Anti-arrhythmic activities of opioid agonists and antagonists and their stereoisomers.

PubMed Central

Sarne, Y.; Flitstein, A.; Oppenheimer, E.

1991-01-01

1. A series of opioid agonists, antagonists and their (+)-stereoisomers were tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2. Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of cardiac arrhythmias, in accordance with previous published studies. 3. The non-opioid stereoisomer, (+)-naloxone, was equipotent with naloxone against occlusion-induced arrhythmia. 4. Similar non-stereospecific antiarrhythmic effects were induced by another opioid antagonist, Win 44,441-3 and its stereoisomer Win 44,441-2. 5. The opioid agonists, morphine and levorphanol, protected against occlusion-induced arrhythmia as did the opioid antagonists, and the (+)-stereoisomer, dextrorphan, was equipotent to levorphanol. 6. It is concluded that the antiarrhythmic effects of opioid drugs are not mediated by opioid receptors. A direct effect on ionic currents in cardiac muscle is suggested as the mechanism of opioid antiarrhythmic activity. PMID:1364840

Dronedarone: a novel antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Duray, Gabor Z; Ehrlich, Joachim R; Hohnloser, Stefan H

2010-01-01

To describe the electrophysiological profile and the clinical portfolio of dronedarone, a new multichannel-blocking antiarrhythmic drug developed for the treatment of atrial fibrillation. Dronedarone is a derivative of amiodarone that is free of iodine and less lipophilic. The drug has - as its predecessor - multichannel-blocking efficacy and in addition vasodilating effects. It reduces the incidence of ventricular fibrillation in several experimental models. Dronedarone has undergone thorough clinical evaluation in various patient populations. In two large trials, the drug was shown to postpone the recurrence of atrial fibrillation after cardioversion relative to placebo. In a trial in unstable heart failure patients, there was excess mortality in the dronedarone arm. This trial was stopped prematurely and prompted the conduct of a large outcome study. The ATHENA trial demonstrated a significant reduction in cardiovascular hospitalizations and death in atrial fibrillation patients randomly assigned to receive dronedarone or placebo. This large trial in more than 4600 patients revealed no signs of excess mortality or morbidity in patients receiving dronedarone. On the basis of the results of five international, multicenter, randomized clinical trials involving nearly 6300 patients, dronedarone was approved by the FDA for treatment of nonpermanent atrial fibrillation to reduce the risk of cardiovascular hospitalization.

Electropharmacological effects of antiarrhythmic drugs on atrial fibrillation termination. Part I: Molecular and ionic fundamentals of antiarrhythmic drug actions.

PubMed

Calò, Leonardo; Sciarra, Luigi; Lamberti, Filippo; Loricchio, Maria Luisa; Castro, Antonio; Bianconi, Leopoldo; Pandozi, Claudio; Gaita, Fiorenzo; Santini, Massimo

2003-07-01

In the last few years many studies have been performed with the aim of gaining a better understanding of the pathophysiological nature of atrial fibrillation. These recent observations provide new insights into the initiation and perpetuation of atrial fibrillation, underlying the importance of the pulmonary veins as major sources of atrial triggers and introducing new concepts such as the atrial electrical remodeling and the spatial heterogeneity of the electrophysiological characteristics of this arrhythmia. The increasing knowledge about the cardiac ion channel structure and function and about the electrophysiological actions of the antiarrhythmic drugs may contribute to a better comprehension of the mechanisms of the pharmacological termination of the arrhythmia. In part I of the review we try to give a unified vision of the old models and new concepts about the molecular and ionic fundamentals of antiarrhythmic drug actions.

Effect of antiarrhythmic therapy with intravenous loading dose of amiodarone: evidence for an altered response in diabetic patients.

PubMed

Iervasi, G; Clerico, A; Bonini, R; Nannipieri, M; Manfredi, C; Sabatino, L; Biagini, A; Donato, L

1998-01-01

Amiodarone, a potent class III antiarrhythmic agent with adrenergic antagonism properties, is administered increasingly to diabetic patients with cardiac arrhythmias refractory to all other available forms of therapy. Because a large percentage of diabetic patients show a perturbed autonomic regulation of the cardiovascular system, including a pertubed regulation of heart rate, we studied the antiarrhythmic response as well as the early effects (within 5 days) on heart rate of an intravenous amiodarone loading dose in diabetic patients. Seven type II (noninsulin-dependent) diabetic patients (age 64.7 +/- 9.7 years), affected by uncontrolled atrial fibrilation or atrial flutter, were enrolled for the study and a group of 12 well-matched (for age, sex and arrhythmia) nondiabetic patients served as a control group. It was found that before amiodarone administration, nondiabetic patients showed significantly wider variations in the circadian rhythm of heart rate values than diabetic patients (p = 0.0062, unpaired t-test). In all patients but one (who was nondiabetic), amiodarone treatment resulted in a cardioversion to sinus rhythm. After amiodarone administration, nondiabetic patients showed a significantly greater decrease (p = 0.0011) in heart rate values in comparison with the diabetic group (-35% vs. -20% on average, at the end of the study). Furthermore, in nondiabetic patients there was also an earlier significant fall (within the first 4 h after the start of treatment with amiodarone, p < 0.001) in the heart rate values in comparison with diabetic patients, in whom a significant decrease (p < 0.001) was found only at the 4th day. A significant (p = 0.0004), more rapid onset of the antiarrhythmic response to the drug was found in nondiabetic patients (6.8 +/- 6.0 h) in comparison with diabetic patients (98.0 +/- 14.8 h). Our findings suggest that the antiarrhythmic effects of amiodarone in diabetic patients with uncontrolled atrial fibrilation or atrial flutter

Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

PubMed Central

Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

2016-01-01

Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are

Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature.

PubMed

Amjad, Waseem; Qureshi, Waqas; Farooq, Ali; Sohail, Umair; Khatoon, Salma; Pervaiz, Sarah; Narra, Pratyusha; Hasan, Syeda M; Ali, Farman; Ullah, Aman; Guttmann, Steven

2017-09-03

Antiarrhythmic drugs are commonly prescribed cardiac drugs. Due to their receptor mimicry with several of the gastrointestinal tract receptors, they can frequently lead to gastrointestinal side effects. These side effects are the most common reasons for discontinuation of these drugs by the patients. Knowledge of these side effects is important for clinicians that manage antiarrhythmic drugs. This review focuses on the gastrointestinal side effects of these drugs and provides a detailed up-to-date literature review of the side effects of these drugs. The review provides case reports reported in the literature as well as possible mechanisms that lead to gastrointestinal side effects.

Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

PubMed

Naito, M; Michelson, E L; Kmetzo, J J; Kaplinsky, E; Dreifus, L S

1981-01-01

Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p < 0.05). The dogs were then stratified into high- and low-risk subgroups based on the arrhythmic events of the antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.

Antiarrhythmic effect of uridine and uridine-5'-monophosphate in acute myocardial ischemia.

PubMed

Bul'on, V V; Krylova, I B; Selina, E N; Rodionova, O M; Evdokimova, N R; Sapronov, N S; Mironova, G D

2014-10-01

Experiments on rats with acute myocardial ischemia accompanied by early postocclusive arrhythmias have shown normalizing, energy-stabilizing, and antiarrhythmic effects of uridine and uridine-5'-monophosphate. The drugs decreased lactate and restored reserves of glycogen and creatine phosphate depleted by ischemia. Uridine and uridine-5'-monophosphate significantly decreased the severity of ventricular arrhythmias. Both drugs reduced the incidence and duration of fibrillation. Uridine -5'-monophosphate demonstrated most pronounced antifibrillatory effectiveness. We hypothesize that the antiarrhythmic effect of the drugs is determined by their capacity to activate energy metabolism.

Aerobic exercise conditioning: a nonpharmacological antiarrhythmic intervention.

PubMed

Billman, George E

2002-02-01

Sudden, unexpected cardiac death due to ventricular fibrillation is the leading cause of death in most industrially developed countries. Yet, despite the enormity of this problem, the development of safe and effective antiarrhythmic therapies has proven to be an elusive goal. In fact, many initially promising antiarrhythmic medications were subsequently found to increase rather than to decrease cardiac mortality. It is now known that cardiac disease alters cardiac autonomic balance and that the patients with the greatest changes in this cardiac neural regulation (i.e., decreased parasympathetic coupled with increased sympathetic activity) are also the patients at the greatest risk for sudden death. A growing body of experimental and epidemiological data demonstrates that aerobic exercise conditioning can dramatically reduce cardiac mortality, even in patients with preexisting cardiac disease. Conversely, the lack of exercise is strongly associated with an increased incidence of many chronic debilitating diseases, including coronary heart disease. Because it is well established that aerobic exercise conditioning can alter autonomic balance (increasing parasympathetic tone and decreasing sympathetic activity), a prudently designed exercise program could prove to be an effective and nonpharmacological way to enhance cardiac electrical stability, thereby protecting against sudden cardiac death.

Positive inotropic effects of RP 62719, a new pure class III antiarrhythmic agent, on guinea pig myocardium.

PubMed

Beregi, J P; Escande, D; Coudray, N; Mery, P; Mestre, M; Chemla, D; Lecarpentier, Y

1992-12-01

The mechanical effects of RP 62719 [(-)1-[-2-(3,4-dihydro-2H-1- benzopyran-4-yl)ethyl]-4-(3,4-dimethoxyphenyl)-piperidine] were tested in vitro on guinea pig left ventricular papillary muscle. RP 62719 is a novel pure class III antiarrhythmic agent known to prolong the cardiac action potential duration by selectively blocking the inward rectifying K+ current. Mechanical parameters were determined from contraction and relaxation phases under isotonic and isometric conditions. At a concentration of 0.02 microM, RP 62719 did not produce significant effects on inotropy or lusitropy. At 0.2 and 2 microM, the drug improved contraction under both heavy and low loading conditions, as evidenced by a 30% increase in maximum unloaded shortening velocity (Vmax, P < .001), peak amplitude of shortening (delta L, P < .001), peak isometric active force normalized per cross-sectional area (AF/s, P < .001) and positive peak of the force derivative per mm2 (+dF/s, P < .001). At the same concentrations, positive lusitropic effects were evidenced by an increase in maximum lengthening velocity (maxVr) and negative peak of force derivative per mm2 (-dF/s, P < .001). At a higher concentration (20 microM), effects of RP 62719 on inotropy and lusitropy were less marked, thus accounting for the bell-shaped form of the dose-response curve. An increase in the extracellular Ca++ concentration from 2.5 to 3.75 mM improved inotropy to a similar extent (+30-50%) as did 2 microM RP 62719. However, lusitropy and mechanical coupling between contraction and relaxation were not modified in the same proportion under RP 62719 and under 3.75 mM Ca++.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular analysis of the Na+ channel blocking actions of the novel class I anti-arrhythmic agent RSD 921.

PubMed

Pugsley, M K; Goldin, A L

1999-05-01

RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xenopus laevis oocytes were examined using a two-electrode voltage clamp. RSD 921 produced similarly potent tonic block of all three wild-type channel isoforms, with EC50 values between 35 and 47 microM, whereas the EC50 for block of the IFMQ3 mutant channel was 110+5.5 microM. Block of Na+ channels by RSD 921 was concentration and use-dependent, with marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle, wild-type neuronal and IFMQ3 mutant channels. RSD 921 produced a minimal hyperpolarizing shift in the steady-state voltage-dependence of inactivation of all three wild-type channel isoforms. Open channel block of the IFMQ3 mutant channel was best fit with a first order blocking scheme with k(on) equal to 0.11+/-0.012x10(6) M(-1) s(-1) and k(off) equal to 12.5+/-2.5 s(-1), resulting in KD of 117+/-31 microM. Recovery from open channel block occurred with a time constant of 14+/-2.7 s(-1). These results suggest that RSD 921 preferentially interacts with the open state of the Na+ channel, and that the drug may produce potent local anaesthetic or anti-arrhythmic action under conditions of shortened action potentials, such as during anoxia or ischaemia.

Evaluation of Teaching Clinical Pharmacology of Antiarrhythmic Drugs to First-Year MBBS Students Through Worksheet-Based Small-Group Discussion.

PubMed

Hasamnis, Ameya A; Arya, Aditya

2017-01-01

Cardiac arrhythmias are a major cause of morbidity and mortality across the world. Learning the science behind the use of antiarrhythmic drugs is essential for all medical graduates. However, many antiarrhythmic drugs are available, and most of them have complex pharmacodynamic and pharmacokinetic profiles. We tried to improvise our teaching by conducting interactive, worksheet-based, small-group discussion on antiarrhythmic drugs with preclinical students of School of Medicine, Taylor's University, Malaysia. This survey was conducted to analyze the outcomes of worksheet-based, small-group discussion.

Assessing the Risk for Peripheral Neuropathy in Patients Treated With Dronedarone Compared With That in Other Antiarrhythmics.

PubMed

Wu, Chuntao; Tcherny-Lessenot, Stephanie; Dai, Wanju; Wang, Yunxun; Kechemir, Hayet; Gandhi, Sampada; Lin, Stephen; Juhaeri, Juhaeri

2018-03-01

There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone. The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011. Peripheral neuropathy that occurred during the treatment period for a study drug was ascertained using ICD-9-CM diagnostic codes. For each antiarrhythmic, the incidence rate of peripheral neuropathy was calculated. The adjusted hazard ratio (aHR) for peripheral neuropathy for dronedarone compared with another antiarrhythmic was obtained, with control for age, sex, diabetes mellitus status, and the presence of other comorbidities. The study population included 106,933 patients treated with dronedarone (n = 12,989), amiodarone (n = 45,173), sotalol (n = 22,036), flecainide (n = 14,244), or propafenone (n = 12,491). The incidence rates (per 1000 person-years) of peripheral neuropathy were 1.33 for dronedarone, 2.38 for amiodarone, 1.20 for sotalol, 1.08 for flecainide, and 1.97 for propafenone. The aHRs for peripheral neuropathy for dronedarone relative to other drugs ranged from 0.53 (95% CI, 0.21-1.34) compared with propafenone, to 0.94 (95% CI, 0.38-2.30) compared with sotalol. A new-user analysis showed similar results. The risks for peripheral neuropathy were not significantly different between dronedarone and other antiarrhythmics. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Molecular analysis of the Na+ channel blocking actions of the novel class I anti-arrhythmic agent RSD 921

PubMed Central

Pugsley, Michael K; Goldin, Alan L

1999-01-01

RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xenopus laevis oocytes were examined using a two-electrode voltage clamp.RSD 921 produced similarly potent tonic block of all three wild-type channel isoforms, with EC50 values between 35 and 47 μM, whereas the EC50 for block of the IFMQ3 mutant channel was 110±5.5 μM.Block of Na+ channels by RSD 921 was concentration and use-dependent, with marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle, wild-type neuronal and IFMQ3 mutant channels.RSD 921 produced a minimal hyperpolarizing shift in the steady-state voltage-dependence of inactivation of all three wild-type channel isoforms.Open channel block of the IFMQ3 mutant channel was best fit with a first order blocking scheme with kon equal to 0.11±0.012×106 M−1 s−1 and koff equal to 12.5±2.5 s−1, resulting in KD of 117±31 μM. Recovery from open channel block occurred with a time constant of 14±2.7 s−1.These results suggest that RSD 921 preferentially interacts with the open state of the Na+ channel, and that the drug may produce potent local anaesthetic or anti-arrhythmic action under conditions of shortened action potentials, such as during anoxia or ischaemia. PMID:10369450

Cost-benefit and cost-savings analyses of antiarrhythmic medication monitoring.

PubMed

Snider, Melissa; Carnes, Cynthia; Grover, Janel; Davis, Rich; Kalbfleisch, Steven

2012-09-15

The economic impact of pharmacist-managed antiarrhythmic drug therapy monitoring on an academic medical center's electrophysiology (EP) program was investigated. Data were collected for the initial two years of patient visits (n = 816) to a pharmacist-run clinic for antiarrhythmic drug therapy monitoring. A retrospective cost analysis was conducted to assess the direct costs associated with three appointment models: (1) a clinic office visit only, (2) a clinic visit involving electrocardiography and basic laboratory tests, and (3) a clinic visit including pulmonary function testing and chest x-rays in addition to electrocardiography and laboratory testing. A subset of patient cases (n = 18) were included in a crossover analysis comparing pharmacist clinic care and usual care in an EP physician clinic. The primary endpoints were the cost benefits and cost savings associated with pharmacy-clinic care versus usual care. A secondary endpoint was improvement of overall EP program efficiency. The payer mix was 61.6% (n = 498) Medicare, 33.2% (n = 268) managed care, and 5.2% (n = 42) other. Positive contribution margins were demonstrated for all appointment models. The pharmacist-managed clinic also yielded cost savings by reducing overall patient care charges by 21% relative to usual care. By the second year, the pharmacy clinic improved EP program efficiency by scheduling an average of 24 patients per week, in effect freeing up one day per week of EP physician time to spend on other clinical activities. Pharmacist monitoring of antiarrhythmic drug therapy in an out-patient clinic provided cost benefits, cost savings, and improved overall EP program efficiency.

Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial.

PubMed

Morillo, Carlos A; Verma, Atul; Connolly, Stuart J; Kuck, Karl H; Nair, Girish M; Champagne, Jean; Sterns, Laurence D; Beresh, Heather; Healey, Jeffrey S; Natale, Andrea

2014-02-19

Atrial fibrillation (AF) is the most common rhythm disorder seen in clinical practice. Antiarrhythmic drugs are effective for reduction of recurrence in patients with symptomatic paroxysmal AF. Radiofrequency ablation is an accepted therapy in patients for whom antiarrhythmic drugs have failed; however, its role as a first-line therapy needs further investigation. To compare radiofrequency ablation with antiarrhythmic drugs (standard therapy) in treating patients with paroxysmal AF as a first-line therapy. A randomized clinical trial involving 127 treatment-naive patients with paroxysmal AF were randomized at 16 centers in Europe and North America to received either antiarrhythmic therapy or ablation. The first patient was enrolled July 27, 2006; the last patient, January 29, 2010. The last follow-up was February 16, 2012. Sixty-one patients in the antiarrhythmic drug group and 66 in the radiofrequency ablation group were followed up for 24 months. The time to the first documented atrial tachyarrhythmia of more than 30 seconds (symptomatic or asymptomatic AF, atrial flutter, or atrial tachycardia), detected by either scheduled or unscheduled electrocardiogram, Holter, transtelephonic monitor, or rhythm strip, was the primary outcome. Secondary outcomes included symptomatic recurrences of atrial tachyarrhythmias and quality of life measures assessed by the EQ-5D tool. Forty-four patients (72.1%) in the antiarrhythmic group and in 36 patients (54.5%) in the ablation group experienced the primary efficacy outcome (hazard ratio [HR], 0.56 [95% CI, 0.35-0.90]; P = .02). For the secondary outcomes, 59% in the drug group and 47% in the ablation group experienced the first recurrence of symptomatic AF, atrial flutter, atrial tachycardia (HR, 0.56 [95% CI, 0.33-0.95]; P = .03). No deaths or strokes were reported in either group; 4 cases of cardiac tamponade were reported in the ablation group. In the standard treatment group, 26 patients (43%) underwent ablation

Antiarrhythmic and proarrhythmic properties of QT-prolonging antianginal drugs.

PubMed

Singh, Bramah N; Wadhani, Nitin

2004-09-01

In recent years there has been a major reorientation of drug therapy for cardiac arrhythmias, its changing role, and above all, a radical change in the class of arrhythmia drugs because of their impact on mortality. The decline in the use of sodium-channel blockers has led to an ex panding use of beta-blockers and simple or complex class III agents for controlling cardiac arrhythmias. Success with these agents in the context of their side effects has spurred the development of compounds with simpler ion-channel blocking properties that have less complex adverse reactions. The resulting so-called pure class III agents, such as dofetilide or ibutilide, were found to have antifibrillatory effects in atrial fibrillation and flutter and in ventricular tachyarrhythmias. Such agents are effective and have diversity, but they have come into therapeutics with a price: the sometimes-fatal torsades de pointes. The drug amiodarone, a complex compound that was synthesized as an antianginal agent, has been an exception in this regard. Its therapeutic use is associated with a negligibly low incidence of torsades de pointes, even though the drug produces significant bradycardia and QT lengthening to 500 to 700 msec. Recent electrophysiologic studies suggest that this paradox is likely due to the differential block of ion channels in endocardium, epicardium, midmyocardial (M) cells, and Purkinje fibers in the ventricular myocardium. There is also clinical evidence suggesting that amiodarone reduces the "torsadogenic" effects of pure class III agents. Ranolazine was also synthesized for the development of antianginal properties that stem from a partial inhibition of fatty acid oxidation; it too has been found to have electrophysioloigic properties. These are somewhat similar to those of amiodarone on ion channels in endocardium, epicardium, M cells, and Purkinje fibers in the ventricular myocardium, but the drug does not prolong the QT interval to the same extent as amiodarone does

Antiarrhythmic activity of n-tyrosol during acute myocardial ischemia and reperfusion.

PubMed

Chernyshova, G A; Plotnikov, M B; Smol'yakova, V I; Golubeva, I V; Aliev, O I; Tolstikova, T G; Krysin, A P; Sorokina, I V

2007-06-01

Antiarrhythmic activity of n-tyrosol was demonstrated on the model of early occlusion and reperfusion arrhythmia. The preparation reduces the incidence of ventricular tachycardia and fibrillation, increases the percent of animals without ventricular arrhythmia, and moderates the severity of developing ventricular arrhythmias.

The cardioprotective and antiarrhythmic effects of Nardostachys chinensis in animal and cell experiments.

PubMed

Li, Min; Xu, Xue; Yang, Xinyu; Kwong, Joey S W; Shang, Hongcai

2017-08-10

Cardiovascular disease (CVD) is the leading cause of premature death throughout the world. An estimated 17.5 million people died from CVD in 2012, representing 31% of all global deaths. Nardostachys chinensis (NC), a typical traditional Chinese medicine (TCM), plays a crucial role in the management of patients with CVD, especially for those with cardiac arrhythmia. The purpose of this study was to evaluate the cardioprotective and antiarrhythmic effects of NC in animal and cell experiments. To review the cardioprotective and antiarrhythmic effects of NC, studies of NC on cardiovascular diseases in animal and cell experiments were identified from five databases through April 2016. Two investigators independently conducted the literature search, study selection, and data extraction. A total of 16 studies were identified, including five animal experiments and eleven cell experiments. Four studies showed significant effects of NC on myocardial protection by inhibiting myocardial apoptosis, inflammation and oxidative stress. Twelve studies indicated significant beneficial effects of NC in cardiac arrhythmia primarily through the modulation of ion channels (I k , I k1 , I Na , I Ca-L , I to ). The above findings showed the possible efficacy of NC via its cardioprotective and antiarrhythmic effects, but the results should be interpreted with caution due to the limitations and the deficiencies in the studies.

Statins as anti-arrhythmics: a systematic review part II: effects on risk of ventricular arrhythmias.

PubMed

Abuissa, Hussam; O'Keefe, James H; Bybee, Kevin A

2009-10-01

Recent studies have demonstrated that statins may possess anti-arrhythmic properties in addition to their lipid-lowering effects. Studies which reported the association of statins with the incidence of ventricular arrhythmias were identified through a systematic review of the published literature. Statins have been associated with a significant reductions in ventricular arrhythmia in cardiomyopathy patients with an implantable cardioverter defibrillator, although randomized trials have not been completed. Published data suggests that statins may possess anti-arrhythmic properties that reduce the propensity for ventricular arrhythmias. Most of this data is observational; more randomized, placebo-controlled trials are needed.

A New Class III Antiarrhythmic Drug Niferidil Prolongs Action Potentials in Guinea Pig Atrial Myocardium via Inhibition of Rapid Delayed Rectifier.

PubMed

Abramochkin, Denis V; Kuzmin, Vladislav S; Rosenshtraukh, Leonid V

2017-12-01

A new class III antiarrhythmic drug niferidil (RG-2) has been introduced as a highly effective therapy for cases of persistent atrial fibrillation, but ionic mechanisms of its action are poorly understood. In the present study, the effects of niferidil on action potential (AP) waveform and potassium currents responsible for AP repolarization were investigated in guinea pig atrial myocardium. APs were recorded with sharp glass microelectrodes in multicellular atrial preparations. Whole-cell patch-clamp technique was used to measure K + currents in isolated myocytes. In multicellular atrial preparations, 10 -8  M niferidil effectively prolonged APs by 15.2 ± 2.8% at 90% repolarization level. However, even the highest tested concentrations, 10 -6  M and 10 -5  M failed to prolong APs more than 32.5% of control duration. The estimated concentration of niferedil for half-maximal AP prolongation was 1.13 × 10 -8  M. Among the potassium currents responsible for AP repolarization phase, I K1 was found to be almost insensitive to niferidil. However, another inward rectifier, I KACh , was effectively suppressed by micromolar concentrations of niferidil with IC 50  = 9.2 × 10 -6  M. I KATP was much less sensitive to the drug with IC 50  = 2.26 × 10 -4  M. The slow component of delayed rectifier, I Ks , also demonstrated low sensitivity to niferidil-the highest used concentration, 10 -4  M, decreased peak I Ks density to 46.2 ± 5.5% of control. Unlike I Ks , the rapid component of delayed rectifier, I Kr , appeared to be extremely sensitive to niferidil. The IC 50 was 1.26 × 10 -9  M. I Kr measured in ventricular myocytes was found to be less sensitive to niferidil with IC 50  = 3.82 × 10 -8  M. Niferidil prolongs APs in guinea pig atrial myocardium via inhibition of I Kr .

Antiarrhythmic effect of IKr activation in a cellular model of LQT3.

PubMed

Diness, Jonas Goldin; Hansen, Rie Schultz; Nissen, Jakob Dahl; Jespersen, Thomas; Grunnet, Morten

2009-01-01

Long QT syndrome type 3 (LQT3) is an inherited cardiac disorder caused by gain-of-function mutations in the cardiac voltage-gated sodium channel, Na(v)1.5. LQT3 is associated with the polymorphic ventricular tachycardia torsades de pointes (TdP), which can lead to syncope and sudden cardiac death. The sea anemone toxin ATX-II has been shown to inhibit the inactivation of Na(v)1.5, thereby closely mimicking the underlying cause of LQT3 in patients. The hypothesis for this study was that activation of the I(Kr) current could counteract the proarrhythmic effects of ATX-II. Two different activators of I(Kr), NS3623 and mallotoxin (MTX), were used in patch clamp studies of ventricular cardiac myocytes acutely isolated from guinea pig to test the effects of selective I(Kr) activation alone and in the presence of ATX-II. Action potentials were elicited at 1 Hz by current injection and the cells were kept at 32 degrees C to 35 degrees C. NS3623 significantly shortened action potential duration at 90% repolarization (APD(90)) compared with controls in a dose-dependent manner. Furthermore, it reduced triangulation, which is potentially antiarrhythmic. Application of ATX-II (10 nM) was proarrhythmic, causing a profound increase of APD(90) as well as early afterdepolarizations and increased beat-to-beat variability. Two independent I(Kr) activators attenuated the proarrhythmic effects of ATX-II. NS3623 did not affect the late sodium current (I(NaL)) in the presence of ATX-II. Thus, the antiarrhythmic effect of NS3623 is likely to be caused by selective I(Kr) activation. The present data show the antiarrhythmic potential of selective I(Kr) activation in a cellular model of the LQT3 syndrome.

[Observation of antiarrhythmic effects of Cinnamomum migao H. W. Li on experimental arrhythmia].

PubMed

Sui, Y; Qiu, D; Xie, C; Chen, K

1998-08-01

To investigate the effects of Cinnamomum migao on experimental arrhythmia. Arrhythmic models of mice, rabbits, guinea pigs and rats were built using chloroform(Chl), adrenalin(Adr), strophanthin-K (Spt-K) and barium chloride (BaCl2). The affected animals were divided randomly into three groups: control group, Cinnamomum migao (CV-3) group and mexiletine (MXL) group, so as to observe and compare the antiarrhythmic effects. CV-3 could reduce the incidence of ventricular fibrillation caused by ch1 in mice and the ventricular tachycardia induced by Adr in rabbits, delay the onset time of this arrhythmia, increase the arrhythmic doses of Spt-K in guinea pigs, reduce the incidence of some arrhythmia caused by BaCl2 in rats and slow down their heart rate. CV-3 has obvious antiarrhythmic effects on experimental arrhythmia. The mechanism of these effects is probably related to the arrest of the intraflow of Na+, Ca2+ in the cardiac cells and the depression of their cardiac autoarrhythmicity and conductivity.

The antiarrhythmic effect of vagal stimulation after acute coronary occlusion: Role of the heart rate.

PubMed

Manati, Waheed; Pineau, Julien; Doñate Puertas, Rosa; Morel, Elodie; Quadiri, Timour; Bui-Xuan, Bernard; Chevalier, Philippe

2018-01-03

Strong evidence suggests a causal link between autonomic disturbances and ventricular arrhythmias. However, the mechanisms underlying the antiarrhythmic effect of vagal stimulation are poorly understood. The vagal antiarrhythmic effect might be modulated by a decrease in heart rate. the proximal anterior interventricular artery was occluded in 16 pigs by clamping under general anaesthesia. Group 1: heart rates remained spontaneous (n = 6; 12 occlusions); Group 2: heart rates were fixed at 190 beats per minute (bpm) with atrial electrical stimulation (n = 10; 20 occlusions). Each pig received two occlusions, 30 min apart, one without and one with vagal stimulation (10 Hz, 2 ms, 5-20 mA). The antiarrhythmic effect of vagal activation was defined as the time to the appearance of ventricular fibrillation (VF) after occlusion. In Group 1, vagal stimulation triggered a significant decrease in basal heart rate (132 ± 4 vs. 110 ± 17 bpm, p < 0.05), and delayed the time to VF after coronary occlusion (1102 ± 85 vs. 925 ± 41 s, p < 0.05). In Group 2, vagal stimulation did not modify the time to VF (103 ± 39 vs. 91 ± 20 s). Analyses revealed that heart rate and the time to VF were positively linearly related. Maintaining a constant heart rate with atrial electrical stimulation in pigs prevented vagal stimulation from modifying the time to VF after acute coronary occlusion.

Anti-arrhythmic strategies for atrial fibrillation

PubMed Central

Grandi, Eleonora; Maleckar, Mary M.

2016-01-01

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with increased risk of cerebrovascular stroke, and with several other pathologies, including heart failure. Current therapies for AF are targeted at reducing risk of stroke (anticoagulation) and tachycardia-induced cardiomyopathy (rate or rhythm control). Rate control, typically achieved by atrioventricular nodal blocking drugs, is often insufficient to alleviate symptoms. Rhythm control approaches include antiarrhythmic drugs, electrical cardioversion, and ablation strategies. Here, we offer several examples of how computational modeling can provide a quantitative framework for integrating multi scale data to: (a) gain insight into multi-scale mechanisms of AF; (b) identify and test pharmacological and electrical therapy and interventions; and (c) support clinical decisions. We review how modeling approaches have evolved and contributed to the research pipeline and preclinical development and discuss future directions and challenges in the field. PMID:27612549

The novel antiarrhythmic drug dronedarone: comparison with amiodarone.

PubMed

Kathofer, Sven; Thomas, Dierk; Karle, Christoph A

2005-01-01

Dronedarone is a noniodinated benzofuran derivative that has been developed to overcome the limiting iodine-associated adverse effects of the commonly used antiarrhythmic drug, amiodarone. It displays a wide cellular electrophysiological spectrum largely similar to amiodarone, inhibiting the potassium currents I(Kr), I(Ks), I(KI), I(KACh), and I(sus), as well as sodium currents and L-type calcium currents in isolated cardiomyocytes. In addition, dronedarone exhibits antiadrenergic properties. In vivo, dronedarone has been shown to be more effective than amiodarone in several arrhythmia models, particularly in preventing ischemia- and reperfusion-induced ventricular fibrillation and in reducing mortality. However, an increased incidence of torsades de pointes with dronedarone in dogs shows that possible proarrhythmic effects of dronedarone require further evaluation. The clinical trails DAFNE, EURIDIS, and ADONIS indicated safety, antiarrhythmic efficacy and low proarrhythmic potential of the drug in low-risk patients. In contrast, the increased incidence of death in the dronedarone group of the discontinued ANDROMEDA trial raises safety concerns for patients with congestive heart failure and moderate to severe left ventricular dysfunction. Dronedarone appears to be effective in preventing relapses of atrial fibrillation and atrial flutter. Torsades de pointes, the most severe adverse effect associated with amiodarone, has not yet been reported in humans with dronedarone. Unlike amiodarone, dronedarone had little effect on thyroid function and hormone levels in animal models and had no significant effects on human thyroid function in clinical trials. In conclusion, dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients. However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone.

Effects of landiolol, an ultra-short-acting beta1-selective blocker, on electrical storm refractory to class III antiarrhythmic drugs.

PubMed

Miwa, Yosuke; Ikeda, Takanori; Mera, Hisaaki; Miyakoshi, Mutsumi; Hoshida, Kyoko; Yanagisawa, Ryoji; Ishiguro, Haruhisa; Tsukada, Takehiro; Abe, Atsuko; Yusu, Satoru; Yoshino, Hideaki

2010-05-01

Occasionally it is difficult to inhibit electrical storm (ES) with standard pharmacological treatment. In the present study the effect of landiolol, an ultra-short-acting beta(1)-selective blocker, on ES refractory to class III antiarrhythmic drugs was evaluated. The study group comprised 42 consecutive patients who developed ES for which intravenous class III antiarrhythmic drugs, such as amiodarone and nifekalant, were ineffective. Landiolol was administered intravenously with an initial dose of 2.5 microg x kg(-1) x min(-1), which was doubled if it was ineffective, up to a maximum dose of 80 microg x kg(-1) x min(-1). Landiolol inhibited ES in 33 patients (79%) at a mean dose of 7.5+/-12.2 microg x kg(-1) x min(-1). All patients in whom landiolol was ineffective died of arrhythmia. Of the 33 patients in whom landiolol was effective, 25 survived and were discharged (60% of all patients). Landiolol significantly decreased heart rate (P<0.0001), but did not affect blood pressure. Landiolol was not discontinued for adverse effects in any of the responders. Age, APACHE II score, and pH of arterial blood gas differed significantly between the responders and nonresponders. Landiolol is useful as a life-saving drug for class III antiarrhythmic drug-resistant ES. The main mechanism of ES refractory to class III antiarrhythmic drugs could be abnormal automaticity but not reentry.

Statins as antiarrhythmics: a systematic review part I: effects on risk of atrial fibrillation.

PubMed

Abuissa, Hussam; O'Keefe, James H; Bybee, Kevin A

2009-10-01

Recent studies have demonstrated that statins may possess antiarrhythmic properties in addition to their lipid-lowering effects. Studies which reported the association of statins with the incidence of atrial arrhythmias were identified through a systematic review of published literature. One randomized, placebo-controlled trial of 200 patients undergoing cardiac surgery showed that atorvastatin decreased the incidence of postoperative atrial fibrillation by 61%. Observational studies in patients with stable coronary disease, left ventricular dysfunction, or those undergoing cardiac or noncardiac surgery show that statin therapy is associated with an approximately 50% lower rate of atrial fibrillation. Two small randomized trials reported conflicting results: one showing that atorvastatin reduced the recurrence of AF after electrical cardioversion and the other finding that pravastatin did not. Published data suggests that statins may possess antiarrhythmic properties that reduce the propensity for atrial fibrillation. Most of this data is observational; more randomized, placebo-controlled trials are needed.

Arctigenin, a potential anti-arrhythmic agent, inhibits aconitine-induced arrhythmia by regulating multi-ion channels.

PubMed

Zhao, Zhenying; Yin, Yongqiang; Wu, Hong; Jiang, Min; Lou, Jianshi; Bai, Gang; Luo, Guo'an

2013-01-01

Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I(Na)), L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to)) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of arctigenin, leading to its antiarrhythmic effect. © 2013 S. Karger AG, Basel.

Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs

PubMed Central

Tribulova, Narcis; Szeiffova Bacova, Barbara; Egan Benova, Tamara; Knezl, Vladimir; Barancik, Miroslav; Slezak, Jan

2017-01-01

Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions. PMID:29084142

Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs.

PubMed

Tribulova, Narcis; Szeiffova Bacova, Barbara; Egan Benova, Tamara; Knezl, Vladimir; Barancik, Miroslav; Slezak, Jan

2017-10-30

Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions.

[New aspects of the molecular effect of anti-arrhythmia agents].

PubMed

Honerjäger, P

1990-04-01

Excitation propagation is mediated by the brief opening of voltage-dependent Na-channels in the plasma membranes of cells of the conduction system and working myocardium. The refractory period is a function of the re-availability of the Na-channel for renewed opening. Most antiarrhythmic agents block cardiac Na-channels and, consequently, affect the desired refractory period prolongation. At the same time, however, dependent on the concentration and the substance, they slow conduction; an effect which can facilitate reentry excitation in the injured heart. The Na-channel blocking drugs, class I antiarrhythmic agents, are distinguished from the beta-receptor blockers, class II, repolarizing prolonging drugs, class III, and the cardiac Ca-channel blocking drugs (class IV) (Table 1). MOLECULAR STRUCTURE OF THE CARDIAC NA-CHANNEL: Voltage-dependent Na-channels which have been structurally elucidated to date are glycoprotein macromolecules of about 2000 amino acids with a molecular weight of about 260,000. Beginning at the amino terminal, four consecutive homologous domains can be differentiated which are composed of six transmembranous segments each. The terminal portion of the chain as well as the connecting segments between the domains appear intracellular. There are important relationships between the molecular structure and the function of the Na-channel (Figure 1). On comparison of the primary structures of neuronal and cardiac Na-channels, domains I to IV as well as the connecting segment between domains III and IV, are nearly identical. Homology in all of the remaining molecular regions, in contrast, is less than 70%. These segments as well as the differing structure of the four S5-S6 connecting chains may be responsible for the varying functional response of the cardiac Na-channels. MOLECULAR SITE OF ACTION OF ANTIARRHYTHMIC AGENTS AT THE CARDIAC NA-CHANNEL: Since most antiarrhythmic agents are weak bases with pK values between 7.5 and 9.5, in the physiologic

Synergistic Anti-arrhythmic Effects in Human Atria with Combined Use of Sodium Blockers and Acacetin

PubMed Central

Ni, Haibo; Whittaker, Dominic G.; Wang, Wei; Giles, Wayne R.; Narayan, Sanjiv M.; Zhang, Henggui

2017-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Developing effective and safe anti-AF drugs remains an unmet challenge. Simultaneous block of both atrial-specific ultra-rapid delayed rectifier potassium (K+) current (IKur) and the Na+ current (INa) has been hypothesized to be anti-AF, without inducing significant QT prolongation and ventricular side effects. However, the antiarrhythmic advantage of simultaneously blocking these two channels vs. individual block in the setting of AF-induced electrical remodeling remains to be documented. Furthermore, many IKur blockers such as acacetin and AVE0118, partially inhibit other K+ currents in the atria. Whether this multi-K+-block produces greater anti-AF effects compared with selective IKur-block has not been fully understood. The aim of this study was to use computer models to (i) assess the impact of multi-K+-block as exhibited by many IKur blokers, and (ii) evaluate the antiarrhythmic effect of blocking IKur and INa, either alone or in combination, on atrial and ventricular electrical excitation and recovery in the setting of AF-induced electrical-remodeling. Contemporary mathematical models of human atrial and ventricular cells were modified to incorporate dose-dependent actions of acacetin (a multichannel blocker primarily inhibiting IKur while less potently blocking Ito, IKr, and IKs). Rate- and atrial-selective inhibition of INa was also incorporated into the models. These single myocyte models were then incorporated into multicellular two-dimensional (2D) and three-dimensional (3D) anatomical models of the human atria. As expected, application of IKur blocker produced pronounced action potential duration (APD) prolongation in atrial myocytes. Furthermore, combined multiple K+-channel block that mimicked the effects of acacetin exhibited synergistic APD prolongations. Synergistically anti-AF effects following inhibition of INa and combined IKur/K+-channels were also observed. The attainable maximal

Contemporary clinical trials in ventricular tachycardia and fibrillation: implications of ESVEM, CASCADE, and CASH for clinical management.

PubMed

Anderson, J L

1995-10-01

Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Holter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N=486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I( conduction slowing) effects, even when guided by EPS or HM.

[HPLC fingerprint of the antiarrhythmic fraction of Valeriana officinalis].

PubMed

Duan, Xue-Yun; Gong, Zhan-Feng; Chen, Shu-He; Fang, Ying; Liu, Yan-Wen

2009-06-01

To establish HPLC fingerprints of the Antiarrhythmic fraction of Valeriana officinalis. Agilent C18 (250 mm x 4.6 mm, 5 microm) column was used and the acetonitrile-water was chosen as the mobile phase in a gradient mode. The column temperature was 380 degrees C and the detection wavelength was 218 nm. The detection time was 70 min, and the flow rate was 1.0 mL/ min. Fifteen characteristic peaks were indicated in HPLC fingerprints. The relative retention time and the ranges of relative areas of the common peaks were also determined. This method is simple and accurate with a good reproducibility and provides a reference standard for the quality control of Valeriana officinalis.

Mod 1 ICS TI Report: ICS Conversion of a 140% HPGe Detector

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

Bounds, John Alan

This report evaluates the Mod 1 ICS, an electrically cooled 140% HPGe detector. It is a custom version of the ORTEC Integrated Cooling System (ICS) modified to make it more practical for us to use in the field. Performance and operating characteristics of the Mod 1 ICS are documented, noting both pros and cons. The Mod 1 ICS is deemed a success. Recommendations for a Mod 2 ICS, a true field prototype, are provided.

The effects of the new antiarrhythmic E 047/1 on postoperative ischemia-induced arrhythmias in dogs.

PubMed

Kulier, A H; Novalija, E; Hogan, Q; Vicenzi, M N; Woehlck, H J; Bajic, J; Atlee, J L; Bosnjak, Z J

1999-12-01

Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.

Impact of the Food and Drug Administration approval of flecainide and encainide on coronary artery disease mortality: putting "Deadly Medicine" to the test.

PubMed

Anderson, J L; Pratt, C M; Waldo, A L; Karagounis, L A

1997-01-01

In his book Deadly Medicine and on television, Thomas Moore impugns the process of antiarrhythmic drug approval in the 1980s, alleging that the new generation of drugs had flooded the marketplace and had caused deaths in numbers comparable to lives lost during war. To assess these important public health allegations, we evaluated annual coronary artery disease death rates in relation to antiarrhythmic drug sales (2 independent marketing surveys). Predicted mortality rates were modeled using linear regression analysis for 1982 through 1991. Deviations from predicted linearity were sought in relation to rising and falling class IC and overall class I antiarrhythmic drug use. Flecainide came to market in 1986 and encainide in 1987. Combined class IC sales peaked in 1987 and 1988 (maximum market penetration, 20%, first quarter 1989). Results of the Cardiac Arrhythmia Suppression Trial (CAST) were disclosed in April 1989. Overall annual class I antiarrhythmic prescription sales actually fell slightly (-3% to -4%/yr) in the 2 years before CAST and then more abruptly (- 12%) in the year after CAST (1990). Sales of class IC drugs fell dramatically after CAST (by 75%). Coronary death rates (age adjusted) fell in a linear fashion during the decade of 1982 through 1991. No deviation from predicted rates was observed during the introduction, rise, and fall in class IC (and other class I) sales: rates were 126/100,000 in 1985 (before flecainide), 114 and 110 in 1987 and 1988 (maximum sales), and 103 in 1990 (after CAST). Deviations in death rates in the postulated range of 6,000 to 25,000 per year were shown to be excluded easily by the 95% confidence intervals about the predicted rates. Entry of new antiarrhythmic drugs in the 1980s did not lead to overall market expansion and had no adverse impact on coronary artery disease death rates, which fell progressively. Thus, the allegations in Deadly Medicine could not be confirmed.

[Antiarrhythmic and cardioprotective effect of stimulation of delta1-opiate receptors in myocardial ischemia and reperfusion].

PubMed

Lasukova, T V; Krylatov, A V; Maslov, L N; Lishmanov, Iu B; Gross, G J; Podoksenov, Iu K; Podoksenov, A Iu

2004-01-01

Pretreatment with intravenous peptide delta1-opioid receptor (OR) agonist DPDPE (0.5 mg/kg) decreases the incidence of occlusion (10 min) and reperfusion (10 min) arrhythmias in rats. The agonist of delta2-OR DSLET has no effect on arrhythmias in coronary artery occlusion and reperfusion. Pretreatment with selective delta-antagonists ICI 174,864 (2.5 mg/kg) eliminates an antiarrhythmic effect of DPDPE. The addition of DPDPE to the perfusion solution in a final concentration of 0.1 mg/l and/or 0.5 mg/l fifteen min before ischemia also decreases the incidence of reperfusion arrhythmias in a concentration-dependent manner. The addition of DPDPE to the perfusion solution in a final concentration of 0.1 mg/l decreases creatine kinase levels in the coronary sinus effluent. However, DPDPE has no cardioprotective effect in a concentration of 0.5 mg/l or after intravenous administration. It is suggested that antiarrhythmic and cardioprotective effects of DPDPE during reperfusion may be due to stimulation of cardiac delta1-receptors.

Adenosine triphosphate-sensitive potassium channel blocking agent ameliorates, but the opening agent aggravates, ischemia/reperfusion-induced injury. Heart function studies in nonfibrillating isolated hearts.

PubMed

Tosaki, A; Hellegouarch, A

1994-02-01

This study was conducted to elucidate the role of the adenosine triphosphate (ATP)-sensitive potassium channel blocking agent glibenclamide and the opener cromakalim in the mechanism of reperfusion-induced injury. Recently, ATP-sensitive potassium channel openers have been proposed to reduce ischemia/reperfusion-induced injury, including arrhythmias and heart function. Thus, one might hypothesize that pharmacologic agents that enhance the loss of potassium ions in the myocardium through ATP-sensitive potassium channels would be arrhythmogenic, and agents that interfere with tissue potassium ion loss would be antiarrhythmic. Isolated "working" guinea pig hearts and phosphorus-31 nuclear magnetic resonance spectroscopy were used to study the recovery of myocardial function and phosphorus compounds after 30, 40 and 50 min of normothermic global ischemia followed by reperfusion in untreated control and glibenclamide- and cromakalim-treated groups. After 30 min of ischemia, 1, 3, 10 and 30 mumol/liter of glibenclamide dose-dependently reduced the incidence of reperfusion-induced ventricular fibrillation (total) from its control value of 92% to 75%, 33% (p < 0.05), 33% (p < 0.05) and 42% (p < 0.05), respectively. The incidence of ventricular tachycardia followed the same pattern. A reduction of arrhythmias was also observed after 40 and 50 min of ischemia followed by reperfusion in the glibenclamide-treated hearts. Cromakalim, at the same concentrations, did not reduce the incidence of reperfusion-induced arrhythmias. During reperfusion, glibenclamide (3 and 10 mumol/liter) improved the recovery of coronary blood flow, aortic flow, myocardial contractility and tissue ATP and creatine phosphate content, but cromakalim failed to ameliorate the recovery of postischemic myocardium compared with that in the drug-free control hearts. The preservation of myocardial potassium ions and phosphorus compounds by glibenclamide can improve the recovery of postischemic function, but

Poly IC therapy in aleutian disease of mink.

PubMed Central

Russell, A S; Percy, J S; Cho, H J

1975-01-01

Twenty-four virgin female aleutian mink were infected with aleutian disease agent and after 24 hours, 12 of these were treated with a course of polyinosinic acid-polycytidilic acid (Poly IC) injections. After six weeks the gammaglobulin level was significantly lower in the treated group but at 12 weeks this difference was no longer present. Four of the treated mink had normal target organ histology when killed at 20 weeks. The untreated group all showed moderate to marked changes but this difference was not statistically significant. There was a marked increase in the reactive lymphocyte blastogenesis index during the first weeks of infection and the phytohaemagglutinin response was seen to fall progressively. The antiglobulin reaction usually became positive after infection but neither antinuclear nor antierythrocyte antibodies were found. Precipitating antibodies to several polynucleotides were frequently present and were unrelated to infection or to Poly IC treatment. Images Fig. 1. Fig. 2A Fig. 2B. PMID:1095164

Emerging role of amiodarone and dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis.

PubMed

Oryan, A; Bemani, E; Bahrami, S

2018-04-22

Leishmaniasis is a group of human and animal diseases causing 20,000-40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca 2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

R&D100: IC ID

ScienceCinema

Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

2018-06-25

Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

Cost-effectiveness of cardioversion and antiarrhythmic therapy in nonvalvular atrial fibrillation.

PubMed

Catherwood, E; Fitzpatrick, W D; Greenberg, M L; Holzberger, P T; Malenka, D J; Gerling, B R; Birkmeyer, J D

1999-04-20

Physicians managing patients with nonvalvular atrial fibrillation must consider the risks, benefits, and costs of treatments designed to restore and maintain sinus rhythm compared with those of rate control with antithrombotic prophylaxis. To compare the cost-effectiveness of cardioversion, with or without antiarrhythmic agents, with that of rate control plus warfarin or aspirin. A Markov decision-analytic model was designed to simulate long-term health and economic outcomes. Published literature and hospital accounting information. Hypothetical cohort of 70-year-old patients with different baseline risks for stroke. 3 months. Societal. Therapeutic strategies using different combinations of cardioversion alone, cardioversion plus amiodarone or quinidine therapy, and rate control with antithrombotic treatment. Expected costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. Strategies involving cardioversion alone were more effective and less costly than those not involving this option. For patients at high risk for ischemic stroke (5.3% per year), cardioversion alone followed by repeated cardioversion plus amiodarone therapy on relapse was most cost-effective ($9300 per QALY) compared with cardioversion alone followed by warfarin therapy on relapse. This strategy was also preferred for the moderate-risk cohort (3.6% per year), but the benefit was more expensive ($18,900 per QALY). In the lowest-risk cohort (1.6% per year), cardioversion alone followed by aspirin therapy on relapse was optimal. The choice of optimal strategy and incremental cost-effectiveness was substantially influenced by the baseline risk for stroke, rate of stroke in sinus rhythm, efficacy of warfarin, and costs and utilities for long-term warfarin and amiodarone therapy. Cardioversion alone should be the initial management strategy for persistent nonvalvular atrial fibrillation. On relapse of arrhythmia, repeated cardioversion plus low-dose amiodarone is cost

Further evidence for the role of gap junctions in the delayed antiarrhythmic effect of cardiac pacing.

PubMed

Miskolczi, Gottfried; Gönczi, Márton; Kovács, Mária; Seprényi, György; Végh, Ágnes

2015-07-01

The objective of this study was to provide evidence that gap junctions are involved in the delayed antiarrhythmic effect of cardiac pacing. Twenty-four dogs were paced through the right ventricle (4 × 5 min, rate of 240 beats/min) 24 h prior to a 25 min occlusion of the left anterior descending coronary artery. Some of these paced dogs were infused with 50 (n = 7) or 100 μmol/L (n = 7) of the gap junction uncoupler carbenoxolone (CBX), prior to and during the occlusion. Ten sham-paced dogs, subjected only to occlusion, served as the controls. Cardiac pacing markedly reduced the number of ectopic beats and episodes of ventricular tachycardia (VT), as well the incidence of VT and ventricular fibrillation during occlusion. The changes in severity of ischaemia and tissue electrical resistance were also less marked compared with the unpaced controls. Pacing also preserved the permeability of gap junctions, the phosphorylation of connexin43, and the structural integrity of the intercalated discs. The closing of gap junctions with CBX prior to and during ischaemia markedly attenuated or even abolished these protective effects of pacing. Our results support the previous findings that gap junctions play a role in the delayed antiarrhythmic effect of cardiac pacing.

In silico assessment of drug safety in human heart applied to late sodium current blockers

PubMed Central

Trenor, Beatriz; Gomis-Tena, Julio; Cardona, Karen; Romero, Lucia; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R; Saiz, Javier

2013-01-01

Drug-induced action potential (AP) prolongation leading to Torsade de Pointes is a major concern for the development of anti-arrhythmic drugs. Nevertheless the development of improved anti-arrhythmic agents, some of which may block different channels, remains an important opportunity. Partial block of the late sodium current (INaL) has emerged as a novel anti-arrhythmic mechanism. It can be effective in the settings of free radical challenge or hypoxia. In addition, this approach can attenuate pro-arrhythmic effects of blocking the rapid delayed rectifying K+ current (IKr). The main goal of our computational work was to develop an in-silico tool for preclinical anti-arrhythmic drug safety assessment, by illustrating the impact of IKr/INaL ratio of steady-state block of drug candidates on “torsadogenic” biomarkers. The O’Hara et al. AP model for human ventricular myocytes was used. Biomarkers for arrhythmic risk, i.e., AP duration, triangulation, reverse rate-dependence, transmural dispersion of repolarization and electrocardiogram QT intervals, were calculated using single myocyte and one-dimensional strand simulations. Predetermined amounts of block of INaL and IKr were evaluated. “Safety plots” were developed to illustrate the value of the specific biomarker for selected combinations of IC50s for IKr and INaL of potential drugs. The reference biomarkers at baseline changed depending on the “drug” specificity for these two ion channel targets. Ranolazine and GS967 (a novel potent inhibitor of INaL) yielded a biomarker data set that is considered safe by standard regulatory criteria. This novel in-silico approach is useful for evaluating pro-arrhythmic potential of drugs and drug candidates in the human ventricle. PMID:23696033

Using lidocaine and benzocaine to link sodium channel molecular conformations to state-dependent antiarrhythmic drug affinity.

PubMed

Hanck, Dorothy A; Nikitina, Elena; McNulty, Megan M; Fozzard, Harry A; Lipkind, Gregory M; Sheets, Michael F

2009-08-28

Lidocaine and other antiarrhythmic drugs bind in the inner pore of voltage-gated Na channels and affect gating use-dependently. A phenylalanine in domain IV, S6 (Phe1759 in Na(V)1.5), modeled to face the inner pore just below the selectivity filter, is critical in use-dependent drug block. Measurement of gating currents and concentration-dependent availability curves to determine the role of Phe1759 in coupling of drug binding to the gating changes. The measurements showed that replacement of Phe1759 with a nonaromatic residue permits clear separation of action of lidocaine and benzocaine into 2 components that can be related to channel conformations. One component represents the drug acting as a voltage-independent, low-affinity blocker of closed channels (designated as lipophilic block), and the second represents high-affinity, voltage-dependent block of open/inactivated channels linked to stabilization of the S4s in domains III and IV (designated as voltage-sensor inhibition) by Phe1759. A homology model for how lidocaine and benzocaine bind in the closed and open/inactivated channel conformation is proposed. These 2 components, lipophilic block and voltage-sensor inhibition, can explain the differences in estimates between tonic and open-state/inactivated-state affinities, and they identify how differences in affinity for the 2 binding conformations can control use-dependence, the hallmark of successful antiarrhythmic drugs.

The slow cell death response when screening chemotherapeutic agents.

PubMed

Blois, Joseph; Smith, Adam; Josephson, Lee

2011-09-01

To examine the correlation between cell death and a common surrogate of death used in screening assays, we compared cell death responses to those obtained with the sulforhodamine B (SRB) cell protein-based "cytotoxicity" assay. With the SRB assay, the Hill equation was used to obtain an IC50 and final cell mass, or cell mass present at infinite agent concentrations, with eight adherent cell lines and four agents (32 agent/cell combinations). Cells were treated with high agent concentrations (well above the SRB IC50) and the death response determined as the time-dependent decrease in cells failing to bind both annexin V and vital fluorochromes by flow cytometry. Death kinetics were categorized as fast (5/32) (similar to the reference nonadherent Jurkat line), slow (17/32), or none (10/32), despite positive responses in the SRB assay in all cases. With slow cell death, a single exposure to a chemotherapeutic agent caused a slow, progressive increase in dead (necrotic) and dying (apoptotic) cells for at least 72 h. Cell death (defined by annexin and/or fluorochrome binding) did not correlate with the standard SRB "cytotoxicity" assay. With the slow cell death response, a single exposure to an agent caused a slow conversion from vital to apoptotic and necrotic cells over at least 72 h (the longest time point examined). Here, increasing the time of exposure to agent concentrations modestly above the SRB IC50 provides a method of maximizing cell kill. If tumors respond similarly, sustained low doses of chemotherapeutic agents, rather than a log-kill, maximum tolerated dose strategy may be an optimal strategy of maximizing tumor cell death.

Using Lidocaine and Benzocaine to Link Sodium Channel Molecular Conformations to State-Dependent Antiarrhythmic Drug Affinity

PubMed Central

Hanck, Dorothy A.; Nikitina, Elena; McNulty, Megan M.; Fozzard, Harry A.; Lipkind, Gregory M.; Sheets, Michael F.

2009-01-01

Rationale Lidocaine and other antiarrhythmic drugs bind in the inner pore of voltage-gated Na channels and affect gating use-dependently. A phenylalanine in domain IV, S6 (Phe1759 in NaV1.5), modeled to face the inner pore just below the selectivity filter, is critical in use-dependent drug block. Objective Measurement of gating currents and concentration-dependent availability curves to determine the role of Phe1759 in coupling of drug binding to the gating changes. Methods & Results The measurements showed that replacement of Phe1759 with a non-aromatic residue permits clear separation of action of lidocaine and benzocaine into two components that can be related to channel conformations. One component represents the drug acting as a voltage-independent, low-affinity blocker of closed channels (designated as lipophilic block), and the second represents high-affinity, voltage-dependent block of open/inactivated channels linked to stabilization of the S4's in domains III and IV (designated as voltage-sensor inhibition) by Phe1759. A homology model for how lidocaine and benzocaine bind in the closed and open/inactivated channel conformation is proposed. Conclusions These two components, lipophilic block and voltage-sensor inhibition, can explain the differences in estimates between tonic and open-state/inactivated-state affinities, and they identify how differences in affinity for the two binding conformations can control use-dependence, the hallmark of successful antiarrhythmic drugs. PMID:19661462

[Safety of new anti-arrhythmic drugs].

PubMed

Touboul, P

2005-04-01

The majority of new antiarrhythmic drugs are still undergoing clinical trials and are not yet available on the French market. The studies of efficacy are mainly targeted on the treatment of atrial fibrillation. Intravenous ibutilide prolongs the duration of the action potential by stimulating sodium exchange during phase 2 of the action potential. Used for terminating episodes of atrial flutter and fibrillation, ibutilide has been shown to have a low proarrhythmic effect. Dofetilide is a pure I(Kr) current antagonist and is given orally. The molecule prolongs the duration of the atrial and ventricular action potentials. The amplitude of this effect is inversely related to the heart rate. No effect has been observed on the mortality rate in the post-infarct period. Adjusting the dosage with respect to renal function has reduced the occurrence of torsades de pointe from 4.8 to 2.9%. Azimilide is an I(Kr) and I(Ks) current blocker and its efficacy decreases at rapid heart rates. After oral administration, azimilide does not appear to have a deleterious effect in patients with a history of myocardial infarction and left ventricular dysfunction. The risk of torsades de pointe is less than 1%. Cases of neutropaenia have been reported. Dronedarone is an amiodarone analogue without iodine. The molecule prolongs atrial and ventricular action potentials and its efficacy is maintained at high heart rates. This drug had deleterious effects when given to patients with coronary artery disease and left ventricular dysfunction. Gastrointestinal side effects may be observed at high dosage. The great advantages of dronedarone are the absence of thyroid complications and of pro-arrhythmic effects.

Add-on LABA in a separate inhaler as asthma step-up therapy versus increased dose of ICS or ICS/LABA combination inhaler.

PubMed

Price, David B; Colice, Gene; Israel, Elliot; Roche, Nicolas; Postma, Dirkje S; Guilbert, Theresa W; van Aalderen, Willem M C; Grigg, Jonathan; Hillyer, Elizabeth V; Thomas, Victoria; Martin, Richard J

2016-04-01

Asthma management guidelines recommend adding a long-acting β 2 -agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12-80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point in comparisons of cohorts matched for asthma severity and control during the baseline year. After 1:2 cohort matching, the increased extrafine ICS versus separate ICS+LABA cohorts included 3232 and 6464 patients, respectively, and the fine-particle ICS/LABA FDC versus separate ICS+LABA cohorts included 7529 and 15 058 patients, respectively (overall mean age 42 years; 61-62% females). Over one outcome year, adjusted OR (95% CI) for achieving asthma control were 1.25 (1.13-1.38) for increased ICS versus separate ICS+LABA and 1.06 (1.05-1.09) for ICS/LABA FDC versus separate ICS+LABA. For patients with asthma, increased dose of extrafine-particle ICS, or add-on LABA via ICS/LABA combination inhaler, is associated with significantly better outcomes than ICS+LABA via separate inhalers.

N-cinnamoylated aminoquinolines as promising antileishmanial agents.

PubMed

Vale-Costa, S; Costa-Gouveia, J; Pérez, B; Silva, T; Teixeira, C; Gomes, P; Gomes, M S

2013-10-01

A series of cinnamic acid conjugates of primaquine and chloroquine were evaluated for their in vitro antileishmanial activities. Although primaquine derivatives had modest activity, chloroquine conjugates exhibited potent activity against both promastigotes (50% inhibitory concentration [IC50] = 2.6 to 21.8 μM) and intramacrophagic amastigotes (IC50 = 1.2 to 9.3 μM) of Leishmania infantum. Both the high activity of these chloroquine analogues and their mild-to-low toxicity toward host cells make them promising leads for the discovery of new antileishmanial agents.

SPROC: A multiple-processor DSP IC

NASA Technical Reports Server (NTRS)

Davis, R.

1991-01-01

A large, single-chip, multiple-processor, digital signal processing (DSP) integrated circuit (IC) fabricated in HP-Cmos34 is presented. The innovative architecture is best suited for analog and real-time systems characterized by both parallel signal data flows and concurrent logic processing. The IC is supported by a powerful development system that transforms graphical signal flow graphs into production-ready systems in minutes. Automatic compiler partitioning of tasks among four on-chip processors gives the IC the signal processing power of several conventional DSP chips.

SEM probe of IC radiation sensitivity

NASA Technical Reports Server (NTRS)

Gauthier, M. K.; Stanley, A. G.

1979-01-01

Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

Oral amiodarone: historical overview and development.

PubMed

Pollak, P T

1998-01-01

To review the historical development of amiodarone and the changing perceptions of the drug, and discuss its electrophysiologic, pharmacologic, and pharmacokinetic properties. Review of relevant literature. In the 1970s and 1980s a plethora of new antiarrhythmic agents, including amiodarone, was introduced. Amiodarone is predominately a class III antiarrhythmic, but also possesses class I, II, and IV effects. By 1977 it was described as the ideal antiarrhythmic agent. However, clinicians underestimated potential difficulties caused by misunderstanding its variable absorption, slow initial response at nonloading dosages, and extended half-life. Elevated dosages also produced frequent adverse effects. Thus, early enthusiasm for the drug's efficacy was gradually replaced by a focus on its toxicity. The 1990s witnessed reacceptance of the agent as more logical initial regimens and lower maintenance dosages decreased adverse effects, and amiodarone emerged as one of the few drugs effective in suppressing and preventing arrhythmias that does not increase mortality. Remaining challenges include delineation of an optimal oral regimen, identification of markers useful in clinical monitoring, and elucidation of the relationship between dose-tissue concentration and response and dose-toxicity associations. Amiodarone is an increasingly valuable component of today's antiarrhythmic therapy.

Present, future of automotive hybrid IC applications discussed

NASA Astrophysics Data System (ADS)

Matsuda, Nobuyoshi; Fukuoka, Atuhisa

1987-09-01

Hybrid ICs are presently utilized in various fields such as commercial televisions, VTRs, and audio devices, industrial usage of communication equipment, computers, terminals, and automobiles. Its applications and environments are various and diverse. The functions required for hybrid ICs vary from simple high density mounting for a system to the realization of high mechanisms with the application of function timing. The functions are properly used depending upon the system with its hybrid ICs and its circuit composition. Considering structure and reliability requirements for automotive hybrid ICs, an application example for hybrid ICs which use the package (COMPACT), will be discussed.

