 8-10%. New drugs are available for assisted reproduction techniques. Two recombinant follicle-stimulating hormone (FSH) products, follitropin-beta (Follistim in the United States, Puregon in Europe) and follitropin-alpha (Gonal-F), join compounds derived through transfecting nonhuman cell lines with genetic material capable of replicating identical amino acid sequences to human compounds. The cell line used for recombinant (r)-FSH production is the Chinese hamster ovary (CHO). Previously, the only agents that showed benefit in controlled ovulatory stimulation were derived from the urine of menopausal women. Those compounds contain additional substances, such as urinary proteins and various amounts of luteininzing hormone. The amino acid sequence of r-FSH is identical to that of human FSH, but the two recombinant products exist in many different isoforms and differ from each other and from human FSH due to varied carbohydrate side chains. Due to variation in the carbohydrate side chains, follitropin-beta in solution has a higher pH than urine-derived FSH, which enhances receptor affinity and therefore is a greater inducer of folliculogenesis. Follitropin-beta does not cause endogenous production of anti-CHO or anti-FSH antibodies, and is well tolerated.

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

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

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.

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.

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

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.

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.

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

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.

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.

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.

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.

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

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

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

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.

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.

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.

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

The atypical cadherin Celsr1 functions non-cell autonomously to block rostral migration of facial branchiomotor neurons in mice.

PubMed

Glasco, Derrick M; Pike, Whitney; Qu, Yibo; Reustle, Lindsay; Misra, Kamana; Di Bonito, Maria; Studer, Michele; Fritzsch, Bernd; Goffinet, André M; Tissir, Fadel; Chandrasekhar, Anand

2016-09-01

The caudal migration of facial branchiomotor (FBM) neurons from rhombomere (r) 4 to r6 in the hindbrain is an excellent model to study neuronal migration mechanisms. Although several Wnt/Planar Cell Polarity (PCP) components are required for FBM neuron migration, only Celsr1, an atypical cadherin, regulates the direction of migration in mice. In Celsr1 mutants, a subset of FBM neurons migrates rostrally instead of caudally. Interestingly, Celsr1 is not expressed in the migrating FBM neurons, but rather in the adjacent floor plate and adjoining ventricular zone. To evaluate the contribution of different expression domains to neuronal migration, we conditionally inactivated Celsr1 in specific cell types. Intriguingly, inactivation of Celsr1 in the ventricular zone of r3-r5, but not in the floor plate, leads to rostral migration of FBM neurons, greatly resembling the migration defect of Celsr1 mutants. Dye fill experiments indicate that the rostrally-migrated FBM neurons in Celsr1 mutants originate from the anterior margin of r4. These data suggest strongly that Celsr1 ensures that FBM neurons migrate caudally by suppressing molecular cues in the rostral hindbrain that can attract FBM neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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.

Minimal functional β-cell mass in intraportal implants that reduces glycemic variability in type 1 diabetic recipients.

PubMed

Gillard, Pieter; Hilbrands, Robert; Van de Velde, Ursule; Ling, Zhidong; Lee, Da Hae; Weets, Ilse; Gorus, Frans; De Block, Christophe; Kaufman, Leonard; Mathieu, Chantal; Pipeleers, Daniel; Keymeulen, Bart

2013-11-01

Previous work has shown a correlation between β-cell number in cultured islet cell grafts and their ability to induce C-peptide secretion after intraportal implantation in C-peptide-negative type1 diabetic patients. In this cross-sectional study, we examined the minimal functional β-cell mass (FBM) in the implant that induces metabolic improvement. Glucose clamps assessed FBM in 42 recipients with established implants. C-peptide release during each phase was expressed as percentage of healthy control values. Its relative magnitude during a second hyperglycemic phase was most discriminative and therefore selected as a parameter to be correlated with metabolic effects. Recipients with functioning β-cell implants exhibited average FBM corresponding to 18% of that in normal control subjects (interquartile range 10-33%). Its relative magnitude negatively correlated with HbA1c levels (r = -0.47), daily insulin dose (r = -0.75), and coefficient of variation of fasting glycemia (CVfg) (r = -0.78, retained in multivariate analysis). A correlation between FBM and CVfg <25% appeared from the receiver operating characteristic curve (0.97 [95% CI 0.93-1.00]). All patients with FBM >37% exhibited CVfg <25% and a >50% reduction of their pretransplant CVfg; this occurred in none with FBM <5%. Implants with FBM >18% reduced CVfg from a median pretransplant value of 46 to <25%. Glucose clamping assesses the degree of restoration in FBM achieved by islet cell implants. Values >37% of normal control subjects appear needed to reduce glycemic variability in type 1 diabetic recipients. Further studies should examine whether the test can help guide decisions on additional islet cell transplants and on adjusting or stopping immunotherapy.

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.

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.

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

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

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.

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.

Association between quantitative measures obtained using fluorescence-based methods and activity status of occlusal caries lesions in primary molars.

PubMed

Novaes, Tatiane Fernandes; Reyes, Alessandra; Matos, Ronilza; Antunes-Pontes, Laura Regina; Marques, Renata Pereira de Samuel; Braga, Mariana Minatel; Diniz, Michele Baffi; Mendes, Fausto Medeiros

2017-05-01

Fluorescence-based methods (FBM) can add objectiveness to diagnosis strategy for caries. Few studies, however, have focused on the evaluation of caries activity. To evaluate the association between quantitative measures obtained with FBM, clinical parameters acquired from the patients, caries detection, and assessment of activity status in occlusal surfaces of primary molars. Six hundred and six teeth from 113 children (4-14 years) were evaluated. The presence of a biofilm, caries experience, and the number of active lesions were recorded. The teeth were assessed using FBM: DIAGNOdent pen (Lfpen) and Quantitative light-induced fluorescence (QLF). As reference standard, all teeth were evaluated using the ICDAS (International Caries Detection and Assessment System) associated with clinical activity assessments. Multilevel regressions compared the FBM values and evaluated the association between the FBM measures and clinical variables related to the caries activity. The measures from the FBM were higher in cavitated lesions. Only, ∆F values distinguished active and inactive lesions. The LFpen measures were higher in active lesions, at the cavitated threshold (56.95 ± 29.60). Following regression analyses, only the presence of visible biofilm on occlusal surfaces (adjusted prevalence ratio = 1.43) and ∆R values of the teeth (adjusted prevalence ratio = 1.02) were associated with caries activity. Some quantitative measures from FBM parameters are associated with caries activity evaluation, which is similar to the clinical evaluation of the presence of visible biofilm. © 2016 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Synthesis of 3 alpha, 5 alpha-tetrahydroaldosterone.

PubMed

Harnik, M; Kashman, Y; Morris, D J

1984-06-01

3 alpha, 5 alpha-Tetrahydroaldosterone (12a), a metabolite of aldosterone, has been synthesized from the lactone 2a or, preferably 11 beta, 21-dihydroxy-5-pregnene-3,20-dione-18-oic acid 3,20-di-(ethylene glycol)-ketal (18----11) lactone 21-acetate (6b), via 11 beta, 21-dihydroxy-5 alpha-pregnane-3,20-dione-18-oic acid 3,20-di-(ethylene glycol) ketal (18----11) lactone 21-acetate (4b). Selective hydrolysis of the latter at C-3 furnished the monoketal 5 which, on reduction with potassium tri-sec-butylborohydride, yielded predominantly 3 alpha, 11 beta, 21-trihydroxy-5 alpha-pregnan-20-one-18-oic acid 20-(ethylene glycol)-ketal (18----11) lactone (8a) and its acetate 8b. Further reduction with diisobutylaluminum hydride afforded 3 alpha, 5 alpha-tetrahydroaldosterone-20-ketal (10a), which was directly hydrolyzed to 12a with dilute acid in tetrahydrofuran-dioxan. Periodate oxidation led to the gamma-etiolactone 14a, which was then further converted into 5 alpha-dihydroaldosterone-gamma-etiolactone (14c).

alpha-Hexachlorocyclohexane (alpha-HCH)

Integrated Risk Information System (IRIS)

alpha - Hexachlorocyclohexane ( alpha - HCH ) ; CASRN 319 - 84 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Ass

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

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.

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.

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.

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

Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration.

PubMed

Walsh, Gregory S; Grant, Paul K; Morgan, John A; Moens, Cecilia B

2011-07-01

Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons.

Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration

PubMed Central

Walsh, Gregory S.; Grant, Paul K.; Morgan, John A.; Moens, Cecilia B.

2011-01-01

Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons. PMID:21693519

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.

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.

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

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.

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.

Feature-based Morphometry

PubMed Central

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

2013-01-01

This paper presents feature-based morphometry (FBM), a new, fully data-driven technique for identifying group-related differences in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between all subjects, FBM models images as a collage of distinct, localized image features which may not be present in all subjects. FBM thus explicitly accounts for the case where the same anatomical tissue cannot be reliably identified in all subjects due to disease or anatomical variability. A probabilistic model describes features in terms of their appearance, geometry, and relationship to sub-groups of a population, and is automatically learned from a set of subject images and group labels. Features identified indicate group-related anatomical structure that can potentially be used as disease biomarkers or as a basis for computer-aided diagnosis. Scale-invariant image features are used, which reflect generic, salient patterns in the image. 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 obtains an equal error classification rate of 0.78 on new subjects. PMID:20426102

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.

Organocatalyzed asymmetric alpha-oxidation, alpha-aminoxylation and alpha-amination of carbonyl compounds.

PubMed

Vilaivan, Tirayut; Bhanthumnavin, Worawan

2010-02-11

Organocatalytic asymmetric alpha-oxidation and amination reactions of carbonyl compounds are highly useful synthetic methodologies, especially in generating chiral building blocks that previously have not been easily accessible by traditional methods. The concept is relatively new and therefore the list of new catalysts, oxidizing and aminating reagents, as well as new substrates, are expanding at an amazing rate. The scope of this review includes new reactions and catalysts, mechanistic aspects and synthetic applications of alpha-oxidation, hydroxylation, aminoxylation, amination, hydrazination, hydroxyamination and related alpha-heteroatom functionalization of aldehydes, ketones and related active methylene compounds published during 2005-2009.

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

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)alpha

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.

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

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.

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.

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.

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.

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...

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...

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...

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;

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

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.

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.

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 ...

Alpha fetoprotein

MedlinePlus

... this page: //medlineplus.gov/ency/article/003573.htm Alpha fetoprotein To use the sharing features on this page, please enable JavaScript. Alpha fetoprotein (AFP) is a protein produced by the liver ...

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.

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.

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.

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.

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.

Preparation of 3 beta, 5 alpha-, 3 alpha, 5 alpha- and 3 alpha, 5 beta-tetrahydro derivatives of 19-noraldosterone by chemical synthesis and microbial bioconversion.

PubMed

Harnik, M; Kashman, Y; Carmely, S; Cojocaru, M

1988-07-01

The 3 beta, 5 alpha-, 3 alpha, 5 alpha- and 3 alpha, 5 beta-tetrahydro derivatives 19, 20 and 27 of 19-noraldosterone (1) were prepared to facilitate the search for these compounds in urine. The diketal 4, consisting of a 2:1 mixture of the 5,6- and 5(10)-ene isomers, was hydrogenated with Pd-C and partially hydrolyzed to 5 alpha, 10 alpha- and 5 alpha, 10 beta-dihydroketals 8 and 10 in a 1:2.5 ratio. Assignment of protons was done with aid of COSY 45 experiments. Compound 10 was reduced with diisobutylaluminum hydride (DIBAH) to 4 products: the 3 alpha- and 3 beta-ol hemiacetals 16 and 15, and the corresponding tetraols 14 and 13. Alternatively, hydrogenation of the 4-en-3-one 2 gave 10, its 5 beta, 10 beta-isomer 21 and the tetrahydro compound 22, in a 4:2:1 ratio. A better way to prepare the 5 beta, 10 beta-series involved microbial conversion of 2 with Clostridium paraputrificum, and the resulting tetrahydrolactone 23 was reduced with DIBAH to the hemiacetal 24. Acid hydrolysis of 16, 15 and 24 afforded 20, 19 and 27, respectively. According to [1H]-NMR, in solution 20 and 24 exist as mixtures of isomers, while 19 appears in one form only. Periodate oxidation converted 19 and 27 into their gamma-etiolactones 18 and 28. EI MS base peaks are different and characteristic for 19, 20 and 27.

[Building immune microsphere against tumor necrosis factor-alpha (TNF-alpha)].

PubMed

Wang, Qin; Wu, Xiongfei; Wang, Junxia; Liu, Hong; Li, Lian; Jin, Xiyu

2005-12-01

We have constructed the immune microsphere against tumor necrosis factor-alpha (TNF-alpha) prospectively, hoping to establish the experiment groundwork in more researches which could be used in specific elimination of the TNF-alpha by blood purification method for the future. The recombinant human tumor necrosis factor-alpha monoclonal antibody (rHTNF-alpha McAb) was wrapped on the polystyrene microsphere (PSM) carrier connecting poly-L-lysine (PLL) beforehand. They were earmarked by the fluorescein isothiocyanate (FITC) respectively. The packing conditions were examined using the inversted and fluorescence microscopes and the spectrophotometer. The results showed that the best conditions for wrapping were 20 degrees C, pH9.5 and 60 minutes. The PLL content was not changed in the washing fluid after coating, which indicated the wrapping was quite firm. At the same temperature and same coating time, the rHTNF-alpha McAb coated on the PLL was obviously substantial when the concentration of glutaraldehyde solution was 0.2%. The findings demonstrated that the built immune microsphers can be used as a novel adsorption material. This method is simple and economic, and it offers a new approach to the related studies.

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.

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.

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.

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.

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.

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.

alpha-decay half-lives and Q{sub a}lpha values of superheavy nuclei

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

Dong Jianmin; Graduate University of Chinese Academy of Sciences, Beijing 100049; School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000

2010-06-15

The alpha-decay half-lives of recently synthesized superheavy nuclei (SHN) are investigated by employing a unified fission model (UFM) where a new method to calculate the assault frequency of alpha emission is used. The excellent agreement with the experimental data indicates the UFM is a useful tool to investigate these alpha decays. It is found that the alpha-decay half-lives become more and more insensitive to the Q{sub a}lpha values as the atomic number increases on the whole, which is favorable for us to predict the half-lives of SHN. In addition, a formula is proposed to compute the Q{sub a}lpha values formore » the nuclei with Z>=92 and N>=140 with a good accuracy, according to which the long-lived SHN should be neutron rich. Several weeks ago, two isotopes of a new element with atomic number Z=117 were synthesized and their alpha-decay chains have been observed. The Q{sub a}lpha formula is found to work well for these nuclei, confirming its predictive power. The experimental half-lives are well reproduced by employing the UFM with the experimental Q{sub a}lpha values. This fact that the experimental half-lives are compatible with experimental Q{sub a}lpha values supports the synthesis of a new element 117 and the experimental measurements to a certain extent.« less

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.

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.

[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.

Folate receptor {alpha} regulates cell proliferation in mouse gonadotroph {alpha}T3-1 cells

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

Yao, Congjun; Evans, Chheng-Orn; Stevens, Victoria L.

We have previously found that the mRNA and protein levels of the folate receptor alpha (FR{alpha}) are uniquely over-expressed in clinically human nonfunctional (NF) pituitary adenomas, but the mechanistic role of FR{alpha} has not fully been determined. We investigated the effect of FR{alpha} over-expression in the mouse gonadotroph {alpha}T3-1 cell line as a model for NF pituitary adenomas. We found that the expression and function of FR{alpha} were strongly up-regulated, by Western blotting and folic acid binding assay. Furthermore, we found a higher cell growth rate, an enhanced percentage of cells in S-phase by BrdU assay, and a higher PCNAmore » staining. These observations indicate that over-expression of FR{alpha} promotes cell proliferation. These effects were abrogated in the same {alpha}T3-1 cells when transfected with a mutant FR{alpha} cDNA that confers a dominant-negative phenotype by inhibiting folic acid binding. Finally, by real-time quantitative PCR, we found that mRNA expression of NOTCH3 was up-regulated in FR{alpha} over-expressing cells. In summary, our data suggests that FR{alpha} regulates pituitary tumor cell proliferation and mechanistically may involve the NOTCH pathway. Potentially, this finding could be exploited to develop new, innovative molecular targeted treatment for human NF pituitary adenomas.« less

Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: no association with neuroaxonal dystrophy?

PubMed

Bakker, H D; de Sonnaville, M L; Vreken, P; Abeling, N G; Groener, J E; Keulemans, J L; van Diggelen, O P

2001-02-01

Two new individuals with alpha-NAGA deficiency are presented. The index patient, 3 years old, has congenital cataract, slight motor retardation and secondary demyelinisation. Screening of his sibs revealed an alpha-NAGA deficiency in his 7-year-old healthy brother who had no clinical or neurological symptoms. Both sibs are homozygous for the E325K mutation, the same genotype that was found in the most severe form of alpha-NAGA deficiency presenting as infantile neuroaxonal dystrophy. Thus, at the age of 7 years the same genotype of alpha-NAGA may present as a 'non-disease' (present healthy case) and can be associated with the vegetative state (the first two patients described with alpha-NAGA deficiency). The clinical heterogeneity among the 11 known individuals with alpha-NAGA deficiency is extreme, with a 'non-disease' (two cases) and infantile neuroaxonal dystrophy (two cases) at the opposite sides of the clinical spectrum. The broad spectrum is completed by a very heterogeneous group of patients with various degrees of epilepsy/behavioural difficulties/psychomotor retardation (four patients) and a mild phenotype in adults without overt neurological manifestations who have angiokeratoma and clear vacuolisation in various cell types (three cases). These observations are difficult to reconcile with a straightforward genotype-phenotype correlation and suggest that factors or genes other than alpha-NAGA contribute to the clinical heterogeneity of the 11 patients with alpha-NAGA deficiency.

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.

In vitro and in vivo expression of interleukin-1alpha and tumor necrosis factor-alpha mRNA in pemphigus vulgaris: interleukin-1alpha and tumor necrosis factor-alpha are involved in acantholysis.

PubMed

Feliciani, C; Toto, P; Amerio, P; Pour, S M; Coscione, G; Shivji, G; Wang, B; Sauder, D N

2000-01-01

Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in pemphigus vulgaris. Nineteen patients with pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied. In situ immunolabeling demonstrated the presence of two cytokines interleukin-1alpha and tumor necrosis factor-alpha, in lesional and perilesional areas. Results were confirmed by reverse transcriptase-polymerase chain reaction, demonstrating overexpression of both cytokines in vivo. To study the role of these cytokines in the pathogenesis of pemphigus vulgaris both in vitro and in vivo studies were performed. The results of the in vitro study demonstrated that pemphigus vulgaris IgG induced interleukin-1alpha and tumor necrosis factor-alpha mRNA in the skin. The potential pathogenic role of these mediators was demonstrated by a blocking study using antibodies against human interleukin-1alpha and tumor necrosis factor-alpha in keratinocytes cultures. A combination of anti-interleukin-1alpha and anti-tumor necrosis factor-alpha antibodies inhibited in vitro pemphigus vulgaris IgG induced acantholysis. To confirm the role of interleukin-1 and tumor necrosis factor-alpha in pemphigus, we utilized passive transfer studies using interleukin-1 deficient mice (ICE-/-, interleukin-1beta-/-) and tumor necrosis factor-alpha receptor deficient mice (TNFR1R2-/-). Both groups demonstrated a decreased susceptibility to the passive transfer of pemphigus. Our data support the role of cytokines interleukin-1 and tumor necrosis factor-alpha in the pathogenesis of pemphigus vulgaris.

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.

Methods for the synthesis and polymerization of .alpha.,.alpha.'-dihalo-p-xylenes

DOEpatents

Ferraris, John P.; Neef, Charles J.

2002-07-30

The present invention describes an improved method for the polymerization of .alpha.,.alpha.-dihalo-p-xylene's such as the .alpha.,.alpha.'-dihalo-2-methoxy-5-(2-ethylhexyloxy)-xylene's. The procedure for synthesis is based on the specific order of addition of reagents and the use of an anionic initiator that allows control of the molecular weight of the polymer. The molecular weight control allows processability of the polymer which is important for its utility in applications including in light-emitting-diodes, field effect transistors and photovoltaic devices.

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.

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.

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

A new stable alpha chain variant: Hb Basel [alpha14(A12)Trp-->Leu (alpha1)].

PubMed

Hergersberg, Martin; Brunner-Agten, Saskia; Kühne, Thomas; Paulussen, Michael; Huber, Andreas R

2010-06-01

We describe a heterozygosity for a new missense mutation on the alpha1-globin gene of an 18-year-old woman of Portuguese ancestry with severe hypochromic anemia and iron deficiency. Hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) found a prominent peak constituting about 12% of total Hb. Sequencing of the globin genes of the index patient found the mutation alpha14(A12)Trp-->Leu (alpha1), HBA1:c.44G

Determination of the alpha(s) using jet rates at LEP

NASA Astrophysics Data System (ADS)

Donkers, Michael A.

Jets are produced in any high energy collision of particles in which quarks are produced in the final state. Using the OPAL detector to measure particles produced in e+e- collisions at the LEP accelerator, the rate of jet formation has been measured at 91 GeV as well as each of the LEP2 energies, ranging from 161 GeV to 207 GeV. The jet rate observables, in particular the differential 2-jet rate and the average jet rate can be used to determine a value of the strong coupling constant, alphas, by fitting to various theoretical predictions. The value of alphas has been determined using data at 91 GeV and a combined sample comprising all of the LEP2 energies with a luminosity weighted centre-of-mass energy of 195.8 GeV for 10 theoretical predictions and two jet clustering algorithms. A fit of the 91 GeV and LEP2 values of alphas determined using the ln R matching prediction is also performed on the D2 and distributions to the 3-loop alphas prediction to produce 4 values of alphas(MZ 0).

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.

Event counting alpha detector

DOEpatents

Bolton, Richard D.; MacArthur, Duncan W.

1996-01-01

An electrostatic detector for atmospheric radon or other weak sources of alpha radiation. In one embodiment, nested enclosures are insulated from one another, open at the top, and have a high voltage pin inside and insulated from the inside enclosure. An electric field is produced between the pin and the inside enclosure. Air ions produced by collision with alpha particles inside the decay volume defined by the inside enclosure are attracted to the pin and the inner enclosure. With low alpha concentrations, individual alpha events can be measured to indicate the presence of radon or other alpha radiation. In another embodiment, an electrical field is produced between parallel plates which are insulated from a single decay cavity enclosure.

The Alpha Centauri System.

ERIC Educational Resources Information Center

Soderblom, David R.

1987-01-01

Describes the Alpha Centauri star system, which is the closest star system to the sun. Discusses the difficulties associated with measurements involving Alpha Centauri, along with some of the recent advances in stellar seismology. Raises questions about the possibilities of planets around Alpha Centauri. (TW)

Alpha Kappa Alpha Sorority's Reading Improvement Program for Minorities.

ERIC Educational Resources Information Center

Marable, June Morehead

This document discusses the founding and establishment of Alpha Kappa Alpha Sorority's reading experience pilot project. The efforts of this project were aligned with those of Right to Read and Reading Is Fundamental (RIF). Because of the response from parents and children, plans are being made to increase present operations within the next…

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

Alpha-Mannosidosis: Therapeutic Strategies.

PubMed

Ceccarini, Maria Rachele; Codini, Michela; Conte, Carmela; Patria, Federica; Cataldi, Samuela; Bertelli, Matteo; Albi, Elisabetta; Beccari, Tommaso

2018-05-17

Alpha-mannosidosis (α-mannosidosis) is a rare lysosomal storage disorder with an autosomal recessive inheritance caused by mutations in the gene encoding for the lysosomal α-d-mannosidase. So far, 155 variants from 191 patients have been identified and in part characterized at the biochemical level. Similarly to other lysosomal storage diseases, there is no relationship between genotype and phenotype in alpha-mannosidosis. Enzyme replacement therapy is at the moment the most effective therapy for lysosomal storage disease, including alpha-mannosidosis. In this review, the genetic of alpha-mannosidosis has been described together with the results so far obtained by two different therapeutic strategies: bone marrow transplantation and enzyme replacement therapy. The primary indication to offer hematopoietic stem cell transplantation in patients affected by alpha-mannosidosis is preservation of neurocognitive function and prevention of early death. The results obtained from a Phase I⁻II study and a Phase III study provide evidence of the positive clinical effect of the recombinant enzyme on patients with alpha-mannosidosis.

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.

Event counting alpha detector

DOEpatents

Bolton, R.D.; MacArthur, D.W.

1996-08-27

An electrostatic detector is disclosed for atmospheric radon or other weak sources of alpha radiation. In one embodiment, nested enclosures are insulated from one another, open at the top, and have a high voltage pin inside and insulated from the inside enclosure. An electric field is produced between the pin and the inside enclosure. Air ions produced by collision with alpha particles inside the decay volume defined by the inside enclosure are attracted to the pin and the inner enclosure. With low alpha concentrations, individual alpha events can be measured to indicate the presence of radon or other alpha radiation. In another embodiment, an electrical field is produced between parallel plates which are insulated from a single decay cavity enclosure. 6 figs.

Distinct expression pattern of IFN-alpha and TNF-alpha in juvenile idiopathic arthritis synovial tissue.

PubMed

Gattorno, M; Chicha, L; Gregorio, A; Ferlito, F; Rossi, F; Jarrossay, D; Lanzavecchia, A; Martini, A; Manz, M G

2007-04-01

Recent laboratory and clinical data suggest that two prototype autoimmune diseases, systemic lupus erythematosus and rheumatoid arthritis are mainly driven by distinct cytokines, interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha, respectively. We here investigated the presence and characteristics of natural type I IFN-producing cells (IPCs), as well as IFN-alpha and TNF-alpha expression at sites of inflammation in juvenile idiopathic arthritis (JIA). Peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MNCs) (n = 25 each) from JIA patients with active disease were studied. IPCs were identified as BCDA-2(+)CD123(+)HLA-DR(+)CD45RA(+) cells, and dendritic cells (DCs) as CD11c(+)CD14(-/low)lin(-) cells by flow cytometry. IPCs and DCs were analysed for Toll-like receptor-7 and -9 mRNA expression by real-time polymerase chain reaction. IFN-alpha was measured by enzyme-linked immunosorbent assay in serum, SF and in supernatants of influenza virus-infected, cultured IPCs. Synovial tissues of n = 6 additional JIA patients were analysed by immunohistochemistry using mAbs against CD123, IFN-alpha, TNF-alpha, CD3, CD19 and CD138. IPCs were enriched in SF MNCs compared with PB MNCs in all JIA patients. Influenza-induced, but no spontaneous IFN-alpha release was detected from SF IPCs, and serum and SF IFN-alpha levels were not elevated. Nonetheless, in synovial tissue IFN-alpha producing cells accumulated at inflammatory lymph-follicular-like structures, while TNF-alpha producing cells were mostly found at the lining and sublining layers. These data suggest that besides TNF-alpha-expressing cells, IFN-alpha-producing IPCs are involved in initiation, maintenance or regulation of the inflammatory response in JIA.

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.

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.

Total alpha-fetoprotein and Lens culinaris agglutinin-reactive alpha-fetoprotein in fetal chromosomal abnormalities.

