Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer.

PubMed

Park, Gab-Jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

2017-01-01

A microdose drug-drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2-9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (C max ) and area under the curve to the last measurement (AUC t ) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for C max , and 4.07 (micro), 4.33 (regular) for AUC t . For the induction study, they were 0.26 (micro) and 0.21 (regular) for C max , and 0.16 (micro) and 0.15 (regular) for AUC t . There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes.

Sensitivity and proportionality assessment of metabolites from microdose to high dose in rats using LC-MS/MS.

PubMed

Ni, Jinsong; Ouyang, Hui; Seto, Carmai; Sakuma, Takeo; Ellis, Robert; Rowe, Josh; Acheampong, Andrew; Welty, Devin; Szekely-Klepser, Gabriella

2010-03-01

The objective of this study was to evaluate the sensitivity requirement for LC-MS/MS as an analytical tool to characterize metabolites in plasma and urine at microdoses in rats and to investigate proportionality of metabolite exposure from a microdose of 1.67 µg/kg to a high dose of 5000 µg/kg for atorvastatin, ofloxacin, omeprazole and tamoxifen. Only the glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole and the hydration metabolite of tamoxifen were characterized in rat plasma at microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and tamoxifen appeared to increase in a nonproportional manner with increasing doses. Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and lactone, increased proportionally with increasing doses. LC-MS/MS has demonstrated its usefulness for detecting and characterizing the major metabolites in plasma and urine at microdosing levels in rats. The exposure of metabolites at microdose could not simply be used to predict their exposure at higher doses.

Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients.

PubMed

Duvan, Candan Iltemir; Berker, Bulent; Turhan, Nilgun Ozturk; Satiroglu, Hakan

2008-01-01

To compare oral contraceptive (OC) pretreatment plus microdose GnRH-a in flare-up protocol and non-OC microdose GnRH-a in flare-up protocol among poor responder ICSI patients. A retrospective analysis of poor responder ICSI patients. Patients were divided into two groups according to used microdose protocol. Precycle treatment with OC followed by follicular phase administration of 40 microg s.c. leuprolide acetate (LA) every 12 h beginning on after 2 day pill-free period and rFSH administration was begun on the third day of LA administration (OC-Group, n=26). Alternatively on day 2 after menses, patients were administered similar stimulation regime (non-OC Group, n=27). There were no significant differences between groups in the number of oocytes, peak estradiol levels, endometrial thickness, fertilization rates and embryo quality. Implantations and pregnancy rates per embryo transfer were similar. OC pretreatment plus microdose GnRHa in flare-up protocol does not offer advantages over non-OC microdose GnRHa in flare-up protocol among poor responder ICSI patients.

Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats

PubMed Central

Lao, Victoria; Ramos, Courtney L.; Ong, Voon S.; Turteltaub, Kenneth W.

2014-01-01

Determining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study assessed the PKs of a novel antimicrobial preclinical drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30 mg/kg of body weight), and PK linearity between a microdose and a pharmacological dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological doses were proportional. Over the 10-fold dose range, the maximum concentration in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold, respectively. PKs from rats dosed with a 14C-labeled microdose versus a 14C-labeled pharmacological dose displayed dose linearity. In the animals receiving a microdose and the therapeutically dosed animals, the AUCs from time zero to infinity were 2.6 ng · h/ml and 1,336 ng · h/ml, respectively, and the terminal half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng · h/ml for the microdose and 418.2 ng · h/ml for the pharmacological dose. This 1.5-fold difference in AUC following a 300-fold difference in dose is considered linear across the dose range. On the basis of the results, the PKs from the microdosed animals were considered to be predictive of the PKs from the therapeutically dosed animals. PMID:25136019

Molecular Layer Deposition of Hybrid Organic-Inorganic Alucone Polymer Films Using a Three-Step ABC Reaction Sequence

DTIC Science & Technology

2009-11-02

versus TMA exposure at 150 C is shown in Figure 4a. The TMA exposure is defined by the number of TMA microdoses . EachTMAmicrodosewas a 0.5 s exposure...at 80mTorr of partial pressure. Figure 4a indicates that the TMA reac- tion is self-limiting and reaches completion after 10 TMA microdoses . The...of EA microdoses . Each EA microdose was a 0.5 s exposure at 20 mTorr of partial pressure. Figure 4b indicates that the EA reaction is self-limiting

A diagnostic microdosing approach to investigate platinum sensitivity in non-small cell lung cancer

DOE PAGES

Wang, Si-Si; Zimmermann, Maike; Zhang, Hongyong; ...

2017-04-24

The platinum-based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug-DNA adducts—the pharmacodynamic drug-target complex for this class of drugs. In this paper, the feasibility of predictive diagnostic microdosing was assessed in non-small cell lung cancer (NSCLC) cell culture and a pilot clinical trial. Accelerator mass spectrometry (AMS) was used to quantify [ 14C]carboplatin-DNA monoadduct levels in themore » cell lines induced by microdoses and therapeutic doses of carboplatin, followed by correlation with carboplatin IC 50 values for each cell line. The adduct levels in cell culture experiments were linearly proportional to dose (R 2 = 0.95, p < 0.0001) and correlated with IC 50 across all cell lines for microdose and therapeutically relevant carboplatin concentrations (p = 0.02 and p = 0.01, respectively). A pilot microdosing clinical trial was conducted to define protocols and gather preliminary data. Plasma pharmacokinetics (PK) and [ 14C]carboplatin-DNA adducts in white blood cells and tumor tissues from six NSCLC patients were quantified via AMS. The blood plasma half-life of [ 14C]carboplatin administered as a microdose was consistent with the known PK of therapeutic dosing. The optimal [ 14C]carboplatin formulation for the microdose was 10 7 dpm/kg of body weight and 1% of the therapeutic dose for the total mass of carboplatin. No microdose-associated toxicity was observed in the patients. Finally, additional accruals are required to significantly correlate adduct levels with response.« less

A diagnostic microdosing approach to investigate platinum sensitivity in non-small cell lung cancer

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

Wang, Si-Si; Zimmermann, Maike; Zhang, Hongyong

The platinum-based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug-DNA adducts—the pharmacodynamic drug-target complex for this class of drugs. In this paper, the feasibility of predictive diagnostic microdosing was assessed in non-small cell lung cancer (NSCLC) cell culture and a pilot clinical trial. Accelerator mass spectrometry (AMS) was used to quantify [ 14C]carboplatin-DNA monoadduct levels in themore » cell lines induced by microdoses and therapeutic doses of carboplatin, followed by correlation with carboplatin IC 50 values for each cell line. The adduct levels in cell culture experiments were linearly proportional to dose (R 2 = 0.95, p < 0.0001) and correlated with IC 50 across all cell lines for microdose and therapeutically relevant carboplatin concentrations (p = 0.02 and p = 0.01, respectively). A pilot microdosing clinical trial was conducted to define protocols and gather preliminary data. Plasma pharmacokinetics (PK) and [ 14C]carboplatin-DNA adducts in white blood cells and tumor tissues from six NSCLC patients were quantified via AMS. The blood plasma half-life of [ 14C]carboplatin administered as a microdose was consistent with the known PK of therapeutic dosing. The optimal [ 14C]carboplatin formulation for the microdose was 10 7 dpm/kg of body weight and 1% of the therapeutic dose for the total mass of carboplatin. No microdose-associated toxicity was observed in the patients. Finally, additional accruals are required to significantly correlate adduct levels with response.« less

Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients

PubMed Central

Berker, Bulent; Turhan, Nilgun Ozturk; Satiroglu, Hakan

2008-01-01

Purpose To compare oral contraceptive (OC) pretreatment plus microdose GnRH-a in flare-up protocol and non-OC microdose GnRH-a in flare-up protocol among poor responder ICSI patients. Methods A retrospective analysis of poor responder ICSI patients. Patients were divided into two groups according to used microdose protocol. Precycle treatment with OC followed by follicular phase administration of 40 μg sc leuprolide acetate (LA) every 12 h beginning on after 2 day pill-free period and rFSH administration was begun on the third day of LA administration (OC-Group, n = 26). Alternatively on day 2 after menses, patients were administered similar stimulation regime (non-OC Group, n = 27). Results There were no significant differences between groups in the number of oocytes, peak estradiol levels, endometrial thickness, fertilization rates and embryo quality. Implantations and pregnancy rates per embryo transfer were similar. Conclusion OC pretreatment plus microdose GnRHa in flare-up protocol does not offer advantages over non-OC microdose GnRHa in flare-up protocol among poor responder ICSI patients. PMID:18253823

Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects.

PubMed

Kusuhara, H; Ito, S; Kumagai, Y; Jiang, M; Shiroshita, T; Moriyama, Y; Inoue, K; Yuasa, H; Sugiyama, Y

2011-06-01

A microdose study of metformin was conducted to investigate the predictability of drug-drug interactions at the therapeutic dose (ThD). Healthy subjects received a microdose (100 µg) or ThD (250 mg) of metformin orally, with or without a potent and competitive multidrug and toxin extrusion (MATE) inhibitor, pyrimethamine (50 mg, p.o.), in a crossover fashion. Pyrimethamine significantly reduced the renal clearance of metformin by 23 and 35% at the microdose and ThD, respectively. At ThD, but not at microdose, it caused significant increases in the maximum concentration (C(max)) and area under the plasma concentration-time curve (AUC) of metformin (142 and 139% of control values, respectively). Human canalicular membrane vesicles showed pyrimethamine-inhibitable metformin uptake. Pyrimethamine did not affect plasma lactate/pyruvate after ThD of metformin but significantly reduced the renal clearance of creatinine, thereby causing elevation of plasma creatinine level. This microdose study quantitatively predicted a drug-drug interaction involving the renal clearance of metformin at ThD by pyrimethamine. Pyrimethamine is a useful in vivo inhibitor of MATE proteins.

Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability.

PubMed

Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Houston, Brian; Oosterhuis, Berend; Bjerrum, Ole J; Rowland, Malcolm; Garner, Colin

2010-05-12

A human pharmacokinetic study was performed to assess the ability of a microdose to predict the pharmacokinetics of a therapeutic dose of fexofenadine and to determine its absolute oral bioavailability. Fexofenadine was chosen to represent an unmetabolized transporter substrate (P-gP and OATP). Fexofenadine was administered to 6 healthy male volunteers in a three way cross-over design. A microdose (100microg) of (14)C-drug was administered orally (period 1) and intravenously by 30min infusion (period 2). In period 3 an intravenous tracer dose (100microg) of (14)C-drug was administered simultaneously with an oral unlabelled therapeutic dose (120mg). Plasma was collected from all 3 periods and analysed for both total (14)C content and parent drug by accelerator mass spectrometry (AMS). For period 3, plasma samples were also analysed using HPLC-fluorescence to determine total drug concentration. Urine was collected and analysed for total (14)C. Good concordance between the microdose and therapeutic dose pharmacokinetics was observed. Microdose: CL 13L/h, CL(R) 4.1L/h, V(ss) 54L, t(1/2) 16h; therapeutic dose: CL 16L/h, CL(R) 6.2L/h, V(ss) 64L, t(1/2) 12h. The absolute oral bioavailability of fexofenadine was 0.35 (microdose 0.41, therapeutic dose 0.30). Despite a 1200-fold difference in dose of fexofenadine, the microdose predicted well the pharmacokinetic parameters following a therapeutic dose for this transporter dependent compound.

Lung nodule detection by microdose CT versus chest radiography (standard and dual-energy subtracted).

PubMed

Ebner, Lukas; Bütikofer, Yanik; Ott, Daniel; Huber, Adrian; Landau, Julia; Roos, Justus E; Heverhagen, Johannes T; Christe, Andreas

2015-04-01

The purpose of this study was to investigate the feasibility of microdose CT using a comparable dose as for conventional chest radiographs in two planes including dual-energy subtraction for lung nodule assessment. We investigated 65 chest phantoms with 141 lung nodules, using an anthropomorphic chest phantom with artificial lung nodules. Microdose CT parameters were 80 kV and 6 mAs, with pitch of 2.2. Iterative reconstruction algorithms and an integrated circuit detector system (Stellar, Siemens Healthcare) were applied for maximum dose reduction. Maximum intensity projections (MIPs) were reconstructed. Chest radiographs were acquired in two projections with bone suppression. Four blinded radiologists interpreted the images in random order. A soft-tissue CT kernel (I30f) delivered better sensitivities in a pilot study than a hard kernel (I70f), with respective mean (SD) sensitivities of 91.1%±2.2% versus 85.6%±5.6% (p=0.041). Nodule size was measured accurately for all kernels. Mean clustered nodule sensitivity with chest radiography was 45.7%±8.1% (with bone suppression, 46.1%±8%; p=0.94); for microdose CT, nodule sensitivity was 83.6%±9% without MIP (with additional MIP, 92.5%±6%; p<10(-3)). Individual sensitivities of microdose CT for readers 1, 2, 3, and 4 were 84.3%, 90.7%, 68.6%, and 45.0%, respectively. Sensitivities with chest radiography for readers 1, 2, 3, and 4 were 42.9%, 58.6%, 36.4%, and 90.7%, respectively. In the per-phantom analysis, respective sensitivities of microdose CT versus chest radiography were 96.2% and 75% (p<10(-6)). The effective dose for chest radiography including dual-energy subtraction was 0.242 mSv; for microdose CT, the applied dose was 0.1323 mSv. Microdose CT is better than the combination of chest radiography and dual-energy subtraction for the detection of solid nodules between 5 and 12 mm at a lower dose level of 0.13 mSv. Soft-tissue kernels allow better sensitivities. These preliminary results indicate that microdose CT has the potential to replace conventional chest radiography for lung nodule detection.

Clinical relevance of liquid chromatography tandem mass spectrometry as an analytical method in microdose clinical studies.

PubMed

Yamane, Naoe; Tozuka, Zenzaburo; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

2011-08-01

To investigate the potency of LC-MS/MS by means of sensitivity and the applicability for cassette dosing in microdose clinical trials. Thirty one top-selling 31 drugs were spiked to human plasma, extracted, and analyzed by LC-MS/MS. The lower limits of quantification for each drug varied from 0.08 to 50 pg/mL, and were lower than one eighth of the assumed maximum plasma concentration at microdose in all drugs except for losartan, indicating the high performance in acquisition of full pharmacokinetic profiles at microdose. We also succeeded in simultaneous analysis of multiple compounds, assuming a situation of cassette dosing in which multiple drug candidates would be administrated simultaneously. Together with the features of LC-MS/MS, such as immediate verification, the utilization of non-radiolabeled drugs and no special facilities, we suppose that LC-MS/MS analysis would be widely applicable in conducting microdose clinical studies.

Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis

PubMed Central

Garner, Colin R; Park, Kevin B; French, Neil S; Earnshaw, Caroline; Schipani, Alessandro; Selby, Andrew M; Byrne, Lindsay; Siner, Sarah; Crawley, Francis P; Vaes, Wouter H J; van Duijn, Esther; deLigt, Rianne; Varendi, Heili; Lass, Jane; Grynkiewicz, Grzegorz; Maruszak, Wioletta; Turner, Mark A

2015-01-01

Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0–2 year old age group. Methods [14C]-PARA concentrations in 10–15 µl plasma samples were measured after enteral or i.v. administration of a single [14C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Results Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h–1, 1.76 (1.07) l h–1, 2.93 (2.08) l h–1 and 2.72 (3.10) l h–1, t1/2 values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l–1 h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). Conclusions All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg–1) and a microdose (ng kg–1) in babies between 35 to 127 weeks post-menstrual age. [14C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies. PMID:25619398

Observational infant exploratory [(14)C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis.

PubMed

Garner, Colin R; Park, Kevin B; French, Neil S; Earnshaw, Caroline; Schipani, Alessandro; Selby, Andrew M; Byrne, Lindsay; Siner, Sarah; Crawley, Francis P; Vaes, Wouter H J; van Duijn, Esther; deLigt, Rianne; Varendi, Heili; Lass, Jane; Grynkiewicz, Grzegorz; Maruszak, Wioletta; Turner, Mark A

2015-07-01

The aims of the study were to compare [(14)C]-paracetamol ([(14)C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group. [(14)C]-PARA concentrations in 10-15 µl plasma samples were measured after enteral or i.v. administration of a single [(14)C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h(-1), 1.76 (1.07) l h(-1), 2.93 (2.08) l h(-1) and 2.72 (3.10) l h(-1), t(1/2) values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l(-1) h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg(-1)) and a microdose (ng kg(-1)) in babies between 35 to 127 weeks post-menstrual age. [(14)C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies. © 2015 The British Pharmacological Society.

Evaluation Of Microdosing Strategies For Studies In Preclinical Drug Development: Demonstration Of Linear Pharmacokinetics In Dogs Of A Nucleoside Analogue Over A 50-Fold Dose Range

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

Sandhu, P; Vogel, J S; Rose, M J

The technique of accelerator mass spectrometry (AMS) was validated successfully and utilized to study the pharmacokinetics and disposition in dogs of a preclinical drug candidate (Compound A), after oral and intravenous administration. The primary objective of this study was to examine whether Compound A displayed linear kinetics across sub-pharmacological (microdose) and pharmacological dose ranges in an animal model, prior to initiation of a human microdose study. The AMS-derived disposition properties of Compound A were comparable to data obtained via conventional techniques such as LC-MS/MS and liquid scintillation counting analyses. Thus, Compound A displayed multiphasic kinetics and possessed low plasma clearancemore » (4.4 mL/min/kg), a long terminal elimination half-life (19.4 hr) and high oral bioavailability (82%). Currently there are no published comparisons of the kinetics of a pharmaceutical compound at pharmacological versus sub-pharmacological doses employing microdosing strategies. The present study thus provides the first description of the pharmacokinetics of a drug candidate assessed under these two dosing regimens. The data demonstrated that the pharmacokinetic properties of Compound A were similar following dosing at 0.02 mg/kg as at 1 mg/kg, indicating that in the case of Compound A, the kinetics of absorption, distribution and elimination in the dog appear to be linear across this 50-fold dose range. Moreover, the exceptional sensitivity of AMS provided a pharmacokinetic profile of Compound A, even following a microdose, which revealed aspects of the disposition of this agent that were inaccessible by conventional techniques. The applications of accelerator mass spectrometry (AMS) are broad ranging and vary from studying environmental and ecological issues such as the isotopic composition of the atmosphere, soil and water (Hughen et al., 2000; Beck et al., 2001; Keith-Roach et al., 2001; Mironov et al., 2002), to archaeology and volcanology (Stafford et al., 1984; Vogel et al., 1990; Smith et al., 1999) to its use as a bioanalytical tool for nutritional research (Buchholz et al., 1999; Deuker et al., 2000; Weaver and Liebman, 2002). Biomedical applications of AMS and its use in the arena of pharmaceutical research also have been detailed in review articles (Barker and Garner, 1999; Garner, 2000; Turteltaub and Vogel, 2000). To date, most studies on the metabolism and disposition of xenobiotics by AMS have focused on how carcinogens bind to DNA and proteins to form adducts (Turteltaub et al., 1990, 1997; Frantz et al., 1995; Dingley et al., 1999; Li et al., 2003). Its application to the field of pharmaceutical sciences has been limited to a few studies (Kaye et al., 1997; Young et al., 2001; Garner et al., 2002). However, the pharmaceutical industry is becoming increasingly aware of the potential benefits that may accrue from the ultra high sensitivity afforded by AMS in terms of evaluating the pharmacokinetics of lead drug candidates in early development. Specifically, AMS allows administration of sub-pharmacological doses (microdoses) of carbon-14 or tritium-labeled investigational drugs to animals or humans at radiologically insignificant levels with the goal of obtaining preliminary information regarding the absorption, distribution, metabolism, and excretion of test compounds (Turteltaub and Vogel, 2000). An unresolved issue, however, is whether the pharmacokinetics determined following a microdose are representative of those following a conventional (pharmacological) dose (Lappin and Garner, 2003). This paper examines the linearity of kinetics of an antiviral nucleoside analogue, Compound A, across sub-pharmacological and pharmacological dose ranges in the dog prior to initiation of a human microdose study. The specific objectives of this study, therefore, were (1) to assess the pharmacokinetics of Compound A in dogs by a conventional dosing approach utilizing LC-MS/MS for sample analysis, (2) to assess the pharmacokinetics of Compound A in dogs by the microdose approach utilizing AMS for sample analysis, (3) to compare the pharmacokinetics of Compound A at a microdose versus a pharmacological dose, and (4) to validate AMS for this application and to compare the sensitivity of AMS to that of LC-MS/MS.« less

Relaxor Ferroelectric Single Crystal Based Hybrid Actuator for Underwater Acoustic Noise Generation

DTIC Science & Technology

2002-05-01

low pres- sure and low flow rate applications [6] [7] [8] [9] [12] such as drug dispensing and microdosing [13] [14] [15]. The higher performing of...as microdosing of fluids. This paper introduces the development a novel class of micromachined transducers called solid- state micro-hydraulic...are mostly geared towards small flow/force applications such as microdosing of fluids. This paper introduces the development a novel class of

[Microdose clinical trial--impact of PET molecular imaging].

PubMed

Yano, Tsuneo; Watanabe, Yasuyoshi

2010-10-01

Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration.

PubMed

Wang, Guan; Durussel, Jérôme; Shurlock, Jonathan; Mooses, Martin; Fuku, Noriyuki; Bruinvels, Georgie; Pedlar, Charles; Burden, Richard; Murray, Andrew; Yee, Brendan; Keenan, Anne; McClure, John D; Sottas, Pierre-Edouard; Pitsiladis, Yannis P

2017-11-14

Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo. Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo. ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%). Current results provide further evidence that transcriptional biomarkers can strengthen the ABP approach by significantly prolonging the detection window and improving the sensitivity and specificity of blood doping detection. Further studies are required to confirm, and if necessary, integrate the confounding effects of altitude training on blood doping.

Ultrasensitive liquid chromatography-tandem mass spectrometric methodologies for quantification of five HIV-1 integrase inhibitors in plasma for a microdose clinical trial.

PubMed

Sun, Li; Li, Hankun; Willson, Kenneth; Breidinger, Sheila; Rizk, Matthew L; Wenning, Larissa; Woolf, Eric J

2012-10-16

HIV-1 integrase strand transfer inhibitors are an important class of compounds targeted for the treatment of HIV-1 infection. Microdosing has emerged as an attractive tool to assist in drug candidate screening for clinical development, but necessitates extremely sensitive bioanalytical assays, typically in the pg/mL concentration range. Currently, accelerator mass spectrometry is the predominant tool for microdosing support, which requires a specialized facility and synthesis of radiolabeled compounds. There have been few studies attempted to comprehensively assess a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach in the context of microdosing applications. Herein, we describe the development of automated LC-MS/MS methods to quantify five integrase inhibitors in plasma with the limits of quantification at 1 pg/mL for raltegravir and 2 pg/mL for four proprietary compounds. The assays involved double extractions followed by UPLC coupled with negative ion electrospray MS/MS analysis. All methods were fully validated to the rigor of regulated bioanalysis requirements, with intraday precision between 1.20 and 14.1% and accuracy between 93.8 and 107% at the standard curve concentration range. These methods were successfully applied to a human microdose study and demonstrated to be accurate, reproducible, and cost-effective. Results of the study indicate that raltegravir displayed linear pharmacokinetics between a microdose and a pharmacologically active dose.

Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study.

PubMed

Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Satıroğlu, Hakan

2010-01-01

To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI.

Intra‐Target Microdosing – A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans

PubMed Central

MacLeod, D; Lee, K; Santoro, A; DeMasi, DK; Hawk, T; Feinglos, M; Rowland, M; Noveck, RJ

2017-01-01

Abstract Intra‐Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first‐in‐human (FIH) testing of new molecular entities (NMEs). ITM combines intra‐target drug delivery and “microdosing,” the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic‐level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18F‐fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well‐tolerated. Results are consistent with ITM proof‐of‐concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach. PMID:28689370

Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions.

PubMed

de Souza, Ana Luiza Ribeiro; Marra, Kayla; Gunn, Jason; Samkoe, Kimberley S; Hoopes, P Jack; Feldwisch, Joachim; Paulsen, Keith D; Pogue, Brian W

2017-02-01

Fluorescence guidance in surgical oncology provides the potential to realize enhanced molecular tumor contrast with dedicated targeted tracers, potentially with a microdose injection level. For most glioma tumors, the blood brain barrier is compromised allowing some exogenous drug/molecule delivery and accumulation for imaging. The aberrant overexpression and/or activation of epidermal growth factor receptor (EGFR) is associated with many types of cancers, including glioblastoma, and so the use of a near-infrared (NIR) fluorescent molecule targeted to the EGFR receptor provides the potential for improving tumor contrast during surgery. Fluorescently labeled affibody molecule (ABY-029) has high EGFR affinity and high potential specificity with reasonably fast plasma clearance. In this study, ABY-29 was evaluated in glioma versus normal brain uptake from intravenous injection at a range of doses, down to a microdose injection level. Nude rats were inoculated with the U251 human glioma cell line in the brain. Tumors were allowed to grow for 3-4 weeks. ABY-029 fluorescence ex vivo imaging of brain slices was acquired at different time points (1-48 h) and varying injection doses from 25 to 122 μg/kg (from human protein microdose equivalent to five times microdose levels). The tumor was most clearly visualized at 1-h post-injection with 8- to 16-fold average contrast relative to normal brain. However, the tumor still could be identified after 48 h. In all cases, the ABY-029 fluorescence appeared to localize preferentially in EGFR-positive regions. Increasing the injected dose from a microdose level to five times, a microdose level increased the signal by 10-fold, and the contrast was from 8 to 16, showing that there was value in doses slightly higher than the microdose restriction. Normal tissue uptake was found to be affected by the tumor size, indicating that edema was a likely factor affecting the expected tumor to normal tissue contrast. These results suggest that the NIR-labeled affibody molecules provide an excellent potential to increase surgical visualization of EGFR-positive tumor regions.

Charge deposition model for investigating SE-microdose effect in trench power MOSFETs

NASA Astrophysics Data System (ADS)

Xin, Wan; Weisong, Zhou; Daoguang, Liu; Hanliang, Bo; Jun, Xu

2015-05-01

It was demonstrated that heavy ions can induce large current—voltage (I-V) characteristics shift in commercial trench power MOSFETs, named single event microdose effect (SE-microdose effect). A model is presented to describe this effect. This model calculates the charge deposition by a single heavy ion hitting oxide and the subsequent charge transport under an electric field. Holes deposited at the SiO2/Si interface by a Xe ion are calculated by using this model. The calculated results were then used in Sentaurus TCAD software to simulate a trench power MOSFET's I-V curve shift after a Xe ion has hit it. The simulation results are consistent with the related experiment's data. In the end, several factors which affect the SE-microdose effect in trench power MOSFETs are investigated by using this model.

Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study

PubMed Central

Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Şatıroğlu, Hakan

2010-01-01

Objective To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). Material and Methods The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. Results There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Conclusion Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI. PMID:24591934

Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection-embryo transfer cycle.

PubMed

Kahraman, Korhan; Berker, Bulent; Atabekoglu, Cem Somer; Sonmezer, Murat; Cetinkaya, Esra; Aytac, Rusen; Satiroglu, Hakan

2009-06-01

To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. Prospective, randomized, clinical study. University hospital. Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. Twenty-one patients received microdose leuprolide acetate (LA) (50 microg twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.

Microdose clinical trial: quantitative determination of nicardipine and prediction of metabolites in human plasma.

PubMed

Yamane, Naoe; Takami, Tomonori; Tozuka, Zenzaburo; Sugiyama, Yuichi; Yamazaki, Akira; Kumagai, Yuji

2009-01-01

A sample treatment procedure and high-sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for quantitative determination of nicardipine in human plasma were developed for a microdose clinical trial with nicardipine, a non-radioisotope labeled drug. The calibration curve was linear in the range of 1-500 pg/mL using 1 mL of plasma. Analytical method validation for the clinical dose, for which the calibration curve was linear in the range of 0.2-100 ng/mL using 20 microL of plasma, was also conducted. Each method was successfully applied to making determinations in plasma using LC/MS/MS after administration of a microdose (100 microg) and clinical dose (20 mg) to each of six healthy volunteers. We tested new approaches in the search for metabolites in plasma after microdosing. In vitro metabolites of nicardipine were characterized using linear ion trap-fourier transform ion cyclotron resonance mass spectrometry (LIT-FTICRMS) and the nine metabolites predicted to be in plasma were analyzed using LC/MS/MS. There is a strong possibility that analysis of metabolites by LC/MS/MS may advance to utilization in microdose clinical trials with non-radioisotope labeled drugs.

Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A.

PubMed

Prueksaritanont, T; Tatosian, D A; Chu, X; Railkar, R; Evers, R; Chavez-Eng, C; Lutz, R; Zeng, W; Yabut, J; Chan, G H; Cai, X; Latham, A H; Hehman, J; Stypinski, D; Brejda, J; Zhou, C; Thornton, B; Bateman, K P; Fraser, I; Stoch, S A

2017-04-01

A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion-transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein (P-gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst-case scenario for P-gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Molecular Layer Deposition of Hybrid Organic-Inorganic Polymer Films using Diethylzinc and Ethylene Glycol

DTIC Science & Technology

2009-01-01

by the number of microdoses of DEZ or EG. Figure 4a indicates that the DEZ reaction is self-limiting and reaches Full Paper Fig. 2. In-situ FTIR...after ten DEZ microdoses . Each DEZ dose was defined by a 0.3 s exposure at 70 mTorr of partial pressure. Likewise, Figure 4b indicates that the EG...the Full Paper Fig. 4. Integrated absorbance for a) CH stretching vibrations versus number of DEZ microdoses , and b) OH stretching vibrations versus

[Impact of microdose clinical trials in the preclinical stage].

PubMed

Kim, Soonih

2014-01-01

A microdose clinical trial may be useful as a safe early-phase exploratory study using doses as low as 100 μg or less for determination of the disposition of a candidate compound in humans in a short period of time. This may increase confidence in candidate compounds, especially those for which it is difficult to predict disposition based on the results of in vitro or preclinical studies. In this study, we examined microdose trials performed in the preclinical stage for two first-in-class compounds with a new mechanism of action. These compounds showed species difference in first pass metabolism in the digestive tract and liver, causing uncertainty in prediction of disposition in humans. For this reason, first-in-human microdose clinical trials were performed. The results showed that the two compounds had effective blood concentrations after oral administration at a dose of 100 mg qd. Administration of an extremely small dose of one (14)C-labeled compound permitted identification of major metabolites. No toxic metabolites were detected. The preclinical toxic dose was determined based on prediction of blood exposure at the estimated maximum clinical dose. For the other candidate compound, the findings of the microdose trial indicated a high bioavailability after oral administration and low hepatic clearance after intravenous administration. These results suggested only a small risk of a change in disposition in patients with hepatic disorder. The data obtained for the two compounds suggest that microdose clinical trials can be useful for improving the process of candidate selection in the preclinical stage.

A human microdose study of the antimalarial drug GSK3191607 in healthy volunteers.

PubMed

Okour, Malek; Derimanov, Geo; Barnett, Rodger; Fernandez, Esther; Ferrer, Santiago; Gresham, Stephanie; Hossain, Mohammad; Gamo, Francisco-Javier; Koh, Gavin; Pereira, Adrian; Rolfe, Katie; Wong, Deborah; Young, Graeme; Rami, Harshad; Haselden, John

2018-03-01

GSK3191607, a novel inhibitor of the Plasmodium falciparum ATP4 (PfATP4) pathway, is being considered for development in humans. However, a key problem encountered during the preclinical evaluation of the compound was its inconsistent pharmacokinetic (PK) profile across preclinical species (mouse, rat and dog), which prevented reliable prediction of PK parameters in humans and precluded a well-founded assessment of the potential for clinical development of the compound. Therefore, an open-label microdose (100 μg, six subjects) first time in humans study was conducted to assess the human PK of GSK3191607 following intravenous administration of [14C]-GSK3191607. A human microdose study was conducted to investigate the clinical PK of GSK3191607 and enable a Go/No Go decision on further progression of the compound. The PK disposition parameters estimated from the microdose study, combined with preclinical in vitro and in vivo pharmacodynamic parameters, were all used to estimate the potential efficacy of various oral dosing regimens in humans. The PK profile, based on the microdose data, demonstrated a half-life (~17 h) similar to other antimalarial compounds currently in clinical development. However, combining the microdose data with the pharmacodynamic data provided results that do not support further clinical development of the compound for a single dose cure. The information generated by this study provides a basis for predicting the expected oral PK profiles of GSK3191607 in man and supports decisions on the future clinical development of the compound. © 2017 The British Pharmacological Society.

Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers.

PubMed

Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Brian Houston, J; Oosterhuis, Berend; Bjerrum, Ole J; Grynkiewicz, Grzegorz; Alder, Jane; Rowland, Malcolm; Garner, Colin

2011-06-14

A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (sumatriptan, propafenone). For all five drugs an oral microdose predicted reasonably well the PK, including the shape of the plasma profile, following an oral therapeutic dose. For clarithromycin, sumatriptan, and propafenone, one parameter, oral bioavailability, was marginally outside of the normally acceptable 2-fold prediction interval around the mean therapeutic dose value. For clarithromycin, sumatriptan and propafenone, data obtained from an oral and iv microdose were compared within the same cohort of subjects used in the study, as well as those reported in the literature. For paracetamol (oral and iv) and phenobarbital (oral), microdose data were compared with those reported in the literature only. Where 100 μg iv (14)C-doses were given alone and with an oral non-labelled therapeutic dose, excellent accord between the PK parameters was observed indicating that the disposition kinetics of the drugs tested were unaffected by the presence of therapeutic concentrations. This observation implies that any deviation from linearity following the oral therapeutic doses occurs during the absorption process. Copyright © 2011 Elsevier B.V. All rights reserved.

Cumulative effective dose and cancer risk for pediatric population in repetitive full spine follow-up imaging: How micro dose is the EOS microdose protocol?

PubMed

Law, Martin; Ma, Wang-Kei; Lau, Damian; Cheung, Kenneth; Ip, Janice; Yip, Lawrance; Lam, Wendy

2018-04-01

To evaluate and to obtain analytic formulation for the calculation of the effective dose and associated cancer risk using the EOS microdose protocol for scoliotic pediatric patients undergoing full spine imaging at different age of exposure; to demonstrate the microdose protocol capable of delivering lesser radiation dose and hence of further reducing cancer risk induction when compared with the EOS low dose protocol; to obtain cumulative effective dose and cancer risk for both genders scoliotic pediatrics of US and Hong Kong population using the microdose protocol. Organ absorbed doses of full spine exposed scoliotic pediatric patients have been simulated with the use of EOS microdose protocol imaging parameters input to the Monte Carlo software PCXMC. Gender and age specific effective dose has been calculated with the simulated organ absorbed dose using the ICRP-103 approach. The associated radiation induced cancer risk, expressed as lifetime attributable risk (LAR), has been estimated according to the method introduced in the Biological Effects of Ionizing Radiation VII report. Values of LAR have been estimated for scoliotic patients exposed repetitively during their follow up period at different age for US and Hong Kong population. The effective doses of full spine imaging with simultaneous posteroanterior and lateral projection for patients exposed at the age between 5 and 18 years using the EOS microdose protocol have been calculated within the range of 2.54-14.75 μSv. The corresponding LAR for US and Hong Kong population was ranged between 0.04 × 10 -6 and 0.84 × 10 -6 . Cumulative effective dose and cancer risk during follow-up period can be estimated using the results and are of information to patients and their parents. With the use of computer simulation and analytic formulation, we obtained the cumulative effective dose and cancer risk at any age of exposure for pediatric patients of US and Hong Kong population undergoing repetitive microdose protocol full spine imaging. Girls would be at a statistically significant higher cumulative cancer risk than boys undergoing the same microdose full spine imaging protocol and the same follow-up schedule. Copyright © 2018 Elsevier B.V. All rights reserved.

Microdosing: Concept, Application and Relevance

PubMed Central

Tewari, Tushar; Mukherjee, Shoibal

2010-01-01

The use of microdose pharmacokinetic studies as an essential tool in drug development is still to catch on. While this approach promises potential cost savings and a quantum leap in efficiencies of the drug development process, major hurdles still need to be overcome before the technique becomes commonplace and part of routine practice. Clear regulations in Europe and the USA have had an enabling effect. The lack of enabling provisions for microdosing studies in Indian regulation, despite low risk and manifest relevance for the local drug development industry, is inconsistent with the country's aspirations to be among the leaders in pharmaceutical research. PMID:21829784

Microdosing: concept, application and relevance.

PubMed

Tewari, Tushar; Mukherjee, Shoibal

2010-04-01

The use of microdose pharmacokinetic studies as an essential tool in drug development is still to catch on. While this approach promises potential cost savings and a quantum leap in efficiencies of the drug development process, major hurdles still need to be overcome before the technique becomes commonplace and part of routine practice. Clear regulations in Europe and the USA have had an enabling effect. The lack of enabling provisions for microdosing studies in Indian regulation, despite low risk and manifest relevance for the local drug development industry, is inconsistent with the country's aspirations to be among the leaders in pharmaceutical research.

Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

PubMed

Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

2011-01-01

Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Ultra-sensitive LC-MS/MS method for the quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine in human plasma for a microdose clinical trial.

PubMed

van Nuland, M; Hillebrand, M J X; Rosing, H; Burgers, J A; Schellens, J H M; Beijnen, J H

2018-03-20

In microdose clinical trials a maximum of 100 μg of drug substance is administered to participants, in order to determine the pharmacokinetic properties of the agents. Measuring low plasma concentrations after administration of a microdose is challenging and requires the use of ulta-sensitive equipment. Novel liquid chromatography-mass spectrometry (LC-MS/MS) platforms can be used for quantification of low drug plasma levels. Here we describe the development and validation of an LC-MS/MS method for quantification of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) in the low picogram per milliliter range to support a microdose trial. The validated assay ranges from 2.5-500 pg/mL for gemcitabine and 250-50,000 pg/mL for dFdU were linear, with a correlation coefficient (r 2 ) of 0.996 or better. Sample preparation with solid phase extraction provided a good and reproducible recovery. All results were within the acceptance criteria of the latest US FDA guidance and EMA guidelines. In addition, the method was successfully applied to measure plasma concentrations of gemcitabine in a patient after administration of a microdose of gemcitabine. Copyright © 2017 Elsevier B.V. All rights reserved.

Calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry assays and its application in supporting microdose absolute bioavailability studies.

PubMed

Gu, Huidong; Wang, Jian; Aubry, Anne-Françoise; Jiang, Hao; Zeng, Jianing; Easter, John; Wang, Jun-sheng; Dockens, Randy; Bifano, Marc; Burrell, Richard; Arnold, Mark E

2012-06-05

A methodology for the accurate calculation and mitigation of isotopic interferences in liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) assays and its application in supporting microdose absolute bioavailability studies are reported for the first time. For simplicity, this calculation methodology and the strategy to minimize the isotopic interference are demonstrated using a simple molecule entity, then applied to actual development drugs. The exact isotopic interferences calculated with this methodology were often much less than the traditionally used, overestimated isotopic interferences simply based on the molecular isotope abundance. One application of the methodology is the selection of a stable isotopically labeled internal standard (SIL-IS) for an LC-MS/MS bioanalytical assay. The second application is the selection of an SIL analogue for use in intravenous (i.v.) microdosing for the determination of absolute bioavailability. In the case of microdosing, the traditional approach of calculating isotopic interferences can result in selecting a labeling scheme that overlabels the i.v.-dosed drug or leads to incorrect conclusions on the feasibility of using an SIL drug and analysis by LC-MS/MS. The methodology presented here can guide the synthesis by accurately calculating the isotopic interferences when labeling at different positions, using different selective reaction monitoring (SRM) transitions or adding more labeling positions. This methodology has been successfully applied to the selection of the labeled i.v.-dosed drugs for use in two microdose absolute bioavailability studies, before initiating the chemical synthesis. With this methodology, significant time and cost saving can be achieved in supporting microdose absolute bioavailability studies with stable labeled drugs.

14C sample preparation for AMS microdosing studies at Lund University using online combustion and septa-sealed vials

NASA Astrophysics Data System (ADS)

Sydoff, Marie; Stenström, Kristina

2010-04-01

The Department of Physics at Lund University is participating in a European Union project called EUMAPP (European Union Microdose AMS Partnership Programme), in which sample preparation and accelerator mass spectrometry (AMS) measurements of biological samples from microdosing studies have been made. This paper describes a simplified method of converting biological samples to solid graphite for 14C analysis with AMS. The method is based on online combustion of the samples, and reduction of CO 2 in septa-sealed vials. The septa-sealed vials and disposable materials are used to eliminate sample cross-contamination. Measurements of ANU and Ox I standards show deviations of 2% and 3%, respectively, relative to reference values. This level of accuracy is sufficient for biological samples from microdosing studies. Since the method has very few handling steps from sample to graphite, the risk of failure during the sample preparation process is minimized, making the method easy to use in routine preparation of samples.

Pediatric microdose study of [(14)C]paracetamol to study drug metabolism using accelerated mass spectrometry: proof of concept.

PubMed

Mooij, Miriam G; van Duijn, Esther; Knibbe, Catherijne A J; Windhorst, Albert D; Hendrikse, N Harry; Vaes, Wouter H J; Spaans, Edwin; Fabriek, Babs O; Sandman, Hugo; Grossouw, Dimitri; Hanff, Lidwien M; Janssen, Paul J J M; Koch, Birgit C P; Tibboel, Dick; de Wildt, Saskia N

2014-11-01

Pediatric drug development is hampered by practical, ethical, and scientific challenges. Microdosing is a promising new method to obtain pharmacokinetic data in children with minimal burden and minimal risk. The use of a labeled oral microdose offers the added benefit to study intestinal and hepatic drug disposition in children already receiving an intravenous therapeutic drug dose for clinical reasons. The objective of this study was to present pilot data of an oral [(14)C]paracetamol [acetaminophen (AAP)] microdosing study as proof of concept to study developmental pharmacokinetics in children. In an open-label microdose pharmacokinetic pilot study, infants (0-6 years of age) received a single oral [(14)C]AAP microdose (3.3 ng/kg, 60 Bq/kg) in addition to intravenous therapeutic doses of AAP (15 mg/kg intravenous every 6 h). Blood samples were taken from an indwelling catheter. AAP blood concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and [(14)C]AAP and metabolites ([(14)C]AAP-Glu and [(14)C]AAP-4Sul) were measured by accelerator mass spectrometry. Ten infants (aged 0.1-83.1 months) were included; one was excluded as he vomited shortly after administration. In nine patients, [(14)C]AAP and metabolites in blood samples were detectable at expected concentrations: median (range) maximum concentration (C max) [(14)C]AAP 1.68 (0.75-4.76) ng/L, [(14)C]AAP-Glu 0.88 (0.34-1.55) ng/L, and [(14)C]AAP-4Sul 0.81 (0.29-2.10) ng/L. Dose-normalized oral [(14)C]AAP C max approached median intravenous average concentrations (C av): 8.41 mg/L (3.75-23.78 mg/L) and 8.87 mg/L (3.45-12.9 mg/L), respectively. We demonstrate the feasibility of using a [(14)C]labeled microdose to study AAP pharmacokinetics, including metabolite disposition, in young children.

Microdose pharmacogenetic study of ¹⁴C-tolbutamide in healthy subjects with accelerator mass spectrometry to examine the effects of CYP2C9∗3 on its pharmacokinetics and metabolism.

PubMed

Ikeda, Toshihiko; Aoyama, Shinsuke; Tozuka, Zenzaburo; Nozawa, Kohei; Hamabe, Yoshimi; Matsui, Takao; Kainuma, Michiko; Hasegawa, Setsuo; Maeda, Kazuya; Sugiyama, Yuichi

2013-07-16

Microdose study enables us to understand the pharmacokinetic profiles of drugs in humans prior to the conventional clinical trials. The advantage of microdose study is that the unexpected pharmacological/toxicological effects of drugs caused by drug interactions or genetic polymorphisms of metabolic enzymes/transporters can be avoided due to the limited dose. With a combination use of accelerator mass spectrometry (AMS) and (14)C-labaled compounds, the pharmacokinetics of both parent drug and its metabolites can be sensitively monitored. Thus, to demonstrate the usability of microdose study with AMS for the prediction of the impact of genetic polymorphisms of CYP enzyme on the pharmacokinetics of unchanged drugs and metabolites, we performed microdose pharmacogenetic study using tolbutamide as a CYP2C9 probe drug. A microdose of (14)C-tolbutamide (100 μg) was administered orally to healthy volunteers with the CYP2C9(∗)1/(∗)1 or CYP2C9(∗)1/(∗)3 diplotype. Area under the plasma concentration-time curve for the (14)C-radioactivity, determined by AMS, or that for the parent drug, determined by liquid chromatography/mass spectrometry, was about 1.6 times or 1.7 times greater in the CYP2C9(∗)1/(∗)3 than in the CYP2C9(∗)1/(∗)1 group, which was comparable to the previous reports at therapeutic dose. In the plasma and urine, tolbutamide, carboxytolbutamide, and 4-hydroxytolbutamide were detected and practically no other metabolites could be found in both diplotype groups. The fraction of metabolites in plasma radioactivity was slightly lower in the CYP2C9(∗)1/(∗)3 group. Microdose study can be used for the prediction of the effects of genetic polymorphisms of enzymes on the pharmacokinetics and metabolic profiles of drugs with minimal care of their pharmacological/toxicological effects. Copyright © 2013 Elsevier B.V. All rights reserved.

Recent Re-Measurement of Neutron and Gamma-Ray Spectra 1080 Meters from the APRD (Army Pulse Radiation Division) Critical Facility,

DTIC Science & Technology

1984-01-01

TISSUE-EQUIVALENT ION CHAMBER GM - GEIGER-MUELLER COUNTER TE-GM - DIFFERENCE BETWEEN TE AND GM DATA MICRODOSE - MICRODOSIMETRY USING 0.5" ROSSI COUNTER...KERMA 4.26+8 1979 APRO NE-213+PR NEUTRON KERMA 4.26+8 1979 WWD NE-213 NEUTRON KERMA 3.10+8 > 550 KEV 1980 DREO MICRODOSE NEUTRON KERMA 4.32+8 1979...APRD GM GAMMA KERMA 3.86+7 1979 WWD NE-213 GAMMA KERMA 4.34+7 > 450 KEV 1980 DREO MICRODOSE GAMMA KERMA 3.90+7 76 1979 APRD TE TOTAL KERMA 4.50+8 50 c.c

Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development.

PubMed

Burt, T; Yoshida, K; Lappin, G; Vuong, L; John, C; de Wildt, S N; Sugiyama, Y; Rowland, M

2016-04-01

A number of drivers and developments suggest that microdosing and other phase 0 applications will experience increased utilization in the near-to-medium future. Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities are important drivers in favor of these approaches, and can be expected only to increase in their relevance. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure, with modeling and simulations capable of extrapolating even non-linear scenarios. An increasing number of applications and design options demonstrate the versatility and flexibility these approaches offer to drug developers including the study of PK, bioavailability, DDI, and mechanistic PD effects. PET microdosing allows study of target localization, PK and receptor binding and occupancy, while Intra-Target Microdosing (ITM) allows study of local therapeutic-level acute PD coupled with systemic microdose-level exposure. Applications in vulnerable populations and extreme environments are attractive due to the unique risks of pharmacotherapy and increasing unmet healthcare needs. All phase 0 approaches depend on the validity of extrapolation from the limited-exposure scenario to the full exposure of therapeutic intent, but in the final analysis the potential for controlled human data to reduce uncertainty about drug properties is bound to be a valuable addition to the drug development process.

Phase-0/microdosing studies using PET, AMS, and LC-MS/MS: a range of study methodologies and conduct considerations. Accelerating development of novel pharmaceuticals through safe testing in humans - a practical guide.

PubMed

Burt, Tal; John, Christy S; Ruckle, Jon L; Vuong, Le T

2017-05-01

Phase-0 studies, including microdosing, also called Exploratory Investigational New Drug (eIND) or exploratory clinical trials, are a regulatory framework for first-in-human (FIH) trials. Common to these approaches is the use and implied safety of limited exposures to test articles. Use of sub-pharmacological doses in phase-0/microdose studies requires sensitive analytic tools such as accelerator mass spectrometer (AMS), Positron Emission Tomography (PET), and Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to determine drug disposition. Areas covered: Here we present a practical guide to the range of methodologies, design options, and conduct strategies that can be used to increase the efficiency of drug development. We provide detailed examples of relevant developmental scenarios. Expert opinion: Validation studies over the past decade demonstrated the reliability of extrapolation of sub-pharmacological to therapeutic-level exposures in more than 80% of cases, an improvement over traditional allometric approaches. Applications of phase-0/microdosing approaches include study of pharmacokinetic and pharmacodynamic properties, target tissue localization, drug-drug interactions, effects in vulnerable populations (e.g. pediatric), and intra-target microdosing (ITM). Study design should take into account the advantages and disadvantages of each analytic tool. Utilization of combinations of these analytic techniques increases the versatility of study designs and the power of data obtained.

A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects

PubMed Central

Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

2009-01-01

AIMS To evaluate the pharmacokinetics (PK) of five H1 receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). METHODS Five H1 receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. RESULTS The median clearance (CL), apparent volume of distribution (Vd) and apparent terminal elimination half-life (t1/2) of diphenhydramine after an i.v. microdose were 24.7 l h−1, 302 l and 9.3 h, and the oral Cmax and AUC0–∞ were 0.195 ng ml−1 and 1.52 ng h ml−1, respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. CONCLUSIONS Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection. PMID:19523012

A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.

PubMed

Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

2009-03-01

To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

Summary of Research 2000: Department of Electrical and Computer Engineering

DTIC Science & Technology

2001-12-01

provides promising radiation hardening characteristics but the effect of microdose issues are not understood. As transistors shrink, trapping of small...examines the effects of enacting a microdose single event effect (SEE) upon a thick gate oxide of an SOI MOS capacitor in order to determine the degree

Microdose analysis of ion strikes on SRAM cells

NASA Astrophysics Data System (ADS)

Scheick, L.

2003-12-01

A method of measuring the effect from exposure to highly localized ionizing radiation on microstructures is described. The voltage at which a commercial SRAM cell cannot hold a programmed state changes with microdose. The microdose distribution across the array, in addition to the analysis of the occurrence of anomalous shifts in operating bias due to rare, large energy-deposition events is studied. The effect of multiple hits on a SRAM cell is presented. A general theory on multiple hits from which basic device parameters can be extracted is presented. SPICE, as well as analysis of basic device physics, is used to analyze the damage to individual transistors and the response of a SRAM cell.

Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development

DOE PAGES

Burt, T.; Yoshida, K.; Lappin, G.; ...

2016-02-26

A number of drivers and developments suggest that microdosing and other phase 0 applications will experience increased utilization in the near-to-medium future. Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities are important drivers in favor of these approaches, and can be expected only to increase in their relevance. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure, with modeling and simulations capable of extrapolating even non-linear scenarios. An increasing number of applications andmore » design options demonstrate the versatility and flexibility these approaches offer to drug developers including the study of PK, bioavailability, DDI, and mechanistic PD effects. PET microdosing allows study of target localization, PK and receptor binding and occupancy, while Intra-Target Microdosing (ITM) allows study of local therapeutic-level acute PD coupled with systemic microdose-level exposure. Applications in vulnerable populations and extreme environments are attractive due to the unique risks of pharmacotherapy and increasing unmet healthcare needs. Lastly, all phase 0 approaches depend on the validity of extrapolation from the limited-exposure scenario to the full exposure of therapeutic intent, but in the final analysis the potential for controlled human data to reduce uncertainty about drug properties is bound to be a valuable addition to the drug development process.« less

Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development

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

Burt, T.; Yoshida, K.; Lappin, G.

A number of drivers and developments suggest that microdosing and other phase 0 applications will experience increased utilization in the near-to-medium future. Increasing costs of drug development and ethical concerns about the risks of exposing humans and animals to novel chemical entities are important drivers in favor of these approaches, and can be expected only to increase in their relevance. An increasing body of research supports the validity of extrapolation from the limited drug exposure of phase 0 approaches to the full, therapeutic exposure, with modeling and simulations capable of extrapolating even non-linear scenarios. An increasing number of applications andmore » design options demonstrate the versatility and flexibility these approaches offer to drug developers including the study of PK, bioavailability, DDI, and mechanistic PD effects. PET microdosing allows study of target localization, PK and receptor binding and occupancy, while Intra-Target Microdosing (ITM) allows study of local therapeutic-level acute PD coupled with systemic microdose-level exposure. Applications in vulnerable populations and extreme environments are attractive due to the unique risks of pharmacotherapy and increasing unmet healthcare needs. Lastly, all phase 0 approaches depend on the validity of extrapolation from the limited-exposure scenario to the full exposure of therapeutic intent, but in the final analysis the potential for controlled human data to reduce uncertainty about drug properties is bound to be a valuable addition to the drug development process.« less

Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer's Disease.

PubMed

Nunes, Marielza Andrade; Schöwe, Natalia Mendes; Monteiro-Silva, Karla Cristina; Baraldi-Tornisielo, Ticiana; Souza, Suzzanna Ingryd Gonçalves; Balthazar, Janaina; Albuquerque, Marilia Silva; Caetano, Ariadiny Lima; Viel, Tania Araujo; Buck, Hudson Sousa

2015-01-01

The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer's disease (AD) patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD. Transgenic mice (Cg-Tg(PDGFB-APPSwInd)20Lms/2J) and their non-transgenic litter mate genetic controls were treated with lithium carbonate (0.25mg/Kg/day in drinking water) for 16 or 8 months starting at two and ten months of age, respectively [corrected]. Similar groups were treated with water. At the end of treatments, both lithium treated transgenic groups and non-transgenic mice showed no memory disruption, different from what was observed in the water treated transgenic group. Transgenic mice treated with lithium since two months of age showed decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice. It is suitable to conclude that these data support the use of microdose lithium in the prevention and treatment of Alzheimer's disease, once the neurohistopathological characteristics of the disease were modified and the memory of transgenic animals was maintained.

Comparison of microdose flare-up and antagonist multiple-dose protocols for poor-responder patients: a randomized study.

PubMed

Demirol, Aygul; Gurgan, Timur

2009-08-01

To compare the efficacy of the microdose flare-up and multiple-dose antagonist protocols for poor-responder patients in intracytoplasmic sperm injection-ET cycles. A randomized, prospective study. Center for assisted reproductive technology in Turkey. Ninety patients with poor ovarian response in a minimum of two previous IVF cycles. All women were prospectively randomized into two groups by computer-assisted randomization. The patients in group 1 were stimulated according to the microdose flare-up protocol (n = 45), while the patients in group 2 were stimulated according to antagonist multiple-dose protocol (n = 45). The mean number of mature oocytes retrieved was the primary outcome measure, and fertilization rate, implantation rate per embryo, and clinical pregnancy rates were secondary outcome measures. The mean age of the women, the mean duration of infertility, basal FSH level, and the number of previous IVF cycles were similar in both groups. The total gonadotropin dose used was significantly higher in group 2, while the number of oocytes retrieved was significantly greater in group 1. Although the fertilization and clinical pregnancy rates were nonsignificantly higher in group 1 compared with group 2, the implantation rate was significantly higher in the microdose flare-up group than in the multiple-dose antagonist group (22% vs. 11%). The microdose flare-up protocol seems to have a better outcome in poor-responder patients, with a significantly higher mean number of mature oocytes retrieved and higher implantation rate.

Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer's Disease

PubMed Central

Monteiro-Silva, Karla Cristina; Baraldi-Tornisielo, Ticiana; Souza, Suzzanna Ingryd Gonçalves; Balthazar, Janaina; Albuquerque, Marilia Silva; Caetano, Ariadiny Lima; Viel, Tania Araujo; Buck, Hudson Sousa

2015-01-01

The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer’s disease (AD) patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD. Transgenic mice (Cg-Tg(PDGFB-APPSwInd)20Lms/2J) and their non-transgenic litter mate genetic controls were treated with lithium carbonate (1.2 mg/Kg/day in drinking water) for 16 or 8 months starting at two and ten months of age, respectively. Similar groups were treated with water. At the end of treatments, both lithium treated transgenic groups and non-transgenic mice showed no memory disruption, different from what was observed in the water treated transgenic group. Transgenic mice treated with lithium since two months of age showed decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice. It is suitable to conclude that these data support the use of microdose lithium in the prevention and treatment of Alzheimer’s disease, once the neurohistopathological characteristics of the disease were modified and the memory of transgenic animals was maintained. PMID:26605788

Human microdose evaluation of the novel EP1 receptor antagonist GSK269984A

PubMed Central

Ostenfeld, Thor; Beaumont, Claire; Bullman, Jonathan; Beaumont, Maria; Jeffrey, Phillip

2012-01-01

AIM The primary objective was to evaluate the pharmacokinetics (PK) of the novel EP1 antagonist GSK269984A in human volunteers after a single oral and intravenous (i.v.) microdose (100 µg). METHOD GSK269984A was administered to two groups of healthy human volunteers as a single oral (n= 5) or i.v. (n= 5) microdose (100 µg). Blood samples were collected for up to 24 h and the parent drug concentrations were measured in separated plasma using a validated high pressure liquid chromatography-tandem mass spectrometry method following solid phase extraction. RESULTS Following the i.v. microdose, the geometric mean values for clearance (CL), steady-state volume of distribution (Vss) and terminal elimination half-life (t1/2) of GSK269984A were 9.8 l h−1, 62.8 l and 8.2 h. Cmax and AUC(0,∞) were 3.2 ng ml−1 and 10.2 ng ml−1 h, respectively; the corresponding oral parameters were 1.8 ng ml−1 and 9.8 ng ml−1 h, respectively. Absolute oral bioavailability was estimated to be 95%. These data were inconsistent with predictions of human PK based on allometric scaling of in vivo PK data from three pre-clinical species (rat, dog and monkey). CONCLUSION For drug development programmes characterized by inconsistencies between pre-clinical in vitro metabolic and in vivo PK data, and where uncertainty exists with respect to allometric predictions of the human PK profile, these data support the early application of a human microdose study to facilitate the selection of compounds for further clinical development. PMID:22497298

Microdose transdermal estrogen therapy for relief of vulvovaginal symptoms in postmenopausal women.

PubMed

Bachmann, Gloria A; Schaefers, Matthias; Uddin, Alkaz; Utian, Wulf H

2009-01-01

The aim of this study was to investigate the effectiveness of microdose transdermal 17beta-estradiol (E2) therapy in postmenopausal women with moderate to severe vulvovaginal symptoms. This report is based on a subset of 121 women who reported most bothersome moderate or severe vulvovaginal symptoms at baseline, from a previous randomized, double-blind, placebo-controlled, multicenter study of 425 healthy, symptomatic, postmenopausal women. Recruits had experienced at least 7 moderate or severe hot flushes daily for at least 1 week or at least 50 moderate or severe hot flushes per week for at least 1 week. Effects on coprimary efficacy variables have been reported previously. Participants received low-dose transdermal E2 plus levonorgestrel (n = 43; nominal delivery 0.023 mg/d E2/0.0075 mg/d levonorgestrel), microdose E2 (n = 42; nominal delivery 0.014 mg/d), or placebo (n = 36) for 12 weeks. Secondary efficacy variables reported herein include mean change from baseline in vaginal pH and vaginal maturation index, the proportion of women with symptoms of vulvar and vaginal atrophy at baseline and week 12, and the proportion of women with moderate-to-severe symptoms of vulvar and vaginal atrophy. Microdose transdermal E2 treatment was associated with a consistent benefit versus placebo in women with vulvovaginal atrophy. There was a statistically significant difference between both E2 versus placebo for changes in vaginal pH and vaginal maturation index. Microdose transdermal E2 offers a useful addition to the therapeutic armamentarium for postmenopausal women in whom vulvovaginal symptoms are particularly troublesome.

Comparison of estradiol and progesterone priming/antagonist/letrozole and microdose flare-up protocols for poor responders undergoing intracytoplasmic sperm injection.

PubMed

Yucel, Oguz; Ekin, Murat; Cengiz, Hüseyin; Zebitay, Ali Galip; Yalcinkaya, Sener; Karahuseyinoglu, Sercin

2014-09-01

To compare the effect of the GnRH antagonist/letrozole/gonadotropin protocol with the microdose GnRH agonist flare-up protocol in poor ovarian responders for intracytoplasmic sperm injection. One hundred twenty-one consecutive patients suspected of having or with a history of poor ovarian response between January 2009 and June 2010, who were undergoing ICSI were enrolled. The microdose flareup (MF) protocol was used in 79 patients and the estradiol + progesterone/letrozole + gonadotropin and GnRH antagonist (EP/ALG) protocol was used in 42 patients. Age of the patients, duration of infertility, basal FSH, the total gonadotropin consumption, duration of stimulation, E2 level on the day of hCG administration, the number of embryo transferred, the fertilization rate, implantation rate, clinical pregnancy rate and the live birth rate were not statistically different (p > 0.05). Only the number of oocytes retrieved was significantly higher in the EP/LGA group (1.7 ± 0.7 versus 2.6 ± 0.6). The EP/LGA protocol has no significant improvement against the microdose flare-up protocol in poor responder patients.

A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil

PubMed Central

Wagner, Claudia C; Simpson, Marie; Zeitlinger, Markus; Bauer, Martin; Karch, Rudolf; Abrahim, Aiman; Feurstein, Thomas; Schütz, Matthias; Kletter, Kurt; Müller, Markus; Lappin, Graham; Langer, Oliver

2013-01-01

Background and Objective In microdose studies, the pharmacokinetic (PK) profile of a drug in blood after administration of a dose up to 100 μg is measured with sensitive analytical techniques, such as accelerator mass spectrometry (AMS). As most drugs exert their effect in tissue rather than blood, methodology is needed for extending PK analysis to different tissue compartments. In the present study, we combined, for the first time, AMS analysis with positron emission tomography (PET) in order to determine the PK profile of the model drug verapamil in plasma and brain of humans. In order to assess PK dose-linearity of verapamil, data were acquired and compared after administration of an intravenous (iv) microdose and an iv microdose dosed concomitantly with an oral therapeutic dose. Methods Six healthy male volunteers received an iv microdose (0.05 mg) (period 1) and an iv microdose dosed concomitantly with an oral therapeutic dose (80 mg) of verapamil (period 2) in a randomized, cross-over, two-period study design. The iv dose was a mixture of (R/S)-[14C]verapamil and (R)-[11C]verapamil and the oral dose was unlabelled racemic verapamil. Brain distribution of radioactivity was measured with PET whereas plasma PK of (R)- and (S)-verapamil was determined with AMS. PET data were analyzed by kinetic modeling to estimate the rate constants for transfer of radioactivity across the blood-brain barrier. Results Most PK parameters of (R)- and (S)-verapamil as well as parameters describing exchange of radioactivity between plasma and brain (K1=0.030±0.003 and 0.031±0.005 mL·mL−1·min−1 and k2=0.099±0.006 and 0.095±0.008 min−1 for period 1 and 2, respectively) were not statistically different between the two periods although there was a trend for non-linear kinetics for the (R)-enantiomer. On the other hand, all PK parameters (except for t1/2) differed significantly between the (R)- and (S)-enantiomers for both periods. Cmax, AUC(0-24) and AUC(0-inf) were higher and CL, V and VSS were lower for the (R)- than for the (S)-enantiomer. Conclusion Combining AMS and PET microdosing allows long term PK data along with information on drug tissue distribution to be acquired in the same subjects thus making it a promising approach to maximize data output from a single clinical study. PMID:21142292

A microdose study of ¹⁴C-AR-709 in healthy men: pharmacokinetics, absolute bioavailability and concentrations in key compartments of the lung.

PubMed

Lappin, G; Boyce, M J; Matzow, T; Lociuro, S; Seymour, M; Warrington, S J

2013-09-01

To explore, in a microdose (phase-0) study, the pharmacokinetics, bioavailability and concentrations in key compartments of the lung, of AR-709, a novel diaminopyrimidine antibiotic for the treatment of respiratory infection. Four healthy men each received two single, 100 μg microdoses of ¹⁴C-AR-709, 7 days apart: the first was administered intravenously (IV), the second orally. Plasma pharmacokinetics of ¹⁴C and unchanged AR-709 were obtained by high-performance liquid chromatography and accelerator mass spectrometry (AMS). Next, 15 healthy men received a single, 100 μg microdose of ¹⁴C-AR-709 IV. Plasma, bronchoalveolar lavage fluid, alveolar macrophages and bronchial mucosal biopsy samples were analysed by AMS. After IV administration, clearance of AR-709 was 496 mL/min, volume of distribution was 1,700 L and the absolute oral bioavailability was 2.5 %. Excretion in urine was negligible. At 8-12 h after IV dosing, ¹⁴C concentrations in lung samples were 15- (bronchial mucosa) to 200- (alveolar macrophages) fold higher than in plasma. In alveolar macrophages, ¹⁴C was still mostly associated with AR-709 at 12 h after dosing. The results of this microdose study indicate that AR-709 attains concentrations appreciably higher within the lung than in plasma. Its low oral bioavailability however, precludes oral administration. Although IV administration would appear to be an effective route of administration, this would limit the use of AR-709 to a clinical setting and would therefore be economically unsustainable. If further clinical development were to be undertaken, therefore, an alternative route of administration would be necessary.

Effect of microdose transdermal 17beta-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women: a 2-year, randomized, double-blind trial.

PubMed

Schaefers, Matthias; Muysers, Christoph; Alexandersen, Peter; Christiansen, Claus

2009-01-01

Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17beta-estradiol (E2) has efficacy and safety comparable to those of raloxifene, a selective estrogen-receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis. This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial in 500 osteopenic postmenopausal women comparing transdermal microdose E2 (0.014 mg/d) versus oral raloxifene (60 mg/d), administered for 2 years. Percent change from baseline in bone mineral density at the lumbar spine was measured after 2 years of treatment. Secondary endpoints included proportion of women with no loss of bone mineral density in lumbar spine, change in bone mineral density at hip, biochemical markers of bone turnover, and safety parameters. In the per protocol set, lumbar spine bone mineral density increased by 2.4% (95% CI, 1.9-2.9) with microdose E2 versus 3.0% (95% CI, 2.5-3.5) with raloxifene after 2 years; 77.3% of E2 recipients and 80.5% of those taking raloxifene had no bone loss in the lumbar spine. Both treatments were well tolerated. Most women (99% in the E2 group and 100% in the raloxifene group) showed no histological evidence of endometrial stimulation after 2 years. Mean dense area in breast mammograms was 19.8% in the E2 group versus 19.0% in the raloxifene group after 2 years. Transdermal microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine. Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.