N-Cinnamoylated Aminoquinolines as Promising Antileishmanial Agents

PubMed Central

Vale-Costa, S.; Costa-Gouveia, J.; Pérez, B.; Silva, T.; Teixeira, C.; Gomes, P.

2013-01-01

A series of cinnamic acid conjugates of primaquine and chloroquine were evaluated for their in vitro antileishmanial activities. Although primaquine derivatives had modest activity, chloroquine conjugates exhibited potent activity against both promastigotes (50% inhibitory concentration [IC50] = 2.6 to 21.8 μM) and intramacrophagic amastigotes (IC50 = 1.2 to 9.3 μM) of Leishmania infantum. Both the high activity of these chloroquine analogues and their mild-to-low toxicity toward host cells make them promising leads for the discovery of new antileishmanial agents. PMID:23917315

The Magnetics Information Consortium (MagIC)

NASA Astrophysics Data System (ADS)

Johnson, C.; Constable, C.; Tauxe, L.; Koppers, A.; Banerjee, S.; Jackson, M.; Solheid, P.

2003-12-01

The Magnetics Information Consortium (MagIC) is a multi-user facility to establish and maintain a state-of-the-art relational database and digital archive for rock and paleomagnetic data. The goal of MagIC is to make such data generally available and to provide an information technology infrastructure for these and other research-oriented databases run by the international community. As its name implies, MagIC will not be restricted to paleomagnetic or rock magnetic data only, although MagIC will focus on these kinds of information during its setup phase. MagIC will be hosted under EarthRef.org at http://earthref.org/MAGIC/ where two "integrated" web portals will be developed, one for paleomagnetism (currently functional as a prototype that can be explored via the http://earthref.org/databases/PMAG/ link) and one for rock magnetism. The MagIC database will store all measurements and their derived properties for studies of paleomagnetic directions (inclination, declination) and their intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). Ultimately, this database will allow researchers to study "on the internet" and to download important data sets that display paleo-secular variations in the intensity of the Earth's magnetic field over geological time, or that display magnetic data in typical Zijderveld, hysteresis/FORC and various magnetization/remanence diagrams. The MagIC database is completely integrated in the EarthRef.org relational database structure and thus benefits significantly from already-existing common database components, such as the EarthRef Reference Database (ERR) and Address Book (ERAB). The ERR allows researchers to find complete sets of literature resources as used in GERM (Geochemical Earth Reference Model), REM (Reference Earth Model) and MagIC. The ERAB contains addresses for all contributors to the EarthRef.org databases, and also for those who participated in data collection, archiving and

New generation QuIC assays for prion seeding activity.

PubMed

Orrù, Christina D; Wilham, Jason M; Vascellari, Sarah; Hughson, Andrew G; Caughey, Byron

2012-01-01

The ability of abnormal TSE-associated forms of PrP to seed the formation of amyloid fibrils from recombinant PrP(Sen) has served as the basis for several relatively rapid and highly sensitive tests for prion diseases. These tests include rPrP-PMCA (rPMCA), standard quaking-induced conversion (S-QuIC), amyloid seeding assay (ASA), real-time QuIC (RT-QuIC) and enhanced QuIC (eQuIC). Here, we summarize recent improvements in the RT-QuIC-based assays that enhance the practicality, sensitivity and quantitative attributes of assays QuIC and promote the detection of prion seeding activity in dilute, inhibitor-laden fluids such as blood plasma.

Dynamical Competition of IC-Industry Clustering from Taiwan to China

NASA Astrophysics Data System (ADS)

Tsai, Bi-Huei; Tsai, Kuo-Hui

2009-08-01

Most studies employ qualitative approach to explore the industrial clusters; however, few research has objectively quantified the evolutions of industry clustering. The purpose of this paper is to quantitatively analyze clustering among IC design, IC manufacturing as well as IC packaging and testing industries by using the foreign direct investment (FDI) data. The Lotka-Volterra system equations are first adopted here to capture the competition or cooperation among such three industries, thus explaining their clustering inclinations. The results indicate that the evolution of FDI into China for IC design industry significantly inspire the subsequent FDI of IC manufacturing as well as IC packaging and testing industries. Since IC design industry lie in the upstream stage of IC production, the middle-stream IC manufacturing and downstream IC packing and testing enterprises tend to cluster together with IC design firms, in order to sustain a steady business. Finally, Taiwan IC industry's FDI amount into China is predicted to cumulatively increase, which supports the industrial clustering tendency for Taiwan IC industry. Particularly, the FDI prediction of Lotka-Volterra model performs superior to that of the conventional Bass model after the forecast accuracy of these two models are compared. The prediction ability is dramatically improved as the industrial mutualism among each IC production stage is taken into account.

High performance MPEG-audio decoder IC

NASA Technical Reports Server (NTRS)

Thorn, M.; Benbassat, G.; Cyr, K.; Li, S.; Gill, M.; Kam, D.; Walker, K.; Look, P.; Eldridge, C.; Ng, P.

1993-01-01

The emerging digital audio and video compression technology brings both an opportunity and a new challenge to IC design. The pervasive application of compression technology to consumer electronics will require high volume, low cost IC's and fast time to market of the prototypes and production units. At the same time, the algorithms used in the compression technology result in complex VLSI IC's. The conflicting challenges of algorithm complexity, low cost, and fast time to market have an impact on device architecture and design methodology. The work presented in this paper is about the design of a dedicated, high precision, Motion Picture Expert Group (MPEG) audio decoder.

Pulmonary Vein Isolation Alone Versus Additional Linear Ablation in Patients With Persistent Atrial Fibrillation Converted to Paroxysmal Type With Antiarrhythmic Drug Therapy: A Multicenter, Prospective, Randomized Study.

PubMed

Yu, Hee Tae; Shim, Jaemin; Park, Junbeom; Kim, In-Soo; Kim, Tae-Hoon; Uhm, Jae-Sun; Joung, Boyoung; Lee, Moon-Hyoung; Kim, Young-Hoon; Pak, Hui-Nam

2017-06-01

Atrial fibrillation (AF) type can vary depending on condition and timing, and some patients who initially present with persistent AF may be changed to paroxysmal AF after antiarrhythmic drug medication and cardioversion. We investigated whether circumferential pulmonary vein isolation (CPVI) alone is an effective rhythm control strategy in patients with persistent AF to paroxysmal AF. We enrolled 113 patients with persistent AF to paroxysmal AF (male 75%, 60.4±10.1 years old) who underwent catheter ablation for nonvalvular AF at 3 tertiary hospitals. The participants were randomly assigned to 2 groups: CPVI alone (n=59) or CPVI plus linear ablation (CPVI+Line; posterior box+anterior line, n=54). Compared with the CPVI+Line, CPVI alone required shorter procedure (187.2±58.0 versus 211.2±63.9 min; P =0.043) and ablation times (4922.1±1110.5 versus 6205.7±1425.2 s; P <0.001) without difference in procedure-related major complication (3% versus 2%; P =0.611). Antiarrhythmic drug utility rates after ablation were not different between the 2 groups (22% versus 30%; P =0.356). Overall, AF-free survival (log-rank; P =0.206) and AF and antiarrhythmic drug-free survival (log-rank; P =0.321) were not different between groups. CPVI alone is an effective rhythm control strategy with a shorter procedure time in persistent AF patients converted to paroxysmal AF compared with CPVI with linear ablation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02176616. © 2017 American Heart Association, Inc.

Mechanisms of pro-arrhythmic abnormalities in ventricular repolarisation and anti-arrhythmic therapies in human hypertrophic cardiomyopathy.

PubMed

Passini, Elisa; Mincholé, Ana; Coppini, Raffaele; Cerbai, Elisabetta; Rodriguez, Blanca; Severi, Stefano; Bueno-Orovio, Alfonso

2016-07-01

Hypertrophic cardiomyopathy (HCM) is a cause of sudden arrhythmic death, but the understanding of its pro-arrhythmic mechanisms and an effective pharmacological treatment are lacking. HCM electrophysiological remodelling includes both increased inward and reduced outward currents, but their role in promoting repolarisation abnormalities remains unknown. The goal of this study is to identify key ionic mechanisms driving repolarisation abnormalities in human HCM, and to evaluate anti-arrhythmic effects of single and multichannel inward current blocks. Experimental ionic current, action potential (AP) and Ca(2+)-transient (CaT) recordings were used to construct populations of human non-diseased and HCM AP models (n=9118), accounting for inter-subject variability. Simulations were conducted for several degrees of selective and combined inward current block. Simulated HCM cardiomyocytes exhibited prolonged AP and CaT, diastolic Ca(2+) overload and decreased CaT amplitude, in agreement with experiments. Repolarisation abnormalities in HCM models were consistently driven by L-type Ca(2+) current (ICaL) re-activation, and ICaL block was the most effective intervention to normalise repolarisation and diastolic Ca(2+), but compromised CaT amplitude. Late Na(+) current (INaL) block partially abolished repolarisation abnormalities, with small impact on CaT. Na(+)/Ca(2+) exchanger (INCX) block effectively restored repolarisation and CaT amplitude, but increased Ca(2+) overload. Multichannel block increased efficacy in normalising repolarisation, AP biomarkers and CaT amplitude compared to selective block. Experimentally-calibrated populations of human AP models identify ICaL re-activation as the key mechanism for repolarisation abnormalities in HCM, and combined INCX, INaL and ICaL block as effective anti-arrhythmic therapies also able to partially reverse the HCM electrophysiological phenotype. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Involvement of IL-1β and IL-6 in antiarrhythmic properties of atorvastatin in ouabain-induced arrhythmia in rats.

PubMed

Najjari, Mahya; Vaezi, Gholamhassan; Hojati, Vida; Mousavi, Zahra; Bakhtiarian, Azam; Nikoui, Vahid

2018-06-01

Evidence show that statins possess wide beneficial cardioprotective and anti-inflammatory effects; therefore, in the present experiment, we investigated the antiarrhythmic properties of atorvastatin in ouabain-induced arrhythmia in isolated rat atria and the role of several inflammatory cytokines in this effect. Male rats were pretreated with either of atorvastatin (10 mg/kg) or vehicle, orally once daily for 6 weeks. After induction of anesthesia, we isolated the atria and after incubation with ouabain, time of onset of arrhythmia and asystole as well as atrial beating rate and contractile force were recorded. We also measured the atrial levels of IL-1β, IL-6, and TNF-α after the injection of ouabain to animals. Pretreatment with atorvastatin significantly delayed the onset of arrhythmia and asystole compared with vehicle-treated group (p < .01, p < .001, respectively). Incubation of ouabain boosted both atrial beating rate and contractile force in vehicle-treated group (p < .05), while these responses in atorvastatin-treated group were not significant (p > .05). Injection of ouabain elevated the atrial levels of IL-1β, IL-6, and TNF-α, while pretreatment of animals with atorvastatin could reverse the ouabain-induced increase in atrial IL-1β and IL-6 (p < .01 and p < .05, respectively). It is concluded that observed antiarrhythmic effects of atorvastatin might be attributed to modulation of some inflammatory cytokines, at least IL-1β and IL-6.

Information Commons for Rice (IC4R)

PubMed Central

2016-01-01

Rice is the most important staple food for a large part of the world's human population and also a key model organism for plant research. Here, we present Information Commons for Rice (IC4R; http://ic4r.org), a rice knowledgebase featuring adoption of an extensible and sustainable architecture that integrates multiple omics data through community-contributed modules. Each module is developed and maintained by different committed groups, deals with data collection, processing and visualization, and delivers data on-demand via web services. In the current version, IC4R incorporates a variety of rice data through multiple committed modules, including genome-wide expression profiles derived entirely from RNA-Seq data, resequencing-based genomic variations obtained from re-sequencing data of thousands of rice varieties, plant homologous genes covering multiple diverse plant species, post-translational modifications, rice-related literatures and gene annotations contributed by the rice research community. Unlike extant related databases, IC4R is designed for scalability and sustainability and thus also features collaborative integration of rice data and low costs for database update and maintenance. Future directions of IC4R include incorporation of other omics data and association of multiple omics data with agronomically important traits, dedicating to build IC4R into a valuable knowledgebase for both basic and translational researches in rice. PMID:26519466

On Patarin's Attack against the lIC Scheme

NASA Astrophysics Data System (ADS)

Ogura, Naoki; Uchiyama, Shigenori

In 2007, Ding et al. proposed an attractive scheme, which is called the l-Invertible Cycles (lIC) scheme. lIC is one of the most efficient multivariate public-key cryptosystems (MPKC); these schemes would be suitable for using under limited computational resources. In 2008, an efficient attack against lIC using Gröbner basis algorithms was proposed by Fouque et al. However, they only estimated the complexity of their attack based on their experimental results. On the other hand, Patarin had proposed an efficient attack against some multivariate public-key cryptosystems. We call this attack Patarin's attack. The complexity of Patarin's attack can be estimated by finding relations corresponding to each scheme. In this paper, we propose an another practical attack against the lIC encryption/signature scheme. We estimate the complexity of our attack (not experimentally) by adapting Patarin's attack. The attack can be also applied to the lIC- scheme. Moreover, we show some experimental results of a practical attack against the lIC/lIC- schemes. This is the first implementation of both our proposed attack and an attack based on Gröbner basis algorithm for the even case, that is, a parameter l is even.

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants

PubMed Central

Tikhonov, Denis B.

2017-01-01

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. PMID:28258204

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.

PubMed

Tikhonov, Denis B; Zhorov, Boris S

2017-04-03

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. © 2017 Tikhonov and Zhorov.

TDR method for determine IC's parameters

NASA Astrophysics Data System (ADS)

Timoshenkov, V.; Rodionov, D.; Khlybov, A.

2016-12-01

Frequency domain simulation is a widely used approach for determine integrated circuits parameters. This approach can be found in most of software tools used in IC industry. Time domain simulation approach shows intensive usage last years due to some advantages. In particular it applicable for analysis of nonlinear and nonstationary systems where frequency domain is inapplicable. Resolution of time domain systems allow see heterogeneities on distance 1mm, determine it parameters and properties. Authors used approach based on detecting reflected signals from heterogeneities - time domain reflectometry (TDR). Field effect transistor technology scaling up to 30-60nm gate length and 10nm gate dielectric, heterojunction bi-polar transistors with 10-30nm base width allows fabricate digital IC's with 20GHz clock frequency and RF-IC's with tens GHz bandwidth. Such devices and operation speed suppose transit signal by use microwave lines. There are local heterogeneities can be found inside of the signal path due to connections between different parts of signal lines (stripe line-RF-connector pin, stripe line - IC package pin). These heterogeneities distort signals that cause bandwidth decrease for RF-devices. Time domain research methods of transmission and reflected signals give the opportunities to determine heterogeneities, it properties, parameters and built up equivalent circuits. Experimental results are provided and show possibility for inductance and capacitance measurement up to 25GHz. Measurements contains result of signal path research on IC and printed circuit board (PCB) used for 12GHz RF chips. Also dielectric constant versus frequency was measured up to 35GHz.

Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

PubMed Central

Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

2016-01-01

Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

The open cluster IC 4665

NASA Technical Reports Server (NTRS)

Prosser, Charles F.

1993-01-01

The results of a combined astrometric, photometric, and spectroscopic program to identify members of the open cluster IC 4665 are presented. Numerous new proper motion/photometric candidate members and at least 23 M dwarfs with H-alpha emission have been identified. A reanalysis of IC 4665 age using different methods yields conflicting results ranging from about 3 X 10 exp 7 yr to the age of the Pleiades. This study provides a list of candidate cluster members in the intermediate and low-mass regime of this cluster. Future spectroscopic observations of these candidates should eventually identify true cluster members.

Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents.

PubMed

Biftu, Tesfaye; Feng, Dennis; Fisher, Michael; Liang, Gui-Bai; Qian, Xiaoxia; Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Liberator, Paul A; Brown, Chris; Gurnett, Anne; Leavitt, Penny S; Thompson, Donald; Mathew, John; Misura, Andrew; Samaras, Samantha; Tamas, Tamas; Sina, Joseph F; McNulty, Kathleen A; McKnight, Crystal G; Schmatz, Dennis M; Wyvratt, Matthew

2006-05-01

Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies.

Semiconductor/High-Tc-Superconductor Hybrid ICs

NASA Technical Reports Server (NTRS)

Burns, Michael J.

1995-01-01

Hybrid integrated circuits (ICs) containing both Si-based semiconducting and YBa(2)Cu(3)O(7-x) superconducting circuit elements on sapphire substrates developed. Help to prevent diffusion of Cu from superconductors into semiconductors. These hybrid ICs combine superconducting and semiconducting features unavailable in superconducting or semiconducting circuitry alone. For example, complementary metal oxide/semiconductor (CMOS) readout and memory devices integrated with fast-switching Josephson-junction super-conducting logic devices and zero-resistance interconnections.

A Way to End the IC Designer Shortage.

ERIC Educational Resources Information Center

Robinson, Arthur L.

1980-01-01

Discusses the problem of the shortage of engineers capable of designing advanced integrated circuits (IC) and presents some suggestions for increasing the number of IC designers in universities and semiconductor companies. (HM)

Cardiovascular drugs inducing QT prolongation: facts and evidence.

PubMed

Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

2010-01-01

Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

Novel modified steroid derivatives of androstanolone as chemotherapeutic anti-cancer agents.

PubMed

El-Far, Mohamed; Elmegeed, Gamal A; Eskander, Emad F; Rady, Hanaa M; Tantawy, Mohamed A

2009-10-01

The aim of the present study is to synthesize and evaluate new potential chemotherapeutic anti-tumor agents. Several thiazolo-, pyrido-, pyrano- and lactam steroid derivatives were obtained using 17beta-hydroxy-5alpha-androstan-3-one (androstanolone) 1 as starting steroid. The structure of the novel steroid derivatives was confirmed using the analytical and spectral data. The most pure and structurally promising compounds 7a, 10a, 12b, 18 and 23 were evaluated as anti-tumor agents. The in vitro cytotoxic activity was evaluated against hepatoma cell lines using MTT assay. Also the in vivo anti-tumor activity was evaluated against Ehrlich ascites carcinoma (EAC). The results of the in vitro study showed that at incubation time 72h, in olive oil, compound 7a was the most effective cytotoxic compound with IC(50) of 30 microM, while the effects of compounds 18 and 23 were approximately similar with IC(50) of 37 microM and 35 microM respectively. While the tested compounds when dissolved in DMSO showed approximately the same IC(50) at both 48 and 72h incubation period, compound 23 was the most effective cytotoxic with IC(50) 42 microM at 48h and 40 microM at 72h. The results of the in vivo study showed that all the tested novel compounds at 25mg/kg were effective against EAC. Our novel steroid derivatives are promising candidates as anti-cancer agents, none of the mice treated with our novel derivatives showed any toxic symptoms, but they also completely inhibited tumor growth and retained the hemoglobin content, body weight, and WBCs near normal values and similar to what obtained for the standard drug 5-flurouracil.

Differential effectiveness of Serratia plymuthica IC1270-induced systemic resistance against hemibiotrophic and necrotrophic leaf pathogens in rice

PubMed Central

De Vleesschauwer, David; Chernin, Leonid; Höfte, Monica M

2009-01-01

Background Induced resistance is a state of enhanced defensive capacity developed by a plant reacting to specific biotic or chemical stimuli. Over the years, several forms of induced resistance have been characterized, including systemic acquired resistance, which is induced upon localized infection by an avirulent necrotizing pathogen, and induced systemic resistance (ISR), which is elicited by selected strains of nonpathogenic rhizobacteria. However, contrary to the relative wealth of information on inducible defense responses in dicotyledoneous plants, our understanding of the molecular mechanisms underlying induced resistance phenomena in cereal crops is still in its infancy. Using a combined cytomolecular and pharmacological approach, we analyzed the host defense mechanisms associated with the establishment of ISR in rice by the rhizobacterium Serratia plymuthica IC1270. Results In a standardized soil-based assay, root treatment with IC1270 rendered foliar tissues more resistant to the hemibiotrophic pathogen Magnaporthe oryzae, causal agent of the devastating rice blast disease. Analysis of the cytological and biochemical alterations associated with restriction of fungal growth in IC1270-induced plants revealed that IC1270 primes rice for enhanced attacker-induced accumulation of reactive oxygen species (ROS) and autofluorescent phenolic compounds in and near epidermal cells displaying dense cytoplasmic granulation. Similar, yet more abundant, phenotypes of hypersensitively dying cells in the vicinity of fungal hyphae were evident in a gene-for-gene interaction with an avirulent M. oryzae strain, suggesting that IC1270-inducible ISR and R protein conditioned effector-triggered immunity (ETI) target similar defense mechanisms. Yet, this IC1270-inducible ISR response seems to act as a double-edged sword within the rice defense network as induced plants displayed an increased vulnerability to the necrotrophic pathogens Rhizoctonia solani and Cochliobolus

Differential effectiveness of Serratia plymuthica IC1270-induced systemic resistance against hemibiotrophic and necrotrophic leaf pathogens in rice.

PubMed

De Vleesschauwer, David; Chernin, Leonid; Höfte, Monica M

2009-01-22

Induced resistance is a state of enhanced defensive capacity developed by a plant reacting to specific biotic or chemical stimuli. Over the years, several forms of induced resistance have been characterized, including systemic acquired resistance, which is induced upon localized infection by an avirulent necrotizing pathogen, and induced systemic resistance (ISR), which is elicited by selected strains of nonpathogenic rhizobacteria. However, contrary to the relative wealth of information on inducible defense responses in dicotyledoneous plants, our understanding of the molecular mechanisms underlying induced resistance phenomena in cereal crops is still in its infancy. Using a combined cytomolecular and pharmacological approach, we analyzed the host defense mechanisms associated with the establishment of ISR in rice by the rhizobacterium Serratia plymuthica IC1270. In a standardized soil-based assay, root treatment with IC1270 rendered foliar tissues more resistant to the hemibiotrophic pathogen Magnaporthe oryzae, causal agent of the devastating rice blast disease. Analysis of the cytological and biochemical alterations associated with restriction of fungal growth in IC1270-induced plants revealed that IC1270 primes rice for enhanced attacker-induced accumulation of reactive oxygen species (ROS) and autofluorescent phenolic compounds in and near epidermal cells displaying dense cytoplasmic granulation. Similar, yet more abundant, phenotypes of hypersensitively dying cells in the vicinity of fungal hyphae were evident in a gene-for-gene interaction with an avirulent M. oryzae strain, suggesting that IC1270-inducible ISR and R protein conditioned effector-triggered immunity (ETI) target similar defense mechanisms. Yet, this IC1270-inducible ISR response seems to act as a double-edged sword within the rice defense network as induced plants displayed an increased vulnerability to the necrotrophic pathogens Rhizoctonia solani and Cochliobolus miyabeanus. Artificial

Embedded I&C for Extreme Environments

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

Kisner, Roger A.

2016-04-01

This project uses embedded instrumentation and control (I&C) technologies to demonstrate potential performance gains of nuclear power plant components in extreme environments. Extreme environments include high temperature, radiation, high pressure, high vibration, and high EMI conditions. For extreme environments, performance gains arise from moment-to-moment sensing of local variables and immediate application of local feedback control. Planning for embedding I&C during early system design phases contrasts with the traditional, serial design approach that incorporates minimal I&C after mechanical and electrical design is complete. The demonstration application involves the development and control of a novel, proof-of-concept motor/pump design. The motor and pumpmore » combination operate within the fluid environment, eliminating the need for rotating seals. Actively controlled magnetic bearings also replace failure-prone mechanical contact bearings that typically suspend rotating components. Such as design has the potential to significantly enhance the reliability and life of the pumping system and would not be possible without embedded I&C.« less

Molecular Hydrogen Fluorescence in IC 63

NASA Technical Reports Server (NTRS)

Andersson, B-G

2005-01-01

This grant has supported the acquisition, reduction and analysis of data targeting the structure and excitation of molecular hydrogen in the reflection nebula IC 63 and in particular the fluorescent emission seen in the UV. In addition to manpower for analyzing the FUSE data, the grant supported the (attempted) acquisition of supporting ground-based data. We proposed for and received observing time for two sets of ground based, data; narrow band imaging ([S II], [O III) at KPNO (July 2002; Observer: Burgh) and imaging spectro-photometry of several of the near-infrared rotation-vibration lines of H2 at the IRTF (October 2003; Observer: Andersson). Unfortunately, both of these runs were failures, primarily because of bad weather, and did not result in any useful data. We combined the FUSE observations with rocket borne observations of the star responsible for exciting the H2 fluorescence in IC 63: gamma Cas, and with archival HUT observations of IC 63, covering the long-wavelength part of the molecular hydrogen fluorescence.

Therapeutic potential of chalcones as cardiovascular agents.

PubMed

Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar

2016-03-01

Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents. Copyright © 2016 Elsevier Inc. All rights reserved.

H I debris in the IC 1459 galaxy group

NASA Astrophysics Data System (ADS)

Saponara, Juliana; Koribalski, Bärbel S.; Benaglia, Paula; Fernández López, Manuel

2018-01-01

We present H I synthesis imaging of the giant elliptical galaxy IC 1459 and its surroundings with the Australia Telescope Compact Array. Our search for extended H I emission revealed a large complex of H I clouds near IC 1459, likely to be the debris from tidal interactions with neighbouring galaxies. The total H I mass (∼109 M⊙) in the detected clouds spans 250 kpc from the north-east of the gas-rich spiral NGC 7418A to the south-east of IC 1459. The extent and mass of the H I debris, which shows rather irregular morphology and kinematics, are similar to those in other nearby groups. Together with H I clouds recently detected near two other IC 1459 group members, namely IC 5270 and NGC 7418, using phased-array feeds on the Australian Square Kilometre Array Pathfinder, the detected debris make up a significant fraction of the group's intergalactic medium.

Saturn V S-IC (First) Stage

NASA Technical Reports Server (NTRS)

2004-01-01

This cutaway illustration shows the Saturn V S-IC (first) stage with detailed callouts of the components. The S-IC Stage is 138 feet long and 33 feet in diameter, producing 7,500,000 pounds of thrust through five F-1 engines that are powered by liquid oxygen and kerosene. Four of the engines are mounted on an outer ring and gimbal for control purposes. The fifth engine is rigidly mounted in the center. When ignited, the roar produced by the five engines equals the sound of 8,000,000 hi-fi sets.

Interband cascade (IC) photovoltaic (PV) architecture for PV devices

DOEpatents

Yang, Rui Q.; Tian, Zhaobing; Mishima, Tetsuya D.; Santos, Michael B.; Johnson, Matthew B.; Klem, John F.

2015-10-20

A photovoltaic (PV) device, comprising a PV interband cascade (IC) stage, wherein the IC PV stage comprises an absorption region with a band gap, the absorption region configured to absorb photons, an intraband transport region configured to act as a hole barrier, and an interband tunneling region configured to act as an electron barrier. An IC PV architecture for a photovoltaic device, the IC PV architecture comprising an absorption region, an intraband transport region coupled to the absorption region, and an interband tunneling region coupled to the intraband transport region and to the adjacent absorption region, wherein the absorption region, the intraband transport region, and the interband tunneling region are positioned such that electrons will flow from the absorption region to the intraband transport region to the interband tunneling region.

EXTRACTION AND DETECTION OF A NEW ARSINE SULFIDE CONTAINING ARSENOSUGAR IN MOLLUSCS BY IC-ICP-MS AND IC-ESI-MS/MS

EPA Science Inventory

Using IC-ICP-MS and IC-ESI-MS/MS, an unknown arsenical compound in mollusks has been identified as a new arsine sulfide containing analog of a known arsenosugar and is referred to as As(498). This species has been observed in four separate shellfish species following a mild metha...

Sedaxicenes: potential new antifungal ferrocene-based agents?

PubMed

Rubbiani, R; Blacque, O; Gasser, G

2016-04-21

Fungal infections are a group of diseases spread all over the world with an extremely high morbidity. Worryingly, although several pathogenic fungi were found to develop resistance towards traditional therapy, research towards the discovery of novel antimycotic agents is very limited. Considering the promising results obtained with the ferrocene-based drug candidates Ferroquine and Ferrocifen as antimalarial and anticancer drug candidates, respectively, we envisaged derivatizing the organic scaffold of a new broad-spectrum fungicide, namely sedaxane, with a ferrocenyl moiety in order to obtain new metal-based antifungal agents. The new ferrocenyl sedaxane derivatives called herein Sedaxicenes (, and ) were characterized using different analytical techniques and the structures were confirmed by X-ray crystallography. As expected for antimycotic agents, , and were found to have a low or even no toxicity towards human cells (IC50 > 100 μM). Interestingly, while the parent drug did not display any mycotoxicity (EC50 > 100 μM), complex was found to have some antifungal activity with an IC50 value of 43 μM under the same experimental conditions. In order to investigate the possible redox-mediated mode of action of , we synthesized the ruthenocene analogue of , namely . Ruthenocene is known to have a completely different electrochemical behaviour from ferrocene although both the compounds are isostructural. As anticipated, complex was found to induce an increase of the reactive oxygen species level in S. cerevisiae, contrary to its analogue and to the parent compound sedaxane.

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Smoking (I-C mines). 57.22102 Section 57.22102... Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a) Persons shall not smoke or carry smoking materials, matches, or lighters underground or within 50 feet of...

Oxabicyclooctane-Linked Novel Bacterial Topoisomerase Inhibitors as Broad Spectrum Antibacterial Agents

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

Singh, Sheo B.; Kaelin, David E.; Wu, Jin

Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating the discovery of new agents. Bacterial type II topoisomerase is a clinically validated, highly effective, and proven drug target. This target is amenable to inhibition by diverse classes of inhibitors with alternative and distinct binding sites to quinolone antibiotics, thus enabling the development of agents that lack cross-resistance to quinolones. Described here are novel bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and topo IV inhibitors and consist of three distinct structural moieties. The substitution of the linker moiety led to discovery of potent broad-spectrum NBTIsmore » with reduced off-target activity (hERG IC50 > 18 μM) and improved physical properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and Staphylococcus aureus gyrase (IC50 = 1.02 μM) and topo IV (IC50 = 10.4 μM). AM8191 showed parenteral and oral efficacy (ED50) at less than 2.5 mg/kg doses in a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S. aureus DNA-gyrase showed binding interactions similar to that reported for GSK299423, displaying a key contact of Asp83 with the basic amine at position-7 of the linker.« less

A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents

NASA Astrophysics Data System (ADS)

Chen, Wen-Shiang; Matula, Thomas J.; Brayman, Andrew A.; Crum, Lawrence A.

2003-01-01

Contrast bubble destruction is important in several new diagnostic and therapeutic applications. The pressure threshold of destruction is determined by the shell material, while the propensity for of the bubbles to undergo inertial cavitation (IC) depends both on the gas and shell properties of the ultrasound contrast agent (UCA). The ultrasonic fragmentation thresholds of three specific UCAs (Optison, Sonazoid, and biSpheres), each with different shell and gas properties, were determined under various acoustic conditions. The acoustic emissions generated by the agents, or their derivatives, characteristic of IC after fragmentation, was also compared, using cumulated broadband-noise emissions (IC ``dose''). Albumin-shelled Optison and surfactant-shelled Sonazoid had low fragmentation thresholds (mean=0.13 and 0.15 MPa at 1.1 MHz, 0.48 and 0.58 MPa at 3.5 MHz, respectively), while polymer-shelled biSpheres had a significant higher threshold (mean=0.19 and 0.23 MPa at 1.1 MHz, 0.73 and 0.96 MPa for thin- and thick-shell biSpheres at 3.5 MHz, respectively, p<0.01). At comparable initial concentrations, surfactant-shelled Sonazoid produced a much larger IC dose after shell destruction than did either biSpheres or Optison (p<0.01). Thick-shelled biSpheres had the highest fragmentation threshold and produced the lowest IC dose. More than two and five acoustic cycles, respectively, were necessary for the thin- and thick-shell biSpheres to reach a steady-state fragmentation threshold.

Does patent foramen ovale closure have an anti-arrhythmic effect? A meta-analysis.

PubMed

Jarral, Omar A; Saso, Srdjan; Vecht, Joshua A; Harling, Leanne; Rao, Christopher; Ahmed, Kamran; Gatzoulis, Michael A; Malik, Iqbal S; Athanasiou, Thanos

2011-11-17

Atrial tachyarrhythmias are associated with patent foramen ovale. The objective was to determine the anti-arrhythmic effect of patent foramen ovale closure on pre-existing atrial tachyarrhythmias. Medline, EMBASE, Cochrane Library, and Google Scholar databases were searched between 1967 and 2010. The search was expanded using the 'related articles' function and reference lists of key studies. All studies reporting pre- and post-closure incidence (or prevalence) of atrial tachyarrhythmia in the same patient population were included. Random and fixed effect meta-analyses were used to aggregate the data. Six studies were identified including 2570 patients who underwent percutaneous closure. Atrial fibrillation was in fact the only AT reported in all studies. Meta-analysis using a fixed effects model demonstrated a significant reduction in the prevalence of atrial fibrillation with an OR of 0.43 (95% CI 0.26-0.71). When using the random-effects model, OR was 0.44 (95% CI 0.18-1.04) with a statistically significant trend demonstrated (test for overall effect: Z=1.87, p=0.06). Closure of a patent foramen ovale may be associated with reduction in the prevalence of atrial fibrillation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A radial velocity survey of the open cluster IC 4665

NASA Technical Reports Server (NTRS)

Prosser, Charles F.; Giampapa, Mark S.

1994-01-01

A radial velocity survey of the open cluster IC 4665 is reported for a group of candidate members previously identified on the basis of proper motion and photometry. Of those candidates observed, 20 out of 42 have radial velocities consistent with membership; these cluster members populate the F5-K0 dwarf region and represent the first relatively conclusive membership determinations for such solar-type stars in IC 4665. Three new spectroscopic binary members of the cluster have been identified. Rotational velocities have also been derived; the v sin i distribution among IC 4665 members reveals that most apparent G dwarf members of IC 4665 are seen to exhibit substantial rotation (v sin i greater than 10 km/s). When compared to evolutionary isochrones, the current list of intermediate-mass members appears to support earlier suggestions that IC 4665 has an age comparable to the Pleiades.

Mitochondrial basis of the anti-arrhythmic action of lidocaine and modulation by the n-6 to n-3 PUFA ratio of cardiac phospholipids.

PubMed

Demaison, Luc; Moreau, Daniel; Clauw, Fabienne; Vergely, Catherine; Rochette, Luc

2013-08-01

The aim of this study was to evaluate the involvement of mitochondria in the mechanism of the anti-arrhythmic lidocaine. Rats were fed with a diet containing either n-6 polyunsaturated fatty acids (PUFAs, SSO group) or an equimolecular mixture of n-3 and n-6 PUFAs (FO group) for 8 weeks. The hearts were perfused according to the working mode using a medium with or without lidocaine 5 μm. They were then subjected to local ischemia (20 min) and reperfusion (30 min). Dietary n-3 PUFAs triggered the expected decrease in the n-6/n-3 PUFA ratio of cardiac phospholipids. Reperfusing the ischemic area favored the incidence of severe arrhythmias. Lidocaine treatment abolished almost completely reperfusion arrhythmias in the FO group, but did not display anti-arrhythmic properties in the SSO group. As it was indicated by measurements of the mitochondrial function, lidocaine seemed to favor mitochondrial calcium retention in the FO group, which might prevent cytosolic calcium spikes and reperfusion arrhythmias. In the SSO group, the resistance to lidocaine was associated with an aggravation of cellular damages. The mitochondrial calcium retention capacities were saturated, and lidocaine was unable to increase them, making the drug inefficient in preventing reperfusion arrhythmias. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.

Design, Synthesis, and Evaluation of Novel Ferroquine and Phenylequine Analogues as Potential Antiplasmodial Agents.

PubMed

Jacobs, Leon; de Kock, Carmen; de Villiers, Katherine A; Smith, Peter J; Smith, Vincent J; van Otterlo, Willem A L; Blackie, Margaret A L

2015-12-01

7-Chloroquinoline-based antimalarial drugs are effective in the inhibition of hemozoin formation in the food vacuole of the Plasmodium parasite, the causative agent of malaria. We synthesized five series of ferroquine (FQ) and phenylequine (PQ) derivatives, which display good in vitro efficacy toward both the chloroquine-sensitive (CQS) NF54 (IC50 : 4.2 nm) and chloroquine-resistant (CQR) Dd2 (IC50 : 33.7 nm) strains of P. falciparum. Several compounds were found to have good inhibitory activity against β-hematin formation in an NP-40 detergent assay, with IC50 values ranging between 10.4 and 19.2 μm. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Antiviral Agents in Equine Abortion Virus-Infected Hamsters1

PubMed Central

Lieberman, Melvin; Pascale, Andrea; Schafer, Thomas W.; Came, Paul E.

1972-01-01

Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-β-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2′-deoxyuridine, distamycin A, and N-ethylisatin β-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group. PMID:4376907

Evaluation of Acanthamoeba Myosin-IC as a Potential Therapeutic Target

PubMed Central

Lorenzo-Morales, Jacob; López-Arencibia, Atteneri; Reyes-Batlle, María; Piñero, José E.; Valladares, Basilio; Maciver, Sutherland K.

2014-01-01

Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a fatal encephalitis. We have targeted myosin-IC by using small interfering RNA (siRNA) silencing as a therapeutic approach, since it is known that the function of this protein is vital for the amoeba. In this work, specific siRNAs against the Acanthamoeba myosin-IC gene were developed. Treated and control amoebae were cultured in growth and encystment media to evaluate the induced effects after myosin-IC gene knockdown, as we have anticipated that cyst formation may be impaired. The effects of myosin-IC gene silencing were inhibition of cyst formation, inhibition of completion of cytokinesis, inhibition of osmoregulation under osmotic stress conditions, and death of the amoebae. The finding that myosin-IC silencing caused incompletion of cytokinesis is in agreement with earlier suggestions that the protein plays a role in cell locomotion, which is necessary to pull daughter cells apart after mitosis in a process known as “traction-mediated cytokinesis”. We conclude that myosin-IC is a very promising potential drug target for the development of much-needed antiamoebal drugs and that it should be further exploited for Acanthamoeba therapy. PMID:24468784

Model-dependent effects of the gap junction conduction-enhancing antiarrhythmic peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs.

PubMed

Shiroshita-Takeshita, Akiko; Sakabe, Masao; Haugan, Ketil; Hennan, James K; Nattel, Stanley

2007-01-23

Abnormal intercellular communication caused by connexin dysfunction may be involved in atrial fibrillation (AF). The present study assessed the effect of the gap junctional conduction-enhancing peptide rotigaptide on AF maintenance in substrates that result from congestive heart failure induced by 2-week ventricular tachypacing (240 bpm), atrial tachypacing (ATP; 400 bpm for 3 to 6 weeks), and isolated atrial myocardial ischemia. Electrophysiological study and epicardial mapping were performed before and after rotigaptide administration in dogs with ATP and congestive heart failure, as well as in similarly instrumented sham dogs that were not tachypaced. For atrial myocardial ischemia, dogs administered rotigaptide before myocardial ischemia were compared with no-drug myocardial ischemia controls. ATP significantly shortened the atrial effective refractory period (P=0.003) and increased AF duration (P=0.008), with AF lasting >3 hours in all 6-week ATP animals. Rotigaptide increased conduction velocity in ATP dogs slightly but significantly (P=0.04) and did not affect the effective refractory period, AF duration, or atrial vulnerability. In dogs with congestive heart failure, rotigaptide also slightly increased conduction velocity (P=0.046) but failed to prevent AF promotion. Rotigaptide had no statistically significant effects in sham dogs. Myocardial ischemia alone increased AF duration and impaired conduction (based on conduction velocity across the ischemic border and indices of conduction heterogeneity). Rotigaptide prevented myocardial ischemia-induced conduction slowing and AF duration increases. Rotigaptide improves conduction in various AF models but suppresses AF only for the acute ischemia substrate. These results define the atrial antiarrhythmic profile of a mechanistically novel antiarrhythmic drug and suggest that gap junction dysfunction may be more important in ischemic AF than in ATP remodeling or congestive heart failure substrates.

ICS logging solution for network-based attacks using Gumistix technology

NASA Astrophysics Data System (ADS)

Otis, Jeremy R.; Berman, Dustin; Butts, Jonathan; Lopez, Juan

2013-05-01

Industrial Control Systems (ICS) monitor and control operations associated with the national critical infrastructure (e.g., electric power grid, oil and gas pipelines and water treatment facilities). These systems rely on technologies and architectures that were designed for system reliability and availability. Security associated with ICS was never an inherent concern, primarily due to the protections afforded by network isolation. However, a trend in ICS operations is to migrate to commercial networks via TCP/IP in order to leverage commodity benefits and cost savings. As a result, system vulnerabilities are now exposed to the online community. Indeed, recent research has demonstrated that many exposed ICS devices are being discovered using readily available applications (e.g., ShodanHQ search engine and Google-esque queries). Due to the lack of security and logging capabilities for ICS, most knowledge about attacks are derived from real world incidents after an attack has already been carried out and the damage has been done. This research provides a method for introducing sensors into the ICS environment that collect information about network-based attacks. The sensors are developed using an inexpensive Gumstix platform that can be deployed and incorporated with production systems. Data obtained from the sensors provide insight into attack tactics (e.g., port scans, Nessus scans, Metasploit modules, and zero-day exploits) and characteristics (e.g., attack origin, frequency, and level of persistence). Findings enable security professionals to draw an accurate, real-time awareness of the threats against ICS devices and help shift the security posture from reactionary to preventative.

Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?

PubMed

Ravens, Ursula

2017-11-01

In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K + ) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two-pore domain K + (K2P) channels (tandem of P domains, weak inward-rectifying K + channels (TWIK-1), TWIK-related acid-sensitive K + channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

Dronedarone: current evidence for its safety and efficacy in the management of atrial fibrillation.

PubMed

Schweizer, Patrick A; Becker, Rüdiger; Katus, Hugo A; Thomas, Dierk

2011-01-06

Atrial fibrillation (AF) is the most common sustained arrhythmia. Management of AF includes rate control, rhythm control if necessary, prevention of thromboembolic events, and treatment of the underlying disease. Rate control is usually achieved by pharmacological suppression of calcium currents or by applying β-blockers or digitalis compounds. In contrast, the number of compounds available for rhythm control is still limited. Class Ic agents increase mortality in patients with structural heart disease, and amiodarone harbors an extensive side effect profile despite its efficacy in maintaining sinus rhythm. Furthermore, rhythm control by these compounds has not been shown to reduce patient mortality. Dronedarone is a new anti-arrhythmic drug that has been developed to provide rhythm and rate control in AF patients with fewer side effects compared with amiodarone. This review primarily focuses on clinical trials evaluating efficacy and safety of the novel drug. Conclusions from these studies are critically reviewed, and recommendations for clinical practice are discussed. Dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation (ATHENA trial). However, dronedarone was less efficient than amiodarone in maintaining normal sinus rhythm (DIONYSOS trial) and is contraindicated in severe or deteriorating heart failure (ANDROMEDA trial). In summary, dronedarone represents a valuable addition to the limited spectrum of antiarrhythmic drugs and is currently recommended in patients with paroxysmal and persistent AF to achieve rate and rhythm control, excluding cases of severe or unstable congestive heart failure.

Development of brain injury criteria (BrIC).

PubMed

Takhounts, Erik G; Craig, Matthew J; Moorhouse, Kevin; McFadden, Joe; Hasija, Vikas

2013-11-01

Rotational motion of the head as a mechanism for brain injury was proposed back in the 1940s. Since then a multitude of research studies by various institutions were conducted to confirm/reject this hypothesis. Most of the studies were conducted on animals and concluded that rotational kinematics experienced by the animal's head may cause axonal deformations large enough to induce their functional deficit. Other studies utilized physical and mathematical models of human and animal heads to derive brain injury criteria based on deformation/pressure histories computed from their models. This study differs from the previous research in the following ways: first, it uses two different detailed mathematical models of human head (SIMon and GHBMC), each validated against various human brain response datasets; then establishes physical (strain and stress based) injury criteria for various types of brain injury based on scaled animal injury data; and finally, uses Anthropomorphic Test Devices (ATDs) (Hybrid III 50th Male, Hybrid III 5th Female, THOR 50th Male, ES-2re, SID-IIs, WorldSID 50th Male, and WorldSID 5th Female) test data (NCAP, pendulum, and frontal offset tests) to establish a kinematically based brain injury criterion (BrIC) for all ATDs. Similar procedures were applied to college football data where thousands of head impacts were recorded using a six degrees of freedom (6 DOF) instrumented helmet system. Since animal injury data used in derivation of BrIC were predominantly for diffuse axonal injury (DAI) type, which is currently an AIS 4+ injury, cumulative strain damage measure (CSDM) and maximum principal strain (MPS) were used to derive risk curves for AIS 4+ anatomic brain injuries. The AIS 1+, 2+, 3+, and 5+ risk curves for CSDM and MPS were then computed using the ratios between corresponding risk curves for head injury criterion (HIC) at a 50% risk. The risk curves for BrIC were then obtained from CSDM and MPS risk curves using the linear relationship

IC-Finder: inferring robustly the hierarchical organization of chromatin folding

PubMed Central

Haddad, Noelle

2017-01-01

Abstract The spatial organization of the genome plays a crucial role in the regulation of gene expression. Recent experimental techniques like Hi-C have emphasized the segmentation of genomes into interaction compartments that constitute conserved functional domains participating in the maintenance of a proper cell identity. Here, we propose a novel method, IC-Finder, to identify interaction compartments (IC) from experimental Hi-C maps. IC-Finder is based on a hierarchical clustering approach that we adapted to account for the polymeric nature of chromatin. Based on a benchmark of realistic in silico Hi-C maps, we show that IC-Finder is one of the best methods in terms of reliability and is the most efficient numerically. IC-Finder proposes two original options: a probabilistic description of the inferred compartments and the possibility to explore the various hierarchies of chromatin organization. Applying the method to experimental data in fly and human, we show how the predicted segmentation may depend on the normalization scheme and how 3D compartmentalization is tightly associated with epigenomic information. IC-Finder provides a robust and generic ‘all-in-one’ tool to uncover the general principles of 3D chromatin folding and their influence on gene regulation. The software is available at http://membres-timc.imag.fr/Daniel.Jost/DJ-TIMC/Software.html. PMID:28130423

Hubble Space Telescope Image: Planetary Nebula IC 4406

NASA Technical Reports Server (NTRS)

2001-01-01

This Hubble Space Telescope image reveals a rainbow of colors in this dying star, called IC 446. Like many other so-called planetary nebulae, IC 4406 exhibits a high degree of symmetry. The nebula's left and right halves are nearly mirror images of the other. If we could fly around IC 446 in a spaceship, we would see that the gas and dust form a vast donut of material streaming outward from the dying star. We do not see the donut shape in this photograph because we are viewing IC 4406 from the Earth-orbiting HST. From this vantage point, we are seeing the side of the donut. This side view allows us to see the intricate tendrils of material that have been compared to the eye's retina. In fact, IC 4406 is dubbed the 'Retina Nebula.' The donut of material confines the intense radiation coming from the remnant of the dying star. Gas on the inside of the donut is ionized by light from the central star and glows. Light from oxygen atoms is rendered blue in this image; hydrogen is shown as green, and nitrogen as red. The range of color in the final image shows the differences in concentration of these three gases in the nebula. This image is a composite of data taken by HST's Wide Field Planetary Camera 2 in June 2001 and in January 2002 by Bob O'Dell (Vanderbilt University) and collaborators, and in January by the Hubble Heritage Team (STScI). Filters used to create this color image show oxygen, hydrogen, and nitrogen gas glowing in this object.

Zoledronic acid induces dose-dependent increase of antigen-specific CD8 T-cell responses in combination with peptide/poly-IC vaccine.

PubMed

Park, Hye-Mi; Cho, Hyun-Il; Shin, Chang-Ae; Shon, Hyun-Jung; Kim, Tai-Gyu

2016-03-04

Zoledronic acid (ZA) is used for treating osteoporosis and for preventing skeletal fractures in cancer patients suffering from myeloma and prostate cancer. It is also reported to directly induce cancer cell apoptosis and indirectly modulate T-cell immune response as an antitumor agent. In this study, the effect of ZA following peptide/polyinosinic-polycytidylic acid (poly-IC) vaccination was investigated in a murine tumor model. The combination of ZA with peptide/poly-IC vaccine showed a synergistic effect on the induction of antigen-specific CD8 T-cell response. Three consecutive intravenous administrations of ZA was defined to induce the highest CD8 T-cell response. Further, total splenocyte counts and antigen-specific CD8 T-cell response gradually increased depending on the dose of ZA. In tumor-bearing mice, ZA showed a dose-dependent decrease of growth and prolonged survival. Treatment with ZA only decreased the number of CD11b(+)Gr1(+) myeloid cells in blood. Our results demonstrate that the use of ZA could improve antitumor immune responses induced by the peptide/poly-IC vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

A newly-detected reductase from Rauvolfia closes a gap in the biosynthesis of the antiarrhythmic alkaloid ajmaline.

PubMed

Gao, Shujuan; von Schumann, Gerald; Stöckigt, Joachim

2002-10-01

A new enzyme, 1,2-dihydrovomilenine reductase (E.C. 1.3.1), has been detected in Rauvolfia cell suspension cultures. The enzyme specifically converts 2beta( R)-1,2-dihydrovomilenine through an NADPH-dependent reaction into 17-O-acetylnorajmaline, a close biosynthetic precursor of the antiarrhythmic alkaloid ajmaline from Rauvolfia. A five-step purification procedure using SOURCE 30Q chromatography, hydroxyapatite chromatography, 2',5'-ADP Sepharose 4B affinity chromatography and ion exchange chromatography on DEAE Sepharose and Mono Q delivered an approximately 200-fold enriched enzyme in a yield of approximately 6%. SDS-PAGE showed an M r for the enzyme of approximately 48 kDa. Optimum pH and optimum temperature of the reductase were at pH 6.0 and 37 degrees C. The enzyme shows a limited distribution in cell cultures expressing ajmaline biosynthesis, and is obviously highly specific for the ajmaline pathway.

Synthesis and evaluation of novel triazolyl quinoline derivatives as potential antileishmanial agents.

PubMed

Upadhyay, Akanksha; Kushwaha, Pragati; Gupta, Sampa; Dodda, Ranga Prasad; Ramalingam, Karthik; Kant, Ruchir; Goyal, Neena; Sashidhara, Koneni V

2018-05-12

The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover novel series of 25 compounds for the development of new antileishmanial agents. A series of triazolyl 2-methyl-4-phenylquinoline-3-carboxylate derivatives has been synthesized via click chemistry inspired molecular hybridization approach and evaluated against Leishmania donovani. Most of the screened derivatives exhibited significant in vitro anti-leishmanial activity against promastigote (IC 50 ranging from 2.43 to 45.75 μM) and intracellular amastigotes (IC 50 ranging from 7.06 to 34.9 μM) than the control, miltefosine (IC 50  = 8.4 μM), with less cytotoxicity in comparison to the standard drugs. Overall results revealed that prototype signify a new structural lead for antileishmanial chemotherapy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Open flames (I-C mines). 57.22104 Section 57... Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C mines). (a) Open flames, including cutting and welding, shall not be used underground. (b) Welding and...

Lithium Abundances in the Young Open Cluster IC 2602

NASA Technical Reports Server (NTRS)

Randich, S.; Aharpour, N.; Pallavicini, R.; Prosser, C. F.; Stauffer, J. R.

1997-01-01

We have obtained high-resolution spectra for 28 candidate late-type stars in the 30 Myr old cluster IC 2602. NLTE Li abundances have been derived from measured equivalent widths. The log n(Li) - T(sub eff) and log n(Li) - mass distributions for our sample stars have been compared with those of the Pleiades and alpha Persei. Our data show that F stars in the three clusters have the same lithium content, which corresponds to the initial content for Pop. I stars. G and early-K IC 2602 stars are, on average, somewhat more Li-rich than their counterparts in the two slightly older clusters. Finally, the latest-type IC 2602 stars are heavily Li depleted, with their Li content being as low as the lowest measured among the Pleiades. As in the Pleiades and alpha Per, a star-to-star scatter in lithium is observed among 30 Myr old late-K/early-K dwarfs in IC 2602, indicating that this spread develops in the pre-main sequence phases.

ASASSN-16fp (SN 2016coi): a transitional supernova between Type Ic and broad-lined Ic

NASA Astrophysics Data System (ADS)

Kumar, Brajesh; Singh, A.; Srivastav, S.; Sahu, D. K.; Anupama, G. C.

2018-01-01

We present results based on a well-sampled optical (UBVRI) and ultraviolet (Swift/UVOT) imaging, and low-resolution optical spectroscopic follow-up observations of the nearby Type Ic supernova (SN) ASASSN-16fp (SN 2016coi). The SN was monitored during the photospheric phase (-10 to +33 d with respect to the B-band maximum light). The rise to maximum light and early post-maximum decline of the light curves are slow. The peak absolute magnitude (MV = -17.7 ± 0.2 mag) of ASASSN-16fp is comparable with broad-lined Ic SN 2002ap, SN 2012ap and transitional Ic SN 2004aw but considerably fainter than the gamma-ray burst/X-ray flash associated SNe (e.g. SN 1998bw, 2006aj). Similar to the light curve, the spectral evolution is also slow. ASASSN-16fp shows distinct photospheric phase spectral lines along with the C II features. The expansion velocity of the ejecta near maximum light reached ∼16 000 km s-1 and settled to ∼8000 km s-1, ∼1 month post-maximum. Analytical modelling of the quasi-bolometric light curve of ASASSN-16fp suggests that ∼0.1 M⊙ 56Ni mass was synthesized in the explosion, with a kinetic energy of 6.9^{+1.5}_{-1.3} × 1051 erg and total ejected mass of ∼4.5 ± 0.3 M⊙.

Study on Mine Emergency Mechanism based on TARP and ICS

NASA Astrophysics Data System (ADS)

Xi, Jian; Wu, Zongzhi

2018-01-01

By analyzing the experiences and practices of mine emergency in China and abroad, especially the United States and Australia, normative principle, risk management principle and adaptability principle of constructing mine emergency mechanism based on Trigger Action Response Plans (TARP) and Incident Command System (ICS) are summarized. Classification method, framework, flow and subject of TARP and ICS which are suitable for the actual situation of domestic mine emergency are proposed. The system dynamics model of TARP and ICS is established. The parameters such as evacuation ratio, response rate, per capita emergency capability and entry rate of rescuers are set up. By simulating the operation process of TARP and ICS, the impact of these parameters on the emergency process are analyzed, which could provide a reference and basis for building emergency capacity, formulating emergency plans and setting up action plans in the emergency process.

Droplet-Wall/Film Impact in IC Engine Applications

DTIC Science & Technology

2017-08-14

Report: Droplet-Wall/Film Impact in IC Engine Applications (ARO Topic 1.4.1 under ARO’s Dr. Ralph A. Anthenien) The views, opinions and/or findings...in IC Engine Applications (ARO Topic 1.4.1 under ARO’s Dr. Ralph A. Anthenien) Report Term: 0-Other Email: cklaw@princeton.edu Distribution Statement...associated with spraying in internal combustion engines (ICEs). Fuels sprayed inside engines can impact with the internal surfaces and thus not only

The jet-ISM interactions in IC 5063

NASA Astrophysics Data System (ADS)

Mukherjee, Dipanjan; Wagner, Alexander Y.; Bicknell, Geoffrey V.; Morganti, Raffaella; Oosterloo, Tom; Nesvadba, Nicole; Sutherland, Ralph S.

2018-05-01

The interstellar medium of the radio galaxy IC 5063 is highly perturbed by an AGN jet expanding in the gaseous disc of the galaxy. We model this interaction with relativistic hydrodynamic simulations and multiphase initial conditions for the interstellar medium and compare the results with recent observations. As the jets flood through the intercloud channels of the disc, they ablate, accelerate, and disperse clouds to velocities exceeding 400 km s-1. Clouds are also destroyed or displaced in bulk from the central regions of the galaxy. Our models with jet powers of 1044 and 1045 erg s-1 are capable of reproducing many of the observed features in the position velocity diagram of IC 5063, and confirm the notion that the jet is responsible for the strongly perturbed gas dynamics seen in the ionized, neutral, and molecular gas phases. In our simulations, we also see strong venting of the jet plasma perpendicular to the disc, which entrains clumps and diffuse filaments into the halo of the galaxy. Our simulations are the first 3D hydrodynamic simulations of the jet and interstellar matter of IC 5063.

The Search for Wolf-Rayet Stars in IC10

NASA Astrophysics Data System (ADS)

Tehrani, Katie; Crowther, Paul; Archer, Isabelle

2017-11-01

We present a deep imaging and spectroscopic survey of the Local Group starburst galaxy IC10 using Gemini North/GMOS to unveil the global Wolf-Rayet population. It has previously been suggested that for IC10 to follow the WC/WN versus metallicity dependence seen in other Local Group galaxies, a large WN population must remain undiscovered. Our search revealed 3 new WN stars, and 5 candidates awaiting confirmation, providing little evidence to support this claim. We also compute an updated nebular derived metallicity of log(O/H)+12=8.40 +/- 0.04 for the galaxy using the direct method. Inspection of IC10 WR average line luminosities show these stars are more similar to their LMC, rather than SMC counterparts.

Purification, Crystallization And Preliminary X-Ray Analysis of Aminoglycoside-2 ''-Phosphotransferase-Ic [APH(2 '')-Ic] From Enterococcus Gallinarum

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

Byrnes, L.J.; /SLAC, SSRL; Badarau, A.

2009-04-30

Bacterial resistance to aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, aminoglycoside-2{double_prime}-phosphotransferase-Ic [APH(2{double_prime})-Ic] from Enterococcus gallinarum, has been cloned and the wild-type protein (comprising 308 amino-acid residues) and three mutants that showed elevated minimum inhibitory concentrations towards gentamicin (F108L, H258L and a double mutant F108L/H258L) were expressed in Escherichia coli and subsequently purified. All APH(2{double_prime})-Ic variants were crystallized in the presence of 14-20%(w/v) PEG 4000, 0.25 M MgCl{sub 2}, 0.1 M Tris-HClmore » pH 8.5 and 1 mM Mg{sub 2}GTP. The crystals belong to the monoclinic space group C2, with one molecule in the asymmetric unit. The approximate unit-cell parameters are a = 82.4, b = 54.2, c = 77.0 {angstrom}, {beta} = 108.8{sup o}. X-ray diffraction data were collected to approximately 2.15 {angstrom} resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA.« less

Discovery of novel taspine derivatives as antiangiogenic agents.

PubMed

Zhang, Jie; Zhang, Yanmin; Zhang, Sanqi; Wang, Sicen; He, Langchong

2010-01-15

VEGFR-2 plays a critical role in vasculogenesis and inhibitors of VEGFR-2 could be used in the treatment of cancer. Taspine was one of the active ingredients screened by using an endothelial cell membrane chromatography and showed inhibition against VEGFR-2. In our research, we explored how the lactone ring and biphenyl scaffold in taspine influence its potent in vitro anticancer and antiangiogenesis activities. Accordingly, we report the design, synthesis, and preliminary evaluation of four novel taspine derivatives as VEGFR-2 inhibitors. The preliminary biological test showed that one of the compounds showed much better inhibitory activities against CACO-2 (IC(50)=52.5nM) and ECV304 (IC(50)=2.67nM) than taspine. This result enlarges the interest in ring-opened taspine derivative skeleton in the search of new antiangiogenesis agents. Copyright 2009 Elsevier Ltd. All rights reserved.

75 FR 54940 - Agency Information Collection (IC) Activities; Revision of an Approved IC; Accident Recordkeeping...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... include the Agency name and the docket number for this Notice. Note that DOT posts all comments received... underlying this IC is 49 CFR 390.15, ``Assistance in investigations and special studies.'' It requires motor... Information Technology. [FR Doc. 2010-22456 Filed 9-8-10; 8:45 am] BILLING CODE 4910-EX-P ...

ICECAP: an integrated, general-purpose, automation-assisted IC50/EC50 assay platform.

PubMed

Li, Ming; Chou, Judy; King, Kristopher W; Jing, Jing; Wei, Dong; Yang, Liyu

2015-02-01

IC50 and EC50 values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC50/EC50 assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC50/EC50 assay throughput demand. A general-purpose, automation-assisted IC50/EC50 assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC50/EC50 values, graphing, and reporting. The automation-assisted IC50/EC50 assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC50/EC50 assay experimental productivity and data processing efficiency. © 2014 Society for Laboratory Automation and Screening.

Wide-Field Structure of Local Group Dwarf Irregular Galaxy IC1613

NASA Astrophysics Data System (ADS)

Pucha, Ragadeepika; Carlin, Jeffrey; Willman, Beth; Sand, David J.; Bechtol, Keith

2018-01-01

IC1613 is a typical dwarf irregular galaxy in the Local Group. Being an isolated dwarf, as opposed to the dwarfs around the Milky Way, it is likely to be subjected to fewer strong environmental effects. As a result, it serves as a good prototype for the study of the structure and evolution of dwarf galaxies. We present g- and i- band photometry from deep imaging of four fields around IC1613, that resolved stars up to ~ 4 magnitudes fainter than the tip of the RGB. This photometry was obtained using Hyper-Suprime Cam (HSC) on the Subaru Telescope. The large (1.5o) field-of-view of HSC provides us with a unique opportunity to study the wide-field structure of this dwarf galaxy. This project explores the structure of IC1613 to radii of about ~ 25 kpc using different types of stellar tracers. The aim is to search for evidence of a stellar halo or stellar over-densities around IC1613. The relative contributions of the different stellar populations as a function of position in IC1613 are also shown.

30 CFR 57.22203 - Main fan operation (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Main fan operation (I-C mines). 57.22203... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22203 Main fan operation (I-C mines). Main fans shall be operated continuously while ore production is in progress. ...

Reactive Oxygen Species (ROS) Inducible DNA Cross-Linking Agents and Their Effect on Cancer Cells and Normal Lymphocytes

PubMed Central

2015-01-01

Reducing host toxicity is one of the main challenges of cancer chemotherapy. Many tumor cells contain high levels of ROS that make them distinctively different from normal cells. We report a series of ROS-activated aromatic nitrogen mustards that selectively kill chronic lymphocytic leukemia (CLL) over normal lymphocytes. These agents showed powerful DNA cross-linking abilities when coupled with H2O2, one of the most common ROS in cancer cells, whereas little DNA cross-linking was detected without H2O2. Consistent with chemistry observation, in vitro cytotoxicity assay demonstrated that these agents induced 40–80% apoptosis in primary leukemic lymphocytes isolated from CLL patients but less than 25% cell death to normal lymphocytes from healthy donors. The IC50 for the most potent compound (2) was ∼5 μM in CLL cells, while the IC50 was not achieved in normal lymphocytes. Collectively, these data provide utility and selectivity of these agents that will inspire further and effective applications. PMID:24801734

Simultaneous detection of three lily viruses using Triplex IC-RT-PCR.

PubMed

Zhang, Yubao; Wang, Yajun; Xie, Zhongkui; Yang, Guo; Guo, Zhihong; Wang, Le

2017-11-01

Viruses commonly infecting lily (Lilium spp.) include: Lily symptomless virus (LSV), Cucumber mosaic virus (CMV) and Lily mottle virus (LMoV). These viruses usually co-infect lilies causing severe economic losses in terms of quantity and quality of flower and bulb production around the world. Reliable and precise detection systems need to be developed for virus identification. We describe the development of a triplex immunocapture (IC) reverse transcription (RT) polymerase chain reaction (PCR) assay for the simultaneous detection of LSV, CMV and LMoV. The triplex IC-RT-PCR was compared with a quadruplex RT-PCR assay. Relative to the quadruplex RT-PCR, the specificity of the triplex IC-RT-PCR system for LSV, CMV and LMoV was 100% for field samples. The sensitivity of the triplex IC-RT-PCR system was 99.4%, 81.4% and 98.7% for LSV, CMV and LMoV, respectively. Agreement (κ) between the results obtained from the two tests was 0.968, 0.844 and 0.984 for LSV, CMV and LMoV, respectively. This is the first report of the simultaneous detection of LSV, CMV and LMoV in a triplex IC-RT-PCR assay. In particular we believe this convenient and reliable triplex IC-RT-PCR method could be used routinely for large-scale field surveys or crop health monitoring of lily. Copyright © 2017. Published by Elsevier B.V.

Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and methodology behind an out-of-hospital cardiac arrest antiarrhythmic drug trial.

PubMed

Kudenchuk, Peter J; Brown, Siobhan P; Daya, Mohamud; Morrison, Laurie J; Grunau, Brian E; Rea, Tom; Aufderheide, Tom; Powell, Judy; Leroux, Brian; Vaillancourt, Christian; Larsen, Jonathan; Wittwer, Lynn; Colella, M Riccardo; Stephens, Shannon W; Gamber, Mark; Egan, Debra; Dorian, Paul

2014-05-01

Despite their wide use, whether antiarrhythmic drugs improve survival after out-of-hospital cardiac arrest (OHCA) is not known. The ROC-ALPS is evaluating the effectiveness of these drugs for OHCA due to shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/VT). ALPS will randomize 3,000 adults across North America with nontraumatic OHCA, persistent or recurring VF/VT after ≥1 shock, and established vascular access to receive up to 450 mg amiodarone, 180 mg lidocaine, or placebo in the field using a double-blind protocol, along with standard resuscitation measures. The designated target population is all eligible randomized recipients of any dose of ALPS drug whose initial OHCA rhythm was VF/VT. A safety analysis includes all randomized patients regardless of their eligibility, initial arrhythmia, or actual receipt of ALPS drug. The primary outcome of ALPS is survival to hospital discharge; a secondary outcome is functional survival at discharge assessed as a modified Rankin Scale score ≤3. The principal aim of ALPS is to determine if survival is improved by amiodarone compared with placebo; secondary aim is to determine if survival is improved by lidocaine vs placebo and/or by amiodarone vs lidocaine. Prioritizing comparisons in this manner acknowledges where differences in outcome are most expected based on existing knowledge. Each aim also represents a clinically relevant comparison between treatments that is worth investigating. Results from ALPS will provide important information about the choice and value of antiarrhythmic therapies for VF/VT arrest with direct implications for resuscitation guidelines and clinical practice. Copyright © 2014 Mosby, Inc. All rights reserved.

AVP-IC50 Pred: Multiple machine learning techniques-based prediction of peptide antiviral activity in terms of half maximal inhibitory concentration (IC50).

PubMed

Qureshi, Abid; Tandon, Himani; Kumar, Manoj

2015-11-01

Peptide-based antiviral therapeutics has gradually paved their way into mainstream drug discovery research. Experimental determination of peptides' antiviral activity as expressed by their IC50 values involves a lot of effort. Therefore, we have developed "AVP-IC50 Pred," a regression-based algorithm to predict the antiviral activity in terms of IC50 values (μM). A total of 759 non-redundant peptides from AVPdb and HIPdb were divided into a training/test set having 683 peptides (T(683)) and a validation set with 76 independent peptides (V(76)) for evaluation. We utilized important peptide sequence features like amino-acid compositions, binary profile of N8-C8 residues, physicochemical properties and their hybrids. Four different machine learning techniques (MLTs) namely Support vector machine, Random Forest, Instance-based classifier, and K-Star were employed. During 10-fold cross validation, we achieved maximum Pearson correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the above MLTs using the best combination of feature sets. All the predictive models also performed well on the independent validation dataset and achieved maximum PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature sets. The AVP-IC50 Pred web server is anticipated to assist the researchers working on antiviral therapeutics by enabling them to computationally screen many compounds and focus experimental validation on the most promising set of peptides, thus reducing cost and time efforts. The server is available at http://crdd.osdd.net/servers/ic50avp. © 2015 Wiley Periodicals, Inc.

Illuminating the Depths of the MagIC (Magnetics Information Consortium) Database

NASA Astrophysics Data System (ADS)

Koppers, A. A. P.; Minnett, R.; Jarboe, N.; Jonestrask, L.; Tauxe, L.; Constable, C.

2015-12-01

The Magnetics Information Consortium (http://earthref.org/MagIC/) is a grass-roots cyberinfrastructure effort envisioned by the paleo-, geo-, and rock magnetic scientific community. Its mission is to archive their wealth of peer-reviewed raw data and interpretations from magnetics studies on natural and synthetic samples. Many of these valuable data are legacy datasets that were never published in their entirety, some resided in other databases that are no longer maintained, and others were never digitized from the field notebooks and lab work. Due to the volume of data collected, most studies, modern and legacy, only publish the interpreted results and, occasionally, a subset of the raw data. MagIC is making an extraordinary effort to archive these data in a single data model, including the raw instrument measurements if possible. This facilitates the reproducibility of the interpretations, the re-interpretation of the raw data as the community introduces new techniques, and the compilation of heterogeneous datasets that are otherwise distributed across multiple formats and physical locations. MagIC has developed tools to assist the scientific community in many stages of their workflow. Contributors easily share studies (in a private mode if so desired) in the MagIC Database with colleagues and reviewers prior to publication, publish the data online after the study is peer reviewed, and visualize their data in the context of the rest of the contributions to the MagIC Database. From organizing their data in the MagIC Data Model with an online editable spreadsheet, to validating the integrity of the dataset with automated plots and statistics, MagIC is continually lowering the barriers to transforming dark data into transparent and reproducible datasets. Additionally, this web application generalizes to other databases in MagIC's umbrella website (EarthRef.org) so that the Geochemical Earth Reference Model (http://earthref.org/GERM/) portal, Seamount Biogeosciences

Istaroxime, a positive inotropic agent devoid of proarrhythmic properties in sensitive chronic atrioventricular block dogs.

PubMed

Bossu, Alexandre; Kostense, Amée; Beekman, Henriette D M; Houtman, Marien J C; van der Heyden, Marcel A G; Vos, Marc A

2018-05-16

Current inotropic agents in heart failure therapy associate with low benefit and significant adverse effects, including ventricular arrhythmias. Istaroxime, a novel Na + /K + -transporting ATPase inhibitor, also stimulates SERCA2a activity, which would confer improved inotropic and lusitropic properties with less proarrhythmic effects. We investigated hemodynamic, electrophysiological and potential proarrhythmic and antiarrhythmic effects of istaroxime in control and chronic atrioventricular block (CAVB) dogs sensitive to drug-induced Torsades de Pointes arrhythmias (TdP). In isolated normal canine ventricular cardiomyocytes, istaroxime (0.3-10 μM) evoked no afterdepolarizations and significantly shortened action potential duration (APD) at 3 and 10 μM. Istaroxime at 3 μg/kg/min significantly increased left ventricular (LV) contractility (dP/dt+) and relaxation (dP/dt-) respectively by 81 and 94% in anesthetized control dogs (n = 6) and by 61 and 49% in anesthetized CAVB dogs (n = 7) sensitive to dofetilide-induced TdP. While istaroxime induced no ventricular arrhythmias in control conditions, only single ectopic beats occurred in 2/7 CAVB dogs, which were preceded by increase of short-term variability of repolarization (STV) and T wave alternans in LV unipolar electrograms. Istaroxime pre-treatment (3 μg/kg/min for 60 min) did not alleviate dofetilide-induced increase in repolarization and STV, and mildly reduced incidence of TdP from 6/6 to 4/6 CAVB dogs. In six CAVB dogs with dofetilide-induced TdP, administration of istaroxime (90 μg/kg/5 min) suppressed arrhythmic episodes in two animals. Taken together, inotropic and lusitropic properties of istaroxime in CAVB dogs were devoid of significant proarrhythmic effects in sensitive CAVB dogs, and istaroxime provides a moderate antiarrhythmic efficacy in prevention and suppression of dofetilide-induced TdP. Copyright © 2018. Published by Elsevier Ltd.

The beautiful side of IC 335

NASA Image and Video Library

2017-12-08

Hubble sees a galaxy 60 million light-years away This new NASA/ESA Hubble Space Telescope image shows the galaxy IC 335 in front of a backdrop of distant galaxies. IC 335 is part of a galaxy group containing three other galaxies, and located in the Fornax Galaxy Cluster 60 million light-years away. As seen in this image, the disk of IC 335 appears edge-on from the vantage point of Earth. This makes it harder for astronomers to classify it, as most of the characteristics of a galaxy’s morphology — the arms of a spiral or the bar across the center — are only visible on its face. Still, the 45 000 light-year-long galaxy could be classified as an S0 type. These lenticular galaxies are an intermediate state in galaxy morphological classification schemes between true spiral and elliptical galaxies. They have a thin stellar disk and a bulge, like spiral galaxies, but in contrast to typical spiral galaxies they have used up most of the interstellar medium. Only a few new stars can be created out of the material that is left and the star formation rate is very low. Hence, the population of stars in S0 galaxies consists mainly of aging stars, very similar to the star population in elliptical galaxies. As S0 galaxies have only ill-defined spiral arms they are easily mistaken for elliptical galaxies if they are seen inclined face-on or edge-on as IC 335 here. And indeed, despite the morphological differences between S0 and elliptical class galaxies, they share some common characteristics, like typical sizes and spectral features. Both classes are also deemed "early-type" galaxies, because they are evolving passively. However, while elliptical galaxies may be passively evolving when we observe them, they have usually had violent interactions with other galaxies in their past. In contrast, S0 galaxies are either aging and fading spiral galaxies, which never had any interactions with other galaxies, or they are the aging result of a single merger between two spiral galaxies

International Space Agency CIO Forum Industrial Control System (ICS) and Cyber

NASA Technical Reports Server (NTRS)

Powell, Robert

2017-01-01

This briefing covers Industrial Control System (ICS) best practices for enhancing cyber protection. The briefing provides a very high-level overview of best practices currently being pursued by NASA as well as by other US government agencies such as NIST and DHS ICS-CERT. All information presented in this slide deck is publicly available and no sensitive information is provided in these slides. These slides will be used to generate discussion around best practices within the international community in the area of ICS cyber protections.

AGB stars as tracers to IC 1613 evolution.

NASA Astrophysics Data System (ADS)

Hashemi, S. A.; Javadi, A.; van Loon, J. Th.

We are going to apply AGB stars to find star formation history for IC 1613 galaxy; this a new and simple method that works well for nearby galaxies. IC 1613 is a Local Group dwarf irregular galaxy that is located at distance of 750 kpc, a gas rich and isolated dwarf galaxy that has a low foreground extinction. We use the long period variable stars (LPVs) that represent the very final stage of evolution of stars with low and intermediate mass at the AGB phase and are very luminous and cool so that they emit maximum brightness in near-infrared bands. Thus near-infrared photometry with using stellar evolutionary models help us to convert brightness to birth mass and age and from this drive star formation history of the galaxy. We will use the luminosity distribution of the LPVs to reconstruct the star formation history-a method we have successfully applied in other Local Group galaxies. Our analysis shows that the IC 1613 has had a nearly constant star formation rate, without any dominant star formation episode.

Use of optical technique for inspection of warpage of IC packages

NASA Astrophysics Data System (ADS)

Toh, Siew-Lok; Chau, Fook S.; Ong, Sim Heng

2001-06-01

The packaging of IC packages has changed over the years, form dual-in-line, wire-bond, and pin-through-hole in printed wiring board technologies in the 1970s to ball grid array, chip scale and surface mount technologies in the 1990s. Reliability has been a big problem for manufacturers for some moisture-sensitive packages. One of the potential problems in plastic IC packages is moisture-induced popcorn effect which can arise during the reflow process. Shearography is a non-destructive inspection technique that may be used to detect the delamination and warpage of IC packages. It is non-contacting and permits a full-field observation of surface displacement derivatives. Another advantage of this technique is that it is able to give the real-time formation of the fringes which indicate flaws in the IC package under real-time simulation condition of Surface Mount Technology (SMT) IR reflow profile. It is extremely fast and convenient to study the true behavior of the packaging deformation during the SMT process. It can be concluded that shearography has the potential for the real- time detection, in situ and non-destructive inspection of IC packages during the surface mount process.

Student Definitions of Intercultural Competence (IC)--Are They Context-Specific?

ERIC Educational Resources Information Center

Binder, Nadine; Odag, Ozen; Leiser, Anne; Ludders, Lisa; Kedzior, Karina Karolina

2018-01-01

Higher education institutions increasingly seek to promote students' intercultural competence (IC), yet its conceptualization remains a challenge. The first aim of this study was to explore how a purposive sample of n = 77 domestic, undergraduate students at a public university in Germany define IC. The second aim was to assess to what extent such…

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

30 CFR 57.22210 - In-line filters (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false In-line filters (I-C mines). 57.22210 Section... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22210 In-line filters (I-C mines). Filters or separators shall be installed on air-lift fan systems to prevent explosive concentrations of...

Industry-Oriented Laboratory Development for Mixed-Signal IC Test Education

ERIC Educational Resources Information Center

Hu, J.; Haffner, M.; Yoder, S.; Scott, M.; Reehal, G.; Ismail, M.

2010-01-01

The semiconductor industry is lacking qualified integrated circuit (IC) test engineers to serve in the field of mixed-signal electronics. The absence of mixed-signal IC test education at the collegiate level is cited as one of the main sources for this problem. In response to this situation, the Department of Electrical and Computer Engineering at…

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Boreholes shall be drilled in such a manner to insure that the advancing face will not accidently break into... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

30 CFR 57.22241 - Advance face boreholes (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Advance face boreholes (I-C mines). 57.22241... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22241 Advance face boreholes (I-C mines). (a) Boreholes shall be drilled at least 25 feet in advance of a face whenever the work place is...

Synthesis and exploration of novel curcumin analogues as anti-malarial agents.

PubMed

Mishra, Satyendra; Karmodiya, Krishanpal; Surolia, Namita; Surolia, Avadhesha

2008-03-15

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC(50) of approximately 3.25 microM (MIC=13.2 microM) and IC(50) 4.21 microM (MIC=14.4 microM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC(50) of 0.48, 0.87, 0.92 microM and CQ-R P. falciparum at IC(50) of 0.45 microM, 0.89, 0.75 microM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.

Investigation on the inertial cavitation threshold and shell properties of commercialized ultrasound contrast agent microbubbles.

PubMed

Guo, Xiasheng; Li, Qian; Zhang, Zhe; Zhang, Dong; Tu, Juan

2013-08-01

The inertial cavitation (IC) activity of ultrasound contrast agents (UCAs) plays an important role in the development and improvement of ultrasound diagnostic and therapeutic applications. However, various diagnostic and therapeutic applications have different requirements for IC characteristics. Here through IC dose quantifications based on passive cavitation detection, IC thresholds were measured for two commercialized UCAs, albumin-shelled KangRun(®) and lipid-shelled SonoVue(®) microbubbles, at varied UCA volume concentrations (viz., 0.125 and 0.25 vol. %) and acoustic pulse lengths (viz., 5, 10, 20, 50, and 100 cycles). Shell elastic and viscous coefficients of UCAs were estimated by fitting measured acoustic attenuation spectra with Sarkar's model. The influences of sonication condition (viz., acoustic pulse length) and UCA shell properties on IC threshold were discussed based on numerical simulations. Both experimental measurements and numerical simulations indicate that IC thresholds of UCAs decrease with increasing UCA volume concentration and acoustic pulse length. The shell interfacial tension and dilatational viscosity estimated for SonoVue (0.7 ± 0.11 N/m, 6.5 ± 1.01 × 10(-8) kg/s) are smaller than those of KangRun (1.05 ± 0.18 N/m, 1.66 ± 0.38 × 10(-7) kg/s); this might result in lower IC threshold for SonoVue. The current results will be helpful for selecting and utilizing commercialized UCAs for specific clinical applications, while minimizing undesired IC-induced bioeffects.

Men Working on Mock-Up of S-IC Thrust Structure

NASA Technical Reports Server (NTRS)

1963-01-01

This photograph depicts Marshall Space Flight Center employees, James Reagin, machinist (top); Floyd McGinnis, machinist; and Ernest Davis, experimental test mechanic (foreground), working on a mock up of the S-IC thrust structure. The S-IC stage is the first stage, or booster, of the 364-foot long Saturn V rocket that ultimately took astronauts to the Moon. The S-IC stage, burned over 15 tons of propellant per second during its 2.5 minutes of operation to take the vehicle to a height of about 36 miles and to a speed of about 6,000 miles per hour. The stage was 138 feet long and 33 feet in diameter. Operating at maximum power, all five of the engines produced 7,500,000 pounds of thrust.

Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine

PubMed Central

Wang, Ying; Mi, Jianxun; Lu, Ka; Lu, Yanxin; Wang, KeWei

2015-01-01

Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain. To gain mechanistic insights into action of anti-arrhythmics, we characterized biophysical properties of Nav1.5 and Nav1.7 channels stably expressed in HEK293 cells and compared their use-dependent block in response to mexiletine and lidocaine using whole-cell patch clamp recordings. While the voltage-dependent activation of Nav1.5 or Nav1.7 was not affected by mexiletine and lidocaine, the steady-state fast and slow inactivation of Nav1.5 and Nav1.7 were significantly shifted to hyperpolarized direction by either mexiletine or lidocaine in dose-dependent manner. Both mexiletine and lidocaine enhanced the slow component of closed-state inactivation, with mexiletine exerting stronger inhibition on either Nav1.5 or Nav1.7. The recovery from inactivation of Nav1.5 or Nav1.7 was significantly prolonged by mexiletine compared to lidocaine. Furthermore, mexiletine displayed a pronounced and prominent use-dependent inhibition of Nav1.5 than lidocaine, but not Nav1.7 channels. Taken together, our findings demonstrate differential responses to blockade by mexiletine and lidocaine that preferentially affect the gating of Nav1.5, as compared to Nav1.7; and mexiletine exhibits stronger use-dependent block of Nav1.5. The differential gating properties of Nav1.5 and Nav1.7 in response to mexiletine and lidocaine may help explain the drug effectiveness and advance in new designs of safe and specific sodium channel blockers for treatment of cardiac arrhythmia or pain. PMID:26068619

3D-ICs created using oblique processing

NASA Astrophysics Data System (ADS)

Burckel, D. Bruce

2016-03-01

This paper demonstrates that another class of three-dimensional integrated circuits (3D-ICs) exists, distinct from through silicon via centric and monolithic 3D-ICs. Furthermore, it is possible to create devices that are 3D at the device level (i.e. with active channels oriented in each of the three coordinate axes), by performing standard CMOS fabrication operations at an angle with respect to the wafer surface into high aspect ratio silicon substrates using membrane projection lithography (MPL). MPL requires only minimal fixturing changes to standard CMOS equipment, and no change to current state-of-the-art lithography. Eliminating the constraint of 2D planar device architecture enables a wide range of new interconnect topologies which could help reduce interconnect resistance/capacitance, and potentially improve performance.

IC [Interior Communications] Electrician 3 and 2: Rate Training Manual. Revised.

ERIC Educational Resources Information Center

Naval Education and Training Command, Pensacola, FL.

The rate training manual provides information related to the tasks assigned to the Interior Communications (IC) Electricians Third and Second Class who operate and maintain the interior communications systems and associated equipment. Chapter one discusses career challenges for the IC Electrician in terms of responsibilities, advancement…

Experimental Genital Infection of Male Guinea Pigs with the Agent of Guinea Pig Inclusion Conjunctivitis and Transmission to Females

PubMed Central

Mount, David T.; Bigazzi, Pierluigi E.; Barron, Almen L.

1973-01-01

Male guinea pigs were inoculated intraurethrally with the agent of guinea pig inclusion conjunctivitis (Gp-ic). Cytoplasmic inclusions were found in superficial epithelial cells of the urethra in smears and stained sections. Gp-ic antigen(s) was detected by immunofluorescent staining of sections. There was no marked urethral exudate, but many animals developed bullous lesions on the glans and the body of the penis and a severe inflammatory lesion of the hind leg. All males demonstrated an antibody response and most of them showed a positive skin test reaction. Venereal transmission to females of Gp-ic infection was shown to occur as determined by detection of inclusions in vaginal smears, antibody response, and positive skin tests. Images PMID:4594119

Do alterations in prostanoid or catecholamine release influence the antiarrhythmic activity of nicergoline?

PubMed

Williams, F M; Coker, S J; Dean, H G; Kane, K A; Parratt, J R

1986-01-01

We examined the effects of nicergoline, an alpha-adrenoceptor blocking drug and an inhibitor of platelet phospholipase, on haemodynamics, blood gases, cardiac arrhythmias, and prostanoid and catecholamine release in anaesthetised greyhounds before, during, and after a 40-min occlusion of the left anterior descending coronary artery. Twenty-five minutes after commencing the intravenous infusion of nicergoline (50 micrograms kg-1 min-1) there were significant reductions in heart rate, arterial blood pressure, left ventricular dP/dtmax, and cardiac output. Nicergoline also increased the 0(2) extraction by the myocardium both before and during coronary artery occlusion. In contrast to control animals, heart rate decreased but there were no further reductions in arterial blood pressure during the occlusion period. Nicergoline improved survival (from 17 in control dogs to 50%) following the combined period of myocardial ischaemia and reperfusion and appeared to suppress the phase 1b occlusion-induced arrhythmias. The release of thromboxane B2 from the ischaemic myocardium was partially suppressed by nicergoline, and the ratio of 6-keto PGF1 alpha/thromboxane B2 (the stable breakdown products of prostacyclin and thromboxane A2, respectively) was increased. The washout of noradrenaline and adrenaline from the ischaemic myocardium following release of the occlusion was slightly enhanced by nicergoline. It is concluded that the beneficial metabolic and prostacyclin-promoting properties of nicergoline may be opposed by its action on noradrenaline washout, thus limiting its antiarrhythmic effectiveness.

Edwards nXDS15iC Vacuum Scroll Pump Pressure Testing

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

Sessions, H.; Morgan, G. A.

2013-07-17

The SRNL High Pressure Laboratory performed testing on an Edwards Model nXDS15iC Vacuum Scroll Pump on July 10th and 11th of 2013 at 723-A. This testing was done in an attempt to obtain initial compression ratio information for the nXDS15iC pump, with compression ratio defined as discharge pressure of the pump divided by suction pressure. Pressure burst testing was also done on the pump to determine its design pressure for pressure safety reasons. The Edwards nXDS15iC pump is being evaluated by SRNL for use part of the SHINE project being executed by SRNL.

Construction Progress of the S-IC Test Stand Complex Bunker House

NASA Technical Reports Server (NTRS)

1963-01-01

At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the S-IC stand, additional related facilities were built during this time frame. Built to the east of the S-IC stand, the block house served as the control room. To the south of the blockhouse was a newly constructed pump house used for delivering water to the S-IC stand during testing. North of the massive test stand, the F-1 Engine test stand was built for testing a single F-1 engine. Just southeast of the S-IC stand a concrete bunker house was constructed. The bunker housed

Innovative Teaching of IC Design and Manufacture Using the Superchip Platform

ERIC Educational Resources Information Center

Wilson, P. R.; Wilcock, R.; McNally, I.; Swabey, M.

2010-01-01

This paper describes how an intelligent chip architecture has allowed a large cohort of undergraduate (UG) students to be given effective practical insight into integrated circuit (IC) design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the "Superchip," was developed, which allows multiple student…

ICS classification system of infected osteosynthesis: Long-term results.

PubMed

Romanò, Carlo L; Morelli, Ilaria; Romanò, Delia; Meani, Enzo; Drago, Lorenzo

2018-03-01

The best treatment strategy for infected osteosyntheses is still debated. While hardware removal or eventually early device exchange may be necessary in most of the cases, temporary hardware retention until fracture healing can be a valid alternative option in others. Aim of the present study is to report the long-term results of 215 patients with infected osteosyntheses, treated according to the ICS (Infection, Callus, Stability) classification in two Italian hospitals. Patients classified as ICS Type 1 (N = 83) feature callus progression and hardware stability, in spite of the presence of infection; these patients were treated with suppressive antibiotic therapy coupled with local debridement in 18.1% of the cases, and no hardware removal until bone healing. Type 2 patients (N = 75) are characterized by the presence of infection and hardware stability, but no callus progression; these patients were treated as Type 1 patients, but with additional callus stimulation therapies. Type 3 patients (N = 57), showing infection, no callus progression and loss of hardware stability, underwent removal and exchange of the fixation device. Considering only the initial treatment, performed according to the ICS classification, at a minimum 5 years follow up, 89.3% achieved bone healing and 93.5% did not show infection recurrence. The ICS classification appears as a useful and reliable tool to help standardizing the decision-making process in treating infected osteosynthesis with the most conservative approach. Copyright © 2018 Elsevier Ltd. All rights reserved.

New cancer cells apoptosis agents: Fluorinated aza-heterocycles

NASA Astrophysics Data System (ADS)

Prima, D. O.; Baev, D. S.; Vorontsova, E. V.; Frolova, T. S.; Bagryanskaya, I. Yu.; Slizhov, Yu. G.; Tolstikova, T. G.; Makarov, A. Yu.; Zibarev, A. V.

2017-09-01

Fluorinated benzo-fused 1,3-diazoles, 1,2,3-triazoles, 1,2,5-thia/selenadiazoles and 1,4-diazines were synthesized and tried for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma) cells. The diazoles, triazoles and selenadiazoles were cytotoxic with IC50 = 2.2-26.4 µM and induced the cells apoptosis at concentrations C = 1-25 µM. At the same time, they were nontoxic towards normal cells. Due to this, these scaffolds were used in the computer-aided molecular design of new antitumor agents. Particularly, novel 1,2,3-triazole and 1,3-diazole derivatives for the binding site of the PAS domain of the transcription factor HIF were designed and some of them synthesized for further study. Overall, new anticancer agents featuring apoptotic activity are suggested.

ICS-II USA research design and methodology.

PubMed

Rana, H; Andersen, R M; Nakazono, T T; Davidson, P L

1997-05-01

The purpose of the WHO-sponsored International Collaborative Study of Oral Health Outcomes (ICS-II) was to provide policy-markers and researchers with detailed, reliable, and valid data on the oral health situation in their countries or regions, together with comparative data from other dental care delivery systems. ICS-II used a cross-sectional design with no explicit control groups or experimental interventions. A standardized methodology was developed and tested for collecting and analyzing epidemiological, sociocultural, economic, and delivery system data. Respondent information was obtained by household interviews, and clinical examinations were conducted by calibrated oral epidemiologists. Discussed are the sampling design characteristics for the USA research locations, response rates, samples size for interview and oral examination data, weighting procedures, and statistical methods. SUDAAN was used to adjust variance calculations, since complex sampling designs were used.

Multicolor CCD Photometry of the Open Cluster IC361

DTIC Science & Technology

2010-01-01

journal Volume 19 Numbers 1/2 2010 Contents V. Straizys, A. Kazlauskas. Young stars in the Camelopardalis dust and molecular clouds. VI. YSOs...Vilnius + I system for 7250 stars down to 1= 19.6 mag has been obtained in the 20’ x 26’ field of the open cluster IC 361 in Camelopardalis . The catalog...1= 19.6 mag has been obtained in the 20’ x 26’ field of the open cluster IC 361 in Camelopardalis . The catalog of 1420 stars down to V ~ 18.5 mag

Classification of fMRI independent components using IC-fingerprints and support vector machine classifiers.

PubMed

De Martino, Federico; Gentile, Francesco; Esposito, Fabrizio; Balsi, Marco; Di Salle, Francesco; Goebel, Rainer; Formisano, Elia

2007-01-01

We present a general method for the classification of independent components (ICs) extracted from functional MRI (fMRI) data sets. The method consists of two steps. In the first step, each fMRI-IC is associated with an IC-fingerprint, i.e., a representation of the component in a multidimensional space of parameters. These parameters are post hoc estimates of global properties of the ICs and are largely independent of a specific experimental design and stimulus timing. In the second step a machine learning algorithm automatically separates the IC-fingerprints into six general classes after preliminary training performed on a small subset of expert-labeled components. We illustrate this approach in a multisubject fMRI study employing visual structure-from-motion stimuli encoding faces and control random shapes. We show that: (1) IC-fingerprints are a valuable tool for the inspection, characterization and selection of fMRI-ICs and (2) automatic classifications of fMRI-ICs in new subjects present a high correspondence with those obtained by expert visual inspection of the components. Importantly, our classification procedure highlights several neurophysiologically interesting processes. The most intriguing of which is reflected, with high intra- and inter-subject reproducibility, in one IC exhibiting a transiently task-related activation in the 'face' region of the primary sensorimotor cortex. This suggests that in addition to or as part of the mirror system, somatotopic regions of the sensorimotor cortex are involved in disambiguating the perception of a moving body part. Finally, we show that the same classification algorithm can be successfully applied, without re-training, to fMRI collected using acquisition parameters, stimulation modality and timing considerably different from those used for training.

Investigations on the destruction of ultrasound contrast agents: Fragmentation thresholds, inertial cavitation, and bioeffects

NASA Astrophysics Data System (ADS)

Chen, Wen-Shiang

Ultrasound contrast agents (UCA) have shown great potential in both diagnostic and therapeutic applications recently. To fully explore the possible applications and the safety concerns of using UCA, a complete understanding of the UCA responses to various acoustic fields is necessary. Therefore, we performed a series of experiments and simulations to investigate the various acoustic properties of UCA with different gases and shells. We also investigated the mechanisms of some UCA-enhanced bioeffects including thrombolysis, hemolysis and high-intensity focused ultrasound (HIFU) tumor ablation. Two pressure thresholds were found: the fragmentation threshold and continuous inertial cavitation (IC) threshold. At the fragmentation threshold, bubbles were destroyed and the released gas dissolved in the surrounding solution at a rate which depended on the bubble's initial size and type of gas. The continuous IC threshold occurred at a higher pressure, where fragments of destroyed UCA (derivative bubbles) underwent violent inertial collapse; the period of activity depending on acoustic parameters such as frequency, pressure, pulse length, and pulse repetition frequency (PRF). Different UCA had different threshold pressures and demonstrated different magnitudes of IC activity after destruction. The amount of derivative bubbles generated by IC was determined by several acoustic parameters including pressure, pulse length and PRE For the same acoustic energy delivered, longer pulses generated more bubbles. More IC could be induced if the derivative bubbles could survive through the 'off' period of the pulsed ultrasound waves, and served as nuclei for the subsequent IC. In therapeutic applications, evidences of IC activity were recorded during the hemolysis, thrombolysis, and the lesion-formation processes with UCA. Hemolysis and thrombolysis were highly correlated to the presence of ultrasound and UCA, and correlated well with the amount of the IC activity. Finally, the

Construction Progress of the S-IC Test Stand-Pumps

NASA Technical Reports Server (NTRS)

1962-01-01

At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken April 4, 1961, shows the S-IC test stand dry once again when workers resumed construction after a 6 month delay due to booster size reconfiguration back in September of 1961. The disturbance of a natural spring during the excavation of the site required water to be pumped from the site continuously. The site was completely flooded after the pumps were shut down during the construction delay.

Galaxy IC 3639 with Obscured Active Galactic Nucleus

NASA Image and Video Library

2017-01-07

IC 3639, a galaxy with an active galactic nucleus, is seen in this image combining data from the Hubble Space Telescope and the European Southern Observatory. This galaxy contains an example of a supermassive black hole hidden by gas and dust. Researchers analyzed NuSTAR data from this object and compared them with previous observations from NASA's Chandra X-Ray Observatory and the Japanese-led Suzaku satellite. The findings from NuSTAR, which is more sensitive to higher energy X-rays than these observatories, confirm the nature of IC 3639 as an active galactic nucleus that is heavily obscured, and intrinsically much brighter than observed. http://photojournal.jpl.nasa.gov/catalog/PIA21087

Toxicity potential of disinfection agent in tannery wastewater.

PubMed

Tisler, Tatjana; Zagorc-Koncan, Jana; Cotman, Magda; Drolc, Andreja

2004-09-01

Wastewater from a tannery was investigated using chemical-specific analyses and assessment of the acute toxicity of the whole effluent over a 2-year period. The wastewater samples were overloaded with organic and inorganic compounds, and measured concentrations of the chemical parameters as well as dilution factors estimating acute toxicity, frequently exceeded the permissible limits for the discharge of wastewater from a tannery into the receiving stream. In the later part of the monitoring programme, the toxicity of the samples was significantly increased in comparison to the previous samples. The agent for hide disinfection was assumed to be the reason for the increased toxicity of the wastewater samples, and the extremely high acute and chronic toxicity of the agent to bacteria, algae, daphnids, and fish confirmed this suspicion. The most sensitive species was Daphnia magna; the 48 h EC50 was 0.70 x 10(-5)v/v% and the 21d IC25 was 0.40 x 10(-6)v/v% of the agent. After withdrawal of this highly toxic agent for hide disinfection from the technological process in the tannery, the toxicity of the wastewater declined to the previous level.

Differential role of PI3K/Akt pathway in the infarct size limitation and antiarrhythmic protection in the rat heart.

PubMed

Ravingerová, Tána; Matejíková, Jana; Neckár, Jan; Andelová, Eva; Kolár, Frantisek

2007-03-01

Endogenous cardiac protection against prolonged ischemic insult can be achieved by repeated brief episodes of ischemia (hypoxia) or by cardiac adaptation to various stresses such as chronic hypoxia. Activation of phosphatidylinositol 3-kinase (PI3K)/Akt is involved in antiapoptotic effects, however, it is not clear whether it is required for overall heart salvage including protection against myocardial infarction and arrhythmias. We focussed on the potential common role of PI3K/Akt in anti-infarct protection, in the experimental settings of long-term adaptation to chronic intermittent hypobaric hypoxia (IHH; 8 h/day, 25-30 exposures, in vivo rats) and acute ischemic preconditioning (IP; Langendorff-perfused hearts). In addition, we explored the role of PI3K/Akt in susceptibility to ischemic ventricular arrhythmias. In normoxic open-chest rats, PI3K/Akt inhibitor LY294002 (LY; 0.3 mg/kg) given 5 min before test occlusion/reperfusion (I/R) did not affect infarct size (IS) normalized to the size of area at risk (AR). In hypoxic rats, LY partially attenuated IS-limiting effect of IHH (IS/AR 59.7 +/- 4.1% vs. 51.8 +/- 4.4% in the non-treated rats; p > 0.05) and increased IS/AR to its value in normoxic rats (64.9 +/- 5.1%). In the isolated hearts, LY (5 muM) applied 15 min prior to I/R completely abolished anti-infarct protection by IP (IS/AR 55.0 +/- 4.9% vs. 15.2 +/- 1.2% in the non-treated hearts and 42.0 +/- 5.5% in the non-preconditioned controls; p < 0.05). In the non-preconditioned hearts, PI3K/Akt inhibition did not modify IS/AR, on the other hand, it markedly suppressed arrhythmias. In the LY-treated isolated hearts, the total number of ventricular premature beats and the incidence of ventricular tachycardia (VT) was reduced from 518 +/- 71 and 100% in the controls to 155 +/- 15 and 12.5%, respectively (p < 0.05). Moreover, bracketing of IP with LY did not reverse antiarrhythmic effect of IP. These results suggest that activation of PI3K/Akt cascade plays a role

Purification, crystallization and preliminary X-ray analysis of aminoglycoside-2′′-phosphotransferase-Ic [APH(2′′)-Ic] from Enterococcus gallinarum

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

Byrnes, Laura J.; Badarau, Adriana; Vakulenko, Sergei B.

2008-02-01

APH(2′′)-Ic is an enzyme that is responsible for high-level gentamicin resistance in E. gallinarum isolates. Crystals of the wild-type enzyme and three mutants have been prepared and a complete X-ray diffraction data set was collected to 2.15 Å resolution from an F108L crystal. Bacterial resistance to aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, aminoglycoside-2′′-phosphotransferase-Ic [APH(2′′)-Ic] from Enterococcus gallinarum, has been cloned and the wild-type protein (comprising 308 amino-acid residues) and threemore » mutants that showed elevated minimum inhibitory concentrations towards gentamicin (F108L, H258L and a double mutant F108L/H258L) were expressed in Escherichia coli and subsequently purified. All APH(2′′)-Ic variants were crystallized in the presence of 14–20%(w/v) PEG 4000, 0.25 M MgCl{sub 2}, 0.1 M Tris–HCl pH 8.5 and 1 mM Mg{sub 2}GTP. The crystals belong to the monoclinic space group C2, with one molecule in the asymmetric unit. The approximate unit-cell parameters are a = 82.4, b = 54.2, c = 77.0 Å, β = 108.8°. X-ray diffraction data were collected to approximately 2.15 Å resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA.« less

Module comprising IC memory stack dedicated to and structurally combined with an IC microprocessor chip

NASA Technical Reports Server (NTRS)

Carson, John C. (Inventor); Indin, Ronald J. (Inventor); Shanken, Stuart N. (Inventor)

1994-01-01

A computer module is disclosed in which a stack of glued together IC memory chips is structurally integrated with a microprocessor chip. The memory provided by the stack is dedicated to the microprocessor chip. The microprocessor and its memory stack may be connected either by glue and/or by solder bumps. The solder bumps can perform three functions--electrical interconnection, mechanical connection, and heat transfer. The electrical connections in some versions are provided by wire bonding.

Tuberculosis vaccine candidate: Characterization of H4-IC31 formulation and H4 antigen conformation.

PubMed

Deshmukh, Sasmit S; Magcalas, Federico Webster; Kalbfleisch, Kristen N; Carpick, Bruce W; Kirkitadze, Marina D

2018-08-05

Tuberculosis (TB) is one of the leading causes of death worldwide, making the development of effective TB vaccines a global priority. A TB vaccine consisting of a recombinant fusion protein, H4, combined with a novel synthetic cationic adjuvant, IC31 ® , is currently being developed. The H4 fusion protein consists of two immunogenic mycobacterial antigens, Ag85 B and TB10.4, and the IC31 ® adjuvant is a mixture of KLK, a leucine-rich peptide (KLKL5KLK), and the oligodeoxynucleotide ODN1a, a TLR9 ligand. However, efficient and robust methods for assessing these formulated components are lacking. Here, we developed and optimized phase analysis light scattering (PALS), electrical sensing zone (ESZ), and Raman, FTIR, and CD spectroscopy methods to characterize the H4-IC31 vaccine formulation. PALS-measured conductivity and zeta potential values could differentiate between the similarly sized particles of IC31 ® adjuvant and the H4-IC31 vaccine candidate and could thereby serve as a control during vaccine formulation. In addition, zeta potential is indicative of the adjuvant to antigen ratio which is the key in the immunomodulatory response of the vaccine. ESZ was used as an orthogonal method to measure IC31 ® and H4-IC31 particle sizes. Raman, FTIR, and CD spectroscopy revealed structural changes in H4 protein and IC31 ® adjuvant, inducing an increase in both the β-sheet and random coil content as a result of adsorption. Furthermore, nanoDSF showed changes in the tertiary structure of H4 protein as a result of adjuvantation to IC31 ® . Our findings demonstrate the applicability of biophysical methods to characterize vaccine components in the final H4-IC31 drug product without the requirement for desorption. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Multi-Wavelength Views of Protostars in IC 1396

NASA Image and Video Library

2003-12-18

This archival image from 2003 captured by NASA Spitzer Space Telescope captured the Elephant Trunk Nebula, an elongated dark globule within the emission nebula IC 1396 in the constellation of Cepheus.

Validating the Implementation Climate Scale (ICS) in Child Welfare Organizations

PubMed Central

Ehrhart, Mark G.; Torres, Elisa M.; Wright, Lisa A.; Martinez, Sandra Y.; Aarons, Gregory A.

2015-01-01

There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization’s climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. PMID:26563643

Validating the Implementation Climate Scale (ICS) in child welfare organizations.

PubMed

Ehrhart, Mark G; Torres, Elisa M; Wright, Lisa A; Martinez, Sandra Y; Aarons, Gregory A

2016-03-01

There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization's climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations. Copyright © 2015 Elsevier Ltd. All rights reserved.

IC97 Is a Novel Intermediate Chain of I1 Dynein That Interacts with Tubulin and Regulates Interdoublet Sliding

PubMed Central

Wirschell, Maureen; Yang, Chun; Yang, Pinfen; Fox, Laura; Yanagisawa, Haru-aki; Kamiya, Ritsu; Witman, George B.; Porter, Mary E.

2009-01-01

Our goal is to understand the assembly and regulation of flagellar dyneins, particularly the Chlamydomonas inner arm dynein called I1 dynein. Here, we focus on the uncharacterized I1-dynein IC IC97. The IC97 gene encodes a novel IC without notable structural domains. IC97 shares homology with the murine lung adenoma susceptibility 1 (Las1) protein—a candidate tumor suppressor gene implicated in lung tumorigenesis. Multiple, independent biochemical assays determined that IC97 interacts with both α- and β-tubulin subunits within the axoneme. I1-dynein assembly mutants suggest that IC97 interacts with both the IC138 and IC140 subunits within the I1-dynein motor complex and that IC97 is part of a regulatory complex that contains IC138. Microtubule sliding assays, using axonemes containing I1 dynein but devoid of IC97, show reduced microtubule sliding velocities that are not rescued by kinase inhibitors, revealing a critical role for IC97 in I1-dynein function and control of dynein-driven motility. PMID:19420136

SN2005da: A Spectroscopic and Photometric Analysis of a Peculiar Type Ic Supernova

NASA Astrophysics Data System (ADS)

Williamson, Jacob

2017-12-01

Core collapse supernovae are an important class of objects in stellar evolution research as they are the final life stage of high mass stars. Supernovae in general are classified into several spectral types; this paper explores SN 2005da, classified as a Type Ic, meaning it lacks hydrogen and helium lines. The supernova was originally classified as a broad-lined Type Ic (Type Ic-BL), with expansion velocities near maximum light greater than or approximately equal to 15000 km/s. However, some of the elements present in the spectrum, namely carbon and oxygen, have narrower lines (FWHM approximately equal to 2300 km/s) than other elements, indicating an interaction with a previously ejected envelope. The supernova is also found to have a decay time, with a change in magnitude over 15 days following maximum light of about 1.4 magnitudes, that is significantly faster than typical Type Ic or Ic-BL. This is more akin to a rarer object type known as a Type Ibn, although it lacks the characteristic narrow helium lines of this type. Therefore, SN 2005da appears to be unlike known examples of Type Ic supernovae.

A Solder Based Self Assembly Project in an Introductory IC Fabrication Course

ERIC Educational Resources Information Center

Rao, Madhav; Lusth, John C.; Burkett, Susan L.

2015-01-01

Integrated circuit (IC) fabrication principles is an elective course in a senior undergraduate and early graduate student's curriculum. Over the years, the semiconductor industry relies heavily on students with developed expertise in the area of fabrication techniques, learned in an IC fabrication theory and laboratory course. The theory course…

TIF-IC, a factor involved in both transcription initiation and elongation of RNA polymerase I.

PubMed

Schnapp, G; Schnapp, A; Rosenbauer, H; Grummt, I

1994-09-01

We have characterized a transcription factor from Ehrlich ascites cells that is required for ribosomal gene transcription by RNA polymerase I (Pol I). This factor, termed TIF-IC, has a native molecular mass of 65 kDa, associates with Pol I, and is required both for the assembly of Sarkosyl-resistant initiation complexes and for the formation of the first internucleotide bonds. In addition to its function in transcription initiation, TIF-IC also plays a role in elongation of nascent RNA chains. At suboptimal levels of TIF-IC, transcripts with heterogeneous 3' ends are formed which are chased into full-length transcripts by the addition of more TIF-IC. Moreover, on a tailed template, which allows initiation in the absence of auxiliary factors, TIF-IC was found to stimulate the overall rate of transcription elongation and suppress pausing of Pol I. Thus TIF-IC appears to serve a function similar to the Pol II-specific factor TFIIF which is required for Pol II transcription initiation and elongation.

Pulsed laser ablation of IC packages for device failure analyses

NASA Astrophysics Data System (ADS)

Hong, Ming Hui; Mai, ZhiHong; Chen, G. X.; Thiam, Thomas; Song, Wen D.; Lu, Yongfeng; Soh, Chye E.; Chong, Tow Chong

2002-06-01

Pulsed laser ablation of mold compounds for IC packaging in air and with steam assistance is investigated. It is applied to decap IC packages and expose computer CPU dies for the device failure analyses. Compared with chemical decapping, the laser ablation has advantages of being fast speed, non- contact and dry processing. Laser ablation with the steam assistance results in higher ablation rate and wider ablated crater with much smoother surface morphology. It implies that the steam assisted laser ablation can achieve a faster and better quality laser processing. Audible acoustic wave and plasma optical signal diagnostics are also carried out to have a better understanding of the mechanisms behind. Light wavelength and laser fluence applied in the decapping are two important parameters. The 532 nm Nd:YAG laser decapping at a low laser fluence can achieve a large decapping area with a fine ablation profile. IC packages decapped by the laser ablation show good quality for the device failure analyses.

Inhaled corticosteroids (ICS) and risk of mycobacterium in patients with chronic respiratory diseases: a meta-analysis.

PubMed

Ni, Songshi; Fu, Zhenxue; Zhao, Jing; Liu, Hua

2014-07-01

Studies have indicated that therapy with inhaled corticosteroids (ICS) can be associated with a higher risk of pneumonia. However, it is not known whether ICS increases the risk of mycobacterium. Most of these published studies were small, and the conclusions were inconsistent. A meta-analysis was conducted into whether ICS increases the risk of mycobacterium in patients with chronic respiratory diseases. PubMed, OVID, EMBASE and Cochrane Library databases were searched. Five studies involving 4,851 cases and 28,477 controls were considered in the meta-analysis. From the pooled analyses, there was significant association between ICS and risk of mycobacterium in all patients with chronic respiratory diseases [risk ratio (RR) =1.81; 95% confidence interval (CI), 1.23-2.68; P=0.003]. Among patients with chronic respiratory diseases, the relationship between ICS and risk of tuberculosis (TB) was also significant (RR =1.34; 95% CI, 1.15-1.55; P=0.0001). And meta-analysis of four studies in patients with chronic obstructive pulmonary disease (COPD) (RR =1.42; 95% CI, 1.18-1.72; P=0.0003) or two studies in patients who have prior pulmonary TB (RR =1.61; 95% CI, 1.35-1.92; P<0.00001) or three studies in patients with high-dose ICS (RR =1.60; 95% CI, 1.28-1.99; P<0.0001) showed a relationship between ICS and risk of mycobacterium. Significant relationship has been shown between ICS use and risk of mycobacterium in all patients with chronic respiratory diseases. ICS use also increases the risk of TB among the patients with chronic respiratory diseases. Use of ICS increases the risk of mycobacterium in patients with COPD or patients with prior pulmonary TB or patients inhaling high-dose corticosteroids. Further research is required to establish the potential adverse effect of ICS as a therapy for chronic respiratory diseases.

The German Intelligibility in Context Scale (ICS-G): Reliability and Validity Evidence

ERIC Educational Resources Information Center

Neumann, Sandra; Rietz, Christian; Stenneken, Prisca

2017-01-01

Background: In 2012 the Intelligibility in Context Scale (ICS) was published as a parent-report screening assessment that considers parents' perceptions of their children's functional intelligibility with a range of communication partners that differ in levels of authority and familiarity in real-life situations. To date, the ICS has been…

Some new results on shock chemistry in IC 443

NASA Technical Reports Server (NTRS)

Denoyer, L. K.; Frerking, M. A.

1981-01-01

New observations have been made of CO, CO-13, SiO, SO, H2CO, HCO(+), N2H(+), CS, OCS, HCN, and OH in the shocked clouds of IC 443. It is found that at position IC 443 B, (1) the shocked CO is optically thin; (2) the HCO(+)/CO abundance ratio is 4-9 x 10 to the -4 th, representing a tenfold enhancement over that of normal interstellar clouds; (3) there is no enhancement of SO or SIO, as occurs in Orion KL; and (4) there is optically thin preshock OH, confirming a hundredfold enhancement of the OH/CO ratio in the shock.

MagIC: Fluid dynamics in a spherical shell simulator

NASA Astrophysics Data System (ADS)

Wicht, J.; Gastine, T.; Barik, A.; Putigny, B.; Yadav, R.; Duarte, L.; Dintrans, B.

2017-09-01

MagIC simulates fluid dynamics in a spherical shell. It solves for the Navier-Stokes equation including Coriolis force, optionally coupled with an induction equation for Magneto-Hydro Dynamics (MHD), a temperature (or entropy) equation and an equation for chemical composition under both the anelastic and the Boussinesq approximations. MagIC uses either Chebyshev polynomials or finite differences in the radial direction and spherical harmonic decomposition in the azimuthal and latitudinal directions. The time-stepping scheme relies on a semi-implicit Crank-Nicolson for the linear terms of the MHD equations and a Adams-Bashforth scheme for the non-linear terms and the Coriolis force.

Development of Quantum Chemical Method to Calculate Half Maximal Inhibitory Concentration (IC50 ).

PubMed

Bag, Arijit; Ghorai, Pradip Kr

2016-05-01

Till date theoretical calculation of the half maximal inhibitory concentration (IC50 ) of a compound is based on different Quantitative Structure Activity Relationship (QSAR) models which are empirical methods. By using the Cheng-Prusoff equation it may be possible to compute IC50 , but this will be computationally very expensive as it requires explicit calculation of binding free energy of an inhibitor with respective protein or enzyme. In this article, for the first time we report an ab initio method to compute IC50 of a compound based only on the inhibitor itself where the effect of the protein is reflected through a proportionality constant. By using basic enzyme inhibition kinetics and thermodynamic relations, we derive an expression of IC50 in terms of hydrophobicity, electric dipole moment (μ) and reactivity descriptor (ω) of an inhibitor. We implement this theory to compute IC50 of 15 HIV-1 capsid inhibitors and compared them with experimental results and available other QASR based empirical results. Calculated values using our method are in very good agreement with the experimental values compared to the values calculated using other methods. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The defective nature of ice Ic and its implications for atmospheric science

NASA Astrophysics Data System (ADS)

Kuhs, W. F.; Hansen, T. C.

2009-04-01

The possible atmospheric implication of ice Ic (cubic ice) has already been suggested some time ago in the context of snow crystal formation [1]. New findings from air-borne measurements in cirrus clouds and contrails have put ice Ic into the focus of interest to understand the so-called "supersaturation puzzle" [2,3,4,5]. Our recent microstructural work on ice Ic [6,7] appears to be highly relevant in this context. We have found that ice Ic is characterized by a complex stacking fault pattern, which changes as a function of temperature as well as time. Indeed, from our own [8] and other group's work [9] one knows that (in contrast to earlier believe) ice Ic can form up to temperatures at least as high as 240K - thus in the relevant range for cirrus clouds. We have good preliminary evidence that the "cubicity" (which can be related to stacking fault probabilities) as well as the particle size of ice Ic are the relevant parameters for this correlation. The "cubicity" of stacking faulty ice Ic (established by diffraction) correlates nicely with the increased supersaturation at decreasing temperatures observed in cirrus clouds and contrails, a fact, which may be considered as further evidence for the presence of ice Ic. Moreover, the stacking faults lead to kinks in the outer shapes of the minute ice Ic crystals as seen by cryo scanning electron microscopy (cryo-SEM); these defective sites are likely to play some role in heterogeneous reactions in the atmosphere. The cryo-SEM work suggests that stacking-faulty ice Ic has many more active centres for such reactions than the usually considered thermodynamically stable form, ice Ih. [1] T Kobayashi & T Kuroda (1987) Snow Crystals. In: Morphology of Crystals (ed. I Sunagawa), Terra Scientific Publishing, Tokyo, pp.649-743. [2] DM Murphy (2003) Dehydration in cold clouds is enhanced by a transition from from cubic to hexagonal ice. Geophys.Res.Lett.,30, 2230, doi:10.1029/2003GL018566. [3] RS Gao & 19 other authors (2004

Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo).

PubMed

Kudenchuk, Peter J; Leroux, Brian G; Daya, Mohamud; Rea, Thomas; Vaillancourt, Christian; Morrison, Laurie J; Callaway, Clifton W; Christenson, James; Ornato, Joseph P; Dunford, James V; Wittwer, Lynn; Weisfeldt, Myron L; Aufderheide, Tom P; Vilke, Gary M; Idris, Ahamed H; Stiell, Ian G; Colella, M Riccardo; Kayea, Tami; Egan, Debra; Desvigne-Nickens, Patrice; Gray, Pamela; Gray, Randal; Straight, Ron; Dorian, Paul

2017-11-28

Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo ( P <0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge ( P =0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant

Properties of Protostars in the Elephant Trunk in the Globule IC 1396A

NASA Astrophysics Data System (ADS)

Reach, William T.; Faied, Dohy; Rho, Jeonghee; Boogert, Adwin; Tappe, Achim; Jarrett, Thomas H.; Morris, Patrick; Cambrésy, Laurent; Palla, Francesco; Valdettaro, Riccardo

2009-01-01

Extremely red objects, identified in the early Spitzer Space Telescope observations of the bright-rimmed globule IC 1396A and photometrically classified as Class I protostars and Class II T Tauri stars based on their mid-infrared (mid-IR) colors, were spectroscopically observed at 5.5-38 μm (Spitzer Infrared Spectrograph), at the 22 GHz water maser frequency (National Radio Astronomy Observatory Green Bank Telescope), and in the optical (Palomar Hale 5 m) to confirm their nature and further elucidate their properties. The sources photometrically identified as Class I, including IC 1396A:α, γ, δ, epsilon, and ζ, are confirmed as objects dominated by accretion luminosity from dense envelopes, with accretion rates 1-10 × 10-6 M sun yr-1 and present stellar masses 0.1-2 M sun. The Class I sources have extremely red continua, still rising at 38 μm, with a deep silicate absorption at 9-11 μm, weaker silicate absorption around 18 μm, and weak ice features including CO2 at 15.2 μm and H2O at 6 μm. The ice/silicate absorption ratio in the envelope is exceptionally low for the IC 1396A protostars, compared to those in nearby star-forming regions, suggesting that the envelope chemistry is altered by the radiation field or globule pressure. Only one 22 GHz water maser was detected in IC 1396A; it is coincident with a faint mid-IR source, offset from near the luminous Class I protostar IC 1396A:γ. The maser source, IC 1396A:γ b , has luminosity less than 0.1 L sun, the first H2O maser from such a low-luminosity object. Two near-infrared (NIR) H2 knots on opposite sides of IC 1396A:γ reveal a jet, with an axis clearly distinct from the H2O maser of IC 1396A:γ b . The objects photometrically classified as Class II, including IC 1396A:β, θ, Two Micron All Sky Survey (2MASS)J 21364964+5722270, 2MASSJ 21362507+5727502, LkHα 349c, Tr 37 11-2146, and Tr 37 11-2037, are confirmed as stars with warm, luminous disks, with a silicate emission feature at 9-11 μm, and

Institutional computing (IC) information session

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

Koch, Kenneth R; Lally, Bryan R

2011-01-19

The LANL Institutional Computing Program (IC) will host an information session about the current state of unclassified Institutional Computing at Los Alamos, exciting plans for the future, and the current call for proposals for science and engineering projects requiring computing. Program representatives will give short presentations and field questions about the call for proposals and future planned machines, and discuss technical support available to existing and future projects. Los Alamos has started making a serious institutional investment in open computing available to our science projects, and that investment is expected to increase even more.

TIF-IC, a factor involved in both transcription initiation and elongation of RNA polymerase I.

PubMed Central

Schnapp, G; Schnapp, A; Rosenbauer, H; Grummt, I

1994-01-01

We have characterized a transcription factor from Ehrlich ascites cells that is required for ribosomal gene transcription by RNA polymerase I (Pol I). This factor, termed TIF-IC, has a native molecular mass of 65 kDa, associates with Pol I, and is required both for the assembly of Sarkosyl-resistant initiation complexes and for the formation of the first internucleotide bonds. In addition to its function in transcription initiation, TIF-IC also plays a role in elongation of nascent RNA chains. At suboptimal levels of TIF-IC, transcripts with heterogeneous 3' ends are formed which are chased into full-length transcripts by the addition of more TIF-IC. Moreover, on a tailed template, which allows initiation in the absence of auxiliary factors, TIF-IC was found to stimulate the overall rate of transcription elongation and suppress pausing of Pol I. Thus TIF-IC appears to serve a function similar to the Pol II-specific factor TFIIF which is required for Pol II transcription initiation and elongation. Images PMID:8076598

Thackeray's Globules in IC 2944

NASA Technical Reports Server (NTRS)

2002-01-01

Strangely glowing dark clouds float serenely in this remarkable and beautiful image taken with NASA's Hubble Space Telescope. These dense, opaque dust clouds - known as 'globules' - are silhouetted against nearby bright stars in the busy star-forming region, IC 2944. These globules were first found in IC 2944 by astronomer A.D. Thackeray in 1950. Although globules like these have been known since Dutch-American astronomer Bart Bok first drew attention to such objects in 1947, little is still known about their origin and nature, except that they are generally associated with areas of star formation, called 'HII regions' due to the presence of hydrogen gas. The largest of the globules in this image is actually two separate clouds that gently overlap along our line of sight. Each cloud is nearly 1.4 light-years (50 arcseconds) along its longest dimension, and collectively, they contain enough material to equal over 15 solar masses. IC 2944, the surrounding HII region, is filled with gas and dust that is illuminated and heated by a loose cluster of O-type stars. These stars are much hotter and much more massive than our Sun. IC 2944 is relatively close by, located only 5900 light-years (1800 parsecs) away in the constellation Centaurus. Thanks to the remarkable resolution offered by the Hubble Space Telescope, astronomers can for the first time study the intricate structure of these globules. The globules appear to be heavily fractured, as if major forces were tearing them apart. When radio astronomers observed the faint hiss of molecules within the globules, they realized that the globules are actually in constant, churning motion, moving supersonically among each other. This may be caused by the powerful ultraviolet radiation from the luminous, massive stars, which also heat up the gas in the HII region, causing it to expand and stream against the globules, leading to their destruction. Despite their serene appearance, the globules may actually be likened to clumps

Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response.

PubMed

Gupta, Shishir Kumar; Yadav, Pavan Kumar; Tiwari, A K; Gandham, Ravi Kumar; Sahoo, A P

2016-09-01

The canine parvovirus NS1 (CPV2.NS1) protein selectively induces apoptosis in the malignant cells. However, for an effective in vivo tumor treatment strategy, an oncolytic agent also needs to induce a potent anti-tumor immune response. In the present study, we used poly (I:C), a TLR3 ligand, as an adjuvant along with CPV2.NS1 to find out if the combination can enhance the oncolytic activity by inducing a potent anti-tumor immune response. The 4T1 mammary carcinoma cells were used to induce mammary tumor in Balb/c mice. The results suggested that poly (I:C), when given along with CPV2.NS1, not only significantly reduced the tumor growth but also augmented the immune response against tumor antigen(s) as indicated by the increase in blood CD4+ and CD8+ counts and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed that Th1 cytokines (IFN-γ and IL-2) were significantly upregulated in the treatment group indicating activation of cell-mediated immune response. The present study reports the efficacy of CPV2.NS1 along with poly (I:C) not only in inhibiting the mammary tumor growth but also in generating an active anti-tumor immune response without any visible toxicity. The results of our study may help in developing CPV2.NS1 and poly (I: C) combination as a cancer therapeutic regime to treat various malignancies.

Specific and highly efficient condensation of GC and IC DNA by polyaza pyridinophane derivatives.

PubMed

Stojković, Marijana Radić; Gonzalez-Garcia, Jorge; Šupljika, Filip; Galiana-Rosello, Cristina; Guijarro, Lluis; Gazze, Salvatore A; Francis, Lewis W; Piantanida, Ivo; Garcia-Espana, Enrique

2018-04-01

Two bis-polyaza pyridinophane derivatives and their monomeric reference compounds revealed strong interactions with ds-DNA and RNA. The bis-derivatives show a specific condensation of GC- and IC-DNA, which is almost two orders of magnitude more efficient than the well-known condensation agent spermine. The type of condensed DNA was identified as ψ-DNA, characterized by the exceptionally strong CD signals. At variance to the almost silent AT(U) polynucleotides, these strong CD signals allow the determination of GC-condensates at nanomolar nucleobase concentrations. Detailed thermodynamic characterisation by ITC reveals significant differences between the DNA binding of the bis-derivative compounds (enthalpy driven) and that of spermine and of their monomeric counterparts (entropy driven). Atomic force microscopy confirmed GC-DNA compaction by the bis-derivatives and the formation of toroid- and rod-like structures responsible for the ψ-type pattern in the CD spectra. Copyright © 2017 Elsevier B.V. All rights reserved.

Optical Spectrum of the Compact Planetary Nebula IC 5117

NASA Technical Reports Server (NTRS)

Hyung, Siek; Aller, Lawrence H.; Feibelman, Walter A.; Lee, Seong-Jae; Fisher, Richard R. (Technical Monitor)

2001-01-01

High resolution spectroscopic data of the very compact planetary nebula IC 5117 are obtained in the optical wavelengths, 3700A - 10050A, with the Hamilton Echelle Spectrograph at Lick Observatory, and which have been analyzed along with the International Ultraviolet Explorer (IUE) UV archive data. Although a diagnostic diagram shows significant density and temperature fluctuations, our analysis indicates that the nebular gas may be represented by a homogeneous shell of extremely high density gas, N(sub epsilon) approx. 90 000 /cu cm. The average electron temperatures, e.g. indicated by the [OIII] diagnostics, are around 12 000 K. We construct a photoionization model to represent most of the observed line intensities, and the physical condition of this compact nebulosity. Based on the semi-empirical ionization correction approach, and model indications, we derived the elemental abundances: He, C, N, O, Ne, and Ar appear to be normal or marginally depleted compared to the average planetary nebula, while the remaining elements, S, Cl, and K appear to be enhanced. IC 5117 is perhaps a very young compact planetary nebula, slightly more evolved than the other well-known compact planetary nebula IC 4997. The central stellar temperature is likely to be around 120 000 K, evolved from a C-rich AGB progenitor.

Safety considerations in the pharmacological management of atrial fibrillation.

PubMed

Camm, A John

2008-07-21

The pharmacological management of atrial fibrillation (AF) requires careful consideration from a safety perspective. This article focuses primarily on maintenance therapy using antiarrhythmic drugs (AADs). The foremost safety issue for AADs is the propensity of class IA and III agents to cause torsade de pointes arrhythmias. Class IA drugs, particularly quinidine, can induce torsade de pointes at low or subtherapeutic doses, but higher doses are not necessarily associated with an increased incidence. 'Pure' class III drugs such as dofetilide induce torsade de pointes in a dose-related manner, but some class III agents with more complex actions such as amiodarone have a markedly lower potential to cause this arrhythmia. The risk of torsade de pointes precludes the use of class IA and 'pure' class III agents in patients with left ventricular hypertrophy and bradycardia. Class IC agents may cause sustained monomorphic ventricular tachycardias and are generally precluded in ischaemic and structural heart disease. Advanced heart failure patients may be treated with amiodarone or dofetilide, but most other AADs are unsuitable. The most important extracardiac toxicities occurring with AADs are those of amiodarone. Drug interactions are a significant safety issue in the management of AF, including pharmacokinetic interactions in which plasma levels of the AAD are raised - increasing the risk of proarrhythmia - and concomitant use of drugs that prolong the QT interval. Notwithstanding these considerations, most patients with AF can be considered for rhythm control, provided there is adequate pre-treatment assessment and protocols for initiation, dosing and monitoring are followed with care.

A GRB and Broad-lined Type Ic Supernova from a Single Central Engine

NASA Astrophysics Data System (ADS)

Barnes, Jennifer; Duffell, Paul C.; Liu, Yuqian; Modjaz, Maryam; Bianco, Federica B.; Kasen, Daniel; MacFadyen, Andrew I.