PubMed

Yamamoto, R; Azuma, M; Kishida, T; Yamada, H; Satomura, S; Fujimoto, S

2001-11-01

To examine the differences in multiples of the median (MoM) of total alpha-fetoprotein, and the proportion of Lens culinaris agglutinin reactive alpha-fetoprotein (% alpha-fetoprotein-L2 + L3) in the maternal serum and amniotic fluid of pregnant women whose fetuses were diagnosed with autosomal or sex chromosomal abnormalities. Prospective consecutive series. University hospital. Maternal sera and amniotic fluids from 46 pregnant women with trisomy 21 fetuses, 10 pregnant women with trisomy 18 fetuses, one pregnant woman with a trisomy 13 fetus, six pregnant women with fetal sex chromosomal abnormalities, and 100 pregnant women for whom the fetal karyotype was diagnosed as normal following a genetic amniocentesis. The proportion of alpha-fetoprotein-L2 + L3 in maternal serum for trisomy 21 (40.3%. P < 0.0001) and trisomy 18 (39.8%, P < 0.05) showed a significantly higher value compared with normal (32.6%). The proportion of alpha-fetoprotein-L2 + L3 in amniotic fluid was significantly higher (P < 0.0001) for trisomy 21 (46.6%) than for a normal karyotype (41.5%). Only for the trisomy 21 group was there a strong correlation in the % alpha-fetoprotein-L2 + L3 between maternal serum and amniotic fluid (r = 0.840, P < 0.0001). For all groups, there was no correlation between alpha-fetoprotein MoM and % alpha-fetoprotein-L2 + L3 in maternal serum and amniotic fluid. The proportion of alpha-fetoprotein-L2 + L3 in maternal serum is an appropriate choice for a trisomy 21 biochemical marker, and it is possible that combining alpha-fetoprotein-L2 + L3 analysis with assays of alpha-fetoprotein in maternal serum could further improve the sensitivity and specificity of multiple marker screening.

Localization and characterization of an alpha-thrombin-binding site on platelet glycoprotein Ib alpha.

PubMed

De Marco, L; Mazzucato, M; Masotti, A; Ruggeri, Z M

1994-03-04

Glycoprotein (GP) Ib alpha is required for expression of the highest affinity alpha-thrombin-binding site on platelets, possibly contributing to platelet activation through a pathway involving cleavage of a specific receptor. This function may be important for the initiation of hemostasis and may also play a role in the development of pathological vascular occlusion. We have now identified a discrete sequence in the extracytoplasmic domain of GP Ib alpha, including residues 271-284 of the mature protein, which appears to be part of the high affinity alpha-thrombin-binding site. Synthetic peptidyl mimetics of this sequence inhibit alpha-thrombin binding to GP Ib as well as platelet activation and aggregation induced by subnanomolar concentrations of the agonist; they also inhibit alpha-thrombin binding to purified glycocalicin, the isolated extracytoplasmic portion of GP Ib alpha. The inhibitory peptides interfere with the clotting of fibrinogen by alpha-thrombin but not with the amidolytic activity of the enzyme on a small synthetic substrate, a finding compatible with the concept that the identified GP Ib alpha sequence interacts with the anion-binding exosite of alpha-thrombin but not with its active proteolytic site. The crucial structural elements of this sequence necessary for thrombin binding appear to be a cluster of negatively charged residues as well as three tyrosine residues that, in the native protein, may be sulfated. GP Ib alpha has no significant overall sequence homology with the thrombin inhibitor, hirudin, nor with the specific thrombin receptor on platelets; all three molecules, however, possess a distinct region rich in negatively charged residues that appear to be involved in thrombin binding. This may represent a case of convergent evolution of unrelated proteins for high affinity interaction with the same ligand.

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

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

The alpha channeling effect

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

Fisch, N. J.

2015-12-10

Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a waymore » that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.« less

The alpha channeling effect

NASA Astrophysics Data System (ADS)

Fisch, N. J.

2015-12-01

Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

Influence of fast alpha diffusion and thermal alpha buildup on tokamak reactor performance

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

Uckan, N.A.; Tolliver, J.S.; Houlberg, W.A.

1987-11-01

The effect of fast alpha diffusion and thermal alpha accumulation on the confinement capability of a candidate Engineering Test Reactor (ETR) plasma (Tokamak Ignition/Burn Experimental Reactor (TIBER-II)) in achieving ignition and steady-state driven operation has been assessed using both global and 1-1/2-D transport models. Estimates are made of the threshold for radial diffusion of fast alphas and thermal alpha buildup. It is shown that a relatively low level of radial transport, when combined with large gradients in the fast alpha density, leads to a significant radial flow with a deleterious effect on plasma performance. Similarly, modest levels of thermal alphamore » concentration significantly influence the ignition and steady-state burn capability. 23 refs., 9 figs., 4 tabs.« less

Resting-State Alpha in Autism Spectrum Disorder and Alpha Associations with Thalamic Volume

ERIC Educational Resources Information Center

Edgar, J. Christopher; Heiken, Kory; Chen, Yu-Han; Herrington, John D.; Chow, Vivian; Liu, Song; Bloy, Luke; Huang, Mingxiong; Pandey, Juhi; Cannon, Katelyn M.; Qasmieh, Saba; Levy, Susan E.; Schultz, Robert T.; Roberts, Timothy P. L.

2015-01-01

Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha…

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.

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...

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

Genetics Home Reference: alpha thalassemia

MedlinePlus

... Facebook Twitter Home Health Conditions Alpha thalassemia Alpha thalassemia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alpha thalassemia is a blood disorder that reduces the production ...

Coaching the alpha male.

PubMed

Ludeman, Kate; Erlandson, Eddie

2004-05-01

Highly intelligent, confident, and successful, alpha males represent about 70% of all senior executives. Natural leaders, they willingly take on levels of responsibility most rational people would find overwhelming. But many of their quintessential strengths can also make alphas difficult to work with. Their self-confidence can appear domineering. Their high expectations can make them excessively critical. Their unemotional style can keep them from inspiring their teams. That's why alphas need coaching to broaden their interpersonal tool kits while preserving their strengths. Drawing from their experience coaching more than 1,000 senior executives, the authors outline an approach tailored specifically for the alpha. Coaches get the alpha's attention by inundating him with data from 360-degree feedback presented in ways he will find compelling--both hard-boiled metrics and vivid verbatim comments from colleagues about his strengths and weaknesses. A 360-degree assessment is a wake-up call for most alphas, providing undeniable proof that their behavior doesn't work nearly as well as they think it does. That paves the way for a genuine commitment to change. In order to change, the alpha must venture into unfamiliar--and often uncomfortable--psychological territory. He must admit vulnerability, accept accountability not just for his own work for others', connect with his underlying emotions, learn to motivate through a balance of criticism and validation, and become aware of unproductive behavior patterns. The goal of executive coaching is not simply to treat the alpha as an individual problem but to improve the entire team dynamic. Initial success creates an incentive to persevere, and the virtuous cycle reverberates throughout the entire organization.

Experimental and Theoretical Electron Density Distribution of Alpha,Alpha-Trehalose Dihydrate

USDA-ARS?s Scientific Manuscript database

Alpha,alpha-rehalose is of interest because of its cryoprotective and antidessicant properties, and because it possesses various technical anomalies such as 13C NMR spectra that give misleading indications of intramolecular structural symmetry. It is a non-reducing disaccharide, with the glycosidic...

Background canceling surface alpha detector

DOEpatents

MacArthur, D.W.; Allander, K.S.; Bounds, J.A.

1996-06-11

A background canceling long range alpha detector which is capable of providing output proportional to both the alpha radiation emitted from a surface and to radioactive gas emanating from the surface. The detector operates by using an electrical field between first and second signal planes, an enclosure and the surface or substance to be monitored for alpha radiation. The first and second signal planes are maintained at the same voltage with respect to the electrically conductive enclosure, reducing leakage currents. In the presence of alpha radiation and radioactive gas decay, the signal from the first signal plane is proportional to both the surface alpha radiation and to the airborne radioactive gas, while the signal from the second signal plane is proportional only to the airborne radioactive gas. The difference between these two signals is proportional to the surface alpha radiation alone. 5 figs.

Background canceling surface alpha detector

DOEpatents

MacArthur, Duncan W.; Allander, Krag S.; Bounds, John A.

1996-01-01

A background canceling long range alpha detector which is capable of providing output proportional to both the alpha radiation emitted from a surface and to radioactive gas emanating from the surface. The detector operates by using an electrical field between first and second signal planes, an enclosure and the surface or substance to be monitored for alpha radiation. The first and second signal planes are maintained at the same voltage with respect to the electrically conductive enclosure, reducing leakage currents. In the presence of alpha radiation and radioactive gas decay, the signal from the first signal plane is proportional to both the surface alpha radiation and to the airborne radioactive gas, while the signal from the second signal plane is proportional only to the airborne radioactive gas. The difference between these two signals is proportional to the surface alpha radiation alone.

Imaging alpha particle detector

DOEpatents

Anderson, D.F.

1980-10-29

A method and apparatus for detecting and imaging alpha particles sources is described. A dielectric coated high voltage electrode and a tungsten wire grid constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source to be quantitatively or qualitatively analyzed. A thin polyester film window allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

Imaging alpha particle detector

DOEpatents

Anderson, David F.

1985-01-01

A method and apparatus for detecting and imaging alpha particles sources is described. A conducting coated high voltage electrode (1) and a tungsten wire grid (2) constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source (3) to be quantitatively or qualitatively analyzed. A thin polyester film window (4) allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

Characterization of Alpha-Toxin hla Gene Variants, Alpha-Toxin Expression Levels, and Levels of Antibody to Alpha-Toxin in Hemodialysis and Postsurgical Patients with Staphylococcus aureus Bacteremia

PubMed Central

Wu, Yuling; Tabor, David E.; Mok, Hoyin; Sellman, Bret R.; Jenkins, Amy; Yu, Li; Jafri, Hasan S.; Rude, Thomas H.; Ruffin, Felicia; Schell, Wiley A.; Park, Lawrence P.; Yan, Qin; Thaden, Joshua T.; Messina, Julia A.; Esser, Mark T.

2014-01-01

Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with S. aureus bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100 postsurgical SAB patients. Isolates underwent spa typing and hla sequencing. Serum anti-alpha-toxin IgG and neutralizing antibody levels were measured by using an enzyme-linked immunosorbent assay and a red blood cell (RBC)-based hemolysis neutralization assay. Neutralization of alpha-toxin by an anti-alpha-toxin monoclonal antibody (MAb MEDI4893) was tested in an RBC-based lysis assay. Most isolates encoded hla (197/200; 98.5%) and expressed alpha-toxin (173/200; 86.5%). In vitro alpha-toxin levels were inversely associated with survival (cure, 2.19 μg/ml, versus failure, 1.09 μg/ml; P < 0.01). Both neutralizing (hemodialysis, 1.26 IU/ml, versus postsurgical, 0.95; P < 0.05) and IgG (hemodialysis, 1.94 IU/ml, versus postsurgical, 1.27; P < 0.05) antibody levels were higher in the hemodialysis population. Antibody levels were also significantly higher in patients infected with alpha-toxin-expressing S. aureus isolates (P < 0.05). Levels of both neutralizing antibodies and IgG were similar among patients who were cured and those not cured (failures). Sequence analysis of hla revealed 12 distinct hla genotypes, and all genotypic variants were susceptible to a neutralizing monoclonal antibody in clinical development (MEDI4893). These data demonstrate that alpha-toxin is highly conserved in clinical S. aureus isolates. Higher in vitro alpha-toxin levels were associated with a positive clinical outcome. Although patients infected with alpha-toxin-producing S. aureus exhibited higher anti-alpha-toxin antibody levels, these levels were not associated with a better clinical outcome in this study. PMID:25392350

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

{alpha}+{alpha} scattering reexamined in the context of the Sao Paulo potential

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

Chamon, L. C.; Gasques, L. R.; Carlson, B. V.

2011-03-15

We have analyzed a large set of {alpha}+{alpha} elastic scattering data for bombarding energies ranging from 0.6 to 29.5 MeV. Because of the complete lack of open reaction channels, the optical interaction at these energies must have a vanishing imaginary part. Thus, this system is particularly important because the corresponding elastic scattering cross sections are very sensitive to the real part of the interaction. The data were analyzed in the context of the velocity-dependent Sao Paulo potential, which is a successful theoretical model for the description of heavy-ion reactions from sub-barrier to intermediate energies. We have verified that, even inmore » this low-energy region, the velocity dependence of the model is quite important for describing the data of the {alpha}+{alpha} system.« less

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...

Importance of agonists in alpha-adrenoceptor classification and localisation of alpha1-adrenoceptors in human prostate.

PubMed

McGrath, J C; Naghadeh, M A; Pediani, J D; Mackenzie, J F; Daly, C J

1999-01-01

alpha-Adrenoceptor blocker drugs are commonly used in the clinical (non-surgical) treatment of BPH. alpha1-adrenoceptors were originally sub-divided using agonists but, subsequently, were sub-divided using only antagonists in ligand-ligand interactions, which did not require agonists at all. Ultimately, proof that adrenoceptors are functional receptors for the natural ligands, noradrenaline and adrenaline, requires that agonists be used. The earlier excitement engendered by finding varying agonist potency series in different tissues has not been revisited to place it in the context of current concepts of alpha1-adrenoceptor subtypes. This review will consider the advantages and limitations of different agonists for the study of alpha1-adrenoceptor subtypes including 'extreme' examples where the archetypal alpha1-adrenoceptor agonist phenylephrine activates alpha2-adrenoceptors and others where UK14304, often the alpha2-adrenoceptor agonist of choice, activates alpha1-adrenoceptors. New work will also be presented showing the interaction between agonists and the fluorescent alpha1-adrenoceptor antagonist QAPB. This introduces the novel point of view of studying the displacement of antagonists by agonists. Possible errors in antagonist classification arising from complexity in the actions of agonists and the recently developed method of fluorescent ligand binding on isolated living human prostatic smooth muscle cells will be discussed.

Alpha-dispersion in human tissue

NASA Astrophysics Data System (ADS)

Grimnes, Sverre; Martinsen, Ørjan G.

2010-04-01

Beta dispersion is found in living tissue in the kilohertz - megahertz range and is caused by the cellular structure of biological materials with low frequency properties caused by cell membranes. Alpha dispersion is found in the hertz range and the causes are not so well known. Alpha dispersions are the first to disappear when tissue dies. Tissue data have often been based upon excised specimen from animals and are therefore not necessarily representative for human tissue alpha dispersions. Here we present data obtained with non-invasive skin surface electrodes for different segments of the living human body. We found alpha dispersions in all cases; the ankle-wrist results had the smallest. Large alpha dispersions were found where the distance between the electrodes and muscle masses was small, e.g. on the calf. Further studies on electrode technique and reciprocity, electrode positioning, statistical variations, gender, age and bodily constitutions are necessary in order to reveal more about the alpha dispersion, its appearance and disappearance.

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

Simultaneous measurements of the hydrogen airglow emissions of Lyman alpha, Lyman beta, and Balmer alpha.

NASA Technical Reports Server (NTRS)

Weller, C. S.; Meier, R. R.; Tinsley, B. A.

1971-01-01

Comparison of Lyman-alpha, 740- to 1050-A, and Balmer-alpha airglow measurements made at 134 deg solar-zenith angle on Oct. 13, 1969, with resonance-scattering models of solar radiation. Model comparison with Lyman-alpha data fixes the hydrogen column abundance over 215 km to 2 x 10 to the 13th per cu cm within a factor of 2. Differences between the Lyman-alpha model and data indicate a polar-equatorial departure from spherical symmetry in the hydrogen distribution. A Lyman-beta model based on the hydrogen distribution found to fit the Lyman-alpha data fits the spatial variation of the 740- to 1050-A data well from 100 to 130 km, but it does not fit the data well at higher altitudes; thus the presence of more rapidly absorbed shorter-wavelength radiation is indicated. This same resonance-scattering model yields Balmer-alpha intensities that result in good spatial agreement with the Balmer-alpha measurements, but a fivefold increase in the measured solar line center Lyman-beta flux is required (as required for the Lyman-beta measurement). The intensity ratio of Lyman-beta and Balmer-alpha at night is found to be a simple measure of the hydrogen optical depth if measurements with good accuracy can be made in the visible and ultraviolet spectrum.

21 CFR 882.1610 - Alpha monitor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and... NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An alpha... electroencephalogram which is referred to as the alpha wave. (b) Classification. Class II (performance standards). ...

21 CFR 882.1610 - Alpha monitor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and... NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An alpha... electroencephalogram which is referred to as the alpha wave. (b) Classification. Class II (performance standards). ...

21 CFR 882.1610 - Alpha monitor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and... NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An alpha... electroencephalogram which is referred to as the alpha wave. (b) Classification. Class II (performance standards). ...

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...

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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...

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.

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.

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

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.

Mind Your p's and Alphas.

ERIC Educational Resources Information Center

Stallings, William M.

1985-01-01

In the educational research literature, alpha and p are often conflated. Paradoxically, alpha retains a prominent place in textbook discussions, but it is often supplanted by p in the results sections of journal articles. Because alpha and p have unique uses, researchers should continue to employ both conventions in summarizing the outcomes of…

Determination of the volume activity concentration of alpha artificial radionuclides with alpha spectrometer.

PubMed

Liu, B; Zhang, Q; Li, Y

1997-12-01

This paper introduces a method to determine the volume activity concentration of alpha and/or beta artificial radionuclides in the environment and radon/thoron progeny background-compensation based on a Si surface-barrier detector. By measuring the alpha peak counts of 218Po and 214Po in two time intervals, the activity concentration of 218Po, 214Pb and 214Bi aerosol particles were determined; meanwhile, the total beta count of 214Pb and 214Bi aerosols was also calculated from their decay scheme. With the average equilibrium factor of thoron progeny in general environment, the alpha and beta counts of thoron progeny were approximately evaluated by 212Po alpha peak counts. The alpha count of transuranic aerosols was determined by subtracting the trail counts of radon/thoron progeny alpha peaks. The total count of beta artificial radionuclides was determined by subtracting the beta counts of radon/thoron progeny aerosol particles. In our preliminary experiments, if the radon progeny concentration is less than 15 Bq m(-3), the lower limit of detection of transuranics concentration is less than 0.1 Bq m(-3). Even if the radon progeny concentration is as high as 75 Bq m(-3), the lower limit of detection of total beta activity concentration of artificial nuclides aerosols is less than 1 Bq m(-3).

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

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

Demonstration of 3 alpha(17 beta)-hydroxysteroid dehydrogenase distinct from 3 alpha-hydroxysteroid dehydrogenase in hamster liver.

PubMed Central

Ohmura, M; Hara, A; Nakagawa, M; Sawada, H

1990-01-01

NAD(+)-linked and NADP(+)-linked 3 alpha-hydroxysteroid dehydrogenases were purified to homogeneity from hamster liver cytosol. The two monomeric enzymes, although having similar molecular masses of 38,000, differed from each other in pI values, activation energy and heat stability. The two proteins also gave different fragmentation patterns by gel electrophoresis after digestion with protease. The NADP(+)-linked enzyme catalysed the oxidoreduction of various 3 alpha-hydroxysteroids, whereas the NAD(+)-linked enzyme oxidized the 3 alpha-hydroxy group of pregnanes and some bile acids, and the 17 beta-hydroxy group of testosterone and androstanes. The thermal stabilities of the 3 alpha- and 17 beta-hydroxysteroid dehydrogenase activities of the NAD(+)-linked enzyme were identical, and the two enzyme activities were inhibited by mixing 17 beta- and 3 alpha-hydroxysteroid substrates, respectively. Medroxyprogesterone acetate, hexoestrol and 3 beta-hydroxysteroids competitively inhibited 3 alpha- and 17 beta-hydroxysteroid dehydrogenase activities of the enzyme. These results show that hamster liver contains a 3 alpha(17 beta)-hydroxysteroid dehydrogenase structurally and functionally distinct from 3 alpha-hydroxysteroid dehydrogenase. Images Fig. 1. Fig. 2. PMID:2317205

Alpha channeling in a rotating plasma.

PubMed

Fetterman, Abraham J; Fisch, Nathaniel J

2008-11-14

The wave-particle alpha-channeling effect is generalized to include rotating plasma. Specifically, radio frequency waves can resonate with alpha particles in a mirror machine with ExB rotation to diffuse the alpha particles along constrained paths in phase space. Of major interest is that the alpha-particle energy, in addition to amplifying the rf waves, can directly enhance the rotation energy which in turn provides additional plasma confinement in centrifugal fusion reactors. An ancillary benefit is the rapid removal of alpha particles, which increases the fusion reactivity.

{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

Alpha Thalassemia (For Parents)

MedlinePlus

... Safe Videos for Educators Search English Español Alpha Thalassemia KidsHealth / For Parents / Alpha Thalassemia What's in this ... Symptoms Diagnosis Treatment Print en español Alfa talasemia Thalassemias Thalassemias are a group of blood disorders that ...

Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts.

PubMed

Rutault, K; Hazzalin, C A; Mahadevan, L C

2001-03-02

Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.

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.

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...

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.

Resolution of G(s)alpha and G(q)alpha/G(11)alpha proteins in membrane domains by two-dimensional electrophoresis: the effect of long-term agonist stimulation.

PubMed

Matousek, P; Novotný, J; Svoboda, P

2004-01-01

Low-density membrane-domain fractions were prepared from S49 lymphoma cells and clone e2m11 of HEK293 cells expressing a large number of thyrotropin-releasing hormone receptor (TRH-R) and G(11)alpha by flotation on sucrose density gradients. The intact cell structure was broken by detergent-extraction, alkaline-treatment or drastic homogenization. Three types of low-density membranes were resolved by two-dimensional electrophoresis and analyzed for G(s)alpha (S49) or G(q)alpha/G11) (e2m11) content. Four individual immunoblot signals of Gsalpha protein were identified in S49 lymphoma cells indicating complete resolution of the long G(s)alpha L+/-ser and short G(s)alpha S+/-ser variants of G(s)alpha. All these were diminished by prolonged agonist (isoprenaline) stimulation. In e2m11-HEK cells, five different immunoblot signals were detected indicating post-translational modification of G proteins of G(q)alpha/G(11)alpha family. The two major spots corresponding to exogenously (over)expressed G(11)alpha and endogenous G(q)alpha were reduced; the minor spots diminished by hormonal stimulation. Parallel analysis by silver staining of the total protein content indicated that no major changes in protein composition occurred under these conditions. Our data thus indicate that agonist-stimulation of target cells results in down-regulation of all different members of G(s) and G(q)/G(11) families. This agonist-specific effect may be demonstrated in crude membrane as well as domain/raft preparations and it is not accompanied by changes in overall protein composition.

Conformational restriction through C alpha i <--> C alpha i cyclization: Ac12c, the largest cycloaliphatic C alpha,alpha- disubstituted glycine known.

PubMed

Saviano, M; Iacovino, R; Menchise, V; Benedetti, E; Bonora, G M; Gatos, M; Graci, L; Formaggio, F; Crisma, M; Toniolo, C

2000-02-01

Two complete series of N-protected, monodispersed oligopeptide esters to the pentamer level from 1-aminocyclododecane-1-carboxylic acid (Ac(12)c), an alpha-amino acid conformationally constrained through C(alpha)(i) <--> C(alpha)(i) cyclization, and either L-Ala or Aib residues, along with the N-protected Ac(12)c homopeptide alkylamide series from monomer to trimer, have been synthesized by solution methods and fully characterized. The solution-preferred conformations of these peptides have been assessed by Fourier transform ir absorption and (1)H-nmr techniques. Moreover, the molecular structures of one derivative (Z-Ac(12)c-OH) and three peptides [the tripeptide ester Z-L-Ala-Ac(12)c-L-Ala-OMe, the tripeptide alkylamide Z-(Ac(12)c)(3)-NHiPr, and the tetrapeptide ester Z-(Aib)(2)-Ac(12)c-Aib-OtBu (Aib, alpha-aminoisobutyric acid)] have been determined in the crystal state by x-ray diffraction. The results obtained point to the conclusion that beta-bends and 3(10)-helices are preferentially adopted by peptides based on Ac(12)c, the largest cycloaliphatic C-disubstituted glycine known. A comparison with the structural tendencies extracted from published works on peptides from Aib, the prototype of C-disubstituted glycines, and the other extensively studied members of the class of 1-aminocycloalkane-1-carboxylic acids (Ac(n) c, with n = 3-9), is made and the implications for the use of the Ac(12)c residue in the Ac(n) c scan approach of conformationally restricted analogues of bioactive peptides are briefly discussed. Copyright 2000 John Wiley & Sons, Inc.

Identification of hydrogen peroxide oxidation sites of alpha A- and alpha B-crystallins.

PubMed

Smith, J B; Jiang, X; Abraham, E C

1997-02-01

The alpha-crystallins are the most abundant structural proteins of the lens and, because of their chaperone activity, contribute to the solubility of the other crystallins. With aging, the lens crystallins undergo a variety of modifications which correlate with a loss of solubility and the development of cataract. A recent study demonstrating that alpha-crystallins exposed in vitro to FeCl3 and H2O2 exhibit decreased chaperone activity, implicates metal catalyzed oxidations of alpha-crystallins in this loss of solubility. The present study has determined that alpha-crystallins incubated with FeCl3 and H2O2 are modified by the nearly complete oxidation of all methionine residues to methionine sulfoxide, with no other detectable reaction products. The modifications were identified from the molecular weights of peptides formed by enzymatic digestion of the alpha-crystallins and located by tandem mass spectrometric analysis of the fragmentation pattern of the mass spectra of the fragments from peptides with oxidized methionine is loss of 64 Da, which corresponds to loss of CH3SOH from the methionine sulfoxide. These fragments are useful in identifying peptides that include oxidized methionine residues.

Alpha-particle emission probabilities of ²³⁶U obtained by alpha spectrometry.

PubMed

Marouli, M; Pommé, S; Jobbágy, V; Van Ammel, R; Paepen, J; Stroh, H; Benedik, L

2014-05-01

High-resolution alpha-particle spectrometry was performed with an ion-implanted silicon detector in vacuum on a homogeneously electrodeposited (236)U source. The source was measured at different solid angles subtended by the detector, varying between 0.8% and 2.4% of 4π sr, to assess the influence of coincidental detection of alpha-particles and conversion electrons on the measured alpha-particle emission probabilities. Additional measurements were performed using a bending magnet to eliminate conversion electrons, the results of which coincide with normal measurements extrapolated to an infinitely small solid angle. The measured alpha emission probabilities for the three main peaks - 74.20 (5)%, 25.68 (5)% and 0.123 (5)%, respectively - are consistent with literature data, but their precision has been improved by at least one order of magnitude in this work. © 2013 Published by Elsevier Ltd.

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

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.

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.

Genomic structure of rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD, AKR1C9).

PubMed

Lin, H K; Hung, C F; Moore, M; Penning, T M

1999-11-01

Rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase (3alpha-HSD/DD) is a member of the aldo-keto reductase (AKR) superfamily. It is involved in the inactivation of steroid hormones and the metabolic activation of polycyclic aromatic hydrocarbons (PAH) by converting trans-dihydrodiols into reactive and redox-active o-quinones. The structure of the 5'-flanking region of the gene and factors involved in the constitutive and regulated expression of this gene have been reported [H.-K. Lin, T.M. Penning, Cloning, sequencing, and functional analysis of the 5'-flanking region of the rat 3alpha-hydroxysteroid/dihydrodiol dehydrogenase gene, Cancer Res. 55 (1995) 4105-4113]. We now describe the complete genomic structure of the rat type 1 3alpha-HSD/DD gene. Charon 4A and P1 genomic clones contained at least three rat genes (type 1, type 2 and type 3 3alpha-HSD/DD) each of which encoded for the same open reading frame (ORF) but differed in their exon-intron organization. 5'-RACE confirmed that the type 1 3alpha-HSD/DD gene encodes for the dominant transcript in rat liver and it was the regulation of this gene that was previously studied. The rat type 1 3alpha-HSD/DD gene is 30 kb in length and consists of nine exons and eight introns. Exon 9 encodes +931 to 966 bp of the ORF and the 1292 bp 3'-UTR implicated in mRNA stability. This genomic structure is nearly identical to the homologous human genes, type 1 3alpha-HSD (chlordecone reductase/DD4, AKR1C4), type 2 3alpha-HSD (AKR1C3) and type 3 3alpha-HSD (bile-acid binding protein, AKR1C2) genes. Three different cDNA's containing identical ORFs for 3alpha-HSD have been reported suggesting that all three genes may be expressed in rat liver. Using 5' primers corresponding to the 5'-UTR's of the three different cDNA's only one PCR fragment was obtained and corresponded to the type 1 3alpha-HSD/DD gene. These data suggested that the type 2 and type 3 3alpha-HSD/DD genes are not abundantly expressed in rat liver. It is unknown

Beta/alpha continuous air monitor

DOEpatents

Becker, Gregory K.; Martz, Dowell E.