Human microdose evaluation of the novel EP1 receptor antagonist GSK269984A.

PubMed

Ostenfeld, Thor; Beaumont, Claire; Bullman, Jonathan; Beaumont, Maria; Jeffrey, Phillip

2012-12-01

The primary objective was to evaluate the pharmacokinetics (PK) of the novel EP(1) antagonist GSK269984A in human volunteers after a single oral and intravenous (i.v.) microdose (100 µg). GSK269984A was administered to two groups of healthy human volunteers as a single oral (n= 5) or i.v. (n= 5) microdose (100 µg). Blood samples were collected for up to 24 h and the parent drug concentrations were measured in separated plasma using a validated high pressure liquid chromatography-tandem mass spectrometry method following solid phase extraction. Following the i.v. microdose, the geometric mean values for clearance (CL), steady-state volume of distribution (V(ss) ) and terminal elimination half-life (t(1/2) ) of GSK269984A were 9.8 l h(-1) , 62.8 l and 8.2 h. C(max) and AUC(0,∞) were 3.2 ng ml(-1) and 10.2 ng ml(-1)  h, respectively; the corresponding oral parameters were 1.8 ng ml(-1) and 9.8 ng ml(-1)  h, respectively. Absolute oral bioavailability was estimated to be 95%. These data were inconsistent with predictions of human PK based on allometric scaling of in vivo PK data from three pre-clinical species (rat, dog and monkey). For drug development programmes characterized by inconsistencies between pre-clinical in vitro metabolic and in vivo PK data, and where uncertainty exists with respect to allometric predictions of the human PK profile, these data support the early application of a human microdose study to facilitate the selection of compounds for further clinical development. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Compatibility study of a parenteral microdose polyethylene glycol formulation in medical devices and identification of degradation impurity by 2D-LC/MS.

PubMed

Dai, Lulu; Yeh, Geoffrey K; Ran, Yingqing; Yehl, Peter; Zhang, Kelly

2017-04-15

Polyethylene glycol (PEG) based formulation and polyvinylchloride (PVC) tubing are frequently used for drug delivery and administration. The compatibility of a parenteral drug microdose formulation in intravenous infusion (IV) devices was studied to support the clinical determination of absolute bioavailability by the microdosing method. The investigational microdose formulation containing PEG was found prone to significant loss of potency within hours of storage in the PVC IV tubing due to degradation. Degradation occurred only when both PEG and PVC tubing were present. The degradation product could not be detected by LC/MS due to the significant interference from the high concentration of PEG (4%) matrix and the extremely low level of drug (0.6ppm). To obtain structural information of the degradation impurity and understand the cause of the degradation, a simple heart-cutting 2D-LC/MS approach was utilized to effectively separate the impurity from the complex PEG oligomers and overcome the matrix interference, enabling mass spectrometric analysis of the impurity. An oxidation- dominated mechanism was proposed in which the combination of PEG auto-oxidation and dehydrochlorination of the PVC tubing yielded an oxidative environment that enhanced radical propagation and accelerated degradation of the investigational parent drug. Copyright © 2017 Elsevier B.V. All rights reserved.

A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil.

PubMed

Wagner, Claudia C; Simpson, Marie; Zeitlinger, Markus; Bauer, Martin; Karch, Rudolf; Abrahim, Aiman; Feurstein, Thomas; Schütz, Matthias; Kletter, Kurt; Müller, Markus; Lappin, Graham; Langer, Oliver

2011-02-01

In microdose studies, the pharmacokinetic profile of a drug in blood after administration of a dose up to 100 μg is measured with sensitive analytical techniques, such as accelerator mass spectrometry (AMS). As most drugs exert their effect in tissue rather than blood, methodology is needed for extending pharmacokinetic analysis to different tissue compartments. In the present study, we combined, for the first time, AMS analysis with positron emission tomography (PET) in order to determine the pharmacokinetic profile of the model drug verapamil in plasma and brain of humans. In order to assess pharmacokinetic dose linearity of verapamil, data were acquired and compared after administration of an intravenous microdose and after an intravenous microdose administered concomitantly with an oral therapeutic dose. Six healthy male subjects received an intravenous microdose [0.05 mg] (period 1) and an intravenous microdose administered concomitantly with an oral therapeutic dose [80 mg] of verapamil (period 2) in a randomized, crossover, two-period study design. The intravenous dose was a mixture of (R/S)-[14C]verapamil and (R)-[11C]verapamil and the oral dose was unlabelled racaemic verapamil. Brain distribution of radioactivity was measured with PET whereas plasma pharmacokinetics of (R)- and (S)-verapamil were determined with AMS. PET data were analysed by pharmacokinetic modelling to estimate the rate constants for transfer (k) of radioactivity across the blood-brain barrier. Most pharmacokinetic parameters of (R)- and (S)-verapamil as well as parameters describing exchange of radioactivity between plasma and brain (influx rate constant [K(1)] = 0.030 ± 0.003 and 0.031 ± 0.005 mL/mL/min and efflux rate constant [k(2)] = 0.099 ± 0.006 and 0.095 ± 0.008 min-1 for period 1 and 2, respectively) were not statistically different between the two periods although there was a trend for nonlinear pharmacokinetics for the (R)-enantiomer. On the other hand, all pharmacokinetic parameters (except for the terminal elimination half-life [t1/2;)]) differed significantly between the (R)- and (S)-enantiomers for both periods. The maximum plasma concentration (C(max)), area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC(24)) and AUC from time zero to infinity (AUC(∞)) were higher and the total clearance (CL), volume of distribution (V(d)) and volume of distribution at steady state (V(ss)) were lower for the (R)- than for the (S)-enantiomer. Combining AMS and PET microdosing allows long-term pharmacokinetic data along with information on drug tissue distribution to be acquired in the same subjects thus making it a promising approach to maximize data output from a single clinical study.

Live birth in a 46-year-old woman using microdose GnRH agonist flare-up protocol combined with GnRH antagonist: a case report.

PubMed

Zhang, Hong; Liu, Ya-Qiong; Lu, Guang-Xiu; Gong, Fei

2016-12-01

Few successful pregnancies after age 45 years with low ovarian reserve have been reported. We report a 46-year-old woman with basal FSH 20.36 mIU/mL and an antral follicle count of four obtained two embryos and delivered a healthy infant with IVF using a microdose GnRH-a flare-up protocol combined with GnRH-ant.

Biphasic Elimination of Tenofovir Diphosphate and Nonlinear Pharmacokinetics of Zidovudine Triphosphate in a Microdosing Study

PubMed Central

Chen, Jianmeng; Flexner, Charles; Liberman, Rosa G.; Skipper, Paul L.; Louissaint, Nicolette; Tannenbaum, Steven R.; Hendrix, Craig; Fuchs, Edward

2012-01-01

Objective Phase 0 studies can provide initial pharmacokinetics (PK) data in humans and help to facilitate early drug development, but their predictive value for standard dosing is controversial. To evaluate the prediction of microdosing for active intracellular drug metabolites, we compared the PK profile of two antiretroviral drugs, zidovudine (ZDV) and tenofovir (TFV), in microdose and standard dosing regimens. Study Design We administered a microdose (100 μg) of 14C-labeled drug (ZDV or tenofovir disoproxil fumarate (TDF)) with or without a standard unlabelled dose (300 mg) to healthy volunteers. Both the parent drug in plasma and the active metabolite, ZDV-triphosphate (ZDV-TP) or TFV-diphosphate (TFV-DP) in PBMCs and CD4+ cells were measured by AMS. Results The intracellular ZDV-TP concentration increased less than proportionally over the dose range studied (100 μg to 300 mg), while the intracellular TFV-DP PK were linear over the same dose range. ZDV-TP concentrations were lower in CD4+ cells versus total peripheral blood mononuclear cells (PBMCs), while TFV-DP concentrations were not different in CD4+ cells and PBMCs. Conclusion Our data were consistent with a rate-limiting step in the intracellular phosphorylation of ZDV but not TFV. AMS shows promise for predicting the PK of active intracellular metabolites of nucleosides, but nonlinearity of PK may be seen with some drugs. PMID:23187888

What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?

PubMed

Berkkanoglu, Murat; Ozgur, Kemal

2010-07-01

To find out the optimum maximal dosage of recombinant follicle stimulating hormone (rFSH) in microdose gonadotropin-releasing hormone analog (GnRH-a) flare cycles in poor responders. Prospective randomized study. Private infertility clinic. A total of 119 women were taken into the study. The study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration. On the third day of GnRH-a administration, 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH (group A, n = 38), or 450 IU of rFSH (group B, n = 39), or 600 IU of rFSH (group C, n = 42). Peak E(2) levels, days of stimulation with rFSH, total rFSH dosage, total number of oocytes retrieved, M2 oocytes retrieved, total number of embryos, number of embryos transferred, number of Grade-1 embryos transferred, clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer. Clinical pregnancy rates were 13.1%, 15.3%, and 16.1% for group A, group B, and group C, respectively. There were no significant differences in the age, peak serum E(2) concentration, days of stimulation with rFSH, total number of M2 oocytes retrieved, number of embryos transferred, clinical pregnancy rates, and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage. There is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles. In addition, because the duration of stimulation does not differ between the groups, the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages, and this would obviously cost less money to the patients. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

PubMed

Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

2015-02-01

Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.

Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans

PubMed Central

Hohmann, Nicolas; Kocheise, Franziska; Carls, Alexandra; Burhenne, Jürgen; Haefeli, Walter E; Mikus, Gerd

2015-01-01

Aim We aimed to establish a method to assess systemic and pre-systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam. Methods In an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to assess the linearity of plasma and urine pharmacokinetics. Results Dose-normalized AUC and Cmax were 37.1 ng ml−1 h [95% CI 35.5, 40.6] and 39.1 ng ml−1 [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml−1 h [95% CI 36.1, 42.1] and 37.1 ng ml−1 [95% CI 26.9, 51.3] for the milligram dose. CLmet was 253 ml min−1 [95% CI 201, 318] vs. 278 ml min−1 [95% CI 248, 311] for intravenous doses and 1880 ml min−1 [95% CI 1590, 2230] vs. 2050 ml min−1 [95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI 0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]). Conclusion The pharmacokinetics of an intravenous midazolam microdose is linear to the applied regular doses and can be used to assess safely systemic CYP3A activity and, in combination with oral microdoses, pre-systemic CYP3A activity. PMID:25588320

Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans.

PubMed

Hohmann, Nicolas; Kocheise, Franziska; Carls, Alexandra; Burhenne, Jürgen; Haefeli, Walter E; Mikus, Gerd

2015-02-01

We aimed to establish a method to assess systemic and pre-systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam. In an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to assess the linearity of plasma and urine pharmacokinetics. Dose-normalized AUC and Cmax were 37.1 ng ml(-1 ) h [95% CI 35.5, 40.6] and 39.1 ng ml(-1) [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml(-1 ) h [95% CI 36.1, 42.1] and 37.1 ng ml(-1) [95% CI 26.9, 51.3] for the milligram dose. CLmet was 253 ml min(-1) [95% CI 201, 318] vs. 278 ml min(-1) [95% CI 248, 311] for intravenous doses and 1880 ml min(-1) [95% CI 1590, 2230] vs. 2050 ml min(-1) [95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI 0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]). The pharmacokinetics of an intravenous midazolam microdose is linear to the applied regular doses and can be used to assess safely systemic CYP3A activity and, in combination with oral microdoses, pre-systemic CYP3A activity. © 2014 The British Pharmacological Society.

Human Lung Cancer Risks from Radon – Part I - Influence from Bystander Effects - A Microdose Analysis

PubMed Central

Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

2010-01-01

Since the publication of the BEIR VI report in 1999 on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, at low domestic and workplace radon levels, in particular the Bystander Effect (BE) and the Adaptive Response radio-protection (AR). We analyzed the microbeam and broadbeam alpha particle data of Miller et al. (1995, 1999), Zhou et al. (2001, 2003, 2004), Nagasawa and Little (1999, 2002), Hei et al. (1999), Sawant et al. (2001a) and found that the shape of the cellular response to alphas is relatively independent of cell species and LET of the alphas. The same alpha particle traversal dose response behavior should be true for human lung tissue exposure to radon progeny alpha particles. In the Bystander Damage Region of the alpha particle response, there is a variation of RBE from about 10 to 35. There is a transition region between the Bystander Damage Region and Direct Damage Region of between one and two microdose alpha particle traversals indicating that perhaps two alpha particle “hits” are necessary to produce the direct damage. Extrapolation of underground miners lung cancer risks to human risks at domestic and workplace levels may not be valid. PMID:21731539

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

PubMed

DiLuigi, Andrea J; Engmann, Lawrence; Schmidt, David W; Benadiva, Claudio A; Nulsen, John C

2011-06-30

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The antiaging activity and cerebral protection of rapamycin at micro-doses.

PubMed

Qi, Haiyan; Su, Feng-Yun; Wan, Shan; Chen, Yongjie; Cheng, Yan-Qiong; Liu, Ai-Jun

2014-11-01

The immunosuppressant drug rapamycin was reported to have an antiaging activity, which was attributed to the TORC1 inhibition that inhibits cell proliferation and increases autophagy. However, rapamycin also exhibits a number of harmful adverse effects. Whether rapamycin can be developed into an antiaging agent remains unclear. We demonstrated that rapamycin at micro-doses (below the TORC1 inhibiting concentration) exhibits a cell-protective activity: (1) It protects cultured neurons against neurotoxin MPP(+) and H2O2. (2) It increases survival time of neuron in culture. (3) It maintains the nonproliferative state of cultured senescent human fibroblasts and prevents cell death induced by telomere dysfunction. (4) In animal models, it decreased the cerebral infarct sizes induced by acute ischemia and dramatically extended the life span of stroke prone spontaneously hypertensive rats (SHR-SPs). We propose that rapamycin at micro-dose can be developed into an antiaging agent with a novel mechanism. © 2014 John Wiley & Sons Ltd.

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

PubMed

Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

2016-10-01

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients.

PubMed

Ozcan Cenksoy, Pinar; Ficicioglu, Cem; Kizilkale, Ozge; Suhha Bostanci, Mehmet; Bakacak, Murat; Yesiladali, Mert; Kaspar, Cigdem

2014-07-01

To compare the effects of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Of 225 patients, 83 patients were in microdose flare-up group (Group 1), 70 patients were in GnRH antagonist/letrozole group (Group 2) and 72 patients were in GnRH antagonist/clomiphene citrate group (Group 3). Demographic and endocrine characteristics, the total number of oocytes retrieved, cancellation rate and clinical pregnancy rate were collected Results: Total dosage of gonadotropins (p=0.002) and serum E2 levels on the day of hCG administration (p=0.010) were significantly higher and duration of stimulations (p=0.03) was significantly longer in group 1. The number of oocytes retrieved was significantly greater in group 1 and 2 when compare to those of group 3 (p=0,000). There was a trend towards increasing cycle cancellation rates with GnRH antagonist/clomiphene citrate and GnRH antagonist/letrozole. Our finding suggest that the results of microdose flare-up protocol are better than other two used treatment protocols, in terms of maximum estradiol levels, number of mature oocytes retrieved, and cancellation rate and it still seems to be superior the ovarian stimulation regime for the poor responder patients.

Detection of recombinant EPO in blood and urine samples with EPO WGA MAIIA, IEF and SAR-PAGE after microdose injections.

PubMed

Dehnes, Yvette; Shalina, Alexandra; Myrvold, Linda

2013-01-01

The misuse of microdoses of performance enhancing drugs like erythropoietin (EPO) constitutes a major challenge in doping analysis. When injected intravenously, the half-life of recombinant human EPO (rhEPO) like epoetin alfa, beta, and zeta is only a few hours and hence, the window for direct detection of rhEPO in urine is small. In order to investigate the detection window for rhEPO directly in blood and urine with a combined affinity chromatography and lateral flow immunoassay (EPO WGA MAIIA), we recruited nine healthy people who each received six intravenously injected microdoses (7.5 IU/kg) of NeoRecormon (epoetin beta) over a period of three weeks. Blood and urine samples were collected in the days following the injections and analyzed with EPO WGA MAIIA as well as the current validated methods for rhEPO; isoelectric focusing (IEF) and sarcosyl polyacrylamide gel electrophoresis (SAR-PAGE). For samples collected 18 h after a microdose, the sensitivity of the EPO WGA MAIIA assay was 100% in plasma and 87.5% in urine samples at the respective 98% specificity threshold levels. In comparison, the sensitivity in plasma and urine was 75% and 100%, respectively, with IEF, and 87.5% in plasma and 100% in urine when analyzed with SAR-PAGE. We conclude that EPO WGA MAIIA is a sensitive assay for the detection of rhEPO, with the potential of being a fast, supplemental screening assay for use in doping analysis.

High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma: application to microdose clinical trials of mirodenafil.

PubMed

Cho, Doo-Yeoun; Bae, Soo Hyeon; Shon, Ji-Hong; Bae, Soo Kyung

2013-03-01

A high-sensitivity LC/MS/MS method was developed and validated for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma. Mirodenafil, SK-3541, and udenafil as an internal standard were extracted from plasma samples with methyl tert-butyl ether. Chromatographic separation was performed on a Luna phenyl-hexyl column (100 × 2.0 mm) with an isocratic mobile phase consisting of 5 mM ammonium formate and ACN (23:77, v/v) at a flow rate of 0.35 mL/min. Detection and quantification were performed using a mass spectrometer in selected reaction monitoring mode with positive ESI at m/z 532.3 → 296.1 for mirodenafil, m/z 488.1 → 296.1 for SK-3541, and m/z 517.3 → 283.2 for udenafil. The calibration curves were linear over a concentration range of 2-500 pg/mL using 0.5 mL plasma for the microdose of mirodenafil (100 μg). Analytical method validation of the clinical dose (100 mg), with a calibration curve range of 2-500 ng/mL using 0.025-mL plasma, was also conducted. The other LC-MS/MS conditions were similar to those used for the microdosing. Each method was applied successfully to pharmacokinetic studies after a microdose or clinical dose of mirodenafil to six healthy Korean male volunteers. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

PubMed

Weitzman, Vanessa N; Engmann, Lawrence; DiLuigi, Andrea; Maier, Donald; Nulsen, John; Benadiva, Claudio

2009-07-01

To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. Retrospective analysis. University-based IVF center. Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.

PubMed

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-08-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

A comparison between r-LH and urinary supplements containing LH activity in patients undergoing the microdose GnRH agonist flare protocol for in-vitro fertilization: a pilot study.

PubMed

Shavit, Tal; Agdi, Mohammed; Son, Weon Y; Hasson, Josseph; Dahan, Michael H

2016-08-01

The aim of this study was to compare pregnancy rates and stimulation parameters in patients with diminished ovarian reserve, who were treated with recombinant human luteinizing hormone (r-LH) or menopausal gonadotropins (hMG), as part of a microdose flare protocol. A retrospective cohort study was performed. Comparisons between the group that was stimulated with r-LH plus follicle stimulating hormone (FSH) to those treated with hMG and FSH, were performed. Measurements included: medication doses, number of oocyte collected, number of embryos obtained, pregnancy and clinical pregnancy rates. Patients in the r-LH group (N.=40) had significant higher clinical pregnancy rates (33% vs. 14%; P=0.04) and used lower dose of LH (1938 IU vs. 2807 IU; P=0.02) compared to patients that were stimulated with hMG (N.=39). r-LH may offer advantages for the treatment of diminished ovarian reserve when performing a microdose flare protocol when compared to hMG. Both larger and prospective studies should be carried out to confirm these findings.

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology

PubMed Central

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-01-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer’s disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD. PMID:28763060

Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease.

PubMed

Nunes, Marielza Andrade; Viel, Tania Araujo; Buck, Hudson Sousa

2013-01-01

A lower incidence of dementia in bipolar patients treated with lithium has been described. This metal inhibits the phosphorylation of glycogen-synthase-kinase 3-α and β, which are related to amyloid precursor protein processing and tau hyperphosphorylation in pathological conditions, respectively. Following the same rationale, a group just found that lithium has disease-modifying properties in amnestic mild cognitive impairment with potential clinical implications for the prevention of Alzheimer's Disease (AD) when a dose ranging from 150 to 600 mg is used. As lithium is highly toxic in regular doses, our group evaluated the effect of a microdose of 300 μg, administered once daily on AD patients for 15 months. In the evaluation phase, the treated group showed no decreased performance in the mini-mental state examination test, in opposition to the lower scores observed for the control group during the treatment, with significant differences starting three months after the beginning of the treatment, and increasing progressively. This data suggests the efficacy of a microdose lithium treatment in preventing cognitive loss, reinforcing its therapeutic potential to treat AD using very low doses.

Comparison of mild and microdose GnRH agonist flare protocols on IVF outcome in poor responders.

PubMed

Karimzadeh, Mohammad Ali; Mashayekhy, Mehri; Mohammadian, Farnaz; Moghaddam, Fatemeh Mansoori

2011-05-01

To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist (mild protocol) and microdose GnRH agonist flare protocols for poor responders undergoing in vitro fertilization. 159 poor responder patients were randomized and ovarian stimulation was performed with clomiphene citrate, gonadotropin and antagonist (group I) or microdose GnRH agonist flare (group II) protocols. Main outcome was clinical pregnancy rate and secondary outcomes were doses of gonadotropin administration and duration of stimulation. There were no significant differences in age, causes of infertility, basal FSH, BMI, duration of infertility, E(2) level on the day of hCG injection in both groups. Although the cancellation, fertilization, and clinical pregnancy rates were similar in both groups, the endometrial thickness, number of retrieved oocytes, mature oocytes and implantation rate were significantly higher in mild protocol. The doses of gonadotropin administration and duration of stimulation were significantly lower in mild protocol. We recommend mild protocol in assisted reproductive technology cycles for poor responders based on our results regarding less doses of used gonadotropin and a shorter duration of stimulation.

An intravenous microdose of bevacizumab for the treatment of pigment epithelial detachment associated to age-related macular degeneration refractory to intravitreal bevacizumab: a case report.

PubMed

Wu, Lihteh; Evans, Teodoro

2011-01-01

The purpose of this study was to report the visual and anatomical outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a vascularized pigment epithelial detachment (PED) associated with exudative age-related macular degeneration refractory to several intravitreal bevacizumab injections. Interventional case report and literature review. A 62-year-old female patient with a PED secondary to age-related macular degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of bevacizumab. Despite an initial response where the PED decreased in size, the subretinal fluid reabsorbed and the visual acuity improved; after the seventh injection, the PED started to grow in size again causing a drop in visual acuity. After an intravenous injection of 10 mg of bevacizumab, the patient experienced an improvement in visual acuity and a flattening of her PED. An intravenous injection of a microdose of bevacizumab appears to have resolved the PED with a sustained improvement of visual acuity.

Development of a highly sensitive methodology for quantitative determination of fexofenadine in a microdose study by multiple injection method using ultra-high performance liquid chromatography with tandem mass spectrometry.

PubMed

Tanaka, Yukari; Yoshikawa, Yutaka; Yasui, Hiroyuki

2012-01-01

An ultra high-sensitivity method for quantifying fexofenadine concentration in rat plasma samples by multiple injection method (MIM) was developed for a microdose study. In this study, MIM involved continuous injections of multiple samples containing the single compound into a column of the ultra-HPLC (UHPLC) system, and then, temporary trapping of the analyte at the column head. This was followed by elution of the compound from the column and detection by mass spectrometer. Fexofenadine, used as a model compound in this study, was extracted from the plasma samples by a protein precipitation method. Chromatographic separation was achieved on a reversed-phase C18 column by using a gradient method with 0.1% formic acid and 0.1% formic acid in acetonitrile as the mobile phase. The analyte was quantified in the positive-ion electrospray ionization mode using selected reaction monitoring. In this study, the analytical time per fexofenadine sample was approximately 2 min according to the UHPLC system. The method exhibited the linear dynamic ranges of 5-5000 pg/mL for fexofenadine in rat plasma. The intra-day precisions were from 3.2 to 8.7% and the accuracy range was 95.2-99.3%. The inter-day precisions and accuracies ranged from 3.5 to 8.4% and from 98.6 to 102.6%, respectively. The validated MIM was successfully applied to a microdose study in the rats that received oral administration of 100 µg/kg fexofenadine. We suggest that this method might be beneficial for the quantification of fexofenadine concentrations in a microdose clinical study.

Microdose computed tomographic cardiac angiography in normal cats.

PubMed

Rodriguez, Kiira T; O'Brien, Mauria A; Hartman, Susan K; Mulherin, Allison C; McReynolds, Casie J; McMichael, Maureen; Rapoport, Gregg; O'Brien, Robert T

2014-03-01

To determine if microdose contrast-enhanced multi-detector computed tomographic angiography (MDCTA) allows characterization of cardiac chambers in lightly sedated normal cats. Seven healthy domestic cats. Lightly sedated normal cats were imaged pre-contrast and with microdose (0.22 ml/kg of non-ionic iodinated contrast medium, 300 mg I/ml) triple-phase MDCTA in a motion restriction device. On pre-contrast images, the aorta (median: 52.43 Hounsfield units [HU], range 27.35-76.74 HU) was outlined by significantly (p = 0.015) lower attenuating periaortic fat (-66.16 HU, -42.62 to -92.77 HU). On post-contrast images, median peak contrast enhancement in the right ventricle (111.77 HU, 36.09-141.60 HU) was achieved in 3.1 s (range 2.9-7.3 s), in the aorta (149.30 HU, 99.43-319.60 HU) and left atrium (180.83 HU, 88.53-266.84 HU) in 6.4 s (range 5.6-7.7 s) and in the left ventricle (147.89 HU, 57.23-245.77 HU) in 7.10 s (range 6.2-11.2 s). Significantly higher attenuation was measured between all chambers and walls, the right ventricular lumen and interventricular septum (median ratio 53.78 HU, range 0.21-83.20 HU), left ventricular lumen and left ventricular free wall (89.32 HU, 38.81-185.95 HU) and aorta and periaortic fat (190.43 HU, 143.22-425.44 HU) on post-contrast images. Sufficient biological contrast is available on survey CT to discriminate between the aorta and the left atrium, and microdose MDCTA provides sufficient contrast enhancement for adequate visualization of the heart chambers in normal cats. Copyright © 2014 Elsevier B.V. All rights reserved.

Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

PubMed

Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

2010-06-01

To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders--an observational pilot study.

PubMed

Mitri, Frederic; Behan, Lucy Ann; Murphy, Courtney A; Hershko-Klement, Anat; Casper, Robert F; Bentov, Yaakov

2016-01-01

To investigate whether temporarily withholding FSH and adding androgen could improve follicular response during a microdose flare protocol in women with slow follicular growth or asynchronous follicular development. Observational pilot study. University-affiliated private fertility center. Twenty-six women aged 34-47 years with poor response to stimulation or a previous cancelled IVF cycle and with slow or asynchronous follicular growth during a microdose flare cycle. For 13 women, after initiation of ovarian stimulation using the microdose flare protocol, gonadotropin administration was interrupted and transdermal testosterone gel was added for several days (4.4 ± 1.2 d) starting after cycle day 7 (mean cycle day 10 ± 2.6). FSH, E2, follicular growth, and total number of mature oocytes retrieved were determined for all of the patients. Cycle cancellation rate as well as pregnancy rate following embryo transfer were also documented when applicable. FSH levels declined (25.2 ± 6.5 to 6.8 ± 3.2 IU/L), E2 levels increased (896 ± 687 to 2,163 ± 1,667 pmol/L), and follicular growth improved significantly during gonadotropin interruption and were tracked for 2 days during this time frame. The average number of oocytes retrieved was 5.3 ± 2.6, and the ratio of mature to total oocytes was 4:5. Four of the 13 women in the interruption group conceived following frozen embryo transfer, whereas none in the control group did. The androgen-interrupted FSH protocol may improve follicular response to gonadotropins in cycles that might otherwise be cancelled. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Micro-Dose Calibrator for Pre-clinical Radiotracer Assays | NCI Technology Transfer Center | TTC

Cancer.gov

Pre-clinical radiotracer biomedical research involves the use of compounds labeled with radioisotopes, including cell binding studies, immune cell labeling techniques, and radio-ligand bio-distribution studies. Before this Micro-Dose Calibrator, measurement of pre-clinical level dosage for small animal studies was inaccurate and unreliable. This dose calibrator is a prototype ready for manufacturing. It is designed to accurately measure radioactive doses in the range of 50 nCi (1.8 kBq) to 100 µCi (3.7 MBq) with 1% precision. The NCI seeks co-development or licensing to commercialize it. Alternative uses will be considered.

Microdose Induced Drain Leakage Effects in Power Trench MOSFETs: Experiment and Modeling

NASA Astrophysics Data System (ADS)

Zebrev, Gennady I.; Vatuev, Alexander S.; Useinov, Rustem G.; Emeliyanov, Vladimir V.; Anashin, Vasily S.; Gorbunov, Maxim S.; Turin, Valentin O.; Yesenkov, Kirill A.

2014-08-01

We study experimentally and theoretically the micro-dose induced drain-source leakage current in the trench power MOSFETs under irradiation with high-LET heavy ions. We found experimentally that cumulative increase of leakage current occurs by means of stochastic spikes corresponding to a strike of single heavy ion into the MOSFET gate oxide. We simulate this effect with the proposed analytic model allowing to describe (including Monte Carlo methods) both the deterministic (cumulative dose) and stochastic (single event) aspects of the problem. Based on this model the survival probability assessment in space heavy ion environment with high LETs was proposed.

“Protective Bystander Effects Simulated with the State-Vector Model”—HeLa x Skin Exposure to 137Cs Not Protective Bystander Response But Mammogram and Diagnostic X-Rays Are

PubMed Central

Leonard, Bobby E.

2008-01-01

The recent Dose Response journal article “Protective Bystander Effects Simulated with the State-Vector Model” (Schollnberger and Eckl 2007) identified the suppressive (below natural occurring, zero primer dose, spontaneous level) dose response for HeLa x skin exposure to 137Cs gamma rays (Redpath et al 2001) as a protective Bystander Effect (BE) behavior. I had previously analyzed the Redpath et al (2001) data with a Microdose Model and conclusively showed that the suppressive response was from Adaptive Response (AR) radio-protection (Leonard 2005, 2007a). The significance of my microdose analysis has been that low LET radiation induced single (i.e. only one) charged particle traversals through a cell can initiate a Poisson distributed activation of AR radio-protection. The purpose of this correspondence is to clarify the distinctions relative to the BE and the AR behaviors for the Redpath groups 137Cs data, show conversely however that the Redpath group data for mammography (Ko et al 2004) and diagnostic (Redpath et al 2003) X-rays do conclusively reflect protective bystander behavior and also herein emphasize the need for radio-biologist to apply microdosimetry in planning and analyzing their experiments for BE and AR. Whether we are adamantly pro-LNT, adamantly anti-LNT or, like most of us, just simple scientists searching for the truth in radio-biology, it is important that we accurately identify our results, especially when related to the LNT hypothesis controversy. PMID:18846260

Pharmacokinetic analysis of 14C-ursodiol in newborn infants using accelerator mass spectrometry.

PubMed

Gordi, Toufigh; Baillie, Rebecca; Vuong, Le T; Abidi, Saira; Dueker, Stephen; Vasquez, Herbert; Pegis, Priscilla; Hopper, Andrew O; Power, Gordon G; Blood, Arlin B

2014-09-01

Pharmacokinetic studies in the neonatal population are often limited by the small volume of blood that can be collected. The high sensitivity of (14) C-accelerator mass spectrometry (AMS) enables pharmacokinetic studies to be conducted with greatly reduced sample volumes. We demonstrated the utility of AMS in infants by studying the plasma pharmacokinetic behavior of nanogram doses of (14) C-ursodiol administered as a non-perturbing microdose or as a microtracer with therapeutic doses of non-labeled ursodiol in infants. Five non-cholestatic infants were administered 3 consecutive oral microdoses of (14) C-ursodiol: 8 ng (1.0 nCi), 26 ng (3.3 nCi), and 80 ng (10 nCi) 48 hours apart. Three additional infants with cholestasis were administered a single 80 ng (10.0 nCi) oral dose of (14) C-ursodiol together with a therapeutic dose of 40 mg/kg of non-labeled ursodiol. A pharmacokinetic model describing ursodiol concentrations was developed using nonlinear mixed-effects modeling. The pharmacokinetics of ursodiol in this pilot study were best described by a two-compartment model with first-order elimination. This study demonstrates the feasibility and utility of microdose and microtrace methodology in pediatric research. © 2014, The American College of Clinical Pharmacology.

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles.

PubMed

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1).

Stochastic Threshold Microdose Model for Cell Killing by Insoluble Metallic Nanomaterial Particles

PubMed Central

Scott, Bobby R.

2010-01-01

This paper introduces a novel microdosimetric model for metallic nanomaterial-particles (MENAP)-induced cytotoxicity. The focus is on the engineered insoluble MENAP which represent a significant breakthrough in the design and development of new products for consumers, industry, and medicine. Increased production is rapidly occurring and may cause currently unrecognized health effects (e.g., nervous system dysfunction, heart disease, cancer); thus, dose-response models for MENAP-induced biological effects are needed to facilitate health risk assessment. The stochastic threshold microdose (STM) model presented introduces novel stochastic microdose metrics for use in constructing dose-response relationships for the frequency of specific cellular (e.g., cell killing, mutations, neoplastic transformation) or subcellular (e.g., mitochondria dysfunction) effects. A key metric is the exposure-time-dependent, specific burden (MENAP count) for a given critical target (e.g., mitochondria, nucleus). Exceeding a stochastic threshold specific burden triggers cell death. For critical targets in the cytoplasm, the autophagic mode of death is triggered. For the nuclear target, the apoptotic mode of death is triggered. Overall cell survival is evaluated for the indicated competing modes of death when both apply. The STM model can be applied to cytotoxicity data using Bayesian methods implemented via Markov chain Monte Carlo. PMID:21191483

Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose.

PubMed

Ieiri, Ichiro; Doi, Yohei; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Hirota, Takeshi; Chiyoda, Takeshi; Miyagawa, Mayuko; Irie, Shin; Iwasaki, Kazuhide; Sugiyama, Yuichi

2012-07-01

The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 µg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC(0-24) of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype-dependent differences disappeared following the MD. Dose-normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems.

Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI.

PubMed

Mohsen, Iman Abdel; El Din, Rasha Ezz

2013-02-01

To compare the IVF outcomes of letrozole/antagonist and microdose GnRH agonist flare up protocols in poor ovarian responders undergoing intracytoplasmic sperm injection. A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which four or less oocytes were retrieved when the gonadotrophin starting dose was at least 300 IU/day. Sixty patients were randomized by computer-generated list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a protocol (microdose flare) n = 30. Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used gonadotropins and the number of stimulation days were significantly lower in the letrozole/antagonist protocol. The peak E2 level on the day of hCG, the endometrial thickness, the retrieved oocytes, the number of fertilized oocytes, the number of transferred embryos and the cancellation rate were statistically similar in both groups. The letrozole/antagonist protocol is a cost-effective and patient-friendly protocol that may be used in poor ovarian responders for IVF/ICSI.

Cost-effectiveness analysis of microdose clinical trials in drug development.

PubMed

Yamane, Naoe; Igarashi, Ataru; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

2013-01-01

Microdose (MD) clinical trials have been introduced to obtain human pharmacokinetic data early in drug development. Here we assessed the cost-effectiveness of microdose integrated drug development in a hypothetical model, as there was no such quantitative research that weighed the additional effectiveness against the additional time and/or cost. First, we calculated the cost and effectiveness (i.e., success rate) of 3 types of MD integrated drug development strategies: liquid chromatography-tandem mass spectrometry, accelerator mass spectrometry, and positron emission tomography. Then, we analyzed the cost-effectiveness of 9 hypothetical scenarios where 100 drug candidates entering into a non-clinical toxicity study were selected by different methods as the conventional scenario without MD. In the base-case, where 70 drug candidates were selected without MD and 30 selected evenly by one of the three MD methods, incremental cost-effectiveness ratio per one additional drug approved was JPY 12.7 billion (US$ 0.159 billion), whereas the average cost-effectiveness ratio of the conventional strategy was JPY 24.4 billion, which we set as a threshold. Integrating MD in the conventional drug development was cost-effective in this model. This quantitative analytical model which allows various modifications according to each company's conditions, would be helpful for guiding decisions early in clinical development.

Intraarterial Microdosing, a Novel Drug Development Approach, Proof-of-Concept PET Study in Rats

PubMed Central

Burt, Tal; Rouse, Douglas C.; Lee, Kihak; Wu, Huali; Layton, Anita T.; Hawk, Thomas C.; Weitzel, Douglas H.; Chin, Bennett B.; Cohen-Wolkowiez, Michael; Chow, Shein-Chung; Noveck, Robert J.

2016-01-01

Intraarterial microdosing (IAM) is a novel drug development approach combining intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM leads to target exposure similar to that of systemic full-dose administration but with minimal systemic exposure. IAM could enable the safe, inexpensive, and early study of novel drugs at the first-in-human stage and the study of established drugs in vulnerable populations. Methods Insulin was administered intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats just before blood sampling or 60-min 18F-FDG uptake PET imaging of ipsilateral and contralateral leg muscles (lateral gastrocnemius) and systemic muscles (spinotrapezius). The 18F-FDG uptake slope analysis was used to compare the interventions. Plasma levels of insulin and glucose were compared using area under the curve calculated by the linear trapezoidal method. A physiologically based computational pharmacokinetics/pharmacodynamics model was constructed to simulate the relationship between the administered dose and response over time. Results 18F-FDG slope analysis found no difference between IAM and systemic full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], −0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly greater than systemic microdose (0.0018; 95% CI, −0.045 to −0.007; P = 0.0147) and sham intervention (−0.0015; 95% CI, 0.023–0.058; P = 0.0052). The pharmacokinetics/pharmacodynamics data were used to identify model parameters that describe membrane insulin binding and glucose–insulin dynamics. Conclusion Target exposure after IAM was similar to systemic full dose administration but with minimal systemic effects. The computational pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body response. Findings should be validated in larger, controlled studies in animals and humans using a range of targets and classes of drugs. PMID:26315828

Accelerator mass spectrometry analysis of background (14)C-concentrations in human blood: aiming at reference data for further microdosing studies.

PubMed

Minamimoto, Ryogo; Hamabe, Yoshimi; Miyaoka, Teiji; Hara, Takamitsu; Yoshida, Keisuke; Oka, Takashi; Inoue, Tomio

2008-12-01

Phase 0 clinical studies, which are known as microdose trials, are expected to promote drug development and reduce development costs. The accelerator mass spectrometry (AMS) system is expected to play an important role in the microdosing tests, as it is a highly sensitive measurement system that can be used to determine the drug concentrations in these tests. Using the AMS system, we measured the background (14)C-concentration in human blood and evaluated the data for use as a reference in microdose studies that administer (14)C-labeled compounds in humans. Blood samples of five healthy Japanese volunteers (three men, two women, median age 40.4 +/- 9.8 years) were collected around the same time and just prior to when the subjects ate a meal (between 12:00 noon and 2:00 pm). Centrifugal separations of blood that was allowed to clot and the plasma were performed at 503 g for 2 min at 4 degrees C. Background (14)C-concentration for each of the samples was measured using the AMS system. The Institute of Accelerator Analysis, which is the first contract research organization in Japan that is capable of providing AMS analysis services for carbon dating and bioanalysis work, performed the AMS analysis. The mean (14)C-concentration in blood was 1.613 +/- 0.125 dpm/ml (men 1.668 +/- 0.114 dpm/ml, women 1.514 +/- 0.076 dpm/ml), in clots 2.373 +/- 0.087 dpm/ml (men 2.381 +/- 0.101 dpm/ml, women 2.357 +/- 0.060 dpm/ ml), and in plasma 0.648 +/- 0.049 dpm/ml (men 0.647 +/- 0.059 dpm/ml, women 0.649 +/- 0.032 dpm/ml). The coefficient variation (CV) for blood was 7.8% (men 6.9%, women 5.0%), for clots 3.7% (men 4.3%, women 2.5%), and for plasma 7.6% (men 9.1%, women 4.9%). The (14)C-concentrations of the clot and blood were higher than those of plasma. The (14)C-concentrations in the blood and plasma were slightly different between individuals when compared with the values for the clot, although the differences were quite small, with a CV value less than 7.8%. Even though the (14)C-concentration differed only slightly between individuals, (14)C-concentrations of the clot and blood were higher than those of the plasma. Therefore, the variation and difference of the background data for blood and plasma might be of use as a reference for microdosing test evaluations.

EOS microdose protocol for the radiological follow-up of adolescent idiopathic scoliosis.

PubMed

Ilharreborde, Brice; Ferrero, Emmanuelle; Alison, Marianne; Mazda, Keyvan

2016-02-01

Imaging plays a key role in adolescent idiopathic scoliosis (AIS) to determine the prognosis and accordingly define the best therapeutic strategy to follow. Conventional radiographs with ionizing radiation have been associated with 1-2 % increased lifetime risk of developing cancer in children, and physicians, therefore, need a sensitive but harmless way to explore patients at risk, according to the "as low as reasonably achievable" concept. The EOS system (EOS imaging, Paris, France) is available in routine clinical use since 2007, and allows 3D reconstructions of the trunk in standing position with significant radiation reduction. With recent technical advances, further dose reduction can be obtained, but at the cost of image quality that might alter the reliability of 3D reconstructions. The aim of the present study was to analyze the reproducibility of a "microdose" protocol, and evaluate its use in clinical practice. 32 consecutive patients followed for AIS were prospectively included. Biplanar radiographs were obtained with the EOS system according to the new microdose protocol. From the microdose images obtained, three experienced operators performed 3D reconstructions, two times for each subject in a random order (total, 192 reconstructions). The intraoperator repeatability and interoperator reproducibility were evaluated, as recommended by the International Organization for Standardization, for the most clinically relevant 3D radiological parameters. The identification of the required anatomical landmarks for the "fast spine" reconstruction process was possible in all cases. None of the patients required a second acquisition for 3D analysis. Mean time for reconstruction was 5 ± 2 min. The intraoperator repeatability was better than interoperator reproducibility for all parameters, with values ranging between 3° and 8° for frontal and sagittal spinal parameters, and between 1° and 8° for pelvic measurements. The agreement was very good for all clinical measurements. No correlation was found between the BMI and the reliability of the measurements. Because children are notably more sensitive to the carcinogenic effects of ionizing radiation, judicious use of imaging methods and a search for newer technologies remain necessary. Results of the current study show that the new microdose acquisition protocol can be used in clinical practice without altering the quality of the images. Relevant clinical measurements can be made manually, but the landmarks are also visible enough to allow accurate 3D reconstructions (ICC >0.91 for all parameters). The resulting radiation exposure was 5.5 times lower than that received with the prior protocol, corresponding now to a 45-fold reduction compared to conventional radiographs, and can, therefore, almost be considered negligible.

Method Of Dispensing Microdoses Of A Aqueous Solutions Of S Ubstances Onto A Carrier And A Device For Carrying Out Said Method

DOEpatents

Ershov, Gennady Moiseevich; Kirillov, Eugenii Vladislavovich; Mirzabekov, Andrei Darievich

1999-10-05

A method and a device for dispensing microdoses of aqueous solutions are provided, whereby the substance is transferred by the free surface end of a rodlike transferring element; the temperature of the transferring element is maintained at essentially the dew point of the ambient air during the transfer. The device may comprise a plate-like base to which are affixed a plurality of rods; the unfixed butt ends of the rods are coplanar. The device further comprises a means for maintaining the temperature of the unfixed butt ends of the rods essentially equal to the dew point of the ambient air during transfer of the aqueous substance

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles

PubMed Central

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

Background: This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. Materials and Methods: In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. Results: There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). Conclusion: According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1). PMID:24520450

A quantified dosing ALD reactor with in-situ diagnostics for surface chemistry studies

NASA Astrophysics Data System (ADS)

Larrabee, Thomas J.

A specialized atomic layer deposition (ALD) reactor has been constructed to serve as an instrument to simultaneously study the surface chemistry of the ALD process, and perform ALD as is conventionally done in continuum flow of inert gas. This reactor is uniquely useful to gain insight into the ALD process because of the combination of its precise, controllable, and quantified dosing/microdosing capability; its in-situ quadrupole mass spectrometer for gas composition analysis; its pair of highly-sensitive in-situ quartz crystal microbalances (QCMs); and its complete spectrum of pressures and operating conditions --- from viscous to molecular flow regimes. Control of the dose is achieved independently of the conditions by allowing a reactant gas to fill a fixed volume and measured pressure, which is held at a controlled temperature, and subsequently dosed into the system by computer controlled pneumatic valves. Absolute reactant exposure to the substrate and QCMs is unambiguously calculated from the molecular impingement flux, and its relationship to dose size is established, allowing means for easily intentionally reproducing specific exposures. Methods for understanding atomic layer growth and adsorption phenomena, including the precursor sticking probability, dynamics of molecular impingement, size of dose, and other operating variables are for the first time quantitatively related to surface reaction rates by mass balance. Extensive characterization of the QCM as a measurement tool for adsorption under realistic ALD conditions has been examined, emphasizing the state-of-the-art and importance of QCM system features required. Finally, the importance of dose-quantification and microdosing has been contextualized in view of the ALD literature, underscoring the significance of more precise condition specification in establishing a better basis for reactor and reactant comparison.

Simultaneous oral therapeutic and intravenous 14C‐microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin

PubMed Central

Boulton, David W.; Kasichayanula, Sreeneeranj; Keung, Chi Fung (Anther); Arnold, Mark E.; Christopher, Lisa J.; Xu, Xiaohui (Sophia); LaCreta, Frank

2013-01-01

Aim To determine the absolute oral bioavailability (Fp.o.) of saxagliptin and dapagliflozin using simultaneous intravenous 14C‐microdose/therapeutic oral dosing (i.v.micro + oraltherap). Methods The Fp.o. values of saxagliptin and dapagliflozin were determined in healthy subjects (n = 7 and 8, respectively) following the concomitant administration of single i.v. micro doses with unlabelled oraltherap doses. Accelerator mass spectrometry and liquid chromatography‐tandem mass spectrometry were used to quantify the labelled and unlabelled drug, respectively. Results The geometric mean point estimates (90% confidence interval) Fp.o. values for saxagliptin and dapagliflozin were 50% (48, 53%) and 78% (73, 83%), respectively. The i.v.micro had similar pharmacokinetics to oraltherap. Conclusions Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability. PMID:22823746

Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model.

PubMed

Zhao, Lei; Gong, Neng; Liu, Meng; Pan, Xiaoli; Sang, Shaoming; Sun, Xiaojing; Yu, Zhe; Fang, Qi; Zhao, Na; Fei, Guoqiang; Jin, Lirong; Zhong, Chunjiu; Xu, Tianle

2014-12-01

Alzheimer's disease (AD) is a complicated, neurodegenerative disorder involving multifactorial pathogeneses and still lacks effective clinical treatment. Recent studies show that lithium exerts disease-modifying effects against AD. However, the intolerant side effects at conventional effective dosage limit the clinical use of lithium in treating AD. To explore a novel AD treatment strategy with microdose lithium, we designed and synthesized a new chemical, tri-lithium pyrroloquinoline quinone (Li3PQQ), to study the synergistic effects of low-dose lithium and pyrroloquinoline quinone, a native compound with powerful antioxidation and mitochondrial amelioration. The results showed that Li3PQQ at a relative low dose (6 and 12 mg/kg) exhibited more powerful effects in restoring the impairment of learning and memory, facilitating hippocampal long-term potentiation, and reducing cerebral amyloid deposition and phosphorylated tau level in APP/PS1 transgenic mice than that of lithium chloride at both low and high dose (5 and 100 mg/kg). We further found that Li3PQQ inhibited the activity of glycogen synthase kinase-3 and increased the activity of β-amyloid-binding alcohol dehydrogenase, which might underlie the beneficial effects of Li3PQQ on APP/PS1 transgenic mice. Our study demonstrated the efficacy of a novel AD therapeutic strategy targeting at multiple disease-causing mechanisms through the synergistic effects of microdose lithium and pyrroloquinoline quinone. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy determinants of subcutaneous microdose glucagon during closed-loop control.

PubMed

Russell, Steven J; El-Khatib, Firas H; Nathan, David M; Damiano, Edward R

2010-11-01

During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BG<70 mg/dl). After a global adjustment of control algorithm parameters used to model insulin absorption and clearance to more closely match insulin pharmacokinetic (PK) parameters observed in the study cohort, administration of glucagon by the control system was more effective in preventing hypoglycemia. We evaluated the role of plasma insulin and plasma glucagon levels in determining whether glucagon was effective in preventing hypoglycemia. We identified and analyzed 36 episodes during which glucagon was given and categorized them as either successful or unsuccessful in preventing hypoglycemia. In 20 of the 36 episodes, glucagon administration prevented hypoglycemia. In the remaining 16, BG fell below 70 mg/dl (12 of the 16 occurred during experiments performed before PK parameters were adjusted). The (dimensionless) levels of plasma insulin (normalized relative to each subject's baseline insulin level) were significantly higher during episodes ending in hypoglycemia (5.2 versus 3.7 times the baseline insulin level, p=.01). The relative error in the control algorithm's online estimate of the instantaneous plasma insulin level was also higher during episodes ending in hypoglycemia (50 versus 30%, p=.003), as were the peak plasma glucagon levels (183 versus 116 pg/ml, p=.007, normal range 50-150 pg/ml) and mean plasma glucagon levels (142 versus 75 pg/ml, p=.02). Relative to mean plasma insulin levels, mean plasma glucagon levels tended to be 59% higher during episodes ending in hypoglycemia, although this result was not found to be statistically significant (p=.14). The rate of BG descent was also significantly greater during episodes ending in hypoglycemia (1.5 versus 1.0 mg/dl/min, p=.02). Microdose glucagon administration was relatively ineffective in preventing hypoglycemia when plasma insulin levels exceeded the controller's online estimate by >60%. After the algorithm PK parameters were globally adjusted, insulin dosing was more conservative and microdose glucagon administration was very effective in reducing hypoglycemia while maintaining normal plasma glucagon levels. Improvements in the accuracy of the controller's online estimate of plasma insulin levels could be achieved if ultrarapid-acting insulin formulations could be developed with faster absorption and less intra- and intersubject variability than the current insulin analogs available today. © 2010 Diabetes Technology Society.

Human Lung Cancer Risks from Radon – Part III - Evidence of Influence of Combined Bystander and Adaptive Response Effects on Radon Case-Control Studies - A Microdose Analysis

PubMed Central

Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

2012-01-01

Since the publication of the BEIR VI (1999) report on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, in particular the potentially deleterious Bystander Effect (BE) and the potentially beneficial Adaptive Response radio-protection (AR). The case-control radon lung cancer risk data of the pooled 13 European countries radon study (Darby et al 2005, 2006) and the 8 North American pooled study (Krewski et al 2005, 2006) have been evaluated. The large variation in the odds ratios of lung cancer from radon risk is reconciled, based on the large variation in geological and ecological conditions and variation in the degree of adaptive response radio-protection against the bystander effect induced lung damage. The analysis clearly shows Bystander Effect radon lung cancer induction and Adaptive Response reduction in lung cancer in some geographical regions. It is estimated that for radon levels up to about 400 Bq m−3 there is about a 30% probability that no human lung cancer risk from radon will be experienced and a 20% probability that the risk is below the zero-radon, endogenic spontaneous or perhaps even genetically inheritable lung cancer risk rate. The BEIR VI (1999) and EPA (2003) estimates of human lung cancer deaths from radon are most likely significantly excessive. The assumption of linearity of risk, by the Linear No-Threshold Model, with increasing radon exposure is invalid. PMID:22942874

Cost-effectiveness comparison between pituitary down-regulation with a gonadotropin-releasing hormone agonist short regimen on alternate days and an antagonist protocol for assisted fertilization treatments.

PubMed

Maldonado, Luiz Guilherme Louzada; Franco, José Gonçalves; Setti, Amanda Souza; Iaconelli, Assumpto; Borges, Edson

2013-05-01

To compare cost-effectiveness between pituitary down-regulation with a GnRH agonist (GnRHa) short regimen on alternate days and GnRH antagonist (GnRHant) multidose protocol on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome. Prospective, randomized. A private center. Patients were randomized into GnRHa (n = 48) and GnRHant (n = 48) groups. GnRHa stimulation protocol: administration of triptorelin on alternate days starting on the first day of the cycle, recombinant FSH (rFSH), and recombinant hCG (rhCG) microdose. GnRHant protocol: administration of a daily dose of rFSH, cetrorelix, and rhCG microdose. ICSI outcomes and treatment costs. A significantly lower number of patients underwent embryo transfer in the GnRHa group. Clinical pregnancy rate was significantly lower and miscarriage rate was significantly higher in the GnRHa group. It was observed a significant lower cost per cycle in the GnRHa group compared with the GnRHant group ($5,327.80 ± 387.30 vs. $5,900.40 ± 472.50). However, mean cost per pregnancy in the GnRHa was higher than in the GnRHant group ($19,671.80 ± 1,430.00 vs. $11,328.70 ± 907.20). Although the short controlled ovarian stimulation protocol with GnRHa on alternate days, rFSH, and rhCG microdose may lower the cost of an individual IVF cycle, it requires more cycles to achieve pregnancy. NCT01468441. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Validation of a liquid chromatography-triple quadrupole mass spectrometric method for the determination of 5-nitro-5'-hydroxy-indirubin-3'-oxime (AGM-130) in human plasma and its application to microdose clinical trial.

PubMed

Park, Min-Ho; Lee, Yun Young; Cho, Kyung Hee; La, Sookie; Lee, Hee Joo; Yim, Dong-Seok; Ban, Sooho; Park, Moon-Young; Kim, Yong-Chul; Kim, Yoon-Gyoon; Shin, Young G

2016-03-01

A liquid chromatography-triple quadrupole mass spectrometric (LC-MS/MS) method was developed and validated for the determination of 5-nitro-5'-hydroxy-indirubin-3'-oxime (AGM-130) in human plasma to support a microdose clinical trial. The method consisted of a liquid-liquid extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray(TM) for analysis. d3 -AGM-130 was used as the internal standard. A linear regression (weighted 1/concentration) was used to fit calibration curves over the concentration range of 10-2000 pg/mL for AGM-130. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 96.6% with a precision (coefficient of variation, CV) of 4.4%. For quality control samples at 30, 160 and 1600 pg/mL, the between run CV was ≤5.0 %. Between-run accuracy ranged from 98.1 to 101.0%. AGM-130 was stable in 50% acetonitrile for 168 h at 4°C and 6 h at room temperature. AGM-130 was also stable in human plasma at room temperature for 6 h and through three freeze-thaw cycles. The variability of selected samples for the incurred sample reanalysis was ≤12.7% when compared with the original sample concentrations. This validated LC-MS/MS method for determination of AGM-130 was used to support a phase 0 microdose clinical trial. Copyright © 2015 John Wiley & Sons, Ltd.

Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP

PubMed Central

Kusuhara, Hiroyuki; Furuie, Hidetoshi; Inano, Akihiro; Sunagawa, Akihiro; Yamada, Saiko; Wu, Chunyong; Fukizawa, Shinya; Morimoto, Nozomi; Ieiri, Ichiro; Morishita, Mariko; Sumita, Kiminobu; Mayahara, Hiroshi; Fujita, Takuya; Maeda, Kazuya; Sugiyama, Yuichi

2012-01-01

BACKGROUND AND PURPOSE An ATP-binding cassette (ABC) transporter, breast cancer resistance protein (BCRP)/ABCG2, limits oral bioavailability of sulphasalazine. Here we examined the effect of curcumin, the principal curcuminoid of turmeric, on oral bioavailability of microdoses and therapeutic doses of sulphasalazine in humans. EXPERIMENTAL APPROACH Effects of curcumin were measured on the ATP-dependent sulphasalazine uptake by hBCRP-expressing membrane vesicles and on oral bioavailability of sulphasalazine in wild-type and Bcrp(–/–) mice. Eight healthy Japanese subjects received an oral dose of sulphasalazine suspension (100 µg) or tablets (2 g) alone or after curcumin tablets (2 g). Uptake of sulphasalazine was studied in HEK293 cells transfected with the influx transporter (OATP)2B1. KEY RESULTS Curcumin was a potent hBCRP inhibitor in vitro (Ki 0.70 ± 0.41 µM). Curcumin increased the area under the curve (AUC)0–8 of plasma sulphasalazine eightfold in wild-type mice at 300 and 400 mg·kg−1, but not in Bcrp(–/–) mice. Curcumin increased AUC0–24 of plasma sulphasalazine 2.0-fold at microdoses and 3.2-fold at therapeutic doses in humans. Non-linearity of the dose–exposure relationship was observed between microdoses and therapeutic doses of sulphasalazine. Sulphasalazine was a substrate for OATP2B1 (Km 1.7 ± 0.3 µM). Its linear index (dose/Km) at the therapeutic dose was high and may saturate OATP2B1. CONCLUSIONS AND IMPLICATIONS Curcumin can be used to investigate effects of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is a possible mechanism underlying non-linearity in the dose–exposure relationship of sulphasalazine. PMID:22300367

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection

PubMed Central

Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

2016-01-01

Background: Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. Methods: In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ2-test were used to compare the groups. The p<0.05 was considered to show a statistically significant result. Results: The mean total gonadotropin doses were 3814±891 IU in group 1 and 3539±877 IU in group 2 (p=0.02). The number of metaphase-II oocytes (3.6±2.4 vs. 2.8±1.9, p=0.005) and implantation rates (27.8% vs. 18.8%, p=0.04) in group 1 and group 2, respectively were significantly different. The fertilization rate in group 1 and group 2 was 73% vs. 68%, respectively (p=0.5) and clinical pregnancy rate was 19.8% vs. 14.4%, respectively (p=0.13). Conclusion: The GnRH agonist microdose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders. PMID:27478770

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection.

PubMed

Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

2016-01-01

Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ (2)-test were used to compare the groups. The p<0.05 was considered to show a statistically significant result. The mean total gonadotropin doses were 3814±891 IU in group 1 and 3539±877 IU in group 2 (p=0.02). The number of metaphase-II oocytes (3.6±2.4 vs. 2.8±1.9, p=0.005) and implantation rates (27.8% vs. 18.8%, p=0.04) in group 1 and group 2, respectively were significantly different. The fertilization rate in group 1 and group 2 was 73% vs. 68%, respectively (p=0.5) and clinical pregnancy rate was 19.8% vs. 14.4%, respectively (p=0.13). The GnRH agonist microdose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders.

Comparison of pharmacokinetics of newly discovered aromatase inhibitors by a cassette microdosing approach in healthy Japanese subjects.

PubMed

Kusuhara, Hiroyuki; Takashima, Tadayuki; Fujii, Hisako; Takashima, Tsutomu; Tanaka, Masaaki; Ishii, Akira; Tazawa, Shusaku; Takahashi, Kazuhiro; Takahashi, Kayo; Tokai, Hidekichi; Yano, Tsuneo; Kataoka, Makoto; Inano, Akihiro; Yoshida, Suguru; Hosoya, Takamitsu; Sugiyama, Yuichi; Yamashita, Shinji; Hojo, Taisuke; Watanabe, Yasuyoshi

2017-12-01

The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16.8 ± 3.5 mL/min/kg and 18.4 ± 12.2% for TMD-322, respectively. The area under the plasma concentration-time curves of cetrozole and TMD-322 after oral administration was markedly lower than that of anastrozole because of their high hepatic clearance. Two subjects out of six exhibited 4- and 17-fold larger exposure of cetrozole than the others following intravenous and oral administration, respectively. Such variation was not observed for TMD-322 and anastrozole. Extensive metabolism of cetrozole and TMD-322 was observed in the CYP2C19 expression system among the test CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). We report the first clinical investigation of our aromatase inhibitors by a cassette microdose strategy in healthy Japanese subjects. This strategy offers an optional approach for candidate selection as a phase zero study in drug development. Copyright © 2017. Published by Elsevier Ltd.

Mobile measurement setup according to IEC 62220-1-2 for DQE determination on digital mammography systems

NASA Astrophysics Data System (ADS)

Greiter, Matthias B.; Hoeschen, Christoph

2010-04-01

The international standard IEC 62220-1-2 defines the measurement procedure for determination of the detective quantum efficiency (DQE) of digital x-ray imaging devices used in mammography. A mobile setup complying to this standard and adaptable to most current systems was constructed in the Helmholtz Zentrum München to allow for an objective technical comparison of current full field digital mammography units employed in mammography screening in Germany. This article demonstrates the setup's capabilities with a focus on the measurement uncertainties of all quantities contributing to DQE measurements. Evaluation of uncertainties encompasses results from measurements on a Sectra Microdose Mammography in clinical use, as well as on a prototype of a Fujifilm Amulet system at various radiation qualities. Both systems have a high spatial resolution of 50 μm × 50 μm. The modulation transfer function (MTF), noise power spectrum (NPS) and DQE of the Sectra MDM are presented in comparison to results previously published by other authors.

Microdose-induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

PubMed Central

Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong; Lin, Tzu-yin; Malfatti, Michael; Haack, Kurt; Ognibene, Ted; Yang, Hongyuan; Airhart, Susan; Turteltaub, Kenneth W.; Cimino, George D.; Tepper, Clifford G.; Drakaki, Alexandra; Chamie, Karim; de Vere White, Ralph; Pan, Chong-xian; Henderson, Paul T.

2017-01-01

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry (AMS) in blood and tumor samples collected within 24 hours, and compared to subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [14C]carboplatin or [14C]gemcitabine and the resulting drug-DNA adduct levels were compared to tumor response to chemotherapy. At least one of the drugs had to induce high drug-DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug-DNA adducts as predictive biomarkers. PMID:27903751

Hot pixel generation in active pixel sensors: dosimetric and micro-dosimetric response

NASA Technical Reports Server (NTRS)

Scheick, Leif; Novak, Frank

2003-01-01

The dosimetric response of an active pixel sensor is analyzed. heavy ions are seen to damage the pixel in much the same way as gamma radiation. The probability of a hot pixel is seen to exhibit behavior that is not typical with other microdose effects.

Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

DOE PAGES

Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong; ...

2016-11-30

Here, we report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [ 14C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice weremore » dosed with [ 14C]carboplatin or [ 14C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers.« less

Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

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

Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong

Here, we report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [ 14C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice weremore » dosed with [ 14C]carboplatin or [ 14C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers.« less

Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice.

PubMed

Zimmermann, Maike; Wang, Si-Si; Zhang, Hongyong; Lin, Tzu-Yin; Malfatti, Michael; Haack, Kurt; Ognibene, Ted; Yang, Hongyuan; Airhart, Susan; Turteltaub, Kenneth W; Cimino, George D; Tepper, Clifford G; Drakaki, Alexandra; Chamie, Karim; de Vere White, Ralph; Pan, Chong-Xian; Henderson, Paul T

2017-02-01

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [ 14 C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [ 14 C]carboplatin or [ 14 C]gemcitabine and the resulting drug-DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug-DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug-DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376-87. ©2016 AACR. ©2016 American Association for Cancer Research.

Hepatic uptake and storage of warfarin. The relation with the target enzyme vitamin K 2,3-epoxide reductase

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

Thijssen, H.H.; Baars, L.G.

The mechanisms of the reported dose-dependent warfarin pharmacokinetics were investigated using (/sup 14/C)warfarin. When administered in microdoses (9 micrograms i.v.) to rats (male Wistars, 270-300 g), a steep distribution phase (T1/2 = 0.25 hr) was followed by a relatively slow beta-phase (T1/2 = 40 hr). The observed volume of distribution was 390 ml. This pharmacokinetic behavior contrasted highly with the one seen for higher (greater than 0.2 mg/kg) doses (unlabeled) warfarin; volume of distribution = 45 ml, T1/2 = 12.5 hr. If a macrodose (0.2 mg/kg) preceded (16 hr) the microdose, normal pharmacokinetics were observed for the latter, suggesting amore » saturable deep compartment. The administration of 4-hydroxycoumarins (i.e., acenocoumarol, phenprocoumon and warfarin) after the microdose of (/sup 14/C)warfarin was in its beta-phase caused a rapid rise of plasma (/sup 14/C)warfarin indicating (/sup 14/C)warfarin to be displaced from the deep compartment. The rate of appearance of (/sup 14/C)warfarin was 0.3 hr-1 irrespective the 4-hydroxycoumarin used. The hepatic distribution of (/sup 14/C)warfarin was investigated and the effect of a displacer thereupon. Fifty-three hours after the (/sup 14/C)warfarin administration, the liver contained about 40% of the dose; 45% of it was bound to microsomes. The administration of acenocoumarol (0.2 mg/kg) at 48 hr, halved the liver content. (/sup 14/C)warfarin was redistributed from microsomes (-65%) and from the 10,000 X g pellet (-65%) into the cytosol (+260%) and the plasma (+320%). Microsomal bound (/sup 14/C)warfarin in vitro could not be washed out or be displaced unless dithiothreitol (50 mM) was included in the washing buffers.« less

Tailored breast cancer screening program with microdose mammography, US, and MR Imaging: short-term results of a pilot study in 40-49-year-old women.