2018-06-01

Unusually high velocities (≳0.1c) and correspondingly high kinetic energies have been observed in a subset of Type Ic supernovae (so-called “broad-lined Ic” supernovae; SNe Ic-BL), prompting a search for a central engine model capable of generating such energetic explosions. A clue to the explosion mechanism may lie in the fact that all supernovae that accompany long-duration gamma-ray bursts (GRBs) belong to the SN Ic-BL class. Using a combination of two-dimensional relativistic hydrodynamics and radiation transport calculations, we demonstrate that the central engine responsible for long GRBs can also trigger an SN Ic-BL. We find that a reasonable GRB engine injected into a stripped Wolf–Rayet progenitor produces a relativistic jet with energy ∼1051 erg, as well as an SN whose synthetic light curves and spectra are fully consistent with observed SNe Ic-BL during the photospheric phase. As a result of the jet’s asymmetric energy injection, the SN spectra and light curves depend on viewing angle. The impact of viewing angle on the spectrum is particularly pronounced at early times, while the viewing-angle dependence for the light curves (∼10% variation in bolometric luminosity) persists throughout the photospheric phase.

New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents.

PubMed

Radini, Ibrahim Ali M; Elsheikh, Tarek M Y; El-Telbani, Emad M; Khidre, Rizk E

2016-07-14

A novel series of dihydropyrimidines (DHPMs) 4a-j; 2-oxopyran-3-carboxylate 7a,b; 1-amino-1,2-dihydropyridine-3-carboxylate 8; and 1,3,4-oxadiazole derivatives 12 with quinolinyl residues have been synthesized in fairly good yields. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. In vitro antimalarial evaluation of the synthesized quinoline derivatives against Plasmodium falciparum revealed them to possess moderate to high antimalarial activities, with IC50 values ranging from 0.014-5.87 μg/mL. Compounds 4b,g,i and 12 showed excellent antimalarial activity against to Plasmodium falciparum compared with the antimalarial agent chloroquine (CQ).

Psychosocial co-morbidities in Interstitial Cystitis/Bladder Pain syndrome (IC/BPS): A systematic review.

PubMed

McKernan, Lindsey C; Walsh, Colin G; Reynolds, William S; Crofford, Leslie J; Dmochowski, Roger R; Williams, David A

2018-03-01

Psychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self-management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment. Following PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics. Thirty-four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta-analyses shows mean Mental Component Score of the Short-Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where <36 is consistent with severe psychological impairment. Averaged across studies, the population scored in the range seen in clinical depression (CES-D 19.89, SD 13.12, N = 564) and generalized anxiety disorder (HADS-A 8.15, SD 4.85, N = 465). The psychological impact of IC/BPS is pervasive and severe. Existing evidence of treatment is lacking and suggests self-management intervention may be helpful. © 2017 Wiley Periodicals, Inc.

Reliability and validity of a new scale on internal coherence (ICS) of cancer patients

PubMed Central

Kröz, Matthias; Büssing, Arndt; von Laue, Hans Broder; Reif, Marcus; Feder, Gene; Schad, Friedemann; Girke, Matthias; Matthes, Harald

2009-01-01

Background Current inventories on quality of life used in oncology mainly focus on functional aspects of patients in the context of disease adaption and treatments (side) effects (EORTC QLQ C30) or generically the status of common functions (Medical Outcome Study SF 36). Beyond circumscribed dimensions of quality of life (i.e., physical, emotional, social, cognitive etc.), there is a lack of inventories which also address other relevant dimensions such as the 'sense of coherence' (SOC) in cancer patients. SOC is important because of its potential prognostic relevance in cancer patients, but the current SOC scale has mainly been validated for psychiatric and psychosomatic patients. Our two-step validation study addresses the internal coherence (ICS) scale, which is based on expert rating, using specific items for oncological patients, with respect to its reliability, validity and sensitivity to chemotherapy. Methods The items were tested on 114 participants (57 cancer patients and a matched control group), alongside questions on autonomic regulation (aR), the Hospital Anxiety and Depression Scale (HADS), self-regulation (SRQ) and Karnofsky the Performance-Index (KPI). A retest of 65 participants was carried out after a median time span of four weeks. In the second part of the study, the ICS was used to assess internal coherence during chemotherapy in 25 patients with colorectal carcinoma (CRC) and 17 breast cancer patients. ICS was recorded before, during and 4 – 8 weeks after treatment. Results The 10-item scale of 'internal coherence' (ICS) shows good to very good reliability: Cronbach-α r = 0.91, retest-reliability r = 0.80. The ICS correlates with r = 0.43 – 0.72 to the convergence criteria (all p < 0.001). We are able to show decreased ICS-values after the third cycle for CRC and breast cancer patients, with a subsequent increase of ICS scores after the end of chemotherapy. Conclusion The ICS has good to very good reliability, validity and sensitivity to

Tests of shock chemistry in IC 443G

NASA Technical Reports Server (NTRS)

Turner, B. E.; Chan, Kin-Wing; Green, S.; Lubowich, D. A.

1992-01-01

Eight molecular species, in the hot dense clump IC 443G, believed to be impacted by the shock wave from the SNR IC 443, are investigated. The clump consists of two distinct regions, one relatively cool, and one hotter and denser. Region 1 contains CO, HCO(+), HCN, and CN, whose abundances may be explained either by ion-molecule chemistry, or by a D shock of 60-90 km/s, passing through a clump of about 100,000/cu cm. Region 2 gives rise to SiO, CS, SO, and H2CO, and requires an ND shock of 5-15 km/s passing through a region of about 1,000,000/cu cm. Observed fractional abundances fit ND shock models if L is about 6.6 x 10 exp 15 cm. In general, observed line widths vary inversely with derived excitation density, while centroid velocities of all species are essentially identical.

Broad-line Type Ic supernova SN 2014ad

NASA Astrophysics Data System (ADS)

Sahu, D. K.; Anupama, G. C.; Chakradhari, N. K.; Srivastav, S.; Tanaka, Masaomi; Maeda, Keiichi; Nomoto, Ken'ichi

2018-04-01

We present optical and ultraviolet photometry and low-resolution optical spectroscopy of the broad-line Type Ic supernova SN 2014ad in the galaxy PGC 37625 (Mrk 1309), covering the evolution of the supernova during -5 to +87 d with respect to the date of maximum in the B band. A late-phase spectrum obtained at +340 d is also presented. With an absolute V-band magnitude at peak of MV = -18.86 ± 0.23 mag, SN 2014ad is fainter than supernovae associated with gamma ray bursts (GRBs), and brighter than most of the normal and broad-line Type Ic supernovae without an associated GRB. The spectral evolution indicates that the expansion velocity of the ejecta, as measured using the Si II line, is as high as ˜33 500 km s-1 around maximum, while during the post-maximum phase it settles at ˜15 000 km s-1. The expansion velocity of SN 2014ad is higher than that of all other well-observed broad-line Type Ic supernovae except for the GRB-associated SN 2010bh. The explosion parameters, determined by applying Arnett's analytical light-curve model to the observed bolometric light-curve, indicate that it was an energetic explosion with a kinetic energy of ˜(1 ± 0.3) × 1052 erg and a total ejected mass of ˜(3.3 ± 0.8) M⊙, and that ˜0.24 M⊙ of 56Ni was synthesized in the explosion. The metallicity of the host galaxy near the supernova region is estimated to be ˜0.5 Z⊙.

Estimation of Ksub Ic from slow bend precracked Charpy specimen strength ratios

NASA Technical Reports Server (NTRS)

Succop, G.; Brown, W. F., Jr.

1976-01-01

Strength ratios are reported which were derived from slow bend tests on 0.25 inch thick precracked Charpy specimens of steels, aluminum alloys, and a titanium alloy for which valid K sub Ic values were established. The strength ratios were used to develop calibration curves typical of those that could be useful in estimating K sub Ic for the purposes of alloy development of quality control.

Nitric oxide fails to confer endogenous antiarrhythmic cardioprotection in the primate heart in vitro.

PubMed

Pabla, R; Curtis, M J

2007-04-01

The role of nitric oxide (NO) in cardiac pathophysiology remains controversial. According to data from several studies using rat and rabbit isolated hearts, NO is an endogenous cardioprotectant against reperfusion-induced ventricular fibrillation (VF). Thus, if cardiac NO production is abolished by perfusion with L-N(G)-nitro-L-arginine methylester (L-NAME) (100 microM) there is a concomittant increase in the incidence of reperfusion-induced VF, with L-NAME's effects on NO and VF prevented by L- (but not D-) arginine co-perfusion. To make a better estimate of the clinical relevance of these findings, 100 microM L-NAME was tested in primate hearts under similar conditions. Marmoset (Callithrix jaccus) hearts, isolated and perfused, were subjected to 60 min left regional ischaemia followed by 10 min reperfusion in vitro. The ECG was recorded and NO in coronary effluent measured by chemiluminescence. L-NAME (100 micro M) decreased NO in coronary effluent throughout ischaemia and reperfusion (e.g. from 3720+/-777 pmol min(-1) g(-1) in controls to 699+/-98 pmol min(-1) g(-1) after 5 min of ischaemia) and, during ischaemia, lowered coronary flow and reduced heart rate, actions identical to those seen in rat and rabbit hearts. However, the incidence of reperfusion-induced VF was unchanged (20%, with or without L-NAME). A species difference exists in the effectiveness of endogenous NO to protect hearts against reperfusion-induced VF. The present primate data, which presumably take precedence over rat and rabbit data, cast doubt on the clinical relevance of NO as an endogenous, antiarrhythmic, cardioprotectant.

Publications - IC 35 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 35 Publication Details Title: Alaska's mineral industry 1991: A summary Authors: Bundtzen, T.K ., 1992, Alaska's mineral industry 1991: A summary: Alaska Division of Geological & Geophysical

Publications - IC 36 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 36 Publication Details Title: Alaska's mineral industry 1992: A summary Authors: Swainbank, R.C ., 1993, Alaska's mineral industry 1992: A summary: Alaska Division of Geological & Geophysical

Publications - IC 40 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 40 Publication Details Title: Alaska's mineral industry 1994: A summary Authors: Swainbank, R.C mineral industry 1994: A summary: Alaska Division of Geological & Geophysical Surveys Information

Watching AGN feedback at its birth: HST observations of nascent outflow host IC860

NASA Astrophysics Data System (ADS)

Alatalo, Katherine

2016-10-01

IC860 is a nearby IR-luminous early-type spiral with a unique set of properties: it is a shocked, poststarburst galaxy that hosts an AGN-driven neutral wind and a compact core of molecular gas. IC860 can serve as a rosetta stone for the early stages of triggering AGN feedback. We propose to use WFC3 on HST to obtain NUV, optical and near-IR imaging of IC860. We will create a spatially-resolved history of star formation quenching through SED-fitting of 7 requested broadband filters, and compare the spatially resolved star formation histories to in different positions within the underlying stellar features (such as spiral structure) that might define a narrative of how star formation is quenching in IC860. These observations will also resolve the super-star cluster sites to trace the most recent star formation. Finally, these observations will trace the mass of the outflow by building an absorption map of the dust. IC860 presents a unique opportunity to study a galaxy at an early stage of transitioning from blue spiral to red early-type galaxy, that also hosts an AGN-driven neutral wind and a compact, turbulent molecular gas core.

A high ratio of IC31® adjuvant to antigen is necessary for H4 TB vaccine immunomodulation

PubMed Central

Aboutorabian, Sepideh; Hakimi, Jalil; Boudet, Florence; Montano, Sandrine; Dookie, Annie; Roque, Cristopher; Ausar, Salvador F; Rahman, Nausheen; Brookes, Roger H

2015-01-01

A tuberculosis (TB) vaccine consisting of a recombinant fusion protein (H4) and a novel TLR9 adjuvant (IC31) is in clinical development. To better understand the H4-IC31 ratio, we measured the binding capacity of IC31 for H4 protein and immunized mice with formulations that contained limiting to excess ratios of IC31 to H4. An immunomodulated H4-specific IFNγ response was only observed when IC31 was present in excess of H4. Since TLR expression is species-specific and the vaccine is intended to boost BCG-primed immunity, we questioned whether data in mice would translate to humans. To address this question, we used the fresh human Whole Blood (hWB) recovered from BCG-vaccinated subjects to screen H4-IC31 formulations. We found IC31 modulation in hWB to be quite distinct from the TLR4-Adjuvant. Unlike TLR4-Adjuvant, IC31 formulations did not induce the pro-inflammatory cytokine TNFα, but modulated a robust H4-specific IFNγ response after 12 d of culture. We then re-stimulated the fresh hWB of 5 BCG-primed subjects with formulations that had excess or limiting IC31 binding for H4 protein and again found that an immunomodulated H4-specific IFNγ response needed an excess of IC31. Finally, we monitored the zeta (ζ) potential of H4-IC31 formulations and found that the overall charge of H4-IC31 particles changes from negative to positive once IC31 is in greater than 9-fold excess. Using two diverse yet mutually supportive approaches, we confirm the need for an excess of IC31 adjuvant in H4 TB vaccine formulations and suggest surface potential may be an important factor. PMID:25997147

A high ratio of IC31(®) adjuvant to antigen is necessary for H4 TB vaccine immunomodulation.

PubMed

Aboutorabian, Sepideh; Hakimi, Jalil; Boudet, Florence; Montano, Sandrine; Dookie, Annie; Roque, Cristopher; Ausar, Salvador F; Rahman, Nausheen; Brookes, Roger H

2015-01-01

A tuberculosis (TB) vaccine consisting of a recombinant fusion protein (H4) and a novel TLR9 adjuvant (IC31) is in clinical development. To better understand the H4-IC31 ratio, we measured the binding capacity of IC31 for H4 protein and immunized mice with formulations that contained limiting to excess ratios of IC31 to H4. An immunomodulated H4-specific IFNγ response was only observed when IC31 was present in excess of H4. Since TLR expression is species-specific and the vaccine is intended to boost BCG-primed immunity, we questioned whether data in mice would translate to humans. To address this question, we used the fresh human Whole Blood (hWB) recovered from BCG-vaccinated subjects to screen H4-IC31 formulations. We found IC31 modulation in hWB to be quite distinct from the TLR4-Adjuvant. Unlike TLR4-Adjuvant, IC31 formulations did not induce the pro-inflammatory cytokine TNFα, but modulated a robust H4-specific IFNγ response after 12 d of culture. We then re-stimulated the fresh hWB of 5 BCG-primed subjects with formulations that had excess or limiting IC31 binding for H4 protein and again found that an immunomodulated H4-specific IFNγ response needed an excess of IC31. Finally, we monitored the zeta (ζ) potential of H4-IC31 formulations and found that the overall charge of H4-IC31 particles changes from negative to positive once IC31 is in greater than 9-fold excess. Using two diverse yet mutually supportive approaches, we confirm the need for an excess of IC31 adjuvant in H4 TB vaccine formulations and suggest surface potential may be an important factor.

Young Low-Mass Stars and Brown Dwarfs in IC 348

NASA Astrophysics Data System (ADS)

Luhman, K. L.

1999-11-01

I present new results from a continuing program to identify and characterize the low-mass stellar and substellar populations in the young cluster IC 348 (0.5-10 Myr). Optical spectroscopy has revealed young objects with spectral types as late as M8.25. The intrinsic J-H and H-K colors of these sources are dwarflike, whereas the R-I and I-J colors appear intermediate between the colors of dwarfs and giants. Furthermore, the spectra from 6500 to 9500 Å are reproduced well with averages of standard dwarf and giant spectra, suggesting that such averages should be used in the classification of young late-type sources. An H-R diagram is constructed for the low-mass population in IC 348 (K6-M8). The presumably coeval components of the young quadruple system GG Tau (White et al.) and the locus of stars in IC 348 are used as empirical isochrones to test the theoretical evolutionary models. The calculations of Burrows et al. do not appear to be consistent with the data at these earliest stages of stellar evolution. There is fair agreement between the data and the model isochrones of D'Antona & Mazzitelli, except near the hydrogen-burning limit. The agreement cannot be improved by changing the conversion between spectral types and effective temperatures. On the other hand, for the models of Baraffe et al., an adjustment of the temperature scale to progressively warmer temperatures at later M types, intermediate between dwarfs and giants, brings all components of GG Tau onto the same model isochrone and gives the population of IC 348 a constant age and age spread as a function of mass. When other observational constraints are considered, such as the dynamical masses of GM Aur, DM Tau, and GG Tau A, the models of Baraffe et al. are the most consistent with observations of young systems. With compatible temperature scales, the models of both D'Antona & Mazzitelli and Baraffe et al. suggest that the hydrogen-burning mass limit occurs near M6 at ages of <~10 Myr. Thus, several

Recent Progresses in Laboratory Astrophysics with Ames’ COSmIC Facility

NASA Astrophysics Data System (ADS)

Salama, Farid; Contreras, Cesar; Sciamma-O'Brien, Ella; Bejaoui, Salma

2016-06-01

We present and discuss the characteristics and the capabilities of the laboratory facility, COSmIC, that was developed at NASA Ames to generate, process and analyze interstellar, circumstellar and planetary analogs in the laboratory [1]. COSmIC stands for “Cosmic Simulation Chamber” and is dedicated to the study of neutral and ionized molecules and nano particles under the low temperature and high vacuum conditions that are required to simulate space environments. COSmIC integrates a variety of state-of-the-art instruments that allow forming, processing and monitoring simulated space conditions for planetary, circumstellar and interstellar materials in the laboratory. COSmIC is composed of a Pulsed Discharge Nozzle (PDN) expansion that generates a plasma in free supersonic jet expansion coupled to two high-sensitivity, complementary in situ diagnostics: a Cavity Ring Down Spectroscopy (CRDS) and laser induced fluorescence (LIF) systems for photonic detection and a Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection [2].Recent laboratory results that were obtained using COSmIC will be presented, in particular the progress that has been achieved in the domain of the diffuse interstellar bands (DIBs) [3] and in monitoring, in the laboratory, the formation of dust grains and aerosols from their gas-phase molecular precursors in environments as varied as stellar/circumstellar outflows [4] and planetary atmospheres [5]. Plans for future, next generation, laboratory experiments on cosmic molecules and grains in the growing field of laboratory astrophysics will also be addressed as well as the implications of the current studies for astronomy.References: [1] Salama F., In Organic Matter in Space, IAU Symposium 251, Kwok & Sandford Eds.Cambridge University Press, Vol. 4, S251, p. 357 (2008) and references therein.[2] Ricketts C., Contreras C., Walker, R., Salama F., Int. J. Mass Spec, 300, 26 (2011)[3] Salama F., Galazutdinov G., Krelowski J

Antidysrhythmic agents at the turn of the twenty-first century: a current review.

PubMed

Haugh, Kathy Henley

2002-03-01

The use of class IA agents is gradually on the decline, primarily as a result of its unfavorable risk-to-benefit ratio. Lidocaine, a class IB agent, has been widely used in the acute treatment of VT. However, alternate drugs are being considered increasingly as first-line agents in the acute treatment of VT. Class IC drugs are contraindicated in patients with structural cardiac abnormalities and have a limited usefulness in the management of dysrhythmias. Beta-blockers continue to increase their role in cardiology, and subsequently their use in managing dysrhythmias. Class III agents, including amiodarone, sotalol, ibutilide, and dofetilide, are among the most widely used antidysrhythmics. Class IV calcium channel blockers have a limited usefulness in tachydysrhythmias. Digoxin and adenosine have unique antidysrhythmic properties and will likely retain their roles as antidysrhythmic agents. In the wake of the effectiveness of amiodarone, the drug that crosses all classes, some now question the benefit of pure agents that block a single, specific ion channel in the heart. After CAST8 demonstrated that antidysrhythmics can increase mortality while seemingly suppressing dysrhythmias, new drugs will continue to undergo intense scrutiny with regard to their efficacy, safety, and usefulness in treating dysrhythmias.

Protecting ICS Systems Within the Energy Sector from Cyber Attacks

NASA Astrophysics Data System (ADS)

Barnes, Shaquille

Advance persistent threat (APT) groups are continuing to attack the energy sector through cyberspace, which poses a risk to our society, national security, and economy. Industrial control systems (ICSs) are not designed to handle cyber-attacks, which is why asset owners need to implement the correct proactive and reactive measures to mitigate the risk to their ICS environments. The Industrial Control Systems Cyber Emergency Response Team (ICS-CERT) responded to 290 incidents for fiscal year 2016, where 59 of those incidents came from the Energy Sector. APT groups know how vulnerable energy sector ICS systems are and the destruction they can cause when they go offline such as loss of production, loss of life, and economic impact. Defending against APT groups requires more than just passive controls such as firewalls and antivirus solutions. Asset owners should implement a combination of best practices and active defense in their environment to defend against APT groups. Cyber-attacks against critical infrastructure will become more complex and harder to detect and respond to with traditional security controls. The purpose of this paper was to provide asset owners with the correct security controls and methodologies to help defend against APT groups.

Definition of intercultural competence (IC) in undergraduate students at a private university in the USA: A mixed-methods study

PubMed Central

Gierke, Lioba; Binder, Nadine; Heckmann, Mark; Odağ, Özen; Leiser, Anne

2018-01-01

Introduction Intercultural competence (IC) is an important skill to be gained from higher education. However, it remains unclear what IC means to students and what factors might influence their definitions of IC. The aim of the current study was to qualitatively assess how students at one higher education institution in the USA define IC and to quantitatively test for relationships among IC components and various demographic characteristics, including intercultural experience and study context. A further aim was to descriptively compare the IC definitions from the US sample with the definitions obtained from another sample of university students in Germany. Materials and methods A purposive sample of n = 93 undergraduate, second semester students at Dickinson College, USA, participated in the study by completing an online questionnaire. The qualitative data were content-analyzed to define the dimensions of IC. The quantitative data were cluster-analyzed to assess the multivariate relationships among the IC components and the demographic characteristics of the sample. Results The most important dimensions of IC were Knowledge, External Outcomes (interaction, communication), and Attitudes (respect, tolerance) according to the US sample. The most frequently chosen dimensions of IC differed between both samples: Knowledge was chosen by the sample in the USA while External Outcomes was chosen by the sample in Germany. Relative to the US sample, significantly more students chose Attitudes, External Outcomes, and Intrapersonal Skills in the sample in Germany. The relationships among IC components and demographic characteristics were only weak in the US sample. A person with IC was rated as Open-minded and Respectful by students who lived predominantly in the USA or Tolerant and Curious by those who lived outside the USA for at least six months. Discussion The current results suggest that students residing in two countries (USA or Germany) define IC using similar

Definition of intercultural competence (IC) in undergraduate students at a private university in the USA: A mixed-methods study.

PubMed

Gierke, Lioba; Binder, Nadine; Heckmann, Mark; Odağ, Özen; Leiser, Anne; Kedzior, Karina Karolina

2018-01-01

Intercultural competence (IC) is an important skill to be gained from higher education. However, it remains unclear what IC means to students and what factors might influence their definitions of IC. The aim of the current study was to qualitatively assess how students at one higher education institution in the USA define IC and to quantitatively test for relationships among IC components and various demographic characteristics, including intercultural experience and study context. A further aim was to descriptively compare the IC definitions from the US sample with the definitions obtained from another sample of university students in Germany. A purposive sample of n = 93 undergraduate, second semester students at Dickinson College, USA, participated in the study by completing an online questionnaire. The qualitative data were content-analyzed to define the dimensions of IC. The quantitative data were cluster-analyzed to assess the multivariate relationships among the IC components and the demographic characteristics of the sample. The most important dimensions of IC were Knowledge, External Outcomes (interaction, communication), and Attitudes (respect, tolerance) according to the US sample. The most frequently chosen dimensions of IC differed between both samples: Knowledge was chosen by the sample in the USA while External Outcomes was chosen by the sample in Germany. Relative to the US sample, significantly more students chose Attitudes, External Outcomes, and Intrapersonal Skills in the sample in Germany. The relationships among IC components and demographic characteristics were only weak in the US sample. A person with IC was rated as Open-minded and Respectful by students who lived predominantly in the USA or Tolerant and Curious by those who lived outside the USA for at least six months. The current results suggest that students residing in two countries (USA or Germany) define IC using similar dimensions. However, IC definitions may depend on the

Publications - IC 58 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 58 Publication Details Title: Alaska's mineral industry 2008: A summary Authors: Szumigala, D.J summary: Alaska Division of Geological & Geophysical Surveys Information Circular 58, 15 p. http

30 CFR 57.22102 - Smoking (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22102 Smoking (I-C mines). (a...

Innate immune responses against rock bream iridovirus (RBIV) infection in rock bream (Oplegnathus fasciatus) following poly (I:C) administration.

PubMed

Jung, Myung-Hwa; Jung, Sung-Ju

2017-12-01

Poly (I:C) showed promise as an immunoprotective agents in rock bream against rock bream iridovirus (RBIV) infection. In this study, we evaluated the time-dependent virus replication pattern and antiviral immune responses in RBIV-infected rock bream with and without poly (I:C) administration. In the poly (I:C)+virus-injected group, virus copy numbers were more than 18.9-, 24.0- and 479.2-fold lower than in the virus only injected group at 4 (4.73 × 10 4 and 8.95 × 10 5 /μl, respectively), 7 (3.67 × 10 5 and 8.81 × 10 6 /μl, respectively) and 10 days post infection (dpi) (1.26 × 10 5 and 6.02 × 10 7 /μl, respectively). Moreover, significantly high expression levels of TLR3 (8.6- and 7.7-fold, at 4 and 7 dpi, respectively) and IL1β (3.6-fold at 2 dpi) were observed in the poly (I:C)+virus-injected group, but the expression levels were not significantly in the virus-injected group. However, IL8 and TNFα expression levels showed no statistical significance in both groups. Mx, ISG15 and PKR were significantly highly expressed from 4 to 10 dpi in the virus-injected group. Nevertheless, in the poly (I:C)+virus-injected group, Mx and ISG15 expression were significantly expressed from 2 dpi. In summary, poly (I:C) administration in rock bream induces TLR3, IL1β, Mx and ISG15-mediated immune responses, which could be a critical factor for inhibition of virus replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model

PubMed Central

Osborne, Ashleigh L; Solowij, Nadia; Babic, Ilijana; Huang, Xu-Feng; Weston-Green, Katrina

2017-01-01

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (p<0.01). CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model (p<0.01 vs POLY+VEH), did not affect total body weight gain, food or water intake, and had no effect in control animals (all p>0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia. PMID:28230072

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model.

PubMed

Osborne, Ashleigh L; Solowij, Nadia; Babic, Ilijana; Huang, Xu-Feng; Weston-Green, Katrina

2017-06-01

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring (PN56) were injected twice daily with 10 mg/kg CBD (CONT+CBD, POLY+CBD; n=12 per group) or vehicle (VEH; CONT+VEH, POLY+VEH; n=12 per group) for 3 weeks. Body weight, food and water intake was measured weekly. The Novel Object Recognition and rewarded T-maze alternation tests assessed recognition and working memory, respectively, and the social interaction test assessed sociability. POLY+VEH offspring exhibited impaired recognition and working memory, and reduced social interaction compared to CONT+VEH offspring (p<0.01). CBD treatment significantly improved recognition, working memory and social interaction deficits in the poly I:C model (p<0.01 vs POLY+VEH), did not affect total body weight gain, food or water intake, and had no effect in control animals (all p>0.05). In conclusion, chronic CBD administration can attenuate the social interaction and cognitive deficits induced by prenatal poly I:C infection. These novel findings present interesting implications for potential use of CBD in treating the cognitive deficits and social withdrawal of schizophrenia.

APC10.1 cells as a model for assessing the efficacy of potential chemopreventive agents in the Apc(Min) mouse model in vivo.

PubMed

Sale, Stewart; Fong, Isabel L; de Giovanni, Carla; Landuzzi, Lorena; Brown, Karen; Steward, William P; Gescher, Andreas J

2009-11-01

Apc(Min) mice are widely used for mechanism and efficacy studies associated with the development of chemopreventive agents. APC10.1 cells have been derived from Apc(Min) mouse adenomas and retain the heterozygous Apc genotype. We tested the hypothesis that this cell type may provide an in vitro model to predict chemopreventive activity of agents in the Apc(Min) mouse in vivo. The growth inhibitory properties of 14 putative colorectal cancer chemopreventive agents, tricin, apigenin, 3',4',5',5,7-pentamethoxyflavone, resveratrol, curcumin, 3,4-methylenedioxy-3',4',5'-trimethoxychalcone (DMU135), 3,4,5,4'-tetramethoxystilbene (DMU212), celecoxib, aspirin, piroxicam, all-trans-retinoic acid, difluoromethylornithine (DFMO), quercetin and cyanidin-3-glucoside, were studied in this cell line, and the IC(50) values were calculated. The IC(50) values were plotted against previously published data of reduction of adenoma numbers caused by these agents in Apc(Min) mice. The correlation co-efficient was 0.678 (p<0.01), suggesting that there was a tentative correlation between the ability to inhibit the growth of APC10.1 cells and the ability to delay adenoma development in vivo. If this relationship is supported by using further agents, APC10.1 cells may serve in the future as an initial screen to prioritise compounds for assessing chemopreventive efficacy in Apc(Min) mice in vivo. Such a screen could reduce the number of animals required to find active agents, help reduce costs and increase throughput.

Ultrafast VHE Gamma-Ray Flares of IC 310

NASA Astrophysics Data System (ADS)

Barkov, Maxim V.; Aharonian, Felix; Khangulyan, Dmitriy V.

In 2012 November MAGIC detected a bright flare from IC 310. The flare consisted of two sharp peaks with a typical duration of ~ 5 min. The energy released during that event has been estimated to be at the level of 2 × 1044 erg s-1. In this work we derive an upper limit on the possible luminosity of flares generated in black hole (BH) magnetosphere, which depends very weakly on the mass of BH and is determined by disk magnetisation, viewing angle, and pair multiplicity. Since all these parameters are smaller than a unit, the luminosity 2 × 1043 erg s-1 can be taken as a strict upper limit for flare luminosity for several minutes variability time. This upper limit appears to be approximately an order of magnitude below the value measured with MAGIC. Thus, we conclude that it seems very unfeasible that the magnetospheric processes can be indeed behind the bright flaring activity recorded from IC 310.

VizieR Online Data Catalog: Optical & Spitzer photometry in IC 1805 (Sung+, 2017)

NASA Astrophysics Data System (ADS)

Sung, H.; Bessell, M. S.; Chun, M.-Y.; Yi, J.; Naze, Y.; Lim, B.; Karimov, R.; Rauw, G.; Park, B.-G.; Hur, H.

2017-06-01

For a study of the IMF and the star-formation history of the young open cluster IC 1805, we obtained deep wide-field VRI and Hα images of IC 1805 using the CFH12K mosaic CCD camera of the CFHT on 2002 January 6 and 7. We also observed several regions in IC 1805, for a study of the reddening and massive star content, using the SITe 2000x800 CCD (Maidanak 2k CCD) and standard UBVRI filters of the AZT-22 1.5m telescope at the Maidanak Astronomical Observatory in Uzbekistan on 2003 August 18 and 2004 december 25,30. Later, we obtained additional images of the central region of IC 1805 with the Fairchild 486 CCD (SNUCam) and UBVI and Hα filters of the AZT-22 telescope on 2007 October 7 and 2009 January 19. The Spitzer mapping observations were performed on 2006 September 20 under program ID 20052 (PI: S. Wolff). For complete photometry of stars in the CFH12K FOV in 3.6 and 4.5um, we also downloaded and reduced the GLIMPSE360 data (AOR: 38753280, 38763264, 38769408, 38799104, 38798592, 38784512, PI: B. A. Whitney). MIPS scans of IC 1805 were obtained on 2005 August 31 and 2005 September 2 (PID 3234, PI: J. S. Greeves). The Chandra X-ray Observatory Observations of IC 1805 (ObsID: 7033, PI: L. Townley) were made on 2006 November 25. The total exposure time was about 79ks. The properties of 647 X-ray sources were published in Townsley+ (2014,J/ApJS/213/1). We searched for the optical and MIR counterparts of these X-ray sources with a matching radius of up to 1.5". (4 data files).

Publications - IC 39 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 39 Publication Details Title: Alaska's mineral industry 1993: A summary Authors: Bundtzen, T.K 1993: A summary: Alaska Division of Geological & Geophysical Surveys Information Circular 39, 11 p

Publications - IC 41 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 41 Publication Details Title: Alaska's mineral industry 1995: A summary Authors: Bundtzen, T.K 1995: A summary: Alaska Division of Geological & Geophysical Surveys Information Circular 41, 12 p

Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent.

PubMed

Patsilinakos, Sotirios; Christou, Apostolos; Kafkas, Nikolaos; Nikolaou, Nikolaos; Antonatos, Dionysios; Katsanos, Spyridon; Spanodimos, Stavros; Babalis, Dimitrios

2010-09-01

Ibutilide is a class III antiarrhythmic agent indicated for cardioversion of atrial fibrillation and atrial flutter to sinus rhythm (SR). The most serious complication of ibutilide is torsades de pointes (TdP). Magnesium has been successfully used for the treatment of TdP, but its use as a prophylactic agent for this arrhythmia has not yet been established. The present study investigated whether high dose of magnesium would increase the safety and efficacy of ibutilide administration. A total of 476 patients with atrial fibrillation or atrial flutter who were candidates for conversion to SR were divided into 2 groups. Group A consisted of 229 patients who received ibutilide to convert atrial fibrillation or atrial flutter to SR. Group B consisted of 247 patients who received an intravenous infusion of 5 g of magnesium sulfate for 1 hour followed by the administration of ibutilide. Then, another 5 g of magnesium were infused for 2 additional hours. Of the patients in groups A and B, 154 (67.3%) and 189 (76.5%), respectively, were converted to SR (p = 0.033). Ventricular arrhythmias (sustained, nonsustained ventricular tachycardia, and TdP) occurred significantly more often in group A than in group B (7.4% vs 1.2%, respectively, p = 0.002). TdP developed in 8 patients (3.5%) in group A and in none (0%) in group B (p = 0.009). The administration of magnesium (despite the high doses used) was well tolerated. In conclusion, the administration of high doses of magnesium probably makes ibutilide a much safer agent, and magnesium increased the conversion efficacy of ibutilide. 2010 Elsevier Inc. All rights reserved.

IC 5181: An S0 Galaxy with Ionized Gas on Polar Orbits

NASA Astrophysics Data System (ADS)

Pizzella, A.; Morelli, L.; Corsini, E. M.; Dalla Bontá, E.; Cesetti, M.

2014-05-01

The nearby S0 galaxy IC 5181 is studied to address the origin of the ionized gas component that orbits the galaxy on polar orbit. We perform detailed photometric and spectroscopic observations measuring the surface brightness distribution of the stars (I band), ionized gas of IC 5181 (Hα narrow band), the ionized-gas and stellar kinematics along both the major and minor axis, and the corresponding line strengths of the Lick indices. We conclude that the galaxy hosts a geometrically and kinematically decoupled component of ionized gas. It is elongated along the galaxy minor axis and in orthogonal rotation with respect to the galaxy disk. The result is suggesting that the gas component is not related to the stars having an external origin. The gas was accreted by IC 5181 on polar orbits from the surrounding environment.

30 CFR 57.22233 - Actions at 0.5 percent methane (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.5 percent methane (I-C mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22233 Actions at 0.5 percent methane (I-C mines). If methane reaches 0.5 percent in the mine atmosphere, ventilation changes...

30 CFR 57.22233 - Actions at 0.5 percent methane (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.5 percent methane (I-C mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22233 Actions at 0.5 percent methane (I-C mines). If methane reaches 0.5 percent in the mine atmosphere, ventilation changes...

BCH codes for large IC random-access memory systems

NASA Technical Reports Server (NTRS)

Lin, S.; Costello, D. J., Jr.

1983-01-01

In this report some shortened BCH codes for possible applications to large IC random-access memory systems are presented. These codes are given by their parity-check matrices. Encoding and decoding of these codes are discussed.

Publications - IC 54 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 54 Publication Details Title: Alaska's mineral industry 2006: A summary Authors: Szumigala, D.J Bibliographic Reference Szumigala, D.J., and Hughes, R.A., 2007, Alaska's mineral industry 2006: A summary

Improvements to the Magnetics Information Consortium (MagIC) Paleo and Rock Magnetic Database

NASA Astrophysics Data System (ADS)

Jarboe, N.; Minnett, R.; Tauxe, L.; Koppers, A. A. P.; Constable, C.; Jonestrask, L.

2015-12-01

The Magnetic Information Consortium (MagIC) database (http://earthref.org/MagIC/) continues to improve the ease of data uploading and editing, the creation of complex searches, data visualization, and data downloads for the paleomagnetic, geomagnetic, and rock magnetic communities. Online data editing is now available and the need for proprietary spreadsheet software is therefore entirely negated. The data owner can change values in the database or delete entries through an HTML 5 web interface that resembles typical spreadsheets in behavior and uses. Additive uploading now allows for additions to data sets to be uploaded with a simple drag and drop interface. Searching the database has improved with the addition of more sophisticated search parameters and with the facility to use them in complex combinations. A comprehensive summary view of a search result has been added for increased quick data comprehension while a raw data view is available if one desires to see all data columns as stored in the database. Data visualization plots (ARAI, equal area, demagnetization, Zijderveld, etc.) are presented with the data when appropriate to aid the user in understanding the dataset. MagIC data associated with individual contributions or from online searches may be downloaded in the tab delimited MagIC text file format for susbsequent offline use and analysis. With input from the paleomagnetic, geomagnetic, and rock magnetic communities, the MagIC database will continue to improve as a data warehouse and resource.

A New Interface for the Magnetics Information Consortium (MagIC) Paleo and Rock Magnetic Database

NASA Astrophysics Data System (ADS)

Jarboe, N.; Minnett, R.; Koppers, A. A. P.; Tauxe, L.; Constable, C.; Shaar, R.; Jonestrask, L.

2014-12-01

The Magnetic Information Consortium (MagIC) database (http://earthref.org/MagIC/) continues to improve the ease of uploading data, the creation of complex searches, data visualization, and data downloads for the paleomagnetic, geomagnetic, and rock magnetic communities. Data uploading has been simplified and no longer requires the use of the Excel SmartBook interface. Instead, properly formatted MagIC text files can be dragged-and-dropped onto an HTML 5 web interface. Data can be uploaded one table at a time to facilitate ease of uploading and data error checking is done online on the whole dataset at once instead of incrementally in an Excel Console. Searching the database has improved with the addition of more sophisticated search parameters and with the ability to use them in complex combinations. Searches may also be saved as permanent URLs for easy reference or for use as a citation in a publication. Data visualization plots (ARAI, equal area, demagnetization, Zijderveld, etc.) are presented with the data when appropriate to aid the user in understanding the dataset. Data from the MagIC database may be downloaded from individual contributions or from online searches for offline use and analysis in the tab delimited MagIC text file format. With input from the paleomagnetic, geomagnetic, and rock magnetic communities, the MagIC database will continue to improve as a data warehouse and resource.

Construction Progress of the S-IC Test Stand-Steel Reinforcements

NASA Technical Reports Server (NTRS)

1961-01-01

At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken September 15, 1961, shows the installation of the reinforcing steel prior to the pouring of the concrete foundation walls.

Metabolism of the tropine indole-3-carboxylate ICS 205-930 by differentiated rat and human hepatoma cells.

PubMed

Fischer, V; Baldeck, J P; Wiebel, F J

The metabolism of the tropine indole-3-carboxylate ICS 205-930 (ICS), a highly potent and selective antagonist of 5-HT3 receptors, was investigated in continuous cell lines derived from rat or human liver and compared to the in vivo metabolism in rat and human. The well-differentiated rat hepatoma line 2sFou extensively metabolized ICS by hydroxylation of the indole moiety and subsequent conjugation to form the corresponding glucuronides and sulfates. The 2sFou cells also oxidized ICS at the tropinyl moiety to form both N-demethyl and N-oxide derivatives. The relative amount of the various metabolites was dependent on the substrate concentration. Pretreatment of the cells with dexamethasone increased the rate of metabolism for all pathways, while benz[a]anthracene caused an increase in hydroxylation at the indole moiety at the expense of N-oxidation. Phenobarbital pretreatment had no effect on ICS metabolism. The pattern of metabolites formed in 2sFou cells was qualitatively similar to that formed in rat urine. The human hepatoma line HepG2 metabolized ICS only to a small extent. The HepG2 cells failed to form detectable amounts of ICS conjugates found in human urine. The N-oxide-ICS was not found in HepG2 cells or in human urine. Virtually no ICS metabolites were found in human lung adenocarcinoma lines NCI-H358 or NCI-H322. The results suggest that continuous cell lines such as the differentiated rat hepatoma cells 2sFou might be used to mimic the metabolism of xenobiotics in rat and to clarify their complex metabolic pathways.

Publications - IC 42 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 42 Publication Details Title: Alaska's mineral industry 1996: A summary Authors: Swainbank, R.C ., Bundtzen, T.K., Clough, A.H., and Henning, M.W., 1997, Alaska's mineral industry 1996: A summary: Alaska

Classification of PSN J12015272-1852183 as a young type Ic SN

NASA Astrophysics Data System (ADS)

Harutyunyan, A.; Benetti, S.; Pastorello, A.; Cappellaro, E.; Tomasella, L.; Ochner, P.; Turatto, M.

2013-06-01

We report the spectroscopic classification (range 335-785 nm; resolution 1.5 nm) of PSN J12015272-1852183 discovered by the CHASE project on June 22.12 UT. The spectrogram obtained on June 23.88 UT with the TNG Telescope (+Dolores), shows that this is a type-Ic supernova. A good match is found with the type-Ic supernova 1994I (Millard et al 1999, ApJ 527, 746) at about six days before maximum light.

The Iron-Responsive Fur/RyhB Regulatory Cascade Modulates the Shigella Outer Membrane Protease IcsP ▿ †

PubMed Central

Africa, Lia A. A.; Murphy, Erin R.; Egan, Nicholas R.; Wigley, Amanda F.; Wing, Helen J.

2011-01-01

Actin-based motility is central to the pathogenicity of the intracellular bacterial pathogen Shigella. Two Shigella outer membrane proteins, IcsA and IcsP, are required for efficient actin-based motility in the host cell cytoplasm, and the genes encoding both proteins are carried on the large virulence plasmid. IcsA triggers actin polymerization on the surface of the bacterium, leading to the formation of an actin tail that allows both intra- and intercellular spread. IcsP, an outer membrane protease, modulates the amount and distribution of the IcsA protein on the bacterial surface through proteolytic cleavage of IcsA. Transcription of icsP is increased in the presence of VirB, a DNA-binding protein that positively regulates many genes carried on the large virulence plasmid. In Shigella dysenteriae, the small regulatory RNA RyhB, which is a member of the iron-responsive Fur regulon, suppresses several virulence-associated phenotypes by downregulating levels of virB in response to iron limitation. Here we show that the Fur/RyhB regulatory pathway downregulates IcsP levels in response to low iron concentrations in Shigella flexneri and that this occurs at the level of transcription through the RyhB-dependent regulation of VirB. These observations demonstrate that in Shigella species the Fur/RyhB regulatory pathway provides a mechanism to finely tune the expression of icsP in response to the low concentrations of free iron predicted to be encountered within colonic epithelial cells. PMID:21859852

Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.

PubMed

Slavik, R S; Tisdale, J E; Borzak, S

2001-01-01

This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (i.v.) procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, i.v. ibutilide is more effective than placebo and i.v. procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred i.v. agent and propafenone a preferred oral agent. For conversion of recent-onset AF of longer duration (less than 90 days), i.v. ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method

Installation of C-6533(XE-2)/ARC ICS in UH-1H helicopter

NASA Astrophysics Data System (ADS)

Hnat, J. A.

1980-07-01

This report documents the results of the installation of the C-6533(XE-2)/ARC ICS in UH-1H helicopter. Installation was performed at the AEL, Inc., Monmouth County Airport facility. Design of each installation was coordinated and approved by the Government. The mechanical and electrical installation drawings for the helicopter are attached as Appendix A of this report. The new ICS system consisted of new cabling, new intercoms and helmets rewired with new microphones. All four crew stations of the helicopter were reconfigured with the new system. Existing cabling for the standard ICS system remained in the aircraft but was securely stowed for later restoration of the aircraft. The helmets (4) were rewired using separate jacks for headphones and microphone lines. Transmit and receive cables were installed in the aircraft with a minimum separation of one inch between cables. A junction box was fabricated and installed on the aft end of the console to house the fan-out terminal strips. Transmit and receive lines' separation was maintained in the junction box. During the test phase the onboard radios were used with the new ICS system.

Publications - IC 50 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

Mapping Advisory Board STATEMAP Publications Geophysics Program Information Geophysical Survey ic050.pdf (999.0 K) Keywords Aeromagnetic; Aeromagnetic Map; Aeromagnetic Survey; Alaska Peninsula ; Coal; Conductivity Survey; Construction Materials; Copper; Cretaceous; Delta River; Diamonds; Drilling

SN 2017dio: A Type-Ic Supernova Exploding in a Hydrogen-rich Circumstellar Medium

NASA Astrophysics Data System (ADS)

Kuncarayakti, Hanindyo; Maeda, Keiichi; Ashall, Christopher J.; Prentice, Simon J.; Mattila, Seppo; Kankare, Erkki; Fransson, Claes; Lundqvist, Peter; Pastorello, Andrea; Leloudas, Giorgos; Anderson, Joseph P.; Benetti, Stefano; Bersten, Melina C.; Cappellaro, Enrico; Cartier, Régis; Denneau, Larry; Della Valle, Massimo; Elias-Rosa, Nancy; Folatelli, Gastón; Fraser, Morgan; Galbany, Lluís; Gall, Christa; Gal-Yam, Avishay; Gutiérrez, Claudia P.; Hamanowicz, Aleksandra; Heinze, Ari; Inserra, Cosimo; Kangas, Tuomas; Mazzali, Paolo; Melandri, Andrea; Pignata, Giuliano; Rest, Armin; Reynolds, Thomas; Roy, Rupak; Smartt, Stephen J.; Smith, Ken W.; Sollerman, Jesper; Somero, Auni; Stalder, Brian; Stritzinger, Maximilian; Taddia, Francesco; Tomasella, Lina; Tonry, John; Weiland, Henry; Young, David R.

2018-02-01

SN 2017dio shows both spectral characteristics of a type-Ic supernova (SN) and signs of a hydrogen-rich circumstellar medium (CSM). Prominent, narrow emission lines of H and He are superposed on the continuum. Subsequent evolution revealed that the SN ejecta are interacting with the CSM. The initial SN Ic identification was confirmed by removing the CSM interaction component from the spectrum and comparing with known SNe Ic and, reversely, adding a CSM interaction component to the spectra of known SNe Ic and comparing them to SN 2017dio. Excellent agreement was obtained with both procedures, reinforcing the SN Ic classification. The light curve constrains the pre-interaction SN Ic peak absolute magnitude to be around {M}g=-17.6 mag. No evidence of significant extinction is found, ruling out a brighter luminosity required by an SN Ia classification. These pieces of evidence support the view that SN 2017dio is an SN Ic, and therefore the first firm case of an SN Ic with signatures of hydrogen-rich CSM in the early spectrum. The CSM is unlikely to have been shaped by steady-state stellar winds. The mass loss of the progenitor star must have been intense, \\dot{M}∼ 0.02{({ε }{{H}α }/0.01)}-1 ({v}{wind}/500 km s‑1) ({v}{shock}/10,000 km s‑1)‑3 M ⊙ yr‑1, peaking at a few decades before the SN. Such a high mass-loss rate might have been experienced by the progenitor through eruptions or binary stripping. Based on observations made with the NOT, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. This work is based (in part) on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile as part of PESSTO, (the Public ESO Spectroscopic Survey for Transient Objects Survey) ESO program 188.D-3003, 191.D-0935, 197.D-1075. Based on observations made with the Liverpool Telescope operated on the

Recent Progress in Laboratory Astrophysics and Astrochemistry Achieved with the COSmIC Facility

NASA Technical Reports Server (NTRS)

Salama, Farid; Sciamma-O'Brien, Ella; Bejaoui, Salma

2017-01-01

We describe the characteristics and the capabilities of the laboratory facility, COSmIC, that was developed at NASA Ames to generate, process and analyze interstellar, circumstellar and planetary analogs in the laboratory. COSmIC stands for "Cosmic Simulation Chamber" and is dedicated to the study of neutral and ionized molecules and nanoparticles under the low temperature and high vacuum conditions that are required to simulate various space environments such as diffuse interstellar clouds, circumstellar outflows and planetary atmospheres. COSmIC integrates a variety of state-of-the-art instruments that allow recreating simulated space conditions to generate, process and monitor cosmic analogs in the laboratory. The COSmIC experimental setup is composed of a Pulsed Discharge Nozzle (PDN) expansion, that generates a plasma in the stream of a free supersonic jet expansion, coupled to high-sensitivity, complementary in situ diagnostics: cavity ring down spectroscopy (CRDS) and laser induced fluorescence (LIF) systems for photonic detection, and Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection. Recent results obtained using COSmIC will be highlighted. In particular, the progress that has been achieved in the domain of the diffuse interstellar bands (DIBs) and in monitoring, in the laboratory, the formation of circumstellar dust grains and planetary atmosphere aerosols from their gas-phase molecular precursors. Plans for future laboratory experiments on interstellar and planetary molecules and grains will also be addressed, as well as the implications of the studies underway for astronomical observations and past and future space mission data analysis.

High ESD Breakdown-Voltage InP HBT Transimpedance Amplifier IC for Optical Video Distribution Systems

NASA Astrophysics Data System (ADS)

Sano, Kimikazu; Nagatani, Munehiko; Mutoh, Miwa; Murata, Koichi

This paper is a report on a high ESD breakdown-voltage InP HBT transimpedance amplifier IC for optical video distribution systems. To make ESD breakdown-voltage higher, we designed ESD protection circuits integrated in the TIA IC using base-collector/base-emitter diodes of InP HBTs and resistors. These components for ESD protection circuits have already existed in the employed InP HBT IC process, so no process modifications were needed. Furthermore, to meet requirements for use in optical video distribution systems, we studied circuit design techniques to obtain a good input-output linearity and a low-noise characteristic. Fabricated InP HBT TIA IC exhibited high human-body-model ESD breakdown voltages (±1000V for power supply terminals, ±200V for high-speed input/output terminals), good input-output linearity (less than 2.9-% duty-cycle-distortion), and low noise characteristic (10.7pA/√Hz averaged input-referred noise current density) with a -3-dB-down higher frequency of 6.9GHz. To the best of our knowledge, this paper is the first literature describing InP ICs with high ESD-breakdown voltages.

Revealing the nebular properties and Wolf-Rayet population of IC10 with Gemini/GMOS

NASA Astrophysics Data System (ADS)

Tehrani, Katie; Crowther, Paul A.; Archer, I.

2017-12-01

We present a deep imaging and spectroscopic survey of the Local Group irregular galaxy IC10 using Gemini North and GMOS to unveil its global Wolf-Rayet (WR) population. We obtain a star formation rate (SFR) of 0.045 ± 0.023 M⊙ yr-1, for IC10 from the nebular H α luminosity, which is comparable to the Small Magellanic Cloud. We also present a revised nebular oxygen abundance of log(O/H) + 12 = 8.40 ± 0.04, comparable to the LMC. It has previously been suggested that for IC10 to follow the WR subtype-metallicity dependance seen in other Local Group galaxies, a large WN population awaits discovery. Our search revealed three new WN stars, and six candidates awaiting confirmation, providing little evidence to support this claim. The new global WR star total of 29 stars is consistent with the Large Magellanic Cloud population when scaled to the reduced SFR of IC10. For spectroscopically confirmed WR stars, the WC/WN ratio is lowered to 1.0; however, including all potential candidates, and assuming those unconfirmed to be WN stars, would reduce the ratio to ∼0.7. We attribute the high WC/WN ratio to the high star formation surface density of IC10 relative to the Magellanic Clouds, which enhances the frequency of high-mass stars capable of producing WC stars.

The effect of electroacupuncture at the MA-IC 3 endocrine ear acupoint on fasting blood glucose levels in type 2 diabetes mellitus patients

NASA Astrophysics Data System (ADS)

Simadibrata, C.; Budihardjo, F. A.; Srilestari, A.

2017-08-01

The management of diabetes mellitus (DM) involves education, nutritional intervention, and physical exercise, in addition to pharmacological interventions, with the long-term goal of preventing complications through the control of blood glucose levels. Several studies have shown that acupuncture, both conventional acupuncture and electroacupuncture, is useful for lowering blood glucose levels in patients with DM. This study aimed to determine the additional effect of electroacupuncture at the MA-IC 3 Endocrine ear acupoint on fasting blood glucose levels in patients with Type 2 DM who were receiving oral hypoglycemic agents at Banjar General Hospital. In this randomized controlled study, fifty-four study participants who were being treated with oral antidiabetics were allocated into two groups, receiving either electroacupuncture (EA) at the MA-IC 3 ear acupoint with dense disperse wave for 30 minutes or acupuncture at the same point and for the same duration but without EA (No EA). Fasting blood glucose levels were measured before and after the intervention. In Group A (EA), the mean fasting blood glucose (FBG) level decreased from 157.26±24.485 to 142.59±26.771 (p < 0.05), whereas in Group B (No EA), the mean FBG decreased from 149.67±21.485 to 148.74±21.326 (p < 0.05). The difference in the amount of FBG decrease between Group A (EA) and Group B (No EA) was statistically significant (p < 0.05). EA at the MA-IC 3 Endocrine lowers FBG levels to a greater degree than acupuncture with no EA in patients with type 2 DM.

Laser mass spectrometry of chemical warfare agents using ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Weickhardt, C.; Grun, C.; Grotemeyer, J.

1998-12-01

Fast relaxation processes in excited molecules such as IC, ISC, and fragmentation are observed in many environmentally and technically relevant substances. They cause severe problems to resonance ionization mass spectrometry because they reduce the ionization yield and lead to mass spectra which do not allow the identification of the compound. By the use of ultrashort laser pulses these problems can be overcome and the advantages of REMPI over conventional ionization techniques in mass spectrometry can be regained. This is demonstrated using soil samples contaminated with a chemical warfare agent.

Detection of kanamycin and gentamicin residues in animal-derived food using IgY antibody based ic-ELISA and FPIA.

PubMed

Li, Cui; Zhang, Yaoyao; Eremin, Sergei A; Yakup, Omar; Yao, Gang; Zhang, Xiaoying

2017-07-15

Our aim in this study is to show that IgY antibody based immunoassays could be used to detect antibiotic residues in animal-derived food. Briefly, full antigens of gentamicin (Gent) and kanamycin (Kana) were used to immunize the laying chickens to prepare IgY antibodies. Then, these antibodies were evaluated by FPIA and ic-ELISA to detect Gent/Kana in animal-derived samples. The IC 50 of FPIA and ic-ELISA based anti-Gent IgY were 7.70±0.6μg/mL and 0.32±0.06μg/mL, respectively. The IC 50 of FPIA and ic-ELISA based anti-Kana IgY were 7.97±0.9μg/mL and 0.15±0.01μg/mL. The limits of detection (LOD, IC 10 ) for FPIA based anti-Gent/Kana IgY were 0.17 and 0.007μg/mL, respectively. The LOD for ic-ELISA were both 0.001μg/mL. These results indicated that the ic-ELISA might more suitable for antibiotic residues detection than FPIA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modernizing the MagIC Paleomagnetic and Rock Magnetic Database Technology Stack to Encourage Code Reuse and Reproducible Science

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A. A. P.; Jarboe, N.; Jonestrask, L.; Tauxe, L.; Constable, C.

2016-12-01

The Magnetics Information Consortium (https://earthref.org/MagIC/) develops and maintains a database and web application for supporting the paleo-, geo-, and rock magnetic scientific community. Historically, this objective has been met with an Oracle database and a Perl web application at the San Diego Supercomputer Center (SDSC). The Oracle Enterprise Cluster at SDSC, however, was decommissioned in July of 2016 and the cost for MagIC to continue using Oracle became prohibitive. This provided MagIC with a unique opportunity to reexamine the entire technology stack and data model. MagIC has developed an open-source web application using the Meteor (http://meteor.com) framework and a MongoDB database. The simplicity of the open-source full-stack framework that Meteor provides has improved MagIC's development pace and the increased flexibility of the data schema in MongoDB encouraged the reorganization of the MagIC Data Model. As a result of incorporating actively developed open-source projects into the technology stack, MagIC has benefited from their vibrant software development communities. This has translated into a more modern web application that has significantly improved the user experience for the paleo-, geo-, and rock magnetic scientific community.

Cobra venom cytotoxins; apoptotic or necrotic agents?

PubMed

Ebrahim, Karim; Shirazi, Farshad H; Mirakabadi, Abbas Zare; Vatanpour, Hossein

2015-12-15

Organs homeostasis is controlled by a dynamic balance between cell proliferation and apoptosis. Failure to induction of apoptosis has been implicated in tumor development. Cytotoxin-I (CTX-I) and cytotoxin-II (CTX-II) are two physiologically active polypeptides found in Caspian cobra venom. Anticancer activity and mechanism of cell death induced by these toxins have been studied. The toxins were purified by different chromatographic steps and their cytotoxicity and pattern of cell death were determined by MTT, LDH release, acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis, caspase-3 activity and neutral red assays. The IC50 of CTX-II in MCF-7, HepG2, DU-145 and HL-60 was 4.1 ± 1.3, 21.2 ± 4.4, 9.4 ± 1.8 μg/mL and 16.3 ± 1.9 respectively while the IC50 of this toxin in normal MDCK cell line was 54.5 ± 3.9 μg/mL. LDH release suddenly increase after a specific toxins concentrations in all cell lines. AO/EtBr double staining, flow cytometric analysis and caspase-3 activity assay confirm dose and time-dependent induction of apoptosis by both toxins. CTX-I and CTX-II treated cells lost their lysosomal membrane integrity and couldn't uptake neutral red day. CTX-I and CTX-II showed significant anticancer activity with minimum effects on normal cells and better IC50 compared to current anticancer drug; cisplatin. They induce their apoptotic effect via lysosomal pathways and release of cathepsins to cytosol. These effects were seen in limited rage of toxins concentrations and pattern of cell death rapidly changes to necrosis by increase in toxin's concentration. In conclusion, significant apoptogenic effects of these toxins candidate them as a possible anticancer agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

PubMed Central

Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.

PubMed

Araya, Romina E; Jury, Jennifer; Bondar, Constanza; Verdu, Elena F; Chirdo, Fernando G

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.

Solving the 56Ni Puzzle of Magnetar-powered Broad-lined Type IC Supernovae

NASA Astrophysics Data System (ADS)

Wang, Ling-Jun; Han, Yan-Hui; Xu, Dong; Wang, Shan-Qin; Dai, Zi-Gao; Wu, Xue-Feng; Wei, Jian-Yan

2016-11-01

Broad-lined Type Ic supernovae (SNe Ic-BL) are of great importance because their association with long-duration gamma-ray bursts (LGRBs) holds the key to deciphering the central engine of LGRBs, which refrains from being unveiled despite decades of investigation. Among the two popularly hypothesized types of central engine, I.e., black holes and strongly magnetized neutron stars (magnetars), there is mounting evidence that the central engine of GRB-associated SNe (GRB-SNe) is rapidly rotating magnetars. Theoretical analysis also suggests that magnetars could be the central engine of SNe Ic-BL. What puzzled the researchers is the fact that light-curve modeling indicates that as much as 0.2{--}0.5 {M}⊙ of 56Ni was synthesized during the explosion of the SNe Ic-BL, which is unfortunately in direct conflict with current state-of-the-art understanding of magnetar-powered 56Ni synthesis. Here we propose a dynamic model of magnetar-powered SNe to take into account the acceleration of the ejecta by the magnetar, as well as the thermalization of the injected energy. Assuming that the SN kinetic energy comes exclusively from the magnetar acceleration, we find that although a major fraction of the rotational energy of the magnetar is to accelerate the SN ejecta, a tiny fraction of this energy deposited as thermal energy of the ejecta is enough to reduce the needed 56Ni to 0.06 M ⊙ for both SN 1997ef and SN 2007ru. We therefore suggest that magnetars could power SNe Ic-BL in aspects both of energetics and of 56Ni synthesis.

75 FR 51499 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Digital I&C...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Digital I&C Systems The ACRS Subcommittee on Digital Instrumentation and Controls (I&C) Systems...: Wednesday, September 8, 2010--8:30 a.m. until 12 p.m. The Subcommittee will review Digital I&C Interim Staff...

[Eosinophilic spongiosis and ICS antibodies in a child with strophulus-like dermatosis].

PubMed

Klein, G F; Hintner, H; Fristch, P O

1984-01-01

Eosinophilic spongiosis associated with in vivo-bound antibodies to the epidermal intercellular space (ICS) were consistently observed in a recurrent strophulus-like eruption in an 11-year-old boy, thus suggesting pemphigus. The clinical course, however, ruled this diagnosis out since neither acantholysis nor the clinical picture of pemphigus developed in a period of 2.5 years. Since in vivo-bound ICS-antibodies have been described in several case reports of bullous impetigo we speculate that immune reactions to bacterial antigens may be involved in producing eruptions mimicking pemphigus vulgaris.

Spatially Resolved Spectroscopy of the SNR IC443

NASA Astrophysics Data System (ADS)

Gorenstein, P.

1998-07-01

IC 443 is a supernova remnant of intermediate age, i.e. a few thousand years. It is especially interesting because part of its periphery is expanding into a molecular cloud while other sections are expanding into a typical interstellar medium of much lower density. Since the evolution of a supernova remnant through its various phases is affected by the density of the medium it expands into with the reasonable assumption that the supernova explosion was approximately symmetric we have an opportunity to observe a single object in two phases simultaneously. It was observed by ASCA in April, 1993 for a short period during the PV phase and more thoroughly in a 42 ksec exposure in March, 1994. The latter measurement provides most of the results that have been reported. Most of the analysis took place after the grant ended but is included here for completeness. The data was sent simultaneously to US and Japanese Pls. We worked independently. The software set of FTOOLs was used to construct images and spectra. They were judged to be rather unintuitive and not at all user friendly. I found I was using one FTOOL to read the header to obtain information that would only be provided to another FTOOL. The Japanese investigators were more successful. They analyzed the data and published results more rapidly. The scientific results summarized below are based primarily on their publications. Since IC 443 is an interesting example of a middle aged SNR in which a variety of processes are occurring it is one of a class. IC 443 exhibits shell-like emission in hard X-rays and extended soft X-rays with thin thermal spectra. It resembles SN 1006 in these respects. IC 443 contains hard X-rays in a semi-circular shell surrounding the thermal component. The total hard X-ray flux in the ASCA FOV is only a half of the Ginga hard component; which suggests that the hard X-rays are not confined only in the shell but some are extended larger than the ASCA FOV of eq 1 degree diameter. Japanese

Spatially Resolved Spectroscopy of the SNR IC443

NASA Technical Reports Server (NTRS)

Gorenstein, P.

1998-01-01

IC 443 is a supernova remnant of intermediate age, i.e. a few thousand years. It is especially interesting because part of its periphery is expanding into a molecular cloud while other sections are expanding into a typical interstellar medium of much lower density. Since the evolution of a supernova remnant through its various phases is affected by the density of the medium it expands into with the reasonable assumption that the supernova explosion was approximately symmetric we have an opportunity to observe a single object in two phases simultaneously. It was observed by ASCA in April, 1993 for a short period during the PV phase and more thoroughly in a 42 ksec exposure in March, 1994. The latter measurement provides most of the results that have been reported. Most of the analysis took place after the grant ended but is included here for completeness. The data was sent simultaneously to US and Japanese Pls. We worked independently. The software set of FTOOLs was used to construct images and spectra. They were judged to be rather unintuitive and not at all user friendly. I found I was using one FTOOL to read the header to obtain information that would only be provided to another FTOOL. The Japanese investigators were more successful. They analyzed the data and published results more rapidly. The scientific results summarized below are based primarily on their publications. Since IC 443 is an interesting example of a middle aged SNR in which a variety of processes are occurring it is one of a class. IC 443 exhibits shell-like emission in hard X-rays and extended soft X-rays with thin thermal spectra. It resembles SN 1006 in these respects. IC 443 contains hard X-rays in a semi-circular shell surrounding the thermal component. The total hard X-ray flux in the ASCA FOV is only a half of the Ginga hard component; which suggests that the hard X-rays are not confined only in the shell but some are extended larger than the ASCA FOV of eq 1 degree diameter. Japanese

Publications - IC 17 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS IC 17 Publication Details Title: Coal resources of Alaska Authors: Alaska Division of Geological Statewide Bibliographic Reference Alaska Division of Geological & Geophysical Surveys, 1983, Coal Alaska Statewide Maps; Coal; Healy; Resource Assessment; Usibelli Mine Top of Page Department of Natural

30 CFR 57.22104 - Open flames (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

....22104 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Fire Prevention and Control § 57.22104 Open flames (I-C...