1989-01-01

A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinguishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts.

Complete primary structure of rainbow trout type I collagen consisting of alpha1(I)alpha2(I)alpha3(I) heterotrimers.

PubMed

Saito, M; Takenouchi, Y; Kunisaki, N; Kimura, S

2001-05-01

The subunit compositions of skin and muscle type I collagens from rainbow trout were found to be alpha1(I)alpha2(I)alpha3(I) and [alpha1(I)](2)alpha2(I), respectively. The occurrence of alpha3(I) has been observed only for bonyfish. The skin collagen exhibited more susceptibility to both heat denaturation and MMP-13 digestion than the muscle counterpart; the former had a lower denaturation temperature by about 0.5 degrees C than the latter. The lower stability of skin collagen, however, is not due to the low levels of imino acids because the contents of Pro and Hyp were almost constant in both collagens. On the other hand, some cDNAs coding for the N-terminal and/or a part of triple-helical domains of proalpha(I) chains were cloned from the cDNA library of rainbow trout fibroblasts. These cDNAs together with the previously cloned collagen cDNAs gave information about the complete primary structure of type I procollagen. The main triple-helical domain of each proalpha(I) chain had 338 uninterrupted Gly-X-Y triplets consisting of 1014 amino acids and was unique in its high content of Gly-Gly doublets. In particular, the bonyfish-specific alpha(I) chain, proalpha3(I) was characterized by the small number of Gly-Pro-Pro triplets, 19, and the large number of Gly-Gly doublets, 38, in the triple-helical domain, compared to 23 and 22, respectively, for proalpha1(I). The small number of Gly-Pro-Pro and the large number of Gly-Gly in proalpha3(I) was assumed to partially loosen the triple-helical structure of skin collagen, leading to the lower stability of skin collagen mentioned above. Finally, phylogenetic analyses revealed that proalpha3(I) had diverged from proalpha1(I). This study is the first report of the complete primary structure of fish type I procollagen.

Alpha particle spectrometry using superconducting microcalorimeters

NASA Astrophysics Data System (ADS)

Horansky, Robert; Ullom, Joel; Beall, James; Hilton, Gene; Stiehl, Gregory; Irwin, Kent; Plionis, Alexander; Lamont, Stephen; Rudy, Clifford; Rabin, Michael

2009-03-01

Alpha spectrometry is the preferred technique for analyzing trace samples of radioactive material because the alpha particle flux can be significantly higher than the gamma-ray flux from nuclear materials of interest. Traditionally, alpha spectrometry is performed with Si detectors whose resolution is at best 8 keV FWHM. Here, we describe the design and operation of a microcalorimeter alpha detector with an energy resolution of 1.06 keV FWHM at 5 MeV. We demonstrate the ability of the microcalorimeter to clearly resolve the alpha particles from Pu-239 and Pu-240, whose ratio differentiates reactor-grade Pu from weapons-grade. We also show the first direct observation of the decay of Po-209 to the ground state of Pb-205 which has traditionally been obscured by a much stronger alpha line 2 keV away. Finally, the 1.06 keV resolution observed for alpha particles is far worse than the 0.12 keV resolution predicted from thermal fluctuations and measurement of gamma-rays. The cause of the resolution degradation may be ion damage in the tin. Hence, alpha particle microcalorimeters may provide a novel tool for studying ion damage and lattice displacement energies in bulk materials.

Alpha voltaic batteries and methods thereof

NASA Technical Reports Server (NTRS)

Jenkins, Phillip (Inventor); Scheiman, David (Inventor); Castro, Stephanie (Inventor); Raffaelle, Ryne P. (Inventor); Wilt, David (Inventor); Chubb, Donald (Inventor)

2011-01-01

An alpha voltaic battery includes at least one layer of a semiconductor material comprising at least one p/n junction, at least one absorption and conversion layer on the at least one layer of semiconductor layer, and at least one alpha particle emitter. The absorption and conversion layer prevents at least a portion of alpha particles from the alpha particle emitter from damaging the p/n junction in the layer of semiconductor material. The absorption and conversion layer also converts at least a portion of energy from the alpha particles into electron-hole pairs for collection by the one p/n junction in the layer of semiconductor material.

Alpha-particle spectrometer experiment

NASA Technical Reports Server (NTRS)

Gorenstein, P.; Bjorkholm, P.

1972-01-01

Mapping the radon emanation of the moon was studied to find potential areas of high activity by detection of radon isotopes and their daughter products. It was felt that based on observation of regions overflown by Apollo spacecraft and within the field of view of the alpha-particle spectrometer, a radon map could be constructed, identifying and locating lunar areas of outgassing. The basic theory of radon migration from natural concentrations of uranium and thorium is discussed in terms of radon decay and the production of alpha particles. The preliminary analysis of the results indicates no significant alpha emission.

Potent and selective agonists of alpha-melanotropin (alphaMSH) action at human melanocortin receptor 5; linear analogs of alpha-melanotropin.

PubMed

Bednarek, Maria A; MacNeil, Tanya; Tang, Rui; Fong, Tung M; Cabello, M Angeles; Maroto, Marta; Teran, Ana

2007-05-01

Alpha-melanotropin, Ac-Ser(1)-Tyr-Ser-Met-Glu-His(6)-Phe(7)-Arg(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2)(1), is a non-selective endogenous agonist for the melanocortin receptor 5; the receptor present in various peripheral tissues and in the brain, cortex and cerebellum. Most of the synthetic analogs of alphaMSH, including a broadly used and more potent the NDP-alphaMSH peptide, Ac-Ser(1)-Tyr-Ser-Nle(4)-Glu-His(6)-D-Phe(7)-Arg(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2), are also not particularly selective for MC5R. To elucidate physiological functions of the melanocortin receptor 5 in rodents and humans, the receptor subtype selective research tools are needed. We report herein syntheses and pharmacological evaluation in vitro of several analogs of NDP-alphaMSH which are highly potent and specific agonists for the human MC5R. The new linear peptides, of structures and solubility properties similar to those of the endogenous ligand alphaMSH, are exemplified by compound 7, Ac-Ser(1)-Tyr-Ser-Met-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8)-Trp(9)-Gly-Lys-Pro-Val(13)-NH(2) (Oic: octahydroindole-2-COOH, 4,4'-Bip: 4,4'-biphenylalanine, Pip: pipecolic acid), shortly NODBP-alphaMSH, which has an IC(50)=0.74 nM (binding assay) and EC(50)=0.41 (cAMP production assay) at hMC5R nM and greater than 3500-fold selectivity with respect to the melanocortin receptors 1b, 3 and 4. A shorter peptide derived from NODBP-alphaMSH: Ac-Nle-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8)-Trp(9) -NH(2) (17) was measured to be an agonist only 10-fold less potent at hMC5R than the full length parent peptide. In the structure of this smaller analog, the Nle-Glu-Oic(6)-D-4,4'-Bip(7)-Pip(8) segment was found to be critical for high agonist potency, while the C-terminal Trp(9) residue was shown to be required for high hMC5R selectivity versus hMC1b,3,4R.

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.

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.

The dark side of the alpha rhythm: fMRI evidence for induced alpha modulation during complete darkness.

PubMed

Ben-Simon, Eti; Podlipsky, Ilana; Okon-Singer, Hadas; Gruberger, Michal; Cvetkovic, Dean; Intrator, Nathan; Hendler, Talma

2013-03-01

The unique role of the EEG alpha rhythm in different states of cortical activity is still debated. The main theories regarding alpha function posit either sensory processing or attention allocation as the main processes governing its modulation. Closing and opening eyes, a well-known manipulation of the alpha rhythm, could be regarded as attention allocation from inward to outward focus though during light is also accompanied by visual change. To disentangle the effects of attention allocation and sensory visual input on alpha modulation, 14 healthy subjects were asked to open and close their eyes during conditions of light and of complete darkness while simultaneous recordings of EEG and fMRI were acquired. Thus, during complete darkness the eyes-open condition is not related to visual input but only to attention allocation, allowing direct examination of its role in alpha modulation. A data-driven ridge regression classifier was applied to the EEG data in order to ascertain the contribution of the alpha rhythm to eyes-open/eyes-closed inference in both lighting conditions. Classifier results revealed significant alpha contribution during both light and dark conditions, suggesting that alpha rhythm modulation is closely linked to the change in the direction of attention regardless of the presence of visual sensory input. Furthermore, fMRI activation maps derived from an alpha modulation time-course during the complete darkness condition exhibited a right frontal cortical network associated with attention allocation. These findings support the importance of top-down processes such as attention allocation to alpha rhythm modulation, possibly as a prerequisite to its known bottom-up processing of sensory input. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

A survey of the alpha-nucleon interaction

NASA Astrophysics Data System (ADS)

Ali, S.; Ahmad, A. A. Z.; Ferdous, N.

1985-10-01

This paper gives a survey of the alpha-nucleon interaction and then describes experimental work on angular distributions of differential scattering cross sections and polarizations in proton-alpha and neutron-alpha scattering. The phenomenological approach, which includes the study of both local and nonlocal potentials reproducing the experimental alpha-nucleon scattering data, is discussed. Basic studies of the alpha-nucleon interaction attempting to build an interaction between an alpha particle and a nucleon from first principles are then described. The authors then present a critical discussion of the results with some concluding remarks suggesting the direction for further investigation.

Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes.

PubMed

Rouppe van der Voort, C; Kavelaars, A; van de Pol, M; Heijnen, C J

1999-03-01

Beta2- and alpha2-adrenergic receptors (AR) are thought to be the main AR subtypes to exert the effects of catecholamines on the immune system. However, in the present study, we demonstrate that another subtype of AR can be induced in human monocytes. Expression of alpha1b- and alpha1d-AR mRNA can be obtained by culturing freshly isolated human peripheral blood monocytes with the neuroendocrine mediators dexamethasone or the beta2-AR agonist terbutaline. Using the human monocytic cell line THP-1, we demonstrate that increased levels of alpha1b- and alpha1d-mRNA are accompanied by increased levels of receptor protein as determined by Western blot analysis and radioligand binding assays. This study describes for the first time regulated expression of alpha1-AR subtypes in human monocytes.

Beta/alpha continuous air monitor

DOEpatents

Becker, G.K.; Martz, D.E.

1988-06-27

A single deep layer silicon detector in combination with a microcomputer, recording both alpha and beta activity and the energy of each pulse, distinquishing energy peaks using a novel curve fitting technique to reduce the natural alpha counts in the energy region where plutonium and other transuranic alpha emitters are present, and using a novel algorithm to strip out radon daughter contribution to actual beta counts. 7 figs.

ASYMMETRIC ABSORPTION PROFILES OF Ly{alpha} AND Ly{beta} IN DAMPED Ly{alpha} SYSTEMS

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

Lee, Hee-Won, E-mail: hwlee@sejong.ac.kr

2013-08-01

Damped Ly{alpha} systems observed in the quasar spectra are characterized by a high neutral hydrogen column density, N{sub HI} > 2 x 10{sup 20} cm{sup -2}. The absorption wing profiles are often fitted using the Voigt function due to the fact that the scattering cross section near the resonant line center is approximately described by the Lorentzian function. Since a hydrogen atom has infinitely many p states that participate in the electric dipole interaction, the cross section starts to deviate from the Lorentzian in an asymmetric way in the line wing regions. We investigate this asymmetry in the absorption linemore » profiles around Ly{alpha} and Ly{beta} as a function of the neutral hydrogen column density N{sub HI}. In terms of {Delta}{lambda} {identical_to} {lambda} - {lambda}{sub {alpha}}, we expand the Kramers-Heisenberg formula around Ly{alpha} to find {sigma}({lambda}) {approx_equal} (0.5f{sub 12}){sup 2}{sigma}{sub T}({Delta}{lambda}/{lambda}{sub {alpha}}){sup -2}[1 + 3.792({Delta}{lambda}/{lambda}{sub {alpha}})], where f{sub 12} and {sigma}{sub T} are the oscillator strength of Ly{alpha} and the Thomson scattering cross section, respectively. In terms of {Delta}{lambda}{sub 2} {identical_to} {lambda} - {lambda}{sub {beta}} in the vicinity of Ly{beta}, the total scattering cross section, given as the sum of cross sections for Rayleigh and Raman scattering, is shown to be {sigma}({lambda}) {approx_equal} {sigma}{sub T}(0.5f{sub 13}){sup 2}(1 + R{sub 0})({Delta}{lambda}{sub 2}/{lambda}{sub {beta}}){sup -2}[1 - 24.68({Delta}{lambda}{sub 2}/{lambda}{sub {beta}})] with f{sub 13} and the factor R{sub 0} = 0.1342 being the oscillator strength for Ly{beta} and the ratio of the Raman cross section to Rayleigh cross section, respectively. A redward asymmetry develops around Ly{alpha}, whereas a blue asymmetry is obtained for Ly{beta}. The absorption center shifts are found to be almost proportional to the neutral hydrogen column density.« less

Association of EEG alpha variants and alpha power with alcohol dependence in Mexican American young adults.

PubMed

Ehlers, Cindy L; Phillips, Evelyn

2007-02-01

Several studies support an association between electroencephalogram (EEG) voltage and alcohol dependence. However, the distribution of EEG variants also appears to differ depending on an individual's ethnic heritage, suggesting significant genetic stratification of this EEG phenotype. The present study's aims were to investigate the incidence of EEG alpha variants and spectral power in the alpha frequency range in Mexican American young adults based on gender, and personal and family history of alcohol dependence. Clinical ratings (high-, medium-, and low alpha voltage variants) and spectral characteristics of the EEG in the alpha frequency range (7.5-12 Hz) were investigated in young adult (age 18-25 years) Mexican American men (n=98) and women (n=138) who were recruited from the community. Nineteen percent (n=45) of the participants had a low-voltage alpha EEG variant, 18% had a high-voltage variant, and 63% had a medium-voltage variant. There were no significant differences in the distribution of the EEG variants based on family history of alcohol dependence. There was a significant relationship between gender and the three alpha variants (chi2=9.7; df=2; P<.008), and there were no male participants with alcohol dependence with high alpha variants (chi2=5.8; df=2; P<.056). Alcohol dependence, but not a family history of alcohol dependence, was associated with lower spectral power in the alpha frequency range in the right (F=4.4; df=1,96; P<.04) and left (F=5.3; df=1.96; P<.02) occipital areas in the men but not in the women. In conclusion, in this select population of Mexican American young adults, male gender and alcohol dependence are associated with an absence of high-voltage alpha variants and lower alpha power in the EEG. These data suggest that EEG low voltage, a highly heritable trait, may represent an important endophenotype in male Mexican Americans that may aid in linking brain function with genetic factors underlying alcohol dependence in this ethnic

Alpha-Driven MHD and MHD-Induced Alpha Loss in TFTR DT Experiments

NASA Astrophysics Data System (ADS)

Chang, Zuoyang

1996-11-01

Theoretical calculation and numerical simulation indicate that there can be interesting interactions between alpha particles and MHD activity which can adversely affect the performance of a tokamak reactor (e.g., ITER). These interactions include alpha-driven MHD, like the toroidicity-induced-Alfven-eigenmode (TAE) and MHD induced alpha particle losses or redistribution. Both phenomena have been observed in recent TFTR DT experiments. Weak alpha-driven TAE activity was observed in a NBI-heated DT experiment characterized by high q0 ( >= 2) and low core magnetic shear. The TAE mode appears at ~30-100 ms after the neutral beam turning off approximately as predicted by theory. The mode has an amplitude measured by magnetic coils at the edge tildeB_p ~1 mG, frequency ~150-190 kHz and toroidal mode number ~2-3. It lasts only ~ 30-70 ms and has been seen only in DT discharges with fusion power level about 1.5-2.0 MW. Numerical calculation using NOVA-K code shows that this type of plasma has a big TAE gap. The calculated TAE frequency and mode number are close to the observation. (2) KBM-induced alpha particle loss^1. In some high-β, high fusion power DT experiments, enhanced alpha particle losses were observed to be correlated to the high frequency MHD modes with f ~100-200 kHz (the TAE frequency would be two-times higher) and n ~5-10. These modes are localized around the peak plasma pressure gradient and have ballooning characteristics. Alpha loss increases by 30-100% during the modes. Particle orbit simulations show the added loss results from wave-particle resonance. Linear instability analysis indicates that the plasma is unstable to the kinetic MHD ballooning modes (KBM) driven primarily by strong local pressure gradients. ----------------- ^1Z. Chang, et al, Phys. Rev. Lett. 76 (1996) 1071. In collaberation with R. Nazikian, G.-Y. Fu, S. Batha, R. Budny, L. Chen, D. Darrow, E. Fredrickson, R. Majeski, D. Mansfield, K. McGuire, G. Rewoldt, G. Taylor, R. White, K

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.

Emphysema and Alpha-1

MedlinePlus

... Healthy Alpha-1 Facts Alpha-1 Links Emphysema Emphysema, which is a form of chronic obstructive pulmonary disease, or COPD, can occur when a person inherits a defective copy of the AAT gene from both parents. People who ... of developing emphysema, but generally they will only develop the disease ...

The generalized liquid drop model alpha-decay formula: Predictability analysis and superheavy element alpha half-lives

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

Dasgupta-Schubert, N.; Reyes, M.A.

2007-11-15

The predictive accuracy of the generalized liquid drop model (GLDM) formula for alpha-decay half-lives has been investigated in a detailed manner and a variant of the formula with improved coefficients is proposed. The method employs the experimental alpha half-lives of the well-known alpha standards to obtain the coefficients of the analytical formula using the experimental Q{sub {alpha}} values (the DSR-E formula), as well as the finite range droplet model (FRDM) derived Q{sub {alpha}} values (the FRDM-FRDM formula). The predictive accuracy of these formulae was checked against the experimental alpha half-lives of an independent set of nuclei (TEST) that span approximatelymore » the same Z, A region as the standards and possess reliable alpha spectroscopic data, and were found to yield good results for the DSR-E formula but not for the FRDM-FRDM formula. The two formulae were used to obtain the alpha half-lives of superheavy elements (SHE) and heavy nuclides where the relative accuracy was found to be markedly improved for the FRDM-FRDM formula, which corroborates the appropriateness of the FRDM masses and the GLDM prescription for high Z, A nuclides. Further improvement resulted, especially for the FRDM-FRDM formula, after a simple linear optimization over the calculated and experimental half-lives of TEST was used to re-calculate the half-lives of the SHE and heavy nuclides. The advantage of this optimization was that it required no re-calculation of the coefficients of the basic DSR-E or FRDM-FRDM formulae. The half-lives for 324 medium-mass to superheavy alpha decaying nuclides, calculated using these formulae and the comparison with experimental half-lives, are presented.« less

Cortical Alpha Activity in Schizoaffective Patients

PubMed Central

Moeini, Mahdi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Zarafshan, Hadi; Fazio, Rachel L.; Majidi, Hamid

2017-01-01

Objective: Electrophysiological studies have identified abnormal oscillatory activities in the cerebral cortex in schizophrenia and mood disorders. Biological and pathophysiological evidence suggests specific deficits in serotonin (5-HT) receptor function in schizoaffective disorder (SA), a clinical syndrome with characteristics of both schizophrenia and bipolar disorder. This study investigated alpha oscillations in patients with SA. Method: Electroencephalography was used to measure ongoing and evoked alpha oscillations in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition (DSM–IV) criteria for SA, and in 39 healthy controls. Results: Spontaneous alpha power of the participants with SA was significantly lower than that of healthy participants [F (1, 75) = 8.81, P < 0.01]. Evoked alpha activity was also decreased in SA compared to controls [F (1, 75) = 5.67, P = 0.025]. Conclusion: A strong reduction of alpha power in the posterior regions may reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and reduced cerebral blood flow is associated with reduced alpha activity among different regions of the brain. Therefore, it can be concluded that greatly decreased alpha activity, particularly in centro-parietal and occipital regions, is related to SA symptoms such as hallucinations. PMID:28496495

Cortical Alpha Activity in Schizoaffective Patients.

PubMed

Moeini, Mahdi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Zarafshan, Hadi; Fazio, Rachel L; Majidi, Hamid

2017-01-01

Objective: Electrophysiological studies have identified abnormal oscillatory activities in the cerebral cortex in schizophrenia and mood disorders. Biological and pathophysiological evidence suggests specific deficits in serotonin (5-HT) receptor function in schizoaffective disorder (SA), a clinical syndrome with characteristics of both schizophrenia and bipolar disorder. This study investigated alpha oscillations in patients with SA. Method: Electroencephalography was used to measure ongoing and evoked alpha oscillations in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria for SA, and in 39 healthy controls. Results: Spontaneous alpha power of the participants with SA was significantly lower than that of healthy participants [F (1, 75) = 8.81, P < 0.01]. Evoked alpha activity was also decreased in SA compared to controls [F (1, 75) = 5.67, P = 0.025]. Conclusion : A strong reduction of alpha power in the posterior regions may reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and reduced cerebral blood flow is associated with reduced alpha activity among different regions of the brain. Therefore, it can be concluded that greatly decreased alpha activity, particularly in centro-parietal and occipital regions, is related to SA symptoms such as hallucinations.

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.

Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and soluble TNF-alpha receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function.

PubMed

Díez, Juan J; Hernanz, Angel; Medina, Sonia; Bayón, Carmen; Iglesias, Pedro

2002-10-01

Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. Receptors for TNF-alpha have been demonstrated in thyroid follicular cells and TNF-alpha and its receptors have been implicated in the cytotoxic mechanisms that characterize the thyroid destruction in autoimmune thyroid disease. In patients with Graves' disease, serum levels of TNF-alpha have been reported to be elevated and administration of TNF-alpha to humans has been shown to induce hormonal alterations resembling those seen in the nonthyroidal illness syndrome. To evaluate serum concentrations of TNF-alpha and the soluble receptor for TNF-alpha (sTNFR-I) in a group of patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. We studied 20 patients with hypothyroidism (18 women and 2 men, mean age +/- SD, 48.8 +/- 16.1 years) and 20 patients with hyperthyroidism (14 women and 6 men, age 44.6 +/- 15.9 years). Patients were assessed at the time of diagnosis and again after normalization of thyroid function tests with appropriate therapy. A group of 20 healthy subjects (15 women and 5 men, age 44.9 +/- 15.1 years) were also studied as a control group. All subjects were ambulatory and were studied as outpatients during visits to the endocrinology clinic. Serum concentrations of free T4 (FT4), total T3, TSH, TNF-alpha and sTNFR-I were measured in all subjects. TNF-alpha and sTNFR-I were measured using a quantitative enzyme immunoassay. In patients with hypothyroidism serum concentrations of TNF-alpha (3.17 +/- 1.18 pg/ml) and sTNFR-I (1273 +/- 364 pg/ml) were significantly higher than those found in controls (2.42 +/- 0.76 pg/ml, P < 0.05, and 971 +/- 235 pg/ml, P < 0.01, respectively). Normalization of thyroid function with l-thyroxine therapy did not significantly modify TNF-alpha or sTNFR-I levels. There were no differences in pre- and post-therapy values of TNF-alpha and sTNFR-I in patients with

21 CFR 882.1610 - Alpha monitor.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An alpha...

21 CFR 882.1610 - Alpha monitor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An alpha...

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.

Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels.

PubMed

Tenenholz, T C; Rogowski, R S; Collins, J H; Blaustein, M P; Weber, D J

1997-03-11

PiTX-K alpha, a 35-residue peptide recently isolated from the venom of Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s) in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very low toxin concentrations (6 nM and 32 pM, respectively) [Rogowski, R. S., Collins, J. H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A., Tenenholz, T. C., Weber, D. J., & Blaustein, M. P. (1996) Mol. Pharmacol. 50, 1167-1177]. The three-dimensional structure of PiTX-K alpha was determined using NMR spectroscopy in order to understand its selectivity and affinity toward K+ channels. PiTX-K alpha was found to have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small antiparallel beta-sheet. Three disulfide bonds, which are conserved in all members of the charybdotoxin family (alpha-K toxins), anchor one face of the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha has three fewer residues than other alpha-K toxins such as charybdotoxin. Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation. This structural difference in PiTX-K alpha together with differences in sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25 in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels. Differences in three-dimensional structure between PiTX-K alpha and charybdotoxin are also observed in both the tight turn and the loop that connects the first beta-strand to the alpha-helix. As a result, side chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha that probably interact with rapidly inactivating A-type K+ channels. The analogous residues in charybdotoxin are positioned differently on the toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in PiTX-K alpha could explain why this toxin blocks A

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.

TNF-alpha infusion impairs corpora cavernosa reactivity.

PubMed

Carneiro, Fernando S; Zemse, Saiprazad; Giachini, Fernanda R C; Carneiro, Zidonia N; Lima, Victor V; Webb, R Clinton; Tostes, Rita C

2009-03-01

Erectile dysfunction (ED), as well as cardiovascular diseases (CVDs), is associated with endothelial dysfunction and increased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha). We hypothesized that increased TNF-alpha levels impair cavernosal function. In vitro organ bath studies were used to measure cavernosal reactivity in mice infused with vehicle or TNF-alpha (220 ng/kg/min) for 14 days. Gene expression of nitric oxide synthase isoforms was evaluated by real-time polymerase chain reaction. Corpora cavernosa from TNF-alpha-infused mice exhibited decreased nitric oxide (NO)-dependent relaxation, which was associated with decreased endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) cavernosal expression. Cavernosal strips from the TNF-alpha-infused mice displayed decreased nonadrenergic-noncholinergic (NANC)-induced relaxation (59.4 +/- 6.2 vs. control: 76.2 +/- 4.7; 16 Hz) compared with the control animals. These responses were associated with decreased gene expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated, as well as phenylephrine (PE)-induced, contractile responses (PE-induced contraction; 1.32 +/- 0.06 vs. control: 0.9 +/- 0.09, mN) were increased in cavernosal strips from TNF-alpha-infused mice. Additionally, infusion of TNF-alpha increased cavernosal responses to endothelin-1 and endothelin receptor A subtype (ET(A)) receptor expression (P < 0.05) and slightly decreased tumor necrosis factor-alpha receptor 1 (TNFR1) expression (P = 0.063). Corpora cavernosa from TNF-alpha-infused mice display increased contractile responses and decreased NANC nerve-mediated relaxation associated with decreased eNOS and nNOS gene expression. These changes may trigger ED and indicate that TNF-alpha plays a detrimental role in erectile function. Blockade of TNF-alpha actions may represent an alternative therapeutic approach for ED, especially in pathologic conditions associated with increased levels

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

Long range alpha particle detector

DOEpatents

MacArthur, Duncan W.; Wolf, Michael A.; McAtee, James L.; Unruh, Wesley P.; Cucchiara, Alfred L.; Huchton, Roger L.

1993-01-01

An alpha particle detector capable of detecting alpha radiation from distant sources. In one embodiment, a high voltage is generated in a first electrically conductive mesh while a fan draws air containing air molecules ionized by alpha particles through an air passage and across a second electrically conductive mesh. The current in the second electrically conductive mesh can be detected and used for measurement or alarm. The detector can be used for area, personnel and equipment monitoring.

Long range alpha particle detector

DOEpatents

MacArthur, D.W.; Wolf, M.A.; McAtee, J.L.; Unruh, W.P.; Cucchiara, A.L.; Huchton, R.L.

1993-02-02

An alpha particle detector capable of detecting alpha radiation from distant sources. In one embodiment, a high voltage is generated in a first electrically conductive mesh while a fan draws air containing air molecules ionized by alpha particles through an air passage and across a second electrically conductive mesh. The current in the second electrically conductive mesh can be detected and used for measurement or alarm. The detector can be used for area, personnel and equipment monitoring.

[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.

Inhibitory spectrum of alpha 2-plasmin inhibitor.