PubMed

Venturini, Elena; Losio, Claudio; Panizza, Pietro; Rodighiero, Maria Grazia; Fedele, Isabella; Tacchini, Simona; Schiani, Elena; Ravelli, Silvia; Cristel, Giulia; Panzeri, Marta Maria; De Cobelli, Francesco; Del Maschio, Alessandro

2013-08-01

To evaluate the feasibility, performance, and cost of a breast cancer screening program aimed at 40-49-year-old women and tailored to their risk profile with supplemental ultrasonography (US) and magnetic resonance (MR) imaging. The institutional review board approved this study, and informed written consent was obtained. A total of 3017 40-49-year-old women were invited to participate. The screening program was tailored to lifetime risk (Gail test) and mammographic density (according to Breast Imaging Reporting and Data Systems [BI-RADS] criteria) with supplemental US or MR imaging and bilateral two-view microdose mammography. The indicators suggested by European guidelines, US incremental cancer detection rate (CDR), and estimated costs were evaluated. A total of 1666 women (67.5% participation rate) were recruited. The average lifetime risk of breast cancer was 11.6%, and nine women had a high risk of breast cancer; 917 women (55.0%) had a high density score (BI-RADS density category 3 or 4). The average glandular dose for screening examinations was 1.49 mGy. Screening US was performed in 835 study participants (50.1%), mostly due to high breast density (800 of 1666 women [48.0%]). Screening MR imaging was performed in nine women (0.5%) at high risk for breast cancer. Breast cancer was diagnosed in 14 women (8.4 cases per 1000 women). Twelve diagnoses were made with microdose mammography, and two were made with supplemental US in dense breasts (2.4 cases per 1000 women). All patients were submitted for surgery, and 10 underwent breast-conserving surgery. The sentinel lymph node was evaluated in 11 patients, resulting in negative findings in six. Pathologic analysis resulted in the diagnosis of four ductal carcinomas in situ and 10 invasive carcinomas (five at stage I). A tailored breast cancer screening program in 40-49-year-old women yielded a greater-than-expected number of cancers, most of which were low-stage disease.

Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

PubMed

Dunne, Caitlin; Seethram, Ken; Roberts, Jeffrey

2015-09-01

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the luteal phase before a microdose GnRH agonist flare protocol for in vitro fertilization did not improve outcomes in "poor responder" patients.

Imaging of Lymph Flow in Breast Cancer Patients after Microdose Administration of a Near-Infrared Fluorophore: Feasibility Study1

PubMed Central

Sevick-Muraca, Eva M.; Sharma, Ruchi; Rasmussen, John C.; Marshall, Milton V.; Wendt, Juliet A.; Pham, Hoang Q.; Bonefas, Elizabeth; Houston, Jessica P.; Sampath, Lakshmi; Adams, Kristen E.; Blanchard, Darlene Kay; Fisher, Ronald E.; Chiang, Stephen B.; Elledge, Richard; Mawad, Michel E.

2011-01-01

Purpose To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM). Materials and Methods Informed consent was obtained from 24 women (age range, 30–85 years) who received intradermal subcutaneous injections of 0.31–100 μg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively. Results Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 μg. When indocyanine green dosages were 10 μg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between “packets” of propelled fluid varied from 14 to 92 seconds. In patients who received 10 μg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore. Conclusion NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs. PMID:18223125

Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

PubMed Central

Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

2013-01-01

Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

PubMed

Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

2013-02-01

Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

Estradiol and Antagonist Pretreatment Prior to Microdose Leuprolide in in Vitro Fertilization. Does It Improve IVF Outcomes in Poor Responders as Compared to Oral Contraceptive Pill?

PubMed

Elassar, Alyaa; Nulsen, John; Engmann, Lawrence; Benadiva, Claudio

2015-01-01

To compare in vitro fertilization (IVF) outcomes in low responders stimulated with microdose leuprolide protocol (ML) following pretreatment with either oral contraceptive pill (OCP) or luteal estradiol (E2) + GnRH antagonist (E2 + antag) for follicular synchronization prior to controlled ovarian hyperstimulation (COH). This was a retrospective study of 130 women, who were poor responders, undergoing IVF with either OCP/ML or E2+ antag/ML protocols. The main outcome measures were ongoing pregnancy rates, number of oocytes retrieved, and cancellation rate. Both groups were similar in baseline characteristics. There were no significant differences in gonadotropin requirement, cancellation rate, and number of embryos transferred. Ongoing pregnancy rates (40% vs. 15%) were significantly higher in the OCP/ML group. Trends toward greater number of oocytes retrieved (7.7 ± 3.4 vs. 5.9 ± 4.2) and improved implantation rates (20% vs. 12%) were also noted, but these did not reach statistical significance. E2+antag pretreatment does not appear to improve IVF outcomes in ML protocol when compared to the standard OCP in poor responders. Randomized trials with adequate power to study the optimal method of steroid pretreatments appear justified.

Follicular synchronization using transdermal estradiol patch and GnRH antagonists in the luteal phase; does it increase oocyte yield in poor responders to gonadotropin stimulation for in vitro fertilization (IVF)? A comparative study with microdose flare-up protocol.

PubMed

Ata, Baris; Zeng, Xing; Son, Weon Y; Holzer, Hananel; Tan, Seang L

2011-11-01

The aim of this retrospective study was to compare the oocyte yield with the luteal estradiol patch (LPA) - GnRH antagonist and microdose (MD) flare-up protocols in anticipated poor responders. Fifty-seven women who underwent IVF treatment following stimulation with LPA or MD protocols at McGill Reproductive Centre were matched for age and markers of ovarian reserve. Numbers of oocytes collected (6 vs 7), mature oocytes collected (5 vs 5), and oocyte maturation rates (72% vs 74%) were similar. The numbers of good quality embryos available (2 vs 1) and embryos transferred (3 vs 3) were likewise similar. Embryo implantation rate of 16.7% and clinical pregnancy rate of 38.9% achieved in the LPA group were almost 50% higher than the corresponding figures at 10.3% and 22.2% in the MD group; however, the differences were not statistically significant (p > 0.05 for all comparisons). Although the results do not suggest an increased oocyte yield or follicular synchronization with the LPA protocol, the observed trend toward higher embryo implantation and clinical pregnancy rates requires further research.

Development and Design of Next-Generation Head-Mounted Ambulatory Microdose Positron-Emission Tomography (AM-PET) System.

PubMed

Melroy, Samantha; Bauer, Christopher; McHugh, Matthew; Carden, Garret; Stolin, Alexander; Majewski, Stan; Brefczynski-Lewis, Julie; Wuest, Thorsten

2017-05-19

Several applications exist for a whole brain positron-emission tomography (PET) brain imager designed as a portable unit that can be worn on a patient's head. Enabled by improvements in detector technology, a lightweight, high performance device would allow PET brain imaging in different environments and during behavioral tasks. Such a wearable system that allows the subjects to move their heads and walk-the Ambulatory Microdose PET (AM-PET)-is currently under development. This imager will be helpful for testing subjects performing selected activities such as gestures, virtual reality activities and walking. The need for this type of lightweight mobile device has led to the construction of a proof of concept portable head-worn unit that uses twelve silicon photomultiplier (SiPM) PET module sensors built into a small ring which fits around the head. This paper is focused on the engineering design of mechanical support aspects of the AM-PET project, both of the current device as well as of the coming next-generation devices. The goal of this work is to optimize design of the scanner and its mechanics to improve comfort for the subject by reducing the effect of weight, and to enable diversification of its applications amongst different research activities.

Development and Design of Next-Generation Head-Mounted Ambulatory Microdose Positron-Emission Tomography (AM-PET) System

PubMed Central

Melroy, Samantha; Bauer, Christopher; McHugh, Matthew; Carden, Garret; Stolin, Alexander; Majewski, Stan; Brefczynski-Lewis, Julie; Wuest, Thorsten

2017-01-01

Several applications exist for a whole brain positron-emission tomography (PET) brain imager designed as a portable unit that can be worn on a patient’s head. Enabled by improvements in detector technology, a lightweight, high performance device would allow PET brain imaging in different environments and during behavioral tasks. Such a wearable system that allows the subjects to move their heads and walk—the Ambulatory Microdose PET (AM-PET)—is currently under development. This imager will be helpful for testing subjects performing selected activities such as gestures, virtual reality activities and walking. The need for this type of lightweight mobile device has led to the construction of a proof of concept portable head-worn unit that uses twelve silicon photomultiplier (SiPM) PET module sensors built into a small ring which fits around the head. This paper is focused on the engineering design of mechanical support aspects of the AM-PET project, both of the current device as well as of the coming next-generation devices. The goal of this work is to optimize design of the scanner and its mechanics to improve comfort for the subject by reducing the effect of weight, and to enable diversification of its applications amongst different research activities. PMID:28534848

Radiation induced leakage due to stochastic charge trapping in isolation layers of nanoscale MOSFETs

NASA Astrophysics Data System (ADS)

Zebrev, G. I.; Gorbunov, M. S.; Pershenkov, V. S.

2008-03-01

The sensitivity of sub-100 nm devices to microdose effects, which can be considered as intermediate case between cumulative total dose and single event errors, is investigated. A detailed study of radiation-induced leakage due to stochastic charge trapping in irradiated planar and nonplanar devices is developed. The influence of High-K insulators on nanoscale ICs reliability is discussed. Low critical values of trapped charge demonstrate a high sensitivity to single event effect.

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF.

PubMed

Çelik, Gayem İnayet Turgay; Sütçü, Havva Kömür; Akpak, Yaşam Kemal; Akar, Münire Erman

2015-01-01

To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). The combination protocol does not provide additional efficacy.

Microdose follicular flare: a viable alternative for normal responding patients undergoing in vitro fertilization?

PubMed Central

Levens, Eric D.; Whitcomb, Brian W.; Kort, Jonathan D.; Materia-Hoover, Donna; Larsen, Frederick W.

2009-01-01

Objective To compare cycle outcomes among normal responding patients ≤30 years receiving microdose follicular flare (MDF) and long-luteal agonist (LL). Design Retrospective cohort study. Setting Military-based ART center. Patients First, autologous ART cycles among 499 women ≤30 years old from 01/1999 to 12/2005. Interventions Following OCP administration prior to cycle start, patients were non-randomly assigned to either LL or MDF for LH surge suppression. LL received 1 mg/d leuprolide acetate (LA) on cycle day 21, which was reduced to 0.25 mg/day 10–14 days later. MDF received LA (40 μg BID) beginning 3 days after discontinuing OCPs. Both groups received a combination of hMG and rFSH. Main Outcome Measures Primary outcomes were implantation, clinical pregnancy and live birth rates; in cycle variables included peak E2, oocytes retrieved, oocyte maturity, and fertilization rate. Results Multivariable models controlling for confounding by treatment indication found no significant differences between groups in implantation (MDF:36%; LL:38%), clinical pregnancy (MDF:53%; LL:56%), and live birth rates (MDF:47%; LL:50%). No differences were observed in peak E2, oocytes retrieved, oocyte maturity, fertilization rate, or embryos transferred. Conclusions MDF use among normal responding ART patients produced no differences in cycle outcome when compared to LL. Resultantly, MDF may be a viable alternative for normal responding patients. PMID:18249365

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF

PubMed Central

Turgay Çelik, Gayem İnayet; Sütçü, Havva Kömür; Akpak, Yaşam Kemal; Akar, Münire Erman

2015-01-01

Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). Conclusion. The combination protocol does not provide additional efficacy. PMID:26161425

Overcoming bioanalytical challenges in an Onglyza(®) intravenous [(14)C]microdose absolute bioavailability study with accelerator MS.

PubMed

Xu, Xiaohui Sophia; Dueker, Stephen R; Christopher, Lisa J; Lohstroh, Pete N; Keung, Chi Fung Anther; Cao, Kai Kevin; Bonacorsi, Samuel J; Cojocaru, Laura; Shen, Jim X; Humphreys, W Griffith; Stouffer, Bruce; Arnold, Mark E

2012-08-01

An absolute bioavailability study that utilized an intravenous [(14)C]microdose was conducted for saxagliptin (Onglyza(®)), a marketed drug product for the treatment of Type 2 diabetes mellitus. Concentrations of [(14)C]saxagliptin were determined by accelerator MS (AMS) after protein precipitation, chromatographic separation by UPLC and analyte fraction collection. A series of investigative experiments were conducted to maximize the release of the drug from high-affinity receptors and nonspecific adsorption, and to determine a suitable quantitation range. A technique-appropriate validation demonstrated the accuracy, precision, specificity, stability and recovery of the AMS methodology across the concentration range of 0.025 to 15.0 dpm/ml (disintegration per minute per milliliter), the equivalent of 1.91-1144 pg/ml. Based on the study sample analysis, the mean absolute bioavailability of saxagliptin was 50% in the eight subjects with a CV of 6.6%. Incurred sample reanalysis data fell well within acceptable limits. This study demonstrated that the optimized sample pretreatment and chromatographic separation procedures were critical for the successful implementation of an UPLC plus AMS method for [(14)C]saxagliptin. The use of multiple-point standards are useful, particularly during method development and validation, to evaluate and correct for concentration-dependent recovery, if observed, and to monitor and control process loss and operational variations.

Accelerator mass spectrometry analysis of 14C-oxaliplatin concentrations in biological samples and 14C contents in biological samples and antineoplastic agents

NASA Astrophysics Data System (ADS)

Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

2015-10-01

Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the 14C concentration in 14C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) - AMS system. The calibration curves of 14C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a 14C content of water in three vacuum blood collection tubes and a syringe were measured. 14C was not detected from water in these devices. The mean 14C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of 14C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, 14C contents of the antineoplastic agents were quantitated. 14C contents were different among 10 antineoplastic agents; 14C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development.

PubMed

Yamashita, Shinji; Kataoka, Makoto; Suzaki, Yuki; Imai, Hiromitsu; Morimoto, Takuya; Ohashi, Kyoichi; Inano, Akihiro; Togashi, Kazutaka; Mutaguchi, Kuninori; Sugiyama, Yuichi

2015-09-01

A cassette-microdose (MD) clinical study was performed to demonstrate its usefulness for identifying the most promising compound for oral use. Three Ca-channel blockers (nifedipine, nicardipine, and diltiazem) were chosen as model drugs. In the MD clinical study, a cassette-dose method was employed in which three model drugs were administered simultaneously. Both intravenous (i.v.) and oral (p.o.) administration studies were conducted to calculate the oral bioavailability (BA). For comparison, p.o. studies with therapeutic dose (ThD) levels were also performed. In all studies, blood concentrations of each drug were successfully determined using liquid chromatography-mass spectrometry with the lower limit of quantification of 0.2-2.0 pg/mL. Oral BA of nifedipine in the MD study was approximately 50% and in the same range with that obtained in the ThD study, whereas other two drugs showed significantly lower BA in the MD study, indicating a dose-dependent absorption. In addition, compared with the ThD study, absorption of nicardipine was delayed in the MD study. As a result, nifedipine was considered to be most promising for oral use. In conclusion, a cassette-MD clinical study is of advantage for oral drug development that enables to identify the candidate having desired properties for oral use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Digital radiography: spatial and contrast resolution

NASA Astrophysics Data System (ADS)

Bjorkholm, Paul; Annis, M.; Frederick, E.; Stein, J.; Swift, R.

1981-07-01

The addition of digital image collection and storage to standard and newly developed x-ray imaging techniques has allowed spectacular improvements in some diagnostic procedures. There is no reason to expect that the developments in this area are yet complete. But no matter what further developments occur in this field, all the techniques will share a common element, digital image storage and processing. This common element alone determines some of the important imaging characteristics. These will be discussed using one system, the Medical MICRODOSE System as an example.

Biological Monitoring of Human Exposure to Neonicotinoids Using Urine Samples, and Neonicotinoid Excretion Kinetics

PubMed Central

Harada, Kouji H.; Tanaka, Keiko; Sakamoto, Hiroko; Imanaka, Mie; Niisoe, Tamon; Hitomi, Toshiaki; Kobayashi, Hatasu; Okuda, Hiroko; Inoue, Sumiko; Kusakawa, Koichi; Oshima, Masayo; Watanabe, Kiyohiko; Yasojima, Makoto; Takasuga, Takumi; Koizumi, Akio

2016-01-01

Background Neonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults. Methodology/Principal Findings Deuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 h pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53–3.66 μg/day. The highest intake of any of the neonicotinoids in the study population was 64.5 μg/day for dinotefuran, and this was <1% of the acceptable daily intake. PMID:26731104

Preclinical Characterization and Human Microdose Pharmacokinetics of ITMN-8187, a Nonmacrocyclic Inhibitor of the Hepatitis C Virus NS3 Protease

PubMed Central

Pan, Lin; Schaefer, Caralee; Nicholas, John; Lim, Sharlene; Misialek, Shawn; Stevens, Sarah; Hooi, Lisa; Aleskovski, Natalia; Ruhrmund, Donald; Kossen, Karl; Huang, Lea; Yap, Sophia; Beigelman, Leonid; Serebryany, Vladimir; Liu, Jyanwei; Sastry, Srikonda; Seiwert, Scott; Buckman, Brad

2016-01-01

Abstract The current paradigm for the treatment of chronic hepatitis C virus (HCV) infection involves combinations of agents that act directly on steps of the HCV life cycle. Here we report the preclinical characteristics of ITMN-8187, a nonmacrocyclic inhibitor of the NS3/4A HCV protease. X-ray crystallographic studies of ITMN-8187 and simeprevir binding to NS3/4A protease demonstrated good agreement between structures. Low nanomolar biochemical potency was maintained against NS3/4A derived from HCV genotypes 1, 2b, 4, 5, and 6. In cell-based potency assays, half-maximal reduction of genotype 1a and 1b HCV replicon RNA was afforded by 11 and 4 nM doses of ITMN-8187, respectively. Combinations of ITMN-8187 with other directly acting antiviral agents in vitro displayed additive antiviral efficacy. A 30-mg/kg of body weight dose of ITMN-8187 administered for 4 days yielded significant viral load reductions through day 5 in a chimeric mouse model of HCV. A 3-mg/kg oral dose administered to rats, dogs, or monkeys yielded concentrations in plasma 16 h after dosing that exceeded the half-maximal effective concentration of ITMN-8187. Human microdose pharmacokinetics showed low intersubject variability and prolonged oral absorption with first-order elimination kinetics compatible with once-daily dosing. These preclinical characteristics compare favorably with those of other NS3/4A inhibitors approved for the treatment of chronic HCV infection. PMID:27795376

Stimulation of the young poor responder: comparison of the luteal estradiol/gonadotropin-releasing hormone antagonist priming protocol versus oral contraceptive microdose leuprolide.

PubMed

Shastri, Shefali M; Barbieri, Elizabeth; Kligman, Isaac; Schoyer, Katherine D; Davis, Owen K; Rosenwaks, Zev

2011-02-01

To evaluate in vitro fertilization (IVF) cycle outcomes in young poor responders treated with a luteal estradiol/gonadotropin-releasing hormone antagonist (E(2)/ANT) protocol versus an oral contraceptive pill microdose leuprolide protocol (OCP-MDL). Retrospective cohort. Academic practice. Poor responders: 186 women, aged <35 years undergoing IVF with either E(2)/ANT or OCP-MDL protocols. None. Clinical pregnancies, oocytes retrieved, cancellation rate. Patients in the E(2)/ANT group had a greater gonadotropin requirement (71.9 ± 22.2 vs. 57.6 ± 25.7) and lower E(2) level (1,178.6 ± 668 vs. 1,627 ± 889), yet achieved similar numbers of oocytes retrieved and fertilized, and a greater number of embryos transferred (2.3 ± 0.9 vs. 2.0 ± 1.1) with a better mean grade (2.14 ± .06 vs. 2.7 ± 1.8) compared with the OCP/MDL group. The E2/ANT group exhibited a trend toward improved implantation rates (30.5% vs. 21.1%) and ongoing pregnancy rates per started cycle: 44 out of 117 (37%) versus 17 out of 69 (25%). Poor responders aged <35 years may be treated with the aggressive E(2)/ANT protocol to improve cycle outcomes. Both protocols remain viable options for this group. Adequately powered, randomized clinical comparison appears justified. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Graphite/epoxy composite adapters for the Space Shuttle/Centaur vehicle

NASA Technical Reports Server (NTRS)

Kasper, Harold J.; Ring, Darryl S.

1990-01-01

The decision to launch various NASA satellite and Air Force spacecraft from the Space Shuttle created the need for a high-energy upper stage capable of being deployed from the cargo bay. Two redesigned versions of the Centaur vehicle which employed a graphite/epoxy composite material for the forward and aft adapters were selected. Since this was the first time a graphite/epoxy material was used for Centaur major structural components, the development of the adapters was a major effort. An overview of the composite adapter designs, subcomponent design evaluation test results, and composite adapter test results from a full-scale vehicle structural test is presented.

Finite Element Analysis of Adaptive-Stiffening and Shape-Control SMA Hybrid Composites

NASA Technical Reports Server (NTRS)

Gao, Xiujie; Burton, Deborah; Turner, Travis L.; Brinson, Catherine

2005-01-01

Shape memory alloy hybrid composites with adaptive-stiffening or morphing functions are simulated using finite element analysis. The composite structure is a laminated fiber-polymer composite beam with embedded SMA ribbons at various positions with respect to the neutral axis of the beam. Adaptive stiffening or morphing is activated via selective resistance heating of the SMA ribbons or uniform thermal loads on the beam. The thermomechanical behavior of these composites was simulated in ABAQUS using user-defined SMA elements. The examples demonstrate the usefulness of the methods for the design and simulation of SMA hybrid composites. Keywords: shape memory alloys, Nitinol, ABAQUS, finite element analysis, post-buckling control, shape control, deflection control, adaptive stiffening, morphing, constitutive modeling, user element

Evaluating average and atypical response in radiation effects simulations

NASA Astrophysics Data System (ADS)

Weller, R. A.; Sternberg, A. L.; Massengill, L. W.; Schrimpf, R. D.; Fleetwood, D. M.

2003-12-01

We examine the limits of performing single-event simulations using pre-averaged radiation events. Geant4 simulations show the necessity, for future devices, to supplement current methods with ensemble averaging of device-level responses to physically realistic radiation events. Initial Monte Carlo simulations have generated a significant number of extremal events in local energy deposition. These simulations strongly suggest that proton strikes of sufficient energy, even those that initiate purely electronic interactions, can initiate device response capable in principle of producing single event upset or microdose damage in highly scaled devices.

Preclinical Characterization and Human Microdose Pharmacokinetics of ITMN-8187, a Nonmacrocyclic Inhibitor of the Hepatitis C Virus NS3 Protease.

PubMed

Rajagopalan, Ravi; Pan, Lin; Schaefer, Caralee; Nicholas, John; Lim, Sharlene; Misialek, Shawn; Stevens, Sarah; Hooi, Lisa; Aleskovski, Natalia; Ruhrmund, Donald; Kossen, Karl; Huang, Lea; Yap, Sophia; Beigelman, Leonid; Serebryany, Vladimir; Liu, Jyanwei; Sastry, Srikonda; Seiwert, Scott; Buckman, Brad

2017-01-01

The current paradigm for the treatment of chronic hepatitis C virus (HCV) infection involves combinations of agents that act directly on steps of the HCV life cycle. Here we report the preclinical characteristics of ITMN-8187, a nonmacrocyclic inhibitor of the NS3/4A HCV protease. X-ray crystallographic studies of ITMN-8187 and simeprevir binding to NS3/4A protease demonstrated good agreement between structures. Low nanomolar biochemical potency was maintained against NS3/4A derived from HCV genotypes 1, 2b, 4, 5, and 6. In cell-based potency assays, half-maximal reduction of genotype 1a and 1b HCV replicon RNA was afforded by 11 and 4 nM doses of ITMN-8187, respectively. Combinations of ITMN-8187 with other directly acting antiviral agents in vitro displayed additive antiviral efficacy. A 30-mg/kg of body weight dose of ITMN-8187 administered for 4 days yielded significant viral load reductions through day 5 in a chimeric mouse model of HCV. A 3-mg/kg oral dose administered to rats, dogs, or monkeys yielded concentrations in plasma 16 h after dosing that exceeded the half-maximal effective concentration of ITMN-8187. Human microdose pharmacokinetics showed low intersubject variability and prolonged oral absorption with first-order elimination kinetics compatible with once-daily dosing. These preclinical characteristics compare favorably with those of other NS3/4A inhibitors approved for the treatment of chronic HCV infection. Copyright © 2016 American Society for Microbiology.

Consumable core for manufacture of composite articles and related method

DOEpatents

Taxacher, Glenn Curtis; de Diego, Peter; Gray, Paul Edward; Monaghan, Philip Harold

2017-09-05

Systems, methods and devices adapted to ease manufacture of composite articles (e.g., ceramic composite articles), particularly composite articles which include a hollow feature are disclosed. In one embodiment, a system includes: a consumable core formed to be disposed within an inner portion of a composite precursor, the consumable core adapted to convert into an infiltrant during a manufacturing process and infiltrate the composite precursor.

Fast adaptive composite grid methods on distributed parallel architectures

NASA Technical Reports Server (NTRS)

Lemke, Max; Quinlan, Daniel

1992-01-01

The fast adaptive composite (FAC) grid method is compared with the adaptive composite method (AFAC) under variety of conditions including vectorization and parallelization. Results are given for distributed memory multiprocessor architectures (SUPRENUM, Intel iPSC/2 and iPSC/860). It is shown that the good performance of AFAC and its superiority over FAC in a parallel environment is a property of the algorithm and not dependent on peculiarities of any machine.

Toxicity and Pharmacokinetic Profile for Single-Dose Injection of ABY-029: a Fluorescent Anti-EGFR Synthetic Affibody Molecule for Human Use.

PubMed

Samkoe, Kimberley S; Gunn, Jason R; Marra, Kayla; Hull, Sally M; Moodie, Karen L; Feldwisch, Joachim; Strong, Theresa V; Draney, Daniel R; Hoopes, P Jack; Roberts, David W; Paulsen, Keith; Pogue, Brian W

2017-08-01

ABY-029, a synthetic Affibody peptide, Z03115-Cys, labeled with a near-infrared fluorophore, IRDye® 800CW, targeting epidermal growth factor receptor (EGFR) has been produced under good manufacturing practices for a US Food and Drug Administration-approved first-in-use human study during surgical resection of glioma, as well as other tumors. Here, the pharmacology, phototoxicity, receptor activity, and biodistribution studies of ABY-029 were completed in rats, prior to the intended human use. Male and female Sprague Dawley rats were administered a single intravenous dose of varying concentrations (0, 245, 2449, and 24,490 μg/kg corresponding to 10×, 100×, and 1000× an equivalent human microdose level) of ABY-029 and observed for up to 14 days. Histopathological assessment of organs and tissues, clinical chemistry, and hematology were performed. In addition, pharmacokinetic clearance and biodistribution of ABY-029 were studied in subgroups of the animals. Phototoxicity and ABY-029 binding to human and rat EGFR were assessed in cell culture and on immobilized receptors, respectively. Histopathological assessment and hematological and clinical chemistry analysis demonstrated that single-dose ABY-029 produced no pathological evidence of toxicity at any dose level. No phototoxicity was observed in EGFR-positive and EGFR-negative glioma cell lines. Binding strength and pharmacokinetics of the anti-EGFR Affibody molecules were retained after labeling with the dye. Based on the successful safety profile of ABY-029, the 1000× human microdose 24.5 mg/kg was identified as the no observed adverse effect level following intravenous administration. Conserved binding strength and no observed light toxicity also demonstrated ABY-029 safety for human use.

Lack of Exposure in a First-in-Man Study Due to Aldehyde Oxidase Metabolism: Investigated by Use of 14C-microdose, Humanized Mice, Monkey Pharmacokinetics, and In Vitro Methods.

PubMed

Jensen, Klaus Gjervig; Jacobsen, Anne-Marie; Bundgaard, Christoffer; Nilausen, Dorrit Østergaard; Thale, Zia; Chandrasena, Gamini; Jørgensen, Martin

2017-01-01

Inclusion of a microdose of 14 C-labeled drug in the first-in-man study of new investigational drugs and subsequent analysis by accelerator mass spectrometry has become an integrated part of drug development at Lundbeck. It has been found to be highly informative with regard to investigations of the routes and rates of excretion of the drug and the human metabolite profiles according to metabolites in safety testing guidance and also when additional metabolism-related issues needed to be addressed. In the first-in-man study with the NCE Lu AF09535, contrary to anticipated, surprisingly low exposure was observed when measuring the parent compound using conventional bioanalysis. Parallel accelerator mass spectrometry analysis revealed that the low exposure was almost exclusively attributable to extensive metabolism. The metabolism observed in humans was mediated via a human specific metabolic pathway, whereas an equivalent extent of metabolism was not observed in preclinical species. In vitro, incubation studies in human liver cytosol revealed involvement of aldehyde oxidase (AO) in the biotransformation of Lu AF09535. In vivo, substantially lower plasma exposure of Lu AF09535 was observed in chimeric mice with humanized livers compared with control animals. In addition, Lu AF09535 exhibited very low oral bioavailability in monkeys despite relatively low clearance after intravenous administration in contrast to the pharmacokinetics in rats and dogs, both showing low clearance and high bioavailability. The in vitro and in vivo methods applied were proved useful for identifying and evaluating AO-dependent metabolism. Different strategies to integrate these methods for prediction of in vivo human clearance of AO substrates were evaluated. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Absolute oral bioavailability and pharmacokinetics of canagliflozin: A microdose study in healthy participants.

PubMed

Devineni, Damayanthi; Murphy, Joseph; Wang, Shean-Sheng; Stieltjes, Hans; Rothenberg, Paul; Scheers, Ellen; Mamidi, Rao N V S

2015-07-01

Absolute oral bioavailability of canagliflozin was assessed by simultaneous oral administration with intravenous [(14) C]-canagliflozin microdose infusion in nine healthy men. Pharmacokinetics of canagliflozin, [(14) C]-canagliflozin, and total radioactivity, and safety and tolerability were assessed at prespecified timepoints. On day 1, single-dose oral canagliflozin (300 mg) followed 105 minutes later by intravenous [(14) C]-canagliflozin (10 µg, 200 nCi) was administered. After oral administration, the mean (SD) Cmax of canagliflozin was 2504 (482) ng/mL at 1.5 hours, AUC∞ 17,375 (3555) ng.h/mL, and t1/2 11.6 (0.70) hours. After intravenous administration, the mean (SD) Cmax of unchanged [(14) C]-canagliflozin was 17,605 (6901) ng/mL, AUC∞ 27,100 (10,778) ng.h/mL, Vdss 83.5 (29.2) L, Vdz 119 (41.6) L, and CL 12.2 (3.79) L/h. Unchanged [(14) C]-canagliflozin and metabolites accounted for about 57% and 43% of the plasma total [(14) C] radioactivity AUC∞ , respectively. For total [(14) C] radioactivity, the mean (SD) Cmax was 15,981 (2721) ng-eq/mL, and AUC∞ 53,755 (15,587) ng-eq.h/mL. Renal (34.5% in urine) and biliary (34.1% in feces) excretions were the major elimination pathways for total [(14) C] radioactivity. The absolute oral bioavailability of canagliflozin was 65% (90% confidence interval: 55.41; 76.07). Overall, oral canagliflozin 300 mg coadministered with intravenous [(14) C]-canagliflozin (10 µg) was generally well-tolerated in healthy men, with no treatment-emergent adverse events. © 2014, The American College of Clinical Pharmacology.

Ultrasensitive quantification of the CYP2E1 probe chlorzoxazone and its main metabolite 6-hydroxychlorzoxazone in human plasma using ultra performance liquid chromatography coupled to tandem mass spectrometry after chlorzoxazone microdosing.

PubMed

Witt, Lukas; Suzuki, Yosuke; Hohmann, Nicolas; Mikus, Gerd; Haefeli, Walter E; Burhenne, Jürgen

2016-08-01

Chlorzoxazone is a probe drug to assess cytochrome P450 (CYP) 2E1 activity (phenotyping). If the pharmacokinetics of the probe drug is linear, pharmacologically ineffective doses are sufficient for the purpose of phenotyping and adverse effects can thus be avoided. For this reason, we developed and validated an assay for the ultrasensitive quantification of chlorzoxazone and 6-hydroxychlorzoxazone in human plasma. Plasma (0.5mL) and liquid/liquid partitioning were used for sample preparation. Extraction recoveries ranged between 76 and 93% for both analytes. Extracts were separated within 3min on a Waters BEH C18 Shield 1.7μm UPLC column with a fast gradient consisting of aqueous formic acid and acetonitrile. Quantification was achieved using internal standards labeled with deuterium or (13)C and tandem mass spectrometry in the multiple reaction monitoring mode using negative electrospray ionization, which yielded lower limits of quantification of 2.5pgmL(-1), while maintaining a precision always below 15%. The calibrated concentration ranges were linear for both analytes (2.5-1000pgmL(-1)) with correlation coefficients of >0.99. Within-batch and batch-to-batch precision in the calibrated ranges for both analytes were <15% and <11% and plasma matrix effects always were below 50%. The assay was successfully applied to assess the pharmacokinetics of chlorzoxazone in two human volunteers after administration of single oral doses (2.5-5000μg). This ultrasensitive assay allowed the determination of chlorzoxazone pharmacokinetics for 8h after microdosing of 25μg chlorzoxazone. Copyright © 2016 Elsevier B.V. All rights reserved.

Finite Element Analysis of Adaptive-Stiffening and Shape-Control SMA Hybrid Composites

NASA Technical Reports Server (NTRS)

Gao, Xiu-Jie; Turner, Travis L.; Burton, Deborah; Brinson, L. Catherine

2005-01-01

The usage of shape memory materials has extended rapidly to many fields, including medical devices, actuators, composites, structures and MEMS devices. For these various applications, shape memory alloys (SMAs) are available in various forms: bulk, wire, ribbon, thin film, and porous. In this work, the focus is on SMA hybrid composites with adaptive-stiffening or morphing functions. These composites are created by using SMA ribbons or wires embedded in a polymeric based composite panel/beam. Adaptive stiffening or morphing is activated via selective resistance heating or uniform thermal loads. To simulate the thermomechanical behavior of these composites, a SMA model was implemented using ABAQUS user element interface and finite element simulations of the systems were studied. Several examples are presented which show that the implemented model can be a very useful design and simulation tool for SMA hybrid composites.

Molecular mechanisms of adaptation emerging from the physics and evolution of nucleic acids and proteins.

PubMed

Goncearenco, Alexander; Ma, Bin-Guang; Berezovsky, Igor N

2014-03-01

DNA, RNA and proteins are major biological macromolecules that coevolve and adapt to environments as components of one highly interconnected system. We explore here sequence/structure determinants of mechanisms of adaptation of these molecules, links between them, and results of their mutual evolution. We complemented statistical analysis of genomic and proteomic sequences with folding simulations of RNA molecules, unraveling causal relations between compositional and sequence biases reflecting molecular adaptation on DNA, RNA and protein levels. We found many compositional peculiarities related to environmental adaptation and the life style. Specifically, thermal adaptation of protein-coding sequences in Archaea is characterized by a stronger codon bias than in Bacteria. Guanine and cytosine load in the third codon position is important for supporting the aerobic life style, and it is highly pronounced in Bacteria. The third codon position also provides a tradeoff between arginine and lysine, which are favorable for thermal adaptation and aerobicity, respectively. Dinucleotide composition provides stability of nucleic acids via strong base-stacking in ApG dinucleotides. In relation to coevolution of nucleic acids and proteins, thermostability-related demands on the amino acid composition affect the nucleotide content in the second codon position in Archaea.

Molecular mechanisms of adaptation emerging from the physics and evolution of nucleic acids and proteins

PubMed Central

Goncearenco, Alexander; Ma, Bin-Guang; Berezovsky, Igor N.

2014-01-01

DNA, RNA and proteins are major biological macromolecules that coevolve and adapt to environments as components of one highly interconnected system. We explore here sequence/structure determinants of mechanisms of adaptation of these molecules, links between them, and results of their mutual evolution. We complemented statistical analysis of genomic and proteomic sequences with folding simulations of RNA molecules, unraveling causal relations between compositional and sequence biases reflecting molecular adaptation on DNA, RNA and protein levels. We found many compositional peculiarities related to environmental adaptation and the life style. Specifically, thermal adaptation of protein-coding sequences in Archaea is characterized by a stronger codon bias than in Bacteria. Guanine and cytosine load in the third codon position is important for supporting the aerobic life style, and it is highly pronounced in Bacteria. The third codon position also provides a tradeoff between arginine and lysine, which are favorable for thermal adaptation and aerobicity, respectively. Dinucleotide composition provides stability of nucleic acids via strong base-stacking in ApG dinucleotides. In relation to coevolution of nucleic acids and proteins, thermostability-related demands on the amino acid composition affect the nucleotide content in the second codon position in Archaea. PMID:24371267

Predicting transporter-mediated drug interactions: Commentary on: "Pharmacokinetic evaluation of a drug transporter cocktail consisting of digoxin, furosemide, metformin and rosuvastatin" and "Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A".

PubMed

Zhang, L; Sparreboom, A

2017-04-01

Transporters, expressed in various tissues, govern the absorption, distribution, metabolism, and excretion of drugs, and consequently their inherent safety and efficacy profiles. Drugs may interact with a transporter as a substrate and/or an inhibitor. Understanding transporter-mediated drug-drug interactions (DDIs), in addition to enzyme-mediated DDIs, is an integral part of risk assessment in drug development and regulatory review because the concomitant use of more than one medication in patients is common. © 2016 ASCPT.

Adaptive evolution of seed oil content in angiosperms: accounting for the global patterns of seed oils.

PubMed

Sanyal, Anushree; Decocq, Guillaume

2016-09-09

Studies of the biogeographic distribution of seed oil content in plants are fundamental to understanding the mechanisms of adaptive evolution in plants as seed oil is the primary energy source needed for germination and establishment of plants. However, seed oil content as an adaptive trait in plants is poorly understood. Here, we examine the adaptive nature of seed oil content in 168 angiosperm families occurring in different biomes across the world. We also explore the role of multiple seed traits like seed oil content and composition in plant adaptation in a phylogenetic and nonphylogenetic context. It was observed that the seed oil content in tropical plants (28.4 %) was significantly higher than the temperate plants (24.6 %). A significant relationship between oil content and latitude was observed in three families Papaveraceae, Sapindaceae and Sapotaceae indicating that selective forces correlated with latitude influence seed oil content. Evaluation of the response of seed oil content and composition to latitude and the correlation between seed oil content and composition showed that multiple seed traits, seed oil content and composition contribute towards plant adaptation. Investigation of the presence or absence of phylogenetic signals across 168 angiosperm families in 62 clades revealed that members of seven clades evolved to have high or low seed oil content independently as they did not share a common evolutionary path. The study provides us an insight into the biogeographical distribution and the adaptive role of seed oil content in plants. The study indicates that multiple seed traits like seed oil content and the fatty acid composition of the seed oils determine the fitness of the plants and validate the adaptive hypothesis that seed oil quantity and quality are crucial to plant adaptation.

Optimization of Adaptive Intraply Hybrid Fiber Composites with Reliability Considerations

NASA Technical Reports Server (NTRS)

Shiao, Michael C.; Chamis, Christos C.

1994-01-01

The reliability with bounded distribution parameters (mean, standard deviation) was maximized and the reliability-based cost was minimized for adaptive intra-ply hybrid fiber composites by using a probabilistic method. The probabilistic method accounts for all naturally occurring uncertainties including those in constituent material properties, fabrication variables, structure geometry, and control-related parameters. Probabilistic sensitivity factors were computed and used in the optimization procedures. For actuated change in the angle of attack of an airfoil-like composite shell structure with an adaptive torque plate, the reliability was maximized to 0.9999 probability, with constraints on the mean and standard deviation of the actuation material volume ratio (percentage of actuation composite material in a ply) and the actuation strain coefficient. The reliability-based cost was minimized for an airfoil-like composite shell structure with an adaptive skin and a mean actuation material volume ratio as the design parameter. At a O.9-mean actuation material volume ratio, the minimum cost was obtained.

Acid Response of Bifidobacterium longum subsp. longum BBMN68 Is Accompanied by Modification of the Cell Membrane Fatty Acid Composition.

PubMed

Liu, Songling; Ren, Fazheng; Jiang, Jingli; Zhao, Liang

2016-07-28

The acid response of Bifidobacterium longum subsp. longum BBMN68 has been studied in our previous study. The fab gene, which is supposed to be involved in membrane fatty acid biosynthesis, was demonstrated to be induced in acid response. In order to investigate the relationship between acid response and cell membrane fatty acid composition, the acid adaptation of BBMN68 was assessed and the membrane fatty acid composition at different adaptation conditions was identified. Indeed, the fatty acid composition was influenced by acid adaptation. Our results showed that the effective acid adaptations were accompanied with decrease in the unsaturated to saturated fatty acids ratio (UFA/SFA) and increase in cyclopropane fatty acid (CFA) content, which corresponded to previous studies. Moreover, both effective and non-effective acid adaptation conditions resulted in decrease in the C18:1 cis-9/C18:1 trans-9 ratio, indicating that the C18:1 cis-9/C18:1 trans-9 ratio is associated with acid tolerance response but not with acid adaptation response. Taken together, this study indicated that the UFA/SFA and CFA content of BBMN68 were involved in acid adaptation and the C18:1 cis-9/C18:1 trans-9 ratio was involved in acid tolerance response.

AdaFF: Adaptive Failure-Handling Framework for Composite Web Services

NASA Astrophysics Data System (ADS)

Kim, Yuna; Lee, Wan Yeon; Kim, Kyong Hoon; Kim, Jong

In this paper, we propose a novel Web service composition framework which dynamically accommodates various failure recovery requirements. In the proposed framework called Adaptive Failure-handling Framework (AdaFF), failure-handling submodules are prepared during the design of a composite service, and some of them are systematically selected and automatically combined with the composite Web service at service instantiation in accordance with the requirement of individual users. In contrast, existing frameworks cannot adapt the failure-handling behaviors to user's requirements. AdaFF rapidly delivers a composite service supporting the requirement-matched failure handling without manual development, and contributes to a flexible composite Web service design in that service architects never care about failure handling or variable requirements of users. For proof of concept, we implement a prototype system of the AdaFF, which automatically generates a composite service instance with Web Services Business Process Execution Language (WS-BPEL) according to the users' requirement specified in XML format and executes the generated instance on the ActiveBPEL engine.

Design of smart composite platforms for adaptive trust vector control and adaptive laser telescope for satellite applications

NASA Astrophysics Data System (ADS)

Ghasemi-Nejhad, Mehrdad N.

2013-04-01

This paper presents design of smart composite platforms for adaptive trust vector control (TVC) and adaptive laser telescope for satellite applications. To eliminate disturbances, the proposed adaptive TVC and telescope systems will be mounted on two analogous smart composite platform with simultaneous precision positioning (pointing) and vibration suppression (stabilizing), SPPVS, with micro-radian pointing resolution, and then mounted on a satellite in two different locations. The adaptive TVC system provides SPPVS with large tip-tilt to potentially eliminate the gimbals systems. The smart composite telescope will be mounted on a smart composite platform with SPPVS and then mounted on a satellite. The laser communication is intended for the Geosynchronous orbit. The high degree of directionality increases the security of the laser communication signal (as opposed to a diffused RF signal), but also requires sophisticated subsystems for transmission and acquisition. The shorter wavelength of the optical spectrum increases the data transmission rates, but laser systems require large amounts of power, which increases the mass and complexity of the supporting systems. In addition, the laser communication on the Geosynchronous orbit requires an accurate platform with SPPVS capabilities. Therefore, this work also addresses the design of an active composite platform to be used to simultaneously point and stabilize an intersatellite laser communication telescope with micro-radian pointing resolution. The telescope is a Cassegrain receiver that employs two mirrors, one convex (primary) and the other concave (secondary). The distance, as well as the horizontal and axial alignment of the mirrors, must be precisely maintained or else the optical properties of the system will be severely degraded. The alignment will also have to be maintained during thruster firings, which will require vibration suppression capabilities of the system as well. The innovative platform has been designed to have tip-tilt pointing and simultaneous multi-degree-of-freedom vibration isolation capability for pointing stabilization. Analytical approaches have been employed for determining the loads in the components as well as optimizing the design of the system. The different critical components such as telescope tube struts, flexure joints, and the secondary mirror mount have been designed and analyzed using finite element technique. The Simultaneous Precision Positioning and Vibration Suppression (SPPVS) smart composites platforms for the adaptive TVC and adaptive composite telescope are analogous (e.g., see work by Ghasemi-Nejhad and co-workers [1, 2]), where innovative concepts and control strategies are introduced, and experimental verifications of simultaneous thrust vector control and vibration isolation of satellites were performed. The smart composite platforms function as an active structural interface between the main thruster of a satellite and the satellite structure for the adaptive TVC application and as an active structural interface between the main smart composite telescope and the satellite structure for the adaptive laser communication application. The cascaded multiple feedback loops compensate the hysteresis (for piezoelectric stacks inside the three linear actuators that individually have simultaneous precision positioning and vibration suppression), dead-zone, back-lash, and friction nonlinearities very well, and provide precision and quick smart platform control and satisfactory thrust vector control capability. In addition, for example for the adaptive TVC, the experimental results show that the smart composite platform satisfactorily provided precision and fast smart platform control as well as the satisfactory thrust vector control capability. The vibration controller isolated 97% of the vibration energy due to the thruster firing.

Disturbance and productivity interactions mediate stability of forest composition and structure.

PubMed

O'Connor, Christopher D; Falk, Donald A; Lynch, Ann M; Swetnam, Thomas W; Wilcox, Craig P

2017-04-01

Fire is returning to many conifer-dominated forests where species composition and structure have been altered by fire exclusion. Ecological effects of these fires are influenced strongly by the degree of forest change during the fire-free period. Response of fire-adapted species assemblages to extended fire-free intervals is highly variable, even in communities with similar historical fire regimes. This variability in plant community response to fire exclusion is not well understood; however, ecological mechanisms such as individual species' adaptations to disturbance or competition and underlying site characteristics that facilitate or impede establishment and growth have been proposed as potential drivers of assemblage response. We used spatially explicit dendrochronological reconstruction of tree population dynamics and fire regimes to examine the influence of historical disturbance frequency (a proxy for adaptation to disturbance or competition), and potential site productivity (a proxy for underlying site characteristics) on the stability of forest composition and structure along a continuous ecological gradient of pine, dry mixed-conifer, mesic mixed-conifer, and spruce-fir forests following fire exclusion. While average structural density increased in all forests, species composition was relatively stable in the lowest productivity pine-dominated and highest productivity spruce-fir-dominated sites immediately following fire exclusion and for the next 100 years, suggesting site productivity as a primary control on species composition and structure in forests with very different historical fire regimes. Species composition was least stable on intermediate productivity sites dominated by mixed-conifer forests, shifting from primarily fire-adapted species to competition-adapted, fire-sensitive species within 20 years of fire exclusion. Rapid changes to species composition and stand densities have been interpreted by some as evidence of high-severity fire. We demonstrate that the very different ecological process of fire exclusion can produce similar changes by shifting selective pressures from disturbance-mediated to productivity-mediated controls. Restoring disturbance-adapted species composition and structure to intermediate productivity forests may help to buffer them against projected increasing temperatures, lengthening fire seasons, and more frequent and prolonged moisture stress. Fewer management options are available to promote adaptation in forest assemblages historically constrained by underlying site productivity. © 2016 by the Ecological Society of America.

Device of dispensing micro doses of aqueous solutions of substances onto a carrier and device for carrying out said method

DOEpatents

Ershow, Gennady Moiseevich; Kirillov, Evgenii Vladislavovich; Mirzabekov, Andrei Darievich

1998-01-01

A device for dispensing microdoses of aqueous solutions are provided, whereby the substance is transferred by the free surface end of a rodlike transferring element; the temperature of the transferring element is maintained at essentially the dew point of the ambient air during the transfer. The device may comprise a plate-like base to which are affixed a plurality of rods; the unfixed butt ends of the rods are coplanar. The device further comprises a means for maintaining the temperature of the unfixed butt ends of the rods essentially equal to the dew point of the ambient air during transfer of the aqueous substance.

Diagnostic Microdosing Approach to Study Gemcitabine Resistance

DOE PAGES

Scharadin, Tiffany M.; Zhang, Hongyong; Zimmermann, Maike; ...

2016-09-22

Gemcitabine metabolites cause the termination of DNA replication and induction of apoptosis. In this paper, we determined whether subtherapeutic “microdoses” of gemcitabine are incorporated into DNA at levels that correlate to drug cytotoxicity. A pair of nearly isogenic bladder cancer cell lines differing in resistance to several chemotherapy drugs were treated with various concentrations of 14C-labeled gemcitabine for 4–24 h. Drug incorporation into DNA was determined by accelerator mass spectrometry. A mechanistic analysis determined that RRM2, a DNA synthesis protein and a known resistance factor, substantially mediated gemcitabine toxicity. Finally, these results support gemcitabine levels in DNA as a potentialmore » biomarker of drug cytotoxicity.« less

Diagnostic Microdosing Approach to Study Gemcitabine Resistance

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

Scharadin, Tiffany M.; Zhang, Hongyong; Zimmermann, Maike

Gemcitabine metabolites cause the termination of DNA replication and induction of apoptosis. In this paper, we determined whether subtherapeutic “microdoses” of gemcitabine are incorporated into DNA at levels that correlate to drug cytotoxicity. A pair of nearly isogenic bladder cancer cell lines differing in resistance to several chemotherapy drugs were treated with various concentrations of 14C-labeled gemcitabine for 4–24 h. Drug incorporation into DNA was determined by accelerator mass spectrometry. A mechanistic analysis determined that RRM2, a DNA synthesis protein and a known resistance factor, substantially mediated gemcitabine toxicity. Finally, these results support gemcitabine levels in DNA as a potentialmore » biomarker of drug cytotoxicity.« less

Enhancement of gold recovery using bioleaching from gold concentrate

NASA Astrophysics Data System (ADS)

Choi, S. H.; Cho, K. H.; Kim, B. J.; Choi, N. C.; Park, C. Y.

2012-04-01

The gold in refractory ores is encapsulated as fine particles (sometimes at a molecular level) in the crystal structure of the sulfide (typically pyrite with or without arsenopyrite) matrix. This makes it impossible to extract a significant amount of refractory gold by cyanidation since the cyanide solution cannot penetrate the pyrite/arsenopyrite crystals and dissolve gold particles, even after fine grinding. To effectively extract gold from these ores, an oxidative pretreatment is necessary to break down the sulfide matrix. The most popular methods of pretreatment include nitric acid oxidation, roasting, pressure oxidation and biological oxidation by microorganisms. This study investigated the bioleaching efficiency of Au concentrate under batch experimental conditions (adaptation cycles and chemical composition adaptation) using the indigenous acidophilic bacteria collected from gold mine leachate in Sunsin gold mine, Korea. We conducted the batch experiments at two different chemical composition (CuSO4 and ZnSO4), two different adaptation cycles 1'st (3 weeks) and 2'nd (6 weeks). The results showed that the pH in the bacteria inoculating sample decreased than initial condition and Eh increased. In the chemical composition adaptation case, the leached accumulation content of Fe and Pb was exhibited in CuSO4 adaptation bacteria sample more than in ZnSO4 adaptation bacteria samples, possibly due to pre-adaptation effect on chalcopyrite (CuFeS2) in gold concentrate. And after 21 days on the CuSO4 adaptation cycles case, content of Fe and Pb was appeared at 1'st adaptation bacteria sample(Fe - 1.82 and Pb - 25.81 times per control sample) lower than at 2'nd adaptation bacteria sample(Fe - 2.87 and Pb - 62.05 times per control sample). This study indicates that adaptation chemical composition and adaptation cycles can play an important role in bioleaching of gold concentrate in eco-/economic metallurgy process.

Probabilistic assessment of uncertain adaptive hybrid composites

NASA Technical Reports Server (NTRS)

Shiao, Michael C.; Singhal, Surendra N.; Chamis, Christos C.

1994-01-01

Adaptive composite structures using actuation materials, such as piezoelectric fibers, were assessed probabilistically utilizing intraply hybrid composite mechanics in conjunction with probabilistic composite structural analysis. Uncertainties associated with the actuation material as well as the uncertainties in the regular (traditional) composite material properties were quantified and considered in the assessment. Static and buckling analyses were performed for rectangular panels with various boundary conditions and different control arrangements. The probability density functions of the structural behavior, such as maximum displacement and critical buckling load, were computationally simulated. The results of the assessment indicate that improved design and reliability can be achieved with actuation material.

Validation of ALFIA: a platform for quantifying near-infrared fluorescent images of lymphatic propulsion in humans

NASA Astrophysics Data System (ADS)

Rasmussen, John C.; Bautista, Merrick; Tan, I.-Chih; Adams, Kristen E.; Aldrich, Melissa; Marshall, Milton V.; Fife, Caroline E.; Maus, Erik A.; Smith, Latisha A.; Zhang, Jingdan; Xiang, Xiaoyan; Zhou, Shaohua Kevin; Sevick-Muraca, Eva M.

2011-02-01

Recently, we demonstrated near-infrared (NIR) fluorescence imaging for quantifying real-time lymphatic propulsion in humans following intradermal injections of microdose amounts of indocyanine green. However computational methods for image analysis are underdeveloped, hindering the translation and clinical adaptation of NIR fluorescent lymphatic imaging. In our initial work we used ImageJ and custom MatLab programs to manually identify lymphatic vessels and individual propulsion events using the temporal transit of the fluorescent dye. In addition, we extracted the apparent velocities of contractile propagation and time periods between propulsion events. Extensive time and effort were required to analyze the 6-8 gigabytes of NIR fluorescent images obtained for each subject. To alleviate this bottleneck, we commenced development of ALFIA, an integrated software platform which will permit automated, near real-time analysis of lymphatic function using NIR fluorescent imaging. However, prior to automation, the base algorithms calculating the apparent velocity and period must be validated to verify that they produce results consistent with the proof-of-concept programs. To do this, both methods were used to analyze NIR fluorescent images of two subjects and the number of propulsive events identified, the average apparent velocities, and the average periods for each subject were compared. Paired Student's t-tests indicate that the differences between their average results are not significant. With the base algorithms validated, further development and automation of ALFIA can be realized, significantly reducing the amount of user interaction required, and potentially enabling the near real-time, clinical evaluation of NIR fluorescent lymphatic imaging.

Design of a sensitive grating-based phase contrast mammography prototype (Conference Presentation)

NASA Astrophysics Data System (ADS)

Arboleda Clavijo, Carolina; Wang, Zhentian; Köhler, Thomas; van Stevendaal, Udo; Martens, Gerhard; Bartels, Matthias; Villanueva-Perez, Pablo; Roessl, Ewald; Stampanoni, Marco

2017-03-01

Grating-based phase contrast mammography can help facilitate breast cancer diagnosis, as several research works have demonstrated. To translate this technique to the clinics, it has to be adapted to cover a large field of view within a limited exposure time and with a clinically acceptable radiation dose. This indicates that a straightforward approach would be to install a grating interferometer (GI) into a commercial mammography device. We developed a wave propagation based optimization method to select the most convenient GI designs in terms of phase and dark-field sensitivities for the Philips Microdose Mammography (PMM) setup. The phase sensitivity was defined as the minimum detectable breast tissue electron density gradient, whereas the dark-field sensitivity was defined as its corresponding signal-to-noise Ratio (SNR). To be able to derive sample-dependent sensitivity metrics, a visibility reduction model for breast tissue was formulated, based on previous research works on the dark-field signal and utilizing available Ultra-Small-Angle X-ray Scattering (USAXS) data and the outcomes of measurements on formalin-fixed breast tissue specimens carried out in tube-based grating interferometers. The results of this optimization indicate the optimal scenarios for each metric are different and fundamentally depend on the noise behavior of the signals and the visibility reduction trend with respect to the system autocorrelation length. In addition, since the inter-grating distance is constrained by the space available between the breast support and the detector, the best way we have to improve sensitivity is to count on a small G2 pitch.

Pollinator adaptation and the evolution of floral nectar sugar composition.

PubMed

Abrahamczyk, S; Kessler, M; Hanley, D; Karger, D N; Müller, M P J; Knauer, A C; Keller, F; Schwerdtfeger, M; Humphreys, A M

2017-01-01

A long-standing debate concerns whether nectar sugar composition evolves as an adaptation to pollinator dietary requirements or whether it is 'phylogenetically constrained'. Here, we use a modelling approach to evaluate the hypothesis that nectar sucrose proportion (NSP) is an adaptation to pollinators. We analyse ~ 2100 species of asterids, spanning several plant families and pollinator groups (PGs), and show that the hypothesis of adaptation cannot be rejected: NSP evolves towards two optimal values, high NSP for specialist-pollinated and low NSP for generalist-pollinated plants. However, the inferred adaptive process is weak, suggesting that adaptation to PG only provides a partial explanation for how nectar evolves. Additional factors are therefore needed to fully explain nectar evolution, and we suggest that future studies might incorporate floral shape and size and the abiotic environment into the analytical framework. Further, we show that NSP and PG evolution are correlated - in a manner dictated by pollinator behaviour. This contrasts with the view that a plant necessarily has to adapt its nectar composition to ensure pollination but rather suggests that pollinators adapt their foraging behaviour or dietary requirements to the nectar sugar composition presented by the plants. Finally, we document unexpectedly sucrose-poor nectar in some specialized nectarivorous bird-pollinated plants from the Old World, which might represent an overlooked form of pollinator deception. Thus, our broad study provides several new insights into how nectar evolves and we conclude by discussing why maintaining the conceptual dichotomy between adaptation and constraint might be unhelpful for advancing this field. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Molecular Imaging and Pharmacokinetic Analysis of Carbon-11 Labeled Antisense Oligonucleotide LY2181308 in Cancer Patients

PubMed Central

Saleem, Azeem; Matthews, Julian C.; Ranson, Malcolm; Callies, Sophie; André, Valérie; Lahn, Michael; Dickinson, Claire; Prenant, Christian; Brown, Gavin; McMahon, Adam; Talbot, Denis C.; Jones, Terry; Price, Patricia M.

2011-01-01

Antisense oligonucleotides (ASOs) have potential as anti-cancer agents by specifically modulating genes involved in tumorigenesis. However, little is known about ASO biodistribution and tissue pharmacokinetics (PKs) in humans, including whether sufficient delivery to target tumor tissue may be achieved. In this preliminary study in human subjects, we used combined positron emission and computed tomography (PET-CT) imaging and subsequent modeling analysis of acquired dynamic data, to examine the in vivo biodistribution and PK properties of LY2181308 - a second generation ASO which targets the apoptosis inhibitor protein survivin. Following radiolabeling of LY2181308 with methylated carbon-11 ([11C]methylated-LY2181308), micro-doses (<1mg) were administered to three patients with solid tumors enrolled in a phase I trial. Moderate uptake of [11C]methylated-LY2181308 was observed in tumors (mean=32.5ng*h /mL, per mg administered intravenously). Highest uptake was seen in kidney and liver and lowest uptake was seen in lung and muscle. One patient underwent repeat analysis on day 15 of multiple dose therapy, during administration of LY2181308 (750mg), when altered tissue PKs and a favorable change in biodistribution was seen. [11C]methylated-LY2181308 exposure increased in tumor, lung and muscle, whereas renal and hepatic exposure decreased. This suggests that biological barriers to ASO tumor uptake seen at micro-doses were overcome by therapeutic dosing. In addition, 18F-labeled fluorodeoxyglucose (FDG) scans carried out in the same patient before and after treatment showed up to 40% decreased tumor metabolism. For the development of anti-cancer ASOs, the results provide evidence of LY2181308 tumor tissue delivery and add valuable in vivo pharmacological information. For the development of novel therapeutic agents in general, the study exemplifies the merits of applying PET imaging methodology early in clinical investigations. PMID:21772926

Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose.

PubMed

Ieiri, Ichiro; Nishimura, Chisa; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Chiyoda, Takeshi; Hirota, Tekeshi; Irie, Shin; Shimizu, Hitoshi; Noguchi, Takanori; Yoshida, Kenji; Sugiyama, Yuichi

2011-08-01

In this study, we evaluated (a) the contribution of SLCO1B3 and UGT1A polymorphisms to the pharmacokinetics of telmisartan in two forms, a microdose (MD) and a therapeutic dose (TD); (b) linkage disequilibrium (LD) between UGT1A1 and UGT1A3; and (c) linearity in the pharmacokinetics of telmisartan between the two forms. Telmisartan was orally administered at MD condition (100 μg), and then at TD condition (80 mg) to 33 healthy volunteers whose genotypes were prescreened by DMET Plus. Plasma concentrations of telmisartan and its glucuronide were measured by LC-MS/MS, and population pharmacokinetic analysis was performed. No obvious effect of SLCO1B3 polymorphisms (334T>G, 699G>A, and rs11045585) on the pharmacokinetics of telmisartan was observed. The strong LD between UGT1A1*6 and UGT1A3*4a, and between UGT1A1*28 and UGT1A3*2a were observed. After both MD and TD administration, the mean area under the curve0-24 (±standard deviation) of telmisartan was significantly lower and higher in individuals with the UGT1A3*2a (TD, 1701±970 ng hr/ml; MD, 978±537 pg hr/ml) and *4a variants (TD, 5340±1168; MD, 3145±1093), respectively, compared with those in individuals with UGT1A3*1/*1 (TD, 2969±1456; MD, 1669±726). These results were quantitatively confirmed by population pharmacokinetic analysis. Nonlinearity of the dose-exposure relationship was observed between the MD and TD. The haplotypes of UGT1A3 significantly influenced pharmacokinetics of telmisartan and a strong LD between UGT1A1 genotype and UGT1A3 haplotype was observed. These findings are potentially of pharmacological and toxicological importance to the development and clinical use of drugs.

Relationships between Endogenous Plasma Biomarkers of Constitutive Cytochrome P450 3A Activity and Single-Time-Point Oral Midazolam Microdose Phenotype in Healthy Subjects.

PubMed

Woolsey, Sarah J; Beaton, Melanie D; Choi, Yun-Hee; Dresser, George K; Gryn, Steven E; Kim, Richard B; Tirona, Rommel G

2016-04-01

Due to high basal interindividual variation in cytochrome P450 3A (CYP3A) activity and susceptibility to drug interactions, there has been interest in the application of efficient probe drug phenotyping strategies, as well as endogenous biomarkers for assessment of in vivo CYP3A activity. The biomarkers 4β-hydroxycholesterol (4βHC) and 6β-hydroxycortisol (6βHCL) are sensitive to CYP3A induction and inhibition. However, their utility for the assessment of constitutive CYP3A activity remains uncertain. We investigated whether endogenous plasma biomarkers (4βHC and 6βHCL) are associated with basal CYP3A metabolic activity in healthy subjects assessed by a convenient single-time-point oral midazolam (MDZ) phenotyping strategy. Plasma 4βHC and 6βHCL metabolic ratios (MRs) were analysed in 51 healthy adult participants. CYP3A activity was determined after administration of an oral MDZ microdose (100 μg). Simple linear and multiple linear regression analyses were performed to assess relationships between MDZ oral clearance, biomarkers and subject covariates. Among study subjects, basal MDZ oral clearance, 4βHC and 6βHCL MRs ranged 6.5-, 10- and 13-fold, respectively. Participant age and alcohol consumption were negatively associated with MDZ oral clearance (p = 0.03 and p = 0.045, respectively), while weight and female sex were associated with lower plasma 4βHC MR (p = 0.0003 and p = 0.032, respectively). Neither 4βHC nor 6βHCL MRs were associated with MDZ oral clearance. Plasma 4βHC and 6βHCL MRs do not relate to MDZ single-time-point metabolic phenotype in the assessment of constitutive CYP3A activity among healthy individuals. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Microdose flare-up vs. flexible-multidose GnRH antagonist protocols for poor responder patients who underwent ICSI.

PubMed

Esinler, I

2014-01-01

To compare the performance of microdose flare-up (MF) and flexible-multidose gonadotropin-releasing hormone (GnRH) antagonist protocols in poor responder patients who underwent intracytoplasmic sperm injection (ICSI). One hundred and 12 consecutive patients (217 cycles) suspected to have poor ovarian response were enrolled. Group 1 (MF GnRH agonist group) constituted 64 patients (135 cycles) who underwent MF GnRH agonist protocol. Group 2 (flexible-multidose GnRH antagonist group) constituted 48 patients (82 cycles) who underwent flexible-multidose GnRH antagonist protocol. The duration of stimulation (d) (11.5 +/- 2.1 vs. 10.4 +/- 2.7, p < 0.01) and the total dose of gonadotropin used (IU) (5,892.9 +/- 1,725.7 vs. 4,367.5 +/- 1,582.1, p < 0.05) were significantly lower in Group 2 when compared to Group 1. The numbers of retrieved oocyte-cumulus complexes (4.5 +/- 3.6 vs. 5.9 +/- 4.9, p < 0.05), metaphase II oocytes (3.6 +/- 3.1 vs. 4.9 +/- 4.2, p < 0.05), two pronucleated oocytes (2.6 +/- 2.3 vs. 4.0 +/- 3.4, p < 0.05), the number of available embryos at day 3 (2.6 +/- 2.2 vs. 4.2 +/- 3.2, p < 0.05) and the rate of embryos with > or = seven blastomeres and < 10% fragmentation at day 3 (35.9% vs. 65.1%, p < 0.05) were significantly lower in Group 1 when compared to Group 2. The number of embryos transferred (2.2 +/- 1.3 vs. 2.4 +/- 0.9), the clinical pregnancy per embryo transfer (16.3% vs. 25.8%), and the implantation rate (8.6% vs. 12.2%) were comparable between groups. Although the flexible-multidose GnRH antagonist protocol produced better oocyte and embryo parameters, the clinical pregnancy rate and the implantation rates were comparable between the flexible-multidose GnRH antagonist and MF protocols in poor responder patients.

Executive Function and Adaptive Behavior in Muenke Syndrome.

PubMed

Yarnell, Colin M P; Addissie, Yonit A; Hadley, Donald W; Guillen Sacoto, Maria J; Agochukwu, Nneamaka B; Hart, Rachel A; Wiggs, Edythe A; Platte, Petra; Paelecke, Yvonne; Collmann, Hartmut; Schweitzer, Tilmann; Kruszka, Paul; Muenke, Maximilian

2015-08-01

To investigate executive function and adaptive behavior in individuals with Muenke syndrome using validated instruments with a normative population and unaffected siblings as controls. Participants in this cross-sectional study included individuals with Muenke syndrome (P250R mutation in FGFR3) and their mutation-negative siblings. Participants completed validated assessments of executive functioning (Behavior Rating Inventory of Executive Function [BRIEF]) and adaptive behavior skills (Adaptive Behavior Assessment System, Second Edition [ABAS-II]). Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). For the General Executive Composite scale of the BRIEF, 32.1% of the cohort had scores greater than +1.5 SD, signifying potential clinical significance. For the General Adaptive Composite of the ABAS-II, 28.2% of affected individuals scored in the 3rd-8th percentile of the normative population, and 56.4% were below the average category (<25th percentile). Multiple regression analysis did not identify craniosynostosis as a predictor of BRIEF (P = .70) or ABAS-II scores (P = .70). In the sibling pair analysis, affected siblings performed significantly poorer on the BRIEF General Executive Composite and the ABAS-II General Adaptive Composite. Individuals with Muenke syndrome are at an increased risk for developing adaptive and executive function behavioral changes compared with a normative population and unaffected siblings. Published by Elsevier Inc.