New Risk Curves for NHTSA's Brain Injury Criterion (BrIC): Derivations and Assessments.

PubMed

Laituri, Tony R; Henry, Scott; Pline, Kevin; Li, Guosong; Frankstein, Michael; Weerappuli, Para

2016-11-01

The National Highway Traffic Safety Administration (NHTSA) recently published a Request for Comments regarding a potential upgrade to the US New Car Assessment Program (US NCAP) - a star-rating program pertaining to vehicle crashworthiness. Therein, NHTSA (a) cited two metrics for assessing head risk: Head Injury Criterion (HIC15) and Brain Injury Criterion (BrIC), and (b) proposed to conduct risk assessment via its risk curves for those metrics, but did not prescribe a specific method for applying them. Recent studies, however, have indicated that the NHTSA risk curves for BrIC significantly overstate field-based head injury rates. Therefore, in the present three-part study, a new set of BrIC-based risk curves was derived, an overarching head risk equation involving risk curves for both BrIC and HIC15 was assessed, and some additional candidatepredictor- variable assessments were conducted. Part 1 pertained to the derivation. Specifically, data were pooled from various sources: Navy volunteers, amateur boxers, professional football players, simple-fall subjects, and racecar drivers. In total, there were 4,501 cases, with brain injury reported in 63. Injury outcomes were approximated on the Abbreviated Injury Scale (AIS). The statistical analysis was conducted subject to ordinal logistic regression analysis (OLR), such that the various levels of brain injury were cast as a function of BrIC. The resulting risk curves, with Goodman Kruksal Gamma=0.83, were significantly different than those from NHTSA. Part 2 pertained to the assessment relative to field data. Two perspectives were considered: "aggregate" (ΔV=0-56 km/h) and "point" (high-speed, regulatory focus). For the aggregate perspective, the new risk curves for BrIC were applied in field models pertaining to belted, mid-size, adult drivers in 11-1 o'clock, full-engagement frontal crashes in the National Automotive Sampling System (NASS, 1993-2014 calendar years). For the point perspective, BrIC data from tests

Rotational Periods and Starspot Activity of Young Solar-Type Dwarfs in the Open Cluster IC 4665

NASA Technical Reports Server (NTRS)

Allain, S.; Bouvier, J.; Prosser, C.; Marschall, L. A.; Laaksonen, B. D.

1995-01-01

We present the results of a V-band photometric monitoring survey of 15 late-type dwarfs in the young open cluster IC 4665. Low-amplitude periodic light variations are found for 8 stars and ascribed to the modulation by starspots that cover typically a few percent of the stellar disk. Periods range from 0.6 to 3.7 d, translating to equatorial velocities between 13 and 93 km/s. That no period longer than 4 d was detected suggests a relative paucity of extremely slow rotators (V(sub eq) much less than 10 km/s) among late-type dwarfs in IC 4665. The fractional number of slow rotators in IC 4665 is similar to that of Alpha Per cluster, suggesting that IC 4665 is close in age to Alpha Per (approx. 50 Myr).

A remarkably large depleted core in the Abell 2029 BCG IC 1101

NASA Astrophysics Data System (ADS)

Dullo, Bililign T.; Graham, Alister W.; Knapen, Johan H.

2017-10-01

We report the discovery of an extremely large (Rb ˜2.77 arcsec ≈ 4.2 kpc) core in the brightest cluster galaxy, IC 1101, of the rich galaxy cluster Abell 2029. Luminous core-Sérsic galaxies contain depleted cores - with sizes (Rb) typically 20-500 pc - that are thought to be formed by coalescing black hole binaries. We fit a (double nucleus) + (spheroid) + (intermediate-scale component) + (stellar halo) model to the Hubble Space Telescope surface brightness profile of IC 1101, finding the largest core size measured in any galaxy to date. This core is an order of magnitude larger than those typically measured for core-Sérsic galaxies. We find that the spheroid's V-band absolute magnitude (MV) of -23.8 mag (˜25 per cent of the total galaxy light, I.e. including the stellar halo) is faint for the large Rb, such that the observed core is 1.02 dex ≈ 3.4σs (rms scatter) larger than that estimated from the Rb-MV relation. The suspected scouring process has produced a large stellar mass deficit (Mdef) ˜4.9 × 1011 M⊙, I.e. a luminosity deficit ≈28 per cent of the spheroid's luminosity prior to the depletion. Using IC 1101's black hole mass (MBH) estimated from the MBH-σ, MBH-L and MBH-M* relations, we measure an excessive and unrealistically high number of 'dry' major mergers for IC 1101 (I.e. N ≳ 76) as traced by the large Mdef/MBH ratios of 38-101. The large core, high mass deficit and oversized Mdef/MBH ratio of IC 1101 suggest that the depleted core was scoured by overmassive SMBH binaries with a final coalesced mass MBH ˜ (4-10) × 1010 M⊙, I.e. ˜ (1.7-3.2) × σs larger than the black hole masses estimated using the spheroid's σ, L and M*. The large core might be partly due to oscillatory core passages by a gravitational radiation-recoiled black hole.

Synthesis and evaluation of new benzodioxole-based dithiocarbamate derivatives as potential anticancer agents and hCA-I and hCA-II inhibitors.

PubMed

Altıntop, Mehlika Dilek; Sever, Belgin; Akalın Çiftçi, Gülşen; Kucukoglu, Kaan; Özdemir, Ahmet; Soleimani, Seyedeh Sara; Nadaroglu, Hayrunnisa; Kaplancıklı, Zafer Asım

2017-01-05

In the current work, new benzodioxole-based dithiocarbamate derivatives were synthesized via the reaction of N-(1,3-benzodioxol-5-ylmethyl)-2-chloroacetamide with appropriate sodium salts of N,N-disubstituted dithiocarbamic acids. These derivatives were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and C6 rat glioma cell lines. N-(1,3-Benzodioxol-5-ylmethyl)-2-[4-(4-nitrophenyl)-1-piperazinylthiocarbamoylthio]acetamide (10) can be identified as the most promising anticancer agent against C6 cell line due to its notable inhibitory effect on C6 cells with an IC 50 value of 23.33 ± 7.63 μg/mL when compared with cisplatin (IC 50  = 19.00 ± 5.29 μg/mL). On the other hand, compound 10 did not show any significant cytotoxic activity against A549 cell line. The compounds were also tested for their in vitro inhibitory effects on hCA-I and hCA-II. Generally, the tested compounds were more effective on CAs than acetazolamide, the reference agent. Among these compounds, N-(1,3-benzodioxol-5-ylmethyl)-2-[(morpholinyl)thiocarbamoylthio]acetamide (3) and N-(1,3-benzodioxol-5-ylmethyl)-2-[(thiomorpholinyl)thiocarbamoylthio]acetamide (4) were found to be the most effective compounds on hCA-I with IC 50 values of 0.346 nM and 0.288 nM, and hCA-II with IC 50 values of 0.287 nM and 0.338 nM, respectively. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

30 CFR 57.22212 - Air flow (I-C, II-A, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Air flow (I-C, II-A, and V-A mines). 57.22212 Section 57.22212 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22212 Air flow (I-C, II-A, and V-A mines...

bop5 mutations reveal new roles for the IC138 phosphoprotein in the regulation of flagellar motility and asymmetric waveforms

PubMed Central

VanderWaal, Kristyn E.; Yamamoto, Ryosuke; Wakabayashi, Ken-ichi; Fox, Laura; Kamiya, Ritsu; Dutcher, Susan K.; Bayly, Phillip V.; Sale, Winfield S.; Porter, Mary E.

2011-01-01

I1 dynein, or dynein f, is a highly conserved inner arm isoform that plays a key role in the regulation of flagellar motility. To understand how the IC138 IC/LC subcomplex modulates I1 activity, we characterized the molecular lesions and motility phenotypes of several bop5 alleles. bop5-3, bop5-4, and bop5-5 are null alleles, whereas bop5-6 is an intron mutation that reduces IC138 expression. I1 dynein assembles into the axoneme, but the IC138 IC/LC subcomplex is missing. bop5 strains, like other I1 mutants, swim forward with reduced swimming velocities and display an impaired reversal response during photoshock. Unlike mutants lacking the entire I1 dynein, however, bop5 strains exhibit normal phototaxis. bop5 defects are rescued by transformation with the wild-type IC138 gene. Analysis of flagellar waveforms reveals that loss of the IC138 subcomplex reduces shear amplitude, sliding velocities, and the speed of bend propagation in vivo, consistent with the reduction in microtubule sliding velocities observed in vitro. The results indicate that the IC138 IC/LC subcomplex is necessary to generate an efficient waveform for optimal motility, but it is not essential for phototaxis. These findings have significant implications for the mechanisms by which IC/LC complexes regulate dynein motor activity independent of effects on cargo binding or complex stability. PMID:21697502

Modeling the spectral energy distribution of the radio galaxy IC310

NASA Astrophysics Data System (ADS)

Fraija, N.; Marinelli, A.; Galván-Gámez, A.; Aguilar-Ruiz, E.

2017-03-01

The radio galaxy IC310 located in the Perseus Cluster is one of the brightest objects in the radio and X-ray bands, and one of the closest active galactic nuclei observed in very-high energies. In GeV - TeV γ-rays, IC310 was detected in low and high flux states by the MAGIC telescopes from October 2009 to February 2010. Taking into account that the spectral energy distribution (SED) up to a few GeV seems to exhibit a double-peak feature and that a single-zone synchrotron self-Compton (SSC) model can explain all of the multiwavelength emission except for the non-simultaneous MAGIC emission, we interpret, in this work, the multifrequency data set of the radio galaxy IC310 in the context of homogeneous hadronic and leptonic models. In the leptonic framework, we present a multi-zone SSC model with two electron populations to explain the whole SED whereas for the hadronic model, we propose that a single-zone SSC model describes the SED up to a few GeVs and neutral pion decay products resulting from pγ interactions could describe the TeV - GeV γ-ray spectra. These interactions occur when Fermi-accelerated protons interact with the seed photons around the SSC peaks. We show that, in the leptonic model the minimum Lorentz factor of second electron population is exceedingly high γe ∼ 105 disfavoring this model, and in the hadronic model the required proton luminosity is not extremely high ∼1044 erg/s, provided that charge neutrality between the number of electrons and protons is given. Correlating the TeV γ-ray and neutrino spectra through photo-hadronic interactions, we find that the contribution of the emitting region of IC310 to the observed neutrino and ultra-high-energy cosmic ray fluxes are negligible.

An NFC-Enabled CMOS IC for a Wireless Fully Implantable Glucose Sensor.

PubMed

DeHennis, Andrew; Getzlaff, Stefan; Grice, David; Mailand, Marko

2016-01-01

This paper presents an integrated circuit (IC) that merges integrated optical and temperature transducers, optical interface circuitry, and a near-field communication (NFC)-enabled digital, wireless readout for a fully passive implantable sensor platform to measure glucose in people with diabetes. A flip-chip mounted LED and monolithically integrated photodiodes serve as the transduction front-end to enable fluorescence readout. A wide-range programmable transimpedance amplifier adapts the sensor signals to the input of an 11-bit analog-to-digital converter digitizing the measurements. Measurement readout is enabled by means of wireless backscatter modulation to a remote NFC reader. The system is able to resolve current levels of less than 10 pA with a single fluorescent measurement energy consumption of less than 1 μJ. The wireless IC is fabricated in a 0.6-μm-CMOS process and utilizes a 13.56-MHz-based ISO15693 for passive wireless readout through a NFC interface. The IC is utilized as the core interface to a fluorescent, glucose transducer to enable a fully implantable sensor-based continuous glucose monitoring system.

How fast can an AGN shut down? XMM-Newton observation of IC 2497

NASA Astrophysics Data System (ADS)

Schawinski, Kevin

2008-10-01

We propose to observe IC 2497 with XMM-Newton to detect, or rule out, an obscured AGN that might account for the illumination of `Hanny's Voorwerp'. The Voorwerp is a highly ionised cloud of gas extended over 15-25 kpc next to the spiral galaxy IC 2497. There is no source of ionisation within the Voorwerp, implicating a luminous 1E44 erg/s AGN in IC 2497 as the source. Swift XRT observations do not yield a detection, allowing the presence of a highly obscured, sufficiently luminous AGN. With 34 ksec of XMM observations, we could detect an obscured AGN down to 1E42 erg/s. We can thus either locate an obscured AGN, or we can for the first time constrain the shutdown time scale for a powerful AGN, as it drops by a factor of 100 in luminosity in 1E5 years.

Development of voice navigation system for the visually impaired by using IC tags.

PubMed

Takatori, Norihiko; Nojima, Kengo; Matsumoto, Masashi; Yanashima, Kenji; Magatani, Kazushige

2006-01-01

There are about 300,000 visually impaired persons in Japan. Most of them are old persons and, cannot become skillful in using a white cane, even if they make effort to learn how to use a white cane. Therefore, some guiding system that supports the independent activities of the visually impaired are required. In this paper, we will describe about a developed white cane system that supports the independent walking of the visually impaired in the indoor space. This system is composed of colored navigation lines that include IC tags and an intelligent white cane that has a navigation computer. In our system colored navigation lines that are put on the floor of the target space from the start point to the destination and IC tags that are set at the landmark point are used for indication of the route to the destination. The white cane has a color sensor, an IC tag transceiver and a computer system that includes a voice processor. This white cane senses the navigation line that has target color by a color sensor. When a color sensor finds the target color, the white cane informs a white cane user that he/she is on the navigation line by vibration. So, only following this vibration, the user can reach the destination. However, at some landmark points, guidance is necessary. At these points, an IC tag is set under the navigation line. The cane makes communication with the tag and informs the user about the land mark pint by pre recorded voice. Ten normal subjects who were blindfolded were tested with our developed system. All of them could walk along navigation line. And the IC tag information system worked well. Therefore, we have concluded that our system will be a very valuable one to support activities of the visually impaired.

Fermi Non-detections of Four X-Ray Jet Sources and Implications for the IC/CMB Mechanism

NASA Astrophysics Data System (ADS)

Breiding, Peter; Meyer, Eileen T.; Georganopoulos, Markos; Keenan, M. E.; DeNigris, N. S.; Hewitt, Jennifer

2017-11-01

Since its launch in 1999, the Chandra X-ray observatory has discovered several dozen X-ray jets associated with powerful quasars. In many cases, the X-ray spectrum is hard and appears to come from a second spectral component. The most popular explanation for the kpc-scale X-ray emission in these cases has been inverse-Compton (IC) scattering of Cosmic Microwave Background (CMB) photons by relativistic electrons in the jet (the IC/CMB model). Requiring the IC/CMB emission to reproduce the observed X-ray flux density inevitably predicts a high level of gamma-ray emission, which should be detectable with the Fermi Large Area Telescope (LAT). In previous work, we found that gamma-ray upper limits from the large-scale jets of 3C 273 and PKS 0637-752 violate the predictions of the IC/CMB model. Here, we present Fermi/LAT flux density upper limits for the X-ray jets of four additional sources: PKS 1136-135, PKS 1229-021, PKS 1354+195, and PKS 2209+080. We show that these limits violate the IC/CMB predictions at a very high significance level. We also present new Hubble Space Telescope observations of the quasar PKS 2209+080 showing a newly detected optical jet, and Atacama Large Millimeter/submillimeter Array band 3 and 6 observations of all four sources, which provide key constraints on the spectral shape that enable us to rule out the IC/CMB model.

A Twisted Star-Forming Web in the Galaxy IC 342

NASA Image and Video Library

2011-07-20

Looking like a spider web swirled into a spiral, galaxy IC 342 presents its delicate pattern of dust in this infrared light image from NASA Spitzer Space Telescope. The very center glows especially brightly in the infrared.

MO-F-CAMPUS-J-01: Effect of Iodine Contrast Agent Concentration On Cerebrovascular Dose for Synchrotron Radiation Microangiography Based On a Simple Mouse Head Model and a Voxel Mouse Head Phantom

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

Lin, H; Jing, J; Xie, C

Purpose: To find effective setting methods to mitigate the irradiation injure in synchrotron radiation microangiography(SRA) by Monte Carlo simulation. Methods: A mouse 1-D head model and a segmented voxel mouse head phantom were simulated by EGSnrc/Dosxyznrc code to investigate the dose enhancement effect of the iodine contrast agent irradiated by a monochromatic synchrotron radiation(SR) source. The influence of, like iodine concentration (IC), vessel width and depth, with and without skull layer protection and the various incident X ray energies, were simulated. The dose enhancement effect and the absolute dose based on the segmented voxel mouse head phantom were evaluated. Results:more » The dose enhancement ratio depends little on the irradiation depth, but strongly on the IC, which is linearly increases with IC. The skull layer protection cannot be ignored in SRA, the 700µm thick skull could decrease 10% of the dose. The incident X-ray energy can significantly affact the dose. E.g. compared to the dose of 33.2keV for 50mgI/ml, the 32.7keV dose decreases 38%, whereas the dose of 33.7 keV increases 69.2%, and the variation will strengthen more with enhanced IC. The segmented voxel mouse head phantom also showed that the average dose enhancement effect and the maximal voxel dose per photon depends little on the iodine voxel volume ratio, but strongly on IC. Conclusion: To decrease dose damage in SRA, the high-Z contrast agent should be used as little as possible, and try to avoid radiating locally the injected position immediately after the contrast agent injection. The fragile vessel containing iodine should avoid closely irradiating. Avoiding irradiating through the no or thin skull region, or appending thin equivalent material from outside to protect is also a better method. As long as SRA image quality is ensured, using incident X-ray energy as low as possible.« less

The gene ICS3 from the yeast Saccharomyces cerevisiae is involved in copper homeostasis dependent on extracellular pH.

PubMed

Alesso, C A; Discola, K F; Monteiro, G

2015-09-01

In the yeast Saccharomyces cerevisiae, many genes are involved in the uptake, transport, storage and detoxification of copper. Large scale studies have noted that deletion of the gene ICS3 increases sensitivity to copper, Sortin 2 and acid exposure. Here, we report a study on the Δics3 strain, in which ICS3 is related to copper homeostasis, affecting the intracellular accumulation of this metal. This strain is sensitive to hydrogen peroxide and copper exposure, but not to other tested transition metals. At pH 6.0, the Δics3 strain accumulates a larger amount of intracellular copper than the wild-type strain, explaining the sensitivity to oxidants in this condition. Unexpectedly, sensitivity to copper exposure only occurs in acidic conditions. This can be explained by the fact that the exposure of Δics3 cells to high copper concentrations at pH 4.0 results in over-accumulation of copper and iron. Moreover, the expression of ICS3 increases in acidic pH, and this is correlated with CCC2 gene expression, since both genes are regulated by Rim101 from the pH regulon. CCC2 is also upregulated in Δics3 in acidic pH. Together, these data indicate that ICS3 is involved in copper homeostasis and is dependent on extracellular pH. Copyright © 2015 Elsevier Inc. All rights reserved.

Good Trellises for IC Implementation of Viterbi Decoders for Linear Block Codes

NASA Technical Reports Server (NTRS)

Moorthy, Hari T.; Lin, Shu; Uehara, Gregory T.

1997-01-01

This paper investigates trellis structures of linear block codes for the integrated circuit (IC) implementation of Viterbi decoders capable of achieving high decoding speed while satisfying a constraint on the structural complexity of the trellis in terms of the maximum number of states at any particular depth. Only uniform sectionalizations of the code trellis diagram are considered. An upper-bound on the number of parallel and structurally identical (or isomorphic) subtrellises in a proper trellis for a code without exceeding the maximum state complexity of the minimal trellis of the code is first derived. Parallel structures of trellises with various section lengths for binary BCH and Reed-Muller (RM) codes of lengths 32 and 64 are analyzed. Next, the complexity of IC implementation of a Viterbi decoder based on an L-section trellis diagram for a code is investigated. A structural property of a Viterbi decoder called add-compare-select (ACS)-connectivity which is related to state connectivity is introduced. This parameter affects the complexity of wire-routing (interconnections within the IC). The effect of five parameters namely: (1) effective computational complexity; (2) complexity of the ACS-circuit; (3) traceback complexity; (4) ACS-connectivity; and (5) branch complexity of a trellis diagram on the very large scale integration (VISI) complexity of a Viterbi decoder is investigated. It is shown that an IC implementation of a Viterbi decoder based on a nonminimal trellis requires less area and is capable of operation at higher speed than one based on the minimal trellis when the commonly used ACS-array architecture is considered.

Observation of supernova remnant IC 443 with the Fermi Large Area Telescope

DOE PAGES

Abdo, A. A.

2010-03-03

Here, we report observation of the supernova remnant (SNR) IC 443 (G189.1+3.0) with the Fermi Gamma-ray Space Telescope Large Area Telescope (LAT) in the energy band between 200 MeV and 50 GeV. IC 443 is a shell-type SNR with mixed morphology located off the outer Galactic plane where high-energy emission has been detected in the X-ray, GeV and TeV gamma-ray bands. Past observations suggest IC 443 has been interacting with surrounding interstellar matter. Proximity between dense shocked molecular clouds and GeV-TeV gamma-ray emission regions detected by EGRET, MAGIC, and VERITAS suggests an interpretation that cosmic-ray (CR) particles are accelerated by the SNR. We accurately characterize the gamma-ray emission produced by the CRs accelerated at IC 443 using the high gamma-ray statistics and broad energy coverage provided by the LAT. The emission region is extended in the energy band with θ 68 = 0more » $$°\\atop{.}$$27 ± 0fdg01(stat) ± 0$$°\\atop{.}$$03(sys) for an assumed two-dimensional Gaussian profile and overlaps almost completely with the extended source region of VERITAS. Its centroid is displaced significantly from the known pulsar wind nebula (PWN) which suggests the PWN is not the major contributor in the present energy band. The observed spectrum changes its power-law slope continuously and continues smoothly to the MAGIC and VERITAS data points. Furthermore, the combined gamma-ray spectrum (200 MeV« less

Good trellises for IC implementation of viterbi decoders for linear block codes

NASA Technical Reports Server (NTRS)

Lin, Shu; Moorthy, Hari T.; Uehara, Gregory T.

1996-01-01

This paper investigates trellis structures of linear block codes for the IC (integrated circuit) implementation of Viterbi decoders capable of achieving high decoding speed while satisfying a constraint on the structural complexity of the trellis in terms of the maximum number of states at any particular depth. Only uniform sectionalizations of the code trellis diagram are considered. An upper bound on the number of parallel and structurally identical (or isomorphic) subtrellises in a proper trellis for a code without exceeding the maximum state complexity of the minimal trellis of the code is first derived. Parallel structures of trellises with various section lengths for binary BCH and Reed-Muller (RM) codes of lengths 32 and 64 are analyzed. Next, the complexity of IC implementation of a Viterbi decoder based on an L-section trellis diagram for a code is investigated. A structural property of a Viterbi decoder called ACS-connectivity which is related to state connectivity is introduced. This parameter affects the complexity of wire-routing (interconnections within the IC). The effect of five parameters namely: (1) effective computational complexity; (2) complexity of the ACS-circuit; (3) traceback complexity; (4) ACS-connectivity; and (5) branch complexity of a trellis diagram on the VLSI complexity of a Viterbi decoder is investigated. It is shown that an IC implementation of a Viterbi decoder based on a non-minimal trellis requires less area and is capable of operation at higher speed than one based on the minimal trellis when the commonly used ACS-array architecture is considered.

The next generation in optical transport semiconductors: IC solutions at the system level

NASA Astrophysics Data System (ADS)

Gomatam, Badri N.

2005-02-01

In this tutorial overview, we survey some of the challenging problems facing Optical Transport and their solutions using new semiconductor-based technologies. Advances in 0.13um CMOS, SiGe/HBT and InP/HBT IC process technologies and mixed-signal design strategies are the fundamental breakthroughs that have made these solutions possible. In combination with innovative packaging and transponder/transceiver architectures IC approaches have clearly demonstrated enhanced optical link budgets with simultaneously lower (perhaps the lowest to date) cost and manufacturability tradeoffs. This paper will describe: *Electronic Dispersion Compensation broadly viewed as the overcoming of dispersion based limits to OC-192 links and extending link budgets, *Error Control/Coding also known as Forward Error Correction (FEC), *Adaptive Receivers for signal quality monitoring for real-time estimation of Q/OSNR, eye-pattern, signal BER and related temporal statistics (such as jitter). We will discuss the theoretical underpinnings of these receiver and transmitter architectures, provide examples of system performance and conclude with general market trends. These Physical layer IC solutions represent a fundamental new toolbox of options for equipment designers in addressing systems level problems. With unmatched cost and yield/performance tradeoffs, it is expected that IC approaches will provide significant flexibility in turn, for carriers and service providers who must ultimately manage the network and assure acceptable quality of service under stringent cost constraints.

30 CFR 57.22209 - Auxiliary fans (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22209 Auxiliary fans (I-C mines.... Tests for methane shall be made at electric auxiliary fans before they are started. Such fans shall not be operated when air passing over or through them contains 0.5 percent or more methane. ...

30 CFR 57.22310 - Electrical cables (I-C mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

30 CFR 57.22310 - Electrical cables (I-C mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

30 CFR 57.22310 - Electrical cables (I-C mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

30 CFR 57.22310 - Electrical cables (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

30 CFR 57.22310 - Electrical cables (I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22310 Electrical cables (I-C mines). Electrical cables used to power submersible sump pumps shall be accepted or approved by MSHA as flame... be sealed to prevent entry of explosive gas or dust. [57 FR 61223, Dec. 23, 1992] ...

30 CFR 57.22209 - Auxiliary fans (I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22209 Auxiliary fans (I-C mines.... Tests for methane shall be made at electric auxiliary fans before they are started. Such fans shall not be operated when air passing over or through them contains 0.5 percent or more methane. ...

Synergetic effect of chelating agent and nonionic surfactant for benzotriazole removal on post Cu-CMP cleaning

NASA Astrophysics Data System (ADS)

Yanlei, Li; Yuling, Liu; Chenwei, Wang; Yue, Li

2016-08-01

The cleaning of copper interconnects after chemical mechanical planarization (CMP) process is a critical step in integrated circuits (ICs) fabrication. Benzotriazole (BTA), which is used as corrosion inhibitor in the copper CMP slurry, is the primary source for the formation of organic contaminants. The presence of BTA can degrade the electrical properties and reliability of ICs which needs to be removed by using an effective cleaning solution. In this paper, an alkaline cleaning solution was proposed. The alkaline cleaning solution studied in this work consists of a chelating agent and a nonionic surfactant. The removal of BTA was characterized by contact angle measurements and potentiodynamic polarization studies. The cleaning properties of the proposed cleaning solution on a 300 mm copper patterned wafer were also quantified, total defect counts after cleaning was studied, scanning electron microscopy (SEM) review was used to identify types of BTA to confirm the ability of cleaning solution for BTA removal. All the results reveal that the chelating agent can effectively remove the BTA residual, nonionic surfactant can further improve the performance. Project supported by the Natural Science Foundation of Hebei Province, China (No. F2015202267) and the Scientific Innovation Grant for Excellent Young Scientists of Hebei University of Technology (No. 2015007).

iPTF15dtg: a double-peaked Type Ic supernova from a massive progenitor

DOE PAGES

Taddia, Francesco; Fremling, C.; Sollerman, J.; ...

2016-08-04

Type Ic supernovae (SNe Ic) arise from the core-collapse of H- (and He-) poor stars, which could either be single Wolf-Rayet (WR) stars or lower-mass stars stripped of their envelope by a companion. Their light curves are radioactively powered and usually show a fast rise to peak (~10-15 d), without any early (in the first few days) emission bumps (with the exception of broad-lined SNe Ic) as sometimes seen for other types of stripped-envelope SNe (e.g., Type IIb SN 1993J and Type Ib SN 2008D). Here, we have studied iPTF15dtg, a spectroscopically normal SN Ic with an early excess inmore » the optical light curves followed by a long (~30 d) rise to the main peak. It is the first spectroscopically-normal double-peaked SN Ic to be observed. Our aim is to determine the properties of this explosion and of its progenitor star. Methods. Optical photometry and spectroscopy of iPTF15dtg was obtained with multiple telescopes. The resulting light curves and spectral sequence are analyzed and modeled with hydrodynamical and analytical models, with particular focus on the early emission. iPTF15dtg is a slow rising SN Ic, similar to SN 2011bm. Hydrodynamical modeling of the bolometric properties reveals a large ejecta mass (~10 M ⊙) and strong 56Ni mixing. The luminous early emission can be reproduced if we account for the presence of an extended (≳500 R ⊙), low-mass (≳0.045 M ⊙) envelope around the progenitor star. Alternative scenarios for the early peak, such as the interaction with a companion, a shock-breakout (SBO) cooling tail from the progenitor surface, or a magnetar-driven SBO are not favored. In conclusion, the large ejecta mass and the presence of H- and He-free extended material around the star suggest that the progenitor of iPTF15dtg was a massive (≳35 M ⊙) WR star that experienced strong mass loss.« less

Engineered Knottin Peptides: A New Class of Agents for Imaging Integrin Expression in Living Subjects

PubMed Central

Kimura, Richard H; Cheng, Zhen; Gambhir, Sanjiv Sam; Cochran, Jennifer R

2009-01-01

There is a critical need for molecular imaging agents to detect cell surface integrin receptors that are present in human cancers. Previously, we used directed evolution to engineer knottin peptides that bind with low nM affinity to integrin receptors that are overexpressed on the surface of tumor cells and the tumor neovasculature. To evaluate these peptides as molecular imaging agents, we site-specifically conjugated Cy5.5 or 64Cu-DOTA to their N-termini, and used optical and positron emission tomography (PET) imaging to measure their uptake and biodistribution in U87MG glioblastoma murine xenograft models. Near-infrared fluorescence and microPET imaging both demonstrated that integrin binding affinity plays a strong role in the tumor uptake of knottin peptides. Tumor uptake at 1 h post injection for two high affinity (IC50 ∼20 nM) 64Cu-DOTA-conjugated knottin peptides was 4.47 ± 1.21 and 4.56 ± 0.64 % injected dose/gram (%ID/g), compared to a low affinity knottin peptide (IC50 ∼0.4 μM; 1.48 ± 0.53 %ID/g) and c(RGDyK) (IC50 ∼1 μM; 2.32 ± 0.55 %ID/g), a low affinity cyclic pentapeptide under clinical development. Furthermore, 64Cu-DOTA-conjugated knottin peptides generated lower levels of non-specific liver uptake (∼2 %ID/g) compared to c(RGDyK) (∼4 %ID/g) 1 h post injection. MicroPET imaging results were confirmed by in vivo biodistribution studies. 64Cu-DOTA-conjugated knottin peptides were stable in mouse serum, and in vivo metabolite analysis showed minimal degradation in the blood or tumor upon injection. Thus, engineered integrin-binding knottin peptides show great potential as clinical diagnostics for a variety of cancers. PMID:19276378

Cost-Effectiveness of Radiofrequency Catheter Ablation Compared with Antiarrhythmic Drug Therapy for Paroxysmal Atrial Fibrillation

PubMed Central

Reynolds, Matthew R.; Zimetbaum, Peter; Josephson, Mark E.; Ellis, Ethan; Danilov, Tatyana; Cohen, David J.

2009-01-01

Background Radiofrequency catheter ablation (RFA) has emerged as an important treatment strategy for AF. The potential cost-effectiveness of RFA for AF, relative to antiarrhythmic drug (AAD) therapy, has not been fully explored from a U.S. perspective. Methods and Results We constructed a Markov disease simulation model for a hypothetical cohort of drug- refractory paroxysmal AF patients managed either with RFA ± AAD or AAD alone. Costs and quality-adjusted life years (QALYs) were projected over 5 years. Model inputs were drawn from published clinical trial and registry data, from new registry and trial data analysis, and from data prospectively collected from AF patients managed with RFA at our institution. We assumed no benefit form ablation on stroke, heart failure or death, but did estimate changes in quality-adjusted life expectancy using data from several AF cohorts. In the base case scenario, cumulative costs with the RFA and AAD strategies were $26,584 and $19,898, respectively. Over 5 years, quality adjusted life expectancy was 3.51 QALYs with RFA, versus 3.38 for the AAD group. The incremental cost-effectiveness ratio for RFA vs. AAD was thus $51,431/QALY. Model results were most sensitive to time horizon, the relative utility weights of successful ablation vs. unsuccessful drug therapy, and to the cost of an ablation procedure. Conclusions RFA ± AAD for symptomatic, drug-refractory paroxysmal AF appears to be reasonably cost-effective compared with AAD therapy alone from the perspective of the US health care system, based on improved quality of life and avoidance of future health care costs. PMID:19808491

Anand constitutive model of lead-free solder joints in 3D IC device

NASA Astrophysics Data System (ADS)

Zhang, Liang; Liu, Zhi-quan; Ji, Yu-tong

2016-08-01

Anand constitutive relation of SnAgCu and SnAgCu-nano Al solders were studied under uniaxial tension, and the constitutive model was used in the finite element simulation to analyze the stress-strain response of lead-free solder joints in 3D IC devices. The results showed that the nine parameters of the Anand model can be determined from separated constitutive relations and experimental results. Based on Anand model, the finite element method was selected to calculate the stress-strain response of lead-free solder joints, it was found that in the 3D IC device the maximum stress-strain concentrated in the concern solder joints, the stress-strain of SnAgCu-nano Al solder joints was lower than that of SnAgCu solder joints, which represented that the addition of nano Al particles can enhance the reliability of lead-free solder joints in 3D IC devices.

Experimental and theoretical analysis of integrated circuit (IC) chips on flexible substrates subjected to bending

NASA Astrophysics Data System (ADS)

Chen, Ying; Yuan, Jianghong; Zhang, Yingchao; Huang, Yonggang; Feng, Xue

2017-10-01

The interfacial failure of integrated circuit (IC) chips integrated on flexible substrates under bending deformation has been studied theoretically and experimentally. A compressive buckling test is used to impose the bending deformation onto the interface between the IC chip and the flexible substrate quantitatively, after which the failed interface is investigated using scanning electron microscopy. A theoretical model is established based on the beam theory and a bi-layer interface model, from which an analytical expression of the critical curvature in relation to the interfacial failure is obtained. The relationships between the critical curvature, the material, and the geometric parameters of the device are discussed in detail, providing guidance for future optimization flexible circuits based on IC chips.

Migration to Current Open Source Technologies by MagIC Enables a More Responsive Website, Quicker Development Times, and Increased Community Engagement

NASA Astrophysics Data System (ADS)

Jarboe, N.; Minnett, R.; Koppers, A.; Constable, C.; Tauxe, L.; Jonestrask, L.

2017-12-01

The Magnetics Information Consortium (MagIC) supports an online database for the paleo, geo, and rock magnetic communities ( https://earthref.org/MagIC ). Researchers can upload data into the archive and download data as selected with a sophisticated search system. MagIC has completed the transition from an Oracle backed, Perl based, server oriented website to an ElasticSearch backed, Meteor based thick client website technology stack. Using JavaScript on both the sever and the client enables increased code reuse and allows easy offloading many computational operations to the client for faster response. On-the-fly data validation, column header suggestion, and spreadsheet online editing are some new features available with the new system. The 3.0 data model, method codes, and vocabulary lists can be browsed via the MagIC website and more easily updated. Source code for MagIC is publicly available on GitHub ( https://github.com/earthref/MagIC ). The MagIC file format is natively compatible with the PmagPy ( https://github.com/PmagPy/PmagPy) paleomagnetic analysis software. MagIC files can now be downloaded from the database and viewed and interpreted in the PmagPy GUI based tool, pmag_gui. Changes or interpretations of the data can then be saved by pmag_gui in the MagIC 3.0 data format and easily uploaded to the MagIC database. The rate of new contributions to the database has been increasing with many labs contributing measurement level data for the first time in the last year. Over a dozen file format conversion scripts are available for translating non-MagIC measurement data files into the MagIC format for easy uploading. We will continue to work with more labs until the whole community has a manageable workflow for contributing their measurement level data. MagIC will continue to provide a global repository for archiving and retrieving paleomagnetic and rock magnetic data and, with the new system in place, be able to more quickly respond to the community

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

The spectrum of the variable planetary nebula IC 4997

NASA Technical Reports Server (NTRS)

Hyung, Siek; Aller, Lawrence H.; Feibelman, Walter A.

1994-01-01

The compact, dusty, presumably young planetary nebula (PN) IC 4997 has been studied extensively since the variability of the lambda 4363/lambda 4340 ratio was established in 1956. Since 1938, other nebular lines have shown changes. IC 4997 is also unique because of the great density range revealed by its spectrum which goes in excitation from Mg I to (Ar IV). We present a detailed listing of spectral lines from 360 to 1005 nm. The diagnostic diagram shows that the spectrum can be interpreted only in terms of strata with a huge density gamut. Essential spectral features can be reproduced approximately by a model consisting of a geometrically thin shell of density around 10(exp 7) atoms cm(exp -3), surrounded by a much larger shell with a density of about 10(exp 4) atoms cm(exp -3). The actual, certainly more complex structure can be evaluated only when high resolution spatial imaging is at hand. The usual method of getting abundances from N(ion)/N(H(+)) and ionization correction factors (ICFs) cannot be applied here. It is argued that a reasonable theoretical model that represents the spectrum provides a valid initial approximation to nebular abundances. We propose that the chemical composition of IC 4997 does not differ greatly from that of the Sun. The finally adopted model suggests that the ejection of the material destined to form the inner shell occurred between 1900 and 1960, but observational evidence of such an ejection event is lacking. Perhaps the shell was accelerated. A need for further study is emphasized, especially the role of dust which appears to contribute 2% of the total mass. More attention to this object is recommended. An accurate measurement of its distance is especially desirable.

PREFACE: IC-MSQUARE 2012: International Conference on Mathematical Modelling in Physical Sciences

NASA Astrophysics Data System (ADS)

Kosmas, Theocharis; Vagenas, Elias; Vlachos, Dimitrios

2013-02-01

The first International Conference on Mathematical Modelling in Physical Sciences (IC-MSQUARE) took place in Budapest, Hungary, from Monday 3 to Friday 7 September 2012. The conference was attended by more than 130 participants, and hosted about 290 oral, poster and virtual papers by more than 460 pre-registered authors. The first IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields in which mathematical modelling is used, such as theoretical/mathematical physics, neutrino physics, non-integrable systems, dynamical systems, computational nanoscience, biological physics, computational biomechanics, complex networks, stochastic modelling, fractional statistics, DNA dynamics, and macroeconomics. The scientific program was rather heavy since after the Keynote and Invited Talks in the morning, two parallel sessions ran every day. However, according to all attendees, the program was excellent with a high level of talks and the scientific environment was fruitful; thus all attendees had a creative time. The mounting question is whether this occurred accidentally, or whether IC-MSQUARE is a necessity in the field of physical and mathematical modelling. For all of us working in the field, the existing and established conferences in this particular field suffer from two distinguished and recognized drawbacks: the first is the increasing orientation, while the second refers to the extreme specialization of the meetings. Therefore, a conference which aims to promote the knowledge and development of high-quality research in mathematical fields concerned with applications of other scientific fields as well as modern technological trends in physics, chemistry, biology, medicine, economics, sociology, environmental sciences etc., appears to be a necessity. This is the key role that IC-MSQUARE will play. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contributions to IC-MSQUARE. We would also

Interdisciplinary Collaboration amongst Colleagues and between Initiatives with the Magnetics Information Consortium (MagIC) Database

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A. A. P.; Jarboe, N.; Tauxe, L.; Constable, C.; Jonestrask, L.; Shaar, R.

2014-12-01

Earth science grand challenges often require interdisciplinary and geographically distributed scientific collaboration to make significant progress. However, this organic collaboration between researchers, educators, and students only flourishes with the reduction or elimination of technological barriers. The Magnetics Information Consortium (http://earthref.org/MagIC/) is a grass-roots cyberinfrastructure effort envisioned by the geo-, paleo-, and rock magnetic scientific community to archive their wealth of peer-reviewed raw data and interpretations from studies on natural and synthetic samples. MagIC is dedicated to facilitating scientific progress towards several highly multidisciplinary grand challenges and the MagIC Database team is currently beta testing a new MagIC Search Interface and API designed to be flexible enough for the incorporation of large heterogeneous datasets and for horizontal scalability to tens of millions of records and hundreds of requests per second. In an effort to reduce the barriers to effective collaboration, the search interface includes a simplified data model and upload procedure, support for online editing of datasets amongst team members, commenting by reviewers and colleagues, and automated contribution workflows and data retrieval through the API. This web application has been designed to generalize to other databases in MagIC's umbrella website (EarthRef.org) so the Geochemical Earth Reference Model (http://earthref.org/GERM/) portal, Seamount Biogeosciences Network (http://earthref.org/SBN/), EarthRef Digital Archive (http://earthref.org/ERDA/) and EarthRef Reference Database (http://earthref.org/ERR/) will benefit from its development.

Realization of MEMS-IC Vertical Integration Utilizing Smart Bumpless Bonding

NASA Astrophysics Data System (ADS)

Shiozaki, Masayoshi; Moriguchi, Makoto; Sasaki, Sho; Oba, Masatoshi

This paper reports fundamental technologies, properties, and new experimental results of SBB (Smart Bumpless Bonding) to realize MEMS-IC vertical integration. Although conventional bonding technologies have had difficulties integrating MEMS and its processing circuit because of their rough bonding surfaces, fragile structures, and thermal restriction, SBB technology realized the vertical integration without thermal treatment, any adhesive materials including bumps, and chemical mechanical polishing. The SBB technology bonds sealing parts for vacuum sealing and electrodes for electrical connection simultaneously as published in previous experimental study. The plasma CVD SiO2 is utilized to realize vacuum sealing as sealing material. And Au projection studs are formed on each electrode and connected electrically between two wafers by compressive plastic deformation and surface activation. In this paper, new experimental results including vacuum sealing properties, electrical improvement, IC bonding results on the described fundamental concept and properties are reported.

A review of the pharmacokinetics, electrophysiology and clinical efficacy of dronedarone.

PubMed

Hynes, B John; Luck, Jerry C; Wolbrette, Deborah L; Khan, Mazhar; Naccarelli, Gerald V

2005-03-01

The results of major clinical trials and advances in pharmacologic and nonpharmacologic therapies are continuing to alter treatment approaches for both atrial and ventricular arrhythmias. Originally developed as an antianginal medication, amiodarone serves as the most effective antiarrhythmic drug in the treatment of both atrial and life-threatening ventricular arrhythmias. However, amiodarone has complex pharmacokinetics and is associated with serious extracardiac side effects, partially due to the presence of an iodine moiety. With a better understanding of the mechanisms of arrhythmias and antiarrhythmic drugs, new antiarrhythmic agents are currently under development with the hope that they will be more effective and safer than currently available drugs. One such drug that might potentially fulfill this hope is dronedarone. This amiodarone-like compound lacks the iodine moiety, and is similar in structure and electrophysiologic mechanisms of action to amiodarone, to date no evidence of liver, thyroid or pulmonary toxicity has been reported. Three clinical trials demonstrate efficacy in suppressing recurrences of atrial fibrillation and there is also evidence of a rate-slowing benefit during atrial fibrillation/flutter. However, the ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity Decrease (ANDROMEDA) study, performed in patients with left ventricular dysfunction, demonstrated excess noncardiac mortality in patients treated with dronedarone. Although effective in the treatment of atrial fibrillation, the future of this novel amiodarone-like drug remains uncertain until further clarification of the excess mortality in heart failure patients is better studied.

Effect of various stabilizing agents on Imperata cylindrica grass pollen allergen extract.

PubMed

Bijli, K M; Singh, B P; Sridhara, S; Gaur, S N; Arora, N

2003-01-01

Allergen extracts are unstable, heat labile or susceptible to proteases. Stability of allergen extracts is important for proper diagnosis and therapy of allergic disorders. The present study was undertaken to determine the preservation and stabilization conditions of Imperata cylindrica (Ic) grass pollen extract. The Ic extract was kept with 0.1 mepsilon-aminocaproic acid (EACA), 0.75 m sucrose, 5% glycerol, 0.03% human serum albumin (HSA) or 0.4% phenol for different time periods. The extracts were stored for 3, 6 and 12 months each at 4 degrees C, 4 degrees C with daily exposure to room temperature (RT) for 1 h, and RT. The quality of extracts was analysed by SDS-PAGE, Western blot, ELISA, ELISA inhibition and skin test. Extracts kept with EACA and sucrose retained most of the protein bands followed by glycerol as determined by SDS-PAGE and Western blot during all storage periods and conditions in comparison with standard extracts. The extracts kept with HSA, phenol and without preservative (WP) showed protein degradation below 33 kDa after 3 months storage at all conditions. However, a 67-kDa allergen was stable in these extracts. EACA extract required 75 to 120 ng of protein for 50% inhibition in IgE binding under different conditions, whereas standard extract required 70 ng for the same. ELISA also demonstrated high allergenic reactivity of EACA extract. ID test on allergy patients with EACA extract demonstrated same allergenic potency as that of standard extract. EACA is the best preservative/stabilizing agent of Ic pollen extract, followed by sucrose and glycerol. Ic extract kept with phenol, HSA and without preservative showed degradation within 3 months. EACA preserved extract is equally potent as that of standard extract up to 1 year's storage.

Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC).

PubMed

Schwalenberg, Thilo; Stolzenburg, Jens-Uwe; Ho, Thi Phuc; Mallock, Tobias; Hartenstein, Siegurd; Alexander, Henry; Zimmermann, Gerolf; Hohenfellner, Rudolf; Denzinger, Stefan; Burger, Maximilian; Horn, Lars-Christian; Neuhaus, Jochen

2012-06-01

Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls. Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction. We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients. The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.

Methods of the pharmacological imaging of the cannabinoid system (PhICS) study: towards understanding the role of the brain endocannabinoid system in human cognition.

PubMed

van Hell, Hendrika H; Bossong, Matthijs G; Jager, Gerry; Kahn, René S; Ramsey, Nick F

2011-03-01

Various lines of (pre)clinical research indicate that cannabinoid agents carry the potential for therapeutic application to reduce symptoms in several psychiatric disorders. However, direct testing of the involvement of cannabinoid brain systems in psychiatric syndromes is essential for further development. In the Pharmacological Imaging of the Cannabinoid System (PhICS) study, the involvement of the endocannabinoid system in cognitive brain function is assessed by comparing acute effects of the cannabinoid agonist Δ9-tetrahydrocannabinol (THC) on brain function between healthy controls and groups of psychiatric patients showing cognitive dysfunction. This article describes the objectives and methods of the PhICS study and presents preliminary results of the administration procedure on subjective and neurophysiological parameters. Core elements in the methodology of PhICS are the administration method (THC is administered by inhalation using a vaporizing device) and a comprehensive use of pharmacological magnetic resonance imaging (phMRI) combining several types of MRI scans including functional MRI (fMRI), Arterial Spin Labeling (ASL) to measure brain perfusion, and resting-state fMRI. Additional methods like neuropsychological testing further specify the exact role of the endocannabinoid system in regulating cognition. Preliminary results presented in this paper indicate robust behavioral and subjective effects of THC. In addition, fMRI paradigms demonstrate activation of expected networks of brain regions in the cognitive domains of interest. The presented administration and assessment protocol provides a basis for further research on the involvement of the endocannabionoid systems in behavior and in psychopathology, which in turn may lead to development of therapeutic opportunities of cannabinoid ligands. Copyright © 2011 John Wiley & Sons, Ltd.

Ionized and Molecular Gas in IC 860: Evidence for an Outflow

NASA Astrophysics Data System (ADS)

Adams, Carson; Alatalo, Katherine; Medling, Anne M.

2018-01-01

Galaxies at present-day fall predominantly in two distinct populations, as either blue, star-forming spirals or red, quiescent early-type galaxies. Blue galaxies appear to evolve onto the red sequence as star formation is quenched. The absence of a significant population falling in the intermediate ‘green valley’ implies that these transitions must occur rapidly. Identifying the initial properties of and pathways taken by these ‘dying galaxies’ is essential to building a complete understanding of galactic evolution. In this work, we investigate these phenomena in action within IC860 — a nearby, early-type spiral in the initial stages of undergoing a rapid transition in the presence of a powerful AGN-driven molecular outflow. As a shocked, post-starburst galaxy with an intermediate-age stellar population which lies on the blue end of the green valley, IC860 provides a window into the early stages of galaxy transition and AGN feedback. We present Hubble Space Telescope imaging of IC860 showing a violent, dusty outflow originating from a compact core. We find that the mean velocity map of the CO(1-0) from CARMA suggests a dynamically excited bar funneling molecular gas into the galactic center. Finally, we present kinematic maps of ionized gas emission lines as well as sodium D absorption tracing neutral winds obtained by the Wide-Field Spectrograph.

15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and Technology...

15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and Technology...

15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and Technology...

A Monte Carlo Approach to Magnetar-powered Transients. II. Broad-lined Type Ic Supernovae Not Associated with GRBs

NASA Astrophysics Data System (ADS)

Wang, L. J.; Cano, Z.; Wang, S. Q.; Zheng, W. K.; Liu, L. D.; Deng, J. S.; Yu, H.; Dai, Z. G.; Han, Y. H.; Xu, D.; Qiu, Y. L.; Wei, J. Y.; Li, B.; Song, L. M.

2017-12-01

Broad-lined type Ic supernovae (SNe Ic-BL) are a subclass of rare core-collapse SNe whose energy source is debated in the literature. Recently, a series of investigations on SNe Ic-BL with the magnetar (plus 56Ni) model were carried out. Evidence for magnetar formation was found for the well-observed SNe Ic-BL 1998bw and 2002ap. In this paper, we systematically study a large sample of SNe Ic-BL not associated with gamma-ray bursts (GRBs). We use photospheric velocity data determined in a homogeneous way. We find that the magnetar+56Ni model provides a good description of the light curves and velocity evolution of our sample of SNe Ic-BL, although some SNe (not all) can also be described by the pure-magnetar model or by the two-component pure-56Ni model (three out of 12 are unlikely to be explained by two-component model). In the magnetar+56Ni model, the amount of 56Ni required to explain their luminosity is significantly reduced, and the derived initial explosion energy is, in general, in accordance with neutrino heating. Some correlations between different physical parameters are evaluated, and their implications regarding magnetic field amplification and the total energy reservoir are discussed.

Bruton's tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-care.

PubMed

Gillooly, Kathleen M; Pulicicchio, Claudine; Pattoli, Mark A; Cheng, Lihong; Skala, Stacey; Heimrich, Elizabeth M; McIntyre, Kim W; Taylor, Tracy L; Kukral, Daniel W; Dudhgaonkar, Shailesh; Nagar, Jignesh; Banas, Dana; Watterson, Scott H; Tino, Joseph A; Fura, Aberra; Burke, James R

2017-01-01

Bruton's tyrosine kinase (BTK) regulates critical signal transduction pathways involved in the pathobiology of rheumatoid arthritis (RA) and other autoimmune disorders. BMS-986142 is a potent and highly selective reversible small molecule inhibitor of BTK currently being investigated in clinical trials for the treatment of both RA and primary Sjögren's syndrome. In the present report, we detail the in vitro and in vivo pharmacology of BMS-986142 and show this agent provides potent and selective inhibition of BTK (IC50 = 0.5 nM), blocks antigen receptor-dependent signaling and functional endpoints (cytokine production, co-stimulatory molecule expression, and proliferation) in human B cells (IC50 ≤ 5 nM), inhibits Fcγ receptor-dependent cytokine production from peripheral blood mononuclear cells, and blocks RANK-L-induced osteoclastogenesis. Through the benefits of impacting these important drivers of autoimmunity, BMS-986142 demonstrated robust efficacy in murine models of rheumatoid arthritis (RA), including collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA). In both models, robust efficacy was observed without continuous, complete inhibition of BTK. When a suboptimal dose of BMS-986142 was combined with other agents representing the current standard of care for RA (e.g., methotrexate, the TNFα antagonist etanercept, or the murine form of CTLA4-Ig) in the CIA model, improved efficacy compared to either agent alone was observed. The results suggest BMS-986142 represents a potential therapeutic for clinical investigation in RA, as monotherapy or co-administered with agents with complementary mechanisms of action.

Towards a better understanding of the evolution of Wolf-Rayet stars and Type Ib/Ic supernova progenitors

NASA Astrophysics Data System (ADS)

Yoon, Sung-Chul

2017-10-01

Hydrogen-deficient Wolf-Rayet (WR) stars are potential candidates of Type Ib/Ic supernova (SN Ib/Ic) progenitors and their evolution is governed by mass-loss. Stellar evolution models with the most popular prescription for WR mass-loss rates given by Nugis & Lamers have difficulties in explaining the luminosity distribution of WR stars of WC and WO types and the SN Ic progenitor properties. Here, we suggest some improvements in the WR mass-loss rate prescription and discuss its implications for the evolution of WR stars and SN Ib/Ic progenitors. Recent studies on Galactic WR stars clearly indicate that the mass-loss rates of WC stars are systematically higher than those of WNE stars for a given luminosity. The luminosity and initial metallicity dependences of WNE mass-loss rates are also significantly different from those of WC stars. These factors have not been adequately considered together in previous stellar evolution models. We also find that an overall increase of WR mass-loss rates by about 60 per cent compared to the empirical values obtained with a clumping factor of 10 is needed to explain the most faint WC/WO stars. This moderate increase with our new WR mass-loss rate prescription results in SN Ib/Ic progenitor models more consistent with observations than those given by the Nugis & Lamers prescription. In particular, our new models predict that the properties of SN Ib and SN Ic progenitors are distinctively different, rather than they form a continuous sequence.

X-Ray Activity in the Open Cluster IC 4665

NASA Technical Reports Server (NTRS)

Giamapapa, Mark S.; Prosser, Charles F.; Fleming, Thomas A.

1997-01-01

We present the results of a joint ROSAT High Resolution Imager (HRI) and optical investigation of the open cluster IC 4665. The ROSAT data contains detections for 28 stellar sources in the field, including 22 cluster members and candidate members spanning the color range -0.18 less than or equal to (B - V(sub o)) less than or equal to +1.63 (approx. B3 - M3). Upper limits are given for the remaining members (or candidate members) in the HRI field. Keck HIRES spectra have been obtained that yield radial and rotational velocity measures, respectively, for faint, low mass candidate members located within the field of the ROSAT HRI observation. In addition, photometry of possible optical counterparts to previously uncatalogued X-ray sources in the HRI field is presented. The trends in X-ray properties with (B - V) color in IC 4665 are found to be quite similar to that for other, more nearby young clusters such as the Pleiades and alpha Persei. In particular, a maximum in normalized X-ray luminosity of log (L(sub x)/L(sub bol)) approx. equal 3 is observed, beginning in the color range of (B - V)(sub o) = 0.7 - 0.8. This is similar to the corresponding color range among Pleiades members, in agreement with the earlier estimate, that the age of IC 4665 is similar to the age of the Pleiades. The correlation of rotation and X-ray emission levels is consistent with that in other young clusters. Among the high mass stars in IC 4665, five B stars are detected as X-ray sources. Of these, one is a spectroscopic binary while the remaining objects are apparently single staxs. The level of intrinsic X-ray emission observed in the rapidly rotating (v sini greater than 200 km/ s), single B stars is consistent with an origin due to shock heating of the ambient medium by radiatively driven, rotationally enhanced winds. On the basis of these observations and the results for other clusters, we argue that observed levels of X-ray emission in high mass stars of log (L(sub x)/L(sub bol

Transforming and differentiation-inducing potential of constitutively activated c-kit mutant genes in the IC-2 murine interleukin-3-dependent mast cell line.

PubMed Central

Hashimoto, K.; Tsujimura, T.; Moriyama, Y.; Yamatodani, A.; Kimura, M.; Tohya, K.; Morimoto, M.; Kitayama, H.; Kanakura, Y.; Kitamura, Y.

1996-01-01

Two mutations of c-kit receptor tyrosine kinase (KIT), valine-559 to glycine (G559) and aspartic acid-814 to valine (V814), resulted in its constitutive activation. To examine the transforming and differentiation-inducing potential of the mutant KIT, we used the murine interleukin-3-dependent IC-2 mast cell line as a transfectant. The IC-2 cells contained few basophilic granules and did not express KIT on the surface. The KITG559 or KITV814 gene was introduced into IC-2 cells using a retroviral vector. KITG559 and KITV814 expressed in IC-2 cells were constitutively phosphorylated on tyrosine and demonstrated kinase activity in the absence of stem cell factor, which is a ligand for KIT. IC-2 cells expressing either KITG559 or KITV814 (IC-2G559 or IC-2V814 cells) showed factor-independent growth in suspension culture and produced tumors in nude athymic mice. In addition, IC-2G559 and IC-2V814 cells showed a more mature phenotype compared with the phenotype of the original IC-2 cells, especially after transplantation into nude mice. The number of basophilic granules and the content of histamine increased remarkably. KITG559 and KITV814 also influenced the transcriptional phenotype of mouse mast cell proteases (MMCP) in IC-2 cells. The expression of MMCP-2, MMCP-4, and MMCP-6 was much greater in IC-2G559 and IC-2V814 cells than in the original IC-2 cells. The results indicated that constitutively activated KIT had not only oncogenic activity but also differentiation-inducing activity in mast cells. Images Figure 1 Figure 4 Figure 5 Figure 6 PMID:8546206

Therapeutic decision-making in elderly patients with acute myeloid leukemia: conventional intensive chemotherapy versus hypomethylating agent therapy.

PubMed

Oh, Sang-Bo; Park, Sung-Woo; Chung, Joo-Seop; Lee, Won-Sik; Lee, Ho-Seop; Cho, Su-Hee; Choi, Yoon-Suk; Lim, Sung-Nam; Shin, Ho-Jin

2017-11-01

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.

A study of H-alpha velocities in NGC 1499, NGC 7000, and IC 1318B/C

NASA Technical Reports Server (NTRS)

Fountain, W. F.; Gary, G. A.; Odell, C. R.

1983-01-01

Multiple slit echelle spectrograph observations of the H-alpha emission line are used to map the radial velocities of the California Nebula (NGC 1499), the North American Nebula complex (NGC 7000 and IC 5070), and IC 1318B/C. The California Nebula is singularly constant in velocity, considering its geometry. The North American Nebula complex reflects a very simple, classical dynamical picture. The expansion discovered earlier in IC 1318B/C is confirmed, detailed, and the model refined. The new data, along with that in earlier papers of this series, show that stellar wind acceleration and champagne flow mechanisms both play important roles in determining the evolution of H II regions.

15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... Controller of Imports and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and...

15 CFR Supplement No. 4 to Part 748 - Authorities Administering Import Certificate/Delivery Verification (IC/DV) and End-User Statement...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 11011 Indian IC For the “organized” sector, except for computers and related equipment: Directorate... 110011 Indian IC For computers and related electronic items: Department of Electronics, Lok Nayak Bhawan... Controller of Imports and Exports 5, Civic Center Islamabad IC Joint Science Advisor, Ministry of Science and...

Quantitative Spectroscopy of Supergiants in the Local Group Dwarf Galaxy IC 1613: Metallicity and Distance

NASA Astrophysics Data System (ADS)

Berger, Travis A.; Kudritzki, Rolf-Peter; Urbaneja, Miguel A.; Bresolin, Fabio; Gieren, Wolfgang; Pietrzyński, Grzegorz; Przybilla, Norbert

2018-06-01

We present a spectral analysis of 21 blue supergiant stars of spectral types late B to early A within the Local Group dwarf galaxy IC 1613, based on VLT Focal Reducer and Low Dispersion Spectrograph 2 low-resolution spectra. Combining our results with studies of early B-type blue supergiants, we report a wide bimodal distribution of metallicities with two peaks around [Z] ∼ ‑0.50 dex and [Z] ∼ ‑0.85 dex. The bimodal distribution correlates with spatial location, when compared with column densities of neutral hydrogen in IC 1613. While the low [Z] objects appear in regions of relatively high ISM H I column densities or close to them, the high [Z] supergiants are found in the central H I hole that is almost devoid of hydrogen. This suggests there are varied chemical evolution histories for the young stellar populations in IC 1613. Utilizing the flux-weighted gravity–luminosity relation, we determine IC 1613's distance modulus as m ‑ M = 24.39 ± 0.11 mag. This value is in agreement within previous distance measurements using the near-infrared period–luminosity relationship of Cepheids and the tip of the red giant branch.

Catecholamine-mediated arrhythmias in acute myocardial infarction. Experimental evidence and role of beta-adrenoceptor blockade.

PubMed

Opie, L H; Lubbe, W F

1979-11-24

Ventricular fibrillation is a major mechanism of sudden death. The cellular link between catecholamine activity and the development of serious ventricular arrhythmias may be in the formation of cyclic adenosine monophosphate (cAMP). Cyclic AMP and agents promoting cAMP accumulation allow development of slow responses which, especially in the presence of regional ischaemia, could develop into ventricular fibrillation. The role of beta-antagonist agents in the therapy of acute myocardial infarction is analysed in relation to the hypothesis linking cAMP and ventricular fibrillation. Reasons for the limited effectiveness of anti-arrhythmic therapy with beta-antagonist agents are given.

Antiarrhythmic Effects of Beta3-adrenergic Receptor Stimulation in a Canine Model of Ventricular Tachycardia

PubMed Central

Zhou, Shengmei; Tan, Alex Y.; Paz, Offir; Ogawa, Masahiro; Chou, Chung-Chuan; Hayashi, Hideki; Nihei, Motoki; Fishbein, Michael C.; Chen, Lan S.; Lin, Shien-Fong; Chen, Peng-Sheng

2009-01-01

Background Beta3-adrenergic receptor (beta3-AR) stimulation inhibits cardiac contractility. Objective To test the hypothesis that beta3-AR stimulation is antiarrhythmic. Methods We implanted a radiotransmitter for continuous ECG monitoring in 18 dogs with a tendency for high incidence of spontaneous ventricular tachycardia (VT). Ten of 18 had subcutaneous continuous BRL37344 (beta3-AR agonist) infusion (experimental group) for 1 month. The other dogs were controls. Western blotting studies were performed on tissues sampled from the noninfarcted left ventricular free wall of all dogs that survived the 60-day follow up period. Results Phase-2 VT appeared significantly later in the experimental group than in the control group (p<0.05). The number of VT episodes in the experimental group was significantly lower than control during both the first month (0.5 ± 0.95 episode/d vs. 2.6 ± 2.3 episode/d) and the second month (0.2 ± 0.2 episode/d vs. 1.2 ± 1.1 episode/d, p<0.05 for both). The experimental group had shorter QTc than control (p<0.002). The experimental group had decreased protein levels for sodium calcium exchanger and dihydropyridine receptor, increased beta3-AR expression, without changes in beta1-AR, beta2-AR. The average heart weight and the left ventricular free wall thickness in the experimental group (226 ± 17 g and 15.1 ± 1.2 mm, respectively) was significantly lower than control (265 ± 21 g and 17.4 ± 2.5 mm, respectively, p<0.05 for both). There was no difference in the incidences of sudden cardiac death (SCD) in these two groups of dogs. Conclusion Beta3-AR stimulation significantly reduces the occurrence of ventricular tachycardia. PMID:18242556

Dynamical histories of the IC 348 and NGC 1333 star-forming regions in Perseus

NASA Astrophysics Data System (ADS)

Parker, Richard J.; Alves de Oliveira, Catarina

2017-07-01

We present analyses of the spatial distributions of stars in the young (1-3 Myr) star-forming regions IC 348 and NGC 1333 in the Perseus giant molecular cloud. We quantify the spatial structure using the Q-parameter and find that both IC 348 and NGC 1333 are smooth and centrally concentrated with Q-parameters of 0.98 and 0.89, respectively. Neither region exhibits mass segregation (Λ _MSR = 1.1^{+0.2}_{-0.3} for IC 348 and Λ _MSR = 1.2^{+0.4}_{-0.3} for NGC 1333, where ΛMSR ˜ 1 corresponds to no mass segregation) nor do the most massive stars reside in areas of enhanced stellar surface density compared to the average surface density, according to the ΣLDR method. We then constrain the dynamical histories and hence initial conditions of both regions by comparing the observed values to N-body simulations at appropriate ages. Stars in both regions likely formed with subvirial velocities that contributed to merging of substructure and the formation of smooth clusters. The initial stellar densities were no higher than ρ ˜ 100-500 M⊙ pc-3 for IC 348 and ρ ˜ 500-2000 M⊙ pc-3 for NGC 1333. These initial densities, in particular that of NGC 1333, are high enough to facilitate dynamical interactions that would likely affect ˜10 per cent of protoplanetary discs and binary stars.