PubMed Central

Saito, H; Goldsmith, G H; Moroi, M; Aoki, N

1979-01-01

alpha 2-Plasmin inhibitor (alpha 2PI) has been recently characterized as a fast-reacting inhibitor of plasmin in human plasma and appears to play an important role in the regulation of fibrinolysis in vivo. We have studied the effect of purified alpha 2PI upon various proteases participating in human blood coagulation and kinin generation. At physiological concentration (50 microgram/ml), alpha 2PI inhibited the clot-promoting and prekallikrein-activating activity of Hageman factor fragments, the amidolytic, kininogenase, and clot-promoting activities of plasma kallikrein, and the clot-promoting properties of activated plasma thromboplastin antecedent (PTA, Factor XIa) and thrombin. alpha 2PI had minimal inhibitory effect on surface-bound activated PTA and activated Stuart factor (Factor Xa). alpha 2PI did not inhibit the activity of activated Christmas factor (Factor IXa) or urinary kallikrein. Heparin (1.5-2.0 units/ml) did not enhance the inhibitory function of alpha 2PI. These results suggest that, like other plasma protease inhibitors, alpha 2PI possesses a broad in vitro spectrum of inhibitory properties. PMID:156364

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

[Anti-TNF alpha in dermatology].

PubMed

Mahe, E; Descamps, V

2002-12-01

The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the development of anti-TNF alpha drugs. These new therapeutic arms issued from bio-technology have rapidly demonstrated their efficacy in the treatment of these two diseases. The anti-TNF alpha arsenal is currently dominated by etanercept, a fusion protein composed of a soluble TNF alpha receptor, and infliximab, a chimeric monoclonal antibody. However, new molecules will soon enrich this arsenal. TNF alpha is a major cytokine of inflammatory diseases of the skin. Many dermatological diseases will probably benefit from these new treatments. Two studies have already demonstrated their interest in cutaneous and articular psoriasis. Encouraging sporadic results suggest other potential indications (Behcet's disease, bullous dermatitis, neutrophilic dermatitis, toxic epidermal necrolysis, systemic vascularitis,.). These promising new treatments, although expensive, and with yet unknown long term side effects, justify rigorous assessment of their efficacy and tolerance in each indication. Here again the dermatologist has a major role to play in post-marketing pharmacovigilance.

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

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.

[Alpha-melanocyte-stimulating hormone. From bench to bedside].

PubMed

Böhm, M; Luger, T A

2010-06-01

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that is produced by the skin itself from the precursor proopiomelanocortin. It crucially mediates ultraviolet light-induced tanning after binding to melanocortin-1 receptors (MC-1R) expressed on the surface of epidermal melanocytes. The potent pigment-inducing and also cytoprotective actions of alpha-MSH are the rationale for the performance of first phase II clinical trials with Nle4-D-Phe7-alpha-MSH (NDP-alpha-MSH), a subcutaneously administered synthetic and superpotent alpha-MSH analogue, in patients with photodermatoses such as erythropoietic protoporphyria. Since alpha-MSH has shown promising anti-inflammatory and antifibrotic properties in numerous preclinical studies, it will be most interesting to evaluate these effects in further clinical pilot studies with NDP-alpha-MSH. In addition to alpha-MSH analogues, truncated tripeptides such as KDPT which do not bind to MC-1R but have sustained anti-inflammatory properties are currently emerging as another novel therapeutic strategy in dermatology.

Far-Infrared and Millimeter Continuum Studies of K-Giants: Alpha Boo and Alpha Tau

NASA Technical Reports Server (NTRS)

Cohen, Martin; Carbon, Duane F.; Welch, William J.; Lim, Tanya; Forster, James R.; Goorvitch, David; Thigpen, William (Technical Monitor)

2002-01-01

We have imaged two normal, non-coronal, infrared-bright K-giants, alpha Boo and alpha Tau, in the 1.4-millimeter and 2.8-millimeter continuum using BIMA. These stars have been used as important absolute calibrators for several infrared satellites. Our goals are: (1) to probe the structure of their upper photospheres; (2) to establish whether these stars radiate as simple photospheres or possess long-wavelength chromospheres; and (3) to make a connection between millimeter-wave and far-infrared absolute flux calibrations. To accomplish these goals we also present ISO Long Wavelength Spectrometer (LWS) measurements of both these K-giants. The far-infrared and millimeter continuum radiation is produced in the vicinity of the temperature minimum in a Boo and a Tau, offering a direct test of the model photospheres and chromospheres for these two cool giants. We find that current photospheric models predict fluxes in reasonable agreement with those observed for those wavelengths which sample the upper photosphere, namely less than or equal to 170 micrometers in alpha Tau and less than or equal to 125 micrometers in alpha Boo. It is possible that alpha Tau is still radiative as far as 0.9 - 1.4 millimeters. We detect chromospheric radiation from both stars by 2.8 millimeters (by 1.4 millimeters in alpha Boo), and are able to establish useful bounds on the location of the temperature minimum. An attempt to interpret the chromospheric fluxes using the two-component "bifurcation model" proposed by Wiedemann et al. (1994) appears to lead to a significant contradiction.

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.

Alpha-driven magnetohydrodynamics (MHD) and MHD-induced alpha loss in the Tokamak Fusion Test Reactor

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

Chang, Z.; Nazikian, R.; Fu, G.Y.

1997-02-01

Alpha-driven toroidal Alfven eigenmodes (TAEs) are observed as predicted by theory in the post neutral beam phase in high central q (safety factor) deuterium-tritium (D-T) plasmas in the Tokamak Fusion Test Reactor (TFTR). The mode location, poloidal structure and the importance of q profile for TAE instability are discussed. So far no alpha particle loss due to these modes was detected due to the small mode amplitude. However, alpha loss induced by kinetic ballooning modes (KBMs) was observed in high confinement D-T discharges. Particle orbit simulation demonstrates that the wave-particle resonant interaction can explain the observed correlation between the increasemore » in alpha loss and appearance of multiple high-n (n {ge} 6, n is the toroidal mode number) modes.« less

Direct catalytic asymmetric alpha-amination of aldehydes.

PubMed

List, Benjamin

2002-05-22

The first direct catalytic asymmetric alpha-amination of aldehydes is described herein. alpha-Unbranched aldehydes react in this novel proline-catalyzed reaction with dialkyl azodicarboxylates to give alpha-amino aldehydes in excellent yields and enantioselectivities.

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.

A new gene deletion in the alpha-like globin gene cluster as the molecular basis for the rare alpha-thalassemia-1(--/alpha alpha) in blacks: HbH disease in sickle cell trait.

PubMed

Steinberg, M H; Coleman, M B; Adams, J G; Hartmann, R C; Saba, H; Anagnou, N P

1986-02-01

A novel deletion of at least 26 kilobase of DNA, including both alpha-globin genes, the psi alpha- and psi zeta-globin genes, but sparing the functional zeta-gene was found in a 10-year-old black boy with HbH disease and sickle cell trait. This particular deletion has not previously been described in blacks. Its existence makes it likely that the absence of Hb Barts hydrops fetalis in blacks is due to the rarity of the chromosome lacking two alpha-globin genes rather than a result of early embryonic death due to the failure to synthesize embryonic hemoglobins because of deletion of functional zeta-globin genes.

Color image enhancement of medical images using alpha-rooting and zonal alpha-rooting methods on 2D QDFT

NASA Astrophysics Data System (ADS)

Grigoryan, Artyom M.; John, Aparna; Agaian, Sos S.

2017-03-01

2-D quaternion discrete Fourier transform (2-D QDFT) is the Fourier transform applied to color images when the color images are considered in the quaternion space. The quaternion numbers are four dimensional hyper-complex numbers. Quaternion representation of color image allows us to see the color of the image as a single unit. In quaternion approach of color image enhancement, each color is seen as a vector. This permits us to see the merging effect of the color due to the combination of the primary colors. The color images are used to be processed by applying the respective algorithm onto each channels separately, and then, composing the color image from the processed channels. In this article, the alpha-rooting and zonal alpha-rooting methods are used with the 2-D QDFT. In the alpha-rooting method, the alpha-root of the transformed frequency values of the 2-D QDFT are determined before taking the inverse transform. In the zonal alpha-rooting method, the frequency spectrum of the 2-D QDFT is divided by different zones and the alpha-rooting is applied with different alpha values for different zones. The optimization of the choice of alpha values is done with the genetic algorithm. The visual perception of 3-D medical images is increased by changing the reference gray line.

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.

A case of alpha-fetoprotein-producing esophageal adenocarcinoma.

PubMed

Chen, Yi-Yu; Hsu, Wen-Hung; Hu, Huang-Ming; Wu, Deng-Chyang; Lin, Wen-Yi

2013-02-01

Alpha-fetoprotein is a well-known tumor marker in the screening and follow-up of hepatocellular carcinoma. In Taiwanese society, a high prevalence of hepatitis and hepatoma and elevation of alpha-fetoprotein associated with liver function impairment usually suggested clinics undertake further examination for liver or genital tumor. We report the case of 45-year-old man who was found to have an alpha-fetoprotein-producing esophageal adenocarcinoma with an initial presentation of liver function impairment and rapid elevation of alpha-fetoprotein. Esophageal cancer was diagnosed via endoscope and a biopsy proved the presence of adenocarcinoma. A small endoscopic biopsy specimen failed to identify the alpha-fetoprotein positive tumor cell. Esophagectomy was performed and histopathological study of surgical specimen revealed grade II adenocarcinoma with regional metastatic lymphadenopathy. Immunohistochemical study was focal positive for alpha-fetoprotein. Serum alpha-fetoprotein declined transiently after esophagectomy and fluctuation of alpha-fetoprotein level was noted during the treatment with adjuvant chemotherapy. Finally, 19 months after the operation, the patient died due to multiple organ metastases with multiple organ failure. Thus, a small specimen for upper endoscopy may not be sufficient in the presence of alpha-fetoprotein-producing adenocarcinoma. Monitoring of serum alpha-fetoprotein may be useful in the evaluation and follow-up of esophageal alpha-fetoprotein-producing adenocarcinoma. Copyright © 2012. Published by Elsevier B.V.

Transcriptional regulation of human retinoic acid receptor-alpha (RAR-{alpha}) by Wilms` tumour gene product

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

Goodyer, P.R.; Torban, E.; Dehbi, M.

1994-09-01

The Wilms` tumor gene encodes a 47-49 kDa transcription factor expressed in kidney, gonads and mesothelium during embryogenesis. Inherited mutations of WT1 lead to aberrant urogenital development and Wilms` tumor, but the role of WT1 in development is not fully understood. Since the human RAR-{alpha} gene contains a potential WT1 binding site at its 5{prime} end, we studied the effect of WT1 co-transfection on expression of an RAR-{alpha} promoter/CAT reporter construct in COS cells. COS cells were plated at 5X10{sup 5} cells/dish in DMEM with 10% FBS and transfected by the Ca/PO4 method with an expression plasmid containing the full-lengthmore » WT1 (-/-) cDNA under the control of the CMV promoter, plasmid containing the RAR-{alpha} promoter (-519 to +36)/CAT reporter and TK/growth hormone plasmid to control for efficiency of transfection. CAT/GH activity at 48 hours was inhibited by co-transfection with increasing amounts of WT1 (-/-); maximum inhibition = 5% of control. WT1 co-transfection did not affect expression of TKGH, nor of a CMV-CAT vector. Expression of WT1 protein in tranfected COS cells was demonstrated by Western blotting. Minimal inhibiton of RAR-{alpha}/CAT activity was seen when cells were co-transfected with vectors containing WT1 deletion mutants, alternate WT1 splicing variants, or WT1 (-/-) cDNA bearing a mutation identified in a patient with Drash syndrome. Gel shift assays indicated binding of WT1 to RAR-{alpha} cDNA but not to an RAR-{alpha} deletion mutant lacking the GCGGGGGGCG site. These observations suggest that WT1 may function to regulate RAR-{alpha} expression during normal development.« less

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.

Grindability of alpha-case formed on cast titanium.

PubMed

Koike, Marie; Jacobson, David; Chan, Kwai S; Okabe, Toru

2009-09-01

The hardened alpha-case (alpha-case) layer inevitably forms on the surface of titanium castings when prepared by investment casting. Because the hardness of the alpha-case is incomparable to that of the interior structure, the perception exists that the alpha-case is difficult to remove during cutting, grinding and polishing. Grindability (ease of grinding) of cast cpTi and cast Ti-6Al-4V was evaluated by grinding cast specimens incrementally using a SiC abrasive wheel. The present study revealed that the presence of the brittle alpha-case with lower fracture toughness is beneficial in grinding titanium. The alpha-case on the ductile cpTi can be ground much easier than its bulk interior structure. In less ductile Ti-6Al-4V, the grinding rate is much higher than that of cpTi, and the alpha-case and its interior structure are at similar levels since the fracture toughness of its alpha-case and the bulk material is not large enough.

Functional and genomic analyses of alpha-solenoid proteins.

PubMed

Fournier, David; Palidwor, Gareth A; Shcherbinin, Sergey; Szengel, Angelika; Schaefer, Martin H; Perez-Iratxeta, Carol; Andrade-Navarro, Miguel A

2013-01-01

Alpha-solenoids are flexible protein structural domains formed by ensembles of alpha-helical repeats (Armadillo and HEAT repeats among others). While homology can be used to detect many of these repeats, some alpha-solenoids have very little sequence homology to proteins of known structure and we expect that many remain undetected. We previously developed a method for detection of alpha-helical repeats based on a neural network trained on a dataset of protein structures. Here we improved the detection algorithm and updated the training dataset using recently solved structures of alpha-solenoids. Unexpectedly, we identified occurrences of alpha-solenoids in solved protein structures that escaped attention, for example within the core of the catalytic subunit of PI3KC. Our results expand the current set of known alpha-solenoids. Application of our tool to the protein universe allowed us to detect their significant enrichment in proteins interacting with many proteins, confirming that alpha-solenoids are generally involved in protein-protein interactions. We then studied the taxonomic distribution of alpha-solenoids to discuss an evolutionary scenario for the emergence of this type of domain, speculating that alpha-solenoids have emerged in multiple taxa in independent events by convergent evolution. We observe a higher rate of alpha-solenoids in eukaryotic genomes and in some prokaryotic families, such as Cyanobacteria and Planctomycetes, which could be associated to increased cellular complexity. The method is available at http://cbdm.mdc-berlin.de/~ard2/.

Functional and Genomic Analyses of Alpha-Solenoid Proteins

PubMed Central

Fournier, David; Palidwor, Gareth A.; Shcherbinin, Sergey; Szengel, Angelika; Schaefer, Martin H.; Perez-Iratxeta, Carol; Andrade-Navarro, Miguel A.

2013-01-01

Alpha-solenoids are flexible protein structural domains formed by ensembles of alpha-helical repeats (Armadillo and HEAT repeats among others). While homology can be used to detect many of these repeats, some alpha-solenoids have very little sequence homology to proteins of known structure and we expect that many remain undetected. We previously developed a method for detection of alpha-helical repeats based on a neural network trained on a dataset of protein structures. Here we improved the detection algorithm and updated the training dataset using recently solved structures of alpha-solenoids. Unexpectedly, we identified occurrences of alpha-solenoids in solved protein structures that escaped attention, for example within the core of the catalytic subunit of PI3KC. Our results expand the current set of known alpha-solenoids. Application of our tool to the protein universe allowed us to detect their significant enrichment in proteins interacting with many proteins, confirming that alpha-solenoids are generally involved in protein-protein interactions. We then studied the taxonomic distribution of alpha-solenoids to discuss an evolutionary scenario for the emergence of this type of domain, speculating that alpha-solenoids have emerged in multiple taxa in independent events by convergent evolution. We observe a higher rate of alpha-solenoids in eukaryotic genomes and in some prokaryotic families, such as Cyanobacteria and Planctomycetes, which could be associated to increased cellular complexity. The method is available at http://cbdm.mdc-berlin.de/~ard2/. PMID:24278209

The ultraviolet spectra of Alpha Aquilae and Alpha Canis Minoris

NASA Technical Reports Server (NTRS)

Morton, D. C.; Bruzual A., G.; Kurucz, R. L.; Spinrad, H.

1977-01-01

Scans of Alpha Aql (A7 IV, V) and Alpha CMi (F5 IV-V) obtained with the Copernicus satellite spectrometer over the wavelength range from 2100 to 3200 A are presented along with a spectrum of the integrated solar disk over the same range procured during a calibrated rocket flight. About 1500 fairly strong absorption lines in the Alpha CMi spectrum between 2400 and 2961 A are identified by comparison with a solar atlas and by using a theoretical spectrum synthesized from a blanketed LTE model with an effective temperature of 6500 K and a surface gravity of 10,000 cm/sec per sec. The Mg II resonance doublet at 2795.528 and 2802.704 A is found to be present in all three stars together with a discontinuity at 2635 A due to Fe II, Fe I, Cr I, and Mn II. It is concluded that the Mg II resonance lines and the 2635-A continuum break would be the best spectral features for estimating the redshift of a galaxy observed at low resolution provided the redshift is not less than about 0.75.

Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

NASA Astrophysics Data System (ADS)

Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David

2016-09-01

The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.

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

No changes in parieto-occipital alpha during neural phase locking to visual quasi-periodic theta-, alpha-, and beta-band stimulation.

PubMed

Keitel, Christian; Benwell, Christopher S Y; Thut, Gregor; Gross, Joachim

2018-05-08

Recent studies have probed the role of the parieto-occipital alpha rhythm (8 - 12 Hz) in human visual perception through attempts to drive its neural generators. To that end, paradigms have used high-intensity strictly-periodic visual stimulation that created strong predictions about future stimulus occurrences and repeatedly demonstrated perceptual consequences in line with an entrainment of parieto-occipital alpha. Our study, in turn, examined the case of alpha entrainment by non-predictive low-intensity quasi-periodic visual stimulation within theta- (4 - 7 Hz), alpha- (8 - 13 Hz) and beta (14 - 20 Hz) frequency bands, i.e. a class of stimuli that resemble the temporal characteristics of naturally occurring visual input more closely. We have previously reported substantial neural phase-locking in EEG recording during all three stimulation conditions. Here, we studied to what extent this phase-locking reflected an entrainment of intrinsic alpha rhythms in the same dataset. Specifically, we tested whether quasi-periodic visual stimulation affected several properties of parieto-occipital alpha generators. Speaking against an entrainment of intrinsic alpha rhythms by non-predictive low-intensity quasi-periodic visual stimulation, we found none of these properties to show differences between stimulation frequency bands. In particular, alpha band generators did not show increased sensitivity to alpha band stimulation and Bayesian inference corroborated evidence against an influence of stimulation frequency. Our results set boundary conditions for when and how to expect effects of entrainment of alpha generators and suggest that the parieto-occipital alpha rhythm may be more inert to external influences than previously thought. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Psychiatric Symptoms in Alpha-Mannosidosis

ERIC Educational Resources Information Center

Malm, D.; Pantel, J.; Linaker, O. M.

2005-01-01

Alpha-mannosidosis is characterized by mild to moderate intellectual disability (ID), moderate to severe neurosensory hearing loss, frequent infections, psychomotor disturbances and skeletal dysmorphism. For the first time, a panel of nine alpha-mannosidosis patients with psychiatric symptoms is presented. The clinical picture has several…

Correcting Coefficient Alpha for Correlated Errors: Is [alpha][K]a Lower Bound to Reliability?

ERIC Educational Resources Information Center

Rae, Gordon

2006-01-01

When errors of measurement are positively correlated, coefficient alpha may overestimate the "true" reliability of a composite. To reduce this inflation bias, Komaroff (1997) has proposed an adjusted alpha coefficient, ak. This article shows that ak is only guaranteed to be a lower bound to reliability if the latter does not include correlated…

Inactivation of chloroplast H(+)-ATPase by modification of Lys beta 359, Lys alpha 176 and Lys alpha 266.

PubMed

Horbach, M; Meyer, H E; Bickel-Sandkötter, S

1991-09-01

Treatment of isolated, latent chloroplast ATPase with pyridoxal-5-phosphate (pyridoxal-P) in presence of Mg2+ causes inhibition of dithiothreitol-activated plus heat-activated ATP hydrolysis. The amount of [3H]pyridoxal-P bound to chloroplast coupling factor 1 (CF1) was estimated to run up to 6 +/- 1 pyridoxal-P/enzyme, almost equally distributed between the alpha- and beta-subunits. Inactivation, however, is complete after binding of 1.5-2 pyridoxal-P/CF1, suggesting that two covalently modified lysines prevent the activation of the enzyme. ADP as well as ATP in presence of Mg2+ protects the enzyme against inactivation and concomittantly prevents incorporation of a part of the 3H-labeled pyridoxal-P into beta- and alpha-subunits. Phosphate prevents labeling of the alpha-subunit, but has only a minor effect on protection against inactivation. The data indicate a binding site at the interface between the alpha- and beta-subunits. Cleavage of the pyridoxal-P-labeled subunits with cyanogen bromide followed by sequence analysis of the labeled peptides led to the detection of Lys beta 359, Lys alpha 176 and Lys alpha 266, which are closely related to proposed nucleotide-binding regions of the alpha- and beta-subunits.

40 CFR 721.10491 - Benzenepropanal,.alpha.-methyl-.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzenepropanal,.alpha.-methyl-. 721... Substances § 721.10491 Benzenepropanal,.alpha.-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzenepropanal,.alpha.-methyl- (PMN P-05...

40 CFR 721.10491 - Benzenepropanal,.alpha.-methyl-.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzenepropanal,.alpha.-methyl-. 721... Substances § 721.10491 Benzenepropanal,.alpha.-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzenepropanal,.alpha.-methyl- (PMN P-05...

[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.

Immunological characterization of eristostatin and echistatin binding sites on alpha IIb beta 3 and alpha V beta 3 integrins.

PubMed Central

Marcinkiewicz, C; Rosenthal, L A; Mosser, D M; Kunicki, T J; Niewiarowski, S

1996-01-01

Two disintegrins with a high degree of amino acid sequence similarity, echistatin and eristostatin, showed a low level of interaction with Chinese hamster ovary (CHO) cells, but they bound to CHO cells transfected with alpha IIb beta 3 genes (A5 cells) and to CHO cells transfected with alpha v beta 3 genes (VNRC3 cells) in a reversible and saturable manner. Scatchard analysis revealed that eristostatin bound to 816000 sites per A5 cell (Kd 28 nM) and to 200000 sites (Kd 14 nM) per VNRC3 cell respectively. However, VNRC3 cells did not bind to immobilized eristostatin. Echistatin bound to 495000 sites (Kd 53 nM) per A5 cell and to 443000 sites (Kd 20 nM) per VNRC3 cell. As determined by flow cytometry, radiobinding assay and adhesion studies, binding of both disintegrins to A5 cells and resting platelets and binding of echistatin to VNRC3 cells resulted in the expression of ligand-induced binding sites (LIBS) on the beta 3 subunit. Eristostatin inhibited, more strongly than echistatin, the binding of three monoclonal antibodies: OPG2 (RGD motif dependent), A2A9 (alpha IIb beta 3 complex dependent) and 7E3 (alpha IIb beta 3 and alpha v beta 3 complex dependent) to A5 cells, to resting and to activated platelets and to purified alpha IIb beta 3. Experiments in which echistatin and eristostatin were used alone or in combination to inhibit the binding of 7E3 and OPG2 antibodies to resting platelets suggested that these two disintegrins bind to different but overlapping sites on alpha IIb beta 3 integrin. Monoclonal antibody LM 609 and echistatin seemed to bind to different sites on alpha v beta 3 integrin. However, echistatin inhibited binding of 7E3 antibody to VNRC3 cells and to purified alpha v beta 3 suggesting that alpha v beta 3 and alpha IIb beta 3 might share the same epitope to which both echistatin and 7E3 bind. Eristostatin had no effect in these systems, providing further evidence that it binds to a different epitope on alpha v beta 3. PMID:8760368

Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha (IFN-alpha) in metastatic melanoma.

PubMed

Young, A M; Marsden, J; Goodman, A; Burton, A; Dunn, J A

2001-01-01

Dacarbazine (DTIC) has been the mainstay of chemotherapy for metastatic melanoma for over two decades, but only 15%-20% of patients respond and benefit is usually transient. Randomized studies combining DTIC with interferon-alpha (IFN-alpha) in advanced disease have so far been inconclusive in terms of response and survival. We report a randomized prospective pilot Phase III trial of DTIC +IFN-alpha in patients with metastatic melanoma. The primary endpoint was death. A total of 61 patients were randomized between April 1995 and April 1998. Differences in survival between groups were assessed using log-rank analysis. Quality of life was measured using the European Organization for Research on Treatment of Cancer QLQ C30 (+3) questionnaire. Fifty-seven patients died during the study. The median survival for patients receiving DTIC was 7.2 months (95% confidence interval (CI) 4.4-9.0); it was 4.8 months for DTIC + IFN-alpha (95% CI 2.0-8.0). There was no significant difference in survival between the two treatment arms (chi2 unadjusted = 0.15, P = 0.70; chi2 adjusted = 0.01, P = 0.91). The 6-month survival of those patients randomized to DTIC alone was 58% compared with 40% for those patients randomized to DTIC + IFN-alpha. There were no differences in quality of life between treatment groups. This study failed to demonstrate a survival benefit for patients receiving IFN-alpha in combination with DTIC. These results are inconclusive primarily owing to the small size of the trial. A meta-analysis is required to determine whether there is a role for the addition of IFN-alpha to DTIC in the treatment of this disease.

Alpha Particle Detection Using Alpha-Induced Air Radioluminescence: A Review and Future Prospects for Preliminary Radiological Characterisation for Nuclear Facilities Decommissioning

PubMed Central

Crompton, Anita J.; Jenkins, Alex

2018-01-01

The United Kingdom (UK) has a significant legacy of nuclear installations to be decommissioned over the next 100 years and a thorough characterisation is required prior to the development of a detailed decommissioning plan. Alpha radiation detection is notoriously time consuming and difficult to carry out due to the short range of alpha particles in air. Long-range detection of alpha particles is therefore highly desirable and this has been attempted through the detection of secondary effects from alpha radiation, most notably the air-radioluminescence caused by ionisation. This paper evaluates alpha induced air radioluminescence detectors developed to date and looks at their potential to develop a stand-off, alpha radiation detector which can be used in the nuclear decommissioning field in daylight conditions to detect alpha contaminated materials. PMID:29597340

Multiple Binding Modes between HNF4[alpha] and the LXXLL Motifs of PGC-1[alpha] Lead to Full Activation

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

Rha, Geun Bae; Wu, Guangteng; Shoelson, Steven E.