Convergent Aeronautics Solutions (CAS) Showcase Presentation on Mission Adaptive Digital Composite Aerostructure Technologies (MADCAT)

NASA Technical Reports Server (NTRS)

Swei, Sean; Cheung, Kenneth

2016-01-01

This project is to develop a novel aerostructure concept that takes advantage of emerging digital composite materials and manufacturing methods to build high stiffness-to-density ratio, ultra-light structures that can provide mission adaptive and aerodynamically efficient future N+3N+4 air vehicles.

Functional adaptation of long bone extremities involves the localized ``tuning'' of the cortical bone composition; evidence from Raman spectroscopy

NASA Astrophysics Data System (ADS)

Buckley, Kevin; Kerns, Jemma G.; Birch, Helen L.; Gikas, Panagiotis D.; Parker, Anthony W.; Matousek, Pavel; Goodship, Allen E.

2014-11-01

In long bones, the functional adaptation of shape and structure occurs along the whole length of the organ. This study explores the hypothesis that adaptation of bone composition is also site-specific and that the mineral-to-collagen ratio of bone (and, thus, its mechanical properties) varies along the organ's length. Raman spectroscopy was used to map the chemical composition of long bones along their entire length in fine spatial resolution (1 mm), and then biochemical analysis was used to measure the mineral, collagen, water, and sulfated glycosaminoglycan content where site-specific differences were seen. The results show that the mineral-to-collagen ratio of the bone material in human tibiae varies by <5% along the mid-shaft but decreases by >10% toward the flared extremities of the bone. Comparisons with long bones from other large animals (horses, sheep, and deer) gave similar results with bone material composition changing across tens of centimeters. The composition of the bone apatite also varied with the phosphate-to-carbonate ratio decreasing toward the ends of the tibia. The data highlight the complexity of adaptive changes and raise interesting questions about the biochemical control mechanisms involved. In addition to their biological interest, the data provide timely information to researchers developing Raman spectroscopy as a noninvasive tool for measuring bone composition in vivo (particularly with regard to sampling and measurement protocol).

Functional adaptation of long bone extremities involves the localized "tuning" of the cortical bone composition; evidence from Raman spectroscopy.

PubMed

Buckley, Kevin; Kerns, Jemma G; Birch, Helen L; Gikas, Panagiotis D; Parker, Anthony W; Matousek, Pavel; Goodship, Allen E

2014-01-01

In long bones, the functional adaptation of shape and structure occurs along the whole length of the organ. This study explores the hypothesis that adaptation of bone composition is also site-specific and that the mineral-to-collagen ratio of bone (and, thus, its mechanical properties) varies along the organ's length. Raman spectroscopy was used to map the chemical composition of long bones along their entire length in fine spatial resolution (1 mm), and then biochemical analysis was used to measure the mineral, collagen, water, and sulfated glycosaminoglycan content where site-specific differences were seen. The results show that the mineral-to-collagen ratio of the bone material in human tibiae varies by <5% along the mid-shaft but decreases by >10% toward the flared extremities of the bone. Comparisons with long bones from other large animals (horses, sheep, and deer) gave similar results with bone material composition changing across tens of centimeters. The composition of the bone apatite also varied with the phosphate-to-carbonate ratio decreasing toward the ends of the tibia. The data highlight the complexity of adaptive changes and raise interesting questions about the biochemical control mechanisms involved. In addition to their biological interest, the data provide timely information to researchers developing Raman spectroscopy as a noninvasive tool for measuring bone composition in vivo (particularly with regard to sampling and measurement protocol).

Flight Test of Composite Model Reference Adaptive Control (CMRAC) Augmentation Using NASA AirSTAR Infrastructure

NASA Technical Reports Server (NTRS)

Gregory, Irene M.; Gadient, ROss; Lavretsky, Eugene

2011-01-01

This paper presents flight test results of a robust linear baseline controller with and without composite adaptive control augmentation. The flight testing was conducted using the NASA Generic Transport Model as part of the Airborne Subscale Transport Aircraft Research system at NASA Langley Research Center.

Family Cohesion, Adaptability and Composition in Adolescents from Callao, Peru

ERIC Educational Resources Information Center

Villarreal-Zegarra, David; Paz-Jesús, Angel

2017-01-01

The objective of the study was to analyze if there are significant differences between family cohesion and adaptability according to the type of family composition (nuclear, extended, single parent and non-nuclear). This is a non-experimental and empirical research, in which a non-probabilistic, cross-sectional, selective and associative strategy…

Laboratory tests for assessing adaptability and stickiness of dental composites.

PubMed

Rosentritt, Martin; Buczovsky, Sebastian; Behr, Michael; Preis, Verena

2014-09-01

Handling (stickiness, adaptability) of a dental composite does strongly influence quality and success of a dental restoration. The purpose was to develop an in vitro test, which allows for evaluating adaptability and stickiness. 15 dentists were asked for providing individual assessment (school scores 1-6) of five dental composites addressing adaptability and stickiness. Composites were applied with a dental plugger (d=1.8 mm) in a class I cavity (human tooth 17). The tooth was fixed on a force gauge for simultaneous determination of application forces with varying storage (6/25°C) and application temperatures (6/25°C). On basis of these data tensile tests were performed with a dental plugger (application force 1N/2N; v=35 mm/min) on PMMA- or human tooth plates. Composite was dosed onto the tip of the plugger and applied. Application and unplugging was performed once and unplugging forces (UF) and length of the adhesive flags (LAF) were determined at different storage (6/25°C) and application temperatures (25/37°C). Unplugging work (UW) was calculated from area of UF and LAF data. The individual assessment revealed significantly different temperature-dependent application forces between 0.58 N and 2.23 N. Adaptability was assessed between 2.1 and 2.8 school scores. Stickiness varied significantly between the materials (scores: 2-3.2). UW differed significantly between the materials with values between 3.20 N mm and 37.83 N mm. Between PMMA substrate or tooth slides and between 1N or 2N application force only small UW differences were found. The presented in vitro unplugging work allows for an in vitro estimation of the handling parameters adaptability and stickiness. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

In situ simultaneous strain and temperature measurement of adaptive composite materials using a fiber Bragg grating based sensor

NASA Astrophysics Data System (ADS)

Yoon, Hyuk-Jin; Costantini, Daniele M.; Michaud, Veronique; Limberger, Hans G.; Manson, Jan-Anders; Salathe, Rene P.; Kim, Chun-Gon; Hong, Chang-Sun

2005-05-01

An optical fiber sensor to simultaneously measure strain and temperature was designed and embedded into an adaptive composite laminate which exhibits a shape change upon thermal activation. The sensor is formed by two fiber Bragg gratings, which are written in optical fibers with different core dopants. The two gratings were spliced close to each other and a sensing element resulted with Bragg gratings of similar strain sensitivity but different response to temperature. This is due to the dependence of the fiber thermo-optic coefficient on core dopants and relative concentrations. The sensor was tested on an adaptive composite laminate made of unidirectional Kevlar-epoxy pre-preg plies. Several 150μm diameter pre-strained NiTiCu shape memory alloy wires were embedded in the composite laminate together with one fiber sensor. Simultaneous monitoring of strain and temperature during the curing process and activation in an oven was demonstrated.

Development of Mission Adaptive Digital Composite Aerostructure Technologies (MADCAT)

NASA Technical Reports Server (NTRS)

Cheung, Kenneth; Cellucci, Daniel; Copplestone, Grace; Cramer, Nick; Fusco, Jesse; Jenett, Benjamin; Kim, Joseph; Mazhari, Alex; Trinh, Greenfield; Swei, Sean

2017-01-01

This paper reviews the development of the Mission Adaptive Digital Composite Aerostructures Technologies (MADCAT) v0 demonstrator aircraft, utilizing a novel aerostructure concept that combines advanced composite materials manufacturing and fabrication technologies with a discrete construction approach to achieve high stiffness-to-density ratio ultra-light aerostructures that provide versatility and adaptability. This revolutionary aerostructure concept has the potential to change how future air vehicles are designed, built, and flown, with dramatic reductions in weight and manufacturing complexity the number of types of structural components needed to build air vehicles while enabling new mission objectives. We utilize the innovative digital composite materials and discrete construction technologies to demonstrate the feasibility of the proposed aerostructure concept, by building and testing a scaled prototype UAV, MADCAT v0. This paper presents an overview of the design and development of the MADCAT v0 flight demonstrator.

Prism adaptation does not alter configural processing of faces

PubMed Central

Bultitude, Janet H.; Downing, Paul E.; Rafal, Robert D.

2013-01-01

Patients with hemispatial neglect (‘neglect’) following a brain lesion show difficulty responding or orienting to objects and events on the left side of space. Substantial evidence supports the use of a sensorimotor training technique called prism adaptation as a treatment for neglect. Reaching for visual targets viewed through prismatic lenses that induce a rightward shift in the visual image results in a leftward recalibration of reaching movements that is accompanied by a reduction of symptoms in patients with neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Interestingly, prism adaptation can also alter aspects of non-lateralised spatial attention. We previously demonstrated that prism adaptation alters the extent to which neglect patients and healthy participants process local features versus global configurations of visual stimuli. Since deficits in non-lateralised spatial attention are thought to contribute to the severity of neglect symptoms, it is possible that the effect of prism adaptation on these deficits contributes to its efficacy. This study examines the pervasiveness of the effects of prism adaptation on perception by examining the effect of prism adaptation on configural face processing using a composite face task. The composite face task is a persuasive demonstration of the automatic global-level processing of faces: the top and bottom halves of two familiar faces form a seemingly new, unknown face when viewed together. Participants identified the top or bottom halves of composite faces before and after prism adaptation. Sensorimotor adaptation was confirmed by significant pointing aftereffect, however there was no significant change in the extent to which the irrelevant face half interfered with processing. The results support the proposal that the therapeutic effects of prism adaptation are limited to dorsal stream processing. PMID:25110574

Prism adaptation does not alter configural processing of faces.

PubMed

Bultitude, Janet H; Downing, Paul E; Rafal, Robert D

2013-01-01

Patients with hemispatial neglect ('neglect') following a brain lesion show difficulty responding or orienting to objects and events on the left side of space. Substantial evidence supports the use of a sensorimotor training technique called prism adaptation as a treatment for neglect. Reaching for visual targets viewed through prismatic lenses that induce a rightward shift in the visual image results in a leftward recalibration of reaching movements that is accompanied by a reduction of symptoms in patients with neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Interestingly, prism adaptation can also alter aspects of non-lateralised spatial attention. We previously demonstrated that prism adaptation alters the extent to which neglect patients and healthy participants process local features versus global configurations of visual stimuli. Since deficits in non-lateralised spatial attention are thought to contribute to the severity of neglect symptoms, it is possible that the effect of prism adaptation on these deficits contributes to its efficacy. This study examines the pervasiveness of the effects of prism adaptation on perception by examining the effect of prism adaptation on configural face processing using a composite face task. The composite face task is a persuasive demonstration of the automatic global-level processing of faces: the top and bottom halves of two familiar faces form a seemingly new, unknown face when viewed together. Participants identified the top or bottom halves of composite faces before and after prism adaptation. Sensorimotor adaptation was confirmed by significant pointing aftereffect, however there was no significant change in the extent to which the irrelevant face half interfered with processing. The results support the proposal that the therapeutic effects of prism adaptation are limited to dorsal stream processing.

Getting It Out, Getting It Down: Adapting Zoellner's Talk-Write.

ERIC Educational Resources Information Center

Wixon, Vincent; Stone, Patty

The Talk-Write method of teaching college composition, developed by Robert Zoellner, can be adapted for use in secondary and upper elementary classrooms. The method, which focuses on the process of writing, involves teaming students in pairs. One student then talks out a composition, sentence by sentence, while the partner asks questions to draw…

Chameleon Coatings: Adaptive Surfaces to Reduce Friction and Wear in Extreme Environments

NASA Astrophysics Data System (ADS)

Muratore, C.; Voevodin, A. A.

2009-08-01

Adaptive nanocomposite coating materials that automatically and reversibly adjust their surface composition and morphology via multiple mechanisms are a promising development for the reduction of friction and wear over broad ranges of ambient conditions encountered in aerospace applications, such as cycling of temperature and atmospheric composition. Materials selection for these composites is based on extensive study of interactions occurring between solid lubricants and their surroundings, especially with novel in situ surface characterization techniques used to identify adaptive behavior on size scales ranging from 10-10 to 10-4 m. Recent insights on operative solid-lubricant mechanisms and their dependency upon the ambient environment are reviewed as a basis for a discussion of the state of the art in solid-lubricant materials.

Marginal adaptation of composite resins under two adhesive techniques.

PubMed

Dačić, Stefan; Veselinović, Aleksandar M; Mitić, Aleksandar; Nikolić, Marija; Cenić, Milica; Dačić-Simonović, Dragica

2016-11-01

In the present research, different adhesive techniques were used to set up fillings with composite resins. After the application of etch and rinse or self etch adhesive technique, marginal adaptation of composite fillings was estimated by the length of margins without gaps, and by the microretention of resin in enamel and dentin. The study material consisted of 40 extracted teeth. Twenty Class V cavities were treated with 35% phosphorous acid and restored after rinsing by Adper Single Bond 2 and Filtek Ultimate-ASB/FU 3M ESPE composite system. The remaining 20 cavities were restored by Adper Easy One-AEO/FU 3M ESPE composite system. Marginal adaptation of composite fillings was examined using a scanning electron microscope (SEM). The etch and rinse adhesive technique showed a significantly higher percentage of margin length without gaps (in enamel: 92.5%, in dentin: 57.3%), compared with the self-etch technique with lower percentage of margin length without gaps, in enamel 70.4% (p < .001), and in dentin-22.6% (p < .05). In the first technique, microretention was composed of adhesive and hybrid layers as well as resin tugs in interprismatic spaces of enamel, while the dentin microretention was composed of adhesive and hybrid layers with resin tugs in dentin canals. In the second technique, resin tugs were rarely seen and a microgap was dominant along the border of restoration margins. The SEM analysis showed a better marginal adaptation of composite resin to enamel and dentin with better microretention when the etch and rinse adhesive procedure was applied. © 2016 Wiley Periodicals, Inc.

Antifouling composites with self-adaptive controlled release based on an active compound intercalated into layered double hydroxides

NASA Astrophysics Data System (ADS)

Yang, Miaosen; Gu, Lianghua; Yang, Bin; Wang, Li; Sun, Zhiyong; Zheng, Jiyong; Zhang, Jinwei; Hou, Jian; Lin, Cunguo

2017-12-01

This paper reports a novel method to prepare the antifouling composites with properties of self-adaptive controlled release (defined as control the release rate autonomously and adaptively according to the change of environmental conditions) by intercalation of sodium paeonolsilate (PAS) into MgAl and ZnAl layered double hydroxide (LDH) with the molar ratio (M2+/M3+) of 2:1 and 3:1, respectively. The powder X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) confirm the intercalation of PAS into the galleries of LDH. The controlled release behavior triggered by temperature for the PAS-LDH composites has been investigated, and the results show that the release rate of all PAS-LDH composites increases as the increase of temperature. However, the MgAl-PAS-LDH composites (Mg2Al-PAS-LDH and Mg3Al-PAS-LDH) exhibit the increased release rate of 0.21 ppm/°C from 15 to 30 °C in 3.5% NaCl solution, more than three times of the ZnAl-PAS-LDH composites (0.06 ppm/°C), owing to the confined microenvironment influenced by metal types in LDH layers. In addition, a possible diffusion-controlled process with surface diffusion, bulk diffusion and heterogeneous flat surface diffusion has been revealed via fitting four kinetic equations. Moreover, to verify the practical application of the PAS-LDH composites, a model coating denoted as Mg2Al-PAS-LDH coating was fabricated. The release result displays that the release rate increases or decreases as temperature altered at 15 and 25 °C alternately, indicating its self-adaptive controlled release behavior with temperature. Moreover, the superior resistance to the settlement of Ulva spores at 15 and 25 °C was observed for the Mg2Al-PAS-LDH coating, as a result of the controllable release of antifoulant. Therefore, this work provides a facile and effective method for the fabrication of antifouling composites with self-adaptive controlled release behavior in response to temperature, which can be used to prolong the lifetime of antifouling coatings.

ICAN Computer Code Adapted for Building Materials

NASA Technical Reports Server (NTRS)

Murthy, Pappu L. N.

1997-01-01

The NASA Lewis Research Center has been involved in developing composite micromechanics and macromechanics theories over the last three decades. These activities have resulted in several composite mechanics theories and structural analysis codes whose applications range from material behavior design and analysis to structural component response. One of these computer codes, the Integrated Composite Analyzer (ICAN), is designed primarily to address issues related to designing polymer matrix composites and predicting their properties - including hygral, thermal, and mechanical load effects. Recently, under a cost-sharing cooperative agreement with a Fortune 500 corporation, Master Builders Inc., ICAN was adapted to analyze building materials. The high costs and technical difficulties involved with the fabrication of continuous-fiber-reinforced composites sometimes limit their use. Particulate-reinforced composites can be thought of as a viable alternative. They are as easily processed to near-net shape as monolithic materials, yet have the improved stiffness, strength, and fracture toughness that is characteristic of continuous-fiber-reinforced composites. For example, particlereinforced metal-matrix composites show great potential for a variety of automotive applications, such as disk brake rotors, connecting rods, cylinder liners, and other hightemperature applications. Building materials, such as concrete, can be thought of as one of the oldest materials in this category of multiphase, particle-reinforced materials. The adaptation of ICAN to analyze particle-reinforced composite materials involved the development of new micromechanics-based theories. A derivative of the ICAN code, ICAN/PART, was developed and delivered to Master Builders Inc. as a part of the cooperative activity.

Resistance Training: Physiological Responses and Adaptations (Part 3 of 4).

ERIC Educational Resources Information Center

Fleck, Steven J.; Kraemer, William J.

1988-01-01

The physiological responses and adaptations which occur as a result of resistance training, such as cardiovascular responses, serum lipid count, body composition, and neural adaptations are discussed. Changes in the endocrine system are also described. (JL)

Importance of target-mediated drug disposition for small molecules.

PubMed

Smith, Dennis A; van Waterschoot, Robert A B; Parrott, Neil J; Olivares-Morales, Andrés; Lavé, Thierry; Rowland, Malcolm

2018-06-18

Target concentration is typically not considered in drug discovery. However, if targets are expressed at relatively high concentrations and compounds have high affinity, such that most of the drug is bound to its target, in vitro screens can give unreliable information on compound affinity. In vivo, a similar situation will generate pharmacokinetic (PK) profiles that deviate greatly from those normally expected, owing to target binding affecting drug distribution and clearance. Such target-mediated drug disposition (TMDD) effects on small molecules have received little attention and might only become apparent during clinical trials, with the potential for data misinterpretation. TMDD also confounds human microdosing approaches by providing therapeutically unrepresentative PK profiles. Being aware of these phenomena will improve the likelihood of successful drug discovery and development. Copyright © 2018. Published by Elsevier Ltd.

Evolution of the Crop Rhizosphere: Impact of Domestication on Root Exudates in Tetraploid Wheat (Triticum turgidum L.)

PubMed Central

Iannucci, Anna; Fragasso, Mariagiovanna; Beleggia, Romina; Nigro, Franca; Papa, Roberto

2017-01-01

Domestication has induced major genetic changes in crop plants to satisfy human needs and as a consequence of adaptation to agroecosystems. This adaptation might have affected root exudate composition, which can influence the interactions in the rhizosphere. Here, using two different soil types (sand, soil), we provide an original example of the impact of domestication and crop evolution on root exudate composition through metabolite profiling of root exudates for a panel of 10 wheat genotypes that correspond to the key steps in domestication of tetraploid wheat (wild emmer, emmer, durum wheat). Our data show that soil type can dramatically affect the composition of root exudates in the rhizosphere. Moreover, the composition of the rhizosphere metabolites is associated with differences among the genotypes of the wheat domestication groups, as seen by the high heritability of some of the metabolites. Overall, we show that domestication and breeding have had major effects on root exudates in the rhizosphere, which suggests the adaptive nature of these changes. PMID:29326736

Toward a Theory of Adaptive Transfer: Expanding Disciplinary Discussions of "Transfer" in Second-Language Writing and Composition Studies

ERIC Educational Resources Information Center

DePalma, Michael-John; Ringer, Jeffrey M.

2011-01-01

In this paper, we argue that discussions of transfer in L2 writing and composition studies have focused primarily on the reuse of past learning and thus have not adequately accounted for the adaptation of learned writing knowledge in unfamiliar situations. In an effort to expand disciplinary discussions of transfer in L2 writing and composition…

Composition of Estonian Infants' Expressive Lexicon According to the Adaptation of CDI/Words and Gestures

ERIC Educational Resources Information Center

Schults, Astra; Tulviste, Tiia

2016-01-01

The growth rate and the composition of expressive lexicon was studied in a sample of 903 infants between the age of 0;8 and 1;4 whose parents completed the Estonian adaptation of the MacArthur-Bates Communicative Development Inventory-Words and Gestures. As expected, older children had on average larger vocabularies compared to younger children.…

Nanostructural self-organization and dynamic adaptation of metal-polymer tribosystems

NASA Astrophysics Data System (ADS)

Mashkov, Yu. K.

2017-02-01

The results of investigating the effect of nanosize modifiers of a polymer matrix on the nanostructural self-organization of polymer composites and dynamic adaptation of metal-polymer tribosystems, which considerably affect the wear resistance of polymer composite materials, have been analyzed. It has been shown that the physicochemical nanostructural self-organization processes are developed in metal-polymer tribosystems with the formation of thermotropic liquid-crystal structures of the polymer matrix, followed by the transition of the system to the stationary state with a negative feedback that ensures dynamic adaptation of the tribosystem to given operating conditions.

Glassy composition for hermetic seals

DOEpatents

Wilder, Jr., James A.

1980-01-01

The invention relates to a glassy composition adaptable for sealing to aluminum-based alloys to form a hermetically-sealed insulator body. The composition may either be employed as a glass or, after devitrifying heat treatment, as a glass-ceramic.

A novel composite adaptive flap controller design by a high-efficient modified differential evolution identification approach.

PubMed

Li, Nailu; Mu, Anle; Yang, Xiyun; Magar, Kaman T; Liu, Chao

2018-05-01

The optimal tuning of adaptive flap controller can improve adaptive flap control performance on uncertain operating environments, but the optimization process is usually time-consuming and it is difficult to design proper optimal tuning strategy for the flap control system (FCS). To solve this problem, a novel adaptive flap controller is designed based on a high-efficient differential evolution (DE) identification technique and composite adaptive internal model control (CAIMC) strategy. The optimal tuning can be easily obtained by DE identified inverse of the FCS via CAIMC structure. To achieve fast tuning, a high-efficient modified adaptive DE algorithm is proposed with new mutant operator and varying range adaptive mechanism for the FCS identification. A tradeoff between optimized adaptive flap control and low computation cost is successfully achieved by proposed controller. Simulation results show the robustness of proposed method and its superiority to conventional adaptive IMC (AIMC) flap controller and the CAIMC flap controllers using other DE algorithms on various uncertain operating conditions. The high computation efficiency of proposed controller is also verified based on the computation time on those operating cases. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Comparative evaluation of effects of bleaching on color stability and marginal adaptation of discolored direct and indirect composite laminate veneers under in vivo conditions.

PubMed

Jain, Veena; Das, Taposh K; Pruthi, Gunjan; Shah, Naseem; Rajendiran, Suresh

2015-01-01

Change in color and loss of marginal adaptation of tooth colored restorative materials is not acceptable. Bleaching is commonly used for treating discolored teeth. However, the literature is scanty regarding its effect on color and marginal adaptation of direct and indirect composite laminate veneers (CLVs) under in vivo conditions. Purpose of the study was to determine the effect of bleaching on color change and marginal adaptation of direct and indirect CLVs over a period of time when exposed to the oral environment. For this purpose, a total of 14 subjects irrespective of age and sex indicated for CLV restorations on maxillary anterior teeth were selected following the inclusion and exclusion criteria. For each subject, indirect CLVs were fabricated and looted in the first quadrant (Group 1) and direct CLV's (Group 2), were given in the second quadrant. Color change was assessed clinically using intra-oral digital spectrophotometer and marginal adaptation was assessed on epoxy resin replica of the tooth-restoration interface under scanning electron microscope. After 6 months, the subjects underwent a home bleaching regimen for 14 days using 10% carbamide peroxide. The assessment of color change and marginal adaptation was done at 6 months after veneering (0-180 days), immediately after the bleaching regimen (0-194 days) and 3 months after the bleaching regimen (0-284 days). The difference in median color change (ΔE) between the groups was tested using Wilcoxon rank sum test while the median color change with time within the groups was tested using Wilcoxon signed rank test. The difference in the rates of marginal adaptation was tested between the groups using Chi-square/Fisher's exact test. Bleaching led to statistically significant color change at cervical (CE), middle and incisal (IE) regions when direct and indirect composites were compared (P < 0.05). During intra-group comparison, direct CLV's showed significant color change at CE and IE regions when ΔE was compared at 180 days and 284 days (CE 10 vs. CE 30, P = 0.008, IE 10 vs. IE 30, P = 0.003). No significant differences were found when within group comparison was made for indirect laminates. Intergroup comparison between the groups showed significant difference in marginal adaptation at CE margin at all.time points (at baseline, P = 0.005; at 180 days, P = 0.007; 194 days, P = 0.025; at 284 days, P = 0.067). After bleaching, indirect CLVs performed better in terms of color stability whereas direct CLVs performed better in terms of marginal adaptation. Indirect composites should be preferred to direct composites as veneering materials as they have better color stability. Special attention should be given to their marginal adaptation especially in the CE region. Bleaching should be avoided in patients with composite restorations in the mouth.

Human in Vivo pharmacokinetics of [ 14C]Dibenzo[ def,p]chrysene by accelerator mass spectrometry following oral microdosing

DOE PAGES

Madeen, Erin; Corley, Richard A.; Crowell, Susan; ...

2014-11-24

Dibenzo( def,p)chrysene (DBC), (also known as dibenzo[a,l]pyrene), is a high molecular weight polycyclic aromatic hydrocarbon (PAH) found in the environment, including food, produced by the incomplete combustion of hydrocarbons. DBC, classified by IARC as a 2A probable human carcinogen, has a relative potency factor (RPF) in animal cancer models 30-fold higher than benzo[ a]pyrene. No data are available describing the disposition of high molecular weight (>4 rings) PAHs in humans to compare to animal studies. Pharmacokinetics of DBC was determined in 3 female and 6 male human volunteers following oral microdosing (29 ng, 5 nCi) of [ 14C]-DBC. This studymore » was made possible with highly sensitive accelerator mass spectrometry (AMS), capable of detecting [ 14C]-DBC equivalents in plasma and urine following a dose considered of de minimus risk to human health. Plasma and urine were collected over 72 h. The plasma C max was 68.8 ± 44.3 fg·mL –1 with a T max of 2.25 ± 1.04 h. Elimination occurred in two distinct phases: a rapid (α)-phase, with a T 1/2 of 5.8 ± 3.4 h and an apparent elimination rate constant (K el) of 0.17 ± 0.12 fg·h –1, followed by a slower (β)-phase, with a T 1/2 of 41.3 ± 29.8 h and an apparent K el of 0.03 ± 0.02 fg·h –1. In spite of the high degree of hydrophobicity (log Kow of 7.4), DBC was eliminated rapidly in humans, as are most PAHs in animals, compared to other hydrophobic persistent organic pollutants such as, DDT, PCBs and TCDD. Preliminary examination utilizing a new UHPLC-AMS interface, suggests the presence of polar metabolites in plasma as early as 45 min following dosing. Finally, this is the first in vivo data set describing pharmacokinetics in humans of a high molecular weight PAH and should be a valuable addition to risk assessment paradigms.« less

Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[ def,p ]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

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

Madeen, Erin P.; Ognibene, Ted J.; Corley, Richard A.

Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novelmore » “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.« less

Human Micro-Dosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[def,p]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

PubMed Central

Madeen, Erin P.; Ognibene, Ted J.; Corley, Richard A.; McQuistan, Tammie J.; Baird, William M.; Bench, Graham; Turteltaub, Ken W.; Williams, David E.

2017-01-01

Metabolism is a key health risk factor for exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novel “moving wire” interface between ultra-performance liquid chromatography (UPLC) and the AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/−)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Deconjugated and conjugated metabolites were detected in urine with [14C]-(+/−)-DBC-tetraol identified as the major metabolite, 88.7% of which was detected upon enzymatic deconjugation (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6–12 h pool). [14C]-DBC-11,12-diol, of which 94.4% was conjugated and identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6–12 h pool). Parent [14C]-DBC was not detected in the urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose laboratory animal models to human translation for environmental health risk assessment. PMID:27494294

Human in Vivo pharmacokinetics of [ 14C]Dibenzo[ def,p]chrysene by accelerator mass spectrometry following oral microdosing

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

Madeen, Erin; Corley, Richard A.; Crowell, Susan

Dibenzo( def,p)chrysene (DBC), (also known as dibenzo[a,l]pyrene), is a high molecular weight polycyclic aromatic hydrocarbon (PAH) found in the environment, including food, produced by the incomplete combustion of hydrocarbons. DBC, classified by IARC as a 2A probable human carcinogen, has a relative potency factor (RPF) in animal cancer models 30-fold higher than benzo[ a]pyrene. No data are available describing the disposition of high molecular weight (>4 rings) PAHs in humans to compare to animal studies. Pharmacokinetics of DBC was determined in 3 female and 6 male human volunteers following oral microdosing (29 ng, 5 nCi) of [ 14C]-DBC. This studymore » was made possible with highly sensitive accelerator mass spectrometry (AMS), capable of detecting [ 14C]-DBC equivalents in plasma and urine following a dose considered of de minimus risk to human health. Plasma and urine were collected over 72 h. The plasma C max was 68.8 ± 44.3 fg·mL –1 with a T max of 2.25 ± 1.04 h. Elimination occurred in two distinct phases: a rapid (α)-phase, with a T 1/2 of 5.8 ± 3.4 h and an apparent elimination rate constant (K el) of 0.17 ± 0.12 fg·h –1, followed by a slower (β)-phase, with a T 1/2 of 41.3 ± 29.8 h and an apparent K el of 0.03 ± 0.02 fg·h –1. In spite of the high degree of hydrophobicity (log Kow of 7.4), DBC was eliminated rapidly in humans, as are most PAHs in animals, compared to other hydrophobic persistent organic pollutants such as, DDT, PCBs and TCDD. Preliminary examination utilizing a new UHPLC-AMS interface, suggests the presence of polar metabolites in plasma as early as 45 min following dosing. Finally, this is the first in vivo data set describing pharmacokinetics in humans of a high molecular weight PAH and should be a valuable addition to risk assessment paradigms.« less

A double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]-basimglurant and absolute bioavailability after oral administration and concomitant intravenous microdose administration of [13C6]-labeled basimglurant in humans.

PubMed

Guerini, Elena; Schadt, Simone; Greig, Gerard; Haas, Ruth; Husser, Christophe; Zell, Manfred; Funk, Christoph; Hartung, Thomas; Gloge, Andreas; Mallalieu, Navita L

2017-02-01

1. The emerging technique of employing intravenous microdose administration of an isotope tracer concomitantly with an [ 14 C]-labeled oral dose was used to characterize the disposition and absolute bioavailability of a novel metabotropic glutamate 5 (mGlu5) receptor antagonist under clinical development for major depressive disorder (MDD). 2. Six healthy volunteers received a single 1 mg [ 12 C/ 14 C]-basimglurant (2.22 MBq) oral dose and a concomitant i.v. tracer dose of 100 μg of [ 13 C 6 ]-basimglurant. Concentrations of [ 12 C]-basimglurant and the stable isotope [ 13 C 6 ]-basimglurant were determined in plasma by a specific LC/MS-MS method. Total [ 14 C] radioactivity was determined in whole blood, plasma, urine and feces by liquid scintillation counting. Metabolic profiling was conducted in plasma, urine, blood cell pellet and feces samples. 3. The mean absolute bioavailability after oral administration (F) of basimglurant was ∼67% (range 45.7-77.7%). The major route of [ 14 C]-radioactivity excretion, primarily in form of metabolites, was in urine (mean recovery 73.4%), with the remainder excreted in feces (mean recovery 26.5%). The median t max for [ 12 C]-basimglurant after the oral administration was 0.71 h (range 0.58-1.00) and the mean terminal half-life was 77.2 ± 38.5 h. Terminal half-life for the [ 14 C]-basimglurant was 178 h indicating presence of metabolites with a longer terminal half-life. Five metabolites were identified with M1-Glucuronide as major and the others in trace amounts. There was minimal binding of drug to RBCs. IV pharmacokinetics was characterized with a mean ± SD CL of 11.8 ± 7.4 mL/h and a Vss of 677 ± 229 L. 4. The double-tracer technique used in this study allowed to simultaneously characterize the absolute bioavailability and disposition characteristics of the new oral molecular entity in a single study.

Adaptation of model proteins from cold to hot environments involves continuous and small adjustments of average parameters related to amino acid composition.

PubMed

De Vendittis, Emmanuele; Castellano, Immacolata; Cotugno, Roberta; Ruocco, Maria Rosaria; Raimo, Gennaro; Masullo, Mariorosario

2008-01-07

The growth temperature adaptation of six model proteins has been studied in 42 microorganisms belonging to eubacterial and archaeal kingdoms, covering optimum growth temperatures from 7 to 103 degrees C. The selected proteins include three elongation factors involved in translation, the enzymes glyceraldehyde-3-phosphate dehydrogenase and superoxide dismutase, the cell division protein FtsZ. The common strategy of protein adaptation from cold to hot environments implies the occurrence of small changes in the amino acid composition, without altering the overall structure of the macromolecule. These continuous adjustments were investigated through parameters related to the amino acid composition of each protein. The average value per residue of mass, volume and accessible surface area allowed an evaluation of the usage of bulky residues, whereas the average hydrophobicity reflected that of hydrophobic residues. The specific proportion of bulky and hydrophobic residues in each protein almost linearly increased with the temperature of the host microorganism. This finding agrees with the structural and functional properties exhibited by proteins in differently adapted sources, thus explaining the great compactness or the high flexibility exhibited by (hyper)thermophilic or psychrophilic proteins, respectively. Indeed, heat-adapted proteins incline toward the usage of heavier-size and more hydrophobic residues with respect to mesophiles, whereas the cold-adapted macromolecules show the opposite behavior with a certain preference for smaller-size and less hydrophobic residues. An investigation on the different increase of bulky residues along with the growth temperature observed in the six model proteins suggests the relevance of the possible different role and/or structure organization played by protein domains. The significance of the linear correlations between growth temperature and parameters related to the amino acid composition improved when the analysis was collectively carried out on all model proteins.

Conception et optimisation d'une peau en composite pour une aile adaptative =

NASA Astrophysics Data System (ADS)

Michaud, Francois

Les preoccupations economiques et environnementales constituent des enjeux majeurs pour le developpement de nouvelles technologies en aeronautique. C'est dans cette optique qu'est ne le projet MDO-505 intitule Morphing Architectures and Related Technologies for Wing Efficiency Improvement. L'objectif de ce projet vise a concevoir une aile adaptative active servant a ameliorer sa laminarite et ainsi reduire la consommation de carburant et les emissions de l'avion. Les travaux de recherche realises ont permis de concevoir et optimiser une peau en composite adaptative permettant d'assurer l'amelioration de la laminarite tout en conservant son integrite structurale. D'abord, une methode d'optimisation en trois etapes fut developpee avec pour objectif de minimiser la masse de la peau en composite en assurant qu'elle s'adapte par un controle actif de la surface deformable aux profils aerodynamiques desires. Le processus d'optimisation incluait egalement des contraintes de resistance, de stabilite et de rigidite de la peau en composite. Suite a l'optimisation, la peau optimisee fut simplifiee afin de faciliter la fabrication et de respecter les regles de conception de Bombardier Aeronautique. Ce processus d'optimisation a permis de concevoir une peau en composite dont les deviations ou erreurs des formes obtenues etaient grandement reduites afin de repondre au mieux aux profils aerodynamiques optimises. Les analyses aerodynamiques realisees a partir de ces formes ont predit de bonnes ameliorations de la laminarite. Par la suite, une serie de validations analytiques fut realisee afin de valider l'integrite structurale de la peau en composite suivant les methodes generalement utilisees par Bombardier Aeronautique. D'abord, une analyse comparative par elements finis a permis de valider une rigidite equivalente de l'aile adaptative a la section d'aile d'origine. Le modele par elements finis fut par la suite mis en boucle avec des feuilles de calcul afin de valider la stabilite et la resistance de la peau en composite pour les cas de chargement aerodynamique reels. En dernier lieu, une analyse de joints boulonnes fut realisee en utilisant un outil interne nomme LJ 85 BJSFM GO.v9 developpe par Bombardier Aeronautique. Ces analyses ont permis de valider numeriquement l'integrite structurale de la peau de composite pour des chargements et des admissibles de materiaux aeronautiques typiques.

The influence of FRCs reinforcement on marginal adaptation of CAD/CAM composite resin endocrowns after simulated fatigue loading.

PubMed

Rocca, Giovanni Tommaso; Saratti, Carlo Massimo; Poncet, Antoine; Feilzer, Albert J; Krejci, Ivo

2016-05-01

To evaluate the marginal adaptation of endodontically treated molars restored with CAD/CAM composite resin endocrowns either with or without reinforcement by fibre reinforced composites (FRCs), used in different configurations. 32 human endodontically treated molars were cut 2 mm over the CEJ. Two interproximal boxes were created with the margins located 1 mm below the CEJ (distal box) and 1 mm over the CEJ (mesial box). All specimens were divided in four groups (n = 8). The pulp chamber was filled with: group 1 (control), hybrid resin composite (G-aenial Posterior, GC); group 2, as group 1 but covered by 3 meshes of E-glass fibres (EverStick NET, Stick Tech); group 3, FRC resin (EverX Posterior, GC); group 4, as group 3 but covered by 3 meshes of E-glass fibres. The crowns of all teeth were restored with CAD/CAM composite resin endocrowns (LAVA Ultimate, 3M). All specimens were thermo-mechanically loaded in a computer-controlled chewing machine (600,000 cycles, 1.6 Hz, 49 N and simultaneously 1500 thermo-cycles, 60 s, 5-55 °C). Marginal analysis before and after the loading was carried out on epoxy replicas by SEM at 200× magnification. For all the groups, the percentage values of perfect marginal adaptation after loading were always significantly lower than before loading (p < 0.05). The marginal adaptation before and after loading was not significantly different between the experimental groups (p > 0.05). Within the limitations of this in vitro study, the use of FRCs to reinforce the pulp chamber of devitalized molars restored with CAD/CAM composite resin restorations did not significantly influenced their marginal quality.

Initial Trial using Embedded Fibre Bragg Gratings for Distributed Strain Monitoring in a Shape Adaptive Composite Foil

DTIC Science & Technology

2012-02-01

available for interrogation. Although commercially available fibre Bragg grating ( FBG ) sensors have emerged in the marketplace over the past decade...the results from a preliminary trial investigating the feasibility of using embedded FBG arrays in a shape adaptive composite foil to characterise...The response from the FBG sensors was also monitored during fabrication of the foil during the resin infusion and curing stages of the process

Building team adaptive capacity: the roles of sensegiving and team composition.

PubMed

Randall, Kenneth R; Resick, Christian J; DeChurch, Leslie A

2011-05-01

The current study draws on motivated information processing in groups theory to propose that leadership functions and composition characteristics provide teams with the epistemic and social motivation needed for collective information processing and strategy adaptation. Three-person teams performed a city management decision-making simulation (N=74 teams; 222 individuals). Teams first managed a simulated city that was newly formed and required growth strategies and were then abruptly switched to a second simulated city that was established and required revitalization strategies. Consistent with hypotheses, external sensegiving and team composition enabled distinct aspects of collective information processing. Sensegiving prompted the emergence of team strategy mental models (i.e., cognitive information processing); psychological collectivism facilitated information sharing (i.e., behavioral information processing); and cognitive ability provided the capacity for both the cognitive and behavioral aspects of collective information processing. In turn, team mental models and information sharing enabled reactive strategy adaptation.

Programmable snapping composites with bio-inspired architecture.

PubMed

Schmied, Jascha U; Le Ferrand, Hortense; Ermanni, Paolo; Studart, André R; Arrieta, Andres F

2017-03-13

The development of programmable self-shaping materials enables the onset of new and innovative functionalities in many application fields. Commonly, shape adaptation is achieved by exploiting diffusion-driven swelling or nano-scale phase transition, limiting the change of shape to slow motion predominantly determined by the environmental conditions and/or the materials specificity. To address these shortcomings, we report shape adaptable programmable shells that undergo morphing via a snap-through mechanism inspired by the Dionaea muscipula leaf, known as the Venus fly trap. The presented shells are composite materials made of epoxy reinforced by stiff anisotropic alumina micro-platelets oriented in specific directions. By tailoring the microstructure via magnetically-driven alignment of the platelets, we locally tune the pre-strain and stiffness anisotropy of the composite. This novel approach enables the fabrication of complex shapes showing non-orthotropic curvatures and stiffness gradients, radically extending the design space when compared to conventional long-fibre reinforced multi-stable composites. The rare combination of large stresses, short actuation times and complex shapes, results in hinge-free artificial shape adaptable systems with large design freedom for a variety of morphing applications.

Adaptive composites with embedded NiTiCu wires

NASA Astrophysics Data System (ADS)

Balta-Neumann, J. Antonio; Michaud, Veronique J.; Parlinska, Magdelena; Gotthardt, Rolf; Manson, Jan-Anders E.

2001-07-01

Adaptive composites have been produced by embedding prestrained shape memory alloy (SMA) wires into an epoxy matrix, reinforced with aramid fibers. These materials demonstrate attractive effects such as shape change or a shift in the vibration frequency upon activation. When heated above their transformation temperature, the wires' strain recovery is confined, and recovery stresses are generated. As a result, if the wires are placed along the neutral axis of a composite beam, a shift in resonance vibration frequency can be observed. To optimize the design of such composites, the matrix - SMA wire interfacial shear strength has been analyzed with the pull out testing technique. It is shown that the nature of the wire surface influences the interfacial shear strength, and that satisfactory results are obtained for SMA wires with a thin oxide layer. Composite samples consisting of two different types of pre- strained NiTiCu wires embedded in either pure epoxy matrix or Kevlar-epoxy matrix were produced. The recovery force and vibration response of composites were measured in a clamped-clamped configuration, to assess the effect of wire type and volume fraction. The results are highly reproducible in all cases with a narrow hysteresis loop, which makes NiTiCu wires good candidates for adaptive composites. The recovery forces increase with the volume fraction of the embedded wires, are higher when the wires are embedded in a low CTE matrix and, at a given temperature, are higher when the wire transformation temperature is lower.

Characterization of a highly hop-resistant Lactobacillus brevis strain lacking hop transport.

PubMed

Behr, Jürgen; Gänzle, Michael G; Vogel, Rudi F

2006-10-01

Resistance to hops is a prerequisite for lactic acid bacteria to spoil beer. In this study we analyzed mechanisms of hop resistance of Lactobacillus brevis at the metabolism, membrane physiology, and cell wall composition levels. The beer-spoiling organism L. brevis TMW 1.465 was adapted to high concentrations of hop compounds and compared to a nonadapted strain. Upon adaptation to hops the metabolism changed to minimize ethanol stress. Fructose was used predominantly as a carbon source by the nonadapted strain but served as an electron acceptor upon adaptation to hops, with concomitant formation of acetate instead of ethanol. Furthermore, hop adaptation resulted in higher levels of lipoteichoic acids (LTA) incorporated into the cell wall and altered composition and fluidity of the cytoplasmic membrane. The putative transport protein HitA and enzymes of the arginine deiminase pathway were overexpressed upon hop adaptation. HorA was not expressed, and the transport of hop compounds from the membrane to the extracellular space did not account for increased resistance to hops upon adaptation. Accordingly, hop resistance is a multifactorial dynamic property, which can develop during adaptation. During hop adaptation, arginine catabolism contributes to energy and generation of the proton motive force until a small fraction of the population has established structural improvements. This acquired hop resistance is energy independent and involves an altered cell wall composition. LTA shields the organism from accompanying stresses and provides a reservoir of divalent cations, which are otherwise scarce as a result of their complexation by hop acids. Some of the mechanisms involved in hop resistance overlap with mechanisms of pH resistance and ethanol tolerance and as a result enable beer spoilage by L. brevis.

Radiation effects in advanced microelectronics technologies

NASA Astrophysics Data System (ADS)

Johnston, A. H.

1998-06-01

The pace of device scaling has increased rapidly in recent years. Experimental CMOS devices have been produced with feature sizes below 0.1 /spl mu/m, demonstrating that devices with feature sizes between 0.1 and 0.25 /spl mu/m will likely be available in mainstream technologies after the year 2000. This paper discusses how the anticipated changes in device dimensions and design are likely to affect their radiation response in space environments. Traditional problems, such as total dose effects, SEU and latchup are discussed, along with new phenomena. The latter include hard errors from heavy ions (microdose and gate-rupture errors), and complex failure modes related to advanced circuit architecture. The main focus of the paper is on commercial devices, which are displacing hardened device technologies in many space applications. However, the impact of device scaling on hardened devices is also discussed.

Adaptive, Active and Multifunctional Composite and Hybrid Materials Program: Composite and Hybrid Materials ERA

DTIC Science & Technology

2014-04-01

Microvascular Self - Healing Composites Mechanical Evaluation ................................................................................11...Thermoplastic SMP Foam Microstructure- Mechanical Stress-Strain Relationships 2.2.2 Microvascular Self - Healing Composites Mechanical Evaluation 2.3.1 Z...materials, and embedded sensory and circulatory systems. Damage repair of torn or injured tissue was demonstrated by the use of self - healing polymer

An adaptive DPCM algorithm for predicting contours in NTSC composite video signals

NASA Astrophysics Data System (ADS)

Cox, N. R.

An adaptive DPCM algorithm is proposed for encoding digitized National Television Systems Committee (NTSC) color video signals. This algorithm essentially predicts picture contours in the composite signal without resorting to component separation. The contour parameters (slope thresholds) are optimized using four 'typical' television frames that have been sampled at three times the color subcarrier frequency. Three variations of the basic predictor are simulated and compared quantitatively with three non-adaptive predictors of similar complexity. By incorporating a dual-word-length coder and buffer memory, high quality color pictures can be encoded at 4.0 bits/pel or 42.95 Mbit/s. The effect of channel error propagation is also investigated.

Adaptable piezoelectric hemispherical composite strips using a scalable groove technique for a self-powered muscle monitoring system.

PubMed

Alluri, Nagamalleswara Rao; Vivekananthan, Venkateswaran; Chandrasekhar, Arunkumar; Kim, Sang-Jae

2018-01-18

Contrary to traditional planar flexible piezoelectric nanogenerators (PNGs), highly adaptable hemispherical shape-flexible piezoelectric composite strip (HS-FPCS) based PNGs are required to harness/measure non-linear surface motions. Therefore, a feasible, cost-effective and less-time consuming groove technique was developed to fabricate adaptable HS-FPCSs with multiple lengths. A single HS-CSPNG generates 130 V/0.8 μA and can also work as a self-powered muscle monitoring system (SP-MMS) to measure maximum human body part movements, i.e., spinal cord, throat, jaw, elbow, knee, foot stress, palm hand/finger force and inhale/exhale breath conditions at a time or at variable time intervals.

Marginal adaptation of full-coverage CAD/CAM restorations: in vitro study using a non-destructive method.

PubMed

Romeo, E; Iorio, M; Storelli, S; Camandona, M; Abati, S

2009-03-01

Marginal fit of full-coverage crowns is a major requirement for long term success of this kind of restorations. The purpose of the study was to verify the marginal adaptation of computer assisted design (CAD)/computer assisted manufacturing (CAM) crowns on prepared teeth and on plaster dies. Four couples of materials: zirconia-ceramic veneering (DC-Zircon, DCS Dental, Allschwill, CH/Cercon S, Degussa, DeguDent GmbH, Hanau, Germany), fiber-reinforced composite-composite veneering (DC-Tell, DCS Dental/Gradia, GC Europe, LEuven, Belgium), titanium-ceramic veneering (DC Titan, DCS Dental/Tikrom, Orotig, Verona, Italy) and titanium-composite veneering (DC Titan, DCS Dental/Gradia, GC Europe) were evaluated following the guidelines provided by ADA specific #8. Five crowns were fabricated for each material. Marginal gap values were measured at four points (0 degrees, 90 degrees, 180 degrees and 270 degrees starting from the centre of the vestibular surface) around the finishing line, on prepared teeth and on plaster dies at each step of the fabrication process. Digital photographs were taken at each reference point and a computer software was used to measure the amount of marginal discrepancy in microm. Statistical analysis was performed using t test at 95 percent confidence interval. All the tested materials, except for fiber-reinforced composite, show a marginal adaptation within the limits of ADA specification (25-40 microm). The application of veneering material causes decay in marginal adaptation, except for fiber-reinforced composite. Within the limitations of this study, it was concluded that marginal fit of CAD/CAM restoration is within the limits considered clinically acceptable by ADA specification #8. From the results of this in vitro study, it can be stated that CAD/CAM crowns produced with DCS system show a marginal adaptation within the limits of ADA specific #8, therefore milled CAD/CAM crowns can be considered a good alternative to more traditional waxing-investing-casting technique.

Collector surface for a microwave tube comprising a carbon-bonded carbon-fiber composite

DOEpatents

Lauf, Robert J.; McMillan, April D.; Johnson, Arvid C.; Moorhead, Arthur J.

1998-01-01

In a microwave tube, an improved collector surface coating comprises a porous carbon composite material, preferably a carbon-bonded carbon fiber composite having a bulk density less than about 2 g/cc. Installation of the coating is readily adaptable as part of the tube manufacturing process.

Lipid remodelling in the reef-building honeycomb worm, Sabellaria alveolata, reflects acclimation and local adaptation to temperature

PubMed Central

Muir, Anna P.; Nunes, Flavia L. D.; Dubois, Stanislas F.; Pernet, Fabrice

2016-01-01

Acclimation and adaptation, which are key to species survival in a changing climate, can be observed in terms of membrane lipid composition. Remodelling membrane lipids, via homeoviscous adaptation (HVA), counteracts membrane dysfunction due to temperature in poikilotherms. In order to assess the potential for acclimation and adaptation in the honeycomb worm, Sabellaria alveolata, a reef-building polychaete that supports high biodiversity, we carried out common-garden experiments using individuals from along its latitudinal range. Individuals were exposed to a stepwise temperature increase from 15 °C to 25 °C and membrane lipid composition assessed. Our results suggest that S. alveolata was able to acclimate to higher temperatures, as observed by a decrease in unsaturation index and 20:5n-3. However, over the long-term at 25 °C, lipid composition patterns are not consistent with HVA expectations and suggest a stress response. Furthermore, unsaturation index of individuals from the two coldest sites were higher than those from the two warmest sites, with individuals from the thermally intermediate site being in-between, likely reflecting local adaptation to temperature. Therefore, lipid remodelling appears limited at the highest temperatures in S. alveolata, suggesting that individuals inhabiting warm environments may be close to their upper thermal tolerance limits and at risk in a changing climate. PMID:27762300

Cognitive and adaptive advantages of growth hormone treatment in children with Prader-Willi syndrome.

PubMed

Dykens, Elisabeth M; Roof, Elizabeth; Hunt-Hawkins, Hailee

2017-01-01

People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient groups, have not been well studied in PWS. Study 1 included 96 children and youth with PWS aged 4-21 years who naturalistically varied in their exposures to GHT. Controlling for socioeconomic status, analyses compared cognitive and adaptive behavior test scores across age-matched treatment naïve versus growth hormone treated children. Study II assessed if age of treatment initiation or treatment duration was associated with subsequent cognition or adaptive behavior in 127, 4- to 21-year olds with PWS. Study III longitudinally examined cognitive and adaptive behavior in 168 participants who were either consistently on versus off GHT for up to 4-5 years. Compared to the treatment naïve group, children receiving GHT had significantly higher Verbal and Composite IQs, and adaptive communication and daily living skills. Children who began treatment before 12 months of age had higher Nonverbal and Composite IQs than children who began treatment between 1 and 5 years of age. Longitudinally, the groups differed in their intercepts, but not slopes, with each group showing stable IQ and adaptive behavior scores over time. Cognitive and adaptive advantages should be considered an ancillary benefit and additional justification for GHT in people with PWS. Future efforts need to target apparent socioeconomic inequities in accessing GHT in the PWS population. © 2016 Association for Child and Adolescent Mental Health.

Cognitive and adaptive advantages of growth hormone treatment in children with Prader-Willi syndrome

PubMed Central

Dykens, Elisabeth M; Roof, Elizabeth; Hunt-Hawkins, Hailee

2016-01-01

Background People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient groups, have not been well studied in PWS. Methods Study 1 included 96 children and youth with PWS aged 4 to 21 years who naturalistically varied in their exposures to GHT. Controlling for socio-economic status, analyses compared cognitive and adaptive behavior test scores across age-matched treatment naïve versus growth hormone treated children. Study II assessed if age of treatment initiation or treatment duration was associated with subsequent cognition or adaptive behavior in 127, 4- to-21 year olds with PWS. Study III longitudinally examined cognitive and adaptive behavior in 168 participants who were either consistently on versus off GHT for up to 4–5 years. Results Compared to the treatment naïve group, children receiving growth hormone treatment had significantly higher Verbal and Composite IQs, and adaptive communication and daily living skills. Children who began treatment before 12 months of age had higher Nonverbal and Composite IQs than children who began treatment between 1 to 5 years of age. Longitudinally, the groups differed in their intercepts, but not slopes, with each group showing stable IQ and adaptive behavior scores over time. Conclusions Cognitive and adaptive advantages should be considered an ancillary benefit and additional justification for GHT in people with PWS. Future efforts need to target apparent socio-economic inequities in accessing GHT in the PWS population. PMID:27481444

Comparison of the marginal adaptation of direct and indirect composite inlay restorations with optical coherence tomography.

PubMed

Türk, Ayşe Gözde; Sabuncu, Metin; Ünal, Sena; Önal, Banu; Ulusoy, Mübin

2016-01-01

The purpose of the study was to use the photonic imaging modality of optical coherence tomography (OCT) to compare the marginal adaptation of composite inlays fabricated by direct and indirect techniques. Class II cavities were prepared on 34 extracted human molar teeth. The cavities were randomly divided into two groups according to the inlay fabrication technique. The first group was directly restored on cavities with a composite (Esthet X HD, Dentsply, Germany) after isolating. The second group was indirectly restored with the same composite material. Marginal adaptations were scanned before cementation with an invisible infrared light beam of OCT (Thorlabs), allowing measurement in 200 µm intervals. Restorations were cemented with a self-adhesive cement resin (SmartCem2, Dentsply), and then marginal adaptations were again measured with OCT. Mean values were statistically compared by using independent-samples t-test and paired samples t-test (p<0.05), before and after cementation. Direct inlays presented statistically smaller marginal discrepancy values than indirect inlays, before (p=0.00001442) and after (p=0.00001466) cementation. Marginal discrepancy values were increased for all restorations after cementation (p=0.00008839, p=0.000000952 for direct and indirect inlays, respectively). The mean marginal discrepancy value of the direct group increased from 56.88±20.04 µm to 91.88±31.7 µm, whereas the indirect group increased from 107.54±35.63 µm to 170.29±54.83 µm. Different techniques are available to detect marginal adaptation of restorations, but the OCT system can give quantitative information about resin cement thickness and its interaction between tooth and restoration in a nondestructive manner. Direct inlays presented smaller marginal discrepancy than indirect inlays. The marginal discrepancy values were increased for all restorations that refer to cement thickness after cementation.

Dynamic optimization of metabolic networks coupled with gene expression.

PubMed

Waldherr, Steffen; Oyarzún, Diego A; Bockmayr, Alexander

2015-01-21

The regulation of metabolic activity by tuning enzyme expression levels is crucial to sustain cellular growth in changing environments. Metabolic networks are often studied at steady state using constraint-based models and optimization techniques. However, metabolic adaptations driven by changes in gene expression cannot be analyzed by steady state models, as these do not account for temporal changes in biomass composition. Here we present a dynamic optimization framework that integrates the metabolic network with the dynamics of biomass production and composition. An approximation by a timescale separation leads to a coupled model of quasi-steady state constraints on the metabolic reactions, and differential equations for the substrate concentrations and biomass composition. We propose a dynamic optimization approach to determine reaction fluxes for this model, explicitly taking into account enzyme production costs and enzymatic capacity. In contrast to the established dynamic flux balance analysis, our approach allows predicting dynamic changes in both the metabolic fluxes and the biomass composition during metabolic adaptations. Discretization of the optimization problems leads to a linear program that can be efficiently solved. We applied our algorithm in two case studies: a minimal nutrient uptake network, and an abstraction of core metabolic processes in bacteria. In the minimal model, we show that the optimized uptake rates reproduce the empirical Monod growth for bacterial cultures. For the network of core metabolic processes, the dynamic optimization algorithm predicted commonly observed metabolic adaptations, such as a diauxic switch with a preference ranking for different nutrients, re-utilization of waste products after depletion of the original substrate, and metabolic adaptation to an impending nutrient depletion. These examples illustrate how dynamic adaptations of enzyme expression can be predicted solely from an optimization principle. Copyright © 2014 Elsevier Ltd. All rights reserved.

Aerobic Exercise Training Adaptations Are Increased by Postexercise Carbohydrate-Protein Supplementation

PubMed Central

Ferguson-Stegall, Lisa; McCleave, Erin; Ding, Zhenping; Doerner III, Phillip G.; Liu, Yang; Wang, Bei; Healy, Marin; Kleinert, Maximilian; Dessard, Benjamin; Lassiter, David G.; Kammer, Lynne; Ivy, John L.

2011-01-01

Carbohydrate-protein supplementation has been found to increase the rate of training adaptation when provided postresistance exercise. The present study compared the effects of a carbohydrate and protein supplement in the form of chocolate milk (CM), isocaloric carbohydrate (CHO), and placebo on training adaptations occurring over 4.5 weeks of aerobic exercise training. Thirty-two untrained subjects cycled 60 min/d, 5 d/wk for 4.5 wks at 75–80% of maximal oxygen consumption (VO2 max). Supplements were ingested immediately and 1 h after each exercise session. VO2 max and body composition were assessed before the start and end of training. VO2 max improvements were significantly greater in CM than CHO and placebo. Greater improvements in body composition, represented by a calculated lean and fat mass differential for whole body and trunk, were found in the CM group compared to CHO. We conclude supplementing with CM postexercise improves aerobic power and body composition more effectively than CHO alone. PMID:21773022

Relationship between non-destructive OCT evaluation of resins composites and bond strength in a cavity

NASA Astrophysics Data System (ADS)

Bakhsh, T. A.; Sadr, A.; Shimada, Y.; Khunkar, S.; Tagami, J.; Sumi, Y.

2012-01-01

Objectives: Formation of microgaps under the composite restorations due to polymerization stress and other causes compromise the adhesion to the dental substrate and restoration durability. However, the relationship between cavity adaptation and bond strength is not clear. In this paper, we introduce a new testing method to assess cavity adaptation by swept-source optical coherence tomography (SS-OCT) and microtensile bond strength (MTBS) in the same class-I cavity. Methods: Round class-I cavities 3 mm in diameter and 1.5 mm in depth were prepared on 10 human premolars. After application of Tokuyama Bond Force adhesive, the cavities were filled by one of the two techniques; incremental technique using Estelite Sigma Quick universal composite or flowable lining using Palfique Estelite LV with bulk filling using the universal composite. Ten serial B-scan images were obtained throughout each cavity by SS-OCT. Significant peaks in the signal intensity were detected at the bonded interface of the cavity floor and to compare the different filling techniques. The specimens were later cut into beams (0.7x0.7 mm) and tested to measure MTBS at the cavity floor. Results: Flowable lining followed by bulk filling was inferior in terms of cavity adaptation and MTBS compared to the incremental technique (p<0.05, t-test). The adaptation (gap free cavity floor) and MTBS followed similar trends in both groups. Conclusion: Quantitative assessment of dental restorations by OCT can provide additional information on the performance and effectiveness of dental composites and restoration techniques. This study was supported by Global Center of Excellence, Tokyo Medical and Dental University and King Abdulaziz University.

Pixelized Device Control Actuators for Large Adaptive Optics

NASA Technical Reports Server (NTRS)

Knowles, Gareth J.; Bird, Ross W.; Shea, Brian; Chen, Peter

2009-01-01

A fully integrated, compact, adaptive space optic mirror assembly has been developed, incorporating new advances in ultralight, high-performance composite mirrors. The composite mirrors use Q-switch matrix architecture-based pixelized control (PMN-PT) actuators, which achieve high-performance, large adaptive optic capability, while reducing the weight of present adaptive optic systems. The self-contained, fully assembled, 11x11x4-in. (approx.= 28x28x10-cm) unit integrates a very-high-performance 8-in. (approx.=20-cm) optic, and has 8-kHz true bandwidth. The assembled unit weighs less than 15 pounds (=6.8 kg), including all mechanical assemblies, power electronics, control electronics, drive electronics, face sheet, wiring, and cabling. It requires just three wires to be attached (power, ground, and signal) for full-function systems integration, and uses a steel-frame and epoxied electronics. The three main innovations are: 1. Ultralightweight composite optics: A new replication method for fabrication of very thin composite 20-cm-diameter laminate face sheets with good as-fabricated optical figure was developed. The approach is a new mandrel resin surface deposition onto previously fabricated thin composite laminates. 2. Matrix (regenerative) power topology: Waveform correction can be achieved across an entire face sheet at 6 kHz, even for large actuator counts. In practice, it was found to be better to develop a quadrant drive, that is, four quadrants of 169 actuators behind the face sheet. Each quadrant has a single, small, regenerative power supply driving all 169 actuators at 8 kHz in effective parallel. 3. Q-switch drive architecture: The Q-switch innovation is at the heart of the matrix architecture, and allows for a very fast current draw into a desired actuator element in 120 counts of a MHz clock without any actuator coupling.

Martensitelike spontaneous relaxor-normal ferroelectric transformation in Pb(Zn1/3Nb2/3)O3-PbLa(ZrTi)O3 system

NASA Astrophysics Data System (ADS)

Deng, Guochu; Ding, Aili; Li, Guorong; Zheng, Xinsen; Cheng, Wenxiu; Qiu, Pingsun; Yin, Qingrui

2005-11-01

The spontaneous relaxor-normal ferroelectric transformation was found in the tetragonal composition of Pb(Zn1/3Nb2/3)O3-PbLa(ZrTi)O3 (0.3PZN-0.7PLZT) complex ABO3 system. The corresponding dielectric permittivities and losses of different compositions located near the morphotrophic phase boundary were analyzed. By reviewing all of the results about this type of transformation in previous references, the electric, compositional, structural, and thermodynamic characteristics of the spontaneous relaxor-normal transformation were proposed. Additionally, the adaptive phase model for martensite transformation proposed by Khachaturyan et al. [Phys. Rev. B 43, 10832 (1991)] was introduced into this ferroelectric transformation to explain the unique transformation pathway and associated features such as the tweedlike domain patterns and the dielectric dispersion under the critical transition temperature. Due to the critical compositions near the MPB, the ferroelectric materials just fulfill the condition, in which the adaptive phases can form in the transformation procedure. The formation of the adaptive phases, which are composed of stress-accommodating twinned domains, makes the system bypass the energy barrier encountered in conventional martensite transformations. The twinned adaptive phase corresponds to the tweedlike domain pattern under a transmission electronic microscope. At lower temperature, these precursor phases transform into the conventional ferroelectric state with macrodomains by the movement of domain walls, which causes a weak dispersion in dielectric permittivity.

Cavity Adaptation of Water-Based Restoratives Placed as Liners under a Resin Composite

PubMed Central

Gaintantzopoulou, Maria D.; Eliades, George

2017-01-01

Purpose. To investigate the cavity adaptation of mineral trioxide (ProRoot MTA/MT), tricalcium silicate (Biodentine/BD), and glass ionomer (Equia Fil/EF) cements used as liners and the interfacial integrity between those liners and a composite resin placed as the main restorative material. Materials and Methods. Standardized class I cavities (n: 8 per group) were prepared in upper premolars. Cavities were lined with a 1 mm thick layer of each of the tested materials and restored with Optibond FL adhesive and Herculite Precis composite resin. Cavity adaptation of the restorations was investigated by computerized X-ray microtomography. The regions of interest (ROI) were set at the cavity-liner (CL) interface and the liner-resin (LR) interface. The percentage void volume fraction (%VVF) in the ROI was calculated. The specimens were then sectioned and the interfaces were evaluated by reflection optical microscopy, to measure the % length (%LD) of the interfacial gaps. Selected samples were further evaluated by scanning electron microscopy. Statistical analysis was performed by two-way ANOVA and Student-Newman-Keuls multiple comparison test (a = 0.05). Results. MT showed significantly higher %VVF and %LD values in CL interfaces than BD and EF (p < 0.05). No significant differences were found among the materials for the same values at the LR interfaces. Conclusions. When used as a composite liner, ProRoot MTA showed inferior cavity adaptation at dentin/liner interface when compared to Biodentine and Equia Fil. PMID:28465685

Susceptibility of malaria vectors to DDT in Greece

PubMed Central

Livadas, Gregory A.; Thymakis, Kyriacos

1956-01-01

The authors describe an investigation, started in Greece in the autumn of 1953 and continued during the 1954 malaria-transmission season, to determine the variations in the susceptibility to DDT of the anophelines in different localities, with a view to establishing a point of departure which would make it possible to follow any future changes in susceptibility to this insecticide. The degree of susceptibility of the mosquitos to DDT was assessed numerically by both the technique of topical application of microdoses of the insecticide and the technique devised by Busvine & Nash. The villages of Elos and Asterion (Skála area), the Agoulinitsa area, and the Georgioupolis (Crete) area were chosen for the investigation. The findings disclosed considerable differences in the susceptibility to DDT in the above areas, but showed that, on the whole, the tendency for anophelines to acquire resistance to DDT seemed to be continuing in Greece. PMID:13404428

Intracavity optogalvanic spectroscopy. An analytical technique for 14C analysis with subattomole sensitivity.