Analog/digital pH meter system I.C.

NASA Technical Reports Server (NTRS)

Vincent, Paul; Park, Jea

1992-01-01

The project utilizes design automation software tools to design, simulate, and fabricate a pH meter integrated circuit (IC) system including a successive approximation type seven-bit analog to digital converter circuits using a 1.25 micron N-Well CMOS MOSIS process. The input voltage ranges from 0.5 to 1.0 V derived from a special type pH sensor, and the output is a three-digit decimal number display of pH with one decimal point.

Model Checking with Multi-Threaded IC3 Portfolios

DTIC Science & Technology

2015-01-15

different runs varies randomly depending on the thread interleaving. The use of a portfolio of solvers to maximize the likelihood of a quick solution is...empirically show (cf. Sec. 5.2) that the predictions based on this formula have high accuracy. Note that each solver in the portfolio potentially searches...speedup of over 300. We also show that widening the proof search of ic3 by randomizing its SAT solver is not as effective as paral- lelization

Bioactive metabolites from the fungus Nectria galligena, the main apple canker agent in Chile.

PubMed

Gutiérrez, Margarita; Theoduloz, Cristina; Rodríguez, Jaime; Lolas, Mauricio; Schmeda-Hirschmann, Guillermo

2005-10-05

The phytopathogenic fungus Nectria galligena Bres. is the most common canker disease agent of hardwood trees. The terpenoids colletochlorin B, colletorin B, ilicicolin C, E, and F, as well as the phytotoxin alpha,beta-dehydrocurvularin have been isolated from liquid cultures of N. galligena obtained from the xylem of infected apple trees in central Chile. Ilicicolin C and F and alpha,beta-dehydrocurvularin were active against Pseudomonas syringae with IC50 values of 28.5, 28.5, and 14.2 microg/mL, respectively, in the same range as streptomycin and penicillin G (11 and 15 microg/mL, respectively). All of the compounds showed moderate inhibitory activity toward the enzymes acetylcholinesterase (AChE) and beta-glucuronidase. The most active enzyme inhibitors were colletochlorin B and ilicicolin C and E, with IC50 values of 30-36 microg/mL in the AChE assay and 32-43 microg/mL in the beta-glucuronidase test. All of the chlorinated compounds showed some toxicity toward human lung fibroblasts, with IC50 values in the range of 64-120 microg/mL. alpha,beta-Dehydrocurvularin proved to be the most toxic compound, showing IC50 values less than 12 microg/mL. The effect of the isolated compounds on seed germination and radicle and epicotyl growth was assessed in lettuce and millet seeds. At 100 and 200 microg/disk, alpha,beta-dehydrocurvularin significantly reduced radicle length and epicotyl growth in Lactuca sativa. This is the first report on the occurrence of colletochlorin B, colletorin B, ilicicolin C, E, and F, as well as alpha,beta-dehydrocurvularin associated to N. galligena.

Catalytic superoxide scavenging by metal complexes of the calcium chelator EGTA and contrast agent EHPG.

PubMed

Fisher, Anna E O; Hague, Theresa A; Clarke, Charlotte L; Naughton, Declan P

2004-10-08

Metal ion chelators widely used in experimental protocols and clinical diagnosis are generally assumed to be inert. We previously reported that the ubiquitous chelator EDTA has high levels of superoxide suppressing activity. Here, we report that the common chelators calcium chelator EGTA and contrast agent EHPG have significant activities in suppressing superoxide levels depending on the nature of metal ion chelated. The most active species is Mn(II)-EGTA which exhibited an IC50 value of 0.19 microM for superoxide destruction. In addition, IC50 values for Mn(II)-EHPG and 2Cu(II)-EGTA were 0.69 and 0.60 microM, respectively. In conclusion, Mn(II) and Cu(II) complexes of the common chelators EGTA and EHPG exhibit considerable superoxide scavenging activities. Caution should be employed in their use in biological systems where superoxide has a key role and they may be useful for the development of catalytic anti-oxidants. Copyright 2004 Elsevier Inc.

The size and structure of the spheroid of IC 1613

NASA Astrophysics Data System (ADS)

Battinelli, P.; Demers, S.; Artigau, É.

2007-05-01

Context: Nearby galaxies, spirals as well as irregulars, have been found to be much larger than previously believed. The structure of the huge spheroid surrounding dwarf galaxies could give clues to their past gravitational history. Thanks to wide field imagers, nearby galaxies with diameter of dozens of arcmin can be effectively surveyed. Aims: We obtain, from the CFHT archives, a series of i' and g' MegaCam images of IC 1613 in order to determine the stellar surface density of the field and determine the shape of its spheroid. Methods: From the colour magnitude diagram we select some 36 000 stars, in the first three magnitudes of the red giant branch. The spatial distribution of these stars is used to establish the structure of the spheroid. Results: The position angle of the major axis of the stellar spheroid is found to be ≈90°, some 30° from the major axis of the HI cloud surrounding IC 1613. The surface density profile of the spheroid is not exponential over all the length of the major axis. A King profile, with a core radius of 4.5' and a tidal radius of 24' fits the data. The tidal truncation of the spheroid suggests that IC 1613 is indeed a satellite of M 31. Based on observations obtained with MegaPrime/MegaCam, a joint project of CFHT and CEA/DAPNIA, at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council (NRC) of Canada, the Institute National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and the University of Hawaii.

A Pilot Study of the Kinematics of the Open Cluster IC 4756.

NASA Astrophysics Data System (ADS)

Upgren, A. R.; Lee, J. T.; Weis, E. W.

1998-12-01

In 1982 a working group of I.A.U. Commission 24 was established in order to provide parallax standard fields (IAU Transactions, XVIIIB,127 1982). Three of these fields for regular trigonometric parallax observation are centered on open clusters; the Pleiades, Praesepe and IC4756. Very few studies on IC4756 have been made; one is by Herzog and Sanders (AAPS, 19, 211 1975). The Van Vleck Observatory began normal parallax observations of IC4756 with its 0.5m astrometric refractor in 1980. A few observations were also obtained in 1963. Using Yale PDS machine, Lee has measured two of these early plates and two from 1997-98. The proper motion differences among the stars from different plate pair solutions are about 0.0008"/yr, and the mean proper motion of member stars is about 0.003"/yr, with respect to the mean motion of the field stars. The epoch difference of 34 years appears sufficient for accurate measures of the internal motion of the member stars. This cluster has also been observed with the 1.5m reflector of the U.S. Naval Observatory and the 0.65m McCormick Observatory refractor. These observations may also become available for the motion study.

The optical design of 3D ICs for smartphone and optro-electronics sensing module

NASA Astrophysics Data System (ADS)

Huang, Jiun-Woei

2018-03-01

Smartphone require limit space for image system, current lens, used in smartphones are refractive type, the effective focal length is limited the thickness of phone physical size. Other, such as optro-electronics sensing chips, proximity optical sensors, and UV indexer chips are integrated into smart phone with limit space. Due to the requirement of multiple lens in smartphone, proximity optical sensors, UV indexer and other optro-electronics sensing chips in a limited space of CPU board in future smart phone, optro-electronics 3D IC's integrated with optical lens or components may be a key technology for 3 C products. A design for reflective lens is fitted to CMOS, proximity optical sensors, UV indexer and other optro-electronics sensing chips based on 3-D IC. The reflective lens can be threes times of effective focal lens, and be able to resolve small object. The system will be assembled and integrated in one 3-D IC more easily.

Comparison of ion chromatographic methods based on conductivity detection, post-column-reaction and on-line-coupling IC-ICP-MS for the determination of bromate.

PubMed

Schminke, G; Seubert, A

2000-02-01

An established method for the determination of the disinfection by-product bromate is ion chromatography (IC). This paper presents a comparison of three IC methods based on either conductivity detection (IC-CD), a post-column-reaction (IC-PCR-VIS) or the on-line-coupling with inductively coupled plasma mass spectrometry (IC-ICP-MS). Main characteristics of the methods such as method detection limits (MDL), time of analysis and sample pretreatment are compared and applicability for routine analysis is critically discussed. The most sensitive and rugged method is IC-ICP-MS, followed by IC-PCR-VIS. The photometric detection is subject to a minor interference in real world samples, presumably caused by carbonate. The lowest sensitivity is shown by the IC-CD method as slowest method compared, which, in addition, requires a sample pretreatment. The highest amount of information is delivered by IC-PCR-VIS, which allows the simultaneous determination of the seven standard anions and bromate.

Body malodours and their topical treatment agents.

PubMed

Kanlayavattanakul, M; Lourith, N

2011-08-01

Body malodour, including foot odour, suppresses social interaction by diminishing self-confidence and accelerating damage to the wearer's clothes and shoes. Most treatment agents, including aluminium anti-perspirant salts, inhibit the growth of malodourous bacteria. These metallic salts also reduce sweat by blocking the excretory ducts of sweat glands, minimizing the water source that supports bacterial growth. However, there are some drawback effects that limit the use of aluminium anti-perspirant salts. In addition, over-the-counter anti-perspirant and deodourant products may not be sufficiently effective for heavy sweaters, and strong malodour producers. Body odour treatment agents are rarely mentioned in the literature compared with other cosmetic ingredients. This review briefly summarizes the relationship among sweat, skin bacteria, and body odour; describes how odourous acids, thiols, and steroids are formed; and discusses the active ingredients, including metallic salts and herbs, that are used to treat body odour. A new class of ingredients that function by regulating the release of malodourants will also be described. These ingredients do not alter the balance of the skin flora. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy.

PubMed

Alcorlo, Martin; Martínez-Barricarte, Ruben; Fernández, Francisco J; Rodríguez-Gallego, César; Round, Adam; Vega, M Cristina; Harris, Claire L; de Cordoba, Santiago Rodríguez; Llorca, Oscar

2011-08-09

Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities.

Polysaccharide of radix pseudostellariae improves chronic fatigue syndrome induced by poly I:C in mice.

PubMed

Sheng, Rong; Xu, Xianxiang; Tang, Qin; Bian, Difei; Li, Ying; Qian, Cheng; He, Xin; Gao, Xinghua; Pan, Rong; Wang, Chong; Luo, Yubin; Xia, Yufeng; Dai, Yue

2011-01-01

Radix Pseudostellariae is used as a tonic drug in traditional Chinese medicine with immunomodulating and anti-fatigue activities, and the polysaccharide is considered as the main active component. The purpose of this study is to examine the effect of the polysaccharide isolated from Radix Pseudostellariae (PRP) on mouse chronic fatigue syndrome (CFS) induced by intraperitoneal injection of polyriboinosinic:polyribocytidylic acid (poly I:C), a double-stranded synthetic RNA. It has shown that the fatigue symptom of mice lasted at least 1 week as evaluated by forced swimming time. PRP (100, 200, 400 mg kg(-1)), orally administered 3 days before poly I:C injection, showed dose-dependent anti-fatigue effects. In addition, poly I:C led to evident alternations in neuroendocrine and immune systems of mice, such as reduced spontaneous activity and learning ability, declined serum level of corticosterone, increased weight indexes and T lymphocyte numbers in thymuses and spleens, and increased CD4(+)/CD8(+) ratio but decreased proliferation ability of T lymphocytes in spleens. PRP alleviated the abnormalities caused by poly I:C, and restored the function of hosts to normal conditions. The findings suggest that PRP is beneficial to CFS, and the underlying mechanisms of action involve neuroendocrine and immune systems.

The Evolution of Stellar Coronae: Initial Results from a ROSAT PSPC Observation of IC 2391

NASA Technical Reports Server (NTRS)

Patten, Brian M.; Simon, Theodore

1993-01-01

A 23 ks ROSAT PSPC image of the young star cluster, IC 2391, reveals 76 soft x-ray sources with L(sub x)(0.2-2.0 keV) greater than or equal to 2 x 10(exp 28) ergs/s in the direction of the cluster center. Nineteen of these sources are associated with known cluster members. We find that x-ray emission from the IC 2391 B stars deviates widely from the L(sub x)/L(sub bol) = 10(exp -7) relation based on Einstein observations of O and early B stars. Instead, we observe a wide range in L(sub x) with an order of magnitude spread at any given mass and no apparent dependence on spectral type. A comparison of the spread of L(sub x) as a function of B-V for low-mass stars between IC 2391 and the much older Hyades cluster shows that despite the factor of approx. 10 difference in their ages, these two clusters exhibit very similar dispersions in levels of stellar activity. We conclude that the low-mass stars in IC 2391 have arrived on the ZAMS with a wide range of coronal activity levels, from very strong to very weak, and that existing empirical activity-age scaling laws therefore cannot be valid.

Uploading, Searching and Visualizing of Paleomagnetic and Rock Magnetic Data in the Online MagIC Database

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A.; Tauxe, L.; Constable, C.; Donadini, F.

2007-12-01

The Magnetics Information Consortium (MagIC) is commissioned to implement and maintain an online portal to a relational database populated by both rock and paleomagnetic data. The goal of MagIC is to archive all available measurements and derived properties from paleomagnetic studies of directions and intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). MagIC is hosted under EarthRef.org at http://earthref.org/MAGIC/ and will soon implement two search nodes, one for paleomagnetism and one for rock magnetism. Currently the PMAG node is operational. Both nodes provide query building based on location, reference, methods applied, material type and geological age, as well as a visual map interface to browse and select locations. Users can also browse the database by data type or by data compilation to view all contributions associated with well known earlier collections like PINT, GMPDB or PSVRL. The query result set is displayed in a digestible tabular format allowing the user to descend from locations to sites, samples, specimens and measurements. At each stage, the result set can be saved and, where appropriate, can be visualized by plotting global location maps, equal area, XY, age, and depth plots, or typical Zijderveld, hysteresis, magnetization and remanence diagrams. User contributions to the MagIC database are critical to achieving a useful research tool. We have developed a standard data and metadata template (version 2.3) that can be used to format and upload all data at the time of publication in Earth Science journals. Software tools are provided to facilitate population of these templates within Microsoft Excel. These tools allow for the import/export of text files and provide advanced functionality to manage and edit the data, and to perform various internal checks to maintain data integrity and prepare for uploading. The MagIC Contribution Wizard at http://earthref.org/MAGIC/upload.htm executes the upload

Magnetic force microscopy/current contrast imaging: A new technique for internal current probing of ICs

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

Campbell, A.N.; Cole, E.I. Jr.; Dodd, B.A.

This invited paper describes recently reported work on the application of magnetic force microscopy (MFM) to image currents in IC conductors [1]. A computer model for MFM imaging of IC currents and experimental results demonstrating the ability to determine current direction and magnitude with a resolution of {approximately} 1 mA dc and {approximately} 1 {mu}A ac are presented. The physics of MFM signal generation and applications to current imaging and measurement are described.

Observation of Nonthermal Emission from the Supernova Remnant IC443 with RXTE

NASA Technical Reports Server (NTRS)

Sturner, S. J.; Keohane, J. W.; Reimer, O.

2002-01-01

In this paper we present analysis of X-ray spectra from the supernova remnant IC443 obtained using the PCA on RXTE. The spectra in the 3 - 20 keV band are well fit by a two-component model consisting of thermal and nonthermal components. We compare these results with recent results of other X-ray missions and discuss the need for a cut-off in the nonthermal spectrum. Recent Chandra and XMM-Newton observations suggest that much of the nonthermal emission from IC443 can be attributed to a pulsar wind nebula. We present the results of our search for periodic emission in the RXTE PCA data. We then discuss the origin o f the nonthermal component and its possible association with the unidentified EGRET source.

IC 4663: The First Unambiguous [WN] Wolf-Rayet Central Star of a Planetary Nebula

NASA Astrophysics Data System (ADS)

Miszalski, B.; Crowther, P. A.; De Marco, O.; Köppen, J.; Moffat, A. F. J.; Acker, A.; Hillwig, T. C.

2013-01-01

Several [WC]-type central stars of planetary nebulae (PNe) are known to mimic the spectroscopic appearance of massive carbon-rich or WC-type Wolf-Rayet stars. In stark contrast, no [WN]-type central stars have yet been identified as clear-cut analogues of the common nitrogen-rich or WN-type Wolf-Rayet stars. We have identified the [WN3] central star of IC 4663 to be the first unambiguous example in PNe. The low luminosity nucleus and an asymptotic giant branch (AGB) halo surrounding the main nebula prove the bona-fide PN nature of IC 4663. Model atmosphere analysis reveals the [WN3] star to have an exotic chemical composition of helium (95%), hydrogen (<2%), nitrogen (0.8%), neon (0.2%) and oxygen (0.05%) by mass. Such an extreme helium-dominated composition cannot be predicted by current evolutionary scenarios for hydrogen deficient [WC]-type central stars. Only with the discovery of IC 4663 and its unusual composition can we now connect [WN] central stars to the O(He) central stars in a second H-deficient and He-rich evolutionary sequence, [WN]→O(He), that exists in parallel to the carbon-rich [WC]→PG1159 sequence. This suggests a simpler mechanism, perhaps a binary merger, can better explain H-deficiency in PNe and potentially other H-deficient/He-rich stars. In this respect IC 4663 is the best supported case for a possible merged binary central star of a PN.

In vivo tumor characterization using both MR and optical contrast agents with a hybrid MRI-DOT system

NASA Astrophysics Data System (ADS)

Lin, Yuting; Ghijsen, Michael; Thayer, David; Nalcioglu, Orhan; Gulsen, Gultekin

2011-03-01

Dynamic contrast enhanced MRI (DCE-MRI) has been proven to be the most sensitive modality in detecting breast lesions. Currently available MR contrast agent, Gd-DTPA, is a low molecular weight extracellular agent and can diffuse freely from the vascular space into interstitial space. Due to this reason, DCE-MRI has low sensitivity in differentiating benign and malignant tumors. Meanwhile, diffuse optical tomography (DOT) can be used to provide enhancement kinetics of an FDA approved optical contrast agent, ICG, which behaves like a large molecular weight optical agent due to its binding to albumin. The enhancement kinetics of ICG may have a potential to distinguish between the malignant and benign tumors and hence improve the specificity. Our group has developed a high speed hybrid MRI-DOT system. The DOT is a fully automated, MR-compatible, multi-frequency and multi-spectral imaging system. Fischer-344 rats bearing subcutaneous R3230 tumor are injected simultaneously with Gd-DTPA (0.1nmol/kg) and IC-Green (2.5mg/kg). The enhancement kinetics of both contrast agents are recorded simultaneously with this hybrid MRI-DOT system and evaluated for different tumors.

Individual receptor profiling as a novel tool to support diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC).

PubMed

Neuhaus, Jochen; Schulte-Baukloh, Heinrich; Stolzenburg, Jens-Uwe; Speroni di Fenizio, Pietro; Horn, Lars-Christian; Rüffert, Henrik; Hartenstein, Siegurd; Burger, Maximilian; Schulze, Matthias; Schwalenberg, Thilo

2012-10-01

Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor. Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n = 44; age 60.64 ± 13.78, mean ± SD) and carcinoma patients (n = 11; age 58.91 ± 12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1-3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR). M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2 > M3 and M3 > M2) were observed, which differed in associated purinergic and histamine receptor expression. M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.

Missing the Mark: Is ICS Training Achieving Its Goal

DTIC Science & Technology

2016-12-01

method achieves learning and actually gives students new knowledge, skills, and 281 Ibid. 282 Ibid...designed to be five days (40 hours) long.331 The class assumes that the student already has a general understanding of ICS and completion of at least...35–37. 64 The entire process is time consuming, as the student must complete the in- class time (as required for the specific class ) and

[Antifibrillatory activity of anti-arrhythmia agents in maximally high ligation of the coronary artery and its reperfusion in cats].

PubMed

Storozhuk, B G

1985-01-01

Experiments on anesthesized cats were performed to study antifibrillatory action of the basic antiarrhythmic remedies and a new Soviet drug, phenicaberan. It was established that phenicaberan and lidocaine compare very favourably with other drugs under study as regards the antifibrillatory effect. For that reason these drugs can be recommended for use in the prophylaxis of fatal arrhythmias.

Optimizing catecholaminergic polymorphic ventricular tachycardia therapy in calsequestrin-mutant mice

PubMed Central

Katz, Guy; Khoury, Assad; Kurtzwald, Efrat; Hochhauser, Edith; Porat, Eyal; Shainberg, Asher; Seidman, Jonathan G.; Seidman, Christine E.; Lorber, Abraham; Eldar, Michael; Arad, Michael

2014-01-01

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal arrhythmia provoked by physical or emotional stress and mediated by spontaneous Ca2+ release and delayed after-depolarizations. Beta-adrenergic blockers are the therapy of choice but fail to control arrhythmia in up to 50% of patients. OBJECTIVE To optimize antiarrhythmic therapy in recessively inherited CPVT caused by calsequestrin (CASQ2) mutations. METHODS Murine heart rhythm telemetry was obtained at rest, during treadmill exercise, and after injection of epinephrine. The protocol was repeated after injection of different antiarrhythmic drugs. Results were then validated in human patients. RESULTS Adult CASQ2 mutant mice had complex ventricular arrhythmia at rest and developed bidirectional and polymorphic ventricular tachycardia on exertion. Class I antiarrhythmic agents (procainamide, lidocaine, flecainide) were ineffective in controlling arrhythmia. Propranolol and sotalol attenuated arrhythmia at rest but failed to prevent VT during sympathetic stimulation. The calcium channel blocker verapamil showed a dose-dependent protection against CPVT. Verapamil was more effective than the dihydropyridine L-type Ca2+ channel blocker nifedipine, and its activity was markedly enhanced when combined with propranolol. Human patients homozygous for CASQ2D307H mutation, remaining symptomatic despite chronic β-blocker therapy, underwent exercise testing according to the Bruce protocol with continuous electrocardiogram recording. Verapamil was combined with propranolol at maximum tolerated doses. Adding verapamil attenuated ventricular arrhythmia and prolonged exercise duration in five of 11 patients. CONCLUSION Verapamil is highly effective against catecholamine-induced arrhythmia in mice with CASQ2 mutations and may potentiate the antiarrhythmic activity of β-blockers in humans with CPVT2. PMID:20620233

Growing Aligned Carbon Nanotubes for Interconnections in ICs

NASA Technical Reports Server (NTRS)

Li, Jun; Ye, Qi; Cassell, Alan; Ng, Hou Tee; Stevens, Ramsey; Han, Jie; Meyyappan, M.

2005-01-01

A process for growing multiwalled carbon nanotubes anchored at specified locations and aligned along specified directions has been invented. Typically, one would grow a number of the nanotubes oriented perpendicularly to a silicon integrated-circuit (IC) substrate, starting from (and anchored on) patterned catalytic spots on the substrate. Such arrays of perpendicular carbon nanotubes could be used as electrical interconnections between levels of multilevel ICs. The process (see Figure 1) begins with the formation of a layer, a few hundred nanometers thick, of a compatible electrically insulating material (e.g., SiO(x) or Si(y)N(z) on the silicon substrate. A patterned film of a suitable electrical conductor (Al, Mo, Cr, Ti, Ta, Pt, Ir, or doped Si), having a thickness between 1 nm and 2 m, is deposited on the insulating layer to form the IC conductor pattern. Next, a catalytic material (usually, Ni, Fe, or Co) is deposited to a thickness between 1 and 30 nm on the spots from which it is desired to grow carbon nanotubes. The carbon nanotubes are grown by plasma-enhanced chemical vapor deposition (PECVD). Unlike the matted and tangled carbon nanotubes grown by thermal CVD, the carbon nanotubes grown by PECVD are perpendicular and freestanding because an electric field perpendicular to the substrate is used in PECVD. Next, the free space between the carbon nanotubes is filled with SiO2 by means of CVD from tetraethylorthosilicate (TEOS), thereby forming an array of carbon nanotubes embedded in SiO2. Chemical mechanical polishing (CMP) is then performed to remove excess SiO2 and form a flat-top surface in which the outer ends of the carbon nanotubes are exposed. Optionally, depending on the application, metal lines to connect selected ends of carbon nanotubes may be deposited on the top surface. The top part of Figure 2 is a scanning electron micrograph (SEM) of carbon nanotubes grown, as described above, on catalytic spots of about 100 nm diameter patterned by

Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart.

PubMed

Osadchii, Oleg E

2016-01-01

Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length. ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation. Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms). Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.

Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

PubMed

Drolet, Benoit; Yang, Tao; Daleau, Pascal; Roden, Dan M; Turgeon, Jacques

2003-06-01

Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms. In human ether-a-go-go (HERG)-transfected Chinese hamster ovary cells (n = 16), risperidone caused concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current with an IC(50) for tail block of 261 nM. Risperidone did not block I(Ks). Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations. Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs).

The use of light emission in failure analysis of CMOS ICs

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

Hawkins, C.F.; Soden, J.M.; Cole, E.I. Jr.

1990-01-01

The use of photon emission for analyzing failure mechanisms and defects in CMOS ICs is presented. Techniques are given for accurate identification and spatial localization of failure mechanisms and physical defects, including defects such as short and open circuits which do not themselves emit photons.

Observation of Extended Very High Energy Emission from the Supernova Remnant IC 443 with VERITAS

NASA Astrophysics Data System (ADS)

Acciari, V. A.; Aliu, E.; Arlen, T.; Aune, T.; Bautista, M.; Beilicke, M.; Benbow, W.; Bradbury, S. M.; Buckley, J. H.; Bugaev, V.; Butt, Y.; Byrum, K.; Cannon, A.; Celik, O.; Cesarini, A.; Chow, Y. C.; Ciupik, L.; Cogan, P.; Colin, P.; Cui, W.; Daniel, M. K.; Dickherber, R.; Duke, C.; Dwarkadas, V. V.; Ergin, T.; Fegan, S. J.; Finley, J. P.; Finnegan, G.; Fortin, P.; Fortson, L.; Furniss, A.; Gall, D.; Gibbs, K.; Gillanders, G. H.; Godambe, S.; Grube, J.; Guenette, R.; Gyuk, G.; Hanna, D.; Hays, E.; Holder, J.; Horan, D.; Hui, C. M.; Humensky, T. B.; Imran, A.; Kaaret, P.; Karlsson, N.; Kertzman, M.; Kieda, D.; Kildea, J.; Konopelko, A.; Krawczynski, H.; Krennrich, F.; Lang, M. J.; LeBohec, S.; Maier, G.; McCann, A.; McCutcheon, M.; Millis, J.; Moriarty, P.; Ong, R. A.; Otte, A. N.; Pandel, D.; Perkins, J. S.; Pohl, M.; Quinn, J.; Ragan, K.; Reyes, L. C.; Reynolds, P. T.; Roache, E.; Rose, H. J.; Schroedter, M.; Sembroski, G. H.; Smith, A. W.; Steele, D.; Swordy, S. P.; Theiling, M.; Toner, J. A.; Valcarcel, L.; Varlotta, A.; Vassiliev, V. V.; Vincent, S.; Wagner, R. G.; Wakely, S. P.; Ward, J. E.; Weekes, T. C.; Weinstein, A.; Weisgarber, T.; Williams, D. A.; Wissel, S.; Wood, M.; Zitzer, B.

2009-06-01

We present evidence that the very high energy (VHE, E > 100 GeV) gamma-ray emission coincident with the supernova remnant IC 443 is extended. IC 443 contains one of the best studied sites of supernova remnant/molecular cloud interaction and the pulsar wind nebula CXOU J061705.3+222127, both of which are important targets for VHE observations. VERITAS observed IC 443 for 37.9 hr during 2007 and detected emission above 300 GeV with an excess of 247 events, resulting in a significance of 8.3 standard deviations (σ) before trials and 7.5σ after trials in a point-source search. The emission is centered at 6h16m51s + 22°30'11'' (J2000) ±0fdg03stat ± 0fdg08sys, with an intrinsic extension of 0fdg16 ± 0fdg03stat ± 0fdg04sys. The VHE spectrum is well fit by a power law (dN/dE = N 0 × (E/TeV)-Γ) with a photon index of 2.99 ± 0.38stat ± 0.3sys and an integral flux above 300 GeV of (4.63 ± 0.90stat ± 0.93sys) × 10-12 cm-2 s-1. These results are discussed in the context of existing models for gamma-ray production in IC 443.

Evaluation of a Cordia-IC enzyme-linked immunosorbent assay kit for the detection of circulating immune complexes.

PubMed Central

Landoy, Z; West, T E; Vladutiu, A O; Fitzpatrick, J E

1985-01-01

A commercial kit (Cordia-IC) from Cordis Laboratory, Miami, Fla., was compared with the Raji cell radioimmunoassay for its ability to detect circulating immune complexes (CIC) in sera from 30 control subjects and 118 patients with infectious diseases. The 118 patients were categorized into the following groups: (i) 23 patients with bacterial endocarditis, (ii) 41 patients with bacteremia from an infected intravascular catheter or access device, and (iii) 54 patients with Staphylococcus aureus bacteremia related to a deep tissue infection. The Cordia-IC was comparable to the Raji cell radioimmunoassay in intraassay variability (4.0 versus 8.0%) and interassay reproducibility (8.7 versus 20.0%). Neither assay found CIC amounts above 12.5 micrograms equivalents (eq) of aggregated human gamma globulin (AHG) per ml in any of the 30 control individuals. In group 1, Cordia-IC detected 19 of 23 positives (mean, 73.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 23 positives (mean, 54.8 micrograms eq of AHG per ml). In group 2, Cordia-IC detected 19 of 41 positives (mean, 20.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 41 positives (mean, 15.1 micrograms eq of AHG per ml). In group 3, Cordia-IC found 38 of 54 positives (mean, 28.0 micrograms eq of AHG per ml), whereas the Raji cell found 32 of 54 positives (mean, 23.9 micrograms eq of AHG per ml). Statistically, these findings were not significantly different in any of the three patient groups (P> 0.15), and there was an overall good correlation between the results obtained by the two assays (r+0.64, P<0.001). The Cordia-IC provided a suitable assay for the detection of CIC and might find application in routine clinical laboratories. PMID:3897269

30 CFR 57.22228 - Preshift examination (I-A, I-C, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Preshift examination (I-A, I-C, II-A, III, and V-A mines). 57.22228 Section 57.22228 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Preshift examination (I-A, I-C, II-A, III, and V-A mines). (a) Preshift examinations shall be conducted...

30 CFR 57.22228 - Preshift examination (I-A, I-C, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Preshift examination (I-A, I-C, II-A, III, and V-A mines). 57.22228 Section 57.22228 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Preshift examination (I-A, I-C, II-A, III, and V-A mines). (a) Preshift examinations shall be conducted...

An attempt to evaluate the effect of vitamin K3 using as an enhancer of anticancer agents.

PubMed

Matzno, Sumio; Yamaguchi, Yuka; Akiyoshi, Takeshi; Nakabayashi, Toshikatsu; Matsuyama, Kenji

2008-06-01

The possibility of vitamin K3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with IC50 of 13.7 microM and Hill coefficient of 3.1 in Hep G2 cells. It also decreased the population of S phase and arrested cell cycle in the G2/M phase in a dose-dependent manner. G2/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G2 phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G2/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G2 phase-dependent drugs in hepatic cancer chemotherapy.

High-resolution radio study of SNR IC 443 at low radio frequencies

NASA Astrophysics Data System (ADS)

Castelletti, G.; Dubner, G.; Clarke, T.; Kassim, N. E.

2011-10-01

Aims: We investigate the morphology at low radio frequencies of the supernova remnant (SNR) IC 443 in detail and accurately establish its radio continuum spectral properties. Methods: We used the VLA in multiple configurations to produce high-resolution radio images of IC 443 at 74 and 330 MHz. From these data we produced the first sensitive, spatially resolved spectral analysis of the radio emission at long wavelengths. The changes with position in the radio spectral index were correlated with data in near infrared (NIR) from 2MASS, in gamma-rays from VERITAS, and with the molecular 12CO (J = 1 - 0) line emission. Results: The new image at 74 MHz has HPBW = 35'' and rms = 30 mJy beam-1 and at 330 MHz HPBW = 17'' and rms = 1.7 mJy beam-1. The integrated flux densities for the whole SNR are S74 MHzSNR=470±51 Jy and S330 MHzSNR=248±15 Jy. Improved estimates of the integrated spectrum were derived taking a turnover into account to fit the lowest frequency measurements in the literature. Combining our measurements with existing data, we derive an integrated spectral index α10 MHz10700 MHz=-0.39±0.01 with a free-free continuum optical depth at 330 MHz τ330 ~ 7 × 10-4 (τ10 = 1.07); all measurements above ~ 10 MHz are equally consistent with a power law spectrum. For the pulsar wind nebula associated with the compact source CXOU J061705.3+222127, we calculated S330 MHzPWN=0.23±0.05 Jy, S1420 MHzPWN=0.20±0.04 Jy, and α330 MHz8460 MHz˜ 0.0. Substantial variations are observed in spectral index between 74 and 330 MHz across IC 443. The flattest spectral components ( - 0.25 ≤ α ≤ - 0.05) coincide with the brightest parts of the SNR along the eastern border, with an impressive agreement with ionic lines as observed in the 2MASS J and H bands. The diffuse interior of IC 443 has a spectrum steeper than found anywhere in the SNR ( - 0.85 ≤ α ≤ - 0.6), while the southern ridge again has a flatter spectrum (α ~ -0.4). With the available statistics the VERITAS

Long-term prediction test procedure for most ICs, based on linear response theory

NASA Technical Reports Server (NTRS)

Litovchenko, V.; Ivakhnenko, I.

1991-01-01

Experimentally, thermal annealing is known to be a factor which enables a number of different integrated circuits (IC's) to recover their operating characteristics after suffering radiation damage in the space radiation environment; thus, decreasing and limiting long term cumulative total-dose effects. This annealing is also known to be accelerated at elevated temperatures both during and after irradiation. Linear response theory (LRT) was applied, and a linear response function (LRF) to predict the radiation/annealing response of sensitive parameters of IC's for long term (several months or years) exposure to the space radiation environment were constructed. Compressing the annealing process from several years in orbit to just a few hours or days in the laboratory is achieved by subjecting the IC to elevated temperatures or by increasing the typical spaceflight dose rate by several orders of magnitude for simultaneous radiation/annealing only. The accomplishments are as follows: (1) the test procedure to make predictions of the radiation response was developed; (2) the calculation of the shift in the threshold potential due to the charge distribution in the oxide was written; (3) electron tunneling processes from the bulk Si to the oxide region in an MOS IC were estimated; (4) in order to connect the experimental annealing data to the theoretical model, constants of the model of the basic annealing process were established; (5) experimental data obtained at elevated temperatures were analyzed; (6) time compression and reliability of predictions for the long term region were shown; (7) a method to compress test time and to make predictions of response for the nonlinear region was proposed; and (8) nonlinearity of the LRF with respect to log(t) was calculated theoretically from a model.

Experimentally Observed Electrical Durability of 4H-SiC JFET ICs Operating from 500 C to 700 C

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Spry, David J.; Chen, Liangyu; Lukco, Dorothy; Chang, Carl W.; Beheim, Glenn M.

2016-01-01

This ECSCRM 2016 submission presents further electrical testing and microscopic post-failure studies aimed at more comprehensive understanding of the durability limits of this extreme temperature IC technology. The results summarized represent an unprecedented combination of T 500 C semiconductor IC durability and functionality.

Amiodarone therapy in chronic heart failure and myocardial infarction: a review of the mortality trials with special attention to STAT-CHF and the GESICA trials. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina.

PubMed

Pinto, J V; Ramani, K; Neelagaru, S; Kown, M; Gheorghiade, M

1997-01-01

Amiodarone appears to reduce sudden death in patients with left ventricular dysfunction resulting from an acute MI or a primary dilated cardiomyopathy, particularly if complex ventricular arrhythmias are present. Amiodarone's beneficial effect on mortality in these patients could be unrelated to its antiarrhythmic effects. Multiple factors could account for the improvement in mortality such as the drug's antiischemic effects, neuromodulating effects, its effect on left ventricular function and on heart rate. Moreover, patients with LV dysfunction who have survived an episode of sudden death would potentially benefit from amiodarone therapy. Future trials are needed to determine the precise subsets(s) of patients who would benefit from the drug and the most efficacious dosing regimen for the drug. Based on available data, amiodarone is the only antiarrhythmic agent which has not been shown to increase mortality in patients with chronic heart failure.

Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.

PubMed

Kaitani, Kazuaki; Inoue, Koichi; Kobori, Atsushi; Nakazawa, Yuko; Ozawa, Tomoya; Kurotobi, Toshiya; Morishima, Itsuro; Miura, Fumiharu; Watanabe, Tetsuya; Masuda, Masaharu; Naito, Masaki; Fujimoto, Hajime; Nishida, Taku; Furukawa, Yoshio; Shirayama, Takeshi; Tanaka, Mariko; Okajima, Katsunori; Yao, Takenori; Egami, Yasuyuki; Satomi, Kazuhiro; Noda, Takashi; Miyamoto, Koji; Haruna, Tetsuya; Kawaji, Tetsuma; Yoshizawa, Takashi; Toyota, Toshiaki; Yahata, Mitsuhiko; Nakai, Kentaro; Sugiyama, Hiroaki; Higashi, Yukei; Ito, Makoto; Horie, Minoru; Kusano, Kengo F; Shimizu, Wataru; Kamakura, Shiro; Morimoto, Takeshi; Kimura, Takeshi; Shizuta, Satoshi

2016-02-14

Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The planetary nebula IC 4776 and its post-common-envelope binary central star

NASA Astrophysics Data System (ADS)

Sowicka, Paulina; Jones, David; Corradi, Romano L. M.; Wesson, Roger; García-Rojas, Jorge; Santander-García, Miguel; Boffin, Henri M. J.; Rodríguez-Gil, Pablo

2017-11-01

We present a detailed analysis of IC 4776, a planetary nebula displaying a morphology believed to be typical of central star binarity. The nebula is shown to comprise a compact hourglass-shaped central region and a pair of precessing jet-like structures. Time-resolved spectroscopy of its central star reveals a periodic radial velocity variability consistent with a binary system. Whilst the data are insufficient to accurately determine the parameters of the binary, the most likely solutions indicate that the secondary is probably a low-mass main-sequence star. An empirical analysis of the chemical abundances in IC 4776 indicates that the common-envelope phase may have cut short the asymptotic giant branch evolution of the progenitor. Abundances calculated from recombination lines are found to be discrepant by a factor of approximately 2 relative to those calculated using collisionally excited lines, suggesting a possible correlation between low-abundance discrepancy factors and intermediate-period post-common-envelope central stars and/or Wolf-Rayet central stars. The detection of a radial velocity variability associated with the binarity of the central star of IC 4776 may be indicative of a significant population of (intermediate-period) post-common-envelope binary central stars that would be undetected by classic photometric monitoring techniques.

Crystallographic Studies of Two Bacterial AntibioticResistance Enzymes: Aminoglycoside Phosphotransferase (2')-Ic and GES-1\\beta-lactamase

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

Brynes, Laura; /Rensselaer Poly.

2007-10-31

Guiana Extended-Spectrum-1 (GES-1) and Aminoglycoside phosphotransferase (2')-Ic (APH(2')-Ic) are two bacteria-produced enzymes that essentially perform the same task: they provide resistance to an array of antibiotics. Both enzymes are part of a growing resistance problem in the medical world. In order to overcome the ever-growing arsenal of antibiotic-resistance enzymes, it is necessary to understand the molecular basis of their action. Accurate structures of these proteins have become an invaluable tool to do this. Using protein crystallography techniques and X-ray diffraction, the protein structure of GES-1 bound to imipenem (an inhibitor) has been solved. Also, APH(2')-Ic has been successfully crystallized, butmore » its structure was unable to be solved using molecular replacement using APH(2')-Ib as a search model. The structure of GES-1, with bound imipenem was solved to a resolution of 1.89A, and though the inhibitor is bound with only moderate occupancy, the structure shows crucial interactions inside the active site that render the enzyme unable to complete the hydrolysis of the {beta}-lactam ring. The APH(2')-Ic dataset could not be matched to the model, APH(2')-Ib, with which it shares 25% sequence identity. The structural information gained from GES-1, and future studies using isomorphous replacement to solve the APH(2')-Ic structure can aid directly to the creation of novel drugs to combat both of these classes of resistance enzymes.« less

Managing Rock and Paleomagnetic Data Flow with the MagIC Database: from Measurement and Analysis to Comprehensive Archive and Visualization

NASA Astrophysics Data System (ADS)

Koppers, A. A.; Minnett, R. C.; Tauxe, L.; Constable, C.; Donadini, F.

2008-12-01

The Magnetics Information Consortium (MagIC) is commissioned to implement and maintain an online portal to a relational database populated by rock and paleomagnetic data. The goal of MagIC is to archive all measurements and derived properties for studies of paleomagnetic directions (inclination, declination) and intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). Organizing data for presentation in peer-reviewed publications or for ingestion into databases is a time-consuming task, and to facilitate these activities, three tightly integrated tools have been developed: MagIC-PY, the MagIC Console Software, and the MagIC Online Database. A suite of Python scripts is available to help users port their data into the MagIC data format. They allow the user to add important metadata, perform basic interpretations, and average results at the specimen, sample and site levels. These scripts have been validated for use as Open Source software under the UNIX, Linux, PC and Macintosh© operating systems. We have also developed the MagIC Console Software program to assist in collating rock and paleomagnetic data for upload to the MagIC database. The program runs in Microsoft Excel© on both Macintosh© computers and PCs. It performs routine consistency checks on data entries, and assists users in preparing data for uploading into the online MagIC database. The MagIC website is hosted under EarthRef.org at http://earthref.org/MAGIC/ and has two search nodes, one for paleomagnetism and one for rock magnetism. Both nodes provide query building based on location, reference, methods applied, material type and geological age, as well as a visual FlashMap interface to browse and select locations. Users can also browse the database by data type (inclination, intensity, VGP, hysteresis, susceptibility) or by data compilation to view all contributions associated with previous databases, such as PINT, GMPDB or TAFI or other user

Somato-Motor Haptic Processing in Posterior Inner Perisylvian Region (SII/pIC) of the Macaque Monkey

PubMed Central

Ishida, Hiroaki; Fornia, Luca; Grandi, Laura Clara; Umiltà, Maria Alessandra; Gallese, Vittorio

2013-01-01

The posterior inner perisylvian region including the secondary somatosensory cortex (area SII) and the adjacent region of posterior insular cortex (pIC) has been implicated in haptic processing by integrating somato-motor information during hand-manipulation, both in humans and in non-human primates. However, motor-related properties during hand-manipulation are still largely unknown. To investigate a motor-related activity in the hand region of SII/pIC, two macaque monkeys were trained to perform a hand-manipulation task, requiring 3 different grip types (precision grip, finger exploration, side grip) both in light and in dark conditions. Our results showed that 70% (n = 33/48) of task related neurons within SII/pIC were only activated during monkeys’ active hand-manipulation. Of those 33 neurons, 15 (45%) began to discharge before hand-target contact, while the remaining neurons were tonically active after contact. Thirty-percent (n = 15/48) of studied neurons responded to both passive somatosensory stimulation and to the motor task. A consistent percentage of task-related neurons in SII/pIC was selectively activated during finger exploration (FE) and precision grasping (PG) execution, suggesting they play a pivotal role in control skilled finger movements. Furthermore, hand-manipulation-related neurons also responded when visual feedback was absent in the dark. Altogether, our results suggest that somato-motor neurons in SII/pIC likely contribute to haptic processing from the initial to the final phase of grasping and object manipulation. Such motor-related activity could also provide the somato-motor binding principle enabling the translation of diachronic somatosensory inputs into a coherent image of the explored object. PMID:23936121

Sulphur-Containing Heterocycles as Antimycobacterial Agents: Recent Advances in Thiophene and Thiadiazole Derivatives.

PubMed

Krátký, Martin; Vinsova, Jarmila

2016-01-01

The global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. Recent development is focused mainly on heterocyclic molecules. In many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. Thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. This review highlights the recent progress in the field with a focus on whole-cell antimycobacterial activity of the agents as well as targeting of enzymes from Mycobacterium tuberculosis. Some of the compounds have exhibited high activity with submicromolar minimum inhibitory concentrations including activity against drug-resistant strains and/or IC50 values for a range of enzymes as their targets (InhA, dehydroquinase, Pks13, carbonic anhydrases, DprE1). Mechanisms of action, toxicity, and structure-activity relationships are also discussed. Several compounds have exhibited promising in vitro and in vivo activities and safety profiles, thus constituting novel, promising leads.

An asymmetric energetic type Ic supernova viewed off-axis, and a link to gamma ray bursts.

PubMed

Mazzali, Paolo A; Kawabata, Koji S; Maeda, Keiichi; Nomoto, Ken'ichi; Filippenko, Alexei V; Ramirez-Ruiz, Enrico; Benetti, Stefano; Pian, Elena; Deng, Jinsong; Tominaga, Nozomu; Ohyama, Youichi; Iye, Masanori; Foley, Ryan J; Matheson, Thomas; Wang, Lifan; Gal-Yam, Avishay

2005-05-27

Type Ic supernovae, the explosions after the core collapse of massive stars that have previously lost their hydrogen and helium envelopes, are particularly interesting because of their link with long-duration gamma ray bursts. Although indications exist that these explosions are aspherical, direct evidence has been missing. Late-time observations of supernova SN 2003jd, a luminous type Ic supernova, provide such evidence. Recent Subaru and Keck spectra reveal double-peaked profiles in the nebular lines of neutral oxygen and magnesium. These profiles are different from those of known type Ic supernovae, with or without a gamma ray burst, and they can be understood if SN 2003jd was an aspherical axisymmetric explosion viewed from near the equatorial plane. If SN 2003jd was associated with a gamma ray burst, we missed the burst because it was pointing away from us.

Self-Patterning of Silica/Epoxy Nanocomposite Underfill by Tailored Hydrophilic-Superhydrophobic Surfaces for 3D Integrated Circuit (IC) Stacking.

PubMed

Tuan, Chia-Chi; James, Nathan Pataki; Lin, Ziyin; Chen, Yun; Liu, Yan; Moon, Kyoung-Sik; Li, Zhuo; Wong, C P

2017-03-15

As microelectronics are trending toward smaller packages and integrated circuit (IC) stacks nowadays, underfill, the polymer composite filled in between the IC chip and the substrate, becomes increasingly important for interconnection reliability. However, traditional underfills cannot meet the requirements for low-profile and fine pitch in high density IC stacking packages. Post-applied underfills have difficulties in flowing into the small gaps between the chip and the substrate, while pre-applied underfills face filler entrapment at bond pads. In this report, we present a self-patterning underfilling technology that uses selective wetting of underfill on Cu bond pads and Si 3 N 4 passivation via surface energy engineering. This novel process, fully compatible with the conventional underfilling process, eliminates the issue of filler entrapment in typical pre-applied underfilling process, enabling high density and fine pitch IC die bonding.

Determination of five antiarrhythmic drugs in human plasma by dispersive liquid-liquid microextraction and high-performance liquid chromatography.

PubMed

Jouyban, Abolghasem; Sorouraddin, Mohammad Hossein; Farajzadeh, Mir Ali; Somi, Mohammad Hossein; Fazeli-Bakhtiyari, Rana

2015-03-01

A fast and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection was developed and validated for the simultaneous quantitation of five antiarrhythmic drugs (metoprolol, propranolol, carvedilol, diltiazem, and verapamil) in human plasma samples. It involves dispersive liquid-liquid microextraction (DLLME) of the desired drugs from 660 µL plasma and separation using isocratic elution with UV detection at 200 nm. The complete separation of all analytes was achieved within 7 min. Acetonitrile (as disperser solvent) resulting from the protein precipitation procedure was mixed with 100 µL dichloromethane (as an extraction solvent) and rapidly injected into 5 mL aqueous solution (pH 11.5) containing 1% (w/v), NaCl. After centrifugation, the sedimented phase containing enriched analytes was collected and evaporated to dryness. The residue was re-dissolved in 50 µL de-ionized water (acidified to pH 3) and injected into the HPLC system for analysis. Under the optimal conditions, the enrichment factors and extraction recoveries ranged between 4.4-10.8 and 33-82%, respectively. The suggested method was linear (r(2) ≥0.997) over a dynamic range of 0.02-0.80 µg mL(-1) in plasma. The intra- and inter-days relative standard deviation (RSD%) and relative error (RE%) values of the method were below 20%, which shows good precision and accuracy. Finally, this method was applied to the analysis of real plasma samples obtained from the patients treated with these drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Publications - IC 57 v. 1.0.1 | Alaska Division of Geological & Geophysical

Science.gov Websites

content DGGS IC 57 v. 1.0.1 Publication Details Title: Alaska's mineral industry 2007: A summary Authors Bibliographic Reference Szumigala, D.J., and Hughes, R.A., 2008, Alaska's mineral industry 2007: A summary

On the Convergence of Ionospheric Constrained Precise Point Positioning (IC-PPP) Based on Undifferential Uncombined Raw GNSS Observations

PubMed Central

Zhang, Hongping; Gao, Zhouzheng; Ge, Maorong; Niu, Xiaoji; Huang, Ling; Tu, Rui; Li, Xingxing

2013-01-01

Precise Point Positioning (PPP) has become a very hot topic in GNSS research and applications. However, it usually takes about several tens of minutes in order to obtain positions with better than 10 cm accuracy. This prevents PPP from being widely used in real-time kinematic positioning services, therefore, a large effort has been made to tackle the convergence problem. One of the recent approaches is the ionospheric delay constrained precise point positioning (IC-PPP) that uses the spatial and temporal characteristics of ionospheric delays and also delays from an a priori model. In this paper, the impact of the quality of ionospheric models on the convergence of IC-PPP is evaluated using the IGS global ionospheric map (GIM) updated every two hours and a regional satellite-specific correction model. Furthermore, the effect of the receiver differential code bias (DCB) is investigated by comparing the convergence time for IC-PPP with and without estimation of the DCB parameter. From the result of processing a large amount of data, on the one hand, the quality of the a priori ionosphere delays plays a very important role in IC-PPP convergence. Generally, regional dense GNSS networks can provide more precise ionosphere delays than GIM and can consequently reduce the convergence time. On the other hand, ignoring the receiver DCB may considerably extend its convergence, and the larger the DCB, the longer the convergence time. Estimating receiver DCB in IC-PPP is a proper way to overcome this problem. Therefore, current IC-PPP should be enhanced by estimating receiver DCB and employing regional satellite-specific ionospheric correction models in order to speed up its convergence for more practical applications. PMID:24253190

On the convergence of ionospheric constrained precise point positioning (IC-PPP) based on undifferential uncombined raw GNSS observations.

PubMed

Zhang, Hongping; Gao, Zhouzheng; Ge, Maorong; Niu, Xiaoji; Huang, Ling; Tu, Rui; Li, Xingxing

2013-11-18

Precise Point Positioning (PPP) has become a very hot topic in GNSS research and applications. However, it usually takes about several tens of minutes in order to obtain positions with better than 10 cm accuracy. This prevents PPP from being widely used in real-time kinematic positioning services, therefore, a large effort has been made to tackle the convergence problem. One of the recent approaches is the ionospheric delay constrained precise point positioning (IC-PPP) that uses the spatial and temporal characteristics of ionospheric delays and also delays from an a priori model. In this paper, the impact of the quality of ionospheric models on the convergence of IC-PPP is evaluated using the IGS global ionospheric map (GIM) updated every two hours and a regional satellite-specific correction model. Furthermore, the effect of the receiver differential code bias (DCB) is investigated by comparing the convergence time for IC-PPP with and without estimation of the DCB parameter. From the result of processing a large amount of data, on the one hand, the quality of the a priori ionosphere delays plays a very important role in IC-PPP convergence. Generally, regional dense GNSS networks can provide more precise ionosphere delays than GIM and can consequently reduce the convergence time. On the other hand, ignoring the receiver DCB may considerably extend its convergence, and the larger the DCB, the longer the convergence time. Estimating receiver DCB in IC-PPP is a proper way to overcome this problem. Therefore, current IC-PPP should be enhanced by estimating receiver DCB and employing regional satellite-specific ionospheric correction models in order to speed up its convergence for more practical applications.

A novel application of t-statistics to objectively assess the quality of IC50 fits for P-glycoprotein and other transporters.

PubMed

O'Connor, Michael; Lee, Caroline; Ellens, Harma; Bentz, Joe

2015-02-01

Current USFDA and EMA guidance for drug transporter interactions is dependent on IC50 measurements as these are utilized in determining whether a clinical interaction study is warranted. It is therefore important not only to standardize transport inhibition assay systems but also to develop uniform statistical criteria with associated probability statements for generation of robust IC50 values, which can be easily adopted across the industry. The current work provides a quantitative examination of critical factors affecting the quality of IC50 fits for P-gp inhibition through simulations of perfect data with randomly added error as commonly observed in the large data set collected by the P-gp IC50 initiative. The types of errors simulated were (1) variability in replicate measures of transport activity; (2) transformations of error-contaminated transport activity data prior to IC50 fitting (such as performed when determining an IC50 for inhibition of P-gp based on efflux ratio); and (3) the lack of well defined "no inhibition" and "complete inhibition" plateaus. The effect of the algorithm used in fitting the inhibition curve (e.g., two or three parameter fits) was also investigated. These simulations provide strong quantitative support for the recommendations provided in Bentz et al. (2013) for the determination of IC50 values for P-gp and demonstrate the adverse effect of data transformation prior to fitting. Furthermore, the simulations validate uniform statistical criteria for robust IC50 fits in general, which can be easily implemented across the industry. A calibration of the t-statistic is provided through calculation of confidence intervals associated with the t-statistic.

A novel application of t-statistics to objectively assess the quality of IC50 fits for P-glycoprotein and other transporters

PubMed Central

O'Connor, Michael; Lee, Caroline; Ellens, Harma; Bentz, Joe

2015-01-01

Current USFDA and EMA guidance for drug transporter interactions is dependent on IC50 measurements as these are utilized in determining whether a clinical interaction study is warranted. It is therefore important not only to standardize transport inhibition assay systems but also to develop uniform statistical criteria with associated probability statements for generation of robust IC50 values, which can be easily adopted across the industry. The current work provides a quantitative examination of critical factors affecting the quality of IC50 fits for P-gp inhibition through simulations of perfect data with randomly added error as commonly observed in the large data set collected by the P-gp IC50 initiative. The types of errors simulated were (1) variability in replicate measures of transport activity; (2) transformations of error-contaminated transport activity data prior to IC50 fitting (such as performed when determining an IC50 for inhibition of P-gp based on efflux ratio); and (3) the lack of well defined “no inhibition” and “complete inhibition” plateaus. The effect of the algorithm used in fitting the inhibition curve (e.g., two or three parameter fits) was also investigated. These simulations provide strong quantitative support for the recommendations provided in Bentz et al. (2013) for the determination of IC50 values for P-gp and demonstrate the adverse effect of data transformation prior to fitting. Furthermore, the simulations validate uniform statistical criteria for robust IC50 fits in general, which can be easily implemented across the industry. A calibration of the t-statistic is provided through calculation of confidence intervals associated with the t-statistic. PMID:25692007

Cost considerations in the management of atrial fibrillation – impact of dronedarone

PubMed Central

Khaykin, Yaariv; Shamiss, Yana

2012-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is associated with significant morbidity and mortality. At the societal level, AF carries an enormous cost. Strategies aimed at reducing AF morbidity and mortality and containing the associated fiscal burden are of paramount importance. This review will discuss AF treatment strategies and economics, focusing on the impact of dronedarone, a novel antiarrhythmic agent. PMID:22427725

NASA Ames’ COSmIC Laboratory Astrophysics Facility: Recent Results and Progress

NASA Astrophysics Data System (ADS)

Salama, Farid; Sciamma-O'Brien, Ella; Bejaoui, Salma

2018-06-01

The COSmIC facility was developed at NASA Ames to study interstellar, circumstellar and planetary analogs in the laboratory [1, 2]. COSmIC stands for “Cosmic Simulation Chamber” and is dedicated to the study of molecules, ions and nanoparticles under the low temperature and high vacuum conditions that are required to simulate space environments. COSmIC integrates a variety of instruments that allow generating; processing and monitoring simulated space conditions in the laboratory. It is composed of a Pulsed Discharge Nozzle expansion that generates a plasma in a free supersonic jet expansion coupled to high-sensitivity, complementary in situ diagnostic tools, used for the detection and characterization of the species present in the expansion: a Cavity Ring Down Spectroscopy (CRDS) and fluorescence spectroscopy systems for photonic detection, and a Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection [3, 4].Recent advances achieved in laboratory astrophysics using COSmIC will be presented, in particular in the domain of the diffuse interstellar bands (DIBs) [5, 6] and the monitoring, in the laboratory, of the formation of dust grains and aerosols from their gas-phase molecular precursors in environments as varied as circumstellar outflows [7] and planetary atmospheres [8, 9, 10]. Plans for future laboratory experiments on cosmic molecules and grains in the growing field of laboratory astrophysics (NIR-MIR CRDS, Laser Induced Fluorescence spectra of cosmic molecule analogs and the laser induced incandescence spectra of cosmic grain analogs) will also be addressed as well as the implications for astronomy.References: [1] Salama F., Proceed. IAU S251, Kwok & Sandford eds. CUP, 4, 357 (2008).[2] Salama F., et al., Proceed. IAU S332, Y. Aikawa, M. Cunningham, T. Millar, eds., CUP (2018)[3] Biennier L., et al., J. Chem. Phys., 118, 7863 (2003)[4] Ricketts C. et al. IJMS, 300, 26 (2011)[5] Salama F., et al., ApJ., 728, 154 (2011)[6] EDIBLES

SN 2017ein and the Possible First Identification of a Type Ic Supernova Progenitor

NASA Astrophysics Data System (ADS)

Van Dyk, Schuyler D.; Zheng, WeiKang; Brink, Thomas G.; Filippenko, Alexei V.; Milisavljevic, Dan; Andrews, Jennifer E.; Smith, Nathan; Cignoni, Michele; Fox, Ori D.; Kelly, Patrick L.; Adamo, Angela; Yunus, Sameen; Zhang, Keto; Kumar, Sahana

2018-06-01

We have identified a progenitor candidate in archival Hubble Space Telescope (HST) images for the Type Ic supernova (SN Ic) SN 2017ein in NGC 3938, pinpointing the candidate’s location via HST Target of Opportunity imaging of the SN itself. This would be the first identification of a stellar-like object as a progenitor candidate for any SN Ic to date. We also present observations of SN 2017ein during the first ∼49 days since explosion. We find that SN 2017ein most resembles the well-studied SN Ic SN 2007gr. We infer that SN 2017ein experienced a total visual extinction of A V ≈ 1.0–1.9 mag, predominantly because of dust within the host galaxy. Although the distance is not well known, if this object is the progenitor, it was likely of high initial mass, ∼47–48 M ⊙ if a single star, or ∼60–80 M ⊙ if in a binary system. However, we also find that the progenitor candidate could be a very blue and young compact cluster, further implying a very massive (>65 M ⊙) progenitor. Furthermore, the actual progenitor might not be associated with the candidate at all and could be far less massive. From the immediate stellar environment, we find possible evidence for three different populations; if the SN progenitor was a member of the youngest population, this would be consistent with an initial mass of ∼57 M ⊙. After it has faded, the SN should be reobserved at high spatial resolution and sensitivity, to determine whether the candidate is indeed the progenitor.

Fully Integrated Biopotential Acquisition Analog Front-End IC

PubMed Central

Song, Haryong; Park, Yunjong; Kim, Hyungseup; Ko, Hyoungho

2015-01-01

A biopotential acquisition analog front-end (AFE) integrated circuit (IC) is presented. The biopotential AFE includes a capacitively coupled chopper instrumentation amplifier (CCIA) to achieve low input referred noise (IRN) and to block unwanted DC potential signals. A DC servo loop (DSL) is designed to minimize the offset voltage in the chopper amplifier and low frequency respiration artifacts. An AC coupled ripple rejection loop (RRL) is employed to reduce ripple due to chopper stabilization. A capacitive impedance boosting loop (CIBL) is designed to enhance the input impedance and common mode rejection ratio (CMRR) without additional power consumption, even under an external electrode mismatch. The AFE IC consists of two-stage CCIA that include three compensation loops (DSL, RRL, and CIBL) at each CCIA stage. The biopotential AFE is fabricated using a 0.18 µm one polysilicon and six metal layers (1P6M) complementary metal oxide semiconductor (CMOS) process. The core chip size of the AFE without input/output (I/O) pads is 10.5 mm2. A fourth-order band-pass filter (BPF) with a pass-band in the band-width from 1 Hz to 100 Hz was integrated to attenuate unwanted signal and noise. The overall gain and band-width are reconfigurable by using programmable capacitors. The IRN is measured to be 0.94 µVRMS in the pass band. The maximum amplifying gain of the pass-band was measured as 71.9 dB. The CIBL enhances the CMRR from 57.9 dB to 67 dB at 60 Hz under electrode mismatch conditions. PMID:26437404

Performance of Machine Learning Algorithms for Qualitative and Quantitative Prediction Drug Blockade of hERG1 channel.

PubMed

Wacker, Soren; Noskov, Sergei Yu

2018-05-01

Drug-induced abnormal heart rhythm known as Torsades de Pointes (TdP) is a potential lethal ventricular tachycardia found in many patients. Even newly released anti-arrhythmic drugs, like ivabradine with HCN channel as a primary target, block the hERG potassium current in overlapping concentration interval. Promiscuous drug block to hERG channel may potentially lead to perturbation of the action potential duration (APD) and TdP, especially when with combined with polypharmacy and/or electrolyte disturbances. The example of novel anti-arrhythmic ivabradine illustrates clinically important and ongoing deficit in drug design and warrants for better screening methods. There is an urgent need to develop new approaches for rapid and accurate assessment of how drugs with complex interactions and multiple subcellular targets can predispose or protect from drug-induced TdP. One of the unexpected outcomes of compulsory hERG screening implemented in USA and European Union resulted in large datasets of IC 50 values for various molecules entering the market. The abundant data allows now to construct predictive machine-learning (ML) models. Novel ML algorithms and techniques promise better accuracy in determining IC 50 values of hERG blockade that is comparable or surpassing that of the earlier QSAR or molecular modeling technique. To test the performance of modern ML techniques, we have developed a computational platform integrating various workflows for quantitative structure activity relationship (QSAR) models using data from the ChEMBL database. To establish predictive powers of ML-based algorithms we computed IC 50 values for large dataset of molecules and compared it to automated patch clamp system for a large dataset of hERG blocking and non-blocking drugs, an industry gold standard in studies of cardiotoxicity. The optimal protocol with high sensitivity and predictive power is based on the novel eXtreme gradient boosting (XGBoost) algorithm. The ML-platform with XGBoost

X-ray Properties of the Young Open Clusters HM1 and IC 2944-2948

NASA Technical Reports Server (NTRS)

Naze, Y.; Rauw, G.; Sana, H.; Corcoran, Michael F.

2013-01-01

Using XMM-Newton data, we study for the first time the X-ray emission of HM1 and IC 2944/2948. Low-mass, pre-main-sequence objects with an age of a few Myr are detected, as well as a few background or foreground objects. Most massive stars in both clusters display the usual high-energy properties of that type of objects, though with log [L(sub X)/L(sub BOL)] apparently lower in HM1 than in IC2944/2948. Compared with studies of other clusters, it seems that a low signal-to-noise ratio at soft energies, due to the high extinction, may be the main cause of this difference. In HM1, the two Wolf-Rayet stars show contrasting behaviors:WR89 is extremely bright, but much softer than WR87. It remains to be seen whether wind-wind collisions or magnetically confined winds can explain these emissions. In IC 2944/2948, the X-ray sources concentrate around HD 101205; a group of massive stars to the north of this object is isolated, suggesting that there exist two subclusters in the field-of-view.