2010-04-15

Hepatocyte nuclear factor 4{alpha} (HNF4{alpha}) is a novel nuclear receptor that participates in a hierarchical network of transcription factors regulating the development and physiology of such vital organs as the liver, pancreas, and kidney. Among the various transcriptional coregulators with which HNF4{alpha} interacts, peroxisome proliferation-activated receptor {gamma} (PPAR{gamma}) coactivator 1{alpha} (PGC-1{alpha}) represents a novel coactivator whose activation is unusually robust and whose binding mode appears to be distinct from that of canonical coactivators such as NCoA/SRC/p160 family members. To elucidate the potentially unique molecular mechanism of PGC-1{alpha} recruitment, we have determined the crystal structure of HNF4{alpha} in complex with amore » fragment of PGC-1{alpha} containing all three of its LXXLL motifs. Despite the presence of all three LXXLL motifs available for interactions, only one is bound at the canonical binding site, with no additional contacts observed between the two proteins. However, a close inspection of the electron density map indicates that the bound LXXLL motif is not a selected one but an averaged structure of more than one LXXLL motif. Further biochemical and functional studies show that the individual LXXLL motifs can bind but drive only minimal transactivation. Only when more than one LXXLL motif is involved can significant transcriptional activity be measured, and full activation requires all three LXXLL motifs. These findings led us to propose a model wherein each LXXLL motif has an additive effect, and the multiple binding modes by HNF4{alpha} toward the LXXLL motifs of PGC-1{alpha} could account for the apparent robust activation by providing a flexible mechanism for combinatorial recruitment of additional coactivators and mediators.« less

Tumor Necrosis Factor alpha (TNF{alpha}) regulates CD40 expression through SMAR1 phosphorylation

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

Singh, Kamini; Sinha, Surajit; Malonia, Sunil Kumar

2010-01-08

CD40 plays an important role in mediating inflammatory response and is mainly induced by JAK/STAT phosphorylation cascade. TNF{alpha} is the key cytokine that activates CD40 during inflammation and tumorigenesis. We have earlier shown that SMAR1 can repress the transcription of Cyclin D1 promoter by forming a HDAC1 dependent repressor complex. In this study, we show that SMAR1 regulates the transcription of NF-{kappa}B target gene CD40. SMAR1 recruits HDAC1 and forms a repressor complex on CD40 promoter and keeps its basal transcription in check. Further, we show that TNF{alpha} stimulation induces SMAR1 phosphorylation at Ser-347 and promotes its cytoplasmic translocation, thusmore » releasing its negative effect. Concomitantly, TNF{alpha} induced phosphorylation of STAT1 at Tyr-701 by JAK1 facilitates its nuclear translocation and activation of CD40 through p300 recruitment and core Histone-3 acetylation. Thus, TNF{alpha} mediated regulation of CD40 expression occurs by dual phosphorylation of SMAR1 and STAT1.« less

Aqueous chemical growth of alpha-Fe2O3-alpha-Cr203 nanocompositethin films

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

Vayssieres, Lionel; Guo, Jinghua; Nordgren, Joseph

2001-06-30

We are reporting here on the inexpensive fabrication and optical properties of an iron(III) oxide chromium(III) oxide nanocomposite thin film of corundum crystal structure. Its novel and unique-designed architecture consists of uniformed, well-defined and oriented nanorods of Hematite (alpha-Fe2O3) of 50 nm in diameter and 500nm in length and homogeneously distributed nonaggregated monodisperse spherical nanoparticles of Eskolaite (alpha-Cr2O3) of 250 nm in diameter. This alpha-Fe2O3 alpha-Cr2O3 nanocomposite thin film is obtained by growing, directly onto transparent polycrystalline conducting substrate, an oriented layer of hematite nanorods and growing subsequently, the eskolaite layer. The synthesis is carried out by a template-free, low-temperature,more » multilayer thin film coating process using aqueous solution of metal salts as precursors. Almost 100 percent of the light is absorbed by the composite film between 300 and 525 nm and 40 percent at 800 nm which yields great expectations as photoanode materials for photovoltaic cells and photocatalytic devices.« less

Solar H-alpha features with hot onsets. III. Long fibrils in Lyman-alpha and with ALMA

NASA Astrophysics Data System (ADS)

Rutten, R. J.

2017-02-01

In H-alpha most of the solar surface is covered by dense canopies of long opaque fibrils, but predictions for quiet-Sun observations with ALMA have ignored this fact. Comparison with Ly-alpha suggests that the extraordinary opacity of H-alpha fibrils is caused by hot precursor events. Application of a recipe that assumes momentary Saha-Boltzmann extinction during their hot onset to millimeter wavelengths suggests that ALMA will observe H-alpha-like fibril canopies, not acoustic shocks underneath, and will yield data more interesting than if these canopies were transparent. An additional file is available at the end of the PDF file of this article.This study is offered as compliment to M.W.M. de Graauw. Our ways, objects, instruments and spectral domains parted after the 1970 eclipse but converge here.

Norepinephrine infusion with and without alpha-adrenergic blockade by phentolamine increases salivary alpha amylase in healthy men.

PubMed

Kuebler, Ulrike; von Känel, Roland; Heimgartner, Nadja; Zuccarella-Hackl, Claudia; Stirnimann, Guido; Ehlert, Ulrike; Wirtz, Petra H

2014-11-01

Mental stress reliably induces increases in salivary alpha amylase (sAA), a suggested surrogate marker for sympathetic nervous system (SNS) reactivity. While stress-induced sAA increases correlate with norepinephrine (NE) secretion, a potential mediating role of noradrenergic mechanisms remains unclear. In this study, we investigated for the first time in humans whether a NE-stress-reactivity mimicking NE-infusion with and without alpha-adrenergic blockade by phentolamine would induce changes in sAA. In a single-blind placebo-controlled within-subjects design, 21 healthy men (29-66 years) took part in three different experimental trials varying in terms of substance infusion with a 1-min first infusion followed by a 15-min second infusion: saline-infusion (trial-1), NE-infusion (5 μg/min) without alpha-adrenergic blockade (trial-2), and with phentolamine-induced non-selective blockade of alpha1- and alpha2-adrenergic receptors (trial-3). Saliva samples were collected immediately before, during, and several times after substance infusion in addition to blood pressure and heart rate readings. Experimental trials significantly differed in sAA reactivity to substance-infusion (p=.001) with higher sAA reactivity following NE-infusion with (trial-3; p=.001) and without alpha-adrenergic-blockade (trial-2; p=.004) as compared to placebo-infusion (trial-1); sAA infusion reactivity did not differ between trial-2 and trial-3 (p=.29). Effective phentolamine application was verified by blood pressure and heart rate infusion reactivity. Salivary cortisol was not affected by NE, either with or without alpha-adrenergic-blockade. We found that NE-infusion stimulates sAA secretion, regardless of co-administered non-selective alpha-adrenergic blockade by phentolamine, suggesting that the mechanism underlying stress-induced sAA increases may involve NE. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lyman alpha radiation in external galaxies

NASA Technical Reports Server (NTRS)

Neufeld, David A.; Mckee, Christopher F.

1990-01-01

The Ly alpha line of atomic hydrogen is often a luminous component of the radiation emitted by distant galaxies. Except for those galaxies which have a substantial central source of non-stellar ionizing radiation, most of the Ly alpha radiation emitted by galaxies is generated within regions of the interstellar medium which are photoionized by starlight. Conversely, much of the energy radiated by photoionized regions is carried by the Ly alpha line. Only hot, massive stars are capable of ionizing hydrogen in the interstellar medium which surrounds them, and because such stars are necessarily short-lived, Ly alpha emission traces regions of active star formation. Researchers argue that the strength of the Ly alpha emission observed from external galaxies may be used to estimate quantitatively the dust content of the emitting region, while the Ly alpha line profile is sensitive to the presence of shock waves. Interstellar dust particles and shock waves are intimately associated with the process of star formation in two senses. First, both dust particles and shock waves owe their existence to stellar activity; second, they may both serve as agents which facilitate the formation of stars, shocks by triggering gravitational instabilities in the interstellar gas that they compress, and dust by shielding star-forming molecular clouds from the ionizing and dissociative effects of external UV radiation. By using Ly alpha observations as a probe of the dust content in diffuse gas at high redshift, we might hope to learn about the earliest epochs of star formation.

Overview Of Suborbital Human Transportation Concept Alpha

NASA Astrophysics Data System (ADS)

Adirim, H.; Pilz, N.; Marini, M.; Hendrick, P.; Schmid, M.; Behr, R.; Barth, T.; Tarfeld, F.; Wiegand, A.; Charbonnier, D.; Haya Ramos, R.; Steeland, J.; Mack, A.

2011-05-01

Within the EC co-funded project FAST20XX (Future high-Altitude high-Speed Transport 20XX), the European suborbital passenger transportation system concept ALPHA (Airplane Launched PHoenix Aircraft), which shall be based to a maximum extent on existing technologies and capabilities, is currently being investigated as collaborative project by a European consortium under coordination of ESA. The ALPHA concept incorporates an air-launch from a carrier aircraft, which shall be used as first stage. The ALPHA vehicle shall be capable of transporting up to four passengers plus one pilot to an altitude of at least 100 km. The ALPHA vehicle is a down-scaled version of the suborbital space transportation concept Hopper, which was already deeply investigated within the European FESTIP System Study and the German ASTRA program including the successfully flown experimental landing demonstrator Phoenix. This approach has allowed the use of existing aerodynamic vehicle data and has led to the adaptation of the external Hopper/Phoenix configuration for ALPHA. In FESTIP and ASTRA, the Hopper configuration showed sufficient stability margins. Due to the geometric similarity of the ALPHA and Hopper vehicles, a trimable and flyable configuration could be derived by means of ALPHA flight trajectory calculations. In its current configuration, the ALPHA vehicle has a length of ca. 9 m and a gross take-off mass of ca. 3.5 Mg. The launch, staging and separation of ALPHA shall be performed either as internal air-launch from the cargo bay of the carrier aircraft, as under-wing air-launch or as towed air-launch. After separation from the carrier aircraft, the ALPHA vehicle ignites its onboard rocket propulsion system. Since conventional liquid and solid propulsion did not seem suitable for ALPHA due to Their high cost, limited safety and toxicity, a low-cost, “green” and non-hazardous hybrid propulsion system based on liquid nitrous oxide in combination with a solid polymer fuel was

Meta-Analysis of Coefficient Alpha

ERIC Educational Resources Information Center

Rodriguez, Michael C.; Maeda, Yukiko

2006-01-01

The meta-analysis of coefficient alpha across many studies is becoming more common in psychology by a methodology labeled reliability generalization. Existing reliability generalization studies have not used the sampling distribution of coefficient alpha for precision weighting and other common meta-analytic procedures. A framework is provided for…

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

An alpha particle instrument with alpha, proton, and X-ray modes for planetary chemical analyses

NASA Technical Reports Server (NTRS)

Economou, T. E.; Turkevich, A. L.

1976-01-01

The interaction of alpha particles with matter is employed in a compact instrument that could provide rather complete in-situ chemical analyses of surfaces and thin atmospheres of extraterrestrial bodies. The instrument is a miniaturized and improved version of the Surveyor lunar instrument. The backscattering of alpha particles and (alpha, p) reactions provide analytical data on the light elements (carbon-iron). An X-ray mode that detects the photons produced by the alpha sources provides sensitivity and resolution for the chemical elements heavier than about silicon. The X-rays are detected by semiconductor detectors having a resolution between 150 and 250 eV at 5.9 keV. Such an instrument can identify and determine with good accuracy 99 percent of the atoms (except hydrogen) in rocks. For many trace elements, the detecting sensitivity is a few ppm. Auxiliary sources could be used to enhance the sensitivities for elements of special interest. The instrument could probably withstand the acceleration involved in semi-hard landings.

Transforming growth factor-alpha (TGF-alpha) in a semisolid dosage form: preservative and vehicle selection.

PubMed

Tan, E L; Shah, H S; Leister, K J; Kozick, L M; Pasciak, P; Vanderlaan, R K; Yu, C D; Patel, B

1993-08-01

The selection of an ideal semisolid vehicle for growth factors presents a challenge. Some antimicrobial agents are known to delay wound healing. The objective of this investigation was to identify appropriate preservatives and vehicles for TGF-alpha. Criteria for acceptance are noninterference with the mitogenic activity of TGF-alpha as well as adequate product preservation. Vehicles considered were o/w creams, ointments, and a gel. Combinations of six preservatives were tested. Selection was determined using both microbial preservative challenge and TGF-alpha mitogenic assay. In the former, 10 species of microorganisms were inoculated into formulation samples. At selected time intervals, it was determined whether colonies decreased, increased, or remained constant. In the mitogenic assay, samples of either preservatives or formulation prototypes were introduced to TGF-alpha-stimulated fibroblast cell cultures. Mitogenesis was determined by measuring 3H-dThd uptake into newly synthesized DNA. As preservatives, sorbic acid and quaternium-15 appear to satisfy both selection criteria. A thermosetting gel appears most promising as vehicle.

Antibody-mediated reduction of {alpha}-ketoamides

DOEpatents

Schultz, P.G.; Gallop, M.A.

1998-06-09

Monoclonal antibodies raised against a 4-nitrophenyl phosphonate hapten catalyze the stereospecific reduction of an {alpha}-ketoamide to the corresponding {alpha}-hydroxyamide in the presence of an appropriate reducing agent.

Antibody-mediated reduction of .alpha.-ketoamides

DOEpatents

Schultz, Peter G.; Gallop, Mark A.

1998-01-01

Monoclonal antibodies raised against a 4-nitrophenyl phosphonate hapten catalyze the stereospecific reduction of an .alpha.-ketoamide to the corresponding .alpha.-hydroxyamide in the presence of an appropriate reducing agent.

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

Identification of 4,5-didemethyl-4-O-alpha-D-glucopyranosylsimmondsin and pinitol alpha-D-galactosides in jojoba seed meal (Simmondsia chinensis).

PubMed

Van Boven, M; Leyssen, T; Busson, R; Holser, R; Cokelaere, M; Flo, G; Decuypere, E

2001-09-01

The isolation and identification of two pinitol alpha-D-galactosides from jojoba meal are described. The products were isolated by a combination of preparative HPLC on silica gel and TLC on amino silica gel and were identified by MS, NMR spectroscopy, and chemical derivatization as 5-O-(alpha-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol or 5-alpha-D-galactopyranosyl-D-pinitol and 2-O-(alpha-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol or 2-alpha-D-galactopyranosyl-D-pinitol. The same preparative HPLC method on silica gel allowed a new simmondsin derivative to be isolated and identified as 4,5-didemethyl-4-O-alpha-D-glucopyranosylsimmondsin mainly by NMR spectroscopy and high-resolution mass spectrometry.

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

Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

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

Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.

2011-03-11

Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomicsmore » screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.« less

Gene transfer mediated by alpha2-macroglobulin.

PubMed Central

Schneider, H; Huse, K; Birkenmeier, G; Otto, A; Scholz, G H

1996-01-01

alpha2-Macroglobulin covalently linked to poly(L)-lysine can be used as a vehicle for receptor-mediated gene transfer. This modified alpha2-macroglobulin maintains its ability to bind to the alpha2-macroglobulin receptor, and was shown to introduce a luciferase reporter gene plasmid into HepG2 human hepatoma cells in vitro. The alpha2-macroglobulin receptor is a very large and multifunctional cell surface receptor, whose rapid and efficient internalization rate makes it attractive for gene therapy, e.g. for hepatic gene targeting via injection into the portal vein. PMID:8871570

Studies on G-protein alpha.betagamma heterotrimer formation reveal a putative S-prenyl-binding site in the alpha subunit.

PubMed Central

Dietrich, Alexander; Scheer, Alexander; Illenberger, Daria; Kloog, Yoel; Henis, Yoav I; Gierschik, Peter

2003-01-01

The alpha and betagamma subunits of heterotrimeric G-proteins contain specific lipid modifications, which are required for their biological function. However, the relevance of these modifications to the interactions within the heterotrimeric G-protein is not fully understood. In order to explore the role of the S-prenyl moiety of the isoprenylated betagamma dimer of retinal transducin, betagamma(t), in the formation of the heterotrimeric complex with the corresponding N-acylated alpha subunit, alpha(t), we employed purified fully processed subunits, which are soluble in aqueous solutions without detergents. Pertussis-toxin-mediated [(32)P]ADP-ribosylation of alpha(t) is strongly stimulated (approximately 10-fold) in the presence of betagamma(t) and can thus serve as a measure for heterotrimer formation. Using this assay, preincubation of alpha(t) with S-prenyl analogues containing farnesyl or geranylgeranyl moieties was found to inhibit heterotrimer formation in a dose-dependent manner. The inhibition was competitive and reversible, as indicated by its reversal upon increase of the betagamma(t) dimer concentration or by removal of the S-prenyl analogue using gel filtration. The competitive nature of the inhibition is supported by the marked attenuation of the inhibition when the S-prenyl analogue was added to alpha(t) together with or after betagamma(t). The inhibition does not involve interaction with the alpha(t) acyl group, since an S-prenyl analogue inhibited the [(32)P]ADP-ribosylation of an unlipidated alpha(t) mutant. These data suggest the existence of a hitherto unrecognized S-prenyl-binding site in alpha(t), which is critical for its interaction with prenylated betagamma(t). PMID:12952523

Reduced Fragment Diversity for Alpha and Alpha-Beta Protein Structure Prediction using Rosetta.

PubMed

Abbass, Jad; Nebel, Jean-Christophe

2017-01-01

Protein structure prediction is considered a main challenge in computational biology. The biannual international competition, Critical Assessment of protein Structure Prediction (CASP), has shown in its eleventh experiment that free modelling target predictions are still beyond reliable accuracy, therefore, much effort should be made to improve ab initio methods. Arguably, Rosetta is considered as the most competitive method when it comes to targets with no homologues. Relying on fragments of length 9 and 3 from known structures, Rosetta creates putative structures by assembling candidate fragments. Generally, the structure with the lowest energy score, also known as first model, is chosen to be the "predicted one". A thorough study has been conducted on the role and diversity of 3-mers involved in Rosetta's model "refinement" phase. Usage of the standard number of 3-mers - i.e. 200 - has been shown to degrade alpha and alpha-beta protein conformations initially achieved by assembling 9-mers. Therefore, a new prediction pipeline is proposed for Rosetta where the "refinement" phase is customised according to a target's structural class prediction. Over 8% improvement in terms of first model structure accuracy is reported for alpha and alpha-beta classes when decreasing the number of 3- mers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development of a transmission alpha particle dosimetry technique using A549 cells and a Ra-223 source for targeted alpha therapy.

PubMed

Al Darwish, R; Staudacher, A H; Li, Y; Brown, M P; Bezak, E

2016-11-01

In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells. In this study, as an initial step, the authors present a transmission dosimetry design for alpha particles using A549 lung carcinoma cells, an external alpha particle emitting source (radium 223; Ra-223) and a Timepix pixelated semiconductor detector. The dose delivery to the A549 lung carcinoma cell line from a Ra-223 source, considered to be an attractive radionuclide for alpha therapy, was investigated in the current work. A549 cells were either unirradiated (control) or irradiated for 12, 1, 2, or 3 h with alpha particles emitted from a Ra-223 source positioned below a monolayer of A549 cells. The Timepix detector was used to determine the number of transmitted alpha particles passing through the A549 cells and DNA double strand breaks (DSBs) in the form of γ-H2AX foci were examined by fluorescence microscopy. The number of transmitted alpha particles was correlated with the observed DNA DSBs and the delivered radiation dose was estimated. Additionally, the dose deposited was calculated using Monte Carlo code SRIM. Approximately 20% of alpha particles were transmitted and detected by Timepix. The frequency and number of γ-H2AX foci increased significantly following alpha particle irradiation as compared to unirradiated controls. The equivalent dose delivered to A549 cells was estimated to be approximately 0.66, 1.32, 2.53, and 3.96 Gy after 12, 1, 2, and 3 h

Abnormal TNF-alpha production in diabetes-prone BB rats: enhanced TNF-alpha expression and defective PGE2 feedback inhibition.

PubMed Central

Rothe, H; Ongören, C; Martin, S; Rösen, P; Kolb, H

1994-01-01

Upon stimulation with lipopolysaccharide (LPS), peritoneal macrophages from diabetes-prone Bio-Breeding (BB) rats secrete more tumour necrosis factor-alpha (TNF-alpha) than macrophages from diabetes-resistant BB or normal Wistar rats. Enhanced transcription was demonstrated by Northern blot analysis and at the single cell level by mRNA: RNA hybridization. Cytofluorometry analysis showed 2-4 times more plasma membrane and total cell-associated TNF-alpha in macrophages of diabetes-prone BB rats. The analysis of fluorescence intensity showed a single peak, and TNF-alpha mRNA was found in > 90% of macrophages. These findings exclude TNF hypersecretion as being due to an abnormal subfraction of cells. TNF-alpha gene hyperexpression in diabetes-prone BB rats was not due to mutations in the regulatory regions of the promoter, which could be shown by cloning and sequencing of the TNF-alpha promoter in the three rat strains. When searching for other regulatory defects we found the production of prostaglandin E2 (PGE2) in response to LPS to be up to 10 times lower in macrophages from diabetes-prone BB rats than from Wistar rats. Furthermore, BB rats macrophages required significantly higher concentrations of PGE2 for suppression of TNF-alpha secretion. We conclude that abnormal TNF-alpha production in macrophages from diabetes-prone BB rats is due to enhanced gene transcription and translation and that this is associated with defective PGE2 feedback inhibition. Images Figure 1 Figure 2 PMID:8206514

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

Alpha1-adrenergic blockers: current usage considerations.

PubMed

Sica, Domenic A

2005-12-01

Alpha1-adrenergic-blocking drugs are effective in reducing blood pressure and do so in a fashion comparable to most other antihypertensive drug classes. These compounds are most effective in patients in the upright position, reducing systolic and diastolic pressures by 8%-10%. Alpha1-adrenergic-blocking drugs incrementally reduce blood pressure when combined with most drug classes and are the only antihypertensive drug class to improve plasma lipid profiles. Alpha1-adrenergic-blocking drugs are also accepted as important elements of the treatment plan for symptomatic benign prostatic hypertrophy. Dose escalation of an alpha1-adrenergic-blocking drug can trigger renal Na+ retention, and the ensuing volume expansion can attenuate its blood pressure-lowering effect. Orthostatic hypotension can occur with these compounds, particularly when a patient is volume-contracted. Dizziness, headache, and drowsiness are common side effects with alpha1-adrenergic blockers. A modest decline in the use of doxazosin and other alpha1-adrenergic-blocking drugs has occurred coincident to the early termination of the doxazosin treatment arm in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Thermal diffusivity of alpha-mercuric iodide

NASA Astrophysics Data System (ADS)

Burger, A.; Morgan, S. H.; Henderson, D. O.; Silberman, E.; Nason, D.

1991-01-01

The thermal diffusivity and its anisotropy is measured along the principal axes of tetragonal alpha-HgI2 semiconductor single crystals grown from vapor. The experiments are carried out using the flash pulse method. The results show that alpha(100-line-type) = 0.00370 sq cm/s + or - 3 percent and alpha(001-line-type = 0.00103 sq cm/s + or - 10 percent. Necessary corrections are made for the experimental variables of heat losses and finite pulse duration in the data analysis.

Alpha-globin gene haplotypes in South American Indians.

PubMed

Zago, M A; Melo Santos, E J; Clegg, J B; Guerreiro, J F; Martinson, J J; Norwich, J; Figueiredo, M S

1995-08-01

The haplotypes of the alpha-globin gene cluster were determined for 99 Indians from the Brazilian Amazon region who belong to 5 tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Three predominant haplotypes were identified: Ia (present in 38.9% of chromosomes), IIIa (25.8%), and IIe (22.1%). The only alpha-globin gene rearrangement detected was alpha alpha alpha 3.7 I gene triplication associated with haplotype IIIa, found in high frequencies (5.6% and 10.6%) in two tribes and absent in the others. alpha-Globin gene deletions that cause alpha-thalassemia were not seen, supporting the argument that malaria was absent in these populations until recently. The heterogeneous distribution of alpha-globin gene haplotypes and rearrangements among the different tribes differs markedly from the homogeneous distribution of beta-globin gene cluster haplotypes and reflects the action of various genetic mechanisms (genetic drift, founder effect, consanguinity) on small isolated population groups with a complicated history of divergence-fusion events. The alpha-globin gene haplotype distribution has some similarities to distributions observed in Southeast Asian and Pacific Island populations, indicating that these populations have considerable genetic affinities. However, the absence of several features of the alpha-globin gene cluster that are consistently present among the Pacific Islanders suggests that the similarity of haplotypes between Brazilian Indians and people from Polynesia, Micronesia, and Melanesia is more likely to result of ancient common ancestry rather than the consequence of recent direct genetic contribution through immigration.

Velocity space instabilities of alpha particles in tokamak reactors

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

Sigmar, D.J.

1979-01-01

In this lecture on high frequency instability due to isotropic hollow alpha velocity distributions it was first shown that such distributions can actually arise under thermonuclear conditions in a tokamak reactor, particularly for the case of imperfect alpha particle confinement. The toroidal geometry (i.e., the poloidal variation of the alpha gyrofrequency) then leads to linear instability of the compressional Alfven wave ..omega.. = C/sub A/k/sub perpendicular/ with k/sub parallel/ congruent to O, k/sub perpendicular/ rho/sub ..cap alpha../ greater than or equal to 1, v/sub ..cap alpha../ > C/sub A/, at the low harmonics ..omega.. congruent to n ..omega../sub c..cap alpha../.more » Thus the free energy of the inverted alpha distribution is accessible and produces anomalously rapid diffusion of F/sub ..cap alpha../(v/sub perpendicular/). (MOW)« less

Evidence for Alpha Receptors in the Human Ureter

NASA Astrophysics Data System (ADS)

Madeb, Ralph; Knopf, Joy; Golijanin, Dragan; Bourne, Patricia; Erturk, Erdal

2007-04-01

An immunohistochemical and western blot expression analysis of human ureters was performed in order to characterize the alpha-1-adrenergic receptor distribution along the length of the human ureteral wall. Mapping the distribution will assist in understanding the potential role alpha -1-adrenergic receptors and their subtype density might have in the pathophysiology of ureteral colic and stone passage. Patients diagnosed with renal cancer or bladder cancer undergoing nephrectomy, nephroureterectomy, or cystectomy had ureteral specimens taken from the proximal, mid, distal and tunneled ureter. Tissues were processed for fresh frozen examination and fixed in formalin. None of the ureteral specimens were involved with cancer. Serial histologic sections and immunohistochemical studies were performed using antibodies specific for alpha-1-adrenergic receptor subtypes (alpha 1a, alpha 1b, alpha 1d). The sections were examined under a light microscope and scored as positive or negative. In order to validate and quantify the alpha receptor subtypes along the human ureter. Western blotting techniques were applied. Human ureter stained positively for alpha -1-adrenergic receptors. Immunostaining appeared red, with intense reaction in the smooth muscle of the ureter and endothelium of the neighboring blood vessels. There was differential expression between all the receptors with the highest staining for alpha-1D subtype. The highest protein expression for all three subtypes was in the renal pelvis and decreased with advancement along the ureter to the distal ureter. At the distal ureter, there was marked increase in expression as one progressed towards the ureteral orifice. The same pattern of protein expression was exhibited for all three alpha -1-adrenergic receptor subtypes. We provide preliminary evidence for the ability to detect and quantify the alpha-1-receptor subtypes along the human ureter which to the best of our knowledge has never been done with

Mind Your p's and Alphas.

ERIC Educational Resources Information Center

Stallings, William M.

In the educational research literature alpha, the a priori level of significance, and p, the a posteriori probability of obtaining a test statistic of at least a certain value when the null hypothesis is true, are often confused. Explanations for this confusion are offered. Paradoxically, alpha retains a prominent place in textbook discussions of…

The alpha-form of the hydroxides of bivalent metals

NASA Technical Reports Server (NTRS)

Feitknecht, W.

1984-01-01

X-ray analyses were made of the hydroxides of the bivalent metals. The freshly pptd. hydroxide is usually in the alpha-form, which on standing is converted to another form or other forms. The alpha and c grating dimensions of the alpha-form and the C6-type of Co, Zn, C, Co-Zn and Ni-Zn hydroxides are tabulated. Ni hydroxide does not exhibit an alpha-form. The alpha-Co(OH)2, the blue form, is stabilized by sugar or by the higher alcohols: these compounds do not stabilize alpha-Zn(OH)2.

Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors.

PubMed

Newman-Tancredi, A; Nicolas, J P; Audinot, V; Gavaudan, S; Verrièle, L; Touzard, M; Chaput, C; Richard, N; Millan, M J

1998-08-01

This study examined the activity of chemically diverse alpha2 adrenoceptor ligands at recombinant human (h) and native rat (r) alpha2A adrenoceptors compared with 5-HT1A receptors. First, in competition binding experiments at h alpha2A and h5-HT1A receptors expressed in CHO cells, several compounds, including the antagonists 1-(2-pyrimidinyl)piperazine (1-PP), (+/-)-idazoxan, benalfocin (SKF 86466), yohimbine and RX 821,002, displayed preference for h alpha2A versus h5-HT1A receptors of only 1.4-, 3.6-, 4-, 10- and 11-fold, respectively (based on differences in pKi values). Clonidine, brimonidine (UK 14304), the benzopyrrolidine fluparoxan and the guanidines guanfacine and guanabenz exhibited intermediate selectivity (22- to 31-fold) for h alpha2A receptors. Only the antagonist atipamezole and the agonist dexmedetomidine (DMT) displayed high preference for alpha2 adrenoceptors (1290- and 91-fold, respectively). Second, the compounds were tested for their ability to induce h5-HT1A receptor-mediated G-protein activation, as indicated by the stimulation of [35S]GTPgammaS binding. All except atipamezole and RX 821,002 exhibited agonist activity, with potencies which correlated with their affinity for h5-HT1A receptors. Relative efficacies (Emax values) were 25-35% for guanabenz, guanfacine, WB 4101 and benalfocin, 50-65% for 1-PP, (+/-)-idazoxan and clonidine, and over 70% for fluparoxan, oxymetazoline and yohimbine (relative to 5-HT = 100%). Yohimbine-induced [35S]GTPgammaS binding was inhibited by the selective 5-HT1A receptor antagonist WAY 100,635. In contrast, RX 821,002 was the only ligand which exhibited antagonist activity at h5-HT1A receptors, inhibiting 5-HT-stimulated [35S]GTPgammaS binding. Atipamezole, which exhibited negligeable affinity for 5-HT1A receptors, was inactive. Third, the affinities for r alpha2A differed considerably from the affinities for h alpha2A receptors whereas the affinities for r5-HT1A differed much less from the affinities for h5-HT

Alpha 1 antitrypsin to treat lung disease in alpha 1 antitrypsin deficiency: recent developments and clinical implications.