PubMed

Murnick, Daniel E; Dogru, Ozgur; Ilkmen, Erhan

2008-07-01

We show a new ultrasensitive laser-based analytical technique, intracavity optogalvanic spectroscopy, allowing extremely high sensitivity for detection of (14)C-labeled carbon dioxide. Capable of replacing large accelerator mass spectrometers, the technique quantifies attomoles of (14)C in submicrogram samples. Based on the specificity of narrow laser resonances coupled with the sensitivity provided by standing waves in an optical cavity and detection via impedance variations, limits of detection near 10(-15) (14)C/(12)C ratios are obtained. Using a 15-W (14)CO2 laser, a linear calibration with samples from 10(-15) to >1.5 x 10(-12) in (14)C/(12)C ratios, as determined by accelerator mass spectrometry, is demonstrated. Possible applications include microdosing studies in drug development, individualized subtherapeutic tests of drug metabolism, carbon dating and real time monitoring of atmospheric radiocarbon. The method can also be applied to detection of other trace entities.

Opportunities in low-level radiocarbon microtracing: applications and new technology

PubMed Central

Vuong, Le Thuy; Song, Qi; Lee, Hee Joo; Roffel, Ad F; Shin, Seok-Ho; Shin, Young G; Dueker, Stephen R

2016-01-01

14C-radiolabeled (radiocarbon) drug studies are central to defining the disposition of therapeutics in clinical development. Concerns over radiation, however, have dissuaded investigators from conducting these studies as often as their utility may merit. Accelerator mass spectrometry (AMS), originally designed for carbon dating and geochronology, has changed the outlook for in-human radiolabeled testing. The high sensitivity of AMS affords human clinical testing with vastly reduced radiative (microtracing) and chemical exposures (microdosing). Early iterations of AMS were unsuitable for routine biomedical use due to the instruments’ large size and associated per sample costs. The situation is changing with advances in the core and peripheral instrumentation. We review the important milestones in applied AMS research and recent advances in the core technology platform. We also look ahead to an entirely new class of 14C detection systems that use lasers to measure carbon dioxide in small gas cells. PMID:28031933

Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer

PubMed Central

Cimino, George D; Pan, Chong-xian; Henderson, Paul T

2013-01-01

The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum–DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications. PMID:23394702

Measurements on a full-field digital mammography system with a photon counting crystalline silicon detector

NASA Astrophysics Data System (ADS)

Lundqvist, Mats; Danielsson, Mats; Cederstroem, Bjoern; Chmill, Valery; Chuntonov, Alexander; Aslund, Magnus

2003-06-01

Sectra Microdose is the first single photon counting mammography detector. An edge-on crystalline silicon detector is connected to application specific integrated circuits that individually process each photon. The detector is scanned across the breast and the rejection of scattered radiation exceeds 97% without the use of a Bucky. Processing of each x-rays individually enables an optimization of the information transfer from the x-rays to the image in a way previously not possible. Combined with an almost absence of noise from scattered radiation and from electronics we foresee a possibility to reduce the radiation dose and/or increase the image quality. We will discuss fundamental features of the new direct photon counting technique in terms of dose efficiency and present preliminary measurements for a prototype on physical parameters such as Noise Power Spectra (NPS), MTF and DQE.

An image analysis system for near-infrared (NIR) fluorescence lymph imaging

NASA Astrophysics Data System (ADS)

Zhang, Jingdan; Zhou, Shaohua Kevin; Xiang, Xiaoyan; Rasmussen, John C.; Sevick-Muraca, Eva M.

2011-03-01

Quantitative analysis of lymphatic function is crucial for understanding the lymphatic system and diagnosing the associated diseases. Recently, a near-infrared (NIR) fluorescence imaging system is developed for real-time imaging lymphatic propulsion by intradermal injection of microdose of a NIR fluorophore distal to the lymphatics of interest. However, the previous analysis software3, 4 is underdeveloped, requiring extensive time and effort to analyze a NIR image sequence. In this paper, we develop a number of image processing techniques to automate the data analysis workflow, including an object tracking algorithm to stabilize the subject and remove the motion artifacts, an image representation named flow map to characterize lymphatic flow more reliably, and an automatic algorithm to compute lymph velocity and frequency of propulsion. By integrating all these techniques to a system, the analysis workflow significantly reduces the amount of required user interaction and improves the reliability of the measurement.

Collaborative adaptive rangeland management fosters management-science partnerships

USDA-ARS?s Scientific Manuscript database

Rangelands of the western Great Plains of North America are complex social-ecological systems where management objectives for livestock production, grassland bird conservation and vegetation structure and composition converge. The Collaborative Adaptive Rangeland Management (CARM) experiment is a 10...

Collector surface for a microwave tube comprising a carbon-bonded carbon-fiber composite

DOEpatents

Lauf, R.J.; McMillan, A.D.; Johnson, A.C.; Moorhead, A.J.

1998-07-28

In a microwave tube, an improved collector surface coating comprises a porous carbon composite material, preferably a carbon-bonded carbon fiber composite having a bulk density less than about 2 g/cc. Installation of the coating is readily adaptable as part of the tube manufacturing process. 4 figs.

Agent-based user-adaptive service provision in ubiquitous systems

NASA Astrophysics Data System (ADS)

Saddiki, H.; Harroud, H.; Karmouch, A.

2012-11-01

With the increasing availability of smartphones, tablets and other computing devices, technology consumers have grown accustomed to performing all of their computing tasks anytime, anywhere and on any device. There is a greater need to support ubiquitous connectivity and accommodate users by providing software as network-accessible services. In this paper, we propose a MAS-based approach to adaptive service composition and provision that automates the selection and execution of a suitable composition plan for a given service. With agents capable of autonomous and intelligent behavior, the composition plan is selected in a dynamic negotiation driven by a utility-based decision-making mechanism; and the composite service is built by a coalition of agents each providing a component necessary to the target service. The same service can be built in variations for catering to dynamic user contexts and further personalizing the user experience. Also multiple services can be grouped to satisfy new user needs.

The role of adaptive immunity as an ecological filter on the gut microbiota in zebrafish.

PubMed

Stagaman, Keaton; Burns, Adam R; Guillemin, Karen; Bohannan, Brendan Jm

2017-07-01

All animals live in intimate association with communities of microbes, collectively referred to as their microbiota. Certain host traits can influence which microbial taxa comprise the microbiota. One potentially important trait in vertebrate animals is the adaptive immune system, which has been hypothesized to act as an ecological filter, promoting the presence of some microbial taxa over others. Here we surveyed the intestinal microbiota of 68 wild-type zebrafish, with functional adaptive immunity, and 61 rag1 - zebrafish, lacking functional B- and T-cell receptors, to test the role of adaptive immunity as an ecological filter on the intestinal microbiota. In addition, we tested the robustness of adaptive immunity's filtering effects to host-host interaction by comparing the microbiota of fish populations segregated by genotype to those containing both genotypes. The presence of adaptive immunity individualized the gut microbiota and decreased the contributions of neutral processes to gut microbiota assembly. Although mixing genotypes led to increased phylogenetic diversity in each, there was no significant effect of adaptive immunity on gut microbiota composition in either housing condition. Interestingly, the most robust effect on microbiota composition was co-housing within a tank. In all, these results suggest that adaptive immunity has a role as an ecological filter of the zebrafish gut microbiota, but it can be overwhelmed by other factors, including transmission of microbes among hosts.

[Change in the lipid composition of the inner mitochondrial membranes in rat organs during adaptation to heat].

PubMed

Zubareva, E V; Seferova, R I; Denisova, N A

1991-01-01

Under conditions of adaptation to heating lipid composition in mitochondrial membranes of rat inner tissues was altered as follows: an increase in relative concentration of plasmalogenous forms of phospholipids (kidney, heart) and in content of saturated fatty acids (liver tissue), a decrease in the index of fatty acids unsaturation and in the ratio of fatty acids omega-3/omega-6. The alterations observed enabled the membranes to keep sufficient amount of liquidity essential for functional activity of mitochondria in heating.

Does Cultural Adaptation Have a Role in Substance Abuse Treatment?

PubMed Central

Burlew, A. Kathleen; Copeland, Valire Carr; Ahuama-Jonas, Chizara; Calsyn, Donald A.

2013-01-01

The changing ethnic composition of the nation and increasing requirements to use evidence-based treatments (EBTs) challenge mental health professionals to adapt treatments and interventions to be appropriate for their clients. This article applies the available information on cultural adaptation to substance abuse. The authors’ review suggests that the most common approaches for adapting substance use interventions include some combination of either community involvement in the adaptation, existing research and literature, and/or consultation from experts to adapt EBTs. The challenges facing the development of culturally adapted interventions include the need for additional research to determine which specific EBTs warrant adaptation, the responsibility of maintaining the balance between fidelity and adaptation, and the challenge of intragroup diversity. PMID:23731430

Neural adaptive control for vibration suppression in composite fin-tip of aircraft.

PubMed

Suresh, S; Kannan, N; Sundararajan, N; Saratchandran, P

2008-06-01

In this paper, we present a neural adaptive control scheme for active vibration suppression of a composite aircraft fin tip. The mathematical model of a composite aircraft fin tip is derived using the finite element approach. The finite element model is updated experimentally to reflect the natural frequencies and mode shapes very accurately. Piezo-electric actuators and sensors are placed at optimal locations such that the vibration suppression is a maximum. Model-reference direct adaptive neural network control scheme is proposed to force the vibration level within the minimum acceptable limit. In this scheme, Gaussian neural network with linear filters is used to approximate the inverse dynamics of the system and the parameters of the neural controller are estimated using Lyapunov based update law. In order to reduce the computational burden, which is critical for real-time applications, the number of hidden neurons is also estimated in the proposed scheme. The global asymptotic stability of the overall system is ensured using the principles of Lyapunov approach. Simulation studies are carried-out using sinusoidal force functions of varying frequency. Experimental results show that the proposed neural adaptive control scheme is capable of providing significant vibration suppression in the multiple bending modes of interest. The performance of the proposed scheme is better than the H(infinity) control scheme.

Adaptive Changes in Membrane Lipids of Barophilic Bacteria in Response to Changes in Growth Pressure

PubMed Central

Yano, Yutaka; Nakayama, Akihiko; Ishihara, Kenji; Saito, Hiroaki

1998-01-01

The lipid compositions of barophilic bacterial strains which contained docosahexaenoic acid (DHA [22:6n-3]) were examined, and the adaptive changes of these compositions were analyzed in response to growth pressure. In the facultatively barophilic strain 16C1, phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) were major components which had the same fatty acid chains. However, in PE, monounsaturated fatty acids such as hexadecenoic acid were major components, and DHA accounted for only 3.7% of the total fatty acids, while in PG, DHA accounted for 29.6% of the total fatty acids. In response to an increase in growth pressure in strain 16C1, the amounts of saturated fatty acids in PE were reduced, and these decreases were mainly balanced by an increase in unsaturated fatty acids, including DHA. In PG, the decrease in saturated fatty acids was mainly balanced by an increase in DHA. Similar adaptive changes in fatty acid composition were observed in response to growth pressure in obligately barophilic strain 2D2. Furthermore, these adaptive changes in response were also observed in response to low temperature in strain 16C1. These results confirm that the general shift from saturated to unsaturated fatty acids including DHA is one of the adaptive changes in response to increases in pressure and suggest that DHA may play a role in maintaining the proper fluidity of membrane lipids under high pressure. PMID:16349499

Quantitation of anacetrapib, stable-isotope labeled-anacetrapib (microdose), and four metabolites in human plasma using liquid chromatography tandem mass spectrometry.

PubMed

Chavez-Eng, C M; Lutz, R W; Li, H; Goykhman, D; Bateman, K P; Woolf, E

2016-02-01

An ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of (4S,5R)-5-[3,5-bis (trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl] methyl}-4-methyl-1,3-oxazolidin-2-one (anacetrapib, I) and [(13)C5(15)N]-anacetrapib, II in human plasma has been developed to support a clinical study to determine the absolute bioavailability of I. The analytes and the stable-isotope labeled internal standard ([(13)C7(15)N(2)H7]-anacetrapib, III) were extracted from 100μL of human plasma by liquid-liquid extraction using 20/80 isopropyl alcohol/hexane (v/v). The chromatographic separation of the analytes was achieved using Waters BEH Shield RP 18 (50×2.1mm×1.7μm) column and mobile phase gradient of 0.1% formic acid in water (Solvent A) and 0.1% formic acid in acetonitrile (Solvent B) at 0.6mL/min flow rate. The MS/MS detection was performed on AB Sciex 5000 or AB 5500 in positive electrospray ionization mode, operated in selected reaction monitoring mode. The assay was validated in the concentration range 1-2000ng/mL for I; and a lower curve range, 0.025-50ng/mL for II. In addition to the absolute bioavailability determination, it was desired to better elucidate the pharmacokinetic behavior of several hydroxylated metabolites of I. Toward this end, two exploratory assays for the hydroxy metabolites of I were qualified in the concentration range 0.5-500ng/mL. All metabolites were separated on a Supelco Ascentis Express Phenyl-Hexyl (50×2.1mm, 2.7μm) column. Metabolite M4 was analyzed in the negative mode with a mobile phase consisting of a gradient mixture of water (A) and acetonitrile (B). The other three metabolites, M1-M3 were analyzed in the positive mode using a mobile phase gradient of water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B). The assays were utilized to support a clinical study in which a microdosing approach was used to determine the pharmacokinetics of anacetrapib and its metabolites. Copyright © 2016 Elsevier B.V. All rights reserved.

Virtual Manufacturing of Composite Structures for Ground Platforms, A DARPA Instant Foundry Adaptive Through Bits (iFAB) Program

DTIC Science & Technology

2012-08-01

This document contains color. 14. ABSTRACT This effort focused specifically on the Liquid Composite Molding (LCM) class of processes as they...SUBJECT TERMS Liquid Composite Molding (LCM), fabrication, manufacturability assessment 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF... Molding (LCM) .......................................................................... 2 1.1.1 LCM Process Variations

The Development of Composition Skills via Directed Writing.

ERIC Educational Resources Information Center

Rahilly, Leonard J.

To alleviate problems associated with free composition as a method of foreign language writing instruction, the directed writing method was adapted for use in a college French composition course. High-quality French texts, often of only a page or two and written by native speakers, are used as a basis for grammatical analysis and discussion and a…

Reorganization of Azospirillum brasilense cell membrane is mediated by lipid composition adjustment to maintain optimal fluidity during water deficit.

PubMed

Cesari, A B; Paulucci, N S; Biasutti, M A; Reguera, Y B; Gallarato, L A; Kilmurray, C; Dardanelli, M S

2016-01-01

We study the Azospirillum brasilense tolerance to water deficit and the dynamics of adaptive process at the level of the membrane. Azospirillum brasilense was exposed to polyethylene glycol (PEG) growth and PEG shock. Tolerance, phospholipids and fatty acid (FA) composition and membrane fluidity were determined. Azospirillum brasilense was able to grow in the presence of PEG; however, its viability was reduced. Cells grown with PEG showed membrane fluidity similar to those grown without, the lipid composition was modified, increasing phosphatidylcholine and decreasing phosphatidylethanolamine amounts. The unsaturation FAs degree was reduced. The dynamics of the adaptive response revealed a decrease in fluidity 20 min after the addition of PEG, indicating that the PEG has a fluidizing effect on the hydrophobic region of the cell membrane. Fluidity returned to initial values after 60 min of PEG exposure. Azospirillum brasilense is able to perceive osmotic changes by changing the membrane fluidity. This effect is offset by changes in the composition of membrane phospholipid and FA, contributing to the homeostasis of membrane fluidity under water deficit. This knowledge can be used to develop new Azospirillum brasilense formulations showing an adapted membrane to water deficit. © 2015 The Society for Applied Microbiology.

Base compositions of genes encoding alpha-actin and lactate dehydrogenase-A from differently adapted vertebrates show no temperature-adaptive variation in G + C content.

PubMed

Ream, Rachael A; Johns, Glenn C; Somero, George N

2003-01-01

There is a long-standing debate in molecular evolution concerning the putative importance of GC content in adapting the thermal stabilities of DNA and RNA. Most studies of this relationship have examined broad-scale compositional patterns, for example, total GC percentages in genomes and occurrence of GC-rich isochores. Few studies have systematically examined the GC contents of individual orthologous genes from differently thermally adapted species. When this has been done, the emphasis has been on comparing large numbers of genes in only a few species. We have approached the GC-adaptation temperature hypothesis in a different manner by examining patterns of base composition of genes encoding lactate dehydrogenase-A (ldh-a) and alpha-actin (alpha-actin) from 51 species of vertebrates whose adaptation temperatures ranged from -1.86 degrees C (Antarctic fishes) to approximately 45 degrees C (desert reptile). No significant positive correlation was found between any index of GC content (GC content of the entire sequence, GC content of the third codon position [GC(3)], and GC content at fourfold degenerate sites [GC(4)]) and any index of adaptation temperature (maximal, mean, or minimal body temperature). For alpha-actin, slopes of regression lines for all comparisons did not differ significantly from zero. For ldh-a, negative correlations between adaptation temperature and total GC content, GC(3), and GC(4) were observed but were shown to be due entirely to phylogenetic influences (as revealed by independent contrast analyses). This comparison of GC content across a wide range of ectothermic ("cold-blooded") and endothermic ("warm-blooded") vertebrates revealed that frogs of the genus Xenopus, which have commonly been used as a representative cold-blooded species, in fact are outliers among ectotherms for the alpha-actin analyses, raising concern about the appropriateness of choosing these amphibians as representative of ectothermic vertebrates in general. Our study indicates that, whereas GC contents of isochores may show variation among different classes of vertebrates, there is no consistent relationship between adaptation temperature and the percentage of thermal stability-enhancing G + C base pairs in protein-coding genes.

A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]tofogliflozin after oral administration and concomitant intravenous microdose administration of [13C]tofogliflozin in humans.

PubMed

Schwab, Dietmar; Portron, Agnes; Backholer, Zoe; Lausecker, Berthold; Kawashima, Kosuke

2013-06-01

Human mass balance studies and the assessment of absolute oral bioavailability (F) are usually assessed in separate studies. Intravenous microdose administration of an isotope tracer concomitant to an unlabeled oral dose is an emerging technique to assess F. We report a novel double-tracer approach implemented for tofogliflozin combining oral administration of a radiolabel tracer with concomitant intravenous administration of a stable isotope tracer. Tofogliflozin is a potent and selective sodium/glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus currently in clinical development. The objectives of the present study were to assess the systemic exposure of major circulating metabolites, excretion balance, F and contribution of renal clearance (CLR) to total clearance (CL) of tofogliflozin in healthy subjects within one study applying a novel double-tracer technique. Six healthy male subjects received 20 mg [(12)C/(14)C]tofogliflozin (3.73 MBq) orally and a concomitant microdose of 0.1 mg [(13)C]tofogliflozin intravenously. Pharmacokinetics of tofogliflozin were determined for the oral and intravenous route; the pharmacokinetics of the metabolites M1 and M5 were determined for the oral route. Quantification of [(12)C]tofogliflozin in plasma and urine and [(13)C]tofogliflozin in plasma was performed by selective LC-MS/MS methods. For the pre-selected metabolites of tofogliflozin, M1 and M5, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to plasma and urine samples. Total radioactivity was assessed in plasma, urine and feces. Pharmacokinetic analysis was conducted by non-compartmental methods. The pharmacokinetics of tofogliflozin in healthy subjects were characterized by an F of 97.5 ± 12.3 %, CL of 10.0 ± 1.3 l/h and volume of distribution at steady-state (V(ss)) of 50.6 ± 6.7 l. The main route of elimination of total drug-related material was by excretion into urine (77.0 ± 4.1 % of the dose). The observed CL(R) of 25.7 ± 5.0 ml/min was higher than the product of the estimated glomerular filtration rate (eGFR) and fraction unbound in plasma (f(u)) (eGFR × f(u) 15 ml/min), indicating the presence of net active tubular secretion in the renal elimination of tofogliflozin. However, CLR contributed only 15.5 % to the CL of tofogliflozin, suggesting that reductions in CLR by renal impairment won't significantly affect systemic exposure to tofogliflozin. Tofogliflozin and its metabolite M1 were the only major circulating entities accounting for 46 ± 8.6 and 50 ± 8.2 %, respectively, of total circulating drug-related material, while the metabolite M5 was a minor circulating metabolite accounting for 3.0 ± 0.3 % of total circulating drug-related material. Both the M1 and M5 metabolites were excreted into urine and the major metabolite M1 did not exhibit active tubular secretion. These results demonstrate the utility of the double-tracer approach to provide essential pharmacokinetic data and excretion data for drug-related material in one study at the same dosing occasion. The data obtained allowed the characterization of absorption, distribution, metabolism and excretion of tofogliflozin. Tofogliflozin exhibited highly favorable pharmacokinetic properties as demonstrated by its high F, low CL and a low V(ss. The presence of only one major circulating metabolite of tofogliflozin was unambiguously demonstrated. As a drug targeting the kidney, luminal exposure of the kidney is achieved by renal filtration and active tubular secretion.

Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study.

PubMed

Peng, Mei; Gao, Keming; Ding, Yiling; Ou, Jianjun; Calabrese, Joseph R; Wu, Renrong; Zhao, Jingping

2013-08-01

This study aims to investigate the developmental effects of atypical antipsychotics on infants who were born to mothers taking an atypical antipsychotic throughout pregnancy. The developmental progress of 76 infants who experienced fetal exposure to atypical antipsychotics was compared to that of 76 matched control infants who had no fetal exposure to any antipsychotics. Planned assessment included Apgar score, body weight, height, and the cognitive, language, motor, social-emotional, and adaptive behavior composite scores of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Student's t test and Chi-square analysis were used as appropriate. Repeated measurements were evaluated by analysis of covariance. At 2 months of age, the mean composite scores of cognitive, motor, social-emotional, and adaptive behavior of BSID-III were significantly lower in atypical antipsychotic-exposed infants than the controls. More atypical antipsychotic-exposed infants had delayed development in cognitive, motor, social-emotional, and adaptive behavior domains as defined by the composite score of <85 in these subscales of BSID-III. At 12 months of age, there were no significant differences between the two groups in all mean composite scores of BSID-III. More atypical antipsychotic-exposed infants had low birth weight than the controls (13.2 vs. 2.6 %, P = 0.031), although there were no significant difference in mean birth weight and height between the two groups. Fetal exposure to atypical antipsychotics may cause short-term delayed development in cognitive, motor, social-emotional, and adaptive behavior, but not in language, body weight, or height.

Electric Field Activated Shape Memory Polymer Composite

NASA Technical Reports Server (NTRS)

Kang, Jin Ho (Inventor); Turner, Travis L. (Inventor); Siochi, Emilie J. (Inventor); Penner, Ronald K. (Inventor)

2017-01-01

Provided is an electrically activated shape memory polymer composite capable of thermal shape reformation using electric power to heat the composite through its matrix glass transition temperature. The composite includes an adaptable polymer matrix component using a diglycidyl ether resin, at least one substantially well-dispersed conductive or magnetic nano-filler component, and at least one elastic, laminated layer. Also provided are methods of preparing the composite and methods of activating the composite. A shape reformation of the composite is triggered by applying an electric field at DC and/or at a frequency above about 1.mu.Hz for a sufficient time.

Desert Perennial Shrubs Shape the Microbial-Community Miscellany in Laimosphere and Phyllosphere Space.

PubMed

Martirosyan, Varsik; Unc, Adrian; Miller, Gad; Doniger, Tirza; Wachtel, Chaim; Steinberger, Yosef

2016-10-01

Microbial function, composition, and distribution play a fundamental role in ecosystem ecology. The interaction between desert plants and their associated microbes is expected to greatly affect their response to changes in this harsh environment. Using comparative analyses, we studied the impact of three desert shrubs, Atriplex halimus (A), Artemisia herba-alba (AHA), and Hammada scoparia (HS), on soil- and leaf-associated microbial communities. DNA extracted from the leaf surface and soil samples collected beneath the shrubs were used to study associated microbial diversity using a sequencing survey of variable regions of bacterial 16S rRNA and fungal ribosomal internal transcribed spacer (ITS1). We found that the composition of bacterial and fungal orders is plant-type-specific, indicating that each plant type provides a suitable and unique microenvironment. The different adaptive ecophysiological properties of the three plant species and the differential effect on their associated microbial composition point to the role of adaptation in the shaping of microbial diversity. Overall, our findings suggest a link between plant ecophysiological adaptation as a "temporary host" and the biotic-community parameters in extreme xeric environments.

Influence of different sizes of composite femora on the biomechanical behavior of cementless hip prosthesis.

PubMed

Schmidutz, Florian; Woiczinski, Mathias; Kistler, Manuel; Schröder, Christian; Jansson, Volkmar; Fottner, Andreas

2017-01-01

For the biomechanical evaluation of cementless stems different sizes of composite femurs have been used in the literature. However, the impact of different specimen sizes on test results is unknown. To determine the potential effect of femur size the biomechanical properties of a conventional stem (CLS Spotorno) were examined in 3 different sizes (small, medium and large composite Sawbones®). Primary stability was tested under physiologically adapted dynamic loading conditions measuring 3-dimensional micromotions. For the small composite femur the dynamic load needed to be adapted since fractures occurred when reaching 1700N. Additionally, surface strain distribution was recorded before and after implantation to draw conclusions about the tendency for stress shielding. All tested sizes revealed similar micromotions only reaching a significant different level at one measurement point. The highest micromotions were observed at the tip of the stems exceeding the limit for osseous integration of 150μm. Regarding strain distribution the highest strain reduction after implantation was registered in all sizes at the level of the lesser trochanter. Specimen size seems to be a minor influence factor for biomechanical evaluation of cementless stems. However, the small composite femur is less suitable for biomechanical testing since this size failed under physiological adapted loads. For the CLS Spotorno osseous integration is unlikely at the tip of the stem and the tendency for stress shielding is the highest at the level of the lesser trochanter. Copyright © 2016 Elsevier Ltd. All rights reserved.

Predicting metabolic adaptation, body weight change, and energy intake in humans

PubMed Central

2010-01-01

Complex interactions between carbohydrate, fat, and protein metabolism underlie the body's remarkable ability to adapt to a variety of diets. But any imbalances between the intake and utilization rates of these macronutrients will result in changes in body weight and composition. Here, I present the first computational model that simulates how diet perturbations result in adaptations of fuel selection and energy expenditure that predict body weight and composition changes in both obese and nonobese men and women. No model parameters were adjusted to fit these data other than the initial conditions for each subject group (e.g., initial body weight and body fat mass). The model provides the first realistic simulations of how diet perturbations result in adaptations of whole body energy expenditure, fuel selection, and various metabolic fluxes that ultimately give rise to body weight change. The validated model was used to estimate free-living energy intake during a long-term weight loss intervention, a variable that has never previously been measured accurately. PMID:19934407

Effect of flowable composite liner and glass ionomer liner on class II gingival marginal adaptation of direct composite restorations with different bonding strategies.

PubMed

Aggarwal, Vivek; Singla, Mamta; Yadav, Suman; Yadav, Harish

2014-05-01

The purpose of the present study was to comparatively evaluate the effect of flowable composite resin liner and resin modified glass ionomer liner on gingival marginal adaptation of class II cavities restored using three bonding agents (Single Bond 3M ESPE, One Coat Self Etching Bond Coltene Whaledent; Adper Easy Bond Self-Etch Adhesive 3M ESPE) and respective composite resins, under cyclic loading. The marginal adaptation was evaluated in terms of 'continuous margin' (CM) at the gingival margin. Ninety class II cavities with margins extending 1mm below the cement-enamel junction were prepared in extracted mandibular third molars. The samples were divided into three groups: no liner placement; 0.5-1mm thick flowable resin liner placement (Filtek Z350 XT flowable resin) on gingival floor and; light cure glass ionomer (Ketac N100) liner. The groups were further subdivided into three sub-groups on the basis of the bonding agents used. Cavities were restored with composite resins (Z350 for Single Bond and Adper Easy Bond; and Synergy D6 Universal, for One Coat Self Etching Bond) in 2mm increments and the samples were mechanically loaded (60N, 1,50,000 cycles). Marginal adaptation was evaluated using a low vacuum scanning electron microscope. Statistical analysis was done with two way ANOVA with Holm-Sidak's correction for multiple comparisons. Placement of flowable composite liner significantly improved the CM values of Single Bond (78±11%) and One Coat Self Etching Bond (77±9%) compared with no liner group, but the values of CM of Adper Easy Bond were not improved (61±12%). Placement of glass ionomer liner significantly improved the values of CM in all the sub-groups (78±9%, 72±10% and 77±10% for Single Bond, One Coat Self Etching Bond & Adper Easy Bond respectively) compared with no liner group. Placement of liners improved the values of 'continuous margin' in the gingival floor of the proximal cavities restored with composite resins using different bonding agent. Placement of flowable composite liner or glass ionomer liner will improve the marginal integrity of composite restorations using etch-and-rinse and two bottle-two step self etch adhesives. To improve the marginal integrity of a single bottle adhesive, glass ionomer liner should be applied. Copyright © 2014 Elsevier Ltd. All rights reserved.

Marginal and internal fit of CAD-CAM-fabricated composite resin and ceramic crowns scanned by 2 intraoral cameras.

PubMed

de Paula Silveira, Alessandra C; Chaves, Sacha B; Hilgert, Leandro A; Ribeiro, Ana Paula D

2017-03-01

The precision of fit of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) complete crowns is affected by digital impression and restorative material. The purpose of this in vitro study was to evaluate by microcomputed tomography (μCT) the marginal and internal adaptation of composite resin and ceramic complete crowns fabricated with 2 different intraoral cameras and 2 restorative materials. Ten extracted human third molars received crown preparations. For each prepared molar, 2 digital impressions were made with different intraoral cameras of the CEREC system, Bluecam and Omnicam. Four groups were formed: LB (Lava Ultimate+Bluecam), EB (Emax+Bluecam), LO (Lava Ultimate+Omnicam), and EO (Emax+Omnicam). Before measuring the precision of fit, all crowns were stabilized with a silicone material. Each unit (crown + prepared tooth) was imaged with μCT, and marginal and internal discrepancies were analyzed. For the 2D analysis, 120 measurements were made of each crown for marginal adaptation, 20 for marginal discrepancy (MD), and 20 for absolute marginal discrepancy (AMD); and for internal adaptation, 40 for axial space (AS) and 40 for occlusal space (OS). After reconstructing the 3D images, the average internal space (AIS) was calculated by dividing the total volume of the internal space by the contact surface. Data were analyzed with 2-way ANOVA and quantile regression. Regarding marginal adaptation, no significant differences were observed among groups. For internal adaptation measured in the 2D evaluation, a significant difference was observed between LO and EO for the AS variable (Mann-Whitney test; P<.008). In assessment of AIS by the 3D reconstruction, LB presented significantly lower values than the other groups (Tukey post hoc test; P<.05). Bluecam presented lower values of AIS than Omnicam, and composite resin crowns showed less discrepancy than did ceramic crowns. The marginal adaptations assessed in all groups showed values within the clinically accepted range. Moreover, the composite resin blocks associated with the Bluecam intraoral camera demonstrated the best results for AIS compared with those of the other groups. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

A novel adaptive sun tracker for spacecraft solar panel based on hybrid unsymmetric composite laminates

NASA Astrophysics Data System (ADS)

Wu, Zhangming; Li, Hao

2017-11-01

This paper proposes a novel adaptive sun tracker which is constructed by hybrid unsymmetric composite laminates. The adaptive sun tracker could be applied on spacecraft solar panels to increase their energy efficiency through decreasing the inclined angle between the sunlight and the solar panel normal. The sun tracker possesses a large rotation freedom and its rotation angle depends on the laminate temperature, which is affected by the light condition in the orbit. Both analytical model and finite element model (FEM) are developed for the sun tracker to predict its rotation angle in different light conditions. In this work, the light condition of the geosynchronous orbit on winter solstice is considered in the numerical prediction of the temperatures of the hybrid laminates. The final inclined angle between the sunlight and the solar panel normal during a solar day is computed using the finite element model. Parametric study of the adaptive sun tracker is conducted to improve its capacity and effectiveness of sun tracking. The improved adaptive sun tracker is lightweight and has a state-of-the-art design. In addition, the adaptive sun tracker does not consume any power of the solar panel, since it has no electrical driving devices. The proposed adaptive sun tracker provides a potential alternative to replace the traditional sophisticated electrical driving mechanisms for spacecraft solar panels.

Using the adaptive SMA composite cylinder concept to reduce radial dilation in composite pressure vessels

NASA Astrophysics Data System (ADS)

Paine, Jeffrey S.; Rogers, Craig A.

1995-05-01

Composite materials are widely used in the design of pressurized gas and fluid vessels for applications ranging from underground gasoline storage tanks to rocket motors for the space shuttle. In the design of a high pressure composite vessel (Pi > 12 Ksi), thick-wall (R/h < 15) vessels are required. For efficient material use in composite material vessels, the radial dilation (expansion or swelling) of the composite vessel can often approach values nearing 2 percent of the diameter. Over long periods of internal pressure loading over elevated temperatures, composite material cylinders may also experience substantial creep. The short term dilation and long term creep are not problematic for applications requiring only the containment of the pressurized fluid. In applications where metallic liners are required, however, substantial dilation and creep causes plastic yielding which leads to reduced fatigue life. To applications such as a hydraulic accumulator, where a piston is employed to fit and seal the fluid in the composite cylinder, the dilation and creep may allow leakage and pressure loss around the piston. A concept called the adaptive composite cylinder is experimentally presented. Shape memory alloy wire in epoxy resin is wrapped around or within polymer matrix composite cylinders to reduce radial dilation of the cylinder. Experimental results are presented that demonstrate the ability of the SMA wire layers to reduce radial dilation. Results from experimental testing of the recovery stress fatigue response of nitinol shape memory alloy wires is also presented.

Comparison of the marginal adaptation of direct and indirect composite inlay restorations with optical coherence tomography

PubMed Central

TÜRK, Ayşe Gözde; SABUNCU, Metin; ÜNAL, Sena; ÖNAL, Banu; ULUSOY, Mübin

2016-01-01

ABSTRACT Objective The purpose of the study was to use the photonic imaging modality of optical coherence tomography (OCT) to compare the marginal adaptation of composite inlays fabricated by direct and indirect techniques. Material and Methods Class II cavities were prepared on 34 extracted human molar teeth. The cavities were randomly divided into two groups according to the inlay fabrication technique. The first group was directly restored on cavities with a composite (Esthet X HD, Dentsply, Germany) after isolating. The second group was indirectly restored with the same composite material. Marginal adaptations were scanned before cementation with an invisible infrared light beam of OCT (Thorlabs), allowing measurement in 200 µm intervals. Restorations were cemented with a self-adhesive cement resin (SmartCem2, Dentsply), and then marginal adaptations were again measured with OCT. Mean values were statistically compared by using independent-samples t-test and paired samples t-test (p<0.05), before and after cementation. Results Direct inlays presented statistically smaller marginal discrepancy values than indirect inlays, before (p=0.00001442) and after (p=0.00001466) cementation. Marginal discrepancy values were increased for all restorations after cementation (p=0.00008839, p=0.000000952 for direct and indirect inlays, respectively). The mean marginal discrepancy value of the direct group increased from 56.88±20.04 µm to 91.88±31.7 µm, whereas the indirect group increased from 107.54±35.63 µm to 170.29±54.83 µm. Different techniques are available to detect marginal adaptation of restorations, but the OCT system can give quantitative information about resin cement thickness and its interaction between tooth and restoration in a nondestructive manner. Conclusions Direct inlays presented smaller marginal discrepancy than indirect inlays. The marginal discrepancy values were increased for all restorations that refer to cement thickness after cementation. PMID:27556210

An adaptive DPCM encoder for NTSC composite video signals

NASA Astrophysics Data System (ADS)

Cox, N. R.

An adaptive DPCM algorithm is proposed for encoding digitized National Television Systems Committee (NTSC) color video signals. This algorithm essentially predicts picture contours in the composite signal without resorting to component separation. Preliminary subjective and objective tests performed on an experimental encoder/simulator indicate that high quality color pictures can be encoded at 4.0 bits/pel or 42.95 Mbit/s. This requires the use of a 4/8 bit dual-word-length coder and buffer memory. Such a system might be useful in certain short hop applications if both large-signal and small-signal responses can be preserved.

Motion planning for an adaptive wing structure with macro-fiber composite actuators

NASA Astrophysics Data System (ADS)

Schröck, J.; Meurer, T.; Kugi, A.

2009-05-01

A systematic approach for flatness-based motion planning and feedforward control is presented for the transient shaping of a piezo-actuated rectangular cantilevered plate modeling an adaptive wing. In the first step the consideration of an idealized infinite-dimensional input allows to determine the state and input parametrization in terms of a flat or basic output, which is used for a systematic motion planning approach. Subsequently, the obtained idealized input function is projected onto a finite number of suitably placed Macro-fiber Composite (MFC) patch actuators. The tracking performance of the proposed approach is evaluated in a simulation scenario.

MADCAT Aircraft Wings Optimize Their Shape For Efficient Flight

NASA Image and Video Library

2016-11-09

The Mission Adaptive Digital Composites Aerostructures Technology (MADCAT) project is designing an aircraft wing that can change its shape to adapt to changing flight conditions. Constructed of lightweight lattice structures made of carbon fiber materials, the goal is to reduce drag, leading to more efficient airplanes.

Grid adaption using Chimera composite overlapping meshes

NASA Technical Reports Server (NTRS)

Kao, Kai-Hsiung; Liou, Meng-Sing; Chow, Chuen-Yen

1993-01-01

The objective of this paper is to perform grid adaptation using composite over-lapping meshes in regions of large gradient to capture the salient features accurately during computation. The Chimera grid scheme, a multiple overset mesh technique, is used in combination with a Navier-Stokes solver. The numerical solution is first converged to a steady state based on an initial coarse mesh. Solution-adaptive enhancement is then performed by using a secondary fine grid system which oversets on top of the base grid in the high-gradient region, but without requiring the mesh boundaries to join in any special way. Communications through boundary interfaces between those separated grids are carried out using tri-linear interpolation. Applications to the Euler equations for shock reflections and to a shock wave/boundary layer interaction problem are tested. With the present method, the salient features are well resolved.

Grid adaptation using chimera composite overlapping meshes

NASA Technical Reports Server (NTRS)

Kao, Kai-Hsiung; Liou, Meng-Sing; Chow, Chuen-Yen

1994-01-01

The objective of this paper is to perform grid adaptation using composite overlapping meshes in regions of large gradient to accurately capture the salient features during computation. The chimera grid scheme, a multiple overset mesh technique, is used in combination with a Navier-Stokes solver. The numerical solution is first converged to a steady state based on an initial coarse mesh. Solution-adaptive enhancement is then performed by using a secondary fine grid system which oversets on top of the base grid in the high-gradient region, but without requiring the mesh boundaries to join in any special way. Communications through boundary interfaces between those separated grids are carried out using trilinear interpolation. Application to the Euler equations for shock reflections and to shock wave/boundary layer interaction problem are tested. With the present method, the salient features are well-resolved.

Grid adaptation using Chimera composite overlapping meshes

NASA Technical Reports Server (NTRS)

Kao, Kai-Hsiung; Liou, Meng-Sing; Chow, Chuen-Yen

1993-01-01

The objective of this paper is to perform grid adaptation using composite over-lapping meshes in regions of large gradient to capture the salient features accurately during computation. The Chimera grid scheme, a multiple overset mesh technique, is used in combination with a Navier-Stokes solver. The numerical solution is first converged to a steady state based on an initial coarse mesh. Solution-adaptive enhancement is then performed by using a secondary fine grid system which oversets on top of the base grid in the high-gradient region, but without requiring the mesh boundaries to join in any special way. Communications through boundary interfaces between those separated grids are carried out using tri-linear interpolation. Applications to the Euler equations for shock reflections and to a shock wave/boundary layer interaction problem are tested. With the present method, the salient features are well resolved.

Distributed and self-adaptive vehicle speed estimation in the composite braking case for four-wheel drive hybrid electric car

NASA Astrophysics Data System (ADS)

Zhao, Z.-G.; Zhou, L.-J.; Zhang, J.-T.; Zhu, Q.; Hedrick, J.-K.

2017-05-01

Considering the controllability and observability of the braking torques of the hub motor, Integrated Starter Generator (ISG), and hydraulic brake for four-wheel drive (4WD) hybrid electric cars, a distributed and self-adaptive vehicle speed estimation algorithm for different braking situations has been proposed by fully utilising the Electronic Stability Program (ESP) sensor signals and multiple powersource signals. Firstly, the simulation platform of a 4WD hybrid electric car was established, which integrates an electronic-hydraulic composited braking system model and its control strategy, a nonlinear seven degrees-of-freedom vehicle dynamics model, and the Burckhardt tyre model. Secondly, combining the braking torque signals with the ESP signals, self-adaptive unscented Kalman sub-filter and main-filter adaptable to the observation noise were, respectively, designed. Thirdly, the fusion rules for the sub-filters and master filter were proposed herein, and the estimation results were compared with the simulated value of a real vehicle speed. Finally, based on the hardware in-the-loop platform and by picking up the regenerative motor torque signals and wheel cylinder pressure signals, the proposed speed estimation algorithm was tested under the case of moderate braking on the highly adhesive road, and the case of Antilock Braking System (ABS) action on the slippery road, as well as the case of ABS action on the icy road. Test results show that the presented vehicle speed estimation algorithm has not only a high precision but also a strong adaptability in the composite braking case.

Mind the gut: genomic insights to population divergence and gut microbial composition of two marine keystone species.

PubMed

Fietz, Katharina; Rye Hintze, Christian Olaf; Skovrind, Mikkel; Kjærgaard Nielsen, Tue; Limborg, Morten T; Krag, Marcus A; Palsbøll, Per J; Hestbjerg Hansen, Lars; Rask Møller, Peter; Gilbert, M Thomas P

2018-05-02

Deciphering the mechanisms governing population genetic divergence and local adaptation across heterogeneous environments is a central theme in marine ecology and conservation. While population divergence and ecological adaptive potential are classically viewed at the genetic level, it has recently been argued that their microbiomes may also contribute to population genetic divergence. We explored whether this might be plausible along the well-described environmental gradient of the Baltic Sea in two species of sand lance (Ammodytes tobianus and Hyperoplus lanceolatus). Specifically, we assessed both their population genetic and gut microbial composition variation and investigated not only which environmental parameters correlate with the observed variation, but whether host genome also correlates with microbiome variation. We found a clear genetic structure separating the high-salinity North Sea from the low-salinity Baltic Sea sand lances. The observed genetic divergence was not simply a function of isolation by distance, but correlated with environmental parameters, such as salinity, sea surface temperature, and, in the case of A. tobianus, possibly water microbiota. Furthermore, we detected two distinct genetic groups in Baltic A. tobianus that might represent sympatric spawning types. Investigation of possible drivers of gut microbiome composition variation revealed that host species identity was significantly correlated with the microbial community composition of the gut. A potential influence of host genetic factors on gut microbiome composition was further confirmed by the results of a constrained analysis of principal coordinates. The host genetic component was among the parameters that best explain observed variation in gut microbiome composition. Our findings have relevance for the population structure of two commercial species but also provide insights into potentially relevant genomic and microbial factors with regards to sand lance adaptation across the North Sea-Baltic Sea environmental gradient. Furthermore, our findings support the hypothesis that host genetics may play a role in regulating the gut microbiome at both the interspecific and intraspecific levels. As sequencing costs continue to drop, we anticipate that future studies that include full genome and microbiome sequencing will be able to explore the full relationship and its potential adaptive implications for these species.

Evolution mediates the effects of apex predation on aquatic food webs

PubMed Central

Urban, Mark C.

2013-01-01

Ecological and evolutionary mechanisms are increasingly thought to shape local community dynamics. Here, I evaluate if the local adaptation of a meso-predator to an apex predator alters local food webs. The marbled salamander (Ambystoma opacum) is an apex predator that consumes both the spotted salamander (Ambystoma maculatum) and shared zooplankton prey. Common garden experiments reveal that spotted salamander populations which co-occur with marbled salamanders forage more intensely than those that face other predator species. These foraging differences, in turn, alter the diversity, abundance and composition of zooplankton communities in common garden experiments and natural ponds. Locally adapted spotted salamanders exacerbate prey biomass declines associated with apex predation, but dampen the top-down effects of apex predation on prey diversity. Countergradient selection on foraging explains why locally adapted spotted salamanders exacerbate prey biomass declines. The two salamander species prefer different prey species, which explains why adapted spotted salamanders buffer changes in prey composition owing to apex predation. Results suggest that local adaptation can strongly mediate effects from apex predation on local food webs. Community ecologists might often need to consider the evolutionary history of populations to understand local diversity patterns, food web dynamics, resource gradients and their responses to disturbance. PMID:23720548

Evolution mediates the effects of apex predation on aquatic food webs.

PubMed

Urban, Mark C

2013-07-22

Ecological and evolutionary mechanisms are increasingly thought to shape local community dynamics. Here, I evaluate if the local adaptation of a meso-predator to an apex predator alters local food webs. The marbled salamander (Ambystoma opacum) is an apex predator that consumes both the spotted salamander (Ambystoma maculatum) and shared zooplankton prey. Common garden experiments reveal that spotted salamander populations which co-occur with marbled salamanders forage more intensely than those that face other predator species. These foraging differences, in turn, alter the diversity, abundance and composition of zooplankton communities in common garden experiments and natural ponds. Locally adapted spotted salamanders exacerbate prey biomass declines associated with apex predation, but dampen the top-down effects of apex predation on prey diversity. Countergradient selection on foraging explains why locally adapted spotted salamanders exacerbate prey biomass declines. The two salamander species prefer different prey species, which explains why adapted spotted salamanders buffer changes in prey composition owing to apex predation. Results suggest that local adaptation can strongly mediate effects from apex predation on local food webs. Community ecologists might often need to consider the evolutionary history of populations to understand local diversity patterns, food web dynamics, resource gradients and their responses to disturbance.

Evaluation of Columbia, USMARC-Composite, Suffolk, and Texel rams at terminal sires in an extensive rangeland production system

USDA-ARS?s Scientific Manuscript database

Crossing proven, superior terminal-sire sheep breeds with well-adapted maternal breeds provide opportunity to increase lamb carcass value, while maintaining acceptable environmental adaptation in crossbred lambs. Large, lean terminal-sire breeds, such as the Suffolk and Columbia, have been typicall...

Whole genome analysis for backfat thickness in a tropically adapted, composite cattle breed from Brazil

USDA-ARS?s Scientific Manuscript database

Backfat thickness affects preservation of the beef carcass after slaughter and confers organoleptic characteristics assessed by the consumer. One of the breeding goals for Canchim, a tropically adapted breed, is to comprehensively increase fat thickness. Our goal was to identify genomic regions ass...

Adaptation of Rhodopseudomonas acidophila strain 7050 to growth at different light intensities: what are the benefits to changing the type of LH2?

DOE PAGES

Gardiner, A. T.; Niedzwiedzki, D. M.; Cogdell, R. J.

2018-01-01

Femto-second time resolved absorption has been used to investigate how the energy transfer properties in the membranes of high-light and low-light adapted cells change as the composition of the LH2 complexes varies.

Adaptation of Rhodopseudomonas acidophila strain 7050 to growth at different light intensities: what are the benefits to changing the type of LH2?

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

Gardiner, A. T.; Niedzwiedzki, D. M.; Cogdell, R. J.

Femto-second time resolved absorption has been used to investigate how the energy transfer properties in the membranes of high-light and low-light adapted cells change as the composition of the LH2 complexes varies.

Policing of gut microbiota by the adaptive immune system.

PubMed

Dollé, Laurent; Tran, Hao Q; Etienne-Mesmin, Lucie; Chassaing, Benoit

2016-02-12

The intestinal microbiota is a large and diverse microbial community that inhabits the intestine, containing about 100 trillion bacteria of 500-1000 distinct species that, collectively, provide benefits to the host. The human gut microbiota composition is determined by a myriad of factors, among them genetic and environmental, including diet and medication. The microbiota contributes to nutrient absorption and maturation of the immune system. As reciprocity, the host immune system plays a central role in shaping the composition and localization of the intestinal microbiota. Secretory immunoglobulins A (sIgAs), component of the adaptive immune system, are important player in the protection of epithelium, and are known to have an important impact on the regulation of microbiota composition. A recent study published in Immunity by Fransen and colleagues aimed to mechanistically decipher the interrelationship between sIgA and microbiota diversity/composition. This commentary will discuss these important new findings, as well as how future therapies can ultimately benefit from such discovery.

Risk of Behavioral and Adaptive Functioning Difficulties in Youth with Previous and Current Sleep Disordered Breathing

PubMed Central

Perfect, Michelle M.; Archbold, Kristen; Goodwin, James L.; Levine-Donnerstein, Deborah; Quan, Stuart F.

2013-01-01

Objectives: To examine the rates of behavioral and adaptive functioning difficulties among youth who never had sleep disordered breathing (SDB), had remitted SDB, had incident SDB, or had persistent SDB; and to determine if there were increased odds of behavioral difficulties among youth with varying SDB histories relative to those who never had SDB. Methods: 263 youth had valid polysomnography and neurobehavioral data at two time points approximately 5 years apart from the prospective Tucson Children's Assessment of Sleep Apnea study. Primary outcomes were the Behavior Assessment Scale for Children-2nd Edition Parent Report Form (BASC-PRF) and Self-Report of Personality (SRP), and the Adaptive Behavior Assessment System-2nd Edition (ABAS-2). Results: Compared to those who never had SDB, individuals with persistent SDB had significant odds and met more cutoff scores on the BASC-2-PRF Externalizing Problems Composite (odds ratio [OR] 3.29; 8.92% vs. 35.3%), Behavioral Symptoms Index (OR 6.82; 7.4% vs. 35.3%) and Hyperactivity subscale (OR 6.82; 11.1% vs. 41.2%). Similarly, greater difficulties was seen for the group with persistent SDB (relative to never) on the ABAS-2 Social Domain (OR 3.39; 22% vs. 50%), and Communication (OR 4.26; 15% vs. 42.9%) and Self-Care subscales (OR = 2.97; 25.2% vs. 50%). Relative to youth who never had SDB, youth who developed SDB at Time 2 had compromised adaptive skills as evidenced by the BASC-2 PRF Adaptive Behavior Composite (OR 3.34; 15.6% vs. 38.1%) and the ABAS-2 General Adaptive Composite (OR 2.83; 20.5% vs. 42.1%). Conclusions: Youth with current SDB exhibited hyperactivity, attention problems, aggressivity, lower social competency, poorer communication, and/or diminished adaptive skills. Citation: Perfect MM; Archbold K; Goodwin JL; Levine-Donnerstein D; Quan SF. Risk of behavioral and adaptive functioning difficulties in youth with previous and current sleep disordered breathing. SLEEP 2013;36(4):517-525. PMID:23543901

Composite membrane with integral rim

DOEpatents

Routkevitch, Dmitri; Polyakov, Oleg G

2015-01-27

Composite membranes that are adapted for separation, purification, filtration, analysis, reaction and sensing. The composite membranes can include a porous support structure having elongate pore channels extending through the support structure. The composite membrane also includes an active layer comprising an active layer material, where the active layer material is completely disposed within the pore channels between the surfaces of the support structure. The active layer is intimately integrated within the support structure, thus enabling great robustness, reliability, resistance to mechanical stress and thermal cycling, and high selectivity. Methods for the fabrication of composite membranes are also provided.

Using Principles of Complex Adaptive Systems to Implement Secondary Prevention of Coronary Heart Disease in Primary Care

PubMed Central

Kottke, Thomas E; Huebsch, Jacquelyn A; McGinnis, Paul; Nichols, Jolleen M; Parker, Emily D; Tillema, Juliana O; Maciosek, Michael V

2016-01-01

Context: Primary care practice. Objective: To test whether the principles of complex adaptive systems are applicable to implementation of team-based primary care. Design: We used complex adaptive system principles to implement team-based care in a private, five-clinic primary care practice. We compared randomly selected samples of patients with coronary heart disease (CHD) and diabetes before system implementation (March 1, 2009, to February 28, 2010) and after system implementation (December 1, 2011, to March 31, 2013). Main Outcome Measures: Rates of patients meeting the composite goals for CHD (blood pressure < 140/90 mmHg, low-density lipoprotein cholesterol level < 100 mg/dL, tobacco-free, and using aspirin unless contraindicated) and diabetes (CHD goal plus hemoglobin A1c concentration < 8%) before and after the intervention. We also measured provider and patient satisfaction with preventive services. Results: The proportion of patients with CHD who met the composite goal increased from 40.3% to 59.9% (p < 0.0001) because documented aspirin use increased (65.2%–97.5%, p < 0.0001) and attainment of the cholesterol goal increased (77.0%–83.9%, p = 0.0041). The proportion of diabetic patients meeting the composite goal rose from 24.5% to 45.4% (p < 0.0001) because aspirin use increased (58.6%–97.6%, p < 0.0001). Increased percentages of patients meeting the CHD and diabetes composite goals were not significantly different (p = 0.2319). Provider satisfaction with preventive services delivery increased significantly (p = 0.0017). Patient satisfaction improved but not significantly. Conclusion: Principles of complex adaptive systems can be used to implement team-based care systems for patients with CHD and possibly diabetic patients. PMID:26784851

Using Principles of Complex Adaptive Systems to Implement Secondary Prevention of Coronary Heart Disease in Primary Care.

PubMed

Kottke, Thomas E; Huebsch, Jacquelyn A; Mcginnis, Paul; Nichols, Jolleen M; Parker, Emily D; Tillema, Juliana O; Maciosek, Michael V

2016-01-01

Primary care practice. To test whether the principles of complex adaptive systems are applicable to implementation of team-based primary care. We used complex adaptive system principles to implement team-based care in a private, five-clinic primary care practice. We compared randomly selected samples of patients with coronary heart disease (CHD) and diabetes before system implementation (March 1, 2009, to February 28, 2010) and after system implementation (December 1, 2011, to March 31, 2013). Rates of patients meeting the composite goals for CHD (blood pressure < 140/90 mmHg, low-density lipoprotein cholesterol level < 100 mg/dL, tobacco-free, and using aspirin unless contraindicated) and diabetes (CHD goal plus hemoglobin A1c concentration < 8%) before and after the intervention. We also measured provider and patient satisfaction with preventive services. The proportion of patients with CHD who met the composite goal increased from 40.3% to 59.9% (p < 0.0001) because documented aspirin use increased (65.2%-97.5%, p < 0.0001) and attainment of the cholesterol goal increased (77.0%-83.9%, p = 0.0041). The proportion of diabetic patients meeting the composite goal rose from 24.5% to 45.4% (p < 0.0001) because aspirin use increased (58.6%-97.6%, p < 0.0001). Increased percentages of patients meeting the CHD and diabetes composite goals were not significantly different (p = 0.2319). Provider satisfaction with preventive services delivery increased significantly (p = 0.0017). Patient satisfaction improved but not significantly. Principles of complex adaptive systems can be used to implement team-based care systems for patients with CHD and possibly diabetic patients.

Tags, wireless communication systems, tag communication methods, and wireless communications methods

DOEpatents

Scott,; Jeff W. , Pratt; Richard, M [Richland, WA

2006-09-12

Tags, wireless communication systems, tag communication methods, and wireless communications methods are described. In one aspect, a tag includes a plurality of antennas configured to receive a plurality of first wireless communication signals comprising data from a reader, a plurality of rectifying circuits coupled with. respective individual ones of the antennas and configured to provide rectified signals corresponding to the first wireless communication signals, wherein the rectified signals are combined to produce a composite signal, an adaptive reference circuit configured to vary a reference signal responsive to the composite signal, a comparator coupled with the adaptive reference circuit and the rectifying circuits and configured to compare the composite signal with respect to the reference signal and to output the data responsive to the comparison, and processing circuitry configured to receive the data from the comparator and to process the data.

Increased Isoprenoid Quinone Concentration Modulates Membrane Fluidity in Listeria monocytogenes at Low Growth Temperatures.

PubMed

Seel, Waldemar; Flegler, Alexander; Zunabovic-Pichler, Marija; Lipski, André

2018-07-01

Listeria monocytogenes is a food pathogen capable of growing at a broad temperature range from 50°C to refrigerator temperatures. A key requirement for bacterial activity and growth at low temperatures is the ability to adjust the membrane lipid composition to maintain cytoplasmic membrane fluidity. In this study, we confirmed earlier findings that the extents of fatty acid profile adaptation differed between L. monocytogenes strains. We were able to demonstrate for isolates from food that growth rates at low temperatures and resistance to freeze-thaw stress were not impaired by a lower adaptive response of the fatty acid composition. This indicated the presence of a second adaptation mechanism besides temperature-regulated fatty acid synthesis. For strains that showed weaker adaptive responses in their fatty acid profiles to low growth temperature, we could demonstrate a significantly higher concentration of isoprenoid quinones. Three strains even showed a higher quinone concentration after growth at 6°C than at 37°C, which is contradictory to the reduced respiratory activity at lower growth temperatures. Analyses of the membrane fluidity in vivo by measuring generalized polarization and anisotropy revealed modulation of the transition phase. Strains with increased quinone concentrations showed an expanded membrane transition phase in contrast to strains with pronounced adaptations of fatty acid profiles. The correlation between quinone concentration and membrane transition phase expansion was confirmed by suppression of quinone synthesis. A reduced quinone concentration resulted in a narrower transition phase. Expansion of the phase transition zone by increasing the concentration of non-fatty acid membrane lipids is discussed as an additional mechanism improving adaptation to temperature shifts for L. monocytogenes strains. IMPORTANCE Listeria monocytogenes is a foodborne pathogen with an outstanding temperature range for growth. The ability for growth at temperatures close to the freezing point constitutes a serious contamination potential for cold stored food. The only known mechanism of the species for adaptation of membrane fluidity is modification of the membrane fatty acid composition. We were able to demonstrate that, at least for some strains, this adaptation mechanism is supported by regulation of the menaquinone concentration. The increase of this neutral membrane lipid is correlated with fluidization of the membrane under low-temperature conditions and therefore represents a fatty acid-independent mechanism for adaptation to low temperatures. Copyright © 2018 American Society for Microbiology.

Adaptive tuned vibration absorber based on magnetorheological elastomer-shape memory alloy composite

NASA Astrophysics Data System (ADS)

Kumbhar, Samir B.; Chavan, S. P.; Gawade, S. S.

2018-02-01

Shape memory alloy (SMA) is an attractive smart material which could be used as stiffness tuning element in adaptive tuned vibration absorber (ATVA). The sharp modulus change in SMA material during phase transformation creates difficulties for smooth tuning to track forcing frequency to minimize vibrations of primary system. However, high hysteresis damping at low temperature martensitic phase degrades performance of vibration absorber. This paper deals with the study of dynamic response of system in which SMA and magnetorheological elastomer (MRE) are combined together to act as a smart spring- mass-damper system in a tuned vibration absorber. This composite is used as two way stiffness tuning element in ATVA for smooth and continuous tuning and to minimize the adverse effect at low temperature by increasing equivalent stiffness. The stiffnesses of SMA element and MRE are varied respectively by changing temperature and strength of external magnetic field. The two way stiffness tuning ability and adaptivity have been demonstrated analytically and experimentally. The experimental results show good agreement with analytical results. The proposed composite is able to shift the stiffness consequently the natural frequency of primary system as well as reduce the vibration level of primary system by substantial mount.

Static aeroelastic behavior of an adaptive laminated piezoelectric composite wing

NASA Technical Reports Server (NTRS)

Weisshaar, T. A.; Ehlers, S. M.

1990-01-01

The effect of using an adaptive material to modify the static aeroelastic behavior of a uniform wing is examined. The wing structure is idealized as a laminated sandwich structure with piezoelectric layers in the upper and lower skins. A feedback system that senses the wing root loads applies a constant electric field to the piezoelectric actuator. Modification of pure torsional deformaton behavior and pure bending deformation are investigated, as is the case of an anisotropic composite swept wing. The use of piezoelectric actuators to create an adaptive structure is found to alter static aeroelastic behavior in that the proper choice of the feedback gain can increase or decrease the aeroelastic divergence speed. This concept also may be used to actively change the lift effectiveness of a wing. The ability to modify static aeroelastic behavior is limited by physical limitations of the piezoelectric material and the manner in which it is integrated into the parent structure.

An integration time adaptive control method for atmospheric composition detection of occultation

NASA Astrophysics Data System (ADS)

Ding, Lin; Hou, Shuai; Yu, Fei; Liu, Cheng; Li, Chao; Zhe, Lin

2018-01-01

When sun is used as the light source for atmospheric composition detection, it is necessary to image sun for accurate identification and stable tracking. In the course of 180 second of the occultation, the magnitude of sun light intensity through the atmosphere changes greatly. It is nearly 1100 times illumination change between the maximum atmospheric and the minimum atmospheric. And the process of light change is so severe that 2.9 times per second of light change can be reached. Therefore, it is difficult to control the integration time of sun image camera. In this paper, a novel adaptive integration time control method for occultation is presented. In this method, with the distribution of gray value in the image as the reference variable, and the concepts of speed integral PID control, the integration time adaptive control problem of high frequency imaging. The large dynamic range integration time automatic control in the occultation can be achieved.

The Role of Adaptive Behavior in Autism Spectrum Disorders: Implications for Functional Outcome

ERIC Educational Resources Information Center

Kanne, Stephen M.; Gerber, Andrew J.; Quirmbach, Linda M.; Sparrow, Sara S.; Cicchetti, Domenic V.; Saulnier, Celine A.

2011-01-01

The relationship between adaptive functioning and autism symptomatology was examined in 1,089 verbal youths with ASD examining results on Vineland-II, IQ, and measures of ASD severity. Strong positive relationships were found between Vineland subscales and IQ. Vineland Composite was negatively associated with age. IQ accounted a significant amount…

Personalisation for All: Making Adaptive Course Composition Easy

ERIC Educational Resources Information Center

Dagger, Declan; Wade, Vincent; Conlan, Owen

2005-01-01

The goal of personalised eLearning is to support e-learning content, activities and collaboration, adapted to the specific needs and influenced by specific preferences of the learner and built on sound pedagogic strategies. One of the major challenges to the mainstream adoption of personalised eLearning is the complexity and time involved in…

Forest management for mitigation and adaptation: insights from long-term silvicultural experiments

Treesearch

Anthony W. D' Amato; John B. Bradford; Shawn Fraver; Brian J. Palik

2011-01-01

Developing management strategies for addressing global climate change has become an increasingly important issue influencing forest management around the globe. Currently, management approaches are being proposed that intend to (1) mitigate climate change by enhancing forest carbon stores and (2) foster adaptation by maintaining compositionally and structurally complex...

The Halophile protein database.

PubMed

Sharma, Naveen; Farooqi, Mohammad Samir; Chaturvedi, Krishna Kumar; Lal, Shashi Bhushan; Grover, Monendra; Rai, Anil; Pandey, Pankaj

2014-01-01

Halophilic archaea/bacteria adapt to different salt concentration, namely extreme, moderate and low. These type of adaptations may occur as a result of modification of protein structure and other changes in different cell organelles. Thus proteins may play an important role in the adaptation of halophilic archaea/bacteria to saline conditions. The Halophile protein database (HProtDB) is a systematic attempt to document the biochemical and biophysical properties of proteins from halophilic archaea/bacteria which may be involved in adaptation of these organisms to saline conditions. In this database, various physicochemical properties such as molecular weight, theoretical pI, amino acid composition, atomic composition, estimated half-life, instability index, aliphatic index and grand average of hydropathicity (Gravy) have been listed. These physicochemical properties play an important role in identifying the protein structure, bonding pattern and function of the specific proteins. This database is comprehensive, manually curated, non-redundant catalogue of proteins. The database currently contains 59 897 proteins properties extracted from 21 different strains of halophilic archaea/bacteria. The database can be accessed through link. Database URL: http://webapp.cabgrid.res.in/protein/ © The Author(s) 2014. Published by Oxford University Press.

Polymer ceramic composite that follows the rules of bone growth

NASA Astrophysics Data System (ADS)

Dry, Carolyn M.; Warner, Carrie

1998-07-01

Research at the University of Illinois School of Architecture Material's Lab is being done on a biomimetic building material with the unique properties of bone. This polymer/ceramic composite will mimic bone by controlling the (1) the structure and form of the material, (2) chemical makeup and sequencing of fabrication, (3) ability to adapt to environmental changes during fabrication, and (4) ability to later adapt and repair itself. Bones and shells obtain their great toughness and strength as a result of careful control of these four factors. The organic fibers are made first and the matrix grown around them as opposed to conventional ceramics in which any fibers are added to the matrix. Constituents are also placed in the material which allow it to later adapt to outside changes. The rules under which bone material naturally forms and adapts, albeit at a macroscale, are followed. Our efforts have concentrated on the chemical makeup, and basic sequencing of fabrication. Our research sought to match the intimate connection between material phases of bone by developing the chemical makeup.

Adaptive Same Frequency Repeater (SFR) Study

DTIC Science & Technology

1976-03-01

Formulation 13 (2) Evaluation of the Steady State Weights!.’.’.’!.*!!."!! 21 (3) Evaluation of the Composite Transfer Function.... 2^ (4) Simplified...well as possible the amplitude and phase of the composite coupling path. Because the coupling paths have frequency-dependent transfer functions...34), (35) and the notch filter and channel transfer .’unctions (3fi) and (39). The composite transfer function Hc(f ’ ^’.f) is then found and

Effects of cooking methods on starch and sugar composition of sweetpotato storage roots

USDA-ARS?s Scientific Manuscript database

Sweet potato has rich nutrition, good ecological adaptability and high yield. There was a lack of knowledge about the relationship among cooking methods, sugar components and cultivars. The objective of this study was to determine sugar composition of four sweet potato cultivars under three cooking ...

Functional adaptation of crustacean exoskeletal elements through structural and compositional diversity: a combined experimental and theoretical study.