PREFACE: 3rd International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE 2014)

NASA Astrophysics Data System (ADS)

2015-01-01

The third International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place at Madrid, Spain, from Thursday 28 to Sunday 31 August 2014. The Conference was attended by more than 200 participants and hosted about 350 oral, poster, and virtual presentations. More than 600 pre-registered authors were also counted. The third IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics etc. The scientific program was rather heavy since after the Keynote and Invited Talks in the morning, three parallel oral sessions and one poster session were running every day. However, according to all attendees, the program was excellent with high level of talks and the scientific environment was fruitful, thus all attendees had a creative time. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee.

Zinc Oxide Nanoparticle-Poly I:C RNA Complexes: Implication as Therapeutics against Experimental Melanoma.

PubMed

Ramani, Meghana; Mudge, Miranda C; Morris, R Tyler; Zhang, Yuntao; Warcholek, Stanislaw A; Hurst, Miranda N; Riviere, Jim E; DeLong, Robert K

2017-03-06

There is current interest in harnessing the combined anticancer and immunological effect of nanoparticles (NPs) and RNA. Here, we evaluate the bioactivity of poly I:C (pIC) RNA, bound to anticancer zinc oxide NP (ZnO-NP) against melanoma. Direct RNA association to unfunctionalized ZnO-NP is shown by observing change in size, zeta potential, and absorption/fluorescence spectra upon complexation. RNA corona was visualized by transmission electron microscopy (TEM) for the first time. Binding constant (K b = 1.6-2.8 g -1 L) was determined by modified Stern-Volmer, absorption, and biological surface activity index analysis. The pIC-ZnO-NP complex increased cell death for both human (A375) and mouse (B16F10) cell lines and suppressed tumor cell growth in BALB/C-B16F10 mouse melanoma model. Ex vivo tumor analysis indicated significant molecular activity such as changes in the level of phosphoproteins JNK, Akt, and inflammation markers IL-6 and IFN-γ. High throughput proteomics analysis revealed zinc oxide and poly I:C-specific and combinational patterns that suggested possible utility as an anticancer and immunotherapeutic strategy against melanoma.

Design and performance of clock-recovery GaAs ICs for high-speed optical communication systems

NASA Astrophysics Data System (ADS)

Imai, Yuhki; Sano, Eiichi; Nakamura, Makoto; Ishihara, Noboru; Kikuchi, Hiroyuki; Ono, Takashi

1993-05-01

Design and performance of clock-recovery GaAs ICs are presented. Four kinds of ICs were developed: a limiting amplifier, a tuning amplifier, a rectifier, and a differentiator. The cascaded limiting amplifier together with a tuning amplifier achieved a 58-dB gain and a 10-degree phase deviation with 20-dB input dynamic range at 10 GHz. A clock-recovery circuit successfully extracts a low-jitter 10-GHz clock signal of 1-dBm constant power from 10-Gb/s NRZ pseudorandom bit streams using a pulse pattern generator.

Amplified Detection of Prions and Other Amyloids by RT-QuIC in Diagnostics and the Evaluation of Therapeutics and Disinfectants.

PubMed

Caughey, Byron; Orru, Christina D; Groveman, Bradley R; Hughson, Andrew G; Manca, Matteo; Raymond, Lynne D; Raymond, Gregory J; Race, Brent; Saijo, Eri; Kraus, Allison

2017-01-01

Among the most sensitive, specific and practical of methods for detecting prions are the real-time quaking-induced conversion (RT-QuIC) assays. These assays exploit the fundamental self-propagating activity of prions to amplify the presence of prion seeds by as much as a trillion-fold. The reactions can detect most of the known mammalian prion diseases, often with sensitivities greater than those of animal bioassays. RT-QuIC assays are performed in multiwell plates with fluorescence detection and have now reached the sensitivity and practicality required for routine prion disease diagnostics. Some key strains of prions within particular host species, e.g., humans, cattle, and sheep, can be discriminated by comparison of RT-QuIC responses with different recombinant prion protein substrates. The most thoroughly validated diagnostic application of RT-QuIC is in the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) using cerebrospinal fluid. Diagnostic sensitivities as high as 96% can be achieved in less than 24h with specificities of 98%-100%. The ability, if needed, to also test nasal swab samples can increase the RT-QuIC sensitivity for sCJD to virtually 100%. In addition to diagnostic applications, RT-QuIC has also been used in the testing of prion disinfectants and potential therapeutics. Mechanistically related assays are also now being developed for other protein misfolding diseases. © 2017 Elsevier Inc. All rights reserved.

HUNTING FOR YOUNG DISPERSING STAR CLUSTERS IN IC 2574

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

Pellerin, Anne; Meyer, Martin M.; Calzetti, Daniella

2012-12-01

Dissolving stellar groups are very difficult to detect using traditional surface photometry techniques. We have developed a method to find and characterize non-compact stellar systems in galaxies where the young stellar population can be spatially resolved. By carrying out photometry on individual stars, we are able to separate the luminous blue stellar population from the star field background. The locations of these stars are used to identify groups by applying the HOP algorithm, which are then characterized using color-magnitude and stellar density radial profiles to estimate age, size, density, and shape. We test the method on Hubble Space Telescope Advancedmore » Camera for Surveys archival images of IC 2574 and find 75 dispersed stellar groups. Of these, 20 highly dispersed groups are good candidates for dissolving systems. We find few compact systems with evidence of dissolution, potentially indicating that star formation in this galaxy occurs mostly in unbound clusters or groups. These systems indicate that the dispersion rate of groups and clusters in IC 2574 is at most 0.45 pc Myr{sup -1}. The location of the groups found with HOP correlate well with H I contour map features. However, they do not coincide with H I holes, suggesting that those holes were not created by star-forming regions.« less

77 FR 67688 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Digital I&C...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-13

... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on Digital I&C; Notice of Meeting The ACRS Subcommittee on Digital I&C will hold a meeting on November 16, 2012, Room T-2B1, 11545 Rockville Pike, Rockville, Maryland. The entire meeting will be open...

Advances in Interstellar and Planetary Laboratory Astrophysics with Ames’ COSmIC Facility

NASA Astrophysics Data System (ADS)

Salama, Farid; Sciamma-O'Brien, Ella; Bejaoui, Salma

2017-06-01

The COSmIC facility was developed at NASA Ames to study interstellar, circumstellar and planetary analogs in the laboratory [1]. COSmIC stands for “Cosmic Simulation Chamber” and is dedicated to the study of neutral and ionized molecules and nanoparticles under the low temperature and high vacuum conditions that are required to simulate space environments. COSmIC integrates a variety of instruments that allow forming, processing and monitoring simulated space conditions in the laboratory. It is composed of a Pulsed Discharge Nozzle (PDN) expansion that generates a plasma in a free supersonic jet expansion coupled to high-sensitivity, complementary in situ diagnostics tools, used for the detection and characterization of the species present in the expansion: a Cavity Ring Down Spectroscopy (CRDS) and fluorescence spectroscopy systems for photonic detection and a Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection [2].Recent advances achieved in laboratory astrophysics using COSmIC will be presented, in particular the advances that have been achieved in the domain of the diffuse interstellar bands (DIBs) [3] and in monitoring, in the laboratory, the formation of dust grains and aerosols from their gas-phase molecular precursors in environments as varied as circumstellar outflows [4] and planetary atmospheres [5, 6]. Plans for future laboratory experiments on cosmic molecules and grains in the growing field of laboratory astrophysics (NIR-MIR CRDS, Laser Induced Fluorescence spectra of cosmic molecule analogs and the laser induced incandescence spectra of cosmic grain analogs will also be addressed as well as the implications of the on-going studies for astronomy.References: [1] Salama F., In Organic Matter in Space, IAU S251, Kwok & Sandford eds.CUP, 4, 357 (2008).[2] Ricketts C., Contreras C., Walker, R., Salama F., Int. J. Mass Spec, 300, 26 (2011)[3] Salama F., Galazutdinov G., Krelowski J., Biennier L., Beletsky Y., In-Ok Song, The

IC-tagged proteins are able to interact with each other and perform complex reactions when integrated into muNS-derived inclusions.

PubMed

Brandariz-Nuñez, Alberto; Otero-Romero, Iria; Benavente, Javier; Martinez-Costas, Jose M

2011-09-20

We have recently developed a versatile tagging system (IC-tagging) that causes relocation of the tagged proteins to ARV muNS-derived intracellular globular inclusions. In the present study we demonstrate (i) that the IC-tag can be successfully fused either to the amino or carboxyl terminus of the protein to be tagged and (ii) that IC-tagged proteins are able to interact between them and perform complex reactions that require such interactions while integrated into muNS inclusions, increasing the versatility of the IC-tagging system. Also, our studies with the DsRed protein add some light on the structure/function relationship of the evolution of DsRed chromophore. Copyright © 2011 Elsevier B.V. All rights reserved.

Two families from New England with usher syndrome type IC with distinct haplotypes.

PubMed

DeAngelis, M M; McGee, T L; Keats, B J; Slim, R; Berson, E L; Dryja, T P

2001-03-01

To search for patients with Usher syndrome type IC among those with Usher syndrome type I who reside in New England. Genotype analysis of microsatellite markers closely linked to the USH1C locus was done using the polymerase chain reaction. We compared the haplotype of our patients who were homozygous in the USH1C region with the haplotypes found in previously reported USH1C Acadian families who reside in southwestern Louisiana and from a single family residing in Lebanon. Of 46 unrelated cases of Usher syndrome type I residing in New England, two were homozygous at genetic markers in the USH1C region. Of these, one carried the Acadian USH1C haplotype and had Acadian ancestors (that is, from Nova Scotia) who did not participate in the 1755 migration of Acadians to Louisiana. The second family had a haplotype that proved to be the same as that of a family with USH1C residing in Lebanon. Each of the two families had haplotypes distinct from the other. This is the first report that some patients residing in New England have Usher syndrome type IC. Patients with Usher syndrome type IC can have the Acadian haplotype or the Lebanese haplotype compatible with the idea that at least two independently arising pathogenic mutations have occurred in the yet-to-be identified USH1C gene.

Antiarrhythmics

MedlinePlus

... even over-the-counter medicines and vitamin or herbal supplements), so he or she can make you aware ... or interactions with other medicines and vitamin or herbal supplements. This information should not be used as medical ...

Modulation of hepatocyte growth factor secretion in human female reproductive tract stromal fibroblasts by poly (I:C) and estradiol.

PubMed

Coleman, Kimberly D; Ghosh, Mimi; Crist, Sarah G; Wright, Jacqueline A; Rossoll, Richard M; Wira, Charles R; Fahey, John V

2012-01-01

Hepatocyte Growth Factor (HGF) secretion facilitates epithelial cell growth and development in the female reproductive tract (FRT) and may contribute to pathological conditions such as cancer and endometriosis. We hypothesized that estradiol and poly (I:C), a synthetic RNA mimic, may have a regulatory effect on HGF secretion by stromal fibroblasts from FRT tissues. Following hysterectomies, normal tissue from the uterus, endocervix, and ectocervix were dispersed into stromal cell fractions by enzymatic digestion and differential filtering. Stromal fibroblasts were cultured and treated with estradiol and/or poly (I:C), and conditioned media were analyzed for HGF via enzyme-linked immunosorbent assay. Treating uterine fibroblasts with estradiol or poly (I:C) significantly increased HGF secretion. When uterine fibroblasts were co-treated with estradiol and poly (I:C), the effect on HGF secretion was additive. In contrast, stromal fibroblasts from endo- and ecto-cervix were unresponsive to estradiol, but were stimulated to secrete HGF by poly (I:C). HGF secretion is uniquely regulated in the uterus, but not in ecto- and endo-cervix, by estradiol. Moreover, potential viral pathogens further induce HGF. These findings have potential applications in understanding both hormonal regulation of normal tissue as well as the role of HGF in tumorogenesis, endometriosis, and human immunodeficiency virus infection. © 2011 John Wiley & Sons A/S.

Developing a Decision Support System for Flood Response: NIMS/ICS Fundamentals

NASA Astrophysics Data System (ADS)

Gutenson, J. L.; Zhang, X.; Ernest, A. N. S.; Oubeidillah, A.; Zhu, L.

2015-12-01

Effective response to regional disasters such as floods requires a multipronged, non-linear approach to reduce loss of life, property and harm to the environment. These coordinated response actions are typically undertaken by multiple jurisdictions, levels of government, functional agencies and other responsible entities. A successful response is highly dependent on the effectiveness and efficiency of each coordinated response action undertaken across a broad spectrum of organizations and activities. In order to provide a unified framework for those responding to incidents or planned events, FEMA provides a common and flexible approach for managing incidents, regardless of cause, size, location or complexity, referred to as the National Incident Management System (NIMS). Integral to NIMS is the Incident Command System (ICS), which establishes a common, pre-defined organizational structure to ensure coordination and management of procedures, resources and communications, for efficient incident management. While being both efficient and rigorous, NIMS, and ICS to a lesser extent, is an inherently complex framework that requires significant amount of training for planners, responders and managers to master, especially considering the wide array of incident types that Local Emergency Planning Committees (LEPCs) must be prepared to respond to. The existing Water-Wizard Decision Support System (DSS), developed to support water distribution system recovery operations for Decontamination (Decon), Operational Optimization (WDS), and Economic Consequence Assessment (Econ), is being evolved to integrate incident response functions. Water-Wizard runs on both mobile and desktop devices, and is being extended to utilize smartphone and mobile device specific data streams (e.g GPS location) to augment its fact-base in real-time for situational-aware DSS recommendations. In addition, the structured NIMS and ICS frameworks for incident management and response are being incorporated

Correlation of the ionisation response at selected points of IC sensitive regions with SEE sensitivity parameters under pulsed laser irradiation

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

Gordienko, A V; Mavritskii, O B; Egorov, A N

2014-12-31

The statistics of the ionisation response amplitude measured at selected points and their surroundings within sensitive regions of integrated circuits (ICs) under focused femtosecond laser irradiation is obtained for samples chosen from large batches of two types of ICs. A correlation between these data and the results of full-chip scanning is found for each type. The criteria for express validation of IC single-event effect (SEE) hardness based on ionisation response measurements at selected points are discussed. (laser applications and other topics in quantum electronics)

78 FR 50457 - Advisory Committee on Reactor Safeguards (ACRS) Meeting of the ACRS Subcommittee on Digital I&C...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... Subcommittee on Digital I&C; Notice of Meeting The ACRS Subcommittee on Digital I&C will hold a briefing on..., 2013-8:30 a.m. until 5:00 p.m. The Subcommittee will review the results and status of NRC research... handout should be provided to the DFO thirty minutes before the meeting. In addition, one electronic copy...

The Carnegie Hubble Program: The Infrared Leavitt Law in IC 1613

NASA Technical Reports Server (NTRS)

Scowcroft, Victoria; Freedman, Wendy L.; Madore, Barry F.; Monson, Andrew J.; Persson, S. E.; Seibert, Mark; Rigby, Jane R.; Melbourne, Jason

2013-01-01

We have observed the dwarf galaxy IC 1613 at multiple epochs in the midinfrared using Spitzer and the in the near-infrared using the new FourStar near-IR camera on Magellan. We have constructed Cepheid period luminosity relations in the J, H, Ks, [3.6] and [4.5] bands and have used the run of their apparent distance moduli as a function of wavelength to derive the line of sight reddening and distance to IC 1613. Using a nineband fit, we find E(BV ) = 0.050.01 mag and an extinction corrected distance modulus of 0 = 24.29 0.03statistical 0.03systematic mag. By comparing our multiband and [3.6] distance moduli to results from the tip of the red giant branch and red clump distance indicators, we find that metallicity has no measurable effect on Cepheid distances at 3.6 m in the metallicity range 1.0 [Fe/H] 0.2, hence derivations of the Hubble constant at this wavelength require no correction for metallicity.

DE-Cadherin regulates unconventional Myosin ID and Myosin IC in Drosophila left-right asymmetry establishment.

PubMed

Petzoldt, Astrid G; Coutelis, Jean-Baptiste; Géminard, Charles; Spéder, Pauline; Suzanne, Magali; Cerezo, Delphine; Noselli, Stéphane

2012-05-01

In bilateria, positioning and looping of visceral organs requires proper left-right (L/R) asymmetry establishment. Recent work in Drosophila has identified a novel situs inversus gene encoding the unconventional type ID myosin (MyoID). In myoID mutant flies, the L/R axis is inverted, causing reversed looping of organs, such as the gut, spermiduct and genitalia. We have previously shown that MyoID interacts physically with β-Catenin, suggesting a role of the adherens junction in Drosophila L/R asymmetry. Here, we show that DE-Cadherin co-immunoprecipitates with MyoID and is required for MyoID L/R activity. We further demonstrate that MyoIC, a closely related unconventional type I myosin, can antagonize MyoID L/R activity by preventing its binding to adherens junction components, both in vitro and in vivo. Interestingly, DE-Cadherin inhibits MyoIC, providing a protective mechanism to MyoID function. Conditional genetic experiments indicate that DE-Cadherin, MyoIC and MyoID show temporal synchronicity for their function in L/R asymmetry. These data suggest that following MyoID recruitment by β-Catenin at the adherens junction, DE-Cadherin has a twofold effect on Drosophila L/R asymmetry by promoting MyoID activity and repressing that of MyoIC. Interestingly, the product of the vertebrate situs inversus gene inversin also physically interacts with β-Catenin, suggesting that the adherens junction might serve as a conserved platform for determinants to establish L/R asymmetry both in vertebrates and invertebrates.

Host-pathogen-interaction reconstituted in 3-dimensional cocultures of mucosa and <i>C. albicans.

PubMed

Buchs, Romina; Lehner, Bruno; Meuwly, Phillippe; Schnyder, Bruno

2018-06-14

<i>C. albicans frequently causes recurrent intimal infectious disease (ID). This demands the treatment of multiple phases of the infection. The objective of this study was to uncover the host-pathogen-interaction using 2D epithelium cell-barrier and 3D subepithelium tissue cells of human mucosa. The 2D cell cultures assessed <i>C. albicans adhesion. Addition of the anti-fungal drug Fluconazol did not inhibit the adhesion, despite its pathogen growth inhibition (MIC value 0.08μg/mL). A 3D tissue was engineered in multi-transwells by placing human fibroblast cultures on a thick porous scaffold. This contained the yeast placed in the top compartment and prevented passive penetration. After 28h the pathogen transmigrated the barrier and was collected in the bottom compartment. A change in pathogen morphology was observed where hypha formed and grew to be 231μm long after 28h. The hypha was thus long enough to cross the 200μm thick 3D tissue. The 3D infection was inhibited by addition of Fluconazol (0.08μg/mL), confirming that penetration is dependent on pathogen growth. In conclusion, ID was reconstituted step-by-step on 2D epithelium surface and in 3D connective tissue of human mucosa. Fluconazol growth-inhibition of the pathogen <i>C. albicans was confirmed in the 3D tissue. We thus propose that this ID in vitro test is suitable for the identification and characterization of new treatments against <i>C. albicans..

Interpretation of two compact planetary nebulae, IC 4997 and NGC 6572, with aid of theoretical models.

PubMed Central

Hyung, S; Aller, L H

1993-01-01

Observations of two dense compact planetary nebulae secured with the Hamilton Echelle spectrograph at Lick Observatory combined with previously published UV spectra secured with the International Ultraviolet Explorer enable us to probe the electron densities and temperatures (plasma diagnostics) and ionic concentrations in these objects. The diagnostic diagrams show that no homogenous model will work for these nebulae. NGC 6572 may consist of an inner torordal ring of density 25,000 atoms/cm3 and an outer conical shell of density 10,000 atoms/cm3. The simplest model of IC 4997 suggests a thick inner shell with a density of about 107 atoms/cm3 and an outer envelope of density 10,000 atoms/cm3. The abundances of all elements heavier than He appear to be less than the solar values in NGC 6572, whereas He, C, N, and O may be more abundant in IC 4997 than in the sun. IC 4997 presents puzzling problems. PMID:11607347

Appropriate and inappropriate use of dronedarone in 2013.

PubMed

Naccarelli, Gerald V

2013-08-01

Dronedarone is a multichannel blocking antiarrhythmic agent that has been shown to prevent atrial fibrillation/flutter (AF/AFl) recurrences in several multi-center trials. In the ANDROMEDA trial, dronedarone treatment increased mortality and cardiovascular hospitalizations patients with decompensated heart failure. In the ATHENA trial, dronedarone was used in elderly high risk patients with paroxysmal or persistent AF/AFl, excluding those with advanced heart failure, cardiovascular hospitalizations were significantly reduced. Dronedarone increased mortality and cardiovascular hospitalizations in a different patient group with permanent AF/AFl. Although organic toxicity from the drug is very rare, post-marketing data has reported rare hepatic toxicity associated with dronedarone use. Current guidelines position dronedarone as a front-line antiarrhythmic in many patients with AF/Fl. However, dronedarone should not be used in patients with advanced heart failure or in permanent AF. Clinical trial results have helped us define appropriate and inappropriate candidates for dronedarone.

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2013 CFR

2013-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2012 CFR

2012-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2014 CFR

2014-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

40 CFR 180.1154 - CryIA(c) and CryIC derived delta-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated...

Code of Federal Regulations, 2011 CFR

2011-07-01

...-endotoxins of Bacillus thuringiensis var. kurstaki encapsulated in killed Pseudomonas fluorescens, and the... RESIDUES IN FOOD Exemptions From Tolerances § 180.1154 CryIA(c) and CryIC derived delta-endotoxins of... plasmid and cloning vector genetic constructs. CryIA(c) and CryIC derived delta-endotoxins of Bacillus...

Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine.

PubMed

Firbas, Christa; Boehm, Thomas; Buerger, Vera; Schuller, Elisabeth; Sabarth, Nicolas; Jilma, Bernd; Klade, Christoph S

2010-03-11

An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [(3)H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-gamma) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays. More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-gamma CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema. Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.

Momordin Ic couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS)-mediated PI3K/Akt and MAPK signaling pathways.

PubMed

Mi, Yashi; Xiao, Chunxia; Du, Qingwei; Wu, Wanqiang; Qi, Guoyuan; Liu, Xuebo

2016-01-01

Momordin Ic is a principal saponin constituent of Fructus Kochiae, which acts as an edible and pharmaceutical product more than 2000 years in China. Our previous research found momordin Ic induced apoptosis by PI3K/Akt and MAPK signaling pathways in HepG2 cells. While the role of autophagy in momordin Ic induced cell death has not been discussed, and the connection between the apoptosis and autophagy is not clear yet. In this work, we reported momordin Ic promoted the formation of autophagic vacuole and expression of Beclin 1 and LC-3 in a dose- and time-dependent manner. Compared with momordin Ic treatment alone, the autophagy inhibitor 3-methyladenine (3-MA) also can inhibit apoptosis, while autophagy activator rapamycin (RAP) has the opposite effect, and the apoptosis inhibitor ZVAD-fmk also inhibited autophagy induced by momordin Ic. Momordin Ic simultaneously induces autophagy and apoptosis by suppressing the ROS-mediated PI3K/Akt and activating the ROS-related JNK and P38 pathways. Additionally, momordin Ic induces apoptosis by suppressing PI3K/Akt-dependent NF-κB pathways and promotes autophagy by ROS-mediated Erk signaling pathway. Those results suggest that momordin Ic has great potential as a nutritional preventive strategy in cancer therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Agents of Change: The Role of Healthcare Workers in the Prevention of Nosocomial and Occupational Tuberculosis

PubMed Central

Nathavitharana, Ruvandhi R.; Bond, Patricia; Dramowski, Angela; Kotze, Koot; Lederer, Philip; Oxley, Ingrid; Peters, Jurgens A.; Rossouw, Chanel; van der Westhuizen, Helene-Mari; Willems, Bart; Ting, Tiong Xun; von Delft, Arne; von Delft, Dalene; Duarte, Raquel; Nardell, Edward; Zumla, Alimuddin

2018-01-01

Healthcare workers (HCWs) play a central role in global tuberculosis (TB) elimination efforts but their contributions are undermined by occupational TB. HCWs have higher rates of latent and active TB than the general population due to persistent occupational TB exposure, particularly in settings where there is a high prevalence of undiagnosed TB in healthcare facilities and TB infection control (TB-IC) programmes are absent or poorly implemented. Occupational health programmes in high TB burden settings are often weak or non-existent and thus data that record the extent of the increased risk of occupational TB globally are scarce. HCWs represent a limited resource in high TB burden settings and occupational TB can lead to workforce attrition. Stigma plays a role in delayed diagnosis, poor treatment outcomes and impaired wellbeing in HCWs who develop TB. Ensuring the prioritization and implementation of TB-IC interventions and occupational health programmes, which include robust monitoring and evaluation, is critical to reduce nosocomial TB transmission to patients and HCWs. The provision of preventive therapy for HCWs with latent TB infection can also prevent progression to active TB. Unlike other patient groups, HCWs are in a unique position to serve as agents of change to raise awareness, advocate for necessary resource allocation and implement TB-IC interventions, with appropriate support from dedicated TB-IC officers at the facility and national TB programme level. Students and community health workers (CHWs) must be engaged and involved in these efforts. Nosocomial TB transmission is an urgent public health problem and adopting rights-based approaches can be helpful. However, these efforts cannot succeed without increased political will, supportive legal frameworks and financial investments to support HCWs in efforts to decrease TB transmission. PMID:28256382

Agents of change: The role of healthcare workers in the prevention of nosocomial and occupational tuberculosis.

PubMed

Nathavitharana, Ruvandhi R; Bond, Patricia; Dramowski, Angela; Kotze, Koot; Lederer, Philip; Oxley, Ingrid; Peters, Jurgens A; Rossouw, Chanel; van der Westhuizen, Helene-Mari; Willems, Bart; Ting, Tiong Xun; von Delft, Arne; von Delft, Dalene; Duarte, Raquel; Nardell, Edward; Zumla, Alimuddin

2017-03-01

Healthcare workers (HCWs) play a central role in global tuberculosis (TB) elimination efforts but their contributions are undermined by occupational TB. HCWs have higher rates of latent and active TB than the general population due to persistent occupational TB exposure, particularly in settings where there is a high prevalence of undiagnosed TB in healthcare facilities and TB infection control (TB-IC) programmes are absent or poorly implemented. Occupational health programmes in high TB burden settings are often weak or non-existent and thus data that record the extent of the increased risk of occupational TB globally are scarce. HCWs represent a limited resource in high TB burden settings and occupational TB can lead to workforce attrition. Stigma plays a role in delayed diagnosis, poor treatment outcomes and impaired well-being in HCWs who develop TB. Ensuring the prioritization and implementation of TB-IC interventions and occupational health programmes, which include robust monitoring and evaluation, is critical to reduce nosocomial TB transmission to patients and HCWs. The provision of preventive therapy for HCWs with latent TB infection (LTBI) can also prevent progression to active TB. Unlike other patient groups, HCWs are in a unique position to serve as agents of change to raise awareness, advocate for necessary resource allocation and implement TB-IC interventions, with appropriate support from dedicated TB-IC officers at the facility and national TB programme level. Students and community health workers (CHWs) must be engaged and involved in these efforts. Nosocomial TB transmission is an urgent public health problem and adopting rights-based approaches can be helpful. However, these efforts cannot succeed without increased political will, supportive legal frameworks and financial investments to support HCWs in efforts to decrease TB transmission. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

PREFACE: 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSquare2015)

NASA Astrophysics Data System (ADS)

Vlachos, Dimitrios; Vagenas, Elias C.

2015-09-01

The 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place in Mykonos, Greece, from Friday 5th June to Monday 8th June 2015. The Conference was attended by more than 150 participants and hosted about 200 oral, poster, and virtual presentations. There were more than 600 pre-registered authors. The 4th IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics etc. The scientific program was rather intense as after the Keynote and Invited Talks in the morning, three parallel oral and one poster session were running every day. However, according to all attendees, the program was excellent with a high quality of talks creating an innovative and productive scientific environment for all attendees. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee.

On the Distance Measurements toward Young Milky Way Objects. I. Study of IC 2944

NASA Astrophysics Data System (ADS)

Krełowski, J.; Strobel, A.; Godunova, V.; Bondar, A.

2017-12-01

We compare distances to a very young stellar aggregate, IC 2944, using three methods: direct parallaxes of Gaia, spectrophotometric parallax and our method based on intensities of interstellar CaII lines. The discrepancies between spectrophotometric distances and those, based on CaII K and H lines, were already reported. The interstellar CaII H and K lines allow one to determine both distances and radial velocities of the intervening clouds. Thus, these data allow us to check the aggregate membership. It is also possible to check the spectral classification of considered targets which is necessary for spectrophotometric parallaxes. Using three methods, we determined distances to IC 2944 stars. We demonstrate that CaII based distances agree very well with the kinematic ones but are generally much smaller than the spectrophotometric ones. We conclude that the majority of IC 2944 objects is obscured by clouds producing neutral ("gray") extinction which diminishes their brightness exactly like extended distances. This influences spectrophotometric parallaxes while those, based on the CaII lines, do not depend on extinction and this method seems to be the most reliable one inside the thin disk of our Galaxy. The Gaia trigonometric parallaxes lead to distances similar to those obtained using the CaII method if their errors are reasonably small.

VizieR Online Data Catalog: IN-SYNC. III. Radial velocities of IC348 stars (Cottaar+, 2015)

NASA Astrophysics Data System (ADS)

Cottaar, M.; Covey, K. R.; Foster, J. B.; Meyer, M. R.; Tan, J. C.; Nidever, D. L.; Drew Chojnowski, S.; da Rio, N.; Flaherty, K. M.; Frinchaboy, P. M.; Majewski, S.; Skrutskie, M. F.; Wilson, J. C.; Zasowski, G.

2015-11-01

Cottaar et al. (Paper I, 2014, J/ApJ/794/125) describes the analysis of the high-resolution near-infrared spectra obtained by the APOGEE multi-object spectrograph from stars in IC 348, NGC 1333, NGC 2264, and Orion A as part of the INfrared Spectroscopy of Young Nebulous Clusters (IN-SYNC) ancillary program. Using radial velocities determined from APOGEE spectra of 380 likely cluster members, we have measured the radial velocity distribution of the young (2-6Myr) cluster IC 348. (2 data files).

The remarkable infrared galaxy Arp 220 = IC 4553

NASA Technical Reports Server (NTRS)

Soifer, B. T.; Neugebauer, G.; Helou, G.; Lonsdale, C. J.; Hacking, P.; Rice, W.; Houck, J. R.; Low, F. J.; Rowan-Robinson, M.

1984-01-01

IRAS observations of the peculiar galaxy Arp 220 = IC 4553 show that it is extremely luminous in the far-infrared, with a total luminosity of 2 x 10 to the 12th solar luminosities. The infrared-to-blue luminosity ratio of this galaxy is about 80, which is the largest value of the ratio for galaxies in the UGC catalog, and places it in the range of the 'unidentified' infrared sources recently reported by Houck et al. in the IRAS all-sky survey. Other observations of Arp 220, combined with the luminosity in the infrared, allow either a Seyfert-like or starburst origin for this luminosity.

Instantaneous flywheel torque of IC engine grey-box identification

NASA Astrophysics Data System (ADS)

Milašinović, A.; Knežević, D.; Milovanović, Z.; Škundrić, J.

2018-01-01

In this paper a mathematical model developed for the identification of excitation torque acting on the IC engine flywheel is presented. The excitation torque gained through internal combustion of the fuel in the IC engine is transmitted from the flywheel to the transmission. The torque is not constant but variable and is a function of the crank angle. The verification of the mathematical model was done on a 4-cylinder 4-stroke diesel engine for which the in-cylinder pressure was measured in one cylinder and the instantaneous angular speed of the crankshaft at its free end. The research was conducted on a hydraulic engine brake. Inertial forces of all rotational parts, from flywheel to the turbine wheel of the engine brake, are acting on the flywheel due to the nonuniform motion of the flywheel. It is known from the theory of turbomachinery that the torque on the hydraulic brake is a quadratic function of angular speed. Due to that and the variable angular speed of the turbine wheel of the engine brake, the torque during one engine cycle is also variable. The motivation for this research was the idea (intention) to determine the instantaneous torque acting on the flywheel as a function of the crank angle with a mathematical model without any measuring and based on this to determine the quality of work of specific cylinders of the multi-cylinder engine. The crankshaft was considered elastic and also its torsional vibrations were taken into account.

Improved Anticancer Photothermal Therapy Using the Bystander Effect Enhanced by Antiarrhythmic Peptide Conjugated Dopamine-Modified Reduced Graphene Oxide Nanocomposite.

PubMed

Yu, Jiantao; Lin, Yu-Hsin; Yang, Lingyan; Huang, Chih-Ching; Chen, Liliang; Wang, Wen-Cheng; Chen, Guan-Wen; Yan, Junyan; Sawettanun, Saranta; Lin, Chia-Hua

2017-01-01

Despite tremendous efforts toward developing novel near-infrared (NIR)-absorbing nanomaterials, improvement in therapeutic efficiency remains a formidable challenge in photothermal cancer therapy. This study aims to synthesize a specific peptide conjugated polydopamine-modified reduced graphene oxide (pDA/rGO) nanocomposite that promotes the bystander effect to facilitate cancer treatment using NIR-activated photothermal therapy. To prepare a nanoplatform capable of promoting the bystander effect in cancer cells, we immobilized antiarrhythmic peptide 10 (AAP10) on the surface of dopamine-modified rGO (AAP10-pDA/rGO). Our AAP10-pDA/rGO could promote the bystander effect by increasing the expression of connexin 43 protein in MCF-7 breast-cancer cells. Because of its tremendous ability to absorb NIR absorption, AAP10-pDA/rGO offers a high photothermal effect under NIR irradiation. This leads to a massive death of MCF-7 cells via the bystander effect. Using tumor-bearing mice as the model, it is found that NIR radiation effectively ablates breast tumor in the presence of AAP10-pDA/rGO and inhibits tumor growth by ≈100%. Therefore, this research integrates the bystander and photothermal effects into a single nanoplatform in order to facilitate an efficient photothermal therapy. Furthermore, our AAP10-pDA/rGO, which exhibits both hyperthermia and the bystander effect, can prevent breast-cancer recurrence and, therefore, has great potential for future clinical and research applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The H I chronicles of little things BCDs II: The origin of IC 10's H I structure

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

Ashley, Trisha; Simpson, Caroline E.; Pokhrel, Nau Raj

In this paper we analyze Very Large Array (VLA) telescope and Green Bank Telescope (GBT) atomic hydrogen (H I) data for the LITTLE THINGS (Local Irregulars That Trace Luminosity Extremes, The H I Nearby Galaxy Survey; https://science.nrao.edu/science/surveys/littlethings) blue compact dwarf galaxy IC 10. The VLA data allow us to study the detailed H I kinematics and morphology of IC 10 at high resolution while the GBT data allow us to search the surrounding area at high sensitivity for tenuous H I. IC 10's H I appears highly disturbed in both the VLA and GBT H I maps with a kinematicallymore » distinct northern H I extension, a kinematically distinct southern plume, and several spurs in the VLA data that do not follow the general kinematics of the main disk. We discuss three possible origins of its H I structure and kinematics in detail: a current interaction with a nearby companion, an advanced merger, and accretion of intergalactic medium. We find that IC 10 is most likely an advanced merger or a galaxy undergoing accretion.« less

Comparison of antifungal activities of various essential oils on the Phytophthora drechsleri, the causal agent of fruit decay

PubMed Central

Mohammadi, Ali; Hashemi, Maryam; Hosseini, Seyed Masoud

2015-01-01

Background and Objectives: The efficacy of Mentha piperita L, Zataria multiflora Boiss and Thymus vulgaris L essential oils (EOs) was evaluated for controlling the growth of Phytophthora drechsleri, the causative agent of damage to many crops that is consumed directly by humans. Materials and Methods: The EOs used in this study was purchased from Magnolia Co, Iran. The pour plate method in petri dishes containing Potato Dextrose Agar (PDA) was used to evaluate the antifungal properties of EOs. The minimal inhibitory concentrations (MIC), minimum fungicidal concentration (MFC) as well as mycelial growth inhibition (MGI) were measured. The IC50 value (the concentration inhibited 50% of the mycelium growth) was calculated by probit analysis. Results and Conclusion: The fungal growth was significantly reduced by increasing concentrations of tested EOs. The complete reduction was obtained with Shirazi thyme at all concentrations, whereas the complete reduction for peppermint and thyme was observed at 0.4% and 0.8% (v/v) concentrations, respectively. Meanwhile, the minimum inhibition was observed when 0.1% peppermint (MGI values of 9.37%) was used. The IC50, MIC and MFC values of Shirazi thyme was 0.053, 0.1% and 0.2%, respectively. Similarly, MIC and MFC values of peppermint and thyme were recorded 0.4% and 0.8%, respectively. The results obtained from this study may contribute to the development of new antifungal agents to protect the crops from this pathogenic fungus and many agricultural plant pathogens causing drastic crop losses. PMID:26644871

Lysosomotropic properties of weakly basic anticancer agents promote cancer cell selectivity in vitro.

PubMed

Ndolo, Rosemary A; Luan, Yepeng; Duan, Shaofeng; Forrest, M Laird; Krise, Jeffrey P

2012-01-01

Drug distribution in cells is a fundamentally important, yet often overlooked, variable in drug efficacy. Many weakly basic anticancer agents accumulate extensively in the acidic lysosomes of normal cells through ion trapping. Lysosomal trapping reduces the activity of anticancer drugs, since anticancer drug targets are often localized in the cell cytosol or nucleus. Some cancer cells have defective acidification of lysosomes, which causes a redistribution of trapped drugs from the lysosomes to the cytosol. We have previously established that such differences in drug localization between normal and cancer cells can contribute to the apparent selectivity of weakly basic drugs to cancer cells in vitro. In this work, we tested whether this intracellular distribution-based drug selectivity could be optimized based on the acid dissociation constant (pKa) of the drug, which is one of the determinants of lysosomal sequestration capacity. We synthesized seven weakly basic structural analogs of the Hsp90 inhibitor geldanamycin (GDA) with pKa values ranging from 5 to 12. The selectivity of each analog was expressed by taking ratios of anti-proliferative IC(50) values of the inhibitors in normal fibroblasts to the IC(50) values in human leukemic HL-60 cells. Similar selectivity assessments were performed in a pair of cancer cell lines that differed in lysosomal pH as a result of siRNA-mediated alteration of vacuolar proton ATPase subunit expression. Optimal selectivity was observed for analogs with pKa values near 8. Similar trends were observed with commercial anticancer agents with varying weakly basic pKa values. These evaluations advance our understanding of how weakly basic properties can be optimized to achieve maximum anticancer drug selectivity towards cancer cells with defective lysosomal acidification in vitro. Additional in vivo studies are needed to examine the utility of this approach for enhancing selectivity.

Lysosomotropic Properties of Weakly Basic Anticancer Agents Promote Cancer Cell Selectivity In Vitro

PubMed Central

Ndolo, Rosemary A.; Luan, Yepeng; Duan, Shaofeng; Forrest, M. Laird; Krise, Jeffrey P.

2012-01-01

Drug distribution in cells is a fundamentally important, yet often overlooked, variable in drug efficacy. Many weakly basic anticancer agents accumulate extensively in the acidic lysosomes of normal cells through ion trapping. Lysosomal trapping reduces the activity of anticancer drugs, since anticancer drug targets are often localized in the cell cytosol or nucleus. Some cancer cells have defective acidification of lysosomes, which causes a redistribution of trapped drugs from the lysosomes to the cytosol. We have previously established that such differences in drug localization between normal and cancer cells can contribute to the apparent selectivity of weakly basic drugs to cancer cells in vitro. In this work, we tested whether this intracellular distribution-based drug selectivity could be optimized based on the acid dissociation constant (pKa) of the drug, which is one of the determinants of lysosomal sequestration capacity. We synthesized seven weakly basic structural analogs of the Hsp90 inhibitor geldanamycin (GDA) with pKa values ranging from 5 to 12. The selectivity of each analog was expressed by taking ratios of anti-proliferative IC50 values of the inhibitors in normal fibroblasts to the IC50 values in human leukemic HL-60 cells. Similar selectivity assessments were performed in a pair of cancer cell lines that differed in lysosomal pH as a result of siRNA-mediated alteration of vacuolar proton ATPase subunit expression. Optimal selectivity was observed for analogs with pKa values near 8. Similar trends were observed with commercial anticancer agents with varying weakly basic pKa values. These evaluations advance our understanding of how weakly basic properties can be optimized to achieve maximum anticancer drug selectivity towards cancer cells with defective lysosomal acidification in vitro. Additional in vivo studies are needed to examine the utility of this approach for enhancing selectivity. PMID:23145164

The MusIC method: a fast and quasi-optimal solution to the muscle forces estimation problem.

PubMed

Muller, A; Pontonnier, C; Dumont, G

2018-02-01

The present paper aims at presenting a fast and quasi-optimal method of muscle forces estimation: the MusIC method. It consists in interpolating a first estimation in a database generated offline thanks to a classical optimization problem, and then correcting it to respect the motion dynamics. Three different cost functions - two polynomial criteria and a min/max criterion - were tested on a planar musculoskeletal model. The MusIC method provides a computation frequency approximately 10 times higher compared to a classical optimization problem with a relative mean error of 4% on cost function evaluation.

Congenital disorder of glycosylation Ic due to a de novo deletion and an hALG-6 mutation.

PubMed

Eklund, Erik A; Sun, Liangwu; Yang, Samuel P; Pasion, Romela M; Thorland, Erik C; Freeze, Hudson H

2006-01-20

We describe a new cause of congenital disorder of glycosylation-Ic (CDG-Ic) in a young girl with a rather mild CDG phenotype. Her cells accumulated lipid-linked oligosaccharides lacking three glucose residues, and sequencing of the ALG6 gene showed what initially appeared to be a homozygous novel point mutation (338G>A). However, haplotype analysis showed that the patient does not carry any paternal DNA markers extending 33kb in the telomeric direction from the ALG6 region, and microsatellite analysis extended the abnormal region to at least 2.5Mb. We used high-resolution karyotyping to confirm a deletion (10-12Mb) [del(1)(p31.2p32.3)] and found no structural abnormalities in the father, suggesting a de novo event. Our findings extend the causes of CDG to larger DNA deletions and identify the first Japanese CDG-Ic mutation.

Introducing a New Interface for the Online MagIC Database by Integrating Data Uploading, Searching, and Visualization

NASA Astrophysics Data System (ADS)

Jarboe, N.; Minnett, R.; Constable, C.; Koppers, A. A.; Tauxe, L.

2013-12-01

The Magnetics Information Consortium (MagIC) is dedicated to supporting the paleomagnetic, geomagnetic, and rock magnetic communities through the development and maintenance of an online database (http://earthref.org/MAGIC/), data upload and quality control, searches, data downloads, and visualization tools. While MagIC has completed importing some of the IAGA paleomagnetic databases (TRANS, PINT, PSVRL, GPMDB) and continues to import others (ARCHEO, MAGST and SECVR), further individual data uploading from the community contributes a wealth of easily-accessible rich datasets. Previously uploading of data to the MagIC database required the use of an Excel spreadsheet using either a Mac or PC. The new method of uploading data utilizes an HTML 5 web interface where the only computer requirement is a modern browser. This web interface will highlight all errors discovered in the dataset at once instead of the iterative error checking process found in the previous Excel spreadsheet data checker. As a web service, the community will always have easy access to the most up-to-date and bug free version of the data upload software. The filtering search mechanism of the MagIC database has been changed to a more intuitive system where the data from each contribution is displayed in tables similar to how the data is uploaded (http://earthref.org/MAGIC/search/). Searches themselves can be saved as a permanent URL, if desired. The saved search URL could then be used as a citation in a publication. When appropriate, plots (equal area, Zijderveld, ARAI, demagnetization, etc.) are associated with the data to give the user a quicker understanding of the underlying dataset. The MagIC database will continue to evolve to meet the needs of the paleomagnetic, geomagnetic, and rock magnetic communities.

VizieR Online Data Catalog: Absorption velocities for 21 super-luminous SNe Ic (Liu+, 2017)

NASA Astrophysics Data System (ADS)

Liu, Y.-Q.; Modjaz, M.; Bianco, F. B.

2018-04-01

We have collected the spectra of all available super-luminous supernovae (SLSNe) Ic that have a date of maximum light published before April of 2016. These SLSNe Ic were mainly discovered and observed by the All-Sky Automated Survey for Supernovae (ASAS-SN), the Catalina Real-Time Transient Survey, the Dark Energy Survey (DES), the Hubble Space Telescope Cluster Supernova Survey, the Pan-STARRS1 Medium Deep Survey (PS1), the Public ESO Spectroscopic Survey of Transient Objects (PESSTO), the Intermediate Palomar Transient Factory (iPTF) as well as the Palomar Transient Factory (PTF), and the Supernova Legacy Survey (SNLS). See table 1. (2 data files).

2nd International Conference on Rheology and Modeling of Materials (IC-RMM2)

NASA Astrophysics Data System (ADS)

2017-01-01

Understanding the rheological properties of materials and their rheological behaviors during their manufacturing processes and in their applications in many cases can help to increase the efficiency and competitiveness not only of the finished goods and products but the organizations and societies also. The more scientific supported and prepared organizations develop more competitive products with better thermal, mechanical, physical, chemical and biological properties and the leading companies apply more competitive equipment and technology processes. The aims of the 2nd International Conference on Rheology and Modeling of Materials (ic-rmm2) and the parallel organized symposiums of the 1st International Symposium on Powder Injection Molding (is-pim1) and the 1st International Symposium on Rheology and Fracture of Solids (is-rfs1) are the followings: Promote new methods and results of scientific research in the fields of modeling and measurements of rheological properties and behavior of materials under processing and applications; Change information between the theoretical and applied sciences as well as technical and technological implantations. Promote the communication and collaboration between the scientists, researchers and engineers of different disciplines, different nations, countries and continents. The international conference ic-rmm2 and symposiums of is-pim1 and is-rfs1 provide a platform among the leading international scientists, researchers, PhD students and engineers for discussing recent achievements in measurement, modeling and application of rheology in materials technology and materials science of liquids, melts, solids, crystals and amorphous structures. Among thr major fields of interest are the influence of materials structures, mechanical stresses, temperatures, deformation speeds and shear rates on rheological and physical properties, phase transformation of foams, foods, polymers, plastics and other competitive materials like ceramics

The Influence of Cyst Emptying, Lymph Node Resection and Chemotherapy on Survival in Stage IA and IC1 Epithelial Ovarian Cancer.

PubMed

Rosendahl, Mikkel; Mosgaard, Berit Jul; Høgdall, Claus

2016-10-01

To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node resection is associated with improved survival in stage IA and IC1. Chemotherapy should only be offered where randomized controlled studies have shown a benefit. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

ic-cmtp3: 3rd International Conference on Competitive Materials and Technology Processes

NASA Astrophysics Data System (ADS)

2016-04-01

Competitiveness is one of the most important factors in our lives and it plays a key role in the efficiency both of organizations and societies. The more scientifically advanced and prepared organizations develop more competitive materials with better physical, chemical, and biological properties, and the leading companies apply more competitive equipment and technological processes. The aims of the 3rd International Conference on Competitive Materials and Technology Processes (ic-cmtp3), and the 1st International Symposium on Innovative Carbons and Carbon Based Materials (is-icbm1) and the 1st International Symposium on Innovative Construction Materials (is-icm1) organized alongside are the following: —Promote new methods and results of scientific research in the fields of material, biological, environmental and technological sciences; —Exchange information between the theoretical and applied sciences as well as technical and technological implementations; —Promote communication and collaboration between the scientists, researchers and engineers of different nations, countries and continents. Among the major fields of interest are advanced and innovative materials with competitive characteristics, including mechanical, physical, chemical, biological, medical and thermal, properties and extreme dynamic strength. Their crystalline, nano - and micro-structures, phase transformations as well as details of their technological processes, tests and measurements are also in the focus of the ic-cmtp3 conference and the is-scbm1 and is-icm1 symposia. Multidisciplinary applications of material science and the technological problems encountered in sectors like ceramics, glasses, thin films, aerospace, automotive and marine industries, electronics, energy, construction materials, medicine, biosciences and environmental sciences are of particular interest. In accordance with the program of the ic-cmtp3 conference and is-icbm1 and is-icm1 symposia we have received more

Nasal and skin delivery of IC31(®)-adjuvanted recombinant HSV-2 gD protein confers protection against genital herpes.

PubMed

Wizel, Benjamin; Persson, Josefine; Thörn, Karolina; Nagy, Eszter; Harandi, Ali M

2012-06-19

Genital herpes caused by herpes simplex virus type 2 (HSV-2) remains the leading cause of genital ulcers worldwide. Given the disappointing results of the recent genital herpes vaccine trials in humans, development of novel vaccine strategies capable of eliciting protective mucosal and systemic immune responses to HSV-2 is urgently required. Here we tested the ability of the adjuvant IC31(®) in combination with HSV-2 glycoprotein D (gD) used through intranasal (i.n.), intradermal (i.d.), or subcutaneous (s.c.) immunization routes for induction of protective immunity against genital herpes infection in C57BL/6 mice. Immunization with gD plus IC31(®) through all three routes of immunization developed elevated gD-specific serum antibody responses with HSV-2 neutralizing activity. Whereas the skin routes promoted the induction of a mixed IgG2c/IgG1 isotype profile, the i.n. route only elicited IgG1 antibodies. All immunization routes were able to induce gD-specific IgG antibody responses in the vaginas of mice immunized with IC31(®)-adjuvanted gD. Although specific lymphoproliferative responses were observed in splenocytes from mice of most groups vaccinated with IC31(®)-adjuvanted gD, only i.d. immunization resulted in a significant splenic IFN-γ response. Further, immunization with gD plus IC31(®) conferred 80-100% protection against an otherwise lethal vaginal HSV-2 challenge with amelioration of viral replication and disease severity in the vagina. These results warrant further exploration of IC31(®) for induction of protective immunity against genital herpes and other sexually transmitted infections. Copyright © 2012 Elsevier Ltd. All rights reserved.

Triggered star-formation in the bright rimmed globule IC1396A

NASA Astrophysics Data System (ADS)

Patel, Nimesh A.; Sicilia-Aguilar, Aurora; Goldsmith, Paul

2015-01-01

IC1396 is a well known HII region and molecular cloud complex surrounding the Trumpler 37 cluster of OB stars in the Cepheus OB2 association. The dense, elephant trunk shaped globules in this region typically show bright rims facing the central exciting O6 star HD~206267. This region, at a distance of 870 pc, is an excellent astrophysical laboratory for studying the feedback effects of massive stars on neighboring molecular clouds. Triggered star formation occurs when dense cores (which would otherwise remain stable) are compressed and made unstable by the sustained energy input from the OB association. Observationally it remains challenging to prove whether the onset of star-formation in such globules is triggered or spontaneous.Using the Submillimeter Array (SMA), we observed IC1396 globule A (Pottasch 1958 nomenclature), targeting four newly discovered protostars from recent Herschel PACS observations. Here we present 230 GHz molecular line (CO, 13CO, C18O, N2D+ and H2CO) and continuum results for the source IC1396A-PACS-1 (Sicilia-Aguilar et al. 2014). This is a Class 0 source very close to the edge of the ionization front and Herschel observations show this to be a most promisingcase of triggered star-formation. The SMA 230 GHz continuum source has a flux density of 280 mJy. We estimate a dust mass of about 0.1 Msun in this source which appears very compact in our 5" beam. CO, 13CO and C18O emission is largely resolved out by the interferometer and will require combined imaging with single-dish observations. (We have a parallel ongoing study being carried out with the IRAM 30m telescope). SMA N2D+ emission peaks on the continuum sourceand is partially resolved. H2CO emission appears to avoid the peak of continuum and N2D+, suggesting depletion. Both the morphology and kinematics in H2CO emission are indicative of internal disturbance, away from the PDR region into the globule.

Multispectral analysis of Cygnus Loop and IC 443 with iFTS

NASA Astrophysics Data System (ADS)

Alarie, Alexandre

2016-06-01

Cygnus Loop and IC 443 are supernova remnants (SNRs) recognized as excellent laboratories to study the interaction between the SNR and the surrounding interstellar medium. The overall complex morphologies and large dimensions of those SNRs have always represented an observational challenge. This is especially true for optical observations for which the data available are very scarce. In order to palliate this scarcity in the optical regime, we are using two wide field-imaging Fourier transform spectrometers (iFTS): SpIOMM, attached to the Mont Megantic 1.6-m telescope and SITELLE recently installed at the Canada-France-Hawaii Telescope. Both instruments are capable of obtaining the spatially resolved visible spectrum of every source of light in an 11 arc minute field of view, in selected bandpasses. Using those iFTS on extended object such as Cygnus Loop and IC 443, we have obtained millions of spectra covering all major emission lines. Due to the large projected surface of Cygnus Loop and IC 443, we started a survey and the latest dataset will be presented. The extended 2D mappings of several emission lines ([O II] 3727, [O III] 4363, Hb, [O III] 4959, 5007, Ha, [N II] 6548, 6583 and [S II] 6716, 6731) allowed the creation of numerous ratios maps useful for shock diagnostics: shock velocity, electronic and temperature densities, location of incomplete shocks and extinction maps. These maps are then used to determine key parameters needed to compare the observations with theoretical shock models. Using the shock modeling code MAPPINGS, we can create abundances maps of nitrogen, oxygen and sulfur for an appreciable fraction of the observed regions. Furthermore, using the radial velocity as well as the spectro-imagery capability of the iFTS, we can have a glimpse of the three-dimensional structure of the remnants. All those data allow us to forge a coherent analysis of the complex interaction between the SNRs and their surrounding environment.

Terpenes increase the lipid dynamics in the Leishmania plasma membrane at concentrations similar to their IC50 values.

PubMed

Camargos, Heverton Silva; Moreira, Rodrigo Alves; Mendanha, Sebastião Antonio; Fernandes, Kelly Souza; Dorta, Miriam Leandro; Alonso, Antonio

2014-01-01

Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×10(6) parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4-9%) at their respective IC50 values. For assays with high cell concentrations (2×10(9) parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis.

Terpenes Increase the Lipid Dynamics in the Leishmania Plasma Membrane at Concentrations Similar to Their IC50 Values

PubMed Central

Camargos, Heverton Silva; Moreira, Rodrigo Alves; Mendanha, Sebastião Antonio; Fernandes, Kelly Souza; Dorta, Miriam Leandro; Alonso, Antonio

2014-01-01

Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×106 parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4–9%) at their respective IC50 values. For assays with high cell concentrations (2×109 parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis. PMID:25101672

XMM-Newton observations of the supernova remnant IC 443. II. Evidence of stellar ejecta in the inner regions

NASA Astrophysics Data System (ADS)

Troja, E.; Bocchino, F.; Miceli, M.; Reale, F.

2008-07-01

Aims: We investigate the spatial distribution of the physical and chemical properties of the hot X-ray emitting plasma of the supernova remnant IC 443, to derive important constraints on its ionization stage, on the progenitor supernova explosion, on the age of the remnant, and its physical association with a close pulsar wind nebula. Methods: We present XMM-Newton images of IC 443, a median photon energy map, silicon and sulfur equivalent width maps, and a spatially resolved spectral analysis of a set of homogeneous regions. Results: The hard X-ray thermal emission (1.4-5.0 keV) of IC 443 displays a centrally-peaked morphology, its brightness peaks being associated with hot (kT > 1 keV) X-ray emitting plasma. A ring-shaped structure, characterized by high values of equivalent widths and median photon energy, encloses the PWN. Its hard X-ray emission is spectrally characterized by a collisional ionization equilibrium model, and strong emission lines of Mg, Si, and S, requiring oversolar metal abundances. Dynamically, the location of the ejecta ring suggests an SNR age of ~4000 yr. The presence of overionized plasma in the inner regions of IC 443, addressed in previous works, is much less evident in our observations.

Creating a FIESTA (Framework for Integrated Earth Science and Technology Applications) with MagIC

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A. A. P.; Jarboe, N.; Tauxe, L.; Constable, C.

2017-12-01

The Magnetics Information Consortium (https://earthref.org/MagIC) has recently developed a containerized web application to considerably reduce the friction in contributing, exploring and combining valuable and complex datasets for the paleo-, geo- and rock magnetic scientific community. The data produced in this scientific domain are inherently hierarchical and the communities evolving approaches to this scientific workflow, from sampling to taking measurements to multiple levels of interpretations, require a large and flexible data model to adequately annotate the results and ensure reproducibility. Historically, contributing such detail in a consistent format has been prohibitively time consuming and often resulted in only publishing the highly derived interpretations. The new open-source (https://github.com/earthref/MagIC) application provides a flexible upload tool integrated with the data model to easily create a validated contribution and a powerful search interface for discovering datasets and combining them to enable transformative science. MagIC is hosted at EarthRef.org along with several interdisciplinary geoscience databases. A FIESTA (Framework for Integrated Earth Science and Technology Applications) is being created by generalizing MagIC's web application for reuse in other domains. The application relies on a single configuration document that describes the routing, data model, component settings and external services integrations. The container hosts an isomorphic Meteor JavaScript application, MongoDB database and ElasticSearch search engine. Multiple containers can be configured as microservices to serve portions of the application or rely on externally hosted MongoDB, ElasticSearch, or third-party services to efficiently scale computational demands. FIESTA is particularly well suited for many Earth Science disciplines with its flexible data model, mapping, account management, upload tool to private workspaces, reference metadata, image

A SCUBA-2 850-μm survey of protoplanetary discs in the IC 348 cluster

NASA Astrophysics Data System (ADS)

Cieza, L.; Williams, J.; Kourkchi, E.; Andrews, S.; Casassus, S.; Graves, S.; Schreiber, M. R.

2015-12-01

We present 850-μm observations of the 2-3 Myr cluster IC 348 in the Perseus molecular cloud using the SCUBA-2 camera on the James Clerk Maxwell Telescope. Our SCUBA-2 map has a diameter of 30 arcmin and contains ˜370 cluster members, including ˜200 objects with IR excesses. We detect a total of 13 discs. Assuming standard dust properties and a gas-to-dust-mass ratio of 100, we derive disc masses ranging from 1.5 to 16 MJUP. We also detect six Class 0/I protostars. We find that the most massive discs (MD > 3 MJUP; 850-μm flux > 10 mJy) in IC 348 tend to be transition objects according to the characteristic `dip' in their infrared spectral energy distributions (SEDs). This trend is also seen in other regions. We speculate that this could be an initial conditions effect (e.g. more massive discs tend to form giant planets that result in transition disc SEDs) and/or a disc evolution effect (the formation of one or more massive planets results in both a transition disc SED and a reduction of the accretion rate, increasing the lifetime of the outer disc). A stacking analysis of the discs that remain undetected in our SCUBA-2 observations suggests that their median 850-μm flux should be ≲1 mJy, corresponding to a disc mass ≲0.3 MJUP (gas plus dust) or ≲1 M⊕ of dust. While the available data are not deep enough to allow a meaningful comparison of the disc luminosity functions between IC 348 and other young stellar clusters, our results imply that disc masses exceeding the minimum-mass solar nebula are very rare (≲1per cent) at the age of IC 348, especially around very low-mass stars.

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). 57.22235 Section 57.22235 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22235 Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

Alma Survey of Circumstellar Disks in the Young Stellar Cluster IC 348

NASA Astrophysics Data System (ADS)

Ruíz-Rodríguez, D.; Cieza, L. A.; Williams, J. P.; Andrews, S. M.; Principe, D. A.; Caceres, C.; Canovas, H.; Casassus, S.; Schreiber, M. R.; Kastner, J. H.

2018-05-01

We present a 1.3 mm continuum survey of the young (2-3 Myr) stellar cluster IC 348, which lies at a distance of 310 pc, and is dominated by low-mass stars (M⋆ ˜ 0.1-0.6 M⊙). We observed 136 Class II sources (disks that are optically thick in the infrared) at 0.8″ (200 au) resolution with a 3σ sensitivity of ˜ 0.45 mJy (Mdust ˜ 1.3 M⊕). We detect 40 of the targets and construct a mm-continuum luminosity function. We compare the disk mass distribution in IC 348 to those of younger and older regions, taking into account the dependence on stellar mass. We find a clear evolution in disk masses from 1 to 5-10 Myr. The disk masses in IC 348 are significantly lower than those in Taurus (1-3 Myr) and Lupus (1-3 Myr), similar to those of Chamaleon I, (2-3 Myr) and σ Ori (3-5 Myr) and significantly higher than in Upper Scorpius (5-10 Myr). About 20 disks in our sample (˜5% of the cluster members) have estimated masses (dust + gas) >1 MJup and hence might be the precursors of giant planets in the cluster. Some of the most massive disks include transition objects with inner opacity holes based on their infrared SEDs. From a stacking analysis of the 96 non-detections, we find that these disks have a typical dust mass of just ≲ 0.4 M⊕, even though the vast majority of their infrared SEDs remain optically thick and show little signs of evolution. Such low-mass disks may be the precursors of the small rocky planets found by Kepler around M-type stars.

The Magnetics Information Consortium (MagIC) Online Database: Uploading, Searching and Visualizing Paleomagnetic and Rock Magnetic Data

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A.; Tauxe, L.; Constable, C.; Pisarevsky, S. A.; Jackson, M.; Solheid, P.; Banerjee, S.; Johnson, C.

2006-12-01

The Magnetics Information Consortium (MagIC) is commissioned to implement and maintain an online portal to a relational database populated by both rock and paleomagnetic data. The goal of MagIC is to archive all measurements and the derived properties for studies of paleomagnetic directions (inclination, declination) and intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). MagIC is hosted under EarthRef.org at http://earthref.org/MAGIC/ and has two search nodes, one for paleomagnetism and one for rock magnetism. Both nodes provide query building based on location, reference, methods applied, material type and geological age, as well as a visual map interface to browse and select locations. The query result set is displayed in a digestible tabular format allowing the user to descend through hierarchical levels such as from locations to sites, samples, specimens, and measurements. At each stage, the result set can be saved and, if supported by the data, can be visualized by plotting global location maps, equal area plots, or typical Zijderveld, hysteresis, and various magnetization and remanence diagrams. User contributions to the MagIC database are critical to achieving a useful research tool. We have developed a standard data and metadata template (Version 2.1) that can be used to format and upload all data at the time of publication in Earth Science journals. Software tools are provided to facilitate population of these templates within Microsoft Excel. These tools allow for the import/export of text files and provide advanced functionality to manage and edit the data, and to perform various internal checks to maintain data integrity and prepare for uploading. The MagIC Contribution Wizard at http://earthref.org/MAGIC/upload.htm executes the upload and takes only a few minutes to process several thousand data records. The standardized MagIC template files are stored in the digital archives of EarthRef.org where they

The Magnetics Information Consortium (MagIC) Online Database: Uploading, Searching and Visualizing Paleomagnetic and Rock Magnetic Data

NASA Astrophysics Data System (ADS)

Koppers, A.; Tauxe, L.; Constable, C.; Pisarevsky, S.; Jackson, M.; Solheid, P.; Banerjee, S.; Johnson, C.; Genevey, A.; Delaney, R.; Baker, P.; Sbarbori, E.

2005-12-01

The Magnetics Information Consortium (MagIC) operates an online relational database including both rock and paleomagnetic data. The goal of MagIC is to store all measurements and their derived properties for studies of paleomagnetic directions (inclination, declination) and their intensities, and for rock magnetic experiments (hysteresis, remanence, susceptibility, anisotropy). MagIC is hosted under EarthRef.org at http://earthref.org/MAGIC/ and has two search nodes, one for paleomagnetism and one for rock magnetism. These nodes provide basic search capabilities based on location, reference, methods applied, material type and geological age, while allowing the user to drill down from sites all the way to the measurements. At each stage, the data can be saved and, if the available data supports it, the data can be visualized by plotting equal area plots, VGP location maps or typical Zijderveld, hysteresis, FORC, and various magnetization and remanence diagrams. All plots are made in SVG (scalable vector graphics) and thus can be saved and easily read into the user's favorite graphics programs without loss of resolution. User contributions to the MagIC database are critical to achieve a useful research tool. We have developed a standard data and metadata template (version 1.6) that can be used to format and upload all data at the time of publication in Earth Science journals. Software tools are provided to facilitate easy population of these templates within Microsoft Excel. These tools allow for the import/export of text files and they provide advanced functionality to manage/edit the data, and to perform various internal checks to high grade the data and to make them ready for uploading. The uploading is all done online by using the MagIC Contribution Wizard at http://earthref.org/MAGIC/upload.htm that takes only a few minutes to process a contribution of approximately 5,000 data records. After uploading these standardized MagIC template files will be stored in the

Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains.