PubMed

Chapman, Kenneth R; Chorostowska-Wynimko, Joanna; Koczulla, A Rembert; Ferrarotti, Ilaria; McElvaney, Noel G

2018-01-01

Alpha 1 antitrypsin deficiency is a hereditary condition characterized by low alpha 1 proteinase inhibitor (also known as alpha 1 antitrypsin [AAT]) serum levels. Reduced levels of AAT allow abnormal degradation of lung tissue, which may ultimately lead to the development of early-onset emphysema. Intravenous infusion of AAT is the only therapeutic option that can be used to maintain levels above the protective threshold. Based on its biochemical efficacy, AAT replacement therapy was approved by the US Food and Drug administration in 1987. However, there remained considerable interest in selecting appropriate outcome measures that could confirm clinical efficacy in a randomized controlled trial setting. Using computed tomography as the primary measure of decline in lung density, the capacity for intravenously administered AAT replacement therapy to slow and modify the course of disease progression was demonstrated for the first time in the Randomized, Placebo-controlled Trial of Augmentation Therapy in Alpha-1 Proteinase Inhibitor Deficiency (RAPID) trial. Following these results, an expert review forum was held at the European Respiratory Society to discuss the findings of the RAPID trial program and how they may change the landscape of alpha 1 antitrypsin emphysema treatment. This review summarizes the results of the RAPID program and the implications for clinical considerations with respect to diagnosis, treatment and management of emphysema due to alpha 1 antitrypsin deficiency.

NMR study of the transforming growth factor-alpha (TGF-alpha)-epidermal growth factor receptor complex. Visualization of human TGF-alpha binding determinants through nuclear Overhauser enhancement analysis.

PubMed

McInnes, C; Hoyt, D W; Harkins, R N; Pagila, R N; Debanne, M T; O'Connor-McCourt, M; Sykes, B D

1996-12-13

The study of human transforming growth factor-alpha (TGF-alpha) in complex with the epidermal growth factor (EGF) receptor extracellular domain has been undertaken in order to generate information on the interactions of these molecules. Analysis of 1H NMR transferred nuclear Overhauser enhancement data for titration of the ligand with the receptor has yielded specific data on the residues of the growth factor involved in contact with the larger protein. Significant increases and decreases in nuclear Overhauser enhancement cross-peak intensity occur upon complexation, and interpretation of these changes indicates that residues of the A- and C-loops of TGF-alpha form the major binding interface, while the B-loop provides a structural scaffold for this site. These results corroborate the conclusions from NMR relaxation studies (Hoyt, D. W., Harkins, R. N., Debanne, M. T., O'Connor-McCourt, M., and Sykes, B. D. (1994) Biochemistry 33, 15283-15292), which suggest that the C-terminal residues of the polypeptide are immobilized upon receptor binding, while the N terminus of the molecule retains considerable flexibility, and are consistent with structure-function studies of the TGF-alpha/EGF system indicating a multidomain binding model. These results give a visualization, for the first time, of native TGF-alpha in complex with the EGF receptor and generate a picture of the ligand-binding site based upon the intact molecule. This will undoubtedly be of utility in the structure-based design of TGF-alpha/EGF agonists and/or antagonists.

Three dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes.

PubMed

Kanekura, Takuro; Sakuraba, Hitoshi; Matsuzawa, Fumiko; Aikawa, Seiichi; Doi, Hirofumi; Hirabayashi, Yoshio; Yoshii, Noriko; Fukushige, Tomoko; Kanzaki, Tamotsu

2005-01-01

Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. Missense mutations, R329W or R329Q were identified in two Japanese Kanzaki patients. Although they are on the same codon, the clinical manifestation was more severe in R329W because an amino acid substitution led to protein instability resulting in structural change, which is greater in R329W than in R329Q. To examine whether the different clinical phenotypes are attributable to the two mutations. Plasma alpha-NAGA activity and urinary excreted glycopeptides were measured and three-dimensional models of human alpha-NAGA and its complexes with GalNAcalpha1-O-Ser and GalNAcalpha1-O-Thr were constructed by homology modeling. Residual enzyme activity was significantly higher in the R329Q- than the R329W mutant (0.022+/-0.005 versus 0.005+/-0.001 nmol/h/ml: p<0.05); the urinary ratios of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr were 2:10 and 8:10, respectively. GalNAcalpha1-O-Ser/Thr fit tightly in a narrow space of the active site pocket of alpha-NAGA. GalNAcalpha1-O-Thr requires a larger space to associate with alpha-NAGA because of the side chain (CH3) of the threonine residue. Our findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation. Structural analysis revealed biochemical and phenotypic differences in these Kanzaki patients with the R329Q and R329W mutation.

Computational studies of H5N1 hemagglutinin binding with SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal

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

Li Minyong; Wang Binghe

2006-09-01

For influenza H5N1 hemagglutinin, a switch from SA-{alpha}-2, 3-Gal to SA-{alpha}-2, 6-Gal receptor specificity is a critical step leading to the conversion from avian-to-human to human-to-human infection. Therefore, the understanding of the binding modes of SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal to H5N1 hemagglutinin will be very important for the examination of possible mutations needed for going from an avian to a human flu virus. Based on the available H5N1 hemagglutinin crystal structure, the binding profiles between H5N1 hemagglutinin and two saccharide ligands, SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal, were investigated by ab initio quantum mechanics, molecular docking, molecular mechanics, and molecularmore » dynamics simulations. It was found that SA-{alpha}-2, 3-Gal has strong multiple hydrophobic and hydrogen bond interactions in its trans conformation with H5N1 hemagglutinin, whereas the SA-{alpha}-2, 6-Gal only shows weak interactions in a different conformation (cis type)« less

Alpha 2 LASSO Data Bundles

DOE Data Explorer

Gustafson, William Jr; Vogelmann, Andrew; Endo, Satoshi; Toto, Tami; Xiao, Heng; Li, Zhijin; Cheng, Xiaoping; Kim, Jinwon; Krishna, Bhargavi

2015-08-31

The Alpha 2 release is the second release from the LASSO Pilot Phase that builds upon the Alpha 1 release. Alpha 2 contains additional diagnostics in the data bundles and focuses on cases from spring-summer 2016. A data bundle is a unified package consisting of LASSO LES input and output, observations, evaluation diagnostics, and model skill scores. LES input include model configuration information and forcing data. LES output includes profile statistics and full domain fields of cloud and environmental variables. Model evaluation data consists of LES output and ARM observations co-registered on the same grid and sampling frequency. Model performance is quantified by skill scores and diagnostics in terms of cloud and environmental variables.

Density-induced suppression of the {alpha}-particle condensate in nuclear matter and the structure of {alpha}-cluster states in nuclei

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

Funaki, Y.; Horiuchi, H.; International Institute for Advanced Studies, Kizugawa 619-0225

2008-06-15

At low densities, with decreasing temperatures, in symmetric nuclear matter {alpha} particles are formed, which eventually give raise to a quantum condensate with four-nucleon {alpha}-like correlations (quartetting). Starting with a model of {alpha} matter, where undistorted {alpha} particles interact via an effective interaction such as the Ali-Bodmer potential, the suppression of the condensate fraction at zero temperature with increasing density is considered. Using a Jastrow-Feenberg approach, it is found that the condensate fraction vanishes near saturation density. Additionally, the modification of the internal state of the {alpha} particle due to medium effects will further reduce the condensate. In finite systems,more » an enhancement of the S-state wave function of the center-of-mass orbital of {alpha}-particle motion is considered as the correspondence to the condensate. Wave functions have been constructed for self-conjugate 4n nuclei that describe the condensate state but are fully antisymmetrized on the nucleonic level. These condensate-like cluster wave functions have been successfully applied to describe properties of low-density states near the n{alpha} threshold. Comparison with orthogonality condition model calculations in {sup 12}C and {sup 16}O shows strong enhancement of the occupation of the S-state center-of-mass orbital of the {alpha} particles. This enhancement is decreasing if the baryon density increases, similar to the density-induced suppression of the condensate fraction in {alpha} matter. The ground states of {sup 12}C and {sup 16}O show no enhancement at all, thus a quartetting condensate cannot be formed at saturation densities.« less

Teaching Calculus with Wolfram|Alpha

ERIC Educational Resources Information Center

Dimiceli, Vincent E.; Lang, Andrew S. I. D.; Locke, LeighAnne

2010-01-01

This article describes the benefits and drawbacks of using Wolfram|Alpha as the platform for teaching calculus concepts in the lab setting. It is a result of our experiences designing and creating an entirely new set of labs using Wolfram|Alpha. We present the reasoning behind our transition from using a standard computer algebra system (CAS) to…

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.

Sensitization to the mammalian oligosaccharide galactose-alpha-1,3-galactose (alpha-gal): experience in a Flemish case series.

PubMed

Ebo, D G; Faber, M; Sabato, V; Leysen, J; Gadisseur, A; Bridts, C H; De Clerck, L S

2013-01-01

Recent observations have disclosed that the galactose-alpha (1,3)-galactose (alpha-gal) moiety of non-primate glycoproteins can constitute a target for meat allergy. To describe adults with allergic reactions to mammalian meat, dairy products and gelatin. To investigate whether patients could demonstrate sensitization to activated recombinant human coagulation factor VII ectapog alpha that is produced in baby hamster kidney cells. Ten adults with mammalian meat, dairy products and gelatin allergies were examined using quantification of specific IgE and/or skin prick test for red meat, milk, milk components, gelatin, cetuximab and eptacog alpha. Most patients demonstrate quite typical clinical histories and serological profiles, with anti-alpha-gal titers varying from less than 1% to over 25% of total serum IgE. All patients demonstrate negative sIgE for gelatin, except the patient with a genuine gelatin allergy. All patients also demonstrated a negative sIgE to recombinant milk components casein, lactalbumin and lactoglobulin. Specific IgE to eptacog was positive in 5 out of the 9 patients sensitized to alpha-gal and none of the 10 control individuals. This series confirms the importance of the alpha-gal carbohydrate moiety as a potential target for allergy to mammalian meat, dairy products and gelatin (oral, topical or parenteral) in a Flemish population of meat allergic adults. It also confirms in vitro tests to mammalian meat generally to be more reliable than mammalian meat skin tests, but that diagnosis can benefit from skin testing with cetuximab. Specific IgE to gelatin is far too insensitive to diagnose alphaa-gal related gelatin allergy. IgE binding studies indicate a potential risk of alpha-gal-containing human recombinant proteins produced in mammalians.

Q (Alpha) Function and Squeezing Effect

NASA Technical Reports Server (NTRS)

Yunjie, Xia; Xianghe, Kong; Kezhu, Yan; Wanping, Chen

1996-01-01

The relation of squeezing and Q(alpha) function is discussed in this paper. By means of Q function, the squeezing of field with gaussian Q(alpha) function or negative P(a)function is also discussed in detail.

Endocytosis of GPI-linked membrane folate receptor-alpha

PubMed Central

1996-01-01

GPI-linked membrane folate receptors (MFRs) have been implicated in the receptor-mediated uptake of reduced folate cofactors and folate-based chemotherapeutic drugs. We have studied the biosynthetic transport to and internalization of MFR isoform alpha in KB-cells. MFR-alpha was synthesized as a 32-kD protein and converted in a maturely glycosylated 36-38-kD protein 1 h after synthesis. 32-kD MFR-alpha was completely soluble in Triton X-100 at 0 degree C. In contrast, only 33% of the 36- 38-kD species could be solubilized at these conditions whereas complete solubilization was obtained in Triton X-100 at 37 degrees C or in the presence of saponin at 0 degree C. Similar solubilization characteristics were found when MFR-alpha at the plasma membrane was labeled with a crosslinkable 125I-labeled photoaffinity-analog of folic acid as a ligand. Triton X-100-insoluble membrane domains containing MFR-alpha could be separated from soluble MFR-alpha on sucrose flotation gradients. Only Triton X-100 soluble MFR-alpha was internalized from the plasma membrane. The reduced-folate-carrier, an integral membrane protein capable of translocating (anti-)folates across membranes, was completely excluded from the Triton X-100- resistant membrane domains. Internalized MFR-alpha recycled slowly to the cell surface during which it remained soluble in Triton X-100 at 0 degree C. Using immunoelectron microscopy, we found MFR-alpha along the entire endocytic pathway: in clathrin-coated buds and vesicles, and in small and large endosomal vacuoles. In conclusion, our data indicate that a large fraction, if not all, of internalizing MFR-alpha bypasses caveolae. PMID:8567728

Endocytosis of GPI-linked membrane folate receptor-alpha.

PubMed

Rijnboutt, S; Jansen, G; Posthuma, G; Hynes, J B; Schornagel, J H; Strous, G J

1996-01-01

GPI-linked membrane folate receptors (MFRs) have been implicated in the receptor-mediated uptake of reduced folate cofactors and folate-based chemotherapeutic drugs. We have studied the biosynthetic transport to and internalization of MFR isoform alpha in KB-cells. MFR-alpha was synthesized as a 32-kD protein and converted in a maturely glycosylated 36-38-kD protein 1 h after synthesis. 32-kD MFR-alpha was completely soluble in Triton X-100 at 0 degree C. In contrast, only 33% of the 36-38-kD species could be solubilized at these conditions whereas complete solubilization was obtained in Triton X-100 at 37 degrees C or in the presence of saponin at 0 degree C. Similar solubilization characteristics were found when MFR-alpha at the plasma membrane was labeled with a crosslinkable 125I-labeled photoaffinity-analog of folic acid as a ligand. Triton X-100-insoluble membrane domains containing MFR-alpha could be separated from soluble MFR-alpha on sucrose flotation gradients. Only Triton X-100 soluble MFR-alpha was internalized from the plasma membrane. The reduced-folate-carrier, an integral membrane protein capable of translocating (anti-)folates across membranes, was completely excluded from the Triton X-100-resistant membrane domains. Internalized MFR-alpha recycled slowly to the cell surface during which it remained soluble in Triton X-100 at 0 degree C. Using immunoelectron microscopy, we found MFR-alpha along the entire endocytic pathway: in clathrin-coated buds and vesicles, and in small and large endosomal vacuoles. In conclusion, our data indicate that a large fraction, if not all, of internalizing MFR-alpha bypasses caveolae.

Luminescence imaging of water during alpha particle irradiation

NASA Astrophysics Data System (ADS)

Yamamoto, Seiichi; Komori, Masataka; Koyama, Shuji; Toshito, Toshiyuki

2016-05-01

The luminescence imaging of water using the alpha particle irradiation of several MeV energy range is thought to be impossible because this alpha particle energy is far below the Cerenkov-light threshold and the secondary electrons produced in this energy range do not emit Cerenkov-light. Contrary to this consensus, we found that the luminescence imaging of water was possible with 5.5 MeV alpha particle irradiation. We placed a 2 MBq of 241Am alpha source in water, and luminescence images of the source were conducted with a high-sensitivity, cooled charge-coupled device (CCD) camera. We also carried out such imaging of the alpha source in three different conditions to compare the photon productions with that of water, in air, with a plastic scintillator, and an acrylic plate. The luminescence imaging of water was observed from 10 to 20 s acquisition, and the intensity was linearly increased with time. The intensity of the luminescence with the alpha irradiation of water was 0.05% of that with the plastic scintillator, 4% with air, and 15% with the acrylic plate. The resolution of the luminescence image of water was better than 0.25 mm FWHM. Alpha particles of 5.5 MeV energy emit luminescence in water. Although the intensity of the luminescence was smaller than that in air, it was clearly observable. The luminescence of water with alpha particles would be a new method for alpha particle detection and distribution measurements in water.

The alpha glycerophosphate cycle in Drosophila melanogaster V. molecular analysis of alpha glycerophosphate dehydrogenase and alpha glycerophosphate oxidase mutants.

PubMed

Carmon, Amber; Chien, Jeff; Sullivan, David; MacIntyre, Ross

2010-01-01

Two enzymes, alpha glycerophosphate dehydrogenase (GPDH-1) in the cytoplasm and alpha glycerophosphate oxidase (GPO-1) in the mitochondrion cooperate in Drosophila flight muscles to generate the ATP needed for muscle contraction. Null mutants for either enzyme cannot fly. Here, we characterize 15 ethyl methane sulfonate (EMS)-induced mutants in GPDH-1 at the molecular level and assess their effects on structural and evolutionarily conserved domains of this enzyme. In addition, we molecularly characterize 3 EMS-induced GPO-1 mutants and excisions of a P element insertion in the GPO-1 gene. The latter represent the best candidate for null or amorphic mutants in this gene.

Partitioning diversity into independent alpha and beta components.

PubMed

Jost, Lou

2007-10-01

Existing general definitions of beta diversity often produce a beta with a hidden dependence on alpha. Such a beta cannot be used to compare regions that differ in alpha diversity. To avoid misinterpretation, existing definitions of alpha and beta must be replaced by a definition that partitions diversity into independent alpha and beta components. Such a unique definition is derived here. When these new alpha and beta components are transformed into their numbers equivalents (effective numbers of elements), Whittaker's multiplicative law (alpha x beta = gamma) is necessarily true for all indices. The new beta gives the effective number of distinct communities. The most popular similarity and overlap measures of ecology (Jaccard, Sorensen, Horn, and Morisita-Horn indices) are monotonic transformations of the new beta diversity. Shannon measures follow deductively from this formalism and do not need to be borrowed from information theory; they are shown to be the only standard diversity measures which can be decomposed into meaningful independent alpha and beta components when community weights are unequal.

Reduced variability of auditory alpha activity in chronic tinnitus.

PubMed

Schlee, Winfried; Schecklmann, Martin; Lehner, Astrid; Kreuzer, Peter M; Vielsmeier, Veronika; Poeppl, Timm B; Langguth, Berthold

2014-01-01

Subjective tinnitus is characterized by the conscious perception of a phantom sound which is usually more prominent under silence. Resting state recordings without any auditory stimulation demonstrated a decrease of cortical alpha activity in temporal areas of subjects with an ongoing tinnitus perception. This is often interpreted as an indicator for enhanced excitability of the auditory cortex in tinnitus. In this study we want to further investigate this effect by analysing the moment-to-moment variability of the alpha activity in temporal areas. Magnetoencephalographic resting state recordings of 21 tinnitus subjects and 21 healthy controls were analysed with respect to the mean and the variability of spectral power in the alpha frequency band over temporal areas. A significant decrease of auditory alpha activity was detected for the low alpha frequency band (8-10 Hz) but not for the upper alpha band (10-12 Hz). Furthermore, we found a significant decrease of alpha variability for the tinnitus group. This result was significant for the lower alpha frequency range and not significant for the upper alpha frequencies. Tinnitus subjects with a longer history of tinnitus showed less variability of their auditory alpha activity which might be an indicator for reduced adaptability of the auditory cortex in chronic tinnitus.

Identification of functional domains within the alpha and beta subunits of beta-hexosaminidase A through the expression of alpha-beta fusion proteins.

PubMed

Tse, R; Wu, Y J; Vavougios, G; Hou, Y; Hinek, A; Mahuran, D J

1996-08-20

There are three human beta-hexosaminidase isozymes which are composed of all possible dimeric combinations of an alpha and/or a beta subunit; A (alpha beta), and B (beta beta), and S (alpha alpha). The amino acid sequences of the two subunits are 60% identical. The homology between the two chains varies with the middle > the carboxy-terminal > > the amino-terminal portions. Although dimerization is required for activity, each subunit contains its own active site and differs in its substrate specificity and thermal stability. The presence of the beta subunit in hexosaminidase A also influences the substrate specificity of the alpha subunit; e.g., in vivo only the A heterodimer can hydrolyze GM2 ganglioside. In this report, we localize functional regions in the two subunits by cellular expression of alpha/beta fusion proteins joined at adjacently aligned residues. First, a chimeric alpha/beta chain was made by replacing the least well-conserved amino-terminal section of the beta chain with the corresponding alpha section. The biochemical characteristics of this protein were nearly identical to hexosaminidase B. Therefore, the most dissimilar regions in the subunits are not responsible for their dissimilar biochemical properties. A second fusion protein was made that also included the more homologous middle section of the alpha chain. This protein expressed the substrate specificity unique to isozymes containing an alpha subunit (A and S). We conclude that the region responsible for the ability of the alpha subunit to bind negatively charged substrates is located within residues alpha 132-283. Interestingly, the remaining carboxy-terminal section from the beta chain, beta 316-556, was sufficient to allow this chimera to hydrolyze GM2 ganglioside with 10% the specific activity of heterodimeric hexosaminidase A. Thus, the carboxy-terminal section of each subunit is likely involved in subunit-subunit interactions.

The role of alpha oscillations for illusory perception

PubMed Central

Lange, Joachim; Keil, Julian; Schnitzler, Alfons; van Dijk, Hanneke; Weisz, Nathan

2014-01-01

Alpha oscillations are a prominent electrophysiological signal measured across a wide range of species and cortical and subcortical sites. Alpha oscillations have been viewed for a long time as an “idling” rhythm, purely reflecting inactive sites. Despite earlier evidence from neurophysiology, awareness that alpha oscillations can substantially influence perception and behavior has grown only recently in cognitive neuroscience. Evidence for an active role of alpha for perception comes mainly from several visual, near-threshold experiments. In the current review, we extend this view by summarizing studies showing how alpha-defined brain states relate to illusory perception, i.e. cases of perceptual reports that are not “objectively” verifiable by distinct stimuli or stimulus features. These studies demonstrate that ongoing or prestimulus alpha oscillations substantially influence the perception of auditory, visual or multisensory illusions. PMID:24931795

Secondary reduction of alpha7B integrin in laminin alpha2 deficient congenital muscular dystrophy supports an additional transmembrane link in skeletal muscle.

PubMed

Cohn, R D; Mayer, U; Saher, G; Herrmann, R; van der Flier, A; Sonnenberg, A; Sorokin, L; Voit, T

1999-03-01

The integrins are a large family of heterodimeric transmembrane cellular receptors which mediate the association between the extracellular matrix (ECM) and cytoskeletal proteins. The alpha7beta1 integrin is a major laminin binding integrin in skeletal and cardiac muscle and is thought to be involved in myogenic differentiation and migration processes. The main binding partners of the alpha7 integrin are laminin-1 (alpha1-beta1-gamma1), laminin-2 (alpha2-beta1-gamma1) and laminin-4 (alpha2-beta2-gamma1). Targeted deletion of the gene for the alpha7 integrin subunit (ITGA7) in mice leads to a novel form of muscular dystrophy. In the present study we have investigated the expression of two alternative splice variants, the alpha7B and beta1D integrin subunits, in normal human skeletal muscle, as well as in various forms of muscular dystrophy. In normal human skeletal muscle the expression of the alpha7 integrin subunit appeared to be developmentally regulated: it was first detected at 2 years of age. In contrast, the beta1D integrin could be detected in immature and mature muscle in the sarcolemma of normal fetal skeletal muscle at 18 weeks gestation. The expression of alpha7B integrin was significantly reduced at the sarcolemma in six patients with laminin alpha2 chain deficient congenital muscular dystrophy (CMD) (age >2 years). However, this reduction was not correlated with the amount of laminin alpha2 chain expressed. In contrast, the expression of the laminin alpha2 chain was not altered in the skeletal muscle of the alpha7 knock-out mice. These data argue in favor that there is not a tight correlation between the expression of the alpha7 integrin subunit and that of the laminin alpha2 chain in either human or murine dystrophic muscle. Interestingly, in dystrophinopathies (Duchenne and Becker muscular dystrophy; DMD/BMD) expression of alpha7B was upregulated irrespective of the level of dystrophin expression as shown by a strong sarcolemmal staining pattern even

TNF-alpha SNP haplotype frequencies in equidae.

PubMed

Brown, J J; Ollier, W E R; Thomson, W; Matthews, J B; Carter, S D; Binns, M; Pinchbeck, G; Clegg, P D

2006-05-01

Tumour necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine that plays a crucial role in the regulation of inflammatory and immune responses. In all vertebrate species the genes encoding TNF-alpha are located within the major histocompatability complex. In the horse TNF-alpha has been ascribed a role in a variety of important disease processes. Previously two single nucleotide polymorphisms (SNPs) have been reported within the 5' un-translated region of the equine TNF-alpha gene. We have examined the equine TNF-alpha promoter region further for additional SNPs by analysing DNA from 131 horses (Equus caballus), 19 donkeys (E. asinus), 2 Grant's zebras (E. burchellii boehmi) and one onager (E. hemionus). Two further SNPs were identified at nucleotide positions 24 (T/G) and 452 (T/C) relative to the first nucleotide of the 522 bp polymerase chain reaction product. A sequence variant at position 51 was observed between equidae. SNaPSHOT genotyping assays for these and the two previously reported SNPs were performed on 457 horses comprising seven different breeds and 23 donkeys to determine the gene frequencies. SNP frequencies varied considerably between different horse breeds and also between the equine species. In total, nine different TNF-alpha promoter SNP haplotypes and their frequencies were established amongst the various equidae examined, with some haplotypes being found only in horses and others only in donkeys or zebras. The haplotype frequencies observed varied greatly between different horse breeds. Such haplotypes may relate to levels of TNF-alpha production and disease susceptibility and further investigation is required to identify associations between particular haplotypes and altered risk of disease.

Alpha particle confinement in tandem mirrors

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

Devoto, R.S.; Ohnishi, M.; Kerns, J.

1980-10-10

Mechanisms leading to loss of alpha particles from non-axisymmetric tandem mirrors are considered. Stochastic diffusion due to bounce-drift resonances, which can cause rapid radial losses of high-energy alpha particles, can be suppressed by imposing a 20% rise in axisymmetric fields before the quadrupole transition sections. Alpha particles should then be well-confined until thermal energies when they enter the resonant plateau require. A fast code for computation of drift behavior in reactors is described. Sample calculations are presented for resonant particles in a proposed coil set for the Tandem Mirror Next Step.

Variable displacement alpha-type Stirling engine

NASA Astrophysics Data System (ADS)

Homutescu, V. M.; Bălănescu, D. T.; Panaite, C. E.; Atanasiu, M. V.

2016-08-01

The basic design and construction of an alpha-type Stirling engine with on load variable displacement is presented. The variable displacement is obtained through a planar quadrilateral linkage with one on load movable ground link. The physico-mathematical model used for analyzing the variable displacement alpha-type Stirling engine behavior is an isothermal model that takes into account the real movement of the pistons. Performances and power adjustment capabilities of such alpha-type Stirling engine are calculated and analyzed. An exemplification through the use of the numerical simulation was performed in this regard.

Molecular basis of maple syrup urine disease: Novel mutations at the E1[alpha] locus that impair E1([alpha][sub 2][beta][sub 2]) assembly or decrease steady-state E1[alpha] mRNA levels of branched-chain [alpha]-keto acid dehydrogenase complex

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

Chuang, J.L.; Fisher, C.R.; Chuang, D.T.