PubMed

Fabritius, Helge-Otto; Ziegler, Andreas; Friák, Martin; Nikolov, Svetoslav; Huber, Julia; Seidl, Bastian H M; Ruangchai, Sukhum; Alagboso, Francisca I; Karsten, Simone; Lu, Jin; Janus, Anna M; Petrov, Michal; Zhu, Li-Fang; Hemzalová, Pavlína; Hild, Sabine; Raabe, Dierk; Neugebauer, Jörg

2016-09-09

The crustacean cuticle is a composite material that covers the whole animal and forms the continuous exoskeleton. Nano-fibers composed of chitin and protein molecules form most of the organic matrix of the cuticle that, at the macroscale, is organized in up to eight hierarchical levels. At least two of them, the exo- and endocuticle, contain a mineral phase of mainly Mg-calcite, amorphous calcium carbonate and phosphate. The high number of hierarchical levels and the compositional diversity provide a high degree of freedom for varying the physical, in particular mechanical, properties of the material. This makes the cuticle a versatile material ideally suited to form a variety of skeletal elements that are adapted to different functions and the eco-physiological strains of individual species. This review presents our recent analytical, experimental and theoretical studies on the cuticle, summarising at which hierarchical levels structure and composition are modified to achieve the required physical properties. We describe our multi-scale hierarchical modeling approach based on the results from these studies, aiming at systematically predicting the structure-composition-property relations of cuticle composites from the molecular level to the macro-scale. This modeling approach provides a tool to facilitate the development of optimized biomimetic materials within a knowledge-based design approach.

Characterization of Metal Matrix Composites

NASA Technical Reports Server (NTRS)

Daniel, I. M.; Chun, H. J.; Karalekas, D.

1994-01-01

Experimental methods were developed, adapted, and applied to the characterization of a metal matrix composite system, namely, silicon carbide/aluminim (SCS-2/6061 Al), and its constituents. The silicon carbide fiber was characterized by determining its modulus, strength, and coefficient of thermal expansion. The aluminum matrix was characterized thermomechanically up to 399 C (750 F) at two strain rates. The unidirectional SiC/Al composite was characterized mechanically under longitudinal, transverse, and in-plane shear loading up to 399 C (750 F). Isothermal and non-isothermal creep behavior was also measured. The applicability of a proposed set of multifactor thermoviscoplastic nonlinear constitutive relations and a computer code was investigated. Agreement between predictions and experimental results was shown in a few cases. The elastoplastic thermomechanical behavior of the composite was also described by a number of new analytical models developed or adapted for the material system studied. These models include the rule of mixtures, composite cylinder model with various thermoelastoplastic analyses and a model based on average field theory. In most cases satisfactory agreement was demonstrated between analytical predictions and experimental results for the cases of stress-strain behavior and thermal deformation behavior at different temperatures. In addition, some models yielded detailed three-dimensional stress distributions in the constituents within the composite.

Hybrid passive/active damping for robust multivariable acoustic control in composite plates

NASA Astrophysics Data System (ADS)

Veeramani, Sudha; Wereley, Norman M.

1996-05-01

Noise transmission through a flexible kevlar-epoxy composite trim panel into an acoustic cavity or box is studied with the intent of controlling the interior sound fields. A hybrid noise attenuation technique is proposed which uses viscoelastic damping layers in the composite plate for passive attenuation of high frequency noise transmission, and uses piezo-electric patch actuators for active control in the low frequency range. An adaptive feedforward noise control strategy is applied. The passive structural damping augmentation incorporated in the composite plates is also intended to increase stability robustness of the active noise control strategy. A condenser microphone in the interior of the enclosure functions as the error sensor. Three composite plates were experimentally evaluated: one with no damping layer, the second with a 10 mil damping layer, and the third with a 15 mil damping layer. The damping layer was cocured in the kevlar-epoxy trim panels. Damping in the plates was increased from 1.6% for the plate with no damping layer, to 5.9% for the plate with a 15 mil damping layer. In experimental studies, the improved stability robustness of the controller was demonstrated by improved adaptive feedforward control algorithm convergence. A preliminary analytical model is presented that describes the dynamic behavior of a composite panel actuated by piezoelectric actuators bonded to its surface.

Dynamic grid refinement for partial differential equations on parallel computers

NASA Technical Reports Server (NTRS)

Mccormick, S.; Quinlan, D.

1989-01-01

The fast adaptive composite grid method (FAC) is an algorithm that uses various levels of uniform grids to provide adaptive resolution and fast solution of PDEs. An asynchronous version of FAC, called AFAC, that completely eliminates the bottleneck to parallelism is presented. This paper describes the advantage that this algorithm has in adaptive refinement for moving singularities on multiprocessor computers. This work is applicable to the parallel solution of two- and three-dimensional shock tracking problems.

Accelerator mass spectrometry of small biological samples.

PubMed

Salehpour, Mehran; Forsgard, Niklas; Possnert, Göran

2008-12-01

Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for isotopic ratio measurements. In the biomedical field, AMS can be used to measure femtomolar concentrations of labeled drugs in body fluids, with direct applications in early drug development such as Microdosing. Likewise, the regenerative properties of cells which are of fundamental significance in stem-cell research can be determined with an accuracy of a few years by AMS analysis of human DNA. However, AMS nominally requires about 1 mg of carbon per sample which is not always available when dealing with specific body substances such as localized, organ-specific DNA samples. Consequently, it is of analytical interest to develop methods for the routine analysis of small samples in the range of a few tens of microg. We have used a 5 MV Pelletron tandem accelerator to study small biological samples using AMS. Different methods are presented and compared. A (12)C-carrier sample preparation method is described which is potentially more sensitive and less susceptible to contamination than the standard procedures.

The influence of non-DNA-targeted effects on carbon ion–induced low-dose hyper-radiosensitivity in MRC-5 cells

PubMed Central

Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

2016-01-01

Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation–induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion–induced LDHRS. PMID:26559335

UVPROM dosimetry, microdosimetry and applications to SEU and extreme value theory

NASA Astrophysics Data System (ADS)

Scheick, Leif Zebediah

A new method is described for characterizing a device in terms of the statistical distribution of first failures. The method is based on the erasure of a commercial Ultra- Violet erasable Programmable Read Only Memory (UVPROM). The method of readout would be used on a spacecraft or in other restrictive radiation environments. The measurement of the charge remaining on the floating gate is used to determine absorbed dose. The method of determining dose does not require the detector to be destroyed or erased nor does it effect the ability for taking further measurements. This is compared to extreme value theory applied to the statistical distributions that apply to this device. This technique predicts the threshold of Single Event Effects (SEE), like anomalous changes in erasure time in programmable devices due to high microdose energy-deposition events. This technique also allows for advanced non-destructive, screening of a single microelectronic devices for predictable response in a stressful, i.e. radiation, environments.

Determination of quality factors by microdosimetry

NASA Astrophysics Data System (ADS)

Al-Affan, I. A. M.; Watt, D. E.

1987-03-01

The application of microdose parameters for the specification of a revised scale of quality factors which would be applicable at low doses and dose rates is examined in terms of an original proposal by Rossi. Two important modifications are suggested to enable an absolute scale of quality factors to be constructed. Allowance should be made to allow for the dependence of the saturation threshold of lineal energy on the type of heavy charged particle. Also, an artificial saturation threshold should be introduced for electron tracks as a mean of modifying the measurements made in the microdosimeter to the more realistic site sizes of nanometer dimensions. The proposed absolute scale of quality factors nicely encompasses the high RBEs of around 3 observed at low doses for tritium β rays and is consistent with the recent recommendation of the ICRP that the quality factor for fast neutrons be increased by a factor of two, assuming that there is no biological repair for the reference radiation.

Methods in Clinical Pharmacology Series

PubMed Central

Beaumont, Claire; Young, Graeme C; Cavalier, Tom; Young, Malcolm A

2014-01-01

Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (ADME) properties of a drug. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical ADME and pharmacokinetic (PK) information. These include microdose and microtracer approaches using accelerator mass spectrometry, and the identification and quantification of metabolites in samples from classical human PK studies using technologies suitable for non-radiolabelled drug molecules, namely liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. These recently developed approaches are described here together with relevant examples primarily from experiences gained in support of drug development projects at GlaxoSmithKline. The advantages of these study designs together with their limitations are described. We also discuss special considerations which should be made for a successful outcome to these new approaches and also to the more traditional human radiolabel study in order to maximize knowledge around the human ADME properties of drug molecules. PMID:25041729

Numerical investigation of active porous composites with enhanced acoustic absorption

NASA Astrophysics Data System (ADS)

Zieliński, Tomasz G.

2011-10-01

The paper presents numerical analysis - involving an advanced multiphysics modeling - of the concept of active porous composite sound absorbers. Such absorbers should be made up of a layer or layers of poroelastic material (porous foams) with embedded elastic inclusions having active (piezoelectric) elements. The purpose of such active composite material is to significantly absorb the energy of acoustic waves in a wide frequency range, particularly, at lower frequencies. At the same time the total thickness of composite should be very moderate. The active parts of composites are used to adapt the absorbing properties of porous layers to different noise conditions by affecting the so-called solid-borne wave - originating mainly from the vibrations of elastic skeleton of porous medium - to counteract the fluid-borne wave - resulting mainly from the vibrations of air in the pores; both waves are strongly coupled, especially, at lower frequencies. In fact, since the traction between the air and the solid frame of porous medium is the main absorption mechanism, the elastic skeleton is actively vibrated in order to adapt and improve the dissipative interaction of the skeleton and air in the pores. Passive and active performance of such absorbers is analyzed to test the feasibility of this approach.

An evaluation of unisensory and multisensory adaptive flight-path navigation displays

NASA Astrophysics Data System (ADS)

Moroney, Brian W.

1999-11-01

The present study assessed the use of unimodal (auditory or visual) and multimodal (audio-visual) adaptive interfaces to aid military pilots in the performance of a precision-navigation flight task when they were confronted with additional information-processing loads. A standard navigation interface was supplemented by adaptive interfaces consisting of either a head-up display based flight director, a 3D virtual audio interface, or a combination of the two. The adaptive interfaces provided information about how to return to the pathway when off course. Using an advanced flight simulator, pilots attempted two navigation scenarios: (A) maintain proper course under normal flight conditions and (B) return to course after their aircraft's position has been perturbed. Pilots flew in the presence or absence of an additional information-processing task presented in either the visual or auditory modality. The additional information-processing tasks were equated in terms of perceived mental workload as indexed by the NASA-TLX. Twelve experienced military pilots (11 men and 1 woman), naive to the purpose of the experiment, participated in the study. They were recruited from Wright-Patterson Air Force Base and had a mean of 2812 hrs. of flight experience. Four navigational interface configurations, the standard visual navigation interface alone (SV), SV plus adaptive visual, SV plus adaptive auditory, and SV plus adaptive visual-auditory composite were combined factorially with three concurrent tasks (CT), the no CT, the visual CT, and the auditory CT, a completely repeated measures design. The adaptive navigation displays were activated whenever the aircraft was more than 450 ft off course. In the normal flight scenario, the adaptive interfaces did not bolster navigation performance in comparison to the standard interface. It is conceivable that the pilots performed quite adequately using the familiar generic interface under normal flight conditions and hence showed no added benefit of the adaptive interfaces. In the return-to-course scenario, the relative advantages of the three adaptive interfaces were dependent upon the nature of the CT in a complex way. In the absence of a CT, recovery heading performance was superior with the adaptive visual and adaptive composite interfaces compared to the adaptive auditory interface. In the context of a visual CT, recovery when using the adaptive composite interface was superior to that when using the adaptive visual interface. Post-experimental inquiry indicated that when faced with a visual CT, the pilots used the auditory component of the multimodal guidance display to detect gross heading errors and the visual component to make more fine-grained heading adjustments. In the context of the auditory CT, navigation performance using the adaptive visual interface tended to be superior to that when using the adaptive auditory interface. Neither CT performance nor NASA-TLX workload level was influenced differentially by the interface configurations. Thus, the potential benefits associated with the proposed interfaces appear to be unaccompanied by negative side effects involving CT interference and workload. The adaptive interface configurations were altered without any direct input from the pilot. Thus, it was feared that pilots might reject the activation of interfaces independent of their control. However, pilots' debriefing comments about the efficacy of the adaptive interface approach were very positive. (Abstract shortened by UMI.)

EDITORIAL Smart materials, multifunctional composites, and morphing structures: selected papers from the 20th International Conference on Adaptive Structures and Technologies (ICAST 2009) Smart materials, multifunctional composites, and morphing structures: selected papers from the 20th International Conference on Adaptive Structures and Technologies (ICAST 2009)

NASA Astrophysics Data System (ADS)

Liao, Wei-Hsin

2010-12-01

The 20th International Conference on Adaptive Structures and Technologies (ICAST) was held on 20-22 October 2009 in Hong Kong. This special section of Smart Materials and Structures is derived from the research papers presented at the conference. Of the 106 papers presented at the conference, 11 papers were reviewed and accepted for this special section, following the regular review procedures of the journal. This special section is focused on smart materials, multifunctional composites, and applications on morphing structures. Smart materials. Smart materials are the foundation of adaptive structures and intelligent systems. The development of new materials will lead to significant improvement in various applications. Three articles are focused on the fabrication of new materials and investigation of their behaviors: Barium strontium zirconate titanate ((Ba1-xSrx)(ZrxTi1-x)O3; BSZT, x = 0.25 and 0.75) ceramics with a highly crystalline structure were fabricated using the combustion technique. The microstructure of BSZT powders exhibited an almost-spherical morphology and had a porous agglomerated form. Polyaniline (PANI)/clay nanoparticles with unique core-shell structure were synthesized via Pickering emulsion polymerization. By dispersing PANI/clay nanoparticles in silicone oil, the ER fluid was made. Magnetic field effects were investigated on the deposition rate and surface morphology of chromium nitride coatings deposited by magnetron sputtering for superior hardness, excellent wear and oxidation resistance. The surface morphology of chromium nitride films was also examined by a scanning electron microscope (SEM). Multifunctional composites. Composites are made from two or more constituent materials so they can combine the best properties of different materials. Five papers deal with fabrication, testing, and modeling of various multifunctional composites: A new active structural fiber (ASF) was fabricated by coating a single carbon fiber with a concentric PZT (PbZr0.52Ti0.48O3) shell using electrolytic deposition. This new ASF is expected to have broader applications due to the higher piezoelectric coupling effect with the use of carbon fiber and PZT. The sol-gel technique was employed to deposit lead zirconium titanium (PZT) and silica composite film onto a copper (Cu)/polyimide (PI) flexible structure. The fabricated PZT-silica composite films were then used for flexible actuator and sensor applications. Interfacial properties and hydrophobicity of multifunctional Ni-nanopowder/epoxy composites were evaluated for self-sensing and actuation. The effects of water content on the actuation performance of ionic polymer-metal composites (IPMCs) were investigated experimentally. Multiscale modelling of a composite electroactive polymer structure was developed, in particular for tubular actuators. The models were validated with experimental data. Morphing structures. Three papers relate to morphing skins and structures. Several issues including stiffness and energy consumption were explored: Composite corrugated structures were used as morphing skin panels (MSPs) in the trailing edge region of a scaled morphing aerofoil section. Wind tunnel testing was carried out to demonstrate the MSP concept. Optimization of a variable-stiffness skin was performed for morphing high-lift devices. The objective is to design the structure to have high enough stiffness to withstand aerodynamic loading and yet low enough stiffness to enable morphing. The aerodynamic and actuation loads were taken into consideration during the optimization. Two adaptive and morphing structures were proposed for low-energy consumption or even energy-harvesting green buildings with the use of an optimization process. Searching for optimal solutions was done by means of an evolutionary technique while the compatibility of the resulting configurations of the adaptive envelope was ensured by the virtual force density method. We would like to thank all of the authors for their significant contributions to this special section for Smart Materials and Structures. We are also grateful to all of the reviewers and associate editors who handled the reviews for their time and effort. I would like to express my sincere appreciation to Professor E Garcia, Editor-in-Chief, for his encouragement by providing the opportunity to make this special section. I am indebted to IOP Publishing for their strong support and the staff, in particular publisher Natasha Leeper, for their special attention and excellent service.

Composite membranes and methods for making same

DOEpatents

Routkevitch, Dmitri; Polyakov, Oleg G

2012-07-03

Composite membranes that are adapted for separation, purification, filtration, analysis, reaction and sensing. The composite membranes can include a porous support structure having elongate pore channels extending through the support structure. The composite membrane also includes an active layer comprising an active layer material, where the active layer material is completely disposed within the pore channels between the surfaces of the support structure. The active layer is intimately integrated within the support structure, thus enabling great robustness, reliability, resistance to mechanical stress and thermal cycling, and high selectivity. Methods for the fabrication of composite membranes are also provided.

Adaptation of the membrane in Archaea.

PubMed

Oger, Philippe M; Cario, Anaïs

2013-12-15

Microbes often face contrasted and fluctuating environmental conditions, to which they need to adapt or die. Because membranes play a central role in regulating fluxes inward and outward from the cells, maintaining the appropriate structure of the membrane is crucial to maintain cellular integrity and functions. This is achieved in bacteria and eucarya by a modification of the membrane lipid compositions, a strategy termed homeoviscous adaptation. We review here evidence for homeoviscous adaptation in Archaea, and discuss the limits of this strategy and our knowledge in this very peculiar domain of life. © 2013 Elsevier B.V. All rights reserved.

Aridification of the Indian Subcontinent during the Holocene: Implications for Landscape Evolution, Sedimentation, Carbon Cycle, and Human Civilizations

DTIC Science & Technology

2012-06-01

of flora for both sites. For the Godavari River basin the  13 Cwax record shows a gradual increase in aridity- adapted vegetation from ~4,000 until...1,700 years ago followed by the persistence of aridity- adapted plants to the present. The oxygen isotopic composition of planktonic foraminifera...for a gradual increase in the proportion of aridity- adapted vegetation from ~4,000 until 1,700 years ago followed by the persistence of aridity

A comparison of locally adaptive multigrid methods: LDC, FAC and FIC

NASA Technical Reports Server (NTRS)

Khadra, Khodor; Angot, Philippe; Caltagirone, Jean-Paul

1993-01-01

This study is devoted to a comparative analysis of three 'Adaptive ZOOM' (ZOom Overlapping Multi-level) methods based on similar concepts of hierarchical multigrid local refinement: LDC (Local Defect Correction), FAC (Fast Adaptive Composite), and FIC (Flux Interface Correction)--which we proposed recently. These methods are tested on two examples of a bidimensional elliptic problem. We compare, for V-cycle procedures, the asymptotic evolution of the global error evaluated by discrete norms, the corresponding local errors, and the convergence rates of these algorithms.

ARABIC TRANSLATION AND ADAPTATION OF THE HOSPITAL CONSUMER ASSESSMENT OF HEALTHCARE PROVIDERS AND SYSTEMS (HCAHPS) PATIENT SATISFACTION SURVEY INSTRUMENT.

PubMed

Dockins, James; Abuzahrieh, Ramzi; Stack, Martin

2015-01-01

To translate and adapt an effective, validated, benchmarked, and widely used patient satisfaction measurement tool for use with an Arabic-speaking population. Translation of survey's items, survey administration process development, evaluation of reliability, and international benchmarking Three hundred-bed tertiary care hospital in Jeddah, Saudi Arabia. 645 patients discharged during 2011 from the hospital's inpatient care units. INTERVENTIONS; The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) instrument was translated into Arabic, a randomized weekly sample of patients was selected, and the survey was administered via telephone during 2011 to patients or their relatives. Scores were compiled for each of the HCAHPS questions and then for each of the six HCAHPS clinical composites, two non-clinical items, and two global items. Clinical composite scores, as well as the two non-clinical and two global items were analyzed for the 645 respondents. Clinical composites were analyzed using Spearman's correlation coefficient and Cronbach's alpha to demonstrate acceptable internal consistency for these items and scales demonstrated acceptable internal consistency for the clinical composites. (Spearman's correlation coefficient = 0.327 - 0.750, P < 0.01; Cronbach's alpha = 0.516 - 0.851) All ten HCAHPS measures were compared quarterly to US national averages with results that closely paralleled the US benchmarks. . The Arabic translation and adaptation of the HCAHPS is a valid, reliable, and feasible tool for evaluation and benchmarking of inpatient satisfaction in Arabic speaking populations.

Age-related patterns of forest complexity and carbon storage in pine and aspen-birch ecosystems of northern Minnesota, USA

Treesearch

John B. Bradford; Douglas N. Kastendick

2010-01-01

Forest managers are seeking strategies to create stands that can adapt to new climatic conditions and simultaneously help mitigate increases in atmospheric CO2. Adaptation strategies often focus on enhancing resilience by maximizing forest complexity in terms of species composition and size structure, while mitigation involves sustaining carbon...

Molybdenum sealing glass-ceramic composition

DOEpatents

Eagan, Robert J.

1976-01-01

The invention relates to a glass-ceramic composition having low hydrogen and helium permeability properties, along with high fracture strength, a thermal coefficient of expansion similar to that of molybdenum, and adaptable for hermetically sealing to molybdenum at temperatures of between about 900.degree. and about 950.degree.C. to form a hermatically sealed insulator body.

Fragmentation of forest communities in the eastern United States

Treesearch

Kurt Riitters; John Coulston; James Wickham

2011-01-01

Forest fragmentation threatens the sustainability of forest communities in the eastern United States. Forest communities exhibiting either a low total area or low percentage of intact forest are subject to relatively higher risk of shifts in stand composition towards edge-adapted and invasive species. Such changes in stand composition could result in local extirpation...

Infant Manual Exploration of Composite Substrates

ERIC Educational Resources Information Center

Fontenelle, Sarah A.; Kahrs, Bjorn Alexander; Neal, S. Ashley; Newton, A. Taylor; Lockman, Jeffrey J.

2007-01-01

Everyday environments, even small regions within reach, vary dramatically in terms of material composition. Adapting one's manual behavior to such transitions can be considered to be an important element of skilled action. To investigate the origins of this ability, we presented 8-month-olds (n=24) and 10-month-olds (n=24) hard or soft objects on…

Marginal integrity of resin composite restorations restored with PPD initiatorcontaining resin composite cured by QTH, monowave and polywave LED units.

PubMed

Bortolotto, Tissiana; Betancourt, Francisco; Krejci, Ivo

2016-12-01

This study evaluated the influence of curing devices on marginal adaptation of cavities restored with self-etching adhesive containing CQ and PPD initiators and hybrid composite. Twenty-four class V (3 groups, n=8) with margins located on enamel and dentin were restored with Clearfil S3 Bond and Clearfil APX PLT, light-cured with a monowave LED, multiwave LED and halogen light-curing unit (LCU). Marginal adaptation was evaluated with SEM before/after thermo-mechanical loading (TML). On enamel, significantly lower % continuous margins (74.5±12.6) were found in group cured by multiwave LED when compared to monowave LED (87.6±9.5) and halogen LCU (94.4±9.1). The presence of enamel and composite fractures was significantly higher in the group light-cured with multiwave LED, probably due to an increased materials' friability resulted from an improved degree of cure. The clinician should aware that due to a distinct activation of both initiators, marginal quality may be influenced on the long-term.

Association between adaptive behaviour and age in adults with Down syndrome without dementia: examining the range and severity of adaptive behaviour problems.

PubMed

Makary, A T; Testa, R; Tonge, B J; Einfeld, S L; Mohr, C; Gray, K M

2015-08-01

Studies on adaptive behaviour and ageing in adults with Down syndrome (DS) (without dementia) have typically analysed age-related change in terms of the total item scores on questionnaires. This research extends the literature by investigating whether the age-related changes in adaptive abilities could be differentially attributed to changes in the number or severity (intensity) of behavioural questionnaire items endorsed. The Adaptive Behaviour Assessment System-II Adult (ABAS-II Adult) was completed by parents and caregivers of 53 adults with DS aged between 16 and 56 years. Twenty adults with DS and their parents/caregivers were a part of a longitudinal study, which provided two time points of data. In addition 33 adults with DS and their parents/caregivers from a cross-sectional study were included. Random effects regression analyses were used to examine the patterns in item scores associated with ageing. Increasing age was found to be significantly associated with lower adaptive behaviour abilities for all the adaptive behaviour composite scores, expect for the practical composite. These associations were entirely related to fewer ABAS-II Adult items being selected as present for the older participants, as opposed to the scores being attributable to lower item severity. This study provides evidence for a differential pattern of age-related change for various adaptive behaviour skills in terms of range, but not severity. Possible reasons for this pattern will be discussed. Overall, these findings suggest that adults with DS may benefit from additional support in terms of their social and conceptual abilities as they age. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

A Microdose PET Study of the Safety, Immunogenicity, Biodistribution, and Radiation Dosimetry of 18F-FB-A20FMDV2 for Imaging the Integrin αvβ6.

PubMed

Keat, Nicholas; Kenny, Julia; Chen, Keguan; Onega, Mayca; Garman, Nadia; Slack, Robert J; Parker, Christine A; Lumbers, R Thomas; Hallett, Will; Saleem, Azeem; Passchier, Jan; Lukey, Pauline T

2018-06-01

The α v β 6 integrin is involved in the pathogenesis of cancer and fibrosis. A radiolabeled 20-amino-acid α v β 6 -binding peptide, derived from the foot and mouth virus (NAVPNLRGDLQVLAQKVART [A20FMDV2]), has been developed to image α v β 6 levels preclinically. This study was designed to translate these findings into a clinical PET imaging protocol to measure the expression of α v β 6 in humans. Methods: Preclinical toxicology was undertaken, and a direct immunoassay was developed for 4-fluorobenzamide (FB)-A20FMDV2. Four healthy human subjects (2 male and 2 female) received a single microdose of 18 F-FB-A20FMDV2 followed by a multibed PET scan of the whole body over more than 3 h. Results: There were no findings in the preclinical toxicology assessments, and no anti-A20FMDV2 antibodies were detected before or after dosing with the PET ligand. The mean and SD of the administered mass of 18 F-FB-A20FMDV2 was 8.7 ± 4.4 μg (range, 2.7-13.0 μg). The mean administered activity was 124 ± 20 MBq (range, 98-145 MBq). There were no adverse or clinically detectable pharmacologic effects in any of the subjects. No significant changes in vital signs, laboratory study results, or electrocardiography results were observed. Uptake of radioactivity was observed in the thyroid, salivary glands, liver, stomach wall, spleen, kidneys, ureters, and bladder. Time-activity curves indicated that the highest activity was in the bladder content, followed by the kidneys, small intestine, stomach, liver, spleen, thyroid, and gallbladder. The largest component of the residence times was the voided urine, followed by muscle, bladder, and liver. Using the mean residence time over all subjects as input to OLINDA/EXM, the effective dose was determined to be 0.0217 mSv/MBq; using residence times from single subjects gave an SD of 0.0020 mSv/MBq from the mean. The critical organ was the urinary bladder, with an absorbed dose of 0.18 mGy/MBq. Conclusion: 18 F-FB-A20FMDV2 successfully passed toxicology criteria, showed no adverse effects in this first-in-humans study, and has an effective dose that enables multiple scans in a single subject. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Marginal adaptation and retention of a glass-ionomer, resin-modified glass-ionomers and a polyacid-modified resin composite in cervical Class-V lesions.

PubMed

Gladys, S; Van Meerbeek, B; Lambrechts, P; Vanherle, G

1998-07-01

An 18-month follow-up clinical trial of one conventional glass-ionomer (HIFI Master Palette), three resin-modified glass-ionomers (Fuji II LC, Vitremer, 3M Exp. 155) and one polyacid-modified resin composite (Dyract) was conducted to evaluate their clinical effectiveness in Class-V cervical lesions. In addition, the interface between dentin and two resin-modified glass-ionomers and one polyacid-modified resin composite was examined by scanning electron microscopy (SEM). After evaluation of the restorations immediately following placement (baseline), all patients were subjected to a strict recall schedule with controls at 6, 12 and 18 months. The clinical effectiveness was recorded in terms of retention and marginal integrity, clinical microleakage, caries recurrence, and tooth vitality. A chi 2-test (p < 0.05) was used to test for significant differences between materials. In case of restoration loss or special defects, a replica was made to examine the surface texture and restoration margins by SEM. In vitro, the interface was examined by SEM after an argon-ion-beam etching technique was used to enhance surface relief and disclose interfacial substructures. Retention appeared to be good for all the materials tested. Marginal discrepancies were localized at the incisal enamel and/or the cervical dentin margin, except for the polyacid-modified resin composite that showed most of the defects at the incisal enamel margin. None of the systems could guarantee margins free of microleakage for a long time. In vitro, the type of dentin pre-treatment defines to a great extent the morphology of the resultant interface between dentin and the restorative material tested. In this clinical study, the retention rate of the tested materials was good and even excellent for some products. Perfect marginal adaptation deteriorated too fast. The marginal adaptation of the polyacid-modified resin composite at the enamel site would probably have been better by the use of selective enamel or total acid etching. Marginal sealing remains a problem. Future research should concentrate on improving the marginal adaptation and sealing capacities before a broader clinical use can be advocated.

Nectar sugar composition of European Caryophylloideae (Caryophyllaceae) in relation to flower length, pollination biology and phylogeny.

PubMed

Witt, T; Jürgens, A; Gottsberger, G

2013-10-01

Floral nectar composition has been explained as an adaptation to factors that are either directly or indirectly related to pollinator attraction. However, it is often unclear whether the sugar composition is a direct adaptation to pollinator preferences. Firstly, the lower osmolality of sucrose solutions means that they evaporate more rapidly than hexose solutions, which might be one reason why sucrose-rich nectar is typically found in flowers with long tubes (adapted to long-tongued pollinators), where it is better protected from evaporation than in open or short-tubed flowers. Secondly, it can be assumed that temperature-dependent evaporation is generally lower during the night than during the day so that selection pressure to secrete nectar with high osmolality (i.e. hexose-rich solutions) is relaxed for night-active flowers pollinated at night. Thirdly, the breeding system may affect selection pressure on nectar traits; that is, for pollinator-independent, self-pollinated plants, a lower selective pressure on nectar traits can be assumed, leading to a higher variability of nectar sugar composition independent of pollinator preferences, nectar accessibility and nectar protection. To analyse the relations between flower tube length, day vs. night pollination and self-pollination, the nectar sugar composition was investigated in 78 European Caryophylloideae (Caryophyllaceae) with different pollination modes (diurnal, nocturnal, self-pollination) using high-performance liquid chromatography (HPLC). All Caryophylleae species (Dianthus and relatives) were found to have nectar with more than 50% sucrose, whereas the sugar composition of Sileneae species (Silene and relatives) ranged from 0% to 98.2%. In the genus Silene, a clear dichotomous distribution of sucrose- and hexose-dominant nectars is evident. We found a positive correlation between the flower tube length and sucrose content in Caryophylloideae, particularly in day-flowering species, using both conventional analyses and phylogenetically independent contrasts. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

A Decentralized Compositional Framework for Dependable Decision Process in Self-Managed Cyber Physical Systems

PubMed Central

Hou, Kun-Mean; Zhang, Zhan

2017-01-01

Cyber Physical Systems (CPSs) need to interact with the changeable environment under various interferences. To provide continuous and high quality services, a self-managed CPS should automatically reconstruct itself to adapt to these changes and recover from failures. Such dynamic adaptation behavior introduces systemic challenges for CPS design, advice evaluation and decision process arrangement. In this paper, a formal compositional framework is proposed to systematically improve the dependability of the decision process. To guarantee the consistent observation of event orders for causal reasoning, this work first proposes a relative time-based method to improve the composability and compositionality of the timing property of events. Based on the relative time solution, a formal reference framework is introduced for self-managed CPSs, which includes a compositional FSM-based actor model (subsystems of CPS), actor-based advice and runtime decomposable decisions. To simplify self-management, a self-similar recursive actor interface is proposed for decision (actor) composition. We provide constraints and seven patterns for the composition of reliability and process time requirements. Further, two decentralized decision process strategies are proposed based on our framework, and we compare the reliability with the static strategy and the centralized processing strategy. The simulation results show that the one-order feedback strategy has high reliability, scalability and stability against the complexity of decision and random failure. This paper also shows a way to simplify the evaluation for dynamic system by improving the composability and compositionality of the subsystem. PMID:29120357

A Decentralized Compositional Framework for Dependable Decision Process in Self-Managed Cyber Physical Systems.

PubMed

Zhou, Peng; Zuo, Decheng; Hou, Kun-Mean; Zhang, Zhan

2017-11-09

Cyber Physical Systems (CPSs) need to interact with the changeable environment under various interferences. To provide continuous and high quality services, a self-managed CPS should automatically reconstruct itself to adapt to these changes and recover from failures. Such dynamic adaptation behavior introduces systemic challenges for CPS design, advice evaluation and decision process arrangement. In this paper, a formal compositional framework is proposed to systematically improve the dependability of the decision process. To guarantee the consistent observation of event orders for causal reasoning, this work first proposes a relative time-based method to improve the composability and compositionality of the timing property of events. Based on the relative time solution, a formal reference framework is introduced for self-managed CPSs, which includes a compositional FSM-based actor model (subsystems of CPS), actor-based advice and runtime decomposable decisions. To simplify self-management, a self-similar recursive actor interface is proposed for decision (actor) composition. We provide constraints and seven patterns for the composition of reliability and process time requirements. Further, two decentralized decision process strategies are proposed based on our framework, and we compare the reliability with the static strategy and the centralized processing strategy. The simulation results show that the one-order feedback strategy has high reliability, scalability and stability against the complexity of decision and random failure. This paper also shows a way to simplify the evaluation for dynamic system by improving the composability and compositionality of the subsystem.

A new composite adaptive controller featuring the neural network and prescribed sliding surface with application to vibration control

NASA Astrophysics Data System (ADS)

Phu, Do Xuan; Huy, Ta Duc; Mien, Van; Choi, Seung-Bok

2018-07-01

This work proposes a novel composite adaptive controller based on the prescribed performance of the sliding surface and applies it to vibration control of a semi-active vehicle seat suspension system subjected to severe external disturbances. As a first step, the online fast interval type 2 fuzzy neural network system is adopted to establish a model and two sliding surfaces are used; conventional surface and prescribed surface. Then, an equivalent control is determined by assuming the derivative of the prescribed surface is zero, followed by the design of a controller which can guarantee both stability and robustness. Then, two controllers are combined and integrated with adaptation laws using the projection algorithm. The effectiveness of the proposed composite controller is validated through both simulation and experiment by undertaking vibration control of a semi-active seat suspension system equipped with a magneto-rheological (MR) damper. It is shown from both simulation and experimental realization that excellent vibration control performances are achieved with a small tracking error between the proposed and prescribed objectives. In addition, the control superiority of the proposed controller to conventional sliding mode controller featuring one sliding surface and proportional-integral-derivative (PID) controllers are demonstrated through a comparative work.

Design, Fabrication, and Testing of SMA Enabled Adaptive Chevrons for Jet Noise Reduction

NASA Technical Reports Server (NTRS)

Turner, Travis L.; Buehrle, Ralph D.; Cano, Roberto J.; Fleming, Gary A.

2004-01-01

This study presents the status and results from an effort to design, fabricate, and test an adaptive jet engine chevron concept based upon embedding shape memory alloy (SMA) actuators in a composite laminate, termed a SMA hybrid composite (SMAHC). The approach for fabricating the adaptive SMAHC chevrons involves embedding prestrained Nitinol actuators on one side of the mid-plane of the composite laminate such that thermal excitation generates a thermal moment and deflects the structure. A glass-epoxy pre-preg/Nitinol ribbon material system and a vacuum hot press consolidation approach are employed. A versatile test system for control and measurement of the chevron deflection performance is described. Projection moire interferometry (PMI) is used for global deformation measurement and infrared (IR) thermography is used for 2-D temperature measurement and feedback control. A recently commercialized constitutive model for SMA and SMAHC materials is used in the finite element code ABAQUS to perform nonlinear static analysis of the chevron prototypes. Excellent agreement is achieved between the predicted and measured chevron deflection performance, thereby validating the design tool. Although the performance results presented in this paper fall short of the requirement, the concept is proven and an approach for achieving the performance objectives is evident.

Global Shifts in Genome and Proteome Composition Are Very Tightly Coupled

PubMed Central

Brbić, Maria; Warnecke, Tobias; Kriško, Anita; Supek, Fran

2015-01-01

The amino acid composition (AAC) of proteomes differs greatly between microorganisms and is associated with the environmental niche they inhabit, suggesting that these changes may be adaptive. Similarly, the oligonucleotide composition of genomes varies and may confer advantages at the DNA/RNA level. These influences overlap in protein-coding sequences, making it difficult to gauge their relative contributions. We disentangle these effects by systematically evaluating the correspondence between intergenic nucleotide composition, where protein-level selection is absent, the AAC, and ecological parameters of 909 prokaryotes. We find that G + C content, the most frequently used measure of genomic composition, cannot capture diversity in AAC and across ecological contexts. However, di-/trinucleotide composition in intergenic DNA predicts amino acid frequencies of proteomes to the point where very little cross-species variability remains unexplained (91% of variance accounted for). Qualitatively similar results were obtained for 49 fungal genomes, where 80% of the variability in AAC could be explained by the composition of introns and intergenic regions. Upon factoring out oligonucleotide composition and phylogenetic inertia, the residual AAC is poorly predictive of the microbes’ ecological preferences, in stark contrast with the original AAC. Moreover, highly expressed genes do not exhibit more prominent environment-related AAC signatures than lowly expressed genes, despite contributing more to the effective proteome. Thus, evolutionary shifts in overall AAC appear to occur almost exclusively through factors shaping the global oligonucleotide content of the genome. We discuss these results in light of contravening evidence from biophysical data and further reading frame-specific analyses that suggest that adaptation takes place at the protein level. PMID:25971281

Presettlement fire regime and vegetation mapping in Southeastern Coastal Plain forest ecosystems

Treesearch

Andrew D. Bailey; Robert Mickler; Cecil Frost

2007-01-01

Fire-adapted forest ecosystems make up 95 percent of the historic Coastal Plain vegetation types in the Southeastern United States. Fire suppression over the last century has altered the species composition of these ecosystems, increased fuel loads, and increased wildfire risk. Prescribed fire is one management tool used to reduce fuel loading and restore fire-adapted...

Site Directed Nucleation and Growth of Ceramic Films on Metallic Surfaces

DTIC Science & Technology

2009-04-30

ceramics and other nanoscale composite materials research with the ultimate goal being the cell-free, nanocrystalline assembly of adaptive bioceramic...for high temperature or high wear environments. Other applications/technology developments for this research include adaptive materials, wear...bound vesicles that form the surface membrane of gastropod nacre. 19 Folia formation was observed by recovering titanium and aluminum disc implants

Frequent fire protects shortleaf pine (Pinus echinata) from introgression by loblolly pine (P. taeda).

Treesearch

John F Stewart; Rodney E Will; Kevin M Robertson; Dana Nelson

2014-01-01

Across much of the globe, fire is a major disturbance agent of forest and grassland communities. The removal of fire from previously fire-maintained ecosystems, which has occurred in many areas, changes species composition, favoring later less fire tolerant species over fire-adapted ones. A recent measured increase in the rate of hybridization between the fire-adapted...

Taxon-Function Decoupling as an Adaptive Signature of Lake Microbial Metacommunities Under a Chronic Polymetallic Pollution Gradient

PubMed Central

Cheaib, Bachar; Le Boulch, Malo; Mercier, Pierre-Luc; Derome, Nicolas

2018-01-01

Adaptation of microbial communities to anthropogenic stressors can lead to reductions in microbial diversity and disequilibrium of ecosystem services. Such adaptation can change the molecular signatures of communities with differences in taxonomic and functional composition. Understanding the relationship between taxonomic and functional variation remains a critical issue in microbial ecology. Here, we assessed the taxonomic and functional diversity of a lake metacommunity system along a polymetallic pollution gradient caused by 60 years of chronic exposure to acid mine drainage (AMD). Our results highlight three adaptive signatures. First, a signature of taxon—function decoupling was detected in the microbial communities of moderately and highly polluted lakes. Second, parallel shifts in taxonomic composition occurred between polluted and unpolluted lakes. Third, variation in the abundance of functional modules suggested a gradual deterioration of ecosystem services (i.e., photosynthesis) and secondary metabolism in highly polluted lakes. Overall, changes in the abundance of taxa, function, and more importantly the polymetallic resistance genes such as copA, copB, czcA, cadR, cCusA, were correlated with trace metal content (mainly Cadmium) and acidity. Our findings highlight the impact of polymetallic pollution gradient at the lowest trophic levels. PMID:29774016

Taxon-Function Decoupling as an Adaptive Signature of Lake Microbial Metacommunities Under a Chronic Polymetallic Pollution Gradient.

PubMed

Cheaib, Bachar; Le Boulch, Malo; Mercier, Pierre-Luc; Derome, Nicolas

2018-01-01

Adaptation of microbial communities to anthropogenic stressors can lead to reductions in microbial diversity and disequilibrium of ecosystem services. Such adaptation can change the molecular signatures of communities with differences in taxonomic and functional composition. Understanding the relationship between taxonomic and functional variation remains a critical issue in microbial ecology. Here, we assessed the taxonomic and functional diversity of a lake metacommunity system along a polymetallic pollution gradient caused by 60 years of chronic exposure to acid mine drainage (AMD). Our results highlight three adaptive signatures. First, a signature of taxon-function decoupling was detected in the microbial communities of moderately and highly polluted lakes. Second, parallel shifts in taxonomic composition occurred between polluted and unpolluted lakes. Third, variation in the abundance of functional modules suggested a gradual deterioration of ecosystem services (i.e., photosynthesis) and secondary metabolism in highly polluted lakes. Overall, changes in the abundance of taxa, function, and more importantly the polymetallic resistance genes such as copA, copB, czcA, cadR, cCusA , were correlated with trace metal content (mainly Cadmium) and acidity. Our findings highlight the impact of polymetallic pollution gradient at the lowest trophic levels.

The Temperature Dependence of Phytoplankton Stoichiometry: Investigating the Roles of Species Sorting and Local Adaptation

PubMed Central

Yvon-Durocher, Gabriel; Schaum, Charlotte-Elisa; Trimmer, Mark

2017-01-01

The elemental composition of phytoplankton (C:N:P stoichiometry) is a critical factor regulating nutrient cycling, primary production and energy transfer through planktonic food webs. Our understanding of the multiple direct and indirect mechanisms through which temperature controls phytoplankton stoichiometry is however incomplete, increasing uncertainty in the impacts of global warming on the biogeochemical functioning of aquatic ecosystems. Here, we use a decade-long warming experiment in outdoor freshwater ponds to investigate how temperature-driven turnover in species composition and shifts in stoichiometric traits within species through local thermal adaptation contribute to the effects of warming on seston stoichiometry. We found that experimental warming increased seston C:P and N:P ratios, while the C:N ratio was unaffected by warming. Temperature was also the dominant driver of seasonal variation in seston stoichiometry, correlating positively with both C:P and N:P ratios. The taxonomic composition of the phytoplankton community differed substantially between the warmed and ambient treatments indicating that warming resulted in differential sorting of species from the regional pool. Furthermore, taxonomic composition also changed markedly over the year within each of the warmed and ambient treatments, highlighting substantial temporal turnover in species. To investigate whether local adaptation also played an important role in shaping the effects of warming on seston stoichiometry, we isolated multiple strains of the cosmopolitan alga, Chlamydomonas reinhardtii from across the warmed and ambient mesocosms. We found that warmed isolates had higher C:P and N:P ratios, shifts that were comparable in direction and magnitude to the effects of warming on seston stoichiometry. Our results suggest that both species sorting and local adaptation are likely to play important roles in shaping the effects of warming on bulk phytoplankton stoichiometry and indicate that major shifts in aquatic biogeochemistry should be expected in a warmer world. PMID:29109703

Closed-Cycle Nutrient Supply For Hydroponics

NASA Technical Reports Server (NTRS)

Schwartzkopf, Steven H.

1991-01-01

Hydroponic system controls composition and feed rate of nutrient solution and recovers and recycles excess solution. Uses air pressure on bladders to transfer aqueous nutrient solution. Measures and adjusts composition of solution before it goes to hydroponic chamber. Eventually returns excess solution to one of tanks. Designed to operate in microgravity, also adaptable to hydroponic plant-growing systems on Earth.

Disturbance and productivity interactions mediate stability of forest composition and structure

Treesearch

Christopher D. O' Connor; Donald A. Falk; Ann M. Lynch; Thomas W. Swetnam; Craig P. Wilcox

2017-01-01

Fire is returning to many conifer-dominated forests where species composition and structure have been altered by fire exclusion. Ecological effects of these fires are influenced strongly by the degree of forest change during the fire-free period. Response of fire-adapted species assemblages to extended fire-free intervals is highly variable, even in communities with...

Effects of carbohydrate quantity and glycemic index on resting metabolic rate and body composition during weight loss

USDA-ARS?s Scientific Manuscript database

Objective: To examine the effects of diets varying in carbohydrate and glycemic index (GI) on changes in body composition, resting metabolic rate (RMR), and metabolic adaptation during and after weight loss. Methods: Adults with obesity (n = 91) were randomized to one of four provided-food diets f...

Highly Stretchable Superhydrophobic Composite Coating Based on Self-Adaptive Deformation of Hierarchical Structures.

PubMed

Hu, Xin; Tang, Changyu; He, Zhoukun; Shao, Hong; Xu, Keqin; Mei, Jun; Lau, Woon-Ming

2017-05-01

With the rapid development of stretchable electronics, functional textiles, and flexible sensors, water-proof protection materials are required to be built on various highly flexible substrates. However, maintaining the antiwetting of superhydrophobic surface under stretching is still a big challenge since the hierarchical structures at hybridized micro-nanoscales are easily damaged following large deformation of the substrates. This study reports a highly stretchable and mechanically stable superhydrophobic surface prepared by a facile spray coating of carbon black/polybutadiene elastomeric composite on a rubber substrate followed by thermal curing. The resulting composite coating can maintain its superhydrophobic property (water contact angle ≈170° and sliding angle <4°) at an extremely large stretching strain of up to 1000% and can withstand 1000 stretching-releasing cycles without losing its superhydrophobic property. Furthermore, the experimental observation and modeling analysis reveal that the stable superhydrophobic properties of the composite coating are attributed to the unique self-adaptive deformation ability of 3D hierarchical roughness of the composite coating, which delays the Cassie-Wenzel transition of surface wetting. In addition, it is first observed that the damaged coating can automatically recover its superhydrophobicity via a simple stretching treatment without incorporating additional hydrophobic materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigations on the magnetization behavior of magnetic composite particles

NASA Astrophysics Data System (ADS)

Eichholz, Christian; Knoll, Johannes; Lerche, Dietmar; Nirschl, Hermann

2014-11-01

In life sciences the application of surface functionalized magnetic composite particles is establishing in diagnostics and in downstream processing of modern biotechnology. These magnetic composite particles consist of non-magnetic material, e.g. polystyrene, which serves as a matrix for the second magnetic component, usually colloidal magnetite. Because of the multitude of magnetic cores these magnetic beads show a complex magnetization behavior which cannot be described with the available approaches for homogeneous magnetic material. Therefore, in this work a new model for the magnetization behavior of magnetic composite particles is developed. By introducing an effective magnetization and considering an overall demagnetization factor the deviation of the demagnetization of homogeneously magnetized particles is taken into account. Calculated and experimental results show a good agreement which allows for the verification of the adapted model of particle magnetization. Besides, a newly developed magnetic analyzing centrifuge is used for the characterization of magnetic composite particle systems. The experimental results, also used for the model verification, give both, information about the magnetic properties and the interaction behavior of particle systems. By adding further components to the particle solution, such as salts or proteins, industrial relevant systems can be reconstructed. The analyzing tool can be used to adapt industrial processes without time-consuming preliminary tests with large samples in the process equipments.

Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C2C12 skeletal muscle cells.

PubMed

Zebedin, Eva; Sandtner, Walter; Galler, Stefan; Szendroedi, Julia; Just, Herwig; Todt, Hannes; Hilber, Karlheinz

2004-08-01

Each skeletal muscle of the body contains a unique composition of "fast" and "slow" muscle fibers, each of which is specialized for certain challenges. This composition is not static, and the muscle fibers are capable of adapting their molecular composition by altered gene expression (i.e., fiber type conversion). Whereas changes in the expression of contractile proteins and metabolic enzymes in the course of fiber type conversion are well described, little is known about possible adaptations in the electrophysiological properties of skeletal muscle cells. Such adaptations may involve changes in the expression and/or function of ion channels. In this study, we investigated the effects of fast-to-slow fiber type conversion on currents via voltage-gated Na+ channels in the C(2)C(12) murine skeletal muscle cell line. Prolonged treatment of cells with 25 nM of the Ca2+ ionophore A-23187 caused a significant shift in myosin heavy chain isoform expression from the fast toward the slow isoform, indicating fast-to-slow fiber type conversion. Moreover, Na+ current inactivation was significantly altered. Slow inactivation less strongly inhibited the Na+ currents of fast-to-slow fiber type-converted cells. Compared with control cells, the Na+ currents of converted cells were more resistant to block by tetrodotoxin, suggesting enhanced relative expression of the cardiac Na+ channel isoform Na(v)1.5 compared with the skeletal muscle isoform Na(v)1.4. These results imply that fast-to-slow fiber type conversion of skeletal muscle cells involves functional adaptation of their electrophysiological properties.

Dimensional assessment of self- and interpersonal functioning in adolescents: implications for DSM-5's general definition of personality disorder.

PubMed

DeFife, Jared A; Goldberg, Melissa; Westen, Drew

2015-04-01

Central to the proposed DSM-5 general definition of personality disorder (PD) are features of self- and interpersonal functioning. The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G) is a coding system that assesses eight dimensions of self- and relational experience that can be applied to narrative data or used by clinically experienced observers to quantify observations of patients in ongoing psychotherapy. This study aims to evaluate the relationship of SCORS-G dimensions to personality pathology in adolescents and their incremental validity for predicting multiple domains of adaptive functioning. A total of 294 randomly sampled doctoral-level clinical psychologists and psychiatrists described an adolescent patient in their care based on all available data. Individual SCORS-G variables demonstrated medium-to-large effect size differences for PD versus non-PD identified adolescents (d = .49-1.05). A summary SCORS-Composite rating was significantly related to composite measurements of global adaptive functioning (r = .66), school functioning (r = .47), externalizing behavior (r = -.49), and prior psychiatric history (r = -.31). The SCORS-Composite significantly predicted variance in domains of adaptive functioning above and beyond age and DSM-IV PD diagnosis (ΔR(2)s = .07-.32). As applied to adolescents, the SCORS-G offers a framework for a clinically meaningful and empirically sound dimensional assessment of self- and other representations and interpersonal functioning capacities. Our findings support the inclusion of self- and interpersonal capacities in the DSM-5 general definition of personality disorder as an improvement to existing PD diagnosis for capturing varied domains of adaptive functioning and psychopathology.

Hybrid Decompositional Verification for Discovering Failures in Adaptive Flight Control Systems

NASA Technical Reports Server (NTRS)

Thompson, Sarah; Davies, Misty D.; Gundy-Burlet, Karen

2010-01-01

Adaptive flight control systems hold tremendous promise for maintaining the safety of a damaged aircraft and its passengers. However, most currently proposed adaptive control methodologies rely on online learning neural networks (OLNNs), which necessarily have the property that the controller is changing during the flight. These changes tend to be highly nonlinear, and difficult or impossible to analyze using standard techniques. In this paper, we approach the problem with a variant of compositional verification. The overall system is broken into components. Undesirable behavior is fed backwards through the system. Components which can be solved using formal methods techniques explicitly for the ranges of safe and unsafe input bounds are treated as white box components. The remaining black box components are analyzed with heuristic techniques that try to predict a range of component inputs that may lead to unsafe behavior. The composition of these component inputs throughout the system leads to overall system test vectors that may elucidate the undesirable behavior

Induction of Fatty Acid Composition Modifications and Tolerance to Biocides in Salmonella enterica Serovar Typhimurium by Plant-Derived Terpenes▿

PubMed Central

Dubois-Brissonnet, Florence; Naïtali, Murielle; Mafu, Akier Assanta; Briandet, Romain

2011-01-01

To enhance food safety and stability, the food industry tends to use natural antimicrobials such as plant-derived compounds as an attractive alternative to chemical preservatives. Nonetheless, caution must be exercised in light of the potential for bacterial adaptation to these molecules, a phenomenon previously observed with other antimicrobials. The aim of this study was to characterize the adaptation of Salmonella enterica serovar Typhimurium to sublethal concentrations of four terpenes extracted from aromatic plants: thymol, carvacrol, citral, and eugenol, or combinations thereof. Bacterial adaptation in these conditions was demonstrated by changes in membrane fatty acid composition showing (i) limitation of the cyclization of unsaturated fatty acids to cyclopropane fatty acids when cells entered the stationary phase and (ii) bacterial membrane saturation. Furthermore, we demonstrated an increased cell resistance to the bactericidal activity of two biocides (peracetic acid and didecyl dimethyl ammonium bromide). The implications of membrane modifications in terms of hindering the penetration of antimicrobials through the bacterial membrane are discussed. PMID:21131520

Microbial Lifestyle and Genome Signatures

PubMed Central

Dutta, Chitra; Paul, Sandip

2012-01-01

Microbes are known for their unique ability to adapt to varying lifestyle and environment, even to the extreme or adverse ones. The genomic architecture of a microbe may bear the signatures not only of its phylogenetic position, but also of the kind of lifestyle to which it is adapted. The present review aims to provide an account of the specific genome signatures observed in microbes acclimatized to distinct lifestyles or ecological niches. Niche-specific signatures identified at different levels of microbial genome organization like base composition, GC-skew, purine-pyrimidine ratio, dinucleotide abundance, codon bias, oligonucleotide composition etc. have been discussed. Among the specific cases highlighted in the review are the phenomena of genome shrinkage in obligatory host-restricted microbes, genome expansion in strictly intra-amoebal pathogens, strand-specific codon usage in intracellular species, acquisition of genome islands in pathogenic or symbiotic organisms, discriminatory genomic traits of marine microbes with distinct trophic strategies, and conspicuous sequence features of certain extremophiles like those adapted to high temperature or high salinity. PMID:23024607

Community change and evidence for variable warm-water temperature adaptation of corals in Northern Male Atoll, Maldives.

PubMed

McClanahan, T R; Muthiga, N A

2014-03-15

This study provides a descriptive analysis of the North Male, Maldives seven years after the 1998 bleaching disturbance to determine the state of the coral community composition, the recruitment community, evidence for recovery, and adaptation to thermal stress. Overall, hard coral cover recovered at a rate commonly reported in the literature but with high spatial variability and shifts in taxonomic composition. Massive Porites, Pavona, Synarea, and Goniopora were unusually common in both the recruit and adult communities. Coral recruitment was low and some coral taxa, namely Tubipora, Seriatopora, and Stylophora, were rarer than expected. A study of the bleaching response to a thermal anomaly in 2005 indicated that some taxa, including Leptoria, Platygyra, Favites, Fungia, Hydnophora, and Galaxea astreata, bleached as predicted while others, including Acropora, Pocillopora, branching Porites, Montipora, Stylophora, and Alveopora, bleached less than predicted. This indicates variable-adaptation potentials among the taxa and considerable potential for ecological reorganization of the coral community. Copyright © 2014 Elsevier Ltd. All rights reserved.

Demographic aspects of climate change mitigation and adaptation.

PubMed

Lutz, Wolfgang; Striessnig, Erich

2015-01-01

This paper addresses the contribution of changes in population size and structures to greenhouse gas emissions and to the capacity to adapt to climate change. The paper goes beyond the conventional focus on the changing composition by age and sex. It does so by addressing explicitly the changing composition of the population by level of educational attainment, taking into account new evidence about the effect of educational attainment in reducing significantly the vulnerability of populations to climatic challenges. This evidence, which has inspired a new generation of socio-economic climate change scenarios, is summarized. While the earlier IPCC-SRES (Intergovernmental Panel on Climate Change-Special Report on Emissions Scenarios) scenarios only included alternative trajectories for total population size (treating population essentially as a scaling parameter), the Shared Socio-economic Pathways (SSPs) in the new scenarios were designed to capture the socio-economic challenges to climate change mitigation and adaptation, and include full age, sex, and education details for all countries.

NEUTRON ABSORPTION AND SHIELDING DEVICE

DOEpatents

Axelrad, I.R.

1960-06-21

A neutron absorption and shielding device is described which is adapted for mounting in a radiation shielding wall surrounding a radioactive area through which instrumentation leads and the like may safely pass without permitting gamma or neutron radiation to pass to the exterior. The shielding device comprises a container having at least one nonrectilinear tube or passageway means extending therethrough, which is adapted to contain instrumentation leads or the like, a layer of a substance capable of absorbing gamma rays, and a solid resinous composition adapted to attenuate fast-moving neutrons and capture slow- moving or thermal neutrons.

Margin adaptation of indirect composite inlays fabricated on flexible dies.

PubMed

Price, R B; Gerrow, J D

2000-03-01

Indirect composite restorations can be made in 1 appointment using a flexible die. Interactions between different impression materials and flexible die materials may affect the accuracy of fit and margin adaptation of the restoration. This study compared the margin adaptation of composite inlays made using the following 5 impression/flexible die material combinations; condensation silicone/polyvinyl siloxane (CS/PVS), wash viscosity polyvinyl siloxane/medium or heavy viscosity polyvinyl siloxane (PVS/PVS), irreversible hydrocolloid impression/medium viscosity polyvinyl siloxane (IH/PVS), wash viscosity polyvinyl siloxane impression/polyether (PVS/PE), with composite inlays made using a control system of a wash viscosity polyvinyl siloxane impression and a type IV stone die. For each test and control system, 10 impressions were made of a class II composite inlay preparation in a metal master die. One die was made from each impression and one composite inlay was made and finished on each die (a total of 60 inlays). Inlays were placed on the master die and the margin opening at the buccal, distal, and gingival sites was recorded with a measuring microscope (x40 magnification). The overall mean +/- SD margin openings of inlays made from the systems were as follows: PVS wash/PVS heavy viscosity 149.5 +/- 107. 4 microm; PVS wash/PVS medium viscosity 87.4 +/- 63.0 microm; IH/PVS medium viscosity 76.7 +/- 48.9 microm; CS/PVS 73.3 +/- 48.7 microm, PVS wash viscosity/PE 64.0 +/- 44.3 microm, PVS wash viscosity/stone 53.9 +/- 48.3 microm. Composite inlays made using the PVS wash viscosity/PVS heavy viscosity system had significantly larger distal, gingival, and overall mean margin openings than all other inlays (ANOVA and Fisher PLSD test; P =.05). The separating medium required between some impression and die materials did not work consistently. Composite inlays fabricated on dies made of material different than the impression material had mean buccal, distal, gingival, and overall margin openings < or =100 microm. Composite inlays made on the CS/PVS, IH/PVS medium viscosity, PVS wash viscosity/PE flexible dies, and control PVS wash viscosity/stone dies had statistically similar (P =.05) mean buccal, distal, gingival, and overall mean margin openings that were < or =100 microm. Composite inlays made on dies that were made of the same type of material as the impression material (PVS/PVS) had mean gingival margin openings >100 microm that were significantly larger than all other systems tested (P =.05).

Composite materials with metal oxide attached to lead chalcogenide nanocrystal quantum dots with linkers

DOEpatents

Fuke, Nobuhiro; Koposov, Alexey Y; Sykora, Milan; Hoch, Laura

2014-12-16

Composite materials useful for devices such as photoelectrochemical solar cells include a substrate, a metal oxide film on the substrate, nanocrystalline quantum dots (NQDs) of lead sulfide, lead selenide, and lead telluride, and linkers that attach the NQDs to the metal oxide film. Suitable linkers preserve the 1s absorption peak of the NQDs. A suitable linker has a general structure A-B-C where A is a chemical group adapted for binding to a MO.sub.x and C is a chemical group adapted for binding to a NQD and B is a divalent, rigid, or semi-rigid organic spacer moiety. Other linkers that preserve the 1s absorption peak may also be used.

Outsourcing neural active control to passive composite mechanics: a tissue engineered cyborg ray

NASA Astrophysics Data System (ADS)

Gazzola, Mattia; Park, Sung Jin; Park, Kyung Soo; Park, Shirley; di Santo, Valentina; Deisseroth, Karl; Lauder, George V.; Mahadevan, L.; Parker, Kevin Kit

2016-11-01

Translating the blueprint that stingrays and skates provide, we create a cyborg swimming ray capable of orchestrating adaptive maneuvering and phototactic navigation. The impossibility of replicating the neural system of batoids fish is bypassed by outsourcing algorithmic functionalities to the body composite mechanics, hence casting the active control problem into a design, passive one. We present a first step in engineering multilevel "brain-body-flow" systems that couple sensory information to motor coordination and movement, leading to behavior. This work paves the way for the development of autonomous and adaptive artificial creatures able to process multiple sensory inputs and produce complex behaviors in distributed systems and may represent a path toward soft-robotic "embodied cognition".

Investigation of light-induced conformation changes in spiropyran-modified succinylated poly(L-lysine).

PubMed

Cooper, T M; Stone, M O; Natarajan, L V; Crane, R L

1995-08-01

To determine the maximum range of coupling between side-chain photochromism and polypeptide conformation change, we modified the carboxylate side chains of succinylated poly(L-lysine) with a spiropyran to form polypeptide I. The extent of modification was determined to be 35.5%. The spacer group length between the polypeptide alpha-carbon and the dye was 12 atoms, providing minimum polypeptide-dye interaction. Conformation changes were monitored by circular dichroism as a function of light adaptation and solvent composition (hexafluoroisopropanol [HFIP] vs trifluoroethanol [TFE]). Under all solvent compositions, the dark-adapted dye was in the merocyanine form. Light adaptation by visible light converted the dye to the spiropyran form. When dissolved in TFE, I adopted a helical conformation insensitive to light adaptation. With increasing percentage HFIP, a solvent-induced helix-to-coil transition was observed around 80% (vol/vol) HFIP. At 100% HFIP, both light- and dark-adapted forms of I were in the coil state. Near the midpoint of the solvent-induced helix-to-coil transition, light adaptation caused conformation changes. Applying helix-to-coil transition theory, we measured a statistically significant difference in coil segment-HFIP binding constant for light- vs dark-adapted solutions (6.38 +/- 0.03 M-1 vs 6.56 +/- 0.03 M-1), but not for the nucleation parameter sigma (1.2 +/- 0.4 10(-3) vs 1.3 +/- 0.3 x 10(-3). The small binding constant difference translated to a light-induced binding energy difference of 17 cal/mol/monomer. Near the midpoint of the helix-to-coil transition, collective interactions between monomer units made possible the translation of a small energy difference (less than RT) into large macromolecular conformation changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Glass fiber reinforced composite resin as an intracanal post--a clinical study.

PubMed

Subramaniam, Priya; Babu, K L Girish; Sunny, Raju

2008-01-01

Restoration of primary incisors, which have been severely damaged by early childhood caries or trauma, is a difficult task for the pediatric dentist. With the introduction of new adhesive systems and restorative materials, alternative approaches for treating these teeth have been proposed. Ten healthy children aged between 3-4 years who had 28 grossly destructed primary maxillary incisors requiring intra canal retention were selected for the study. Following root canal treatment, either a Glass Fiber Reinforced Composite Resin (GFRCR everStick,, Finland) or an omega shaped stainless steel wire were placed as intracanal posts in these teeth. Flowable composite was used for cementation of posts and also to build up the coronal structure using celluloid strip crowns. Both types of intracanal posts were evaluated for retention and marginal adaptation at 1, 6 and 12 months. The data obtained was subjected to statistical analysis. GFRCR intracanal posts showed better retention and marginal adaptation than omega shaped stainless steel wire posts.

Study of Personnel Attrition and Revocation within U.S. Marine Corps Air Traffic Control Specialties

DTIC Science & Technology

2012-03-01

Entrance Processing Stations (MEPS) and recruit depots, to include non-cognitive testing, such as Navy Computer Adaptive Personality Scales ( NCAPS ...Revocation, Selection, MOS, Regression, Probit, dProbit, STATA, Statistics, Marginal Effects, ASVAB, AFQT, Composite Scores, Screening, NCAPS 15. NUMBER...Navy Computer Adaptive Personality Scales ( NCAPS ), during recruitment. It is also recommended that an economic analysis be conducted comparing the

Multidimensional CAT Item Selection Methods for Domain Scores and Composite Scores with Item Exposure Control and Content Constraints

ERIC Educational Resources Information Center

Yao, Lihua

2014-01-01

The intent of this research was to find an item selection procedure in the multidimensional computer adaptive testing (CAT) framework that yielded higher precision for both the domain and composite abilities, had a higher usage of the item pool, and controlled the exposure rate. Five multidimensional CAT item selection procedures (minimum angle;…

Determination of the Subunit Molecular Mass and Composition of Alcohol Dehydrogenase by SDS-PAGE

ERIC Educational Resources Information Center

Nash, Barbara T.

2007-01-01

SDS-PAGE is a simple, rapid technique that has many uses in biochemistry and is readily adaptable to the undergraduate laboratory. It is, however, a technique prone to several types of procedural pitfalls. This article describes the use of SDS-PAGE to determine the subunit molecular mass and composition of yeast alcohol dehydrogenase employing…

St. Augustine and the Christian College Composition Classroom: Water into Flame

ERIC Educational Resources Information Center

Veach, Grace

2009-01-01

Today's Christian college students are more engaged in popular youth culture and less reflective than in the past. St. Augustine's On Christian Doctrine, Book IV, gives advice to preachers, but it can easily be adapted to apply to Christian college composition classrooms. The two main sections of the article cover how to teach and what to teach…

Adaptive plasma for cancer therapy: physics, mechanism and applications

NASA Astrophysics Data System (ADS)

Keidar, Michael

2017-10-01

One of the most promising applications of cold atmospheric plasma (CAP) is the cancer therapy. The uniqueness of plasma is in its ability to change composition in situ. Plasma self-organization could lead to formation of coherent plasma structures. These coherent structures tend to modulate plasma chemistry and composition, including reactive species, the electric field and charged particles. Formation of coherent plasma structures allows the plasma to adapt to external boundary conditions, such as different cells types and their contextual tissues. In this talk we will explore possibilities and opportunities that the adaptive plasma therapeutic system might offer. We shall define such an adaptive system as a plasma device that is able to adjust the plasma composition to obtain optimal desirable outcomes through its interaction with cells and tissues. The efficacy of cold plasma in a pre-clinical model of various cancer types such as lung, bladder, breast, head, neck, brain and skin has been demonstrated. Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. Recently mechanism of plasma selectivity based on aquaporin hypothesis has been proposed. Aquaporins (AQPs) are the confirmed membrane channels of H2O2 and other large molecules. We have demonstrated that the anti-cancer capacity of plasma could be inhibited by silencing the expression of AQPs. Additional possible cell feedback mechanism was recently discovered. It is associated with production of reactive species during direct CAP treatment by cancer cells. Selective production of hydrogen peroxide by different cells can lead to adaptation of chemistry at the plasma-cell interface based on the cellular input. In particular we have found that the discharge voltage is an important factor affecting the ratio of reactive oxygen species to reactive nitrogen species in the gas phase and this correlates well with effect of hydrogen peroxide production by cells. This work was supported by a National Science Foundation, Grant No. 1465061.