PubMed

Orrú, Christina D; Groveman, Bradley R; Raymond, Lynne D; Hughson, Andrew G; Nonno, Romolo; Zou, Wenquan; Ghetti, Bernardino; Gambetti, Pierluigi; Caughey, Byron

2015-06-01

Prions propagate as multiple strains in a wide variety of mammalian species. The detection of all such strains by a single ultrasensitive assay such as Real Time Quaking-induced Conversion (RT-QuIC) would facilitate prion disease diagnosis, surveillance and research. Previous studies have shown that bank voles, and transgenic mice expressing bank vole prion protein, are susceptible to most, if not all, types of prions. Here we show that bacterially expressed recombinant bank vole prion protein (residues 23-230) is an effective substrate for the sensitive RT-QuIC detection of all of the different prion types that we have tested so far--a total of 28 from humans, cattle, sheep, cervids and rodents, including several that have previously been undetectable by RT-QuIC or Protein Misfolding Cyclic Amplification. Furthermore, comparison of the relative abilities of different prions to seed positive RT-QuIC reactions with bank vole and not other recombinant prion proteins allowed discrimination of prion strains such as classical and atypical L-type bovine spongiform encephalopathy, classical and atypical Nor98 scrapie in sheep, and sporadic and variant Creutzfeldt-Jakob disease in humans. Comparison of protease-resistant RT-QuIC conversion products also aided strain discrimination and suggested the existence of several distinct classes of prion templates among the many strains tested.

Radio Non-Detections of SN 2010cu and PSN J13203538+3408222 in IC 883

NASA Astrophysics Data System (ADS)

Romero-Canizales, Cristina; Perez-Torres, Miguel A.; Alberdi, Antxon; Kankare, Erkki; Ryder, Stuart D.; Mattila, Seppo

2011-04-01

We report 5 GHz eEVN observations of the luminous infrared galaxy IC 883 intended as a radio follow-up of SN 2010cu (CBET # 2213 and 2286) and PSN J13203538+3408222 (ATel # 3245) that were recently discovered within the nuclear regions of IC 883 by near-IR adaptive-optics observations. The observations were carried out on 23rd March 2011 between 0200UT and 0400UT (total time on source ~1.3 hours) and included the following antennae (diameter, location): Effelsberg (100m, Germany), Jodrell Bank (25m, UK), Medicina (32 m, Italy), Onsala (25 m, Sweden), Torun (32 m, Poland), Westerbork array (14x25 m, NL) and Yebes (40 m, Spain).

The time-dependence of the defective nature of ice Ic (cubic ice) and its implications for atmospheric science

NASA Astrophysics Data System (ADS)

Sippel, Christian; Koza, Michael M.; Hansen, Thomas C.; Kuhs, Werner F.

2010-05-01

The possible atmospheric implication of ice Ic (cubic ice) has already been suggested some time ago in the context of snow crystal formation [1]. New findings from air-borne measurements in cirrus clouds and contrails have put ice Ic into the focus of interest to understand the so-called "supersaturation puzzle" [2,3,4]. Our recent microstructural work on ice Ic [5,6] appears to be highly relevant in this context. We have found that ice Ic is characterized by a complex stacking fault pattern, which changes as a function of temperature as well as time. Indeed, from our own [7] and other group's work [8] one knows that (in contrast to earlier believe) ice Ic can form up to temperatures at least as high as 240K - thus in the relevant range for cirrus clouds. We have good preliminary evidence that the "cubicity" (which can be related to stacking fault probabilities) as well as the particle size of ice Ic are the relevant parameters for this correlation. The "cubicity" of stacking faulty ice Ic (established by diffraction) correlates nicely with the increased supersaturation at decreasing temperatures observed in cirrus clouds and contrails, a fact, which may be considered as further evidence for the presence of ice Ic. Recently, we have studied the time-dependency of the changes in both "cubicity" and particle size at various temperatures of relevance for cirrus clouds and contrails by in-situ neutron powder diffraction. The timescales over which changes occur (several to many hours) are similar to the life-time of cirrus clouds and contrails and suggest that the supersaturation situation may change within this time span in the natural environment too. Some accompanying results obtained by cryo-SEM (scanning electron microscopy) work will also be presented and suggest that stacking-faulty ice Ic has kinky surfaces providing many more active centres for heterogeneous reactions on the surface than in the usually assumed stable hexagonal form of ice Ih with its rather

High Resolution X-ray Spectroscopy and Star Formation: HETG Observations of the Pre-Main Sequence Stellar Cluster IC 348

NASA Astrophysics Data System (ADS)

Principe, David; Huenemoerder, David P.; Schulz, Norbert; Kastner, Joel H.; Weintraub, David; Preibisch, Thomas

2018-01-01

We present Chandra High Energy Transmission Grating (HETG) observations of the ∼3 Myr old pre-main sequence (pre-MS) stellar cluster IC 348. With 400-500 cluster members at a distance of ∼300 pc, IC 348 is an ideal target to observe a large number of X-ray sources in a single pointing and is thus an extremely efficient use of Chandra-HETG. High resolution X-ray spectroscopy offers a means to investigate detailed spectral characteristic of X-ray emitting plasmas and their surrounding environments. We present preliminary results where we compare X-ray spectral signatures (e.g., luminosity, temperature, column density, abundance) of the X-ray brightest pre-MS stars in IC 348 with spectral type, multiwavelength signatures of accretion, and the presence of circumstellar disks at multiple stages of pre-MS stellar evolution. Assuming all IC 348 members formed from the same primordial molecular cloud, any disparity between coronal abundances of individual members, as constrained by the identification and strength of emission lines, will constrain the source(s) of coronal chemical evolution at a stage of pre-MS evolution vital to the formation of planets.

PREFACE: 2nd International Conference on Mathematical Modeling in Physical Sciences 2013 (IC-MSQUARE 2013)

NASA Astrophysics Data System (ADS)

2014-03-01

The second International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place at Prague, Czech Republic, from Sunday 1 September to Thursday 5 September 2013. The Conference was attended by more than 280 participants and hosted about 400 oral, poster, and virtual presentations while counted more than 600 pre-registered authors. The second IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics. The scientific program was rather heavy since after the Keynote and Invited Talks in the morning, three parallel sessions were running every day. However, according to all attendees, the program was excellent with high level of talks and the scientific environment was fruitful, thus all attendees had a creative time. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee. Further information on the editors, speakers and committees is available in the attached pdf.

The young stellar population of IC 1613. III. New O-type stars unveiled by GTC-OSIRIS

NASA Astrophysics Data System (ADS)

Garcia, M.; Herrero, A.

2013-03-01

Context. Very low-metallicity massive stars are key to understanding the reionization epoch. Radiation-driven winds, chief agents in the evolution of massive stars, are consequently an important ingredient in our models of the early-Universe. Recent findings hint that the winds of massive stars with poorer metallicity than the SMC may be stronger than predicted by theory. Besides calling the paradigm of radiation-driven winds into question, this result would affect the calculated ionizing radiation and mechanical feedback of massive stars, as well as the role these objects play at different stages of the Universe. Aims: The field needs a systematic study of the winds of a large sample of very metal-poor massive stars. The sampling of spectral types is particularly poor in the very early types. This paper's goal is to increase the list of known O-type stars in the dwarf irregular galaxy IC 1613, whose metallicity is lower than the SMC's roughly by a factor 2. Methods: Using the reddening-free Q pseudo-colour, evolutionary masses, and GALEX photometry, we built a list of very likely O-type stars. We obtained low-resolution (R ~ 1000) GTC-OSIRIS spectra for a fraction of them and performed spectral classification, the only way to unequivocally confirm candidate OB-stars. Results: We have discovered 8 new O-type stars in IC 1613, increasing the list of 7 known O-type stars in this galaxy by a factor of 2. The best quality spectra were analysed with the model atmosphere code FASTWIND to derive stellar parameters. We present the first spectral type - effective temperature scale for O-stars beyond the SMC. Conclusions: The target selection method is successful. From the pre-selected list of 13 OB star candidates, we have found 8 new O-stars and 4 early-B stars and provided a similar type for a formerly known early-O star. Further tests are needed, but the presented procedure can eventually make preliminary low-resolution spectroscopy to confirm candidates unnecessary. The

Screening of proteins based on macro-algae from West Java coast in Indonesian marine as a potential anti-aging agent

NASA Astrophysics Data System (ADS)

Putri, Arlina Prima; Dewi, Rizna Triana; Handayani, Aniek Sri; Harjanto, Sri; Chalid, Mochamad

2018-02-01

Algae has been known as one of the potential marine bio-resources that have been used in many fields such as bio-energy, food, pharmaceutical and medical applications. Study of macro-algae or seaweed for medicine application, in particular, highlights to empower their ingredients as a promising antioxidant like anti-aging agent due to their diversity in biological activity. The tropical climate of Indonesia with the highest marine biodiversity puts this country an auspicious source of numerous alga species as a novel antioxidant source. A Sample of 29 species of macroalgae has been collected from Coast of Pari Island as a part of Seribu Islands, Indonesia. Screening and extracting of aqueous tropical marine alga protein as a potential source for an antioxidant agent has been done by using 2,2-diphenyl-1-picrylhydrazyl scavenging method, and protein contents have been determined by Lowry method. Sample number 26 of the phylum Rhodophyta have 9.00±0.03 % protein content, which is potential for nutritional food in form of nutraceutical. That sample demonstrated the maximum DPPH scavenging activity 79.27±1.81 %. Moreover, crude extract from another species from phylum Rhodophyta had the very lower IC50 (3.4333±0.29 mg/ml) followed by Chlorophyta species (7.1069±1.78 mg/ml). In general, this study found that algae from phylum Rhodophyta possess a high content of protein, high activity towards free radical. Nevertheless, algae acquire the lowest IC50 value not only dominated by Rhodophyta but also from phylum Chlorophyta. The conclusion of this study leads to empowering high antioxidant activity algae as an anti-aging agent, which can be used in pharmaceutical applications. Therefore, the next study should be concerned on the properties of the algae which has been known to be suitable for pharmaceutical fields.

[Positive inotropic and lusitropic effect of RP 62719, a new class III antiarrhythmia agent].

PubMed

Beregi, J P; Escande, D; Coudray, N; Chemla, D; Mestre, M; Péry, N; Lecarpentier, Y

1994-02-01

Antiarrhythmic drugs, especially the Class I family, exert a negative inotropic effect on the myocardium which is particularly undesirable in patients with depressed left ventricular function. Therefore, research has been directed to the development of new, more specific molecules of the Class III family. The authors studies the mechanical effects of RP 62719 on guinea pig left ventricular papillary muscle. This new molecule is a pure Class III antiarrhythmic, known to lengthen the duration of the cardiac action potential by selectively blocking the potassium current iK1 (inward rectifier K+ current). The mechanical parameters were determined during the phases of contraction and relaxation under isotonic and isometric conditions. At 0.2 and 2 microM concentrations, RP 62719 improved cardiac contraction under both isotonic and isometric conditions with an increase of about 30% of Vmax (p < 0.001), the maximum unloaded shortening velocity delta 1 (p < 0.001), the peak isometric active force normalized per cross-sectional area [AF/S (p < 0.001)]. At these two concentrations, a positive lusitropic effect (improved relaxation) was demonstrated by an increase in negative peak of derivative per mm2-dF/s and maximum lengthening velocity VR max (p < 0.01). At higher concentrations (20 microM), the inotropic and lusitropic effects were less marked with a bell-shaped form of the dose-effect curve. This study indicates that RP 62719 has moderate but significant positive inotropic and lusitropic effects. These actions could provide significant therapeutic advantages especially in patients cardiac failure.

Changing adherence-related beliefs about ICS maintenance treatment for asthma: feasibility study of an intervention delivered by asthma nurse specialists.

PubMed

Chapman, Sarah C E; Barnes, Neil; Barnes, Mari; Wilkinson, Andrea; Hartley, John; Piddock, Cher; Weinman, John; Horne, Rob

2015-06-05

The Necessity-Concerns Framework (NCF) posits that non-adherence to inhaled corticosteroids (ICS) in asthma is influenced by doubts about the necessity for ICS and concerns about their potential adverse effects. This feasibility study examined whether these beliefs could be changed by briefing asthma nurse specialists on ways of addressing necessity beliefs and concerns within consultations. Pre-post intervention study. Secondary care. Patients with a diagnosis of moderate to severe asthma who were prescribed daily ICS were recruited to either a hospital care group (n=79; 71.0% female) or intervention group (n=57; 66.7% female). Asthma nurse specialists attended a 1.5-day NCF briefing. Beliefs about ICS (primary outcome) and self-reported adherence were measured preconsultation and 1 month postconsultation. Participants also rated their satisfaction with their consultations immediately after the consultation. Consultation recordings were coded to assess intervention delivery. After the NCF briefing, nurse specialists elicited and addressed beliefs about medicine more frequently. The frequency of using the NCF remained low, for example, open questions eliciting adherence were used in 0/59 hospital care versus 14/49 (28.6%) intervention consultations. Doubts about personal necessity for, and concerns about, ICS were reduced at 1 month postbriefing (p<0.05), but the intervention was not applied extensively enough to improve adherence. The intervention changed nurse consultations, but not sufficiently enough to fully address non-adherence or adherence-related ICS beliefs (necessity and concerns). More effective techniques are needed to support nurse specialists and other practitioners to apply the intervention in hospital asthma review consultations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The basic circuit of the IC: tectothalamic neurons with different patterns of synaptic organization send different messages to the thalamus

PubMed Central

Ito, Tetsufumi; Oliver, Douglas L.

2012-01-01

The inferior colliculus (IC) in the midbrain of the auditory system uses a unique basic circuit to organize the inputs from virtually all of the lower auditory brainstem and transmit this information to the medial geniculate body (MGB) in the thalamus. Here, we review the basic circuit of the IC, the neuronal types, the organization of their inputs and outputs. We specifically discuss the large GABAergic (LG) neurons and how they differ from the small GABAergic (SG) and the more numerous glutamatergic neurons. The somata and dendrites of LG neurons are identified by axosomatic glutamatergic synapses that are lacking in the other cell types and exclusively contain the glutamate transporter VGLUT2. Although LG neurons are most numerous in the central nucleus of the IC (ICC), an analysis of their distribution suggests that they are not specifically associated with one set of ascending inputs. The inputs to ICC may be organized into functional zones with different subsets of brainstem inputs, but each zone may contain the same three neuron types. However, the sources of VGLUT2 axosomatic terminals on the LG neuron are not known. Neurons in the dorsal cochlear nucleus, superior olivary complex, intermediate nucleus of the lateral lemniscus, and IC itself that express the gene for VGLUT2 only are the likely origin of the dense VGLUT2 axosomatic terminals on LG tectothalamic neurons. The IC is unique since LG neurons are GABAergic tectothalamic neurons in addition to the numerous glutamatergic tectothalamic neurons. SG neurons evidently target other auditory structures. The basic circuit of the IC and the LG neurons in particular, has implications for the transmission of information about sound through the midbrain to the MGB. PMID:22855671

An Ultra-Low-Power RFID/NFC Frontend IC Using 0.18 μm CMOS Technology for Passive Tag Applications.

PubMed

Bhattacharyya, Mayukh; Gruenwald, Waldemar; Jansen, Dirk; Reindl, Leonhard; Aghassi-Hagmann, Jasmin

2018-05-07

Battery-less passive sensor tags based on RFID or NFC technology have achieved much popularity in recent times. Passive tags are widely used for various applications like inventory control or in biotelemetry. In this paper, we present a new RFID/NFC frontend IC (integrated circuit) for 13.56 MHz passive tag applications. The design of the frontend IC is compatible with the standard ISO 15693/NFC 5. The paper discusses the analog design part in details with a brief overview of the digital interface and some of the critical measured parameters. A novel approach is adopted for the demodulator design, to demodulate the 10% ASK (amplitude shift keying) signal. The demodulator circuit consists of a comparator designed with a preset offset voltage. The comparator circuit design is discussed in detail. The power consumption of the bandgap reference circuit is used as the load for the envelope detection of the ASK modulated signal. The sub-threshold operation and low-supply-voltage are used extensively in the analog design—to keep the power consumption low. The IC was fabricated using 0.18 μ m CMOS technology in a die area of 1.5 mm × 1.5 mm and an effective area of 0.7 m m 2 . The minimum supply voltage desired is 1.2 V, for which the total power consumption is 107 μ W. The analog part of the design consumes only 36 μ W, which is low in comparison to other contemporary passive tags ICs. Eventually, a passive tag is developed using the frontend IC, a microcontroller, a temperature and a pressure sensor. A smart NFC device is used to readout the sensor data from the tag employing an Android-based application software. The measurement results demonstrate the full passive operational capability. The IC is suitable for low-power and low-cost industrial or biomedical battery-less sensor applications. A figure-of-merit (FOM) is proposed in this paper which is taken as a reference for comparison with other related state-of-the-art researches.

An Ultra-Low-Power RFID/NFC Frontend IC Using 0.18 μm CMOS Technology for Passive Tag Applications

PubMed Central

Gruenwald, Waldemar; Jansen, Dirk; Aghassi-Hagmann, Jasmin

2018-01-01

Battery-less passive sensor tags based on RFID or NFC technology have achieved much popularity in recent times. Passive tags are widely used for various applications like inventory control or in biotelemetry. In this paper, we present a new RFID/NFC frontend IC (integrated circuit) for 13.56 MHz passive tag applications. The design of the frontend IC is compatible with the standard ISO 15693/NFC 5. The paper discusses the analog design part in details with a brief overview of the digital interface and some of the critical measured parameters. A novel approach is adopted for the demodulator design, to demodulate the 10% ASK (amplitude shift keying) signal. The demodulator circuit consists of a comparator designed with a preset offset voltage. The comparator circuit design is discussed in detail. The power consumption of the bandgap reference circuit is used as the load for the envelope detection of the ASK modulated signal. The sub-threshold operation and low-supply-voltage are used extensively in the analog design—to keep the power consumption low. The IC was fabricated using 0.18 μm CMOS technology in a die area of 1.5 mm × 1.5 mm and an effective area of 0.7 mm2. The minimum supply voltage desired is 1.2 V, for which the total power consumption is 107 μW. The analog part of the design consumes only 36 μW, which is low in comparison to other contemporary passive tags ICs. Eventually, a passive tag is developed using the frontend IC, a microcontroller, a temperature and a pressure sensor. A smart NFC device is used to readout the sensor data from the tag employing an Android-based application software. The measurement results demonstrate the full passive operational capability. The IC is suitable for low-power and low-cost industrial or biomedical battery-less sensor applications. A figure-of-merit (FOM) is proposed in this paper which is taken as a reference for comparison with other related state-of-the-art researches. PMID:29735939

Electrical Characterization of 4H-SiC JFET Wafer: DC Parameter Variations for Extreme Temperature IC Design

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Chen, Liangyu; Spry, David J.; Beheim, Glenn M.; Chang, Carl W.

2014-01-01

This work reports DC electrical characterization of a 76 mm diameter 4H-SiC JFET test wafer fabricated as part of NASA's on-going efforts to realize medium-scale ICs with prolonged and stable circuit operation at temperatures as high as 500 degC. In particular, these measurements provide quantitative parameter ranges for use in JFET IC design and simulation. Larger than expected parameter variations were observed both as a function of position across the wafer as well as a function of ambient testing temperature from 23 degC to 500 degC.

Simulation of a class of hazardous situations in the ICS «INM RAS - Baltic Sea»

NASA Astrophysics Data System (ADS)

Zakharova, Natalia; Agoshkov, Valery; Aseev, Nikita; Parmuzin, Eugene; Sheloput, Tateana; Shutyaev, Victor

2017-04-01

Development of Informational Computational Systems (ICS) for data assimilation procedures is one of multidisciplinary problems. To study and solve these problems one needs to apply modern results from different disciplines and recent developments in mathematical modeling, theory of adjoint equations and optimal control, inverse problems, numerical methods theory, numerical algebra, scientific computing and processing of satellite data. In this work the results on the ICS development for PC-ICS "INM RAS - Baltic Sea" are presented. We discuss practical problems studied by ICS. The System includes numerical model of the Baltic Sea thermodynamics, the new oil spill model describing the propagation of a slick at the Sea surface (Agoshkov, Aseev et al., 2014) and the optimal ship route calculating block (Agoshkov, Zayachkovsky et al., 2014). The ICS is based on the INMOM numerical model of the Baltic Sea thermodynamics (Zalesny et al., 2013). It is possible to calculate main hydrodynamic parameters (temperature, salinity, velocities, sea level) using user-friendly interface of the ICS. The System includes data assimilation procedures (Agoshkov, 2003, Parmuzin, Agoshkov, 2012) and one can use the block of variational assimilation of the sea surface temperature in order to obtain main hydrodynamic parameters. Main possibilities of the ICS and several numerical experiments are presented in the work. By the problem of risk control is meant a problem of determination of optimal resources quantity which are necessary for decreasing the risk to some acceptable value. Mass of oil slick is chosen as a function of control. For the realization of the random variable the quadratic "functional of cost" is introduced. It comprises cleaning costs and deviation of damage of oil pollution from its acceptable value. The problem of minimization of this functional is solved based on the methods of optimal control and the theory of adjoint equations. The solution of this problem is

Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC).

PubMed

Wang, G S; Levitan, R; Wiegand, T J; Lowry, J; Schult, R F; Yin, S

2016-03-01

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for toxicological exposure. There were 26,271 exposures (60 % female) reported to the ToxIC Registry, 10 (0.0004 %) received ECMO: 4 pediatric (< 12 years), 2 adolescent (12-18 years), and 4 adults (>18 years). Time of initiation of ECMO ranged from 4 h to 4 days, with duration from 15 h to 12 days. Exposures included carbon monoxide/smoke inhalation (2), bitter almonds, methanol, and several medications including antihistamines (2), antipsychotic/antidepressant (2), cardiovascular drugs (2), analgesics (2), sedative/hypnotics (2), and antidiabetics (2). Four ECMO patients received cardiopulmonary resuscitation (CPR) during their hospital course, and the overall survival rate was 80 %. ECMO was rarely used for poisoning exposures in the ACMT ToxIC Registry. ECMO was utilized for a variety of ages and for pharmaceutical and non-pharmaceutical exposures. In most cases, ECMO was administered prior to cardiovascular failure, and survival rate was high. If available, ECMO may be a valid treatment modality.

Making the MagIC (Magnetics Information Consortium) Web Application Accessible to New Users and Useful to Experts

NASA Astrophysics Data System (ADS)

Minnett, R.; Koppers, A.; Jarboe, N.; Tauxe, L.; Constable, C.; Jonestrask, L.

2017-12-01

Challenges are faced by both new and experienced users interested in contributing their data to community repositories, in data discovery, or engaged in potentially transformative science. The Magnetics Information Consortium (https://earthref.org/MagIC) has recently simplified its data model and developed a new containerized web application to reduce the friction in contributing, exploring, and combining valuable and complex datasets for the paleo-, geo-, and rock magnetic scientific community. The new data model more closely reflects the hierarchical workflow in paleomagnetic experiments to enable adequate annotation of scientific results and ensure reproducibility. The new open-source (https://github.com/earthref/MagIC) application includes an upload tool that is integrated with the data model to provide early data validation feedback and ease the friction of contributing and updating datasets. The search interface provides a powerful full text search of contributions indexed by ElasticSearch and a wide array of filters, including specific geographic and geological timescale filtering, to support both novice users exploring the database and experts interested in compiling new datasets with specific criteria across thousands of studies and millions of measurements. The datasets are not large, but they are complex, with many results from evolving experimental and analytical approaches. These data are also extremely valuable due to the cost in collecting or creating physical samples and the, often, destructive nature of the experiments. MagIC is heavily invested in encouraging young scientists as well as established labs to cultivate workflows that facilitate contributing their data in a consistent format. This eLightning presentation includes a live demonstration of the MagIC web application, developed as a configurable container hosting an isomorphic Meteor JavaScript application, MongoDB database, and ElasticSearch search engine. Visitors can explore the MagIC

A Quantitative Ethnopharmacological Documentation of Natural Pharmacological Agents Used by Pediatric Patients in Mauritius

PubMed Central

Mahomoodally, M. Fawzi; Sreekeesoon, D. Priyamka

2014-01-01

The pediatric population constitutes the most vulnerable patients due to a dearth of approved drugs. Consequently, there is a pressing need to probe novel natural pharmacological agents in an endeavour to develop new drugs to address pediatric illnesses. To date, no studies have explored the use of natural therapies for pediatric health care in Mauritius. Parents (n = 325) from different regions of the island were interviewed. Quantitative indexes such as fidelity level (FL), informant consensus factor (F IC), and use-value (UV) were calculated. Thirty-two plants were reported to be used by pediatric patients. Gastrointestinal disorders (F IC = 0.97) encompassing regurgitation, infantile colic, and stomach aches were the most common ailments managed with herbs. Matricaria chamomilla used for infantile colic and its pharmacological properties has previously been documented for pediatric patients. Product from A. mellifera (UV = 0.75) was the most utilized zootherapy for managing cough. Most plants and animal products reported in this study have bioactive constituents supported by existing scientific literature but their use for the pediatric population is scant. The present ethnopharmacological study has opened new perspectives for further research into their pharmacology, which can subsequently support and facilitate timely pediatric medicinal product development. PMID:24949418

Calcium channel currents in bovine adrenal chromaffin cells and their modulation by anaesthetic agents.

PubMed Central

Charlesworth, P; Pocock, G; Richards, C D

1994-01-01

1. The calcium channel currents of bovine adrenal chromaffin cells were characterized using a variety of voltage pulse protocols and selective channel blockers before examination of their modulation by anaesthetic agents. 2. All the anaesthetics studied (halothane, methoxyflurane, etomidate and methohexitone) inhibited the calcium channel currents in a concentration-dependent manner and increased the rate of current decay. 3. The anaesthetics did not shift the current-voltage relation nor did they change the voltage for half-maximal channel activation derived from analysis of the voltage dependence of the tail currents. None of the anaesthetics appeared to alter the time constant of tail current decay. 4. To complement earlier studies of the inhibitory actions of anaesthetics on K(+)-evoked catecholamine secretion and the associated Ca2+ uptake, the IC50 values for etomidate and methohexitone were determined using a biochemical assay. The IC50 values for anaesthetic inhibition of calcium channel currents corresponded closely with those for inhibition of K(+)-evoked calcium uptake and catecholamine secretion. 5. The inhibitory effect of the volatile anaesthetics and etomidate is best explained by dual action: a reduction in the probability of channel opening coupled with an increase in the rate of channel inactivation. Methohexitone appeared to inhibit the currents by a use-dependent slow block. PMID:7707224

Using Tablet PCs and Interactive Software in IC Design Courses to Improve Learning

ERIC Educational Resources Information Center

Simoni, M.

2011-01-01

This paper describes an initial study of using tablet PCs and interactive course software in integrated circuit (IC) design courses. A rapidly growing community is demonstrating how this technology can improve learning and retention of material by facilitating interaction between faculty and students via cognitive exercises during lectures. While…

The Formation of Solid Particles from their Gas-Phase Molecular Precursors in Cosmic Environments with NASA Ames' COSmIC Facility

NASA Technical Reports Server (NTRS)

Salama, Farid

2014-01-01

We present and discuss the unique characteristics and capabilities of the laboratory facility, COSmIC, that was developed at NASA Ames to generate, process and analyze interstellar, circumstellar and planetary analogs in the laboratory. COSmIC stands for Cosmic Simulation Chamber and is dedicated to the study of molecules and ions under the low temperature and high vacuum conditions that are required to simulate interstellar, circumstellar and planetary physical environments in space. COSmIC integrates a variety of state-of-the-art instruments that allow forming, processing and monitoring simulated space conditions for planetary, circumstellar and interstellar materials in the laboratory. COSmIC is composed of a Pulsed Discharge Nozzle (PDN) expansion that generates a free jet supersonic expansion coupled to two ultrahigh-sensitivity, complementary in situ diagnostics: a Cavity Ring Down Spectroscopy (CRDS) system for photonic detection and a Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection. Recent, unique, laboratory astrophysics results that were obtained using the capabilities of COSmIC will be discussed, in particular the progress that have been achieved in monitoring in the laboratory the formation of solid gains from their gas-phase molecular precursors in environments as varied as stellar/circumstellar outflow and planetary atmospheres. Plans for future, next generation, laboratory experiments on cosmic molecules and grains in the growing field of laboratory astrophysics will also be addressed as well as the implications of these studies for current and upcoming space missions.

IN-SYNC. III. The Dynamical State of IC 348 - A Super-virial Velocity Dispersion and a Puzzling Sign of Convergence

NASA Astrophysics Data System (ADS)

Cottaar, Michiel; Covey, Kevin R.; Foster, Jonathan B.; Meyer, Michael R.; Tan, Jonathan C.; Nidever, David L.; Chojnowski, S. Drew; da Rio, Nicola; Flaherty, Kevin M.; Frinchaboy, Peter M.; Majewski, Steve; Skrutskie, Michael F.; Wilson, John C.; Zasowski, Gail

2015-07-01

Most field stars will have encountered the highest stellar density and hence the largest number of interactions in their birth environment. Yet the stellar dynamics during this crucial phase are poorly understood. Here we analyze the radial velocities measured for 152 out of 380 observed stars in the 2-6 Myr old star cluster IC 348 as part of the SDSS-III APOGEE. The radial velocity distribution of these stars is fitted with one or two Gaussians, convolved with the measurement uncertainties including binary orbital motions. Including a second Gaussian improves the fit; the high-velocity outliers that are best fit by this second component may either (1) be contaminants from the nearby Perseus OB2 association, (2) be a halo of ejected or dispersing stars from IC 348, or (3) reflect that IC 348 has not relaxed to a Gaussian velocity distribution. We measure a velocity dispersion for IC 348 of 0.72 ± 0.07 km s-1 (or 0.64 ± 0.08 km s-1 if two Gaussians are fitted), which implies a supervirial state, unless the gas contributes more to the gravitational potential than expected. No evidence is found for a dependence of this velocity dispersion on distance from the cluster center or stellar mass. We also find that stars with lower extinction (in the front of the cloud) tend to be redshifted compared with stars with somewhat higher extinction (toward the back of the cloud). This data suggest that the stars in IC 348 are converging along the line of sight. We show that this correlation between radial velocity and extinction is unlikely to be spuriously caused by the small cluster rotation of 0.024 ± 0.013 km s-1 arcmin-1 or by correlations between the radial velocities of neighboring stars. This signature, if confirmed, will be the first detection of line of sight convergence in a star cluster. Possible scenarios for reconciling this convergence with IC 348's observed supervirial state include: (a) the cluster is fluctuating around a new virial equilibrium after a recent

30 CFR 57.22212 - Air flow (I-C, II-A, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22212 Air flow (I-C, II-A, and V-A mines). Air flow across each working face shall be sufficient to carry away any accumulation of methane, smoke...

ALMA Survey of Class II Disks in the Young Stellar Cluster IC 348

NASA Astrophysics Data System (ADS)

Ruiz, Dary; Cieza, Lucas; Williams, Jonathan; Andrews, Sean; Principe, David

2018-01-01

We present a 1.3 mm continuum survey of the young (2-3 Myr) stellar cluster IC 348 at a distance of 270 pc, which is dominated by low-mass stars. We observed 146 Class II sources (disks that are optically thick in the infrared) at 0.8 '' (200 au) resolution with a 3σ sensitivity of 0.2 MEarth. We detect 46 of the targets and construct a disk luminosity function. We compare the disk mass distribution in IC 348 to those of younger and older regions, taking into account the dependence on stellar mass. We find a clear evolution in disk masses from 1 to 5-10 Myr. The disk masses in IC 348 are significantly lower than those in Taurus (1-2 Myr) and Lupus (1-3 Myr), similar to those of Chamaleon I, (2-3 Myr) and σ-Ori (3-5 Myr) and significantly higher than in Upper Scorpius (5-10 Myr). About 20 disks in our sample (~5% of the cluster members) have estimated masses (dust + gas) of >1 MJUP. and might be the precursors of giant planets in the cluster. Some of the most massive disks include transition objects with inner opacity holes based on their infrared SEDs. From an stacking analysis of the 90 non-detections, we find that these disks have a typical dust mass of just ≤ 0.1 MEarth, even though the vast majority of their infrared SEDs remain optically thick and show little signs of evolution. Such low-mass disks are likely to be the precursors of the small rocky planets found by Kepler around M-type stars.

Exploring physical and chemical factors influencing the properties of recombinant prion protein and the real-time quaking-induced conversion (RT-QuIC) assay.

PubMed

Cheng, Keding; Sloan, Angela; Avery, Kristen M; Coulthart, Michael; Carpenter, Michael; Knox, J David

2014-01-01

Real-time quaking-induced conversion (RT-QuIC), a highly specific and sensitive assay able to detect low levels of the disease-inducing isoform of the prion protein (PrP(d)) in brain tissue biopsies and cerebral spinal fluid, has great potential to become a method for diagnosing prion disease ante mortem. In order to standardize the assay method for routine analysis, an understanding of how physical and chemical factors affect the stability of the recombinant prion protein (rPrP) substrate and the RT-QuIC assay's sensitivity, specificity, and reproducibility is required. In this study, using sporadic Creutzfeldt-Jakob Disease brain homogenate to seed the reactions and an in vitro-expressed recombinant prion protein, hamster rPrP, as the substrate, the following factors affecting the RT-QuIC assay were examined: salt and substrate concentrations, substrate storage, and pH. Results demonstrated that both the generation of the quality and quantities of rPrP substrate critical to the reaction, as well as the RT-QuIC reaction itself required strict adherence to specific physical and chemical conditions. Once optimized, the RT-QuIC assay was confirmed to be a very specific and sensitive assay method for sCJD detection. Findings in this study indicate that further optimization and standardization of RT-QuIC assay is required before it can be adopted as a routine diagnostic test.

Giant Spherical Cluster with I-C140 Fullerene Topology**

PubMed Central

Heinl, Sebastian; Peresypkina, Eugenia; Sutter, Jörg; Scheer, Manfred

2015-01-01

We report on an effective cluster expansion of CuBr-linked aggregates by the increase of the steric bulk of the CpR ligand in the pentatopic molecules [CpRFe(η5-P5)]. Using [CpBIGFe(η5-P5)] (CpBIG=C5(4-nBuC6H4)5), the novel multishell aggregate [{CpBIGFe(η5:2:1:1:1:1:1-P5)}12(CuBr)92] is obtained. It shows topological analogy to the theoretically predicted I-C140 fullerene molecule. The spherical cluster was comprehensively characterized by various methods in solution and in the solid state. PMID:26411255

Surprisingly high-pressure shocks in the supernova remnant IC 443

NASA Technical Reports Server (NTRS)

Moorhouse, A.; Brand, P. W. J. L.; Geballe, T. R.; Burton, M. G.

1991-01-01

The intensities of several lines of molecular hydrogen have been measured from two regions of the supernova-remnant/molecular-cloud shock in IC 443. The lines measured have upper-state energies ranging from 7000 K to 23,000 K. Their relative intensities differ in the two regions, but are consistent with those predicted from the post-shock regions of simple jump-type shocks of different pressure. The pressures so derived are far higher than the pressure in the supernova remnant itself, and a possible reason for this discrepancy is discussed.

An abundance study of IC 418 using high-resolution, signal-to-noise emission spectra

NASA Astrophysics Data System (ADS)

Sharpee, Brian David

2003-11-01

An on-going problem in astrophysics involves the large and varying disagreement between abundances measurements made in planetary nebulae (PNe), determined from the strengths of emission lines arising from the same source ion, but excited by differing mechanisms (recombination and collisional excitation) in planetary nebulae (PNe). We investigate the extent of this problem in IC 418, a PN chosen for its great surface brightness and perceived visually uncomplicated geometry, through the use of high resolution (R ≈ 30000 = 10 km sec-1 at 6500Å) echelle emission spectroscopy in the optical regime (3500 9850Å). These observations allow us to construct the most detailed list of atomic emission lines ever compiled for IC 418, and among the most detailed from among all PNe. Ionic abundances are calculated from the fluxes of numerous weak (1 × 10-5 Hβ) atomic emission lines from the ions of C,N,O, and Ne, using the most recent and accurate atomic transition information presently available. The high resolution of these spectra provides well-defined line profiles, which, coupled with the perceived simplicity of the object's expansion velocity distribution, allows us to better determine where in the nebula lines are formed, and where the ions that produce them are concentrated. Evidence for “non-conventional” line excitation mechanisms, such as continuum fluorescence from the ground state or enhanced dielectronic recombination, is sought in the profile morphologies and relative line strengths. Non-conventional excitation processes may influence the strengths of lines enough to significantly alter abundances calculated from them. Our calculations show that recombination line-derived abundances exceed those derived from collisionally excited lines, for those ions for which we observed lines of both types: O+, O+2, and Ne +2 by real and varying amounts. We find that both continuum fluorescence and dielectronic recombination excites numerous lines in IC 418, but that

Design, synthesis and biological evaluation of 4'-aminochalcone-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

PubMed

Xiao, Ganyuan; Li, Yan; Qiang, Xiaoming; Xu, Rui; Zheng, Yunxiaozhu; Cao, Zhongcheng; Luo, Li; Yang, Xia; Sang, Zhipei; Su, Fu; Deng, Yong

2017-02-01

A series of 4'-aminochalcone-revastigmine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. The results showed that most of these compounds exhibited good multifunctional activities. In particular, compound 6c displayed the best inhibitory potency on acetylcholinesterase (IC 50 =4.91μM), and significant antioxidative activity with a value 2.83-fold of Trolox. The kinetic analysis of AChE inhibition revealed that 6c showed mixed-type inhibition, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. In addition, 6c inhibited self-induced Aβ 1-42 aggregation and Cu 2+ -induced Aβ 1-42 aggregation by 89.5% and 79.7% at 25μM respectively, as well as acted as a selective monoamine oxidase B inhibitor (IC 50 =0.29μM) and a selective biometal chelator. Furthermore, 6c could cross the blood-brain barrier in vitro. Based on these results, Compound 6c could be considered as a very promising lead compound for Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative safety and effectiveness of long-acting inhaled agents for treating chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

PubMed

Tricco, Andrea C; Strifler, Lisa; Veroniki, Areti-Angeliki; Yazdi, Fatemeh; Khan, Paul A; Scott, Alistair; Ng, Carmen; Antony, Jesmin; Mrklas, Kelly; D'Souza, Jennifer; Cardoso, Roberta; Straus, Sharon E

2015-10-26

To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD). Systematic review and network meta-analysis (NMA). 208 randomised clinical trials (RCTs) including 134,692 adults with COPD. LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo. The proportion of patients with moderate-to-severe exacerbations. The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes. NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26,141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol. Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve). NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%). NMA was conducted on CVM (37 RCTs, 55,156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR). Triamcinolone acetonide was the most harmful (SUCRA=81%). NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol. The most harmful agent was fluticasone/salmeterol (SUCRA=89%). NMA was conducted

Nitrotriazole- and Imidazole-Based Amides and Sulfonamides as Antitubercular Agents

PubMed Central

Bloomer, William D.; Rosenzweig, Howard S.; Arena, Alexander; Arrieta, Francisco; Rebolledo, Joseph C. J.; Smith, Diane K.

2014-01-01

Twenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti-TB) activity in aerobic Mycobacterium tuberculosis H37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole-based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 μM (compound 4), 0.57, 0.98, and 3.13 μM (compound 2), and 0.79, 0.87, and 3.13 μM (compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole-based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid-resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents. PMID:25182645

An ultra low-power front-end IC for wearable health monitoring system.

PubMed

Yu-Pin Hsu; Zemin Liu; Hella, Mona M

2016-08-01

This paper presents a low-power front-end IC for wearable health monitoring systems. The IC, designed in a standard 0.13μm CMOS technology, fully integrates a low-noise analog front-end (AFE) to process the weak bio-signals, followed by an analog-to-digital converter (ADC) to digitize the extracted signals. An AC-coupled driving buffer, that interfaces between the AFE and the ADC is introduced to scale down the power supply of the ADC. The power consumption decreases by 50% compared to the case without power supply scaling. The AFE passes signals from 0.5Hz to 280Hz and from 0.7Hz to 160Hz with a simulated input referred noise of 1.6μVrms and achieves a maximum gain of 35dB/41dB respectively, with a noise-efficiency factor (NEF) of the AFE is 1. The 8-bit ADC achieves a simulated 7.96-bit resolution at 10KS/s sampling rate under 0.5V supply voltage. The overall system consumes only 0.86μW at dual supply voltages of 1V (AFE) and 0.5 V (ADC).

Preclinical evaluation of a novel cyanine dye for tumor imaging with in vivo photoacoustic imaging.

PubMed

Temma, Takashi; Onoe, Satoru; Kanazaki, Kengo; Ono, Masahiro; Saji, Hideo

2014-09-01

Photoacoustic imaging (PA imaging or PAI) has shown great promise in the detection and monitoring of cancer. Although nanocarrier-based contrast agents have been studied for use in PAI, small molecule contrast agents are required due to their ease of preparation, costeffectiveness, and low toxicity. Here, we evaluated the usefulness of a novel cyanine dye IC7-1-Bu as a PAI contrast agent without conjugated targeting moieties for in vivo tumor imaging in a mice model. Basic PA characteristics of IC7-1-Bu were compared with indocyanine green (ICG), a Food and Drug Administration approved dye, in an aqueous solution. We evaluated the tumor accumulation profile of IC7-1-Bu and ICG by in vivo fluorescence imaging. In vivo PAI was then performed with a photoacoustic tomography system 24 and 48 h after intravenous injection of IC7-1-Bu into tumor bearing mice. IC7-1-Bu showed about a 2.3-fold higher PA signal in aqueous solution compared with that of ICG. Unlike ICG, IC7-1-Bu showed high tumor fluorescence after intravenous injection. In vivo PAI provided a tumor to background PA signal ratio of approximately 2.5 after intravenous injection of IC7-1-Bu. These results indicate that IC7-1-Bu is a promising PAI contrast agent for cancer imaging without conjugation of targeting moieties.

Development of a new benzophenone-diketopiperazine-type potent antimicrotubule agent possessing a 2-pyridine structure.

PubMed

Hayashi, Yoshiki; Takeno, Haruka; Chinen, Takumi; Muguruma, Kyohei; Okuyama, Kohei; Taguchi, Akihiro; Takayama, Kentaro; Yakushiji, Fumika; Miura, Masahiko; Usui, Takeo; Hayashi, Yoshio

2014-10-09

A new benzophenone-diketopiperazine-type potent antimicrotubule agent was developed by modifying the structure of the clinical candidate plinabulin (1). Although the right-hand imidazole ring with a branched alkyl chain at the 5-position in 1 was critical for the potency of the antimicrotubule activity, we successfully substituted this moiety with a simpler 2-pyridyl structure by converting the left-hand ring from a phenyl to a benzophenone structure without decreasing the potency. The resultant compound 6b (KPU-300) exhibited a potent cytotoxicity, with an IC50 value of 7.0 nM against HT-29 cells, by strongly binding to tubulin (K d = 1.3 μM) and inducing microtubule depolymerization.

Synthesis, biological evaluation, and molecular modeling of cinnamic acyl sulfonamide derivatives as novel antitubulin agents.

PubMed

Luo, Yin; Qiu, Ke-Ming; Lu, Xiang; Liu, Kai; Fu, Jie; Zhu, Hai-Liang

2011-08-15

A series of novel cinnamic acyl sulfonamide derivatives (9a-16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitro, with an IC(50) value of 0.8μg/mL. Docking simulation was performed to insert compound 10c into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10c with potent inhibitory activity in tumor growth may be a potential anticancer agent. Copyright © 2011 Elsevier Ltd. All rights reserved.

Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation.

PubMed

Moore, S Jo; West Greenlee, M Heather; Kondru, Naveen; Manne, Sireesha; Smith, Jodi D; Kunkle, Robert A; Kanthasamy, Anumantha; Greenlee, Justin J

2017-10-01

Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated ( n = 20), orally inoculated ( n = 19), and noninoculated ( n = 9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled ("market weight" groups). The remaining pigs ("aged" groups) were allowed to incubate for up to 73 months postinoculation (mpi). Tissues collected at necropsy were examined for disease-associated prion protein (PrP Sc ) by Western blotting (WB), antigen capture enzyme immunoassay (EIA), immunohistochemistry (IHC), and in vitro real-time quaking-induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC, and/or WB. By RT-QuIC, PrP Sc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. The bioassay was positive in four out of five pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrP Sc ) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6

Properties of the molecular gas in the fast outflow in the Seyfert galaxy IC 5063

NASA Astrophysics Data System (ADS)

Oosterloo, Tom; Raymond Oonk, J. B.; Morganti, Raffaella; Combes, Françoise; Dasyra, Kalliopi; Salomé, Philippe; Vlahakis, Nektarios; Tadhunter, Clive

2017-12-01

We present a detailed study of the properties of the molecular gas in the fast outflow driven by the active galactic nucleus (AGN) in the nearby radio-loud Seyfert galaxy IC 5063. By using ALMA observations of a number of tracers of the molecular gas (12CO(1-0), 12CO(2-1), 12CO(3-2), 13CO(2-1) and HCO+(4-3)), we map the differences in excitation, density and temperature of the gas as function of position and kinematics. The results show that in the immediate vicinity of the radio jet, a fast outflow, with velocities up to 800 km s-1, is occurring of which the gas has high excitation with excitation temperatures in the range 30-55 K, demonstrating the direct impact of the jet on the ISM. The relative brightness of the 12CO lines, as well as that of 13CO(2-1) vs. 12CO(2-1), show that the outflow is optically thin. We estimate the mass of the molecular outflow to be at least 1.2 × 106 M⊙ and likely to be a factor between two and three larger than this value. This is similar to that of the outflow of atomic gas, but much larger than that of the ionised outflow, showing that the outflow in IC 5063 is dominated by cold gas. The total mass outflow rate we estimated to be 12 M⊙ yr-1. The mass of the outflow is much smaller than the total gas mass of the ISM of IC 5063. Therefore, although the influence of the AGN and its radio jet is very significant in the inner regions of IC 5063, globally speaking the impact will be very modest. We used RADEX non-LTE modelling to explore the physical conditions of the molecular gas in the outflow. Models with the outflowing gas being quite clumpy give the most consistent results and our preferred solutions have kinetic temperatures in the range 20-100 K and densities between 105 and 106 cm-3. The resulting pressures are 106-107.5 K cm-3, about two orders of magnitude higher than in the outer quiescent disk. The highest densities and temperatures are found in the regions with the fastest outflow. The results strongly suggest that

Optical Follow-Up Observations of PTF10qts, a Luminous Broad-Lined Type Ic Supernova Found by the Palomar Transient Factory

NASA Technical Reports Server (NTRS)

Walker, E. S.; Mazzali, P. A.; Pian, E.; Hurley, K.; Arcavi, I.; Cenko, S. B.; Gal-Yam, A.; Horesh, A.; Kasliwal, M.; Poznanski, D.;

Advanced Cyber Industrial Control System Tactics, Techniques, and Procedures (ACI TTP) for Department of Defense (DOD) Industrial Control Systems (ICS)

DTIC Science & Technology

2016-08-10

enable JCS managers to detect advanced cyber attacks, mitigate the effects of those attacks, and recover their networks following an attack. It also... managers of ICS networks to Detect, Mitigate, and Recover from nation-state-level cyber attacks (strategic, deliberate, well-trained, and funded...Successful Detection of cyber anomalies is best achieved when IT and ICS managers remain in close coordination. The Integrity Checks Table

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K as anti-malarial agents

NASA Astrophysics Data System (ADS)

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-06-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K As Anti-Malarial Agents.

PubMed

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-01-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme ( Pf LDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The Pf LDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of Pf LDH, we have used Discovery studio to perform molecular docking in the active binding pocket of Pf LDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q 2 of 0.516. The model has predicted r 2 of 0.91 showing that predicted IC 50 values are in good agreement with experimental IC 50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K As Anti-Malarial Agents

PubMed Central

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-01-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors. PMID:28664157

Variability in P-Glycoprotein Inhibitory Potency (IC50) Using Various in Vitro Experimental Systems: Implications for Universal Digoxin Drug-Drug Interaction Risk Assessment Decision Criteria

PubMed Central

Bentz, Joe; O’Connor, Michael P.; Bednarczyk, Dallas; Coleman, JoAnn; Lee, Caroline; Palm, Johan; Pak, Y. Anne; Perloff, Elke S.; Reyner, Eric; Balimane, Praveen; Brännström, Marie; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hanna, Imad; Herédi-Szabó, Krisztina; Hillgren, Kate; Li, Libin; Hollnack-Pusch, Evelyn; Jamei, Masoud; Lin, Xuena; Mason, Andrew K.; Neuhoff, Sibylle; Patel, Aarti; Podila, Lalitha; Plise, Emile; Rajaraman, Ganesh; Salphati, Laurent; Sands, Eric; Taub, Mitchell E.; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yabut, Jocelyn; Yamagata, Tetsuo; Zhang, Lei

2013-01-01

A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC50 determinations. Each laboratory followed its in-house protocol to determine in vitro IC50 values for 16 inhibitors using four different test systems: human colon adenocarcinoma cells (Caco-2; eleven laboratories), Madin-Darby canine kidney cells transfected with MDR1 cDNA (MDCKII-MDR1; six laboratories), and Lilly Laboratories Cells—Porcine Kidney Nr. 1 cells transfected with MDR1 cDNA (LLC-PK1-MDR1; four laboratories), and membrane vesicles containing human P-glycoprotein (P-gp; five laboratories). For cell models, various equations to calculate remaining transport activity (e.g., efflux ratio, unidirectional flux, net-secretory-flux) were also evaluated. The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20- and 24-fold between lowest and highest IC50 values for sertraline and isradipine, to a maximum of 407- and 796-fold for telmisartan and verapamil, respectively. For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case. Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69- and 159-fold. The efflux ratio-based equation generally resulted in severalfold lower IC50 values compared with unidirectional or net-secretory-flux equations. Statistical analysis indicated that variability in IC50 values was mainly due to interlaboratory variability, rather than an implicit systematic difference between test systems. Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC50 determination proposed. The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens et al., 2013) and recommendations

PREFACE: 8th International Conference on 3D Radiation Dosimetry (IC3DDose)

NASA Astrophysics Data System (ADS)

Olsson, Lars E.; Bäck, S.; Ceberg, Sofie

2015-01-01

IC3DDose 2014, the 8th International Conference on 3D Radiation Dosimetry was held in Ystad, Sweden, from 4-7 September 2014. This grew out of the DosGel series, which began as DosGel99, the 1st International Workshop on Radiation Therapy Gel Dosimetry in Lexington, Kentucky. Since 1999 subsequent DoSGel conferences were held in Brisbane, Australia (2001), Ghent, Belgium (2004), Sherbrooke, Canada (2006) and Crete, Greece (2008). In 2010 the conference was held on Hilton Head Island, South Carolina and underwent a name-change to IC3DDose. The 7th and last meeting was held in Sydney, Australia from 4-8 November 2012. It is worth remembering that the conference series started at the very beginning of the intensity modulated radiotherapy era and that the dosimeters being developed then were, to some extent, ahead of the clinical need of radiotherapy. However, since then the technical developments in radiation therapy have been dramatic, with dynamic treatments, including tracking, gating and volumetric modulated arc therapy, widely introduced in the clinic with the need for 3D dosimetry thus endless. This was also reflected by the contributions at the meeting in Ystad. Accordingly the scope of the meeting has also broadened to IC3DDOSE - I See Three-Dimensional Dose. A multitude of dosimetry techniques and radiation detectors are now represented, all with the common denominator: three-dimensional or 3D. Additionally, quality assurance (QA) procedures and other aspects of clinical dosimetry are represented. The implementation of new dosimetric techniques in radiotherapy is a process that needs every kind of caution, carefulness and thorough validation. Therefore, the clinical needs, reformulated as the aims for IC3DDOSE - I See Three-Dimensional Dose, are: • Enhance the quality and accuracy of radiation therapy treatments through improved clinical dosimetry. • Investigate and understand the dosimetric challenges of modern radiation treatment techniques. • Provide

Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice.

PubMed

Otani, Sanae; Ayata, Minoru; Takeuchi, Kaoru; Takeda, Makoto; Shintaku, Haruo; Ogura, Hisashi

2014-08-01

Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. Copyright © 2014 Elsevier Inc. All rights reserved.

Unveiling the AGN in IC 883: discovery of a parsec-scale radio jet

NASA Astrophysics Data System (ADS)

Romero-Cañizales, C.; Alberdi, A.; Ricci, C.; Arévalo, P.; Pérez-Torres, M. Á.; Conway, J. E.; Beswick, R. J.; Bondi, M.; Muxlow, T. W. B.; Argo, M. K.; Bauer, F. E.; Efstathiou, A.; Herrero-Illana, R.; Mattila, S.; Ryder, S. D.

2017-05-01

IC 883 is a luminous infrared galaxy (LIRG) classified as a starburst-active galactic nucleus (AGN) composite. In a previous study, we detected a low-luminosity AGN (LLAGN) radio candidate. Here, we report on our radio follow-up at three frequencies that provides direct and unequivocal evidence of the AGN activity in IC 883. Our analysis of archival X-ray data, together with the detection of a transient radio source with luminosity typical of bright supernovae, gives further evidence of the ongoing star formation activity, which dominates the energetics of the system. At sub-parsec scales, the radio nucleus has a core-jet morphology with the jet being a newly ejected component showing a subluminal proper motion of 0.6-1 c. The AGN contributes less than 2 per cent of the total IR luminosity of the system. The corresponding Eddington factor is ˜10-3, suggesting this is a low-accretion rate engine, as often found in LLAGNs. However, its high bolometric luminosity (˜1044 erg s-1) agrees better with a normal AGN. This apparent discrepancy may just be an indication of the transition nature of the nucleus from a system dominated by star formation, to an AGN-dominated system. The nucleus has a strongly inverted spectrum and a turnover at ˜4.4 GHz, thus qualifying as a candidate for the least luminous (L5.0 GHz ˜ 6.3 × 1028 erg s-1 Hz-1) and one of the youngest (˜3 × 103 yr) gigahertz-peaked spectrum (GPS) sources. If the GPS origin for the IC 883 nucleus is confirmed, then advanced mergers in the LIRG category are potentially key environments to unveil the evolution of GPS sources into more powerful radio galaxies.

Interstellar Lithium and Rubidium in the Diffuse Gas Near IC 443

NASA Astrophysics Data System (ADS)

Ritchey, Adam M.; Taylor, C. J.; Federman, S. R.; Lambert, D. L.

2011-01-01

We present an analysis of interstellar lithium and rubidium from observations made with the Hobby-Eberly Telescope at McDonald Observatory of the Li I λ6707 and Rb I λ7800 absorption lines along four lines of sight through the supernova remnant IC 443. The observations probe interstellar material polluted by the ejecta of a core-collapse (Type II) supernova and can thus be used to constrain the contribution from massive stars to the synthesis of lithium and rubidium. Production of 7Li is expected to occur through neutrino spallation in the helium and carbon shells of the progenitor star during the terminal supernova explosion, while both 6Li and 7Li are synthesized via spallation and fusion reactions involving cosmic rays accelerated by the remnant. Gamma-ray emission from IC 443 provides strong evidence for the interaction of accelerated cosmic rays with the ambient atomic and molecular gas. Rubidium is also produced by massive stars through the weak s-process in the He- and C-burning shells and the r-process during core collapse. We examine interstellar 7Li/6Li isotope ratios as well as Li/K and Rb/K ratios along each line of sight, and discuss the implications of our results in the context of nucleosynthesis associated with Type II supernovae.

A linear acoustic model for intake wave dynamics in IC engines

NASA Astrophysics Data System (ADS)

Harrison, M. F.; Stanev, P. T.

2004-01-01

In this paper, a linear acoustic model is described that has proven useful in obtaining a better understanding of the nature of acoustic wave dynamics in the intake system of an internal combustion (IC) engine. The model described has been developed alongside a set of measurements made on a Ricardo E6 single cylinder research engine. The simplified linear acoustic model reported here produces a calculation of the pressure time-history in the port of an IC engine that agrees fairly well with measured data obtained on the engine fitted with a simple intake system. The model has proved useful in identifying the role of pipe resonance in the intake process and has led to the development of a simple hypothesis to explain the structure of the intake pressure time history: the early stages of the intake process are governed by the instantaneous values of the piston velocity and the open area under the valve. Thereafter, resonant wave action dominates the process. The depth of the early depression caused by the moving piston governs the intensity of the wave action that follows. A pressure ratio across the valve that is favourable to inflow is maintained and maximized when the open period of the valve is such to allow at least, but no more than, one complete oscillation of the pressure at its resonant frequency to occur while the valve is open.

Experimentally Observed Electrical Durability of 4H-SiC JFET ICs Operating from 500 C to 700 C

NASA Technical Reports Server (NTRS)

Neudeck, Philip G.; Spry, David J.; Chen, Liangyu; Lukco, Dorothy; Chang, Carl W.; Beheim, Glenn M.

2016-01-01

Prolonged 500 degrees Celsius to 700 degrees Celsius electrical testing data from 4H-SiC junction field effect transistor (JFET) integrated circuits (ICs) are combined with post-testing microscopic studies in order to gain more comprehensive understanding of the durability limits of the present version of NASA Glenn's extreme temperature microelectronics technology. The results of this study support the hypothesis that T = 500 degrees Celsius durability-limiting IC failure initiates with thermal-stress-related crack formation where dielectric passivation layers overcoat micron-scale vertical features including patterned metal traces.

Rapid and multiband variability of the TeV bright active nucleus of the galaxy IC 310

DOE PAGES

Aleksić, J.; Antonelli, L. A.; Antoranz, P.; ...

2014-03-14

Recently the radio galaxy IC 310 was identified as a γ-ray emitter based on observations at GeV energies with Fermi-LAT and at very high energies (VHE, E > 100 GeV) with the MAGIC telescopes. Originally classified as a head-tail radio galaxy, the nature of this object is subject of controversy since its nucleus shows blazar-like behavior. In order to understand the nature of IC 310 and the origin of the VHE emission, we studied the spectral and flux variability of IC 310 from the X-ray band to the VHE γ-ray regime. The light curve of IC 310 above 300 GeVmore » has been measured with the MAGIC telescopes from 2009 October to 2010 February. Contemporaneous Fermi-LAT data (2008-2011) in the 10-500 GeV energy range were also analyzed. In the X-ray regime, archival observations from 2003 to 2007 with XMM-Newton, Chandra, and Swift-XRT in the 0.5-10 keV band were studied. The VHE light curve reveals several high-amplitude and short-duration flares. Day-to-day flux variability is clearly present (>5σ). The photon index between 120 GeV and 8 TeV remains at the value Γ ~ 2.0 during both low and high flux states. The VHE spectral shape does not show significant variability, whereas the flux at 1 TeV changes by a factor of ~7. Fermi-LAT detected only eight γ-ray events in the energy range 10 GeV–500 GeV in three years of observation. Moreover, the measured photon index of Γ = 1.3 ± 0.5 in the Fermi-LAT range is very hard. The X-ray measurements show strong variability in both flux and photon index. The latter varied from 1.76 ± 0.07 to 2.55 ± 0.07. The rapid variability measured in γ-rays and X-rays confirms the blazar-like behavior of IC 310. The multi-TeV γ-ray emission seems to originate from scales of less than 80 Schwarzschild radii (for a black hole mass of 2 × 10 8 M⊙) within the compact core of its FR I radio jet with orientation angle 10°-38°. The spectral energy distribution resembles that of an extreme blazar, albeit the luminosity is more than

A multifactor regulatory circuit involving H-NS, VirF and an antisense RNA modulates transcription of the virulence gene icsA of Shigella flexneri.

PubMed

Tran, Chi Nhan; Giangrossi, Mara; Prosseda, Gianni; Brandi, Anna; Di Martino, Maria Letizia; Colonna, Bianca; Falconi, Maurizio

2011-10-01

The icsA gene of Shigella encodes a structural protein involved in colonization of the intestinal mucosa by bacteria. This gene is expressed upon invasion of the host and is controlled by a complex regulatory circuit involving the nucleoid protein H-NS, the AraC-like transcriptional activator VirF, and a 450 nt antisense RNA (RnaG) acting as transcriptional attenuator. We investigated on the interplay of these factors at the molecular level. DNase I footprints reveal that both H-NS and VirF bind to a region including the icsA and RnaG promoters. H-NS is shown to repress icsA transcription at 30°C but not at 37°C, suggesting a significant involvement of this protein in the temperature-regulated expression of icsA. We also demonstrate that VirF directly stimulates icsA transcription and is able to alleviate H-NS repression in vitro. According to these results, icsA expression is derepressed in hns- background and overexpressed when VirF is provided in trans. Moreover, we find that RnaG-mediated transcription attenuation depends on 80 nt at its 5'-end, a stretch carrying the antisense region. Bases engaged in the initial contact leading to sense-antisense pairing have been identified using synthetic RNA and DNA oligonucleotides designed to rebuild and mutagenize the two stem-loop motifs of the antisense region.

Fall-related injuries in a nursing home setting: is polypharmacy a risk factor?

PubMed

Baranzini, Federico; Diurni, Marcello; Ceccon, Francesca; Poloni, Nicola; Cazzamalli, Sara; Costantini, Chiara; Colli, Cristiano; Greco, Laura; Callegari, Camilla

2009-12-11

Polypharmacy is regarded as an important risk factor for fallingand several studies and meta-analyses have shown an increased fall risk in users of diuretics, type 1a antiarrhythmics, digoxin and psychotropic agents. In particular, recent evidence has shown that fall risk is associated with the use of polypharmacy regimens that include at least one established fall risk-increasing drug, rather than with polypharmacy per se. We studied the role of polypharmacy and the role of well-known fall risk-increasing drugs on the incidence of injurious falls. A retrospective observational study was carried out in a population of elderly nursing home residents. An unmatched, post-stratification design for age class, gender and length of stay was adopted. In all, 695 falls were recorded in 293 residents. 221 residents (75.4%) were female and 72 (24.6%) male, and 133 (45.4%) were recurrent fallers. 152 residents sustained no injuries when they fell, whereas injuries were sustained by 141: minor in 95 (67.4%) and major in 46 (32.6%). Only fall dynamics (p = 0.013) and drugs interaction between antiarrhythmic or antiparkinson class and polypharmacy regimen (> or =7 medications) seem to represent a risk association for injuries (p = 0.024; OR = 4.4; CI 95% 1.21 - 15.36). This work reinforces the importance of routine medication reviews, especially in residents exposed to polypharmacy regimens that include antiarrhythmics or antiparkinson drugs, in order to reduce the risk of fall-related injuries during nursing home stays.

Analysis of iodinated X-ray contrast agents in water samples by ion chromatography and inductively-coupled plasma mass spectrometry.

PubMed

Sacher, Frank; Raue, Brigitte; Brauch, Heinz-Jürgen

2005-08-26

In this paper, an analytical method for the determination of six iodinated X-ray contrast agents (amidotrizoic acid, iohexol, iomeprol, iopamidol, iopromide, and ioxitalamic acid), iodide, and iodate in water samples is presented. The method is based on a separation of the analytes by ion chromatography (IC) and a subsequent detection by inductively-coupled plasma mass spectrometry (ICP-MS). The method was optimised with respect to separation conditions (column type and eluent composition) and extensively validated. Without pre-concentration of the samples, limits of detection below 0.2 microg/l could be achieved whereby reproducibility was below 6% for all compounds under investigation.