1994-08-01

The authors report the occurrence of three novel mutations in the E1[alpha] (BCKDHA) locus of the branched-chain [alpha]-keto acid dehydrogenase (BCKAD) complex that cause maple syrup urine disease (MSUD). An 8-bp deletion in exon 7 is present in one allele of a compound-heterozygous patient (GM-649). A single C nucleotide insertion in exon 2 occurs in one allele of an intermediate-MSUD patient (Lo). The second allele of patient Lo carries an A-to-G transition in exon 9 of the E1[alpha] gene. This missense mutation changes Tyr-368 to Cys (Y368C) in the E1[alpha] subunit. Both the 8-bp deletion and the single C insertionmore » generate a downstream nonsense codon. Both mutations appear to be associated with a low abundance of the mutant E1[alpha] mRNA, as determined by allele-specific oligonucleotide probing. Transfection studies strongly suggest that the Y368C substitution in the E1[alpha] subunit impairs its proper assembly with the normal E1[beta]. Unassembled as well as misassembled E1[alpha] and E1[beta] subunits are degraded in the cell. 32 refs., 8 figs.« less

Producing alpha-olefins using polyketide synthases

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

Fortman, Jeffrey L.; Katz, Leonard; Steen, Eric J.

2018-01-02

The present invention provides for a polyketide synthase (PKS) capable of synthesizing an .alpha.-olefin, such as 1-hexene or butadiene. The present invention also provides for a host cell comprising the PKS and when cultured produces the .alpha.-olefin.

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 866.5080 - 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...

Synthesis of peptide .alpha.-thioesters

DOEpatents

Camarero, Julio A [Livermore, CA; Mitchell, Alexander R [Livermore, CA; De Yoreo, James J [Clayton, CA

2008-08-19

Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.

The Apollo Alpha Spectrometer.

NASA Technical Reports Server (NTRS)

Jagoda, N.; Kubierschky, K.; Frank, R.; Carroll, J.

1973-01-01

Located in the Science Instrument Module of Apollo 15 and 16, the Alpha Particle Spectrometer was designed to detect and measure the energy of alpha particles emitted by the radon isotopes and their daughter products. The spectrometer sensor consisted of an array of totally depleted silicon surface barrier detectors. Biased amplifier and linear gate techniques were utilized to reduce resolution degradation, thereby permitting the use of a single 512 channel PHA. Sensor identification and in-flight radioactive calibration were incorporated to enhance data reduction.

New Complexity-Building Reactions of Alpha-Keto Esters

NASA Astrophysics Data System (ADS)

Bartlett, Samuel L.

I. Introduction: Importance of Asymmetric Catalysis and the Reactivity Patterns of alpha-Keto Esters. II. Synthesis of Complex Tertiary Glycolates by Enantioconvergent Arylation of Stereochemically Labile alpha-Keto Esters. Enantioconvergent arylation reactions of boronic acids and racemic ?-stereogenic alpha-keto esters have been developed. The reactions are catalyzed by a chiral (diene)Rh(I) complex and provide a wide array of beta-stereogenic tertiary aryl glycolate derivatives with high levels of diastereo- and enantioselectivity. Racemization studies employing a series of sterically differentiated tertiary amines suggest that the steric nature of the amine base additive exerts a significant influence on the rate of substrate racemization. III. Palladium-Catalyzed beta-Arylation of alpha-Keto Esters . A catalyst system derived from commercially available Pd2(dba) 3 and PtBu3 has been applied to the coupling of alpha-keto ester enolates and aryl bromides. The reaction provides access to an array of beta-stereogenic alpha-keto ester derivatives. When the air stable ligand precursor PtBu 3˙HBF4 is employed, the reaction can be carried out without use of a glovebox. The derived products are of broad interest given the prevalence of the alpha-keto acid substructure in biologically important molecules. IV. Catalytic Enantioselective [3+2] Cycloaddition of alpha-Keto Ester Enolates and Nitrile Oxides. An enantioselective [3+2] cycloaddition reaction between nitrile oxides and transiently generated enolates of alpha-keto esters has been developed. The catalyst system was found to be compatible with in situ nitrile oxide generation conditions. A versatile array of nitrile oxides and alpha-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reaction via O-imidoylation and hetero-[3

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 866.5620 - 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 866.5620 - 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...

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...

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

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

Mid-aged and aged wild-type and progestin receptor knockout (PRKO) mice demonstrate rapid progesterone and 3alpha,5alpha-THP-facilitated lordosis.

PubMed

Frye, C A; Sumida, K; Lydon, J P; O'Malley, B W; Pfaff, D W

2006-05-01

Progesterone (P) and its 5alpha-reduced metabolite, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP), facilitate sexual behavior of rodents via agonist-like actions at intracellular progestin receptors (PRs) and membrane GABA(A)/benzodiazepine receptor complexes (GBRs), respectively. Given that ovarian secretion of progestins declines with aging, whether or not senescent mice are responsive to progestins was of interest. Homozygous PR knockout (PRKO) or wild-type mice that were between 10-12 (mid-aged) or 20-24 (aged) months of age were administered P or 3alpha,5alpha-THP, and the effect on lordosis were examined. Effects of a progestin-priming regimen that enhances PR-mediated (experiment 1) or more rapid, PR-independent effects of progestins (experiments 2 and 3) on sexual behavior were examined. Levels of P, 3alpha,5alpha-THP, and muscimol binding were examined in tissues from aged mice (experiment 4). Wild-type, but not PRKO, mice were responsive when primed with 17beta-estradiol (E(2); 0.5 microg) and administered P (500 microg, subcutaneously). Mid-aged wild-type mice demonstrated greater increases in lordosis 6 h later compared to their pre-P, baseline test than did aged wild-type mice (experiment 1). Lordosis of younger and older wild-type, but not PRKO, mice was significantly increased within 5 min of intravenous (IV) administration of P (100 ng), compared with E(2)-priming alone (experiment 2). However, wild-type and PRKO mice demonstrated significant increases in lordosis 5 min after IV administration of 3alpha,5alpha-THP, an effect which was more pronounced in mid-aged than in aged animals (100 ng-experiment 3). In tissues from aged wild-type and PRKO mice, levels of P, 3alpha,5alpha-THP, and muscimol binding were increased by P administration (experiment 4). PR binding was lower in the cortex of PRKO than that of wild-type mice. Mid-aged and aged PRKO and wild-type mice demonstrated rapid P or 3alpha,5alpha-THP-facilitated lordosis that may be

Behavioural characterisation of the alpha-mannosidosis guinea pig.

PubMed

Robinson, A J; Crawley, A C; Auclair, D; Weston, P F; Hirte, C; Hemsley, K M; Hopwood, J J

2008-01-25

alpha-Mannosidosis is a lysosomal storage disorder resulting from a functional deficiency of the lysosomal enzyme alpha-mannosidase. This deficiency results in the accumulation of various oligosaccharides in the lysosomes of affected individuals, causing somatic pathology and progressive neurological degeneration that results in cognitive deficits, ataxia, and other neurological symptoms. We have a naturally occurring guinea pig model of this disease which exhibits a deficiency of lysosomal alpha-mannosidase and has a similar clinical presentation to human alpha-mannosidosis. Various tests were developed in the present study to characterise and quantitate the loss of neurological function in alpha-mannosidosis guinea pigs and to follow closely the progression of the disease. General neurological examinations showed progressive differences in alpha-mannosidosis animals from approximately 1 month of age. Significant differences were observed in hind limb gait width from 2 months of age and significant cognitive (memory and learning) deficits were observed from 3 months of age. Evoked response tests showed an increase in somatosensory P1 peak latency in alpha-mannosidosis guinea pigs from approximately 2 months of age, as well as progressive hearing loss using auditory brainstem evoked responses. The alpha-mannosidosis guinea pig therefore appears to exhibit many of the characteristics of the human disease, and will be useful in evaluating therapies for treatment of central nervous system pathology.

Functional characterization of mongoose nicotinic acetylcholine receptor alpha-subunit: resistance to alpha-bungarotoxin and high sensitivity to acetylcholine.

PubMed

Asher, O; Lupu-Meiri, M; Jensen, B S; Paperna, T; Fuchs, S; Oron, Y

1998-07-24

The mongoose is resistant to snake neurotoxins. The mongoose muscle nicotinic acetylcholine receptor (AChR) alpha-subunit contains a number of mutations in the ligand-binding domain and exhibits poor binding of alpha-bungarotoxin (alpha-BTX). We characterized the functional properties of a hybrid (alpha-mongoose/beta gamma delta-rat) AChR. Hybrid AChRs, expressed in Xenopus oocytes, respond to acetylcholine with depolarizing current, the mean maximal amplitude of which was greater than that mediated by the rat AChR. The IC50 of alpha-BTX to the hybrid AChR was 200-fold greater than that of the rat, suggesting much lower affinity for the toxin. Hybrid AChRs exhibited an apparent higher rate of desensitization and higher affinity for ACh (EC50 1.3 vs. 23.3 microM for the rat AChR). Hence, changes in the ligand-binding domain of AChR not only affect the binding properties of the receptor, but also result in marked changes in the characteristics of the current.

Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects.

PubMed

Cynober, L; Coudray-Lucas, C; de Bandt, J P; Guéchot, J; Aussel, C; Salvucci, M; Giboudeau, J

1990-02-01

Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.

PubMed

Mutimer, D; Naoumov, N; Honkoop, P; Marinos, G; Ahmed, M; de Man, R; McPhillips, P; Johnson, M; Williams, R; Elias, E; Schalm, S

1998-06-01

Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Metathesis process for preparing an alpha, omega-functionalized olefin

DOEpatents

Burdett, Kenneth A.; Mokhtarzadeh, Morteza; Timmers, Francis J.

2010-10-12

A cross-metathesis process for preparing an .alpha.,.omega.-functionalized olefin, such as methyl 9-decenoate, and an .alpha.-olefin having three or more carbon atoms, such as 1-decene. The process involves contacting in a first reaction zone an .alpha.-functionalized internal olefin, such as methyl oleate, and an .alpha.-olefinic monomer having three or more carbon atoms, such as 1-decene, with a first metathesis catalyst to prepare an effluent stream containing the .alpha.,.omega.-functionalized olefin, such as methyl 9-decenoate, an unfunctionalized internal olefin, such as 9-octadecene, unconverted reactant olefins, and optionally, an .alpha.,.omega.-difunctionalized internal olefinic dimer, such as dimethyl 9-octadecen-1,18-dioate; separating said effluent streams; then contacting in a second reaction zone the unfunctionalized internal olefin with ethylene in the presence of a second metathesis catalyst to obtain a second product effluent containing the .alpha.-olefinic monomer having three or more carbon atoms; and cycling a portion of the .alpha.-olefinic monomer stream(s) to the first zone.

29 CFR 1915.1004 - alpha-Naphthylamine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 7 2011-07-01 2011-07-01 false alpha-Naphthylamine. 1915.1004 Section 1915.1004 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1004 alpha-Naphthylamine. Note: The requirements applicable to shipyard employment under this...

29 CFR 1910.1004 - alpha-Naphthylamine.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 6 2010-07-01 2010-07-01 false alpha-Naphthylamine. 1910.1004 Section 1910.1004 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... alpha-Naphthylamine. See § 1910.1003, 13 carcinogens. [61 FR 9245, Mar. 7, 1996] ...

29 CFR 1915.1004 - alpha-Naphthylamine.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 7 2014-07-01 2014-07-01 false alpha-Naphthylamine. 1915.1004 Section 1915.1004 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1004 alpha-Naphthylamine. Note: The requirements applicable to shipyard employment under this...

29 CFR 1915.1004 - alpha-Naphthylamine.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false alpha-Naphthylamine. 1915.1004 Section 1915.1004 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1004 alpha-Naphthylamine. Note: The requirements applicable to shipyard employment under this...

29 CFR 1915.1004 - alpha-Naphthylamine.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 7 2013-07-01 2013-07-01 false alpha-Naphthylamine. 1915.1004 Section 1915.1004 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1004 alpha-Naphthylamine. Note: The requirements applicable to shipyard employment under this...

29 CFR 1910.1004 - alpha-Naphthylamine.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 6 2012-07-01 2012-07-01 false alpha-Naphthylamine. 1910.1004 Section 1910.1004 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... alpha-Naphthylamine. See § 1910.1003, 13 carcinogens. [61 FR 9245, Mar. 7, 1996] ...

29 CFR 1910.1004 - alpha-Naphthylamine.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 6 2013-07-01 2013-07-01 false alpha-Naphthylamine. 1910.1004 Section 1910.1004 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... alpha-Naphthylamine. See § 1910.1003, 13 carcinogens. [61 FR 9245, Mar. 7, 1996] ...

29 CFR 1915.1004 - alpha-Naphthylamine.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 7 2012-07-01 2012-07-01 false alpha-Naphthylamine. 1915.1004 Section 1915.1004 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1004 alpha-Naphthylamine. Note: The requirements applicable to shipyard employment under this...

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.

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.

Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

PubMed

Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

2009-11-01

To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

Alpha Centauri at a Crossroads

NASA Astrophysics Data System (ADS)

Ayres, Thomas

2014-09-01

Nearby Alpha Centauri (G2V+K1V) contains the two best characterized solar-like dwarf stars, which also have the best studied X-ray activity cycles, extending back to the 1970's. Objective is to continue tracking the evolving multi-decadal high-energy narrative of Alpha Cen with semiannual HRC-I pointings in Cycles 16-18, as the system reaches a coronal crossroads: solar twin A rising toward cycle maximum, K-type companion B sinking into a minimum. HST/STIS UV spectra will support and leverage the X-ray measurements by probing subcoronal dynamics, with connection to the corona through the FUV Fe XII forbidden line. Only Chandra can resolve the AB X-ray sources as the Alpha Cen orbit also reaches a crossroads in 2016.

Enzyme replacement therapy in alpha-mannosidosis guinea-pigs.

PubMed

Crawley, Allison C; King, Barbara; Berg, Thomas; Meikle, Peter J; Hopwood, John J

2006-01-01

alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity of lysosomal alpha-mannosidase and is characterised by massive accumulation of mannose-containing oligosaccharides in affected individuals. Patients develop behaviour and learning difficulties, skeletal abnormalities, immune deficiency and hearing impairment. Disease in alpha-mannosidosis guinea-pigs resembles the clinical, histopathological, biochemical and molecular features of the human disease. We have used the guinea-pig model to investigate efficacy of enzyme replacement therapy as a treatment for alpha-mannosidosis. Intravenous recombinant human lysosomal alpha-mannosidase, administered at a dose of 1mg/kg, was cleared from circulation with a half-life of 53 h, with significant enzyme activity (1.4x normal levels) detected in circulation one week post-injection. alpha-Mannosidase administered to alpha-mannosidosis guinea-pigs at 1mg/kg (onset at birth or approximately 30 days) and 10mg/kg (at birth) was distributed widely amongst tissues, including to capillary depleted brain. By monitoring with tandem mass spectrometry, enzyme replacement therapy was found to be effective in reducing stored substrates in peripheral tissues at both dose rates, and in brain by up to 39% at the 10mg/kg dose, compared with untreated alpha-mannosidosis controls. Reductions of up to 60% of urinary mannose containing oligosaccharides were also observed. No histological improvements were seen in the brain at either dose, however marked decreases in lysosomal vacuolation in liver, kidney, spleen and endocrine pancreas, as well as a significant reduction in trigeminal ganglion neurons were observed. Multiple injections of 1mg/kg recombinant enzyme in alpha-mannosidosis guinea-pigs induced a very rapid humoral immune response precluding long-term intravenous treatment.

29 CFR 1926.1104 - alpha-Naphthylamine.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 8 2012-07-01 2012-07-01 false alpha-Naphthylamine. 1926.1104 Section 1926.1104 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1104 alpha...

29 CFR 1926.1104 - alpha-Naphthylamine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 8 2011-07-01 2011-07-01 false alpha-Naphthylamine. 1926.1104 Section 1926.1104 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1104 alpha...

29 CFR 1926.1104 - alpha-Naphthylamine.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 8 2014-07-01 2014-07-01 false alpha-Naphthylamine. 1926.1104 Section 1926.1104 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1104 alpha...

29 CFR 1926.1104 - alpha-Naphthylamine.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 8 2013-07-01 2013-07-01 false alpha-Naphthylamine. 1926.1104 Section 1926.1104 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1104 alpha...

[Low level alpha activity measurements with pulse shape discrimination--application to the determination of alpha-nuclides in environmental samples].

PubMed

Satoh, K; Noguchi, M; Higuchi, H; Kitamura, K

1984-12-01

Liquid scintillation counting of alpha rays with pulse shape discrimination was applied to the analysis of 226Ra and 239+240Pu in environmental samples and of alpha-emitters in/on a filter paper. The instrument used in this study was either a specially designed detector or a commercial liquid scintillation counter with an automatic sample changer, both of which were connected to the pulse shape discrimination circuit. The background counting rate in alpha energy region of 5-7 MeV was 0.01 or 0.04 cpm/MeV, respectively. The figure of merit indicating the resolving power for alpha- and beta-particles in time spectrum was found to be 5.7 for the commercial liquid scintillation counter.

Molecular cloning and characterization of Hymenolepis diminuta alpha-tubulin gene.

PubMed

Mohajer-Maghari, Behrokh; Amini-Bavil-Olyaee, Samad; Webb, Rodney A; Coe, Imogen R

2007-02-01

To isolate a full-length alpha-tubulin cDNA from an eucestode, Hymenolepis diminuta, a lambda phage cDNA library was constructed. The alpha-tubulin gene was cloned, sequenced and characterized. The H. diminuta alpha-tubulin consisted of 450 amino acids. This protein contained putative sites for all posttranslational modifications as detyrosination/tyrosination at the carboxyl-terminal of protien, phosphorylation at residues R79 and K336, glycylation/glutamylation at residue G445 and acetylation at residue K40. Comparisons of H. diminuta alpha-tubulin with all full-length alpha-tubulin proteins revealed that H. diminuta alpha-tubulin possesses 10 distinctive residues, which are not found in any other alpha-tubulins. Phylogenetic analysis showed that H. diminuta alpha-tubulin has grouped in a separated branch adjacent eucestode and trematodes branch with 92% bootstrap value (1000 replicates). In conclusion, this is the first report of H. diminuta cDNA library construction, cloning and characterization of H. diminuta alpha-tubulin gene.

Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

PubMed

Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

2009-01-01

Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

Bayesian Meta-Analysis of Coefficient Alpha

ERIC Educational Resources Information Center

Brannick, Michael T.; Zhang, Nanhua

2013-01-01

The current paper describes and illustrates a Bayesian approach to the meta-analysis of coefficient alpha. Alpha is the most commonly used estimate of the reliability or consistency (freedom from measurement error) for educational and psychological measures. The conventional approach to meta-analysis uses inverse variance weights to combine…

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

Object-based attentional selection modulates anticipatory alpha oscillations

PubMed Central

Knakker, Balázs; Weiss, Béla; Vidnyánszky, Zoltán

2015-01-01

Visual cortical alpha oscillations are involved in attentional gating of incoming visual information. It has been shown that spatial and feature-based attentional selection result in increased alpha oscillations over the cortical regions representing sensory input originating from the unattended visual field and task-irrelevant visual features, respectively. However, whether attentional gating in the case of object based selection is also associated with alpha oscillations has not been investigated before. Here we measured anticipatory electroencephalography (EEG) alpha oscillations while participants were cued to attend to foveal face or word stimuli, the processing of which is known to have right and left hemispheric lateralization, respectively. The results revealed that in the case of simultaneously displayed, overlapping face and word stimuli, attending to the words led to increased power of parieto-occipital alpha oscillations over the right hemisphere as compared to when faces were attended. This object category-specific modulation of the hemispheric lateralization of anticipatory alpha oscillations was maintained during sustained attentional selection of sequentially presented face and word stimuli. These results imply that in the case of object-based attentional selection—similarly to spatial and feature-based attention—gating of visual information processing might involve visual cortical alpha oscillations. PMID:25628554

In vitro C3 mRNA expression in Pemphigus vulgaris: complement activation is increased by IL-1alpha and TNF-alpha.

PubMed

Feliciani, C; Toto, P; Amerio, P

1999-01-01

Pemphigus vulgaris (PV) is a potentially life-threatening disease, characterized immunohistologically by IgG deposits and complement activation on the surface of keratinocytes. Complement activation has been implicated in the pathogenesis with C3 deposits in about 90% of patients. In order to further elucidate the role of complement in PV and to define which cytokines play a role in C3 mRNA expression, we performed an in vitro study in human keratinocytes. Normal human epidermal keratinocytes (NHuK) were incubated with PV serum and C3 mRNA was measured. We previously had shown that IL-1alpha and TNF-alpha are expressed in PV in vivo and in vitro. Since cytokines are able to modulate complement activation, mRNA expression was evaluated in a similar experiment after pretreatment using antibodies against IL-1alpha and TNF-alpha. Incubation of NHuK with PV sera caused their detachment from the plates after 20-30 minutes with a complete acantholysis within 12 hours. An early C3 mRNA expression was seen after 30 minutes with a peak level after 1 hour. Blocking studies, using antibodies against human IL-1alpha and TNF-alpha in NHuK together with PV-IgG, showed reduction of in vitro induced acantholysis and inhibition of C3 mRNA expression. This study supports the hypothesis that complement C3 is important in PV acantholysis and that complement activation is increased by IL-1alpha and TNF-alpha.

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

Alpha Centauri at a Crossroads

NASA Astrophysics Data System (ADS)

Ayres, Thomas

2015-10-01

Nearby Alpha Centauri AB (G2V+K1V) contains the two best characterized solar-like dwarf stars, which also have the best studied multi-MK coronal X-ray activity cycles, extending back to the 1970's. Objective is to continue tracking the evolving multi-decadal high-energy narrative of Alpha Cen with semiannual X-ray pointings in Chandra Cycles 16-18, as the system reaches a coronal crossroads: solar twin A rising toward starspot cycle maximum, K-type companion B sinking into a minimum. HST/STIS UV spectra will support and leverage the X-ray measurements by probing chromospheric and subcoronal dynamics, with connection to the corona through the FUV Fe XII 1242 forbidden line. Only Chandra can resolve the AB X-ray pair as the Alpha Cen orbit also reaches a crossroads in 2016 (only 4 separation), and only HST/STIS can measure the bright Alpha Cen stars with sufficient UV spectral resultion and wavelength coherence. What's more, the recent validation of the STIS NDA,B,C long slits for echelle use now make feasible NUV E230H measurements (e.g., of key chromospheric tracers Mg II 2800 and Mg I 2852) which heretofore were not practical in a long-term program of this nature.

Alpha Centauri at a Crossroads

NASA Astrophysics Data System (ADS)

Ayres, Thomas

2016-10-01

Nearby Alpha Centauri AB (G2V+K1V) contains the two best characterized solar-like dwarf stars, which also have the best studied multi-MK coronal X-ray activity cycles, extending back to the 1970's. Objective is to continue tracking the evolving multi-decadal high-energy narrative of Alpha Cen with semiannual X-ray pointings in Chandra Cycles 16-18, as the system reaches a coronal crossroads: solar twin A rising toward starspot cycle maximum, K-type companion B sinking into a minimum. HST/STIS UV spectra will support and leverage the X-ray measurements by probing chromospheric and subcoronal dynamics, with connection to the corona through the FUV Fe XII 1242 forbidden line. Only Chandra can resolve the AB X-ray pair as the Alpha Cen orbit also reaches a crossroads in 2016 (only 4 separation), and only HST/STIS can measure the bright Alpha Cen stars with sufficient UV spectral resolution and wavelength coherence. What's more, the recent validation of the STIS NDA,B,C long slits for echelle use now make feasible NUV E230H measurements (e.g., of key chromospheric tracers Mg II 2800 and Mg I 2852) which heretofore were not practical in a long-term program of this nature.

Deletion of alpha-synuclein decreases impulsivity in mice.

PubMed

Peña-Oliver, Y; Buchman, V L; Dalley, J W; Robbins, T W; Schumann, G; Ripley, T L; King, S L; Stephens, D N

2012-03-01

The presynaptic protein alpha-synuclein, associated with Parkinson's Disease (PD), plays a role in dopaminergic neurotransmission and is implicated in impulse control disorders (ICDs) such as drug addiction. In this study we investigated a potential causal relationship between alpha-synuclein and impulsivity, by evaluating differences in motor impulsivity in the 5-choice serial reaction time task (5-CSRTT) in strains of mice that differ in the expression of the alpha-synuclein gene. C57BL/6JOlaHsd mice differ from their C57BL/6J ancestors in possessing a chromosomal deletion resulting in the loss of two genes, snca, encoding alpha-synuclein, and mmrn1, encoding multimerin-1. C57BL/6J mice displayed higher impulsivity (more premature responding) than C57BL/6JOlaHsd mice when the pre-stimulus waiting interval was increased in the 5-CSRTT. In order to ensure that the reduced impulsivity was indeed related to snca, and not adjacent gene deletion, wild type (WT) and mice with targeted deletion of alpha-synuclein (KO) were tested in the 5-CSRTT. Similarly, WT mice were more impulsive than mice with targeted deletion of alpha-synuclein. Interrogation of our ongoing analysis of impulsivity in BXD recombinant inbred mouse lines revealed an association of impulsive responding with levels of alpha-synuclein expression in hippocampus. Expression of beta- and gamma-synuclein, members of the synuclein family that may substitute for alpha-synuclein following its deletion, revealed no differential compensations among the mouse strains. These findings suggest that alpha-synuclein may contribute to impulsivity and potentially, to ICDs which arise in some PD patients treated with dopaminergic medication. © 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Alpha Rhythms in Audition: Cognitive and Clinical Perspectives

PubMed Central

Weisz, Nathan; Hartmann, Thomas; Müller, Nadia; Lorenz, Isabel; Obleser, Jonas

2011-01-01

Like the visual and the sensorimotor systems, the auditory system exhibits pronounced alpha-like resting oscillatory activity. Due to the relatively small spatial extent of auditory cortical areas, this rhythmic activity is less obvious and frequently masked by non-auditory alpha-generators when recording non-invasively using magnetoencephalography (MEG) or electroencephalography (EEG). Following stimulation with sounds, marked desynchronizations can be observed between 6 and 12 Hz, which can be localized to the auditory cortex. However knowledge about the functional relevance of the auditory alpha rhythm has remained scarce so far. Results from the visual and sensorimotor system have fuelled the hypothesis of alpha activity reflecting a state of functional inhibition. The current article pursues several intentions: (1) Firstly we review and present own evidence (MEG, EEG, sEEG) for the existence of an auditory alpha-like rhythm independent of visual or motor generators, something that is occasionally met with skepticism. (2) In a second part we will discuss tinnitus and how this audiological symptom may relate to reduced background alpha. The clinical part will give an introduction into a method which aims to modulate neurophysiological activity hypothesized to underlie this distressing disorder. Using neurofeedback, one is able to directly target relevant oscillatory activity. Preliminary data point to a high potential of this approach for treating tinnitus. (3) Finally, in a cognitive neuroscientific part we will show that auditory alpha is modulated by anticipation/expectations with and without auditory stimulation. We will also introduce ideas and initial evidence that alpha oscillations are involved in the most complex capability of the auditory system, namely speech perception. The evidence presented in this article corroborates findings from other modalities, indicating that alpha-like activity functionally has an universal inhibitory role across sensory

Space Station alpha joint bearing

NASA Technical Reports Server (NTRS)

Everman, Michael R.; Jones, P. Alan; Spencer, Porter A.

1987-01-01

Perhaps the most critical structural system aboard the Space Station is the Solar Alpha Rotary Joint which helps align the power generation system with the sun. The joint must provide structural support and controlled rotation to the outboard transverse booms as well as power and data transfer across the joint. The Solar Alpha Rotary Joint is composed of two transition sections and an integral, large diameter bearing. Alpha joint bearing design presents a particularly interesting problem because of its large size and need for high reliability, stiffness, and on orbit maintability. The discrete roller bearing developed is a novel refinement to cam follower technology. It offers thermal compensation and ease of on-orbit maintenance that are not found in conventional rolling element bearings. How the bearing design evolved is summarized. Driving requirements are reviewed, alternative concepts assessed, and the selected design is described.

Evidence for a temperature rise in the outer layers of alpha Lyrae, from Copernicus observations of Lyman-alpha

NASA Technical Reports Server (NTRS)

Praderie, F.; Simonneau, E.; Snow, T. P., Jr.