Research Opportunities from Emerging Atmospheric Observing and Modeling Capabilities.

NASA Astrophysics Data System (ADS)

Dabberdt, Walter F.; Schlatter, Thomas W.

1996-02-01

The Second Prospectus Development Team (PDT-2) of the U.S. Weather Research Program was charged with identifying research opportunities that are best matched to emerging operational and experimental measurement and modeling methods. The overarching recommendation of PDT-2 is that inputs for weather forecast models can best be obtained through the use of composite observing systems together with adaptive (or targeted) observing strategies employing both in situ and remote sensing. Optimal observing systems and strategies are best determined through a three-part process: observing system simulation experiments, pilot field measurement programs, and model-assisted data sensitivity experiments. Furthermore, the mesoscale research community needs easy and timely access to the new operational and research datasets in a form that can readily be reformatted into existing software packages for analysis and display. The value of these data is diminished to the extent that they remain inaccessible.The composite observing system of the future must combine synoptic observations, routine mobile observations, and targeted observations, as the current or forecast situation dictates. High costs demand fuller exploitation of commercial aircraft, meteorological and navigation [Global Positioning System (GPS)] satellites, and Doppler radar. Single observing systems must be assessed in the context of a composite system that provides complementary information. Maintenance of the current North American rawinsonde network is critical for progress in both research-oriented and operational weather forecasting.Adaptive sampling strategies are designed to improve large-scale and regional weather prediction but they will also improve diagnosis and prediction of flash flooding, air pollution, forest fire management, and other environmental emergencies. Adaptive measurements can be made by piloted or unpiloted aircraft. Rawinsondes can be launched and satellites can be programmed to make adaptive observations at special times or in specific regions. PDT-2 specifically recommends the following forms of data gathering: a pilot field and modeling study should be designed and executed to assess the benefit of adaptive observations over the eastern Pacific for mesoscale forecasts over the contiguous United

Thermal adaptation of the crucian carp (Carassius carassius) cardiac delayed rectifier current, IKs, by homomeric assembly of Kv7.1 subunits without MinK.

PubMed

Hassinen, Minna; Laulaja, Salla; Paajanen, Vesa; Haverinen, Jaakko; Vornanen, Matti

2011-07-01

Ectothermic vertebrates experience acute and chronic temperature changes which affect cardiac excitability and may threaten electrical stability of the heart. Nevertheless, ectothermic hearts function over wide range of temperatures without cardiac arrhythmias, probably due to special molecular adaptations. We examine function and molecular basis of the slow delayed rectifier K(+) current (I(Ks)) in cardiac myocytes of a eurythermic fish (Carassius carassius L.). I(Ks) is an important repolarizing current that prevents excessive prolongation of cardiac action potential, but it is extremely slowly activating when expressed in typical molecular composition of the endothermic animals. Comparison of the I(Ks) of the crucian carp atrial myocytes with the currents produced by homomeric K(v)7.1 and heteromeric K(v)7.1/MinK channels in Chinese hamster ovary cells indicates that activation kinetics and pharmacological properties of the I(Ks) are similar to those of the homomeric K(v)7.1 channels. Consistently with electrophysiological properties and homomeric K(v)7.1 channel composition, atrial transcript expression of the MinK subunit is only 1.6-1.9% of the expression level of the K(v)7.1 subunit. Since activation kinetics of the homomeric K(v)7.1 channels is much faster than activation of the heteromeric K(v)7.1/MinK channels, the homomeric K(v)7.1 composition of the crucian carp cardiac I(Ks) is thermally adaptive: the slow delayed rectifier channels can open despite low body temperatures and curtail the duration of cardiac action potential in ectothermic crucian carp. We suggest that the homomeric K(v)7.1 channel assembly is an evolutionary thermal adaptation of ectothermic hearts and the heteromeric K(v)7.1/MinK channels evolved later to adapt I(Ks) to high body temperature of endotherms.

Developing Large-Scale Bayesian Networks by Composition: Fault Diagnosis of Electrical Power Systems in Aircraft and Spacecraft

NASA Technical Reports Server (NTRS)

Mengshoel, Ole Jakob; Poll, Scott; Kurtoglu, Tolga

2009-01-01

In this paper, we investigate the use of Bayesian networks to construct large-scale diagnostic systems. In particular, we consider the development of large-scale Bayesian networks by composition. This compositional approach reflects how (often redundant) subsystems are architected to form systems such as electrical power systems. We develop high-level specifications, Bayesian networks, clique trees, and arithmetic circuits representing 24 different electrical power systems. The largest among these 24 Bayesian networks contains over 1,000 random variables. Another BN represents the real-world electrical power system ADAPT, which is representative of electrical power systems deployed in aerospace vehicles. In addition to demonstrating the scalability of the compositional approach, we briefly report on experimental results from the diagnostic competition DXC, where the ProADAPT team, using techniques discussed here, obtained the highest scores in both Tier 1 (among 9 international competitors) and Tier 2 (among 6 international competitors) of the industrial track. While we consider diagnosis of power systems specifically, we believe this work is relevant to other system health management problems, in particular in dependable systems such as aircraft and spacecraft. (See CASI ID 20100021910 for supplemental data disk.)

Effect of dual-cure composite resin as restorative material on marginal adaptation of class 2 restorations.

PubMed

Bortolotto, Tissiana; Melian, Karla; Krejci, Ivo

2013-10-01

The present study attempted to find a simple direct adhesive restorative technique for the restoration of Class 2 cavities. A self-etch adhesive system with a dual-cured core buildup composite resin (paste 1 + paste 2) was evaluated in its ability to restore proximo-occlusal cavities with margins located on enamel and dentin. The groups were: A, cavity filling (cf) with paste 1 (light-curing component) by using a layering technique; B, cf by mixing both pastes, bulk insertion, and dual curing; and C, cf by mixing both pastes, bulk insertion, and chemical curing. Two control groups (D, negative, bulk; and E, positive, layering technique) were included by restoring cavities with a classic three-step etch-and-rinse adhesive and a universal restorative composite resin. SEM margin analysis was performed before and after thermomechanical loading in a chewing simulator. Percentages (mean ± SD) of "continuous margins" were improved by applying the material in bulk and letting it self cure (54 ± 6) or dual cure (59 ± 9), and no significant differences were observed between these two groups and the positive control (44 ± 19). The present study showed that the dual-cured composite resin tested has the potential to be used as bulk filling material for Class 2 restorations. When used as filling materials, dual-cure composite resins placed in bulk can provide marginal adaptation similar to light-cured composites applied with a complex stratification technique.

Adaptive Evolution of Synthetic Cooperating Communities Improves Growth Performance

PubMed Central

Zhang, Xiaolin; Reed, Jennifer L.

2014-01-01

Symbiotic interactions between organisms are important for human health and biotechnological applications. Microbial mutualism is a widespread phenomenon and is important in maintaining natural microbial communities. Although cooperative interactions are prevalent in nature, little is known about the processes that allow their initial establishment, govern population dynamics and affect evolutionary processes. To investigate cooperative interactions between bacteria, we constructed, characterized, and adaptively evolved a synthetic community comprised of leucine and lysine Escherichia coli auxotrophs. The co-culture can grow in glucose minimal medium only if the two auxotrophs exchange essential metabolites — lysine and leucine (or its precursors). Our experiments showed that a viable co-culture using these two auxotrophs could be established and adaptively evolved to increase growth rates (by ∼3 fold) and optical densities. While independently evolved co-cultures achieved similar improvements in growth, they took different evolutionary trajectories leading to different community compositions. Experiments with individual isolates from these evolved co-cultures showed that changes in both the leucine and lysine auxotrophs improved growth of the co-culture. Interestingly, while evolved isolates increased growth of co-cultures, they exhibited decreased growth in mono-culture (in the presence of leucine or lysine). A genome-scale metabolic model of the co-culture was also constructed and used to investigate the effects of amino acid (leucine or lysine) release and uptake rates on growth and composition of the co-culture. When the metabolic model was constrained by the estimated leucine and lysine release rates, the model predictions agreed well with experimental growth rates and composition measurements. While this study and others have focused on cooperative interactions amongst community members, the adaptive evolution of communities with other types of interactions (e.g., commensalism, ammensalism or parasitism) would also be of interest. PMID:25299364

Beyond cool: adapting upland streams for climate change using riparian woodlands.

PubMed

Thomas, Stephen M; Griffiths, Siân W; Ormerod, Steve J

2016-01-01

Managed adaptation could reduce the risks of climate change to the world's ecosystems, but there have been surprisingly few practical evaluations of the options available. For example, riparian woodland is advocated widely as shade to reduce warming in temperate streams, but few studies have considered collateral effects on species composition or ecosystem functions. Here, we use cross-sectional analyses at two scales (region and within streams) to investigate whether four types of riparian management, including those proposed to reduce potential climate change impacts, might also affect the composition, functional character, dynamics and energetic resourcing of macroinvertebrates in upland Welsh streams (UK). Riparian land use across the region had only small effects on invertebrate taxonomic composition, while stable isotope data showed how energetic resources assimilated by macroinvertebrates in all functional guilds were split roughly 50:50 between terrestrial and aquatic origins irrespective of riparian management. Nevertheless, streams draining the most extensive deciduous woodland had the greatest stocks of coarse particulate matter (CPOM) and greater numbers of 'shredding' detritivores. Stream-scale investigations showed that macroinvertebrate biomass in deciduous woodland streams was around twice that in moorland streams, and lowest of all in streams draining non-native conifers. The unexpected absence of contrasting terrestrial signals in the isotopic data implies that factors other than local land use affect the relative incorporation of allochthonous subsidies into riverine food webs. Nevertheless, our results reveal how planting deciduous riparian trees along temperate headwaters as an adaptation to climate change can modify macroinvertebrate function, increase biomass and potentially enhance resilience by increasing basal resources where cover is extensive (>60 m riparian width). We advocate greater urgency in efforts to understand the ecosystem consequences of climate change adaptation to guide future actions. © 2015 John Wiley & Sons Ltd.

Soil fungal communities respond compositionally to recurring frequent prescribed burning in a managed southeastern US forest ecosystem

Treesearch

Alena K. Oliver; Mac A. Callaham; Ari Jumpponen

2015-01-01

Prescribed fire is an important management tool to reduce fuel loads, to remove non-fire adapted species and to sustain fire-adapted taxa in many forested ecosystems of the southeastern USA. Yet, the long-term effects of recurring prescribed fires on soil fungi and their communities in these ecosystems remain unclear. We Illumina MiSeq sequenced and analyzed fungal...

Adaptive structures flight experiments

NASA Astrophysics Data System (ADS)

Martin, Maurice

The topics are presented in viewgraph form and include the following: adaptive structures flight experiments; enhanced resolution using active vibration suppression; Advanced Controls Technology Experiment (ACTEX); ACTEX program status; ACTEX-2; ACTEX-2 program status; modular control patch; STRV-1b Cryocooler Vibration Suppression Experiment; STRV-1b program status; Precision Optical Bench Experiment (PROBE); Clementine Spacecraft Configuration; TECHSAT all-composite spacecraft; Inexpensive Structures and Materials Flight Experiment (INFLEX); and INFLEX program status.

Adaptive Structures Flight Experiments

NASA Technical Reports Server (NTRS)

Martin, Maurice

1992-01-01

The topics are presented in viewgraph form and include the following: adaptive structures flight experiments; enhanced resolution using active vibration suppression; Advanced Controls Technology Experiment (ACTEX); ACTEX program status; ACTEX-2; ACTEX-2 program status; modular control patch; STRV-1b Cryocooler Vibration Suppression Experiment; STRV-1b program status; Precision Optical Bench Experiment (PROBE); Clementine Spacecraft Configuration; TECHSAT all-composite spacecraft; Inexpensive Structures and Materials Flight Experiment (INFLEX); and INFLEX program status.

Influence of artificial aging in marginal adaptation of mixed class V cavities.

PubMed

Tonetto, Mateus Rodrigues; Bandéca, Matheus Coelho; Barud, Hélida Gomes de Oliveira; Pinto, Shelon Cristina Souza; Lima, Darlon Martins; Borges, Alvaro Henrique; de Campos, Edson Alves; de Andrade, Marcelo Ferrarezi

2013-03-01

The aim of this study was to investigate whether the artificial aging by thermal cycling had influenced the marginal adaptation of class V restorations with/without chlorhexidine application in the bond process. Twelve intact human third molars were used. Class V cavity preparations were performed on the buccal surface and the teeth received 35% phosphoric acid-etching procedure (Ultradent Products Inc., South Jordan, Utah, USA). Subsequently, the samples were divided in two groups: Untreated acid-etched dentin and chlorhexidine application as an adjunct in the bond process. The adhesive Single Bond 2 (3M ESPE, St. Paul, MN, USA) was used after 2% chlorhexidine application, and the restorations were performed with Filtek™ Z350 XT (3M ESPE) composite resin. The specimens were submitted to artificial aging by thermal cycling with 3,000 cycles. Analyzes were performed on scanning electron microscopy using replicas of marginal adaptation in percentage of continuous margin before and after the artificial aging. The data were analyzed by paired test and the results showed statistically significant differences in the percentage of continuous margin with/without chlorhexidine treatment before and after thermal cycling. This study concluded that the artificial aging by thermal cycling influenced the marginal adaptation of mixed class V composite restorations.

Models of energy homeostasis in response to maintenance of reduced body weight

PubMed Central

Rosenbaum, Michael; Leibel, Rudolph L.

2016-01-01

Objective To test 3 proposed models for adaptive thermogenesis in compartments of energy expenditure following different degrees of weight loss. Specifically, 1.) There is no adaptive thermogenesis (constant relationship of energy expenditure (EE) to metabolic mass). 2.) There is a fixed degree of adaptive thermogenesis once fat stores are below a “threshold”. 3.) The degree of adaptive thermogenesis is proportional to weight loss. Methods The relationship between weight loss and EE was examined in seventeen weight stable in-patient subjects with obesity studied at usual weight and again following a 10% and a 20% weight loss. Results Following initial weight loss (10%), resting (REE) and non-resting (NREE) EE were significantly below those predicted on the basis of the amount and composition of weight lost. Further reductions below predicted values of NREE but not REE occurred following an additional 10% weight loss. Changes in body weight, composition, and/or energy stores were significantly correlated with changes in EE. Conclusion All models are applicable to the decline in EE following weight loss. The disproportionate decline in REE is consistent with a threshold model (no change with further weight loss) while the disproportionate decline in NREE is largely reflective of the degree of weight loss. PMID:27460711

Unique biochemical and mineral composition of whale ear bones.

PubMed

Kim, Sora L; Thewissen, J G M; Churchill, Morgan M; Suydam, Robert S; Ketten, Darlene R; Clementz, Mark T

2014-01-01

Abstract Cetaceans are obligate aquatic mammals derived from terrestrial artiodactyls. The defining characteristic of cetaceans is a thick and dense lip (pachyosteosclerotic involucrum) of an ear bone (the tympanic). This unique feature is absent in modern terrestrial artiodactyls and is suggested to be important in underwater hearing. Here, we investigate the mineralogical and biochemical properties of the involucrum, as these may hold clues to the aquatic adaptations of cetaceans. We compared bioapatites (enamel, dentine, cementum, and skeletal bone) of cetaceans with those of terrestrial artiodactyls and pachyosteosclerotic ribs of manatees (Sirenia). We investigated organic, carbonate, and mineral composition as well as crystal size and crystallinity index. In all studied variables, bioapatites of the cetacean involucrum were intermediate in composition and structure between those of tooth enamel on the one hand and those of dentine, cementum, and skeletal bone on the other. We also studied the amino acid composition of the cetacean involucrum relative to that of other skeletal bone. The central involucrum had low glycine and hydroxyproline concentrations but high concentrations of nonessential amino acids, unlike most bone samples but similar to the tympanic of hippos and the (pachyosteosclerotic) ribs of manatees. These amino acid results are evidence of rapid bone development. We hypothesize that the mineralogical and amino acid composition of cetacean bullae differs from that of other bone because of (1) functional modifications for underwater sound reception and (2) structural adaptations related to rapid ossification.

High temperature resistant cermet and ceramic compositions

NASA Technical Reports Server (NTRS)

Phillips, W. M. (Inventor)

1978-01-01

Cermet compositions having high temperature oxidation resistance, high hardness and high abrasion and wear resistance, and particularly adapted for production of high temperature resistant cermet insulator bodies are presented. The compositions are comprised of a sintered body of particles of a high temperature resistant metal or metal alloy, preferably molybdenum or tungsten particles, dispersed in and bonded to a solid solution formed of aluminum oxide and silicon nitride, and particularly a ternary solid solution formed of a mixture of aluminum oxide, silicon nitride and aluminum nitride. Also disclosed are novel ceramic compositions comprising a sintered solid solution of aluminum oxide, silicon nitride and aluminum nitride.

Chromosomal Thermal Index: a comprehensive way to integrate the thermal adaptation of Drosophila subobscura whole karyotype.

PubMed

Arenas, Conxita; Zivanovic, Goran; Mestres, Francesc

2018-02-01

Drosophila has demonstrated to be an excellent model to study the adaptation of organisms to global warming, with inversion chromosomal polymorphism having a key role in this adaptation. Here, we introduce a new index (Chromosomal Thermal Index or CTI) to quantify the thermal adaptation of a population according to its composition of "warm" and "cold" adapted inversions. This index is intuitive, has good statistical properties, and can be used to hypothesis on the effect of global warming on natural populations. We show the usefulness of CTI using data from European populations of D. subobscura, sampled in different years. Out of 15 comparisons over time, nine showed significant increase of CTI, in accordance with global warming expectations. Although large regions of the genome outside inversions contain thermal adaptation genes, our results show that the total amount of warm or cold inversions in populations seems to be directly involved in thermal adaptation, whereas the interactions between the inversions content of homologous and non-homologous chromosomes are not relevant.

The Irony and the Ecstasy: How Holden Caulfield Helped My Advanced Composition Students Find Their Voices.

ERIC Educational Resources Information Center

Huff, Linda

An instructor of an advanced composition course (adapted from one taught by James Seitz at the University of Pittsburgh) at the University of California Riverside took her students through a series of reading and writing assignments that asked them to "engage in a wide variety of prose styles and...consider what style suggests about language,…

Tales of Wisdom in Folly. A Course in Controlled Composition. Program and Training Journal Reprint Series, No. 13.

ERIC Educational Resources Information Center

Kayeum, Joan

This booklet is a collection of Mullah Nasruddin tales that are commonly enjoyed in Afghanistan. These tales have been adapted to form a course in controlled composition for students studying English as a foreign language. After reading each tale the student is asked to carry out certain tasks. In addition to the simplest task, copying the passage…

Current markers of the Athlete Blood Passport do not flag microdose EPO doping.

PubMed

Ashenden, Michael; Gough, Clare E; Garnham, Andrew; Gore, Christopher J; Sharpe, Ken

2011-09-01

The Athlete Blood Passport is the most recent tool adopted by anti-doping authorities to detect athletes using performance-enhancing drugs such as recombinant human erythropoietin (rhEPO). This strategy relies on detecting abnormal variations in haematological variables caused by doping, against a background of biological and analytical variability. Ten subjects were given twice weekly intravenous injections of rhEPO for up to 12 weeks. Full blood counts were measured using a Sysmex XE-2100 automated haematology analyser, and total haemoglobin mass via a carbon monoxide rebreathing test. The sensitivity of the passport to flag abnormal deviations in blood values was evaluated using dedicated Athlete Blood Passport software. Our treatment regimen elicited a 10% increase in total haemoglobin mass equivalent to approximately two bags of reinfused blood. The passport software did not flag any subjects as being suspicious of doping whilst they were receiving rhEPO. We conclude that it is possible for athletes to use rhEPO without eliciting abnormal changes in the blood variables currently monitored by the Athlete Blood Passport.

The puzzle of homeopathy.

PubMed

Reilly, D

2001-01-01

Homeopathy is a branch of Western medicine that has mostly been rejected by Western orthodoxy for the last 200 years because of conceptual and scientific clashes. Homeopathy uses microdoses of potential toxins to provoke defense and self-regulatory responses, rather than the more orthodox approach of blocking body reactions. This approach hints at its clinical scope: it can help, at times resolve, conditions that are intrinsically reversible rather than mechanical problems, deficiencies, or irreversible breakdowns in body functions where it is only palliative. In recent years, there has been a renaissance of interest. Public demand has soared, and with it professional interest. Approximately 20% of Scotland's general practitioners have completed basic training. This is partly occasioned by public interest in complementary medicine and a sympathy with the more mind-body approach of homeopathy, and partly by recent scientific evidence. Some homeopathic dilutions are so extreme they are dismissed by critics as only placebo. Yet trials and meta-analyses of controlled trials are pointing toward real effects, mechanism of action unknown. Clinical outcome studies suggest useful clinical impact and excellent safety. There seems to be a potential to enhance patient care by integrating the two systems.

Fabrication of graphite/polyimide composite structures.

NASA Technical Reports Server (NTRS)

Varlas, M.

1972-01-01

Selection of graphite/polyimide composite as a prime candidate for high-temperature structural applications involving long-duration temperature environments of 400 to 600 F. A variety of complex graphite/polyimide components has been fabricated, using a match-metal die approach developed for making fiber-reinforced resin composites. Parts produced include sections of a missile adapter skin flange, skin frame section, and I-beam and hat-section stringers, as well as unidirectional (0 deg) and plus or minus 45 deg oriented graphite/polyimide tubes in one-, two-, and six-inch diameters.

Active telescope systems; Proceedings of the Meeting, Orlando, FL, Mar. 28-31, 1989

NASA Astrophysics Data System (ADS)

Roddier, Francois J.

1989-09-01

The present conference discusses topics in the fundamental limitations of adaptive optics in astronomical telescopy, integrated telescope systems designs, novel components for adaptive telescopes, active interferometry, flexible-mirror and segmented-mirror telescopes, and various aspects of the NASA Precision Segmented Reflectors Program. Attention is given to near-ground atmospheric turbulence effects, a near-IR astronomical adaptive optics system, a simplified wavefront sensor for adaptive mirror control, excimer laser guide star techniques for adaptive astronomical imaging, active systems in long-baseline interferometry, mirror figure control primitives for a 10-m primary mirror, and closed-loop active optics for large flexible mirrors subject to wind buffet deformations. Also discussed are active pupil geometry control for a phased-array telescope, extremely lightweight space telescope mirrors, segmented-mirror manufacturing tolerances, and composite deformable mirror design.

Video personalization for usage environment

NASA Astrophysics Data System (ADS)

Tseng, Belle L.; Lin, Ching-Yung; Smith, John R.

2002-07-01

A video personalization and summarization system is designed and implemented incorporating usage environment to dynamically generate a personalized video summary. The personalization system adopts the three-tier server-middleware-client architecture in order to select, adapt, and deliver rich media content to the user. The server stores the content sources along with their corresponding MPEG-7 metadata descriptions. Our semantic metadata is provided through the use of the VideoAnnEx MPEG-7 Video Annotation Tool. When the user initiates a request for content, the client communicates the MPEG-21 usage environment description along with the user query to the middleware. The middleware is powered by the personalization engine and the content adaptation engine. Our personalization engine includes the VideoSue Summarization on Usage Environment engine that selects the optimal set of desired contents according to user preferences. Afterwards, the adaptation engine performs the required transformations and compositions of the selected contents for the specific usage environment using our VideoEd Editing and Composition Tool. Finally, two personalization and summarization systems are demonstrated for the IBM Websphere Portal Server and for the pervasive PDA devices.

Load attenuating passively adaptive wind turbine blade

DOEpatents

Veers, Paul S.; Lobitz, Donald W.

2003-01-07

A method and apparatus for improving wind turbine performance by alleviating loads and controlling the rotor. The invention employs the use of a passively adaptive blade that senses the wind velocity or rotational speed, and accordingly modifies its aerodynamic configuration. The invention exploits the load mitigation prospects of a blade that twists toward feather as it bends. The invention includes passively adaptive wind turbine rotors or blades with currently preferred power control features. The apparatus is a composite fiber horizontal axis wind-turbine blade, in which a substantial majority of fibers in the blade skin are inclined at angles of between 15 and 30 degrees to the axis of the blade, to produces passive adaptive aeroelastic tailoring (bend-twist coupling) to alleviate loading without unduly jeopardizing performance.

Load attenuating passively adaptive wind turbine blade

DOEpatents

Veers, Paul S.; Lobitz, Donald W.

2003-01-01

A method and apparatus for improving wind turbine performance by alleviating loads and controlling the rotor. The invention employs the use of a passively adaptive blade that senses the wind velocity or rotational speed, and accordingly modifies its aerodynamic configuration. The invention exploits the load mitigation prospects of a blade that twists toward feather as it bends. The invention includes passively adaptive wind turbine rotors or blades with currently preferred power control features. The apparatus is a composite fiber horizontal axis wind-turbine blade, in which a substantial majority of fibers in the blade skin are inclined at angles of between 15 and 30 degrees to the axis of the blade, to produces passive adaptive aeroelastic tailoring (bend-twist coupling) to alleviate loading without unduly jeopardizing performance.

A 4-year clinical evaluation of direct composite build-ups for space closure after orthodontic treatment.

PubMed

Demirci, Mustafa; Tuncer, Safa; Öztaş, Evren; Tekçe, Neslihan; Uysal, Ömer

2015-12-01

To evaluate the medium-term clinical performance of direct composite build-ups for diastema closures and teeth recontouring using a nano and a nanohybrid composite in combination with three- or two-step etch-and-rinse adhesives following treatment with fixed orthodontic appliances. A total of 30 patients (mean age, 19.5 years) received 147 direct composite additions for teeth recontouring and diastema closures. A nano and a nanohybrid composite (Filtek Supreme XT and CeramX Duo) were bonded to tooth structure by using a three-step (Scotchbond Multipurpose) or a two-step (XP Bond) etch and rinse adhesive. Ten out of 147 composite build-ups (composite addition) constituted tooth recontouring cases, and the remaining 137 constituted diastema closure cases. The restorations were evaluated by two experienced, calibrated examiners according to modified Ryge criteria at the following time intervals: baseline, 1, 2, 3, and 4 years. The 4-year survival rates were 92.8 % for Filtek Supreme XT/Scotchbond Multi-Purpose Plus and 93 % for CeramX Duo/XP Bond. Only ten restorations failed (5 Filtek Supreme XT and 5 CeramX Duo). Statistical analysis revealed no significant differences between the two composite-adhesive combinations with respect to color match, marginal discoloration, wear/loss of anatomical form, caries formation, marginal adaptation, and surface texture on comparing the five time periods (baseline, 1, 2, 3, and 4 years) The 4-year survival rates in the present study were favorable. The restorations exhibited excellent scores with regard to color match, marginal adaptation, surface texture, marginal discoloration, wear/loss of anatomical form, and caries formation, after 4 years of clinical evaluation. Clinical relevance An alternative clinical approach for correcting discrepancies in tooth size and form, such as performing direct composite restorations following fixed orthodontic treatment, may be an excellent and minimally invasive treatment.

Class II composite resin restorations: faster, easier, predictable.

PubMed

Jackson, R D

2016-11-18

Composite resin continues to displace amalgam as the preferred direct restorative material in developed countries. Even though composite materials have evolved to include nanoparticles with high physical properties and low shrinkage stress, dentists have been challenged to efficiently create quality, long lasting, predictable restorations. Unlike amalgam, composite resin cannot be condensed making the establishment of a predictable, proper contact more difficult. In addition, composite requires an understanding of adhesives and an appreciation for their exacting application. These facts combined with the precise adaptation and light-curing of multiple layers makes placement of quality Class II composite restorations tedious and time-consuming. For private practicing dentists, it can also have an effect on economic productivity. Clinicians have always wanted an easier, efficient placement technique for posterior composite restorations that rivals that for amalgam. It appears that advances in instrumentation, materials and technology have finally delivered it.

Five-year evaluation of a low-shrinkage Silorane resin composite material: a randomized clinical trial.

PubMed

Schmidt, Malene; Dige, Irene; Kirkevang, Lise-Lotte; Vaeth, Michael; Hørsted-Bindslev, Preben

2015-03-01

The aim of the present study was to investigate the clinical performance of a low-shrinkage silorane-based composite material (Filtek™ Silorane, 3 M-Espe) by comparing it with a methacrylate-based composite material (Ceram•X™, Dentsply DeTrey). A number of 72 patients (158 restorations) participated in the study. After 5 years, a total of 107 restorations (52 Filtek™ Silorane, 55 Ceram•X™) in 48 patients were evaluated. Only class II restorations were included. All the restorations were placed by the same dentist, and the restorations were scored by one experienced dentist/evaluator. Materials were applied following the manufacturer's instructions. The primary outcome was marginal adaptation. Secondary outcomes were: marginal discoloration, approximal contact, anatomic form, fracture, secondary caries, and hypersensitivity. After 5 years, no statistically significant differences between the two materials were found in marginal adaptation either occlusally (p = 0.96) or approximally (p = 0.62). No statistically significant differences were found between the two materials in terms of approximal contact, anatomic form, fractures, or discoloration. Secondary caries was found in two teeth (Filtek™ Silorane). One tooth showed hypersensitivity (Ceram•X™). Restorations of both materials were clinically acceptable after 5 years. This study did not find any advantage of the silorane-based composite over the methacrylate-based composite, which indicates that the low-shrinkage of Filtek™ Silorane may not be a determinant factor for clinical success in class II cavities. This paper is the first to evaluate the 5-year clinical performance of a low-shrinkage composite material.

Comparison of GnRh Agonist Microdose Flare Up and GnRh Antagonist/Letrozole in Treatment of Poor Responder Patients in Intra Cytoplaspic Sperm Injection: Randomized Clinical Trial.

PubMed

Nabati, Azar; Peivandi, Sepideh; Khalilian, Alireza; Mirzaeirad, Sina; Hashemi, Seyyed Abbas

2015-08-06

the prevalence of infertility is up to 10 to 15 % which 9 to 24 % of them are Poor Ovarian Responders (POR). This study was designed to compare two methods of GnRH Agonist Microdose Flareup (MF) and GnRH Antagonist/Letrozole (AL) in treatment of these patients. this randomized clinical trial study consisted of 123 patients. In the first step of treatment in both methods FSH, LH, estradiol, anderostandion, testestron in third day of menstruation period and the thickness of endometrium by Transvaginal sonography were evaluated. At the time of HCG injection the thickness of endometrium and follicles which were more than 14mm ware established and hormones were evaluated. Two weeks later serum βhCG and after 6 to 8 weeks Transvaginal sonography were applied to prove the pregnancy. there were 61 patients with mean age of 38.7±4.58 in MF group and 62 patients with mean age of 38.5±4.6 in AL group (P=0.80). At the time of hCG injection there were significant increase in the level of LH,estradiol, thickness of endometrium and follicles more than 14mm in MF patients (P<0.0001). The mean time of ovary stimulation in MF group was 10.72±1.5 and in AL was 8.45±1.2 (P<0.0001). The mean level of gonadotropin which were used was 80.6±20.1 in MF patients and 64.7±16.4 in AL group (P<0.0001). 18 % of MF group and 38.7% in AL group had no normal cycle of ovulation (OR: 2.87, 95% CI: 1.25-6.57, P=0.011). The mean numbers of oocyte and normal fetus in MF was 5.83±3.5 and 3.7±2.5 and in AL was 3±1.69 and 1.4±1.33 (P<0.0001). The number of chemical pregnancy in MF group was 10 (16.4%) and in AL was 3 (4.8%) (OR:3.85, 95%CI:1.06-14.77, P=0.037). Clinical pregnancy in 10 patients (16.4%) of MF group and 3 (4.8%)in AL was reported. OR: 3.85, 95%CI: 1.06-14.77, P=0.037). this study showed that MF method of pregnancy leads to more positive results in pregnancy based on chemical and clinical evaluation in comparison with AL and is advised for poor responder patients.

Comparison of GnRh Agonist Microdose Flare Up and GnRh Antagonist/Letrozole in Treatment of Poor Responder Patients in Intra Cytoplaspic Sperm Injection: Randomized Clinical Trial

PubMed Central

Nabati, Azar; Peivandi, Sepideh; Khalilian, Alireza; Mirzaeirad, Sina; Hashemi, Seyyed Abbas

2016-01-01

Backgrounds: the prevalence of infertility is up to 10 to 15 % which 9 to 24 % of them are Poor Ovarian Responders (POR). This study was designed to compare two methods of GnRH Agonist Microdose Flareup (MF) and GnRH Antagonist/Letrozole (AL) in treatment of these patients. Methods and Materials: this randomized clinical trial study consisted of 123 patients. In the first step of treatment in both methods FSH, LH, estradiol, anderostandion, testestron in third day of menstruation period and the thickness of endometrium by Transvaginal sonography were evaluated. At the time of HCG injection the thickness of endometrium and follicles which were more than 14mm ware established and hormones were evaluated. Two weeks later serum βhCG and after 6 to 8 weeks Transvaginal sonography were applied to prove the pregnancy. Results: there were 61 patients with mean age of 38.7±4.58 in MF group and 62 patients with mean age of 38.5±4.6 in AL group (P=0.80). At the time of hCG injection there were significant increase in the level of LH, estradiol, thickness of endometrium and follicles more than 14mm in MF patients (P<0.0001). The mean time of ovary stimulation in MF group was 10.72±1.5 and in AL was 8.45±1.2 (P<0.0001). The mean level of gonadotropin which were used was 80.6±20.1 in MF patients and 64.7±16.4 in AL group (P<0.0001). 18 % of MF group and 38.7% in AL group had no normal cycle of ovulation (OR: 2.87, 95% CI: 1.25-6.57, P=0.011). The mean numbers of oocyte and normal fetus in MF was 5.83±3.5 and 3.7±2.5 and in AL was 3±1.69 and 1.4±1.33 (P<0.0001). The number of chemical pregnancy in MF group was 10 (16.4%) and in AL was 3 (4.8%) (OR 3.85, 95% CI: 1.06-14.77, P=0.037). Clinical pregnancy in 10 patients (16.4%) of MF group and 3 (4.8%)in AL was reported. OR 3.85, 95% CI: 1.06-14.77, P=0.037). Conclusion: this study showed that MF method of pregnancy leads to more positive results in pregnancy based on chemical and clinical evaluation in comparison with AL and is advised for poor responder patients. PMID:26573041

Gravitational effects on body composition in birds

NASA Technical Reports Server (NTRS)

Smith, A. H.; Sanchez P., O.; Burton, R. R.

1975-01-01

Gallinaceous birds, presenting a wide range of body size, were adapted physiologically to hyperdynamic environments, provided by chronic centrifugation. Chemical composition was measured directly on prepared carcasses, which were anatomically comparable, and more amenable to analysis than the intact body. Body mass and body fat decreased arithmetically with increasing field strength and also with increasing body mass. Water content of lean tissue increased in hyperdynamic environments, but irrespectively of body size.

Nanostructured Shape Memory Alloys: Adaptive Composite Materials and Components

DTIC Science & Technology

2007-12-01

placing the composites between two stainless steel sheets to minimize contamination. The process described was effective in breaking the nickel...pieced, the discs were heat-treated at 9000C for 1 hour and quenched in ice water. Each quarter piece was placed between two stainless steel sheets of 0.15... martensite interfaces. Additionally a surface preparation technique was developed to provide minimal surface deformation necessary for observation of

Optimal design of composite hip implants using NASA technology

NASA Technical Reports Server (NTRS)

Blake, T. A.; Saravanos, D. A.; Davy, D. T.; Waters, S. A.; Hopkins, D. A.

1993-01-01

Using an adaptation of NASA software, we have investigated the use of numerical optimization techniques for the shape and material optimization of fiber composite hip implants. The original NASA inhouse codes, were originally developed for the optimization of aerospace structures. The adapted code, which was called OPORIM, couples numerical optimization algorithms with finite element analysis and composite laminate theory to perform design optimization using both shape and material design variables. The external and internal geometry of the implant and the surrounding bone is described with quintic spline curves. This geometric representation is then used to create an equivalent 2-D finite element model of the structure. Using laminate theory and the 3-D geometric information, equivalent stiffnesses are generated for each element of the 2-D finite element model, so that the 3-D stiffness of the structure can be approximated. The geometric information to construct the model of the femur was obtained from a CT scan. A variety of test cases were examined, incorporating several implant constructions and design variable sets. Typically the code was able to produce optimized shape and/or material parameters which substantially reduced stress concentrations in the bone adjacent of the implant. The results indicate that this technology can provide meaningful insight into the design of fiber composite hip implants.

The composition of cell walls from grape skin in Vitis vinifera intraspecific hybrids.

PubMed

Apolinar-Valiente, Rafael; Gómez-Plaza, Encarna; Terrier, Nancy; Doco, Thierry; Ros-García, José María

2017-09-01

Monastrell is a red grape cultivar adapted to the dry environmental conditions of Murcia, SE Spain. Its berries seem to be characterized by a rigid cell wall structure, which could make difficult the winemaking process. Cabernet Sauvignon cultivar is used to complement Monastrell wines in this region owing to its high phenolic content with high extractability. This study explores the skin cell wall composition of grapes from plants resulting from intraspecific crosses of Vitis vinifera cultivars Monastrell × Cabernet Sauvignon. Moreover, the morphology of the cell wall material (CWM) from some representative samples was visualized by transmission optical microscopy. The total sugar content of CWM from nine out of ten genotypes of the progeny was lower than that from Monastrell. Seven out of ten genotypes showed lower phenolic content than Cabernet Sauvignon. The CWM from nine out of ten hybrids presented lower protein content than that from Monastrell. This study confirms that skin cell walls from Monastrell × Cabernet Sauvignon hybrid grapes presented major differences in composition compared with their parents. These data could help in the development of new cultivars adapted to the dry conditions of SE Spain and with a cell wall composition favouring extractability. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Hybrid ray-FDTD model for the simulation of the ultrasonic inspection of CFRP parts

NASA Astrophysics Data System (ADS)

Jezzine, Karim; Ségur, Damien; Ecault, Romain; Dominguez, Nicolas; Calmon, Pierre

2017-02-01

Carbon Fiber Reinforced Polymers (CFRP) are commonly used in structural parts in the aeronautic industry, to reduce the weight of aircraft while maintaining high mechanical performances. Simulation of the ultrasonic inspections of these parts has to face the highly heterogeneous and anisotropic characteristics of these materials. To model the propagation of ultrasound in these composite structures, we propose two complementary approaches. The first one is based on a ray model predicting the propagation of the ultrasound in an anisotropic effective medium obtained from a homogenization of the material. The ray model is designed to deal with possibly curved parts and subsequent continuously varying anisotropic orientations. The second approach is based on the coupling of the ray model, and a finite difference scheme in time domain (FDTD). The ray model handles the ultrasonic propagation between the transducer and the FDTD computation zone that surrounds the composite part. In this way, the computational efficiency is preserved and the ultrasound scattering by the composite structure can be predicted. Inspections of flat or curved composite panels, as well as stiffeners can be performed. The models have been implemented in the CIVA software platform and compared to experiments. We also present an application of the simulation to the performance demonstration of the adaptive inspection technique SAUL (Surface Adaptive Ultrasound).

Low expansion superalloy with improved toughness

DOEpatents

Smith, Darrell F.; Stein, Larry I.; Hwang, Il S.

1995-01-01

A high strength, low coefficient of thermal expansion superalloy exhibiting improved toughness over a broad temperature range down to about 4.degree. K. The composition is adapted for use with wrought superconducting sheathing.

Microbial survival strategies in ancient permafrost: insights from metagenomics

USGS Publications Warehouse

Mackelprang, Rachel; Burkert, Alexander; Haw, Monica; Mahendrarajah, Tara; Conaway, Christopher H.; Douglas, Thomas A.; Waldrop, Mark P.

2017-01-01

In permafrost (perennially frozen ground) microbes survive oligotrophic conditions, sub-zero temperatures, low water availability and high salinity over millennia. Viable life exists in permafrost tens of thousands of years old but we know little about the metabolic and physiological adaptations to the challenges presented by life in frozen ground over geologic time. In this study we asked whether increasing age and the associated stressors drive adaptive changes in community composition and function. We conducted deep metagenomic and 16 S rRNA gene sequencing across a Pleistocene permafrost chronosequence from 19 000 to 33 000 years before present (kyr). We found that age markedly affected community composition and reduced diversity. Reconstruction of paleovegetation from metagenomic sequence suggests vegetation differences in the paleo record are not responsible for shifts in community composition and function. Rather, we observed shifts consistent with long-term survival strategies in extreme cryogenic environments. These include increased reliance on scavenging detrital biomass, horizontal gene transfer, chemotaxis, dormancy, environmental sensing and stress response. Our results identify traits that may enable survival in ancient cryoenvironments with no influx of energy or new materials.

Phospholipids and protein adaptation of Pseudomonas sp. to the xenoestrogen tributyltin chloride (TBT).

PubMed

Bernat, Przemysław; Siewiera, Paulina; Soboń, Adrian; Długoński, Jerzy

2014-09-01

A tributyltin (TBT)-resistant strain of Pseudomonas sp. isolated from an overworked car filter was tested for its adaptation to TBT. The isolate was checked for organotin degradation ability, as well as membrane lipid and cellular protein composition in the presence of TBT. The phospholipid profiles of bacteria, grown with and without increased amounts of TBT, were characterized using liquid chromatography/electrospray ionization/mass spectrometry. The strain reacted to the biocide by changing the composition of its phospholipids. TBT induced a twofold decline in the amounts of many molecular species of phosphatidylglycerol and an increase in the levels of phosphatidic acid (by 58%) and phosphatidylethanolamine (by 70%). An increase in the degree of saturation of phospholipid fatty acids of TBT exposed Pseudomonas sp. was observed. These changes in the phospholipid composition and concentration reflect the mechanisms which support optimal lipid ordering in the presence of toxic xenobiotic. In the presence of TBT the abundances of 16 proteins, including TonB-dependent receptors, porins and peroxidases were modified, which could indicate a contribution of some enzymes to TBT resistance.

Microbial survival strategies in ancient permafrost: insights from metagenomics.

PubMed

Mackelprang, Rachel; Burkert, Alexander; Haw, Monica; Mahendrarajah, Tara; Conaway, Christopher H; Douglas, Thomas A; Waldrop, Mark P

2017-10-01

In permafrost (perennially frozen ground) microbes survive oligotrophic conditions, sub-zero temperatures, low water availability and high salinity over millennia. Viable life exists in permafrost tens of thousands of years old but we know little about the metabolic and physiological adaptations to the challenges presented by life in frozen ground over geologic time. In this study we asked whether increasing age and the associated stressors drive adaptive changes in community composition and function. We conducted deep metagenomic and 16 S rRNA gene sequencing across a Pleistocene permafrost chronosequence from 19 000 to 33 000 years before present (kyr). We found that age markedly affected community composition and reduced diversity. Reconstruction of paleovegetation from metagenomic sequence suggests vegetation differences in the paleo record are not responsible for shifts in community composition and function. Rather, we observed shifts consistent with long-term survival strategies in extreme cryogenic environments. These include increased reliance on scavenging detrital biomass, horizontal gene transfer, chemotaxis, dormancy, environmental sensing and stress response. Our results identify traits that may enable survival in ancient cryoenvironments with no influx of energy or new materials.

Microbial survival strategies in ancient permafrost: insights from metagenomics

PubMed Central

Mackelprang, Rachel; Burkert, Alexander; Haw, Monica; Mahendrarajah, Tara; Conaway, Christopher H; Douglas, Thomas A; Waldrop, Mark P

2017-01-01

In permafrost (perennially frozen ground) microbes survive oligotrophic conditions, sub-zero temperatures, low water availability and high salinity over millennia. Viable life exists in permafrost tens of thousands of years old but we know little about the metabolic and physiological adaptations to the challenges presented by life in frozen ground over geologic time. In this study we asked whether increasing age and the associated stressors drive adaptive changes in community composition and function. We conducted deep metagenomic and 16 S rRNA gene sequencing across a Pleistocene permafrost chronosequence from 19 000 to 33 000 years before present (kyr). We found that age markedly affected community composition and reduced diversity. Reconstruction of paleovegetation from metagenomic sequence suggests vegetation differences in the paleo record are not responsible for shifts in community composition and function. Rather, we observed shifts consistent with long-term survival strategies in extreme cryogenic environments. These include increased reliance on scavenging detrital biomass, horizontal gene transfer, chemotaxis, dormancy, environmental sensing and stress response. Our results identify traits that may enable survival in ancient cryoenvironments with no influx of energy or new materials. PMID:28696425

FISHER'S GEOMETRIC MODEL WITH A MOVING OPTIMUM

PubMed Central

Matuszewski, Sebastian; Hermisson, Joachim; Kopp, Michael

2014-01-01

Fisher's geometric model has been widely used to study the effects of pleiotropy and organismic complexity on phenotypic adaptation. Here, we study a version of Fisher's model in which a population adapts to a gradually moving optimum. Key parameters are the rate of environmental change, the dimensionality of phenotype space, and the patterns of mutational and selectional correlations. We focus on the distribution of adaptive substitutions, that is, the multivariate distribution of the phenotypic effects of fixed beneficial mutations. Our main results are based on an “adaptive-walk approximation,” which is checked against individual-based simulations. We find that (1) the distribution of adaptive substitutions is strongly affected by the ecological dynamics and largely depends on a single composite parameter γ, which scales the rate of environmental change by the “adaptive potential” of the population; (2) the distribution of adaptive substitution reflects the shape of the fitness landscape if the environment changes slowly, whereas it mirrors the distribution of new mutations if the environment changes fast; (3) in contrast to classical models of adaptation assuming a constant optimum, with a moving optimum, more complex organisms evolve via larger adaptive steps. PMID:24898080

Finite element analysis of Al 2024/Cu-Al-Ni shape memory alloy composites with defects/cracks

NASA Astrophysics Data System (ADS)

Kotresh, M.; Benal, M. M., Dr; Siddalinga Swamy, N. H., Dr

2018-02-01

In this work, a numerical approach to predict the stress field behaviour of defect/crack in shape memory alloy (SMA) particles reinforced composite known as the adaptive composite is presented. Simulation is based on the finite element method. The critical stress field approach was used to determine the stresses around defect/crack. Thereby stress amplification issue is being resolved. In this paper, the effect volume % of shape memory alloy and shape memory effect of reinforcement for as-cast and SME trained composites are examined and discussed. Shape memory effect known as training is achieved by pre-straining of reinforcement particles by equivalent changes in their expansion coefficients.

Electrically Conductive TPU Nanofibrous Composite with High Stretchability for Flexible Strain Sensor

NASA Astrophysics Data System (ADS)

Tong, Lu; Wang, Xiao-Xiong; He, Xiao-Xiao; Nie, Guang-Di; Zhang, Jun; Zhang, Bin; Guo, Wen-Zhe; Long, Yun-Ze

2018-03-01

Highly stretchable and electrically conductive thermoplastic polyurethane (TPU) nanofibrous composite based on electrospinning for flexible strain sensor and stretchable conductor has been fabricated via in situ polymerization of polyaniline (PANI) on TPU nanofibrous membrane. The PANI/TPU membrane-based sensor could detect a strain from 0 to 160% with fast response and excellent stability. Meanwhile, the TPU composite has good stability and durability. Besides, the composite could be adapted to various non-flat working environments and could maintain opportune conductivity at different operating temperatures. This work provides an easy operating and low-cost method to fabricate highly stretchable and electrically conductive nanofibrous membrane, which could be applied to detect quick and tiny human actions.

Flexible, wearable, and functional graphene-textile composites

NASA Astrophysics Data System (ADS)

Liu, Ying; Zhang, Kun-Ning; Zhang, Ying; Tao, Lu-Qi; Li, Yu-Xing; Wang, Dan-Yang; Yang, Yi; Ren, Tian-Ling

2017-06-01

In this paper, a flexible, wearable, and functional graphene-textile composite is demonstrated. Laser scribing technology is applied to fabricate a graphene film. The thin layer of polydimethylsiloxane is covered on the surface of the graphene-textile film evenly, which would improve the abrasive resistance of the film, enhance the ability to adapt to environmental changes, and extend the service life, while maintaining the device's excellent flexibility and comfort. The graphene-textile composite can achieve constant temperature heating by controlling the input voltage, detect the human movement, and perceive the human pulse signal. The composite presents great commercial prospects and a large value in the medical, daily wear, and other areas that are closely related to human lives.

Low expansion superalloy with improved toughness

DOEpatents

Smith, D.F.; Stein, L.I.; Hwang, I.S.

1995-06-20

A high strength, low coefficient of thermal expansion superalloy exhibiting improved toughness over a broad temperature range down to about 4 K is disclosed. The composition is adapted for use with wrought superconducting sheathing.

[Renal physiology].

PubMed

Gueutin, Victor; Deray, Gilbert; Isnard-Bagnis, Corinne

2012-03-01

The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. The flow of plasma is filtered in the range of 120 mL/min, and depends on the systemic and renal hemodynamics which is subject to self-regulation. The original urine will then be modified in successive segments of the nephron. The proximal nephron is to lead the massive reabsorption of water and essential elements such as sodium, bicarbonates, amino-acids and glucose. The distal nephron includes the distal convoluted tubule, the connector tube and the collecting duct. Its role is to adapt the quality composition of urine to the needs of the body.

Fructan metabolism and changes in fructan composition during cold acclimation in perennial ryegrass

PubMed Central

Abeynayake, Shamila W.; Etzerodt, Thomas P.; Jonavičienė, Kristina; Byrne, Stephen; Asp, Torben; Boelt, Birte

2015-01-01

Perennial ryegrass (Lolium perenne L.) produces high levels of fructans as a mixture of oligosaccharides and polysaccharides with different degrees of polymerization (DP). The present study describes the analysis of the compositional changes in the full spectrum of fructans, fructan distribution between above ground biomass (top) and the roots, and the transcription of candidate genes involved in fructan metabolism during cold acclimation in perennial ryegrass variety “Veyo” and ecotype “Falster” from distinct geographical origins. We observed changes in fructan composition and induction of low-DP fructans, especially DP = 4, in both the top and the roots of “Veyo” and “Falster” in response to low-temperature stress. The accumulation of DP > 50 fructans was only apparent in the top tissues where the Lp1-FFT expression is higher compared to the roots in both “Veyo” and “Falster.” Our results also show the accumulation and depolymerization of fructans with different DP, together with the induction of genes encoding fructosyltransferases and fructan exohydrolases in both “Veyo” and “Falster” during cold acclimation, supporting the hypothesis that fructan synthesis and depolymerization occurring simultaneously. The ecotype “Falster,” adapted to cold climates, increased total fructan content and produced more DP > 7 fructans in the roots than the variety “Veyo,” adapted to warmer climates. This indicates that high-DP fructan accumulation in roots may be an adaptive trait for plant recovery after abiotic stresses. PMID:26029229

Coupled mixed-field laminate theory and finite element for smart piezoelectric composite shell structures

NASA Technical Reports Server (NTRS)

Saravanos, Dimitris A.

1996-01-01

Mechanics for the analysis of laminated composite shells with piezoelectric actuators and sensors are presented. A new mixed-field laminate theory for piezoelectric shells is formulated in curvilinear coordinates which combines single-layer assumptions for the displacements and a layerwise representation for the electric potential. The resultant coupled governing equations for curvilinear piezoelectric laminates are described. Structural mechanics are subsequently developed and an 8-node finite-element is formulated for the static and dynamic analysis of adaptive composite structures of general laminations containing piezoelectric layers. Evaluations of the method and comparisons with reported results are presented for laminated piezoelectric-composite plates, a closed cylindrical shell with a continuous piezoceramic layer and a laminated composite semi-circular cantilever shell with discrete cylindrical piezoelectric actuators and/or sensors.

Time-Dependent Behavior of a Graphite/Thermoplastic Composite and the Effects of Stress and Physical Aging

NASA Technical Reports Server (NTRS)

Gates, Thomas S.; Feldman, Mark

1995-01-01

Experimental studies were performed to determine the effects of stress and physical aging on the matrix dominated time dependent properties of IM7/8320 composite. Isothermal tensile creep/aging test techniques developed for polymers were adapted for testing of the composite material. Time dependent transverse and shear compliance's for an orthotropic plate were found from short term creep compliance measurements at constant, sub-T(8) temperatures. These compliance terms were shown to be affected by physical aging. Aging time shift factors and shift rates were found to be a function of temperature and applied stress.

The effects of stress and physical aging on the creep compliance of a polymeric composite

NASA Technical Reports Server (NTRS)

Gates, Thomas E.; Feldman, Mark

1993-01-01

An experimental study was performed to determine the effects of stress and physical aging on the matrix dominated viscoelastic properties of IM7/8320, a high temperature fiber reinforced thermoplastic composite. Established creep/aging test techniques developed for polymers were adapted for testing of the composite material. The transverse and shear compliance for an orthotropic plate were found from creep compliance measurements at constant, sub-Tg temperatures. These compliance terms were shown to be effected by physical aging. Aging time shift factors and shift rates were found to be a function of applied stress.

Mechanical characterization of glass fiber (woven roving/chopped strand mat E-glass fiber) reinforced polyester composites

NASA Astrophysics Data System (ADS)

Bhaskar, V. Vijaya; Srinivas, Kolla

2017-07-01

Polymer reinforced composites have been replacing most of the engineering material and their applications become more and more day by day. Polymer composites have been analyzing from past thirty five years for their betterment for adapting more applications. This paper aims at the mechanical properties of polyester reinforced with glass fiber composites. The glass fiber is reinforced with polyester in two forms viz Woven Rovings (WRG) and Chopped Strand Mat (CSMG) E-glass fibers. The composites are fabricated by hand lay-up technique and the composites are cut as per ASTM Standard sizes for corresponding tests like flexural, compression and impact tests, so that flexural strength, compression strength, impact strength and inter laminar shear stress(ILSS) of polymer matrix composites are analyzed. From the tests and further calculations, the polyester composites reinforced with Chopped Strand Mat glass fiber have shown better performance against flexural load, compression load and impact load than that of Woven Roving glass fiber.

Cultural adaptation of the Latin American version of the World Health Organization Composite International Diagnostic Interview (WHO-CIDI) (v 3.0) for use in Spain.

PubMed

Navarro-Mateu, Fernando; Morán-Sánchez, Inés; Alonso, Jordi; Tormo, Ma José; Pujalte, Ma Luisa; Garriga, Ascensión; Aguilar-Gaxiola, Sergio; Navarro, Carmen

2013-01-01

To develop a Spanish version of the WHO-Composite International Diagnostic Interview (WHO-CIDI) applicable to Spain, through cultural adaptation of its most recent Latin American (LA v 20.0) version. A 1-week training course on the WHO-CIDI was provided by certified trainers. An expert panel reviewed the LA version, identified words or expressions that needed to be adapted to the cultural or linguistic norms for Spain, and proposed alternative expressions that were agreed on through consensus. The entire process was supervised and approved by a member of the WHO-CIDI Editorial Committee. The changes were incorporated into a Computer Assisted Personal Interview (CAPI) format and the feasibility and administration time were pilot tested in a convenience sample of 32 volunteers. A total of 372 questions were slightly modified (almost 7% of approximately 5000 questions in the survey) and incorporated into the CAPI version of the WHO-CIDI. Most of the changes were minor - but important - linguistic adaptations, and others were related to specific Spanish institutions and currency. In the pilot study, the instrument's mean completion administration time was 2h and 10min, with an interquartile range from 1.5 to nearly 3h. All the changes made were tested and officially approved. The Latin American version of the WHO-CIDI was successfully adapted and pilot-tested in its computerized format and is now ready for use in Spain. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.

Fatty acid composition modulates sensitivity of Legionella pneumophila to warnericin RK, an antimicrobial peptide.

PubMed

Verdon, Julien; Labanowski, Jérome; Sahr, Tobias; Ferreira, Thierry; Lacombe, Christian; Buchrieser, Carmen; Berjeaud, Jean-Marc; Héchard, Yann

2011-04-01

Warnericin RK is an antimicrobial peptide, produced by a Staphyloccocus warneri strain, described to be specifically active against Legionella, the pathogenic bacteria responsible for Legionnaires' disease. Warnericin RK is an amphiphilic alpha-helical peptide, which possesses a detergent-like mode of action. Two others peptides, δ-hemolysin I and II, produced by the same S. warneri strain, are highly similar to S. aureus δ-hemolysin and also display anti-Legionella activity. It has been recently reported that S. aureus δ-hemolysin activity on vesicles is likewise related to phospholipid acyl-chain structure, such as chain length and saturation. As staphylococcal δ-hemolysins were highly similar, we thus hypothesized that fatty acid composition of Legionella's membrane might influence the sensitivity of the bacteria to warnericin RK. Relationship between sensitivity to the peptide and fatty acid composition was then followed in various conditions. Cells in stationary phase, which were already described as less resistant than cells in exponential phase, displayed higher amounts of branched-chain fatty acids (BCFA) and short chain fatty acids. An adapted strain, able to grow at a concentration 33 fold higher than minimal inhibitory concentration of the wild type (i.e. 1μM), was isolated after repeated transfers of L. pneumophila in the presence of increased concentrations of warnericin RK. The amount of BCFA was significantly higher in the adapted strain than in the wild type strain. Also, a transcriptomic analysis of the wild type and adapted strains showed that two genes involved in fatty acid biosynthesis were repressed in the adapted strain. These genes encode enzymes involved in desaturation and elongation of fatty acids respectively. Their repression was in agreement with the decrease of unsaturated fatty acids and fatty acid chain length in the adapted strain. Conclusively, our results indicate that the increase of BCFA and the decrease of fatty acid chain length in membrane were correlated with the increase in resistance to warnericin RK. Therefore, fatty acid profile seems to play a critical role in the sensitivity of L. pneumophila to warnericin RK. Copyright © 2010 Elsevier B.V. All rights reserved.

Experimental study of an adaptive CFRC reflector for high order wave-front error correction

NASA Astrophysics Data System (ADS)

Lan, Lan; Fang, Houfei; Wu, Ke; Jiang, Shuidong; Zhou, Yang

2018-03-01

The recent radio frequency communication system developments are generating the need for creating space antennas with lightweight and high precision. The carbon fiber reinforced composite (CFRC) materials have been used to manufacture the high precision reflector. The wave-front errors caused by fabrication and on-orbit distortion are inevitable. The adaptive CFRC reflector has received much attention to do the wave-front error correction. Due to uneven stress distribution that is introduced by actuation force and fabrication, the high order wave-front errors such as print-through error is found on the reflector surface. However, the adaptive CFRC reflector with PZT actuators basically has no control authority over the high order wave-front errors. A new design architecture assembled secondary ribs at the weak triangular surfaces is presented in this paper. The virtual experimental study of the new adaptive CFRC reflector has conducted. The controllability of the original adaptive CFRC reflector and the new adaptive CFRC reflector with secondary ribs are investigated. The virtual experimental investigation shows that the new adaptive CFRC reflector is feasible and efficient to diminish the high order wave-front error.

Ephrin-A/EphA specific co-adaptation as a novel mechanism in topographic axon guidance

PubMed Central

Fiederling, Felix; Weschenfelder, Markus; Fritz, Martin; von Philipsborn, Anne; Bastmeyer, Martin; Weth, Franco

2017-01-01

Genetic hardwiring during brain development provides computational architectures for innate neuronal processing. Thus, the paradigmatic chick retinotectal projection, due to its neighborhood preserving, topographic organization, establishes millions of parallel channels for incremental visual field analysis. Retinal axons receive targeting information from quantitative guidance cue gradients. Surprisingly, novel adaptation assays demonstrate that retinal growth cones robustly adapt towards ephrin-A/EphA forward and reverse signals, which provide the major mapping cues. Computational modeling suggests that topographic accuracy and adaptability, though seemingly incompatible, could be reconciled by a novel mechanism of coupled adaptation of signaling channels. Experimentally, we find such ‘co-adaptation’ in retinal growth cones specifically for ephrin-A/EphA signaling. Co-adaptation involves trafficking of unliganded sensors between the surface membrane and recycling endosomes, and is presumably triggered by changes in the lipid composition of membrane microdomains. We propose that co-adaptative desensitization eventually relies on guidance sensor translocation into cis-signaling endosomes to outbalance repulsive trans-signaling. DOI: http://dx.doi.org/10.7554/eLife.25533.001 PMID:28722651

Developments in Signature Process Control

NASA Astrophysics Data System (ADS)

Keller, L. B.; Dominski, Marty

1993-01-01

Developments in the adaptive process control technique known as Signature Process Control for Advanced Composites (SPCC) are described. This computer control method for autoclave processing of composites was used to develop an optimum cure cycle for AFR 700B polyamide and for an experimental poly-isoimide. An improved process cycle was developed for Avimid N polyamide. The potential for extending the SPCC technique to pre-preg quality control, press modeling, pultrusion and RTM is briefly discussed.

Evaluation of the pH of a Self-Adhesive Flowable Composite Over 3 Months

DTIC Science & Technology

2016-04-01

Flowable Materials. Dental Research Journal 2012; 9(4): 460-465. 12. Goracci C, Margvelashvili M, Giovannetti A, Vichi A, Ferrari M: Shear Bond...responsible for the vast field of current products on the dental market today. These developments have led researchers to focus on combining the...reduces internal voids. Some studies even show better marginal adaptation when a flowable composite is used, though some research shows it doesn’t

Acoustic transmission and radiation analysis of adaptive shape-memory alloy reinforced laminated plates

NASA Astrophysics Data System (ADS)

Liang, C.; Rogers, C. A.; Fuller, C. R.

1991-02-01

A theoretical analysis of sound transmission/radiation of shape-memory alloy (SMA) hybrid composite panels is presented. Unlike other composite materials, SMA hybrid composite is dynamically tunable by electrical activation of the SMA fibers and has numerous active control capabilities. Two of the concepts that will be briefly described and utilized in this paper are referred to as active property tuning (APT) and active strain energy tuning (ASET). Tuning or activating the embedded shape-memory alloy fibers in conventional composite materials changes the overall stiffness of the SMA hybrid composite structure and consequently changes natural frequency and mode shapes. The sound transmission and radiation from a composite panel is related to its frequency and mode shapes. Because of the capability to change both the natural frequency and mode shapes, the acoustic characteristics of SMA hybrid composite plates can be changed as well. The directivity pattern, radiation efficiency, and transmission loss of laminated composite materials are investigated based on 'composite' mode shapes in order to derive a basic understanding of the nature and authority of acoustic control by use of SMA hybrid composites.

Container and method for absorbing and reducing hydrogen concentration

DOEpatents

Wicks, George G.; Lee, Myung W.; Heung, Leung K.

2001-01-01

A method for absorbing hydrogen from an enclosed environment comprising providing a vessel; providing a hydrogen storage composition in communication with a vessel, the hydrogen storage composition further comprising a matrix defining a pore size which permits the passage of hydrogen gas while blocking the passage of gaseous poisons; placing a material within the vessel, the material evolving hydrogen gas; sealing the vessel; and absorbing the hydrogen gas released into the vessel by the hydrogen storage composition. A container for absorbing evolved hydrogen gas comprising: a vessel having an interior and adapted for receiving materials which release hydrogen gas; a hydrogen absorbing composition in communication with the interior, the composition defining a matrix surrounding a hydrogen absorber, the matrix permitting the passage of hydrogen gas while excluding gaseous poisons; wherein, when the vessel is sealed, hydrogen gas, which is released into the vessel interior, is absorbed by the hydrogen absorbing composition.

The bottlenose dolphin (Tursiops truncatus) faecal microbiota.

PubMed

Soverini, Matteo; Quercia, Sara; Biancani, Barbara; Furlati, Stefano; Turroni, Silvia; Biagi, Elena; Consolandi, Clarissa; Peano, Clelia; Severgnini, Marco; Rampelli, Simone; Brigidi, Patrizia; Candela, Marco

2016-04-01

Cetaceans have evolved from herbivorous terrestrial artiodactyls closely related to ruminants and hippopotamuses. Delphinidae, a family included in this order, represent an extreme and successful re-adaptation of mammalian physiology to the marine habitat and piscivorous diet. The anatomical aspects of Delphinidae success are well understood, whereas some physiological aspects of their environmental fitness are less defined, such as the gut microbiota composition and its adaptation to their dietary niche. Here, we explored the faecal microbiota structure of nine adult bottlenose dolphins (Tursiops truncatus) and one breast-fed calf living in a controlled environment. According to our findings, dolphins possess a unique microbiota profile within the Mammalia class, highly resembling that of carnivorous marine fishes. The breast-fed calf showed a distinctive compositional structure of the gut microbial ecosystem, which partially overlaps with the mother's milk microbiota. Taken together, our data indicate that in dolphins the adaptation to the marine niche and piscivorous diet involved the convergence of their gut microbiota structure with that of marine fishes, overcoming the gut microbiota phylogenetic inertia previously described in terrestrial mammalians. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Body mass, composition, and food intake in rabbits during altered acceleration fields

NASA Technical Reports Server (NTRS)

Katovich, M. J.; Smith, A. H.

1978-01-01

Mature male Polish rabbits were subjected to varying gravitational fields in an animal centrifuge in order to evaluate the effects of acceleration and deacceleration on body mass, body composition, and food intake. The acceleration field intensity was increased by 0.25-G increments to a maximum of 2.5 G at intervals which permitted physiological adaptation at each field. Control animals of the same age were maintained at earth gravity under identical conditions of constant-light environment at a room temperature of 23 + or - 5 C. It is shown that increasing the acceleration-field intensity leads to a decrease in body mass. The regulated nature of this decreased body mass is tested by the response to an additional three-day fasting of animals adapted physiologically to 2.5 G. Ad libitum food intake per kg body mass per day tends to increase in chronically accelerated animals above 1.75 G. Increase in water content in centrifuged animals after physiological adaptation to 2.5 G is the result of decreasing body fat. Body mass and food intake returned to the precentrifuged levels of control animals within six weeks after cessation of centrifugation.