1975-01-01

Copernicus satellite observations of the Ly-alpha profiles in alpha Lyrae (Vega) are used to determine whether classical radiative-equilibrium LTE model atmospheres can fit the thermal structure in the outer layers of that star. Two plane-parallel LTE model photospheres of alpha Lyrae are considered: a line-blanketed radiative-equilibrium model with an effective temperature of 9650 K and log g of 4.05, and the same model with a temperature of 9500 K and log g of 4.0. The profiles of the Ly-alpha wings are computed, and it is found that classical LTE models are unable to predict either the observed violet wing or the red wing longwards of 1239 A, regardless of the line source function. It is concluded that the electron temperature must increase outwards over the surface value reached in radiative equilibrium.

7alpha- and 12alpha-Hydroxysteroid dehydrogenases from Acinetobacter calcoaceticus lwoffii: a new integrated chemo-enzymatic route to ursodeoxycholic acid.

PubMed

Giovannini, Pier Paolo; Grandini, Alessandro; Perrone, Daniela; Pedrini, Paola; Fantin, Giancarlo; Fogagnolo, Marco

2008-12-22

We report the very efficient biotransformation of cholic acid to 7-keto- and 7,12-diketocholic acids with Acinetobacter calcoaceticus lwoffii. The enzymes responsible of the biotransformation (i.e. 7alpha- and 12alpha-hydroxysteroid dehydrogenases) are partially purified and employed in a new chemo-enzymatic synthesis of ursodeoxycholic acid starting from cholic acid. The first step is the 12alpha-HSDH-mediated total oxidation of sodium cholate followed by the Wolf-Kishner reduction of the carbonyl group to chenodeoxycholic acid. This acid is then quantitatively oxidized with 7alpha-HSDH to 7-ketochenodeoxycholic acid, that was chemically reduced to ursodeoxycholic acid (70% overall yield).

Imaging of alpha(v)beta(3) expression by a bifunctional chimeric RGD peptide not cross-reacting with alpha(v)beta(5).

PubMed

Zannetti, Antonella; Del Vecchio, Silvana; Iommelli, Francesca; Del Gatto, Annarita; De Luca, Stefania; Zaccaro, Laura; Papaccioli, Angela; Sommella, Jvana; Panico, Mariarosaria; Speranza, Antonio; Grieco, Paolo; Novellino, Ettore; Saviano, Michele; Pedone, Carlo; Salvatore, Marco

2009-08-15

To test whether a novel bifunctional chimeric peptide comprising a cyclic Arg-Gly-Asp pentapeptide covalently bound to an echistatin domain can discriminate alpha(v)beta(3) from alpha(v)beta(5) integrin, thus allowing the in vivo selective visualization of alpha(v)beta(3) expression by single-photon and positron emission tomography (PET) imaging. The chimeric peptide was preliminarily tested for inhibition of alpha(v)beta(3)-dependent cell adhesion and competition of 125I-echistatin binding to membrane of stably transfected K562 cells expressing alpha(v)beta(3) (Kalpha(v)beta(3)) or alpha(v)beta(5) (Kalpha(v)beta(5)) integrin. The chimeric peptide was then conjugated with diethylenetriaminepentaacetic acid and labeled with 111In for single-photon imaging, whereas a one-step procedure was used for labeling the full-length peptide and a truncated derivative, lacking the last five C-terminal amino acids, with 18F for PET imaging. Nude mice bearing tumors from Kalpha(v)beta(3), Kalpha(v)beta(5), U87MG human glioblastoma, and A431 human epidermoid cells were subjected to single-photon and PET imaging. Adhesion and competitive binding assays showed that the novel chimeric peptide selectively binds to alpha(v)beta(3) integrin and does not cross-react with alpha(v)beta(5). In agreement with in vitro findings, single-photon and PET imaging studies showed that the radiolabeled chimeric peptide selectively localizes in tumor xenografts expressing alphavbeta3 and fails to accumulate in those expressing alpha(v)beta(5) integrin. When 18F-labeled truncated derivative was used for PET imaging, alphavbeta3- and alpha(v)beta(5)-expressing tumors were visualized, indicating that the five C-terminal amino acids are required to differentially bind the two integrins. Our findings indicate that the novel chimeric Arg-Gly-Asp peptide, having no cross-reaction with alphavbeta5 integrin, allows highly selective alphavbeta3 expression imaging and monitoring.

Alpha-fetoprotein (AFP) Test: MedlinePlus Lab Test Information

MedlinePlus

... medlineplus.gov/labtests/alphafetoproteinafptest.html Alpha-fetoprotein (AFP) Test To use the sharing features on this page, ... enable JavaScript. What is an Alpha-fetoprotein (AFP) Test? Alpha-fetoprotein (AFP) is a protein produced in ...

Positional preference of proline in alpha-helices.

PubMed Central

Kim, M. K.; Kang, Y. K.

1999-01-01

Conformational free energy calculations have been carried out for proline-containing alanine-based pentadecapeptides with the sequence Ac-(Ala)n-Pro-(Ala)m-NHMe, where n + m = 14, to figure out the positional preference of proline in alpha-helices. The relative free energy of each peptide was calculated by subtracting the free energy of the extended conformation from that of the alpha-helical one, which is used here as a measure of preference. The highest propensity is found for the peptide with proline at the N-terminus (i.e., Ncap + 1 position), and the next propensities are found at Ncap, N' (Ncap - 1), and C' (Ccap + 1) positions. These computed results are reasonably consistent with the positional propensities estimated from X-ray structures of proteins. The breaking in hydrogen bonds around proline is found to play a role in destabilizing alpha-helical conformations, which, however, provides the favored hydration of the corresponding N-H and C=O groups. The highest preference of proline at the beginning of alpha-helix appears to be due to the favored electrostatic and nonbonded energies between two residues preceding proline and the intrinsic stability of alpha-helical conformation of the proline residue itself as well as no disturbance in hydrogen bonds of alpha-helix by proline. The average free energy change for the substitution of Ala by Pro in a alpha-helix is computed to be 4.6 kcal/mol, which is in good agreement with the experimental value of approximately 4 kcal/mol estimated for an oligopeptide dimer and proteins of barnase and T4 lysozyme. PMID:10422838

The effect of thermal cycling to 1100 C on the alpha /Mo/ phase in directionally solidified gamma/gamma-prime-alpha alloys

NASA Technical Reports Server (NTRS)

Harf, F. H.

1981-01-01

Specimens of gamma/gamma-prime-alpha (Mo) eutectic alloy were thermally cycled or isothermally exposed at temperatures of 1075 to 1100 C. Transmission electron microscopy examination of cycled specimens indicated that even an exposure of 10 minutes effected noticeable changes in the shape of the alpha phase, and that the changes were cumulative as more cycles were added. The cross sections of fine, smooth fibers changed from rectangles to octagons, while lamellae and irregular shapes spheroidized. These effects are attributed to the differences in thermal expansion coefficients between the alpha phase and the gamma/gamma-prime matrix, and to the higher diffusion rates prevailing at elevated temperatures. Where the configuration of the alpha phase is a simple shape, such as a fiber, increasing the temperature eventually brings about a stress free interface between the alpha phase and the matrix by differential thermal expansion. Where the shape of the alpha phase is more complex, a stressed interface persists to higher temperatures where diffusion produces the more drastic morphological changes.

Venus - False Color Image of Alpha Regio

NASA Image and Video Library

1996-02-07

NASA's Magellan radar image shows Alpha Regio, a topographic upland. In 1963 Alpha Regio was the first feature on Venus to be identified from Earth based radar. http://photojournal.jpl.nasa.gov/catalog/PIA00147

IGFBP-3, hypoxia and TNF-{alpha} inhibit adiponectin transcription

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

Zappala, Giovanna, E-mail: zappalag@mail.nih.gov; Rechler, Matthew M.; Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

2009-05-15

The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-{gamma}, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin. It activates PPAR-{gamma}-RXR-{alpha} heterodimers bound to PPAR-{gamma} response elements in the adiponectin promoter. Rosiglitazone-stimulated adiponectin protein synthesis in 3T3-L1 mouse adipocytes has been shown to be inhibited by IGFBP-3, which can be induced by hypoxia and the proinflammatory cytokine, TNF-{alpha}, two inhibitors of adiponectin transcription. The present study demonstrates that IGFBP-3, the hypoxia-mimetic agent cobalt chloride, and TNF-{alpha} inhibit rosiglitazone-induced adiponectin transcription in mouse embryo fibroblasts that stably express PPAR-{gamma}2. Native IGFBP-3 can bind RXR-{alpha} andmore » inhibited rosiglitazone stimulated promoter activity, whereas an IGFBP-3 mutant that does not bind RXR-{alpha} did not. These results suggest that IGFBP-3 may mediate the inhibition of adiponectin transcription by hypoxia and TNF-{alpha}, and that IGFBP-3 binding to RXR-{alpha} may be required for the observed inhibition.« less

Effect of thalidomide on the expression of TNF-alpha m-RNA and synthesis of TNF-alpha in cells from leprosy patients with reversal reaction.

PubMed

Tadesse, Azeb; Abebe, Markos; Bizuneh, Elizabeth; Mulugeta, Wondwossen; Aseffa, Abraham; Shannon, E J

2006-01-01

Hypersensitivity reactions called reversal reaction (RR) and erythema nodosum leprosum (ENL) occur in leprosy. They are characterized by an increase in tumor necrosis factor-alpha (TNF-alpha). Thalidomide is an effective treatment for ENL but not RR. Its effectiveness in ENL is attributed to inhibition of TNF-alpha, and this does not explain its failure to treat RR. We assessed thalidomide's effect on TNF-alpha in RR. Mononuclear cells from RR and non-RR patients and healthy individuals were treated with thalidomide and M.leprae (AFB), a cytosol fraction of M. leprae or Dharmendra lepromin. Thalidomide suppressed TNF-alpha, but when some RR patients' cells were stimulated with AFB, it enhanced TNF-alpha.

Women with steroid 5 alpha-reductase 2 deficiency have normal concentrations of plasma 5 alpha-dihydroprogesterone during the luteal phase.

PubMed

Milewich, L; Mendonca, B B; Arnhold, I; Wallace, A M; Donaldson, M D; Wilson, J D; Russell, D W

1995-11-01

Steroid 5 alpha-reductase 2 deficiency has been identified in two adult women from unrelated families, one a homozygote and the other a compound heterozygote. The homozygote carries the G183S mutation and is the sister of an affected male; the compound heterozygote (R246W/splice junction abnormality) is married to a heterozygote (splice junction abnormality) and is the mother of two compound heterozygotes and two homozygotes. The fact that these two women are the mothers of seven children and appear to be endocrinologically normal confirms the previous deduction that this disorder is not manifest in women. Concentrations of plasma 5 alpha-dihydroprogesterone were normal in these two women during the luteal phase; this finding implies that circulating 5 alpha-dihydroprogesterone in women is derived principally from the steroid 5 alpha-reductase 1 isoenzyme and leaves unresolved the question of whether 5 alpha-dihydroprogesterone plays a physiological role in women.

Detection of alpha radiation in a beta radiation field

DOEpatents

Mohagheghi, Amir H.; Reese, Robert P.

2001-01-01

An apparatus and method for detecting alpha particles in the presence of high activities of beta particles utilizing an alpha spectrometer. The apparatus of the present invention utilizes a magnetic field applied around the sample in an alpha spectrometer to deflect the beta particles from the sample prior to reaching the detector, thus permitting detection of low concentrations of alpha particles. In the method of the invention, the strength of magnetic field required to adequately deflect the beta particles and permit alpha particle detection is given by an algorithm that controls the field strength as a function of sample beta energy and the distance of the sample to the detector.

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.

EEG alpha power and creative ideation☆

PubMed Central

Fink, Andreas; Benedek, Mathias

2014-01-01

Neuroscientific studies revealed first insights into neural mechanisms underlying creativity, but existing findings are highly variegated and often inconsistent. Despite the disappointing picture on the neuroscience of creativity drawn in recent reviews, there appears to be robust evidence that EEG alpha power is particularly sensitive to various creativity-related demands involved in creative ideation. Alpha power varies as a function of creativity-related task demands and the originality of ideas, is positively related to an individuals’ creativity level, and has been observed to increase as a result of creativity interventions. Alpha increases during creative ideation could reflect more internally oriented attention that is characterized by the absence of external bottom-up stimulation and, thus, a form of top-down activity. Moreover, they could indicate the involvement of specific memory processes such as the efficient (re-)combination of unrelated semantic information. We conclude that increased alpha power during creative ideation is among the most consistent findings in neuroscientific research on creativity and discuss possible future directions to better understand the manifold brain mechanisms involved in creativity. PMID:23246442

Spatial heterodyne interferometry of VY Canis Major's, alpha Orionis, alpha Scorpii, and R leonis at 11 microns

NASA Technical Reports Server (NTRS)

Sutton, E. C.; Storey, J. W. V.; Betz, A. L.; Townes, C. H.; Spears, D. L.

1977-01-01

Using the technique of heterodyne interferometry, measurements were made of the spatial distribution of 11 micron radiation from four late type stars. The circumstellar shells surrounding VY Canis Majoris, alpha Orionis, and alpha Scorpii were resolved, whereas that of R Leonis was only partially resolved at a fringe spacing of 0.4 sec.

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...

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 866.5580 - 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...

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...

Tobacco plants transformed with the bean. alpha. ai gene express an inhibitor of insect. alpha. -amylase in their seeds. [Nicotiana tabacum; Tenebrio molitor

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

Altabella, T.; Chrispeels, M.J.

Bean (Phaseolus vulgaris L.) seeds contain a putative plant defense protein that inhibits insect and mammalian but not plant {alpha}-amylases. We recently presented strong circumstantial evidence that this {alpha}-amylase inhibitor ({alpha}Al) is encoded by an already-identified lectin gene whose product is referred to as lectin-like-protein (LLP). We have now made a chimeric gene consisting of the coding sequence of the lectin gene that encodes LLP and the 5{prime} and 3{prime} flanking sequences of the lectin gene that encodes phytohemagglutinin-L. When this chimeric gene was expressed in transgenic tobacco (Nicotiana tabacum), we observed in the seeds a series of polypeptides (M{submore » r} 10,000-18,000) that cross-react with antibodies to the bean {alpha}-amylase inhibitor. Most of these polypeptides bind to a pig pancreas {alpha}-amylase affinity column. An extract of the seeds of the transformed tobacco plants inhibits pig pancreas {alpha}-amylase activity as well as the {alpha}-amylase present in the midgut of Tenebrio molitor. We suggest that introduction of this lectin gene (to be called {alpha}ai) into other leguminous plants may be a strategy to protect the seeds from the seed-eating larvae of Coleoptera.« less

27 CFR 21.95 - Alpha terpineol.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c) Refractive...

27 CFR 21.95 - Alpha terpineol.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c) Refractive...

27 CFR 21.95 - Alpha terpineol.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c) Refractive...

27 CFR 21.95 - Alpha terpineol.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c) Refractive...

27 CFR 21.95 - Alpha terpineol.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Alpha terpineol. (a) Boiling point at 752mm 218.8-219.4 °C. (b) Density at 15° 0.9386. (c) Refractive...

Confined trapped alpha behaviour in TFTR deuterium-tritium plasmas

NASA Astrophysics Data System (ADS)

Medley, S. S.; Budny, R. V.; Duong, H. H.; Fisher, R. K.; Petrov, M. P.; Gorelenkov, N. N.; Redi, M. H.; Roquemore, A. L.; White, R. B.

1998-09-01

Confined trapped alpha energy spectra and differential radial density profiles in TFTR D-T plasmas were obtained with the pellet charge exchange (PCX) diagnostic, which measures high energy (Eα = 0.5-3.5 MeV) trapped alphas (v||/v = -0.048) at a single time slice (Δt approx 1 ms) with a spatial resolution of Δr approx 5 cm. Tritons produced in D-D plasmas and RF driven ion tails (H, 3He or T) were also observed and energetic tritium ion tail measurements are discussed. PCX alpha and triton energy spectra extending up to their birth energies were measured in the core of MHD quiescent discharges where the expected classical slowing down and pitch angle scattering effects are not complicated by stochastic ripple diffusion and sawtooth activity. Both the shape of the measured alpha and triton energy distributions and their density ratios are in good agreement with TRANSP predictions, indicating that the PCX measurements are consistent with classical thermalization of the fusion generated alphas and tritons. From calculations, these results set an upper limit on possible anomalous radial diffusion for trapped alphas of Dα <= 0.01 m2·s-1. Outside the core, where the trapped alphas are influenced by stochastic ripple diffusion effects, the PCX measurements are consistent with the functional dependence of the Goldston-White-Boozer stochastic ripple threshold on the alpha energy and the q profile. In the presence of strong sawtooth activity, the PCX diagnostic observes significant redistribution of the alpha signal radial profile wherein alphas are depleted in the core and redistributed to well outside the q = 1 radius, but apparently not beyond the energy dependent stochastic ripple loss boundary. The helical electric field produced during the sawtooth crash plays an essential role in modelling the sawtooth redistribution data. In sawtooth free discharge scenarios with reversed shear operation, the PCX diagnostic also observes radial profiles of the alpha signal that

Bovine alpha-lactalbumin stimulates mucus metabolism in gastric mucosa.

PubMed

Ushida, Y; Shimokawa, Y; Toida, T; Matsui, H; Takase, M

2007-02-01

Bovine alpha-lactalbumin (alpha-LA), a major milk protein, exerts strong gastroprotective activity against rat experimental gastric ulcers induced by ethanol or stress. To elucidate the mechanisms underlying this activity, the influence of alpha-LA on gastric mucus metabolism was investigated in vitro and in vivo. For the in vitro study, RGM1 cells (a rat gastric epithelial cell line) were selected for observation of the direct activity of alpha-LA on gastric mucosal cells and cultured in the presence of either alpha-LA or ovalbumin (OVA), a reference protein showing no gastroprotective activity. Amounts of synthesized and secreted mucin, a major component of mucus, were determined using [3H]glucosamine as a tracer, and prostaglandin E2 (PGE2) levels in the culture medium were determined by RIA. For the in vivo study, the thickness of the mucus gel layer, a protective barrier for gastric mucosa, was evaluated histochemically in rat gastric mucosa. alpha-Lactalbumin (3 mg/mL) significantly stimulated mucin synthesis and secretion in RGM1 cells and also increased PGE2 levels in the culture medium. In contrast, OVA showed no enhancing effects under identical conditions. Neither indomethacin, a cyclo-oxygenase inhibitor, nor AH23848, a prostaglandin EP4 receptor antagonist, affected alpha-LA-induced enhancement of mucin synthesis and secretion. In vivo, oral administration of alpha-LA (300 mg/kg x 3 times/d x 7 d) increased the thickness of the mucus gel layer in rats. These results indicate that alpha-LA fortifies the mucus gel layer by stimulating mucin production and secretion in gastric mucus-producing cells, and that this enhancing effect is independent of endogenous PGE2. Comparison of the efficacy of alpha-LA with OVA suggests that the activities observed in RGM1 cells are closely related to the gastroprotective effects in rat gastric ulcer models. In conclusion, alpha-LA stimulates mucus metabolism, and this action may be responsible for its gastroprotective

Frontal alpha asymmetry and sexually motivated states.

PubMed

Prause, Nicole; Staley, Cameron; Roberts, Verena

2014-03-01

Anterior alpha asymmetry of electroencephalographic (EEG) signals has been suggested to index state approach (or avoidance) motivation. This model has not yet been extended to high approach-motivation sexual stimuli, which may represent an important model of reward system function. Sixty-five participants viewed a neutral and a sexually motivating film while their EEG was recorded, and reported their sexual feelings after each film. Greater alpha power in the left hemisphere during sexually motivated states was evident. A positive relationship between self-reported mental sexual arousal and alpha asymmetry was identified, where coherence between these indicators was higher in women. Notably, coherence was stronger when mental versus physical sexual arousal was rated. Alpha asymmetry appears to offer a new method for further examining this novel coherence pattern across men and women. Copyright © 2014 Society for Psychophysiological Research.

Unraveling double stranded alpha-helical coiled coils: an x-ray diffraction study on hard alpha-keratin fibers.

PubMed

Kreplak, L; Doucet, J; Briki, F

2001-04-15

Transformations of proteins secondary and tertiary structures are generally studied in globular proteins in solution. In fibrous proteins, such as hard alpha-keratin, that contain long and well-defined double stranded alpha-helical coiled coil domains, such study can be directly done on the native fibrous tissue. In order to assess the structural behavior of the coiled coil domains under an axial mechanical stress, wide angle x-ray scattering and small angle x-ray scattering experiments have been carried out on stretched horse hair fibers at relative humidity around 30%. Our observations of the three major axial spacings as a function of the applied macroscopic strain have shown two rates. Up to 4% macroscopic strain the coiled coils were slightly distorted but retained their overall conformation. Above 4% the proportion of coiled coil domains progressively decreased. The main and new result of our study is the observation of the transition from alpha-helical coiled coils to disordered chains instead of the alpha-helical coiled coil to beta-sheet transition that occurs in wet fibers.

Hubble's Best Image of Alpha Centauri A and B

NASA Image and Video Library

2017-12-08

The closest star system to the Earth is the famous Alpha Centauri group. Located in the constellation of Centaurus (The Centaur), at a distance of 4.3 light-years, this system is made up of the binary formed by the stars Alpha Centauri A and Alpha Centauri B, plus the faint red dwarf Alpha Centauri C, also known as Proxima Centauri. This NASA/ESA Hubble Space Telescope has given us this stunning view of the bright Alpha Centauri A (on the left) and Alpha Centauri B (on the right), shining like huge cosmic headlamps in the dark. The image was captured by the Wide-Field and Planetary Camera 2 (WFPC2). WFPC2 was Hubble’s most used instrument for the first 13 years of the space telescope’s life, being replaced in 2009 by Wide-Field Camera 3 (WFC3) during Servicing Mission 4. This portrait of Alpha Centauri was produced by observations carried out at optical and near-infrared wavelengths. Compared to the sun, Alpha Centauri A is of the same stellar type, G2, and slightly bigger, while Alpha Centauri B, a K1-type star, is slightly smaller. They orbit a common center of gravity once every 80 years, with a minimum distance of about 11 times the distance between Earth and the sun. Because these two stars are, together with their sibling Proxima Centauri, the closest to Earth, they are among the best studied by astronomers. And they are also among the prime targets in the hunt for habitable exoplanets. Using the European Space Organization's HARPS instrument, astronomers already discovered a planet orbiting Alpha Centauri B. Then on Aug. 24, 2016, astronomers announced the intriguing discovery of a nearly Earth-sized planet in the habitable zone orbiting the star Proxima Centauri Image credit: ESA/NASA

[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

A synopsis of collective alpha effects and implications for ITER

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

Sigmar, D.J.

1990-10-01

This paper discusses the following: Alpha Interaction with Toroidal Alfven Eigenmodes; Alpha Interaction with Ballooning Modes; Alpha Interaction with Fishbone Oscillations; and Implications for ITER.

Test chamber for alpha spectrometry

DOEpatents

Larsen, Robert P.

1977-01-01

Alpha emitters for low-level radiochemical analysis by measurement of alpha spectra are positioned precisely with respect to the location of a surface-barrier detector by means of a chamber having a removable threaded planchet holder. A pedestal on the planchet holder holds a specimen in fixed engagement close to the detector. Insertion of the planchet holder establishes an O-ring seal that permits the chamber to be pumped to a desired vacuum. The detector is protected against accidental contact and resulting damage.

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)

Regulation of bovine kidney alpha-ketoglutarate dehydrogenase complex by calcium ion and adenine nucleotides. Effects on S0.5 for alpha-ketoglutarate.

PubMed

Lawlis, V B; Roche, T E

1981-04-28

Regulation of bovine kidney alpha-ketoglutarate dehydrogenase complex by energy-linked metabolites was investigated. Ca2+, ADP, or inorganic phosphate markedly enhanced the activity of the complex, and ATP or, to a lesser extent, GTP decreased the activity of the complex. Initial velocity studies with alpha-ketoglutarate as the varied substrate demonstrated that these modulators induced large changes in S0.5 for alpha-ketoglutarate (based on analysis in Hill plots) with no change in the maximum velocity (as determined by double-reciprocal plots). For all conditions studied, the Hill coefficients were significantly less than 1.0 with slopes that were linear over wide ranges of alpha-ketoglutarate concentrations, indicating negative cooperativity that probably resulted from multiple site-site interactions. Ca2+ (maintained at 10 muM by a Ca2+ buffer) decreased the S0.5 for alpha-ketoglutarate 63-fold (from 25 to 0.40 mM); even in the presence of a positive effector, ADP or phosphate, Ca2+ decreased the S0.5 for alpha-ketoglutarate 7.8- or 28-fold, respectively. Consistent with a mechanism of action dependent of Ca2+, ADP (1.60 mM) or phosphate (20 mM) reduced the S0.5 for alpha-ketoglutarate in the presence of Ca2+ (i.e., 4.5- or 1.67-fold, respectively); however, these effectors elicited larger decreases in S0.5 in the absence of Ca2+ (i.e., 37- or 3.7-fold, respectively). ATP (1.6 mM) increased the S0.5 for alpha-ketoglutarate, and Ca2+ appreciably reduced the effect, lowering the S0.5 98-fold from 66 to 0.67 mM. Thus the activity of the kidney alpha-ketoglutarate dehydrogenase complex is poised to increase as the energy potential in mitochondria declines, and Ca2+ has a pronounced modulatory effect. Comparative studies on bovine heart alpha-ketoglutarate dehydrogenase complex and the effects of varying the ADP/ATP ratio in the presence or absence of Ca2+ or phosphate are also described.

Measurement of alpha particle energy using windowless electret ion chambers.

PubMed

Dua, S K; Kotrappa, P; Srivastava, R; Ebadian, M A; Stieff, L R

2002-10-01

Electret ion chambers are inexpensive, lightweight, robust, commercially available, passive, charge-integrating devices for accurate measurement of different ionizing radiations. In an earlier work a chamber of dimensions larger than the range of alpha particles having aluminized Mylar windows of different thickness was used for measurement of alpha radiation. Correlation between electret mid-point voltage, alpha particle energy, and response was developed and it was shown that this chamber could be used for estimating the effective energy of an unknown alpha source. In the present study, the electret ion chamber is used in the windowless mode so that the alpha particles dissipate their entire energy inside the volume, and the alpha particle energy is determined from the first principles. This requires that alpha disintegration rate be accurately known or measured by an alternate method. The measured energies were within 1 to 4% of the true values for different sources (230Th, 237Np, 239Pu, 241Am, and 224Cm). This method finds application in quantitative determination of alpha energy absorbed in thin membrane and, hence, the absorbed dose.

Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha.

PubMed

Leibovich, S J; Polverini, P J; Shepard, H M; Wiseman, D M; Shively, V; Nuseir, N

Macrophages are important in the induction of new blood vessel growth during wound repair, inflammation and tumour growth. We show here that tumour necrosis factor-alpha (TNF-alpha), a secretory product of activated macrophages that is believed to mediate tumour cytotoxicity, is a potent inducer of new blood vessel growth (angiogenesis). In vivo, TNF-alpha induces capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membrane at very low doses. In vitro, TNF-alpha stimulates chemotaxis of bovine adrenal capillary endothelial cells and induces cultures of these cells grown on type-1 collagen gels to form capillary-tube-like structures. The angiogenic activity produced by activated murine peritoneal macrophages is completely neutralized by a polyclonal antibody to TNF-alpha, suggesting immunological features are common to TNF-alpha and the protein responsible for macrophage-derived angiogenic activity. In inflammation and wound repair, TNF-alpha could augment repair by stimulating new blood vessel growth; in tumours, TNF-alpha might both stimulate tumour development by promoting vessel growth and participate in tumour destruction by direct cytotoxicity.

Autoradiography imaging in targeted alpha therapy with Timepix detector.

PubMed

A L Darwish, Ruqaya; Staudacher, Alexander Hugo; Bezak, Eva; Brown, Michael Paul

2015-01-01