Preschoolers with Autism Spectrum Disorder Followed for 2 Years: Those Who Gained and Those Who Lost the Most in Terms of Adaptive Functioning Outcome

ERIC Educational Resources Information Center

Hedvall, Åsa; Westerlund, Joakim; Fernell, Elisabeth; Norrelgen, Fritjof; Kjellmer, Liselotte; Olsson, Martina Barnevik; Carlsson, Lotta Höglund; Eriksson, Mats A.; Billstedt, Eva; Gillberg, Christopher

2015-01-01

Clinical predictors of 2-year outcome in preschoolers with ASD were studied in a population-based group of very young children with ASD (n = 208). Children who gained the most (n = 30) and lost the most (n = 23), i.e., increased or decreased their adaptive functioning outcome according to the Vineland Composite Score between study entry (T1) and…

The 2004 Opposition of Ceres Observed with Adaptive Optics on the VLT

NASA Technical Reports Server (NTRS)

Erard, S.; Frorni, O.; Ollivier, M.; Dotto, E.; Roush, T.; Poulet, F.; Mueller, T.

2005-01-01

The close opposition of Ceres in January 2004 has been observed with the NACO adaptive optics system on the VLT. Both imaging and spectroscopy were performed in the 1.1-4.1 m range. Extensive longitudinal coverage was acquired during a three days run, with spatial resolution up to 50 km in imaging mode. The scientific objectives are 1) to provide the first IR map of Ceres; 2) to map possible compositional variations at the surface. Only imaging results are presented here.

Processing of Aluminum-Graphite Particulate Metal Matrix Composites by Advanced Shear Technology

NASA Astrophysics Data System (ADS)

Barekar, N.; Tzamtzis, S.; Dhindaw, B. K.; Patel, J.; Hari Babu, N.; Fan, Z.

2009-12-01

To extend the possibilities of using aluminum/graphite composites as structural materials, a novel process is developed. The conventional methods often produce agglomerated structures exhibiting lower strength and ductility. To overcome the cohesive force of the agglomerates, a melt conditioned high-pressure die casting (MC-HPDC) process innovatively adapts the well-established, high-shear dispersive mixing action of a twin screw mechanism. The distribution of particles and properties of composites are quantitatively evaluated. The adopted rheo process significantly improved the distribution of the reinforcement in the matrix with a strong interfacial bond between the two. A good combination of improved ultimate tensile strength (UTS) and tensile elongation (ɛ) is obtained compared with composites produced by conventional processes.

The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology

PubMed Central

Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

2017-01-01

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days −30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella, and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus, on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to confer better stress response adaptation following weaning. This study identified potential microbial biomarkers that could predict the likelihood for physiological adaptations to weaning in horses, although causality remains to be addressed. PMID:28790932

The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology.

PubMed

Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

2017-01-01

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days -30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella , and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus , on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to confer better stress response adaptation following weaning. This study identified potential microbial biomarkers that could predict the likelihood for physiological adaptations to weaning in horses, although causality remains to be addressed.

48 CFR 227.7106 - Contracts for special works.

Code of Federal Regulations, 2012 CFR

2012-10-01

... works. 227.7106 Section 227.7106 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in... software documentation, scripts, soundtracks, musical compositions, and adaptations; histories of...

48 CFR 227.7205 - Contracts for special works.

Code of Federal Regulations, 2013 CFR

2013-10-01

... works. 227.7205 Section 227.7205 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in..., scripts, soundtracks, musical compositions, and adaptations; histories of departments, agencies, services...

48 CFR 227.7205 - Contracts for special works.

Code of Federal Regulations, 2012 CFR

2012-10-01

... works. 227.7205 Section 227.7205 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in..., scripts, soundtracks, musical compositions, and adaptations; histories of departments, agencies, services...

48 CFR 227.7106 - Contracts for special works.

Code of Federal Regulations, 2013 CFR

2013-10-01

... works. 227.7106 Section 227.7106 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in... software documentation, scripts, soundtracks, musical compositions, and adaptations; histories of...

48 CFR 227.7106 - Contracts for special works.

Code of Federal Regulations, 2010 CFR

2010-10-01

... works. 227.7106 Section 227.7106 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in... software documentation, scripts, soundtracks, musical compositions, and adaptations; histories of...

48 CFR 227.7106 - Contracts for special works.

Code of Federal Regulations, 2011 CFR

2011-10-01

... works. 227.7106 Section 227.7106 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in... software documentation, scripts, soundtracks, musical compositions, and adaptations; histories of...

48 CFR 227.7205 - Contracts for special works.

Code of Federal Regulations, 2011 CFR

2011-10-01

... works. 227.7205 Section 227.7205 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in..., scripts, soundtracks, musical compositions, and adaptations; histories of departments, agencies, services...

48 CFR 227.7106 - Contracts for special works.

Code of Federal Regulations, 2014 CFR

2014-10-01

... works. 227.7106 Section 227.7106 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in... software documentation, scripts, soundtracks, musical compositions, and adaptations; histories of...

Drama and Composition in the Classroom

ERIC Educational Resources Information Center

Urkowitz, Steven

1978-01-01

Reports on the success of a remedial English class that read and performed plays by Euripides, William Shakespeare, and Arthur Miller. Describes the practical details of the course's organization and classroom management that other teachers can adapt. (RL)

Bend-Twist Coupled Carbon-Fiber Laminate Beams: Fundamental Behavior and Applications

NASA Astrophysics Data System (ADS)

Babuska, Pavel

Material-induced bend-twist coupling in laminated composite beams has seen applications in engineered structures for decades, ranging from airplane wings to turbine blades. Symmetric, unbalanced, carbon fiber laminates which exhibit bend-twist coupling can be difficult to characterize and exhibit unintuitive deformation states which may pose challenges to the engineer. In this thesis, bend-twist coupled beams are investigated comprehensively, by experimentation, numerical modeling, and analytical methods. Beams of varying fiber angle and amount of coupling were manufactured and physically tested in both linear and nonlinear static and dynamic settings. Analytical mass and stiffness matrices were derived for the development of a beam element to use in the stiffness matrix analysis method. Additionally, an ABAQUS finite element model was used in conjunction with the analytical methods to predict and further characterize the behavior of the beams. The three regimes, experimental, analytical, and numerical, represent a full-field characterization of bend-twist coupling in composite beams. A notable application of bend-twist coupled composites is for passively adaptive turbine blades whereby the deformation coupling can be built into the blade structure to simultaneously bend and twist, thus pitching the blade into or away from the fluid flow, changing the blade angle of attack. Passive pitch adaptation has been implemented successfully in wind turbine blades, however, for marine turbine blades, the technology is still in the development phase. Bend-twist coupling has been shown numerically to be beneficial to the tidal turbine performance, however little validation has been conducted in the experimental regime. In this thesis, passively adaptive experiment scale tidal turbine blades were designed, analyzed, manufactured, and physically tested, validating the foundational numerical work. It was shown that blade forces and root moments as well as turbine thrust and power coefficients can be manipulated by inclusion of passive pitch adaption by bend-twist coupling.

Neurodevelopmental Outcome in Children after Fetal Cardiac Intervention for Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome.

PubMed

Laraja, Kristin; Sadhwani, Anjali; Tworetzky, Wayne; Marshall, Audrey C; Gauvreau, Kimberlee; Freud, Lindsay; Hass, Cara; Dunbar-Masterson, Carolyn; Ware, Janice; Lafranchi, Terra; Wilkins-Haug, Louise; Newburger, Jane W

2017-05-01

To characterize neurodevelopmental outcomes after fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome and determine the risk factors for adverse neurodevelopment. Questionnaires were mailed to families of children who underwent fetal aortic valvuloplasty from 2000 to 2012, and medical records were reviewed retrospectively. The primary outcome was the General Adaptive Composite score of the Adaptive Behavior Assessment System Questionnaire-Second Edition. Other questionnaires included the Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, and Pediatric Quality of Life Inventory. Among 69 eligible subjects, 52 (75%) completed questionnaires at median age of 5.5 (range 1.3-12) years; 30 (58%) had biventricular status circulation. The General Adaptive Composite mean score (92 ± 17) was lower than population norms (P < .001) and similar to published reports in patients with hypoplastic left heart syndrome without fetal intervention; scores in the single ventricular versus biventricular group were 97 ± 19 vs 89 ± 14, respectively (P = .10). On multivariable analysis, independent predictors of a lower General Adaptive Composite score were total hospital duration of stay in the first year of life (P = .001) and, when forced into the model, biventricular status (P = .02). For all other neurodevelopmental questionnaires (Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, Pediatric Quality of Life Inventory), most subscale scores for patients with biventricular and single ventricular status were similar. Children who underwent fetal aortic valvuloplasty have neurodevelopmental delay, similar to patients with hypoplastic left heart syndrome without fetal intervention. Achievement of biventricular circulation was not associated with better outcomes. We infer that innate patient factors and morbidity during infancy have the greatest effect on neurodevelopmental outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development

PubMed Central

2012-01-01

Background Influenza A virus (IAV) is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity. The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed. Results We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly influenced by underlying biases in base composition. When correspondence analysis (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process. Conclusions A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies. These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments. Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines. PMID:23134595

Phylogenetic Diversity in the Macromolecular Composition of Microalgae

PubMed Central

Finkel, Zoe V.; Follows, Mick J.; Liefer, Justin D.; Brown, Chris M.; Benner, Ina; Irwin, Andrew J.

2016-01-01

The elemental stoichiometry of microalgae reflects their underlying macromolecular composition and influences competitive interactions among species and their role in the food web and biogeochemistry. Here we provide a new estimate of the macromolecular composition of microalgae using a hierarchical Bayesian analysis of data compiled from the literature. The median macromolecular composition of nutrient-sufficient exponentially growing microalgae is 32.2% protein, 17.3% lipid, 15.0% carbohydrate, 17.3% ash, 5.7% RNA, 1.1% chlorophyll-a and 1.0% DNA as percent dry weight. Our analysis identifies significant phylogenetic differences in macromolecular composition undetected by previous studies due to small sample sizes and the large inherent variability in macromolecular pools. The phylogenetic differences in macromolecular composition lead to variations in carbon-to-nitrogen ratios that are consistent with independent observations. These phylogenetic differences in macromolecular and elemental composition reflect adaptations in cellular architecture and biochemistry; specifically in the cell wall, the light harvesting apparatus, and storage pools. PMID:27228080

Molding apparatus. [for thermosetting plastic compositions

NASA Technical Reports Server (NTRS)

Heier, W. C. (Inventor)

1974-01-01

Apparatus for compression molding of thermosetting plastics compositions including interfitting hollow male and female components is reported. The components are adapted to be compressed to form a rocket nozzle in a cavity. A thermal jacket is provided exteriorly adjacent to the female component for circulating a thermal transfer fluid to effect curing of a thermosetting plastics material being molded. Each of the male and female components is provided with suitable inlets and outlets for circulating a thermal transfer fluid.

[Qualitative composition of dominating forms of microorganisms isolated from radionuclide contaminated soil and their ability to accumulate 137Cs].

PubMed

Pareniuk, O Iu; Moshynets', O V; Tytova, L V; Levchuk, S Ie

2013-01-01

Qualitative composition of the dominating forms of microorganisms isolated from radionuclide contaminated soils has been studied. The ability to accumulate 137Cs by freshly isolated species and collection cultures that were not adapted to the presence of the radionuclide has been analyzed. It is shown that among the analyzed microorganisms the greatest ability to accumulate the radionuclide is inherent in the collection culture Bacillus megaterium UKMV-5724.

Design of adaptive load mitigating materials usingnonlinear stress wave tailoring

DTIC Science & Technology

2016-02-24

for granular material use). 3 • Prof. Trudy Kriven (UIUC, Materials Science) is an expert in ceramic and geopolymer fabrication. • Prof. John...Figure A5.1: Schematic diagram showing the 1D chain of spherical elements in contact with (a) a uniform linear medium and (b) a composite linear...each material point to consisting of one of the given material constituents, we allow each material point to be assigned a composite material that is

Implementation of an improved adaptive-implicit method in a thermal compositional simulator

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

Tan, T.B.

1988-11-01

A multicomponent thermal simulator with an adaptive-implicit-method (AIM) formulation/inexact-adaptive-Newton (IAN) method is presented. The final coefficient matrix retains the original banded structure so that conventional iterative methods can be used. Various methods for selection of the eliminated unknowns are tested. AIM/IAN method has a lower work count per Newtonian iteration than fully implicit methods, but a wrong choice of unknowns will result in excessive Newtonian iterations. For the problems tested, the residual-error method described in the paper for selecting implicit unknowns, together with the IAN method, had an improvement of up to 28% of the CPU time over the fullymore » implicit method.« less

Nyx: Adaptive mesh, massively-parallel, cosmological simulation code

NASA Astrophysics Data System (ADS)

Almgren, Ann; Beckner, Vince; Friesen, Brian; Lukic, Zarija; Zhang, Weiqun

2017-12-01

Nyx code solves equations of compressible hydrodynamics on an adaptive grid hierarchy coupled with an N-body treatment of dark matter. The gas dynamics in Nyx use a finite volume methodology on an adaptive set of 3-D Eulerian grids; dark matter is represented as discrete particles moving under the influence of gravity. Particles are evolved via a particle-mesh method, using Cloud-in-Cell deposition/interpolation scheme. Both baryonic and dark matter contribute to the gravitational field. In addition, Nyx includes physics for accurately modeling the intergalactic medium; in optically thin limits and assuming ionization equilibrium, the code calculates heating and cooling processes of the primordial-composition gas in an ionizing ultraviolet background radiation field.

Are interpretations of ancient marine temperatures constrained by the presence of ancient marine organisms?

NASA Technical Reports Server (NTRS)

Valentine, J. W.

1985-01-01

The relationship between marine temperature and marine organisms is investigated. The adaptation of organisms to extreme temperatures is studied; it is observed that chemautotrophic and chemoheterotrophic prokaryotes adapt to 100 C, photoautotrophic prokaryotes to 73 C, and fungi to 60 C. The physiological and molecular factors related to thermal limits in organisms such as enzymes, lipids, or plasma membranes, are examined. Two types of thermal adaptations, resistance and capacity, are detected in organisms. Reasons for species distributions according to temperature barriers are proposed by Read (1967) and Bullock (1955) and are related to enzyme limits. The effects of an organism's composition on thermal stability is analyzed.

Ultrastructure and mineral composition of the cornea cuticle in the compound eyes of a supralittoral and a marine isopod.

PubMed

Alagboso, Francisca I; Reisecker, Christian; Hild, Sabine; Ziegler, Andreas

2014-08-01

The cuticle of the cornea in Crustacea is an interesting example of a composite material compromising between two distinct functions. As part of the dioptric apparatus of the ommatidia within the complex eye it forms transparent micro-lenses that should as well maintain the mechanical stability of the head capsule. We analyzed the ultrastructure and composition of the isopod cornea cuticle of the terrestrial species Ligia oceanica and the marine Sphaeroma serratum. We used a variety of tissue preparation methods, electron microscopic techniques as well as electron microprobe analysis and Raman spectroscopic imaging. The results reveal various structural adaptations that likely increase light transmission. These are an increase in the thickness of the epicuticle, a reduction of the thickness of the outer layer of calcite, a spatial restriction of pore canals to interommatidial regions, and, for S. serratum only, an increase in calcite crystal size. In both species protein-chitin fibrils within the proximal exocuticle form a peculiar reticular structure that does not occur within the cuticle of the head capsule. In L. oceanica differential mineralization results in a spherically shaped interface between mineralized and unmineralized endocuticle, likely an adaptation to increase the refractive power of the cornea maintaining the mechanical stability of the cuticle between the ommatidia. The results show that the habitat and differences in the general structure of the animal's cuticle affect the way in which the cornea is adapted to its optical function. Copyright © 2014 Elsevier Inc. All rights reserved.

Structural integrated sensor and actuator systems for active flow control

NASA Astrophysics Data System (ADS)

Behr, Christian; Schwerter, Martin; Leester-Schädel, Monika; Wierach, Peter; Dietzel, Andreas; Sinapius, Michael

2016-04-01

An adaptive flow separation control system is designed and implemented as an essential part of a novel high-lift device for future aircraft. The system consists of MEMS pressure sensors to determine the flow conditions and adaptive lips to regulate the mass flow and the velocity of a wall near stream over the internally blown Coanda flap. By the oscillating lip the mass flow in the blowing slot changes dynamically, consequently the momentum exchange of the boundary layer over a high lift flap required mass flow can be reduced. These new compact and highly integrated systems provide a real-time monitoring and manipulation of the flow conditions. In this context the integration of pressure sensors into flow sensing airfoils of composite material is investigated. Mechanical and electrical properties of the integrated sensors are investigated under mechanical loads during tensile tests. The sensors contain a reference pressure chamber isolated to the ambient by a deformable membrane with integrated piezoresistors connected as a Wheatstone bridge, which outputs voltage signals depending on the ambient pressure. The composite material in which the sensors are embedded consists of 22 individual layers of unidirectional glass fiber reinforced plastic (GFRP) prepreg. The results of the experiments are used for adapting the design of the sensors and the layout of the laminate to ensure an optimized flux of force in highly loaded structures primarily for future aeronautical applications. It can be shown that the pressure sensor withstands the embedding process into fiber composites with full functional capability and predictable behavior under stress.

Light adaptation of the unicellular red alga, Cyanidioschyzon merolae, probed by time-resolved fluorescence spectroscopy.

PubMed

Ueno, Yoshifumi; Aikawa, Shimpei; Kondo, Akihiko; Akimoto, Seiji

2015-08-01

Photosynthetic organisms change the quantity and/or quality of their pigment-protein complexes and the interactions among these complexes in response to light conditions. In the present study, we analyzed light adaptation of the unicellular red alga Cyanidioschyzon merolae, whose pigment composition is similar to that of cyanobacteria because its phycobilisomes (PBS) lack phycoerythrin. C. merolae were grown under different light qualities, and their responses were measured by steady-state absorption, steady-state fluorescence, and picosecond time-resolved fluorescence spectroscopies. Cells were cultivated under four monochromatic light-emitting diodes (blue, green, yellow, and red), and changes in pigment composition and energy transfer were observed. Cells grown under blue and green light increased their relative phycocyanin levels compared with cells cultured under white light. Energy-transfer processes to photosystem I (PSI) were sensitive to yellow and red light. The contribution of direct energy transfer from PBS to PSI increased only under yellow light, while red light induced a reduction in energy transfer from photosystem II to PSI and an increase in energy transfer from light-harvesting chlorophyll protein complex I to PSI. Differences in pigment composition, growth, and energy transfer under different light qualities are discussed.

Learning multivariate distributions by competitive assembly of marginals.

PubMed

Sánchez-Vega, Francisco; Younes, Laurent; Geman, Donald

2013-02-01

We present a new framework for learning high-dimensional multivariate probability distributions from estimated marginals. The approach is motivated by compositional models and Bayesian networks, and designed to adapt to small sample sizes. We start with a large, overlapping set of elementary statistical building blocks, or "primitives," which are low-dimensional marginal distributions learned from data. Each variable may appear in many primitives. Subsets of primitives are combined in a Lego-like fashion to construct a probabilistic graphical model; only a small fraction of the primitives will participate in any valid construction. Since primitives can be precomputed, parameter estimation and structure search are separated. Model complexity is controlled by strong biases; we adapt the primitives to the amount of training data and impose rules which restrict the merging of them into allowable compositions. The likelihood of the data decomposes into a sum of local gains, one for each primitive in the final structure. We focus on a specific subclass of networks which are binary forests. Structure optimization corresponds to an integer linear program and the maximizing composition can be computed for reasonably large numbers of variables. Performance is evaluated using both synthetic data and real datasets from natural language processing and computational biology.

The influence of climate on species distribution over time and space during the late Quaternary

NASA Astrophysics Data System (ADS)

Carotenuto, F.; Di Febbraro, M.; Melchionna, M.; Castiglione, S.; Saggese, F.; Serio, C.; Mondanaro, A.; Passaro, F.; Loy, A.; Raia, P.

2016-10-01

Understanding the effect of climate on the composition of communities and its change over time and space is one of the major aims in ecology and paleoecology. Herein, we tackled on this issue by studying late Quaternary large mammal paleocommunities of Eurasia. The late Quaternary was a period of strong environmental instability, especially characterized by the occurrence of the last glacial maximum (LGM). We used community phylogenetics and joint species distribution models in order to understand the factors determining paleocommunity composition in the late Quaternary. Our results support the existence of strong climatic selection operating on the LGM fauna, both through the disappearance of warm-adapted species such as Elephas antiquus, Hippopothamus amphibious, and Stephanorhinus hemitoechus, and by setting the stage for the existence of a community characterized by cold-adapted large mammals. Patterns of abundance in the fossil record, co-occurrence between species pairs, and the extent of climatic forcing on faunal composition, differ between paleocommunities, but not between extinct and extant species, which is consistent with the idea that climate change, rather than the presence of humans, exerted a major effect on the survival of the late Quaternary megafauna.

[Breast milk: its nutritional composition and functional properties].

PubMed

Tackoen, M

2012-09-01

Human milk is a complex biological fluid with thousands of components. The milk composition in the mammalian species is specific and adapted to the needs of the offspring. It contains macronutrients (proteins, lipids and carbohydrates), micronutrients (minerals and vitamins) and numerous biologically active substrates. Human milk not only covers the nutritional needs of the newborn but protects the baby against infection, inflammation and oxidative stress. It has immunomodulation properties and confers trophical protection to the intestinal mucosa. The newborn infant is particularly immature: innate immunity, adaptive immunity and intestinal immaturity. Human milk will offer this exogenous protective and immunomodulating source. The development of the composition of the intestinal microflora of the neonate will be impacted by pre- and probiotic components of human milk. Current scientific knowledge of human milk properties highlights interdependency of the different components, ontogeny of the intestinal function, development of the mucosal intestinal immune system, colonization by the intestinal microbiota and protection against pathogens. Quality of these interactions influences the newborn's short and long-term health status. The promotion of breastfeeding with the support of the Baby Friendly Hospital Initiative (BFHI) program and labeling has been shown to have positive impact in public health.

Ultra low friction carbon/carbon composites for extreme temperature applications

DOEpatents

Erdemir, Ali; Busch, Donald E.; Fenske, George R.; Lee, Sam; Shepherd, Gary; Pruett, Gary J.

2001-01-01

A carbon/carbon composite in which a carbon matrix containing a controlled amount of boron or a boron compound is reinforced with carbon fiber exhibits a low coefficient of friction, i.e., on the order of 0.04 to 0.1 at temperatures up to 600.degree. C., which is one of the lowest frictional coefficients for any type of carbonaceous material, including graphite, glassy carbon, diamond, diamond-like carbon and other forms of carbon material. The high degree of slipperiness of the carbon composite renders it particularly adapted for limiting friction and wear at elevated temperatures such as in seals, bearings, shafts, and flexible joints

Abrasion resistant composition

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

Fischer, Keith D; Barnes, Christopher A; Henderson, Stephen L

A surface covering composition of abrasion resistant character adapted for disposition in overlying bonded relation to a metal substrate. The surface covering composition includes metal carbide particles within a metal matrix at a packing factor of not less than about 0.6. Not less than about 40 percent by weight of the metal carbide particles are characterized by an effective diameter in the range of +14-32 mesh prior to introduction to the metal matrix. Not less than about 3 percent by weight of the metal carbide particles are characterized by an effective diameter of +60 mesh prior to introduction to themore » metal matrix.« less

Thermally emissive sensing materials for chemical spectroscopy analysis

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

Poole, Zsolt; Ohodnicki, Paul R.

A sensor using thermally emissive materials for chemical spectroscopy analysis includes an emissive material, wherein the emissive material includes the thermally emissive materials which emit electromagnetic radiation, wherein the electromagnetic radiation is modified due to chemical composition in an environment; and a detector adapted to detect the electromagnetic radiation, wherein the electromagnetic radiation is indicative of the chemical interaction changes and hence chemical composition and/or chemical composition changes of the environment. The emissive material can be utilized with an optical fiber sensor, with the optical fiber sensor operating without the emissive material probed with a light source external to themore » material.« less

Nonlinear behavior of matrix-inclusion composites under high confining pressure: application to concrete and mortar

NASA Astrophysics Data System (ADS)

Le, Tuan Hung; Dormieux, Luc; Jeannin, Laurent; Burlion, Nicolas; Barthélémy, Jean-François

2008-08-01

This paper is devoted to a micromechanics-based simulation of the response of concrete to hydrostatic and oedometric compressions. Concrete is described as a composite made up of a cement matrix in which rigid inclusions are embedded. The focus is put on the role of the interface between matrix and inclusion which represent the interfacial transition zone (ITZ). A plastic behavior is considered for both the matrix and the interfaces. The effective response of the composite is derived from the modified secant method adapted to the situation of imperfect interfaces. To cite this article: T.H. Le et al., C. R. Mecanique 336 (2008).

Design concepts for low-cost composite engine frames

NASA Technical Reports Server (NTRS)

Chamis, C. C.

1983-01-01

Design concepts for low-cost, lightweight composite engine frames were applied to the design requirements for the frame of commercial, high-bypass turbine engines. The concepts consist of generic-type components and subcomponents that could be adapted for use in different locations in the engine and to different engine sizes. A variety of materials and manufacturing methods were assessed with a goal of having the lowest number of parts possible at the lowest possible cost. The evaluation of the design concepts resulted in the identification of a hybrid composite frame which would weigh about 70 percent of the state-of-the-art metal frame and cost would be about 60 percent.

The architecture of the joint head cuticle and its transition to the arthrodial membrane in the terrestrial crustacean Porcellio scaber.

PubMed

Ruangchai, Sukhum; Reisecker, Christian; Hild, Sabine; Ziegler, Andreas

2013-04-01

The cuticle of terrestrial isopods is an interesting model for the study of structure-function relationships in biological composite materials. Its organic matrix has a hierarchically organised structure, and type and phase of the mineral compound can vary. The cuticle forms functionally diverse skeletal elements whose properties are adapted to their specific functions. In order to better understand the relation between structure, composition and function of isopod cuticle, we studied the structure and composition of the joint head that is part of the pereiopod's basis. It consists of a central region, whose shape fits well into the joint socket, and an edge region that is connected to the soft arthrodial membrane and protects the central region from mechanical load. The cuticle architecture of the joint head has local variations in structure and composition. In the central region the cuticle is similar to the previously published tergite cuticle. High concentrations of amorphous calcium phosphate are located in the endocuticle suggesting a coexistence with amorphous calcium carbonate. The edge region has an unexpected organisation characterised by thickening of the epi- and exocuticle and an unusual unidirectional orientation of chitin-protein fibrils within the endocuticle. The concentrations of phosphate are considerably higher than in the central region. The overall differentiation in the cuticular architecture of the edge in comparison to the central region reflects the adaptation to mechanical strains the cuticle has to sustain during contraction of extensor muscles, and to the structural and compositional transition from the edge to the connecting arthrodial membrane. Copyright © 2013 Elsevier Inc. All rights reserved.

Music and the Three Appeals of Classical Rhetoric

ERIC Educational Resources Information Center

LeCoat, Gerard G.

1976-01-01

Contends that rhetorical theory of the sixteenth through the eighteenth centuries influenced the theory of the composition of music and offers examples of vocal music which was adapted to the rhetorical appeals of logos, ethos, and pathos. (MH)

Adaptation to new nutritional environments: larval performance, foraging decisions, and adult oviposition choices in Drosophila suzukii.

PubMed

Silva-Soares, Nuno F; Nogueira-Alves, A; Beldade, P; Mirth, Christen Kerry

2017-06-07

Understanding how species adapt to new niches is a central issue in evolutionary ecology. Nutrition is vital for the survival of all organisms and impacts species fitness and distribution. While most Drosophila species exploit rotting plant parts, some species have diversified to use ripe fruit, allowing earlier colonization. The decomposition of plant material is facilitated by yeast colonization and proliferation. These yeasts serve as the main protein source for Drosophila larvae. This dynamic rotting process entails changes in the nutritional composition of the food and other properties, and animals feeding on material at different stages of decay are expected to have behavioural and nutritional adaptations. We compared larval performance, feeding behaviour and adult oviposition site choice between the ripe fruit colonizer and invasive pest Drosophila suzukii, and a closely-related rotting fruit colonizer, Drosophila biarmipes. Through the manipulation of protein:carbohydrate ratios in artificial diets, we found that D. suzukii larvae perform better at lower protein concentrations and consume less protein rich diets relative to D. biarmipes. For adult oviposition, these species differed in preference for substrate hardness, but not for the substrate nutritional composition. Our findings highlight that rather than being an exclusive specialist on ripe fruit, D. suzukii's adaptation to use ripening fruit allow it to colonize a wider range of food substrates than D. biarmipes, which is limited to soft foods with higher protein concentrations. Our results underscore the importance of nutritional performance and feeding behaviours in the colonization of new food niches.

Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

PubMed

Őri, Zsolt P

2017-05-01

A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

Micro-feeding and dosing of powders via a small-scale powder pump.

PubMed

Besenhard, M O; Fathollahi, S; Siegmann, E; Slama, E; Faulhammer, E; Khinast, J G

2017-03-15

Robust and accurate powder micro-feeding (<100mg/s) and micro-dosing (<5 mg) are major challenges, especially with regard to regulatory limitations applicable to pharmaceutical development and production. Since known micro-feeders that yield feed rates below 5mg/s use gravimetric feeding principles, feed rates depend primarily on powder properties. In contrast, volumetric powder feeders do not require regular calibration because their feed rates are primarily determined by the feeder's characteristic volume replacement. In this paper, we present a volumetric micro-feeder based on a cylinder piston system (i.e., a powder pump), which allows accurate micro-feeding and feed rates of a few grams per hours even for very fine powders. Our experimental studies addressed the influence of cylinder geometries, the initial conditions of bulk powder, and the piston speeds. Additional computational studies via Discrete Element Method simulations offered a better understanding of the feeding process, its possible limitations and ways to overcome them. The powder pump is a simple yet valuable tool for accurate powder feeding at feed rates of several orders of magnitude. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct Measurements of Half-Cycle Reaction Heats during Atomic Layer Deposition by Calorimetry

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

Lownsbury, James M.; Gladden, James A.; Campbell, Charles T.

We introduce a new high-temperature adsorption calorimeter that approaches the ideal limit of a heat detector whereby the signal at any time is proportional to the heat power being delivered to the sample and prove its sensitivity for measuring pulse-to-pulse heats of half-reactions during atomic layer deposition (ALD) at 400 K. The heat dynamics of amorphous Al2O3 growth via sequential self-limiting surface reaction of trimethylaluminum (TMA) and H2O is clearly resolved. Calibration enables quantitation of the exothermic TMA and H2O half-reactions with high precision, -343 kJ/mol TMA and -251 kJ/mol H2O, respectively. A time resolution better than 1 ms ismore » demonstrated, allowing for the deconvolution of at least two distinct surface reactions during TMA microdosing. It is further demonstrated that this method can provide the heat of reaction versus extent of reaction during each precursors half-reaction, thus providing even richer mechanistic information on the surface processes involved. The broad applicability of this novel calorimeter is demonstrated through excellent signal-to-noise ratios of less exothermic ALD half-reactions to produce TiO2 and MnO.« less

Recent advances in biomedical applications of accelerator mass spectrometry.

PubMed

Hah, Sang Soo; Henderson, Paul T; Turteltaub, Kenneth W

2009-06-17

The use of radioisotopes has a long history in biomedical science, and the technique of accelerator mass spectrometry (AMS), an extremely sensitive nuclear physics technique for detection of very low-abundant, stable and long-lived isotopes, has now revolutionized high-sensitivity isotope detection in biomedical research, because it allows the direct determination of the amount of isotope in a sample rather than measuring its decay, and thus the quantitative analysis of the fate of the radiolabeled probes under the given conditions. Since AMS was first used in the early 90's for the analysis of biological samples containing enriched 14C for toxicology and cancer research, the biomedical applications of AMS to date range from in vitro to in vivo studies, including the studies of 1) toxicant and drug metabolism, 2) neuroscience, 3) pharmacokinetics, and 4) nutrition and metabolism of endogenous molecules such as vitamins. In addition, a new drug development concept that relies on the ultrasensitivity of AMS, known as human microdosing, is being used to obtain early human metabolism information of candidate drugs. These various aspects of AMS are reviewed and a perspective on future applications of AMS to biomedical research is provided.

Correlation of PET and AMS analyses for early kinetics of 2-fluoro-2-deoxyglucose (FDG)

NASA Astrophysics Data System (ADS)

Minamimoto, Ryogo; Hamabe, Yoshimi; Miyaoka, Teiji; Theeraladanon, Chumpol; Oka, Takashi; Matsui, Takao; Inoue, Tomio

2010-04-01

The draft of the guidelines for microdosing in clinical trials was published in Japan in 2008 following the guidelines of the European Medicines Agency (EMEA) and the Food and Drug Administration (FDA). It recommends utilizing accelerator mass spectrometry (AMS), liquid chromatography/mass spectrometry (LC/MS/MS), and positron emission tomography (PET) for monitoring drug metabolites in preclinical studies. In this study, we clarified the correlation in measuring result between PET and AMS. The AMS measurement was undergone by using AMS system of Institute of Accelerator Analysis Ltd. (IAA, Kawasaki, Japan). First the back ground 14C level of blood in mice was measured by AMS. Second, we clarified the relationship between AMS and PET by using 2-fluoro-2-deoxyglucose (FDG). The correlation coefficient ( r) of the measurements using PET ( 18F-FDG) and AMS ( 14C-FDG) were quite high at 0.97 ( Y = 7.54 E - 05 X + 0.02, p < 0.001). The blood clearance profile of 18F-FDG was nearly identical with that of 14C-FDG. These results indicate that the AMS analysis has excellent correlation with the PET method.

Recent advances in biomedical applications of accelerator mass spectrometry

PubMed Central

Hah, Sang Soo

2009-01-01

The use of radioisotopes has a long history in biomedical science, and the technique of accelerator mass spectrometry (AMS), an extremely sensitive nuclear physics technique for detection of very low-abundant, stable and long-lived isotopes, has now revolutionized high-sensitivity isotope detection in biomedical research, because it allows the direct determination of the amount of isotope in a sample rather than measuring its decay, and thus the quantitative analysis of the fate of the radiolabeled probes under the given conditions. Since AMS was first used in the early 90's for the analysis of biological samples containing enriched 14C for toxicology and cancer research, the biomedical applications of AMS to date range from in vitro to in vivo studies, including the studies of 1) toxicant and drug metabolism, 2) neuroscience, 3) pharmacokinetics, and 4) nutrition and metabolism of endogenous molecules such as vitamins. In addition, a new drug development concept that relies on the ultrasensitivity of AMS, known as human microdosing, is being used to obtain early human metabolism information of candidate drugs. These various aspects of AMS are reviewed and a perspective on future applications of AMS to biomedical research is provided. PMID:19534792

[Study of the intracerebral connections after intracortical administration of glutamate].

PubMed

Otellin, V A; Rybakov, V L; Grigor'ev, I P

1980-10-01

Various microdoses of monosubstituted sodium L-glutamate (MSG) were injected into zone AI of the cat cerebral acoustic cortex. In 2 h--14 days, it was stated light optically that the place of injection was slightly stained, and most of neurons failed to stain. At the place of MSG injection, electron microscopic investigation revealed neurons with various degree of pathologic changes up to the lethal ones. Astroglia was edematous, oligodendrocytes and pericytes had normal appearance. In field 4 and in zone AII of the acoustic cortex, separate neural cells with sharply increasing number of ribosomes and polysomes were noted. Anterograde axonal degeneration in the lesioned neurons and their terminals was revealed in frontal sections impregnated after Wiitanen. In the cortical field 7, in zones AII, AIV, Ep of the acoustic cortex, in the head of the nucleus caudatus and in the internal geniculate body, terminal boutons degenerating after the dark type and at the same time as after surgical extirpation of zone AI were revealed. Owing to the fact that the lesions are of local character and the trauma is small, it is possible to use neuronal glutamate-induced degeneration as a method for investigating intracerebral connections.

Direct Measurements of Half-Cycle Reaction Heats during Atomic Layer Deposition by Calorimetry

DOE PAGES

Lownsbury, James M.; Gladden, James A.; Campbell, Charles T.; ...

2017-10-05

We introduce a new high-temperature adsorption calorimeter that approaches the ideal limit of a heat detector whereby the signal at any time is proportional to the heat power being delivered to the sample and prove its sensitivity for measuring pulse-to-pulse heats of half-reactions during atomic layer deposition (ALD) at 400 K. The heat dynamics of amorphous Al2O3 growth via sequential self-limiting surface reaction of trimethylaluminum (TMA) and H2O is clearly resolved. Calibration enables quantitation of the exothermic TMA and H2O half-reactions with high precision, -343 kJ/mol TMA and -251 kJ/mol H2O, respectively. A time resolution better than 1 ms ismore » demonstrated, allowing for the deconvolution of at least two distinct surface reactions during TMA microdosing. It is further demonstrated that this method can provide the heat of reaction versus extent of reaction during each precursors half-reaction, thus providing even richer mechanistic information on the surface processes involved. The broad applicability of this novel calorimeter is demonstrated through excellent signal-to-noise ratios of less exothermic ALD half-reactions to produce TiO2 and MnO.« less

Two-year clinical comparison of a flowable-type nano-hybrid composite and a paste-type composite in posterior restoration.

PubMed

Hirata-Tsuchiya, Shizu; Yoshii, Shinji; Ichimaru-Suematsu, Miki; Washio, Ayako; Saito, Noriko; Urata, Mariko; Hanada, Kaori; Morotomi, Takahiko; Kitamura, Chiaki

2017-08-01

The purpose of the present study was to compare the clinical efficacy between a flowable-type nano-hybrid composite and a paste-type composite for posterior restoration. Of 62 posterior teeth in 33 patients (mean age: 34.1 years), 31 were filled with a paste-type composite (Heliomolar [HM] group), and another 31 with a flowable nano-hybrid composite (MI FIL [MI] group). Clinical efficacy was evaluated at 2 years after the restoration. There were no differences for retention, surface texture deterioration, anatomical form change, deterioration of marginal adaptation, and secondary caries, while a statistical difference was found for marginal discoloration, which was significantly greater in the HM group (P < 0.05). Furthermore, color matching in the MI group was superior to that in the HM group immediately after the restoration throughout the study period. The present 2-year clinical evaluation of different composites showed that the flowable nano-hybrid composite could be an effective esthetic material for posterior restoration. © 2016 John Wiley & Sons Australia, Ltd.

Efficient dynamic coherence transfer relying on offset locking using optical phase-locked loop

NASA Astrophysics Data System (ADS)

Xie, Weilin; Dong, Yi; Bretenaker, Fabien; Shi, Hongxiao; Zhou, Qian; Xia, Zongyang; Qin, Jie; Zhang, Lin; Lin, Xi; Hu, Weisheng

2018-01-01

We design and experimentally demonstrate a highly efficient coherence transfer based on composite optical phaselocked loop comprising multiple feedback servo loops. The heterodyne offset-locking is achieved by conducting an acousto-optic frequency shifter in combination with the current tuning and the temperature controlling of the semiconductor laser. The adaptation of the composite optical phase-locked loop enables the tight coherence transfer from a frequency comb to a semiconductor laser in a fully dynamic manner.

A fiber-reinforced composite prosthesis restoring a lateral midfacial defect: a clinical report.

PubMed

Kurunmäki, Hemmo; Kantola, Rosita; Hatamleh, Muhanad M; Watts, David C; Vallittu, Pekka K

2008-11-01

This clinical report describes the use of a glass fiber-reinforced composite (FRC) substructure to reinforce the silicone elastomer of a large facial prosthesis. The FRC substructure was shaped into a framework and embedded into the silicone elastomer to form a reinforced facial prosthesis. The prosthesis is designed to overcome the disadvantages associated with traditionally fabricated prostheses; namely, delamination of the silicone of the acrylic base, poor marginal adaptation over time, and poor simulation of facial expressions.

Approaches to polymer-derived CMC matrices

NASA Technical Reports Server (NTRS)

Hurwitz, Frances I.

1992-01-01

The use of polymeric precursors to ceramics permits the fabrication of large, complex-shaped ceramic matrix composites (CMC's) at temperatures which do not degrade the fiber. Processing equipment and techniques readily available in the resin matrix composite industry can be adapted for CMC fabrication using this approach. Criteria which influence the choice of candidate precursor polymers, the use of fillers, and the role of fiber architecture and ply layup are discussed. Three polymer systems, polycarbosilanes, polysilazanes, and polysilsesquioxanes, are compared as candidate ceramic matrix precursors.

Spectral composition of light and growing of plants in controlled environments

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

Tikhomirov, A.A.

1994-12-31

The curve of the action spectrum of photosynthesis is examined under the controlled influence of light that involves av 3-5 minutes irradiation with one specific spectral flux. Different curves were obtained for spectral affectivity of green leaf photosynthesis when plants have had long duration adaptation to lamps of different spectral composition and PAR intensity. The author suggests that the illumination of plants in natural conditions does not have to be copied for growing plants in controlled environments.

Eddy current modeling in linear and nonlinear multifilamentary composite materials

NASA Astrophysics Data System (ADS)

Menana, Hocine; Farhat, Mohamad; Hinaje, Melika; Berger, Kevin; Douine, Bruno; Lévêque, Jean

2018-04-01

In this work, a numerical model is developed for a rapid computation of eddy currents in composite materials, adaptable for both carbon fiber reinforced polymers (CFRPs) for NDT applications and multifilamentary high temperature superconductive (HTS) tapes for AC loss evaluation. The proposed model is based on an integro-differential formulation in terms of the electric vector potential in the frequency domain. The high anisotropy and the nonlinearity of the considered materials are easily handled in the frequency domain.

Final Report: Design of adaptive load mitigating materials using nonlinear stress wave tailoring

DTIC Science & Technology

2016-02-26

for granular material use). 3 • Prof. Trudy Kriven (UIUC, Materials Science) is an expert in ceramic and geopolymer fabrication. • Prof. John...Figure A5.1: Schematic diagram showing the 1D chain of spherical elements in contact with (a) a uniform linear medium and (b) a composite linear...each material point to consisting of one of the given material constituents, we allow each material point to be assigned a composite material that is

Neural network based adaptive control for nonlinear dynamic regimes

NASA Astrophysics Data System (ADS)

Shin, Yoonghyun

Adaptive control designs using neural networks (NNs) based on dynamic inversion are investigated for aerospace vehicles which are operated at highly nonlinear dynamic regimes. NNs play a key role as the principal element of adaptation to approximately cancel the effect of inversion error, which subsequently improves robustness to parametric uncertainty and unmodeled dynamics in nonlinear regimes. An adaptive control scheme previously named 'composite model reference adaptive control' is further developed so that it can be applied to multi-input multi-output output feedback dynamic inversion. It can have adaptive elements in both the dynamic compensator (linear controller) part and/or in the conventional adaptive controller part, also utilizing state estimation information for NN adaptation. This methodology has more flexibility and thus hopefully greater potential than conventional adaptive designs for adaptive flight control in highly nonlinear flight regimes. The stability of the control system is proved through Lyapunov theorems, and validated with simulations. The control designs in this thesis also include the use of 'pseudo-control hedging' techniques which are introduced to prevent the NNs from attempting to adapt to various actuation nonlinearities such as actuator position and rate saturations. Control allocation is introduced for the case of redundant control effectors including thrust vectoring nozzles. A thorough comparison study of conventional and NN-based adaptive designs for a system under a limit cycle, wing-rock, is included in this research, and the NN-based adaptive control designs demonstrate their performances for two highly maneuverable aerial vehicles, NASA F-15 ACTIVE and FQM-117B unmanned aerial vehicle (UAV), operated under various nonlinearities and uncertainties.

High-Temperature Graphite/Phenolic Composite

NASA Technical Reports Server (NTRS)

Seal, Ellis C.; Bodepudi, Venu P.; Biggs, Robert W., Jr.; Cranston, John A.

1995-01-01

Graphite-fiber/phenolic-resin composite material retains relatively high strength and modulus of elasticity at temperatures as high as 1,000 degrees F. Costs only 5 to 20 percent as much as refractory materials. Fabrication composite includes curing process in which application of full autoclave pressure delayed until after phenolic resin gels. Curing process allows moisture to escape, so when composite subsequently heated in service, much less expansion of absorbed moisture and much less tendency toward delamination. Developed for nose cone of external fuel tank of Space Shuttle. Other potential aerospace applications for material include leading edges, parts of nozzles, parts of aircraft engines, and heat shields. Terrestrial and aerospace applications include structural firewalls and secondary structures in aircraft, spacecraft, and ships. Modified curing process adapted to composites of phenolic with other fiber reinforcements like glass or quartz. Useful as high-temperature circuit boards and electrical insulators.

Effect of HNT on the Microstructure, Thermal and Mechanical Properties of Al/FACS-HNT Composites Produced by GPI

NASA Astrophysics Data System (ADS)

Siewiorek, A.; Malczyk, P.; Sobczak, N.; Sobczak, J. J.; Czulak, A.; Kozera, R.; Gude, M.; Boczkowska, A.; Homa, M.

2016-08-01

To develop an optimised manufacturing method of fly ash-reinforced metal matrix composites, the preliminary tests were performed on the cenospheres selected from fly ash (FACS) with halloysite nanotubes (HNTs) addition. The preform made out of FACS with and without the addition of HNT (with 5 and 10 wt.%) has been infiltrated by the pure aluminium (Al) via adapted gas pressure infiltration process. This paper reveals the influence of HNT addition on the microstructure (analysis was done by computed tomography and scanning electron microscopy combined with energy-dispersive x-ray spectroscopy), thermal properties (thermal expansion coefficient, thermal conductivity and specific heat) and the mechanical properties (hardness and compression test) of manufactured composites. The analysis of structure-property relationships for Al/FACS-HNT composites produced shows that the addition of 5 wt.% of HNT to FACS preform contributes to receiving of the best mechanical and structural properties of investigated composites.

Glass Fibre-Reinforced Composite Post and Core Used in Decayed Primary Anterior Teeth: A Case Report

PubMed Central

Verma, Leena; Passi, Sidhi

2011-01-01

Aesthetic requirement of severely mutilated primary anterior teeth in the case of early childhood caries has been a challenge to pediatric dentist. Among restorative treatment options, prefabricated crown and biological and resin composite restoration either by means of direct or indirect technique are mentioned in the literature. This paper presents the clinical sequence of rehabilitation of maxillary anterior primary teeth. Endodontic treatment was followed by the placement of a glass fibre-reinforced composite resin post. The crown reconstruction was done with composite restoration. Resin glass fibre post has best properties in elasticity, translucency, adaptability, tenaciousness, and resistance to traction and to impact. Along with ease of application, fiber can be used as an alternative to traditionally used materials in the management of early childhood caries. PMID:22567447

Smart composites with embedded shape memory alloy actuators and fibre Bragg grating sensors: activation and control

NASA Astrophysics Data System (ADS)

Balta, J. A.; Bosia, F.; Michaud, V.; Dunkel, G.; Botsis, J.; Månson, J.-A.

2005-08-01

This paper describes the production of an adaptive composite by embedding thin pre-strained shape memory alloy actuators into a Kevlar-epoxy host material. In order to combine the activation and sensing capabilities, fibre Bragg grating sensors are also embedded into the specimens, and the strain measured in situ during activation. The effect of manufacturing conditions, and hence of the initial stress state in the composite before activation, on the magnitude of the measured strains is discussed. The results of stress and strain simulations are compared with experimental data, and guidelines are provided for the optimization of the composite. Finally, a pilot experiment is carried out to provide an example of how a strain-stabilizing feedback mechanism can be implemented in the smart structure.

Application of the Refined Zigzag Theory to the Modeling of Delaminations in Laminated Composites

NASA Technical Reports Server (NTRS)

Groh, Rainer M. J.; Weaver, Paul M.; Tessler, Alexander

2015-01-01

The Refined Zigzag Theory is applied to the modeling of delaminations in laminated composites. The commonly used cohesive zone approach is adapted for use within a continuum mechanics model, and then used to predict the onset and propagation of delamination in five cross-ply composite beams. The resin-rich area between individual composite plies is modeled explicitly using thin, discrete layers with isotropic material properties. A damage model is applied to these resin-rich layers to enable tracking of delamination propagation. The displacement jump across the damaged interfacial resin layer is captured using the zigzag function of the Refined Zigzag Theory. The overall model predicts the initiation of delamination to within 8% compared to experimental results and the load drop after propagation is represented accurately.

The life of a dead ant: the expression of an adaptive extended phenotype.

PubMed

Andersen, Sandra B; Gerritsma, Sylvia; Yusah, Kalsum M; Mayntz, David; Hywel-Jones, Nigel L; Billen, Johan; Boomsma, Jacobus J; Hughes, David P

2009-09-01

Specialized parasites are expected to express complex adaptations to their hosts. Manipulation of host behavior is such an adaptation. We studied the fungus Ophiocordyceps unilateralis, a locally specialized parasite of arboreal Camponotus leonardi ants. Ant-infecting Ophiocordyceps are known to make hosts bite onto vegetation before killing them. We show that this represents a fine-tuned fungal adaptation: an extended phenotype. Dead ants were found under leaves, attached by their mandibles, on the northern side of saplings approximately 25 cm above the soil, where temperature and humidity conditions were optimal for fungal growth. Experimental relocation confirmed that parasite fitness was lower outside this manipulative zone. Host resources were rapidly colonized and further secured by extensive internal structuring. Nutritional composition analysis indicated that such structuring allows the parasite to produce a large fruiting body for spore production. Our findings suggest that the osmotrophic lifestyle of fungi may have facilitated novel exploitation strategies.

The adaptive use of recognition in group decision making.

PubMed

Kämmer, Juliane E; Gaissmaier, Wolfgang; Reimer, Torsten; Schermuly, Carsten C

2014-06-01

Applying the framework of ecological rationality, the authors studied the adaptivity of group decision making. In detail, they investigated whether groups apply decision strategies conditional on their composition in terms of task-relevant features. The authors focused on the recognition heuristic, so the task-relevant features were the validity of the group members' recognition and knowledge, which influenced the potential performance of group strategies. Forty-three three-member groups performed an inference task in which they had to infer which of two German companies had the higher market capitalization. Results based on the choice data support the hypothesis that groups adaptively apply the strategy that leads to the highest theoretically achievable performance. Time constraints had no effect on strategy use but did have an effect on the proportions of different types of arguments. Possible mechanisms underlying the adaptive use of recognition in group decision making are discussed. © 2014 Cognitive Science Society, Inc.

Asynchronous multilevel adaptive methods for solving partial differential equations on multiprocessors - Performance results

NASA Technical Reports Server (NTRS)

Mccormick, S.; Quinlan, D.

1989-01-01

The fast adaptive composite grid method (FAC) is an algorithm that uses various levels of uniform grids (global and local) to provide adaptive resolution and fast solution of PDEs. Like all such methods, it offers parallelism by using possibly many disconnected patches per level, but is hindered by the need to handle these levels sequentially. The finest levels must therefore wait for processing to be essentially completed on all the coarser ones. A recently developed asynchronous version of FAC, called AFAC, completely eliminates this bottleneck to parallelism. This paper describes timing results for AFAC, coupled with a simple load balancing scheme, applied to the solution of elliptic PDEs on an Intel iPSC hypercube. These tests include performance of certain processes necessary in adaptive methods, including moving grids and changing refinement. A companion paper reports on numerical and analytical results for estimating convergence factors of AFAC applied to very large scale examples.

Fuzzy Modal Control Applied to Smart Composite Structure

NASA Astrophysics Data System (ADS)

Koroishi, E. H.; Faria, A. W.; Lara-Molina, F. A.; Steffen, V., Jr.

2015-07-01

This paper proposes an active vibration control technique, which is based on Fuzzy Modal Control, as applied to a piezoelectric actuator bonded to a composite structure forming a so-called smart composite structure. Fuzzy Modal Controllers were found to be well adapted for controlling structures with nonlinear behavior, whose characteristics change considerably with respect to time. The smart composite structure was modelled by using a so called mixed theory. This theory uses a single equivalent layer for the discretization of the mechanical displacement field and a layerwise representation of the electrical field. Temperature effects are neglected. Due to numerical reasons it was necessary to reduce the size of the model of the smart composite structure so that the design of the controllers and the estimator could be performed. The role of the Kalman Estimator in the present contribution is to estimate the modal states of the system, which are used by the Fuzzy Modal controllers. Simulation results illustrate the effectiveness of the proposed vibration control methodology for composite structures.

Adaptive quantum computation in changing environments using projective simulation

NASA Astrophysics Data System (ADS)

Tiersch, M.; Ganahl, E. J.; Briegel, H. J.

2015-08-01

Quantum information processing devices need to be robust and stable against external noise and internal imperfections to ensure correct operation. In a setting of measurement-based quantum computation, we explore how an intelligent agent endowed with a projective simulator can act as controller to adapt measurement directions to an external stray field of unknown magnitude in a fixed direction. We assess the agent’s learning behavior in static and time-varying fields and explore composition strategies in the projective simulator to improve the agent’s performance. We demonstrate the applicability by correcting for stray fields in a measurement-based algorithm for Grover’s search. Thereby, we lay out a path for adaptive controllers based on intelligent agents for quantum information tasks.

Adaptive quantum computation in changing environments using projective simulation

PubMed Central

Tiersch, M.; Ganahl, E. J.; Briegel, H. J.

2015-01-01

Quantum information processing devices need to be robust and stable against external noise and internal imperfections to ensure correct operation. In a setting of measurement-based quantum computation, we explore how an intelligent agent endowed with a projective simulator can act as controller to adapt measurement directions to an external stray field of unknown magnitude in a fixed direction. We assess the agent’s learning behavior in static and time-varying fields and explore composition strategies in the projective simulator to improve the agent’s performance. We demonstrate the applicability by correcting for stray fields in a measurement-based algorithm for Grover’s search. Thereby, we lay out a path for adaptive controllers based on intelligent agents for quantum information tasks. PMID:26260263

Detection of circuit-board components with an adaptive multiclass correlation filter

NASA Astrophysics Data System (ADS)

Diaz-Ramirez, Victor H.; Kober, Vitaly

2008-08-01

A new method for reliable detection of circuit-board components is proposed. The method is based on an adaptive multiclass composite correlation filter. The filter is designed with the help of an iterative algorithm using complex synthetic discriminant functions. The impulse response of the filter contains information needed to localize and classify geometrically distorted circuit-board components belonging to different classes. Computer simulation results obtained with the proposed method are provided and compared with those of known multiclass correlation based techniques in terms of performance criteria for recognition and classification of objects.

Communication system analysis for manned space flight

NASA Technical Reports Server (NTRS)

Schilling, D. L.

1978-01-01

The development of adaptive delta modulators capable of digitizing a video signal is summarized. The delta modulator encoder accepts a 4 MHz black and white composite video signal or a color video signal and encodes it into a stream of binary digits at a rate which can be adjusted from 8 Mb/s to 24 Mb/s. The output bit rate is determined by the user and alters the quality of the video picture. The digital signal is decoded using the adaptive delta modulator decoder to reconstruct the picture.

Vibrational behavior of adaptive aircraft wing structures modelled as composite thin-walled beams

NASA Technical Reports Server (NTRS)

Song, O.; Librescu, L.; Rogers, C. A.

1992-01-01

The vibrational behavior of cantilevered aircraft wings modeled as thin-walled beams and incorporating piezoelectric effects is studied. Based on the converse piezoelectric effect, the system of piezoelectric actuators conveniently located on the wing yield the control of its associated vertical and lateral bending eigenfrequencies. The possibility revealed by this study enabling one to increase adaptively the eigenfrequencies of thin-walled cantilevered beams could play a significant role in the control of the dynamic response and flutter of wing and rotor blade structures.

Metabolic adaptation to weight loss: implications for the athlete

PubMed Central

2014-01-01

Optimized body composition provides a competitive advantage in a variety of sports. Weight reduction is common among athletes aiming to improve their strength-to-mass ratio, locomotive efficiency, or aesthetic appearance. Energy restriction is accompanied by changes in circulating hormones, mitochondrial efficiency, and energy expenditure that serve to minimize the energy deficit, attenuate weight loss, and promote weight regain. The current article reviews the metabolic adaptations observed with weight reduction and provides recommendations for successful weight reduction and long term reduced-weight maintenance in athletes. PMID:24571926

Investigation of Tribological Behavior of a Novel Hybrid Composite Prepared with Al-Coconut Shell Ash Mixed with Graphite

NASA Astrophysics Data System (ADS)

Siva Sankara Raju, R.; Panigrahi, M. K.; Ganguly, R. I.; Srinivasa Rao, G.

2017-08-01

The present investigation develops a next-generation hybrid Al metal matrix composite using coconut shell ash (CSA) and graphite (Gr) reinforcement. Stir-casting is adapted to prepare an Al-1100-based composite. Three other composites of Al-Al2O3, Al-Al2O3-Gr, and Al-CSA are prepared that contain equivalent volume fractions of Al2O3, CSA, and Gr. These assist in comparisons among the three composites and the developed hybrid Al-CSA-Gr composite. The study reveals that the addition of 3 pct Gr improves the specific strength, toughness, and tribological properties. The Al-CSA composite shows better mechanical properties, such as tensile strength and hardness, than the other three composites. Gr addition helps the hybrid Al-CSA-Gr composite to attain better tribological properties with a slightly lower specific strength. Scanning electron microscopy studies of the worn material surfaces corroborate the findings of the abrasion testing. Elemental analyses by energy-dispersive X-ray spectroscopy of the debris from the counter-face of the tribo surface confirm the presence of Al, O, Si, Fe, Mn, and C.

A note on the special fillet fatty acid composition of the dwarf carp (Cyprinus carpio carpio) living in thermal Lake Hévíz, Hungary.

PubMed

Varga, D; Müller, T; Specziár, A; Fébel, H; Hancz, Cs; Bázár, Gy; Urbányi, B; Szabó, A

2013-03-01

Fatty acid (FA) composition of the fillet and the intestinal content of dwarf common carp (Cyprinus carpio carpio) living in Lake Hévíz was determined in wintertime collected samples and results were compared to widespread literature data on carp. Fillet FA profile of the thermally adapted (28 °C) Hévíz dwarf carps differed from profiles originated from divergent culture and feeding conditions in the overall level of saturation. Fillet myristic acid proportions largely exceeded all literature data in spite of poor dietary supply. Fillet fatty acid results indicate the effects of thermal adaptation (high saturation level) and the correlative effects of feed components rich in omega-3 fatty acids, with special respect to docosahexaenoic acid. With the application of discriminant factor analysis the Hévíz sample was accurately differentiated from the literature data on carp fillet fatty acid profile, mostly based on C14:0, C18:1 n9, C18:2 n6, C20:1 n9 and C20:4 n6 FAs. In summary, fillet FA profile suggested thermal adaptation, location specificity and the ingestion of algal and bacterial material.

A counter-reductionist argument for the influence of solute composition on ostracode distribution: Implications for paleoecology

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

Taylor, L.C.; Howard, K.W.F.

The utility of fossil ostracodes for tracking climatically-driven Holocene physicochemical changes of lakes has been a recurrent theme in paleoenvironmental research. Recent studies, aimed at improving the precision of ostracode-mediated environmental reconstructions, have attempted to decipher this robust, ostracode-climate, couplet, and strong correlational evidence concerning the influence of solute composition on ostracode distribution has emerged. By drawing on two examples, namely the response of ostracodes to (1) Holocene hydrocompositional changes in a lake from Russell, Manitoba, and (2) the anthropogenic contamination of groundwater along an urban-rural transect in south-central Ontario, a hypothesis is generated to explain this apparent association. Contrarymore » to the reductionist opinions (i.e. that hydrochemistry operates on ostracode distribution through the direct imposition of physiological barriers), solute composition is viewed as a surrogate variable through which to evaluate cumulative, immeasurable effects of climate, geology, hydrology and the biosphere (including humans). By virtue of their short life-cycles, it is suggested that ostracodes would overcome evolutionary barriers imposed by gradual changes in solute composition if it uniquely controlled their occurrence. Solving this problem would enhance the resolving power of paleoenvironmental reconstructions and, if the proposed argument is valid, it may lend credibility to uniformitarian principles operative in Quaternary paleoecology. The replacement of one group of species by another better adapted to an environment in its totality, seems more likely to hold up in ecological time, than adaptation to a single, specific, overriding hydrochemical parameter.« less

[Genetic improvement of breeding materials in tropical and sub- tropical maize].

PubMed

Sansern, Jampatong; Chaba, Jampatong

2011-12-01

In the present study, 122 maize local cultivars and adapted exotic germplasm from Thailand were used to develop open pollinate varieties (OPVs) using modified ear-to-row scheme, top-cross or test-cross programmes. Ten new maize OPVs with distinct characters were created based on the precise breeding objectives and directional design. The selection of breeding materials was based upon three factors: elite performance, broad adaptability, and genetic diversity. The synthesizing system provided four features: genetic mixing and recombination, equal comparable genetic contribution, mild selection pressure, and maximum intermating for genetic equilibrium (i.e., the female traits were close for the genetic com-positions). Subsequently, Suwan 1 composite and its deritives (Suwan 2, Suwan 3 composite, Suwan 5 and KS24 synthetics), KS6 and KS28 synthetics with the dent type of different origins, and Caripeno DMR composite, KS23, and KS27 synthetics with the dent type of Non-Suwan 1 origin were developed. These OPVs had been improved for 2~13 cycles using S1 recurrent selection method. About 50 inbred lines were developed from these OPVs, and 16 elite single (three-way) crosses were combined and released from these inbred lines. At present, at least one parental inbred line of all the tropical hybrids was derived from Suwan (KS) germplasm in Thailand. Based on the theory of the synthesizing OPVs and developing inbred lines, this paper discussed the genetic moderate diversity, relationship, heterotic group, and patterns for synthesizing OPVs, and inspiration for composed OPVs to heterosis breeding.

Novel Repair Concept for Composite Materials by Repetitive Geometrical Interlock Elements

PubMed Central

Hufenbach, Werner; Adam, Frank; Heber, Thomas; Weckend, Nico; Bach, Friedrich-Wilhelm; Hassel, Thomas; Zaremba, David

2011-01-01

Material adapted repair technologies for fiber-reinforced polymers with thermosetting matrix systems are currently characterized by requiring major efforts for repair preparation and accomplishment in all industrial areas of application. In order to allow for a uniform distribution of material and geometrical parameters over the repair zone, a novel composite interlock repair concept is introduced, which is based on a repair zone with undercuts prepared by water-jet technology. The presented numerical and experimental sensitivity analyses make a contribution to the systematic development of the interlock repair technology with respect to material and geometrical factors of influence. The results show the ability of the novel concept for a reproducible and automatable composite repair. PMID:28824134

Micromechanics of composite laminate compression failure

NASA Technical Reports Server (NTRS)

Guynn, E. Gail; Bradley, Walter L.

1986-01-01

The Dugdale analysis for metals loaded in tension was adapted to model the failure of notched composite laminates loaded in compression. Compression testing details, MTS alignment verification, and equipment needs were resolved. Thus far, only 2 ductile material systems, HST7 and F155, were selected for study. A Wild M8 Zoom Stereomicroscope and necessary attachments for video taping and 35 mm pictures were purchased. Currently, this compression test system is fully operational. A specimen is loaded in compression, and load vs shear-crippling zone size is monitored and recorded. Data from initial compression tests indicate that the Dugdale model does not accurately predict the load vs damage zone size relationship of notched composite specimens loaded in compression.

3D-Printing of Meso-structurally Ordered Carbon Fiber/Polymer Composites with Unprecedented Orthotropic Physical Properties

NASA Astrophysics Data System (ADS)

Lewicki, James P.; Rodriguez, Jennifer N.; Zhu, Cheng; Worsley, Marcus A.; Wu, Amanda S.; Kanarska, Yuliya; Horn, John D.; Duoss, Eric B.; Ortega, Jason M.; Elmer, William; Hensleigh, Ryan; Fellini, Ryan A.; King, Michael J.

2017-03-01

Here we report the first example of a class of additively manufactured carbon fiber reinforced composite (AMCFRC) materials which have been achieved through the use of a latent thermal cured aromatic thermoset resin system, through an adaptation of direct ink writing (DIW) 3D-printing technology. We have developed a means of printing high performance thermoset carbon fiber composites, which allow the fiber component of a resin and carbon fiber fluid to be aligned in three dimensions via controlled micro-extrusion and subsequently cured into complex geometries. Characterization of our composite systems clearly show that we achieved a high order of fiber alignment within the composite microstructure, which in turn allows these materials to outperform equivalently filled randomly oriented carbon fiber and polymer composites. Furthermore, our AM carbon fiber composite systems exhibit highly orthotropic mechanical and electrical responses as a direct result of the alignment of carbon fiber bundles in the microscale which we predict will ultimately lead to the design of truly tailorable carbon fiber/polymer hybrid materials having locally programmable complex electrical, thermal and mechanical response.

Composite synchronization of three eccentric rotors driven by induction motors in a vibrating system

NASA Astrophysics Data System (ADS)

Kong, Xiangxi; Chen, Changzheng; Wen, Bangchun

2018-03-01

This paper addresses the problem of composite synchronization of three eccentric rotors (ERs) driven by induction motors in a vibrating system. The composite synchronous motion of three ERs is composed of the controlled synchronous motion of two ERs and the self-synchronous motion of the third ER. Combining an adaptive sliding mode control (ASMC) algorithm with a modified master-slave control structure, the controllers are designed to implement controlled synchronous motion of two ERs with zero phase difference. Based on Lyapunov stability theorem and Barbalat's lemma, the stability of the designed controllers is verified. On basis of controlled synchronization of two ERs, self-synchronization of the third ER is introduced to implement composite synchronous motion of three ERs. The feasibility of the proposed composite synchronization method is analyzed by numerical method. The effects of motor and structure parameters on composite synchronous motion are discussed. Experiments on a vibrating test bench driven by three ERs are operated to validate the effectiveness of the proposed composite synchronization method, including a comparison with self-synchronization method.